Search Results (715)

Plant aquaporin proteins (AQPs) are categorized into seven distinct families, among which, plasma membrane intrinsic proteins (PIPs) play pivotal roles in plant growth and physiological processes. In this study, we identified 11 CpPIP genes in wintersweet (Chimonanthus praecox (L.) Link) based on bioinformatic characterization of gene structural organization, chromosomal localization, and phylogenetic relationships. Subsequent phylogenetic reconstruction resolved two evolutionarily distinct CpPIP subclasses. We focused on the isolation and characterization of CpPIP1;1, which showed the highest expression in floral organs. During flowering, a significant increase was observed in the expression of the CpPIP1;1 gene in response to a gradual reduction in environmental temperature. Moreover, the overexpression of CpPIP1;1 in Arabidopsis thaliana resulted in early flowering and an enhanced tolerance to salt, drought, and cold stress. We subsequently transcriptionally fused the CpPIP1;1 promoter containing MYC and MYB low-temperature response elements to the β-glucuronidase (GUS) reporter gene and introduced this construct into Nicotiana tabacum. GUS activity assays of the transgenic plants revealed that the CpPIP1;1 promoter was effectively expressed in flowers. Furthermore, the promoter transcriptional activity was enhanced in response to salt, drought, cold, gibberellic acid, and methyl jasmonate treatments. Collectively, our findings in this study revealed that CpPIP1;1 plays a key role in the regulation of flowering and stress tolerance in wintersweet plants. Full article

Probiotics have gained increasing recognition for their potential to mitigate antibiotic-associated diarrhea (AAD). However, the precise mechanisms underlying their effects remain unclear. This study developed a mouse model of AAD using ceftriaxone to investigate the alleviating effects and mechanisms of Bifidobacterium animalis A6 (A6). The findings indicated that A6 supplementation effectively attenuated ceftriaxone-associated diarrhea in mice. The morphological damage to the villi and crypts was partially restored and more neatly reorganized following the A6 intervention. Additionally, intestinal morphology observations revealed a significant increase in the thickness of the mucus layer in the A6-treated group. Further examination of key regulatory genes associated with mucus secretion demonstrated that the A6 intervention effectively upregulated the expression of mucin1, thereby reinforcing the mucus layer. Concurrently, the A6 intervention upregulated the expression of the AQP4 and SLC26A3 genes in the intestine, which is responsible for restoring water absorption capacity in AAD mice. Additionally, the A6 treatment reduced ceftriaxone-induced harm to the intestinal microbiota of the mice, boosting beneficial bacteria like Bacteroidales, Akkermansia, Bifidobacterium, and Lactobacillus. Overall, this study offers valuable insights into the potential therapeutic role of A6 in restoring intestinal homeostasis and alleviating symptoms associated with AAD. Full article

Dehydrins (DHNs; late embryogenesis-abundant D11 family) are a class of hydrophilic proteins involved in plant abiotic stress response. However, there is less information regarding DHN gene function in cucurbit crops. Herein, 34 DHN gene family members were identified and characterized in Cucumis sativus, Cucumis melo, Citrullus lanatus, Benincasa hispida, Lagenaria siceraria, and Cucurbita maxima. The DHN genes in the six cucurbit crops exhibited greater collinearity within subfamilies than between different subfamilies. Responses to stress (including low-temperature, salt, cadmium, and aluminum stress) varied among the DHN members, with a significant alteration in the expression of the acidic SnKn-type DHN gene CmDHN3 in response to aluminum stress. Subcellular localization analysis confirmed that CmDHN3 is expressed in the nucleus and cytoplasm. Virus-induced gene silencing (VIGS) revealed a remarkable decrease in CmDHN3 expression, which markedly increased malondialdehyde content, relative conductivity, and proline content in the roots and leaves of plants under aluminum stress. Transcriptome analysis showed that the decreased CmDHN3 expression reduced the expression of water channel protein-encoding genes. Interactions between CmDHN3 and CmAQP1 (MELO3C007188) and between CmDHN3 and CmAQP2 (MELO3C020774) were confirmed using yeast two-hybrid assays. These results clarify the pathway by which dehydrin genes are involved in the transcriptional-level response of melon to aluminum stress and provide a theoretical basis to comprehensively analyze the functions of this gene family in cucurbit crops. Full article

Background/Objectives: The human kallikrein-related peptidase 6 (KLK6), a serine protease with trypsin-like properties, belongs to the 15-member kallikrein (KLK) gene family and is predominantly recognized for its role in oncogenesis, neurodegenerative disorders, and skin conditions. Aquaporins (AQPs) are integral membrane proteins that facilitate water transport across cell membranes. AQP1 is constitutively active in the kidneys and plays a crucial role in reabsorbing filtered water, while AQP2 is regulated by vasopressin and is essential for maintaining body fluid homeostasis. The primary objective of the present study is to investigate the spatio-temporal expression patterns of KLK6, AQP1, and AQP2 throughout normal human nephrogenesis and congenital kidney and urinary tract (CAKUT) abnormalities: duplex kidneys, horseshoe kidneys, and dysplastic kidneys. Methods: An immunofluorescence analysis of KLK6, AQP1, and AQP2 was performed on 37 paraffin-embedded fetal kidney samples. The area percentage of KLK6 in the kidney cortex was calculated in normal developing samples during developmental phases 2, 3, and 4 and compared with CAKUT samples. Results: KLK6 exhibits distinct spatiotemporal expression patterns during human kidney development, with consistent localization in proximal tubules. Its subcellular positioning shifts from the basolateral cytoplasm in early phases to the apical cytoplasm in later stages, which may be strategically positioned to act on its substrate in either the peritubular space or the tubular fluid. KLK6 expression followed a quadratic trajectory, peaking at Ph4. This marked increase in the final developmental phase aligns with its strong expression in mature kidneys, suggesting a potential role in proximal tubule differentiation and functional maturation through facilitating extracellular matrix remodeling and activating proteinase-activated receptors, modulating the signaling pathways that are essential for tubular development. In duplex kidneys, structural abnormalities such as ureteral obstruction and hydronephrosis may upregulate KLK6 as part of a reparative response, while its downregulation could impair epithelial remodeling and cytoskeletal integrity, exacerbating dysplastic phenotypes. Conclusions: These findings highlight the potential of KLK6 involvement in normal kidney development and the pathology of CAKUT. Full article

To clarify T-cell responses in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), we cultured the peripheral blood mononuclear cells of 24 patients with MOGAD and 20 with aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorders (NMOSD), and those of 17 healthy controls (HCs), in the presence of fourteen MOG peptides covering the full-length MOG, five AQP4 peptides, two myelin basic protein peptides, or two proteolipid protein peptides. Then, we measured T-cell activation markers, such as cell surface CD69 and the intracellular production of granulocyte–macrophage colony-stimulating factor (GM-CSF) and interferon-γ in CD4-positive T-cells, with a flow cytometer. The expression of CD69 in response to MOG p16–40 and MOG p181–205 was significantly higher (Stimulation Index > 2) in MOGAD than in HCs. Also, CD69 for AQP4 p21–40, AQP4 p211–230, and MOG p166–190 were significantly increased in NMOSD than in HCs. Intracellular GM-CSF production responding to MOG p16–40 was significantly higher in MOGAD than in HCs (p < 0.05), although intracellular interferon-γ was not elevated. None of the responses to the other peptides were different between the groups. The present study showed subtle CD4-positive T-cell activation elicited by some MOG peptides alone in patients with MOGAD. Further studies of cytokines or other stimulation and alternative assay markers and metrics are needed to delineate the immunopathological roles of T-cells in MOGAD. Full article

The limited availability of primary normal human epidermal keratinocyte (NHEK) has hampered the large-scale implementation of skin models in biomedical, toxicological, and pharmaceutical research. Therefore, in this study, we aimed to establish an induced pluripotent stem cell (iPSC)-derived epidermal skin model that is not limited by donor type and cell lifespan, and evaluate whether it is equivalent to the primary NHEK-derived reconstructed epidermal skin model (RHE) for skin irritation testing. The results show that high expression of OCT4, SOX2, KLF4, c-MYC, and SSEA-4, TRA-1-60, TRA-1-81 indicated that iPSCs were successfully generated from human fibroblasts in vitro. The expression levels of ectoderm or KC marker genes CGB, IVL, KRT10, KRT14, TP63, and TBP were close to those of NHEKs. This result confirms that iPSCs were successfully differentiated into iPSC-KCs. The expression levels of iPSC-derived-RHE in FLG (60), AQP3 (151), CLDN1 (30.6), IVL (209), KRT5 (39.3), KRT10 (39.2), TSLP (99), IL-6 (53.1), IL-8 (79.4), and TNF-a (91.5) were significantly higher than those in RHE. These results indicate that iPSC-derived RHE has extremely strong vitality and renewal capacity. Meanwhile, there was no significant difference between iPSC-derived RHE and SkinEthic in predicting skin irritation, which means that our iPSC-derived RHE performed well in the test. iPSC-derived RHE can replace other skin models for skin irritation testing related to cosmetics. This technology has the potential to generate an unlimited number of genetically identical skin models and improve the reproducibility of experiments. Full article

The escalation of industrialization has worsened air quality, underscoring the essential need for accurate forecasting to inform policies and protect public health. Current research has primarily emphasized individual spatiotemporal features for prediction, neglecting the interconnections between these features. To address this, we proposed the generative Comprehensive Scale Spatiotemporal Fusion Air Quality Predictor (CSST-AQP). The novel dual-branch architecture combines multi-scale spatial correlation analysis with adaptive temporal modeling to capture the complex interactions in pollutant dispersion and enhanced pollution forecasting. Initially, a fusion preprocessing module based on localized high-correlation spatiotemporal features encodes multidimensional air quality indicators and geospatial data into unified spatiotemporal features. Then, the core architecture employs a dual-branch collaborative framework: a multi-scale spatial processing branch extracts features at varying granularities, and an adaptive temporal enhancement branch concurrently models local periodicities and global evolutionary trends. The feature fusion engine hierarchically integrates spatiotemporally relevant features at individual and regional scales while aggregating local spatiotemporal features from related sites. In experimental results across 14 Chinese regions, CSST-AQP achieves state-of-the-art performance compared to LSTM-based networks with RMSE 6.11–9.13 μg/m³ and R² 0.91–0.93, demonstrating highly robust 60 h forecasting capabilities for diverse pollutants. Full article

Aging involves progressive physiological changes, including the dysregulation of water homeostasis, essential for cellular function, neuronal signaling, and musculoskeletal integrity. This review explores the emerging role of water loss as a central and underestimated driver of functional decline in aging, with a focus on the dog, both as a clinically relevant target species and as a model for human aging. Age-related alterations in water metabolism—driven by changes in body composition, aquaporin (AQP) expression, electrolyte imbalances, reduced thirst perception, and impaired urine concentration—lead to intracellular and extracellular dehydration, exacerbating functional decline. We examine molecular mechanisms of water regulation involving AQPs and osmolytes, and describe how dehydration contributes to structural and metabolic dysfunction across key biological compartments, including the kidney, brain, bone, and skeletal muscle. Physiological dehydration, a hallmark of aging, intensifies inflammaging, accelerating tissue degeneration. In particular, we highlight how water loss impairs solvent capacity, solute transport, protein conformation, and cellular communication. Despite the known role of macronutrients in geriatric nutrition, hydration remains an often-overlooked factor in aging management. We argue for its inclusion as a fourth pillar in the nutritional approach to veterinary geriatrics, alongside protein, fat, and fiber. By investigating aging-associated water loss in dogs—species that share environments and lifestyle patterns with humans—we propose hydration-centered strategies to promote healthy aging in both veterinary and comparative medicine. Full article

Breast cancer is a heterogeneous disease with varying responses to therapies. While targeted treatments have advanced, conventional therapies inducing oxidative stress remain widely used. H₂O₂ has emerged as a therapeutic candidate due to its role in signaling and cell-function regulation. Its transport is tightly regulated through peroxiporins such as AQP5, expression of which is linked to poor prognosis and metastatic spread, and its role in therapy resistance remains underexplored. This study examined AQP5’s role in the acute oxidative stress response. We overexpressed AQP5 in breast cancer cell lines with low basal levels—HR+ (MCF7), HER2+ (SkBr-3), and TNBC (SUM 159)—and exposed them to H₂O₂ for 24 h. We assessed cell viability, intracellular ROS, changes in AQP3 and AQP5, and key antioxidative and cancer-related pathways (NRF2, PI3K/AKT, FOXOs). AQP5 overexpression elicited a cell-type-specific response. H₂O₂ treatment reduced viability in SkBr-3-AQP5 and MCF7-AQP5 cells, increased ROS levels in MCF7-AQP5, and decreased ROS in SUM 159-AQP5. It also increased AQP3 in MCF7-AQP5 and differentially affected NRF2, FOXOs, and PI3K/AKT signaling, notably activating NRF2/AKR1B10 axis in MCF7-AQP5 and decreasing FOXO1 in SUM 159-AQP5. These findings highlight the need for further research into AQP5’s role in the oxidative stress response in breast cancer cells. Full article

Pancreatic cancer is one of the most lethal and challenging malignancies. Its severity is primarily linked to the constitutively activated mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. Aquaporins (AQPs) are frequently overexpressed in pancreatic cancer, playing crucial roles in cell signaling, and consequently promoting cell migration, proliferation, and invasion. Here, we investigate the transcriptomics of key players in epithelial–mesenchymal transition (EMT) and the MAPK/ERK signaling pathway in pancreatic cancer tissues, correlating them with tumor AQP expression to highlight their potential as diagnostic or prognostic tools. The transcriptomics analysis was conducted in 24 paired pancreatic tumors and adjacent healthy tissues, and analyses were performed considering the patients’ age and gender, as well as tumor invasiveness and aggressiveness. Our results revealed strong positive Pearson correlation coefficients between AQP3 and c-Jun, and between AQP5 and CDH1/EGFR in pancreatic tumors but not in healthy tissues, with posterior in vitro confirmation in pancreatic cancer BxPC3 cells, suggesting a shift in the regulatory mechanisms of gene expression that certainly affect the physiology of the tissue, influencing cancer initiation and progression. This study underscores the interplay between AQPs and cancer signaling pathways, opening new avenues for defining novel clinical biomarkers and improving the early detection of pancreatic cancer. Full article

Grass carp (Ctenopharyngodon idella) is a key aquaculture species, and understanding its adaptation mechanisms to saline environments is crucial for addressing the global freshwater salinization challenge. In this study, juvenile grass carp were acclimated to three salinity levels (0, 4, and 8 ppt) for 30 days, after which gill and intestinal tissues were sampled to quantify cortisol concentrations and conduct RNA-seq. Results showed that cortisol levels exhibited a salinity-dependent increase, with significantly higher concentrations in gill tissues than in intestinal tissues, suggesting that cortisol plays an important role in the salt adaptation of grass carp. RNA-seq revealed that ion transport-related genes were upregulated in gills, whereas biosynthesis, oxygen transport, and energy metabolism genes were downregulated. In the intestine, genes involved in taurine transport and intercellular junctions were highly expressed, while immune-related genes showed reduced expression. These findings suggest that high salinity suppresses respiration and energy metabolism efficiency, with ion exchange primarily occurring in gills. Functional annotation identified seven candidate genes (LOC127513882, aqp9b, ca4a, ca5a, igfbp1b, slc12a2, and slc12a4) as key regulators of salinity adaptation. Overall, our study provides valuable insights into the mechanisms underlying the salt tolerance of grass carp. Full article

To understand the biological effects of residual radioactivity after the atomic bomb explosion in Hiroshima and Nagasaki, we previously investigated the effects of ⁵⁶Mn, a major residual radioisotope. Our rat study demonstrated that inhalation exposure to ⁵⁶MnO₂ microparticles affected gene expression in the lungs, testes, and liver, despite the low radiation doses. Because ⁵⁶Mn is a β- and γ-emitter, the differential effects between β- and γ-rays should be clarified. In this study, ³¹Si, a β-emitter with a radioactive half-life similar to that of ⁵⁶Mn, was used to determine its effects. Male Wistar rats were exposed to sprayed neutron-activated ³¹SiO₂ microparticles, stable SiO₂ microparticles, or X-rays. The animals were examined on days 3 and 14 after irradiation. The expression of radiation-inducible marker genes, including Ccng1, Cdkn1a, and Phlda3, was measured in the spleen, lungs, and liver. Furthermore, the expressions of pathophysiological marker genes, including Aqp1, Aqp5, and Smad7 in the lungs and Cth, Ccl2, and Nfkb1 in the liver, were determined. Impacts of ³¹SiO₂ exposure were observed mainly in the liver, where the expression of Cth markedly increased on post-exposure days 3 and 14. Our data suggest that internal exposure to β-emitted microparticles has significant biological effects and its possible roles as residual radiation after atomic bombing. Full article

The impact of dietary lipid sources on nutrient metabolism and reproductive development is a critical focus in aquaculture broodstock nutrition. Previous studies have demonstrated that fish oil supplementation modulates the expression of genes involved in steroid hormone synthesis, glucose, and lipid metabolism promoting ovarian development in female Scatophagus argus (spotted scat). However, the effects of fish oil on hepatic function at the protein level remain poorly characterized. In this study, female S. argus were fed diets containing 8% fish oil (FO, experimental group) or 8% soybean oil (SO, control group) for 60 days. Comparative proteomic analysis of liver tissue identified significant differential protein expression between groups. The FO group exhibited upregulation of lipid metabolism-related proteins, including COMM domain-containing protein 1 (Commd1), tetraspanin 8 (Tspan8), myoglobin (Mb), transmembrane protein 41B (Tmem41b), stromal cell-derived factor 2-like protein 1 (Sdf2l1), and peroxisomal biogenesis factor 5 (Pex5). Additionally, glucose metabolism-associated proteins, such as Sdf2l1 and non-POU domain-containing octamer-binding protein (Nono), were elevated in the FO group. Moreover, proteins linked to inflammation and antioxidant responses, including G protein-coupled receptor 108 (Gpr108), protein tyrosine phosphatase non-receptor type 2 (Ptpn2), Pex5, p120 catenin (Ctnnd1), tripartite motif-containing protein 16 (Trim16), and aquaporin 11 (Aqp11), were elevated in the FO group, while proteins involved in oxidative stress, such as reactive oxygen species modulator 1 (Romo1), cathepsin A (Ctsa), and Cullin 4A (Cul4a), were downregulated. These proteomic findings align with prior transcriptomic data, indicating that dietary fish oil enhances hepatic lipid metabolism, mitigates oxidative stress, and strengthens antioxidant capacity. Furthermore, these hepatic adaptations may synergistically support ovarian maturation in S. argus. This study provides novel proteomic-level evidence supporting the role of fish oil in modulating hepatic lipid and energy metabolism, thereby elucidating the role of fish oil in optimizing hepatic energy metabolism and redox homeostasis to influence reproductive processes, advancing our understanding of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) in teleost liver physiology. Full article

In this study, we investigated the antiaging potential of dendropanoxide (DP), an active compound derived from Dendropanax morbiferus, in human dermal fibroblasts (NHDFs) induced by Tumor Necrosis Factor-alpha (TNF-α) and in human epidermal keratinocytes (NHEKs) induced by TNF-α and interferon gamma (IFN-γ). We induced oxidative stress related to ultraviolet (UV) radiation with TNF-α and IFN-γ and then treated the cells with various concentrations of DP to evaluate its effects on reactive oxygen species (ROS) production, matrix metalloproteinase-1 (MMP-1) expression, collagen synthesis, inflammatory cytokine expression, and skin barrier protection. The results showed that DP significantly reduced ROS production, indicating its potential to alleviate oxidative stress in the skin. Additionally, DP effectively inhibited MMP-1 production, suggesting that it could prevent collagen degradation in the dermis, significantly increase the secretion of pro-collagen I, promote collagen synthesis, and protect the dermal extracellular matrix (ECM). Moreover, DP significantly reduced the expression of inflammatory cytokines IL-1β and IL-6, thereby inhibiting excessive inflammatory responses in the skin. DP also enhanced the gene expression of key factors involved in skin barrier maintenance, including Kazal-type 5 (SPINK5), loricrin (LOR), aquaporin-3 (AQP3), filaggrin (FLG), and keratin 1 (KRT1), suggesting its potential to maintain and protect the skin barrier. Western blot analysis revealed that DP inhibited TNF-α-induced phosphorylation of JNK and p38, implying that DP exerts antiaging effects through the regulation of the JNK and p38 signaling pathways. Collectively, these findings suggest that DP has significant potential as an antiaging agent. Full article