[This corrects the article DOI: 10.1016/j.apsb.2021.07.004.].

OBJECTIVES: To explore the mechanism of Circ-MYOCD back-splicing and its regulatory role in myocardial hypertrophy. METHODS: Sanger sequencing and RNase R assays were performed to verify the circularity and stability of Circ-MYOCD, whose subcellular distribution was determined by nuclear-cytoplasmic fractionation. Bioinformatics analysis and mass spectrometry from pull-down assays were conducted to predict the RNA-binding proteins (RBPs) interacting with Circ-MYOCD. In rat cardiomyocytes H9C2 cells, the effects of HNRNPH1 and HNRNPL knockdown and overexpression on Circ-MYOCD back-splicing were evaluated. In a H9C2 cell model of angiotensin II (Ang II)-induced myocardial hypertrophy, the expression of HNRNPH1 was detected, the effects of HNRNPH1 knockdown and overexpression on progression of myocardial hypertrophy were assessed, and the regulatory effect of HNRNPH1 on Circ-MYOCD back-splicing was analyzed. RESULTS: Sanger sequencing confirmed that the junction primers could amplify the correct Circ-MYOCD sequence. RNase R and nuclear-cytoplasmic fractionation assays showed that Circ-MYOCD was stable and predominantly localized in the cytoplasm. Bioinformatics analysis and mass spectrometry from the Circ-MYOCD pull-down assay identified HNRNPH1 and HNRNPL as the RBPs interacting with Circ-MYOCD. In H9C2 cells, HNRNPH1 knockdown significantly enhanced while its overexpression inhibited Circ-MYOCD back-splicing; HNRNPH1 overexpression obviously increased the expressions of myocardial hypertrophy markers ANP and BNP, while its knockdown produced the opposite effect. In Ang II-induced H9C2 cells, which exhibited a significant increase of HNRNPH1 expression and increased expressions of ANP and BNP, HNRNPH1 knockdown obviously increased Circ-MYOCD expression, decreased MYOCD expression and lowered both ANP and BNP expressions. CONCLUSIONS HNRNPH1 regulates Circ-MYOCD back-splicing to influence the progression of myocardial hypertrophy.
Animals ; Rats ; RNA, Circular/genetics* ; Cardiomegaly/metabolism* ; Myocytes, Cardiac/metabolism* ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H/metabolism* ; Cell Line ; RNA Splicing ; Angiotensin II ; RNA-Binding Proteins

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

MicroRNA(miRNA) affect various biological processes such as cell differentiation, proliferation, and apoptosis by inhibiting the translation of target genes after transcription and are widely involved in the regulation of immune and inflammatory responses in organisms. Autoimmune liver diseases are a group of chronic inflammatory diseases of the hepatobiliary system mediated by abnormal immunity, and abnormal immune inflammatory response of liver tissue with the involvement of miRNA is closely associated with the development and progression of autoimmune liver diseases. This article reviews the current research advances in miRNA in autoimmune liver diseases.

Objective:To explore the clinical characteristics of perioperative euglycemic diabetic ketoacidosis (euDKA) induced by sodium-glucose cotransporter 2 (SGLT2) inhibitors.Methods:The case reports of perioperative euDKA caused by SGLT2 inhibitors published up to June 30, 2019 were collected by searching the relevant databases and the following information of patients including demographic characteristics, types of diabetes, use of SGLT2 inhibitors, onset time and clinical manifestation of euDKA, the blood glucose and pH, serum bicarbonate and anion gap, β-hydroxybutyric acid and ketone body concentration in urine when diagnosing euDKA, predisposing factors of euDKA, as well as the treatments and outcomes were collected. The clinical characteristics of perioperative euDKA induced by SGLT2 inhibitors were analyzed descriptively.Results:A total of 27 patients (from 20 articles) were collected, including 13 males and 14 females with an age of (58±12) years; 26 patients were with type 2 diabetes mellitus and 1 with type 1 diabetes mellitus. Of them, 15 cases were treated with canagliflozin, 6 cases were treated with dapagliflozin, and 6 cases were treated with empagliflozin; the onset time of euDKA was 10 hours to 10 days after operation and within 3 days after operation in 21 cases (77.8%); 24 cases had similar symptoms as ketoacidosis and 3 cases had no obvious symptoms; the blood glucose was (9.5±2.2) mmol/L when diagnosing euDKA and the other laboratory test results were similar to those of ketoacidosis. The main factors inducing euDKA were operation and low carbohydrate diet. After the occurrence of euDKA, all patients received insulin and rehydration therapy, and then 26 cases (96.3%) got better and 1 (3.7%) died.Conclusions:The perioperative euDKA mainly occurred within 3 days after operation. The main inducing factors of euDKA were operation and low carbohydrate diet. After insulin and rehydration therapy, most patients had a good prognosis.

A 77-year-old female patient received an intravenous infusion of zoledronic acid injection 5 mg for osteoporosis. The patient had a history of asthma and no asthma attacks before medication. Nineteen hours after the intravenous infusion of zoledronic acid injection, the patient developed asthma, dyspnea, and wheezing in both lungs. Bronchial asthma attack was diagnosed, which was considered to be induced by zoledronic acid injection. An IV infusion of methylprednisolone, venous pumping of doxofylline, and aerosol inhalation of salbutamol, ipratropium bromide, and budesonide for inhalation were given immediately. Thirty minutes later, her symptoms of asthma and dyspnea were relieved. Twenty-six hours later, bronchial asthma recurred and was improved again after the above treatments. However, the patient′s exercise tolerance decreased. After 3 months of treatments with inhalation of budesonide and formoterol fumarate powder for inhalation and oral administration of montelukast, her exercise tolerance returned as before zoledronic acid injection.

Objective:To explore the clinical characteristics of perioperative euglycemic diabetic ketoacidosis (euDKA) induced by sodium-glucose cotransporter 2 (SGLT2) inhibitors.Methods:The case reports of perioperative euDKA caused by SGLT2 inhibitors published up to June 30, 2019 were collected by searching the relevant databases and the following information of patients including demographic characteristics, types of diabetes, use of SGLT2 inhibitors, onset time and clinical manifestation of euDKA, the blood glucose and pH, serum bicarbonate and anion gap, β-hydroxybutyric acid and ketone body concentration in urine when diagnosing euDKA, predisposing factors of euDKA, as well as the treatments and outcomes were collected. The clinical characteristics of perioperative euDKA induced by SGLT2 inhibitors were analyzed descriptively.Results:A total of 27 patients (from 20 articles) were collected, including 13 males and 14 females with an age of (58±12) years; 26 patients were with type 2 diabetes mellitus and 1 with type 1 diabetes mellitus. Of them, 15 cases were treated with canagliflozin, 6 cases were treated with dapagliflozin, and 6 cases were treated with empagliflozin; the onset time of euDKA was 10 hours to 10 days after operation and within 3 days after operation in 21 cases (77.8%); 24 cases had similar symptoms as ketoacidosis and 3 cases had no obvious symptoms; the blood glucose was (9.5±2.2) mmol/L when diagnosing euDKA and the other laboratory test results were similar to those of ketoacidosis. The main factors inducing euDKA were operation and low carbohydrate diet. After the occurrence of euDKA, all patients received insulin and rehydration therapy, and then 26 cases (96.3%) got better and 1 (3.7%) died.Conclusions:The perioperative euDKA mainly occurred within 3 days after operation. The main inducing factors of euDKA were operation and low carbohydrate diet. After insulin and rehydration therapy, most patients had a good prognosis.

A 77-year-old female patient received an intravenous infusion of zoledronic acid injection 5 mg for osteoporosis. The patient had a history of asthma and no asthma attacks before medication. Nineteen hours after the intravenous infusion of zoledronic acid injection, the patient developed asthma, dyspnea, and wheezing in both lungs. Bronchial asthma attack was diagnosed, which was considered to be induced by zoledronic acid injection. An IV infusion of methylprednisolone, venous pumping of doxofylline, and aerosol inhalation of salbutamol, ipratropium bromide, and budesonide for inhalation were given immediately. Thirty minutes later, her symptoms of asthma and dyspnea were relieved. Twenty-six hours later, bronchial asthma recurred and was improved again after the above treatments. However, the patient′s exercise tolerance decreased. After 3 months of treatments with inhalation of budesonide and formoterol fumarate powder for inhalation and oral administration of montelukast, her exercise tolerance returned as before zoledronic acid injection.

Department of Regenerative Medicine of Tongji University School of Medicine intro-duced the standardized question library construction-based separation of teaching from testing system into integrated life science course. By establishing the question library, professional teachers in the assessment center are responsible for making and correcting test papers of final exam for students. In addition to the separation of teaching and testing, regular quiz during the semester is also involved in the final grades of students. The results show that high-quality question library effectively promotes implementation of separation of teaching from testing. The question library construction is a dynamic and long-term task that requires real-time updates along with knowledge updates. This preliminary practice of separation of teaching from testing system in the integrated life sciences curriculum has proved to be useful for improving teaching style and the style of study significantly.

ABSTRACTOBJECTIVE To observe the effect of active components from Lycii cortex on the proliferation of high glucose?in-duced glomerular mesangial cells GMCs and the secretion of extracellular matrix ECM.To investigate the protective mechanism of diabetic nephropathy.METHODS GMCs were cultured and divided into high glucose groupfinal glucose con-centration of 30 mmol/Lblank groupfinal glucose concentration of 5.5 mmol/Lbetaine and kaempferol groups of 5 dif-ferent concentrations of 0.010.1110100 μmol/L.The proliferation of high glucose?induced GMCs were observed by MTT method and secretion of ECM was detected by ELISA assay.RESULTS Different doses of betaine and kaempferol inhib-ited the proliferation of GMCsand decreased the content of ECMcompared with high glucose group P < 0.05 ~ 0.01. CONCLUSION Betaine and kaempferol can protect the high glucose?induced GMCs through inhibiting the proliferation of GMCs and decreasing the content of ECM.