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1.
Artigo em Inglês | MEDLINE | ID: mdl-38906440

RESUMO

BACKGROUND AND AIMS: The global rise of chronic hepatitis B (CHB) superimposed on hepatic steatosis (HS) warrants non-invasive, precise tools for assessing fibrosis progression. This study leveraged machine learning (ML) to develop diagnostic models for advanced fibrosis and cirrhosis in this patient population. METHODS: Treatment-naive CHB patients with concurrent HS who underwent liver biopsy in ten medical centers were enrolled as a training cohort and an independent external validation cohort (NCT05766449). Six ML models were implemented to predict advanced fibrosis and cirrhosis. The final models, derived from Shapley Additive exPlanations, were compared to Fibrosis-4 Index (FIB-4), Nonalcoholic fatty liver disease Fibrosis Score (NFS), and Aspartate transaminase to platelet ratio index (APRI) using the area under receiver operating characteristic curve (AUROC), and decision curve analysis (DCA). RESULTS: Of 1,198 eligible patients, the random forest (RF) model achieved AUROCs of 0.778 [95% confidence interval (CI) 0.749-0.807] for diagnosing advanced fibrosis (RF-AF model) and 0.777 (95%CI 0.748-0.806) for diagnosing cirrhosis (RF-C model) in the training cohort, and maintained high AUROCs in the validation cohort. In the training cohort, the RF-AF model obtained an AUROC of 0.825 (95% CI 0.787-0.862) in patients with HBV DNA ≥105 IU/ml, and RF-C model had an AUROC of 0.828 (95% CI 0.774-0.883) in female patients. The two models outperformed FIB-4, NFS, and APRI in the training cohort, and also performed well in the validation cohort. CONCLUSION: The RF models provide reliable, non-invasive tools for identifying advanced fibrosis and cirrhosis in CHB patients with concurrent HS, offering a significant advancement in the co-management of the two diseases.

2.
Future Microbiol ; 19: 413-429, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38305222

RESUMO

Aims: To investigate the effects of Ferrostatin-1 (Fer-1) on improving the prognosis of liver transplant recipients with steatotic liver grafts and regulating gut microbiota in rats. Methods: We obtained steatotic liver grafts and established a liver transplantation model. Recipients were divided into sham, liver transplantation and Fer-1 treatment groups, which were assessed 1 and 7 days after surgery (n = 6). Results & conclusion: Fer-1 promotes recovery of the histological structure and function of steatotic liver grafts and the intestinal tract, and improves inflammatory responses of recipients following liver transplantation. Fer-1 reduces gut microbiota pathogenicity, and lowers iron absorption and improves fat metabolism of recipients, thereby protecting steatotic liver grafts.


Assuntos
Cicloexilaminas , Fígado Gorduroso , Microbioma Gastrointestinal , Transplante de Fígado , Fenilenodiaminas , Animais , Ratos , Fígado/patologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Prognóstico
3.
EClinicalMedicine ; 68: 102419, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38292041

RESUMO

Background: With increasingly prevalent coexistence of chronic hepatitis B (CHB) and hepatic steatosis (HS), simple, non-invasive diagnostic methods to accurately assess the severity of hepatic inflammation are needed. We aimed to build a machine learning (ML) based model to detect hepatic inflammation in patients with CHB and concurrent HS. Methods: We conducted a multicenter, retrospective cohort study in China. Treatment-naive CHB patients with biopsy-proven HS between April 2004 and September 2022 were included. The optimal features for model development were selected by SHapley Additive explanations, and an ML algorithm with the best accuracy to diagnose moderate to severe hepatic inflammation (Scheuer's system ≥ G3) was determined and assessed by decision curve analysis (DCA) and calibration curve. This study is registered with ClinicalTrials.gov (NCT05766449). Findings: From a pool of 1,787 treatment-naive patients with CHB and HS across eleven hospitals, 689 patients from nine of these hospitals were chosen for the development of the diagnostic model. The remaining two hospitals contributed to two independent external validation cohorts, comprising 509 patients in validation cohort 1 and 589 in validation cohort 2. Eleven features regarding inflammation, hepatic and metabolic functions were identified. The gradient boosting classifier (GBC) model showed the best performance in predicting moderate to severe hepatic inflammation, with an area under the receiver operating characteristic curve (AUROC) of 0.86 (95% CI 0.83-0.88) in the training cohort, and 0.89 (95% CI 0.86-0.92), 0.76 (95% CI 0.73-0.80) in the first and second external validation cohorts, respectively. A publicly accessible web tool was generated for the model. Interpretation: Using simple parameters, the GBC model predicted hepatic inflammation in CHB patients with concurrent HS. It holds promise for guiding clinical management and improving patient outcomes. Funding: This research was supported by the National Natural Science Foundation of China (No. 82170609, 81970545), Natural Science Foundation of Shandong Province (Major Project) (No. ZR2020KH006), Natural Science Foundation of Jiangsu Province (No.BK20231118), Tianjin Key Medical Discipline (Specialty), Construction Project, TJYXZDXK-059B, Tianjin Health Science and Technology Project key discipline special, TJWJ2022XK034, and Research project of Chinese traditional medicine and Chinese traditional medicine combined with Western medicine of Tianjin municipal health and Family Planning Commission (2021022).

4.
Front Cell Infect Microbiol ; 13: 1284166, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38035331

RESUMO

Background: Enterotoxigenic Escherichia coli (ETEC), an important intestinal pathogen, poses a significant threat to the intestinal health of piglets. Bacillus coagulans (BC), a potential feed additive, can improve the intestinal function of piglets. However, the effects of BC on growth performance and intestinal function in ETEC-infected piglets are still unclear. In this study, 24 7-day-old piglets were randomly assigned to three treatment groups: control group (fed a basal diet), ETEC group (fed a basal diet and challenged with ETEC K88) and BC+ETEC group (fed a basal diet, orally administered BC, challenged with ETEC K88). During Days 1-6 of the trial, piglets in the BC+ETEC group were orally administered BC (1×108CFU/kg). On Day 5 of the trial, piglets in the ETEC and BC+ETEC groups were orally administered ETEC K88 (5×109CFU/piglet). Blood, intestinal tissue, and content samples were collected from the piglets on Day 7 of the trial. Results: The average daily feed intake in the ETEC group was significantly reduced compared to that of the control group. Further research revealed that ETEC infection significantly damaged the structure of the small intestine. Compared to the control group, the villus height and surface area of the jejunum, the ratio of villus height to crypt depth in the duodenum and jejunum, and the activities of catalase and total superoxide dismutase in the jejunum were significantly reduced. Additionally, the levels of myeloperoxidase in the jejunum, malondialdehyde in the plasma and jejunum, and intestinal epithelial apoptosis were significantly increased in the ETEC group. However, BC supplementation had significantly mitigated these negative effects in the BC+ETEC group by Day 7 of the trial. Moreover, BC supplementation improved the gut microbiota imbalance by reversing the decreased numbers of Enterococcus, Clostridium and Lactobacillus in jejunum and Escherichia coli, Bifidobacterium and Lactobacillus in the colon, as well as the increased number of Escherichia coli in the jejunum induced by ETEC K88. Conclusions: Overall, BC supplementation reduced the decline in average daily feed intake in ETEC K88-infected piglets by attenuating intestinal epithelial apoptosis and oxidative stress and regulating the gut microbiota. This suggests that BC may be used to prevent intestinal infections caused by ETEC in piglets.


Assuntos
Bacillus coagulans , Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Microbioma Gastrointestinal , Doenças dos Suínos , Animais , Ingestão de Alimentos , Escherichia coli Enterotoxigênica/fisiologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/microbiologia , Intestinos/microbiologia , Suínos , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/microbiologia
5.
Curr Res Food Sci ; 7: 100631, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38021263

RESUMO

Staphylococcus aureus is widely recognized as a highly hazardous pathogen that poses significant threats to food safety and public health. This study aimed to assess the prevalence, antimicrobial resistance, and genetic characteristics of S. aureus isolates recovered from 288 frozen flour and rice product samples in Shanghai, China, between September 2019 and May 2020. A total of 81 S. aureus isolates were obtained, representing 25 sequence types (STs), with ST7 being the most prevalent (17.28%, n = 14). The majority of S. aureus isolates (85.19%, n = 69) carried at least one enterotoxin gene, with the seg gene being the most frequently detected (51.85%, n = 42). Additionally, 12 isolates (14.81%) were identified as methicillin-resistant S. aureus (MRSA) through mecA gene detection. Notably, this study reported the presence of an ST398 MRSA isolate in frozen flour and rice products for the first time. All MRSA isolates displayed multidrug resistance, with the highest resistance observed against cefoxitin (100.00%), followed by penicillin (91.67%) and erythromycin (66.67%). Genomic analysis of the 12 MRSA isolates revealed the presence of twenty distinct acquired antimicrobial resistance genes (ARGs), eight chromosomal point mutations, and twenty-four unique virulence genes. Comparative genome analysis indicated close genetic relationships between these MRSA isolates and previously reported MRSA isolates from clinical infections, highlighting the potential transmission of MRSA through the food chain and its implications for public health. Significantly, the identification of three plasmids harboring ARGs, insertion sequences (ISs), the origin of transfer site (oriT), and the relaxase gene suggested the potential for horizontal transfer of ARGs via conjugative plasmids in S. aureus. In conclusion, this study revealed significant contamination of retail frozen flour and rice products with S. aureus, and provided essential data for ensuring food safety and protecting public health.

6.
Dig Dis Sci ; 68(11): 4196-4211, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37707747

RESUMO

BACKGROUND: Ischemia-reperfusion injury (IRI) is an important cause of graft dysfunction post-liver transplantation, where donor liver with severe steatosis is more sensitive to IRI. Liver IRI involves ferroptosis and can be alleviated by heme oxygenase-1-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs). AIMS: To explore the role and mechanism of HO-1/BMMSCs in severe steatotic liver IRI. METHODS: A severe steatotic liver IRI rat model and a hypoxia/reoxygenation (H/R) of severe steatosis hepatocyte model were established. Liver and hepatocyte damage was evaluated via liver histopathology and cell activity. Ferroptosis was evaluated through ferroptosis indexes. Nuclear factor erythroid 2-related factor 2 (Nrf2) was knocked down in severe steatotic hepatocytes. The role of Nrf2 and AMPK in HO-1/BMMSC inhibition of ferroptosis was examined using the AMP-activated protein kinase (AMPK) pathway inhibitor Compound C. RESULTS: The HO-1/BMMSCs alleviated severe steatotic liver IRI and ferroptosis. HO-1/BMMSCs promoted ferritin heavy chain 1(FTH1), Nrf2, and phosphorylated (p)-AMPK expression in the H/R severe steatotic hepatocytes. Nrf2 knockdown decreased FTH1 expression levels but did not significantly affect p-AMPK expression levels. The protective effect of HO-1/BMMSCs against H/R injury in severe steatotic hepatocytes and the inhibitory effect on ferroptosis were reduced. Compound C decreased p-AMPK, Nrf2, and FTH1 expression levels, weakened the HO-1/BMMSC protective effect against severe steatotic liver IRI and H/R-injured severe steatotic hepatocytes, and reduced the inhibition of ferroptosis. CONCLUSIONS: Ferroptosis was involved in HO-1/BMMSC reduction of severe steatotic liver IRI. HO-1/BMMSCs protected against severe steatotic liver IRI by inhibiting ferroptosis through the AMPK-Nrf2-FTH1 pathway. HO-1/BMMSCs activate AMPK, which activates Nrf2, promotes its nuclear transcription, then promotes the expression of its downstream protein FTH1, thereby inhibiting ferroptosis and attenuating severe steatotic liver IRI in rats. Glu: glutamic acid; Cys: cystine; GSH: glutathione; GPX4: glutathione peroxidase 4; HO-1/BMMSCs: HO-1-modified BMMSCs; Fer-1: ferrostatin-1; DFO: deferoxamine; FTH1: ferritin heavy chain1; p-AMPK: phosphorylated AMP-activated protein kinase; Nrf2: nuclear factor erythroid 2-related factor 2; IRI: ischemia-reperfusion injury; MCD: methionine-choline deficiency.

7.
J Appl Microbiol ; 134(7)2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37422440

RESUMO

AIM: Staphylococcus aureus causes several complicated infections. Despite decades of research on developing new antimicrobials, methicillin-resistant S. aureus (MRSA) remains a global health problem. Hence, there is a dire need to identify potent natural antibacterial compounds as an alternative to antimicrobials. In this light, the present work divulges the antibacterial efficacy and the action mechanism of 2-hydroxy-4-methoxybenzaldehyde (HMB) isolated from Hemidesmus indicus against S. aureus. METHODS AND RESULTS: Antimicrobial activity of HMB was assessed. HMB exhibited 1024 µg ml-1 as the minimum inhibitory concentration (MIC) and 2 × MIC as the minimum bactericidal concentration against S. aureus. The results were validated by spot assay, time kill, and growth curve analysis. In addition, HMB treatment increased the release of intracellular proteins and nucleic acid contents from MRSA. Additional experiments assessing the structural morphology of bacterial cells using SEM analysis, ß-galactosidase enzyme activity, and the fluorescence intensities of propidium iodide and rhodamine123 dye divulged that the cell membrane as one of the targets of HMB to hinder S. aureus growth. Moreover, the mature biofilm eradication assay revealed that HMB dislodged nearly 80% of the preformed biofilms of MRSA at the tested concentrations. Further, HMB treatment was found to sensitize MRSA cells upon combining tetracycline treatment. CONCLUSIONS: The present study suggests that HMB is a promising compound with antibacterial and antibiofilm activities and could act as a lead structure for developing new antibacterial drugs against MRSA.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Benzaldeídos/farmacologia , Infecções Estafilocócicas/microbiologia , Testes de Sensibilidade Microbiana , Biofilmes
8.
Cell Signal ; 109: 110793, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37414107

RESUMO

Donor shortage is a major problem that limits liver transplantation availability. Steatotic donor liver presents a feasible strategy to solve this problem. However, severe ischemia-reperfusion injury (IRI) is an obstacle to the adoption of steatotic transplanted livers. Evidence from our prior studies indicated that bone marrow mesenchymal stem cells modified with heme oxygenase-1 (HMSCs) can attenuate non-steatotic liver IRI. However, the contribution of HMSCs in transplanted steatotic liver IRI is unclear. Here, HMSCs and their derived small extracellular vesicles (HM-sEVs) alleviated IRI in transplanted steatotic livers. After liver transplantation, there was significant enrichment of the differentially expressed genes in the glutathione metabolism and ferroptosis pathways, accompanied by ferroptosis marker upregulation. The HMSCs and HM-sEVs suppressed ferroptosis and attenuated IRI in the transplanted steatotic livers. MicroRNA (miRNA) microarray and validation experiments indicated that miR-214-3p, which was abundant in the HM-sEVs, suppressed ferroptosis by targeting cyclooxygenase 2 (COX2). In contrast, COX2 overexpression reversed this effect. Knockdown of miR-214-3p in the HM-sEVs diminished its ability to suppress ferroptosis and protect liver tissues/cells. The findings suggested that HM-sEVs suppressed ferroptosis to attenuate transplanted steatotic liver IRI via the miR-214-3p-COX2 axis.


Assuntos
Vesículas Extracelulares , Fígado Gorduroso , Ferroptose , Transplante de Fígado , Células-Tronco Mesenquimais , MicroRNAs , Traumatismo por Reperfusão , Humanos , Transplante de Fígado/efeitos adversos , Ciclo-Oxigenase 2 , Medula Óssea , Doadores Vivos , Fígado , Traumatismo por Reperfusão/genética , MicroRNAs/genética
9.
Ther Hypothermia Temp Manag ; 13(3): 92-101, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36449377

RESUMO

Intraoperative hypothermia is very common and harmful in adult patients undergoing laparoscopic surgery. A variety of active warming systems has received close attention and has been researched by related scholars. However, the relative efficacy of these systems and which active warming system is preferred for such patients remain unclear. The aim of this study was to compare and rank six active warming systems regarding intraoperative warming efficacy in adult patients undergoing laparoscopic surgery. Following the PRISMA 2020 guidelines, relevant randomized controlled trials (RCTs) on the efficacy of different active warming systems in warming adult patients undergoing laparoscopic surgery were searched from five English databases and three Chinese databases. The quality of the studies was assessed using the Cochrane Risk of Bias tool (RoB2). The outcome was the final intraoperative core temperature. We estimated direct effects by using pairwise meta-analysis, estimated relative effects and ranking with the consistency model to conduct an NetworkMeta-Analysis (NMA). We used GRADE (Grading of Recommendations Assessment, Development, and Evaluation) to assess the certainty of the evidence. Sensitivity analysis was performed to test the robustness of the results. This study is registered with PROSPERO, with number CRD42022309057. In total, 19 RCTs involving 6 active warming systems and comprising 1364 patients were included in this NMA. The NMA once again confirmed the validity of forced-air warming (FAW) systems compared with other active warming systems, and further showed that underbody FAW was associated with more remarkable warming efficacy in different types of FAW systems. NMA was used to perform an exhaustive comparison of the warming efficacy of six active warming systems and indicated that underbody FAW was most likely to be the most effective warming system in adult patients undergoing laparoscopic surgery; however, considering the sparsity of the network, our results should be cautiously interpreted. Furthermore, a large number of high-quality RCTs comparing the warming efficacy of different competitive active warming systems are needed.


Assuntos
Hipotermia Induzida , Hipotermia , Laparoscopia , Humanos , Adulto , Metanálise em Rede , Hipotermia/prevenção & controle
10.
Foods ; 11(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36360050

RESUMO

Staphylococcus aureus biofilms are a serious problem in the food industry. Wall teichoic acid (WTA) is crucial in S. aureus biofilm formation. Overexpression of the WTA-hydrolyzing enzyme glycerophosphoryl diester phosphodiesterase (GlpQ), induced by lactobionic acid (LBA), may be related to biofilm formation. We investigated the relationship between the regulation on GlpQ degradation of WTA by LBA and S. aureus biofilm formation. LBA minimum inhibitory concentration for S. aureus was 12.5 mg/mL. Crystal violet staining revealed the LBA-mediated inhibition of S. aureus adhesion and biofilm formation. RT-qPCR revealed the repressed expression of adhesion-related genes by LBA. Scanning electron microscopy revealed the obvious disruption of S. aureus surface structure, confirming the repression of S. aureus adhesion and biofilm formation by LBA. Native-PAGE results suggested that the WTA content of S. aureus was reduced under the inhibition of LBA. Additionally, LBA induced the overexpression of glpQ. Combined with our previous work, these results suggest that glpQ is induced in S. aureus to function in WTA degradation with the addition of LBA, resulting in decreased WTA content and subsequent reduction of adhesion and biofilm formation. The findings provide new insight into the degradation mechanism of S. aureus WTA and indicate the potential of LBA as an anti-biofilm agent.

11.
Antibiotics (Basel) ; 11(8)2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35892388

RESUMO

Colistin resistance in bacteria has become a significant threat to food safety and public health, and its development was mainly attributed to the plasmid-mediated mcr genes. This study aimed to determine the global prevalence and molecular characteristics of mcr-producing Salmonella enterica isolates. A total of 2279 mcr-producing Salmonella genomes were obtained from the public database, which were disseminated in 37 countries from five continents worldwide, including Asia, Europe, America, Australia, and Africa. Human samples (39.5%; 900/2279) were the predominant sources of mcr-producing Salmonella isolates, followed by foods (32.6%), animals (13.7%), and environment (4.4%). Furthermore, 80 Salmonella serotypes were identified, and Typhimurium and 1,4,[5],12:i:- were the predominant serotypes, accounting for 18.3% and 18.7%, respectively. Twenty mcr variants were identified, and the most common ones were mcr-9.1 (65.2%) and mcr-1.1 (24.4%). Carbapenems-resistance gene blaNDM-1 and tigecycline-resistance gene tet(X4) were identified in one isolate, respectively. Phylogenetic results indicated that mcr-producing Salmonella fell into nine lineages (Lineages I-IX), and Salmonella Typhimurium, 1,4,[5],12:i:- and 4,[5],12:i:- isolates from different countries were mixed in Lineages I, II and III, suggesting that international spread occurred. These findings underline further challenges for the spread of Salmonella-bearing mcr genes.

12.
Oxid Med Cell Longev ; 2022: 6520789, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720183

RESUMO

Hepatic ischemia-reperfusion injury (IRI) is an inevitable result of liver surgery. Steatotic livers are extremely sensitive to IRI and have worse tolerance. Ferroptosis is considered to be one of the main factors of organ IRI. This study is aimed at exploring the role of ferroptosis in the effect of heme oxygenase-1-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs) on steatotic liver IRI and its mechanism. An IRI model of a steatotic liver and a hypoxia reoxygenation (HR) model of steatotic hepatocytes (SHPs) were established. Rat BMMSCs were extracted and transfected with the Ho1 gene to establish HO-1/BMMSCs, and their exosomes were extracted by ultracentrifugation. Ireb2 was knocked down to verify its role in ferroptosis and cell injury in SHP-HR. Public database screening combined with quantitative real-time reverse transcription PCR identified microRNAs (miRNAs) targeting Ireb2 in HO-1/BMMSCs exosomes. miR-29a-3p mimic and inhibitor were used for functional verification experiments. Liver function, histopathology, terminal deoxynulceotidyl transferase nick-end-labeling staining, cell viability, mitochondrial membrane potential, and cell death were measured to evaluate liver tissue and hepatocyte injury. Ferroptosis was assessed by detecting the levels of IREB2, Fe2+, malondialdehyde, glutathione, lipid reactive oxygen species, glutathione peroxidase 4, prostaglandin-endoperoxide synthase 2 mRNA, and mitochondrial morphology. The results revealed that HO-1/BMMSCs improved liver tissue and hepatocyte injury and suppressed ferroptosis in vivo and in vitro. The expression of IREB2 was increased in steatotic liver IRI and SHP-HR. Knocking down Ireb2 reduced the level of Fe2+ and inhibited ferroptosis. HO-1/BMMSC exosomes reduced the expression of IREB2 and inhibited ferroptosis and cell damage. Furthermore, we confirmed high levels of miR-29a-3p in HO-1/BMMSCs exosomes. Overexpression of miR-29a-3p downregulated the expression of Ireb2 and inhibited ferroptosis. Downregulation of miR-29a-3p blocked the protective effect of HO-1/BMMSC exosomes on SHP-HR cell injury. In conclusion, ferroptosis plays an important role in HO-1/BMMSC-mediated alleviation of steatotic liver IRI. HO-1/BMMSCs could suppress ferroptosis by targeting Ireb2 via the exosomal transfer of miR-29a-3p.


Assuntos
Exossomos , Fígado Gorduroso , Ferroptose , Células-Tronco Mesenquimais , MicroRNAs , Traumatismo por Reperfusão , Animais , Apoptose , Exossomos/metabolismo , Fígado Gorduroso/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Proteína 2 Reguladora do Ferro/metabolismo , Fígado/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Traumatismo por Reperfusão/patologia
13.
Front Microbiol ; 13: 905567, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756057

RESUMO

The present study aimed to explore whether heme oxygenase-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) have a protective effect on liver transplantation with steatotic liver grafts in rats, and to determine the role of the intestinal microbiota in such protection. HO-1/BMMSCs were obtained by transduction of Hmox1 gene [encoding heme oxygenase (HO-1)]-encoding adenoviruses into primary rat BMMSCs. Steatotic livers were obtained by feeding rats a high-fat diet, and a model of liver transplantation with steatotic liver grafts was established. The recipients were treated with BMMSCs, HO-1/BMMSCs, or neither, via the portal vein. Two time points were used: postoperative day 1 (POD 1) and POD 7. The results showed that under the effect of HO-1/BMMSCs, the degree of steatosis in the liver grafts was significantly reduced, and the level of liver enzymes and the levels of pro-inflammatory cytokines in plasma were reduced. The effect of HO-1/BMMSCs was better than that of pure BMMSCs in the prolongation of the rats' postoperative time. In addition, HO-1/BMMSCs promoted the recovery of recipients' intestinal structure and function, especially on POD 7. The intestinal villi returned to normal, the expression of tight junction proteins was restored, and intestinal permeability was reduced on POD 7. The intestinal bacterial of the LT group showed significantly weakened energy metabolism and overgrowth. On POD 1, the abundance of Akkermansiaceae was higher. On POD 7, the abundance of Clostridiaceae increased, the level of lipopolysaccharide increased, the intestinal mucosal barrier function was destroyed, and the levels of several invasive bacteria increased. When treated with HO-1/BMMSCs, the energy metabolism of intestinal bacteria was enhanced, and on POD 1, levels bacteria that protect the intestinal mucosa, such as Desulfovibrionaceae, increased significantly. On POD 7, the changed intestinal microbiota improved lipid metabolism and increased the levels of butyrate-producing bacteria, such as Lachnospiraceae. In conclusion, HO-1/BMMSCs have protective effects on steatotic liver grafts and the intestinal barrier function of the recipients. By improving lipid metabolism and increasing the abundance of butyrate-producing bacteria, the changed intestinal microbiota has a protective effect and prolongs the recipients' survival time.

14.
J Nanobiotechnology ; 20(1): 196, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459211

RESUMO

BACKGROUND: Steatotic livers tolerate ischemia-reperfusion injury (IRI) poorly, increasing the risk of organ dysfunction. Ferroptosis is considered the initiating factor of organ IRI. Heme oxygenase oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) (HO-1/BMMSCs) can reduce hepatic IRI; however, the role of ferroptosis in IRI of steatotic grafts and the effect of HO-1/BMMSCs-derived exosomes (HM-exos) on ferroptosis remain unknown. METHODS: A model of rat liver transplantation (LT) with a severe steatotic donor liver and a model of hypoxia and reoxygenation (H/R) of steatotic hepatocytes were established. Exosomes were obtained by differential centrifugation, and the differentially expressed genes (DEGs) in liver after HM-exo treatment were detected using RNA sequencing. The expression of ferroptosis markers was analyzed. microRNA (miRNA) sequencing was used to analyze the miRNA profiles in HM-exos. RESULTS: We verified the effect of a candidate miRNA on ferroptosis of H/R treated hepatocytes, and observed the effect of exosomes knockout of the candidate miRNA on hepatocytes ferroptosis. In vitro, HM-exo treatment reduced the IRI in steatotic grafts, and enrichment analysis of DEGs suggested that HM-exos were involved in the regulation of the ferroptosis pathway. In vitro, inhibition of ferroptosis by HM-exos reduced hepatocyte injury. HM-exos contained more abundant miR-124-3p, which reduced ferroptosis of H/R-treated cells by inhibiting prostate six transmembrane epithelial antigen 3 (STEAP3), while overexpression of Steap3 reversed the effect of mir-124-3p. In addition, HM-exos from cell knocked out for miR-124-3p showed a weakened inhibitory effect on ferroptosis. Similarly, HM-exo treatment increased the content of miR-124-3p in grafts, while decreasing the level of STEAP3 and reducing the degree of hepatic ferroptosis. CONCLUSION: Ferroptosis is involved in the IRI during LT with a severe steatotic donor liver. miR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft IRI, which might be a promising strategy to treat IRI in steatotic grafts.


Assuntos
Exossomos , Ferroptose , Transplante de Fígado , Células-Tronco Mesenquimais , MicroRNAs , Traumatismo por Reperfusão , Animais , Exossomos/metabolismo , Ferroptose/fisiologia , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Doadores Vivos , Masculino , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle
15.
Int Immunopharmacol ; 107: 108643, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35240383

RESUMO

Immature dendritic cells induce immune tolerance and mature dendritic cells induce acute rejection. We infused bone marrow mesenchymal stem cells (BMMSCs) expressing heme oxygenase 1 (HO-1) (HO-1/BMMSCs) into donation after circulatory death (DCD) livers using normothermic machine perfusion (NMP), and then performed transplantation, with the aim of determining the effects of HO 1/BMMSCs on liver DC maturation and graft rejection. A rat model of acute liver transplantation rejection was established from Lewis to BN rats, in which six experimental groups were set up: Sham operation, static cold storage, NMP, BMMSCs + NMP, HO-1/BMMSCs + NMP (HBP), and NMP + FK506 gavage. Flow cytometry was performed to detect the maturation of DCs and the activation of CD4+ T cells in the liver. In vitro, HO-1/BMMSCs were cocultured with liver DCs, and then the phenotype and ability to stimulate lymphocyte proliferation of DCs were measured. MAPK inhibitors were added to observe the effect of MAPK signaling on DC maturation. The resultsindicatedthatHO-1/BMMSCs could stably colonize the transplanted liver. In the HBP group, rejection was reduced, the maturation of DCs was inhibited, and the infiltration and activation of CD4+ T cells were reduced. In vitro, DCs cocultured with HO-1/BMMSCs showed an immature phenotype and inhibited T cell proliferation. HO-1/BMMSCs inhibited the maturation of DCs by blocking the phosphorylation of p38 and ERK1/2. This study suggested that infusion of HO-1/BMMSCs into DCD livers could reduce acute rejection significantly by inhibiting DC maturation. DC maturation regulation by HO-1/BMMSCs involves ERK1/2/MAPK and p38/MAPK signaling.


Assuntos
Transplante de Fígado , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Células da Medula Óssea/metabolismo , Células Dendríticas/metabolismo , Heme Oxigenase-1/metabolismo , Células-Tronco Mesenquimais/fisiologia , Ratos , Ratos Endogâmicos Lew
16.
Stem Cell Res Ther ; 12(1): 587, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819139

RESUMO

BACKGROUND: Liver transplantation (LT) is required in many end-stage liver diseases. Donation after cardiac death (DCD) livers are often used, and treatment of acute rejection (ACR) requires the use of immunosuppressive drugs that are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in treatment following LT; however, they have limitations, including low colonization in the liver. An optimized BMMSC application method is required to suppress ACR. METHODS: BMMSCs were isolated and modified with the heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT into rats. The severity of ACR was evaluated based on liver histopathology. Gene chip technology was used to detect differential gene expression, and flow cytometry to analyze changes in natural killer (NK) T cells. RESULTS: NMP induced BMMSCs to colonize the donor liver during in vitro preservation. The survival of HO-1/BMMSCs in liver grafts was significantly longer than that of unmodified BMMSCs. When the donor liver contained HO-1/BMMSCs, the local immunosuppressive effect was improved and prolonged, ACR was controlled, and survival time was significantly prolonged. The application of HO-1/BMMSCs reduced the number of NKT cells in liver grafts, increased the expression of NKT cell co-inhibitory receptors, and reduced NKT cell expression of interferon-γ. CONCLUSIONS: NK cell and CD8+ T cell activation was inhibited by application of HO-1/BMMSCs, which reduced ACR of transplanted liver. This approach could be developed to enhance the success rate of LT.


Assuntos
Transplante de Fígado , Células-Tronco Mesenquimais , Células T Matadoras Naturais , Animais , Humanos , Fígado/metabolismo , Transplante de Fígado/métodos , Doadores Vivos , Células-Tronco Mesenquimais/metabolismo , Perfusão/métodos , Ratos
17.
Int J Syst Evol Microbiol ; 70(1): 172-179, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31622230

RESUMO

Two Gram-stain-negative, catalase- and oxidase-positive, facultative anaerobic and rod-shaped motile bacteria, designated strains BEI176T and BEI207T, were isolated from seawater collected in the East China Sea. Phylogenetic analysis based on 16S rRNA gene sequences showed that strains BEI176T and BEI207T belonged to the genus Vibrio and were closely related to each other with 98.18 % similarity. The closest phylogenetic relatives of strain BEI176T were Vibrio alginolyticus LMG 4409T (98.85 %) and Vibrio campbellii LMG 11216T (98.81 %), whereas the closest relative of strain BEI207T was Vibrio hepatarius LMG 20362T (98.64 %). The two strains showed growth at different conditions; while strain BEI176T grew at 16-37 °C, pH 5.0-9.5 and 0-7.0 % (w/v) NaCl, the growth of strain BEI207T occurred at 10-37 °C, pH 6.0-9.5 and 1.0-7.0 % (w/v) NaCl. Both strains shared the same major fatty acid components of summed feature 3 (C16 : 1ω7c or C16 : 1ω6c), C16 : 0 and summed feature 8 (C18 : 1ω6c or C18 : 1ω7c). The DNA G+C contents of the assembled genomic sequences were 44.73 and 45.06 mol% for strains BEI176T and BEI207T, respectively. Average nucleotide identity values between the two strains and their reference species were lower than the threshold for species delineation (95-96 %); in silico DNA-DNA hybridization further showed that the two strains had less than 70 % similarity to their relatives. Therefore, two novel Vibrio species are proposed to accommodate them: Vibrioouci sp. nov. (type strain, BEI176T=MCCC 1K03515T=JCM 32690T= KCTC 62616T) and Vibrioaquaticus sp. nov. (type strain, BEI207T=MCCC 1K03516T=JCM 32691T=KCTC 62617T).


Assuntos
Filogenia , Água do Mar/microbiologia , Vibrio/classificação , Microbiologia da Água , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vibrio/isolamento & purificação
18.
Antonie Van Leeuwenhoek ; 112(11): 1691-1697, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31289978

RESUMO

A novel Gram-stain negative, strictly aerobic, rod-shaped motile bacterium with a single flagellum, designated strain DASS28T, was isolated from surface sediment of Bohai Sea in China. Growth occurred in the presence of 1.0-4.0% NaCl (w/v, optimum 2.0%), at 10-37 °C (optimum 20 °C) on the Marine agar 2216E and pH 6.0-10.0 (optimum pH 8.0). The major fatty acids (> 10% of total fatty acids) were summed feature 3 (C16:1ω7c and/or iso-C15:0 2-OH), C16:0 and C18:1ω7c. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, an unidentified aminolipid and two unidentified polar lipids. The major respiratory quinone was ubiquinone-8 (Q-8). The genomic DNA G + C content calculated from the genome sequence of strain DASS28T was 48.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain DASS28T belongs to the genus Corallincola and shows high 16S rRNA gene sequence similarity of 96.7% to Corallincola platygyrae JLT 2006T (= JCM18796T = CGMCC 1.10992T). On the basis of the polyphasic evidence, strain DASS28T is considered to represent a novel species in the genus Corallincola, for which the name Corallincola luteus sp. nov. is proposed. The type strain is DASS28T (= KCTC 52376T = MCCC 1K03208T).


Assuntos
Organismos Aquáticos/classificação , Organismos Aquáticos/isolamento & purificação , Gammaproteobacteria/classificação , Gammaproteobacteria/isolamento & purificação , Sedimentos Geológicos/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Filogenia , RNA Ribossômico 16S/genética , Água do Mar/microbiologia
19.
Mar Drugs ; 17(2)2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30795579

RESUMO

Quorum sensing (QS) is closely associated with the production of multiple virulence factors in bacterial pathogens. N-acyl homoserine lactones (AHLs) are important QS signal molecules that modulate the virulence of gram-negative pathogenic bacteria. Enzymatic degradation of AHLs to interrupt QS, termed quorum quenching (QQ), has been considered a novel strategy for reduction of pathogenicity and prevention of bacterial disease. However, the low expression levels of QQ proteins in the original host bacteria has affected the applications of these proteins. Previously, we identified a novel marine QQ enzyme, named MomL, with high activity and promising biocontrol function. In this study, we linked the target fragment momL to pNCMO2, which provided a basis for the first heterologous expression of MomL in the antifungal and anti-gram-positive-bacteria biocontrol strain Bacillus brevis, and obtaining the recombinant strain named BbMomL. The QQ activity of BbMomL was confirmed using a series of bioassays. BbMomL could not only degrade the exogenous signal molecule C6-HSL, but also the AHL signal molecules produced by the gram-negative pathogens Pectobacterium carotovorum subsp. carotovorum (Pcc) and Pseudomonas aeruginosa PAO1. In addition, BbMomL significantly reduced the secretion of pathogenic factors and the pathogenicity of Pcc and P. aeruginosa PAO1. We tested the biocontrol function of BbMomL for prevention of plant diseases in vitro. The result indicates that BbMomL has a broad antibacterial spectrum. Compared with wild-type B. brevis, BbMomL not only inhibited fungi and gram-positive bacterial pathogens but also considerably inhibited gram-negative bacterial pathogens. Moreover, the Bacillus brevis expression system has good application prospects and is an ideal host for expression and secretion of foreign proteins.


Assuntos
Bacillus/enzimologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Percepção de Quorum , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bacillus/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , DNA Recombinante/genética , Regulação Bacteriana da Expressão Gênica , Pectobacterium carotovorum/metabolismo , Doenças das Plantas/microbiologia , Pseudomonas aeruginosa/metabolismo , Fatores de Virulência/biossíntese
20.
Int J Syst Evol Microbiol ; 69(4): 920-925, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30628878

RESUMO

A novel Gram-stain-negative, strictly aerobic, rod-shaped motile bacterium with a single flagellum, designated strain WRAS1T, was isolated from deep seawater of the Okinawa Trough. Growth occurred in the presence of 0.0-9.0 % NaCl (w/v; optimum, 3.0-4.0 %), at 4-45 °C (optimum, 28-37 °C) and pH 7.0-10.0 (optimum, pH 7.0-8.0). The major fatty acid (>10 % of total fatty acids) was summed feature 8, comprising C18:1ω6c and/or C18:1ω7c. The major polar lipids were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine and three unidentified lipids. The major respiratory quinone was ubiquinone-10. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain WRAS1T was in the genus Thalassococcus and showed the highest 16S rRNA gene sequence similarity of 97.5 % to Thalassococcus halodurans JCM13833T. Genome relatedness between strain WRAS1T and T. halodurans JCM13833T was computed using both average nucleotide identity and DNA-DNA hybridization with values of 74.11 % and 22.70±2.3 %, respectively. The genomic DNA G+C content calculated from the genome sequence of strain WRAS1T was 65.6 %. On the basis of polyphasic analyses, strain WRAS1T is considered to represent a novel species in the genus Thalassococcus, for which the name Thalassococcusprofundi sp. nov. is proposed. The type strain is WRAS1T (=CGMCC 1.16123T=MCCC 1K03253T =KCTC 52696T).


Assuntos
Filogenia , Rhodobacteraceae/classificação , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Oceano Pacífico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Rhodobacteraceae/isolamento & purificação , Análise de Sequência de DNA , Ubiquinona/química
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