A5086871265- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Cancer, Lipids, and Metabolism
- Cytokine Signaling Pathways and Interactions
- Multiple Sclerosis Research Studies
- Immune cells in cancer
- Peroxisome Proliferator-Activated Receptors
- Ovarian cancer diagnosis and treatment
- Metabolomics and Mass Spectrometry Studies
- NF-κB Signaling Pathways
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Diet and metabolism studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Nanomaterials in Catalysis
- Adipose Tissue and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Nanocluster Synthesis and Applications
- Lysosomal Storage Disorders Research
- Calcium signaling and nucleotide metabolism
- Cancer-related Molecular Pathways
- Mitochondrial Function and Pathology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pancreatic function and diabetes
- Diet, Metabolism, and Disease
Henry Ford Health System
2016-2025
Henry Ford Hospital
2014-2024
Hemwati Nandan Bahuguna Garhwal University
2023-2024
Wayne State University
2016-2021
Michigan United
2019-2021
Ford Motor Company (United States)
2018
Albany Medical Center Hospital
2016
New York University
2016
Georgetown University
2016
Universitätsklinikum Erlangen
2016
Abstract Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated disease of the CNS. Metformin most widely used drug for diabetes and mediates its action via activating AMP-activated protein kinase (AMPK). We provide evidence that metformin attenuates induction EAE by restricting infiltration mononuclear cells into CNS, down-regulating expression proinflammatory cytokines (IFN-γ, TNF-α, IL-6, IL-17, inducible NO synthase (iNOS)), cell adhesion molecules, matrix metalloproteinase...
Ovarian cancer is the most lethal gynecologic in women. Its high mortality rate (68%) reflects fact that 75% of patients have extensive (>stage III) disease at diagnosis and also limited efficacy currently available therapies. Consequently, there clearly a great need to develop improved upfront salvage therapies for ovarian cancer. Here, we investigated metformin alone combination with cisplatin vivo. A2780 cells were injected intraperitoneally nude mice; A2780-induced tumors mice, when...
Ovarian cancer (OvCa) is the fifth most common cause of death from all cancers among women in United Sates and leading gynecological malignancies. While OvCa patients initially respond to surgical debulking chemotherapy, 75% later succumb disease. Thus, there an urgent need test novel therapeutic agents counteract high mortality rate associated with OvCa. In this context, we have developed engineered Nanoceria (NCe), nanoparticles cerium oxide, possessing anti-oxidant properties, be used as...
Significance Cancer cells reprogram their metabolism for optimal growth and survival. AMPK-activated protein kinase (AMPK) is a key energy sensor that controls many metabolic pathways including reprogramming. However, its role in cancer poorly understood. Some studies claim it has tumor suppressor while others show protumor role. Two AMPK-activating compounds (including metformin, now clinical trials) are widely used to suppress cell proliferation. We found AMPK abundantly expressed...
5-Aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) is widely used as an AMP-kinase activator, which regulates energy homeostasis and response to metabolic stress. Here, we investigated the effect of AICAR, AMPK on proliferation various cancer cells observed that all examined cell lines was significantly inhibited by AICAR treatment due arrest in S-phase accompanied with increased expression p21, p27, p53 proteins inhibition PI3K-Akt pathway. Inhibition vitro growth mirrored vivo...
AMP-activated protein kinase (AMPK) is tightly regulated by the cellular AMP:ATP ratio and plays a central role in regulation of energy homeostasis metabolic stress. A pharmacological activator AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR) inhibited lipopolysaccharide (LPS)-induced expression proinflammatory cytokines (tumor necrosis factor α, interleukin-1β, interleukin-6) inducible nitric oxide synthase primary rat astrocytes, microglia, peritoneal macrophages. AICAR attenuates...
Abstract Free radicals and inflammatory mediators are involved in transient focal cerebral ischemia (FCI). Preadministration of N‐acetylcysteine (NAC) has been found to attenuate the ischemia‐reperfusion injury a rat model experimental stroke. This study was undertaken investigate neuroprotective potential NAC administered after ischemic events FCI induced for 30 min by occluding middle artery (MCA). (150 mg/kg) intraperitoneally at time reperfusion followed another dose 6 hr later. Animals...
Metformin, the most widely used drug for type 2 diabetes activates 59 adenosine monophosphate (AMP)-activated protein kinase (AMPK), which regulates cellular energy metabolism. Here, we report that ovarian cell lines VOSE, A2780, CP70, C200, OV202, OVCAR3, SKOV3ip, PE01 and PE04 predominantly express -α(1), -β(1), -γ(1) -γ(2) isoforms of AMPK subunits. Our studies show metformin treatment (1) significantly inhibited proliferation diverse chemo-responsive -resistant cancer (A2780, SKVO3ip,...
HIV's ability to establish long-lived latent infection is mainly due transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load patients treated with potent antiretrovirals, current therapy unable purge the virus from these reservoirs. In order broaden inhibitory range effectiveness of potential bryostatin was investigated as HIV inhibitor activator. Bryostatin revealed antiviral activity against R5-...
The prevalence of hepatitis E virus (HEV) infections among 55 domestic swine living in the Kathmandu Valley Nepal was investigated. Sera and stool specimens were collected from 47 free-roaming examined for presence HEV genomic sequences by reverse transcription-polymerase chain reaction. these animals, as well sera eight other swine, also HEV-specific antibodies an enzyme-linked immunosorbent assay a fluorescent antibody blocking assay. Hepatitis RNA detected and/or three while 18 swine....
Aims: Melanoma is the most aggressive type of malignant skin cancer derived from uncontrolled proliferation melanocytes. cells possess a high potential to metastasize, and prognosis for advanced melanoma rather poor due its strong resistance conventional chemotherapeutics. Nanomaterials are at cutting edge rapidly developing area nanomedicine. The nanoparticles use as carrier in drug delivery infinite with novel applications constantly being tested. noncarrier cerium oxide (CNPs) promising...
Abstract Background Obesity is one of the principal causative factors involved in development metabolic syndrome. AMP-activated protein kinase (AMPK) an energy sensor that regulates cellular metabolism. The role adipocyte differentiation not completely understood, therefore, we examined effect 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), a pharmacological activator on 3T3L1 cells and mouse D iet i nduced o besity (DIO) model. Methods To examine AICAR model, were...
Abstract BACKGROUND: The objective of this case‐control study was to identify any association metformin intake with the survival patients ovarian cancer. METHODS: In retrospective study, women cancer who received (cases) were compared did not receive (controls). A 2‐layered analysis conducted. preliminary analysis, all cases (the OC cohort) controls at a 1:2 ratio. Subsequently, in definitive only had epithelial EOC 1:3 cohort, matched for age (±5 years), International Federation Gynecology...
Abstract Earlier investigations have revealed that tumor cells undergo metabolic reprogramming and mainly derive their cellular energy from aerobic glycolysis rather than oxidative phosphorylation even in the presence of oxygen. However, recent studies shown certain cancer display increased or high metabolically active phenotype. Cellular bioenergetic profiling 13 established 12 patient derived ovarian cell lines significant bioenergetics diversity. The phenotype correlated with functional...
Nanomedicine is a very promising field and nanomedical drugs have recently been used as therapeutic agents against cancer. In previous study, we showed that Nanoceria (NCe), nanoparticles of cerium oxide, significantly inhibited production reactive oxygen species, cell migration invasion ovarian cancer cells in vitro, without affecting proliferation reduced tumor growth an xenograft nude model. Increased expression folate receptor-α, isoform membrane-bound receptors, has described To enable...
The NAD(+)-dependent deacetylase SIRT1 is a key regulator of several aspects metabolism and aging. activation beneficial for human diseases, including metabolic syndrome, diabetes, obesity, liver steatosis, Alzheimer disease. We have recently shown that the protein deleted in breast cancer 1 (DBC1) activity vivo. Furthermore, DBC1 form dynamic complex regulated by energetic state organism. Understanding how interaction between therefore essential to design strategies aimed activate SIRT1....
Significance The role of cellular metabolism in conventional T cell fate and functions has been established, but little is understood about how metabolic pathways nutrient requirements are controlled natural killer (NKT) cells. present study shows that, unlike CD4 cells, activation NKT cells metabolize glucose to the pentose phosphate pathway TCA cycle instead converting into lactate. In line with this, a high lactate microenvironment detrimental for homeostasis effector function. Glucose...
Abstract Viruses are known to perturb host cellular metabolism enable their replication and spread. However, little is about the interactions between Zika virus (ZIKV) infection metabolism. Using primary human retinal vascular endothelial cells an established cell line, we investigated role of AMP-activated protein kinase (AMPK), a master regulator energy metabolism, in response ZIKV challenge. caused time-dependent reduction active phosphorylated state AMPK its downstream target acetyl-CoA...
Metabolic aberrations impact the pathogenesis of multiple sclerosis (MS) and possibly can provide clues for new treatment strategies. Using untargeted metabolomics, we measured serum metabolites from 35 patients with relapsing-remitting (RRMS) 14 healthy age-matched controls. Of 632 known detected, 60 were significantly altered in RRMS. Bioinformatics analysis identified an metabotype RRMS, represented by four changed metabolic pathways glycerophospholipid, citrate cycle, sphingolipid,...
Abstract The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins are newly identified immunomodulators. In vivo treatment of SJL/J mice with lovastatin reduced the duration and clinical severity active passive experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Lovastatin induced expression GATA3 phosphorylation STAT6, whereas it inhibited tyrosine Janus kinase 2, STAT4. Inhibition kinase-STAT4 pathway by modulated T0 to Th1...
Preservation of endothelial functions with low-dose nitric oxide (NO) and inhibition excessive production NO from inducible synthase (iNOS) is a potential therapeutic approach for acute stroke. Based on this hypothesis, an modulator, S-nitrosoglutathione (GSNO) was used, which provided neuroprotection in rat model focal cerebral ischemia. Administration GSNO after the onset ischemia reduced infarction improved blood flow. To understand mechanism protection, involvement inflammation ischemic...
Abstract Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is a Th1-mediated inflammatory demyelinating disease the CNS. AMP-activated protein kinase was reported recently to have anti-inflammatory activities by negatively regulating NF-κB signaling. In this study, we investigated prophylactic and therapeutic efficacy activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), in active passive EAE induced immunization with PLP139–151 or MOG35–55...