Exploring the immune-inflammatory mechanism of Maxing Shigan Decoction in treating influenza virus A-induced pneumonia based on an integrated strategy of single-cell transcriptomics and systems biology.

BACKGROUND: Influenza is an acute respiratory infection caused by influenza virus. Maxing Shigan Decoction (MXSGD) is a commonly used traditional Chinese medicine prescription for the prevention and treatment of influenza. However, its mechanism remains unclear. METHOD: The mice model of influenza A virus pneumonia was established by nasal inoculation. After 3 days of intervention, the lung index was calculated, and the pathological changes of lung tissue were detected by HE staining. Firstly, transcriptomics technology was used to analyze the differential genes and important pathways in mouse lung tissue regulated by MXSGD. Then, real-time fluorescent quantitative PCR (RT-PCR) was used to verify the changes in mRNA expression in lung tissues. Finally, intestinal microbiome and intestinal metabolomics were performed to explore the effect of MXSGD on gut microbiota. RESULTS: The lung inflammatory cell infiltration in the MXSGD group was significantly reduced (p < 0.05). The results of bioinformatics analysis for transcriptomics results show that these genes are mainly involved in inflammatory factors and inflammation-related signal pathways mediated inflammation biological modules, etc. Intestinal microbiome showed that the intestinal flora Actinobacteriota level and Desulfobacterota level increased in MXSGD group, while Planctomycetota in MXSGD group decreased. Metabolites were mainly involved in primary bile acid biosynthesis, thiamine metabolism, etc. This suggests that MXSGD has a microbial-gut-lung axis regulation effect on mice with influenza A virus pneumonia. CONCLUSION: MXSGD may play an anti-inflammatory and immunoregulatory role by regulating intestinal microbiome and intestinal metabolic small molecules, and ultimately play a role in the treatment of influenza A virus pneumonia.

Advancements in research on the immune-inflammatory mechanisms mediated by NLRP3 inflammasome in ischemic stroke and the regulatory role of natural plant products.

Ischemic stroke (IS) is a major cause of mortality and disability among adults. Recanalization of blood vessels to facilitate timely reperfusion is the primary clinical approach; however, reperfusion itself may trigger cerebral ischemia-reperfusion injury. Emerging evidence strongly implicates the NLRP3 inflammasome as a potential therapeutic target, playing a key role in cerebral ischemia and reperfusion injury. The aberrant expression and function of NLRP3 inflammasome-mediated inflammation in cerebral ischemia have garnered considerable attention as a recent research focus. Accordingly, this review provides a comprehensive summary of the signaling pathways, pathological mechanisms, and intricate interactions involving NLRP3 inflammasomes in cerebral ischemia-reperfusion injury. Moreover, notable progress has been made in investigating the impact of natural plant products (e.g., Proanthocyanidins, methylliensinine, salidroside, α-asarone, acacia, curcumin, morin, ginsenoside Rd, paeoniflorin, breviscapine, sulforaphane, etc.) on regulating cerebral ischemia and reperfusion by modulating the NLRP3 inflammasome and mitigating the release of inflammatory cytokines. These findings aim to present novel insights that could contribute to the prevention and treatment of cerebral ischemia and reperfusion injury.

Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials.

BACKGROUND: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).

Exploring the mechanism of Celastrol in the treatment of rheumatoid arthritis based on systems pharmacology and multi-omics.

To explore the molecular network mechanism of Celastrol in the treatment of rheumatoid arthritis (RA) based on a novel strategy (integrated systems pharmacology, proteomics, transcriptomics and single-cell transcriptomics). Firstly, the potential targets of Celastrol and RA genes were predicted through the database, and the Celastrol-RA targets were obtained by taking the intersection. Then, transcriptomic data and proteomic data of Celastrol treatment of RA were collected. Subsequently, Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were imported into Metascape for enrichment analysis, and related networks were constructed. Finally, the core targets of Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were mapped to synoviocytes of RA mice to find potential cell populations for Celastrol therapy. A total of 195 Celastrol-RA targets, 2068 differential genes, 294 differential proteins were obtained. The results of enrichment analysis showed that these targets, genes and proteins were mainly related to extracellular matrix organization, TGF-ß signaling pathway, etc. The results of single cell sequencing showed that the main clusters of these targets, genes, and proteins could be mapped to RA synovial cells. For example, Mmp9 was mainly distributed in Hematopoietic cells, especially in Ptprn+fibroblast. The results of molecular docking also suggested that Celastrol could stably combine with molecules predicted by network pharmacology. In conclusion, this study used systems pharmacology, transcriptomics, proteomics, single-cell transcriptomics to reveal that Celastrol may regulate the PI3K/AKT signaling pathway by regulating key targets such as TNF and IL6, and then play an immune regulatory role.

Uncovering the pharmacological mechanism of Shou Tai Wan on recurrent spontaneous abortion: A integrated pharmacology strategy-based research.

ETHNOPHARMACOLOGICAL RELEVANCE: Shou Tai Wan (STW), a traditional Chinese medicine formula, has been historically used for the treatment of recurrent spontaneous abortion (RSA). Despite its long-standing usage, the exact mechanism underlying the therapeutic effects of STW remains unclear in the existing literature. AIMS OF THIS STUDY: To explore the Pharmacological Mechanism of STW on RSA. METHODS: A network pharmacological methodology was utilized to predict the active compounds and potential targets of STW, collect the RSA targets and other human proteins of STW, and analyze the STW related networks. The animal experiments were also performed to validate the effect of STW on RSA. RESULTS: The results of network analysis showed that STW may regulate PI3K/AKT, MAPK, FoxO signaling pathways and so on. Animal experiment established the RSA model with CBA/J × DBA/2 mice. It was found that STW can reduce the embryo absorption rate of RSA group (p < 0.05) and balance the expression of Th 1/Th2 type cytokines compared with the model group. After 14 days of administration, the decidual and placental tissues were taken and the CD4+ T cells were isolated, and the phosphorylation level of signaling pathway was detected by Springbio720 antibody microarray. This experiment found that STW can significantly up-regulate the phosphorylation levels of STAT3 and STAT6 proteins in the STAT signaling pathway, and down-regulating the phosphorylation level of STAT1 protein. STW also significantly up-regulated the phosphorylation levels of Raf1, A-Raf, Ask1, Mek1, Mek2, JKK1, ERK1, ERK2, c-fos, c-Jun and CREB proteins in the MAPK signaling pathway, and down-regulate the phosphorylation levels of MEK6 and IKKb proteins. Compared with the RSA group, the STW group increased the expression levels of ERK1/2 mRNA and proteins and p-ERK1/2 proteins, and there was a statistical difference (p < 0.05). This is consistent with the chip results. CONCLUSION: STW may achieve therapeutic effects by interfering with the signaling pathways, biological processes and targets discovered in this study. It provides a new perspective for revealing the immunological mechanism of STW in the treatment of RSA, and also provides a theoretical basis for the clinical use of STW in the treatment of RSA.

Efficacy and safety of iguratimod in the treatment of rheumatic and autoimmune diseases: a meta-analysis and systematic review of 84 randomized controlled trials.

Objective: To evaluate efficacy and safety of iguratimod (IGU) in the treatment of rheumatic and autoimmune diseases. Methods: Databases such as Pubmed, Embase, Sinomed were searched (as of July 2022) to collect randomized controlled trials (RCTs) of IGU in the treatment of rheumatic and autoimmune diseases. Two researchers independently screened the literature, extracted data, assessed the risk of bias of the included literature, and performed meta-analysis using RevMan 5.4 software. Results: A total of 84 RCTs and 4 types of rheumatic and autoimmune diseases [rheumatoid arthritis (RA), ankylosing spondylitis (AS), primary Sjögren's syndrome (PSS) and Autoimmune disease with interstitial pneumonia]. Forty-three RCTs reported RA and showed that IGU + MTX therapy can improve ACR20 (RR 1.45 [1.14, 1.84], p = 0.003), ACR50 (RR 1.80 [1.43, 2.26], p < 0.0000), ACR70 (RR 1.84 [1.27, 2.67], p = 0.001), DAS28 (WMD -1.11 [-1.69, -0.52], p = 0.0002), reduce ESR (WMD -11.05 [-14.58, -7.51], p < 0.00001), CRP (SMD -1.52 [-2.02, -1.02], p < 0.00001), RF (SMD -1.65 [-2.48, -0.82], p < 0.0001), and have a lower incidence of adverse events (RR 0.84 [0.78, 0.91], p < 0.00001) than the control group. Nine RCTs reported AS and showed that IGU can decrease the BASDAI score (SMD -1.62 [-2.20, -1.05], p < 0.00001), BASFI score (WMD -1.07 [-1.39, -0.75], p < 0.00001), VAS (WMD -2.01 [-2.83, -1.19], p < 0.00001), inflammation levels (decreasing ESR, CRP and TNF-α). Thirty-two RCTs reported PSS and showed that IGU can reduce the ESSPRI score (IGU + other therapy group: WMD -1.71 [-2.44, -0.98], p < 0.00001; IGU only group: WMD -2.10 [-2.40, -1.81], p < 0.00001) and ESSDAI score (IGU + other therapy group: WMD -1.62 [-2.30, -0.94], p < 0.00001; IGU only group: WMD -1.51 [-1.65, -1.37], p < 0.00001), inhibit the inflammation factors (reduce ESR, CRP and RF) and increase Schirmer's test score (IGU + other therapy group: WMD 2.18 [1.76, 2.59], p < 0.00001; IGU only group: WMD 1.55 [0.35, 2.75], p = 0.01); The incidence of adverse events in IGU group was also lower than that in control group (IGU only group: RR 0.66 [0.48, 0.98], p = 0.01). Three RCTs reported Autoimmune disease with interstitial pneumonia and showed that IGU may improve lung function. Conclusion: Based on current evidence, IGU may be a safe and effective therapy for RA, AS, PSS and autoimmune diseases with interstitial pneumonia. Systematic Review Registration: (CRD42021289489).

Research progress on the clinical application and mechanism of iguratimod in the treatment of autoimmune diseases and rheumatic diseases.

Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren 's syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod's unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.

Research progress in the molecular mechanism of ferroptosis in Parkinson's disease and regulation by natural plant products.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder of the central nervous system after Alzheimer's disease. The current understanding of PD focuses mainly on the loss of dopamine neurons in the substantia nigra region of the midbrain, which is attributed to factors such as oxidative stress, alpha-synuclein aggregation, neuroinflammation, and mitochondrial dysfunction. These factors together contribute to the PD phenotype. Recent studies on PD pathology have introduced a new form of cell death known as ferroptosis. Pathological changes closely linked with ferroptosis have been seen in the brain tissues of PD patients, including alterations in iron metabolism, lipid peroxidation, and increased levels of reactive oxygen species. Preclinical research has demonstrated the neuroprotective qualities of certain iron chelators, antioxidants, Fer-1, and conditioners in Parkinson's disease. Natural plant products have shown significant potential in balancing ferroptosis-related factors and adjusting their expression levels. Therefore, it is vital to understand the mechanisms by which natural plant products inhibit ferroptosis and relieve PD symptoms. This review provides a comprehensive look at ferroptosis, its role in PD pathology, and the mechanisms underlying the therapeutic effects of natural plant products focused on ferroptosis. The insights from this review can serve as useful references for future research on novel ferroptosis inhibitors and lead compounds for PD treatment.

Iguratimod suppresses Tfh cell differentiation in primary Sjögren's syndrome patients through inhibiting Akt/mTOR/STAT3 signaling.

BACKGROUND: Iguratimod (IGU) reduces hypergammaglobulinemia and disease activity in pSS (primary Sjögren's syndrome) patients. However, the therapeutical mechanism of IGU for pSS remains largely unknown. This study aimed to investigate the regulation of Tfh cell differentiation by IGU in pSS patients. METHODS: We prospectively enrolled 13 pSS patients treated with IGU for 3 months and examined circulating T cell and B cell subsets by flow cytometry. We measured Tfh cell differentiation treated by IGU in pSS patients and healthy controls. Transcriptome analysis combined with molecular docking were employed to identify potential therapeutical targets of IGU, which were verified by Western blot and Tfh cell differentiation. RESULTS: Tfh, plasmablast, and plasma cells were suppressed by IGU treatment at 1 and 3 months. Tfh cell differentiation and function were significant inhibited by IGU in pSS patients and healthy controls in vitro. Pyruvate dehydrogenase kinase 1 (PDK1) was identified as a target of IGU during Tfh cell differentiation, and the downstream Akt phosphorylation was attenuated by IGU. Moreover, the activity of mTORC1 and phosphorylation of STAT3 were suppressed by IGU, with downregulation of BCL6 and upregulation of PRDM1. Finally, Akt activator restored IGU-suppressed Tfh cell differentiation. CONCLUSIONS: IGU suppresses Tfh cell differentiation in pSS patients through interacting with PDK1 and suppressing Akt-mTOR-STAT3 signaling.

Efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis: A systematic review and meta-analysis.

OBJECTIVE: To evaluate efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis METHODS: Databases such as Pubmed, Cochran Library, Embase were searched to collect RCTs about TGP in the treatment of inflammatory arthritis. Then, the RCTs were assessed for risk of bias and RCT data were extracted. Finally, RevMan 5.4 was used for the meta-analysis. RESULTS: A total of 63 RCTs were finally included, involving 5293 participants and 5 types of types of inflammatory arthritis: rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoarthritis (OA), juvenile idiopathic arthritis (JIA), psoriatic arthritis. For AS, TGP may improve AS disease activity score (ASDAS), decrease erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor (TNF)- α and interleukin (IL)- 6; for RA, TGP may improve disease activity of 28 joints (DAS28), decrease ESR, CRP, rheumatoid factor (RF), TNF-α and IL-6; for psoriatic arthritis, TGP may improve psoriasis area and severity index (PASI) and decrease ESR; for OA, TGP may improve visual analogue scale (VAS) and decrease nitric oxide (NO); for JIA, TGP may increase total efficiency rate, decrease ESR, CRP and TNF-α. For safety, RCTs showed that the addition of TGP did not increase adverse events, and may even reduce adverse events. CONCLUSION: TGP may improve symptoms and inflammation levels in patients with inflammatory arthritis. However, due to the low quality and small number of RCTs, large-sample, multi-center clinical trials are still needed for revision or validation.

Mechanisms of ferroptosis in Alzheimer's disease and therapeutic effects of natural plant products: A review.

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by massive loss of specific neurons. It is a progressive disabling, severe and fatal complex disease. Due to its complex pathogenesis and limitations of clinical treatment strategies, it poses a serious medical challenge and medical burden worldwide. The pathogenesis of AD is not clear, and its potential biological mechanisms include aggregation of soluble amyloid to form insoluble amyloid plaques, abnormal phosphorylation of tau protein and formation of intracellular neurofibrillary tangles (NFT), neuroinflammation, ferroptosis, oxidative stress and metal ion disorders. Among them, ferroptosis is a newly discovered programmed cell death induced by iron-dependent lipid peroxidation and reactive oxygen species. Recent studies have shown that ferroptosis is closely related to AD, but the mechanism remains unclear. It may be induced by iron metabolism, amino acid metabolism and lipid metabolism affecting the accumulation of iron ions. Some iron chelating agents (deferoxamine, deferiprone), chloroiodohydroxyquine and its derivatives, antioxidants (vitamin E, lipoic acid, selenium), chloroiodohydroxyquine and its derivatives Fer-1, tet, etc. have been shown in animal studies to be effective in AD and exert neuroprotective effects. This review summarizes the mechanism of ferroptosis in AD and the regulation of natural plant products on ferroptosis in AD, in order to provide reference information for future research on the development of ferroptosis inhibitors.

Efficacy and safety of dietary polyphenols in rheumatoid arthritis: A systematic review and meta-analysis of 47 randomized controlled trials.

Objective: To evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA). Methods: CNKI, Pubmed, Cochrane library, Embase were searched to collect randomized controlled trials (RCTs) of dietary polyphenols in the treatment of RA. The databases were searched from the time of their establishment to November 8nd, 2022. After 2 reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies, Meta-analysis was performed using RevMan5.4 software. Results: A total of 49 records (47 RCTs) were finally included, involving 3852 participants and 15 types of dietary polyphenols (Cinnamon extract, Cranberry extract, Crocus sativus L. extract, Curcumin, Garlic extract, Ginger extract, Hesperidin, Olive oil, Pomegranate extract, Puerarin, Quercetin, Resveratrol, Sesamin, Tea polyphenols, Total glucosides of paeony). Pomegranate extract, Resveratrol, Garlic extract, Puerarin, Hesperidin, Ginger extract, Cinnamon extract, Sesamin only involve in 1 RCT. Cranberry extract, Crocus sativus L. extract, Olive oil, Quercetin, Tea polyphenols involve in 2 RCTs. Total glucosides of paeony and Curcumin involve in more than 3 RCTs. These RCTs showed that these dietary polyphenols could improve disease activity score for 28 joints (DAS28), inflammation levels or oxidative stress levels in RA. The addition of dietary polyphenols did not increase adverse events. Conclusion: Dietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc. However, more RCTs are needed to verify or modify the efficacy and safety of dietary polyphenols. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.

Efficacy and safety of Iguratimod in the treatment of Ankylosing Spondylitis: A systematic review and meta-analysis of randomized controlled trials.

Objective: To explore the efficacy and safety of Iguratimod (IGU) intervention in the treatment of Ankylosing Spondylitis (AS). Methods: We used computer to search literature databases, collected randomized controlled trials (RCTs) related to IGU treatment of AS, and searched the relevant literature in each database until Sep. 2022. Two researchers independently carried out literature screening, data extraction, and evaluation and analysis of the risk of bias in the included studies, and then used Rev Man5.3 software for meta-analysis. The protocol is CRD42020220798. Results: A total of 10 RCTs involves in 622 patients were collected. The statistical analysis showed that IGU can decrease the BASDAI score (SMD -1.62 [-2.20, -1.05], P<0.00001. Quality of evidence: low), the BASFI score (WMD -1.30 [-1.48, -1.12], P<0.00001. Quality of evidence: low) and the VAS (WMD -2.01 [-2.83, -1.19], P<0.00001. Quality of evidence: very low). Meanwhile, the addition of IGU into the conventional therapy would not increase the adverse events (RR 0.65 [0.43, 0.98], P=0.04. Quality of evidence: moderate). Conclusion: IGU may be an effective and safe intervention for AS. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42020220798.

The mechanism of intestinal microbiota regulating immunity and inflammation in ischemic stroke and the role of natural botanical active ingredients in regulating intestinal microbiota: A review.

Intestinal microbiota is a unique ecosystem, known as the "second genome" of human beings. With the widespread application of next generation sequencing (NGS), especially 16 S rRNA and shotgun sequencing, numerous studies have shown that dysregulation of intestinal microbiota is associated with many central nervous system diseases. Ischemic stroke (IS) is a cerebrovascular disease with high morbidity and mortality. Brain damage in IS affects intestinal function, and intestinal dysfunction further aggravates brain damage, forming a vicious circle of mutual interference in pathology. The microbiota-gut-brain axis study based on the intestinal microbiota has opened up broader ideas for exploring its pathogenesis and risk factors, and also provided more possibilities for the selection of therapeutic targets for this type of drug. This review discussed the application of NGS technology in the study of intestinal microbiota and the research progress of microbiota-gut-brain axis in recent years, and systematically sorts out the literature on the relationship between ischemic stroke and intestinal microbiota. It starts with the characteristics of microbiota-gut-brain axis' bidirectional regulation, respectively discusses the high risk factors of IS under intestinal microbiota imbalance and the physiological and pathological changes of intestinal microbiota after IS, and summarizes the related targets, in order to provide reliable reference for the treatment of IS from intestinal microbiota. In addition, natural botanical active ingredients have achieved good results in the treatment of IS based on regulating the homeostasis of gut microbiota, providing new evidence for studying the potential targets and therapies of IS based on the microbiota-gut-brain axis.

Research progress on pyroptosis-mediated immune-inflammatory response in ischemic stroke and the role of natural plant components as regulator of pyroptosis: A review.

Ischemic stroke (IS) is one of the leading causes of death and disability. Its pathogenesis is not completely clear, and inflammatory cascade is one of its main pathological processes. The current clinical practice of IS is to restore the blood supply to the ischemic area after IS as soon as possible through thrombolytic therapy to protect the vitality and function of neurons. However, blood reperfusion further accelerates ischemic damage and cause ischemia-reperfusion injury. The pathological process of cerebral ischemia-reperfusion injury involves multiple mechanisms, and the exact mechanism has not been fully elucidated. Pyroptosis, a newly discovered form of inflammatory programmed cell death, plays an important role in the initiation and progression of inflammation. It is a pro-inflammatory programmed death mediated by caspase Caspase-1/4/5/11, which can lead to cell swelling and rupture, release inflammatory factors IL-1ß and IL-18, and induce an inflammatory cascade. Recent studies have shown that pyroptosis and its mediated inflammatory response are important factors in aggravating ischemic brain injury, and inhibition of pyroptosis may alleviate the ischemic brain injury. Furthermore, studies have found that natural plant components may have a regulatory effect on pyroptosis. Therefore, this review not only summarizes the molecular mechanism of pyroptosis and its role in ischemic stroke, but also the role of natural plant components as regulator of pyroptosis, in order to provide reference information on pyroptosis for the treatment of IS in the future.

TOX promotes follicular helper T cell differentiation in patients with primary Sjögren's syndrome.

OBJECTIVES: Whether naive CD4+ T cells are dysregulated and associated with the overactivation of CD4+ T cells in primary SS (pSS) remains unclear. We aimed to explore the role and underlying mechanism of naive CD4+ T cells in pSS. METHODS: We examined the activation, proliferation and differentiation of naive CD4+ T cells from pSS patients and healthy controls. Differentially expressed genes were identified using RNA sequencing, and were overexpressed or silenced to determine the gene regulating follicular helper T (Tfh) cells. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) with chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) was performed to explore the epigenetic mechanism. Naive CD4+ T cells were treated with pSS-related cytokines to explore the upstream signalling pathway. RESULTS: pSS naive CD4+ T cells had higher potentials of activation, proliferation and differentiation towards Tfh cells. Thymocyte selection-associated high mobility group box protein (TOX) was upregulated in pSS naive CD4+ T cells and promoted T cell activation and Tfh cell polarization. TOX silencing in pSS naive CD4+ T cells downregulated B cell lymphoma 6 (BCL6) expression and altered levels of multiple Tfh-associated genes. ChIP-seq analysis implied that TOX bound to the BCL6 locus, where there were accessible regions found by ATAC-seq. IFN-α induced TOX overexpression, which was attenuated by Janus kinase (JAK) and signal transducer and activator of transcription 1 (STAT1) inhibitors. CONCLUSION: Our data suggest that TOX in pSS naive CD4+ T cells is upregulated, which facilitates Tfh cell differentiation. Mechanistically, IFN-α induces TOX overexpression in naive CD4+ T cells through JAK-STAT1 signalling and TOX regulates BCL6 expression. Therefore, IFN-α-JAK-STAT1 signalling and TOX might be potential therapeutic targets in pSS.

Safety and efficacy of probiotic supplementation in 8 types of inflammatory arthritis: A systematic review and meta-analysis of 34 randomized controlled trials.

Objective: To evaluate Safety and efficacy of probiotic supplementation in inflammatory arthritis. Methods: The literature on the treatment of inflammatory arthritis with probiotics has been collected in databases such as CNKI, Pubmed, Cochrane library, Embase, etc. The search time is for them to build the database until May 2022. The included literatures are randomized controlled trials (RCTs) of probiotics in the treatment of hyperuricemia and gout. The Cochrane risk assessment tool was used for quality evaluation, and the Rev Man5.3 software was used for meta-analysis. Results: A total of 37 records were finally included, involving 34 RCTs and 8 types of autoimmune disease (Hyperuricemia and gout, Inflammatory bowel disease arthritis, juvenile idiopathic arthritis [JIA], Osteoarthritis [OA], Osteoporosis and Osteopenia, Psoriasis, rheumatoid arthritis (RA), Spondyloarthritis). RA involved 10 RCTs (632 participants) whose results showed that probiotic intervention reduced CRP. Psoriasis involved 4 RCTs (214 participants) whose results showed that probiotic intervention could reduce PASI scores. Spondyloarthritis involved 2 RCTs (197 participants) whose results showed that probiotic intervention improved symptoms in patients. Osteoporosis and Ostepenia involving 10 RCTs (1156 participants) showed that probiotic intervention improved bone mineral density in patients. Hyperuricemia and gout involving 4 RCTs (294 participants) showed that probiotic intervention improved serum uric acid in patients. OA involving 1 RCTs (433 participants) showed that probiotic intervention improved symptoms in patients. JIA involving 2 RCTs (72 participants) showed that probiotic intervention improved symptoms in patients. Inflammatory bowel disease arthritis involving 1 RCTs (120 participants) showed that probiotic intervention improved symptoms in patients. All of the above RCTs showed that probiotics did not increase the incidence of adverse events. Conclusion: Probiotic supplements may improve Hyperuricemia and gout, Inflammatory bowel disease arthritis, JIA, OA, Osteoporosis and Osteopenia, Psoriasis, RA, Spondyloarthritis. However, more randomized controlled trials are needed in the future to determine the efficacy and optimal dosing design of probiotics. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021286425, identifier CRD42021286425.

Research progress of single-cell transcriptome sequencing in autoimmune diseases and autoinflammatory disease: A review.

Autoimmunity refers to the phenomenon that the body's immune system produces antibodies or sensitized lymphocytes to its own tissues to cause an immune response. Immune disorders caused by autoimmunity can mediate autoimmune diseases. Autoimmune diseases have complicated pathogenesis due to the many types of cells involved, and the mechanism is still unclear. The emergence of single-cell research technology can solve the problem that ordinary transcriptome technology cannot be accurate to cell type. It provides unbiased results through independent analysis of cells in tissues and provides more mRNA information for identifying cell subpopulations, which provides a novel approach to study disruption of immune tolerance and disturbance of pro-inflammatory pathways on a cellular basis. It may fundamentally change the understanding of molecular pathways in the pathogenesis of autoimmune diseases and develop targeted drugs. Single-cell transcriptome sequencing (scRNA-seq) has been widely applied in autoimmune diseases, which provides a powerful tool for demonstrating the cellular heterogeneity of tissues involved in various immune inflammations, identifying pathogenic cell populations, and revealing the mechanism of disease occurrence and development. This review describes the principles of scRNA-seq, introduces common sequencing platforms and practical procedures, and focuses on the progress of scRNA-seq in 41 autoimmune diseases, which include 9 systemic autoimmune diseases and autoinflammatory diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.) and 32 organ-specific autoimmune diseases (5 Skin diseases, 3 Nervous system diseases, 4 Eye diseases, 2 Respiratory system diseases, 2 Circulatory system diseases, 6 Liver, Gallbladder and Pancreas diseases, 2 Gastrointestinal system diseases, 3 Muscle, Bones and joint diseases, 3 Urinary system diseases, 2 Reproductive system diseases). This review also prospects the molecular mechanism targets of autoimmune diseases from the multi-molecular level and multi-dimensional analysis combined with single-cell multi-omics sequencing technology (such as scRNA-seq, Single cell ATAC-seq and single cell immune group library sequencing), which provides a reference for further exploring the pathogenesis and marker screening of autoimmune diseases and autoimmune inflammatory diseases in the future.

Safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases: A systematic review and meta-analysis.

Objective: To evaluate the safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases. Methods: Relevant literature was retrieved from the PubMed database, Embase database, Cochrane Library database, etc. The search period is from the establishment of the database to January 2022. The outcomes include clinical symptoms, improvement in biochemistry, improvement in intestinal microbiota, improvement in the immune system, and adverse events. Literature screening and data extraction were independently carried out by two researchers according to the inclusion and exclusion criteria, and RevMan 5.3 software was used for statistics and analysis. Results: Overall, a total of 14 randomized controlled trials (RCTs) involving six types of autoimmune diseases were included. The results showed the following. 1) Type 1 diabetes mellitus (T1DM): compared with the autologous fecal microbiota transplantation (FMT) group (control group), the fasting plasma C peptide in the allogenic FMT group at 12 months was lower. 2) Systemic sclerosis: at week 4, compared with one of two placebo controls, three patients in the experimental group reported a major improvement in fecal incontinence. 3) Ulcerative colitis, pediatric ulcerative colitis, and Crohn's disease: FMT may increase clinical remission, clinical response, and endoscopic remission for patients with ulcerative colitis and increase clinical remission for patients with Crohn's disease. 4) Psoriatic arthritis: there was no difference in the ratio of ACR20 between the two groups. Conclusion: Based on current evidence, the application of FMT in the treatment of autoimmune diseases is effective and relatively safe, and it is expected to be used as a method to induce remission of active autoimmune diseases. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235055, identifier CRD42021235055.

A systematic review of the research progress of non-coding RNA in neuroinflammation and immune regulation in cerebral infarction/ischemia-reperfusion injury.

Cerebral infarction/ischemia-reperfusion injury is currently the disease with the highest mortality and disability rate of cardiovascular disease. Current studies have shown that nerve cells die of ischemia several hours after ischemic stroke, which activates the innate immune response in the brain, promotes the production of neurotoxic substances such as inflammatory cytokines, chemokines, reactive oxygen species and - nitrogen oxide, and mediates the destruction of blood-brain barrier and the occurrence of a series of inflammatory cascade reactions. Meanwhile, the expression of adhesion molecules in cerebral vascular endothelial cells increased, and immune inflammatory cells such as polymorphonuclear neutrophils, lymphocytes and mononuclear macrophages passed through vascular endothelial cells and entered the brain tissue. These cells recognize antigens exposed by the central nervous system in the brain, activate adaptive immune responses, and further mediate secondary neuronal damage, aggravating neurological deficits. In order to reduce the above-mentioned damage, the body induces peripheral immunosuppressive responses through negative feedback, which increases the incidence of post-stroke infection. This process is accompanied by changes in the immune status of the ischemic brain tissue in local and systemic systems. A growing number of studies implicate noncoding RNAs (ncRNAs) as novel epigenetic regulatory elements in the dysfunction of various cell subsets in the neurovascular unit after cerebral infarction/ischemia-reperfusion injury. In particular, recent studies have revealed advances in ncRNA biology that greatly expand the understanding of epigenetic regulation of immune responses and inflammation after cerebral infarction/ischemia-reperfusion injury. Identification of aberrant expression patterns and associated biological effects of ncRNAs in patients revealed their potential as novel biomarkers and therapeutic targets for cerebral infarction/ischemia-reperfusion injury. Therefore, this review systematically presents recent studies on the involvement of ncRNAs in cerebral infarction/ischemia-reperfusion injury and neuroimmune inflammatory cascades, and elucidates the functions and mechanisms of cerebral infarction/ischemia-reperfusion-related ncRNAs, providing new opportunities for the discovery of disease biomarkers and targeted therapy. Furthermore, this review introduces clustered regularly interspaced short palindromic repeats (CRISPR)-Display as a possible transformative tool for studying lncRNAs. In the future, ncRNA is expected to be used as a target for diagnosing cerebral infarction/ischemia-reperfusion injury, judging its prognosis and treatment, thereby significantly improving the prognosis of patients.