Search Results (1,798)

Hyperlipidemia is a major risk factor for vascular lesions in diabetes mellitus and other metabolic disorders, although its basis remains poorly understood. One of the key pathogenetic events in this condition is mitochondrial dysfunction associated with the opening of the mitochondrial permeability transition (MPT) pore, a drop in the membrane potential, and ROS overproduction. Here, we investigated the effects of bongkrekic acid and carboxyatractyloside, a potent blocker and activator of the MPT pore opening, respectively, acting through direct interaction with the adenine nucleotide translocator, on the progression of mitochondrial dysfunction in mouse primary lung endothelial cells exposed to elevated levels of palmitic acid. Palmitate treatment (0.75 mM palmitate/BSA for 6 days) resulted in an 80% decrease in the viability index of endothelial cells, which was accompanied by mitochondrial depolarization, ROS hyperproduction, and increased colocalization of mitochondria with lysosomes. Bongkrekic acid (25 µM) attenuated palmitate-induced lipotoxicity and all the signs of mitochondrial damage, including increased spontaneous formation of the MPT pore. In contrast, carboxyatractyloside (10 μM) stimulated cell death and failed to prevent the progression of mitochondrial dysfunction under hyperlipidemic stress conditions. Silencing of gene expression of the predominate isoform ANT2, similar to the action of carboxyatractyloside, led to increased ROS generation and cell death under conditions of palmitate-induced lipotoxicity in a stably transfected HEK293T cell line. Altogether, these results suggest that targeted manipulation of the permeability transition pore through inhibition of ANT may represent an alternative approach to alleviate mitochondrial dysfunction and cell death in cell culture models of fatty acid overload. Full article

(1) Background: The effects of Zn and caffeine as promoters of fruit quality in the Solanum lycopersicum L. cultivar ‘Panarea’ were tested. (2) Methods: During the 56 days of the experiment, plants were treated weekly with 100 mL of 1 mM Zn (Zn), 1 mg L⁻¹ caffeine trimethyl-¹³C (caffeine), and 1 mM Zn + 1 mg L⁻¹ caffeine trimethyl-¹³C (Zn + caffeine) and compared to plants that were given tap water (control). (3) Results: Caffeine was taken up by the roots and translocated to the leaves, which positively influenced the number of fruits per plant. After 56 days of treatment, Zn induced a positive increase in tomato dry weight, reducing shoot length (−16.7%) compared to the other treatments. Zn + caffeine had a positive effect on the phenylpropanoid pathway of fruits, and 4-coumaric acid, caffeic acid, and t-ferulic acid were significantly increased, as well as the total antioxidant capacity of the tomatoes. In the flavonoid pathway, only apigenin and luteolin contents were reduced by treatments. The tomatoes showed similar concentrations of the mineral elements Cu, Mn, Fe, Na, Ca, Mg, and K. The Zn and caffeine target hazard quotients were <1, indicating that health risks via the consumption of these tomatoes did not occur. (4) Conclusions: Tomato plants could be irrigated with water containing lower values of Zn, caffeine, and a combination of the two. The treated fruits are rich in antioxidant compounds, such as coumaric acid, caffeic acid, and t-ferulic acid, which are beneficial for human health. No considerable health risks associated with human consumption have been detected. Full article

Cadmium (Cd) is a naturally occurring element often associated with lead (Pb) in the Earth’s crust, particularly in karst regions, posing significant safety hazards for locally grown rice. Identifying the key factors controlling Cd and Pb content in local rice is essential under the natural soil condition, as this will provide a crucial theoretical foundation for implementing security intervention measures within the local rice-growing industry. This study collected three types of paddy field soils with varying Cd concentrations from karst areas for pot experiments. The rice varieties tested included a low-Cd-accumulating variety, a high-Cd-accumulating variety, and a locally cultivated variety. Soil physicochemical properties and plant physiological indices were monitored throughout the rice growth stages. These data were used to construct a segmented regression model of Cd and Pb levels in rice grains based on the plant’s metabolic pathways and the structure of polynomial regression equations. Stepwise regression identified the key factors controlling Cd and Pb accumulation in rice grains. In conclusion, the key factors controlling Cd and Pb levels in rice grains should be classified into two categories: (i) factors influencing accumulation in roots and (ii) factors regulating transport from roots to grains. The aboveground translocation abilities for Cd, Pb, zinc (Zn), iron (Fe), manganese (Mn), calcium (Ca), and magnesium (Mg) in soil among the three rice varieties showed no significant interspecific differences under identical soil conditions. Soil Mg uptake by rice roots may represent a key mechanism for inhibiting soil Cd uptake by rice roots. In karst areas with high background soil Cd, increased soil organic matter (SOM) levels enhance Pb bioavailability. Additionally, the rice YXY may possess a potential for low Cd accumulation. Full article

The disposal of coal fly ash (CFA) generated from coal-fired power stations has serious impact on the ecosystem, by converting large pieces of land to barren ash dams with the potential to contaminate groundwater, surface water, air and soil. The aim of this study was to clarify the potential of phytoremediation using Helichrysum splendidum (Thunb.) Less. in areas polluted by CFA through conduction of pot trial experiments for 14 weeks. Plants of the same age were cultivated in CFA to assess their growth, photosynthetic rate and tolerance towards metal toxicity. This study revealed that the CFA was moderately polluted with heavy metals, and a lower photosynthetic rate was recorded for the CFA plants in comparison to the controls (plants grown in soil). Although the CO₂ assimilation rate was lower for the CFA plants, increased growth was recorded for all the plants tested. Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify the amount of trace elements in samples and parameters including translocation factor (TF) and bioconcentration factor (BCF) were used to evaluate the phytoremediation potential of H. splendidum (Thunb.) Less. The results revealed that higher concentrations of Cd, Co, Cr, Cu, Mn and Pb were accumulated in the roots, while As, Ni and Zn were found in the shoots. Elements including As, Cr and Zn reported TF values above 1, indicating the plants’ phytoextraction potential. The BCF values for As, Cu and Zn were 1.22, 1.19 and 1.03, indicating effectiveness in the phytostabilization processes. A removal rate efficiency ranging from 18.0 to 56.7% was recorded confirming that, H. splendidum (Thunb.) Less. can be employed for restoration of CFA dams. Full article

Dermatofibrosarcoma protuberans (DFSP) is a rare proliferative condition representing skin sarcomas which is known to locally recur yet very rarely metastasizes. Its genetic background is a reciprocal translocation t(17;22)(q22;q13) that produces COL1A1-PDGFB gene fusion. Complete resection is the primary treatment. The aim of this review is to outline the pathogenesis, diagnosis, and management of DFSP. A clear-cut distinction between low-to-moderate-grade DFSP with excellent prognosis and high-grade fibrosarcomatous DFSP with a much worse prognosis is underlined. Malignant transformation within DFSP (or high histologic grade), older age, being female, large primary tumor size (≥10 cm), narrow surgical margins of excision (<3 cm), surgical margin positivity for tumor cells, short time to recurrence, numerous recurrences, tumor that was recently rapidly enlarging, and presence of pain in the tumor have all been proposed as clinicopathological risk factors for recurrence and metastasis. A tendency for local growth and local relapses of well- and moderately differentiated DFSPs is an argument for their surgical excision, possibly combined with reconstructive surgery, even in patients of advanced age. Another main point of this review is that cases of DFSP with fibrosarcomatous transformation are a challenge and require careful medical attention. Both anatomopathological evaluation of the presence of lymphovascular space invasion and sentinel lymph node biopsy at DFSP surgery merit further study. Full article

To investigate the effects and mechanism of prolonged inorganic nitrogen (N) fertilization on the N-use efficiency of spring wheat (Triticum aestivum L.), a long-term study initiated in 2003 was conducted. The study analyzed how N fertilization affects dry matter translocation, N translocation, soil NO₃-N, and N-use efficiency. Five different N-fertilizer rate treatments were tested: N0, N52.5, N105, N157.5, and N210, corresponding to annual N fertilizer doses of 0, 52.5, 105.0, 157.5, and 210.0 kg N ha⁻¹, respectively. Results showed that increasing N-fertilizer rates significantly enhanced the two-year average dry matter accumulation amount (DMA) at maturity by 22.97–56.25% and pre-flowering crop growth rate (CGR) by 17.11–92.85%, with no significant increase beyond 105 kg N ha⁻¹. However, no significant correlation was observed between the dry matter translocation efficiency (DTE) and wheat grain yield. Both insufficient and excessive N applications resulted in an imbalanced N distribution favoring vegetative growth over reproductive growth, thus negatively impacting N-use efficiency. At maturity, the N-fertilized treatments significantly increased the two-year average N accumulation amount (NAA) by 52.04–129.98%, with no further increase beyond 105 kg N ha⁻¹. N fertilization also improved the two-year average N translocation efficiency (NTE) by 56.89–63.80% and the N contribution proportion (NCP) of wheat vegetative organs by 27.79–57.83%, peaking in the lower-N treatment (N52.5). However, high-N treatment (N210) led to an increase in NO₃-N accumulation in the 0–100 cm soil layer, with an increase of 26.27% in 2018 and 122.44% in 2019. This higher soil NO₃-N accumulation in the 0–100 cm layer decreased NHI, NUE, NAE, NPFP, and NMB. Additionally, N fertilization significantly reduced the two-year average N harvest index (NHI) by 9.89–12.85% and N utilization efficiency (NUE) by 11.14–20.79%, both decreasing with higher N application rates. The NAA followed the trend of anthesis > maturity > jointing. At the 105 kg N ha⁻¹ rate, the highest N agronomic efficiency (NAE) (9.31 kg kg⁻¹), N recovery efficiency (NRE) (38.32%), and N marginal benefit (NMB) (10.67 kg kg⁻¹) were observed. Higher dry matter translocation amount (DTA) and N translocation amount (NTA) reduced NHI and NUE, whereas higher NTE improved NHI, NUE, and N partial factor productivity (NPFP). Overall, N fertilization enhanced N-use efficiency in spring wheat by improving N translocation rather than dry matter translocation. Full article

M₂-polarized, tumor-associated macrophages (TAMs) produce pro-tumorigenic and angiogenic mediators, such as interleukin-8 (IL-8) and IL-10. Leucine-rich repeat-containing protein 8 members (LRRC8s) form volume-regulated anion channels and play an important role in macrophage functions by regulating cytokine and chemokine production. We herein examined the role of LRRC8A in IL-8 and IL-10 expression in THP-1-differentiated M₂-like macrophages (M₂-MACs), which are a useful tool for investigating TAMs. In M₂-MACs, the pharmacological inhibition of LRRC8A led to hyperpolarizing responses after a transient depolarization phase, followed by a slight elevation in the intracellular concentration of Ca²⁺. Both the small interfering RNA-mediated and pharmacological inhibition of LRRC8A repressed the transcriptional expression of IL-8 and IL-10, resulting in a significant reduction in their secretion. The inhibition of LRRC8A decreased the nuclear translocation of phosphorylated nuclear factor-erythroid 2-related factor 2 (Nrf2), while the activation of Nrf2 reversed the LRRC8A inhibition-induced transcriptional repression of IL-8 and IL-10 in M₂-MACs. We identified the CCAAT/enhancer-binding protein isoform B, CEBPB, as a downstream target of Nrf2 signaling in M₂-MACs. Moreover, among several upstream candidates, the inhibition of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) suppressed the Nrf2–CEBPB transcriptional axis in M₂-MACs. Collectively, the present results indicate that the inhibition of LRRC8A repressed IL-8 and IL-10 transcription in M₂-MACs through the NOX2–Nrf2–CEBPB axis and suggest that LRRC8A inhibitors suppress the IL-10-mediated evasion of tumor immune surveillance and IL-8-mediated metastasis and neovascularization in TAMs. Full article

Spring bread wheat (Triticum aestivum) is a major crop in Russia and in Kazakhstan. The rust pathogens, leaf rust caused by the fungus Puccinia triticina, stem rust incited by P. graminis and yellow rust caused by P. striiformis, are the significant biotic factors affecting wheat production. In this study, 40 new promising spring wheat genotypes from the Kazakhstan-Siberia Network for Spring Wheat Improvement (KASIB) were tested for resistance to leaf, stem and yellow rust at the seedling stage, and for identification of rust resistance genes using molecular markers. In addition, the collection was tested for leaf rust resistance and grain yields in the South Urals agroclimatic zone of Russia in 2023. As a result, 16 accessions with seedling resistance to leaf rust, 21 to stem rust and 4 to yellow rust were identified. Three breeding accessions were resistant to all rust species, and nine to P. triticina and P. graminis. Wheat accessions resistant to leaf rust at the seedling stage were also resistant in the field. Molecular analysis showed the presence of cataloged resistance genes, Lr1, Lr3a, Lr9, Lr10, Lr19, Lr20, Lr24, Lr26, Sr15, Sr24, Sr25, Sr31, Sr38, Yr9 and Yr18; uncatalogued genes Lr6Agi1 and Lr6Agi2 from Thinopyrum intermedium and LrAsp from Aegilops speltoides; and 1AL.1RS translocation. The current analysis showed an increase in leaf and stem rust resistance of new KASIB genotypes and their genetic diversity due to the inclusion of alien genetic material in breeding. Full article

Cardiolipin (CL), a critical phospholipid situated within the mitochondrial membrane, plays a significant role in modulating intramitochondrial processes, especially in the context of certain cardiac pathologies; however, the exact effects of alterations in cardiolipin on septic cardiomyopathy (SCM) are still debated and the underlying mechanisms remain incompletely understood. This study highlights a notable increase in the expressions of ALCAT1 and PLSCR3 during the advanced stage of lipopolysaccharide (LPS)-induced SCM. This up-regulation potential contribution to mitochondrial dysfunction and cellular apoptosis—as indicated by the augmented oxidative stress and cytochrome c (Cytc) release—coupled with reduced mitophagy, decreased levels of the antiapoptotic protein B-cell lymphoma-2 (Bcl-2) and lowered cell viability. Additionally, the timing of LPS-induced apoptosis coincides with the decline in both autophagy and mitophagy at the late stages, implying that these processes may serve as protective factors against LPS-induced SCM in HL-1 cells. Together, these findings reveal the mechanism of LPS-induced CL changes in the center of SCM, with a particular emphasis on the importance of pathological remodeling and translocation of CL to mitochondrial function and apoptosis. Additionally, it highlights the protective effect of mitophagy in the early stage of SCM. This study complements previous research on the mechanism of CL changes in mediating SCM. These findings enhance our understanding of the role of CL in cardiac pathology and provide a new direction for future research. Full article

Variations in the cadmium (Cd) accumulation and root characteristics of different genotypes of rice during three developmental periods of dry cultivation were investigated in pot experiments in which two levels of Cd were added to the soil (0 and 10 mg kg⁻¹). The results show that the Cd concentration in each organ of the different rice genotypes decreased in both the order of roots > shoots > grains and during the three developmental periods in the order of the maturity stage > booting stage > tillering stage. The lowest bioaccumulation factor (BCF) and translocation factor (TF) were found in Yunjing37 (YJ37) under Cd stress. At maturity, Cd stress inhibited the root length of Dianheyou34 (DHY34) the most and that of Dianheyou 918 (DHY918) the least, also affecting the root volume of DHY34 and Dianheyou615 (DHY615) the most and that of YJ37 and Yiyou 673 (YY673) the least; the inhibition rates were 41.80, 5.09, 40.95, and 10.51%, respectively. The exodermis showed the greatest thickening in YY673 and the lowest thickening in DHY615, while the endodermis showed the opposite result. The rates of change were 16.48, 2.45, 5.10, and 8.49%, respectively. The stele diameter of DHY615 decreased the most, and that of YY673 decreased the least, while the secondary xylem area showed the opposite result; the rates of change were −21.50, −14.29, −5.86, and −26.35%, respectively. Under Cd stress treatment at maturity, iron plaque was extracted using the dithionite–citrate–bicarbonate (DCB) method. The concentration of iron (DCB-Fe) was highest in YJ37, and the concentration of cadmium (DCB-Cd) was lowest in DHY34. YJ37 was screened as a low Cd-accumulating variety. The concentration of available Cd in the rhizosphere soil, iron plaque, root morphology, and anatomy affect Cd accumulation in rice with genotypic differences. Our screening of Cd-accumulating rice varieties provides a basis for the dry cultivation of rice in areas with high background values of Cd in order to avoid the health risks of Cd intake. Full article

Proteins are the most common types of biomarkers used in breast cancer (BC) theranostics and management. By definition, a biomarker must be a relevant, objective, stable, and quantifiable biomolecule or other parameter, but proteins are known to exhibit the most variate and profound structural and functional variation. Thus, the proteome is highly dynamic and permanently reshaped and readapted, according to changing microenvironments, to maintain the local cell and tissue homeostasis. It is known that protein posttranslational modifications (PTMs) can affect all aspects of protein function. In this review, we focused our analysis on the different types of PTMs of histological biomarkers in BC. Thus, we analyzed the most common PTMs, including phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, palmitoylation, myristoylation, and glycosylation/sialylation/fucosylation of transcription factors, proliferation marker Ki-67, plasma membrane proteins, and histone modifications. Most of these PTMs occur in the presence of cellular stress. We emphasized that these PTMs interfere with these biomarkers maintenance, turnover and lifespan, nuclear or subcellular localization, structure and function, stabilization or inactivation, initiation or silencing of genomic and non-genomic pathways, including transcriptional activities or signaling pathways, mitosis, proteostasis, cell–cell and cell–extracellular matrix (ECM) interactions, membrane trafficking, and PPIs. Moreover, PTMs of these biomarkers orchestrate all hallmark pathways that are dysregulated in BC, playing both pro- and/or antitumoral and context-specific roles in DNA damage, repair and genomic stability, inactivation/activation of tumor-suppressor genes and oncogenes, phenotypic plasticity, epigenetic regulation of gene expression and non-mutational reprogramming, proliferative signaling, endocytosis, cell death, dysregulated TME, invasion and metastasis, including epithelial–mesenchymal/mesenchymal–epithelial transition (EMT/MET), and resistance to therapy or reversal of multidrug therapy resistance. PTMs occur in the nucleus but also at the plasma membrane and cytoplasmic level and induce biomarker translocation with opposite effects. Analysis of protein PTMs allows for the discovery and validation of new biomarkers in BC, mainly for early diagnosis, like extracellular vesicle glycosylation, which may be considered as a potential source of circulating cancer biomarkers. Full article

The increasing incidence of antibiotic resistance in bacteria is a major problem in terms of therapeutic options, especially in immunocompromised patients, such as patients from intensive care units (ICUs), HIV-positive patients, patients with malignancies or transplant patients. Commensal bacteria, especially anaerobes, serve to maintain microbial stability by preventing overpopulation with pathogenic bacteria. In immunocompromised patients, microbiota imbalance caused by antibiotic therapy and decreased host immunity favors intestinal overpopulation with pathogenic species, leading to increased bacterial translocation and susceptibility to systemic infections. Infections with multidrug-resistant (MDR) bacteria pose major challenges to the establishment of appropriate treatment and lead to increased mortality. Asymptomatic colonization with MDR bacteria usually precedes infection and tends to persist for long periods of time, and in immunocompromised patients, colonization with MDR bacteria is a risk factor for systemic infections. This review aims to assess the relation between colonization and infection with MDR bacteria in immunocompromised patients such as ICU patients, HIV-positive patients and cancer patients and to identify the prevalence and patterns of MDR bacterial colonization and infection in this category of patients. Full article

Wild-grown edible mushrooms are important in world diets and are also efficient metal accumulators. Yunnan, Southwest China, is the main producing region, with typically high levels of geochemical metals. The environmental factors, bioaccumulation, distribution and human health risks of metals were examined in paired soil and Tricholoma matsutake (n = 54). T. matsutake grows on acidified soils (pH = 3.95–6.56), and metals show a strong heterogeneity, with Fe, Mn, Zn and Cu in the ranges of 16–201, 0.046–8.58 g kg⁻¹, and 22.6–215, 3.7–155 mg kg⁻¹. High soil Fe content led to great accumulation in T. matsutake (0.24–18.8 g kg⁻¹). However, though the soil Mn content was higher than that of Zn and Cu, their concentrations in T. matsutake were comparable (21.1–487 vs. 38.7–329 and 24.9–217 mg kg⁻¹). This suggested that T. matsutake prefers to accumulate Zn and Cu compared to Mn, and this is supported by the bioaccumulation factors (BAFs = 0.32–17.1 vs. 0.006–1.69). Fe was mainly stored in stipes, while Mn, Zn and Cu were stored in caps, and the translocation factors (TFs) were 0.58 vs. 1.28–1.94. Therefore, stipe Fe showed the highest health risk index (HRI) at 1.28–26.9, followed by cap Cu (1.01–2.33), while 98–100% of the Mn and Zn were risk-free. The higher concentration and greater risk of Fe was attributed to the significant effect of soil Fe content (R = 0.34) and soil pH (R = −0.57). This study suggested that Fe, as an essential mineral, may exert toxic effects via the consumption of T. matsutake from high geochemical background areas. Full article

This study aimed to assess the anti-inflammatory properties of a bioactive glutamic-alanine rich glycoprotein (GP) derived from Undaria pinnatifida on both LPS-stimulated RAW264.7 cells, peritoneal macrophages, and mouse models of carrageenan- and xylene-induced inflammation, investigating the underlying molecular mechanisms. In both in-vitro and in-vivo settings, GP was found to reduce the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) while also inhibiting the production of nitric oxide (NO) and prostaglandin E₂ (PGE₂) in response to lipopolysaccharide (LPS) stimulation. GP treatment significantly impeded the nuclear translocation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by blocking the phosphorylation of IKKα and IκBα, leading to a reduction in proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Additionally, GP effectively inhibited the activation of mitogen-activated protein kinases (MAPKs), with specific inhibitors of p38 and extra-cellular signal regulated kinase (ERK) enhancing GP’s anti-inflammatory efficacy. Notably, GP administration at 10 mg/kg/day (p.o.) markedly reduced carrageenan-induced paw inflammation and xylene-induced ear edema by preventing the infiltration of inflammatory cells into targeted tissues. GP treatment also downregulated key inflammatory markers, including iNOS, COX-2, IκBα, and NF-κB, by suppressing the phosphorylation of p38 and ERK, thereby improving the inflammatory index in both carrageenan- and xylene-induced mouse models. These findings suggest that marine resources, particularly seaweeds like U. pinnatifida, could serve as valuable sources of natural anti-inflammatory proteins for the effective treatment of inflammation and related conditions. Full article

Microsatellite instability (MSI) has been recognized as an important factor in colorectal cancer (CRC). It arises due to deficient mismatch repair (MMR), mostly attributed to MLH1 and MSH2 loss of function leading to a global MMR defect affecting mononucleotide and longer microsatellite loci. Recently, microsatellite instability at tetranucleotide loci, independent of the global MMR defect context, has been suggested to represent a distinct entity with possibly different consequences for tumorigenesis. It arises as a result of an isolated MSH3 loss of function due to its translocation from the nucleus to the cytoplasm under the influence of interleukin-6 (IL-6). In this study the influence of MSH3 and IL-6 signaling pathway polymorphisms (MSH3 exon 1, MSH3+3133A/G, IL-6-174G/C, IL-6R+48892A/C, and gp130+148G/C) on the occurrence of different types of microsatellite instability in sporadic CRC was examined by PCR–RFLP and real-time PCR SNP analyses. A significant difference in distribution of gp130+148G/C genotypes (p = 0.037) and alleles (p = 0.031) was observed in CRC patients with the C allele being less common in tumors with di- and tetranucleotide instability (isolated MSH3 loss of function) compared to tumors without microsatellite instability. A functional polymorphism in gp130 might modulate the IL-6 signaling pathway, directing it toward the occurrence of microsatellite instability corresponding to the IL-6-mediated MSH3 loss of function. Full article