Since December, 2019, coronavirus disease 2019 (COVID-19) has affected more than 100 000 patients globally.1 COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ...has a case-fatality rate of 2·3%, with higher rates among elderly patients and patients with comorbidities.2 Person-to-person transmission is efficient, with multiple clusters reported. ...the IgG and IgM antibody level against the SARS-CoV-2 internal nucleoprotein and the surface spike receptor binding domain correlated with neutralising activity. ...age was associated with viral load in this study, which could explain the high degree of severe disease in older patients with SARS-CoV-2.5,6 The high viral load in elderly patients is associated not only with low immunity but also with high expression of the ACE2 receptor (the cell-entry receptor for SARS-CoV-2) in older adults.7 The timing of antibody seroconversion is crucial for determining the optimum timepoints for collecting serum specimens for antibody testing for diagnosis.
Xonghong Xiao and colleagues analyze the challenge of antimicrobial resistance in China. A government strategy to promote rational use of antimicrobials in health care reduced antibiotic sales and ...percentage of prescriptions for antimicrobials for both hospitalized patients and outpatients, and offers insights to shape future initiatives. Please see later in the article for the Editors' Summary.
Acetaminophen (APAP)-induced injury is a common clinical phenomenon that not only occurs in a dose-dependent manner but also occurs in some idiosyncratic individuals in a dose-independent manner. ...APAP overdose generally results in acute liver injury via the initiation of oxidative stress, endoplasmic reticulum (ER) stress, autophagy, liver inflammation, and microcirculatory dysfunction. Liver transplantation is the only effective strategy for treating APAP-induced liver failure, but liver transplantation is inhibited by scarce availability of donor liver grafts, acute graft rejection, lifelong immunosuppression, and unbearable costs. Currently, N-acetylcysteine (NAC) effectively restores liver functions early after APAP intake, but it does not protect against APAP-induced injury at the late stage. An increasing number of animal studies have demonstrated that mesenchymal stem cells (MSCs) significantly attenuate acute liver injury through their migratory capacity, hepatogenic differentiation, immunoregulatory capacity, and paracrine effects in acute liver failure (ALF). In this review, we comprehensively discuss the mechanisms of APAP overdose-induced liver injury and current therapies for treating APAP-induced liver injury. We then comprehensively summarize recent studies about transplantation of MSC and MSC derivatives for treating APAP-induced liver injury. We firmly believe that MSCs and their derivatives will effectively promote liver regeneration and liver injury repair in APAP overdose-treated animals and patients. To this end, MSC-based therapies may serve as an effective strategy for patients who are waiting for liver transplantation during the early and late stages of APAP-induced ALF in the near future.
Intimate metabolic host-microbiome crosstalk regulates immune, metabolic, and neuronal response in health and disease, yet remains untapped for biomarkers or intervention for disease. Our recent ...study identified an altered microbiome in patients with pre-onset amnestic mild cognitive impairment (aMCI) and dementia Alzheimer's disease (AD). Thus, we aimed to characterize the gut microbial metabolites among AD, aMCI, and healthy controls (HC). Here, a cohort of 77 individuals (22 aMCI, 27 AD, and 28 HC) was recruited. With the use of liquid-chromatography/gas chromatography mass spectrometry metabolomics profiling, we identified significant differences between AD and HC for tryptophan metabolites, short-chain fatty acids (SCFAs), and lithocholic acid, the majority of which correlated with altered microbiota and cognitive impairment. Notably, tryptophan disorders presented in aMCI and SCFAs decreased progressively from aMCI to AD. Importantly, indole-3-pyruvic acid, a metabolite from tryptophan, was identified as a signature for discrimination and prediction of AD, and five SCFAs for pre-onset and progression of AD. This study showed fecal-based gut microbial signatures were associated with the presence and progression of AD, providing a potential target for microbiota or dietary intervention in AD prevention and support for the host-microbe crosstalk signals in AD pathophysiology.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with gut microbiota imbalance playing a significant role. There are increasing numbers of research studies exploring treatment ...options involving probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), but it is still uncertain which treatment option is superior. The research was conducted on various databases and unpublished trial data (up to February 2023). Randomized controlled trials (RCTs) were screened for adult patients with IBS comparing interventions with placebo. Probiotics, prebiotics, synbiotics, and FMT were assessed for their impact using mean difference and Bayesian network meta-analysis. Out of 6528 articles, 54 were included for probiotics, 7 for prebiotics/synbiotics, and 6 for FMT. Probiotics showed improvement in IBS symptoms, particularly with Bifidobacterium and Lactobacillus strains. Prebiotics and synbiotics did not show significant improvement. Network meta-analysis indicated the favorable effects of probiotics (OR = 0.53, 95% CI, 0.48 to 0.59) and FMT (OR = 0.46, 95% CI, 0.33 to 0.64) on IBS, with no serious adverse events reported. In short, probiotics and FMT are effective for managing IBS, with Bifidobacterium and Lactobacillus being dominant strains. However, the most effective probiotic combination or strain remains unclear, while prebiotics and synbiotics did not show significant improvement.
Summary Infection with either influenza A H5N1 virus in 1997 or avian influenza A H7N9 virus in 2013 caused severe pneumonia that did not respond to typical or atypical antimicrobial treatment, and ...resulted in high mortality. Both viruses are reassortants with internal genes derived from avian influenza A H9N2 viruses that circulate in Asian poultry. Both viruses have genetic markers of mammalian adaptation in their haemagglutinin and polymerase PB2 subunits, which enhanced binding to human-type receptors and improved replication in mammals, respectively. Hong Kong (affected by H5N1 in 1997) and Shanghai (affected by H7N9 in 2013) are two rapidly flourishing cosmopolitan megacities that were increasing in human population and poultry consumption before the outbreaks. Both cities are located along the avian migratory route at the Pearl River delta and Yangtze River delta. Whether the widespread use of the H5N1 vaccine in east Asia—with suboptimum biosecurity measures in live poultry markets and farms—predisposed to the emergence of H7N9 or other virus subtypes needs further investigation. Why H7N9 seems to be more readily transmitted from poultry to people than H5N1 is still unclear.
Orally administered probiotics encounter various challenges on their journey through the mouth, stomach, intestine and colon. The health benefits of probiotics are diminished mainly due to the ...substantial reduction of viable probiotic bacteria under the harsh conditions in the gastrointestinal tract and the colonization resistance caused by commensal bacteria. In this review, we illustrate the factors affecting probiotic viability and their mucoadhesive properties through their journey in the gastrointestinal tract, including a discussion on various mucosadhesion-related proteins on the probiotic cell surface which facilitate colonization.
Summary Hepatitis B virus (HBV) vaccination has been recommended for all neonates in China since 1992. This article reviews the impact of HBV vaccination throughout the past 20 years in China. Before ...the introduction of the HBV vaccination program, approximately 9.8% of the general Chinese population tested positive for hepatitis B virus surface antigen (HBsAg). Since 1992, vaccination coverage has increased each year. In 1999, a National Expanded Programme on Immunization (EPI) review showed that the immunization coverage with three doses of HBV vaccine was 70.7%, and reached 99.0% in Beijing. The HBsAg carrier rate in the general population decreased to 7.2% in 2006. In particular, the prevalence of HBsAg decreased to 2.3% among children aged 5–14 years and to 1.0% among children younger than 5 years. In addition, the administration of the HBV vaccine may have reduced the risk of hepatocellular carcinoma among adults. Despite the administration of hepatitis B immunoglobulin and the HBV vaccine to children with HBsAg-positive mothers, the failure rate of HBV immunoprophylaxis was 5–10%. In China, vaccine failure was related to HBV S gene mutation and inadequate administration of HBV vaccine. The prevalence of HBV carriers in China was markedly reduced after the introduction of the universal HBV vaccination program. If we immunize all susceptible individuals with the hepatitis B vaccine (especially children), interrupt transmission, and provide antiviral treatment for existing HBV carriers, the number of new cases may be reduced to close to zero in the future and this may eventually result in the eradication of HBV.
The human body is actually a super-organism that is composed of 10 times more microbial cells than our body cells. Metagenomic study of the human microbiome has demonstrated that there are 3.3 ...million unique genes in human gut, 150 times more genes than our own genome, and the bacterial diversity analysis showed that about 1000 bacterial species are living in our gut and a majority of them belongs to the divisions of Firmicutes and Bacteriodetes. In addition, most people share a core microbiota that comprises 50–100 bacterial species when the frequency of abundance at phylotype level is not considered, and a core microbiome harboring more than 6000 functional gene groups is present in the majority of human gut surveyed till now. Gut bacteria are not only critical for regulating gut metabolism, but also important for host immune system as revealed by animal studies.
Acetaminophen (APAP)-induced liver injury (AILI), even liver failure, is a significant challenge due to the limited availability of therapeutic medicine. Christensenella minuta (C. minuta), as a ...probiotic therapy, has shown promising prospects in metabolism and inflammatory diseases. Our research aimed to examine the influence of C. minuta on AILI and explore the molecular pathways underlying it. We found that administration of C. minuta remarkably alleviated AILI in a mouse model, as evidenced by decreased levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and improvements in the histopathological features of liver sections. Additionally, there was a notable decrease in malondialdehyde (MDA), accompanied by restoration of the reduced glutathione/oxidized glutathione (GSH/GSSG) balance, and superoxide dismutase (SOD) activity. Furthermore, there was a significant reduction in inflammatory markers (IL6, IL1β, TNF-α). C. minuta regulated phenylalanine metabolism. No significant difference in intestinal permeability was observed in either the model group or the treatment group. High levels of phenylalanine aggravated liver damage, which may be linked to phenylalanine-induced dysbiosis and dysregulation in cytochrome P450 metabolism, sphingolipid metabolism, the PI3K-AKT pathway, and the Integrin pathway. Furthermore, C. minuta restored the diversity of the microbiota, modulated metabolic pathways and MAPK pathway. Overall, this research demonstrates that supplementing with C. minuta offers both preventive and remedial benefits against AILI by modulating the gut microbiota, phenylalanine metabolism, oxidative stress, and the MAPK pathway, with high phenylalanine supplementation being identified as a risk factor exacerbating liver injury.
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