Bone marrow-derived mesenchymal stem cells repair severe acute pancreatitis by secreting miR-181a-5p to target PTEN/Akt/TGF-β1 signaling

BackgroundSevere acute pancreatitis (SAP) is associated with high morbidity and mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown obvious protective effect on SAP. However, little is known about the underlying mechanism. The objective of this study is to unravel the role and regulatory mechanism of miR-181a-5p in BMSCs-mediated pancreatic repair.MethodsBMSCs were isolated from Sprague-Dawley rats and characterized by flow cytometry and Oil Red O staining. Sodium taurocholate- and caerulein-induced models were used as SAP models in vivo and in vitro, respectively. Pancreatic injury were evaluated by H&E and histopathological analysis, as well as by measuring levels of amylase, lipase and cytokines. qRT-PCR and western blotting were performed to detect the level of miR-181a-5p and the protein levels of PTEN/Akt, respectively. ELISA was conducted to detect the levels of TNF-α, IL-1β, IL-6, angiopoietin, IL-4, IL-10 and TGF-β1. The apoptotic rate of AR42 J cells was quantitated by concurrent staining with Annexin-V-FITC and PI.ResultsBMSCs significantly attenuated pancreatic injury in SAP rats by reducing inflammatory infiltration and necrosis, and this effect was abolished by CXCR4 agonist AMD3100. ADM3100 exhibited more severe pancreatic injury and decreased miR-181a-5p levels in the pancreas and serum compared to SAP group. Overexpression of miR-181a-5p in BMSCs (BMSCs-miR-181a-5p) markedly potentiated the protective effect of BMSCs by reducing histological damage and levels of amylase and lipase. Moreover, BMSCs-miR-181a-5p dramatically reduced levels of angiopoietin, TNF-α, IL-1β and IL-6, but induced the levels of IL-4 and IL-10. In caerulein-treated AR42 J cells, co-culturing of BMSCs-miR-181a-5p alleviated caerulein-induced increase of amylase and lipase, and apoptosis via PTEN/Akt/TGF-β1 signaling.ConclusionBMSCs alleviate SAP and reduce inflammatory responses and apoptosis by secreting miR-181a-5p to target PTEN/Akt/TGF-β1 signaling. Hence, BMSCs-miR-181a-5p could serve as potential therapeutic target for SAP.     

Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

1. Download : Download high-res image (212KB)
2. Download : Download full-size image

     

An increased number of circulating γ/δ TCR + T cells in patients with chronic viral hepatitis

Abstract There is evidence that γ/δ TCR + T cells are specialized in recognizing different antigens, but their immunologic role as a second TCR is still unclear. The aim of this study was to investigate the percentage and absolute numbers of circulating γ/δ TCR + T cells in patients with chronic viral hepatitis (CVH) and to compare with HBsAg⁺, HCV healthy carriers and healthy subjects. Forty nine patients with CVH-24 with chronic active (CAH) and 25 with chronic persistent hepatitis (CPH)-, 21 HBsAg⁺, 20 HCV asymptomatic carriers and 20 healthy subjects were enrolled in the study. Lymphocyte subsets were determined after incubation with monoclonal antibodies to T total (CD5) and T γ/δ cells (γ/δ-1) using immunofluorescence microscopy. An increased number of circulating γ/δ TCR + T cells was found in patients with CVH in comparison with asymptomatic carriers and normal controls: this increase was more profound in patients with CAH, compared to CPH patients. These results indicate a correlation between circulating γ/δ TCR + T cells in CVH patients and activity and chronicity of the disease.     

肠内营养支持联合益生菌促进重症急性胰腺炎患者恢复的临床机制研究

目的阐述益生菌联合肠内营养支持对改善重症急性胰腺炎患者肠道微生态以及粘膜屏障功能的临床应用价值。方法选取我院收治的100例重症急性胰腺炎患者作为研究对象,随机分为观察组和对照组,各50例。观察组患者接受益生菌制剂联合肠内营养,对照组患者仅接受肠内营养,持续2周。比较两组患者的血浆生化指标、胃肠道功能、肠粘膜屏障功能、并发症发生率、病死率及住院时间。收集两组患者的粪便,检测菌群变化。结果在治疗第7 d,观察组患者的白细胞数和血浆生化指标明显低于对照组。治疗第14 d,观察组生化检测指标均明显低于对照组。胃肠道功能评分方面,治疗第7、14 d,观察组评分均较对照组明显降低；治疗第7 d、14 d,两组患者血浆MDA、ET、CRP水平和尿L/M均出现明显下降,观察组较对照组下降更明显；观察组的总体并发症发生率及住院时间与对照组比较,具有统计学差异。实时荧光定量PCR结果显示,经过14 d治疗后观察组患者大肠埃希菌、肺炎克雷伯菌的数量明显低于对照组。对照组病人双歧杆菌和乳酸菌数量明显高于对照组。结论肠内营养治疗联合益生菌有利于促进重症急性胰腺炎肠道功能的恢复,值得在临床上应用推广。     

Winter in the Ouchitas—A severe winter storm signature in Pinus echinata in the Ouachita Mountains of Oklahoma and Arkansas,USA

Each year severe winter storms (≈ice storms) damage trees throughout the southern USA. Arkansas and Oklahoma have a history of severe winter storms. To extend that history back beyond the reach of written records, a distinctive tree ring pattern or signature is needed. Storm-caused breakage, branch loss and bending stress provide that signature. We found a severe storm signature in shortleaf pine (Pinus echinata). We used three published site chronologies, a set of five new site chronologies from a growth-and-yield study conducted by Oklahoma State University and the unpublished Shortleaf Canyon chronology from a master’s thesis at the University of Arkansas. Our method is based on two ring width values for the first and second growing seasons after the storm standardized to the ring widths of the seven growing seasons after the storm. Concordance between storm years predicted by tree ring patterns and actual storm years was tested using Cohen’s Kappa. Concern about confounding of ice storm signals by droughts led us to test concordance between severe storms and drought in July, August and September; results were inconclusive but stand as a warning that these two phenomena cannot be distinguished with certainty in the tree ring record. Damaging severe storms occurred in about 2.8% of all years. Two out of three storms identified as “severe” produced glaze icing.     

Emergence,evolution, and vaccine production approaches of SARS-CoV-2 virus: Benefits of getting vaccinated and common questions

The emergence of coronavirus disease 2019 (COVID-19) pandemic in Wuhan city, China at the end of 2019 made it urgent to identify the origin of the causal pathogen and its molecular evolution, to appropriately design an effective vaccine. This study analyzes the evolutionary background of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS-2) in accordance with its close relative SARS-CoV (SARS-1), which was emerged in 2002. A comparative genomic and proteomic study was conducted on SARS-2, SARS-1, and Middle East respiratory syndrome coronavirus (MERS), which was emerged in 2012. In silico analysis inferred the genetic variability among the tested viruses. The SARS-1 genome harbored 11 genes encoding 12 proteins, while SARS-2 genome contained only 10 genes encoding for 10 proteins. MERS genome contained 11 genes encoding 11 proteins. The analysis also revealed a slight variation in the whole genome size of SARS-2 comparing to its siblings resulting from sequential insertions and deletions (indels) throughout the viral genome particularly ORF1AB, spike, ORF10 and ORF8. The effective indels were observed in the gene encoding the spike protein that is responsible for viral attachment to the angiotensin-converting enzyme 2 (ACE2) cell receptor and initiating infection. These indels are responsible for the newly emerging COVID-19 variants αCoV, βCoV, γCoV and δCoV. Nowadays, few effective COVID-19 vaccines developed based on spike (S) glycoprotein were approved and become available worldwide. Currently available vaccines can relatively prevent the spread of COVID-19 and suppress the disease. The traditional (killed or attenuated virus vaccine and antibody-based vaccine) and innovated vaccine production technologies (RNA- and DNA-based vaccines and viral vectors) are summarized in this review. We finally highlight the most common questions related to COVID-19 disease and the benefits of getting vaccinated.     

Suppressive Effect of Caffeine on Hepatitis and Apoptosis Induced by Tumor Necrosis Factor-α, but Not by the Anti-Fas Antibody,in Mice

Tumor necrosis factor (TNF)-α-induced hepatitis and apoptosis, as respectively assessed by serum enzyme activities and hepatic DNA fragmentation were effectively suppressed by a single force-feeding of caffeine (100 mg/kg) 1.5 h before injecting the drug. In contrast, caffeine had no significant effect on anti-Fas antibody-induced hepatitis and apoptosis. These results suggest that caffeine differentially affected TNF-α receptor- and Fas-mediated hepatitis and apoptosis.     

促肝细胞生长素联合前列腺素E1治疗慢性乙型重型肝炎疗效观察

目的探讨促肝细胞生长素(PHGF)联合前列腺素E1(PGE1)在慢性乙型重型肝炎中的疗效.方法60例慢性乙型重型肝炎患者随机分为治疗组30例和对照组30例,对照组采用常规治疗,治疗组在常规治疗的基础上加用PGE1、PHGF,治疗前后分别检测肝功能、PT.结果治疗30 d后,治疗组显效率、死亡率、SB和PTA值分别为43.3%、36.7%、(120士102)μmol/L和(70±23)%,对照组分别为13.3%、63.3%、(202±87)μmol/L和(40±18%).2组间显效率、死亡率、SB及PTA值差异存在显著性(P＜0.01或0.05).结论 PGE1联合PHGF在治疗慢性乙型重型肝炎中有较好疗效.