A5002198660- Dermatology and Skin Diseases
- Neurotransmitter Receptor Influence on Behavior
- Estrogen and related hormone effects
- Heat shock proteins research
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- T-cell and B-cell Immunology
- Migraine and Headache Studies
- Hormonal Regulation and Hypertension
- Skin Protection and Aging
- Nitric Oxide and Endothelin Effects
- Renal cell carcinoma treatment
- Legume Nitrogen Fixing Symbiosis
- Prostate Cancer Treatment and Research
- Protein Degradation and Inhibitors
- Urticaria and Related Conditions
- Toxic Organic Pollutants Impact
- Trigeminal Neuralgia and Treatments
- Endoplasmic Reticulum Stress and Disease
- Chromatin Remodeling and Cancer
- Mast cells and histamine
- Ubiquitin and proteasome pathways
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Amino Acid Enzymes and Metabolism
- melanin and skin pigmentation
Northwestern University
2012-2023
Lilavati Hospital & Research Centre
2012
Midwestern University
2012
Erasmus University Rotterdam
2000-2002
Indian Institute of Toxicology Research
1998
University of Lucknow
1995
Abstract Cutaneous atrophy is the major adverse effect of topical glucocorticoids; however, its molecular mechanisms are poorly understood. Here, we identify stress‐inducible mTOR inhibitor REDD1 (regulated in development and DNA damage response 1) as a target glucocorticoids, which mediates cutaneous atrophy. In knockout (KO) mice, all skin compartments (epidermis, dermis, subcutaneous fat), epidermal stem, progenitor cells were protected from atrophic effects glucocorticoids. Moreover,...
Androgen (AR) and glucocorticoid (GR) receptor signaling play opposing roles in prostate tumorigenesis: prostate, AR acts as an oncogene, GR is a tumor suppressor. Recently, we found that non-steroidal phyto-chemical Compound A (CpdA) AR/GR modulator acting anti-inflammatory anti-androgen. CpdA inhibits prevents transactivation while enhancing transrepression. are controlled by proteasomal degradation. We prolonged exposure of LNCaP, LNCaP-GR, DU145 PC3 carcinoma (PCa) cells to proteasome...
Aberrant activity of the H3K27 modifiers EZH2 and BRD4 is an important oncogenic driver for atypical teratoid/rhabdoid tumor (AT/RT), each potentially a possible therapeutic target treating AT/RT. We, therefore, determined whether targeting distinct histone modifier activities was effective approach The effects inhibition on modification, cell proliferation, invasion were analyzed by immunoblotting, MTS assay, colony formation assay. RNA- chromatin immunoprecipitation-sequencing used to...
Glucocorticoids have excellent therapeutic properties; however, they cause significant adverse atrophogenic effects. The mTORC1 inhibitor REDD1 has been recently identified as a key mediator of glucocorticoid-induced atrophy. We performed computational screening connectivity map database to identify putative inhibitors. top selected candidates included rapamycin, which was unexpected because it inhibits pro-proliferative mTOR signaling. Indeed, rapamycin inhibited induction by...
// Gleb Baida 1 , Pankaj Bhalla Alexander Yemelyanov 2 Lance A. Stechschulte 3 Weinian Shou 4 Ben Readhead 5, 6 Joel T. Dudley Edwin R. Sánchez and Irina Budunova Department of Dermatology, Northwestern University, Chicago, IL, USA Medicine, Pulmonary Division, Physiology & Pharmacology, The Center for Diabetes Endocrine Research, University Toledo College Toledo, OH, Wells Pediatric Indiana School Indianapolis, IN, 5 Genetics Genomic Sciences, Icahn Medicine at Mount Sinai, New York, NY,...
The 5-HT(1B/1D) receptor agonist sumatriptan is effective in aborting acute attacks of migraine and known to cause constriction cranial arteries as well some peripheral blood vessels. present study set out investigate whether 5-HT(1B) and/or 5-HT(1D) receptors mediate contractions the human isolated middle meningeal temporal (models for anti-migraine efficacy) coronary artery saphenous vein side-effect potential). Concentration-response curves were made with (1 nm-100 microm) vessels absence...
Glucocorticoids are effective anti-inflammatory drugs widely used in dermatology and for the treatment of blood cancer patients. Unfortunately, chronic with glucocorticoids results serious metabolic atrophogenic adverse effects including skin atrophy. act via glucocorticoid receptor (GR), a transcription factor that causes either gene transactivation (TA) or transrepression (TR). Compound A (CpdA), novel non-steroidal GR ligand, does not promote dimerization TA, retains potential but induces...
One of the major adverse effects topical glucocorticoids is cutaneous atrophy often followed by development resistance to steroids (tachyphylaxis). Previously we showed that after two weeks, interfollicular mouse keratinocytes acquired anti-proliferative glucocorticoid fluocinolone acetonide (FA). top genes activated FA during tachyphylaxis was Klk6 encoding kallikrein-related peptidase 6, known enhance keratinocyte proliferation. KLK6 also strongly induced chronic in human skin. Double...
Using a combination of RT – PCR and inverse‐PCR techniques, we amplified, cloned sequenced full‐length porcine 5‐HT 1B receptor cDNA derived from cerebral cortex. Sequence analysis revealed 1170 bp encoding an open reading frame 390 amino acids showing 95% similarity with the human receptor. The recombinant was expressed in monkey Cos‐7 cells its pharmacological profile determined by radioligand binding assay using [ 3 H]‐GR125743. affinities several agonists (L694247>ergotamine...
1 Hexachlorocyclohexane (HCH), an organochlorine pesticide having hydrophobic molecule is known to act on membranes. HCH mediated alterations in erythrocyte membrane occur through disorganization of the lipid bilayer. Therefore changes fluidity, osmotic fragility and certain bound enzymes were studied. Administration (technical) rats at 5 mg/kg, orally, days a week for 1, 2 3 months caused marked increase anddecreaseinlevelsofNa + , K -ATPase, acetylcholinesterase erythrocytes glutathione...
A cDNA encoding the full‐length 5‐HT 1D receptor derived from porcine cerebral cortex was amplified, cloned and sequenced, using guinea‐pig coding sequence oligonucleotide primers in reverse transcription‐polymerase chain reaction (RT–PCR). The 5′ 3′ ends of were verified by inverse PCR. Sequence analysis revealed an open reading frame 1134 nucleotides a polypeptide 377 amino acids having 92% homology with human 88–90% other species homologues. further subcloned into mammalian expression...
Abstract The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China late 2019 and has now caused a global pandemic. disease by SARS-CoV-2 is known as COVID-19. To date, few treatments for COVID-19 have proven effective, the current standard of care primarily supportive. As result, therapeutic strategies are high demand. Viral entry into target cells frequently sensitive to cell membrane lipid composition organization. Evidence suggests...
Abstract Androgen (AR) and glucocorticoid (GR) receptor signaling play opposing roles in prostate tumorigenesis: AR acts as an oncogene GR is a tumor suppressor. Here we explored novel strategy of simultaneous inhibition activation for cancer treatment using non-steroidal AR/GR modulator Compound A (CpdA) combination with proteasome inhibitor Bortezomib (BZ). We others found that CpdA anti-inflammatory anti-androgen. It inhibits basal DHT-induced activity; does not induce dimerization...
Glucocorticoids (GCs) are widely used for the treatment of inflammatory skin diseases despite significant adverse effects including atrophy. Effects GCs mediated by glucocorticoid receptor (GR), a well-known transcription factor. Previously, we discovered that one GR target genes, REDD1, is causatively involved in Here, investigated its role function using HaCaT REDD1 knockout (KO) keratinocytes. We found large differences transcriptome KO and control Cas9 cells response to fluocinolone...
Abstract Glucocorticoids are important physiological and pharmacological regulators of epidermal proliferation, differentiation skin tumorigenesis. The glucocorticoid effects mediated via the receptor (GR), a transcription factor that regulates genes expression by DNA-binding dependent transactivation, independent transrepression through negative interaction with other factors. Our previous studies demonstrated keratin5.GR transgenic animals resistant to carcinogenesis. We also found GR...