[Changes in T helper lymphocytes and their subsets in children with tic disorders].

OBJECTIVE: To explore the changes in T helper lymphocytes and their subsets in children with tic disorders (TD) and their clinical significance. METHODS: Flow cytometry was used to measure the percentages of T helper lymphocytes and their subsets in the peripheral blood of children with TD and healthy children (controls). RESULTS: The percentage of T helper lymphocytes was significantly lower in the TD group than in the control group (P<0.001). The abnormal rate of T helper lymphocytes in the TD group was significantly higher than that in the control group (68.7% vs 18.8%; P<0.001). The percentage of T helper lymphocytes was negatively correlated with Yale Global Tic Severity Scale score (r=-0.3945, P<0.001). As for the subsets of T helper lymphocytes, the TD group had a significantly higher percentage of Th1 cells and a significantly lower percentage of Th2 cells compared with the control group (P<0.001). CONCLUSIONS: The abnormality of T helper lymphocytes and the imbalance of their subsets may be associated with the pathogenesis of TD in children. The percentage of T helper lymphocytes can be used as an indicator for assessing the severity of TD.

Shen Qi Wan ameliorates nephritis in chronic kidney disease via AQP1 and DEFB1 regulation.

Shen Qi Wan (SQW) has been proven to exert anti-inflammatory effects in the kidneys of CKD models accompanied by unclear therapeutic mechanisms. This study aims to evaluate the kidney-protective and anti-inflammatory effects of SQW and to elucidate its fundamental mechanisms for CKD treatment. Firstly, the main active components of SQW were identified by UPLC-Q-TOF/MS technique. Subsequently, we evaluated inflammatory factors, renal function and renal pathology changes following SQW treatment utilizing adenine-induced CKD mice and aquaporin 1 knockout (AQP1-/-) mice. Additionally, we conducted RNA-seq analysis and bioinformatics analysis to predict the SQW potential therapeutic targets and anti-nephritis pathways. Simultaneously, WGCNA analysis method and machine learning algorithms were used to perform a clinical prognostic analysis of potential biomarkers in CKD patients from the GEO database and validated through clinical samples. Lipopolysaccharide-induced HK-2 cells were further used to explore the mechanism. We found that renal collagen deposition was reduced, serum inflammatory cytokine levels decreased, and renal function was improved after SQW intervention. It can be inferred that ß-defensin 1 (DEFB1) may be a pivotal target, as confirmed by serum and renal tissue samples from CKD patients. Furthermore, SQW assuages inflammatory responses by fostering AQP1-mediated DEFB1 expression was confirmed in in vitro and in vivo studies. Significantly, the renal-protective effect of SQW is to some extent attenuated after AQP1 gene knockout. SQW could reduce inflammatory responses by modulating AQP1 and DEFB1. These findings underscore the potential of SQW as a promising contender for novel prevention and treatment strategies within the ambit of CKD management.

Empagliflozin alleviates neuroinflammation by inhibiting astrocyte activation in the brain and regulating gut microbiota of high-fat diet mice.

A high-fat diet can modify the composition of gut microbiota, resulting in dysbiosis. Changes in gut microbiota composition can lead to increased permeability of the gut barrier, allowing bacterial products like lipopolysaccharides (LPS) to enter circulation. This process can initiate systemic inflammation and contribute to neuroinflammation. Empagliflozin (EF), an SGLT2 inhibitor-type hypoglycemic drug, has been reported to treat neuroinflammation. However, there is a lack of evidence showing that EF regulates the gut microbiota axis to control neuroinflammation in HFD models. In this study, we explored whether EF could improve neuroinflammation caused by an HFD via regulation of the gut microbiota and the mechanism underlying this phenomenon. Our data revealed that EF alleviates pathological brain injury, reduces the reactive proliferation of astrocytes, and increases the expression of synaptophysin. In addition, the levels of inflammatory factors in hippocampal tissue were significantly decreased after EF intervention. Subsequently, the results of 16S rRNA gene sequencing showed that EF could change the microbial community structure of mice, indicating that the abundance of Lactococcus, Ligilactobacillus and other microbial populations decreased dramatically. Therefore, EF alleviates neuroinflammation by inhibiting gut microbiota-mediated astrocyte activation in the brains of high-fat diet-fed mice. Our study focused on the gut-brain axis, and broader research on neuroinflammation can provide a more holistic understanding of the mechanisms driving neurodegenerative diseases and inform the development of effective strategies to mitigate their impact on brain health. The results provide strong evidence supporting the larger clinical application of EF.

Prevalence of periodontal disease in middle-aged and elderly patients and its influencing factors.

OBJECTIVE: To explore the prevalence of periodontal disease in middle-aged and elderly patients and analyze its influencing factors. METHODS: A total of 521 patients admitted to the Department of Stomatology of Fuyang District Chinese Medicine Hospital of Hangzhou from January 2019 to January 2022 were retrospectively collected as study subjects, including 176 patients aged 35-44 years old, 175 patients aged 45-64 years old, and 170 patients aged 65-74 years old. Community Periodontal Index (CPI) probe was used to detect gingival bleeding, periodontal pockets and attachment loss, and the prevalence of periodontal disease and its influencing factors were analyzed. RESULTS: In the age group of 35-44, gingival bleeding was detected in 165 (93.75%) cases and dental calculus was detected in 176 (100.00%) cases; in the age group of 45-64, gingival bleeding was detected in 163 (93.14%) cases and dental calculus was detected in 161 (92.00%) cases; in the age group of 65-74, gingival bleeding was detected in 150 (88.24%) cases and dental calculus was detected in 162 (95.29%) cases. There were statistically significant differences in the detection rates of shallow periodontal pockets, deep periodontal pockets, and loss of periodontal attachment among the three groups (P<0.05). There wasalso asignificant difference in the detection rate of periodontitis among the three groups (P<0.05). Univariate analysis showed that gender, age, place of residence, smoking, alcohol consumption, brushing frequency, and dental cleaning in the past year were all associated with the occurrence of periodontitis (P<0.05). Logistic multi-factor regression analysis showed that age was a risk factor for the development of periodontitis in middle-aged and elderly patients (P<0.05). CONCLUSION: The prevalence of periodontal disease in middle-aged and elderly individuals is high, with a high prevalence of gingival bleeding and shallow periodontal pockets. Age is an influencing factor on the incidence of periodontitis in middle-aged and elderly individuals.

The Food Additive ß-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway.

Despite extensive research on Alzheimer's disease (AD), its diagnosis and treatment remain challenging, and no effective therapies are currently available. Amyloid ß (Aß) extracellular plaques and intracellular neurofibrillary tangles are the histological characteristics of AD that have been directly linked to neuropathological events such as synaptic and neuronal cell loss. In this study, we explored whether the "JAK2-STAT3-BACE1" pathway is involved in neuroprotection conferred by the food flavouring agent ß-caryophyllene (BCP). PC-12 cells with overexpressed amyloid-ß protein precursor (APP) were utilised to construct an AD model in vitro, which was then split into four groups, namely control, empty vector, APP overexpression, and BCP (5, 10, and 20 µM). CCK-8 was used to evaluate cell viability, immunofluorescence was utilised to examine synaptic morphology, and quantitative real-time polymerase chain reaction and western blot were used to examine gene and protein expression levels. The relative expression levels of JAK2, STAT3, and BACE1 mRNA in the transfected PC-12 cells were found to be significantly upregulated. The cell morphology altered dramatically 72 h after transfection, becoming rounder, with a decrease in cell number. BCP exhibited the potential to dramatically increase PC-12 cell viability while protecting cell morphology. BCP inhibited APP, JAK2, STAT3, BACE1 mRNA and BACE1 protein overexpression, as well as JAK2 and STAT3 hyperphosphorylation. Molecular docking simulated the docking of BCP with JAK2, STAT3, BACE1, CB2. And JAK2 was found to be the most stable protein. In conclusion, inhibition of the "JAK2-STAT3-BACE1" signalling pathway may be one of the mechanisms through which BCP protects neurons and antagonises Aß's neurotoxicity.

Developmental expression and immune role of the class B scavenger receptor cd36 in zebrafish.

CD36 is a transmembrane glycoprotein belonging to the scavenger receptor class B family which plays crucial roles in innate immunity. Although CD36 is widely documented in mammals, the study of its functions in fish is still limited. Here we report the identification of a zebrafish cd36 homologue. Zebrafish cd36 has a higher gene expression in the tissues of intestine and liver but very low in kidney and swim bladder. We find cd36 mRNA is maternally expressed and is mainly restricted to the intestine, branchial arches and regions around the lips after the segmentation stage during embryogenesis. Functionally, the recombinant Cd36 corresponding to the large extracellular loop is capable of binding both the Gram-negative and Gram-positive bacteria. These results indicate that zebrafish Cd36 is a microbial-binding molecule. The study expands our knowledge of the function of scavenger receptor molecules in fish innate immune process.

A medium-chain fatty acid receptor Gpr84 in zebrafish: expression pattern and roles in immune regulation.

Gpr84 was recently identified as a receptor for medium-chain fatty acids, but its functions remain to be clarified. We reported the identification of a zebrafish Gpr84 homologue (zGpr84), which has a higher gene expression in the tissues of intestine, heart and liver. During embryogenesis, zGpr84 is maternally expressed and a significant increase is observed at segmentation period, and it is mainly restricted to the head region, pectoral fins, branchial arches, intestine and lateral line neuromast. Fasting or treatment with lipopolysaccharide (LPS) can induce significant up-regulation of zGpr84. We further demonstrated that zGpr84 is involved in the accumulation of lipid droplets in cells. Moreover, undecanoic acid (UA) can amplify LPS induced production of the proinflammatory cytokine IL-12 p40 through zGpr84, supporting the proposal that Gpr84 may play a role in directly linking fatty acid metabolism to immunological regulation. The resulting data in fish lay a foundation for a comprehensive exploration of the functions and evolution of Gpr84.

A novel galanin receptor 1a gene in zebrafish: tissue distribution, developmental expression roles in nutrition regulation.

Galanin (Gal), a 29 (30 in human) amino acid neuropeptide, exerts its biological activities through three different G protein-coupled receptors, namely GalR1, GalR2 and GalR3. However, we previously found that only GalR1 and GalR2 exist in fish, and fish GalR1 has two genes (GalR1a and GalR1b), with GalR1a possibly representing the primitive gene form during fish evolution. To uncover the functions of GalR1a in fish, here the tissue distribution, developmental expression and the role in nutrition regulation of GalR1a were investigated in zebrafish (Danio rerio). Interestingly, the expression of GalR1a mRNA was restricted to the intestine and brain in adult zebrafish, while GalR1b mRNA was present in all tissues tested. During embryogenesis, GalR1a mRNA was abundant at 1hpf (hour past fertilization) and decreased gradually in abundance from 3 hpf to 10 hpf; then a significant increase in the amount of GalR1a transcripts was observed at 35 hpf, and this high level was maintained until 5 dpf (day past fertilization). In situ hybridization of embryos and larvae, expression pattern of GalR1a was mainly restricted to the intestine, pectoral fin, branchial arches and head, indicating a role of GalR1a during zebrafish embryogenesis. Quantitative real-time PCR assay suggested that fasting, high fat feeding or linoleic acid (LA) all could significantly induce up-regulation of GalR1a both in vitro and in vivo, suggesting roles of GalR1a in control of nutrition intake, especially to fat. In addition, a potential role of zebrafish GalR1a in accumulation of lipid droplets in cells was also demonstrated. Our study lays a foundation for further investigation of GalR1a function and evolution in fish.