Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

There is growing recognition of the role of diet and other environmental factors in modulating the composition and metabolic activity of the human gut microbiota, which in turn can impact health. This narrative review explores the relevant contemporary scientific literature to provide a general perspective of this broad area. Molecular technologies have greatly advanced our understanding of the complexity and diversity of the gut microbial communities within and between individuals. Diet, particularly macronutrients, has a major role in shaping the composition and activity of these complex populations. Despite the body of knowledge that exists on the effects of carbohydrates there are still many unanswered questions. The impacts of dietary fats and protein on the gut microbiota are less well defined. Both short- and long-term dietary change can influence the microbial profiles, and infant nutrition may have life-long consequences through microbial modulation of the immune system. The impact of environmental factors, including aspects of lifestyle, on the microbiota is particularly poorly understood but some of these factors are described. We also discuss the use and potential benefits of prebiotics and probiotics to modify microbial populations. A description of some areas that should be addressed in future research is also presented.

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The Impact of Diet and Lifestyle on Gut Microbiota and Human Health

MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Two broad categories of extracellular vesicles (EVs), exosomes and shed microvesicles (sMVs), which differ in size distribution as well as protein and RNA profiles, have been described. EVs are known to play key roles in cell-cell communication, acting proximally as well as systemically. This Review discusses the nature of EV subtypes, strategies for isolating EVs from both cell-culture media and body fluids, and procedures for quantifying EVs. We also discuss proteins selectively enriched in exosomes and sMVs that have the potential for use as markers to discriminate between EV subtypes, as well as various applications of EVs in clinical diagnosis.

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Extracellular vesicle isolation and characterization: toward clinical application

Semen contains relatively ill-defined regulatory components that likely aid fertilization, but which could also interfere with defense against infection. Each ejaculate contains trillions of exosomes, membrane-enclosed subcellular microvesicles, which have immunosuppressive effects on cells important in the genital mucosa. Exosomes in general are believed to mediate inter-cellular communication, possibly by transferring small RNA molecules. We found that seminal exosome (SE) preparations contain a substantial amount of RNA from 20 to 100 nucleotides (nts) in length. We sequenced 20–40 and 40–100 nt fractions of SE RNA separately from six semen donors. We found various classes of small non-coding RNA, including microRNA (21.7% of the RNA in the 20–40 nt fraction) as well as abundant Y RNAs and tRNAs present in both fractions. Specific RNAs were consistently present in all donors. For example, 10 (of ∼2600 known) microRNAs constituted over 40% of mature microRNA in SE. Additionally, tRNA fragments were strongly enriched for 5’-ends of 18–19 or 30–34 nts in length; such tRNA fragments repress translation. Thus, SE could potentially deliver regulatory signals to the recipient mucosa via transfer of small RNA molecules.

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Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions

Probiotics are live microbial food supplements or their components, which have been shown to have beneficial effects on human health. Probiotics can be bacteria, molds, or yeasts, but most of them fall into the group known as lactic acid bacteria and are normally consumed in the form of yogurt, fermented milk, or other fermented foods. Data from clinical trials have shown contrasting effects and should be interpreted with caution. A large variety of potential beneficial effects have been reported including improvement of intestinal tract health, enhancing the immune system, reducing symptoms of lactose intolerance, decreasing the prevalence of allergy in susceptible individuals, reducing risk of certain cancers, treating colitis, lowering serum cholesterol concentrations, reducing blood pressure in hypertensives, and improving female urogenital infections and Helicobacter pylori infections. The aim of this article is to present a review of the current expanding knowledge of applications of utilizing probiotic microorganisms in the prevention and treatment of several diseases.

Probiotics as an alternative strategy for prevention and treatment of human diseases: a review.

The inhibitory impacts of Lactobacillus rhamnosus GG-derived extracellular vesicles on the growth of hepatic cancer cells

The apoptotic impact of nisin as a potent bacteriocin on the colon cancer cells.

An exosome is a nano vesicle that buds from the endosomal compartment; it is produced and released by allkinds of mammalian cells. This vesicle contains a variety of proteins, lipids, mRNAs and miRNAs. These components arespecific to the origin of the exosomes and contribute to cell-cell communications. Recently, it has been reported that a fewsingle cell eukaryotic pathogens such as Cryptoccoccus neoformance and Leishmania major and donovanican secrete anexosome and influence the host immune system. In addition, it has been observed that cells infected by intracellularpathogens are capable of secreting an exosome which is involved in the fate of the infection. Furthermore, retrovirusesrecruit the host`s endosomal compartments in order to generate viral vesicles which are similar to the exosome. Most ofthe exosomes involved in infectious biology can either spread or limit an infection based on the type of pathogen and itstarget cells. Hence, an exosome may be an appropriate candidate for a vaccine therapy in prophylaxis and treatment.

The Role of Exosomes in Infectious Diseases

Context A symbiotic relationship between the liver and intestinal tract enables the healthy status of both organs Microflora resident in intestinal lumen plays a significant role in hepatocytes function Alterations to the type and amount of microorganisms that live in the intestinal tract can result in serious and harmful liver dysfunctions such as cirrhosis, nonalcoholic fatty liver disease, alcoholic liver disease, and hepatic encephalopathy An increased number of pathogens, especially enterobacteriaceae, enterococci, and streptococci species causes the elevation of intestinal permeability and bacterial translocation The presence of high levels of lipopolysaccharide (LPS) and bacterial substances in the blood result in a portal hypertension and ensuing hepatocytes damage Several methods including the usage of antibiotics, prebiotics, and probiotics can be used to prevent the overgrowth of pathogens Compared to prebiotic and antibiotic therapy, probiotics strains are a safer and less expensive therapy Probiotics are "live microorganisms (according to the FAO/WHO) which when administered in adequate amounts confer a health benefit on the host" Evidence acquisitions Data from numerous preclinical and clinical trials allows for control of the flora bacteria quantity, decreases in compounds derived from bacteria, and lowers proinflammatory production such as TNF-α, IL-6 and IFN-γ via down-regulation of the nuclear factor kappa B (NF-κ B) Results On the other hand, probiotic can reduce the urease activity of bacterial microflora Furthermore, probiotic decreases fecal pH value and reduces ammonia adsorption In addition, the serum level of liver enzymes and other substances synthesized by the liver are modulated subsequent to probiotic consumption Conclusions According to our knowledge, Probiotic therapy as a safe, inexpensive and a noninvasive strategy can reduce pathophysiological symptoms and improve different types of liver diseases without side effects

Hamideh Mahmoodzadeh Hosseini

Papers

Probiotics as an alternative strategy for prevention and treatment of human diseases: a review.

The inhibitory impacts of Lactobacillus rhamnosus GG-derived extracellular vesicles on the growth of hepatic cancer cells

The apoptotic impact of nisin as a potent bacteriocin on the colon cancer cells.

The Role of Exosomes in Infectious Diseases

Probiotic as a novel treatment strategy against liver disease.