Effect of MiR-320 on Intestinal Injury in Rats With Acute Pancreatitis by Regulating JAK2/STAT3 and NF-κB Signaling Pathways / 胃肠病学

Background: Expression of microRNA⁃320 (miR⁃320) is down regulated in acute pancreatitis, and the mechanism of its effect on acute pancreatitis is still unclear. Aims: To investigate the effect of miR⁃320 on intestinal injury in rats with acute pancreatitis and its mechanism. Methods: Rats were randomly divided into sham operation group, model group, miR⁃ 320 agonist group (agomir miR ⁃ 320 group), miR ⁃ 320 agonist control group (agomir NC group), JAK2 inhibitor group (AG490 group), and NF⁃κB pathway inhibitor group (PDTC group). The rat model of acute pancreatitis was established by retrograde injection of 5% sodium taurocholate to the bile duct. The automatic biochemical analyzer was used to detect serum levels of amylase and lipase; ELISA assay was used to detect serum levels of TNF⁃α and IL⁃1β; HE staining was used to observe the pathological changes of rat pancreas and ileum; TUNEL staining was used to observe cell apoptosis in rat ileum; real⁃time fluorescent quantitative PCR (RT⁃qPCR) was used to detect the expression of miR⁃320 in ileum tissue; Western blotting method was used to detect the expressions of JAK2/STAT3 and NF⁃κB signaling pathway related proteins in ileum. Results: Compared with sham operation group, the pancreas and ileum were severely injured in model group, and the pathological score and ileum cell apoptosis were significantly increased (P<0.05), serum levels of amylase, lipase, TNF⁃ α, and IL⁃1β were significantly increased (P<0.05), the expression of miR⁃320 in ileum tissue was significantly decreased (P<0.05), the ratios of p⁃JAK2/JAK2, p⁃STAT3/STAT3, p⁃p65/p65, and p⁃IκBα/IκBα in ileum tissue were significantly increased (P<0.05). Compared with model group, the pathological damages of pancreas and ileum in agomir miR ⁃ 320 group, AG490 group and PDTC group were reduced, and the pathological score and ileum cell apoptosis were significantly decreased (P<0.05), serum levels of amylase, lipase, TNF ⁃ α, and IL ⁃ 1β were significantly decreased (P<0.05), the expression of miR⁃320 in ileum tissue was significantly increased (P<0.05), the ratios of p⁃JAK2/JAK2, p⁃STAT3/STAT3, p⁃ p65/p65, and p⁃IκBα/IκBα in ileum tissue were significantly decreased (P<0.05). Conclusions: MiR⁃320 can improve the intestinal injury in rats with acute pancreatitis by inhibiting the activation of JAK2/STAT3 and NF⁃κB signaling pathways.

Clinical value of ultrasonographic assessment for the risk of lower limb deep vein thrombosis defluvium / 中华超声影像学杂志

Objective To evaluate the possibility of deep vein thrombosis defluvium of lower limb using ultrasonography to provide important reference for the implantation and retrieve of retrievable inferior vena cave (IVC ) filters.Methods Sixty-four patients who were diagnosed as lower limb deep vein thrombosis using ultrasonography were enrolled.Fourteen patients with critical values were allocated to high risk group,50 patients without critical value to low risk group.All the patients underwent inferior vena cava filter operation.Of all these patients,ultrosonography were performed once again before IVC filters were retrieved.Seventeen patients with broken thrombosis were allocated to unstable group,47 patients with stable thrombosis to stable group.Relationships between conditions of thrombosis and ultrasonography results were analysed.The conditions of thrombosis were recorded.The rates of thrombosis defluvium were compared.Results In high risk group,10 patients (71 .43%)had thrombosis.In low risk group,8 patients (16%)had thrombosis.There were significant differences in the rates of thrombosis defluvium beteen the high risk group and low risk group(P <0.05).In unstable group,12 patients (70.59%)had thrombosis.In stable group,6 patients (12.77%) had thrombosis,there were significant differences in the rates of thrombosis defluvium between the unstable group and stable group (P < 0.05 ).Conclusions Ultrasonography can be used to evaluate the possibility of lower extremity deep vein thrombosis defluvium which will guide the pratice of the retrievable inferior vena cava filter.

Multiple Roles of BRIT1/MCPH1 in DNA Damage Response, DNA Repair, and Cancer Suppression

Mammalian cells are frequently at risk of DNA damage from both endogenous and exogenous sources. Accordingly, cells have evolved the DNA damage response (DDR) pathways to monitor and assure the integrity of their genome. In cells, the intact and effective DDR is essential for the maintenance of genomic stability and it acts as a critical barrier to suppress the development of cancer in humans. Two central kinases for the DDR pathway are ATM and ATR, which can phosphorylate and activate many downstream proteins for cell cycle arrest, DNA repair, or apoptosis if the damages are irreparable. In the last several years, we and others have made significant progress to this field by identifying BRIT1 (also known as MCPH1) as a novel key regulator in the DDR pathway. BRIT1 protein contains 3 breast cancer carboxyl terminal (BRCT) domains which are conserved in BRCA1, MDC1, 53BP1, and other important molecules involved in DNA damage signaling, DNA repair, and tumor suppression. Our in vitro studies revealed BRIT1 to be a chromatin-binding protein required for recruitment of many important DDR proteins (ATM, MDC1, NBS1, RAD51, BRCA2) to the DNA damage sites. We recently also generated the BRIT1 knockout mice and demonstrated its essential roles in homologous recombination DNA repair and in maintaining genomic stability in vivo. In humans, BRIT1 is located on chromosome 8p23.1, where loss of hetero-zigosity is very common in many types of cancer. In this review, we will summarize the novel roles of BRIT1 in DDR, describe the relationship of BRIT1 deficiency with cancer development, and also discuss the use of synthetic lethality approach to target cancers with HR defects due to BRIT1 deficiency.

Multiple Roles of BRIT1/MCPH1 in DNA Damage Response, DNA Repair, and Cancer Suppression

Mammalian cells are frequently at risk of DNA damage from both endogenous and exogenous sources. Accordingly, cells have evolved the DNA damage response (DDR) pathways to monitor and assure the integrity of their genome. In cells, the intact and effective DDR is essential for the maintenance of genomic stability and it acts as a critical barrier to suppress the development of cancer in humans. Two central kinases for the DDR pathway are ATM and ATR, which can phosphorylate and activate many downstream proteins for cell cycle arrest, DNA repair, or apoptosis if the damages are irreparable. In the last several years, we and others have made significant progress to this field by identifying BRIT1 (also known as MCPH1) as a novel key regulator in the DDR pathway. BRIT1 protein contains 3 breast cancer carboxyl terminal (BRCT) domains which are conserved in BRCA1, MDC1, 53BP1, and other important molecules involved in DNA damage signaling, DNA repair, and tumor suppression. Our in vitro studies revealed BRIT1 to be a chromatin-binding protein required for recruitment of many important DDR proteins (ATM, MDC1, NBS1, RAD51, BRCA2) to the DNA damage sites. We recently also generated the BRIT1 knockout mice and demonstrated its essential roles in homologous recombination DNA repair and in maintaining genomic stability in vivo. In humans, BRIT1 is located on chromosome 8p23.1, where loss of hetero-zigosity is very common in many types of cancer. In this review, we will summarize the novel roles of BRIT1 in DDR, describe the relationship of BRIT1 deficiency with cancer development, and also discuss the use of synthetic lethality approach to target cancers with HR defects due to BRIT1 deficiency.