Glycaemic status, insulin resistance, and risk of infection-related mortality:a cohort study

Importance: the impact of non-diabetic hyperglycaemia and insulin resistance on infection-related mortality risk remains unknown.Objective: we investigated the association of glycaemic status and insulin resistance with infection-related mortality in individuals with and without diabetes.Design: cohort study based on Kangbuk Samsung Health Study and national death records.Participants: about 666 888 Korean adults who underwent fasting blood measurements including glucose, glycated haemoglobin (HbA1c), and insulin during health-screening examinations were followed for up to 15.8 years.Main outcome and measures: infection-related mortality, therefore we used Cox proportional hazards regression analyses to estimate hazard ratios (HRs) and 95% CIs for infection-related mortality. Vital status and infection-related mortality were ascertained through national death records. Variable categories were created based on established cut-offs for glucose and HbA1c levels and homeostatic model assessment of insulin resistance (HOMA-IR) quintiles.Results: during a median follow-up of 8.3 years, 313 infectious disease deaths were dentified. The associations of glucose and HbA1c levels with infection-related mortality were J-shaped (P for quadratic trend&lt;.05). The multivariable-adjusted HR (95% CIs) for infection-related mortality comparing glucose levels &lt;5, 5.6-6.9, and ≥7.0 mmol/L to 5.0–5.5 mmol/L (the reference) were 2.31 (1.47–3.64), 1.65 (1.05–2.60), and 3.41 (1.66–7.00), respectively. Among individuals without diabetes, the multivariable-adjusted HR for infection-related mortality for insulin resistance (HOMA-IR ≥75th centile versus &lt;75th centile) was 1.55 (1.04–2.32).Conclusions and relevance: both low and high glycaemic levels and insulin resistance were independently associated with increased infection-related mortality risk, indicating a possible role of abnormal glucose metabolism in increased infection-related mortality.<br/

Regional prevalence of non-alcoholic fatty liver disease in Seoul and Gyeonggi-do, Korea

Background/AimsThe prevalence of nonalcoholic fatty liver disease (NAFLD) in Korea has increased recently. The aim of the present study was to determine the regional differences in the prevalence and characteristics of NAFLD.MethodsFrom January 2009 to December 2010, 161,891 Seoul and Gyeonggi-do residents receiving a health examination at our institution were enrolled in this cross-sectional study. After applying exclusion criteria, the data of 141,610 subjects (80,943 males, 60,667 females) were analyzed. The presence of NAFLD was established by ultrasound examination.ResultsThe overall prevalence of NAFLD was 27.3% (38.3% in men, 12.6% in women). When standardized according to age, area, and sex, the prevalence of NAFLD was 25.2%. The age and area standardized prevalence of NAFLD was higher for men (34.4%) than for women (12.2%; P<0.001). The overall prevalence of NAFLD was higher in Gyeonggi-do (27.7%) than in Seoul (26.9%; P<0.001). Among the men, the prevalence of NAFLD was higher in Gyeonggi-do (39.2%) than in Seoul (37.4%; P<0.001), while for the women it was higher in Seoul (13.2%) than in Gyeonggi-do (12.0%; P<0.001).ConclusionsThe regional prevalence of NAFLD differed between Seoul and Gyeonggi-do. Further studies are needed to establish the etiology of this difference

Activation of Protein Kinase G After Repeated Cocaine Administration Is Necessary for the Phosphorylation of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor GluA1 at Serine 831 in the Rat Nucleus Accumbens

Phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the striatum plays a crucial role in regulating the receptor-coupled signaling cascades leading to behavioral changes associated with psychostimulant exposure. The present study determined if activation of protein kinase G (PKG) contributes to the phosphorylation of AMPA receptor GluA1 subunit at the position of serine 831 (GluA1-S831) in the rat nucleus accumbens (NAc) after repeated cocaine administration. The results demonstrated that repeated intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once a day for seven consecutive days significantly increased the level of phosphorylated (p)GluA1-S831. This increase was decreased by the intra-NAc infusion of either the cyclic guanosine monophosphate (cGMP) analog, Rp-8-Br-PET-cGMPS (5 nmol/1 μL), or the PKG inhibitor, KT5823 (2 nmol/1 μL). Repeated cocaine administration increased PKG binding activity to GluA1. This increase in GluA1-S831 phosphorylation after repeated cocaine administration was decreased by the intra-NAc infusion of the synthetic peptide (Tat-tagged interfering peptide (Tat-GluA1-i)), that interferes with the binding of PKG to GluA1. Intra-NAc infusion of the interfering peptide also reduced the repeated cocaine-induced increase in locomotor activity. These findings suggest that activated PKG, after repeated exposure to cocaine, binds to AMPA receptor GluA1 and is required for the phosphorylation of S831, contributing to behavioral changes

Caloric restriction of db/db mice reverts hepatic steatosis and body weight with divergent hepatic metabolism

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver disease and its prevalence is a serious and growing clinical problem. Caloric restriction (CR) is commonly recommended for improvement of obesity-related diseases such as NAFLD. However, the effects of CR on hepatic metabolism remain unknown. We investigated the effects of CR on metabolic dysfunction in the liver of obese diabetic db/db mice. We found that CR of db/db mice reverted insulin resistance, hepatic steatosis, body weight and adiposity to those of db/m mice. H-NMR- and UPLC-QTOF-MS-based metabolite profiling data showed significant metabolic alterations related to lipogenesis, ketogenesis, and inflammation in db/db mice. Moreover, western blot analysis showed that lipogenesis pathway enzymes in the liver of db/db mice were reduced by CR. In addition, CR reversed ketogenesis pathway enzymes and the enhanced autophagy, mitochondrial biogenesis, collagen deposition and endoplasmic reticulum stress in db/db mice. In particular, hepatic inflammation-related proteins including lipocalin-2 in db/db mice were attenuated by CR. Hepatic metabolomic studies yielded multiple pathological mechanisms of NAFLD. Also, these findings showed that CR has a therapeutic effect by attenuating the deleterious effects of obesity and diabetes-induced multiple complications

Development of a CHO cell line for stable production of recombinant antibodies against human MMP9

Abstract Background Human matrix metalloproteinase 9 (hMMP9) is a biomarker in several diseases, including cancer, and the need for developing detectors and inhibitors of hMMP9 is increasing. As an antibody against hMMP9 can be selectively bound to hMMP9, the use of anti-MMP9 antibody presents new possibilities to address hMMP9-related diseases. In this study, we aimed to establish a stable Chinese hamster ovary (CHO) cell line for the stable production of antibodies against hMMP9. Results Weconstructed recombinant anti-hMMP9 antibody fragment-expressing genes and transfected these to CHO cells. We chose a single clone, and successfully produced a full-sized antibody against hMMP9 with high purity, sensitivity, and reproducibility. Subsequently, we confirmed the antigen-binding efficiency of the antibody. Conclusions We developed a novel recombinant anti-hMMP9 antibody via a CHO cell-based mammalian expression system, which has a high potential to be used in a broad range of medical and industrial areas

Prognostic significance of respiratory quotient in patients undergoing extracorporeal cardiopulmonary resuscitation in Korea

Background Respiratory quotient (RQ) may be used as a tissue hypoxia marker in various clinical settings but its prognostic significance in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) is not known. Methods Medical records of adult patients admitted to the intensive care units after ECPR in whom RQ could be calculated from May 2004 to April 2020 were retrospectively reviewed. Patients were divided into good neurologic outcome and poor neurologic outcome groups. Prognostic significance of RQ was compared to other clinical characteristics and markers of tissue hypoxia. Results During the study period, 155 patients were eligible for analysis. Of them, 90 (58.1%) had a poor neurologic outcome. The group with poor neurologic outcome had a higher incidence of out-of-hospital cardiac arrest (25.6% vs. 9.2%, P=0.010) and longer cardiopulmonary resuscitation to pump-on time (33.0 vs. 25.2 minutes, P=0.001) than the group with good neurologic outcome. For tissue hypoxia markers, the group with poor neurologic outcome had higher RQ (2.2 vs. 1.7, P=0.021) and lactate levels (8.2 vs. 5.4 mmol/L, P=0.004) than the group with good neurologic outcome. On multivariable analysis, age, cardiopulmonary resuscitation to pump-on time, and lactate levels above 7.1 mmol/L were significant predictors for a poor neurologic outcome but not RQ. Conclusions In patients who received ECPR, RQ was not independently associated with poor neurologic outcome