Hypobaric hypoxia drives selection of altitude-associated adaptative alleles in the Himalayan population.

Genetic variants play a crucial role in shaping the adaptive phenotypes associated with high-altitude populations. Nevertheless, a comprehensive understanding of the specific impacts of different environments associated with increasing altitudes on the natural selection of these genetic variants remains undetermined. Hence, this study aimed to identify genetic markers responsible for high-altitude adaptation with specific reference to different altitudes, majorly focussing on an altitude elevation range of ∼1500 m and a corresponding decrease of ≥5 % in ambient oxygen availability.

Dexamethasone prophylaxis protects from acute high-altitude illness by modifying the peripheral blood mononuclear cell inflammatory transcriptome.

Acute high-altitude (HA) exposure can induce several pathologies. Dexamethasone (DEX) can be taken prophylactically to prevent HA disease, but the mechanism by which it acts in this setting is unclear. We studied the transcriptome of peripheral blood mononuclear cells (PBMCs) from 16 subjects at low altitude (LA, 225 m) and then 3 days after acute travel to HA (3500 m) during the India-Leh-Dexamethasone-Expedition-2020 (INDEX2020).

Disparities in COVID-19 incidence and fatality rates at high-altitude.

Background: SARS-CoV-2 has affected every demography disproportionately, including even the native highland populations. Hypobaric-hypoxic settings at high-altitude (HA, >2,500 masl) present an extreme environment that impacts the survival of permanent residents, possibly including SARS-CoV-2. Conflicting hypotheses have been presented for COVID-19 incidence and fatality at HA.

The Telomere-Telomerase System Is Detrimental to Health at High-Altitude.

The hypobaric-hypoxia environment at high-altitude (HA, >2500 m) may influence DNA damage due to the production of reactive molecular species and high UV radiation. The telomere system, vital to chromosomal integrity and cellular viability, is prone to oxidative damages contributing to the severity of high-altitude disorders such as high-altitude pulmonary edema (HAPE). However, at the same time, it is suggested to sustain physical performance.

Molecular Mechanisms of High-Altitude Acclimatization.

High-altitude illnesses (HAIs) result from acute exposure to high altitude/hypoxia. Numerous molecular mechanisms affect appropriate acclimatization to hypobaric and/or normobaric hypoxia and curtail the development of HAIs. The understanding of these mechanisms is essential to optimize hypoxic acclimatization for efficient prophylaxis and treatment of HAIs.

Sexual Dimorphism of Dexamethasone as a Prophylactic Treatment in Pathologies Associated With Acute Hypobaric Hypoxia Exposure.

Dexamethasone can be taken prophylactically to prevent hypobaric hypoxia-associated disorders of high-altitude. While dexamethasone-mediated protection against high-altitude disorders has been clinically evaluated, detailed sex-based mechanistic insights have not been explored. As part of our India-Leh-Dexamethasone-expedition-2020 (INDEX 2020) programme, we examined the phenotype of control ( = 14) and dexamethasone ( = 13) groups, which were airlifted from Delhi (∼225 m elevation) to Leh, Ladakh (∼3,500 m), India, for 3 days.

Seeding drug discovery: Telomeric tankyrase as a pharmacological target for the pathophysiology of high-altitude hypoxia.

Cellular exposure to extreme environments leads to the expression of multiple proteins that participate in pathophysiological manifestations. Hypobaric hypoxia at high altitude (HA) generates reactive oxygen species (ROS) that can damage telomeres. Tankyrase (TNKS) belongs to multiple telomeric protein complexes and is actively involved in DNA damage repair.

Pathophysiology and potential future therapeutic targets using preclinical models of COVID-19.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) gains entry into the lung epithelial cells by binding to the surface protein angiotensin-converting enzyme 2. Severe SARS-CoV-2 infection, also known as coronavirus disease 2019 (COVID-19), can lead to death due to acute respiratory distress syndrome mediated by inflammatory immune cells and cytokines. In this review, we discuss the molecular and biochemical bases of the interaction between SARS-CoV-2 and human cells, and in doing so we highlight knowledge gaps currently precluding development of new effective therapies.

Shorter telomere length, higher telomerase activity in association with tankyrase gene polymorphism contribute to high-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a noncardiogenic form of pulmonary edema, which is induced upon exposure to hypobaric hypoxia at high altitude (HA). Hypobaric hypoxia generates reactive oxygen species that may damage telomeres and disturb normal physiological processes. Telomere complex comprises of multiple proteins, of which, tankyrase (TNKS) is actively involved in DNA damage repairs.

Sex-derived attributes contributing to SARS-CoV-2 mortality.

Epidemiological data in COVID-19 mortality indicate that men are more prone to die of SARS-CoV-2 infection than women, but biological causes for this sexual dimorphism are unknown. We discuss the prospective behavioral and biological differences between the sexes that could be attributed to this sex-based differentiation. The female sex hormones and the immune stimulatory genes, including Toll-like receptors, interleukins, and micro-RNAs present on X-chromosome, may impart lesser infectivity and mortality of the SARS-CoV-2 in females over males.

Tumor necrosis factor-alpha -308G/A gene polymorphism and novel biomarker profiles in patients with Takayasu arteritis.

Background: Takayasu arteritis (TA) is an idiopathic chronic inflammatory disease of the aorta and its branches, leading to stenosis, occlusion, and aneurysmal dilatation. Tumor necrosis factor-alpha (TNF-α) is a cytokine with pleomorphic actions and plays a pivotal role in inflammation; the serum level of TNF-α is genetically determined. However, the literature lacks adequate information on the association of TNF-α polymorphisms with TA.

Role of ApoE gene polymorphism and nonconventional biochemical risk factors among very young individuals (aged less than 35 years) presenting with acute myocardial infarction.

Background: Incidence rate of acute myocardial infarction (MI) has increased in younger population over the years. The young patients have a different risk profile, presentation, and prognosis than the elderly. Hence, it is essential to understand the risk factors in young patients for proper treatment.

Elevated Vasodilatory Cyclases and Shorter Telomere Length Contribute to High-Altitude Pulmonary Edema.

Unlabelled: Rain, Manjari, Himanshi Chaudhary, Ritushree Kukreti, Tashi Thinlas, Ghulam Mohammad, and Qadar Pasha. Elevated vasodilatory cyclases and shorter telomere length contribute to high-altitude pulmonary edema. High Alt Med Biol.

Biochemical and genetic role of apelin in essential hypertension and acute coronary syndrome.

Background: Apelin-APJ pathway has emerged as a potent regulator of blood pressure (BP) and blood flow in vasculature and heart. Variants in apelin gene may affect the vascular tone in peripheral circulation or heart, thereby predisposing to cardiovascular diseases. The aim of our study was to investigate the association of two apelin gene polymorphisms rs3761581 and rs2235312, and apelin levels in patients with essential hypertension (EH) and acute coronary syndrome (ACS).

Unveiling the interactions among BMPR-2, ALK-1 and 5-HTT genes in the pathophysiology of HAPE.

Context: Few potential candidate genes coding for type I and II receptors of transforming growth factor beta signaling pathway and the serotonin transporter have been associated with pulmonary hypertension (PH). The latter being a phenotype for high altitude pulmonary edema (HAPE), these genes are hypothesized to be crucial markers to investigate under the hypobaric hypoxic environment of high altitude.

Aims: We hence aimed to investigate bone-morphogenetic protein-2 (BMP2), bone morphogenetic protein receptor type-II (BMPR-2), activin receptor-like kinase-1 (ALK-1), serotonin transporter (5-HTT) and serotonin (5-HT) for their contribution, individually/epistatically, to clinical endpoints by altering downstream signaling molecules.

ROCK2 and MYLK variants under hypobaric hypoxic environment of high altitude associate with high altitude pulmonary edema and adaptation.

Objective: To date, a major class of kinases, serine-threonine kinase, has been scantly investigated in stress-induced rare, fatal (if not treated early), and morbid disorder, high altitude pulmonary edema (HAPE). This study examined three major serine-threonine kinases, ROCK2, MYLK, and JNK1, along with six other genes, tyrosine hydroxylase, G-protein subunits GNA11 and GNB3, and alpha1 adrenergic receptor isoforms 1A, 1B, and 1D as candidate gene markers of HAPE and adaptation.

Methods: For this, 57 variants across these nine genes were genotyped in HAPE patients (n=225), HAPE controls (n=210), and highlanders (n=259) by Sequenom MS (TOF)-based MassARRAY® platform using iPLEX™ Gold technology.

β-T594M epithelial sodium channel gene polymorphism and essential hypertension in individuals of Indo-Aryan ancestry in Northern India.

Background: The T594M variant of the β-subunit of the sodium epithelial channel (ENaC) gene may contribute to hypertension in individuals of Indo-Aryan origin.

Methods: Present study was performed to assess the role of the ENaC gene variant as an independent risk factor for hypertension in subjects of Indo-Aryan ancestry. A total of 150 patients of recently detected essential hypertension and 150 matched controls were genotyped for the T594M polymorphism of the ENaC gene by PCR-RFLP method.

Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Genetics of pulmonary hypertension.

Pulmonary hypertension (PH) is a phenotype characterized by functional and structural changes in the pulmonary vasculature, leading to increased vascular resistance.[12] The World Health Organization has classified PH into five different types: arterial, venous, hypoxic, thromboembolic or miscellaneous; details are available in the main guidelines. Group I of this classification, designated as pulmonary arterial hypertension (PAH), will remain the main focus here.

Saudi guidelines on the diagnosis and treatment of pulmonary hypertension: 2014 updates.

The Saudi Association for Pulmonary Hypertension (previously called Saudi Advisory Group for Pulmonary Hypertension) has published the first Saudi Guidelines on Diagnosis and Treatment of Pulmonary Arterial Hypertension back in 2008.[1] That guideline was very detailed and extensive and reviewed most aspects of pulmonary hypertension (PH). One of the disadvantages of such detailed guidelines is the difficulty that some of the readers who just want to get a quick guidance or looking for a specific piece of information might face.

Effect of a 6-month intervention with cooking oils containing a high concentration of monounsaturated fatty acids (olive and canola oils) compared with control oil in male Asian Indians with nonalcoholic fatty liver disease.

Objective: We investigated the effects of dietary intervention with canola or olive oil in comparison with commonly used refined oil in Asian Indians with nonalcoholic fatty liver disease (NAFLD).

Subjects And Methods: This was a 6-month intervention study including 93 males with NAFLD, matched for age and body mass index (BMI). Subjects were randomized into three groups to receive olive oil (n=30), canola oil (n=33), and commonly used soyabean/safflower oil (control; n=30) as cooking medium (not exceeding 20 g/day) along with counseling for therapeutic lifestyle changes.

Association between the Glu298Asp and 4b/4a polymorphisms of endothelial nitric oxide synthase and coronary slow flow in the North Indian population.

Rationale: Genetic variants in endothelial nitric oxide synthase gene (NOS3) leading to endothelial dysfunction may be predispose to the coronary slow-flow phenomenon (CSFP).

Methods And Results: In this study, we examined the relationship between Glu298Asp (894G/T) and 4b/4a polymorphisms of NOS3 and CSFP. A total of 27 patients with CSFP but otherwise normal coronary arteries (mean age 50.