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1.
Hortic Res ; 7: 161, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082968

RESUMO

The carotenoid isomerase gene (BoaCRTISO) of Chinese kale was targeted and edited using the CRISPR/Cas9 system in the present study. The results showed a high mutation rate (81.25%), and 13 crtiso mutants were obtained. Only two types of mutations, insertions and replacements, were found. Both the total and individual carotenoid and chlorophyll concentrations of the biallelic and homozygous mutants were reduced, and the total levels declined by 11.89-36.33%. The color of the biallelic and homozygous mutants changed from green to yellow, likely reflecting a reduction in the color-masking effect of chlorophyll on carotenoids. The expression levels of most carotenoid and chlorophyll biosynthesis-related genes, including CRTISO, were notably lower in the mutants than in the WT plants. In addition, the functional differences between members of this gene family were discussed. In summary, these findings indicate that CRISPR/Cas9 is a promising technique for the quality improvement of Chinese kale and other Brassica vegetables.

2.
Sci Rep ; 10(1): 17757, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082501

RESUMO

Paraquat (PQ), a widely used herbicide, could cause neurodegenerative diseases, yet the mechanism remains incompletely understood. This study aimed to investigate the direct effect of PQ on NSC in vivo and its possible mechanism. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control once a week for 2 weeks, and sacrificed 1 week after the last PQ injection. Furthermore, extra experiments with Tauroursodeoxycholic Acid (TUDCA) intervention were performed to observe the relationship between ER stress, neuroinflammation and the neural stem cell (NSC) impairment. The results showed that 20 mg/kg PQ caused the NSC number decrease in both subgranular zones (SGZ) and subventricular zone (SVZ). Further analysis indicated that the 20 mg/kg PQ suppressed the proliferation of NSC, without affecting the apoptosis. Moreover, 20 mg/kg PQ also induced ER stress in microglia and caused neuroinflammation in SGZ and SVZ. Interestingly, the ER stress inhibitor could simultaneously ameliorate the neuroinflammation and NSC reduction. These data suggested that increased ER stress in microglia might be a possible pathway for PQ-induced neuroinflammation and NSC impairment. That is a previously unknown mechanism for PQ neurotoxicity.

3.
Sci Rep ; 10(1): 18128, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093629

RESUMO

Increased oxidative stress levels play a key role in idiosyncratic drug-induced liver injury (DILI) pathogenesis. To investigated whether advanced oxidation protein products (AOPPs) and ischaemia-modified albumin (IMA) can be used to monitor oxidative stress in DILI patients and to assess disease severity. We performed spectrophotometric assays to assess AOPPs and IMA in 68 DILI patients with severity grade 0-2 (non-severe group), 60 with severity grade 3-5 (severe group), and 38 healthy controls. The results showed that baseline AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios were significantly higher in DILI patients than in healthy controls. Besides, in comparison to the non-severe group, the severe group showed higher baseline AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios. AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios decreased after treatment in both patient groups. Combining the correlation analysis and areas under the receiver operating curve (AUROCs) analysis results, that IMA outperformed to be one is the most reliable marker to assess disease severity of DILI. Our findings indicated that AOPPs and IMA can serve as key biomarkers for monitoring oxidative stress levels in DILI patients and can indicate disease severity. The IMA outperformed to be one of the most reliable oxidative stress biomarkers to assess disease severity of DILI.

4.
Sci Rep ; 10(1): 16970, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046732

RESUMO

Ammonia is thought to be central to the pathogenesis of hepatic encephalopathy (HE), but its prognostic role in acute-on-chronic liver failure (ACLF) is still unknown. We aimed to determine the association between serum ammonia level and short-term prognosis in ACLF. Furthermore, we performed an in-depth evaluation of the independent effect of serum ammonia level on the short-term prognosis of hepatitis B virus (HBV) reactivation-induced ACLF patients. We identified 174 patients as part of prospective observational studies in patients with ACLF. Plasma ammonia levels were measured on admission, and several prognostic scores were used to determine the prognostic effect of ammonia. The 28-day patient survival was determined. Receiver operating characteristic analysis was used to identify the cut-off points for ammonia values, and multivariable analysis was performed using the Cox proportional hazard regression model. Plasma ammonia was significantly higher in nonsurvivors (83.53 ± 43.78 versus 67.13 ± 41.77 µmol/L, P = 0.013), and ACLF patients with hyperammonemia had significantly higher 28-day mortality than those without hyperammonemia. Ammonia was also closely related to ACLF grade (P < 0.001) and organ failure, including liver (P = 0.048), coagulation (P < 0.001) and brain (P < 0.001). HBV reactivation serves as the main precipitating factor in the ACLF population. Subgroup analysis showed that ammonia is also a strong prognostic factor in the HBV reactivation-induced ACLF population. Ammonia level is closely correlated with failure of other organs and is an independent risk factor for mortality in ACLF and the special population defined as HBV reactivation-related ACLF. Based on the results from our study, we measured serum ammonia in the population with ACLF, which strongly indicates their prognosis. It serves as an important biomarker and a therapeutic target.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32910902

RESUMO

The human-gut-DNA virome is highly diverse and individual specific, but little is known of its variation at a population level. Here, we report the fecal DNA virome of 930 healthy adult subjects from two regions in China (Hong Kong and Yunnan) spanning six ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), and including urban and rural residents for each ethnicity. Twenty host factors were found to significantly correlate with the human-gut virome variation, with geography carrying the strongest impact and ethnicity-distinct diets associating with certain viral species. Urbanization enhances interindividual dissimilarities between gut viromes, with the duration of urban residence associating with multiple bacteriophages, including Lactobacillus phage and Lactococcus phage. Overall, the gut virome presents more heterogeneity relative to the bacterial microbiome across the examined Chinese populations. This study highlights population-based variations and the importance of host and environmental factors in shaping the DNA virome in the human gut.

6.
Gastroenterology ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32956679

RESUMO

BACKGROUND & AIMS: Beyond bacteria, the human gastrointestinal tract is host to a vast diversity of fungi, collectively known as the gut mycobiome. Little is known of the impact of geography, ethnicity and urbanization on the gut mycobiome at a large population level. We aim to delineate the variation of human gut mycobiome and its association with host factors, environmental factors and diets. METHODS: Using shotgun metagenomic sequencing, we profiled and compared the fecal mycobiome of 942 healthy individuals across different geographic regions in China (Hong Kong and Yunnan), spanning six ethnicities, Han, Zang, Bai, Hani, Dai, and Miao (including both urban and rural residents to each ethnicity). In parallel to fecal sampling, we collected subject metadata (environmental exposure, bowel habits, anthropometrics and medication), diet and clinical blood measurement results (a total of 118 variables) and investigated their impact on the gut mycobiome variation in humans. RESULTS: The human gut mycobiome was highly variable across populations. Urbanization-related factors had the strongest impact on gut mycobiome variation, followed by geography, dietary habit, and ethnicity. The Hong Kong population (highly urbanized) had a significantly lower fungal richness compared with Yunnan population. Saccharomyces cerevisiae was highly enriched in urban compared with rural populations, and showed significant inverse correlations with liver pathology-associated blood parameters, including aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyltransferase (GGT), and direct bilirubin. Candida dubliniensis, which was decreased in urban relative to rural populations, showed correlations with host metabolism-related parameters in blood, including a positive correlation with fasting high-density lipoprotein cholesterol (HDL-C) levels and a negative correlation with fasting glucose levels. The fungal-blood parameter correlations were highly geography- and ethnicity-specific. Food choices had differential influences on gut mycobiome and bacterial microbiome, where taxa from the same genus tended to be co-regulated by food and thereby co-bloom. Ethnicity-specific fungal signatures were associated with distinct habitual foods in each ethnic group. CONCLUSIONS: Our data highlight for the first time that geography, urbanization, and ethnicity, and habitual diets play an important role in shaping the gut mycobiome composition. Gut fungal configurations in combination with population characteristics (such as residing region, ethnicity, diet, lifestyle) influence host metabolism and health.

7.
Food Chem ; 339: 128057, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32947106

RESUMO

The effect of light exposure on sensory quality, health-promoting phytochemical contents, and antioxidant capacity in the lateral buds of baby mustard plants was investigated at ambient storage temperature (20 °C). The results showed that light exposure (36 µmol m-2 s-1) during post-harvest storage significantly prolonged shelf life (more than 1.75-fold), delayed the weight loss and the decrease of firmness. Light treatments also enhanced chlorophyll and carotenoid contents, and retarded declines in contents of soluble sugars, ascorbic acid, flavonoids and glucosinolates, as well as antioxidant capacity. The quality of baby mustard plants receiving 24 h daily light treatment was superior to those in plants receiving 12 h treatment and constant darkness at 20 °C. These findings indicate that light exposure, especially 24 h treatment, is an effective method of prolonging shelf life and maintaining sensory and nutritional qualities in baby mustard plants stored at ambient temperature.

8.
Echocardiography ; 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32777148

RESUMO

BACKGROUND: Assessment of left ventricular (LV) diastolic function is part of routine echocardiographic examinations. Accuracy of the 2016 ASE/EACVI algorithm to detect LV diastolic dysfunction in patients with a normal LV ejection fraction (LVEF) has been examined but simultaneous measurements of LV pressures and echocardiographic parameters of diastolic function are sparse. METHODS: The accuracy of multiple echo parameters of diastolic dynamics and the 2016 guidelines were assessed by simultaneous transthoracic echocardiography and LV pressure recordings in 120 patients (derivation cohort) and 60 patients (validation cohort) with suspected coronary artery disease and normal LVEF. Receiver-operating characteristic (ROC) curves defined optimal cut points for each echocardiographic parameter. A new algorithm was proposed to estimate LV diastolic pressures using 5 parameters based on ROC data: tricuspid regurgitation velocity >280cm/s, average e' <9 cm/s, average E/e' ratio >13, velocity of pulmonary vein A-wave reversal >32 cm/s, and left atrial volume index >32 mL/m2 . Performances of the 2016 guidelines and a proposed algorithm were examined for detecting a LV pre-A >12 and LV end-diastolic pressure (LVEDP) >15 mm Hg. RESULTS: In the derivation cohort, the 2016 algorithm identified an elevated LVEDP >15 mm Hg with an accuracy of 74.2% (63.8-82.9); the modified algorithm improved accuracy to 86.0% (77.6-92.1), P < .05. In the validation cohort, the proposed algorithm improved sensitivities with accuracies remaining like the 2016 algorithm. CONCLUSIONS: LV diastolic pressures in patients with normal LVEF were reliably assessed by the 2016 guidelines. The proposed algorithm improved sensitivities and may improve the accuracies for detecting abnormal LV filling pressures.

9.
ACS Infect Dis ; 6(9): 2451-2467, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32786271

RESUMO

Infections caused by drug-resistant pathogens are a worldwide challenge for public health. Antimicrobial peptides (AMPs) are regarded as promising antibiotic alternatives for the treatment of drug-resistant infections. In the present study, a series of small peptides were designed based on our previously reported sea snake AMP Hc-CATH. From them, the lead peptide HC1-D2, a truncated peptide entirely substituted by d-amino acids, was selected. HC1-D2 exhibited significantly improved stability and antibiofilm and anti-inflammatory activities. Meanwhile, HC1-D2 retained potent, broad-spectrum, and rapid antimicrobial properties against bacteria and fungi, especially drug-resistant bacteria. Moreover, HC1-D2 showed low propensity to induce bacterial resistance and low cytotoxicity and hemolytic activity. Notably, HC1-D2 showed potent in vivo anti-infective ability in mouse peritonitis models infected by both standard and drug-resistant bacteria. It significantly decreased the bacterial counts in the abdominal cavity and spleen of mice and apparently increased the survival rates of the mice. Acting through the MAPKs inflammatory pathway, HC1-D2 selectively induced the production of chemokine and the subsequent immune cell recruitment to the infection site, while inhibiting the production of pro-inflammatory cytokines with undesirable toxicities. These much improved properties make HC1-D2 a promising candidate for the development of novel peptide anti-infective agents against drug-resistant infections.

10.
Echocardiography ; 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32777137

RESUMO

BACKGROUND: Ischemia-reperfusion injury (IRI) frequently follows successful PCI for STEMI and is recognized by multiple modalities. Multilayer speckle tracking echocardiography (STE) has the potential of detecting myocardial dysfunction in different myocardial layers. Our objective was to describe the changes in layer-specific myocardial function over the 24 hours after successful PCI for ST-elevation myocardial infarction (STEMI). METHODS: Patients (n = 120) with STEMI and no prior myocardial infarction underwent echocardiography prior to PCI, immediately after and at 3- and 24-hours post-PCI. Worsening focal dysfunction (WFD) was defined as an immediate reduction, compared to the pre-PCI value, in the amplitude of endo-myocardial longitudinal strain (endo-MLS) within the infarction territory. RESULTS: Patients with WFD (52%) had further reductions in endo-MLS, mid-MLS, and epi-MLS in the infarction region immediately post-PCI; at 3 hours strain began to improve and continued to improve at 24 hours. Reductions of endo-MLS strain were more evident than those of global, mid-MLS, and epi-MLS. This same pattern was seen in each of the ischemic territories of the anterior descending, circumflex, and right coronary arteries. Immediate improvement in endo-MLS following PCI was seen in 48% of patients. The time from symptom onset to balloon time was markedly longer in those with WFD (P < .0001). CONCLUSIONS: Multilayer SPE is a sensitive method that identifies serial alterations in focal myocardial function following successful PCI for STEMI. Layer-specific reductions in endo-MLS appeared more evident than decreases in global LV strain. Prolonged total ischemic time prior to PCI was directly related to the incidence of WFD.

11.
Heart Lung Circ ; 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32736962

RESUMO

BACKGROUND: Interleukin (IL)-17 and its related cytokines have been shown to be involved in myocardial fibrosis and irreversible ventricular remodelling, which have predictive values in the development of left ventricular diastolic dysfunction (LVDD). This study aimed to assess the correlation between IL-17 and LVDD, and investigate the prognostic value of IL-17 among patients with normal left ventricular ejection fraction (LVEF). METHODS: A total of 120 patients with normal LVEF underwent left ventricular (LV) catheterisation for LV end-diastolic pressure (LVEDP) measurement and routine echocardiography. The follow-up period was 30 (18, 35) months. RESULTS: The levels of IL-17 and IL-6 from the systemic blood were significantly increased in non-heart failure (HF) patients with LVDD (p<0.001). Receiver operating characteristic (ROC) revealed that the combination of IL-17 and IL-6 showed the highest diagnostic accuracy in predicting LVDD (AUC, 0.890; 95% CI, 0.835-0.945; p<0.001), and the cut-off value was 41.5 pg/mL. On logistic regression analysis, the increment of the combination of IL-17 and IL-6 was an independent predictor for the prognosis of LVDD (odds ratio, 1.25; 95% CI, 1.01-1.12; p<0.05). According to the cut-off value of the combination of IL-17 and IL-6, the patients with lower levels of IL-17 and IL-6 (<41.5 pg/mL group) had a better prognosis. The increased levels of IL17 and IL-6 were significantly correlated with the levels of fibrotic parameters. CONCLUSIONS: Assessment of LVDD by measuring the combination of IL-17 and IL-6 might provide valuable prognostic significance for non-HF patients with LVDD.

12.
Gut ; 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32690600

RESUMO

OBJECTIVE: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19. DESIGN: We performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19. Sequencing coverage of the SARS-CoV-2 genome was quantified. We assessed faecal microbiome composition and microbiome functionality in association with signatures of faecal SARS-CoV-2 infectivity. RESULTS: Seven (46.7%) of 15 patients with COVID-19 had stool positivity for SARS-CoV-2 by viral RNA metagenomic sequencing. Even in the absence of GI manifestations, all seven patients showed strikingly higher coverage (p=0.0261) and density (p=0.0094) of the 3' vs 5' end of SARS-CoV-2 genome in their faecal viral metagenome profile. Faecal viral metagenome of three patients continued to display active viral infection signature (higher 3' vs 5' end coverage) up to 6 days after clearance of SARS-CoV-2 from respiratory samples. Faecal samples with signature of high SARS-CoV-2 infectivity had higher abundances of bacterial species Collinsella aerofaciens, Collinsella tanakaei, Streptococcus infantis, Morganella morganii, and higher functional capacity for nucleotide de novo biosynthesis, amino acid biosynthesis and glycolysis, whereas faecal samples with signature of low-to-none SARS-CoV-2 infectivity had higher abundances of short-chain fatty acid producing bacteria, Parabacteroides merdae, Bacteroides stercoris, Alistipes onderdonkii and Lachnospiraceae bacterium 1_1_57FAA. CONCLUSION: This pilot study provides evidence for active and prolonged 'quiescent' GI infection even in the absence of GI manifestations and after recovery from respiratory infection of SARS-CoV-2. Gut microbiota of patients with active SARS-CoV-2 GI infection was characterised by enrichment of opportunistic pathogens, loss of salutary bacteria and increased functional capacity for nucleotide and amino acid biosynthesis and carbohydrate metabolism.

13.
Huan Jing Ke Xue ; 41(7): 3410-3417, 2020 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608915

RESUMO

To quantify the net greenhouse gas emissions (NGHGE) of typical open-field vegetables production in China and analyze potential mitigation measures, the life cycle assessment (LCA) method was used to calculate the agricultural inputs, carbon sequestration, and greenhouse gas emissions of open-field tomato, cucumber, Chinese cabbage, and radish production in China based on national statistical data. The results showed that greenhouse gas emissions of typical vegetable production in China were much higher than the associated carbon sequestration, suggesting that they were net greenhouse gas emitters. The weighted average net greenhouse gas emissions of open-field tomato, cucumber, Chinese cabbage, and radish production when expressed on an area basis were 4149, 3718, 3780, and 2427 kg·hm-2(CO2-eq), respectively. The results from this study also indicated significant differences in the spatial distribution of greenhouse gas emissions for open-field vegetable production in China, and open-field tomato, cucumber, Chinese cabbage, and radish had higher greenhouse gas emissions in Hainan, Yunnan, Shaanxi, and Shandong, respectively, than in the other provinces. Fertilizer production, transportation, and application were the most significant contributors to the greenhouse gas emissions, contributing 86.8%-90.8% of the total emissions. This is significant for improving industry technology during fertilizer production and optimizing fertilizer management in open-field vegetable production based on different vegetables and provinces, which could achieve a double-win strategy in terms of increasing open-field vegetable yield and minimizing greenhouse gas emissions simultaneously.


Assuntos
Gases de Efeito Estufa , Agricultura , China , Fertilizantes , Efeito Estufa , Óxido Nitroso/análise , Verduras
14.
Gastroenterology ; 159(4): 1302-1310.e5, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32598884

RESUMO

BACKGROUND & AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects intestinal cells, and might affect the intestinal microbiota. We investigated changes in the fecal fungal microbiomes (mycobiome) of patients with SARS-CoV-2 infection during hospitalization and on recovery. METHODS: We performed deep shotgun metagenomic sequencing analysis of fecal samples from 30 patients with coronavirus disease 2019 (COVID-19) in Hong Kong, from February 5 through May 12, 2020. Fecal samples were collected 2 to 3 times per week from time of hospitalization until discharge. We compared fecal mycobiome compositions of patients with COVID-19 with those from 9 subjects with community-acquired pneumonia and 30 healthy individuals (controls). We assessed fecal mycobiome profiles throughout time of hospitalization until clearance of SARS-CoV-2 from nasopharyngeal samples. RESULTS: Patients with COVID-19 had significant alterations in their fecal mycobiomes compared with controls, characterized by enrichment of Candia albicans and a highly heterogeneous mycobiome configuration, at time of hospitalization. Although fecal mycobiomes of 22 patients with COVID-19 did not differ significantly from those of controls during times of hospitalization, 8 of 30 patients with COVID-19 had continued significant differences in fecal mycobiome composition, through the last sample collected. The diversity of the fecal mycobiome of the last sample collected from patients with COVID-19 was 2.5-fold higher than that of controls (P < .05). Samples collected at all timepoints from patients with COVID-19 had increased proportions of opportunistic fungal pathogens, Candida albicans, Candida auris, and Aspergillus flavus compared with controls. Two respiratory-associated fungal pathogens, A. flavus and Aspergillus niger, were detected in fecal samples from a subset of patients with COVID-19, even after clearance of SARS-CoV-2 from nasopharyngeal samples and resolution of respiratory symptoms. CONCLUSIONS: In a pilot study, we found heterogeneous configurations of the fecal mycobiome, with enrichment of fungal pathogens from the genera Candida and Aspergillus, during hospitalization of 30 patients with COVID-19 compared with controls. Unstable gut mycobiomes and prolonged dysbiosis persisted in a subset of patients with COVID-19 up to 12 days after nasopharyngeal clearance of SARS-CoV-2. Studies are needed to determine whether alterations in intestinal fungi contribute to or result from SARS-CoV-2 infection, and the effects of these changes in disease progression.

15.
J Med Virol ; 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32525562

RESUMO

This study investigated the safety and efficacy of ravidasvir (RDV) plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimens for treatment-naïve non-cirrhotic patients with hepatitis C virus (HCV) genotype 1b in mainland China. We also gained insight into HCV-host interactions during anti-HCV treatment. 16 patients with HCV and 10 healthy people enrolled the study. Three of 16 patients received 12-weeks' placebo treatment first and served as the placebo controls. All (n = 16) patients received 12-weeks' RDV plus DNVr and RBV treatment. The adverse effects (AEs), viral loads, alanine transaminase, and aspartate aminotransferase were recorded during study. We also performed multianalyte profiling of 48 cytokines/chemokines in 16 patients with HCV and 10 normal controls. Seventy-five percent patients treated with RDV plus DNVr and RBV experienced AEs. No death, treatment-related serious AEs or AEs leading to discontinuation were reported. The serum HCV-RNA levels remained extremely high in 3 placebo controls after treated with placebo. After RDV plus DNVr and RBV treatment, all patients achieved sustained virologic response (SVR) at posttreatment week 12, but 1 patient experienced viral relapse at SVR 24. The cytokine/chemokine expression pattern was markedly altered in patients with HCV as compared with healthy controls. The interferon-inducible protein-10 (IP-10) decreased after anti-HCV treatment, and dramatically increased in one patient with viral relapse. The regimen of RDV and DNVr plus RBV represents a highly safe and effective treatment option for HCV patients in mainland China. The IP-10 has the potential to be an indicator of innate immune viral recognition.

16.
Gastroenterology ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: covidwho-324569

RESUMO

BACKGROUD & AIMS: Although SARS-CoV-2 infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus. METHODS: We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with COVID-19 in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate ≥30/min, or oxygen saturation ≤93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with community-acquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2. RESULTS: Patients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an anti-inflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of ACE2 in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients. CONCLUSIONS: In a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity.

17.
Gastroenterology ; 159(3): 944-955.e8, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32442562

RESUMO

BACKGROUND & AIMS: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus. METHODS: We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with Coronavirus Disease 2019 (COVID-19) in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate ≥30/min, or oxygen saturation ≤93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with community-acquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2. RESULTS: Patients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an anti-inflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of angiotensin-converting enzyme 2 (ACE2) in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients. CONCLUSIONS: In a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity.


Assuntos
Betacoronavirus , Infecções por Coronavirus/microbiologia , Disbiose/virologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Pneumonia Viral/microbiologia , Adulto , Idoso , Feminino , Trato Gastrointestinal/microbiologia , Hong Kong/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Projetos Piloto
18.
Anal Chem ; 92(10): 7200-7208, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32233451

RESUMO

The health impact of environmental pollution involving an increase in human diseases has been subject to extensive study in recent decades. The methodology in biomimetic investigation of these pathophysiologic events is still in progress to uncover the gaps in knowledge associated with pollution and its influences on health. Herein, we describe a comprehensive evaluation of environmental pollutant-caused lung inflammation and injury using a microfluidic pulmonary alveolus platform with alveolar-capillary interfaces. We performed a microfluidic three-dimensional coculture with physiological microenvironment simulation at microscale control and demonstrated a reliable reconstruction of tissue layers including alveolar epithelium and microvascular endothelium with typical mechanical, structural, and junctional integrity, as well as viability. On-chip detection and analysis of pulmonary alveolus responses focusing on various inflammatory and injurious dynamics to the respective pollutant stimulations were achieved in the coculture-based microfluidic pulmonary alveolus model, in comparison with common on-chip monoculture and off-chip culture tools. We confirmed the synergistic effects of the epithelial and endothelial interfaces on the stimuli resistance and verified the importance of creating complex tissue microenvironments in vitro to explore pollution-involved human pathology. We believe the microfluidic approach presents great promise in environmental monitoring, drug discovery, and tissue engineering.

19.
Clin Cancer Res ; 26(14): 3760-3770, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32234760

RESUMO

PURPOSE: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. EXPERIMENTAL DESIGN: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). RESULTS: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. CONCLUSIONS: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.

20.
Biomed Res Int ; 2020: 2018035, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32016113

RESUMO

The use of a large number of cardiovascular biomarkers, meant to complement the use of the electrocardiogram, echocardiography cardiac imaging, and clinical symptom assessment, has become a routine in clinical diagnosis, differential diagnosis, risk stratification, and prognosis and guides the management of patients with suspected cardiovascular diseases. There is a broad consensus that cardiac troponin and natriuretic peptides are the preferred biomarkers in clinical practice for the diagnosis of the acute coronary syndrome and heart failure, respectively, while the roles and possible clinical applications of several other potential biomarkers are still under study. This review mainly focuses on the recent studies of the roles and clinical applications of troponin and natriuretic peptides, which seem to be the best-validated markers in distinguishing and predicting the future cardiac events of patients with suspected cardiovascular diseases. Additionally, the review briefly discusses some of the large number of potential markers that may play a more prominent role in the future.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Biomarcadores/análise , Insuficiência Cardíaca/diagnóstico , Infarto do Miocárdio/diagnóstico , Peptídeos Natriuréticos/análise , Troponina/análise , Síndrome Coronariana Aguda/metabolismo , Diagnóstico Diferencial , Eletrocardiografia , Insuficiência Cardíaca/metabolismo , Humanos , Infarto do Miocárdio/metabolismo , Prognóstico , Medição de Risco
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