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

113

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

Numerous studies have demonstrated that estrogens may exert multifaceted effects on the cardiovascular system via activating the classical nuclear receptors ERα or ERβ and the novel G protein coupled estrogen receptor (Gper). However, some studies have reported inconsistent cardiovascular phenotypes in Gper-deficient mice. The current study was aimed to reveal the effects of genetic deletion of Gper on the arterial blood pressure (ABP) and heart rate in rats. Gper-deficient Sprague-Dawley rats were generated by utilizing the CRISPR-Cas9 gene-editing technique. ABP of 10-week old male (n = 6) and 12-week old female (n = 6) Gper-deficient rats and age-matched wild type (WT) rats (6 females and 6 males) were measured under awake and restrained conditions through the non-invasive tail-cuff method daily for 8 (females) or 9 days (males). In the male WT rats, ABP and heart rate were slightly higher in day 1 to 4 than those in day 5 to 9, indicative of stress-related sympathoexcitation in the first few days and gradual adaptation to the restrained stress in later days. Gper-deficient rats had significantly higher ABP initially (male: day 1 to day 5; female: day 1 to day 3) and similar ABP in later days of measurement compared with the WT rats. The heart rate of male Gper-deficient rats was consistently higher than that of the male WT rats from day 1 to day 8. Both male and female Gper-deficient rats appeared to show slower body weight gain than the WT counterparts during the study period. Under anesthesia, ABP of Gper-deficient rats was not significantly different from their WT counterparts. These results indicate that Gper-deficient rats may be more sensitive to stress-induced sympathoexcitation and highlight the importance of Gper in the regulation of the cardiovascular function in stressful conditions.

Concepts: Male, Blood, Female, Hypertension, Heart, Blood pressure, Estrogen, Cardiovascular system

0

Growth hormone (GH), as a vital hormone, has to experience a series of processes to fulfill its function including secretion, entering the circulation to reach target tissues (pre-receptor process), binding on the GH receptor (GHR) and triggering signaling inside cells (post-GHR process). Insulin can directly or indirectly influence part of these processes. GH secretion from pituitary somatotropes is regulated by GH-releasing hormone (GHRH) and somatostatin (SS) from hypothalamus. Insulin may exert positive or negative effects on the neurons expressing GHRH and SS and somatotropes under healthy and pathological conditions including obesity and diabetes. Glucose and lipid levels in circulation and dietary habits may influence the effect of insulin on GH secretion. Insulin may also affect GHR sensitivity and the level of insulin-like growth factor 1 (IGF-1), thus influence the level of GH. The GH signaling is also important for GH to play its role. GH signaling involves GHR/JAK2/STATs, GHR/JAK2/SHC/MAPK and GH/insulin receptor substrate (IRS)/PI3K/Akt pathways. These pathways may be shared by insulin, which is the basis for the interaction between insulin and GH, and insulin may attenuate or facilitate the GH signal by influencing molecules in the pathways. Many factors are related to the effect of insulin, among them the most important ones are duration of action and amount of insulin. The tendency of insulin-reduced GH signaling becomes obvious with increased dose and acting time of insulin. The participation of suppressor of cytokine signaling (SOCS), the interaction between JAK2 and IRS, and GHR sensitivity should also be considered when discovering GH signal. The involvement of SS in response to insulin is not clear yet. The details of how GH secretion, level and signaling change in response to time and dose of insulin treatment warrant further studies.

Concepts: Immune system, Protein, Signal transduction, Insulin, Hormone, Endocrinology, Growth hormone, Peptide hormone

0

Nitric oxide (NO), well known as the endothelium-derived relaxing factor (EDRF), has become increasingly recognized as an important determinant of cardiovascular diseases. A molecular pathway by which NO accomplishes various biochemical processes is the cGMP-independent post-translational modification of protein, S-nitrosylation. Here we review the biochemistry and regulating mechanisms of NO-related S-nitrosylation of proteins, and discuss the multiple roles of S-nitrosylation in vascular functions and pathology in particular.

Concepts: DNA, Protein, Amino acid, Molecular biology, Signal transduction, Metabolism, Biochemistry, Nitric oxide

0

Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide. The regeneration capacity of the adult mammalian heart is very limited, so that the lost cells are replaced by fibrotic scar. This is followed by remodeling of the surrounding myocardium, which includes cardiac hypertrophy and fibrosis, and makes the ventricular wall thicken and stiffen. This adverse cardiac remodeling leads to impaired cardiac function and eventually leads to heart failure. Extensive studies have revealed that microRNAs (miRNAs) play an essential role in cardiovascular diseases. microRNA-22 (miR-22) is one of the most abundant miRNA in the heart. Many studies have demonstrated that miR-22 plays critical roles in MI and subsequent cardiac remodeling. In this review, we summarized the recent research progresses, including the regulatory effects of miR-22 in oxidative stress, cardiac apoptosis, autophagy, hypertrophy, fibrosis and regeneration.

Concepts: Myocardial infarction, Scar, Cardiology, Heart, MicroRNA, Cardiac muscle, Circulatory system, Mammal

0

Ischemic heart disease (IHD) is the life-threatening cardiovascular disease. Mitochondria have emerged as key participants and regulators of cellular energy demands and signal transduction. Mitochondrial quality is controlled by a number of coordinated mechanisms including mitochondrial fission, fusion and mitophagy, which plays an important role in maintaining healthy mitochondria and cardiac function. Recently, dysfunction of each process in mitochondrial quality control has been observed in the ischemic hearts. This review describes the mechanism of mitochondrial dynamics and mitophagy as well as its performance linked to myocardial ischemia. Moreover, in combination with our study, we will discuss the effect of vagal nerve on mitochondria in cardio-protection.

Concepts: Myocardial infarction, Heart, Blood vessel, Muscle, Heart disease, Circulatory system, Ischemia, Ischaemic heart disease

0

Hypertension is a serious world-wide health problem as it increases cardiovascular atherosclerotic risk, stroke and attending morbidity and mortality. Both systolic and diastolic blood pressures and particularly systolic pressure increase with aging. The downsides from pharmacological therapy have led to consideration of additional treatments, including acupuncture, which evokes endogenous neural-hormonal systems to lower blood pressure. Using basic science studies to guide clinical approaches to research, it is apparent that low frequency, low intensity electroacupuncture reduces sympathetic outflow in approximately 70% of patients with mild to moderate hypertension who are off antihypertensive drugs. Systolic and, to a lesser extent, diastolic arterial blood pressures can be lowered over two to four weeks for prolonged periods, lasting as long as one month, after cessation of an eight weeks of once weekly stimulation. Many questions about long-term therapy, treatment of resistant patients and efficacy in patients on medication remain to be studied. Current data, however, suggest that there may be a role of acupuncture in treatment of hypertension.

Concepts: Blood, Myocardial infarction, Atherosclerosis, Hypertension, Stroke, Blood pressure, Artery, Orthostatic hypotension