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Ameeta S Kalokhe, Sandhya R Iyer, Keshav Gadhe, Tuman Katendra, Anuradha Paranjape, Carlos Del Rio, Rob Stephenson, Seema Sahay
Domestic violence (DV) is prevalent in low-income and slum-dwelling communities in India. To date, the focus of DV prevention in resource-poor settings has largely been with women. We herein aim to identify correlates of DV perpetration to help inform future primary prevention efforts that focus on behavioral change in men. Utilizing a cross-sectional design, potential correlates of DV perpetration were explored among a geographically-clustered random sample of 100 recently-married men residing in slums in Pune, India...
2018: PloS One
Ganesh M Mohite, Rakesh Kumar, Rajlaxmi Panigrahi, Ambuja Navalkar, Nitu Singh, Debalina Datta, Surabhi Mehra, Soumik Ray, Laxmikant G Gadhe, Subhadeep Das, Namrata Singh, Debdeep Chatterjee, Ashutosh Kumar, Samir K Maji
The involvement of α-synuclein (α-Syn) amyloid formation in Parkinson's disease (PD) pathogenesis is supported by the discovery of α-Syn gene (SNCA) mutations linked with familial PD, which are known to modulate the oligomerization and aggregation of α-Syn. Recently, the A53V mutation has been discovered, which leads to the late-onset PD. In the present study, we characterized for the first time the biophysical properties including the aggregation propensities, toxicity of aggregated species and membrane binding capability of A53V along with all familial mutations at A53 position...
May 17, 2018: Biochemistry
Gadh I Al-Basher, Hanan Aljabal, Rafa S Almeer, Ahmed A Allam, Ayman M Mahmoud
The worldwide consumption of energy drinks (EDs) has increased in recent years. EDs have several side effects and can be linked to liver injury, kidney damage and risk-seeking behavior. The impact of perinatal consumption of EDs on the newborns has not been previously investigated. In this study, we evaluated the effects of perinatal exposure to a caffeinated ED on the liver, kidney, brain, locomotor activity and anxiety in mice newborns. Pregnant mice received 2.5 or 5 ml ED by oral gavage from the first day of pregnancy until day 15 after birth...
March 29, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zhenghuan Fang, Boreum Han, Kyung Hee Jung, Ju-Hyeon Lee, Ashraf Kareem El-Damasy, Changdev G Gadhe, Soo Jung Kim, Hong Hua Yan, Jung Hee Park, Ji Eun Lee, Yeo Wool Kang, Ae Nim Pae, Gyochang Keum, Soon-Sun Hong
Tropomyosin-related kinase A (TrkA) plays important roles in tumor cell growth and survival signaling and contributes to chemo-resistance in pancreatic cancer. Therefore, we developed KK5101, a novel TrkA target inhibitor and assessed its anti-cancer effects and investigated underlying mechanism of action in pancreatic cancer. KK5101 was characterized to inhibit TrkA selectively and potently by protein binding assay. It effectively inhibited the growth and proliferation of pancreatic cancer cells. Also, KK5101 increased apoptosis with loss of mitochondrial membrane potential, as evidenced by increases of cytochrome c releases...
March 29, 2018: Cancer Letters
Mousa O Germoush, Sarah I Othman, Maha A Al-Qaraawi, Hanan M Al-Harbi, Omnia E Hussein, Gadh Al-Basher, Mohammed F Alotaibi, Hassan A Elgebaly, Mansur A Sandhu, Ahmed A Allam, Ayman M Mahmoud
Hepatic encephalopathy (HE) is a serious neuropsychiatric complication that occurs as a result of liver failure. Umbelliferone (UMB; 7-hydroxycoumarin) is a natural product with proven hepatoprotective activity; however, nothing has yet been reported on its protective effect against hyperammonemia, the main culprit behind the symptoms of HE. Here, we evaluated the effect of UMB against ammonium chloride (NH4 Cl)-induced hyperammonemia, oxidative stress, inflammation and hematological alterations in rats. We demonstrated the modulatory role of UMB on the glutamate-nitric oxide (NO)-cGMP pathways in the cerebrum of rats...
March 21, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Varsha Pokharkar, Arpana Patil-Gadhe, Prathyusha Palla
Intranasal delivery is a potential platform that can be employed in targeting the antiretrovirals (ARVs) to reach HIV that harbors in the central nervous system. The objective of the study was to develop an optimized efavirenz (EFV) loaded nanostructured lipid carrier (ENLC) and deliver it through intranasal route for brain targeting. Factorial design (2(3)) was used to identify the key formulation variables influencing particle size and percent drug encapsulation of efavirenz in the NLC. Optimised ENLC-6 batch exhibited a spherical morphology with a mean particle size of 162nm, high drug encapsulation of 95...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jamaan S Ajarem, Gadh Al-Basher, Ahmed A Allam, Ayman M Mahmoud
Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea ( Camellia sinensis ) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15...
2017: Oxidative Medicine and Cellular Longevity
Florencia Sainz, María Jesús Torija, Minenosuke Matsutani, Naoya Kataoka, Toshiharu Yakushi, Kazunobu Matsushita, Albert Mas
Acetic acid bacteria (AAB) are known for rapid and incomplete oxidation of an extensively variety of alcohols and carbohydrates, resulting in the accumulation of organic acids as the final products. These oxidative fermentations in AAB are catalyzed by PQQ- or FAD- dependent membrane-bound dehydrogenases. In the present study, the enzyme activity of the membrane-bound dehydrogenases [membrane-bound PQQ-glucose dehydrogenase (mGDH), D-gluconate dehydrogenase (GADH) and membrane-bound glycerol dehydrogenase (GLDH)] involved in the oxidation of D-glucose and D-gluconic acid (GA) was determined in six strains of three different species of AAB (three natural and three type strains)...
2016: Frontiers in Microbiology
Arpana Patil-Gadhe, Varsha Pokharkar
Rosuvastatin (RSVS), an anti-lipidemic agent suggested for the treatment of airway remodeling in chronic obstructive pulmonary disease (COPD). It shows a pleiotropic effect on airway smooth muscles and inhibits proliferative activities of physiological mitogens. The aim of the present study was to develop and investigate the targeting potential of rosuvastatin (RSVS) to lung as loaded in nanostructured lipid carrier dry powder for inhalation (RNLC-DPI). RNLC dispersion was converted into respirable particle by lyophilization using 5% mannitol as cryoprotectant-carrier...
March 30, 2016: International Journal of Pharmaceutics
Changdev G Gadhe, Eunhee Lee, Mi-Hyun Kim
The STAT/JAK3 pathway is a well-known therapeutic target in various diseases (ex. rheumatoid arthritis and psoriasis). The therapeutic advantage of JAK3 inhibition motivated to find new scaffolds with desired DMPK. For the purpose, in silico high-throughput sieves method is developed consisting of a receptor-guided three-dimensional quantitative structure-activity relationship study and shape-based virtual screening. We developed robust and predictive comparative molecular field analysis (q (2) = 0.760, r (2) = 0...
November 2015: Archives of Pharmacal Research
Arpana A Patil-Gadhe, Abhay Y Kyadarkunte, Michael Pereira, Gauri Jejurikar, Milind S Patole, Arun Risbud, Varsha B Pokharkar
BACKGROUND: Oral therapy for pulmonary tuberculosis (TB) treatment suffers from the limitation of hepatic metabolism leading insufficient concentration of antitubercular (anti-TB) drugs in alveolar macrophage which harbors Mycobacterium tuberculosis (MTB). Targeted aerosol delivery of antituberculous drug to lung is efficient for treating local lung TB infection. OBJECTIVE: The present study was aimed to evaluate rifapentine (RPT) loaded proliposomal dry powder for inhalation (RLDPI) for anti-TBactivity and cytotoxicity in vitro...
September 2014: Toxicology International
Changdev G Gadhe, Anand Balupuri, Seung Joo Cho
Human CC-chemokine receptor 8 (CCR8) is a crucial drug target in asthma that belongs to G-protein-coupled receptor superfamily, which is characterized by seven transmembrane helices. To date, there is no X-ray crystal structure available for CCR8; this hampers active research on the target. Molecular basis of interaction mechanism of antagonist with CCR8 remains unclear. In order to provide binding site information and stable binding mode, we performed modeling, docking and molecular dynamics (MD) simulation of CCR8...
2015: Journal of Biomolecular Structure & Dynamics
Changdev G Gadhe, Mi-hyun Kim
CC chemokine receptor 4 (CCR4), a G protein-coupled receptor (GPCR), plays a vital role in the progression of asthma, T-cell lymphoma, inflammation, and Alzheimer's disease. To date, the structure of CCR4 has not been determined. Therefore, the nature of the interactions between inhibitors and CCR4 is not well known. In this study, we used CCR5 as a template to model the structure of CCR4. Docking studies were performed for four naphthalene-sulphonamide derivatives and crucial ligand-protein interactions were analysed...
February 2015: Molecular BioSystems
Gugan Kothandan, Changdev G Gadhe, Anand Balupuri, Jagadeesan Ganapathy, Seung Joo Cho
The nociceptin receptor (NOPR) is an orphan G protein-coupled receptor that contains seven transmembrane helices. NOPR has a distinct mechanism of activation, though it shares a significant homology with other opioid receptors. Previously there have been reports on homology modeling of NOPR and also molecular dynamics simulation studies for a short period. Recently the crystal structure of NOPR was reported. In this study, we analyzed the time dependent behavior of NOPR docked with clinically important agonist molecules such as NOP (natural agonist) peptide and compound 10 (SCH-221510 derivative) using molecular dynamics simulations (MDS) for 100 ns...
December 2014: Molecular BioSystems
Arpana Patil-Gadhe, Abhay Kyadarkunte, Milind Patole, Varsha Pokharkar
The aim of the present study was to establish the potential of montelukast loaded nanostructured lipid carrier (MNLC) for pulmonary application. The formulated nanoparticles were evaluated in vitro for aerodynamic characterization and in vivo for pulmokinetics in Wistar rats. The in vitro cytotoxicity was performed on A549 cell line and compared with montelukast-aqueous solution. MNLC was prepared with montelukast (0.2%), Precirol ATO5 (solid lipid), and Capryol-90 (liquid lipid) in the ratio of 7:3 using melt-emulsification-homogenization method...
September 2014: European Journal of Pharmaceutics and Biopharmaceutics
Ching-Yen Chung, Joshua Chynoweth, Chi-Cheng Chu, Rajit Gadh
WINSmartEV is a software based plug-in electric vehicle (PEV) monitoring, control, and management system. It not only incorporates intelligence at every level so that charge scheduling can avoid grid bottlenecks, but it also multiplies the number of PEVs that can be plugged into a single circuit. This paper proposes, designs, and executes many upgrades to WINSmartEV. These upgrades include new hardware that makes the level 1 and level 2 chargers faster, more robust, and more scalable. It includes algorithms that provide a more optimal charge scheduling for the level 2 (EVSE) and an enhanced vehicle monitoring/identification module (VMM) system that can automatically identify PEVs and authorize charging...
2014: TheScientificWorldJournal
A Balupuri, P K Balasubramanian, C G Gadhe, S J Cho
Checkpoint kinase 1 (Chk1) is a promising target for the design of novel anticancer agents. In the present work, molecular docking simulations and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on pyridyl aminothiazole derivatives as Chk1 inhibitors. AutoDock was used to determine the probable binding conformations of all the compounds inside the active site of Chk1. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were developed based on the docking conformations and alignments...
2014: SAR and QSAR in Environmental Research
Arpana Patil-Gadhe, Varsha Pokharkar
The purpose of the study was to formulate montelukast-loaded nanostructured lipid carrier (MNLC) to improve its systemic bioavailability, avoid hepatic metabolism and reduce hepatic cellular toxicity due to metabolites. MNLC was prepared using melt-emulsification-homogenization method. Preformulation study was carried out to evaluate drug-excipient compatibility. MNLCs were prepared using spatially different solid and liquid lipid triglycerides. CAE (DL-Pyrrolidonecarboxylic acid salt of L-cocyl arginine ethyl ester), a cationic, biodegradable, biocompatible surfactant was used to stabilize the system...
September 2014: European Journal of Pharmaceutics and Biopharmaceutics
Namil Kim, Jeongyeon Park, Changdev G Gadhe, Seung Joo Cho, Youngjin Oh, Donghyun Kim, Kiwon Song
A protoberberine derivative library was used to search for selective inhibitors against kinases of the mitogen-activated protein kinase (MAPK) cascades in mammalian cells. Among kinases in mammalian MAPK pathways, we identified a compound (HWY336) that selectively inhibits kinase activity of mitogen-activated protein kinase kinase 4 and 7 (MKK4 and MKK7). The IC50 of HWY336 was 6 µM for MKK4 and 10 µM for MKK7 in vitro. HWY336 bound to both kinases reversibly via noncovalent interactions, and inhibited their activity by interfering with access of a protein substrate to its binding site...
2014: PloS One
Linnea K Ista, Gabriel P López
Colloidal models are frequently used to model the thermodynamics of bacterial attachment to surfaces. The most commonly used of such models is that proposed by van Oss, Chaudhury and Good, which includes both non-polar and polar (including hydrogen bonding) interactions between the attaching bacterium, the attachment substratum and the aqueous environment. We use this model to calculate the free energy of adhesion, ∆Gadh, for attachment of the marine bacterium Cobetia marina to well defined attachment substrata that systematically vary in their chemistry and their ability to attach bacteria, namely a series of oligo(ethylene glycol) (OEG) terminated self-assembled monolayers that vary in the number of OEG moieties...
December 2013: Biointerphases
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