A Spike-destructing human antibody effectively neutralizes Omicron-included SARS-CoV-2 variants with therapeutic efficacy.

Neutralizing antibodies (nAbs) are important assets to fight COVID-19, but most existing nAbs lose the activities against Omicron subvariants. Here, we report a human monoclonal antibody (Ab08) isolated from a convalescent patient infected with the prototype strain (Wuhan-Hu-1). Ab08 binds to the receptor-binding domain (RBD) with pico-molar affinity (230 pM), effectively neutralizes SARS-CoV-2 and variants of concern (VOCs) including Alpha, Beta, Gamma, Mu, Omicron BA.1 and BA.2, and to a lesser extent for Delta and Omicron BA.4/BA.5 which bear the L452R mutation. Of medical importance, Ab08 shows therapeutic efficacy in SARS-CoV-2-infected hACE2 mice. X-ray crystallography of the Ab08-RBD complex reveals an antibody footprint largely in the ß-strand core and away from the ACE2-binding motif. Negative staining electron-microscopy suggests a neutralizing mechanism through which Ab08 destructs the Spike trimer. Together, our work identifies a nAb with therapeutic potential for COVID-19.

Prediction of blood-brain barrier penetrating peptides based on data augmentation with Augur.

BACKGROUND: The blood-brain barrier serves as a critical interface between the bloodstream and brain tissue, mainly composed of pericytes, neurons, endothelial cells, and tightly connected basal membranes. It plays a pivotal role in safeguarding brain from harmful substances, thus protecting the integrity of the nervous system and preserving overall brain homeostasis. However, this remarkable selective transmission also poses a formidable challenge in the realm of central nervous system diseases treatment, hindering the delivery of large-molecule drugs into the brain. In response to this challenge, many researchers have devoted themselves to developing drug delivery systems capable of breaching the blood-brain barrier. Among these, blood-brain barrier penetrating peptides have emerged as promising candidates. These peptides had the advantages of high biosafety, ease of synthesis, and exceptional penetration efficiency, making them an effective drug delivery solution. While previous studies have developed a few prediction models for blood-brain barrier penetrating peptides, their performance has often been hampered by issue of limited positive data. RESULTS: In this study, we present Augur, a novel prediction model using borderline-SMOTE-based data augmentation and machine learning. we extract highly interpretable physicochemical properties of blood-brain barrier penetrating peptides while solving the issues of small sample size and imbalance of positive and negative samples. Experimental results demonstrate the superior prediction performance of Augur with an AUC value of 0.932 on the training set and 0.931 on the independent test set. CONCLUSIONS: This newly developed Augur model demonstrates superior performance in predicting blood-brain barrier penetrating peptides, offering valuable insights for drug development targeting neurological disorders. This breakthrough may enhance the efficiency of peptide-based drug discovery and pave the way for innovative treatment strategies for central nervous system diseases.

Hypoxic nasopharyngeal carcinoma-derived exosomal miR-455 increases vascular permeability by targeting ZO-1 to promote metastasis.

Nasopharyngeal carcinoma (NPC), the most frequent reason for treatment failure in head and neck tumors, has the greatest incidence of distant metastases. Increased vascular permeability facilitates metastasis. Exosomal microRNAs (miRNAs) have been implicated in the development of the premetastatic niche and are emerging as prospective biomarkers in cancer patients. We discovered that a higher level of miR-455 was connected to a larger propensity for NPC metastasis based on deep sequencing and RT-qPCR. We found that hypoxia promoted NPC exosomes release and increased miR-455 expression in a way that was hypoxia-inducible factor 1-alpha (HIF-1α) dependent. Exosomes from NPC cells with high levels of miR-455 were found to specifically target zonula occludens 1 (ZO-1), increasing the permeability of endothelial monolayers in vitro vascular permeability and transendothelial invasion experiments. Additional in vivo studies showed that zebrafish with sustained miR-455-overexpressing NPC cell xenografts displayed increased tumor cell mass throughout the body. In vivo, zebrafish vascular tight junction integrity was disrupted by exosomes produced by NPC cells with elevated miR-455 expression. Mice-bearing xenografts further supported the finding that exosomes containing miR-455 might reduce ZO-1 expression in addition to promote NPC cell growth. These findings suggest that in a hypoxic microenvironment, exosomal miR-455 released by NPC cells enhances vascular permeability and promotes metastasis by targeting ZO-1. The HIF-1α-miR-455-ZO-1 signaling pathway may be a promising predictor and potential therapeutic target for NPC with metastasis.

Transcriptomic analysis revealed the dynamic response mechanism to acute ammonia exposure in the ivory shell, Babylonia areolata.

The ivory shell (Babylonia areolata) is an economically important shellfish in tropical and subtropical regions, but its intensive culture and biological characteristic of hiding in the sandy substrate make it highly susceptible to ammonia stress. In this study, we investigated the dynamic changes in histopathology, oxidative stress, and transcriptome of the ivory shell at different time points under high concentration (60 mg/L) ammonia exposure. With prolonged exposure to stress, vacuoles appeared in the hepatopancreas while cell volume and intercellular space increased. The activities of superoxide dismutase (SOD) and catalase (CAT) decreased significantly under high concentrations of ammonia-induced stress while malondialdehyde (MDA) levels increased significantly. Integrated analysis of differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that lipid transport primarily contributed to maintaining cellular homeostasis during the early stage of stress (6 and 12 h). Subsequently, a significant upregulation of oxidation-reduction reactions occurred at the middle stage (24 h), leading to oxidative stress. Finally, during the later stage (48 h), metabolic decomposition provided energy for survival maintenance. Additionally, lysosome and apoptosis were identified as potential key pathways in response to acute ammonia toxicity. Overall, our findings suggest that ivory shells can respond to acute ammonia toxicity via immune and antioxidant defense mechanisms but sustained high concentrations may cause irreversible damage. This study provides valuable insights into the response mechanism of mollusks towards ammonia and serves as a data reference for breeding ammonia-tolerant varieties of ivory shells.

Identification of adaptor proteins using the ANOVA feature selection technique.

The adaptor proteins play a crucially important role in regulating lymphocyte activation. Rapid and efficient identification of adaptor proteins is essential for understanding their functions. However, biochemical methods require not only expensive experimental costs, but also long experiment cycles and more personnel. Therefore, a computational method that could accurately identify adaptor proteins is urgently needed. To solve this issue, we developed a classifier that combined the support vector machine (SVM) with the composition of k-Spaced Amino Acid Pairs (CKSAAP) and the amino acid composition (AAC) to identify adaptor proteins. Analysis of variance (ANOVA) was used to select the optimized features which could generate the maximum prediction performance. By examining the proposed model on independent data, we found that the 447 optimized features could achieve an accuracy of 92.39% with an AUC of 0.9766, demonstrating the powerful capabilities of our model. We hope that the proposed model could provide more clues for studying adaptor proteins.

miRNASNP-v3: a comprehensive database for SNPs and disease-related variations in miRNAs and miRNA targets.

MicroRNAs (miRNAs) related single-nucleotide variations (SNVs), including single-nucleotide polymorphisms (SNPs) and disease-related variations (DRVs) in miRNAs and miRNA-target binding sites, can affect miRNA functions and/or biogenesis, thus to impact on phenotypes. miRNASNP is a widely used database for miRNA-related SNPs and their effects. Here, we updated it to miRNASNP-v3 (http://bioinfo.life.hust.edu.cn/miRNASNP/) with tremendous number of SNVs and new features, especially the DRVs data. We analyzed the effects of 7 161 741 SNPs and 505 417 DRVs on 1897 pre-miRNAs (2630 mature miRNAs) and 3'UTRs of 18 152 genes. miRNASNP-v3 provides a one-stop resource for miRNA-related SNVs research with the following functions: (i) explore associations between miRNA-related SNPs/DRVs and diseases; (ii) browse the effects of SNPs/DRVs on miRNA-target binding; (iii) functional enrichment analysis of miRNA target gain/loss caused by SNPs/DRVs; (iv) investigate correlations between drug sensitivity and miRNA expression; (v) inquire expression profiles of miRNAs and their targets in cancers; (vi) browse the effects of SNPs/DRVs on pre-miRNA secondary structure changes; and (vii) predict the effects of user-defined variations on miRNA-target binding or pre-miRNA secondary structure. miRNASNP-v3 is a valuable and long-term supported resource in functional variation screening and miRNA function studies.

Multidimensional fatigue in Chinese patients with newly diagnosed meningiomas: Prevalence, severity and associated factors.

OBJECTIVE: The purpose of this study was to explore the prevalence, severity, and factors associated with multidimensional fatigue in Chinese patients with newly diagnosed meningiomas. METHODS: This cross-sectional study included 120 Chinese meningioma patients. Data were collected before surgery, including demographic, clinical, psychological, and sleep characteristics, as well as fatigue scores based on completion of the Multidimensional Fatigue Inventory (MFI-20). Mann-Whitney U tests, Kruskal-Wallis H tests, Spearman correlation and multiple linear regression were used to analyze the data. RESULTS: The results showed there was a high prevalence of severe fatigue for each dimension: general fatigue (33.3%), physical fatigue (27.5%), reduced activity (28.3%), reduced motivation (12.5%), mental fatigue (11.7%), and total fatigue (23.3%). Headache and anxiety were found to be associated with general fatigue. Depression was related with physical fatigue. The Karnofsky Performance Status (KPS) score and depression were associated with reduced activity. Depression and the Epworth Sleepiness Scale (ESS) score were correlated with reduced motivation, while the KPS score and anxiety were associated with mental fatigue. Importantly, comorbidity, the KPS score, headache, depression, sleep disturbances, and the ESS score remained strong correlates of total fatigue. CONCLUSIONS: Our findings indicate that newly diagnosed meningioma patients are affected by multidimensional fatigue. For patients with risk factors of fatigue, targeted interventions are advised to decrease fatigue and improve HRQoL.

The Complete Mitochondrial Genomes of Two Rock Scallops (Bivalvia: Spondylidae) Indicate Extensive Gene Rearrangements and Adaptive Evolution Compared with Pectinidae.

Different from the diverse family Pectinidae, the Spondylidae is a small group with a single genus that shares the sedentary life habit of cementing themselves to the substrate. However, little information related to the genetic diversity of Spondylidae has been reported. In the present study, the complete mitochondrial genomes of Spondylus versicolor and S. spinosus were sequenced and compared with those of pectinids. The mtDNA of S. versicolor and S. spinosus show similar patterns with respect to genome size, AT content, AT skew, GC skew, and codon usage, and their mitogenomic sizes are longer than most pectinid species. The mtDNA of S. spinosus is 27,566 bp in length, encoding 13 protein-coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes, while an additional tRNA-Met was found in the mtDNA of S. versicolor, which is 28,600 bp in length. The monophylies of Spondylidae and Pectinidae were well supported, but the internal relationships within Pectinidae remain unresolved due to the paraphyly of the genus Mimachlamy and the controversial position of the tribe Aequipectinini. The gene orders of S. versicolor and S. spinosus are almost identical but differ greatly from species of the Pectinidae, indicating extensive gene rearrangements compared with Pectinidae. Positive selection analysis revealed evidence of adaptive evolution in the branch of Spondylidae. The present study could provide important information with which to understand the evolutionary progress of the diverse and economically significant marine bivalve Pectinoidea.

A study on the impact of the number of family generations on intergenerational support for centenarians: a study in a Chinese 'longevity city'.

BACKGROUND: As a natural source of support for the elderly, the family is an important channel for achieving a sense of security, happiness, and worthiness in old age. In this study, we analysed the characteristics of intergenerational support in families of centenarians and explored the impact of the number of family generations on intergenerational support. METHODS: We conducted a cross-sectional survey between April 2020 and January 2021 among 62 elderly people aged 99+ in Rugao, China, one of six 'longevity cities' in the world. Assisted by the researchers, centenarians completed questionnaires with details pertaining to general demographics, intergenerational support, and other aspects. We used a logistic regression model to analyse the influence of the number of family generations on intergenerational support that the centenarians received with respect to economic, living, and emotional aspects. RESULTS: Centenarians were primarily recipients of care in their families, and received intergenerational support mainly for their declined physical functions and limited self-care ability. The study results revealed that the greater the number of generations comprising the family, the greater was the intergenerational life care and emotional comfort provided for centenarians by the family. CONCLUSIONS: In this study, we found a positive effect of the number of family generations on intergenerational support for centenarians. The government and society should promote the tradition of respecting, caring for, and honouring the elderly while paying close attention to the dynamic changes in the family structure of centenarians in promoting high-quality and sustainable development of the people, economy, and society.

Prevalence, correlates, and impact of sleep disturbance in Chinese meningioma patients.

PURPOSE: Sleep disturbance is common in meningioma patients and may lead to disease aggravation and decreases health-related quality of life (HRQoL). However, the sleep quality of meningioma patients newly diagnosed and ready for surgery has not been well clarified in China. This study aims to evaluate the prevalence, correlates, and impact of sleep disturbance among Chinese meningioma patients. METHODS: In this cross-sectional study, meningioma patients were recruited from the Affiliated Hospital of Nantong University from January 2020 to November 2020. A series of questionnaires were applied: the 0-10 Numerical Rating Scale (NRS), the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Fatigue Inventory (MFI-20), the Epworth Sleepiness Scale (ESS), the Short-Form 36 (SF-36), the Pittsburgh Sleep Quality Index (PSQI). Independent samples t test, Mann-Whitney U test, chi-square analysis, Pearson/Spearman correlation, and binary logistic regression were used to analyze the data. RESULTS: One hundred meningioma patients completed the questionnaires. Sleep disturbance affected 43% of the meningioma patients and was linked to many concomitant symptoms, such as headache, fatigue, anxiety, and depression. Binary logistic regression indicated that fatigue and headache were independently associated with sleep disturbance of meningioma patients. Meanwhile, severe sleep disturbance led to lower quality of life. CONCLUSIONS: These findings demonstrated that a considerable number of meningioma patients newly diagnosed and ready for surgery suffered from sleep disturbance, potentially contributing to impair HRQoL. Medical personnel should pay more attention to meningioma patients with sleep disturbance and take effective measures to improve sleep quality, with the ultimate goal to improve their HRQoL.

Hydrogen sulfide as a potent scavenger of toxicant acrolein.

Acrolein (ACR) is a metabolic byproduct in vivo and a ubiquitous environmental toxicant. It is implicated in the initiation and development of many diseases through multiple mechanisms, including the induction of oxidative stress. Currently, our understanding of the body defense mechanism against ACR toxicity is still limited. Given that hydrogen sulfide (H2S) has strong antioxidative actions and it shares several properties of ACR scavenger glutathione (GSH), we, therefore, tested whether H2S could be involved in ACR detoxification. Taking advantage of two cell lines that produced different levels of endogenous H2S, we found that the severity of ACR toxicity was reversely correlated with H2S-producing ability. In further support of the role of H2S, supplementing cells with exogenous H2S increased cell resistance to ACR, whereas inhibition of endogenous H2S sensitized cells to ACR. In vivo experiments showed that inhibition of endogenous H2S with CSE inhibitor markedly increased mouse susceptibility to the toxicity of cyclophosphamide and ACR, as evidenced by the increased mortality and worsened organ injury. Further analysis revealed that H2S directly reacted with ACR. It promoted ACR clearance and prevented ACR-initiated protein carbonylation. Collectively, this study characterized H2S as a presently unrecognized endogenous scavenger of ACR and suggested that H2S can be exploited to prevent and treat ACR-associated diseases.

Healthy nutritional status among Centenarians in Rugao, China, is associated with bean consumption, daily activity, and muscle mass retention.

BACKGROUND AND OBJECTIVES: Nutritional status is presumed essential for healthy longevity. The city of Rugao in Jiangsu province recognized as a long-lived area on the coastal plain of China, with a higher proportion of centenarians than Chinese elsewhere or in the world at large. The nutritional status and related factors of centenarians in Rugao, along with muscle mass and activities of daily living (ADL) have been documented with a view to improved nutritional and health approaches to healthy ageing. METHODS AND STUDY DESIGN: A cross-sectional study was conducted in Rugao from April 2020 to December 2020. 116 local centenarians agreed to participate in the study. Nutritional status was evaluated by the Mini Nutritional Assessment Short Form (MNA-SF), and ADL was assessed by the Barthel Index (BI). Anthropometric data (e.g., calf circumference) and body composition data (e.g., skeletal muscle mass) were collected as muscle mass variables. RESULTS: The age of centenarians ranged from 100 to 109 years. According to MNA-SF assessment, only 6 (5.2%) of 116 centenarians were malnourished, and 57 (49.1%) were at risk of malnutrition. Binary logistic regression results indicated that prealbumin, albumin, bean product consumption, and current exercise status were independent determinants of centenarians' nutritional status. Centenarians with poor nutritional status tended to have worse muscle mass and BI scores. CONCLUSIONS: Nearly half of the centenarians maintained normal nutritional status, insofar as muscle mass condition and function were concerned. Frequent bean product consumption and routine exercise were conducive to healthier centenarian nutritional status.

Effects of High Hydrostatic Pressure and Storage Temperature on Fatty Acids and Non-Volatile Taste Active Compounds in Red Claw Crayfish (Cherax quadricarinatus).

The effects of high hydrostatic pressure (treated with 200, 400 and 600 MPa) and storage temperatures (4 °C and −20 °C) on the fatty acids and flavor compounds of red claw crayfish were studied. HHP decreased the PUFA, GMP, IMP and AMP, citric and lactic acids, and PO43− contents, but the FAA, Ca2+ and Cl− contents increased in HHP-treated crayfish compared to untreated crayfish at 0 d. Storage at −20 °C could restrain the fatty acids and flavor contents compared to those stored at 4 °C. The GMP, AMP, citric acid and PO43− contents decreased, and Ca2+ and Cl− contents increased after storage at 4 °C for 15 d (p < 0.05). HHP at 200 and 400 MPa increased EUC on 0 d. No significant changes in EUC were observed after storage at −20 °C for 15 d, significant decreases were noted at 4 °C than the crayfish stored for 0 d (p < 0.05), except for the untreated group. Generally, HHP at 200 or 400 MPa, and storage at −20 °C is beneficial according to the shelling rates and EUC of crayfish.

The therapeutic role of mesenchymal stem cell-derived exosomes in the autoimmune diseases.

Autoimmune diseases are characterized by damage and dysfunction of multiple organs and various complications. Recently, new therapies for autoimmune diseases have been proposed extensively, and there are growing researches focusing on the immunomodulatory abilities of mesenchymal stem cells (MSCs). As a kind of small vesicles secreted by cells, exosomes can be released by MSCs and other cells. Being enriched with protein, mRNA, microRNA, lipids and other cell contents, exosomes participate in the transfer of substances and information between cells, and regulate the biological functions of recipient cells, which may be a potential mechanism of the immunomodulation abilities of MSCs. A growing number of studies have shown that the exosomes secreted by MSCs have similar or even better immunomodulation abilities than MSCs, and their roles in the treatment of several autoimmune diseases have been confirmed in animal models. In this review, we briefly summarize the effects of MSCs and the MSCs-derived exosomes on the immune system and immune cells, especially focusing on the research progress of MSCs-derived exosomes in autoimmune diseases in recent years.

Therapeutic effects of bone marrow mesenchymal stem cells-derived exosomes on osteoarthritis.

Mesenchymal stem cells (MSCs) have shown chondroprotective effects in clinical models of osteoarthritis (OA). However, effects of MSC-derived exosomes on OA remain unclear. The study aimed to investigate the therapeutic potential of exosomes from human bone marrow MSCs (BM-MSCs) in alleviating OA. The anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) surgery were performed on the knee joints of a rat OA model, followed by intra-articular injection of BM-MSCs or their exosomes. In addition, BM-MSC-derived exosomes were administrated to primary human chondrocytes to observe the functional and molecular alterations. Both of BM-MSCs and BM-MSC-derived exosomes alleviated cartilage destruction and subchondral bone remodelling in OA rat model. Administration of BM-MSCs and exosomes could reduce joint damage and restore the trabecular bone volume fraction, trabecular number and connectivity density of OA rats. In addition, in vitro assays showed that BM-MSCs-exosomes could maintain the chondrocyte phenotype by increasing collagen type II synthesis and inhibiting IL-1ß-induced senescence and apoptosis. Furthermore, exosomal lncRNA MEG-3 also reduced the senescence and apoptosis of chondrocytes induced by IL-1ß, indicating that lncRNA MEG-3 might partially account the anti-OA effects of BM-MSC exosomes. The exosomes from BM-MSCs exerted beneficial therapeutic effects on OA by reducing the senescence and apoptosis of chondrocytes, suggesting that MSC-derived exosomes might provide a candidate therapy for OA treatment.

[Exosomal microRNAs: an emerging player in systemic lupus erythematosus].

Exosomes are nanometer-sized membranous extracellular vesicles that can be secreted by almost all types of cells in the body. Exosomes are involved in cell-to-cell communication through autocrine and paracrine forms. Exosomal microRNAs (miRNAs) are stable in plasma, urine and other body fluids, and have various biological functions. They play an irreplaceable role in the occurrence, development, immune regulation of systemic lupus erythematosus (SLE). Recent studies have proposed that exosomal miRNAs have promising application prospects in the pathogenesis, early diagnosis, and treatment of SLE. Therefore, this review aims to introduce the current research progress on exosomal miRNAs in SLE and analyze their potential application value.

Psychological status and disease activity were major predictors of body image disturbances in patients with Sjögren's syndrome.

Sjögren's syndrome (SS) often leads to disease-related body defects and functional impairments, which may result in the body image disturbances (BID) of patients. The aim of this study was to investigate the severity and predictors of BID among SS patients. Two hundred and thirty-one SS patients [mean (IQR) age: 51 (42-58); females: 94.4%] and 224 age and sex-matched healthy controls were included in this cross-sectional study. Questionnaires were applied: body image disturbance questionnaire (BIDQ), the hospital anxiety and depression scale (HADS), fatigue severity scale (FSS), the 10-cm pain Visual Analog Scale (VAS), the oral health impact profile-14 (OHIP-14), the ocular surface disease index (OSDI), the social support rate scale (SSRS). Independent sample t-test, Mann-Whitney U-test, Chi-square test, spearman rank correlation, and stepwise linear regression were performed by SPSS version 20.0 to analyze these data. In 231 SS patients, the mean of the overall BIDQ score was 1.80 ± 1.21, and SS patients had significantly higher scores in each domain of BIDQ compared with healthy controls (p < 0.05). The stepwise multiple linear regression analysis revealed that high BIDQ score was predicted by severe anxiety (ß = 0.081; p < 0.001), high disease activity (ß = 0.038; p < 0.001) and poor oral health (ß = 0.017; p = 0.007) in SS patients. Patients with SS suffer from severe BID and it is necessary for rheumatologists to pay more attention to SS patients' body image disturbance, especially those with high disease activity, severe anxiety, and poor oral health to improve patients' quality of life.

Associated factors with adherence to standard exercise therapy and health-related quality of life in Chinese patients with ankylosing spondylitis.

Objectives: The aim of this study is to assess the current situations of standard exercise treatment and predictors of non-standard exercise in Chinese patients with ankylosing spondylitis (AS). An analysis of the effect of standard exercise on health-related quality of life (HR-QoL) was also conducted.Methods: In the cross-sectional study, a total of 259 AS patients were constantly invited to participate in this study and complete the questionnaire under the researchers' supervision in a clinical setting including sociodemographic variables, clinical variables, psychological variables, and HR-QoL. Data were analyzed by Mann-Whitney U test, Chi-square test as well as multivariable analysis of Binary Stepwise Logistic Regression.Results: The data showed that just 20.5% of them could complete the standard exercise. Exercise adherence was associated with employment, educational level, marital status, place of residence, treatment of Tumor Necrosis Factor-α inhibitor, knowledge about exercise, disease duration, clinical variables, and anxiety. The HR-QoL in the group of standard exercise was better than that in the non-standard exercise group. Logistic Regression Analysis showed that lower educational level, less knowledge about benefits of exercise treatment and higher score of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were the independent risk factors of exercise treatment non-adherence.Conclusion: AS patients educated less than 9 years or with higher BASDAI score were more likely not to adhere to standard exercise treatment. Non-adherence to exercise treatment among AS patients is exceedingly common, particularly in patients without knowledge about benefits of exercise treatment. Standard exercise treatment can also improve HR-QoL of AS patients.

Exosomal microRNA-155-5p from PDLSCs regulated Th17/Treg balance by targeting sirtuin-1 in chronic periodontitis.

The mechanism of local inflammation and systemic injury in chronic periodontitis is complicated, in which and exosomes play an important role. In our study, we found that T helper cell 17 (Th17)/regulatory T cell (Treg) balance is destabilized in the peripheral blood of patients with periodontitis, with upregulated Th17 or downregulated Treg, respectively. Porphyromonas gingivalis lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment of chronic periodontitis. The exosomes were extracted from periodontal ligament stem cells (PDLSCs) in LPS-induced periodontitis environment, which inversely effected on CD4+ T cells under normal and inflammatory conditions. Furthermore, compared with exosomes from normal PDLSCs, lower expression of microRNA-155-5p (miR-155-5p) and higher expression of Sirtuin-1 (SIRT1) were observed in exosomes from LPS-stimulated PDLSCs. Exosomes from PDLSCs alleviated inflammatory microenvironment through Th17/Treg/miR-155-5p/SIRT1 regulatory network. This study aimed to find the "switching" factors that affected the further deterioration of periodontitis to maximally control the multiple downstream damage signal factors to further understand periodontitis and find new targets for its treatment.

B7-H3 participates in human salivary gland epithelial cells apoptosis through NF-κB pathway in primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disorder mainly characterized by exocrine gland injury. Costimulatory molecules play an important role in immune-regulatory networks. Although B7 family costimulatory molecules were previously discovered in human salivary gland epithelial (HSGE) cells in pSS, the effects of the B7 family member B7-H3 (CD276) have not been well elucidated. Thus, this study aimed to investigate the role and mechanism of B7-H3 in HSGE cells in pSS. METHODS: The expression of B7-H3, B7-H1, PD-1 in serum, saliva and salivary gland were examined by immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to test the expression and distribution of B7-H3, AQP5 and CK-8 in salivary gland tissues. Flow cytometry, Cell Counting Kit 8 (CCK-8) and western blot (WB) were performed to research the apoptotic, proliferative and inflammatory effects of B7-H3 in primary HSGE cells and HSGE cell lines. RESULTS: Our results showed that the expression of PD-1, B7-H1 and B7-H3 in peripheral blood, and salivary glands in pSS patients was higher than that in healthy controls, which was positive correlation with the grade of the salivary glands. The expression of B7-H3 in saliva was higher in pSS patients than that in healthy controls, which was detected with the most significant difference of them. The expression of B7-H3 in primary HSGE cells of pSS patients was significantly higher than healthy controls. B7-H3 increased activity of NF-κB pathway and promoted inflammation of HSGE cells, decreasing the expression of AQP5. Furthermore, B7-H3 overexpression inhibited proliferation and induced apoptosis in HSGE cell lines. CONCLUSION: B7-H3 could promote inflammation and induce apoptosis of HSGE cells by activating NF-κB pathway, which might be a promising therapeutic target for pSS.