Search Results (2,150)

Background: Acute pancreatitis (AP) is characterized by the abnormal activation of pancreatic enzymes due to various causes, leading to local pancreatic inflammation. This can trigger systemic inflammatory response syndrome and multi-organ dysfunction. Hyperlipidemia, mainly resulting from lipid metabolism disorders and elevated triglyceride levels, is a major etiological factor in AP. This study aims to investigate the role of lipid metabolism-related genes in the pathogenesis of AP and to propose novel strategies for its prevention and treatment. Methods: We obtained AP-related datasets GSE3644, GSE65146, and GSE121038 from the GEO database. Differentially expressed genes (DEGs) were identified using DEG analysis and gene set enrichment analysis (GSEA). To identify core lipid metabolism genes in AP, we performed least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) analysis. Gene and protein interactions were predicted using GeneMANIA and AlphaFold. Finally, biomarker expression levels were quantified using Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) in an AP mouse model. Results: Seven lipid metabolism-related genes were identified as key biomarkers in AP: Amacr, Cyp39a1, Echs1, Gpd2, Osbpl9, Acsl4, and Mcee. The biological roles of these genes mainly involve fatty acid metabolism, cholesterol metabolism, lipid transport across cellular membranes, and mitochondrial function. Conclusions: Amacr, Cyp39a1, Echs1, Gpd2, Osbpl9, Acsl4, and Mcee are characteristic biomarkers of lipid metabolism abnormalities in AP. These findings are crucial for a deeper understanding of lipid metabolism pathways in AP and for the early implementation of preventive clinical measures, such as the control of blood lipid levels. Full article

Background: Premenopausal women typically exhibit superior glucose metabolism compared to males, but this metabolic advantage is lost after menopause. The primary cause is the sharp decline in estrogen levels post-menopause. Genistein, a natural compound predominantly derived from leguminous plants, possesses structural similarity to estrogen. This enables specific binding to estrogen receptors, allowing genistein to exert estrogen-mimicking effects under conditions of estrogen deficiency. The aim of this study was to investigate the effects and potential mechanisms of genistein on glucose metabolism in the liver and skeletal muscle of ovariectomized (OVX) mice fed a high-fat diet (HFD). Methods: Animal experiments were performed using 8-week-old mice that were OVX to construct a model of estrogen deficiency and impaired their glucose metabolism by a continuous HFD. Genistein was administered by gavage (50 mg/kg-day) for 10 weeks and 17β-estradiol was administered subcutaneously (50 μg/kg) every 4 days for 10 weeks as a positive control. Results: Genistein significantly improved glucose metabolism (including fasting glucose, postprandial glucose, serum glucose levels, and HOMA-IR index) but did not affect serum estrogen levels and uterine weights in OVX mice. Genistein promoted increased expression and translocation of glucose transporter 4 (GLUT4) in the gastrocnemius muscle, enhanced phosphorylation of the PI3K/AKT pathway, and upregulated expression of the G protein-coupled estrogen receptor (GPER). Concurrently, it stimulates hepatic glycogen accumulation and upregulates GLUT2 expression in the liver. Conclusions: GEN improves glucose metabolism in ovariectomized mice, and this improvement is primarily attributed to increased expression and membrane translocation of GLUT4 in the gastrocnemius muscle mediated by the GPER-PI3K/AKT pathway. Full article

The TMEM16 (Anoctamin) family comprises a group of transmembrane proteins involved in diverse physiological processes, including ion transport and phospholipid scrambling. TMEM16F (Anoctamin 6), a phospholipid scramblase and nonselective ion channel, plays a central role in membrane remodeling, blood coagulation, immune responses, and cell death pathways through its ability to externalize phosphatidylserine in response to elevated intracellular calcium levels. Consequently, modulating TMEM16F activity has emerged as a promising strategy for the development of new therapeutic applications. Despite the functional importance of TMEM16F, TMEM16F modulators have received little study. In a previous study, we generated TMEM16F-specific affibodies by biopanning a phage display library for affibodies that bind to brain-specific TMEM16F (hTMEM16F) variant 1. In this study, we selected six other affibodies from among the 38 previously sequenced affibody candidates and characterized them. After purification, we confirmed that two of these affibodies bound to human TMEM16F with high affinity. To provide functional insights into how these affibodies modulate TMEM16F activity, we tested whether they could exert functional effects at the cellular level. Finally, we show that TMEM16F affibody attenuated the neuronal cell death induced by glutamate and microglial phagocytosis, suggesting that these affibodies might have potential therapeutic and diagnostic applications. Full article

The NRAMP (Natural Resistance-Associated Macrophage Protein) family plays a pivotal role as membrane transporters in plants’ responses to heavy metal stress. This study identified 12 NRAMP genes in Sorghum bicolor (sorghum) and performed a comprehensive bioinformatics analysis. The SbNRAMP genes are distributed across seven sorghum chromosomes. In-depth analyses of gene structure, conserved motifs, collinearity, and phylogeny indicated that the SbNRAMP family is divided into three subfamilies, each exhibiting unique structural and motif characteristics. Collinearity analysis suggested that large-fragment duplications, rather than tandem duplications, were responsible for the expansion of the SbNRAMP family, resulting in a greater number of genes compared to Arabidopsis thaliana and rice. Transcriptome analysis of the aboveground and underground parts of sorghum seedlings under saline–alkali stress revealed that SbNRAMP5 is a key hub gene exhibiting tissue-specific expression. Furthermore, qRT-PCR analysis following exposure to Cd, Mn, or Zn treatments revealed differential expression among the SbNRAMP genes. Subcellular localization predictions indicated that all twelve NRAMPs are primarily located in the plasma membrane, with nine to twelve transmembrane domains, consistent with their function in metal ion transport. Experimental evidence confirmed that SbNRAMP6 is localized in the plasma membrane. These findings establish a foundation for a deeper understanding of the structure and function of the sorghum NRAMP gene family. Full article

Hypovirus infection is known to reduce the pathogenicity of Cryphonectria parasitica, the causative agent of chestnut blight. Isoforms derived from a viral protein p48 have been discovered in host mitochondria and vesicles, which may contribute to virulence attenuation, as reported in earlier work using two-dimensional electrophoresis (2-DE). In this study, a total of 1739 fungal proteins were identified in fungal vesicles through Tandem Mass Tag (TMT)-based quantitative proteomics. The infection of CHV1-EP713 was associated with 75 up-regulated and 201 down-regulated proteins, predominantly involved in vesicular transport process and related cellular functions, including protein folding, membrane fusion, retrograde transport, autophagy, and ER stress responses. The down-regulation of calnexin, COPI, ArfGAP, importin-β, and Atg8 is consistent with impairments in protein folding, retrograde transport, and autophagy. Meanwhile, the up-regulation of clathrin, dynamin, Vps10p, HSP70, and t-SNAREs indicated enhanced trafficking to vacuoles and increased stress response activity. Overall, our findings indicate that hypoviral infection is associated with extensive alterations in the vesicular transport system of C. parasitica, likely mediated through changes in the abundance of multiple key protein regulators. These alterations may underlie attenuation of virulence by impacting crucial cellular processes. Full article

Alcohol Use Disorder (AUD) poses global health challenges, and causes hematological alterations such as macrocytosis and oxidative stress. Disruption of protein structures by alcohol and/or its metabolites may exacerbate AUDs; proteomics can elucidate the underlying biological mechanisms. This study examined the proteins differentially expressed in the cytosol and membrane fractions of erythrocytes obtained from 30 male patients with AUD, comparing them to samples from 15 age- and BMI-matched social drinkers (SDs) and 15 non-drinkers (control). The analysis aimed to identify the molecular differences related to alcohol consumption. The AUD patient subgrouping was based on mean corpuscular volume (MCV), with 16 individuals classified as having a normal MCV and 14 having a high MCV. Proteins were separated via two-dimensional(2D)-gel electrophoresis, digested with trypsin, and identified via Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (TOF) mass spectrometry (MALDI-TOF/TOF). Additionally, levels of malondialdehyde and 4-hydroxyalkenals (MDA + HAE), reduced glutathione (GSH), oxidized glutathione (GSSG), serum carbohydrate-deficient transferrin (%CDT), disialotransferrin (%DST), and sialic acid (SA) were analyzed. The results showed increased MDA + HAE and decreased total thiols in AUD patients, with GSSG elevated and the GSH/GSSG ratio reduced in the AUD MCV-high subgroup. Serum %CDT, %DST, and SA were significantly higher in AUD. Compared to the control profiles, the AUD group exhibited differential protein expression. Few proteins, such as bisphosphoglycerate mutase, were downregulated in AUD versus control and SD, as well as in the MCV-high AUD subgroup. Conversely, endoplasmin and gelsolin were upregulated in AUD relative to control. Cytoskeletal proteins, including spectrin-alpha chain, actin cytoplasmic 2, were overexpressed in the AUD group and MCV-high AUD subgroup. Several proteins, such as 14-3-3 isoforms, alpha-synuclein, translation initiation factors, heat shock proteins, and others, were upregulated in the MCV-high AUD subgroup. Under-expressed proteins in this subgroup include band 3 anion transport protein, bisphosphoglycerate mutase, tropomyosin alpha-3 chain, uroporphyrinogen decarboxylase, and WD repeat-containing protein 1. Our findings highlight the specific changes in protein expression associated with oxidative stress, cytoskeletal alterations, and metabolic dysregulation, specifically in AUD patients with an elevated MCV. Understanding these mechanisms is crucial for developing targeted interventions and identifying biomarkers of alcohol-induced cellular damage. The complex interplay between oxidative stress, membrane composition, and cellular function illustrates how chronic alcohol exposure affects cellular physiology. Full article

Aquaporins (AQPs) are membrane proteins that facilitate the transport of water and solutes. Among AQPs, plasma membrane intrinsic proteins (PIPs) play a critical role in maintaining water balance between the internal and external cell environments. This study focuses on the tomato due to its economic importance and cultivation under moderate salinity conditions in Japan. A swelling assay using X. laevis oocyte confirmed that all five examined tomato SlPIP2 isoforms showed water transport activity. Among them, two-electrode voltage clamp (TEVC) experiments showed that only SlPIP2;1, SlPIP2;4, and SlPIP2;8 transport Na⁺ and K⁺, with no transport activity for Cs⁺, Rb⁺, Li⁺, or Cl⁻. CaCl₂ (1.8 mM) reduced ionic currents by approximately 45% compared to 30 µM free-Ca²⁺. These isoforms function as very low-affinity Na⁺ and K⁺ transporters. Expression analysis showed that SlPIP2;4 and SlPIP2;8 had low, stable expression, while SlPIP2;1 was strongly upregulated in roots NaCl treatment (200 mM, 17days), suggesting distinct physiological roles for these ion-conducting AQPs (icAQPs). These data hypothesized that tomato icAQPs play a critical role in ion homeostasis, particularly under salinity stress. In conclusion, the first icAQPs have been identified in the dicotyledonous crop. These icAQPs are essential for plant resilience under salt stress. Full article

Microbial reduction in hexavalent chromium (Cr(VI)) is a well characterized bioremediation strategy, yet the mechanistic diversity among bacterial taxa necessitates detailed investigations into strain-specific pathways. Here, we report the isolation and characterization of Bacillus safensis BSF-4, a halophilic bacterium derived from saline-alkali soil, which demonstrates efficient Cr(VI) reduction capacity. Physiological assays showed that BSF-4 achieved 89.15% reduction of 20 mg/L Cr(VI) within 72 h, with Cr(III) identified as the primary extracellular end product. Resting cell assays and subcellular fractionation analyses confirmed that Cr(VI) reduction predominantly occurs in the extracellular milieu. X-ray photoelectron spectroscopy (XPS) further revealed soluble Cr(III) complexed with extracellular polymeric substances (EPS). Transcriptomic profiling indicated upregulation of membrane-associated transport systems (facilitating Cr(VI) exclusion) and quorum sensing (QS) pathways (mediating adaptive stress responses). These findings highlight a dual mechanism: (1) extracellular enzymatic reduction mediated by EPS-bound redox proteins, and (2) intracellular detoxification via QS-regulated defense pathways. Collectively, Bacillus safensis BSF-4 exhibits robust Cr(VI) reduction capacity under saline conditions, positioning it as a promising candidate for bioremediation of Cr(VI)-contaminated saline soils and aquatic ecosystems. Full article

Extracellular vesicles (EVs) are nanoscale, membrane-bound particles secreted by diverse cell types and act as pivotal mediators of intercellular communication during bone regeneration. These vesicles transport bioactive cargo including proteins, lipids, mRNAs, and microRNAs that modulate osteogenesis, angiogenesis, and immune responses within the bone microenvironment. EVs originating from mesenchymal stem cells, osteoblasts, endothelial cells, and macrophages have demonstrated substantial potential to promote bone formation, inhibit bone resorption, and enhance vascularization. This review examines the biogenesis, classification, and cellular uptake mechanisms of EVs, focusing on their roles in osteogenesis and their therapeutic applications in fracture healing, osteoporosis, and bone tissue engineering. Despite their promise, significant challenges remain, including the need for standardization, scalable production, and assessment of long-term safety to enable clinical translation of EV-based therapies. Here, we provide a comprehensive overview of EV biology, elucidate the molecular mechanisms of EVs in bone regeneration, and discuss innovative strategies to optimize their therapeutic efficacy, highlighting their potential as next-generation orthobiologics. Full article

Maize ear rot is an important fungal disease in maize production, mainly caused by pathogens such as Fusarium graminearum, which seriously affects the yield and quality of maize. This study investigated the changes in the activity of defense-related enzymes in maize grains and their transcriptome response characteristics after exogenous SA treatment under Fusarium graminearum stress. The results showed that treatment with 0.01 mmol/L salicylic acid (SA) significantly inhibited the growth of Fusarium graminearum hyphae, while enhancing the activities of phenylalanine ammonia-lyase (PAL), superoxide dismutase (SOD), β-1,3-glucanase (β-1,3-GA), and polyphenol oxidase (PPO) in maize grains, and reducing the content of malondialdehyde (MDA), effectively alleviating the damage of Fusarium graminearum to the maize grain membrane system. Transcriptome analysis identified multiple key genes involved in SA-mediated disease resistance pathways, including disease-related proteins (PR10), acidic terpenoids, aspartic proteases, proteins containing BTB/POZ and MATH domains (BPM4), and PPT3 transporters. This study reveals the physiological and molecular mechanisms by which exogenous SA enhances maize resistance to ear rot, providing an important theoretical basis for further understanding the regulatory network of SA in plant disease resistance. Full article

The GLABROUS1 Enhancer Binding Protein (GeBP) gene family plays a crucial role in plant growth, development, and stress responses. In this study, 28 GeBP genes were identified in Brassica oleracea using HMMER and validated through multiple conserved domain databases. A phylogenetic tree was constructed based on the GeBP protein sequences from B. oleracea, Arabidopsis thaliana, Brassica rapa, and Brassica napus, dividing them into four evolutionary clades (A–D), which revealed a close evolutionary relationship within the genus Brassica. Conserved motif and gene structure analyses showed clade-specific features, while physicochemical property analysis indicated that most BoGeBP proteins are hydrophilic, nuclear-localized, and structurally diverse. Gene duplication and chromosomal localization analyses suggested that both segmental and tandem duplication events have contributed to the expansion of this gene family. Promoter cis-element analysis revealed a dominance of light-responsive and hormone-responsive elements, implying potential roles in photomorphogenesis and stress signaling pathways. Notably, the protein encoded by BolC01g019630.2J possesses both a transmembrane domain and characteristics of the Major Facilitator Superfamily (MFS) transporter family, and it is predicted to localize to the plasma membrane. This suggests that it may act as a molecular bridge between environmental signal perception and transcriptional regulation, potentially representing a novel signaling mechanism within the GeBP family. This unique feature implies its involvement in transmembrane signal perception and downstream transcriptional regulation under environmental stimuli, providing valuable insights for further investigation of its role in stress responses and metabolic regulation. Overall, this study provides a theoretical foundation for understanding the evolutionary patterns and functional diversity of the GeBP gene family in B. oleracea and lays a basis for future functional validation and breeding applications. Full article

Background and Objectives: Hypocitraturia is a major risk factor for calcium-containing kidney stone disease. Citrate inhibits stone formation by binding calcium in the urine. The SLC13A2 gene encodes the sodium-dependent dicarboxylate cotransporter 1 (NaDC1), a membrane transport protein that facilitates citrate reabsorption in the proximal renal tubules. Variants in this gene, such as rs11568476 (V477M), have been shown to significantly impair transporter activity. This study aimed to investigate the presence of the rs11568476 polymorphism in SLC13A2 and its association with hypocitraturia in Turkish patients with calcium-containing kidney stones. To our knowledge, this is the first genetic study evaluating this polymorphism in a Turkish cohort. Materials and Methods: This prospective cross-sectional study included 90 patients diagnosed with calcium-containing kidney stones at Düzce University Faculty of Medicine, Department of Urology. Based on 24 h urinary citrate levels, patients were divided into two groups: normocitraturic (n = 38) and hypocitraturic (n = 52). Blood and 24 h urine samples were analyzed for biochemical parameters. The rs11568476 polymorphism in SLC13A2 was analyzed using Real-Time PCR. Results: There were no significant differences between the two groups in terms of age, gender, and most biochemical parameters. Serum uric acid levels were significantly higher in the hypocitraturic group (p = 0.002), whereas family history of stone disease was more prevalent in the normocitraturic group (p = 0.024). Genetic analysis revealed no polymorphism in the rs11568476 region; all patients exhibited the homozygous wild-type genotype (GG). Conclusions: No association was observed between the rs11568476 polymorphism and hypocitraturia in this cohort. The absence of the polymorphism suggests that this variant may be rare or absent in the Turkish population. These findings highlight the importance of investigating additional genetic and environmental contributors to hypocitraturia and nephrolithiasis through larger, multicenter studies. Full article

The ATP-binding cassette (ABC) gene family represents one of the most extensive and evolutionarily conserved groups of proteins, characterized by ATP-dependent transporters that mediate the movement of substrates across cellular membranes. Despite their well-documented functions in various biological processes, the specific contributions of ABC transporters in eggplant (Solanum melongena L.) remain unexplored. To address this gap, we conducted a comprehensive genome-wide identification and expression profiling of ABC transporter-encoding genes in eggplant. Our investigation identified 159 SmABC genes encoding ABC transporter that were irregularly dispersed across all 12 chromosomes. The encoded proteins exhibited considerable diversity in size, with amino acid lengths varying from 55 to 2628 residues, molecular weights ranging between 4.04 and 286.42 kDa, and isoelectric points spanning from 4.89 to 11.62. Phylogenetic analysis classified the SmABC transporters into eight distinct subfamilies, with the ABCG subfamily being the most predominant. Subcellular localization predictions revealed that most SmABC proteins were localized to the plasma membrane. Members within the same subfamily exhibited conserved motif arrangements and exon–intron structures, suggesting functional and evolutionary conservation. Promoter analysis identified both shared and unique cis-regulatory elements associated with transcriptional regulation. We identified 9 tandem duplication gene pairs and 20 segmental duplication pairs in the SmABC gene family, with segmental duplication being the major mode of expansion. Non-synonymous to synonymous substitutions (Ka/Ks) analysis revealed that paralogs of SmABC family genes underwent mainly purifying selection during the evolutionary process. Comparative genomic analysis demonstrated collinearity between eggplant, Arabidopsis thaliana, and tomato (Solanum lycopersicum), confirming homology among SmABC, AtABC, and SlABC genes. Tissue-specific expression profiling revealed differential SmABC expression patterns, with three distinct genes, SmABCA16, SmABCA17 and SmABCG15, showing preferential expression in purple-peeled fruits (A1, A3, and A5 accessions), implicating their potential involvement in anthocyanin transport. Functional validation via SmABCA16 silencing led to a significant downregulation of SmABCA16 and reduced purple coloration, indicating its regulatory role in anthocyanin transport in eggplant fruit peel. This comprehensive genomic and functional characterization of ABC transporters in eggplant establishes a critical foundation for understanding their biological roles and supports targeted breeding strategies to enhance fruit quality traits. Full article

Obesity is a complex chronic inflammatory condition that results from excess fat accumulation. It increases the risk of developing numerous co-morbidities such as Type 2 diabetes mellitus, cardiovascular disease, hypertension, and stroke. The adipose tissue is itself a vital endocrine organ that secretes numerous adipokines, cytokines, and exosomes, which are collectively known as the adipose-derived secretome (ADS). This ADS has been shown to influence and modulate many physiological processes. During obesity, the composition of ADS is altered, which may contribute to the development of obesity-associated diseases. Type-2 diabetes mellitus is one of the most common complications of obesity due to alterations in glucose homeostasis. Glucose absorption occurs via Na-glucose co-transport via SGLT1 at the brush border membrane (BBM) of small intestinal villus cells. This process of transepithelial glucose uptake is the primary method of glucose absorption from diet. However, how ADS mediates the function of SGLT1 is not yet known. This study aims to determine the mechanism of regulation of SGLT1 by ADS in intestinal epithelial cells. We show that ADS from OZR (but not LZR) stimulates SGLT1 in IEC-18 cells. OZR-ADS treatment diminished Na/K-ATPase activity in IEC-18 cells. Kinetic studies indicated that the mechanism of stimulation for SGLT1 during OZR-ADS treatment was secondary to an increase in the affinity (1/K_m) of the co-transporter for glucose without a change in co-transporter number. Western blot studies revealed that SGLT1 protein expression was unaltered in the two groups, confirming our kinetic studies. Immunoprecipitation demonstrated that an increase in the affinity of the SGLT1 protein was mediated by altered phosphorylation. In conclusion, during obesity, the adipose tissue secretome stimulates SGLT1 in intestinal epithelial cells, leading to an increase in affinity for glucose. The affinity change is due to alterations in SGLT1 phosphorylation. Together, these results may provide important insight into the mechanisms underlying altered glucose homeostasis in obesity and how this may lead to the development of Type 2 diabetes mellitus. Full article

The natural resistance-associated macrophage proteins (NRAMPs) gene family represents a group of membrane transporter proteins with wide distribution in plants. This family of membrane transporters plays a pivotal role in mediating plant responses to metal stress by coordinating ion transport processes and maintaining cellular metal homeostasis, thereby effectively mitigating the detrimental effects of metal ion stress on plant growth and development. This study conducted a comprehensive genome-wide analysis of the NRAMP gene family in A. tauschii using integrated bioinformatics approaches, as well as the expression pattern when exposed to heavy metal-induced stress. By means of phylogenetic investigation, eleven AetNRAMP proteins were categorized into five distinct subgroups. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that the majority of NRAMP genes exhibited marked differential expression patterns under specific stress treatments. Subsequently, yeast cells were employed to validate the functions of AetNRAMP1 and AetNRAMP3. It was confirmed that AetNRAMP1 functioned in copper transport, and AetNRAMP3 showed an increase in its expression level under manganese stress. These findings establish a molecular foundation for elucidating the functional specialization of NRAMP gene family members in A. tauschii’s heavy metal detoxification pathways, providing critical genetic evidence for their stress-responsive regulatory networks. Nevertheless, significant knowledge gaps persist regarding its functions in A. tauschii. Research on metal stress resistance in this wheat progenitor species may establish a theoretical foundation for enhancing wheat tolerance and developing improved cultivars. Full article