Search Results (4,129)

Viticis Fructus (VF), a fruit known for its unique flavor profile and various health benefits, demonstrates substantial quality variations depending on its area of production. Traditional methods of production area verification based on internal compound analysis are hampered by a number of technical limitations. This investigation systematically characterized the cuticular wax composition of VF sample from a diverse variety of production areas. Quantitative analyses were conducted to evaluate the spatial distribution patterns of the wax constituents. Significant regional variations were observed: Anhui sample exhibited the highest total wax content (21.39 μg/cm²), with n-alkanes dominating at 76.67%. High-latitude regions showed elevated triterpenoid acid levels, with maslinic acid (0.53 μg/cm²) and ursolic acid (0.34 μg/cm²) concentrations exceeding those of their low-latitude counterparts by four- and three-fold, respectively. Altitudinal influence manifested in long-chain alcohol accumulation, as triacontanol reached 0.87 μg/cm²in high-altitude sample. Five key biomarkers demonstrated direct quality correlations: eicosanoic acid, n-triacontane, dotriacontanol, β-amyrin, and α-amyrin. This study established three novel origin identification protocols: single-component quantification, multi-component wax profiling, and wax ratio analysis. This work not only reveals the latitudinal dependence of VF wax composition, but also provides a scientific framework for geographical authentication. Our findings advance wax-based quality evaluation methodologies for fruit products, offering practical solutions for production area verification challenges in food raw materials. Full article

The life cycle of the hepatitis C virus (HCV) is closely linked to lipid metabolism. Recently, the stress defence transcription factor, nuclear factor erythroid 2 related factor-1 (Nrf1), has been described as a cholesterol sensor that protects the liver from excess cholesterol. Nrf1, like its homologue Nrf2, further responds to oxidative stress by binding with small Maf proteins (sMaf) to the promotor antioxidant response element (ARE). Given these facts, investigating the crosstalk between Nrf1 and HCV was a logical next step. In HCV-replicating cells, we observed reduced levels of Nrf1. Furthermore, activation of Nrf1-dependent target genes is impaired due to sMaf sequestration in replicase complexes. This results in a shortage of sMaf proteins in the nucleus, trapping Nrf1 at the replicase complexes and further limiting its function. Weakened Nrf1 activity contributes to impaired cholesterol removal, which occurs alongside an elevated intracellular cholesterol level and inhibited LXRα promoter activation. Furthermore, inhibition of Nrf1 activity correlated with a kinome profile characteristic of steatosis and enhanced inflammation—factors contributing to HCV pathogenesis. Our results indicate that activation of Nrf1-dependent target genes is impaired in HCV-positive cells. This, in turn, favours viral morphogenesis, as evidenced by enhanced replication and increased production of viral progeny. Full article

Modern life, characterized by constant exposure to artificial light from electronic devices, such as light-emitting diodes (LEDs), disrupts the natural circadian rhythm and induces important metabolic changes. The impact of blue light exposure on male and female rat’s onset of puberty, hormonal and biochemical parameters was assessed by comparison between the four study groups: the control group (CTRL) maintained under normal light conditions, the group exposed to blue light from a mobile phone (MP), the group subjected to blue light from a computer screen (PC), and the group exposed to blue light from an LED lamp (LED). Both female and male rats exposed to PC and LED failed to thrive, with a significantly lower body weight intake than the CTRL group. All three distinct sources of blue light interfered with the cyclicity of the estrous cycle in female rats. A marked decrease in the number of complete estrous cycles and the highest incidence of incomplete cycles were noticed in the LED group. Elevated ALT, AST, glucose, and insulin levels were influenced in a gender-specific manner, and depending on the source of emitted light. Prolonged blue light exposure induces significant metabolic disruptions and possesses important future research potential in identifying explicit pathways regarding this environmental stressor. Full article

Grape pomace (GP), the main by-product of the wine industry, represents a valuable source of bioactive metabolites with significant potential for valorization in the context of sustainable bioresource management. This study systematically characterizes the fatty acid methyl ester (FAME) profile, total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activities (DPPH, ABTS, ORAC) of GP derived from seven grape varieties across three consecutive vintages (2022–2024). White GP, particularly Verdelho and Sercial, exhibited a superior lipid quality with high concentrations of methyl linoleate (up to 1997 mg/100 g DW) and methyl oleate (up to 1294 mg/100 g DW), low atherogenic (AI < 0.05) and thrombogenic indices (TI ≤ 0.13), and elevated PUFA/SFA ratios (≥8.2). In contrast, red GP, especially from Complexa and Tinta Negra, demonstrated the highest antioxidant potential, with TPC values up to 6687 mgGAE/100 g DW, TFC up to 4624 mgQE/100 g DW, and antioxidant activities reaching 5399 mgTE/100 g (DPPH) and 7219 mgTE/100 g (ABTS). Multivariate statistical analyses (PCA, PLS-DA, HCA) revealed distinct varietal and vintage-dependent clustering and identified key discriminant fatty acids, including linolenic acid (C18:3), lauric acid (C12:0), and arachidic acid (C20:0). These findings underscore the compositional diversity and functional potential of GP, reinforcing its suitability for applications in functional foods, nutraceuticals, and cosmetics, in alignment with circular economy principles. Full article

Background and Objectives: Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies worldwide. Although chemotherapy is an effective treatment for colorectal cancer (CRC), its effectiveness is frequently hindered by the emergence of resistant cancer cells. Studies have demonstrated a linkage between drug resistance and the pregnane X receptor (PXR), which influences the metabolism and the transport of chemotherapeutic agents. Likewise, autophagy is also a well-established mechanism that contributes to chemotherapy resistance, and it is closely tied to tumor progression. This pre-clinical study aims to investigate the role of mtKRAS-dependent autophagy with PXR expression after treatment with Irinotecan in colorectal cancer. Methods: CRC lines were treated with specific inhibitors, such as 3-methyladeninee, hydroxychloroquine PI-103, and irinotecan hydrochloride, and subjected to various assays, including MTT for cell viability, Western blot for protein expression, siRNA-mediated PXR knock-out, and confocal microscopy for autophagic vacuole visualization. Protein quantification, gene knockdown, and subcellular localization studies were performed under standardized conditions to investigate treatment effects on autophagy and apoptosis pathways. Conclusions: Our experiments showed that PXR knockdown does not alter autophagy levels following Irinotecan treatment, but it promotes apoptotic cell death despite elevated autophagy. Moreover, late-stage autophagy inhibition reduces PXR expression, whereas induction through PI3K/AKT/mTOR inhibition leads to increased expression of PXR. Our experiments uncover a mechanism by which autophagy facilitates the nuclear translocation of the PXR, thereby promoting resistance to Irinotecan across multiple cell lines. Full article

Background: Stress hyperglycemia (SH), a transient elevation in blood glucose levels during acute stress such as stroke, has been increasingly recognized as a critical determinant of clinical outcomes. This review aims to evaluate the association between SH and clinical outcomes across different stroke subtypes and its role as a prognostic indicator. Methods: The current literature review was conducted through a comprehensive literature search of PubMed, Scopus, and Web of Science electronic databases. Initial title and abstract screening was conducted by two independent reviewers depending on the relevance to the topic of interest. Final study inclusion was based on the clinical relevance and agreement between reviewers. Results: Current evidence links SH with higher stroke severity (Higher national institutes of health stroke scale (NIHSS)), larger infarct volumes, increased risk of hemorrhagic transformation, and worse functional recovery (Lower modified rankin scale (mRS)), especially in ischemic stroke. In hemorrhagic stroke, SH is associated with hematoma expansion, perihematomal edema, and worsening neurological function. Although SH has been shown to be a reliable stroke outcome predictor, there is no scientific consensus regarding the most reliable measurement method. The use of absolute blood glucose values may not accurately reflect SH, particularly in diabetic patients, where chronic baseline hyperglycemia complicates interpretation. This underscores the necessity for individualized assessment rather than a uniform interpretation. Clinically, the early detection of SH may provide enhanced monitoring and supportive care; however, rigorous glucose management remains contentious due to the risk of hypoglycemia. Conclusions: This review synthesizes evidence from recent studies and supports SH as a prognostic marker of both short- and long-term adverse outcomes in stroke patients. Further research is warranted to evaluate the efficacy of targeted glycemic treatments on such outcomes. Full article

Helium (He) accumulation in tungsten—widely used as a plasma-facing material in fusion reactors—can lead to clustering, trap mutation, and eventual formation of helium bubbles, critically impacting material performance. To clarify the atomic-scale mechanisms governing this process, we conducted systematic molecular statics and molecular dynamics simulations across a wide range of vacancy cluster sizes (n = 1–27) and temperatures (500–2000 K). We identified the onset of trap mutation through abrupt increases in tungsten atomic displacement. At 0 K, the critical helium-to-vacancy (He/V) ratio required to trigger mutation was found to scale inversely with cluster size, converging to ~5.6 for large clusters. At elevated temperatures, thermal activation lowered the mutation threshold and introduced a distinct He/V stability window. Below this window, clusters tend to dissociate; above it, trap mutation occurs with near certainty. This critical He/V ratio exhibits a linear dependence on temperature and can be described by a size- and temperature-dependent empirical relation. Our results provide a quantitative framework for predicting trap mutation behavior in tungsten, offering key input for multiscale models and informing the design of radiation-resistant materials for fusion applications. Full article

Nonspecific toxicity to normal and malignant cells restricts the clinical utility of many anticancer drugs. In particular, anemia in cancer patients develops due to drug-induced toxicity to red blood cells (RBCs). The anticancer alkaloid, cepharanthine (CEP), elicits distinct forms of cell death including apoptosis and autophagy, but its cytotoxicity to RBCs has not been investigated. Colorimetric and fluorometric techniques were used to assess eryptosis and hemolysis in control and CEP-treated RBCs. Cells were labeled with Fluo4/AM and annexin-V-FITC to measure Ca²⁺ and phosphatidylserine (PS) exposure, respectively. Forward scatter (FSC) was detected to estimate cell size, and extracellular hemoglobin along with lactate dehydrogenase and aspartate transaminase activities were assayed to quantify hemolysis. Physiological manipulation of the extracellular milieu and various signaling inhibitors were tested to dissect the underlying mechanisms of CEP-induced RBC death. CEP increased PS exposure and hemolysis indices and decreased FSC in a concentration-dependent manner with prominent membrane blebbing. Although no Ca²⁺ elevation was detected, chelation of intracellular Ca²⁺ by BAPTA-AM reduced hemolysis. Whereas SB203580, D4476, acetylsalicylic acid, necrosulfonamide, and melatonin inhibited both PS exposure and hemolysis, staurosporin, L-NAME, ascorbate, caffeine, adenine, and guanosine only prevented hemolysis. Interestingly, sucrose had a unique dual effect by exacerbating PS exposure and reversing hemolysis. Of note, blocking KCl efflux augmented PS exposure while aggravating hemolysis only under Ca²⁺-depleted conditions. CEP activates Ca²⁺-independent pathways to promote eryptosis and hemolysis. The complex cytotoxic profile of CEP can be mitigated by targeting the identified modulatory pathways to potentiate its anticancer efficacy. Full article

Protein degradation plays a fundamental role in maintaining protein homeostasis and ensures proper cellular function by regulating protein quality and quantity. Heat shock protein 100 (Hsp100), found in bacteria, plants, and fungi, is a unique chaperone family responsible for rescuing misfolded proteins from aggregated states in an ATP-dependent manner. To date, they are primarily known to mediate heat stress adaptation and enhance cellular survival under extreme conditions in higher plants and algae. Resting cyst formation in dinoflagellates is widely recognized as a response to adverse conditions, which offers an adaptive advantage to endure harsh environmental extremes that are unsuitable for vegetative cell growth and survival. In this study, based on a full-length cDNA sequence, we characterized an Hsp100 gene (SaHsp100) from the cosmopolitan bloom-forming dinoflagellate Scrippsiella acuminata, aiming to examine its life stage-specific expression patterns and preliminarily explore its potential functions. The qPCR results revealed that Hsp100 transcript levels were significantly elevated in newly formed resting cysts compared to vegetative cells and continued to increase during storage under simulated marine sediment conditions (darkness, low temperature, and anoxia). Parallel reaction monitoring (PRM)-based quantification further confirmed that Hsp100 protein levels were significantly higher in resting cysts than in vegetative cells and increased after three months of storage. These findings collectively highlighted the fundamental role of Hsp100 in the alteration of the life cycle and dormancy maintenance of S. acuminata, likely by enhancing stress adaptation and promoting cell survival through participation in proteostasis maintenance, particularly under natural sediment-like conditions that trigger severe abiotic stress. Our work deepens the current understanding of Hsp family members in dinoflagellates, paving the way for future investigations into their ecological relevance within this ecologically significant group. Full article

This study evaluated the activity concentrations of radionuclides in honey, bee pollen, bee bread, and propolis from multiple regions in Poland (Europe) to assess the levels of radiological contamination and their implications for public health. Furthermore, the work considers the use of bee products as bioindicators of the state of environmental contamination with radionuclides. The apiaries from which the samples were collected were selected in eight provinces in Poland, and are also complemented by reference data from soil contamination monitoring. Radionuclide measurements included both natural (e.g., ⁴⁰K, ²²⁶Ra) and anthropogenic isotopes (e.g., ¹³⁷Cs). The results show that although the overall activity concentrations were generally low, certain locations exhibited elevated levels of ¹³⁷Cs in bee products, likely reflecting historical deposition in soils. Propolis was best correlated with ¹³⁷Cs deposited in soil compared to the other products studied. The patterns observed substantiate the hypothesis that bee products, predominantly propolis, accurately reflect local radiological conditions, thereby providing a practical and non-intrusive approach to monitoring radionuclide contamination and informing risk management strategies. An assessment of potential health risks indicates that the effective dose is safe and ranges from 0.02 to 10.3 µSv per year, depending on the type of product and consumption. Full article

Infant clothing represents a critical yet overlooked exposure pathway for heavy metals, with significant implications for child health and sustainable consumption. This study investigates cadmium (Cd) and chromium (Cr) contamination in 33 textile samples, integrating in vitro bioaccessibility assays, cytotoxicity analysis, and risk assessment models to evaluate dermal exposure risks. Results reveal that 80% of samples exceeded OEKO-TEX Class I limits for As (mean 1.01 mg/kg), Cd (max 0.25 mg/kg), and Cr (max 4.32 mg/kg), with infant clothing showing unacceptable hazard indices (HI = 1.13) due to Cd (HQ = 1.12). Artificial sweat extraction demonstrated high bioaccessibility for Cr (37.8%) and Ni (28.5%), while keratinocyte exposure triggered oxidative stress (131% ROS increase) and dose-dependent cytotoxicity (22–59% viability reduction). Dark-colored synthetic fabrics exhibited elevated metal loads, linking industrial dye practices to health hazards. These findings underscore systemic gaps in textile safety regulations, particularly for low- and middle-income countries reliant on cost-effective apparel. We propose three policy levers: (1) tightening infant textile standards for Cd/Cr, (2) incentivizing non-toxic dye technologies, and (3) harmonizing global labeling requirements. By bridging toxicological evidence with circular economy principles, this work advances strategies to mitigate heavy metal exposure while supporting Sustainable Development Goals (SDGs) 3 (health), 12 (responsible consumption), and 12.4 (chemical safety). Full article

Systemic lupus erythematosus (SLE) is characterized by autoimmune dysregulation, elevated autoantibody production, and persistent inflammation, predisposing patients to atherosclerosis (AS). Atherogenesis is dependent on lipid homeostasis and inflammatory processes, with the formation of lipid-laden, macrophage-derived foam cells (MDFC) essential for atherosclerotic lesion progression. Elevated cholesterol levels within lipid rafts trigger heightened pro-inflammatory responses in macrophages via Toll-like receptor 9 (TLR9). Artesunate (ART), an artemisinin derivative sourced from Artemisia annua, exhibits therapeutic potential in modulating inflammation and autoimmune conditions. Nonetheless, its impact and mechanisms in SLE-associated AS (SLE-AS) remain largely unexplored. Our investigation demonstrated that ART could effectively ameliorate lupus-like symptoms and atherosclerotic plaque development in SLE-AS mice. Moreover, ART enhanced cholesterol efflux from MDFC by upregulating ABCA1, ABCG1, and SR-B1 both in vivo and in vitro. Moreover, ART reduced cholesterol accumulation in bone marrow-derived macrophages (BMDMs), thereby diminishing TLR9 recruitment to lipid rafts. ART also suppressed TLR9 expression and its downstream effectors in the kidney and aorta of SLE-AS mice, attenuating the TLR9-mediated inflammatory cascade in CPG2395 (ODN2395)-stimulated macrophages. Through bioinformatics analysis and experimental validation, PPARγ was identified as a pivotal downstream mediator of ART in macrophages. Depleting PPARγ levels reduced the expression of ABCA1, ABCG1, and SR-B1 in macrophages, consequently impeding cholesterol efflux. In conclusion, these findings suggest that ART ameliorates SLE-AS by restoring cholesterol homeostasis through the PPARγ-ABCA1/ABCG1/SR-B1 pathway and suppressing lipid raft-driven TLR9/MyD88 inflammation. Full article

Enterotoxigenic Escherichia coli (ETEC) leads to severe diarrhea in piglets. Naringenin (Nar), a natural flavonoid compound, is known for its antibacterial and anti-antioxidant properties. However, the protective effects of Nar against ETEC-induced diarrhea have not been reported yet. This study investigated the protective mechanisms of Nar against ETEC infection in porcine intestinal epithelial cells (IPEC-J2). ETEC infection induced oxidative stress and ferroptosis in IPEC-J2 cells by elevating intracellular iron content and ROS accumulation, increasing MDA levels, downregulating SOD activity and GPX4 expression, and upregulating the transcription of CHAC1 and SLC7A11. In contrast, Nar suppressed ETEC-induced ferroptosis of IPEC-J2 cells by inhibiting the SLC7A11/GPX4 pathway. Specifically, Nar mitigated mitochondrial damage, reduced intracellular iron levels and ROS accumulation, and ultimately reversed the oxidative stress. Network pharmacology and molecular docking identified heat-shock protein 90 (HSP90) as a potential target of Nar. Overexpression and knockdown experiments revealed that ETEC-induced ferroptosis was mediated by upregulation of HSP90, while the protective effects of Nar against ETEC-induced ferroptosis were dependent on the downregulation of HSP90. In conclusion, Nar targets host HSP90 to protect IPEC-J2 cells from ferroptosis caused by ETEC infection. This study demonstrates that Nar is a potent antioxidant natural compound with potential for preventing ETEC-induced intestinal damage. Full article

Background and Objectives: This study aimed to investigate the anticancer effects and potential synergistic interactions of quercetin (Q) and doxorubicin (Dox) on the MG-63 osteosarcoma (OS) cell line. Specifically, the effects of these agents on cell viability, apoptosis, reactive oxygen species (ROS) generation, antioxidant defense, and the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt1) signaling pathway were evaluated. Material and Methods: MG-63 cells were cultured and treated with varying concentrations of Q and Dox, both individually and in combination (fixed 5:1 molar ratio), for 48 h. Cell viability was assessed using an MTT assay, and IC₅₀ values were calculated. Synergistic effects were analyzed using the Chou–Talalay combination index (CI). Apoptosis was evaluated via Annexin V-FITC/PI staining and caspase-3/7 activity. ROS levels were quantified using DCFH-DA probe, and antioxidant enzymes (SOD, GPx) were measured spectrophotometrically. Gene expression (Runx2, PI3K, Akt1, caspase-3) was analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: Q and Dox reduced cell viability in a dose-dependent manner, with IC₅₀ values of 70.3 µM and 1.14 µM, respectively. The combination treatment exhibited synergistic cytotoxicity (CI < 1), especially in the Q50 + Dox5 group (CI = 0.23). Apoptosis was significantly enhanced in the combination group, evidenced by increased Annexin V positivity and caspase-3 activation. ROS levels were markedly elevated, while antioxidant enzyme activities declined. RT-qPCR revealed upregulation of caspase-3 and downregulation of Runx2, PI3K, and Akt1 mRNA levels. Conclusions: The combination of Q and Dox exerts synergistic anticancer effects in MG-63 OS cells by inducing apoptosis, elevating oxidative stress, suppressing antioxidant defense, and inhibiting the PI3K/Akt1 signaling pathway and Runx2 expression. These findings support the potential utility of Q as an adjuvant to enhance Dox efficacy in OS treatment. Full article

Flammulina velutipes is a widely cultivated edible mushroom in East Asia, recognized for its nutritional benefits and distinct morphology characterized by a long stipe and a compact, hemispherical pileus. The pileus not only plays a critical biological role in reproduction through spore formation but also serves as a key commercial trait influencing consumer preference and market value. Despite its economic importance, pileus development in F. velutipes is highly sensitive to environmental factors, among which carbon dioxide (CO₂) concentration is particularly influential under indoor cultivation conditions. While previous studies have reported that elevated CO₂ levels can inhibit pileus expansion in other mushroom species, the molecular mechanisms by which CO₂ affects pileus growth in F. velutipes remain poorly understood. In this study, we investigated the impact of CO₂ concentration on pileus morphology and gene expression in F. velutipes by cultivating fruiting bodies under two controlled atmospheric conditions: low (1000 ppm) and high (10,000 ppm) CO₂. Morphometric analysis revealed that elevated CO₂ levels significantly suppressed pileus expansion, reducing the average diameter by more than 50% compared to the low CO₂ condition. To elucidate the underlying genetic response, we conducted RNA sequencing and identified 102 differentially expressed genes (DEGs), with 78 being downregulated under elevated CO₂. Functional enrichment analysis highlighted the involvement of cyclin-dependent protein kinase regulatory pathways in this response. Two cyclin genes were found to be significantly downregulated under elevated CO₂ conditions, and their suppression was validated through quantitative real-time PCR. These genes, possessing conserved cyclin_N domains, are implicated in the regulation of the eukaryotic cell cycle, particularly in mitotic growth. These results indicate that CO₂-induced downregulation of cyclin genes may underlie cell cycle arrest, contributing to inhibited pileus development. This study is the first to provide transcriptomic evidence that elevated CO₂ concentrations specifically repress PHO80-like cyclin genes in F. velutipes, revealing a molecular mechanism by which CO₂ stress inhibits pileus development. These findings suggest that elevated CO₂ triggers a morphogenetic checkpoint by repressing PHO80-like cyclins, thereby modulating cell cycle progression during fruiting body development. This study provides the first evidence of such a transcriptional response in edible mushrooms and offers promising molecular targets for breeding CO₂-resilient strains and optimizing commercial cultivation conditions. Full article