External pathogenic microorganisms and commensal microorganisms in the body have either harmful or beneficial impacts on the regenerative repair of tissues, and the immune system plays a crucial regulatory role in this process. This review summarises our current understanding of microorganism-immune system interactions, with a focus on how these interactions impact the renewal and repair ability of tissues, including skin, bone, gut, liver, and nerves. This review concludes with a discussion of the mechanisms by which microbes act on various types of immune cells to affect tissue regeneration, offers potential strategies for using microbial therapies to enhance the regenerative repair function of tissues, and suggest novel therapeutic approaches for regenerative medicine. Statement of significance Microbiological communities have crucial impacts on human health and illness by participating in energy collection and storage and performing various metabolic processes. External pathogenic microorganisms and commensal microorganisms in the body have either harmful or beneficial impacts on the regenerative repair of tissues, and the immune system plays a critical regulatory role in this process. This study reviews the important correlation between microorganisms and the immune system and investigates the mechanism of various microorganism that participate in the regeneration and repair of tissues and organs by modulating immune system. (c) 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Current research has described improving multisystem disease and organ function through dietary nitrate (DN) supplementation. They have provided some evidence that these floras with nitrate (NO3-) reductase are mediators of the underlying mechanism. Symbiotic bacteria with nitrate reductase activity (NRA) are found in the human digestive tract, including the mouth, esophagus and gastrointestinal tract (GT). Nitrate in food can be converted to nitrite under the tongue or in the stomach by these symbiotic bacteria. Then, nitrite is transformed to nitric oxide (NO) by non-enzymatic synthesis. NO is currently recognized as a potent bioactive agent with biological activities, such as vasodilation, regulation of cardiomyocyte function, neurotransmission, suppression of platelet agglutination, and prevention of vascular smooth muscle cell proliferation. NO also can be produced through the conventional L-arginine-NO synthase (L-NOS) pathway, whereas endogenous NO production by L-arginine is inhibited under hypoxia-ischemia or disease conditions. In contrast, exogenous NO3-/NO2-/NO activity is enhanced and becomes a practical supplemental pathway for NO in the body, playing an essential role in various physiological activities. Moreover, many diseases (such as metabolic or geriatric diseases) are primarily associated with disorders of endogenous NO synthesis, and NO generation from the exogenous NO3-/NO2-/NO route can partially alleviate the disease progression. The imbalance of NO in the body may be one of the potential mechanisms of disease development. Therefore, the impact of these floras with nitrate reductase on host systemic health through exogenous NO3-/NO2-/NO pathway production of NO or direct regulation of floras ecological balance is essential (e.g., regulation of body homeostasis, amelioration of diseases, etc.). This review summarizes the bacteria with nitrate reductase in humans, emphasizing the relationship between the metabolic processes of this microflora and host systemic health and disease. The potential effects of nitrate reduction bacteria on human health and disease were also highlighted in disease models from different human systems, including digestive, cardiovascular, endocrine, nervous, respiratory, and urinary systems, providing innovative ideas for future disease diagnosis and treatment based on nitrate reduction bacteria.

Background:Current electrocardiogram (ECG) criteria of left ventricular hypertrophy (LVH) have low sensitivity. Deep learning (DL) techniques have been widely used to detect cardiac diseases due to its ability of automatic feature extraction of ECG. However, DL was rarely applied in LVH diagnosis. Our study aimed to construct a DL model for rapid and effective detection of LVH using 12-lead ECG. Methods:We built a DL model based on convolutional neural network-long short-term memory (CNN-LSTM) to detect LVH using 12-lead ECG. The echocardiogram and ECG of 1,863 patients obtained within 1 week after hospital admission were analyzed. Patients were evenly allocated into 3 sets at 3:1:1 ratio: the training set (n = 1,120), the validation set (n = 371) and the test set 1 (n = 372). In addition, we recruited 453 hospitalized patients into the internal test set 2. Different DL model of each subgroup was developed according to gender and relative wall thickness (RWT). Results:The LVH was predicted by the CNN-LSTM model with an area under the curve (AUC) of 0.62 (sensitivity 68%, specificity 57%) in the test set 1, which outperformed Cornell voltage criteria (AUC: 0.57, sensitivity 48%, specificity 72%) and Sokolow-Lyon voltage (AUC: 0.51, sensitivity 14%, specificity 96%). In the internal test set 2, the CNN-LSTM model had a stable performance in predicting LVH with an AUC of 0.59 (sensitivity 65%, specificity 57%). In the subgroup analysis, the CNN-LSTM model predicted LVH by 12-lead ECG with an AUC of 0.66 (sensitivity 72%, specificity 60%) for male patients, which performed better than that for female patients (AUC: 0.59, sensitivity 50%, specificity 71%). Conclusion:Our study established a CNN-LSTM model to diagnose LVH by 12-lead ECG with higher sensitivity than current ECG diagnostic criteria. This CNN-LSTM model may be a simple and effective screening tool of LVH.

Fermented foods are ancient and ubiquitous, thought to be consumed in nearly every culture over the last 10,000 years and as part of the hominin diet for millions of years. A growing body of evidence supports their potential health benefits, but the mechanistic basis of their effects on the gut microbiome and host immunity remain to be elucidated. Fermented foods are diverse, each representing a complex mixture of food, microbes, and metabolites creating a significant challenge to disentangle the effects of individual components. Herein, we further define the chemical signature of individual fermented foods to categorize them based on the primary metabolic end-products of fermentation. Using mouse models, we find that fermented foods have both microbiome directed as well as differential host directed effects that correspond to their metabolite composition. Fermented food brine drink shows site-specific restructuring of the gut microbiome and promotion of tolerogenic barrier immunity; fractionation of the brine to examine the effects of the microbe-free, metabolite rich supernatant shows similar activity. Lactate, the main metabolite of lactic acid fermentation and the major metabolite within the brine drink, when administered in water, fuels a trans-kingdom metabolic network to selectively promote the growth of Akkermansia muciniphila . in the small intestine, while promoting immune tolerance via an increase in microbiota-dependent Regulatory T-cells. These findings suggest that the beneficial effects of fermented food consumption can be mediated by microbial metabolites within fermented foods, independent of microbial content, and highlight the importance of further defining the diverse chemical landscape of fermented foods to inform their potential health benefits and therapeutic use.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory and autoimmune disease mainly affecting the sacroiliac joints and axial skeleton. Its pathogenetic mechanism is unclear. Previous reports have shown that genetic factors, immune axial, and gut microbiota factors are involved in the development of AS. In this study, we investigated the molecular mechanism whereby gut microbiota dysbiosis induces activation of the TLR-4/NLRP3 inflammasome pathway in AS.Methods: We applied proteoglycan and dimethyldioctadecylammonium (DDA) adjuvants to construct a murine AS model and used antibiotics to create gut microbiota deficiency conditions in animals. Inflammation status in target tissues, including blood, intestine, peripheral joints, and the axial spine was measured using clinical grade, enzyme-linked immunosorbent assay (ELISA), magnetic resonance imaging (MRI), and histology techniques. Western blotting was also used to evaluate the expression of NLRP3 inflammasome associated proteins. 16s rDNA sequencing was performed to analyze the abundance of gut microbiota in different groups.Results: Antibiotic treatment induced gut microbiota deficiency in AS mice by eliminating most gut bacteria and the endotoxin, lipopolysaccharide (LPS). Gut microbiota deficiency appeared to alleviate the inflammation status of peripheral joints and the axial spine in AS, including inflammatory infiltration, synovial hyperplasia and bone matrix formation. Also, gut microbiota deficiency suppressed intestinal barrier dysfunction and bacterial metabolite translocation. Meanwhile, such condition inhibited TLR-4/NLRP3 pathway and down-regulated inflammatory factors, such as IL-17, IL-23, TNF-α, IL-1β, and IL-18.Conclusions: We hypothesize that gut dysbiosis damages the intestinal barrier, induces LPS translocation to bind the toll-like-receptor 4 (TLR-4) which activates the NLRP3 pathway to facilitate the release of excess inflammatory cytokines

Ankylosing spondylitis (AS) is a systemic, chronic, and inflammatory autoimmune disease associated with the disorder of intestinal microbiota. Unfortunately, effective therapies for AS are lacking. Recent evidence has indicated that indole-3-acetic acid (IAA), an important microbial tryptophan metabolite, can modulate intestinal homeostasis and suppress inflammatory responses. However, reports have not examined the in vivo protective effects of IAA against AS. In this study, we investigated the protective effects and underlying mechanisms through which IAA acts against AS. We constructed a proteoglycan (PG)-induced AS mouse model and administered IAA (50 mg/kg body weight) by intraperitoneal injection daily for 4 weeks. The effects of IAA on AS mice were evaluated by examining disease severity, intestinal barrier function, aryl hydrocarbon receptor (AhR) pathway, T-helper 17 (Th17)/T regulatory (Treg) balance, and inflammatory cytokine levels. The intestinal microbiota compositions were profiled through whole-genome sequencing. We observed that IAA decreased the incidence and severity of AS in mice, inhibited the production of pro-inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-6, IL-17A, and IL-23), promoted the production of the anti-inflammatory cytokine IL-10, and reduced the ratios of pro-/anti- inflammatory cytokines. IAA ameliorated pathological changes in the ileum and improved intestinal mucosal barrier function. IAA also activated the AhR pathway, upregulated the transcription factor forehead box protein P3 (FoxP3) and increased Treg cells, and downregulated the transcription factors retinoic acid receptor–related orphan receptor gamma t (RORγt) and signal transducer and activator of transcription 3 (STAT3) and decreased Th17 cells. Furthermore, IAA altered the composition of the intestinal microbiota composition by increasing Bacteroides and decreasing Proteobacteria and Firmicutes, in addition to increasing the abundances of Bifidobacterium pseudolongum and Mucispirillum schaedleri. In conclusion, IAA exerted several protective effects against PG-induced AS in mice, which was mediated by the restoration of balance among the intestinal microbial community, activating the AhR pathway, and inhibiting inflammation. IAA might represent a novel therapeutic approach for AS.

Recently, accumulating evidence has suggested that gut microbiota may be involved in the occurrence and development of ankylosing spondylitis (AS). It has been suggested that rifaximin have the ability to modulate the gut bacterial communities, prevent inflammatory response, and modulate gut barrier function. The goal of this work is to evaluate the protective effects of rifaximin in fighting AS and to elucidate the potential underlying mechanism. Rifaximin were administered to the proteoglycan (PG)-induced AS mice for 4 consecutive weeks. The disease severity was measured with the clinical and histological of arthritis and spondylitis. Intestinal histopathological, pro-inflammatory cytokine levels and the intestinal mucosal barrier were evaluated. Then, western blot was performed to explore the toll-like receptor 4 (TLR-4) signal transducer and NF-κB expression. Stool samples were collected to analyze the differences in the gut microbiota via next-generation sequencing of 16S rDNA. We found that rifaximin significantly reduced the severity of AS and resulted in down-regulation of inflammatory factors, such as TNF-α, IL-6, IL-17A, and IL-23. Meanwhile, rifaximin prevented ileum histological alterations, restored intestinal barrier function and inhibited TLR-4/NF-κB signaling pathway activation. Rifaximin also changed the gut microbiota composition with increased Bacteroidetes/Firmicutes phylum ratio, as well as selectively promoting some probiotic populations, including Lactobacillales. Our results suggest that rifaximin suppressed progression of AS and regulated gut microbiota in AS mice. Rifaximin might be useful as a novel treatment for AS.

AbstractAnkylosing spondylitis is a chronic, progressive disease, and its treatment is relevant to the gut microbiota. Anti‐tumor necrosis factor‐alpha (anti‐TNF‐α) therapy alters the gut microbiota in many diseases, including inflammatory bowel disease. However, little is known about the effect of TNF‐α blocker treatment on the gut microbiota in ankylosing spondylitis. Herein, the effect of a TNF‐α blocker on the gut microbiota in proteoglycan‐induced arthritis was investigated. Proteoglycan‐induced mice were treated with an rhTNFR:Fc solution of etanercept (5 µg/g) for 4 weeks. rhTNFR:Fc treatment attenuated the arthritis incidence and severity of arthritis in the proteoglycan‐induced mice and decreased inflammation in the ankle joints and ameliorated ileal tissue destruction. Moreover, high gut permeability occurred, and zonula occludens‐1 and occludin protein levels were reduced in proteoglycan‐induced mice. These levels were significantly restored by the administration of rhTNFR:Fc. The serum TNF‐α and IL‐17 levels were also decreased. In addition, flora analysis via 16S rDNA high‐throughput sequencing revealed that rhTNFR:Fc treatment restored the gut microbiota composition to a composition similar to that in control mice. In conclusion, anti‐TNF‐α therapy attenuated proteoglycan‐induced arthritis progression and modulated the gut microbiota and intestinal barrier function. These results provide new insights for anti‐TNF‐α therapy strategies via regulating the gut microbiota in ankylosing spondylitis.

Overweight and obesity have become a public health problem. In obese state, abundant fatty free acids (FFA) were released from hyperplastic adipose tissue and were release to adipocytes, skeletal muscle, liver, then leading to adipocytes inflammation and insulin resistance. Ginsenoside Rb1 was

To study the mechanism of the transforming growth factor-β(TGF-β) in Ginsenoside Rb1 against the replicative senescence of human umbilical vein endothelial cells (HUVECs). Replicative Senescence model was established by serial subcultivation of primary HUVECs in vitro. Then, Cells were divided