Search Results (2,003)

Dengue virus serotype 2 (DENV-2) is a predominant cause of severe dengue and a key determinant of dengue-associated liver injury. This review integrates recent findings on the molecular and cellular mechanisms of DENV-2 hepatotropism, focusing on viral replication, cellular stress responses, and immune-mediated damage. The interplay between hepatocytes, Kupffer cells, and innate and adaptive immune responses, culminating in cytokine storm and immune-mediated hepatocyte apoptosis, is dissected. Integrating in vitro and in vivo findings, this review highlights how viral replication and immune dysregulation converge to cause hepatic injury. Future research should prioritize antiviral, immunomodulatory, and hepatoprotective approaches aimed at reducing the risk of dengue-associated liver failure. Full article

Background/Objective: Accurate quantification of RNA is critical for RNA-based experiments such as polysome profiling and RT-qPCR. These techniques often rely on control RNA to ensure consistency and reliability across experiments. Commonly used spike-in controls, including in vitro-synthesized mRNA or ERCC mixes, are expensive and time-consuming, limiting accessibility for many laboratories. This study aims to evaluate the use of cross-species total RNA as a cost-effective and reliable spike-in control. Methods: We developed a method using total RNA from a non-homologous species—specifically, yeast RNA—as a spike-in control for experiments involving human cells. The approach was tested across multiple RNA-based assays to assess its impact on quantification accuracy, reproducibility, and interference with endogenous RNA measurements. Additionally, we applied this method to evaluate the translation efficiency of Bcl-xL mRNA in mammalian cells under hypertonic stress. Results: Cross-species spike-in RNA demonstrated minimal interference with experimental outcomes and provided consistent normalization across replicates. The use of yeast RNA enabled accurate fold-change calculations and improved detection of experimental variability. In the case study involving Bcl-xL mRNA, the spike-in control facilitated reliable assessment of translation efficiency under stress conditions. Conclusions: Using total RNA from a non-related species as a spike-in control offers a practical, economical alternative to conventional methods. This approach enhances the reliability of RNA quantification without compromising experimental integrity, making it especially valuable for resource-limited settings, particularly in polysome and RT-qPCR workflows. Full article

Weaning is known to induce oxidative stress and dysregulated inflammatory responses, thus damaging performance growth. This research was conducted to investigate the effects of dulcitol (Dul) on the growth performance and gut health of weaned piglets using multi-omics technologies. Two groups (n = 6, 6 pigs per replicate) of piglets (28 days old, BW, 8.91 ± 0.18 kg) were randomly assigned to receive either a basal diet supplemented with Dul (500 mg/kg) or without it for a period of 28 days. The findings indicated that the addition of Dul to the diet improved growth performance and had positive effects on antioxidant and anti-inflammatory statuses in weaned piglets (p < 0.05). Dul also strengthened intestinal barrier integrity via decreased diamine oxidase and D-lactate and elevated tight junction proteins (i.e., ZO-1, CLDN, and OCLN, p < 0.05). Multi-omics analyses demonstrated that Dul induced modifications in colonic protein expression associated with oxidative stress and glucose metabolism, altered linoleic acid metabolic pathways, and restructured the gut microbiota. This restructuring was characterized by a decreased prevalence of genera linked to inflammation and oxidative stress, including Proteobacteria, Prevotella, and Prevotellaceae_NK3B31_group. Collectively, the findings indicate that Dul promotes intestinal wellness and growth in weaned piglets through intricate interactions between gut microbiota and host metabolic processes. Full article

Papaya is an economically important crop, but its production in semiarid regions is severely limited by water scarcity. However, microorganism-based biostimulants have been studied as a promising strategy to mitigate water stress and support plant growth. Therefore, the objective of this study was to evaluate the effect of microorganism-based biostimulants on gas exchange, photochemical efficiency, and growth of ‘Formosa’ papaya under water deficit in a semiarid area. The experimental design was a randomized complete block design with split plots. The plots considered three irrigation depths (100, 75, and 50% of crop evapotranspiration-ETc) and the subplots the application of four biostimulants (control (no biostimulant application); Trichoderma harzianum; Ascophyllum nodosum; Bacillus aryabhattai), with three plants per plot and four replicates. B. aryabhattai mitigated the effects of deficit irrigation at 50% ETc on ‘Formosa’ papaya, increasing transpiration, CO₂ assimilation rate, and instantaneous carboxylation efficiency. Under irrigation at 50% ETc, T. harzianum provided beneficial effects on water use efficiency, instantaneous carboxylation efficiency, and photosystem II quantum efficiency. A. nodosum stimulated chlorophyll a synthesis in ‘Formosa’ papaya plants irrigated at 75% ETc during the fruiting stage, but reduced the absolute and relative growth rate in stem diameter under 50% ETc. Irrigation at 50% ETc reduced stomatal conductance and growth of ‘Formosa’ papaya plants 235 days after transplanting. We conclude that the application of B. aryabhattai and T. harzianum is a viable strategy to increase the tolerance of ‘Formosa’ papaya to the adverse effects of water deficit in semiarid regions. Full article

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic immune-mediated disorders characterized by mucosal injury, cycles of inflammation and repair, and tissue damage. Persistent inflammation accelerates epithelial turnover, generates oxidative and replication stress, and remodels the stromal niche, contributing to the risk of colorectal cancer (CRC). Systematic dysplasia surveillance remains essential. Cellular senescence has emerged as a unifying mechanism linking inflammation, impaired epithelial repair, fibrosis, and neoplasia. In UC, p16/p21 upregulation, telomere erosion, and loss of lamin B1 accumulate and adopt a senescence-associated secretory phenotype (SASP) that perpetuates barrier dysfunction. In CD, senescence within stem and stromal compartments limits regeneration, promotes pro-fibrotic remodeling, and sustains cycles of injury and repair via chronic SASP signaling. IBD prevalence continues to rise from environmental factors, dietary changes, antibiotic exposures, and gut microbiota alterations. Pathogenesis integrates genetic factors (e.g., NOD2, IL23R, HLA, and ATG16L1 mutations), environmental modifiers, dysbiosis characterized by loss of short-chain fatty-acid-producing Gram-positive bacteria and expansion of Proteobacteria, and a dysregulated immune system. Therapeutic strategies have shifted toward targeted biologics and small molecules to promote mucosal healing. In this review, we recapitulate the mechanistic axes of inflammation, oxidative stress, and senescence in IBD and then critically evaluate emerging targeted therapies. Topics include anti-TNFα, integrin blockade, IL-12/23 and IL-23 inhibition, JAK inhibitors, S1P receptor modulators, microRNA modulation, senomorphics, mesenchymal cell therapy, and microbiome interventions. We endorse biomarker-guided therapy and propose future directions to break the SASP-driven inflammatory loop and mitigate long-term carcinogenic risk. Full article

This study aimed to investigate the role of ganoderma lucidum polysaccharides (GLP) in mitigating dexamethasone (DEX)-induced immune injury in goslings. Dexamethasone (DEX) is commonly used to establish an animal model of immune suppression, which mimics the immune injury caused by stress or certain pathological conditions in poultry. A total of 180 one-day-old goslings were randomly assigned to three groups: control (Con), DEX, and DEX + GLP, with six replicates of 10 goslings each. The Con and DEX groups were fed a basal diet, whereas the DEX + GLP group received feed supplemented with 0.2% GLP. From days 14 to 21, the DEX and DEX + GLP groups were injected with 3.5 mg/kg body weight (BW) of DEX, while the Con group received normal saline. Growth performance, immune organ indices, serum parameters, organ morphology, and intestinal microbiota were evaluated at 21 and 35 days. At day 21, the Con group exhibited significantly higher BW, average daily gain (ADG), spleen, thymus, and bursa indices, as well as serum total protein (TP), albumin (ALB), globulin (GLOB), IL-6, IgA, and IgG compared to the DEX and DEX + GLP groups (p < 0.01). By day 35, the DEX + GLP group demonstrated greater ADG than the DEX group (p < 0.01) and showed improved TP, ALB, and immune organ indices relative to DEX alone (p < 0.05). Histological analysis indicated that DEX induced bursa plica disorder, spleen parenchyma loosening, and thymus lobule atrophy, all of which were alleviated by GLP supplementation. Regarding the gut microbiota, the Con group displayed higher α-diversity at day 21 than the DEX group (p < 0.05), while at day 35, β-diversity in the DEX group differed markedly from that in the Con and DEX + GLP groups. Furthermore, DEX + GLP was associated with an enrichment of Bacteroidetes, Flavobacterium, and Lactococcus as microbial biomarkers. Overall, GLP effectively mitigated DEX-induced immune injury and partially restored growth performance by improving immune organ morphology, modulating serum factors, and reshaping gut microbiota. Full article

Climate change causes unpredictable weather patterns, leading to more frequent and severe droughts. Investigating the effects of drought and irrigation on soil water status and the performance of various cassava genotypes can provide valuable insights for mitigating drought through designing appropriate genotypes and water management strategies. The objective of this research was to evaluate soil moisture, growth rates, and final yields (total dry weight, storage root dry weight, harvest index and starch yield) of six cassava genotypes cultivated under drought conditions during the late growth phase, as well as under full irrigation. The study utilized a split-plot randomized complete block design with four replications, conducted over two growing seasons (2022/2023 and 2023/2024). The main plots were assigned as two water regimes to prevent water movement between plots: full irrigation and drought treatments. The subplot consisted of six cassava genotypes. Measurements included soil properties before planting, weather data, soil moisture content, relative water content (RWC) in cassava leaves, and several growth rates: leaf growth rate (LGR), stem growth rate (SGR), storage root growth rate (SRGR), crop growth rate (CGR), relative growth rate (RGR), as well as final yields. The results revealed that low soil moisture contents for drought treatment led to variation in RWC, growth, and yield among cassava genotypes. Variations in soil and weather conditions between the 2022/2023 and 2023/2024 growing seasons resulted in differences in the performance of the genotypes. Kasetsart 50 (2022/2023) and CMR38–125–77 (2023/2024) were top performers under late drought stress regarding storage root dry weight and starch yield, showing vigorous recovery upon re-watering, evidenced by their significant increase in LGR (between 240 and 270 DAP) and their high RGR (240–360 DAP). Rayong 9 (2023/2024) demonstrated strong performance in both during the drought period (180–240 DAP), efficiently allocating resources under water scarcity, with SRGR and starch yield reduced by 26.4% and 9.5%, respectively, compared to full irrigation. These cassava genotypes are valuable genetic resources for cassava cultivation and can be used as parental material in breeding programs aimed at improving drought tolerance. Full article

Soft biological tissues display highly nonlinear and anisotropic mechanical behavior, which is critical to their physiological function. Replicating these mechanical properties using engineered materials and additive manufacturing represents a significant challenge in biomedical engineering, particularly for surgical simulation, device development, and preclinical testing. The left atrial appendage (LAA) was selected since it plays a central role in thrombus formation during atrial fibrillation, significantly contributing to cardioembolic stroke. This study proposes a framework for reproducing the nonlinear stress–strain behavior of soft tissue using 3D-printed models. The methodology integrates experimental material selection with optimization of key printing parameters to ensure structural reliability and functional mechanical performance. Two polymers—polyurethane (TPU) and a thermoplastic with elastomer-type behavior (TPE)—were selected for their tunable hardness and elasticity. A parametric study was conducted to investigate the effects of Shore A hardness (60A to 100A), infill density (0% to 100%), and external shell number (zero to two) on the tensile performance of printed models. Mechanical testing was performed to extract stress–strain curves and evaluate the mechanical response. The practical implications of this study are significant, demonstrating the potential of additive manufacturing for anatomical reproduction and replicating functional mechanical properties in soft tissue models. Full article

The picornavirus 3CD protein is a precursor to the 3C main protease and the 3D RNA-dependent RNA polymerase. In addition to its functions in proteolytic processing of the virus polyprotein and cleavage of key host factors, the 3C domain interacts with cis-acting replication elements (CREs) within the viral genome to regulate replication and translation events. We investigated the molecular determinants of RNA binding to 3C using a wide range of biophysical and computational methods. These studies showed that 3C binds to a broad spectrum of RNA oligonucleotides, displaying minimal sequence and structure dependence, at least for these shorter RNAs. However, they also uncovered a novel aspect of these interactions, that is, 3C-RNA binding can induce liquid–liquid phase separation (LLPS), with 3CD–RNA interactions likewise leading to LLPS. This may be a general phenomenon for other 3C and 3C-like proteases and polyproteins incorporating 3C domains. These findings have potential implications in understanding virally induced apoptosis and the control of stress granules, which involve LLPS and include other proteins with known interactions with 3C/3CD. Full article

Our research investigated how a smartphone application utilizing behavioral activation principles affects depression levels in young adult populations. A total of 67 participants aged 20–30 years with clinically significant depressive symptoms (CESD-11 ≥ 16) were divided into treatment (n = 31) and comparison conditions (n = 36) through randomization procedures. Participants in the experimental group engaged with a BA-based mobile application (Maummove) over an eight-week period, while those in the control group completed weekly assessments without intervention. Depression, perceived stress, and life satisfaction were measured at baseline and postintervention using the CESD-11, PSS, and SWLS, respectively. The results indicated that the experimental group exhibited significant reductions in depression (Cohen’s d = 1.03) and stress (Cohen’s d = 0.99) compared to the control group, which showed minimal changes. Improvements in life satisfaction were observed in the experimental group, with a smaller effect size (Cohen’s d = 0.23). Time-series analyses demonstrated that depressive symptoms decreased progressively throughout the intervention period, falling below the clinical cutoff by the seventh week. These findings provide preliminary evidence that BA-based mobile applications may offer a promising, accessible approach to reducing depressive symptoms and perceived stress in young adults, though replication in larger samples with longer follow-up periods is needed to establish generalizability. This study highlights the potential of digitally delivered BA interventions as a viable alternative or complement traditional mental health services, particularly for populations facing barriers to face-to-face care. Full article

Pancreatic cancer is an aggressive malignancy with a poor prognosis. It is characterized by low surgical resection rates, frequent development of chemoresistance, unsatisfactory treatment outcomes, and a high potential for recurrence and metastasis. Compound F41, a naturally occurring indole-diterpenoid secondary metabolite, was isolated from the entomopathogenic fungus Penicillium sp. Its anti-pancreatic cancer activity has not been previously reported. Our study demonstrates that F41 significantly inhibits DNA replication, invasion, and proliferation in pancreatic cancer cells. By elevating intracellular reactive oxygen species (ROS) levels in pancreatic cancer cells, F41 induces endoplasmic reticulum stress, ultimately leading to apoptosis. These findings suggest that F41 could effectively overcome gemcitabine resistance in a clinical setting, indicating its promise as a potential therapeutic agent for pancreatic cancer. Full article

Previous studies have demonstrated that high-yielding dairy cows experience endoplasmic reticulum (ER) stress in the liver during early lactation. To date, most insights into the role of ER stress in metabolism and disease pathophysiology have been derived from rodent and human models. In dairy cattle, however, the specific impact of ER stress on metabolic pathways and its contribution to disease development remain insufficiently characterized. The objective of this study was therefore to investigate the molecular effects of ER stress using a bovine liver cell model (BFH12 cells). ER stress was induced by incubation with Tunicamycin (TM) and Thapsigargin (TG). Molecular responses to ER stress were assessed via a whole-genome array analysis and PCR targeting genes involved in selected metabolic pathways. Incubation with both ER stress inducers resulted in a marked upregulation of genes associated with the unfolded protein response (UPR) within a 4 to 24-h time frame, indicative of the production of robust ER stress in these cells. Unexpectedly, treatment with TM led to a downregulation of numerous genes involved in lipid biosynthesis, including those related to lipogenesis and cholesterol synthesis. Furthermore, incubation with TM and TG induced upregulation of genes involved in fatty acid oxidation and was accompanied by a reduction in intracellular triglyceride concentrations. Genes associated with inflammatory responses were upregulated by both TM and TG, whereas genes encoding antioxidant enzymes were downregulated. Genes involved in ketogenesis did not exhibit a consistent pattern of regulation. Overall, several effects of ER stress previously described in rodent models could not be replicated in this bovine liver cell system. Extrapolating these findings to dairy cows suggests that while ER stress may contribute to hepatic inflammation, it is unlikely to play a significant role in the development of hepatic lipidosis or ketosis. Full article

Fruit sunburn is a major abiotic stress limiting apple production worldwide, with losses potentially reaching 50% due to climate change-driven heat events. This study aimed to evaluate sustainable strategies to mitigate or reduce sunburn on ‘Gala Galaxy Selecta’ apple trees. Field trials conducted in summer 2021 compared eight treatments: silicon-based application (Eckosil^®), foliar fertilization with algae extracts, macro- and micronutrients, and amino acids, increased irrigation (+35% ET_c), mineral particle films (Surround^®, Vegepron Sun^®, Agrowhite^®, Sunstop^®), and an untreated control. Randomized block designs with replicates were used. Agronomic parameters, including particle film coverage, trunk cross-sectional area, yield, and fruit quality (color, sunburn incidence, firmness, soluble solids content, dry matter, starch), were measured at harvest. Physiological responses, such as net photosynthesis, maximum quantum yield of Photosystem II, specific leaf area, fruit surface temperature, photoprotective pigments, antioxidants, and heat shock protein gene expression, were also assessed. Foliar fertilization, Agrowhite^®, and water reinforcement produced the highest yield per trunk cross-sectional area, with increased soluble solids content and enhanced red pigmentation. Surround^® minimized sunburn incidence but reduced photosynthetic activity, as did Vegepron Sun^®. Agrowhite^® balanced sunburn protection with maintenance of fruit quality and physiological function. These findings provide practical guidance for growers to select effective treatments, balancing sunburn mitigation, fruit quality, and tree physiological performance, while offering researchers insights into integrating agronomic and physiological strategies for climate-resilient apple production. Full article

Although antiviral therapy has improved quality of life, around 50% of people with HIV (PWH) experience neurodegeneration and cognitive decline. This is prompted in part by the migration of HIV-infected monocyte-derived macrophages (MDMs) to the brain, leading to neuronal death. Previous studies in our lab have shown that HIV-infected MDMs secrete cathepsin B (CATB), which is a pro-inflammatory neurotoxic enzyme that is reduced by the addition of cannabinoid receptor-2 (CB2R) agonist JWH-133 to cell cultures. In this study, we aimed to identify the proteins secreted (secretome) by HIV-infected macrophages exposed to JWH-133 and quantify them using tandem mass tag (TMT) mass spectrometry. Frozen 13-day MDM supernatants from (1) an MDM negative control; (2) HIV+MDM, and (3) HIV+MDM-JWH-133 were compared in triplicate by mass spectrometry (LC/MS/MS) and analyzed for protein identification. Subsequently, the same samples were labeled by TMT labeling and quantified by LC/MS/MS. After a database search, 528 proteins were identified from all groups. Thereafter, proteins with more than three unique peptides and more than 10% coverage were selected for protein identification. Venn diagrams revealed one unique protein secreted by MDM-HIV, 10 unique proteins in HIV+MDM-JWH-133, and 15 common proteins in the three groups. CATB was unique to HIV+MDM. HIV+MDM exposed to JWH-133 showed proteins related to metabolism, cell organization, antiviral activity, and stress response. TMT analysis revealed 1454 proteins with abundance for statistical analysis based on FC ≥ |1.5| and p-value ≤ 0.05, of which Ruvb-like 1 and Hornerin decreased significantly with JWH-133 treatment. Both proteins stimulate HIV replication. In addition, HIV infection upregulated proteins associated with pathways of viral latency that were inhibited by JWH-133. In conclusion, JWH-133 treatment in HIV-infected macrophages leads to the secretion of antiviral host factors and decreases the secretion of proviral, inflammatory, and neurotoxic host factors. Full article

Cold stress adversely affects crop growth, and climate change is increasing its severity and frequency in many agricultural regions. Tomato plants are sensitive to low temperatures, although they activate some stress response mechanisms. Beneficial microorganisms can enhance cold-stress acclimation in tomato plants, but the transcriptional regulation underlying this process remains poorly understood. This study aimed to investigate the transcriptional processes activated by cold stress in tomato plants following inoculation with cold-tolerant bacteria isolated from alpine plants to identify genes potentially involved in cold stress acclimation. Among 41 cold-tolerant bacterial isolates tested, Chryseobacterium sp. GRCS301 and Pseudomonas sp. GRCS202 inoculation in sterilized soil promoted tomato growth under controlled non-stress (25 ± 2 °C) and cold-stress (10 ± 2 °C) conditions. Bacterial inoculations lowered H₂O₂ content and affected the transcriptional regulations activated in tomato shoots after one day and 14 days of incubation under cold-stress conditions. In mock-inoculated plants, cold stress downregulated genes related to energy generation, photosynthesis, and reproductive processes, highlighting its detrimental effects. Conversely, plants inoculated with Chryseobacterium and Pseudomonas upregulated genes involved in DNA replication, galactose metabolism, polysaccharide metabolism, photosynthesis, and protein metabolism in response to cold stress. Bacterial inoculation induced the expression of genes involved in reactive oxygen species homeostasis, cold-stress response, and hormonal signaling, suggesting that cold-tolerant bacteria trigger key transcriptional changes in tomato plants and enhance cold-stress acclimation. Full article