Role of allograft inflammatory factor-1 in bleomycin-induced lung fibrosis

Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries in a rat ectopic cardiac allograft model. We previously reported that AIF-1 is associated with the pathogenesis of rheumatoid arthritis and skin fibrosis in sclerodermatous graft-versus-host disease mice. Here, we used an animal model of bleomycin-induced lung fibrosis to analyze the expression of AIF-1 and examine its function in lung fibrosis. The results showed that AIF-1 was expressed on lung tissues, specifically macrophages, from mice with bleomycin-induced lung fibrosis. Recombinant AIF-1 increased the production of TGF-β which plays crucial roles in the mechanism of fibrosis by mouse macrophage cell line RAW264.7. Recombinant AIF-1 also increased both the proliferation and migration of lung fibroblasts compared with control group. These results suggest that AIF-1 plays an important role in the mechanism underlying lung fibrosis, and may provide an attractive new therapeutic target.     

Macroscopic features of scurvy in human skeletal remains: A literature synthesis and diagnostic guide

The past two decades have seen a proliferation in bioarchaeological literature on the identification of scurvy, a disease caused by chronic vitamin C deficiency, in ancient human remains. This condition is one of the few nutritional deficiencies that can result in diagnostic osseous lesions. Scurvy is associated with low dietary diversity and its identification in human skeletal remains can provide important contextual information on subsistence strategy, resource allocation, and human-environmental interactions in past populations. A large and robust methodological body of work on the paleopathology of scurvy exists. However, the diagnostic criteria for this disease employed by bioarchaeologists have not always been uniform. Here we draw from previous research on the skeletal manifestations of scurvy in adult and juvenile human skeletal remains and propose a weighted diagnostic system for its identification that takes into account the pathophysiology of the disease, soft tissue anatomy, and clinical research. Using a sample of individuals from the prehistoric Atacama Desert in Northern Chile, we also provide a practical example of how diagnostic value might be assigned to skeletal lesions of the disease that have not been previously described in the literature.     

PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p

MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, what makes it necessary to establish a better understanding of the molecular mechanisms underlying its pathogenesis. In this context, we have recently shown that cyclooxygenase-2 (COX-2) expression in hepatocytes restricts activation of hepatic stellate cells (HSCs), a pivotal event in the initiation and progression of hepatic fibrosis. Here, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs on a mouse model of CCl₄ and bile duct ligation (BDL)-induced liver fibrosis. Our results provide evidence that COX-2 represses miR-23a-5p and miR-28-5p expression in HSC. The decrease of miR-23a-5p and miR-28-5p expression promotes protection against fibrosis by decreasing the levels of pro-fibrogenic markers α-SMA and COL1A1 and increasing apoptosis of HSC. Moreover, we demonstrate that serum levels of miR-28-5p are decreased in patients with chronic liver disease. These results suggest a protective effect exerted by COX-2-derived prostanoids in the process of hepatofibrogenesis.     

Optimising the clinical strategy for autoimmune liver diseases: Principles of value-based medicine

Background

Autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis represent the three major autoimmune liver diseases (AILDs). Their management is highly specialized, requires a multidisciplinary approach and often relies on expensive, orphan drugs. Unfortunately, their treatment is often unsatisfactory, and the care pathway heterogeneous across different centers. Disease-specific clinical outcome indicators (COIs) able to evaluate the whole cycle of care are needed to assist both clinicians and administrators in improving quality and value of care. Aim of our study was to generate a set of COIs for the three AILDs. We then prospectively validated these indicators based on a series of consecutive patients recruited at three tertiary clinical centers in Lombardy, Italy.

羊骨酶解液的植物乳杆菌发酵

为进一步提高羊骨酶解液的营养价值和生物利用度,探讨乳酸菌发酵对钙离子释放、短肽形成以及酶解液抗氧化活性的影响。首先从7株乳酸菌中筛选出了产蛋白酶能力最强的植物乳杆菌,接种羊骨酶解液,以发酵液中Ca~(2+)浓度为指标,响应面法优化得到发酵工艺:酶解液中添加1%的麦芽糖,调节起始pH为5.5,以4%接种量接种驯化好的植物乳杆菌,37℃摇床发酵14 h。发酵过程中,植物乳杆菌活菌数与Ca~(2+)含量(R=0.495,P0.01)和短肽得率(R=0.655,P0.01)呈极显著正相关,而多肽生成量与短肽得率呈负相关(R=–0.013)。发酵液中的Ca~(2+)浓度(P0.05)、水解度(P0.01)、短肽得率(P0.01)、羟脯氨酸含量(P0.01)均显著高于酶解液(P0.01),植物乳杆菌活菌数达到94.6×10~8 CFU/m L。发酵还可使酶解液对DPPH、·OH、O_2~-·三种自由基的清除能力显著提高(P0.01,P0.05)。综上所述,以植物乳杆菌发酵羊骨酶解液可进一步促进骨钙的转化和胶原短肽的生成并显著提高其体外抗氧化能力,短肽和Ca~(2+)反过来促进植物乳杆菌的繁殖,增强了酶解液的益生功能,乳酸菌产生的维生素、胞外多糖等物质使羊骨酶解液更富营养。