Correction: Circulating microRNAs as potential biomarkers of early vascular damage in vitamin D deficiency, obese, and diabetic patients.

[This corrects the article DOI: 10.1371/journal.pone.

Gut matters in microgravity: potential link of gut microbiota and its metabolites to cardiovascular and musculoskeletal well-being.

The gut microbiota and its secreted metabolites play a significant role in cardiovascular and musculoskeletal health and diseases. The dysregulation of the intestinal microbiota poses a significant threat to cardiovascular and skeletal muscle well-being. Nonetheless, the precise molecular mechanisms underlying these changes remain unclear.

Retinal vascular changes and arterial stiffness during 8-month isolation and confinement: the SIRIUS-21 space analog mission.

Introduction: Isolation and confinement are significant stressors during space travel that can impact crewmembers' physical and mental health. Space travel has been shown to accelerate vascular aging and increase the risk of cardiovascular and cerebrovascular disorders. However, the effect of prolonged isolation and confinement on microvascular function has not yet been thoroughly investigated.

Cardiovascular changes under the microgravity environment and the gut microbiome.

In view of the critical role the gut microbiome plays in human health, it has become clear that astronauts' gut microbiota composition changes after spending time in space. Astronauts are exposed to several risks in space, including a protracted period of microgravity, radiation, and mechanical unloading of the body. Several deleterious effects of such an environment are reported, including orthostatic intolerance, cardiovascular endothelial dysfunction, cellular and molecular changes, and changes in the composition of the gut microbiome.

Enhancing microbial diversity as well as multi-organ health in hind-limb unloaded mice.

During space travel, the gut microbiota is changed which can lead to health-related issues. Previously, we utilized the hind-limb unloaded (HU) mouse, which is an established ground-based in-vivo model of microgravity and observed altered gut microbiota. In this study, we evaluated the beneficial effects of novel bacterial conditioned media in HU mice to understand if they can offset the effects of unloading in the HU mouse model.

Serum multi-omics analysis in hindlimb unloading mice model: Insights into systemic molecular changes and potential diagnostic and therapeutic biomarkers.

Microgravity, in space travel and prolonged bed rest conditions, induces cardiovascular deconditioning along with skeletal muscle mass loss and weakness. The findings of microgravity research may also aid in the understanding and treatment of human health conditions on Earth such as muscle atrophy, and cardiovascular diseases. Due to the paucity of biomarkers and the unknown underlying mechanisms of cardiovascular and skeletal muscle deconditioning in these environments, there are insufficient diagnostic and preventative measures.

Space medicine: gut microbiome of hardy species is a potential source to counter disorders during space travel.

It is proposed that gut microbiome of species like cockroaches may offer a potential source of novel mechanisms/molecules that can be translated into humans to safeguard astronauts against stressors of the space environment during deep space exploration missions.

RhoA/ROCK inhibition attenuates endothelin-1-induced glomerulopathy in the rats.

Endothelin-1 (ET-1) contributes to the development of kidney diseases. However, the underlying molecular mechanism is largely undefined. Here we sought to investigate the potential role of ET-1 receptors, ET and ET in the regulation of increased glomerular permeability and underlying signaling pathways post-ET-1 infusion.

Advantages of Understanding the Molecular Mechanisms of Angiogenesis in Various Physiological and Pathological Conditions.

The aim of this Special Issue is to highlight the diverse benefits and approaches to studying angiogenesis in various physiological and pathological conditions, such as damaged tissues, impaired embryonic development, cancer progression, and cardiovascular and chronic inflammatory disorders [...

Circulating microRNAs as potential biomarkers of early vascular damage in vitamin D deficiency, obese, and diabetic patients.

Vitamin D3 deficiency, obesity, and diabetes mellitus (DM) have been shown to increase the risk of cardiovascular diseases (CVDs). However, the early detection of vascular damage in those patients is still difficult to ascertain. MicroRNAs (miRNAs) are recognized to play a critical role in initiation and pathogenesis of vascular dysfunction.

Effect of Microgravity on the Gut Microbiota Bacterial Composition in a Hindlimb Unloading Model.

We utilised a ground-based microgravity hindlimb unloading (HU) mouse model to elucidate the gut microbiota bacterial changes in mice under a simulated microgravity environment. Four-month-old, male C57/Bl6 mice were randomly divided into ground-based controls and the HU groups and kept under controlled environmental conditions. For the microgravity environment, the mice were suspended in special cages individually for 20 days.

Hindlimb unloading induces time-dependent disruption of testicular histology in mice.

Mechanical unloading of the body in the hindlimb unloaded (HU) mice induces pathology in multiple organs, but the effects on testes are poorly characterized. We investigated the histology and Raman spectroscopy of the mouse testes following HU condition. We divided male, c57BL/6j mice into ground-based controls or experimental groups for two and four weeks of HU.

Suppression of endoplasmic reticulum stress prevents disuse muscle atrophy in a mouse model of microgravity.

Background: Hind-limb unloaded (HLU) mouse model exhibits skeletal muscle atrophy and weakness mimicking the conditions such as prolonged spaceflight. However, the molecular mechanisms and interventions of muscle loss during muscle unloading remain elusive. Dysfunction of protein folding by ednoplasmic reticulum (ER), a condition called ER stress, is implicated in diseases of various cell types, but its contribution to skeletal muscle detriment remains elusive.

Mitigating sarcoplasmic reticulum stress limits disuse-induced muscle loss in hindlimb unloaded mice.

Muscle disuse in the hindlimb unloaded (HU) mice causes significant atrophy and weakness. However, the cellular and molecular mechanisms driving disuse-muscle atrophy remain elusive. We investigated the potential contribution of proteins dysregulation by sarcoplasmic reticulum (SR), a condition called SR stress, to muscle loss during HU.

Vitamin D Exerts Significant Antitumor Effects by Suppressing Vasculogenic Mimicry in Breast Cancer Cells.

Background: Numerous clinical and experimental observations have alluded to the substantial anti-neoplastic role of vitamin D in breast cancer (BC), primarily by inducing apoptosis and affecting metastasis. Tumor progression and resistance to chemotherapy have been linked to vasculogenic mimicry (VM), which represents the endothelial-independent formation of microvascular channels by cancer cells. However, the effect of vitamin D on VM formation in BC has not been thoroughly investigated.

Antiamoebic Properties of Laboratory and Clinically Used Drugs against Naegleria fowleri and Balamuthia mandrillaris.

Naegleria fowleri and Balamuthia mandrillaris are pathogenic free-living amoebae that infect the central nervous system with over 95% mortality rates. Although several compounds have shown promise in vitro but associated side effects and/or prolonged approval processes for clinical applications have led to limited success. To overcome this, drug repurposing of marketed compounds with known mechanism of action is considered a viable approach that has potential to expedite discovery and application of anti-amoebic compounds.

N6-Acetyl-L-Lysine and p-Cresol as Key Metabolites in the Pathogenesis of COVID-19 in Obese Patients.

Despite the growing number of the vaccinated population, COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global health burden. Obesity, a metabolic syndrome affecting one-third of the population, has proven to be a major risk factor for COVID-19 severe complications. Several studies have identified metabolic signatures and disrupted metabolic pathways associated with COVID-19, however there are no reports evaluating the role of obesity in the COVID-19 metabolic regulation.

Synergistic Anti-Angiogenic Effect of Combined VEGFR Kinase Inhibitors, Lenvatinib, and Regorafenib: A Therapeutic Potential for Breast Cancer.

Background: Breast cancer currently affects more than two million women worldwide, and its incidence is steadily increasing. One of the most essential factors of invasion and metastasis of breast cancer cells is angiogenesis and non-angiogenic vascularization. Lenvatinib and Regorafenib share the same anti-angiogenic effect by inhibiting vascular endothelial growth factor receptors (VEGFRs subtypes 1 to 3) and have been approved for treating different types of cancer.

Longevity, cellular senescence and the gut microbiome: lessons to be learned from crocodiles.

Crocodiles are flourishing large-bodied ectotherms in a world dominated by endotherms. They survived the Cretaceous extinction event, that eradicated the dinosaurs who are thought to be their ancestral hosts. Crocodiles reside in polluted environments; and often inhabit water which contains heavy metals; frequent exposure to radiation; feed on rotten meat and considered as one of the hardy species that has successfully survived on this planet for millions of years.

Effect of Microgravity Environment on Gut Microbiome and Angiogenesis.

Microgravity environments are known to cause a plethora of stressors to astronauts. Recently, it has become apparent that gut microbiome composition of astronauts is altered following space travel, and this is of significance given the important role of the gut microbiome in human health. Other changes observed in astronauts comprise reduced muscle strength and bone fragility, visual impairment, endothelial dysfunction, metabolic changes, behavior changes due to fatigue or stress and effects on mental well-being.

PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells.

As a therapeutic approach, epigenetic modifiers have the potential to enhance the efficacy of chemotherapeutic agents. Protein arginine methyltransferase 5 (PRMT5), highly expressed in lung adenocarcinoma, was identified to be involved in tumorigenesis. In the current study, we examined the potential antineoplastic activity of PRMT5 inhibitor, arginine methyltransferase inhibitor 1 (AMI-1), and cisplatin on lung adenocarcinoma.

Signature molecular changes in the skeletal muscle of hindlimb unloaded mice.

Hind-limb unloaded (HU) mouse is a well-recognized model of muscle atrophy; however, the molecular changes in the skeletal muscle during unloading are poorly characterized. We have used Raman spectroscopy to evaluate the structure and behavior of signature molecules involved in regulating muscle structural and functional health. The Raman spectroscopic analysis of gastrocnemius muscles was compared between 16-18 weeks old HU c57Bl/6J mice and ground-based controls.

Potential Therapeutic Strategies for Lung and Breast Cancers through Understanding the Anti-Angiogenesis Resistance Mechanisms.

Breast and lung cancers are among the top cancer types in terms of incidence and mortality burden worldwide. One of the challenges in the treatment of breast and lung cancers is their resistance to administered drugs, as observed with angiogenesis inhibitors. Based on clinical and pre-clinical findings, these two types of cancers have gained the ability to resist angiogenesis inhibitors through several mechanisms that rely on cellular and extracellular factors.

Muscle unloading: A comparison between spaceflight and ground-based models.

Prolonged unloading of skeletal muscle, a common outcome of events such as spaceflight, bed rest and hindlimb unloading, can result in extensive metabolic, structural and functional changes in muscle fibres. With advancement in investigations of cellular and molecular mechanisms, understanding of disuse muscle atrophy has significantly increased. However, substantial gaps exist in our understanding of the processes dictating muscle plasticity during unloading, which prevent us from developing effective interventions to combat muscle loss.