Lactobacillus acidophilus ameliorates obesity in mice through modulation of gut microbiota dysbiosis and intestinal permeability.

Obesity associated with low-grade chronic inflammation and intestinal dysbiosis is considered as a worldwide public health crisis. In the meanwhile, different probiotics have demonstrated beneficial effects on this condition, thus increasing the interest in the development of probiotic treatments. In this context, the aim of this study is to investigate the anti-obesity effects of potential probiotic Lactobacillus acidophilus isolated from the porcine gut. Then, it is found that L. acidophilus reduces body weight, fat mass, inflammation and insulin resistance in mice fed with a high-fat diet (HFD), accompanied by activation in brown adipose tissue (BAT) as well as improvements of energy, glucose and lipid metabolism. Besides, our data indicate that L. acidophilus not only reverses HFD-induced gut dysbiosis, as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin bearing Gram-negative bacteria levels, but also maintains intestinal barrier integrity, reduces metabolic endotoxemia, and inhibits the TLR4 / NF- κB signaling pathway. In addition, the results of microbiome phenotype prediction by BugBase and bacterial functional potential prediction using PICRUSt show that L. acidophilus treatment improves the gut microbiota functions involving metabolism, immune response, and pathopoiesia. Furthermore, the anti-obesity effect is transmissible via horizontal faeces transfer from L. acidophilus-treated mice to HFD-fed mice. According to our data, it is seen that L. acidophilus could be a good candidate for probiotic of ameliorating obesity and associated diseases such as hyperlipidemia, nonalcoholic fatty liver diseases, and insulin resistance through its anti-inflammatory properties and alleviation of endothelial dysfunction and gut dysbiosis.

[Mitochondrial calcium uniporter knockdown in hippocampal neurons improved the learning and memory dysfunction of Alzheimer's disease mice].

Alzheimer's disease (AD) is a neurodegenerative disorder, which seriously affects health of the elderly, and is still irreversible up to now. Recent studies have indicated that mitochondrial dysfunction is a direct reason to promote the development of AD. Mitochondrial calcium uniporter (MCU), located in the inner membrane of mitochondria, is a key channel of mitochondrial Ca2+ uptake. Abnormal MCU expression results in imbalance of mitochondrial calcium homeostasis, ultimately leading to mitochondrial dysfunction. The purpose of this study was to determine the effects of MCU knockdown on AD hippocampal neurons and learning and memory function of AD model mice. Lentivirus and adeno-associated virus were used as vectors to transfect shRNA into hippocampal neurons (HT22 cells) and hippocampi of amyloid precursor protein (APP)/presenilin 1 (PS1)/tau AD transgenic mice, respectively, in order to interfere with MCU expression. The cellular activity of HT22 cells was detected by MTS method, and the changes of learning and memory dysfunction in APP/PS1/tau AD transgenic mice were tested by Y maze and Morris water maze. The results showed that MCU knockdown reversed the cellular activity of HT22 cells decreased by amyloid beta protein 1-42 (Aß1-42) or okadaic acid (OA). Knockdown of MCU in hippocampal neurons improved spontaneous alternation (spatial working memory), decreased escape latency, and increased time in target quadrant and number of platform crossing (spatial reference memory) of the APP/PS1/tau mice. This study suggests that MCU knockdown in hippocampal neurons has anti-AD effect, and it is expected to be a new strategy for prevention and treatment of AD.

Mesoporous Silica Carrier-Based Composites for Taste-Masking of Bitter Drug: Fabrication and Palatability Evaluation.

Palatability is one of the most critical characteristics of oral preparations. Therefore, the exploration of new techniques to mask the aversive taste of drugs is in continuous demand. In this study, we fabricated and characterized composites based on mesoporous silica (MPS) that consisted of MPS, a bitter drug, and release regulators. We conducted a palatability evaluation to assess the taste-masking efficacy of the composites. The composites were prepared using the dry impregnation method combined with hot-melt extrusion. Morphology and components distribution in composites were characterized by scanning electron microscopy, confocal laser scanning microscopy, X-ray photoelectron spectroscopy, powder flow properties evaluation, and nitrogen-sorption measurement. The results demonstrated that drugs mainly existed in the inner pore of composites, and release regulators existed in the inner pore and covered the composites' surface. Interactions among the composite components were studied using powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. The drug loaded into the composites was amorphous, and an intermolecular interaction occurred between the drug and the MPS. Taste-masked composites significantly reduced drug release levels under mouth conditions; thus, they prevented the interaction of the dissolved drug with taste receptors and improved palatability. An electronic tongue evaluation and a human taste panel assessment confirmed the better palatability of taste-masked composites. Moreover, the desired drug release behavior can be adjusted by choosing an appropriate release regulator, with stronger hydrophobicity of release regulators resulting in slower drug release. This work has provided new insights into taste-masking strategies for drugs with unpleasant tastes.

Role of sphingosine-1-phosphate mediated signalling in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a highly prevalent autoimmune disease characterized by the malfunction of the immune system and the persistent presence of an inflammatory environment. Multiple organs can be affected during SLE, leading to heterogeneous manifestations, which eventually result in the death of patients. Due to the lack of understanding regarding the pathogenesis of SLE, the currently available treatments remain suboptimal. Sphingosine-1-phosphate (S1P) is a central bioactive lipid of sphingolipid metabolism, which serves a pivotal role in regulating numerous physiological and pathological processes. As a well-recognized regulator of lymphocyte trafficking, S1P has been shown to be closely associated with autoimmune diseases, including SLE. Importantly, S1P levels have been found to be elevated in patients with SLE. In murine models of lupus, the increased levels of S1P also contribute to disease activity and organ impairment. Moreover, data from several studies also support the hypothesis that S1P receptors and its producer-sphingosine kinases (SPHK) may serve as the potential targets for the treatment of SLE and its co-morbidities. Given the significant success that intervening with S1P signaling has achieved in treating multiple sclerosis, further exploration of its role in SLE is necessary. Therefore, the aim of the present review is to summarize the recent advances in understanding the potential mechanism by which S1P influences SLE, with a primary focus on its role in immune regulation and inflammatory responses.

Circular RNA: a novel biomarker and therapeutic target for human cancers.

Circular (circ)RNAs, a newly recognized class of noncoding RNA, have been implicated in the occurrence and development of several diseases, including neurological and cardiovascular diseases. Studies of human tumors, including those of liver cancer, gastric cancer, lung cancer and colorectal cancer, have shown differential expression profiles of circRNAs, suggesting regulatory roles in cancer pathogenesis and metastasis. In this review, we discuss the most recent research into tumor-related circRNAs, providing a comprehensive summary of the expression or/and function of these circRNAs and proposing rational perspectives on the potential clinical application of circRNAs as helpful biomarkers or therapeutic targets in human tumors.

Diverse effects of interleukin-22 on pancreatic diseases.

Interleukin-22 (IL-22) is involved in the development of lymphocytes and serves as a rapid and early source of the effector cytokines that are released in response to pathogen-induced changes in the microenvironment. Recent research has implicated IL-22 as a potential contributing factor to the spectrum of inflammation-related pancreatic diseases, particularly pancreatitis, fibrosis, carcinoma and diabetes. In this review, we summarize the current knowledge on the roles of IL-22 in the various pancreatic pathogenesis, providing insights into the underlying cellular and signaling mechanisms that will help guide future research into promising interventional targets with therapeutic potential.

Effect of Trichinella spiralis-Derived Antigens on Nonalcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice.

Nonalcoholic fatty liver disease (NAFLD) is a liver disease characterized by hepatic steatosis, inflammation, and fibrosis, as well as gut dysbiosis. No approved effective therapeutic medicine is available to date for NAFLD. Helminth therapy is believed to be a novel direction and therapeutic strategy for NAFLD. Our previous study showed that Trichinella spiralis-derived antigens (TsAg) had the potential for partially alleviating obesity via regulating gut microbiota. However, the effect of TsAg on NAFLD remains unclear. In this study, high-fat diet (HFD)-induced model mice were treated with TsAg and microbiota transplantation experiments, and alterations in the pathogenesis of nonalcoholic liver disease were assessed. The results showed that TsAg markedly reduced hepatic steatosis, improved insulin resistance, and regulated the abnormal expression of hepatic lipid-related genes. Of note, TsAg ameliorated hepatic inflammation by decreasing pro-inflammatory TNF-α and IL-1ß, suppressing hepatic macrophage infiltration, as well as promoting M2 macrophage polarization. Moreover, TsAg reversed gut dysbiosis, as especially indicated by an increase in beneficial bacteria (e.g., Akkermansiaceae and Rikenellaceae). Furthermore, our study found that TsAg reduced LPS hepatic translocation and hepatic TLR4/NF-κB signaling, which further contributed to inhibiting hepatic inflammation. In addition, TsAg inhibited hepatic oxidative stress involving Nrf2/NQO-1 signaling. Microbiota transplantation showed that TsAg-altered microbiota is sufficient to confer protection against NAFLD in HFD-induced mice. Overall, these findings suggest that TsAg involving gut-liver axis and Nrf2/NQO-1 signaling is a novel promising candidate for NAFLD treatment. TsAg restores intestinal microbiota and intestinal barrier to inhibit bacteria and LPS translocation into the liver, contributing to reduce inflammation, oxidative stress, and hepatic steatosis in the liver of NAFLD mice. The effects were attributed to, at least in part, the inactivation of NF-κB pathway and the activation of Nrf-2/NQO-1 pathway. This study provides new insights for understanding immune modulation by T. spiralis-derived products as well as the potential application of TsAg as a modality for NAFLD.

Isoliquiritigenin Alleviates Diabetic Kidney Disease via Oxidative Stress and the TLR4/NF-κB/NLRP3 Inflammasome Pathway.

Diabetic kidney disease (DKD) is the primary factor that causes chronic kidney disease and causes increasing mortality and morbidity due to its severe consequences. Isoliquiritigenin (ISL) is the primary element of licorice root that is physiologically active and has antifree radical, antioxidation, and antiapoptotic properties. However, the effect of ISL on DKD is still unclear and needs to be further improved. This study aims to evaluate the renoprotective effects of ISL on diabetes-induced renal injury and explores the underlying mechanisms involved. Male C57BL/6 mice are fed a high-fat diet and then injected with streptozotocin for 2 consecutive days to establish a diabetic model, and high-glucose-treated NRK-52E cells are used to investigate the renoprotective effects of ISL in DKD. The results show that ISL significantly preserves renal function and architecture in DKD. ISL suppresses oxidative stress and reduces ROS levels, inhibiting the activation of the NF-κB and the NLRP3 inflammasome and the occurrence of pyroptosis. Moreover, the study finds that ISL can inhibit the mitochondrial apoptotic pathway. In addition, the study confirms the inhibitory effect of ISL on the TLR4/NF-κB/NLRP3 inflammasome pathway. These observations demonstrate that the natural flavonoid compound ISL can be a promising agent for the treatment of DKD.

Serine protease inhibitor from the muscle larval Trichinella spiralis ameliorates non-alcoholic fatty liver disease in mice via anti-inflammatory properties and gut-liver crosstalk.

Trichinella spiralis is recognized for its ability to regulate host immune responses. The serine protease inhibitor of T. spiralis (Ts-SPI) participates in T. spiralis-mediated immunoregulatory effects. Studies have shown that helminth therapy exhibits therapeutic effects on metabolic diseases. In addition, we previously found that T. spiralis-derived crude antigens could alleviate diet-induced obesity. Thus, Ts-SPI was hypothesized to alleviate non-alcoholic fatty liver disease (NAFLD). Herein, recombinant Ts-SPI (rTs-SPI) was prepared from the muscle larvae T. spiralis. The relative molecular mass of rTs-SPI was approximately 35,000 Da, and western blot analysis indicated good immunoreactivity. rTs-SPI ameliorated hepatic steatosis, inflammation, and pyroptosis in NAFLD mice, which validated the hypothesis. rTs-SPI also reduced macrophage infiltration, significantly expanded Foxp3+ Treg population, and inactivated TLR4/NF-κB/NLRP3 signaling in the liver. Furthermore, rTs-SPI treatment significantly shifted the gut microbiome structure, with a remarkable increase in beneficial bacteria and reduction in harmful bacteria to improve gut barrier integrity. Finally, Abx-treated mice and FMT confirmed that gut-liver crosstalk contributed to NAFLD improvement after rTs-SPI treatment. Taken together, Taken together, these findings suggest that rTs-SPI exerts therapeutic effects in NAFLD via anti-inflammatory activity and gut-liver crosstalk.

Berberine alleviates concanavalin A-induced autoimmune hepatitis in mice by modulating the gut microbiota.

BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology accompanied by intestinal dysbiosis and a damaged intestinal barrier. Berberine (BBR) is a traditional antibacterial medicine that has a variety of pharmacological properties. It has been reported that BBR alleviates AIH, but relevant mechanisms remain to be fully explored. METHODS: BBR was orally administered at doses of 100 mg⋅kg-1⋅d-1 for 7 days to mice before concanavalin A-induced AIH model establishment. Histopathological, immunohistochemical, immunofluorescence, western blotting, ELISA, 16S rRNA analysis, flow cytometry, real-time quantitative PCR, and fecal microbiota transplantation studies were performed to ascertain BBR effects and mechanisms in AIH mice. RESULTS: We found that liver necrosis and apoptosis were decreased upon BBR administration; the levels of serum transaminase, serum lipopolysaccharide, liver proinflammatory factors TNF-α, interferon-γ, IL-1ß, and IL-17A, and the proportion of Th17 cells in spleen cells were all reduced, while the anti-inflammatory factor IL-10 and regulatory T cell proportions were increased. Moreover, BBR treatment increased beneficial and reduced harmful bacteria in the gut. BBR also strengthened ileal barrier function by increasing the expression of the tight junction proteins zonula occludens-1 and occludin, thereby blocking lipopolysaccharide translocation, preventing lipopolysaccharide/toll-like receptor 4 (TLR4)/ NF-κB pathway activation, and inhibiting inflammatory factor production in the liver. Fecal microbiota transplantation from BBR to model mice also showed that BBR potentially alleviated AIH by altering the gut microbiota. CONCLUSIONS: BBR alleviated concanavalin A-induced AIH by modulating the gut microbiota and related immune regulation. These results shed more light on potential BBR therapeutic strategies for AIH.

Gut Microbiome (Bacteria, Fungi, and Viruses) and HIV Infection: Revealing Novel Treatment Strategies.

Plenty of research on microbial-viral interactions has revealed that some commensal microorganisms in the gut, including bacteria, fungi, and viruses, can resist or promote viral infection, whereas other microorganisms are involved in pathogenicity. Therefore, the balance between commensal microorganisms and human organisms is a key factor for determining infection and disease progression, and commensal microorganisms have become a hot research area in the medical field. In this review, the compositional characteristics of gut microbiota (bacteria, fungi, and viruses) during HIV infection are reviewed and changes in gut microbiota among different HIV-infected populations are described. Furthermore, the latest progress of potential microbial therapeutic methods, including a) probiotics, prebiotics, and synbiotics, b) fecal microbiota transplantation (FMT), c) phage therapy, and d) antifungal strategy, microbial enzyme inhibition, and dietary therapeutics, is analyzed based on gut bacteria, fungi, and viruses in the field of HIV infection. This study aims to provide a useful reference for developing novel strategies for the prevention and treatment of HIV infection based on commensal microorganisms.

A Synbiotic Ameliorates Con A-Induced Autoimmune Hepatitis in Mice through Modulation of Gut Microbiota and Immune Imbalance.

SCOPE: Changes in the intestinal flora are related to autoimmune hepatitis (AIH) development. The aim of this study is to investigate the synergistic effects of probiotics and prebiotics on liver injury induced by concanavalin A (Con A). METHODS AND RESULTS: C57BL/6 mice are fed probiotics (Pro), prebiotics (Pre), synbiotic (Syn) for 7 days and then Con A is injected via tail veins to induce AIH. Additionally, methylprednisolone (MP) is gavaged 0.5 h after the Con A injection. It is found that both Pro, Pre, Syn, and MP decrease the levels of serum transaminase, liver F4/80+ macrophage cells, and hepatocellular apoptosis. Pro, Pre, and Syn decrease proinflammatory cytokines, elevate levels of anti-inflammatory as well as restored immune imbalance in AIH. Besides, Pro, Pre, and Syn not only reshape the perturbed gut microbiota, but also maintain intestinal barrier integrity, block the activation of lipopolysaccharide (LPS)/TLR4/NF-κB pathway in the liver. Interestingly, the effects of Syn are superior to Pro or Pre alone in Con A-induced acute liver injury. CONCLUSIONS: Syn obviously facilitates AIH remission. The combined use of Pro and Pre is effective in improving Pro and Pre efficacy and can be an important tool for preventing and adjuvant treating patients for AIH.

S1P/S1PR1 axis promotes macrophage M1 polarization through NLRP3 inflammasome activation in Lupus nephritis.

Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) as well as the leading cause of mortality in patients. Previous studies revealed that S1P level is elevated in plasma samples of SLE patients and murine lupus models. FTY720, targeting S1P receptors, exhibited therapeutic effects in improving the nephritis symptoms of lupus mouse models. However, few studies have discussed the potential relevance of S1P/S1PR to the pathogenesis of LN. Macrophages have been shown to be an important causative agent of renal inflammation, while the pro-inflammatory M1-type promotes kidney injury and inflammation during LN. Importantly, macrophages express various S1P receptors, and how they respond to S1P in the setting of LN remains unclear. Therefore, we examined the level of S1P in the lupus MRL/lpr mice and explored the ensuing interaction of macrophages and S1P. We found that S1P level was elevated in the MRL/lpr mice with a subsequent enhancement of the S1PR1 expression, and blocking S1PR1 by FTY720, the nephritis symptoms of MRL/lpr mice were improved. Mechanistically, we demonstrated that elevated S1P level increase the M1-type macrophage accumulation. And the in-vitro studies proved that S1P/S1PR1 was involved in the promotion of macrophage polarization towards M1 type through activation of NLRP3 inflammasome. These findings confer a novel role to macrophage S1PR1 and provide a new perspective for targeting S1P during LN.

SIRT1 slows the progression of lupus nephritis by regulating the NLRP3 inflammasome through ROS/TRPM2/Ca2+ channel.

Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory disease associated with autoantibody formation. Lupus nephritis (LN) is one of the most severe organ manifestations of SLE. The inflammatory response is a key factor in kidney injury, and the NLRP3 inflammasome is frequently associated with the pathogenesis of LN. Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD +)-dependent histone deacetylase, is a promising therapeutic target for preventing renal injury. However, the mechanism of SIRT1 in LN remains unclear. Here, we aimed to investigate the mechanism by which SIRT inhibits the NLRP3 inflammasome to slow the progression of LN. We detected the expression of SIRT1 and the infiltration of macrophages in MRL/lpr mice; the results showed that the expression of SIRT1 was decreased, and the symptoms of lupus nephritis were relieved after the use of resveratrol, which upregulated SIRT1. In vitro studies showed that after lipopolysaccharide (LPS) stimulation, SIRT1 expression decreased, and the NLRP3 inflammasome was activated. Upregulation of SIRT1 inhibits NLRP3 inflammasome activation and assembly by interfering with two signalling pathways. First, SIRT1 affects NF-κB expression, transcription, and inflammatory cytokine expression. Second, SIRT1 modulates calcium influx induced by transient receptor potential channel M2 (TRPM2), which could be partly due to the inhibition of reactive oxygen species (ROS) production. Our findings suggest that upregulated SIRT1 inhibits the NLRP3 inflammasome to slow the progression of lupus nephritis by regulating NF-κB and ROS/TRPM2/Ca2+ channels. This study reveals a new anti-inflammatory mechanism of SIRT1, suggesting that SIRT1 may be a potential therapeutic target for the prevention of LN.

Compound Probiotic Ameliorates Acute Alcoholic Liver Disease in Mice by Modulating Gut Microbiota and Maintaining Intestinal Barrier.

Alcoholic liver disease (ALD) is a worldwide health threaten lack of effective treatment. Gut dysbiosis and concomitant augmented intestinal permeability are strongly implicated in the pathogenesis and progression of ALD. Research on the protective effect of probiotics on ALD is limited, and more effective intestinal microecological regulators and the related mechanisms still need to be further explored. In the present study, the protective effects and mechanisms of a compound probiotic against acute alcohol-induced liver injury in vivo were explod. It was showed that the compound probiotic ameliorated liver injury in acute ALD mice and stabilized the levels of ALT, AST, and TG in serum. The compound probiotic reversed acute alcohol-induced gut dysbiosis and maintained the intestinal barrier integrity by upregulating the production of mucus and the expression of tight junction (TJ) proteins and thus reduced LPS level in liver. Meanwhile, the compound probiotic reduced inflammation level by inhibiting TLR4/NF-κB signaling pathway and suppressed oxidative stress level in liver. Furthermore, the compound probiotic alleviated liver lipid accumulation by regulating fatty acid metabolism-associated genes and AMPK-PPARα signaling pathway. Noteworthy, fecal microbiota transplantation (FMT) realized comparable protective effect with that of compound probiotic. In conclusion, present study demonstrates the beneficial effects and underlying mechanism of the compound probiotic against acute alcohol-induced liver injury. It provides clues for development of novel strategy for treatment of ALD.

A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway.

Autoimmune hepatitis (AIH) is a liver disease characterized by chronic liver inflammation. The intestinal barrier and microbiome play critical roles in AIH progression. AIH treatment remains challenging because first-line drugs have limited efficacy and many side effects. Thus, there is growing interest in developing synbiotic therapies. This study investigated the effects of a novel synbiotic in an AIH mouse model. We found that this synbiotic (Syn) ameliorated liver injury and improved liver function by reducing hepatic inflammation and pyroptosis. The Syn reversed gut dysbiosis, as indicated by an increase in beneficial bacteria (e.g., Rikenella and Alistipes) and a decrease in potentially harmful bacteria (e.g., Escherichia-Shigella) and lipopolysaccharide (LPS)-bearing Gram-negative bacterial levels. The Syn maintained intestinal barrier integrity, reduced LPS, and inhibited the TLR4/NF-κB and NLRP3/Caspase-1 signaling pathway. In addition, microbiome phenotype prediction by BugBase and bacterial functional potential prediction using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed that Syn improved gut microbiota function involving inflammatory injury, metabolism, immune response, and pathopoiesia. Furthermore, the new Syn was as effective as prednisone against AIH. Therefore, this novel Syn could be a candidate drug for alleviating AIH through its anti-inflammatory and antipyroptosis properties that relieve endothelial dysfunction and gut dysbiosis. IMPORTANCE Synbiotics can ameliorate liver injury and improve liver function by reducing hepatic inflammation and pyroptosis. Our data indicate that our new Syn not only reverses gut dysbiosis by increasing beneficial bacteria and decreasing lipopolysaccharide (LPS)-bearing Gram-negative bacteria but also maintains intestinal barrier integrity. Thus, its mechanism might be associated with modulating gut microbiota composition and intestinal barrier function by inhibiting the TLR4/NF-κB/NLRP3/pyroptosis signaling pathway in the liver. This Syn is as effective as prednisone in treating AIH without side effects. Based on these findings, this novel Syn represents a potential therapeutic agent for AIH in clinical practice.

The Trichinella spiralis-derived antigens alleviate HFD-induced obesity and inflammation in mice.

Obesity, an increasingly prevalent disease worldwide, is accompanied by chronic inflammation and intestinal dysbiosis. Helminth infections have been increasingly proved to exhibit a protective role in several inflammation-associated diseases. Considering the side effects of live parasite therapy, efforts have been made to develop helminth-derived antigens as promising candidates with fewer adverse effects. This study aimed to evaluate the effect and mechanisms of TsAg (T. spiralis-derived antigens) on obesity and the associated inflammation in high-fat diet (HFD)-fed mice. C57BL/6J mice were fed a normal diet or HFD with or without TsAg treatment. The results reported that TsAg treatment alleviated body weight gain and chronic inflammation induced by HFD. In the adipose tissue, TsAg treatment prevented macrophage infiltration, reduced the expression of Th1-type (IFN-γ) and Th17-type (IL-17A) cytokines while upregulating the production of Th2-type (IL-4) cytokines. Furthermore, TsAg treatment enhanced brown adipose tissue activation and energy and lipid metabolism and reduced intestinal dysbiosis, intestinal barrier permeability and LPS/TLR4 axis inflammation. Finally, the protective role of TsAg against obesity was transmissible via the fecal microbiota transplantation approach. For the first time, our findings showed that TsAg alleviated HFD-induced obesity and inflammation via modulation of the gut microbiota and balancing the immune disorders, suggesting that TsAg might be a safer promising therapeutic strategy for obesity.

A Newly Synbiotic Combination Alleviates Obesity by Modulating the Gut Microbiota-Fat Axis and Inhibiting the Hepatic TLR4/NF-κB Signaling Pathway.

SCOPE: Obesity has been recognized as a worldwide public health crisis, this is accompanied by dysregulation of the intestinal microbiota and upregulation of liver steatosis and adipose inflammation. Synbiotic as a novel alternative therapy for obesity have recently gained much attention. METHODS: This study innovatively research the anti-obesity properties of a newly synbiotic composed of Lactobacillus acidophilus, Bifidobacterium infantis and konjac glucomannan oligosaccharides. RESULTS: The synbiotic treatment can reduce body weight, fat mass, blood sugar, liver steatosis and adipose inflammation in obesity mice fed by high-fat diet (HFD). Meanwhile, synbiotic treatment activated brown adipose tissue and improve energy, glucose and lipid metabolism. In addition, synbiotic treatment not solely enhanced the protection of intestinal barrier, but also ameliorated gut microbiota dysbiosis directly by enhancing beneficial microbes and reducing potentially harmful bacteria. Furthermore, the microbiome phenotype and functional prediction showed that synbiotic treatment can improve the gut microbiota functions involving inflammatory state, immune response, metabolism and pathopoiesia. CONCLUSION: The synbiotic may be an effective candidate treatment strategy for the clinical prevention and treatment of obesity and other associated metabolic diseases such as hyperlipidemia, nonalcoholic fatty liver diseases by alleviating inflammatory response, regulating energy metabolism and maintaining the balance of intestinal microecology.

Hydrogen gas ameliorates acute alcoholic liver injury via anti-inflammatory and antioxidant effects and regulation of intestinal microbiota.

Alcoholic liver disease (ALD) is a globally prevalent liver-related disorder characterized by severe oxidative stress and inflammatory liver damage, for which no effective treatment is currently available. Hydrogen gas (H2) has been demonstrated to be an efficient antioxidant in various diseases in animals as well as humans. However, the protective effects of H2 on ALD and its underlying mechanisms remain to be elucidated. The present study demonstrated that H2 inhalation ameliorated liver injury, and attenuated liver oxidative stress, inflammation, and steatosis in an ALD mouse model. Moreover, H2 inhalation improved gut microbiota, including increasing the abundance of Lachnospiraceae and Clostridia, and decreasing the abundance of Prevotellaceae and Muribaculaceae, and also improved intestinal barrier integrity. Mechanistically, H2 inhalation blocked activation of the LPS/TLR4/NF-κB pathway in liver. Notably, it was further demonstrated that the reshaped gut microbiota may accelerate alcohol metabolism, regulate lipid homeostasis and maintain immune balance by bacterial functional potential prediction (PICRUSt). Fecal microbiota transplantation from mice that had undergone H2 inhalation significantly alleviated acute alcoholic liver injury. In summary, the present study showed that H2 inhalation alleviated liver injury by reducing oxidative stress and inflammation, while also improving intestinal flora and enhancing the intestinal barrier. H2 inhalation may serve as an effective intervention for preventing and treating ALD in a clinical context.

Cyclophilin A inhibits rotavirus replication by facilitating host IFN-I production.

Rotavirus (RV) infection causes serious dehydrating diarrhoea in infants and newborn animals. Our previous study revealed that cyclophilin A (CYPA), a peptidyl-prolyl cis-trans isomerase (PPIase), could be temporarily upregulated in RV-infected MA104 cells in early stage of infection (unpublished data). To find out the possible roles of CYPA in RV infection, we overexpressed and silenced CYPA in various cell lines by gene transfection and shRNA. We found that transfection of CYPA significantly inhibited RV replication, while silencing the expression of CYPA significantly increased RV replication. Accordingly, overexpression of CYPA significantly increased IFN-ß production; while silencing CYPA significantly reduced IFN-ß production. This effect of CYPA on IFN-ß production was independent of its PPIase activity. Moreover, IFN-ß secreted by host cells in RV infection had a critical repressive effect on viral replication. Finally, we found that inhibiting JNK pathway by SP600125 and JNK siRNA abrogated the effect of CYPA on IFN-ß transcription in RV-infected MA104 cells. Together, our data suggested that CYPA inhibited RV replication by facilitating host IFN-ß production, which was independent on the PPIase activity of CYPA but dependent on the activation of JNK signaling pathway.