Incidence and outcomes of splanchnic vein thrombosis after diagnosis of COVID-19 or COVID-19 vaccination: a systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) and COVID-19 vaccination may cause splanchnic vein thrombosis (SVT), which is potentially fatal. The present study aims to pool the incidence and outcomes of SVT patients with COVID-19 or having received COVID-19 vaccines. The PubMed, EMBASE, and Cochrane databases were searched. Based on the data from cohort studies, meta-analyses were performed to evaluate the incidence of SVT in COVID-19 patients or people having received COVID-19 vaccines. Pooled proportions were calculated. Based on the individual data from case reports, logistic regression analyses were performed to identify factors associated with death in SVT patients. Odds ratios (ORs) were calculated. Among 654 papers initially identified, 135 were included. Based on 12 cohort studies, the pooled incidence of SVT in COVID-19 patients was 0.6%. Data were insufficient to estimate the incidence of SVT after COVID-19 vaccination. Based on 123 case reports, the mortality was 14% (9/64) in SVT patients with COVID-19 and 25% (15/59) in those who received COVID-19 vaccines. Univariate analyses demonstrated that age (OR = 1.061; p = 0.017), diabetes mellitus (OR = 14.00; p = 0.002), anticoagulation (OR = 0.098; p = 0.004), and bowel resection (OR = 16.00; p = 0.001) were significantly associated with death in SVT patients with COVID-19; and anticoagulation (OR = 0.025; p = 0.003) and intravenous immunoglobulin (OR = 0.175; p = 0.046) were significantly associated with death in SVT patients who received COVID-19 vaccines. Multivariate analyses did not identify any independent factor for death in both patients. SVT in COVID-19 patients and in subjects who received COVID-19 vaccines carries a high mortality, but may be improved by anticoagulation. PROSPERO Identifier CRD42022315254.

RNA-seq analysis of green tea polyphenols modulation of differently expressed genes in Enterococcus faecalis under low pH.

Enterococcus faecasslis (E. faecalis) is a resident bacterium in the host. The increase in internal stress like low pH may affect the biological effects of E. faecalis. The prebiotic-like function of tea polyphenols can enhance the beneficial effects of its tolerance to environmental stress. In this study, RNA-sequence analysis was used to explore the protective effect of green tea polyphenols (GTP) on E. faecalis under low pH stress. A total of 28 genes were found to be responsive to GTP under low pH stress, including 16 up-regulated and 12 down-regulated. GTP intervention can partly relieve some undesired negative influences, such as the down-regulation of the base excision repair gene and amino acid transport and metabolism gene. The significantly changes were associated with selenocompound metabolism and aminoacyl-tRNA biosynthesis after the intervention of GTP. The present study provided new insights into the growth and continuous adaptation of E. faecalis under stress.

A metagenomic analysis of the modulatory effect of Cyclocarya paliurus flavonoids on the intestinal microbiome in a high-fat diet-induced obesity mouse model.

BACKGROUND: As a result of a low bioavailability, the majority of Cyclocarya paliurus flavonoids (CPF) remain in the large intestine where they accumulate to exert a modulatory effect on the intestinal micro-ecology. Therefore, the present study investigated the modulatory effect of CPF on intestinal microbiota. RESULTS: CPF dramatically ameliorated the obesity-induced gut dysbiosis. A significant decrease (P < 0.05) was observed in the ratio of Firmicutes/Bacteroidetes after CPF treatment for 8 weeks. Moreover, Kyoto Encyclopedia of Genes and Genomes pathways of biosynthesis of amino acids, the two-component system and ATP-binding cassette transporters enriched the most differentially expressed genes after CPF intervention. CONCLUSION: The results of the present study indicate that CPF might have prebiotic-like activity and could be used as a functional food component with potential therapeutic utility to prevent obesity-related metabolic disorders by manipulating the gut flora and affecting certain metabolic pathways, thus contributing to the improvement of human health. © 2019 Society of Chemical Industry.

RNA-seq transcriptomic analysis of green tea polyphenols regulation of differently expressed genes in Saccharomyces cerevisiae under ethanol stress.

Saccharomyces cerevisiae has been widely used to produce alcoholic beverages and bio-fuels; however, its performance is remarkably compromised by the increased ethanol concentration during the fermentation process. In this study, RNA-sequence analysis was used to investigate the protective effect of green tea polyphenols (GTP) on S. cerevisiae cells from ethanol-induced damage. GO and KEGG analysis showed that to deal with the stress of ethanol, large amounts of genes related to cell wall, cell membrane, basic metabolism and redox regulation were significantly differentially expressed (P < 0.05), while these undesired changes could be partly relieved by administration of GTP, suggesting its potential to enhance the ethanol tolerance of S. cerevisiae. The present study provided a global view of the transcriptomic changes of S. cerevisiae in response to the accumulation of ethanol and the treatment of GTP, which might deepen our understanding about S. cerevisiae and the fermentation process, and thus benefit the development of the bioethanol production industry.

The evaluation of the quality of Feng Huang Oolong teas and their modulatory effect on intestinal microbiota of high-fat diet-induced obesity mice model.

The variations in the contents of tea catechins and free amino acids in relation to the quality of Fenghuang Oolong teas (FOT) were determined. It demonstrated that in FOT, which were grown at a high altitude, the contents of methylated estered tea catechins were relatively higher. By human flora-associated (HFA) mice model, the effect of FOT on high-fat diet-induced obesity was investigated by high-throughput sequencing. The shifts in relative abundance of the dominant taxa at the phylum, family and genus levels showed their dramatically effects. A large increase in Bacteroidetes with decrease of Firmicutes was observed after the administration of FOT for 8 weeks. Together, these results suggest that FOT are rich in tea catechins, especially O-methylated tea catechin derivatives, which may be affected by the unique growth environment, and FOT may have prebiotic-like activity and can be used as functional food components in manipulating intestinal microbiota.

A transcriptome analysis of the ameliorate effect of Cyclocarya paliurus triterpenoids on ethanol stress in Saccharomyces cerevisiae.

Saccharomyces cerevisiae (S. cerevisiae) plays a critical role in ethanol fermentation. However, during the fermentation, yeast cells are exposed to the accumulation of ethanol, which significantly affect the cell growth and the target product yield. In the present work, we employed RNA-sequence (RNA-seq) to investigate the ameliorate effect of Cyclocarya paliurus (C. paliurus) triterpenoids on S. cerevisiae under the ethanol stress. After C. paliurus triterpenoids intervention (0.3% v/v), 84 differentially expressed genes (DEGs) were identified, including 39 up-regulated and 45 down-regulated genes. The addition of triterpenoids decreased the filamentous and invasive growth of cells, and benefit to the redox balance and glycolysis. This study offers a global view through transcriptome analysis to understand the molecular response to ethanol in Sc131 by the treatment of C. paliurus triterpenoids, which may be helpful to enhance ethanol tolerance of S. cerevisiae in the fermentation of Chinese fruit wine.

Caco-2 cell transport of purple sweet potato anthocyanins-phospholipids complex.

In this study, the role of phospholipids in transepithelial transport and the impact on the antioxidant activity of purple sweet potato anthocyanins (PSPAs) was evaluated. PSPAs were purified by column chromatography, and then PSPAs-phospholipids complex (PSPAs-PC) was prepared. In antioxidant assay in vitro, PSPAs-PC exhibited potential antioxidant activity; meanwhile, it exhibited relatively higher stability in mimic gastrointestinal digestion conditions. The inhibitory effect of PSPAs-PC on the oxidation of soybean oil was significantly higher after 15 days storage. The presence of phospholipids increased the transepithelial transport of PSPAs; its apparent permeability coefficient (Papp) was higher, while its efflux ratio was lower than PSPAs. Based on the above results, it clearly displays the potential of phospholipids in the promotion of intestinal transport of PSPAs, and further studies are needed to explore the in-depth mechanism of the bioavailability promotion effect of phospholipids.

The modulatory effect of polyphenols from green tea, oolong tea and black tea on human intestinal microbiota in vitro.

In the present study, polyphenols from green tea (GTP), oolong tea (OTP) and black tea (BTP) were prepared by extraction with hot water and polyamide column chromatography. In antioxidant assay in vitro, each tea polyphenols exhibited potential activity; the intestinal absorption of GTP, OTP and BTP was investigated individually by Caco-2 transwell system, and each sample was poorly transported, illustrating a low transport rate for tea polyphenols through cell monolayers. The effects of GTP, OTP and BTP on human intestinal microbiota were also evaluated, and each sample induced the proliferation of certain beneficial bacteria and inhibited Bacteroides-Prevotella and Clostridium histolyticum. Moreover, the short-chain fatty acids (SCFA) produced in cultures with tea polyphenols were relatively higher. Together, these results suggested GTP, OTP and BTP may modulate the intestinal flora and generate SCFA, and contribute to the improvements of human health.

ASFV pA151R negatively regulates type I IFN production via degrading E3 ligase TRAF6.

African swine fever (ASF) caused by African swine fever virus (ASFV) is a highly mortal and hemorrhagic infectious disease in pigs. Previous studies have indicated that ASFV modulates interferon (IFN) production. In this study, we demonstrated that ASFV pA151R negatively regulated type I IFN production. Ectopic expression of pA151R dramatically inhibited K63-linked polyubiquitination and Ser172 phosphorylation of TANK-binding kinase 1 (TBK1). Mechanically, we demonstrated that E3 ligase TNF receptor-associated factor 6 (TRAF6) participated in the ubiquitination of TBK1 in cGAS-STING signaling pathway. We showed that pA151R interacted with TRAF6 and degraded it through apoptosis pathway, leading to the disruption of TBK1 and TRAF6 interaction. Moreover, we clarified that the amino acids H102, C109, C132, and C135 in pA151R were crucial for pA151R to inhibit type I interferon production. In addition, we verified that overexpression of pA151R facilitated DNA virus Herpes simplex virus 1 (HSV-1) replication by inhibiting IFN-ß production. Importantly, knockdown of pA151R inhibited ASFV replication and enhanced IFN-ß production in porcine alveolar macrophages (PAMs). Our findings will help understand how ASFV escapes host antiviral immune responses and develop effective ASFV vaccines.

Identification of new hub- ferroptosis-related genes in Lupus Nephritis.

Background: Lupus Nephritis (LN) is the primary causation of kidney injury in systemic lupus erythematosus (SLE). Ferroptosis is a programmed cell death. Therefore, understanding the crosstalk between LN and ferroptosis is still a significant challenge. Methods: We obtained the expression profile of LN kidney biopsy samples from the Gene Expression Omnibus database and utilised the R-project software to identify differentially expressed genes (DEGs). Then, we conducted a functional correlation analysis. Ferroptosis-related genes (FRGs) and differentially expressed genes (DEGs) crossover to select FRGs with LN. Afterwards, we used CIBERSORT to assess the infiltration of immune cells in both LN tissues and healthy control samples. Finally, we performed immunohistochemistry on LN human renal tissue. Results: 10619 DEGs screened from the LN biopsy tissue were identified. 22 hub-ferroptosis-related genes with LN (FRGs-LN) were screened out. The CIBERSORT findings revealed that there were significant statistical differences in immune cells between healthy control samples and LN tissues. Immunohistochemistry further demonstrated a significant difference in HRAS, TFRC, ATM, and SRC expression in renal tissue between normal and control groups. Conclusion: We developed a signature that allowed us to identify 22 new biomarkers associated with FRGs-LN. These findings suggest new insights into the pathology and therapeutic potential of LN ferroptosis inhibitors and iron chelators.

Taurolithocholic acid protects against viral haemorrhagic fever via inhibition of ferroptosis.

Bile acids are microbial metabolites that can impact infection of enteric and hepatitis viruses, but their functions during systemic viral infection remain unclear. Here we show that elevated levels of the secondary bile acid taurolithocholic acid (TLCA) are associated with reduced fatality rates and suppressed viraemia in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne haemorrhagic fever virus. TLCA inhibits viral replication and mitigates host inflammation during SFTSV infection in vitro, and indirectly suppresses SFTSV-mediated induction of ferroptosis by upregulating fatty acid desaturase 2 via the TGR5-PI3K/AKT-SREBP2 axis. High iron and ferritin serum levels during early infection were correlated with decreased TLCA levels and fatal outcomes in SFTSV-infected patients, indicating potential biomarkers. Furthermore, treatment with either ferroptosis inhibitors or TLCA protected mice from lethal SFTSV infection. Our findings highlight the therapeutic potential of bile acids to treat haemorrhagic fever viral infection.

Artificial Intelligence in Liver Diseases: Recent Advances.

Liver diseases cause a significant burden on public health worldwide. In spite of great advances during recent years, there are still many challenges in the diagnosis and treatment of liver diseases. During recent years, artificial intelligence (AI) has been widely used for the diagnosis, risk stratification, and prognostic prediction of various diseases based on clinical datasets and medical images. Accumulative studies have shown its performance for diagnosing patients with nonalcoholic fatty liver disease and liver fibrosis and assessing their severity, and for predicting treatment response and recurrence of hepatocellular carcinoma, outcomes of liver transplantation recipients, and risk of drug-induced liver injury. Herein, we aim to comprehensively summarize the current evidence regarding diagnostic, prognostic, and/or therapeutic role of AI in these common liver diseases.

Inhibitory effect of Dendrobium officinale polysaccharide on oxidative damage of glial cells in aging mice by regulating gut microbiota.

Polysaccharides extracted from Dendrobium officinale have various physiological effects. In this study, we used D-galactose-induced senescent mice as an animal model to investigate the inhibitory effects of Dendrobium officinale polysaccharide (DOP) on oxidative damage in glial cells by attenuating oxidative stress and modulating the gut microbiota. The results showed that DOP significantly alleviated the activation of glial cells, increased the activity of antioxidant enzymes and reduced the MDA content in senescent mice. In addition, DOP reshaped the disordered gut microbiota, decreased the abundance ratio of Firmicutes to Bacteroidetes and increased the abundance of beneficial bacteria Lactobacillus. DOP may reverse the gut microbiota disturbance and alleviate the oxidative damage of glial cells, therefore exert potential neuroprotective effects by modulating gut microbiota.

Effect of Dendrobium officinale polysaccharides on central nervous system disease: Based on gut microbiota.

Dendrobium officinale has anti-inflammatory effects and is one of the well-known functional foods. Dendrobium officinale polysaccharide (DOP) can reduce intestinal barrier disruption and excessive inflammatory response by regulating intestinal bacterial homeostasis as well as short-chain fatty acid levels. It can also inhibit the activation of astrocytes and microglia, further realizing the protective effect on neuronal apoptosis and apoptosis, thus exerting a significant alleviating effect on neurological diseases. There is now evidence that bidirectional communication between the central nervous system and the gastrointestinal tract may influence human neurology, cognition and behavior via the gut-brain axis. In this review, we review the structural characterization, bioactivity and possible bioactive mechanisms of DOP, so as to elucidate the advantages of DOP's action on CNS diseases, with the aim of providing new perspectives for its drug and functional food development as well as clinical applications.

Ameliorative effect of black tea extract on the skin of D-galactose-induced aging mice.

Aging is a universal and irreversible process, and the skin is an important feature that reflects the aging of the organism. Skin aging has been a focus of attention in recent years because it leads to changes in an individual's external features and the loss of many important biological functions. This experiment investigated the improvement effect of black tea extract (BTE) on the skin of aging mice under D-galactose induction. After 6 weeks of administration, the changes in skin bio-chemical indices and tissue structure were compared with the blank and positive control groups. It was observed that BTE increased water and hyaluronic acid (HA) content, decreased malondialdehyde (MDA) content, enhanced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in the skin of aging mice, and improved the structure of aging damaged skin tissues and increased the content of total collagen. The experimental results showed that BTE can play a significant anti-aging effect on the skin, which can be used as a functional food for aging inhibition.

Lead detoxification of edible fungi Auricularia auricula and Pleurotus ostreatus: the purification of the chelation substances and their effects on rats.

Lead is a global pollutant that causes widespread concern. When a lead enters the body, it is distributed throughout the body and accumulates in the brain, bone, and soft tissues such as the kidney, liver, and spleen. Chelators used for lead poisoning therapy all have side effects to some extent and other drawbacks including high cost. Exploration and utilization of natural antidotes become necessary. To date, few substances originating from edible fungi that are capable of adsorbing lead have been reported. In this study, we found that two commonly eaten mushrooms Auricularia auricula and Pleurotus ostreatus exhibited lead adsorption capacity. A. auricula active substance (AAAS) and P. ostreatus active substance (POAS) were purified by hot-water extraction, ethanol precipitation from its fruiting bodies followed by ion exchange chromatography, ultrafiltration, and gel filtration chromatography, respectively. AAAS was 3.6 kDa, while POAS was 4.9 kDa. They were both constituted of polysaccharides and peptides. The peptide sequences obtained by liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) proved that they were rich in amino acids with side chain groups such as hydroxyl, carboxyl, carbonyl, sulfhydryl, and amidogen. Two rat models were established, but only a chronic lead-induced poisoning model was employed to determine the detoxification of AAAS/POAS and their fruiting body powder. For rats receiving continuous lead treatment, either AAAS or POAS could reduce the lead levels in the blood. They also promoted the elimination of the burden of lead in the spleen and kidney. The fruiting bodies were also proved to have lead detoxification effects. This is the first study to identify new functions of A. auricula and P. ostreatus in reducing lead toxicity and to provide dietary strategies for the treatment of lead toxicity.

Treatment and outcomes of immune checkpoint inhibitors-associated colitis/diarrhea: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved the outcomes of cancer patients. However, ICIs often lead to colitis/diarrhea. This study aimed to assess the treatment of ICIs-associated colitis/diarrhea and outcomes. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies which investigated the treatment and outcomes of colitis/diarrhea developing in patients who received ICIs. The pooled incidences of any-grade colitis/diarrhea, low-grade colitis, high-grade colitis, low-grade diarrhea, and high-grade diarrhea as well as the pooled rates of response to treatment, mortality, and ICIs permanent discontinuation and restarts in patients with ICIs-associated colitis/diarrhea were estimated using a random-effects model. RESULTS: Among the 11,492 papers initially identified, 27 studies were included. The pooled incidences of any-grade colitis/diarrhea, low-grade colitis, high-grade colitis, low-grade diarrhea, and high-grade diarrhea were 17%, 3%, 17%, 13%, and 15%, respectively. The pooled rates of overall response, response to corticosteroid therapy, and response to biological agents were 88%, 50%, and 96%, respectively. The pooled short-term mortality in patients with ICIs-associated colitis/diarrhea was 2%. The pooled incidences of ICIs permanent discontinuation and restarts were 43% and 33%, respectively. CONCLUSION: ICIs-associated colitis/diarrhea is common, but rarely lethal. Half of them are responsive to corticosteroid therapy. There is a fairly high rate of response to biological agents in steroid-refractory colitis/diarrhea patients.

Incidence and outcomes of pancreatic encephalopathy in patients with acute pancreatitis: a systematic review and meta-analysis.

Pancreatic encephalopathy (PE) is a lethal complication of acute pancreatitis (AP), but its clinical characteristics and prognosis remain obscure. Herein, we performed a systematic review and meta-analysis to evaluate the incidence and outcomes of PE in AP patients. PubMed, EMBASE, and China National Knowledge Infrastructure were searched. Based on the data from cohort studies, the incidence and mortality of PE in AP patients were pooled. Based on the individual data from case reports, logistic regression analyses were performed to identify the risk factors for death in PE patients. Among 6702 papers initially identified, 148 were included. Based on 68 cohort studies, the pooled incidence and mortality of PE in AP patients were 11% and 43%, respectively. The causes of death were clearly reported in 282 patients, of which the most common was multiple organ failure (n = 197). Based on 80 case reports, 114 AP patients with PE were included. The causes of death were clearly reported in 19 patients, of which the most common was multiple organ failure (n = 8). Univariate analyses showed that multiple organ failure (OR = 5.946; p = 0.009) and chronic cholecystitis (OR = 5.400; p = 0.008) were the significant risk factors of death among patients with PE. PE is not a rare complication of AP and indicates poor prognosis. Such a high mortality of PE patients may be attributed to its coexistence of multiple organ failure.

African swine fever virus S273R protein antagonizes type I interferon production by interfering with TBK1 and IRF3 interaction.

African swine fever (ASF) is originally reported in East Africa as an acute hemorrhagic fever. African swine fever virus (ASFV) is a giant and complex DNA virus with icosahedral structure and encodes a variety of virulence factors to resist host innate immune response. S273R protein (pS273R), as a SUMO-1 specific cysteine protease, can affect viral packaging by cutting polymeric proteins. In this study, we found that pS273R was an important antagonistic viral factor that suppressed cGAS-STING-mediated type I interferon (IFN-I) production. A detailed analysis showed that pS273R inhibited IFN-I production by interacting with interferon regulatory factor 3 (IRF3). Subsequently, we showed that pS273R disrupted the association between TBK1 and IRF3, leading to the repressed IRF3 phosphorylation and dimerization. Deletion and point mutation analysis verified that pS273R impaired IFN-I production independent of its cysteine protease activity. These findings will help us further understand ASFV pathogenesis.

African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation.

Cyclic GMP-AMP synthase (cGAS) recognizes viral DNA and synthesizes cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING/MITA) and downstream mediators to elicit an innate immune response. African swine fever virus (ASFV) proteins can antagonize host immune responses to promote its infection. Here, we identified ASFV protein QP383R as an inhibitor of cGAS. Specifically, we found that overexpression of QP383R suppressed type I interferons (IFNs) activation stimulated by dsDNA and cGAS/STING, resulting in decreased transcription of IFNß and downstream proinflammatory cytokines. In addition, we showed that QP383R interacted directly with cGAS and promoted cGAS palmitoylation. Moreover, we demonstrated that QP383R suppressed DNA binding and cGAS dimerization, thus inhibiting cGAS enzymatic functions and reducing cGAMP production. Finally, the truncation mutation analysis indicated that the 284-383aa of QP383R inhibited IFNß production. Considering these results collectively, we conclude that QP383R can antagonize host innate immune response to ASFV by targeting the core component cGAS in cGAS-STING signaling pathways, an important viral strategy to evade this innate immune sensor.