Molecular mimicry and COVID-19: Potential implications for global fertility.

There has been a concerning increase in the incidence of autoimmune diseases following SARS-CoV-2 infection, with molecular mimicry proposed as a potential mechanism. Our study identified nine fertility-associated proteins (AMH, BMP2, CUBN, DNER, ERCC1, KASH5, MSLN, TPO, and ZP3) that exhibit potential molecular mimicry with MHC-II epitopes of SARS-CoV-2 proteins (N, ORF1A, ORF1AB, and S). We screened for epitopes based on in silico binding using DR-, DQ-, and DP-haplotypes that predispose susceptible individuals to autoimmune diseases.

Ecological and health risks from heavy metal sources surrounding an abandoned mercury mine in the island paradise of Palawan, Philippines.

A recent survey that determined heavy metal concentrations in an abandoned Hg mine in Palawan, Philippines, found the occurrence of Hg with As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sb, Tl, V, and Zn. While the Hg originated from the mine waste calcines, the critical knowledge about the origin of the other heavy metals remains unknown. This study assessed the ecological and health risks from heavy metal pollution surrounding the abandoned Hg mine.

Transport of toxic metals in the bottom sediments and health risk assessment of Corbicula fluminea (Asiatic clam) collected from Laguna de Bay, Philippines.

Laguna de Bay, the 3rd largest lake in Southeast Asia, is the most significant source of freshwater fish in the Philippines. With decades of unregulated discharge of industrial, domestic, and agricultural wastewaters into the lake, this study investigates the apportionment of heavy metals from the bottom sediments and its impact on the toxicity of Corbicula fluminea (Asiatic clam), a popular food item in the markets. The sediment samples from the western part of the lake contained higher Cd, Cu, Pb, and Zn and lower As and Cr concentrations compared to the eastern part.

Analysis of the copper removal kinetics of the Philippine giant bamboo () in hydroponics.

Copper is the third most utilized metal and is a versatile resource with multiple beneficial uses, but it may also become toxic to aquatic life in excess amount. Thus, there is a need to develop methods to reduce the copper contamination in the environment, particularly in bodies of water. Phytoremediation using may offer an environment-benign and potentially effective method for copper removal though its effectiveness may take several years to materialize for this technology to become cost-effective.

AtHDA15 binds directly to COP1 positively regulating photomorphogenesis.

Reversible histone acetylation and deacetylation play crucial roles in modulating light-regulated gene expression during seedling development. However, it remains largely unknown how histone-modifying enzymes interpose within the molecular framework of light signaling network. In this study, we show that AtHDA15 positively regulates photomorphogenesis by directly binding to COP1, a master regulator in the repression of photomorphogenesis.

Druggability of mortalin for cancer and neuro-degenerative disorders.

Mortalin is a member of Hsp70 family of stress chaperones. It was first identified as a protein involved in the senescence of mouse cells. Genetic studies revealed that there are two mouse mortalin alleles coding for two proteins (mot-1 and mot-2) that differ in only two amino acids in the carboxy-terminus, but have contrasting activities.

Mouse Homologue of the Schizophrenia Susceptibility Gene ZNF804A as a Target of Hoxc8.

Using a ChIP-cloning technique, we identified a Zinc finger protein 804a (Zfp804a) as one of the putative Hoxc8 downstream target genes. We confirmed binding of Hoxc8 to an intronic region of Zfp804a by ChIP-PCR in F9 cells as well as in mouse embryos. Hoxc8 upregulated Zfp804a mRNA levels and augmented minimal promoter activity in vitro.

Hoxc8 represses BMP-induced expression of Smad6.

Proper regulation of bone morphogenetic protein (BMP) signaling is critical for correct patterning and morphogenesis of various tissues and organs. A well known feedback mechanism is a BMP-mediated induction of Smad6, an inhibitor of BMP signaling. Hoxc8, one of the Hox family transcription factors, has also been shown to negatively regulate BMP-mediated gene expression.

The versatile stress protein mortalin as a chaperone therapeutic agent.

Age- and stress-induced modulations in chaperone systems result in "chaperono-deficiency" or "chaperon-opulence". Development of modulators, of chaperone function has therefore, become an emerging field in drug development and discovery. This mini-review summarizes (i) the events leading to identification of an Hsp70 family stress chaperone, mortalin, (ii) experimental evidence to its role in old age diseases and cancer, and (iii) proposes it as a chaperono-therapeutic agent.

From proliferative to neurological role of an hsp70 stress chaperone, mortalin.

Although the brain makes up approximately 2% of a person's body weight, it consumes more than 15% of total cardiac output and has a per capita caloric requirement of 10 times more than the rest of the body. Such continuous metabolic demand that supports the generation of action potentials in neuronal cells relies on the mitochondria, the main organelle for power generation. The phenomenon of mitochondrial biogenesis, although has long been a neglected theme in neurobiology, can be regarded as critical to brain physiology.

Enhancing effect of cerebral blood volume by mild exercise in healthy young men: a near-infrared spectroscopy study.

A mechanism by which exercise improves brain function may be attributed to increase in cerebral blood volume (CBV) with physical activity. However, the exact exercise intensity that influences CBV is still uncertain. To clarify this issue, 10 healthy young male participants were asked to perform a graded cycling exercise to the point of exhaustion while their prefrontal cortex CBVs are being monitored using near-infrared spectroscopy.

Merger of ayurveda and tissue culture-based functional genomics: inspirations from systems biology.

Ayurveda is one of the ancient systems of health care of Indian origin. Roughly translated into "Knowledge of life", it is based on the use of natural herbs and herb products for therapeutic measures to boost physical, mental, social and spiritual harmony and improve quality of life. Although sheltered with long history and high trust, ayurveda principles have not entered laboratories and only a handful of studies have identified pure components and molecular pathways for its life-enhancing effects.

Glycerol stimulates innate chaperoning, proteasomal and stress-resistance functions: implications for geronto-manipulation.

Aging is associated with accumulation of toxic intracellular and extracellular protein aggregates. Cells manage "aged" proteins by mobilizing their molecular chaperones or heat shock proteins that are also considered as determinants of lifespan in diverse species. In this study, we tested whether an exogenous addition of the non-toxic chemical chaperone 'glycerol' could elicit stress and geronto-protective activities.

Functional significance of minor structural and expression changes in stress chaperone mortalin.

Mortalin is one of the highly conserved heat-shock chaperones. Some of the established features of mortalin include its various subcellular localizations, multiple binding partners, and differential subcellular distribution in normal and immortal cells. It inhibits nuclear translocation, transcriptional activation, and control of centrosome-duplication functions of p53.

Use of ribozymes in cellular aging research.

Ribozymes are naturally-occurring catalytic RNAs from the viroid world and are being engineered in the laboratory to perform sequence-specific cleavage of a desired mRNA target. Since their Nobel Prize-winning discovery, there has been considerable interest in the utility of ribozymes as gene therapeutic agents to silence disease-causing genes. This technology is not perfect, but extensive efforts to improve upon natural design of ribozymes have enabled these RNA molecules to perform various tasks.

BDNF induction with mild exercise in the rat hippocampus.

Although chronic voluntary physical activity has been shown to enhance hippocampal brain-derived neurotrophic factor (BDNF) expression in animals, the effects of forced exercise on a treadmill have not been fully investigated. We assessed induction of c-fos and BDNF expression with acute exercise at different running intensities. The mRNA for c-fos, a marker for neuronal activation, was up-regulated even under low-intensity running (15 m/min), although its induction appeared to be intensity dependent.

Stress chaperones, mortalin, and pex19p mediate 5-aza-2' deoxycytidine-induced senescence of cancer cells by DNA methylation-independent pathway.

DNA demethylating agents are used to reverse epigenetic silencing of tumor suppressors in cancer therapeutics. Understanding of the molecular and cellular factors involved in DNA demethylation-induced gene desilencing and senescence is still limited. We have tested the involvement of two stress chaperones, Pex19p and mortalin, in 5-Aza-2' deoxycytidine (5AZA-dC; DNA demethylating agent)-induced senescence.

Mortalin sensitizes human cancer cells to MKT-077-induced senescence.

Mortalin is a chaperone protein that functions in many cellular processes such as mitochondrial biogenesis, intracellular trafficking, cell proliferation and signaling. Its upregulation in many human cancers makes it a candidate target for therapeutic intervention by small molecule drugs. In continuation to our earlier studies showing mortalin as a cellular target of MKT-077, a mitochondrion-seeking delocalized cationic dye that causes selective death of cancer cells, in this work, we report that MKT-077 binds to the nucleotide-binding domain of mortalin, causes tertiary structural changes in the protein, inactivates its chaperone function, and induces senescence in human tumor cell lines.

Three faces of mortalin: a housekeeper, guardian and killer.

Mortalin was first cloned as a mortality factor that existed in the cytoplasmic fractions of normal, but not in immortal, mouse fibroblasts. A decade of efforts have expanded its persona from a house keeper protein involved in mitochondrial import, energy generation and chaperoning of misfolded proteins, to a guardian of stress that has multiple binding partners and to a killer protein that contributes to carcinogenesis on one hand and to old age disorders on the other. Being proved to be an attractive target for cancer therapy, it also warrants attention from the perspectives of management of old age diseases and healthy aging.

Inhibitory effects of an orexin-2 receptor antagonist on orexin A- and stress-induced ACTH responses in conscious rats.

Orexins, recognized for their diverse functions in sleep/wakefulness/arousal and appetite regulation, may play provocative roles in stress response. Although the PVN of the hypothalamus expresses an abundance of orexin-2 receptor (OX-2R), the involvement of OX-2R in regulating ACTH response to stress remains unclear. To address this, we examined effects of a selective antagonist to OX-2R (N-{(1S)-1-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]carbonyl}-2,2-dimethylpropyl)-N-{4-pyridinylmethyl}amine upon plasma ACTH concentrations after administration of orexin A and swimming stress.

On the brotherhood of the mitochondrial chaperones mortalin and heat shock protein 60.

The heat shock chaperones mortalin/mitochondrial heat shock protein 70 (mtHsp70) and Hsp60 are found in multiple subcellular sites and function in the folding and intracellular trafficking of many proteins. The chaperoning activity of these 2 proteins involves different structural and functional mechanisms. In spite of providing an excellent model for an evolutionarily conserved molecular "brotherhood", their individual functions, although overlapping, are nonredundant.

Geroprotection by glycerol: insights to its mechanisms and clinical potentials.

Chaperones, particularly the heat-shock proteins, are considered as key players in the maintenance of protein homeostasis and are associated with longevity and cellular immortalization. In this study, we investigated the geroprotective activity of the chemical chaperone glycerol. Glycerol showed significant chaperoning activity in refolding heat-denatured luciferase in vivo and in protecting cells from heat stress-induced cytotoxicity.

Preincubation with the proteasome inhibitor MG-132 enhances proteasome activity via the Nrf2 transcription factor in aging human skin fibroblasts.

Strategies that lead to the upregulation of the proteasome are known to elicit beneficial consequences to the organism by countering oxidative stress-associated disorders, such as protein conformational diseases, cancer, and aging. Mild treatment with proteasome inhibitors has been previously demonstrated to stimulate proteasome activity and cellular resistance against oxidative injury. However, the mechanism for this action has not been clearly defined.