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Mitochondria serve as central hubs for regulating numerous cellular processes that include metabolism, apoptosis, cell cycle progression, proliferation, differentiation, epigenetics, immune signaling, and aging. The voltage-dependent anion channel 1 (VDAC1) functions as a crucial mitochondrial gatekeeper, controlling the flow of ions, such as Ca²⁺, nucleotides, and metabolites across the outer mitochondrial membrane, and is also integral to mitochondria-mediated apoptosis. VDAC1 functions in regulating ATP production, Ca²⁺ homeostasis, and apoptosis, which are essential for maintaining mitochondrial function and overall cellular health. Most cancer cells undergo metabolic reprogramming, often referred to as the “Warburg effect”, supplying tumors with energy and precursors for the biosynthesis of nucleic acids, phospholipids, fatty acids, cholesterol, and porphyrins. Given its multifunctional nature and overexpression in many cancers, VDAC1 presents an attractive target for therapeutic intervention. Our research has demonstrated that silencing VDAC1 expression using specific siRNA in various tumor types leads to a metabolic rewiring of the malignant cancer phenotype. This results in a reversal of oncogenic properties that include reduced tumor growth, invasiveness, stemness, epithelial–mesenchymal transition. Additionally, VDAC1 depletion alters the tumor microenvironment by reducing angiogenesis and modifying the expression of extracellular matrix- and structure-related genes, such as collagens and glycoproteins. Furthermore, VDAC1 depletion affects several epigenetic-related enzymes and substrates, including the acetylation-related enzymes SIRT1, SIRT6, and HDAC2, which in turn modify the acetylation and methylation profiles of histone 3 and histone 4. These epigenetic changes can explain the altered expression levels of approximately 4,000 genes that are associated with reversing cancer cells oncogenic properties. Given VDAC1’s critical role in regulating metabolic and energy processes, targeting it offers a promising strategy for anti-cancer therapy. We also highlight the role of VDAC1 expression in various disease pathologies, including cardiovascular, neurodegenerative, and viral and bacterial infections, as explored through siRNA targeting VDAC1. Thus, this review underscores the potential of targeting VDAC1 as a strategy for addressing high-energy-demand cancers. By thoroughly understanding VDAC1’s diverse roles in metabolism, energy regulation, mitochondrial functions, and other cellular processes, silencing VDAC1 emerges as a novel and strategic approach to combat cancer. Full article

The analysis of skin surface lipid-RNAs (SSL-RNAs) provides a non-invasive method for understanding the molecular pathology of atopic dermatitis (AD), but its relevance to asthma remains uncertain. Although dupilumab, a biologic drug approved for both asthma and AD, has shown efficacy in improving symptoms for both conditions, its impact on SSL-RNAs is unclear. This study aimed to investigate the impact of dupilumab treatment on SSL-RNA profiles in patients with severe asthma. Methods: An SSL-RNA analysis was performed before and after administering dupilumab to asthma patients requiring this intervention. Skin samples were collected non-invasively from patients before and after one year of dupilumab treatment. Although 26 patients were enrolled, an SSL-RNA analysis was feasible in only 7 due to collection challenges. After dupilumab treatment, improvements were observed in asthma symptoms, exacerbation rates, and lung function parameters. Serum levels of total IgE and periostin decreased. The SSL-RNA analysis revealed the differential expression of 218 genes, indicating significant down-regulation of immune responses, particularly those associated with type 2 inflammation, suggesting potential improvement in epithelial barrier function. Dupilumab treatment may not only impact type 2 inflammation but also facilitate the normalization of the skin. Further studies are necessary to fully explore the potential of SSL-RNA analysis as a non-invasive biomarker for evaluating treatment response in asthma. Full article

The γ-aminobutyric acid (GABA) is a widely distributed neurotransmitter in living organisms, known for its inhibitory role in animals. GABA exerts calming effects on the mind, lowers blood pressure in animals, and enhances stress resistance during the growth and development of plants. Enhancing GABA content in plants has become a focal point of current research. In plants, GABA is synthesized through two metabolic pathways, the GABA shunt and the polyamine degradation pathway, with the GABA shunt being the primary route. Extensive studies have investigated the regulatory mechanisms governing GABA synthesis. At the genetic level, GABA production and degradation can be modulated by gene overexpression, signaling molecule-induced expression, transcription factor regulation, and RNA interference. Additionally, at the level of transporter proteins, increased activity of GABA transporters and proline transporters enhances the transport of glutamate and GABA. The activity of glutamate decarboxylase, a key enzyme in GABA synthesis, along with various external factors, also influences GABA synthesis. This paper summarizes the biological functions, metabolic pathways, and regulatory mechanisms of GABA, providing a theoretical foundation for further research on GABA in plants. Full article

Anthracnose of the tea plant (Camellia sinensis), caused by Colletotrichum spp., poses a significant threat to both the yield and quality of tea production. To address this challenge, researchers have looked to the application of endophytic bacteria as a natural alternative to the use chemical pesticides, offering potential for enhancing disease resistance and abiotic stress tolerance in tea plants. This study focused on identifying effective microbial agents to combat tea anthracnose caused by Colletotrichum fructicola. A total of 38 Bacillus-like strains were isolated from the tea rhizosphere, with 8 isolates showing substantial inhibitory effects against the mycelial growth of C. fructicola, achieving an average inhibition rate of 60.68%. Among these, strain T3 was particularly effective, with a 69.86% inhibition rate. Through morphological, physiological, and biochemical characterization, along with 16S rRNA gene phylogenetics analysis, these strains were identified as B. inaquosorum (T1 and T2), B. tequilensis (T3, T5, T7, T8, and T19), and B. spizizenii (T6). Biological and molecular assays confirmed that these strains could induce the expression of genes associated with antimicrobial compounds like iturin, fengycin, subtilosin, and alkaline protease, which effectively reduced the disease index of tea anthracnose and enhanced tea plant growth. In conclusion, this study demonstrates that B. inaquosorum, B. tequilensis, and B. spizizenii strains are promising biocontrol agents for managing tea anthracnose. Full article

The atmospheric environment is formed under the influence of local and distant sources as a result of horizontal and vertical transport. In the present work, microbiological analysis of 604 samples of atmospheric aerosol collected in the period from September 2020 to September 2023 at four sites differing in anthropogenic load, located in Novosibirsk and the region, was carried out. Day and night aerosol samples were collected during 12 h every two weeks by filtration using Sartorius reinforced Teflon membranes, then sown on a set of nutrient media. The taxonomic affiliation of the isolated microbial isolates was determined based on phenotypic characteristics and analysis of 16S rRNA gene nucleotide sequences. Changes in the composition and concentration of culturable microorganisms depending on the season, time of day, and site of aerosol sampling were observed. In winter, lower fungi and bacteria of the genera Bacillus, Staphylococcus, Micrococcus dominated with an average concentration from zero to 12.5 CFU/m³ of aerosol. In the warm period, the concentration and diversity of cocci, spore-forming and non-spore-forming bacteria, actinomycetes, and fungi (up to 1970 CFU/m³), among which pathogenic microorganisms were found, increased sharply in aerosols. The use of 16S metabarcoding techniques has greatly expanded the range of aerosols’ microbial diversity detectable. Full article

Background. Currently, it is known that the gut microbiota plays an important role in the functioning of the immune system, and a rebalancing of the bacterial community can arouse complex immune reactions and lead to immune-mediated responses in an organism, in particular, the development of atopic dermatitis (AD). Cytokines and chemokines are regulators of the innate and adaptive immune response and represent the most important biomarkers of the immune system. It is known that changes in cytokine profiles are a hallmark of many diseases, including atopy. However, it remains unclear how the bacterial imbalance disrupts the function of the immune response in AD. Objectives. We attempted to determine the role of gut bacteria in modulating cytokine pathways and their role in atopic inflammation. Methods. We sequenced the 16S rRNA gene from 50 stool samples of children aged 3–12 years who had confirmed atopic dermatitis, and 50 samples from healthy children to serve as a control group. To evaluate the immune status, we conducted a multiplex immunofluorescence assay and measured the levels of 41 cytokines and chemokines in the serum of all participants. Results. To find out whether changes in the composition of the gut microbiota were significantly associated with changes in the level of inflammatory cytokines, a correlation was calculated between each pair of bacterial family and cytokine. In the AD group, 191 correlations were significant (Spearman’s correlation coefficient, p ≤ 0.05), 85 of which were positive and 106 which were negative. Conclusions. It has been demonstrated that intestinal dysbiosis is associated with alterations in cytokine profiles, specifically an increase in proinflammatory cytokine concentrations. This may indicate a systemic impact of these conditions, leading to an imbalance in the immune system’s response to the Th2 type. As a result, atopic conditions may develop. Additionally, a correlation between known AD biomarkers (IL-5, IL-8, IL-13, CCL22, IFN-γ, TNF-α) and alterations in the abundance of bacterial families (Pasteurellaceae, Barnesiellaceae, Eubacteriaceae) was observed. Full article

Our previous study demonstrated that the acute high-dose-rate (3.3 Gy/min) γ-ray irradiation (γ-irradiation) of postnatal day-3 (P3) mice with 5 Gy induced depression and drastic neuropathological changes in the dentate gyrus of the hippocampus of adult mice. The present study investigated the effects of chronic low-dose-rate (1.2 mGy/h) γ-irradiation from P3 to P180 with a cumulative dose of 5 Gy on animal behaviour, hippocampal cellular change, and miRNA and mRNA expression in the hippocampus and blood in female mice. The radiation exposure did not significantly affect the animal’s body weight, and neuropsychiatric changes such as anxiety and depression were examined by neurobehavioural tests, including open field, light-dark box, elevated plus maze, tail suspension, and forced swim tests. Immunohistochemical staining did not detect any obvious loss of mature and immature neurons (NeuN and DCX) or any inflammatory glial response (IBA1, GFAP, and PDGFRα). Nevertheless, γH2AX foci in the stratum granulosum of the dentate gyrus were significantly increased, suggesting the chronic low-dose-rate irradiation induced persistent DNA damage foci in mice. miRNA sequencing and qRT-PCR indicated an increased expression of miR-448-3p and miR-361-5p but decreased expression of miR-193a-3p in the mouse hippocampus. Meanwhile, mRNA sequencing and qRT-PCR showed the changed expression of some genes, including Fli1, Hs3st5, and Eif4ebp2. Database searching by miRDB and TargetScan predicted that Fli1 and Hs3st5 are the targets of miR-448-3p, and Eif4ebp2 is the target of miR-361-5p. miRNA/mRNA sequencing and qRT-PCR results in blood showed the increased expression of miR-6967-3p and the decreased expression of its target S1pr5. The interactions of these miRNAs and mRNAs may be related to the chronic low-dose-rate radiation-induced persistent DNA damage. Full article

Coccidiosis in broiler chickens continues to be a major disease of the gastrointestinal tract, causing economic losses to the poultry industry worldwide. The goal of this study was to generate a symptomatic Eimeria maxima (1000 oocysts) infection to determine its effect on the luminal and mucosal microbiota populations (L and M) in the jejunum and ileum (J and IL). Samples were taken from day 0 to14 post-infection, and sequencing of 16S rRNA was performed using Illumina technology. Infected birds had significantly (p < 0.0001) lower body weight gain (BWG), higher feed conversion ratio (FCR) (p = 0.0015), increased crypt depth, and decreased villus height (p < 0.05). The significant differences in alpha and beta diversity were observed primarily at height of infection (D7). Analysis of taxonomy indicated that J-L and M were dominated by Lactobacillus, and in IL-M, changeover from Candidatus Arthromitus to Lactobacillus as the major taxon was observed, which occurred quicky in infected animals. LEfSe analysis found that in the J-M of infected chickens, Lactobacillus was significantly more abundant in infected (IF) chickens. These findings show that E. maxima infection affects the microbiota of the small intestine in a time-dependent manner, with different effects on the luminal and mucosal populations. Full article

Human T cell leukaemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes lifelong infection in ~5–10 million individuals globally. It is endemic to certain First Nations populations of Northern and Central Australia, Japan, South and Central America, Africa, and the Caribbean region. HTLV-1 preferentially infects CD4⁺ T cells and remains in a state of reduced transcription, often being asymptomatic in the beginning of infection, with symptoms developing later in life. HTLV-1 infection is implicated in the development of adult T cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathies (HAM), amongst other immune-related disorders. With no preventive or curative interventions, infected individuals have limited treatment options, most of which manage symptoms. The clinical burden and lack of treatment options directs the need for alternative treatment strategies for HTLV-1 infection. Recent advances have been made in the development of RNA-based antiviral therapeutics for Human Immunodeficiency Virus Type-1 (HIV-1), an analogous retrovirus that shares modes of transmission with HTLV-1. This review highlights past and ongoing efforts in the development of HTLV-1 therapeutics and vaccines, with a focus on the potential for gene therapy as a new treatment modality in light of its successes in HIV-1, as well as animal models that may help the advancement of novel antiviral and anticancer interventions. Full article

Chronic venous disease (CVD) is a prevalent condition in adults, significantly affecting the global elderly population, with a higher incidence in women than in men. The modulation of gene expression through microRNA (miRNA) partly regulated the development of cardiovascular disease (CVD). Previous research identified a functional analysis of seven genes (CDS2, HDAC5, PPP6R2, PRRC2B, TBC1D22A, WNK1, and PABPC3) as targets of miRNAs related to CVD. In this context, miRNAs emerge as essential candidates for CVD diagnosis, representing novel molecular and biological knowledge. This work aims to identify, by network analysis, the miRNAs involved in CVD as potential biomarkers, either by interacting with small molecules such as toxins and pollutants or by searching for new drugs. Our study shows an updated landscape of the signaling pathways involving miRNAs in CVD pathology. This latest research includes data found through experimental tests and uses predictions to propose both miRNAs and genes as potential biomarkers to develop diagnostic and therapeutic methods for the early detection of CVD in the clinical setting. In addition, our pharmacological network analysis has, for the first time, shown how to use these potential biomarkers to find small molecules that may regulate them. Between the small molecules in this research, toxins, pollutants, and drugs showed outstanding interactions with these miRNAs. One of them, hesperidin, a widely prescribed drug for treating CVD and modulating the gene expression associated with CVD, was used as a reference for searching for new molecules that may interact with miRNAs involved in CVD. Among the drugs that exhibit the same miRNA expression profile as hesperidin, potential candidates include desoximetasone, curcumin, flurandrenolide, trifluridine, fludrocortisone, diflorasone, gemcitabine, floxuridine, and reversine. Further investigation of these drugs is essential to improve the treatment of cardiovascular disease. Additionally, supporting the clinical use of miRNAs as biomarkers for diagnosing and predicting CVD is crucial. Full article

The avocado crop is relevant for its economic importance and because of its unique evolutionary history. However, there is a lack of information regarding the molecular processes during the defense response against fungal pathogens. Therefore, using a genome-wide approach in this work, we investigated the transcriptional response of the Mexican horticultural race of avocado (Persea americana var. drymifolia), including miRNAs profile and their possible targets. For that, we established an avocado–Fusarium hydroponic pathosystem and studied the response for 21 days. To guarantee robustness in the analysis, first, we improved the avocado genome assembly available for this variety, resulting in 822.49 Mbp in length with 36,200 gene models. Then, using an RNA-seq approach, we identified 13,778 genes differentially expressed in response to the Fusarium infection. According to their expression profile across time, these genes can be clustered into six groups, each associated with specific biological processes. Regarding non-coding RNAs, 8 of the 57 mature miRNAs identified in the avocado genome are responsive to infection caused by Fusarium, and the analysis revealed a total of 569 target genes whose transcript could be post-transcriptionally regulated. This study represents the first research in avocados to comprehensively explore the role of miRNAs in orchestrating defense responses against Fusarium spp. Also, this work provides valuable data about the genes involved in the intricate response of the avocado during fungal infection. Full article

Improving the powdery mildew resistance of bitter gourd is highly important for achieving high yield and high quality. To better understand the genetic basis of powdery mildew resistance in bitter gourd, this study analyzed 300 lines of recombinant inbred lines (RILs) formed by hybridizing the powdery mildew-resistant material MC18 and the powdery mildew-susceptible material MC402. A high-density genetic map of 1222.04 cM was constructed via incorporating 1,996,505 SNPs generated by resequencing data from 180 lines, and quantitative trait locus (QTL) positioning was performed using phenotypic data at different inoculation stages. A total of seven QTLs related to powdery mildew resistance were identified on four chromosomes, among which qPm-3-1 was detected multiple times and at multiple stages after inoculation. By selecting 18 KASP markers that were evenly distributed throughout the region, 250 lines and parents were genotyped, and the interval was narrowed to 207.22 kb, which explained 13.91% of the phenotypic variation. Through RNA-seq analysis of the parents, 11,868 differentially expressed genes (DEGs) were screened. By combining genetic analysis, gene coexpression, and sequence comparison analysis of extreme materials, two candidate genes controlling powdery mildew resistance in bitter gourd were identified (evm.TU.chr3.2934 (C3H) and evm.TU.chr3.2946 (F-box-LRR)). These results represent a step forward in understanding the genetic regulatory network of powdery mildew resistance in bitter gourd and lay a molecular foundation for the genetic improvement in powdery mildew resistance. Full article

Sepsis remains a huge unmet medical need for which no approved drugs, besides antibiotics, are on the market. Despite the clinical impact of sepsis, its molecular mechanism remains inadequately understood. Recent insights have shown that profound hepatic transcriptional reprogramming, leading to fatal metabolic abnormalities, might open a new avenue to treat sepsis. Translation of experimental results from rodents to larger animal models of higher relevance for human physiology, such as pigs, is critical and needs exploration. We performed a comparative analysis of the transcriptome profiles in murine and porcine livers using the following sepsis models: cecal ligation and puncture (CLP) in mice and fecal instillation (FI) in pigs, both of which induce polymicrobial septic peritonitis, and lipopolysaccharide (LPS)-induced endotoxemia in pigs, inducing sterile inflammation. Using bulk RNA sequencing, Metascape pathway analysis, and HOMER transcription factor motif analysis, we were able to identify key genes and pathways affected in septic livers. Conserved upregulated pathways in murine CLP and porcine LPS and FI generally comprise typical inflammatory pathways, except for ER stress, which was only found in the murine CLP model. Conserved pathways downregulated in sepsis comprise almost exclusively metabolic pathways such as monocarboxylic acid, steroid, biological oxidation, and small-molecule catabolism. Even though the upregulated inflammatory pathways were equally induced in the two porcine models, the porcine FI model more closely resembles the metabolic dysfunction observed in the CLP liver compared to the porcine LPS model. This comprehensive comparison focusing on the hepatic responses in mouse CLP versus LPS or FI in pigs shows that the two porcine sepsis models generally resemble quite well the mouse CLP model, with a typical inflammatory signature amongst the upregulated genes and metabolic dysfunction amongst the downregulated genes. The hepatic ER stress observed in the murine model could not be replicated in the porcine models. When studying metabolic dysfunction in the liver upon sepsis, the porcine FI model more closely resembles the mouse CLP model compared to the porcine LPS model. Full article

Rapid Alkalization Factor (RALF) is a signaling molecule in plants that plays a crucial role in growth and development, reproductive processes, and responses to both biotic and abiotic stresses. Although RALF peptides have been characterized in Arabidopsis and rice, a comprehensive bioinformatics analysis of the ZmRALF gene family in maize is still lacking. In this study, we identified 20 RALF genes in the maize genome. Sequence alignment revealed significant structural variation among the ZmRALF family genes. Phylogenetic analysis indicates that RALF proteins from Arabidopsis, rice, and maize can be classified into four distinct clades. Duplication events suggest that the expansion of the RALF gene family in maize primarily relies on whole-genome duplication. ZmRALF genes are widely expressed across various tissues; ZmRALF1/15/18/19 are highly expressed in roots, while ZmRALF6/11/14/16 are predominantly expressed in anthers. RNA-seq and RT-qPCR demonstrated that the expression levels of ZmRALF7, ZmRALF9, and ZmRALF13 were significantly up-regulated and down-regulated in response to PEG and NaCl stresses, respectively. Overall, our study provides new insights into the role of the RALF gene family in abiotic stress. Full article

Background/Objectives: Type 1 diabetes affects cytokines as potential inducers of NFκB signalling involved in inflammation and neuronal survival. Our goal was to assess the expression of NFκB p65 and its negative regulator, Nrf2, in myenteric neurons and adjacent smooth muscle of different gut segments after chronic hyperglycaemia and immediate insulin treatment. Methods: After ten weeks of hyperglycaemia, intestinal samples of control, streptozotocin-induced diabetic and insulin-treated diabetic rats were prepared for fluorescent immunohistochemistry, immunogold electron microscopy, ELISA and qPCR. Results: In the diabetic rats, the proportion of NFκB p65-immunoreactive myenteric neurons decreased significantly in the duodenum and increased in the ileum. The density of NFκB p65-labelling gold particles increased in the ileal but remained unchanged in the duodenal ganglia. Meanwhile, both total and nuclear Nrf2 density increased in the myenteric neurons of the diabetic duodenum. In smooth muscle, NFκB p65 and Nrf2 density increased in the small intestine of diabetic rats. While on the mRNA level, NFκB p65 and Nrf2 were induced, on the protein level, NFκB p65 increased and Nrf2 decreased in muscle/myenteric plexus homogenates. Insulin treatment had protective effects. Conclusions: Our findings reveal a segment-specific NFκB and Nrf expression in myenteric neurons and ganglionic muscular environments, which may contribute to regional neuronal survival and motility disturbances in diabetes. Full article