The ongoing outbreak of a new coronavirus (2019-nCoV, or severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) has caused an epidemic of the acute respiratory syndrome known as coronavirus disease (COVID-19) in humans. SARS-CoV-2 rapidly spread to multiple regions of China and multiple other countries, posing a serious threat to public health. The spike (S) proteins of SARS-CoV-1 and SARS-CoV-2 may use the same host cellular receptor, angiotensin-converting enzyme 2 (ACE2), for entering host cells. The affinity between ACE2 and the SARS-CoV-2 S protein is much higher than that of ACE2 binding to the SARS-CoV S protein, explaining why SARS-CoV-2 seems to be more readily transmitted from human to human. Here, we report that ACE2 can be significantly upregulated after infection of various viruses, including SARS-CoV-1 and SARS-CoV-2, or by the stimulation with inflammatory cytokines such as interferons. We propose that SARS-CoV-2 may positively induce its cellular entry receptor, ACE2, to accelerate its replication and spread; high inflammatory cytokine levels increase ACE2 expression and act as high-risk factors for developing COVID-19, and the infection of other viruses may increase the risk of SARS-CoV-2 infection. Therefore, drugs targeting ACE2 may be developed for the future emerging infectious diseases caused by this cluster of coronaviruses.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causing coronavirus disease 2019 (COVID‐19) has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS‐CoV‐2 infection needs to be determined. Here, 26 cases of COVID‐19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms, and no case of severe symptoms was found among these patients. Strikingly, a subset of these patients had SARS‐CoV‐2 and virus‐specific IgG coexist for an unexpectedly long time, with two cases for up to 50 days. One COVID‐19 patient who did not produce any SARS‐CoV‐2–bound IgG successfully cleared SARS‐CoV‐2 after 46 days of illness, revealing that without antibody‐mediated adaptive immunity, innate immunity alone may still be powerful enough to eliminate SARS‐CoV‐2. This report may provide a basis for further analysis of both innate and adaptive immunity in SARS‐CoV‐2 clearance, especially in nonsevere cases.

ObjectiveLiver fibrosis and cirrhosis resulting from chronic liver injury represent a major healthcare burden worldwide. Growth differentiation factor (GDF) 11 has been recently investigated for its role in rejuvenation of ageing organs, but its role in chronic liver diseases has remained unknown. Here, we investigated the expression and function of GDF11 in liver fibrosis, a common feature of most chronic liver diseases.DesignWe analysed the expression of GDF11 in patients with liver fibrosis, in a mouse model of liver fibrosis and in hepatic stellate cells (HSCs) as well as in other liver cell types. The functional relevance of GDF11 in toxin-induced and cholestasis-induced mouse models of liver fibrosis was examined by in vivo modulation of Gdf11 expression using adeno-associated virus (AAV) vectors. The effect of GDF11 on leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)+ liver progenitor cells was studied in mouse and human liver organoid culture. Furthermore, in vivo depletion of LGR5+ cells was induced by injecting AAV vectors expressing diptheria toxin A under the transcriptional control of Lgr5 promoter.ResultsWe showed that the expression of GDF11 is upregulated in patients with liver fibrosis and in experimentally induced murine liver fibrosis models. Furthermore, we found that therapeutic application of GDF11 mounts a protective response against fibrosis by increasing the number of LGR5+ progenitor cells in the liver.ConclusionCollectively, our findings uncover a protective role of GDF11 during liver fibrosis and suggest a potential application of GDF11 for the treatment of chronic liver disease.

Subacute iliofemoral DVT patients lacking effective therapy during acute phase, might receive more benefits from CDT with additional balloon dilatation. However, CDT alone is highly effective for acute patients.

BackgroundExtracellular histones were recently identified as an inflammatory mediator involved in the pathogenesis of various organ injuries. This study aimed to examine extracellular histone levels and their clinical implications in acute respiratory distress syndrome (ARDS) patients and to explore histone-mediated effects through ex-vivo investigations.MethodsExtracellular histones, cytokine profiles and clinical data from 96 ARDS patients and 30 healthy volunteers were obtained. Human bronchial epithelial cells (BEAS-2B), human pulmonary artery endothelial cells (HPAEC), and human monocytic U937 cells were exposed to bronchoalveolar lavage fluid (BALF) collected from ARDS patients, and cellular damage and cytokine production were assessed. Furthermore, the effect of histone-targeted interventions by heparin or anti-histone antibody was evaluated.ResultsPlasma and BALF extracellular histone levels were much higher in ARDS patients than in healthy controls. There was a significant association between extracellular histones and ARDS severity and mortality. In addition, extracellular histones correlated with an evident systemic inflammation detected in ARDS patients. Ex-vivo analysis further showed that ARDS patient’s BALF remarkably induced epithelial and endothelial cell damage and stimulated cytokine production in the supernatant of U937 cells. The adverse effects on these cells could be abrogated by heparin or anti-histone antibody.ConclusionsExtracellular histones in ARDS patients are excessively increased and may contribute to disease aggravation by inducing cellular damage and promoting systemic inflammation. Targeting extracellular histones may provide a promising approach for treating ARDS.Electronic supplementary materialThe online version of this article (10.1186/s12931-017-0651-5) contains supplementary material, which is available to authorized users.

BackgroundWeanling pigs, with immature immune system and physiological function, usually experience post-weaning diarrhea. This study determined the effects of dietary Clostridium butyricum supplementation on growth performance, diarrhea, and immunity of weaned pigs challenged with lipopolysaccharide (LPS).MethodsIn Experiment (Exp.) 1, 144 weaned piglets were weaned at 21 d and randomly assigned to six groups, with six replicates per group and four pigs per replicate, receiving a control diet (CON) or diet supplemented with antibiotics (AB) or C. butyricum (CB) (0.1%, 0.2%, 0.4%, or 0.8%), respectively. All diets in Exp. 1 were a highly digestible basal diet, with 3,000 mg/kg zinc oxide supplied in the first 2 wk only. In Exp. 2, 180 piglets were weaned at 21 d and randomly assigned to five groups, with six replicates per group and six pigs per replicate, receiving CON, AB, or CB (0.2%, 0.4%, or 0.6%) diets. The digestibility of diets was lower than those in Exp. 1, and did not include zinc oxide. At 36 d of Exp. 2, 12 piglets were selected from each of the CON and 0.4% CB groups, six piglets were intraperitoneally injected with LPS (50 μg/kg body weight) and the other six piglets with normal saline; animals were killed at 4 h after injection to collect blood, intestine, and digesta samples for biochemical analysis.ResultsIn Exp. 1, CB and AB diets had no effect on growth performance of piglets. In Exp. 2, 0.4% CB decreased feed-gain ratio (P < 0.1), diarrhea score (P < 0.05), and increased duodenal, jejunal, and ileal villus height and jejunal villus height/crypt depth (P < 0.05). The 0.4% CB decreased the plasma tumor necrosis factor (TNF) α (P < 0.05) but increased ileal mucosa IL-10 and TLR2 mRNA expression (P < 0.05). Furthermore, 0.4% CB altered the microbial profile, with Bacillus and Ruminococcaceae UGG-003 at genus level and Lactobacillus casei and Parasutterella secunda at species level were higher than CON in colonic content (P < 0.05).ConclusionsDietary C. butyricum supplementation had positive effects on growth of weaned piglets with less digestible diets. There was a tendency to reduce the feed-gain ratio, which could reduce feed costs in pig production. Moreover, C. butyricum decreased post-weaning diarrhea by improving the intestinal morphology, intestinal microflora profile, and immune function.

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