- NMR Spectroscopy, Protein NMR Spectroscopy, NMR relaxation, Protein Dynamics, Protein Folding, Biomolecular NMR, and 28 moreProtein Structure and Function, Protein Structure Prediction, Coordination Chemistry, Peptides, Organic Synthesis, Ancient History, Military History, Ptolemaic Egyptian History, Hellenistic History, Hellenistic history (focus: Bactria, Indo-Greeks), Roman History, Byzantine Studies, Late Antique and Byzantine History, History of Crusades, Crusades and the Latin East, Al-Andalus, Albigensian Crusade, Medieval Occitania, Manichaeism, Gnosticism, Persian history, Japanese History, Chinese history (History), Protein NMR spectoscopy, Proteins, Metabolomics, Natural Products, and Natural Products Chemistryedit
Amylin is part of the endocrine pancreatic system that contributes to glycemic control, regulating blood glucose levels. However, human amylin has a high tendency to aggregate, forming isolated amylin deposits that are observed in... more
Amylin is part of the endocrine pancreatic system that contributes to glycemic control, regulating blood glucose levels. However, human amylin has a high tendency to aggregate, forming isolated amylin deposits that are observed in patients with type 2 diabetes mellitus. In search of new inhibitors of amylin aggregation, we undertook the chemical analyses of five marine macroorganisms encountered in high populations in the Red Sea and selected a panel of 10 metabolites belonging to different chemical classes to evaluate their ability to inhibit the formation of amyloid deposits in the human amylin peptide. The thioflavin T assay was used to examine the kinetics of amyloid aggregation, and atomic force microscopy was employed to conduct a thorough morphological examination of the formed fibrils. The potential ability of these compounds to interact with the backbone of peptides and compete with β-sheet formation was analyzed by quantum calculations, and the interactions with the amylin peptide were computationally examined using molecular docking. Despite their structural similarity, it could be observed that the hydrophobic and hydrogen bond interactions of pyrrolidinones 9 and 10 with the protein sheets result in one case in a stable aggregation, while in the other, they cause distortion from aggregation.
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Human amylin (hIAPP) is found in the form of amyloid deposits within the pancreatic cells of nearly all patients diagnosed with type 2 diabetes mellitus (T2DM). However, rat amylin (rIAPP) and pramlintide - hIAPP analogs - are both... more
Human amylin (hIAPP) is found in the form of amyloid deposits within the pancreatic cells of nearly all patients diagnosed with type 2 diabetes mellitus (T2DM). However, rat amylin (rIAPP) and pramlintide - hIAPP analogs - are both non-toxic and non-amyloidogenic. Their primary sequences exhibit only slight variations in a few amino acid residues, primarily concentrated in the central region, spanning residues 20 to 29. This inspired us to study this fragment and investigate the impact on the aggregation properties of substituting residues within the central region of amylin and its analogs. Six fragments derived from amylin have undergone comprehensive testing against various metal ions by implementing a range of analytical techniques, including Nuclear Magnetic Resonance (NMR) spectroscopy, Thioflavin T (ThT) assays, Atomic Force Microscopy (AFM), and cytotoxicity assays. These methodologies serve to provide a thorough understanding of how the substitutions and interactions with metal ions impact the aggregation behavior of amylin and its analogs.
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Root-knot nematodes (RKNs) are a vital pest that causes significant yield losses and economic damage to potato plants. The use of chemical pesticides to control these nematodes has led to environmental concerns and the development of... more
Root-knot nematodes (RKNs) are a vital pest that causes significant yield losses and economic damage to potato plants. The use of chemical pesticides to control these nematodes has led to environmental concerns and the development of resistance in the nematode populations. Endophytic fungi offer an eco-friendly alternative to control these pests and produce secondary metabolites that have nematicidal activity against RKNs. The objective of this study is to assess the efficacy of Aspergillus flavus (ON146363), an entophyte fungus isolated from Trigonella foenum-graecum seeds, against Meloidogyne incognita in filtered culture broth using GC-MS analysis. Among them, various nematicidal secondary metabolites were produced: Gadoleic acid, Oleic acid di-ethanolamide, Oleic acid, and Palmitic acid. In addition, biochemical compounds such as Gallic acid, Catechin, Protocatechuic acid, Esculatin, Vanillic acid, Pyrocatechol, Coumarine, Cinnamic acid, 4, 3-indol butyl acetic acid and Naphthyl acetic acid by HPLC. The fungus was identified through morphological and molecular analysis, including ITS 1-4 regions of ribosomal DNA. In vitro experiments showed that culture filtrate of A. flavus had a variable effect on reducing the number of egg hatchings and larval mortality, with higher concentrations showing greater efficacy than Abamectin. The fungus inhibited the development and multiplication of M. incognita in potato plants, reducing the number of galls and eggs by 90% and 89%, respectively. A. flavus increased the activity of defense-related enzymes Chitinas, Catalyse, and Peroxidase after 15, 45, and 60 days. Leaching of the concentrated culture significantly reduced the second juveniles' stage to 97% /250 g soil and decreased the penetration of nematodes into the roots. A. flavus cultural filtrates via soil spraying improved seedling growth and reduced nematode propagation, resulting in systemic resistance to nematode infection. Therefore, A. flavus can be an effective biological control agent for root-knot nematodes in potato plants. This approach provides a sustainable solution for farmers and minimizes the environmental impact.
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The NF-κB pathway plays a pivotal role in impeding the diabetic wound healing process, contributing to prolonged inflammation, diminished angiogenesis, and reduced proliferation. In contrast to modern synthetic therapies, naturally... more
The NF-κB pathway plays a pivotal role in impeding the diabetic wound healing process, contributing to prolonged inflammation, diminished angiogenesis, and reduced proliferation. In contrast to modern synthetic therapies, naturally occurring phytoconstituents are well-studied inhibitors of the NF-κB pathway that are now attracting increased attention in the context of diabetic wound healing because of lower toxicity, better safety and efficacy, and cost-effectiveness. This study explores recent research on phytoconstituent-based therapies and delve into their action mechanisms targeting the NF-κB pathway and potential for assisting effective healing of diabetic wounds. For this purpose, we have carried out surveys of recent literature and analyzed studies from prominent databases such as Science Direct, Scopus, PubMed, Google Scholar, EMBASE, and Web of Science. The classification of phytoconstituents into various categorie such as: alkaloids, triterpenoids, phenolics, polyphenols, flavonoids, monoterpene glycosides, naphthoquinones and tocopherols. Noteworthy phytoconstituents, including Neferine, Plumbagin, Boswellic acid, Genistein, Luteolin, Kirenol, Rutin, Vicenin-2, Gamma-tocopherol, Icariin, Resveratrol, Mangiferin, Betulinic acid, Berberine, Syringic acid, Gallocatechin, Curcumin, Loureirin-A, Loureirin-B, Lupeol, Paeoniflorin, and Puerarin emerge from these studies as promising agents for diabetic wound healing through the inhibition of the NF-κB pathway. Extensive research on various phytoconstituents has revealed how they modulate signalling pathways, including NF-κB, studies that demonstrate the potential for development of therapeutic phytoconstituents to assist healing of chronic diabetic wounds.
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Olive oil, being very salubrious, is one of the main ingredients of the Mediterranean diet. However, high oil prices combined with high consumption have increasingly subjected olive oils to fraudulent practices. The large rise in numbers... more
Olive oil, being very salubrious, is one of the main ingredients of the Mediterranean diet. However, high oil prices combined with high consumption have increasingly subjected olive oils to fraudulent practices. The large rise in numbers of producers engaging in this illicit practice has made it necessary to develop a swift, convenient, and consistent analytical methodology to detect adulterating oil products and ensure product quality. In this study, we have merged multivariate statistical analysis with one-dimensional (1D) 700 MHz 1H nuclear magnetic resonance (NMR) to analyze different types of vegetable and olive oil.
Additionally, we have spiked virgin olive oil with varying percentages (1% to 75% (v/v)) of other vegetable oils to obtain the spectra of adulterated olive oil. As a result, the method applied in our study can not only detect adulterated olive oils but also identify mixed adulterants. Ease of sample preparation, quick sample analysis, and straightforward data comprehension distinguishes this method from the currently published ones.
Additionally, we have spiked virgin olive oil with varying percentages (1% to 75% (v/v)) of other vegetable oils to obtain the spectra of adulterated olive oil. As a result, the method applied in our study can not only detect adulterated olive oils but also identify mixed adulterants. Ease of sample preparation, quick sample analysis, and straightforward data comprehension distinguishes this method from the currently published ones.
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A Gold(I)-antipyrine conjugate compound {Au(PPh3)(Ctriple bondCC6H4-4-CH=N-antipyrine) (4) was synthesized and the new complex was characterized by different spectroscopic techniques. DNA-binding and BSA-binding were performed for the... more
A Gold(I)-antipyrine conjugate compound {Au(PPh3)(Ctriple bondCC6H4-4-CH=N-antipyrine) (4) was synthesized and the new complex was characterized by different spectroscopic techniques. DNA-binding and BSA-binding were performed for the Au-antipyrine compound (4), showing that the synthesized complex exhibits better binding affinities against BSA compared to Au(PPh3)(Ctriple bondCPh) (5) while both have comparable DNA-binding. The gold(I)-antipyrine compound was tested against HepG2 and MCF-7 human cancer cell lines, exhibiting better cytotoxic effects compared to its ligand but comparable to that of Au(PPh3)(Ctriple bondCPh) (5). Despite the comparable anticancer properties of both 4 and 5 described herein, the presence of the antipyrine moiety altered the biomolecule-binding of gold(I) alkynyl complexes. Compared to cisplatin, the gold(I) complexes possess slightly less anticancer properties against both cell lines. Flow cytometry analysis was performed for Au-antipyrine complex, indicating apoptotic cell death pathway (late apoptosis) but via different mechanisms from that of cisplatin (early apoptosis) as can be seen from the differences in the cell cycle analysis at different cell phases.
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Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are... more
Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund’s complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy.
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Aim: The indandione nucleus, is one of the most amazing nuclei in medicinal chemistry, is used to design new derivatives. Methods & materials: Novel indandione derivatives are prepared with different electrophilic and nucleophilic... more
Aim: The indandione nucleus, is one of the most amazing nuclei in medicinal chemistry, is used to design new derivatives. Methods & materials: Novel indandione derivatives are prepared with different electrophilic and nucleophilic reagents to yield 3, 4, 8, 11, 14, 16, 19, 20, 21, 22 and 23. Compounds 8, 11, 16, 20 and 23 are investigated against OVCAR-3 and HeLa, using LLC-MK2 and cis-Pt as references. in silico and spectral studies were analyzed for the selected compounds. Results: Compounds 20 and 23 at 100 ns were the most potent compounds, so molecular dynamics studies were performed. Conclusion: Compound 23 was the most active toward the HeLa cervical cell line, and compound 20 was the most active toward the Ovcar-3 cell line.
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Sodium nitrite (NaNO2) is a widely used food ingredient, although excessive concentrations can pose potential health risks. In the present study, we evaluated the deterioration effects of NaNO2 additives on hematology, metabolic profile,... more
Sodium nitrite (NaNO2) is a widely used food ingredient, although excessive concentrations can pose potential health risks. In the present study, we evaluated the deterioration effects of NaNO2 additives on hematology, metabolic profile, liver function, and kidney function of male Wistar rats. We further explored the therapeutic potential of supplementation with S. costus root ethanolic extract (SCREE) to improve NaNO2-induced hepatorenal toxicity. In this regard, 65 adult male rats were divided into eight groups; Group 1: control, Groups 2, 3, and 4 received SCREE in 200, 400, and 600 mg/kg body weight, respectively, Group 5: NaNO2 (6.5 mg/kg body weight), Groups 6, 7 and 8 received NaNO2 (6.5 mg/kg body weight) in combination with SCREE (200, 400, and 600 mg/kg body weight), respectively. Our results revealed that the NaNO2-treated group shows a significant change in deterioration in body and organ weights, hematological parameters, lipid profile, and hepatorenal dysfunction, as well as immunohistochemical and histopathological alterations. Furthermore, the NaNO2-treated group demonstrated a considerable increase in the expression of TNF-α cytokine and tumor suppressor gene P53 in the kidney and liver, while a significant reduction was detected in the anti-inflammatory cytokine IL-4 and the apoptosis suppressor gene BCL-2, compared to the control group. Interestingly, SCREE administration demonstrated the ability to significantly alleviate the toxic effects of NaNO2 and improve liver function in a dose-dependent manner, including hematological parameters, lipid profile, and modulation of histopathological architecture. Additionally, SCREE exhibited the ability to modulate the expression levels of inflammatory cytokines and apoptotic genes in the liver and kidney. The phytochemical analysis revealed a wide set of primary metabolites in SCREE, including phenolics, flavonoids, vitamins, alkaloids, saponins and tannins, while the untargeted UPLC/T-TOF–MS/MS analysis identified 183 metabolites in both positive and negative ionization modes. Together, our findings establish the potential of SCREE in mitigating the toxic effects of NaNO2 by modulating metabolic, inflammatory, and apoptosis. Together, this study underscores the promise of SCREE as a potential natural food detoxifying additive to counteract the harmful impacts of sodium nitrite.
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Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease, that causes joint damage, deformities, and decreased functionality. In addition, RA can also impact organs like the skin, lungs, eyes, and blood vessels. This... more
Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease, that causes joint damage, deformities, and decreased functionality. In addition, RA can also impact organs like the skin, lungs, eyes, and blood vessels. This autoimmune condition arises when the immune system erroneously targets the joint synovial membrane, resulting in synovitis, pannus formation, and cartilage damage. RA treatment is often holistic, integrating medication, physical therapy, and lifestyle modifications. Its main objective is to achieve remission or low disease activity by utilizing a “treat-to-target” approach that optimizes drug usage and dose adjustments based on clinical response and disease activity markers. The primary RA treatment uses disease-modifying antirheumatic drugs (DMARDs) that help to interrupt the inflammatory process. When there is an inadequate response, a combination of biologicals and DMARDs is recommended. Biological therapies target inflammatory pathways and have shown promising results in managing RA symptoms. Close monitoring for adverse effects and disease progression is critical to ensure optimal treatment outcomes. A deeper understanding of the pathways and mechanisms will allow new treatment strategies that minimize adverse effects and maintain quality of life. This review discusses the potential targets that can be used for designing and implementing precision medicine in RA treatment, spotlighting the latest breakthroughs in biologics, JAK inhibitors, IL-6 receptor antagonists, TNF blockers, and disease-modifying noncoding RNAs.
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Diabetes mellitus, a complex metabolic disorder, presents a growing global health challenge. In 2021, there were 529 million diabetics worldwide. At the super-regional level, Oceania, the Middle East, and North Africa had the highest... more
Diabetes mellitus, a complex metabolic disorder, presents a growing global health challenge. In 2021, there were 529 million diabetics worldwide. At the super-regional level, Oceania, the Middle East, and North Africa had the highest age-standardized rates. The majority of cases of diabetes in 2021 (>90.0%) were type 2 diabetes, which is largely indicative of the prevalence of diabetes in general, particularly in older adults (K. L. Ong, et al., Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021, Lancet, 2023, 402(10397), 203–234). Nowadays, slowing the progression of diabetic complications is the only effective way to manage diabetes with the available therapeutic options. However, novel biomarkers and treatments are urgently needed to control cytokine secretion, advanced glycation end products (AGEs) production, vascular inflammatory effects, and cellular death. Emerging research has highlighted the intricate interplay between reactive oxygen species (ROS) and protein aggregation in the pathogenesis of diabetes. In this scenario, the main aim of this paper is to provide a comprehensive review of the current understanding of the molecular mechanisms underlying ROS-induced cellular damage and protein aggregation, specifically focusing on their contribution to diabetes development. The role of ROS as key mediators of oxidative stress in diabetes is discussed, emphasizing their impact on cellular components and signaling. Additionally, the involvement of protein aggregation in impairing cellular function and insulin signaling is explored. The synergistic effects of ROS and protein aggregation in promoting β-cell dysfunction and insulin resistance are examined, shedding light on potential targets for therapeutic intervention.
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The identification of genes involved in salinity tolerance has primarily focused on model plants and crops. However, plants naturally adapted to highly saline environments offer valuable insights into tolerance to extreme salinity.... more
The identification of genes involved in salinity tolerance has primarily focused on model plants and crops. However, plants naturally adapted to highly saline environments offer valuable insights into tolerance to extreme salinity. Salicornia plants grow in coastal salt marshes, stimulated by NaCl. To understand this tolerance, we generated genome sequences of two Salicornia species and analyzed the transcriptomic and proteomic responses of Salicornia bigelovii to NaCl. Subcellular membrane proteomes reveal that SbiSOS1, a homolog of the well-known SALT-OVERLY-SENSITIVE 1 (SOS1) protein, appears to localize to the tonoplast, consistent with subcellular localization assays in tobacco. This neo-localized protein can pump Na+ into the vacuole, preventing toxicity in the cytosol. We further identify 11 proteins of interest, of which SbiSALTY, substantially improves yeast growth on saline media. Structural characterization using NMR identified it as an intrinsically disordered protein, localizing to the endoplasmic reticulum in planta, where it can interact with ribosomes and RNA, stabilizing or protecting them during salt stress.
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[Mn(SCN)2(2,2′-bipy)2] (1) and [Co(SCN)2(2,2′-bipy)2] (2) were synthesized at ambient temperature by adding aqueous solutions of manganese(II) or cobalt(II) chloride hydrate to aqueous acetonitrile solutions of 2,2′-bipyridine (2,2′-bipy)... more
[Mn(SCN)2(2,2′-bipy)2] (1) and [Co(SCN)2(2,2′-bipy)2] (2) were synthesized at ambient temperature by adding aqueous solutions of manganese(II) or cobalt(II) chloride hydrate to aqueous acetonitrile solutions of 2,2′-bipyridine (2,2′-bipy) and potassium thiocyanate. Elemental analyses, FT-IR and UV–vis spectra were used to characterize 1 and 2. Single crystal X-ray diffraction was used to analyze the crystal structures of 1 and 2, revealing that the two are structurally similar. The molecular structures of 1 and 2 consist of Mn or Co ion chelated by two molecules of 2,2′-bipy through four nitrogen atoms and two NCS anions, giving distorted octahedral geometries. The isothiocyanate group is not bridging, instead, two ligands coordinate in a cis arrangement to the manganese or cobalt center by their nitrogen atoms while the sulfur atoms are free. Through hydrogen bonding and π–π stacking interactions, the discrete units of 1 and 2 extend to 3D supramolecular networks with flower and fishbone-like structures. The luminescence behavior of 2,2′-bipy, 1 and 2 were investigated. On HepG2 (liver) and MCF-7 (breast) cancer cells, the anticancer effects of 1 and 2 were evaluated. The activity of 1 and 2 on MCF-7 is more significant than that of HepG2. The IC50 of 1 was lower in HepG2 and MCF-7 cells than for 2.
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Metabolomics, a recent addition to omics sciences, studies small molecules across plants, animals, humans, and marine organisms. Nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC–MS) are widely used in those... more
Metabolomics, a recent addition to omics sciences, studies small molecules across plants, animals, humans, and marine organisms. Nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC–MS) are widely used in those studies, including microalgae metabolomics. NMR is non-destructive and highly reproducible but has limited sensitivity, which could be supplemented by joining GC–MS analysis. Extracting metabolites from macromolecules requires optimization for trustworthy results. Different extraction methods yield distinct profiles, emphasizing the need for optimization. The results indicated that the optimized extraction procedure successfully identified NMR and GC–MS-based metabolites in MeOH, CHCl3, and H2O extraction solvents. The findings represented the spectral information related to carbohydrates, organic molecules, and amino acids from the water-soluble metabolites fraction and a series of fatty acid chains, lipids, and sterols from the lipid fraction. Our study underscores the benefit of combining NMR and GC–MS techniques to comprehensively understand microalgae metabolomes, including high and low metabolite concentrations and abundances.
• In this study, we focused on optimizing the extraction procedure and combining NMR and GC–MS techniques to overcome the low NMR sensitivity and the different detected range limits of NMR and GC–MS.
• We explored metabolome diversity in a tropical strain of the small cells’ diatom Cheatoceros tenuissimus.
• In this study, we focused on optimizing the extraction procedure and combining NMR and GC–MS techniques to overcome the low NMR sensitivity and the different detected range limits of NMR and GC–MS.
• We explored metabolome diversity in a tropical strain of the small cells’ diatom Cheatoceros tenuissimus.
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The unique photophysical properties of single-walled carbon nanotubes (SWCNTs) exhibit great potential for bioimaging applications. This led to extensive exploration of photosensitization methods to improve their faint shortwave infrared... more
The unique photophysical properties of single-walled carbon nanotubes (SWCNTs) exhibit great potential for bioimaging applications. This led to extensive exploration of photosensitization methods to improve their faint shortwave infrared (SWIR) photoluminescence. Here, we report the mechanisms of SWCNT-assisted J-aggregation of cyanine dyes and the associated photoluminescence enhancement of SWCNTs in the SWIR spectral region. Surprisingly, we found that excitation energy transfer between the cyanine dyes and SWCNTs makes a negligible contribution to the overall photoluminescence enhancement. Instead, the shielding of SWCNTs from the surrounding water molecules through hydrogen bond-assisted macromolecular reorganization of ionic surfactants triggered by counterions and the physisorption of the dye molecules on the side walls of SWCNTs play a primary role in the photoluminescence enhancement of SWCNTs. We observed 2 orders of magnitude photoluminescence enhancement of SWCNTs by optimizing these factors. Our findings suggest that the proper shielding of SWCNTs is the critical factor for their photoluminescence enhancement, which has important implications for their application as imaging agents in biological settings.
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While antimicrobial medications are widely available around the world, interactions between antibiotics and biological targets exploit the target, resulting in the development of drug-resistant bacteria and microbiomes. In the case of... more
While antimicrobial medications are widely available around the world, interactions between antibiotics and biological targets exploit the target, resulting in the development of drug-resistant bacteria and microbiomes. In the case of antibiotics, drug-resistant s have developed as a worldwide health concern, necessitating the development of novel antimicrobial medicines that can target these hazardous microbiomes in safe, dependable, and effective ways. In this work, we explore the antimicrobial effects of two newly synthesised Co(II) Schiff base complexes derived from 3-ethoxy-4-hydroxybenzaldehyde and chlorophenyl ethylamine (4a and 4b, respectively). Results demonstrated that both 4a and 4b exhibited antibacterial activity against different Gram-positive and Gram-negative strains as determined by the MIC. The calculations of ADME performed suggested satisfactory results. A computational study was performed by DFT theory, including geometry optimization and molecular docking studies to ascertain the binding of both complexes 4a and 4b to three biological targets, viz., DNA gyrase, and the enzymes involved in type-II fatty acid synthesis, FabZ and FabI. The comparative results of molecular docking suggested a higher binding affinity of complex 4b than 4a with the selected receptors.
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Mitochondria are vital organelles found within living cells and have signalling, biosynthetic, and bioenergetic functions. Mitochondria play a crucial role in metabolic reprogramming, which is a characteristic of cancer cells and allows... more
Mitochondria are vital organelles found within living cells and have signalling, biosynthetic, and bioenergetic functions. Mitochondria play a crucial role in metabolic reprogramming, which is a characteristic of cancer cells and allows them to assure a steady supply of proteins, nucleotides, and lipids to enable rapid proliferation and development. Their dysregulated activities have been associated with the growth and metastasis of different kinds of human cancer, particularly ovarian carcinoma. In this review, we briefly demonstrated the modified mitochondrial function in cancer, including mutations in mtDNA, reactive oxygen species production, dynamics, apoptosis of cells, autophagy, and calcium excess to maintain cancer genesis, progression, and metastasis. Furthermore, the mitochondrial dysfunction pathway for some genomic, proteomic, and metabolomics modifications in ovarian cancer has been studied. Additionally, ovarian cancer has been linked to targeted therapies and biomarkers found through various alteration processes underlying mitochondrial dysfunction, notably targeting reactive oxygen species, metabolites, rewind metabolic pathways, and chemo-resistant ovarian carcinoma cells.
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In this study, we investigated Cu–Co ferrite nanofibers (NFs) that were synthesized for the first time employing the electrospinning technique. The structure, phase purity and crystallite size of all the prepared NFs were revealed by... more
In this study, we investigated Cu–Co ferrite nanofibers (NFs) that were synthesized for the first time employing the electrospinning technique. The structure, phase purity and crystallite size of all the prepared NFs were revealed by powder X-ray diffraction (PXRD) analysis. The NFs crystallized in the Fd[3 with combining macron]m (no. 227) space group and the cation distribution arrangement over distinct sites in their structure was analyzed. Scanning electron microscopy (SEM) together with energy-dispersive X-ray (EDX) spectroscopy analysis showed the microstructure of the NFs and verified their expected chemical compositions. High-resolution transmission electron microscopy (TEM) images confirmed the fibrous nature and the construction of the NFs. The band gap energies derived from the UV-vis reflectance spectra showed a blue shift with an increase in the amount of Cu in the sample from 1.42 eV to 1.86 eV. Magnetization (M) as a function of magnetic field (H) measurements performed at ambient and low temperatures showed the ferrimagnetic behavior of all the NFs. The magnetic parameters including coercivity (Hc), saturation magnetization (Ms), remanent magnetization (Mr), and squareness ratio were determined from the recorded magnetization curves. At 300 K, Ms was reduced from 78.8 to 42.4 emu g−1, Mr reduced from 22.8 to 7.6 emu g−1 and the Bohr magneton reduced from 3.3 to 1.8μB with an increase in the content of Cu in the samples. The same trend was observed at 10 K, where Ms was reduced from 93.7 to 50.9 emu g−1, Mr reduced from 60.9 to 35.9 emu g−1 and the Bohr magneton reduced from 3.94 to 2.16μB. Alternatively, Hc has the highest values for x = 0 (850 Oe at 300 K and 5220 Oe at 10 K) and x = 0.6 (800 Oe at 300 K and 5400 Oe at 10 K). The anti-cancer activity of the NFs was evaluated using the MTT cell viability assay, showing a reduction in the viability of both HCT-116 and HeLa cancer cells compared to non-cancerous HEK-293 cells after treatment with the NFs. Apoptotic activity was examined by DAPI staining, where treatment with the NFs induced chromatin condensation and nuclear disintegration in HCT-116 cells.
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A series of 10 cyclic, biaryl analogs of enkephalin, with Tyr or Phe residues at positions 1 and 4, were synthesized according to the Miyaura borylation and Suzuki coupling methodology. Biaryl bridges formed by side chains of the two... more
A series of 10 cyclic, biaryl analogs of enkephalin, with Tyr or Phe residues at positions 1 and 4, were synthesized according to the Miyaura borylation and Suzuki coupling methodology. Biaryl bridges formed by side chains of the two aromatic amino acid residues are of the meta–meta, meta–para, para–meta, and para–para configuration. Conformational properties of the peptides were studied by CD and NMR. CD studies allowed only to compare conformations of individual peptides while NMR investigations followed by XPLOR calculations provided detailed information on their conformation. Reliability of the XPLOR calculations was confirmed by quantum chemical ones performed for one of the analogs. No intramolecular hydrogen bonds were found in all the peptides. They are folded and adopt the type IV β-turn conformation. Due to a large steric strain, the aromatic carbon atoms forming the biaryl bond are distinctly pyramidalized. Seven of the peptides were tested in vitro for their affinity for the µ-opioid receptor.
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Over the past years, the poultry industry has been assigned to greater production performance but has become highly sensitive to environmental changes. The average world temperature has recently risen and is predicted to continue rising.... more
Over the past years, the poultry industry has been assigned to greater production performance but has become highly sensitive to environmental changes. The average world temperature has recently risen and is predicted to continue rising. In open-sided houses, poultry species confront high outside temperatures, which cause heat stress (HS) problems. Cellular responses are vital in poultry, as they may lead to identifying confirmed HS biomarkers. Heat shock proteins (HSP) are highly preserved protein families that play a significant role in cell function and cytoprotection against various stressors, including HS. The optimal response in which the cell survives the HS elevates HSP levels that prevent cellular proteins from damage caused by HS. The HSP have chaperonic action to ensure that stress-denatured proteins are folded, unfolded, and refolded. The HSP70 and HSP90 are the primary HSP in poultry with a defensive function during HS. HSP70 was the optimal biological marker for assessing HS among the HSP studied. The current review attempts to ascertain the value of HSP as a heat stress defense mechanism in poultry.
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Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease the effectiveness of treatment. They release chemokines and cytokines from the tumor... more
Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease the effectiveness of treatment. They release chemokines and cytokines from the tumor microenvironment (TME). To improve the effectiveness of treatment, researchers emphasize personalized adjuvant therapies along with conventional ones. Targeted chemotherapeutic drug delivery systems and specific pathway-blocking agents using nanocarriers are a few of them. This study explored the nanocarrier roles and strategies to improve the treatment profile’s effectiveness by striving for TME. A biofunctionalized nanocarrier stimulates biosystem interaction, cellular uptake, immune system escape, and vascular changes for penetration into the TME. Inorganic metal compounds scavenge reactive oxygen species (ROS) through their photothermal effect. Stroma, hypoxia, pH, and immunity-modulating agents conjugated or modified nanocarriers co-administered with pathway-blocking or condition-modulating agents can regulate extracellular matrix (ECM), Cancer-associated fibroblasts (CAF),Tyro3, Axl, and Mertk receptors (TAM) regulation, regulatory T-cell (Treg) inhibition, and myeloid-derived suppressor cells (MDSC) inhibition. Again, biomimetic conjugation or the surface modification of nanocarriers using ligands can enhance active targeting efficacy by bypassing the TME. A carrier system with biofunctionalized inorganic metal compounds and organic compound complex-loaded drugs is convenient for NSCLC-targeted therapy.
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Corona has severely impacted many sectors in the past 2. 5 years, and forests are one of the major hits among all sectors affected by the pandemic. This study presents the consolidated data on deforestation patterns across the globe... more
Corona has severely impacted many sectors in the past 2. 5 years, and forests are one of the major hits among all sectors affected by the pandemic. This study presents the consolidated data on deforestation patterns across the globe during COVID and also analyzes in depth the region-specific contributing factors. Exacerbated deforestation during COVID alarms biodiversity conservation concerns and pushes back the long-term efforts to combat pollution and climate change mitigation. Deforestation also increases the risk of the emergence of new zoonotic diseases in future, as deforestation and COVID are intricately related to each other. Therefore, there is a need to check deforestation and inculcation of conservation measures in building back better policies adopted post-COVID. This review is novel in specifically providing insight into the implications of COVID-19 on forests in tropical as well as temperate global regions, causal factors, green policies given by different nations, and recommendations that will help in designing nature-based recovery strategies for combating deforestation and augmenting afforestation, thus providing better livelihood, biodiversity conservation, climate change mitigation, and better environmental quality.
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Background: The present study investigates seven greenness assessment tools to evaluate the greenness of validated novel chromatographic methods used to assess Amlodipine (AML), Hydrochlorothiazide (HYD), Telmisartan (TEL), and their... more
Background: The present study investigates seven greenness assessment tools to evaluate the greenness of validated novel chromatographic methods used to assess Amlodipine (AML), Hydrochlorothiazide (HYD), Telmisartan (TEL), and their related substances in solid formulations under various stress conditions. Objective: The fundamental goal of green analytical chemistry (GAC) is to substitute hazardous materials or waste production with environmentally friendly alternatives. Method: The mobile phase used in the first RP-HPLC system was a gradient program from solution (A) phosphate buffer pH 3.0 and solution (B) acetonitrile with 50 μL injection volume and a flow rate of 1.0 mL/min, whereas the gradient mobile phase used in the second method was composed of solution (A) phosphate buffer pH 3.0 and solution (B), which is made from acetonitrile: methanol (50:50) with 30 μL injection volume, and flow rate of 1.5 mL/min. It has been found that Thermo Hypersil C18 (25 × 0.46 cm, 5 m) and ACE C8 (15 × 0.46 cm, 5 m) analytical columns are the best stationary phases for the first and second RP-HPLC methods, respectively. Results: The statistical data of calibration curves for AML, HYD, and TEL highly indicate linearity with a correlation value greater than 0.999 and acceptable recovery results between 99 and 100 %. Content uniformity testing on finished products revealed that they met the acceptance
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Aims: The development of nanocomposites (NCs) of antitumor activity provides a new paradigm for fighting cancer. Here, a novel NC of green synthetic silver nanoparticles (AgNPs), graphene oxide (GO) and chitosan (Cs) NPs was developed.... more
Aims: The development of nanocomposites (NCs) of antitumor activity provides a new paradigm for fighting cancer. Here, a novel NC of green synthetic silver nanoparticles (AgNPs), graphene oxide (GO) and chitosan (Cs) NPs was developed. Materials & methods: The prepared GO/Cs/Ag NCs were analyzed using various techniques. Cytotoxicity of the NCs was evaluated against different cancer cell lines by Sulforhodamine B (SRB) assay. Results: GO/Cs/Ag NCs are novel and highly stable. UV-Vis showed two peaks at 227 and 469 nm, indicating the decoration of AgNPs on the surface of GO/Cs NPs. All tested cell lines were affected by GO/Cs NPs and GO/Cs/Ag NCs. Conclusion: The results indicate that GO/Cs/Ag NCs were present on tested cell lines and are a promising candidate for cancer therapy.
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Diabetes is an emerging disorder in the world and is caused due to the imbalance of insulin production as well as serious effects on the body. In search of a better treatment for diabetes, we designed a novel class of... more
Diabetes is an emerging disorder in the world and is caused due to the imbalance of insulin production as well as serious effects on the body. In search of a better treatment for diabetes, we designed a novel class of 1,3,4-thiadiazole-bearing Schiff base analogues and assessed them for the α-glucosidase enzyme. In the series (1−12), compounds are synthesized and 3 analogues showed excellent inhibitory activity against αglucosidase enzymes in the range of IC 50 values of 18.10 ± 0.20 to 1.10 ± 0.10 μM. In this series, analogues 4, 8, and 9 show remarkable inhibition profile IC 50 2.20 ± 0.10, 1.10 ± 0.10, and 1.30 ± 0.10 μM by using acarbose as a standard, whose IC 50 is 11.50 ± 0.30 μM. The structure of the synthesized compounds was confirmed through various spectroscopic techniques, such as NMR and HREI-MS. Additionally, molecular docking, pharmacokinetics, cytotoxic evaluation, and density functional theory study were performed to investigate their behavior.
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Folk medicine, rooted in historical practice, has long been used for medicinal purposes, emphasizing the need to ensure the safety, quality, and efficacy of herbal medicines. This imperative has grown over time, prompting collaborative... more
Folk medicine, rooted in historical practice, has long been used for medicinal purposes, emphasizing the need to ensure the safety, quality, and efficacy of herbal medicines. This imperative has grown over time, prompting collaborative efforts to document historical records and preserve invaluable knowledge of medicinal plants. The Lamiaceae (Labiatae) family, renowned for its rich assortment of medicinal plants characterized by high concentrations of volatile oils, stands out in this regard. This review focuses on Clinopodium vulgare (C. vulgare) L., commonly known as wild basil or basil thyme, a significant species within the Lamiaceae family found across diverse global regions. C. vulgare boasts a storied history of application in treating various ailments, such as gastric ulcers, diabetes, and inflammation, dating back to ancient times. Rigorous research has substantiated its pharmacological properties, revealing its antioxidant, antiviral, antibacterial, anti-inflammatory, anticancer, antihypertensive, and enzyme-inhibitory effects. This comprehensive review provides an insightful overview of the Lamiaceae family, elucidates the extraction methods employed to obtain medicinal compounds, explores the phytoconstituents present in C. vulgare, and systematically details its diverse pharmacological properties. Additionally, the review delves into considerations of toxicity. By synthesizing this wealth of information, this study opens avenues for the potential therapeutic applications of C. vulgare. The practical value of this research lies in its contribution to the understanding of medicinal plants, mainly focusing on the pharmacological potential of C. vulgare. This exploration enriches our knowledge of traditional medicine and paves the way for innovative therapeutic approaches, offering promising prospects for future drug development. As the demand for natural remedies continues to increase, this work provides a valuable resource for researchers, practitioners, and stakeholders in herbal medicine and pharmacology.
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Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach... more
Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach extensively employed in treating different types of cancers. The present study reports the synthesis of thirty-two novel bis-amides (SSE1901-SSE1932) and the evaluation of their antiproliferative activities. N-(1-oxo-3-phenyl-1-(phenylamino)propan-2-yl)benzamide (SSE1917) exhibited the most potent activity with GI 50 values of 0.331 ± 0.01 µM in HCT116 colorectal and 0.48 ± 0.27 µM in BT-549 breast cancer cells. SSE1917 stabilized microtubules in biochemical and cellular assays, bound to taxol site in docking studies, and caused aberrant mitosis and G 2 /M arrest in cells. Prolonged treatment of cells with the compound increased p53 expression and triggered apoptotic cell death. Furthermore, SSE1917 suppressed the growth of both mouse and patient-derived human colon cancer organoids, highlighting its potential therapeutic value as an anticancer agent.
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Berberine–encapsulated polyelectrolyte nanocomposite (BR–PolyET–NC) gel was developed as a long-acting improved wound healing therapy. BR–PolyET–NC was developed using an ionic gelation/complexation method and thereafter loaded into... more
Berberine–encapsulated polyelectrolyte nanocomposite (BR–PolyET–NC) gel was developed as a long-acting improved wound healing therapy. BR–PolyET–NC was developed using an ionic gelation/complexation method and thereafter loaded into Carbopol gel. Formulation was optimized using Design-Expert® software implementing a three-level, three-factor Box Behnken design (BBD). The concentrations of polymers, namely, chitosan and alginate, and calcium chloride were investigated based on particle size and %EE. Moreover, formulation characterized in vitro for biopharmaceutical performances and their wound healing potency was evaluated in vivo in adult BALB/c mice. The particle distribution analysis showed a nanocomposite size of 71 ± 3.5 nm, polydispersity index (PDI) of 0.45, ζ–potential of +22 mV, BR entrapment of 91 ± 1.6%, and loading efficiency of 12.5 ± 0.91%. Percentage drug release was recorded as 89.50 ± 6.9% with pH 6.8, thereby simulating the wound microenvironment. The in vitro investigation of the nanocomposite gel revealed uniform consistency, well spreadability, and extrudability, which are ideal for topical wound use. The analytical estimation executed using FT-IR, DSC, and X-ray diffraction (XRD) indicated successful formulation with no drug excipients and without the amorphous state. The colony count of microbes was greatly reduced in the BR–PolyET–NC treated group on the 15th day from up to 6 CFU compared to 20 CFU observed in the BR gel treated group. The numbers of monocytes and lymphocytes counts were significantly reduced following healing progression, which reached to a peak level and vanished on the 15th day. The observed experimental characterization and in vivo study indicated the effectiveness of the developed BR–PolyET–NC gel toward wound closure and healing process, and it was found that >99% of the wound closed by 15th day, stimulated via various anti-inflammatory and angiogenic factors.
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There are an estimated 3 million Chikungunya virus (CHIKV) infections per year, but no vaccines or specific pharmaceutical treatments are available. RNA-dependent RNA polymerase (RdRp) of CHIKV, encoded by nonstructural protein 4 (nsP4),... more
There are an estimated 3 million Chikungunya virus (CHIKV) infections per year, but no vaccines or specific pharmaceutical treatments are available. RNA-dependent RNA polymerase (RdRp) of CHIKV, encoded by nonstructural protein 4 (nsP4), was targeted to identify potential antiviral compounds in this study. A 3D model of the nsP4 was generated by homology modeling technique and Pockdrug-Server was used to predict ligand binding sites. The pharmacophore hypothesis was developed followed by virtual screening. 300 most potential ligands were selected from a library of 3000 compounds, after filtering for the molecules satisfying Lipinski's Rule of Five. Using molecular docking followed by ADMET analysis, 27 leads were then selected. We used MD simulations of the three best compounds that bind to the cataltic, palm, and thumb domains to find out how the ligand-protein interactions change over time. RMSD, RMSF, radius of gyration, free energy landscapes, and principal component analyses revealed that complexes nsP4-ZINC12820763 and nsP4-ZINC33280972 were more stable. Simulated trajectories were further used to compute MMGBSA binding energies of PubChem135638918 (-22.33 kcal/mol), ZINC12820763 (-50.19 kcal/mol) and ZINC33280972 (-32.69 kcal/mol) bound to catalytic, palm and thumb domains, respectively. HOMO and LUMO of potential molecules were also investigated using density functional theory computations. With the support of computational simulations, three compounds were shown to have the potential to inhibit RdRp of CHIKV and need further evaluation using in-vitro and in-vivo analysis.
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Introduction: Nuclear Magnetic Resonance (NMR) spectroscopy stands as a preeminent analytical tool in the field of metabolomics. Nevertheless, when it comes to identifying metabolites present in scant amounts within various types of... more
Introduction: Nuclear Magnetic Resonance (NMR) spectroscopy stands as a preeminent analytical tool in the field of metabolomics. Nevertheless, when it comes to identifying metabolites present in scant amounts within various types of complex mixtures such as plants, honey, milk, and biological fluids and tissues, NMR-based metabolomics presents a formidable challenge. This predicament arises primarily from the fact that the signals emanating from metabolites existing in low concentrations tend to be overshadowed by the signals of highly concentrated metabolites within NMR spectra.
Objectives: The aim of this study is to tackle the issue of intense sugar signals overshadowing the desired metabolite signals, an optimal pulse sequence with band-selective excitation has been proposed for the suppression of sugar's moiety signals (SSMS). This sequence serves the crucial purpose of suppressing unwanted signals, with a particular emphasis on mitigating the interference caused by sugar moieties' signals.
Methods: We have implemented this comprehensive approach to various NMR techniques, including 1D 1 H presaturation (presat), 2D J-resolved (RES), 2D 1 H-1 H Total Correlation Spectroscopy (TOCSY), and 2D 1 H-13 C Heteronuclear Single Quantum Coherence (HSQC) for the samples of dates-flesh, honey, a standard stock solution of glucose, and nine amino acids, and commercial fetal bovine serum (FBS).
Results: The outcomes of this approach were significant. The suppression of the high-intensity sugar signals has considerably enhanced the visibility and sensitivity of the signals emanating from the desired metabolites.
Conclusion: This, in turn, enables the identification of a greater number of metabolites. Additionally, it streamlines the experimental process, reducing the time required for the comparative quantification of metabolites in statistical studies in the field of metabolomics.
Objectives: The aim of this study is to tackle the issue of intense sugar signals overshadowing the desired metabolite signals, an optimal pulse sequence with band-selective excitation has been proposed for the suppression of sugar's moiety signals (SSMS). This sequence serves the crucial purpose of suppressing unwanted signals, with a particular emphasis on mitigating the interference caused by sugar moieties' signals.
Methods: We have implemented this comprehensive approach to various NMR techniques, including 1D 1 H presaturation (presat), 2D J-resolved (RES), 2D 1 H-1 H Total Correlation Spectroscopy (TOCSY), and 2D 1 H-13 C Heteronuclear Single Quantum Coherence (HSQC) for the samples of dates-flesh, honey, a standard stock solution of glucose, and nine amino acids, and commercial fetal bovine serum (FBS).
Results: The outcomes of this approach were significant. The suppression of the high-intensity sugar signals has considerably enhanced the visibility and sensitivity of the signals emanating from the desired metabolites.
Conclusion: This, in turn, enables the identification of a greater number of metabolites. Additionally, it streamlines the experimental process, reducing the time required for the comparative quantification of metabolites in statistical studies in the field of metabolomics.
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The steady increase in the use of electronic cigarettes (ECs) has reached an epidemic level, increasing mortality and morbidity, mainly due to pulmonary toxicity. Several mechanisms are involved in EC-induced toxicity, including oxidative... more
The steady increase in the use of electronic cigarettes (ECs) has reached an epidemic level, increasing mortality and morbidity, mainly due to pulmonary toxicity. Several mechanisms are involved in EC-induced toxicity, including oxidative stress and increased inflammation. Concurrently, the integrity of cellular metabolism is essential for cellular homeostasis and mitigation of toxic insults. However, the effects of EC on cellular metabolism remain largely unknown. In this study, we investigated the metabolic changes induced by EC in human lung epithelial cells (A549) using an untargeted metabolomics approach. A549 cells were exposed to increasing EC vapor extract concentrations, and cell viability, oxidative stress, and metabolomic changes were assessed. Our findings show that ECs induce cell death and increase oxidative stress in a concentration-dependent manner. Metabolomic studies demonstrated that ECs induce unique metabolic changes in key cellular metabolic pathways. Our results revealed that exposure to ECs induced clear segregation in metabolic responses which is driven significantly by number of essential metabolites such as aminoacids, fatty acids, glutathione, and pyruvate. Interstingly, our metabolomics results showed that each concentration of ECs induced unqiues pattern of metabolic changes, suggesting the complexity of ECs induced cytotoxcity. Disrupted metabolites were linked to essential cellular pathways, such as fatty acid biosynthesis, as well as glutathione, pyruvate, nicotinate and nicotinamide, and amino acid metabolisms. These results highlight the potential adverse effects of ECs on cellular metabolism and emphasize the need for further research to fully understand the long-term consequences of EC use. Overall, this study demonstrates that ECs not only induce cell death and oxidative stress but also disrupt cellular metabolism in A549 lung epithelial cells.
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In the present study, we explored the potential of coumarin-based compounds, known for their potent anticancer properties, by designing and synthesizing a novel category of 8-methoxycoumarin-3-carboxamides. Our aim was to investigate... more
In the present study, we explored the potential of coumarin-based compounds, known for their potent anticancer properties, by designing and synthesizing a novel category of 8-methoxycoumarin-3-carboxamides. Our aim was to investigate their antiproliferative activity against liver cancer cells. Toward this, we developed a versatile synthetic approach to produce a series of 8-methoxycoumarin-3-carboxamide analogues with meticulous structural features. Assessment of their antiproliferative activity demonstrated their significant inhibitory effects on the growth of HepG2 cells, a widely studied liver cancer cell line. Among screened compounds, compound 5 exhibited the most potent antiproliferative activity among the screened compounds (IC 50 = 0.9 µM), outperforming the anticancer drug staurosporine (IC 50 = 8.4 µM), while showing minimal impact on normal cells. The flow cytometric analysis revealed that compound 5 induces cell cycle arrest during the G1/S phase and triggers apoptosis in HepG2 cells by increasing the percentage of cells arrested in the G2/M and pre-G1 phases. Annexin V-FITC/PI screening further supported the induction of apoptosis without significant necrosis. Further, compound 5 exhibited the ability to activate cas-pase3/7 protein and substantially inhibited β-tubulin polymerization activity in HepG2 cells. Finally, molecular modelling analysis further affirmed the high binding affinity of compound 5 toward the active cavity of β-tubulin protein, suggesting its mechanistic involvement. Collectively, our findings highlight the therapeutic potential of the presented class of coumarin analogues, especially compound 5, as promising candidates for the development of effective antihepatocellular carcinoma agents.
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Tridentate ligands of the type N^{N^{OH }}were obtained from the reactions between salicylaldehyde derivatives (3-ethoxy, 4-diethylamino, 4-hydroxy) and primary amines (2-picolylamine or N-phenylethylenediamine), and were used to... more
Tridentate ligands of the type N^{N^{OH }}were obtained from the reactions between salicylaldehyde derivatives (3-ethoxy, 4-diethylamino, 4-hydroxy) and primary amines (2-picolylamine or N-phenylethylenediamine), and were used to synthesize a set of five palladium complexes of the general formula Pd(N^{NO})Cl. The new complexes were characterized by NMR spectroscopy and mass spectrometry; further confirmation of the structure of Pd-Py-OEt was provided by single-crystal XRD. A DNA-binding study confirmed the importance of the ligand on the mode of binding with ct-DNA. Four complexes possess apparent binding constants in the same range, and all are higher than that of Pd-EN-NEt2. The BSA-binding proceeds via the formation of BSA-compound adducts, with higher binding constants for the ethylene-containing example due to the more flexible ligand. Molecular docking studies identified the binding site at the cleft of BSA. Anticancer properties of the palladium complexes are poorer than those of their platinum analogues, although Pd-Py-OEt and Pd-Py-NEt2 exhibit cytotoxicity similar to that of cisplatin, and significantly better cytotoxicity towards the cancer cell line over a normal cell line. Flow cytometry analysis suggests a late apoptotic cell death pathway for Pd-Py-OEt. Pd-Py-OEt; they afford different cell cycle accumulation patterns compared to Pt-Py-OEt and cisplatin, which suggests mechanistic differences in their anticancer activities.
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DNA damage is a serious threat to all living organisms and may be induced by environmental stressors. Previous studies have revealed that the tardigrade (Ramazzotius varieornatus) DNA damage suppressor protein Dsup has protective effects... more
DNA damage is a serious threat to all living organisms and may be induced by environmental stressors. Previous studies have revealed that the tardigrade (Ramazzotius varieornatus) DNA damage suppressor protein Dsup has protective effects in human cells and tobacco. However, whether Dsup provides radiation damage protection more widely in crops is unclear. To explore the effects of Dsup in other crops, stable Dsup overexpression lines through Agrobacterium-mediated transformation were generated and their agronomic traits were deeply investigated. In this study, the overexpression of Dsup not only enhanced the DNA damage resistance at the seeds and seedlings stages, they also exhibited grain size enlargement and starch granule structure and cell size alteration by the scanning electron microscopy observation. Notably, the RNA-seq revealed that the Dsup plants increased radiation-related and abiotic stress-related gene expression in comparison to wild types, suggesting that Dsup is capable to coordinate normal growth and abiotic stress resistance in rice. Immunoprecipitation enrichment with liquid chromatography-tandem mass spectrometry (IP-LC-MS) assays uncovered 21 proteins preferably interacting with Dsup in plants, suggesting that Dsup binds to transcription and translation related proteins to regulate the homeostasis between DNA protection and plant development. In conclusion, our data provide a detailed agronomic analysis of Dsup plants and potential mechanisms of Dsup function in crops. Our findings provide novel insights for the breeding of crop radiation resistance.
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Being the sixth most diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide, liver cancer is considered as a serious disease with a high prevalence and poor prognosis. Current anticancer drugs for liver cancer... more
Being the sixth most diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide, liver cancer is considered as a serious disease with a high prevalence and poor prognosis. Current anticancer drugs for liver cancer have drawbacks, such as limited efficacy in later stages of the disease, toxicity to healthy cells, and the potential for drug resistance. There is ample evidence that coumarin-based compounds are potent anticancer agents, with numerous analogues currently being investigated in preclinical and clinical studies. The current study aimed to explore the antitumor potency of a new class of 8-methoxycoumarin-3-carboxamides against liver cancer. Toward this aim, we have designed, synthesized, and characterized a new set of N-(substituted-phenyl)-8-methoxycoumarin-3-carboxamide analogues. The assessment of antitumor activity revealed that the synthesized class of compounds possesses substantial cytotoxicity toward Hep-G2 cells when compared to staurosporine, without significant impact on normal cells. Out of the synthesized compounds, compound 7 demonstrated the most potent cytotoxic effect against Hep-G2 cells with an IC50 of 0.75 µM, which was more potent than the drug staurosporine (IC50 = 8.37 µM). The investigation into the mechanism behind the antiproliferative activity of compound 7 revealed that it interferes with DNA replication and induces DNA damage, leading to cell cycle arrest as demonstrated by a significant decrease in the percentage of cells in the G1 and G2/M phases, along with an increase in the percentage of cells in the S phase. Flow cytometric analysis further revealed that compound 7 has the ability to trigger programmed cell death by inducing necrosis and apoptosis in HepG-2 cells. Further explorations into the mechanism of action demonstrated that compound 7 displays a potent dual-inhibitory activity toward cytochrome P450 and vascular endothelial growth factor receptor-2 (VEGFR-2) proteins, as compared to sorafenib drug. Further, detailed computational studies revealed that compound 7 displays a considerable binding affinity toward the binding cavity of VEGFR2 and CYP450 proteins. Taken together, our findings indicate that the newly synthesized class of compounds, particularly compound 7, could serve as a promising scaffold for the development of highly effective anticancer agents against liver cancer.
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Pyranopyrazole derivatives have a vital role in the class of organic compounds because of their broad spectrum of biological and pharmacological importance. Our current goal is the [3 + 3] cycloaddition of benzoyl isothiocyanate and... more
Pyranopyrazole derivatives have a vital role in the class of organic compounds because of their broad spectrum of biological and pharmacological importance. Our current goal is the [3 + 3] cycloaddition of benzoyl isothiocyanate and pyrazolone 1 to undergo oxidation cyclization, producing pyrazoloxadiazine 3. The diol 5 was obtained as a condensation of two equivalents of 1 with thiophene-2-carboxaldehyde in acetic acid above the sodium acetate mixture. When the condensation was carried out in piperidine under fusion, unsaturated ketone 4 was obtained. The pyrazolo pyran derivative 11 resulted from the [3 + 3] cycloaddition of 1 and cinnamic acid, while the Pyrone derivative was prepared by acylation of 12 with two equivalents of acetic anhydride. Phthalic anhydride undergoes arylation using zinc chloride as a catalyst. The cyclic keto acid 23 was synthesized by the action of succinic anhydride on 12 in the acetic medium, while the latter reacted with cinnamic acid, leading to pyrazole derivative 24. All of these reactions were through the Michael reaction mechanism. All the tested compounds showed good antimicrobial activity against pathogenic microorganisms; newly synthesized compounds were also screened for their antioxidant activity. Rational studies were carried out by the ABTs method to allow a broader choice of activities. In addition, similar offcompounds were conducted. Molecular docking studies with the CB-Dock server and MD simulations were created with the default settings of the Solution Builder on the CHARMM-GUI server at 150 nm. A good correlation was obtained between the experimental results and the theoretical bioavailability predictions using POM theory.
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Autism spectrum disorders (ASD) represent a diverse group of neuropsychiatric conditions, and recent evidence has suggested a connection between ASD and microbial dysbiosis. Immune and gastrointestinal dysfunction are associated with... more
Autism spectrum disorders (ASD) represent a diverse group of neuropsychiatric conditions, and recent evidence has suggested a connection between ASD and microbial dysbiosis. Immune and gastrointestinal dysfunction are associated with dysbiosis, and there are indications that modulating the microbiota could improve ASD-related behaviors. Additionally, recent findings highlighted the significant impact of microbiota on the development of autoimmune liver diseases, and the occurrence of autoimmune liver disease in children with ASD is noteworthy. In the present study, we conducted both an in vivo study and a clinical study to explore the relationship between indomethacin-induced dysbiosis, autoimmune hepatitis (AIH), and the development of ASD. Our results revealed that indomethacin administration induced intestinal dysbiosis and bacterial translocation, confirmed by microbiological analysis showing positive bacterial translocation in blood cultures. Furthermore, indomethacin administration led to disturbed intestinal permeability, evidenced by the activation of the NLRP3 inflammasomes pathway and elevation of downstream biomarkers (TLR4, IL18, caspase 1). The histological analysis supported these findings, showing widened intestinal tight junctions, decreased mucosal thickness, inflammatory cell infiltrates, and collagen deposition. Additionally, the disturbance of intestinal permeability was associated with immune activation in liver tissue and the development of AIH, as indicated by altered liver function, elevated ASMA and ANA in serum, and histological markers of autoimmune hepatitis. These results indicate that NSAID-induced intestinal dysbiosis and AIH are robust triggers for ASD existence. These findings were further confirmed by conducting a clinical study that involved children with ASD, autoimmune hepatitis (AIH), and a history of NSAID intake. Children exposed to NSAIDs in early life and complicated by dysbiosis and AIH exhibited elevated serum levels of NLRP3, IL18, liver enzymes, ASMA, ANA, JAK1, and IL6. Further, the correlation analysis demonstrated a positive relationship between the measured parameters and the severity of ASD. Our findings suggest a potential link between NSAIDs, dysbiosis-induced AIH, and the development of ASD. The identified markers hold promise as indicators for early diagnosis and prognosis of ASD. This research highlights the importance of maintaining healthy gut microbiota and supports the necessity for further investigation into the role of dysbiosis and AIH in the etiology of ASD.
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Since ancient times, the inhabitants of dry areas have depended on the date palm (Phoenix dactylifera L.) as a staple food and means of economic security. For example, dates have been a staple diet for the inhabitants of the Arabian... more
Since ancient times, the inhabitants of dry areas have depended on the date palm (Phoenix dactylifera L.) as a staple food and means of economic security. For example, dates have been a staple diet for the inhabitants of the Arabian Peninsula and Sahara Desert in North Africa for millennia and the local culture is rich in knowledge and experience with the benefits of dates, suggesting that dates contain many substances essential for the human body. Madinah dates are considered one of the most important types of dates in the Arabian Peninsula, with Ajwa being one of the most famous types and grown only in Madinah, Saudi Arabia. Date seeds are traditionally used for animal feed, seed oil production, cosmetics, and as a coffee substitute. Phytochemical compounds that have been detected in date fruits and date seeds include phenolic acids, carotenoids, and flavonoids. Phenolic acids are the most prevalent bioactive constituents that contribute to the antioxidant activity of date fruits. The bioactive properties of these phytochemicals are believed to promote human health by reducing the risk of diseases such as chronic inflammation. Ajwa dates especially are thought to have superior bioactivity properties. To investigate these claims, in this study, we compare the metabolic profiles of Ajwa with different types of dates collected from Saudi Arabia and Tunisia. We show by UHPLC-MS that date seeds contain several classes of flavonoids, phenolic acids, and amino acid derivatives, including citric acid, malic acid, lactic acid, and hydroxyadipic acid. Additionally, GC-MS profiling showed that date seeds are richer in metabolite classes, such as hydrocinnamic acids (caffeic, ferulic and sinapic acids), than flesh samples. Deglet N fruit extract (minimum inhibitory concentration: 27 MIC/μM) and Sukkari fruit extract (IC 50 : 479 ± 0.58μg /mL) have higher levels of antibacterial and antioxidative activity than Ajwa fruits. However, the seed analysis showed that seed extracts have better bioactivity effects than fruit extracts. Specifically, Ajwa extract showed the best MIC and strongest ABTS radical-scavenging activity among examined seed extracts (minimum inhibitory concentration: 20 μM; IC 50 : 54 ± 3.61μg /mL). Our assays are a starting point for more advanced in vitro antibacterial models and investigation into the specific molecules that are responsible for the antioxidative and anti-bacterial activities of dates.
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Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide... more
Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide were living with HIV in 2021. Viral reverse transcriptase (RT) is an excellent target for drug intervention. Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of approved antiretroviral drugs. Later, a new type of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were approved as anti-HIV drugs. Zidovudine, didanosine, and stavudine are FDA-approved NRTIs, while nevirapine, efavirenz, and delavirdine are FDA-approved NNRTIs. Several agents are in clinical trials, including apricitabine, racivir, elvucitabine, doravirine, dapivirine, and elsulfavirine. This review addresses HIV-1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA-approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART).
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ISL1 is a pioneer transcription factor that plays important roles in cell lineage specification and differentiation, by programming the epigenome and recruiting additional regulatory factors. The aim of this study is to determine whether... more
ISL1 is a pioneer transcription factor that plays important roles in cell lineage specification and differentiation, by programming the epigenome and recruiting additional regulatory factors. The aim of this study is to determine whether the human breastmilk contains ISL1-positive stem cells, and, if so, to describe the subcellular localization of ISL1. MATERIALS AND METHODS: Breast milk was obtained from fourteen healthy females during the first 2-6 months of lactation. Cell morphology was examined in the breast milk with the automatic ThinPrep ® processor (Hologic ® Inc.) in commercial Cytological ThinPrep ® solution (Hologic ® Inc.), followed by standard immunohistochemical staining of ISL1. RESULTS: ISL1 had a granular diffuse cytoplasmic localization, with varying intensity of staining in both single and grouped cells. Nuclear staining was also present, as was staining of intracellular and extracellular vesicles with ISL1 antibody. CONCLUSIONS: These preliminary results suggest that ISL1 could distinguish a readily available source of putative stem cells in human breast milk. These stem cells may complete the network created between the mother and the newborn during gestation, thereby improving the efficiency of programming and reprogramming postnatal events.
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Biofuels are emerged as an alternative to fossil fuels due to their sustainable and renewable nature. Among various biofuel sources, algae have gained significant attention due to their high growth rates, photosynthetic efficiency, and... more
Biofuels are emerged as an alternative to fossil fuels due to their sustainable and renewable nature. Among various biofuel sources, algae have gained significant attention due to their high growth rates, photosynthetic efficiency, and ability to produce lipids and carbohydrates required for Biofuels production. Algae cultivation has no special requirements only water, simple salts, minerals, and sunlight are required. Also, biofuel production from algae cultivated in wastewater has an added advantage of wastewater treatment and CO 2 sequestration from the environment. Although, commercial feasibility of algae based biofuel is still uncertain and so far not clear if it could compete equally with other available fuels in the market. The experts are in favour of promotion of algae based biofuels considering the added advantage of carbon sequestration and wastewater treatment approach involved in algae based biofuels. The concept of a circular economy and carbon neutrality in algae cultivation and harvesting are two intertwined approaches that hold great promise for sustainable and environmental friendly algae based biofuel production. This article provides a comprehensive overview of recent advancements in algae-based biofuel production, focusing on cultivation and harvesting techniques, factors affecting algae growth, algae-based biofuel production technologies, and the commercial feasibility of algae for biofuel production. Further, research related to cultivation and harvesting, developing new species, and optimizing the biofuel production process should be carried out to make the prices of algae based biofuels competitive.
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Berberine (BER) is an alkaloid obtained from berberis plant having broad biological activities including anticancer. BER-encapsulated alginate (ALG)/chitosan (CHS) nanoparticles (BER−ALG/CHS-NPs) were developed for long-acting improved... more
Berberine (BER) is an alkaloid obtained from berberis plant having broad biological activities including anticancer. BER-encapsulated alginate (ALG)/chitosan (CHS) nanoparticles (BER−ALG/CHS-NPs) were developed for long-acting improved treatment in breast cancer. The surface of the NPs was activated by a conjugation reaction, and thereafter, the BER−ALG/CHS-NP surface was grafted with folic acid (BER−ALG/CHS-NPs−F) for specific targeting in breast cancer. BER−ALG/CHS-NPs−F was optimized by applying the Box−Behnken design using Expert design software. Moreover, formulations are extensively evaluated in vitro for biopharmaceutical performances and tested for cell viability, cellular uptake, and antioxidant activity. The comparative pharmacokinetic study of formulation and free BER was carried out in animals for estimation of bioavailability. The particle size recorded for the diluted sample using a Malvern Zetasizer was 240 ± 5.6 nm. The ζ-potential and the predicted % entrapment efficiency versus (vs) observed were +18 mV and 83.25 ± 2.3% vs 85 ± 3.5%. The high % drug release from the NPs was recorded. The analytical studies executed using infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction expressed safe combinations of the components in the formulation and physical state of the drug revealed to be amorphous in the formulation. Cytotoxicity testing demonstrated that the formulation effectively lowered the cell viability and IC 50 of the tested cell line in comparison to a raw drug. The cellular uptake of BER−ALG/CHS-NPs−F was 5.5fold higher than that of BER−suspension. The antioxidant capacities of BER−ALG/CHS-NPs−F vs BER−suspension by the DPPH assay were measured to be 62.3 ± 2.5% vs 30 ± 6%, indicating good radical scavenging power of folate-conjugated NPs. The developed formulation showed a 4.4-fold improved oral bioavailability compared to BER−suspension. The hemolytic assay intimated <2% destruction of erythrocytes by the developed formulation. The observed experimental characterization results such as cytotoxicity, cellular uptake, antioxidant activity, and improved absorption suggested the effectiveness of BER−ALG/CHS-NPs−F toward breast cancer.
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New liquid crystalline hydrogen bonded 3- (or 4)-n-alkanoyloxy benzoic acids were synthesized and probed theoretically and experimentally. The molecular structures of these compounds were elucidated by proton NMR, carbon-13 NMR and... more
New liquid crystalline hydrogen bonded 3- (or 4)-n-alkanoyloxy benzoic acids were synthesized and probed theoretically and experimentally. The molecular structures of these compounds were elucidated by proton NMR, carbon-13 NMR and elemental analyses. Differential scanning calorimetry (DSC) was used to investigate the thermal and mesomorphic properties of all the symmetrical dimers that bearing identical alkanoyloxy chains. Moreover, polarized optical microscopy (POM) was used to determine their mesophases. The findings show that all the designed symmetrical dimers exhibit the smectic mesophase with relative thermal stability that depends on the length of their terminal side chain. Additionally, the experimental findings of the mesomorphic behavior are further supported by DFT calculations. The alkanoyloxy benzoic acid para-derivatives (In) were shown to be more stable than their meta-substituted (IIn) analogues due to stronger hydrogen bonding interactions. The computed reactivity parameters showed that the position of ester moiety has a significant impact on the acids reactivity. The absorbance spectra of both the 3- (or 4)-n-alkanoyloxy benzoic acids revealed a blue shift with the increment of the of alkyl chain size; however, the energy band gaps of 3-n-alkanoyloxy benzoic derivatives were found to be slightly higher than those of the 4-n-alkanoyloxy benzoic acids. Moreover, the photoluminescence spectrum of the prepared materials is rather broad, and exhibited a red shift as the alkyl chain length increases. The fluorescence lifetime shown to rise as alkyl chain length grows longer, and 3-n-alkanoyloxy benzoic acids have slightly longer lifetime compared to their 4-n-alkanoyloxy benzoic analogues.
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Microtubules are dynamic structures that form spindle fibers during cell division; pharmacological inhibition of microtubule dynamics arrests cells in mitosis, leading to apoptosis, and they have been extensively used to treat various... more
Microtubules are dynamic structures that form spindle fibers during cell division; pharmacological inhibition of microtubule dynamics arrests cells in mitosis, leading to apoptosis, and they have been extensively used to treat various cancers. However, the efficacy of such drugs is often limited by multidrug resistance. This study synthesized and evaluated 30 novel derivatives of podophyllotoxin, a natural antimitotic compound, for their antiproliferative activities. Compound SSE1806 exhibited the most potent antiproliferative activity with GI 50 values ranging from 1.29 ± 0.01 to 21.15 ± 2.1 μM in cancer cell lines of different origins; it directly inhibited microtubule polymerization, causing aberrant mitosis and G2/M arrest. Prolonged treatment with SSE1806 increased p53 expression, induced cell death in monolayer cultures, and reduced the growth of mouse-and patientderived human colon cancer organoids. Importantly, SSE1806 overcame multidrug resistance in a cell line overexpressing MDR-1. Thus, SSE1806 represents a potential anticancer agent that can overcome multidrug resistance.
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Cancer is a progressive disease of multi-factorial origin that has risen worldwide, probably due to changes in lifestyle, food intake, and environmental changes as some of the reasons. Skin cancer can be classified into melanomas from... more
Cancer is a progressive disease of multi-factorial origin that has risen worldwide, probably due to changes in lifestyle, food intake, and environmental changes as some of the reasons. Skin cancer can be classified into melanomas from melanocytes and nonmelanoma skin cancer (NMSC) from the epidermally-derived cell. Together it constitutes about 95% of skin cancer. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) are creditworthy of 99% of NMSC due to the limited accessibility of conventional formulations in skin cancer cells of having multiple obstacles in treatment reply to this therapeutic regime. Despite this, it often encounters erratic bioavailability and absorption to the target. Nanoparticles developed through nanotechnology platforms could be the better topical skin cancer therapy option. To improve the topical delivery, the nano-sized delivery system is appropriate as it fuses with the cutaneous layer and fluidized membrane; thus, the deeper penetration of therapeutics could be possible to reach the target spot. This review briefly outlooks the various nanoparticle preparations, i.e., liposomes, niosomes, ethosomes, transferosomes, transethosomes, nanoemulsions, and nanoparticles technologies tested into skin cancer and impede their progress tend to concentrate in the skin layers. Nanocarriers have proved that they can considerably boost medication bioavailability, lowering the frequency of dosage and reducing the toxicity associated with high doses of the medication.
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Toxoplasma gondii is deemed a successful parasite worldwide with a wide range of hosts. Currently, a combination of pyrimethamine and sulfadiazine serves as the first-line treatment; however, these drugs have serious adverse effects.... more
Toxoplasma gondii is deemed a successful parasite worldwide with a wide range of hosts. Currently, a combination of pyrimethamine and sulfadiazine serves as the first-line treatment; however, these drugs have serious adverse effects. Therefore, it is imperative to focus on new therapies that produce the desired effect with the lowest possible dose. The designation and synthesis of sulfonamide-1,2,3-triazole hybrids (3a–c) were performed to create hybrid frameworks. The newly synthesized compounds were loaded on chitosan nanoparticles (CNPs) to form nanoformulations (3a.CNP, 3b.CNP, 3c.CNP) for further in vitro investigation as an anti-Toxoplasma treatment. The current study demonstrated that all examined compounds were active against T. gondii in vitro relative to the control drug, sulfadiazine. 3c.CNP showed the best impact against T. gondii with the lowest IC50 value of 3.64 µg/mL. Using light microscopy, it was found that Vero cells treated with the three nanoformulae showed remarkable morphological improvement, and tachyzoites were rarely seen in the treated cells. Moreover, scanning and transmission electron microscopic studies confirmed the efficacy of the prepared nanoformulae on the parasites. All of them caused parasite ultrastructural damage and altered morphology, suggesting a cytopathic effect and hence confirming their promising anti-Toxoplasma activity.
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MEK1/2 are critical components of the RAS–RAF–MEK–ERK or MAPK signalling pathway that regulates a variety of cellular functions including proliferation, survival, and differentiation. In 1997, a lung cancer cell line was first found to... more
MEK1/2 are critical components of the RAS–RAF–MEK–ERK or MAPK signalling pathway that regulates a variety of cellular functions including proliferation, survival, and differentiation. In 1997, a lung cancer cell line was first found to have a MEK mutation (encoding MEK2P298L). MEK is involved in various human cancers such as non-small cell lung cancer (NSCLC), spurious melanoma, and pancreatic, colorectal, basal, breast, and liver cancer. To date, 4 MEK inhibitors i.e., trametinib, cobimetinib, selumetinib, and binimetinib have been approved by the FDA and several are under clinical trials. In this review, we have highlighted structural insights into the MEK1/2 proteins, such as the αC-helix, catalytic loop, P-loop, F-helix, hydrophobic pocket, and DFG motif. We have also discussed current issues with all FDA-approved MEK inhibitors or drugs under clinical trials and combination therapies to improve the efficacy of clinical drugs. Finally, this study addressed recent developments on synthetic MEK inhibitors (from their discovery in 1997 to 2022), their unique properties, and their relevance to MEK mutant inhibition.
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In this work, the biological potency of nitazoxanide (NTZ) was enhanced through coordination with transition metal ions Cu(II), Ni(II), and Zn(II). Initially, complexes with a ligand-metal stoichiometry of 2:1 were successfully... more
In this work, the biological potency of nitazoxanide (NTZ) was enhanced through coordination with transition metal ions Cu(II), Ni(II), and Zn(II). Initially, complexes with a ligand-metal stoichiometry of 2:1 were successfully synthesized and characterized by spectroscopic techniques and thermogravimetric methods. Measurement of the infrared spectrum revealed the bidentate nature of the ligand and excluded the possibility of the metal ion—amide group interaction. Nuclear magnetic resonance spectra showed a reduction in the NH- intensity signal and integration, indicating the possibility of enolization and the formation of keto-enol tautomers. To interpret these results, density functional theory was utilized under B3LYP/6-311G** for the free ligand and B3LYP/LANL2DZ for the metal complexes. We used UV-Vis and fluorescence spectroscopy to understand the biological properties of the complexes. This showed stronger interactions of NTZ-Cu(II) and NTZ-Ni(II) with DNA molecules than the NTZ-Zn(II) compound, with a binding constant (Kb) for the copper complex of 7.00 × 105 M−1. Both Cu(II)- and Ni(II)-NTZ had functional binding to the SARS-CoV-2 (6LU7) protease. Moreover, all metal complexes showed better antioxidation properties than the free ligand, with NTZ-Ni(II) having the best IC50 value of 53.45 μg/mL. NTZ-Ni(II) was an effective antibacterial, with a mean inhibitory concentration of 6 μM, which is close to that of ampicillin (a reference drug). The metal complexes had moderated anticancer potencies, with NTZ-Cu(II) having IC50 values of 24.5 and 21.5 against human breast cancer cells (MCF-7) and cancerous cervical tumor cells (HeLa), respectively. All obtained complexes exhibited high selectivity. Finally, the metal ions showed a practical role in improving the biological effectiveness of NTZ molecules.
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The objective of the current study was to ascertain the effect of using ginger powder or frankincense oil at different levels on the production rate, biochemical properties of blood, and immune response of laying Japanese quail housed... more
The objective of the current study was to ascertain the effect of using ginger powder or frankincense oil at different levels on the production rate, biochemical properties of blood, and immune response of laying Japanese quail housed from 12 to 21 weeks of age. 300 sexually mature quail (200 females and 100 males) were distributed among five groups at 12 weeks of age in a completely randomized design. Group 1: received basal diet not including additives and acted as a control group. Groups 2 and 3: received a basal diet with 250 and 500 mg ginger/kg feed, respectively. Groups 4 and 5: received a basal diet with 200 and 400 mg frankincense oil/kg feed, respectively. Results revealed that egg production parameters of laying Japanese quail were not influenced by ginger or frankincense oil added in all groups tested during experimental periods except at the time (15-18 wks.). Moreover, egg weight was significantly increased only during the period (15-18 wks.) and total period (12-21 weeks of age), and group 5 recorded the highest weight during the two periods studied. Feed additives did not impact feed consumption or feed conversion ratio (FCR). Except for WBCs, Hb, and monocytes, treatments impacted blood hematological parameters. Also, blood serum parameters were influenced by feed additives, except total protein, albumin, globulin and creatinine were not influenced. Moreover, histological examination of the spleen was influenced by feed additives. It is concluded that utilizing frankincense oil or ginger powder in diets of laying Japanese quails enhanced blood serum properties and improved reproductive and productive performance.
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The purpose of this study was to enhance the antimicrobial activity of bagasse paper by coating the paper with bismuth oxide (Bi2O3) and using it to accelerate the process of wound healing. Paper sheets were prepared from sugarcane waste... more
The purpose of this study was to enhance the antimicrobial activity of bagasse paper by coating the paper with bismuth oxide (Bi2O3) and using it to accelerate the process of wound healing. Paper sheets were prepared from sugarcane waste (bagasse). First, the paper sheets were coated with different Bi2O3 concentrations to improve the antimicrobial activity of the paper. After that, the paper sheets were allowed to dry in an oven at 50 °C for 3 h. Then, in vitro antimicrobial activity was evaluated against different microbial species, including Gram-negative bacteria (i.e., Klebsiella pneumonia, Escherichia coli) and Gram-positive bacteria (i.e., Staphylococcus aureus, Streptococcus pyogenes). The obtained results showed that the paper coated with 25% and 100% Bi2O3 had activity against all models of bacteria; however, the paper coated with 100% Bi2O3 composite had the strongest inhibitory effect. Then, bagasse paper was coated with 100% Bi2O3 and different antibiotics, to investigate their wound-healing potency in a wounded rat model for 14 days. Moreover, the paper coated with 100% Bi2O3 inhibited the cellular migration in vitro. Conclusively, coating paper with Bi2O3 enhances the wound-healing potential when applied to wounds. This impact could be ascribed to Bi2O3’s broad antibacterial activity, which reduced infection and accelerated the healing process.
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Surgery, chemotherapy, and radiation are standard cancer therapies to remove or kill cancer cells. These therapies can successfully treat cancer in its early stages but are typically less effective at advanced stages or recurrence. The... more
Surgery, chemotherapy, and radiation are standard cancer therapies to remove or kill cancer cells. These therapies can successfully treat cancer in its early stages but are typically less effective at advanced stages or recurrence. The past few decades have led to a fourth therapy, cancer immunotherapy. Among the immunotherapy approaches for tumors is cancer vaccination. Cancer vaccines can stimulate immunity against tumors through tumor antigens. Ideal cancer vaccines stimulate both cellular and humoral immunity while overcoming tumor-immune suppression to stop tumor growth and eventually kill tumor cells. Cancer vaccines are different from conventional vaccines since their therapeutic goals involve triggering tumor antigen-specific cellular immune responses to destroy the tumor cells. Additionally, tumor antigens are endogenous and have limited immunogenicity, unlike conventional vaccinations that use antigens from exogenous infections.
Although the identification and characterization of several tumor antigens have led to the creation of numerous antigen-derived cancer vaccines, many vaccines lack clinical effectiveness because they are insufficiently immunogenic. Therefore, adjuvants are used in vaccination formulations to promote potent and durable immune responses. In this chapter, we summarize the current standard cancer treatment modalities, highlight the present state of cancer immunotherapy, and describe many platforms and optimization techniques for cancer vaccines.
Although the identification and characterization of several tumor antigens have led to the creation of numerous antigen-derived cancer vaccines, many vaccines lack clinical effectiveness because they are insufficiently immunogenic. Therefore, adjuvants are used in vaccination formulations to promote potent and durable immune responses. In this chapter, we summarize the current standard cancer treatment modalities, highlight the present state of cancer immunotherapy, and describe many platforms and optimization techniques for cancer vaccines.
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Over the course of years healthcare systems have utilized various '-omics' approaches to prognose, diagnose and evaluate the treatment efficacy of cancer diseases. Metabolomics is one of the latest prominent additions to the-omics... more
Over the course of years healthcare systems have utilized various '-omics' approaches to prognose, diagnose and evaluate the treatment efficacy of cancer diseases. Metabolomics is one of the latest prominent additions to the-omics approaches, characterized by its versatile methodology. Owing to constant improvements in the field, a metabolomic aims to provide a faster and a more accurate diagnosis, as well as personalized and optimal strategies of treatment. In recent years, a growing number of studies have utilized metabolomics approach to find new disease-related biomarkers of cancer diseases. Here we present the summary of recent advances in biomarker discovery for various types of cancers such as leukemia, ovarian, lung, breast and liver cancers as well as cancer-related cachexia.
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Nuclear magnetic resonance (NMR) is one of the most common and powerful techniques used in metabolomics. The inherent quantitative, nondestructive, and nonbiased properties, together with minimal sample preparation/manipulation make NMR a... more
Nuclear magnetic resonance (NMR) is one of the most common and powerful techniques used in metabolomics. The inherent quantitative, nondestructive, and nonbiased properties, together with minimal sample preparation/manipulation make NMR a potent approach to any investigative metabolic study involving biological systems. NMR spectroscopy offers several unique monitoring opportunities such as extremely high reproducibility, relatively short experiment times, a wide range of available experiments (e.g., multidimensional and multinuclear based), and advanced highly automated robotic sample handling/exchange technologies enabling potentially hundreds of samples per instrument in a single day.
In this chapter, we highlight the primary advantages and limitations of NMR spectroscopy, introduce the most commonly applied NMR experiments in metabolomics, and review some of the recent advances with selected examples of novel applications, such as high-resolution magic-angle spinning for tissue samples, and pure shift NMR method as an example of a promising new approach that can be used to overcome the overlapping of 1D NMR spectra. The main advantages of NMR spectroscopy with a particular focus on reproducibility are also presented.
In this chapter, we highlight the primary advantages and limitations of NMR spectroscopy, introduce the most commonly applied NMR experiments in metabolomics, and review some of the recent advances with selected examples of novel applications, such as high-resolution magic-angle spinning for tissue samples, and pure shift NMR method as an example of a promising new approach that can be used to overcome the overlapping of 1D NMR spectra. The main advantages of NMR spectroscopy with a particular focus on reproducibility are also presented.
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Structural biology has come a long way since the first inception of multidimensional NMR. The dipole-dipole interaction between two spatially closed spins provides a powerful tool to probe macromolecules' three-dimensional (3D) structure,... more
Structural biology has come a long way since the first inception of multidimensional NMR. The dipole-dipole interaction between two spatially closed spins provides a powerful tool to probe macromolecules' three-dimensional (3D) structure, such as proteins. However, the main challenge for macromolecules is to assign the NMR chemical shifts of all signals of the investigated protein. This chapter presents different 3D triple resonance NMR experiments dedicated to assignments of NMR signals of protein backbone structure. In addition, the through-space correlation experiments, namely NOESY, ROESY, and HOESY, are presented with detailed information about the advantages and limitations of each. The main strength of NMR lies in obtaining molecular structures under natural conditions and detailed information on the molecular dynamics at different timescales. The detailed characterization of sub-nanosecond segmental motions in proteins was characterized long before the advent of the first solution structure by NMR. Herein, the basic concept behind structure determination and elucidating protein dynamics on different timescales is presented. This book chapter will also highlight the NMR methodologies regarding characterizing sparsely populated protein conformations and transient states, vital for macromolecular functions.
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Pharmacology is the predominant first-line treatment for most pathologies. However, various factors, such as genetics, gender, diet, and health status, significantly influence the efficacy of drugs in different patients, sometimes with... more
Pharmacology is the predominant first-line treatment for most pathologies. However, various factors, such as genetics, gender, diet, and health status, significantly influence the efficacy of drugs in different patients, sometimes with fatal consequences. Personalized diagnosis substantially improves treatment efficacy but requires a more comprehensive process for health assessment. Pharmacometabolomics combines metabolomic, genomic, transcriptomic and proteomic approaches and therefore offers data that other analytical methods cannot provide. In this way, pharmacometabolomics more accurately guides medical professionals in predicting an individual's response to selected drugs. In this chapter, we discuss the potentials and the advantages of metabolomics approaches for designing innovative and personalized drug treatments.
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Although nuclear magnetic resonance spectroscopy is a potent analytical tool for identification, quantification, and structural elucidation, it suffers from inherently low sensitivity limitations. This chapter focuses on recently reported... more
Although nuclear magnetic resonance spectroscopy is a potent analytical tool for identification, quantification, and structural elucidation, it suffers from inherently low sensitivity limitations. This chapter focuses on recently reported methods that enable quick acquisition of NMR spectra, as well as new methods of faster, efficient, and informative two-dimensional (2D) NMR methods. Fast and efficient data acquisition has risen in response to an increasing need to investigate chemical and biological processes in real time. Several new techniques have been successfully introduced. One example of this is band-selective optimized-flip-angle short-transient (SOFAST) NMR, which has opened the door to studying the kinetics of biological processes such as the phosphorylation of proteins. The fast recording of NMR spectra allows researchers to investigate time sensitive molecules that have limited stability under experimental conditions. The increasing awareness that molecular structures are dynamic, rather than static, has pushed some researchers to find alternatives to standard, time-consuming methods of 15 N relaxation observ-ables acquisition.