Role of Mitochondria in Exercise Protecting Myocardium From Ischemia-reperfusion Injury / 生物化学与生物物理进展

Acute myocardial infarction (AMI) has become the leading cause of death in cardiovascular diseases. Myocardial ischemia and reperfusion (MI/R) occurs when myocardial blood circulation is reconstructed after blood supply is limited or lack, often after myocardial infarction, and is the main cause of acute myocardial injury. According to the length of ischemia time, arrhythmia, myocardial inhibition, and myocardial infarction may occur in sequence in MI/R. Mitochondria are the key organelles involved in MI/R injury. Mitochondrial ROS eruption, Ca2+ imbalance, mPTP opening, mitochondrial swelling, and release of pro-apoptotic proteins all lead to mitochondrial dysfunction and myocardial function impairment. Exercise is an effective intervention to prevent myocardial ischemia-reperfusion injury, and its protective effect is closely related to the intensity of exercise, the length of exercise time, the type of exercise and the internal exercise ability. The mitochondrial mechanism of exercise protection against myocardial ischemia-reperfusion injury is determined by many factors. During reperfusion, the heart after trained is better able to maintain energy homeostasis, maintain ΔΨm and limit mPTP activation, maintain ATP synthesis. Activation of the sarcoKATP and/or mitoKATP channels by exercise induces cellular and/or myocardial hyperpolarization, protecting the mitochondria and myocardium during MI/R. Exercise-trained hearts can regulate calcium homeostasis during MI/R and limit mitochondrial Ca2+ overload. Exercise training can improve the activity of mitochondrial antioxidant enzymes to clear ROS and regulate mitochondrial Ca2+ concentration during MI/R. Exercise can increase the bioavailability of NO near mitochondria and indirectly achieve exercise-induced myocardial protection through protein S-nitrosylation and the eNOS-NO pathway is related to mitochondrial biogenesis after exercise training. Exercise training can also affect mitochondrial dynamics during MI/R by preventing mitochondrial division and promoting mitochondrial fusion. Exercise training can promote autophagy of damaged mitochondria and reduces apoptosis through mitochondria too, thus helping to maintain the function of mitochondrial bank. Besides these, exercise training leads to the production of motor factors (mainly from the muscles, but also from the brain, red blood cells, and other tissues) that contribute to remote regulation of the heart. This paper reviews the mitochondrial mechanism of MI/R, the protective effect of exercise on MI/R and the role of mitochondria in it, in order to provide more theoretical basis and new therapeutic targets for the diagnosis and treatment of heart disease, and provide new targets for drug research and development. In future clinical treatment, it is expected that sports pills targeted mitochondria can treat MI/R injury for bedridden people who cannot exercise or people who do not want to exercise through new technological means such as nanoparticle packaging.

FGF1-based Drugs for The Treatment of Obesity-related Complications / 生物化学与生物物理进展

At present, the incidence of overweight and obesity has reached epidemic levels worldwide, which call a challenge to the prevention and control of chronic metabolic diseases. Because obesity is a major risk factor for a range of metabolic diseases, including type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cardiovascular and neurodegenerative diseases, sleep apnea, and some types of cancer. However, the drugs remain limited. Therefore, there is an urgent need to develop effective long-term treatments to address obesity-related complications. Fibroblast growth factor 1 (FGF1) is an important regulator of systemic energy homeostasis, glycolipid metabolism and insulin sensitivity. FGF1 is a non-glycosylated polypeptide consisting of 155 amino acids, consisting of 12 inverted parallel β chains with amino and carboxyl terminus, and N-terminus extending freely without the typical secretory signaling sequence, closely related to its own biological activity. Thus, FGF1 mutants or derivatives with different activities can be designed by substitution or splicing modification at theN-terminal. FGF1 plays an irreplaceable role in the development, deposition and function of fat. High-fat diet can regulate available FGF1 through two independent mechanisms of nutritional perception and mechanical perception, and influence the function of fat cells. FGF1 controls blood glucose through peripheral and central effects, enhances insulin sensitivity, improves insulin resistance, and plays a role in diabetic complications, which is expected to become a new target for the treatment of T2DM in the future. FGF1 may be involved in the regulation of NAFLD from mild steatosis to severe non-alcoholic steatohepatitis. FGF1 is closely related to the occurrence and development of a variety of cancers, improve the efficacy of anti-cancer drugs, and play a direct and indirect anti-cancer role. In addition, FGF1 plays an important role in the occurrence and development of the cardiovascular system and the improvement of cardiovascular diseases such as ischemia/reperfusion injury, myocardial infarction, pathological cardiac remodeling, cardiotoxicity. Therefore, FGF1 shows a number of therapeutic benefits in the treatment of obesity and obesity-related complications. But because FGF1 has strong mitotic activity and long-term use has been associated with an increased risk of tumorigenesis, its use in vivo has been limited and enthusiasm for developing it to treat obesity-related complications has been dampened. However, FGF1 was found to induce cell proliferation primarily through FGFR3 and FGFR4, but its metabolic activity was mainly mediated by FGFR1. That is, FGF1 activity that promotes mitosis and anti-obesity-related complications appears to be separable. Currently, many engineered FGF1 variants have been developed, such as FGF1ΔHBS, MT-FGF1ΔHBS, FGF1∆NT, ∆nFGF1, FGF1R50E. Although the effect of FGF1 or its analogues on obesity-related complications has been demonstrated in many rodent studies, there are no relevant clinical results. This may be due to the unknown safety and therapeutic efficacy of FGF1 in large animals and humans, as well as concerns about tumorigenesis that hinder its development into a lifelong therapeutic agent. This review summarizes recent advances in the development of FGF1-based biologic drugs for the treatment of obesity-related complications, highlights major challenges in clinical implementation, and discusses possible strategies to overcome these obstacles.

Comparison of different protocols for protein extraction from formalin-fixed paraffin embedded esophageal squamous cell carcinoma tissues / 解剖学报

Objective To explore protein extraction efficiency from formaldehyde-fixed paraffin embedded (FFPE) esophageal squamous cell carcinoma (ESCC) tissue samples with different protocols. Methods Six different lysis buffers with 100 °C or 105 °C. treatments were used for protein extraction, followed by evaluation of protein quantity and quality with Bradford, sodium dodecyl sulfate Polyacrylamide gel electrophoresis (SDS-PAGE) electrophoresis, Western blotting and immunohistochemistry (IHC), using 8 FFPE samples of ESCC. Results The optimal method for protein extraction from FFPE ESCC tissue was Laemmli lysis buffer (Buffer 4) treated with 100 °C incubation, evidenced by highest amount of protein recovery. Western blotting and IHC method measured consistent 14-3-3σ expression in FFPE ESCC tissue samples. Protein precipitated by two volumes of acetonitrite acetonitrile(ACN) (0.1% trifluoroacetic acid) relative to protein amount reduced background staining on SDS-PAGE gels by commassie staining. Conclusion Laemmli lysis buffer combined with 100 °C incubation has the highest protein extraction efficiency from FFPE ESCC tissue samples for Western blotting measurement of protein biomarkers, and ACN protein precipitation can further eliminate residual cross- linked protein by FFPE.

The breakthrough curve combination for xenon sampling dynamics in a carbon molecular sieve column.

In the research of xenon sampling and xenon measurements, the xenon breakthrough curve plays a significant role in the xenon concentrating dynamics. In order to improve the theoretical comprehension of the xenon concentrating procedure from the atmosphere, the method of the breakthrough curve combination for sampling techniques should be developed and investigated under pulse injection conditions. In this paper, we describe a xenon breakthrough curve in a carbon molecular sieve column, the combination curve method for five conditions is shown and debated in detail; the fitting curves and the prediction equations are derived in theory and verified by the designed experiments. As a consequence, the curves of the derived equations are in good agreement with the fitting curves by tested. The retention times of the xenon in the column are 61.2, 42.2 and 23.5 at the flow rate of 1200, 1600 and 2000 mL min(-1), respectively, but the breakthrough times are 51.4, 38.6 and 35.1 min.

Fitting formula for the injection volume of a gas chromatograph for radio-xenon sampling in the lower troposphere.

GC is usually used for xenon concentration and radon removal in the International Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty. In a gas chromatograph, the injection volume is defined to calculate the column capacity. In this paper, the injection volume was investigated and a fitting formula for the injection volume was derived and discussed subsequently. As a consequence, the xenon injection volume exponentially decreased with the column temperature increased, but exponentially increased as the flow rate increased.