Age-associated temporal decline in butyrate-producing bacteria plays a key pathogenic role in the onset and progression of neuropathology and memory deficits in 3×Tg-AD mice.

Alterations in the gut-microbiome-brain axis are increasingly being recognized to be involved in Alzheimer's disease (AD) pathogenesis. However, the functional consequences of enteric dysbiosis linking gut microbiota and brain pathology in AD progression remain largely undetermined. The present work investigated the causal role of age-associated temporal decline in butyrate-producing bacteria and butyrate in the etiopathogenesis of AD.

Nitric oxide promotes cell-matrix adhesion of endothelial progenitor cells under hypoxia condition via ITGA5 CpG promoter demethylation.

Hypoxia or low oxygen tension causes changes in the structure and functional phenotype of the endothelial progenitor cells (EPCs). EPCs are found to be involved in angiogenesis and vascular repair. However, EPC's role in cell-matrix adhesion under hypoxia conditions is not clearly established.

miRNA-15/IL-10Rα axis promotes Kabasura Kudineer (Indian traditional Siddha formulation) induced immunomodulation by suppressing oxidative stress.

Ethnopharmacological Relevance: Kabasura Kudineer (KK), the traditional Indian medicine of Siddha, effectively manages common respiratory symptoms such as flu, cold, and fever. However, there is no evidence of the immunomodulatory capacity of KK in the cultured Jurkat T-lymphocytes under the LPS insult studied.

Aim Of The Study: Assess the effect of the traditional Indian medicine of Siddha, Kabasura Kudineer (KK) on immunomodulation by suppressing oxidative damage in cultured Jurkat T cells in vitro.

Diabetic Covid-19 severity: Impaired glucose tolerance and pathologic bone loss.

Diabetes mellitus (DM), hypertension, and cardiovascular diseases (CVDs) are the leading chronic comorbidities that enhance the severity and mortality of COVID-19 cases. However, SARS-CoV-2 mediated deregulation of diabetes pathophysiology and comorbidity that links the skeletal bone loss remain unclear. We used both streptozocin-induced type 2 diabetes (T2DM) mouse and hACE2 transgenic mouse to enable SARS-CoV-2-receptor binding domain (RBD) mediated abnormal glucose metabolism and bone loss phenotype in mice.

Exercise-Linked Skeletal Irisin Ameliorates Diabetes-Associated Osteoporosis by Inhibiting the Oxidative Damage-Dependent miR-150-FNDC5/Pyroptosis Axis.

Recent evidence suggests that physical exercise (EX) promotes skeletal development. However, the impact of EX on the progression of bone loss and deterioration of mechanical strength in mice with type 2 diabetic mellitus (T2DM) remains unexplored. In the current study, we investigated the effect of EX on bone mass and mechanical quality using a diabetic mouse model.

Mechanisms of autophagy and mitophagy in skeletal development, diseases and therapeutics.

Autophagy is a highly evolutionarily conserved process in the eukaryotic cellular system by which dysfunctional organelles are selectively degraded through a series of processes of lysosomal activity and then returned to the cytoplasm for reuse. All cells require this process to maintain cellular homeostasis and promote cell survival during stress responses such as deprivation and hypoxia. Osteoblasts and osteoclasts are two cellular phenotypes in the bone that mediate bone homeostasis.

Garlic exosome-like nanoparticles reverse high-fat diet induced obesity via the gut/brain axis.

Obesity is becoming a global epidemic and reversing the pathological processes underlying obesity and metabolic co-morbidities is challenging. Obesity induced chronic inflammation including brain inflammation is a hallmark of obesity via the gut-brain axis. The objective of this study was to develop garlic exosome-like nanoparticles (GaELNs) that inhibit systemic as well as brain inflammatory activity and reverse a HFD induced obesity in mice.

Temporal dynamics of nitric oxide wave in early vasculogenesis.

Endothelium-derived nitric oxide (NO) is a mediator of angiogenesis. However, NO-mediated regulation of vasculogenesis remains largely unknown. In the present study, we show that the inhibition of NO significantly attenuated endothelial migration, ring formation, and tube formation.

Probiotics Stimulate Bone Formation in Obese Mice via Histone Methylations.

Manipulation of the gut microbiome can prevent pathologic bone loss. However, the effects of probiotics on mitochondrial epigenetic remodeling and skeletal homeostasis in the high-fat diet (HFD)-linked obesity remains to be explored. Here, we examined the impact of probiotics supplementation on mitochondrial biogenesis and bone homeostasis through the histone methylation mechanism in HFD fed obese mice.

Exosomal lncRNA-H19 promotes osteogenesis and angiogenesis through mediating Angpt1/Tie2-NO signaling in CBS-heterozygous mice.

Emerging evidence indicates that the growth of blood vessels and osteogenesis is tightly coordinated during bone development. However, the molecular regulators of intercellular communication in the bone microenvironment are not well studied. Therefore, we aim to investigate whether BMMSC-Exo promotes osteogenesis and angiogenesis via transporting lnc-H19 in the CBS- heterozygous mouse model.

Hydrogen sulfide prevents ethanol-induced ZO-1 CpG promoter hypermethylation-dependent vascular permeability via miR-218/DNMT3a axis.

Ethanol (ET) causes cerebrovascular dysfunction by altering homocysteine (Hcy) metabolism and by causing oxidative stress. However, there are no strategies to prevent ET-induced epigenetic deregulation of tight junction protein (hyper-methylation) and endothelial cell permeability to date. Hydrogen sulfide (H S) has an antioxidative, antiapoptotic, and anti-inflammatory effect.

Rebuilding Microbiome for Mitigating Traumatic Brain Injury: Importance of Restructuring the Gut-Microbiome-Brain Axis.

Traumatic brain injury (TBI) is a damage to the brain from an external force that results in temporary or permanent impairment in brain functions. Unfortunately, not many treatment options are available to TBI patients. Therefore, knowledge of the complex interplay between gut microbiome (GM) and brain health may shed novel insights as it is a rapidly expanding field of research around the world.

Allyl sulfide promotes osteoblast differentiation and bone density via reducing mitochondrial DNA release mediated Kdm6b/H3K27me3 epigenetic mechanism.

Age-associated bone loss or osteoporosis is a common clinical manifestation during aging (AG). The mechanism underlying age-associated osteoblast dysfunction induced by oxidative damage in the mitochondria and loss of bone density remains elusive. Here, we demonstrated the effect of allyl sulfide (AS), a natural organosulfur compound, on mitochondrial (mt) function in bone marrow-derived mesenchymal stem cells (BMMSCs) and bone density in AG mice.

The role of gut microbiota in bone homeostasis.

The gut microbiota (GM) is referred to as the second gene pool of the human body and a commensal, symbiotic, and pathogenic microorganism living in our intestines. The knowledge of the complex interaction between intestinal microbiota and health outcomes is a novel and rapidly expanding the field. Earlier studies have reported that the microbial communities affect the cellular responses and shape many aspects of physiology and pathophysiology within the body, including muscle and bone metabolism (formation and resorption).

Nitric oxide restores peripheral blood mononuclear cell adhesion against hypoxia via NO-cGMP signalling.

Hypoxia is the most detrimental threat to humans residing at high altitudes, affecting multifaceted cellular responses that are crucial for normal homeostasis. Inhalation of nitric oxide has been successfully implemented to combat the hypoxia effect in the high altitude patients. We hypothesize that nitric oxide (NO) restores the peripheral blood mononuclear cell-matrix deadhesion during hypoxia.

Role of hydrogen sulfide in the musculoskeletal system.

Hydrogen sulfide (HS) has been known as a gasotransmitter, and it contributes to various physiological and pathological processes. Multiple enzymes such as cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-Mercaptopyruvate sulfurtransferase (MST) produce endogenous HS, and these are differentially expressed in the various tissue systems including the skeletal system. However, abnormal HS production is associated with deregulation of the signaling cascade and imbalanced tissue homeostasis.

Hydrogen sulfide attenuates homocysteine-induced osteoblast dysfunction by inhibiting mitochondrial toxicity.

Homocysteine (Hcy) is detrimental to bone health in a mouse model of diet-induced hyperhomocysteinemia (HHcy). However, little is known about Hcy-mediated osteoblast dysfunction via mitochondrial oxidative damage. Hydrogen sulfide (H S) has potent antioxidant, anti-inflammatory, and antiapoptotic effects.

Hyperhomocysteinemia induced endothelial progenitor cells dysfunction through hyper-methylation of CBS promoter.

Bone marrow (BM)-derived endothelial progenitor cells (EPCs) are the key players in angiogenesis and vascular function. Cystathionine-β-synthase (CBS), an HS-generating enzyme in methionine metabolism, regulates the function of these EPCs. This study aims to examine whether CBS hyper-methylation contributes to the bone marrow endothelial progenitor cell (BM-EPCs) function and subsequent bone blood flow in mice fed with a high methionine diet (HMD).

Tetrahydrocurcumin epigenetically mitigates mitochondrial dysfunction in brain vasculature during ischemic stroke.

The objectives of this study are to identify the mechanism of mitochondrial dysfunction during cerebral ischemic/reperfusion (I/R) injury and the therapeutic potential of tetrahydrocurcumin (THC) to mitigate mitochondrial dysfunction in experimental stroke model. In our study, 8-10 weeks old male C57BL/6 wild-type mice were subjected to middle cerebral artery occlusion (MCAO) for 40 min, followed by reperfusion for 72 h. THC (25mg/kg-BW/day) was injected intraperitoneally once daily for 3 days after 4 h of ischemia.

Hydrogen Sulfide Promotes Bone Homeostasis by Balancing Inflammatory Cytokine Signaling in CBS-Deficient Mice through an Epigenetic Mechanism.

Previously, we have shown hyperhomocysteinemia (HHcy) to have a detrimental effect on bone remodeling, which is associated with osteoporosis. During transsulfuration, Hcy is metabolized into hydrogen sulfide (HS), a gasotransmitter molecule known to regulate bone formation. Therefore, in the present study, we examined whether HS ameliorates HHcy induced epigenetic and molecular alterations leading to osteoporotic bone loss.

Hydrogen sulfide improves postischemic neoangiogenesis in the hind limb of cystathionine-β-synthase mutant mice via PPAR-γ/VEGF axis.

Neoangiogenesis is a fundamental process which helps to meet energy requirements, tissue growth, and wound healing. Although previous studies showed that Peroxisome proliferator-activated receptor (PPAR-γ) regulates neoangiogenesis via upregulation of vascular endothelial growth factor (VEGF), and both VEGF and PPAR-γ expressions were inhibited during hyperhomocysteinemic (HHcy), whether these two processes could trigger pathological effects in skeletal muscle via compromising neoangiogenesis has not been studied yet. Unfortunately, there are no treatment options available to date for ameliorating HHcy-mediated neoangiogenic defects.

Hydrogen sulfide alleviates hyperhomocysteinemia-mediated skeletal muscle atrophy via mitigation of oxidative and endoplasmic reticulum stress injury.

Although hyperhomocysteinemia (HHcy) occurs because of the deficiency in cystathionine-β-synthase (CBS) causing skeletal muscle dysfunction, it is still unclear whether this effect is mediated through oxidative stress, endoplasmic reticulum (ER) stress, or both. Nevertheless, there is no treatment option available to improve HHcy-mediated muscle injury. Hydrogen sulfide (HS) is an antioxidant compound, and patients with CBS mutation do not produce HS.

Exosomes: mediators of bone diseases, protection, and therapeutics potential.

Bone remodeling is a continuous lifelong process in the repair of micro-damage to bone architecture and replacement of aging tissue in bone. A failure to such process leads to pathological destructive bone diseases such as osteoporosis, rheumatoid arthritis, and osteoarthritis. However, this active process is regulated by; osteoclasts, which are involved in the bone resorption process; osteoblasts, with involvement in the bone formation process and bone-derived endothelial cells, which promote angiogenesis.

Hydrogen sulfide epigenetically mitigates bone loss through OPG/RANKL regulation during hyperhomocysteinemia in mice.

Hydrogen sulfide (HS) is a novel gasotransmitter produced endogenously in mammalian cells, which works by mediating diverse physiological functions. An imbalance in HS metabolism is associated with defective bone homeostasis. However, it is unknown whether HS plays any epigenetic role in bone loss induced by hyperhomocysteinemia (HHcy).

Exercise Mitigates Alcohol Induced Endoplasmic Reticulum Stress Mediated Cognitive Impairment through ATF6-Herp Signaling.

Chronic ethanol/alcohol (AL) dosing causes an elevation in homocysteine (Hcy) levels, which leads to the condition known as Hyperhomocysteinemia (HHcy). HHcy enhances oxidative stress and blood-brain-barrier (BBB) disruption through modulation of endoplasmic reticulum (ER) stress; in part by epigenetic alternation, leading to cognitive impairment. Clinicians have recommended exercise as a therapy; however, its protective effect on cognitive functions has not been fully explored.