Protein O-GlcNAcylation and hexokinase mitochondrial dissociation drive heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a common cause of morbidity and mortality worldwide, but its pathophysiology remains unclear. Here, we report a mouse model of HFpEF and show that hexokinase (HK)-1 mitochondrial binding in endothelial cells (ECs) is critical for protein O-GlcNAcylation and the development of HFpEF. We demonstrate increased mitochondrial dislocation of HK1 within ECs in HFpEF mice.

Mitochondria regulate proliferation in adult cardiac myocytes.

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfs1 (mitochondrial Rieske iron-sulfur protein, RISP) in hearts of adult mice.

Iron drives anabolic metabolism through active histone demethylation and mTORC1.

All eukaryotic cells require a minimal iron threshold to sustain anabolic metabolism. However, the mechanisms by which cells sense iron to regulate anabolic processes are unclear. Here we report a previously undescribed eukaryotic pathway for iron sensing in which molecular iron is required to sustain active histone demethylation and maintain the expression of critical components of the pro-anabolic mTORC1 pathway.

SIRT2 inhibition protects against cardiac hypertrophy and ischemic injury.

Sirtuins (SIRT) exhibit deacetylation or ADP-ribosyltransferase activity and regulate a wide range of cellular processes in the nucleus, mitochondria, and cytoplasm. The role of the only sirtuin that resides in the cytoplasm, SIRT2, in the development of ischemic injury and cardiac hypertrophy is not known. In this paper, we show that the hearts of mice with deletion of () display improved cardiac function after ischemia-reperfusion (I/R) and pressure overload (PO), suggesting that SIRT2 exerts maladaptive effects in the heart in response to stress.

DNA Damage and Nuclear Morphological Changes in Cardiac Hypertrophy Are Mediated by SNRK Through Actin Depolymerization.

Background: Proper nuclear organization is critical for cardiomyocyte function, because global structural remodeling of nuclear morphology and chromatin structure underpins the development and progression of cardiovascular disease. Previous reports have implicated a role for DNA damage in cardiac hypertrophy; however, the mechanism for this process is not well delineated. AMPK (AMP-activated protein kinase) family of proteins regulates metabolism and DNA damage response (DDR).

DNA damage and nuclear morphological changes in cardiac hypertrophy are mediated by SNRK through actin depolymerization.

Background: Proper nuclear organization is critical for cardiomyocyte (CM) function, as global structural remodeling of nuclear morphology and chromatin structure underpins the development and progression of cardiovascular disease. Previous reports have implicated a role for DNA damage in cardiac hypertrophy, however, the mechanism for this process is not well delineated. AMPK family of proteins regulate metabolism and DNA damage response (DDR).

Review of electrochemical and optical biosensors for testosterone measurement.

Testosterone is an anabolic steroid and a major sex hormone in males. It plays vital roles, including developing the testis, penis, and prostate, increasing muscle and bone, and sperm production. In both men and women, testosterone levels should be in normal ranges.

Enhancing autophagy in Alzheimer's disease through drug repositioning.

Alzheimer's disease (AD) is one of the biggest human health threats due to increases in aging of the global population. Unfortunately, drugs for treating AD have been largely ineffective. Interestingly, downregulation of macroautophagy (autophagy) plays an essential role in AD pathogenesis.

Mammalian target of rapamycin (mTOR) signaling pathway and traumatic brain injury: A novel insight into targeted therapy.

Traumatic brain injury (TBI) is one of the most concerning health issues in which the normal brain function may be disrupted as a result of a blow, bump, or jolt to the head. Loss of consciousness, amnesia, focal neurological defects, alteration in mental state, and destructive diseases of the nervous system such as cognitive impairment, Parkinson's, and Alzheimer's disease. Parkinson's disease is a chronic progressive neurodegenerative disorder, characterized by the early loss of striatal dopaminergic neurons.

Potential inhibitors of the main protease of SARS-CoV-2 and modulators of arachidonic acid pathway: Non-steroidal anti-inflammatory drugs against COVID-19.

The main protease of SARS-CoV-2 is one of the key targets to develop and design antiviral drugs. There is no general agreement on the use of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19. In this study, we investigated NSAIDs as potential inhibitors for chymotrypsin-like protease (3CLpro) and the main protease of the SARS-CoV-2 to find out the best candidates, which can act as potent inhibitors against the main protease.

Alzheimer's Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia.

Alzheimer's disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including amyloid plaques (Aβ) and tau tangles (tau), are the most studied features of AD.

Plant-derived chemicals as potential inhibitors of SARS-CoV-2 main protease (6LU7), a virtual screening study.

SARS-CoV-2 has caused millions of infections and more than 700,000 deaths. Taking the urgent need to find new therapeutics for coronavirus disease 2019 (COVID-19), a dataset of plant-based natural compounds was selected for the screening of antiviral activity. The viral 3-chymotrypsin-like cysteine protease (Mpro, 3CLpro) was selected as the target.

The effect of kaempferol and apigenin on allogenic synovial membrane-derived stem cells therapy in knee osteoarthritic male rats.

Background: Based on the anti-inflammatory and anti-oxidant properties of kaempferol and apigenin, we hypothesized that co-injection of these phytochemicals would increase the effectiveness of cell therapy in knee osteoarthritic rats.

Methods: Anterior cruciate ligament transection (ACLT) was used to induce osteoarthritis (OA). Animals were treated by weekly intra-articular injections of kaempferol (10 or 20 μM) and/or isolated MSCs from synovial membrane (SMMSCs) (3 × 106 cells), a mixture of apigenin (0.

The role of radiation induced oxidative stress as a regulator of radio-adaptive responses.

Various sources of radiation including radiofrequency, electromagnetic radiation (EMR), low- dose X-radiation, low-level microwave radiation and ionizing radiation (IR) are indispensable parts of modern life. In the current review, we discussed the adaptive responses of biological systems to radiation with a focus on the impacts of radiation-induced oxidative stress (RIOS) and its molecular downstream signaling pathways. A comprehensive search was conducted in Web of Sciences, PubMed, Scopus, Google Scholar, Embase, and Cochrane Library.

Apoptotic Effect of Melittin Purified from Iranian Honey Bee Venom on Human Cervical Cancer HeLa Cell Line.

Melittin, an amphipathic 26-residue peptide, is the main component of honey bee venom. Studies have been demonstrated that melittin has an inhibitory effect on proliferation of cancer cells. However, the precise mechanism of action is not completely understood.

First report on the isolation of melittin from Iranian honey bee venom and evaluation of its toxicity on gastric cancer AGS cells.

Background: It has been previously reported that melittin, the main ingredient of honey bee venom, has anticancer properties. However, there appears to be no earlier study focusing on the isolation of melittin from Iranian honey bee venom (Apis mellifera meda), and evaluation of its effect on cancerous cells.

Methods: We isolated melittin using reversed-phase high performance liquid chromatography, and its potential toxicity on gastric cancer AGS cells was determined with an MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay.

A camelid antibody candidate for development of a therapeutic agent against Hemiscorpius lepturus envenomation.

Hemiscorpius lepturus scorpionism poses one of the most dangerous health problems in many parts of the world. The common therapy consists of using antivenom antibody fragments derived from a polyclonal immune response raised in horses. However, this immunotherapy creates serious side effects, including anaphylactic shock sometimes even leading to death.