The association of rs2233679 in the PIN1 gene promoter with the risk of Coronary Artery Disease in Chinese female individuals.

BACKGROUNDS: Vascular atherosclerosis leads to various cardiovascular and cerebrovascular diseases. Nitric oxide (NO) promotes vasodilatation and prevents Coronary Artery Disease (CAD). Pin1 suppresses NO production by down-regulating the activity of endothelial nitric oxide synthase (eNOS). Whether the genetic polymorphisms of the PIN1 gene (encoding Pin1) are implicated in CAD deserves investigations in human beings. METHODS: A total of 210 CAD patients and control individuals (all females) were enrolled, and their genotypes of rs2233679 (-667C/T, a key SNP in the promoter of PIN1 gene) were sequenced. T-test, chi-square test, odds ratio (OR) and 95% confidence interval (95% CI) were calculated to evaluate Hardy-Weinberg equilibrium, varied genetic distribution and relative CAD risk. RESULTS: The differences in age, BMI, triglyceride, total cholesterol, low-density and high density cholesterol between the CAD and control groups were not significant (all P>0.05), and Hardy-Weinberg equilibrium was observed in the two groups (both P>0.05). The frequency of -667T allele in the CAD group was higher than that in the control group. The genotype -667TT elicited a higher hazardous risk of CAD compared to the genotype -667CC (OR=1.85, 95% CI: 0.75-4.53) as well as the genotypes CC+CT (OR=1.97, 95% CI: 0.86-4.49). CONCLUSIONS: We firstly show that the allele -667T in the PIN1 promoter may elicit a higher CAD-risk than -667C, and the -667TT genotype of PIN1 may be a new genetic biomarker for increased incidence of CAD. These novel observations put forward a new understanding of the PIN1-CAD genetic relationship in humans, potentially contributing to both cardiovascular and cerebrovascular disorders.

A post-surgical adjunctive hypoxic therapy for myocardial infarction: Initiate endogenous cardiomyocyte proliferation in adults.

Myocardial infarction (MI) is a major threat to health worldwide, but today's methods for recovering heart function are limited, which is due largely to the deficient proliferative capacity of adult cardiomyocytes in the human body. To successfully overwhelm this deficiency, we propose a promising hypoxic therapy and highlight its unique role in directly eliciting endogenous myocardial regeneration in vivo. In the hypothesis, sufficient oxygen could be a restrictive factor of myocardial growth, whereas a moderate hypoxia might stimulate cardiomyocyte proliferation and enhance myocardial regeneration, heart weight and cardiac function recovery. The potential involvements of the hypoxia inducible factor-1 (HIF-1) and its downstream oncogenic signalings were hypothesized and evaluated in detail. Notably, the hypoxic treatment may initiate spontaneous proliferation of pre-existing cardiomyocytes in adult human body, which cannot (or hardly) be achieved by current MI-therapeutic approaches such as cardiovascular drugs, cardiac surgeries and aerobic exercise. The hypoxic therapy will lead to lower surgical risks compared with tissue regeneration in vitro and putative cardiac transplantation. With optimized moderately-low oxygen concentration, available therapeutic frequency and cycles, and controllable side effects, the hypoxic therapy will be a non-invasive, non-surgical, low-cost and low-risk approach to promoting myocardial regeneration in vivo and recovering cardiac function for MI patients who have large-area myocardial necrosis, in addition to other current MI-therapeutic methodologies.

Gut microbiome-based medical methodologies for early-stage disease prevention.

Recent advancements highlight the important role of gut microbiome in human health. However, a variety of endogenous and exogenous factors, such as genes, foods, drugs, environmental pollutions, oxidative stress, etc., may interfere with the gut microbiome in vivo and increase risks of digestive system diseases, cardiovascular diseases, neurological diseases, obesity, diabetes, cancers, and so on. Abundant discoveries listed in this work support that changes in the composition of the gut microbiome may be potentially used as sensitive early-stage diagnostic biomarkers and that the gut microbiome could be a promising therapeutic target for systemic prevention of multiple human diseases. Interestingly, the microbial culturomics revolution makes it possible to identify much more species and several new species in the gut microbiome. Several innovative articles published by Science and Nature in 2016 further put forward the feasibility of these perspectives, lay grounds for establishing standardized human gut microbiome compositions, and are particularly important for monitoring dysbiosis of the gut microbiome and for precisely reshaping a dysfunctional gut microbiome. Hypothetically, keeping and reconstructing an optimized gut microbiome would be essential to prevent the occurrence of various human diseases. Hence, these advancements have impressive clinical implications for predicting abnormal healthy status of human beings and for preventing the initiation of systemic disorders at an early stage.