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关键词： CX3CL1   IFN‐   γ   liver‐   infiltrating T cells   primary biliary cholangitis   ursodeoxycholic acid  

摘要： Ursodeoxycholic acid (UDCA) is the primary treatment for primary biliary cholangitis (PBC), but its mechanism of action remains unclear. Studies suggest that UDCA enhances NF erythroid 2-related factor 2 (NFE2L2) expression and that the interaction between IFN-gamma and C-X3-C motif chemokine ligand 1 (CX3CL1) facilitates biliary inflammation in PBC. Therefore, we examined the effects of UDCA on the expression of IFN-gamma and CX3CL1 in in vitro and in vivo PBC models such as human liver tissue, a murine model, cell lines, and isolated human intrahepatic biliary epithelial cells (IHBECs). We observed a significant decrease in IFN-gamma mRNA levels and positive correlations between IFN-gamma and CX3CL1 mRNA levels post-UDCA treatment in PBC livers. NFE2L2-mediated transcriptional activation was significantly enhanced in UDCA-treated Jurkat cells. In 2-octynoic acid-immunized mice, IFN-gamma production by liver-infiltrating T cells was dependent on NFE2L2 activation. IFN-gamma significantly and dose-dependentlyinduced CX3CL1 expression, which was significantly decreased in HuCC-T1 cells and IHBECs upon UDCA treatment. These results suggest that UDCA-induced suppression of IFN-gamma and CX3CL1 production attenuates the chemotactic and adhesive abilities of liver-infiltrating T cells in PBC.

关键词： basal insulin   GLP‐   1 analogue   glycaemic control   insulin therapy   randomized trial   type 2 diabetes  

摘要： Aim Premix insulin is commonly used in some regions of the world, despite the higher risk of hypoglycaemia and weight gain compared with basal insulin, based on the premise that it offers a simplified insulin regimen. iGlarLixi is a once-daily titratable fixed-ratio formulation that combines basal insulin glargine 100 units/mL (iGlar) and the GLP-1 RA, lixisenatide, which offers a single-injection option for treatment intensification, with improved HbA1c reductions, similar hypoglycaemia risk and more favourable bodyweight profiles over iGlar alone. This randomized controlled study directly compares, for the first time, treatment intensification with iGlarLixi versus premix insulin analogue biphasic insulin aspart 30 (BIAsp 30) in adults with T2D inadequately controlled on basal insulin in combination with one or two oral antihyperglycaemic drugs. Materials and Methods This was an open-label, active-controlled, comparative, parallel-group, multicentre, phase 3b study. In total, 887 adults with T2D uncontrolled on basal insulin were randomized to switch to either iGlarLixi once daily, or BIAsp 30 twice daily, for 26 weeks. Results Overall, 887 participants were enrolled (mean age 59.8 years, 50.2% female) from 89 centres in 17 countries. At baseline, 65.6% had a duration of T2D of 10 years or longer, and the mean HbA1c at baseline was 8.6%. Conclusions The study directly compared the efficacy and safety of iGlarLixi versus BIAsp 30 in people with T2D uncontrolled on basal insulin and one or more oral antihyperglycaemic agents. These results provide robust clinical data that may inform clinicians in their therapeutic management of people with T2D uncontrolled on basal insulin requiring additional therapy.

摘要： 898

摘要： 803

关键词： skeletal muscle   muscle fiber   miRNA   miR‐   499   meat quality   pig  

摘要： Muscle fibers are closely related to human diseases and livestock meat quality. However, the genetics basis of microRNAs (miRNAs) in regulating muscle fibers is not completely understood. In this study, we constructed the whole genome-wide miRNA expression profiles of porcine fast-twitch muscle [biceps femoris (Bf)] and slow-twitch muscle [soleus (Sol)], and identified hundreds of miRNAs, including four skeletal muscle-highly expressed miRNAs, ssc-miR-378, ssc-let-7f, ssc-miR-26a, and ssc-miR-27b-3p. Moreover, we identified 63 differentially expressed (DE) miRNAs between biceps femoris vs. soleus, which are the key candidate miRNAs regulating the skeletal muscle fiber types. In addition, we found that the expression of DE ssc-miR-499-5p was significantly correlated to the expression of Myoglobin (r = 0.6872, P < 0.0001) and Myosin heavy chain 7 (MYH7;r = 0.5408, P = 0.0020), and pH(45 min) (r = 0.3806, P = 0.0380) and glucose content (r = -0.4382, P = 0.0154);while the expression of DE ssc-miR-499-3p was significantly correlated to the expression of Myoglobin (r = 0.5340, P = 0.0024) and pH(45 min) (r = 0.4857, P = 0.0065). Taken together, our data established a sound foundation for further studies on the regulatory mechanisms of miRNAs in skeletal muscle fiber conversion and meat quality traits in livestock, and could provide a genetic explanation of the role of miRNAs in human muscular diseases.

摘要： 106

关键词： dairy cattle   bronchopneumonia   clinical score   clinical definition   case definition  

摘要： Bovine respiratory disease complex (BRD) is a worldwide multifactorial infectious disease. Antimicrobials are commonly used for treating BRD because bacteria are often involved. The clinical diagnosis of BRD is a challenge, especially in adult dairy cows, where information on this syndrome is scant. Having a definition based on consistent and reliable clinical signs would improve the accuracy of BRD diagnosis and could help to develop an optimal treatment approach by an early detection. The aim of this scoping review was to review clinical signs that could be recognized by producers in dairy cattle suffering from naturally occurring infectious respiratory disease, as reported in the literature. A review of the literature was performed for articles published between January 1, 1990 and January 1, 2020. The search of literature in English, French, and Italian languages included 2 different databases (Pubmed, https://***/;CAB abstract, https://***/publishing-products/cab-abstracts/ ). Clinical signs were categorized as follows: (1) "general manifestations of disease," which included behavioral changes or fever;(2) "alterations in respiratory function," which included clinical signs specifically associated with the respiratory tract examination;and (3) "clinical signs of other body systems," which included clinical signs related to other systems such as diarrhea or subcutaneous emphysema. The focus of the review was on clinical signs that could be monitored by animal handlers and producers. A total of 1,067 titles were screened, and 23 studies were finally included. The most common general clinical signs were increased body temperature (reported in 83% of studies, n = 19), change in feed intake (26%, n = 6), altered mentation (22%, n = 5), and decreased milk production (17%, n = 4). The alterations in respiratory function noted were nasal discharge (74%, n = 17), cough (65%, n = 15), altered respiratory dynamic or dyspnea (61%, n = 14), incr

摘要： 3128

关键词： lymphoma   in situ hybridisation   immunohistochemistry  

摘要： Aims Primary mediastinal large B-cell lymphoma (PMBL) diagnosis can be challenging on needle biopsies. Robust techniques are needed to ensure diagnosis of this lymphoma which is highly sensitive to recently developed therapy protocols. Methods In this study, we sought to determine precise PMBL phenotype, compared with diffuse large B-cell lymphoma not otherwise specified, by combining immunohistochemistry with anti-MAL antibody and RNA in situ hybridisation (RNAscope) with specific MAL probes. Results The overall MAL positivity level reached 93% (14/15) of cases of PMBL. Among the 15 cases enrolled in the study, 11 were undoubtedly positive for MAL immunostaining whereas 13 were positive by RNA in situ hybridisation. Interestingly, one case that was negative by in situ hybridisation turned out to be positive by immunohistochemistry. Conclusions Taken together, our results demonstrate that in situ detection of both MAL transcripts and protein are complementary and increase the sensitivity and specificity of PMBL diagnosis.

关键词： NMRT   osteoarthritis   miR   MMPs   inflammation  

摘要： Nuclear magnetic resonance therapy (NMRT) is discussed as a participant in repair processes regarding cartilage and as an influence in pain signaling. To substantiate the application of NMRT, the underlying mechanisms at the cellular level were studied. In this study microRNA (miR) was extracted from human primary healthy and osteoarthritis (OA) chondrocytes after NMR treatment and was sequenced by the Ion PI Hi-Q (TM) Sequencing 200 system. In addition, T/C-28a2 chondrocytes grown under hypoxic conditions were studied for IL-1 beta induced changes in expression on RNA and protein level. HDAC activity an NAD((+))/NADH was measured by luminescence detection. In OA chondrocytes miR-106a, miR-27a, miR-34b, miR-365a and miR-424 were downregulated. This downregulation was reversed by NMRT. miR-365a-5p is known to directly target HDAC and NF-kappa B, and a decrease in HDAC activity by NMRT was detected. NAD(+)/NADH was reduced by NMR treatment in OA chondrocytes. Under hypoxic conditions NMRT changed the expression profile of HIF1, HIF2, IGF2, MMP3, MMP13, and RUNX1. We conclude that NMRT changes the miR profile and modulates the HDAC and the NAD((+))/NADH signaling in human chondrocytes. These findings underline once more that NMRT counteracts IL-1 beta induced changes by reducing catabolic effects, thereby decreasing inflammatory mechanisms under OA by changing NF-kappa B signaling.