Pharmacological impacts of tanshinone on osteogenesis and osteoclastogenesis: a review.

Tanshinone, a lipophilic component of Salvia miltiorrhiza, is used to treat diseases like atherosclerosis, hypertension, Alzheimer's disease, and diabetes mellitus through its pharmacological activities like anti-inflammatory, anti-oxidant, and anti-tumor. Excessive inflammation is the primary cause of bone diseases such as osteoporosis and rheumatoid arthritis, affecting more than millions of people across the globe. Recently, tanshinone has shown potential benefits against bone diseases by modulating signaling pathways accountable for the proliferation and differentiation of bone cells.

Development of ELISA-Based Assay for Detection of SARS-CoV-2 Neutralizing Antibody.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the plasma B cells to secrete specific antibodies against the viral antigen. However, not all antibodies can prevent the virus from entering the cells. The subpopulation of antibodies which blocks the entry of the virus into host cells is termed neutralizing antibodies (NAbs).

Effect of hypobaric hypoxia on the fiber type transition of skeletal muscle: a synergistic therapy of exercise preconditioning with a nanocurcumin formulation.

Hypobaric hypoxia (HH) leads to various adverse effects on skeletal muscles, including atrophy and reduced oxidative work capacity. However, the effects of HH on muscle fatigue resistance and myofiber remodeling are largely unexplored. Therefore, the present study aimed to explore the impact of HH on slow-oxidative fibers and to evaluate the ameliorative potential of exercise preconditioning and nanocurcumin formulation on muscle anti-fatigue ability.

Mitochondrial Ca overload due to altered proteostasis amplifies apoptosis in C2C12 myoblasts under hypoxia: Protective role of nanocurcumin formulation.

Severe hypoxia triggers apoptosis leads to myofibers loss and is attributable to impaired intracellular calcium (iCa ) homeostasis, resulting in reduced muscle activity. Hypoxia increases intracellular Ca by activating the release of Ca from iCa stores, however, the effect of increased [iCa ] on the mitochondria of muscle cells at high-altitude hypoxia is largely unexplored. This study examined mitochondrial Ca overload due to altered expression of mitochondrial calcium uptake 1 (MICU1), that is, a gatekeeper of the mitochondrial Ca uniporter, impaired mitochondrial membrane potential (ΔΨm).

A Nanocurcumin and Pyrroloquinoline Quinone Formulation Prevents Hypobaric Hypoxia-Induced Skeletal Muscle Atrophy by Modulating NF-κB Signaling Pathway.

Kushwaha, Asha D., and Deepika Saraswat. A nanocurcumin and pyrroloquinoline quinone formulation prevents hypobaric hypoxia-induced skeletal muscle atrophy by modulating NF-κB signaling pathway.

Dysfunctional State of T Cells or Exhaustion During Chronic Viral Infections and COVID-19: A Review.

Coronavirus disease 2019 (COVID-19) continuously affecting the lives of millions of people. The virus is spread through the respiratory route to an uninfected person, causing mild-to-moderate respiratory disease-like symptoms that sometimes progress to severe form and can be fatal. When the host is infected with the virus, both innate and adaptive immunity comes into play.

Nanocurcumin formulation: a possible therapeutic agent for post COVID inflammatory syndrome.

Over the last twenty months, the attention of the world has been focusing on managing the unprecedented and devastating wave of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) and mitigating its impacts. Recent findings indicated that high levels of pro-inflammatory cytokines are leading cause of poor prognosis in severely ill COVID-19 patients. Presently, the multiple variants and highly contagious nature of virus makes challenge humongous.

The MAPK-activator protein-1 signaling regulates changes in lung tissue of rat exposed to hypobaric hypoxia.

This study reports the role of MAPKs (JNK, ERK, and p38), and activator protein-1 (AP-1) transcription factor in the hypobaric hypoxia induced change in lung tissue. Healthy male Sprague-Dawley rats were exposed to hypobaric hypoxia for 6, 12, 24, 48, 72, and 120 hr. Hypoxia resulted in significant increase in reactive oxygen species (ROS), vascular endothelial growth factor (VEGF) and decreased nitric oxide (NO), these act as signaling molecules for activation of MAPK and also contribute in development of vascular leakage (an indicator of pulmonary edema) as confirmed by histological studies.

Nanocurcumin-pyrroloquinoline formulation prevents hypertrophy-induced pathological damage by relieving mitochondrial stress in cardiomyocytes under hypoxic conditions.

This study investigates the therapeutic effect of a nanocurcumin formulation (NCF) containing nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) on ameliorating hypoxia-induced stress in hypertrophied primary human ventricular cardiomyocytes (HVCM) under hypoxic conditions, as validated in a Sprague-Dawley rat model of chronic hypobaric hypoxia (cHH)-induced right ventricular hypertrophy (RVH). Based on our previous findings, here, we analyzed the improvement in the protective efficacy of NCF against mitochondrial damage. The electron transport chain Complexes' activities were analyzed as a chief operational center for mitochondrial homeostasis, along with key gene and protein markers for mitochondrial biogenesis, redox function, fatty acid oxidation, bio-energetic deficit and cell survival.

Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), as a Cardioprotectant in an Oxygen-Deficient Environment.

Imbalanced oxygen availability is detrimental to normal cell function. Oxygen-sensitive cells such as cardiomyoblasts experience severe irreversible pathophysiological damage under conditions of reduced oxygen availability, such as hypoxia. A number of natural therapeutic agents have been explored for their potential cytoprotective effects, of which medicinal mushrooms are an important source.

Combinatorial therapy of exercise-preconditioning and nanocurcumin formulation supplementation improves cardiac adaptation under hypobaric hypoxia.

Background: Chronic hypobaric hypoxia (cHH) mediated cardiac insufficiencies are associated with pathological damage. Sustained redox stress and work load are major causative agents of cardiac insufficiencies under cHH. Despite the advancements made in pharmacological (anti-oxidants, vasodilators) and non-pharmacological therapeutics (acclimatization strategies and schedules), only partial success has been achieved in improving cardiac acclimatization to cHH.

Preconditioning with ethyl 3,4-dihydroxybenzoate augments aerobic respiration in rat skeletal muscle.

Muscle respiratory capacity decides the amount of exertion one's skeletal muscle can undergo, and endurance exercise is believed to increase it. There are also certain preconditioning methods by which muscle respiratory and exercise performance can be enhanced. In this study, preconditioning with ethyl 3,4-dihydroxybenzoate (EDHB), a prolyl hydroxylase domain enzyme inhibitor, has been investigated to determine its effect on aerobic metabolism and bioenergetics in skeletal muscle, thus facilitating boost in physical performance in a rat model.

Chronic Hypobaric Hypoxia Induces Right Ventricular Hypertrophy and Apoptosis in Rats: Therapeutic Potential of Nanocurcumin in Improving Adaptation.

Nehra, Sarita, Varun Bhardwaj, Santosh Kar, and Deepika Saraswat. Chronic hypobaric hypoxia induces right ventricular hypertrophy and apoptosis in rats: therapeutic potential of nanocurcumin in improving adaptation. High Alt Med Biol.

Nanocurcumin accords protection against acute hypobaric hypoxia induced lung injury in rats.

Decline in oxygen availability experienced under hypobaric hypoxia (HH) mediates imbalance in lung fluid clearance and is a causative agent of acute lung injury. Here, we investigate the pathological events behind acute HH mediated lung injury and assess the therapeutic efficacy of nanocurcumin in its amelioration. We assess the protective efficacy of nanotized curcumin (nanocurcumin) in ameliorating HH induced lung injury and compare to curcumin.

Nanocurcumin Prevents Hypoxia Induced Stress in Primary Human Ventricular Cardiomyocytes by Maintaining Mitochondrial Homeostasis.

Hypoxia induced oxidative stress incurs pathophysiological changes in hypertrophied cardiomyocytes by promoting translocation of p53 to mitochondria. Here, we investigate the cardio-protective efficacy of nanocurcumin in protecting primary human ventricular cardiomyocytes (HVCM) from hypoxia induced damages. Hypoxia induced hypertrophy was confirmed by FITC-phenylalanine uptake assay, atrial natriuretic factor (ANF) levels and cell size measurements.

Nanocurcumin protects cardiomyoblasts H9c2 from hypoxia-induced hypertrophy and apoptosis by improving oxidative balance.

Hypoxia-induced cardiomyocyte hypertrophy is evident; however, the distinct molecular mechanism underlying the oxidative stress-mediated damages to cardiomyocytes remains unknown. Curcumin (diferuloylmethane) is known for anti-hypertrophic effects, but low bioavailability makes it unsuitable to exploit its pharmacological properties. We assessed the efficacy of nanotized curcumin, i.

Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia-induced vascular leakage and oedema in rat brain.

Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia-induced cerebral oedema. In silico identification of novel candidate molecules that block VEGF-A site were identified and validated with a Ramachandran plot.

In-silico screening and in-vitro validation of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) inhibitors.

VEGFR-2 tyrosine kinase receptor draws attention of the scientific fraternity in drug discovery for its important role in cancer, cardiopulmonary, cardiovascular diseases etc. Hence there is a need for novel VEGFR-2 inhibitors screening and testing for their biological activities. The 3D-structure was collected from PDB and stability was checked by using WHATIF and PROCHECK programs and subjected for virtual screening on Zinc database.

Amlodipine protects rat ventricular cardiomyoblast H9c2 From hypoxia-induced apoptosis and restores oxidative balance by Akt-1-dependent manner.

Background: Hypoxia-induced rise in intracellular calcium concentration is a causative agent of apoptosis and oxidative damage in cardiomyocytes. We examined the efficacy of calcium channel blocker amlodipine in preventing hypoxia-induced apoptosis in H9c2 cells and restoring oxidative balance.

Methods: H9c2 cells were exposed to hypoxia (0.

Exogenous sphingosine-1-phosphate boosts acclimatization in rats exposed to acute hypobaric hypoxia: assessment of haematological and metabolic effects.

Background: The physiological challenges posed by hypobaric hypoxia warrant exploration of pharmacological entities to improve acclimatization to hypoxia. The present study investigates the preclinical efficacy of sphingosine-1-phosphate (S1P) to improve acclimatization to simulated hypobaric hypoxia.

Experimental Approach: Efficacy of intravenously administered S1P in improving haematological and metabolic acclimatization was evaluated in rats exposed to simulated acute hypobaric hypoxia (7620 m for 6 hours) following S1P pre-treatment for three days.

Exogenous sphingosine 1-phosphate protects murine splenocytes against hypoxia-induced injury.

Sphingosine-1-phosphate (S1P), a biologically active pleiotropic lipid, is involved in several physiological processes especially in the area of vascular biology and immunology encompassing cell survival, angiogenesis, vascular tone, immune response etc. by interacting with specific cell surface receptors. Hypoxia, a condition common to innumerable pathologies, is known to lethally affect cell survival by throwing off balance global gene expression, redox homeostasis, bioenergetics etc.

Co-expression of S. Typhi GroEL and IL-22 gene augments immune responses against Salmonella infection.

Recombinant DNA vaccines represent a novel method for generating in situ expression of vaccine antigens. Intramuscular injections of naked DNA are able to elicit potent humoral and cellular immune responses but still numerous factors limit the immunogenicity of DNA vaccines. Co-expression of cytokines with antigen encoding genes in DNA vectors can improve the immune responses and modify Th1/Th2 balance.

Synthesis and antimalarial evaluation of 1, 3, 5-trisubstituted pyrazolines.

A series of 1,3,5-trisubstituted pyrazolines were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive (MRC-02) as well as chloroquine resistant (RKL9) strains of Plasmodium falciparum. The activity was at nano molar concentration. beta-hematin formation inhibition activity (BHIA(50)) of the pyrazolines were determined and correlated with antimalarial activity.

Pharmacophore based discovery of potential antimalarial agent targeting haem detoxification pathway.

Pharmacophore hypotheses were generated from molecules having putative antimalarial activities targeting haem detoxification pathway of malarial parasite. A training set consisting of 33 compounds, whose activities were evaluated for haem polymerization inhibition and against chloroquine resistant (K1) strain of Plasmodium falciparum, was optimized to generate hypotheses. The hypothesis showing optimum correlation between actual and estimated activities was validated by Fischer's randomization test at 95% confidence level and used as a model to screen our in-house compound database.