Gene Expression Levels Research Articles (Page 1)

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a low platelet counts and an increased risk of bleeding. Moreover, the apoptotic mechanisms of platelets may influence their production and lifespan. To assess the involvement of apoptotic markers-specifically the B-cell lymphoma protein 2 family proteins Bak and Bcl-Xl in the pathogenesis of acute primary ITP in pediatric patients, and to evaluate the impact of intravenous immunoglobulin (IVIG) therapy on their expression. This study included 24 children with acute primary ITP and 30 healthy controls. Patients were enrolled from the Hematology and Oncology Unit of Menoufia University Hospitals, Egypt. Two peripheral blood samples were obtained from each participant: one prior to receiving IVIG therapy and the other after treatment. Platelet-rich plasma was isolated, and Bak and Bcl-Xl gene expression levels were assessed using reverse transcription quantitative polymerase chain reaction. Before treatment, Bak gene expression and Bak/Bcl-Xl expression ratio were significantly higher in patients versus controls (P=0.001 and P<0.001, respectively), whereas Bcl-Xl gene expression was significantly lower (P=0.029). After treatment, Bak gene expression and the Bak/Bcl-Xl expression ratio decreased significantly (P<0.001 and P=0.001, respectively), whereas Bcl-Xl gene expression increased significantly (P<0.001). Pediatric patients with acute primary ITP exhibited a heightened proapoptotic state, as indicated by an increased Bak expression and Bak/Bcl-Xl expression ratio, as well as a reduced Bcl-Xl expression. IVIG therapy appears to mitigate this pro-apoptotic effect, suggesting its ability to restore platelet homeostasis.

GLP-1/GIP dual agonist tirzepatide alleviates mice model of Parkinson's disease by promoting mitochondrial homeostasis.

Enterotoxigenic Escherichia coli (ETEC) is one of the primary pathogenic bacteria causing intestinal diseases and diarrhea in young animals. Probiotics can enhance intestinal barrier function and alleviate the occurrence of intestinal diseases and diarrhea by regulating the composition and metabolic products of the gut microbiota. In preliminary studies, we isolated a strain of Lactobacillus reuteri L81 with good probiotic properties from the rectal feces of healthy calves. This strain was found to alleviate weaning diarrhea in calves and improve immune function and antioxidant capacity. However, it remains unclear whether it can mitigate intestinal barrier damage caused by Escherichia coli K99 by regulating the composition of the gut microbiota and its metabolites. Therefore, this study selected 24 male SPF-grade ICR mice aged 4 weeks, randomly divided into 4 groups (n = 6): control group, ETEC group, low-dose Lactobacillus reuteri L81 group (L_L81 group), and high-dose Lactobacillus reuteri L81 group (H_L81 group). From days 1 to 17 of the experiment, the L_L81 and H_L81 groups were gavaged with 0.2 mL of bacterial suspensions at concentrations of 1 × 10⁸ CFU/mL and 1 × 10⁹ CFU/mL daily, respectively, while the control and ETEC groups were given an equal volume of physiological saline. From days 18 to 22, the ETEC, L_L81, and H_L81 groups were infected daily with 0.2 mL of an ETEC K99 bacterial suspension at a concentration of 5 × 10⁹ CFU/mL, whereas the control group continued to receive physiological saline. The results showed that the intervention of Lactobacillus reuteri L81 could regulate the gene expression levels of tight junction proteins in the colon tissue of mice. Moreover, the intervention with H_L81 group could increase the gene expression levels of Claudin-1 and ZO-1 ( P < 0.05) in the colon tissue of mice. The intervention with L_L81 group can inhibit the expression of IL-1β, MyD88, and TLR4 genes in the colon tissue of mice. The analysis of gut microbiota composition revealed that the intervention with Lactobacillus reuteri L81 exhibited a trend toward increasing microbial richness and diversity. It elevated the relative abundances of Lactobacillus, Prevotellaceae_UCG-001, and Gordonibacter in the mouse colon, while reducing the relative abundance of Salmonella. The non-targeted metabolomics analysis indicated that the intervention with Lactobacillus reuteri L81 has regulatory effects on multiple metabolic pathways, including bile secretion, β-alanine metabolism, glutathione metabolism, and arginine and proline metabolism. In conclusion, Lactobacillus reuteri L81 can alleviate intestinal barrier damage induced by ETEC K99 in mice by modulating the composition and metabolites of the gut microbiota.

Aging leads to various changes in nervous system functions. Older humans and animals exhibit altered movement patterns and experience alterations in memory and motor functions. Rodent models, particularly aged C57BL/6 mice, have been instrumental in studying behavioral and neurophysiological changes associated with aging. This study aimed to characterize age-related cognitive and motor decline and examine its association with molecular changes in a physiologically aged murine model. For this purpose, female C57BL/6Cenp mice aged 2, 20, and 26 months were used. Several behavioral tests were conducted to evaluate motor and cognitive functions. Additionally, gene expression levels were analyzed in prefrontal cortex and hippocampus samples. Twenty-month-old mice exhibited reduced muscle strength, altered gait patterns, impaired balance on the rotarod test, and deficits in spatial reference memory as assessed by the Barnes maze. Motor function further deteriorated in senescent mice (26-month-old), accompanied by spatial memory impairment as assessed using forced Y-maze test. Moreover, significant changes were observed in the expression of genes associated with synaptic plasticity (ARC, CREB1), neuronal activity (FOS), myelination (OLIG1, MAL), and oxidative stress (CYBA, CYBB, NCF1). These findings confirm that aging is a complex phenomenon marked by progressive cognitive and motor impairments, driven by molecular changes in brain regions involved in critical functions such as motor processes and cognition.

Drought is the major abiotic stress threatening global crop yields, thus identifying potential candidates with promising breeding value has become a central goal of current breeding programmes. Here, we found that miR164b functions as a negative regulator in plant drought tolerance, whose expression is dramatically inhibited under drought stress. Overexpressing MIR164b reduced the drought tolerance, while STTM164 transgenic seedlings showed enhanced drought tolerance in foxtail millet. We further identified that NAC (NAM-ATAF1/2-CUC2) transcription factor SiNAC015 was a target of miR164b. The sinac015 mutants showed attenuated drought tolerance, whereas overexpressing mSiNAC015 (miR164b-resistant version) improved drought tolerance in foxtail millet. Genetic evidence indicated that SiNAC015 could function in the same pathway as miR164b to mediate drought response by directly repressing the expression levels of SitPRX genes, which encoded peroxidase (POD) involved in reactive oxygen species (ROS) scavenging. Additionally, the superior SiNAC015Hap1 possessing higher SiNAC015 expression was found to be associated with enhanced drought tolerance in foxtail millet. Collectively, our study reveals that the miR164b-SiNAC015 module mediates drought stress response and provides a valuable genetic resource for drought-resistant breeding in foxtail millet.

To explore whether mouse short interspersed nuclear element B1 antisense RNA (B1 antisense RNA, B1 asRNA) could improve the proliferation activity and killing tumor function of spleen lymphocytes from aged mice and to investigate the underlying mechanisms, we transfected B1 asRNA into spleen lymphocytes isolated from12-month-old mice. We found that B1 asRNA substantially increased the proliferative rate of lymphocytes, the number of EdU-positive cells and the number of S phase cells. B1 asRNA decreased the apoptosis of lymphocytes and regulated the mRNA expression levels of senescence-related genes and transcription factor genes. B1 asRNA enhanced the ability of killing S180 and H22 tumor cells of lymphocytes. The immunofluorescence results showed that B1 asRNA increased the fluorescence intensity of ZFP92 protein in the nuclei, and the ChIP-qPCR results indicated that B1 asRNA promoted the binding of ZFP92 protein to DNA sequences of Nanog, Oct4, Sox2, Klf4 and Myc genes. We believe that B1 asRNA regulates the expression of senescence-related genes, cell cycle genes and transcription factor genes and that ZFP92 protein may play an important role in the process of B1 asRNA regulating gene expression. These studies suggest that B1 asRNA can enhance immune functions of senescent lymphocytes.

Front-line treatment for psoriatic arthritis (PsA) often involves the use of tumour necrosis factor alpha (TNFα) blocking medications (tumour necrosis factor alpha inhibition [TNFi]). However, more than 40% of patients exhibit inadequate responses, and there is no predictive clinical test available. Our goal is to investigate whether the response to TNFi treatment is associated with TNFα receptor 2 (TNFR2) rs1061622 polymorphic variants, TNFR2-M or TNFR2-R, in PsA. Furthermore, to elucidate the underlying mechanisms, differences in cell signalling and gene expression conferred by TNFR2-M vs TNFR2-R were examined. TNFR2 rs1061622 polymorphism status of 164 patients was assessed using restriction fragment length polymorphisms analysis. Discontinuation of the TNFi agents <12 months due to inadequate efficacy determined by chart review was the primary outcome. Human endothelial cells expressing endogenous or recombinant TNFR2-M or TNFR2-R and Jurkat T cells expressing recombinant TNFR2-M or TNFR2-R were utilised to investigate differences in cell signalling and gene expression. Patients with PsA with TNFR2-R variant had a ∼5-fold increased likelihood of discontinuing TNFi therapy <12 months, vs TNFR2-M carriers (95% CI 1.98-12.78). The cells with TNFR2-R alleles showed higher levels of proinflammatory gene expression in the absence of TNFa stimulation (P < .01). This activity of TNFR2-R was unaffected by a TNFα-neutralising antibody, whereas blocked by a Rho kinase (ROCK)-specific inhibitor. TNFR2 rs1061622 polymorphism significantly influences TNFi therapy responsiveness in PsA. The TNFα-independent, but ROCK activity-dependent gain-of-function activity conferred by TNFR2-R variant potentially serves as a mechanism underlying inadequate responses to TNFi in a subset of patients with PsA.

Regulators of G protein signaling (RGSs) are key modulators of β-cell function and stress adaptation. Similarly, circadian clock components are intricately implicated in the regulation of insulin secretion and β-cell physiology. However, their responses to sustained cellular stimulation under depolarizing conditions remain incompletely understood. We used MIN6 cells subjected to prolonged potassium chloride (KCl) exposure to induce sustained membrane depolarization, mimicking conditions of chronic β-cell stimulation. We analyzed the expression levels of Rgs and core clock genes, and assessed associated changes in cellular stress and differentiation markers. KCl treatment led to the upregulation of endoplasmic reticulum (ER) stress markers, including Chop and Atf4, without inducing oxidative stress. Expression of Rgs2, Rgs4, and Rgs16 was elevated. RGS2 partially co-localized with eIF2α, suggesting a role in translational control during stress. Furthermore, KCl-induced depolarization was associated with characteristic changes in β-cell differentiation markers and disallowed genes, indicative of a dedifferentiation-like state. Transcript levels of several circadian genes were altered, including significant downregulation of Dbp and upregulation of its repressor E4bp4. Notably, Dec1, a clock gene known to be inducible by various external stimuli, was also upregulated, suggesting broader circadian disruption under depolarizing conditions. Sustained membrane depolarization induces ER stress and transcriptional remodeling in MIN6 β-cells, including the modulation of RGS proteins and key circadian regulators such as DBP, E4BP4, and DEC1. These alterations may contribute to functional impairment and a dedifferentiation-like state of β-cells under chronic stimulatory conditions.

This study aims to identify the phytochemical components of Weiweisu (WWS) decoction, evaluate its therapeutic potential for chronic atrophic gastritis (CAG), and elucidate the underlying mechanisms with a focus on antiferroptotic effects. Liquid chromatography-mass spectrometry was used to characterize the phytochemical constituents of WWS. Network pharmacology was applied to predict potential therapeutic targets and signaling pathways. Core compounds and targets were verified through molecular docking and molecular dynamics simulations. Subsequently, a CAG rat model was established. Enzyme-linked immunosorbent assay was used to measure levels of prostaglandins (pepsinogen I/II) and tumor necrosis factor-α in gastric tissue, while Fe2+, glutathione, and malondialdehyde concentrations were assessed. Gene and protein expression levels of key targets were analyzed using quantitative real-time polymerase chain reaction and western blotting. A total of 1017 chemical constituents were identified via liquid chromatography-mass spectrometry. Network pharmacology revealed 20 ferroptosis-related genes associated with WWS and CAG, primarily involving cancer-related signaling pathways. In vivo experiments showed that WWS ameliorated gastric ulcers and mucosal atrophy, downregulated pepsinogen I/II and tumor necrosis factor-α levels, reduced Fe2+ and malondialdehyde concentrations, and increased glutathione levels. WWS treatment also elevated HSP90AA1, MAPK, and mTOR expression while inhibiting GPX4 expression. Molecular docking indicated strong binding affinities between key active compounds and core targets. Molecular dynamics simulations confirmed the stability of these interactions. In summary, WWS decoction can treat CAG through antiferroptosis, and its main mechanism may be related to the regulation of tumor signaling pathways.

Background: Fusarium oxysporum is a soil-borne pathogen and a very common cause of tomato root rot. This pathogen infects the plant’s vascular system, contributing to wilting, stunted growth and stunted growth. Methods: The determination of the minimum inhibitory concentration (MIC) of clove extract against Fusarium oxysporum was used to assess test its antimicrobial activity. The results indicated that the clove extract was effective at low concentrations, inhibiting the growth of a significant proportion of fungal isolates. However, higher concentrations showed a low inhibitory effect. Although these concentrations were sufficient to inhibit growth, they did not lead to complete cell death. Therefore, there is an urgent need to find alternative solutions to combat Fusarium wilt in tomato plants. Clove oil, extracted from the buds of the aromatic Syzygium tree, is known for its antimicrobial and antifungal properties. It contains eugenol, a natural compound that exhibits strong fungicidal activity against various plant pathogens. Previous research has indicated that gene expression of this gene is increased in response to infection with the fungus Fusarium oxysporum. Rusult: In this study, we aimed to investigate the effect of clove oil treatment on the expression of the Xly gene in tomato plants infected with Fusarium wilt. The plants were treated and the expression levels of the Xly gene were measured using quantitative polymerase chain reaction (qPCR) at different time points after treatment. Preliminary results indicate a significant increase in the expression of the Xly gene in tomato plants infected with Fusarium oxporum. However, when the Fusarium-infected tomato plants were treated with clove oil, the expression levels of the Xly gene were found to be significantly lower than in the control group. This finding suggests that clove oil treatment may help modify the defense response of tomato plants and possibly mitigate the effects of Fusarium wilt. The results of this study provide valuable insights into the potential use of clove oil as a natural and environmentally friendly alternative to chemical fungicides in preventing Fusarium wilt in tomato crops. The decreased expression of the Xly gene suggests that treating plants with clove oil may combat the spread of the disease and help them resist Fusarium oxysporum.

Systemic sclerosis is an autoimmune rheumatic disorder characterized by uncontrolled fibroblast activation, skin thickening, and fibrosis. Activated Ras and ERK signaling significantly affect fibrosis and EMT upon TGF-β treatment. RalGDS may play an important role in inflammatory and oncogenic processes. This study investigates the expression of RAF and RalGDS genes in SSc patients compared to healthy individuals before and after treatment with TGF-β. This research included 20 patients with systemic sclerosis and 18 healthy controls matched for age and sex. Skin biopsies were collected, and fibroblasts were grown and expanded. The identity of fibroblasts was confirmed using immunofluorescence labeling. Fibroblasts were subjected to TGF-β1 treatment, and the expression levels of A-RAF, B-RAF, C-RAF, and RalGDS genes were assessed via real-time PCR. Gene expression analysis revealed no significant baseline changes in RAF and RalGDS between groups; however, TGF-β therapy dramatically raised both genes in SSc cells relative to controls. A positive association was identified between the expression levels of the RAF and RalGDS genes. This study investigated A-RAF, B-RAF, C-RAF, and RalGDS gene expression in fibroblasts from SSc patients and healthy controls, focusing on their response to TGF-β treatment. While baseline expression levels were similar between groups, TGF-β significantly upregulated these genes in SSc fibroblasts more than in controls. This suggests that TGF-β signaling may contribute to the dysregulation of RAF and RalGDS pathways in SSc, highlighting their potential as biomarkers and therapeutic targets for the disease. Key Points • No significant difference in gene expression levels between SSc and healthy fibroblasts. • SSc and healthy fibroblasts exhibit upregulated RAF and RalGDS expression at the mRNA level in response to TGF-β treatment. • Positive correlation between the expression levels of A-RAF and B-RAF, B-RAF and C-RAF, and finally between C-RAF and RalGDS genes.

Diabetic foot ulcers (DFU) have become a global health issue. Chronic inflammation is a key pathological feature of DFU; however, its role in the diagnosis of DFU remains unclear. DFU sample data were acquired from public databases, and weighted gene co-expression network analysis (WGCNA) was employed to identify key genes associated with DFU traits. A protein-protein interaction (PPI) network was constructed to screen for diagnostic biomarkers, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy of these key genes. The non-negative matrix factorization algorithm was applied to classify DFU samples. To further investigate the potential molecular mechanisms of these diagnostic genes, single-gene functional enrichment analysis, single-sample gene set enrichment analysis (ssGSEA) for immune infiltration, and construction of upstream transcription factor regulatory networks were conducted. Four feature genes (FOSL1, HBEGF, S100A12, and TICAM1) demonstrating diagnostic potential were identified. ROC curve analysis validated these genes as potential diagnostic biomarkers for DFU. Functional enrichment analysis indicated that these genes are predominantly involved in biological processes related to keratinization and differentiation of epidermal skin cells. Furthermore, the expression levels of these feature genes exhibited a significant negative correlation with the infiltration levels of most immune cells. The regulatory network of upstream transcription factors highlighted the interconnectedness of these feature genes. This study identified DFU diagnostic genes linked to the inflammatory response, revealing their distinct transcriptional profiles and functional enrichment. These discoveries advance understanding of DFU pathology and provide a theoretical foundation for early diagnosis and treatment.

Introduction Focal segmental glomerulosclerosis (FSGS) is a serious disease that culminates in kidney failure. Today, FSGS is diagnosed histologically as a progressive scarring of the glomeruli due to gradual loss or damage of the podocyte layer, making it one of the main targets of FSGS therapeutic approaches. However, given that podocytes are terminally differentiated, post mitotic epithelial cells with limited proliferative capacity, they are considered one of the most vulnerable components of the glomeruli. Aim and Methods We herein investigated the effect of trehalose, a naturally occurring sugar with low toxicity and high stability, on kidney function using a murine model of adriamycin‐induced nephropathy. Results Based on our data, trehalose administration improved proteinuria in mice with FSGS compared to those without FSGS induction (24 h urine protein of 0.30±0.06 versus 0.55±0.08, p-value&amp;lt;0.05, and urine protein to creatinine ratio of 0.78±0.25 versus 1.56±0.17, p-value&amp;lt;0.05, respectively this is accompanied by reduced fibrosis and podocyte damage. Significant reduction in collagen deposition in glomeruli observed in mice treated with trehalose, P-value&amp;lt;0.01 and significant reduction in glomerular basement membrane thickness, P-value&amp;lt;0.001. Moreover, trehalose intake is associated with higher mature podocyte markers at gene and protein expression levels, Nphs1, Nphs2 and Synpo. These favorable effects seem to be mediated mainly via increased WT-1/EZH2 signaling, which is a key pathway in maintaining normal podocyte function and growth. These effects were also observed in the downstream signaling pathway with lower expression of Mmp-7 and Catenin b1 gene expression (p-value&amp;lt;0.05 and &amp;lt;0.01, respectively). Conclusion Our findings suggest that trehalose could be a promising therapeutic agent for FSGS, nevertheless, more studies are necessary to confirm our findings and evaluate trehalose efficacy in clinical settings.

Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with non-small-cell lung cancer (NSCLC), but the cure rate remains low because tolerant persister cancer cells can survive within the tumor during ICI treatment. We have previously reported that plasminogen activator inhibitor-1 (PAI-1) is involved in tolerance acquisition to osimertinib in epidermal growth factor receptor-mutated NSCLC. This study aimed to examine the role of PAI-1 in ICI tolerance and whether PAI-1 may be a therapeutic target to overcome this tolerance. In a mouse subcutaneous tumor model using Lewis lung carcinoma or KLN205 cells, cancer cells surviving within the tumor 7 days after anti-programmed death-1 (aPD-1) antibody treatment were defined as aPD-1 antibody-tolerant persister cells (aPD-1-TPs). PAI-1 and mesenchymal gene expression levels were higher in aPD-1-TPs than in control cells. Immunohistochemical analyses showed higher numbers of tumor-associated macrophages (TAMs), expression of programmed death-ligand 1 (PD-L1) in cancer cells, and degree of angiogenesis. In contrast, the number of tumor-infiltrating lymphocytes (TILs) was lower in aPD-1 antibody-tolerant tumors than in control tumors. Combination treatment with an aPD-1 antibody and the PAI-1 inhibitor TM5614 decreased mesenchymal gene expression, PD-L1 expression, TAM numbers, and angiogenesis and increased TIL counts in tolerant tumors. Furthermore, it resulted in prolonged inhibition of tumor growth. In conclusion, this study underscores the involvement of PAI-1 in the survival of aPD-1-TPs via epithelial-mesenchymal transition and alteration of the tumor microenvironment. Combination treatment with an aPD-1 antibody and TM5614 can be a new therapeutic strategy for NSCLC.

Strawberry (Fragaria × ananassa Duch.) is an important crop in the world. Environmental fluctuations have a significant impact on the growth of strawberries. Photoconversion films can change the environment of facility crops to increase production and improve quality. Therefore, this study investigated the effects of rare earth light conversion films (RPOs) on strawberry cultivation. The temperature, photosynthetic photon flux density, light transmittance and proportion of spectra beneficial to the crop production of RPO greenhouses were all greater than those of the control. Compared with those of the control, spongy tissues were sparser in RPO1 and RPO2 leaves. The cross-sectional surface area of the main vascular bundles of strawberry petioles treated with RPO1 and RPO2 increased slightly. Compared with those of the control, net CO2 assimilation, stomatal conductance, activity of Rubisco and gene expression levels of RPO1 and RPO2 were all increased, and the intercellular CO2 concentration was decreased. Compared with those of the control, yield, soluble solids, soluble sugar content, Vc content, and flavonoid contents of RPO1 and RPO2 increased, while the soluble protein content decreased. In conclusion, RPO promotes photosynthesis in strawberry plants by optimizing photosynthetic photon flux density, spectrum and temperature in greenhouses; adjusting the spectrum to change pigment content, spongy tissue structure, petiole vascular bundles, and Rubisco activity; and regulating the expression of the Rubisco gene, thereby increasing the quality and yield of strawberry plants. Compared with RPO1, RPO2 could be a more suitable film for strawberry production.

Mesenchymal Stem Cells Conditioned Media-Chitosan Nanoparticles against Clinical Carbapenem-Resistant Acinetobacter Baumannii: In-Vitro Study.

Obesity is a risk factor for various diseases. The prevalence of obesity is increasing in cats. The present study aimed to characterize adipose gene expression to obtain basic information for obesity prevention in feline adipose tissues. Visceral fat, subcutaneous fat, or both fat depots were collected from 81 hospitalized cats. The multivariate analysis of covariance revealed that sex and IGF-1 were involved in regulating body condition score (BCS), showing adiposity in both fat depots. BCS was positively and negatively regulated by expression levels of inflammation-related genes in visceral fat, respectively. In addition, subcutaneous Lep expression positively regulated BCS. Positive correlations between gene expression levels were generally detected within the same fat depot, whereas expression levels of genes in visceral fat were less related to those in subcutaneous fat, except for the same gene. Expression levels of Ucp1 were most variable among individuals in visceral fat but not in subcutaneous fat. The extent of individual variability on expression levels in cats was similar to that in the previous results using dogs. Genes related to mitochondrial respiration and uncoupling were relatively variable among individuals. The present study suggests that feline energy metabolism in adipose tissues is finely tuned in a fat depot-dependent manner. In addition, genes related to mitochondrial respiration and uncoupling may be a target for the control of systemic energy status because they can be potentially regulated by every individual.

BK polyomavirus (BKPyV) establishes latent human infections, with reactivation linked to the cellular immune response, particularly in kidney transplant recipients (KTRs). Circular RNAs (circRNAs) and microRNAs (miRNAs), classes of noncoding RNAs, are involved in the pathogenesis of kidney diseases and viral infections. CircRNAs act as miRNA "sponges," diminishing miRNA functions. This study explores the relationship between BKPyV infection and circ-EGLN3 and circ-AKT3, their miRNA targets (miR-1299, miR-296-3p), and their linear counterparts (EGLN3, AKT3), along with miRNA targets (IRF7, CDH1). This cross-sectional study included 20 KTRs, divided into 10 BKPyV-infected and 10 non-infected individuals, with an additional control group of 20 healthy individuals. Expression levels of circRNAs, parental genes, and target miRNAs were assessed in blood and urine samples using SYBR Green real-time PCR. In KTRs with active BKPyV infection, circ-AKT3 and circ-EGLN3 levels were significantly reduced, while their target miRNAs were elevated in both blood and urine compared to non-infected KTRs. ROC curve analysis demonstrated that these circRNAs could significantly differentiate BKPyV-infected individuals from non-infected groups. This research has established the significance of circular RNAs, particularly circ-AKT3 and circ-EGLN3, and suggests that with additional investigation, these molecules may serve as biomarkers for active BKPyV infection in KTRs, thereby improving the comprehension of BKPyV reactivation. Not applicable.

Serotonin (5-hydroxytryptamine) is a key neurotransmitter involved in gastrointestinal and central nervous system functions. Given that approximately 90% of serotonin is synthesized in the gut, dietary interventions targeting the gut microbiota have emerged as promising strategies to modulate serotonin homeostasis. Kefir, a fermented milk beverage rich in probiotics and bioactive compounds, has been suggested to influence gut–brain axis signaling, yet its effects in the pediatric period remain insufficiently characterized. This study aimed to investigate the impact of kefir supplementation on serotonin biosynthesis, receptor expression, and metabolic pathways in a pediatric rat model, focusing on molecular markers across brain, jejunum, and serum tissues. Sixteen male Wistar rats (four weeks old) were divided into kefir and control groups. The kefir group received daily oral gavage of kefir (1 mL/100 g) for eight weeks, while controls received saline. Gene and protein expression levels of serotonergic markers (5-HT, TPH1, TPH2, SLC6A4, VMAT2, 5-HTR2B, 5-HTR3A, and 5-HTR4) were analyzed using quantitative PCR, ELISA, and Western blotting. Serotonin turnover was assessed via 5-HIAA levels. Kefir supplementation significantly increased 5-HT and TPH1 expression in both brain and jejunum tissues. In the brain, kefir elevated TPH2 and upregulated 5-HTR3A and 5-HTR2B, while reducing 5-HIAA levels, suggesting decreased serotonin degradation. In the jejunum, 5-HTR4 expression was markedly increased. Serum analyses revealed reduced TPH1/TPH2 expression but elevated 5-HTR4 levels, indicating systemic modulation of serotonergic signaling. Kefir exerts multifaceted effects on the serotonergic system in pediatric rats by enhancing serotonin biosynthesis, modulating receptor expression, and reducing serotonin turnover. These findings highlight kefir as a potential psychobiotic capable of influencing the gut–brain axis during early life, with implications for pediatric neurodevelopment and mental health. Further research, including clinical trials, is warranted to confirm its translational potential.

Increasing evidence has indicated that metabolic syndrome (MetS) exists in a close link with sarcopenia; however, the potential mechanism and biomarkers between them remain uninvestigated. This study leverages integrative genetics and transcriptome to identify potential biomarkers and immune interactions in MetS-related sarcopenia. We used genome-wide association studies summary statistics for linkage disequilibrium score regression and MiXeR analyses to explore shared genetic architecture between MetS and sarcopenia-related traits. Causal associations were assessed via Mendelian randomization (MR), causal analysis using the summary effect, and summary data-based MR. Cross-phenotype association analysis identified pleiotropic variants, while transcriptome-wide association study revealed shared pleiotropic genes. Single-cell RNA sequencing mapped gene distribution across immune cells and intercellular communication. A clinical predictive model and MetS animal model validated the pleiotropic genes. LDSC analyses uncovered an aggregate group of 13 pairs demonstrating notable genetic correlations. A significant genetic overlap took place between MetS and sarcopenia-related traits. The causal association of MetS with WP and ALM were found. Furthermore, we determined 79 shared risk novel SNPs and 9 pleiotropic genes. These genes had a strong connection to immune cell infiltration, immune-related markers, and immun-related processes. We demonstrated varying levels of gene expression across different immune cell types using scRNA-seq data. Nine genes were selected for developing a clinical predictive model. For the predictive chart used to predict binary risks, the area under the curve in the training data was 0.75, and in the validation data it was 0.72. Finally, five genes were confirmed in the MetS animal model based on mRNA expression level. This research offers compelling proof of a shared genetic architecture and uncovered immune interactions between MetS and sarcopenia. Our unique innovation reveals the comorbidity mechanism of metabolic syndrome and sarcopenia from a genetic perspective. The discovery of pleiotropic genes provided potential targets for intervention in MetS-related sarcopenia.