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1.
Biomed Pharmacother ; 133: 111000, 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33202285

RESUMO

Liver failure is a serious hepatic dysfunction with high mortality. This work aimed to investigate the effect of a famous probiotic and drug, Lactobacillus reuteri DSM 17938, on liver failure in rats. Sprague-Dawley rats were gavaged with 3 × 109 CFU of DSM 17938 for 7 days. d-galactosamine was intraperitoneally injected to induce acute liver failure on the eighth day. Samples were collected to determine the liver function, serum cytokines levels, terminal ileum and liver histology, gut microbiota, metabolome and transcriptome. Our results showed that pretreatment with DSM 17938 not only reduced the elevation in serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, IL-1α, IL-2, IL-18, M-CSF, and MIP-3α levels but also alleviated histological abnormalities of both the terminal ileum and liver induced by d-galactosamine. Additionally, DSM 17938 reduced d-galactosamine-induced enrichment of some taxa of gut Actinobacteria or Firmicutes, including abundant pathogens such as Actinomycetales, Coriobacteriaceae, Staphylococcaceae and Enterococcaceae. Furthermore, DSM 17938 reduced the d-galactosamine-induced increase in not only fecal metabolites such as trisaminol and lithocholic acid but also the transcription of liver inflammatory genes, such as Ccl2, Ccl7, Ccl11, Ccl12, Il6, Il11, Il20rb, Mmp3 and Mmp10. Downregulation of retinol metabolism and PPAR signaling pathway as well as upregulation of viral protein interaction with cytokine and cytokine receptor and central carbon metabolism in cancer signaling pathway were involved in the mechanism of L. reuteri DSM 17938 alleviating liver failure. Our findings suggested that DSM 17938 is a potential probiotic for the prevention or treatment of liver failure.

2.
BMC Infect Dis ; 20(1): 856, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203355

RESUMO

BACKGROUND: Disseminated Nocardia infection is a disease that is easily overlooked in patients with lesions occupying the intracranial space complicated with coma. Early diagnosis and treatment are crucial. CASE PRESENTATION: A 65-year-old man was admitted to the First Affiliated Hospital of Zhejiang University in October 2018 with weakness in the right limbs for 3 days and altered consciousness for 1 day. Five months earlier, he had been diagnosed with membranous kidney disease and had received cyclophosphamide and prednisone. At admission, the white blood cell count was 1.37 × 1010/L (with 86.4% neutrophils), and C-reactive protein was 115.60 mg/L. Imaging examinations revealed a lesion occupying the intracranial space, lung infection, and multiple abscesses in the rhomboid muscle. The abscesses were drained. Pus culture confirmed Nocardia cyriacigeorgica infection. With antibiotics and vacuum-sealed drainage of the back wound, the patient improved and was discharged from the hospital. CONCLUSIONS: This case report shows that infection should be considered during the differential diagnosis of lesions in the intracranial space, especially in patients receiving immunosuppressive treatment. In patients with disseminated N. cyriacigeorgica infection, combination antibiotic therapy and surgical drainage of localised abscesses can be effective.

3.
Int Immunopharmacol ; : 107120, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33162345

RESUMO

OBJECTIVE: To explore the application value of artificial liver support system in the clinical treatment of coronavirus disease 2019 (COVID-19) patients with cytokine storm. METHODS: Six cases of severe or critically severe COVID-19 patients treated in The First Affiliated Hospital, College of Medicine, Zhejiang University from January 22 to February 4, 2020 were recruited, and all of them received artificial liver support treatment. Statistical analysis was carried out on the change of cytokines (TNF-α, IL-10, IL-6, IFN-γ, IL-2, IL-4), inflammation-related indicators (white blood cell, neutrophil, lymphocyte, C-reactive protein and procalcitonin), immune-related indicators (B lymphocyte percentage, natural killer cell percentage, CD3+CD4+CD8 T cell percentage), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 patients before and after treatment, and the proportions of patients with abnormal indicators were analyzed as well. In addition, computed tomography (CT) was used to observe the absorption of pulmonary lesions before and after the artificial liver support treatment. RESULTS: The levels of cytokines (IL-6 and IL-10) were effectively reduced in the 6 patients after treatment with the artificial liver support system. Meanwhile, the proportions of patients with abnormal TNF-α, IL-10, IL-6 and IFN-γ were all decreased (p < 0.05). The levels of inflammation-related indicators including white blood cell, C-reactive protein and procalcitonin, and the proportions of patients with these abnormal indicators were both significantly reduced (p < 0.05). The level of neutrophil was not effectively reduced before and after the treatment, but the proportion was significantly reduced (p < 0.05). However, the abnormality of lymphocyte in the patients was not improved. There was no significant difference in immune-related indicators, AST and ALT before and after the treatment (p > 0.05). CT imaging showed that the artificial liver support treatment contributed to absorption of pulmonary lesions. CONCLUSIONS: The artificial liver support system had a great clinical effect in the treatment of cytokine storm and inflammation in COVID-19 patients, and it could promote the absorption of infected lesions.

4.
World J Gastroenterol ; 26(40): 6224-6240, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33177795

RESUMO

BACKGROUND: Intestinal dysbiosis has been shown to be associated with the pathogenesis of alcoholic liver disease (ALD), which includes changes in the microbiota composition and bacterial overgrowth, but an effective microbe-based therapy is lacking. Pediococcus pentosaceus (P. pentosaceus) CGMCC 7049 is a newly isolated strain of probiotic that has been shown to be resistant to ethanol and bile salts. However, further studies are needed to determine whether P. pentosaceus exerts a protective effect on ALD and to elucidate the potential mechanism. AIM: To evaluate the protective effect of the probiotic P. pentosaceus on ethanol-induced liver injury in mice. METHODS: A new ethanol-resistant strain of P. pentosaceus CGMCC 7049 was isolated from healthy adults in our laboratory. The chronic plus binge model of experimental ALD was established to evaluate the protective effects. Twenty-eight C57BL/6 mice were randomly divided into three groups: The control group received a pair-fed control diet and oral gavage with sterile phosphate buffered saline, the EtOH group received a ten-day Lieber-DeCarli diet containing 5% ethanol and oral gavage with phosphate buffered saline, and the P. pentosaceus group received a 5% ethanol Lieber-DeCarli diet but was treated with P. pentosaceus. One dose of isocaloric maltose dextrin or ethanol was administered by oral gavage on day 11, and the mice were sacrificed nine hours later. Blood and tissue samples (liver and gut) were harvested to evaluate gut barrier function and liver injury-related parameters. Fresh cecal contents were collected, gas chromatography-mass spectrometry was used to measure short-chain fatty acid (SCFA) concentrations, and the microbiota composition was analyzed using 16S rRNA gene sequencing. RESULTS: The P. pentosaceus treatment improved ethanol-induced liver injury, with lower alanine aminotransferase, aspartate transaminase and triglyceride levels and decreased neutrophil infiltration. These changes were accompanied by decreased levels of endotoxin and inflammatory cytokines, including interleukin-5, tumor necrosis factor-α, granulocyte colony-stimulating factor, keratinocyte-derived protein chemokine, macrophage inflammatory protein-1α and monocyte chemoattractant protein-1. Ethanol feeding resulted in intestinal dysbiosis and gut barrier disruption, increased relative abundance of potentially pathogenic Escherichia and Staphylococcus, and the depletion of SCFA-producing bacteria, such as Prevotella, Faecalibacterium, and Clostridium. In contrast, P. pentosaceus administration increased the microbial diversity, restored the relative abundance of Lactobacillus, Pediococcus, Prevotella, Clostridium and Akkermansia and increased propionic acid and butyric acid production by modifying SCFA-producing bacteria. Furthermore, the levels of the tight junction protein ZO-1, mucin proteins (mucin [MUC]-1, MUC-2 and MUC-4) and the antimicrobial peptide Reg3ß were increased after probiotic supplementation. CONCLUSION: Based on these results, the new strain of P. pentosaceus alleviated ethanol-induced liver injury by reversing gut microbiota dysbiosis, regulating intestinal SCFA metabolism, improving intestinal barrier function, and reducing circulating levels of endotoxin and proinflammatory cytokines and chemokines. Thus, this strain is a potential probiotic treatment for ALD.

5.
J Int Med Res ; 48(11): 300060520969582, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33179557

RESUMO

OBJECTIVE: Liver inflammatory activity staging is critical to guide the treatment of chronic hepatitis B virus (CHB) infection. Here, we aimed to identify practical clinical biomarkers of moderate inflammatory activity in hepatitis B e-antigen (HBeAg)-negative CHB patients. METHODS: Treatment-naïve HBeAg-negative CHB patients who underwent liver biopsy at our hospital from 1 January 2013 to 31 December 2016 were enrolled. Markers of inflammatory activity were analyzed using binary logistic regression. The area under the receiver operator characteristic curve (AUROCC) was used to assess diagnostic accuracy. RESULTS: A total of 106 HBeAg-negative treatment-naive CHB patients were enrolled. According to their METAVIR inflammatory scores, 30.2% of patients were in stage ≥A2. Total triiodothyronine (TT3) and hepatitis B virus (HBV) DNA levels were predictors of moderate inflammatory activity (A ≥ 2). The AUROCCs of TT3 and HBV DNA levels were 0.651 and 0.797, respectively. The optimal cut-off values for TT3 and HBV DNA were 1.755 nmol/L and 4.61 log10 IU/mL, respectively. CONCLUSIONS: A sizable proportion of treatment-naive HBeAg-negative CHB patients required antiviral treatment (30.2%) after undergoing liver biopsy. TT3 and HBV DNA helps identify patients with moderate inflammatory activity (A ≥ 2), potentially reducing the need for liver biopsies and helping guide treatment of CHB patients.

7.
Sci Rep ; 10(1): 18128, 2020 10 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.

8.
Ann Clin Lab Sci ; 50(5): 674-680, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33067215

RESUMO

OBJECTIVE: This study aimed to establish a new external quality assessment (EQA) of chromosomal karyotype analysis. METHODS: Chimeric assembly A1 was established by collecting chimeric chromosome images prepared artificially from chromosomally abnormal amniocytes remaining after prenatal diagnosis. Chimeric assembly B1 and nonchimeric assembly C1 were constructed through the collection of chimeric and nonchimeric chromosome images from prenatal diagnosis, respectively. Then, chromosome images were selected randomly from assemblies A1, B1, or C1 to send to 20 technicians via email to verify the validity of a new EQA of chromosomal karyotype analysis. RESULTS: According to the EQA of 20 technicians, 47,XX,+mar from assembly A was easily misdiagnosed as 47,XX,+19 or 47,XXY, and 45,XX,t(13;22) (q10;q10) was misdiagnosed as 45,XX,13S+,-22. The total misdiagnosis rate was 3.8%. For assembly B, 46,X,+mar and 46,X,idic(Y) were easily misdiagnosed as 46,XY and 46,X,+mar, respectively. In addition, some testers missed 47,XXX in 47,XXX[2]/46,XX[48], as well as 47,XX,+18 in 46,XX [47]/47,XX,+18[3], and 45,X and 47,XXX in 46,XX[47]/45,X[2]/47,XXX[1]. The total misdiagnosis rate was 4.2%. All karyo-types from assembly C were correctly diagnosed, although incorrect descriptions used for 4% of cases. CONCLUSION: The quality of chromosome karyotype analysis can be comprehensively evaluated by a new EQA based on assembly A1 or B1.

9.
Cell Death Dis ; 11(10): 829, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024074

RESUMO

Systemic inflammatory processes, including alveolar injury, cytokine induction, and neutrophil accumulation, play key roles in the pathophysiology of acute lung injury (ALI). The immunomodulatory effects of mesenchymal stem cells (MSCs) can contribute to the treatment of inflammatory disorders. In previous studies, the focus was on innate immune cells and the effects of MSCs on ALI through CD8+ T cells remain unclear. In the present study, lipopolysaccharide (LPS) was used to induce ALI in mice. ALI mice were treated with MSCs via intratracheal instillation. Survival rate, histopathological changes, protein levels, total cell count, cytokine levels, and chemokine levels in alveolar lavage fluid were used to determine the efficacy of MSCs. Mass cytometry and single-cell RNA sequencing (scRNA-seq) were used to characterize the CD8+ T cells in the lungs. Ly6C- CD8+ T cells are prevalent in normal mice, whereas a specialized effector phenotype expressing a high level of Ly6C is predominant in advanced disease. MSCs significantly mitigated ALI and improved survival. MSCs decreased the infiltration of CD8+ T cells, especially Ly6C+ CD8+ T cells into the lungs. Mass cytometry revealed that CD8+ T cells expressing high Ly6C and CXCR3 levels caused tissue damage in the lungs of ALI mice, which was alleviated by MSCs. The scRNA-seq showed that Ly6C+ CD8+ T cells exhibited a more activated phenotype and decreased expression of proinflammatory factors that were enriched the most in immune chemotaxis after treatment with MSCs. We showed that CD8+ T cells play an important role in MSC-mediated ALI remission, and both infiltration quantity and proinflammatory function were inhibited by MSCs, indicating a potential mechanism for therapeutic intervention.

11.
Biomed Res Int ; 2020: 1673602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123564

RESUMO

Liver injury has caused significant illness in humans worldwide. The dynamics of intestinal bacterial communities associated with natural recovery and therapy for CCl4-treated liver injury remain poorly understood. This study was designed to determine the recovery dynamics of intestinal bacterial communities in CCl4-treated mice with or without mesenchymal stem cell transplantation (i.e., MSC and CCl4 groups) at 48 h, 1 week (w), and 2 w. MSCs significantly improved the histopathology, survival rate, and intestinal structural integrity in the treated mice. The gut bacterial communities were determined with significant changes in both the MSC and CCl4 groups over time, with the greatest difference between the MSC and CCl4 groups at 48 h. The liver injury dysbiosis ratio experienced a decrease in the MSC groups and a rise in the CCl4 groups over time, suggesting the mice in the MSC group at 48 h and the CCl4 group at two weeks were at the least gut microbial dysbiosis status among the corresponding cohorts. Multiple OTUs and functional categories were associated with each of the bacterial communities in the MSC and CCl4 groups over time. Among these gut phylotypes, OTU1352_S24-7 was determined as the vital member in MSC-treated mice at 48 h, while OTU453_S24-7, OTU1213_Ruminococcaceae, and OTU841_Ruminococcus were determined as the vital phylotypes in CCl4-treated mice at two weeks. The relevant findings could assist the diagnosis of the microbial dysbiosis status of intestinal bacterial communities in the CCl4-treated cohorts with or without MSC transplantation.

12.
Sci Rep ; 10(1): 16970, 2020 10 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.

13.
Virus Res ; 291: 198186, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33075446

RESUMO

Characterization of host adaptation markers among human isolates is important for recognizing the potential for cross-species transmission in avian influenza A viruses. Here, we studied two new potential adaptive mutations, V292I and D740A, in the PB2 protein that were identified by a multi-factor regression model. The study shows that the prevalence of the PB2-V292I mutation is increased in H7N9 influenza viruses isolated from both humans and birds over the past 6 years. The phylogenetic tree showed that influenza A/H7N9 has a lineage based on the strains containing PB2-292I. Polymerase complexes containing PB2-292I/627K derived from H7N9 exhibit increased polymerase activity. PB2-292I coupled with 627K also enhances viral transcription and replication in cells, whereas PB2-292I alone did not show the same effect in the H7N9 virus. However, PB2-740A only had a limited prevalence in 2013, and the change from D to A in PB2-740A may have a negative effect on the replication of the H7N9 virus in cells.

14.
J Viral Hepat ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929826

RESUMO

The interaction between existing chronic liver diseases caused by hepatitis B virus (HBV) infection and COVID-19 has not been studied. We analysed 70 COVID-19 cases combined with HBV infection (CHI) to determine the epidemiological, clinical characteristics, treatment and outcome. We investigated clinical presentation, imaging and laboratory parameters of COVID-19 patients of seven hospitals from Jan 20 to March 20, 2020. Multivariate analysis was used to analyse risk factors for progression of patients with COVID-19 combined with HBV infection. Compared with COVID-19 without HBV infection (WHI) group, patients with dual infection had a higher proportion of severe/critically ill disease (32.86% vs. 15.27%, P = .000), higher levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and activated partial thromboplastin (APTT) [50(28-69)vs 21(14-30), P = .000; 40(25-54) vs 23(18-30), P = .000; 34.0(27.2-38.7) vs 37.2(31.1-41.4), P = .031]. The utilization rates of Arbidol and immunoglobulin were significantly higher than those in the co-infected group [48.57% vs. 35.64%, P < .05; 21.43% vs. 8.18%, P < .001], while the utilization rate of chloroquine phosphate was lower (1.43% vs 14.00%, P < .05) in the co-infected patients group. Age and c-reactive protein (CRP) level were independent risk factors for recovery of patients with COVID-19 combined with HBV infection. The original characteristics of COVID-19 cases combined with HBV infection were higher rate of liver injury, coagulation disorders, severe/critical tendency and increased susceptibility. The elderly and patients with higher level of CRP were more likely to experience a severe outcome of COVID-19.

15.
Asia Pac J Clin Nutr ; 29(3): 593-602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32990620

RESUMO

BACKGROUND AND OBJECTIVES: The high mortality rate of H7N9 strain of avian influenza virus (AIV) infected patients has been a major clinical concern. Iron overload increases the susceptibility of host for several kinds of microbial infection. However, the study on patients' iron and ferritin status associated with clinical outcome of AIVH7N9 virus infection is poorly understood, and in order to explain the linkage we carried out this study. METHODS AND STUDY DESIGN: We retrospectively collected serum from 46 patients infected with H7N9 virus from the hospital in Hangzhou city, Zhejiang province of China in 2013. We measured the level of serum iron and ferritin by Enzyme-Linked Immunosorbent Assay (ELISA). The correlation analysis of iron and ferritin with disease severity was done by SPSS 16.0 and MedCalc Software. RESULTS: After H7N9 infection, there is a reduction in iron level and an increase in ferritin, hepcidin and C-reactive protein (CRP) level in patient's serum compared to those of the control (p<0.001), and there's little correlation between procalcitonin (PCT) level and H7N9 infection. At week 1 and week 2 post-infection, serum iron level is much lower and ferritin level is much higher in the patients who died later than those in the patients who survived. The sensitivity, specificity, and Area Under the Curve (AUC) of the assay was calculated with MedCalc software and they were 85.5%, 65.9% and 0.803 for iron and 84.9%, 80.7% and 0.900 for ferritin, 95.2%, 51.1% and 0.684 for PCT and 100%, 94.6% and 0.988 for CRP, respectively. CONCLUSIONS: Our study found that low serum iron and high serum ferritin levels are correlated with the disease severity of H7N9-infected patients and can predict fatal outcomes.

16.
Clin Lab ; 66(9)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32902232

RESUMO

BACKGROUND: The shortage of quality-control materials caused by non-renewable utilization of rare disease samples is the key factor to limit the quality control of prenatal molecular diagnosis. This study aimed to prepare aneuploid amniocyte lines for the development of quality control cells for fluorescence in situ hybridization (FISH)-mediated detection of aneuploidy. METHODS: Recombinant SV40LTag-pcDNA3.1(-) vectors were transfected into 47,XY,+18 amniotic fluid cells with the use of liposomes. After culturing, these cells were mixed with primary amniocytes with the karyotype 46,XY to prepare four groups of chimeric quality control cells comprising recombinant cells with the karyotypes 47,XY,+18 and primary cells with 46,XY, with theoretical ratios of 47,XY,+18 cells at 5%, 10%, 20%, and 40%. Subsequently, the chimeric quality control cells were tested as clinical samples by three technicians to examine their feasibility for use as internal quality controls (IQC) for FISH detection. RESULTS: After being immortalized by the SV40 large T antigen gene (SV40LT), these aneuploid amniocytes can be cultured indefinitely to prepare chimeric quality control cells. The actual ratio of the 47,XY,+18 cells was identified by FISH to be 1.5 ± 1.1%, 10.3 ± 1.0%, 19.9 ± 0.4%, and 40.8 ± 0.3%, respectively, and the fluorescence signals of chromosomes 13, 18, 21, X, and Y in these cells were consistent with that of the primary cells. CONCLUSIONS: The present study may resolve the shortage of quality control cells in the prenatal detection of chromosomal aneuploidy and may provide a foundation for IQC-based detection in FISH.

17.
Int J Artif Organs ; : 391398820959345, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32969286

RESUMO

The study aimed to develop a biocompatible microcapsule for hepatocytes and create a bio-mimic microenvironment for maintaining hepatic-specific functions of hepatocytes in vitro. The work is proposed for the bioartificial liver system in the treatment of liver failure. In this study, microcapsules were prepared with hyaluronate (HA)/sodium alginate (SA) as an inner core and an outer chitosan (CS) shell via one-step spraying method. C3A cells were encapsulated in microcapsules to examine the biocompatibility of HA-SA-CS microcapsules. MTT and fluorescence microscopy indicated that C3A cells had high viability in the HA-SA-CS microcapsules. The liver-specific functions, such as urea and albumin synthesis, and CYP1A2 and CYP3A4 activities from encapsulated cells were increased in the HA-SA-CS microcapsules compared to the SA-CS microcapsules. The gene expressions of CYP450 related genes were also increased by HA on day 3. The study suggests that HA-SA-CS microcapsules have good biocompatibility and can maintain a favorable environment for hepatocytes. This approach has improved the preservation of liver cells' metabolic functions and could be a candidate for the bioartificial liver system.

18.
Stem Cell Res Ther ; 11(1): 377, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883343

RESUMO

Various hepatoxic factors, such as viruses, drugs, lipid deposition, and autoimmune responses, induce acute or chronic liver injury, and 3.5% of all worldwide deaths result from liver cirrhosis, liver failure, or hepatocellular carcinoma. Liver transplantation is currently limited by few liver donors, expensive surgical costs, and severe immune rejection. Cell therapy, including hepatocyte transplantation and stem cell transplantation, has recently become an attractive option to reduce the overall need for liver transplantation and reduce the wait time for patients. Recent studies showed that mesenchymal stem cell (MSC) administration was a promising therapeutic approach for promoting liver regeneration and repairing liver injury by the migration of cells into liver sites, hepatogenic differentiation, immunoregulation, and paracrine mechanisms. MSCs secrete a large number of molecules into the extracellular space, and soluble proteins, free nucleic acids, lipids, and extracellular vesicles (EVs) effectively repair tissue injury in response to fluctuations in physiological states or pathological conditions. Cell-free-based therapies avoid the potential tumorigenicity, rejection of cells, emboli formation, undesired differentiation, and infection transmission of MSC transplantation. In this review, we focus on the potential mechanisms of MSC-based cell-free strategies for attenuating liver injury in various liver diseases. Secretome-mediated paracrine effects participate in the regulation of the hepatic immune microenvironment and promotion of hepatic epithelial repair. We look forward to completely reversing liver injury through an MSC-based cell-free strategy in regenerative medicine in the near future.

19.
Stem Cell Res Ther ; 11(1): 418, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32977837

RESUMO

BACKGROUND: Immune system disorders play important roles in acute lung injury (ALI), and mesenchymal stem cell (MSC) treatment can reduce inflammation during ALI. In this study, we compared the changes in lung B cells during MSC treatment. METHODS: We investigated the effects of MSCs on lung B cells in a mouse model of lipopolysaccharide (LPS)-induced ALI. MSCs were administered intratracheally 4 h after LPS. As vehicle-treated controls, mice were treated with phosphate-buffered saline (PBS) containing 2% C57BL/6 (PBS group). Histopathological changes, survival rate, inflammatory factor levels, and the number of neutrophils in bronchoalveolar lavage fluid (BALF) were determined. Single-cell RNA sequencing (scRNA-Seq) analysis was performed to evaluate the transcriptional changes in lung B cells between the PBS, LPS, and LPS/MSC groups on days 3 and 7. RESULTS: MSC treatment ameliorated LPS-induced ALI, as indicated by the reductions in mortality, the levels of chemokines and cytokines in BALF, and the severity of lung tissue histopathology in ALI mice. Lung B cells in the PBS group remained undifferentiated and had an inhibitory phenotype. Based on our scRNA-Seq results, the differentially expressed genes (DEGs) in lung B cells in both the PBS group and LPS group were involved in chemotaxis processes and some proinflammatory pathways. MSC treatment inhibited the expression of chemokine genes that were upregulated by LPS and were related to the recruitment of neutrophils into lung tissues. Immunoglobulin-related gene expression was decreased in lung B cells of mice treated with LPS/MSC for 7 days. The DEGs regulated by MSCs were enriched in biological processes, including humoral immune response and apoptotic signaling. CONCLUSIONS: Lung B cells played an important role in the effects of treatment of ALI with MSCs. These observations provide new insights into the mechanisms underlying the effects of MSC treatment for ALI.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32904601

RESUMO

The COVID-19 pandemic has led to worldwide efforts to understand the biological traits of the newly identified HCoV-19 virus. In this mass spectrometry (MS)-based study, we reveal that out of 21 possible glycosites in the HCoV-19 S protein, 20 are completely occupied by N-glycans, predominantly of the oligomannose type. All seven glycosylation sites in human angiotensin I converting enzyme 2 (hACE2) were found to be completely occupied, mainly by complex N-glycans. However, glycosylation did not directly contribute to the binding affinity between HCoV-19 S and hACE2. Additional post-translational modification (PTM) was identified, including multiple methylated sites in both proteins and multiple sites with hydroxylproline in hACE2. Refined structural models of HCoV-19 S and hACE2 were built by adding N-glycan and PTMs to recently published cryogenic electron microscopy (cryo-EM) structures. The PTM and glycan maps of HCoV-19 S and hACE2 provide additional structural details for studying the mechanisms underlying host attachment and the immune response of HCoV-19, as well as knowledge for developing desperately needed remedies and vaccines.

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