A preliminary identification of PIN1 SNP linkage in patients with coronary heart disease from Handan, China.

Our aim was to perform an initial assessment of the polymorphic patterns of the PIN1 gene in patients with coronary heart disease (CHD). The PIN1-encoded protein (Pin1) suppresses eNOS-NO signaling and may impair cardiovascular function. Blood collection, DNA extraction, PCR amplification and gene sequencing were performed for thirty CHD participants living in central China, focusing on nine single nucleotide polymorphisms (SNPs). Their genetic linkages were revealed and their allele frequencies were compared with SNP data from the NCBI. Three major linkage patterns were identified: [1.rs2287839-5.rs2233682], [3.rs2233679-4.rs1077220-8.rs2287838] and [6.rs889162-7.rs2010457], suggesting correlated involvement in CHD and possible simultaneous genetic origin in ancient times. The frequencies of six SNPs are consistent with the NCBI data, while the frequencies of three SNPs (2.rs2233678, 4.rs1077220 and 9.rs4804461) are not consistent with the NCBI. Especially, the 3.rs2233679-4.rs1077220 linkage is different from other populations worldwide and may be an interesting genetic characteristic of Chinese CHD patients. Predictably, 1.rs2287839, 2.rs2233678, 3.rs2233679 and 5.rs2233682 may be strongly associated with CHD risk, although this requires future verification. The PIN1 SNP linkages lay a new genetic foundation for discovering novel molecular mechanisms of CHD and for exploring PIN1-based targeted treatment of CHD with nitric oxide regulatory therapies in clinical practice.

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.

PIN1, a perspective on genetic biomarker for nonalcoholic fatty liver disease (NAFLD).

OBJECTIVE: A novel genetic and molecular basis of nonalcoholic fatty liver disease (NAFLD) was explored. STUDY DESIGN: A 38-year-old male, who has no bad living and dietary habits, was diagnosed as NAFLD. The potential pathogenic role of Pin1 was evaluated by enzyme-linked immunosorbent (ELISA) assay and single nucleotide polymorphism (SNP) sequencing. RESULTS: ELISA determined a six-time higher concentration of plasma Pin1 compared to our previous data. Nine PIN1 SNPs were sequenced and classified according to their NAFLD-pathogenic risks, suggesting that rs2233678 and rs2287839 may be the most important genotypes that result in Pin1 overexpression and NAFLD development. CONCLUSION: In summary, this work explores a novel basis for early-onset NAFLD and highlights that elevated plasma Pin1 may predict NAFLD risk at early stage. Hypothetically, inhibiting Pin1 may benefit NAFLD prevention in the future.

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.

Differences in Bacterial Diversity and Communities Between Glacial Snow and Glacial Soil on the Chongce Ice Cap, West Kunlun Mountains.

A detailed understanding of microbial ecology in different supraglacial habitats is important due to the unprecedented speed of glacier retreat. Differences in bacterial diversity and community structure between glacial snow and glacial soil on the Chongce Ice Cap were assessed using 454 pyrosequencing. Based on rarefaction curves, Chao1, ACE, and Shannon indices, we found that bacterial diversity in glacial snow was lower than that in glacial soil. Principal coordinate analysis (PCoA) and heatmap analysis indicated that there were major differences in bacterial communities between glacial snow and glacial soil. Most bacteria were different between the two habitats; however, there were some common bacteria shared between glacial snow and glacial soil. Some rare or functional bacterial resources were also present in the Chongce Ice Cap. These findings provide a preliminary understanding of the shifts in bacterial diversity and communities from glacial snow to glacial soil after the melting and inflow of glacial snow into glacial soil.

Pin1, endothelial nitric oxide synthase, and amyloid-ß form a feedback signaling loop involved in the pathogenesis of Alzheimer's disease, hypertension, and cerebral amyloid angiopathy.

Although the molecular mechanism has not yet been clarified until now, it is very interesting that Alzheimer's disease (AD), hypertension (HTN), and cerebral amyloid angiopathy (CAA) often occur synchronously and possess many similar pathological characteristics. Herein, we hypothesize that a feedback signaling loop, consisted of Pin1, endothelial nitric oxide synthase (eNOS), and amyloid-ß (Aß), may contribute to the interesting pathological phenomenon. First, Pin1 inhibits the production of Aß, and enhances the activity of eNOS. Second, Aß and eNOS form a mutual inhibition system. Third, the well-balanced feedback signaling loop avoids the development of AD, HTN, and CAA by inhibiting the frequent pathological characteristics of these diseases, including Aß deposition in cerebral microvessels and cerebral microbleeds. On one hand, Pin1 and eNOS not only inhibit Aß production but also accelerate Aß clearance, preventing Aß deposition in cerebral microvessels. On the other hand, Pin1 and eNOS promote vasodilatation and prevent the elevation of blood pressure in brain, alleviating the pathology of cerebral microbleeds. However, once the precise balance is disturbed, it may result in Aß deposition, microbleeds, and elevated blood pressure, possibly leading to the synchronous occurrence of AD, HTN, and CAA. The hypothesis updates the current understanding of the molecular linkage among AD, HTN, and CAA, and lays the ground for developing combined prevention, diagnosis, and treatment of these diseases more efficiently and more economically. Interestingly, biotechnical medicines enhancing the activity of Pin1 and/or eNOS may prevent the development of AD, HTN, and CAA, and targeting Aß deposition may alleviate the clinical pathologies of these related diseases.