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Journal: Sheng li xue bao : [Acta physiologica Sinica]

112

The transcription factor Nrf2, nuclear factor erythroid-2-related factor 2, activates the transcription of over 500 genes in the human genome, most of which have cytoprotective functions. Nrf2 produces cytoprotection by detoxification mechanisms leading to increased detoxification and excretion of both organic xenobiotics and toxic metals; its action via over two dozen genes increases highly coordinated antioxidant activities; it produces major anti-inflammatory changes; it stimulates mitochondrial biogenesis and otherwise improves mitochondrial function; and it stimulates autophagy, removing toxic protein aggregates and dysfunctional organelles. Health-promoting nutrients and other factors act, at least in part by raising Nrf2 including: many phenolic antioxidants; gamma- and delta-tocopherols and tocotrienols; long chain omega-3 fatty acids DHA and EPA; many carotenoids of which lycopene may be the most active; isothiocyanates from cruciferous vegetables; sulfur compounds from allium vegetables; terpenoids. Other health promoting, Nrf2 raising factors include low level oxidative stress (hormesis), exercise and caloric restriction. Raising Nrf2 has been found to prevent and/or treat a large number of chronic inflammatory diseases in animal models and/or humans including various cardiovascular diseases, kidney diseases, lung diseases, diseases of toxic liver damage, cancer (prevention), diabetes/metabolic syndrome/obesity, sepsis, autoimmune diseases, inflammatory bowel disease, HIV/AIDS and epilepsy. Lesser evidence suggests that raising Nrf2 may lower 16 other diseases. Many of these diseases are probable NO/ONOO(-) cycle diseases and Nrf2 lowers effects of NO/ONOO(-) cycle elements. The most healthful diets known, traditional Mediterranean and Okinawan, are rich in Nrf2 raising nutrients as apparently was the Paleolithic diet that our ancestors ate. Modern diets are deficient in such nutrients. Nrf2 is argued to be both lifespan and healthspan extending. Possible downsides to too much Nrf2 are also discussed. Nrf2 is not a magic bullet but is likely to be of great importance in health promotion, particularly in those regularly exposed to toxic chemicals.

Concepts: Inflammation, DNA, Genetics, Nutrition, Fatty acid, Antioxidant, Omega-3 fatty acid, Inflammatory bowel disease

23

Under normal condition, there are a few lipid droplets in skeletal muscle. But in skeletal muscle acute injury, muscular dystrophy, muscle atrophy, obesity, diabetes and other pathological conditions, the fat deposition in skeletal muscle increases, which implicate that the fat deposition may play an important role in the pathogenesis of these diseases. However, the mechanisms of development and regulation of fat deposition in skeletal muscle are not clear. Clarifying the key signaling pathways and regulatory factors that affect fat deposition in skeletal muscle, and exploring new ways to improve the fat deposition in skeletal muscle will not only help to deepen our understanding of the pathogenesis of these diseases, but also provide new ideas for the treatment of these diseases. This paper reviews the research progresses and main mechanisms of fat deposition in skeletal muscle.

Concepts: Metabolism, Pathology, Muscle, Fat, Adipose tissue, Muscle atrophy, Muscular system, Atrophy

23

High altitude hypoxia is an important factor to affect fetal development during pregnancy. In the special environment, maternal physiological functions are regulated to maintain the maternal and fetal homeostasis, so that limited oxygen is to meet the needs of fetal growth and development. In this review, the literatures about the effects of hypoxic environment on fetal development during pregnancy in recent years were summarized, in which the fetal growth characteristics, maternal physiological regulation, genetic and placental influencing factors in high altitude areas were involved. This may be helpful for the reproductive healthcare of women in high altitude region, and also for the treatment and prevention of fetal growth retardation in the hypoxic environment.

Concepts: Pregnancy, Fertility, Embryology, Hypoxia, Implantation, Gestational age, Altitude sickness

1

Despite continued improvement in risk factor recognition and aggressive medical management, heart disease remains the number one killer in the world. Medications for primary or secondary prevention of heart disease can cause unpleasant side effects leading to non-compliance. Novel therapies are needed to serve as a complement to or alternative for current medical management. Acupuncture and more specifically electroacupuncture may serve as a safe and viable option in the cardiology clinic. This review article focuses on both mechanistic and clinical studies evaluating acupuncture’s effectiveness with symptomatic heart disease. Although continued research is needed, currently evidence warrants consideration of acupuncture’s use with myocardial ischemia, hypertension, arrhythmias, heart failure as well as autonomic dysfunction.

Concepts: Medicine, Myocardial infarction, Cardiology, Heart failure, Avicenna, Heart disease, Alternative medicine, Ischaemic heart disease

0

Myocardial fibrosis (MF) is an important pathological process of cardiac remodeling in patients with heart failure; however its etiology has not been clear. It has been known that the angiotensin II type 1 receptor autoantibody (AT1-AA) is present in patients with heart failure, but it is unclear whether this antibody directly causes MF. In this study, we investigated the role of AT1-AA in MF and its effects on cardiac fibroblasts (CFs). The AT1-AA positive rat model was established by active immunization method, and the measurement of indexes were made in the 8th week after active immunity. The results of heart echocardiography showed that the cardiac systolic and diastolic functions of AT1-AA positive rats were impaired with reduced left ventricular wall thickness and enlarged heart chambers. HE staining results showed that the myocardial fibers were disorganized and ruptured, and Masson staining revealed that the area of collagen fibers around the myocardium and coronary arteries was significantly increased in AT1-AA positive group compared with that of the control group (P < 0.05). Moreover, primary CFs isolated from neonatal rats were cultured and treated with AT1-AA for 48 h. CCK-8 and immunofluorescence staining results showed that AT1-AA enhanced proliferation rate of CFs (P < 0.001), and Western blot results showed that AT1-AA significantly increased expressions of collagen I (Col I), Col III, matrix metalloproteinase-2 (MMP-2) and MMP-9 in CFs (all P < 0.05). Taken together, these results suggest that AT1-AA may induce MF and cardiac dysfunction via activating CFs.

0

The purpose of this study is to investigate the effect of the oral endothelin antagonist Bosentan on blood pressure and renal sympathetic nerve activity (RSNA) in rats exposed to chronic intermittent hypoxia (CIH), and to explore the sympathoexcitation mechanism of endothelin-1 (ET-1) in CIH-induced hypertension. Twenty-four male SD rats were randomly divided into normoxia, CIH and Bosentan groups. Rats in the normoxia group were exposed to normoxic environment, and rats in CIH or Bosentan group were exposed to intermittent hypoxia for 3 weeks. Bosentan was given at 50 mg/kg by intragastric administration before intermittent hypoxia exposure in Bosentan group. Systolic blood pressure (SBP) was measured by BP-2000, and the change of RSNA to sodium nitroprusside (SNP) or phenylephrine (PE) was recorded by PowerLab signal acquisition system. Serums of all rats were collected and the contents of ET-1 and norepinephrine (NE) were measured by ELISA. Results showed that blood pressure was gradually increased following CIH exposure compared with the normoxia group during the 3 weeks (P < 0.01, P < 0.01, P < 0.001). The basal RSNA was increased and baroreflex sensitivity was decreased in rats exposed to CIH. Furthermore, the blood pressure was positively correlated with the level of ET-1 in serum in rats exposed to CIH (r = 0.833, P = 0.01). Bosentan administration significantly decreased SBP and basal RSNA, increased the baroreflex sensitivity, and decreased serum NE level in rats exposed to CIH. These results suggest that ET-1 is related with blood pressure elevation in rats exposed to CIH, and Bosentan reverses CIH-induced hypertension by decreasing RSNA.

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The aim of this study was to screen the genes related to the pathogenesis of major depression disorder (MDD) by bioinformatics. Taking GSE98793 chip data from GEO public database of National Biotechnology Information Center (NCBI) website as the research object, 116 differentially expressed genes (DEGs) were screened by R language limma package. Among the 116 DEGs, 66 genes were up-regulated and 50 down-regulated. The results of gene functional annotation analysis of Gene Ontology (GO) showed that the DEGs were mainly distributed in mitochondria intima and mitochondria. They were involved in copper ion binding, cysteine-type endopeptidase activity, the cell response of interleukin-1, protein processing and other biological processes. KEGG pathway enrichment analysis results showed that the DEGs were mainly concentrated in oxidative phosphorylation, Parkinson’s disease, non-alcoholic fatty liver disease, Alzheimer’s disease and Huntington’s disease etc. The results of protein interaction network analysis showed that there were interactions among proteins encoded by 54 DEGs. Combined with the analysis results of the above methods, 11 key genes were screened out, including UQCRC1, GZMB, NDUFB9, NSF, SLC17A5, CTSH, NDUFB10, UQCR10, ATOX1, CST7 and CTSW, which could be used as candidate genes for the diagnosis and treatment of MDD. Taken together, the key genes were obtained by analyzing the microarray and the DEGs of MDD in the present study, which would provide important clues for revealing the molecular mechanism and clinical targeted therapy of depression.

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Neurons with direction-selectivity for vestibular stimuli are found in a number of cortical areas, and neurons in the ventral intraparietal area (VIP) and the dorsal subdivision of the medial superior temporal area (MSTd) of the macaque brain are clustered according to their direction preferences for vestibular signals. This raises the question where the clustering inherits from? Previous work has shown that VIP and MSTd most probably receive vestibular input from the parieto-insular vestibular cortex (PIVC), which processes vestibular signals at the earlier stage. Thus, PIVC is also supposed to show a clustered organization similar to that seen in VIP and MSTd. The present study was aimed to examine clustering properties of vestibular response in PIVC area. To address this issue, we compared the tuning of isolated single unit (SU) with the undifferentiated multiunit (MU) activity of several neighboring neurons recorded from the same microelectrode. When directional tuning was observed in MU activity, the direction preference generally agreed closely with that of a simultaneously recorded SU. These results suggest that PIVC neurons are indeed clustered according to preferred direction for both translational and rotational vestibular stimuli.

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The purpose of this study was to investigate the expression profile of circular RNA (circRNA) in gastric cancer cells MGC-803, SGC-7901 and NCI-N87 with different degrees of differentiation and normal gastric epithelial cells GES-1. High throughput circRNA microarray technique was used to detect the differential expression of circRNA between three kinds of differentiated gastric cancer cells and normal gastric epithelial cells. The interaction of microRNAs (miRNAs) with circRNAs was predicted by bioinformatics software, and circRNA, which might have great significance in gastric cancer, was identified by literature search. The results showed that there were 79 up-regulated circRNAs and 229 down-regulated circRNAs in gastric cancer cells with different degrees of differentiation compared with those in normal gastric epithelial cells. Through bioinformatics software analysis and literature retrieval, it was found that hsa_circ_0001897 was related to the staging and metastasis of gastric cancer, while the miR-150-5p, which combined with it, was closely related to many kinds of digestive tract tumors, such as colon cancer, liver cancer, and cholangiocarcinoma. The miR-16-5p, which has binding sites with hsa_circ_0008106 and hsa_circ_0060456, has been confirmed to be involved in the development of gastric cancer. The above results suggest that hsa_circ_0001897, hsa_circ_0008106 and hsa_circ_0060456 may be closely related to the occurrence and development of gastric cancer by interacting with miRNA.

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The purpose of the study was to investigate the effect of sophoridine on the proliferation and apoptosis of human gastric cancer MKN45 cells and the possible mechanism. MKN45 cells were randomly divided into control and sophoridine (including 6 subgroups) groups. Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) colorimetric method. The protein expression of high mobility group-box 3 (HMGB3) was observed by immunocytochemical staining and Western blot. Hoechst 33342 staining method was used to observe the morphological changes of cells treated with sophoridine. Apoptosis was detected by flow cytometry. The results showed that the proliferation of cells was inhibited by 48-hour treatment of sophoridine in a dose-dependent manner. Compared with control group, sophoridine group showed decreased HMGB3 protein expression and increased apoptotic rate. These results suggest that sophoridine can inhibit the proliferation of MKN45 cells and promote their apoptosis, which may be related to down-regulation of HMGB3 protein expression.