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Ebin Johny,1 Pathoori Bhaskar,1 Md Jahangir Alam,2 Indra Kuladhipati,3 Rupam Das,3 Ramu Adela1 1Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Guwahati, Assam, 781101, India; 2Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Guwahati, Assam, 781101, India; 3Down Town Hospital, Guwahati, Assam, 781006, IndiaCorrespondence: Ramu AdelaDepartment of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Sila Katamur (Halugurisuk), Changsari, Kamrup, Guwahati, Assam, 781101, IndiaTel +91 8860280242Email ramuadela@gmail.comBackground: Type 2 diabetes mellitus (T2DM) is a well-established risk factor for the development of atherosclerotic coronary artery disease. Platelet hyperactivity and inflammation are associated with the development of coronary artery disease (CAD) in T2DM patients. We investigated the status of immune cells, platelet activation, and platelet-immune cell interactions in T2DM_CAD patients.Methodology: The study population consisted of four groups of subjects, healthy control (CT, n = 20), T2DM (n = 44), CAD (n = 20) and T2DM_CAD (n = 38). Platelet activation, immunome profiling and platelet-immune cell interactions were analysed by flow cytometry. The circulatory levels of inflammatory cytokines/chemokines were assessed using multiplex assay.Results: Increased platelet activation and increased platelet-immune cell aggregate formation were observed in T2DM and T2DM_CAD groups compared to the control and CAD groups (p < 0.05). Our immunome profile analysis revealed, altered monocyte subpopulations and dendritic cell populations in T2DM, CAD and T2DM_CAD groups compared to the control group (p < 0.05). Furthermore, significantly increased IL-1β, IL-2, IL-4, IL-6, IL-8, IL12p70, IL-13 IL-18, CCL2, and decreased CXCL1, CCL5 levels were observed in T2DM_CAD group compared to the control group. Our ex-vivo study increased platelet-monocyte aggregate formation was observed upon D-glucose exposure in a time and concentration dependent manner.Conclusion: Our data suggests that T2DM, CAD and T2DM_CAD are associated with altered immune cell populations. Furthermore, it has been confirmed that hyperglycemia induces platelet activation and forms platelet-immune cell aggregation which may lead to the release of inflammatory cytokines and chemokines and contribute to the complexity of CAD and type 2 diabetes.Keywords: platelet, inflammation, monocytes, hyperglycemia, type 2 diabetes, coronary artery disease

Mohammad Amjad Hossain,1 Aravinthan Adithan,1 Md Jahangir Alam,1 Spandana Rajendra Kopalli,2 Bumseok Kim,1 Chang-Won Kang,1 Ki-Chul Hwang,3 Jong-Hoon Kim1 1College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, Iksan-city, Jeollabuk-Do, Republic of Korea; 2Department of Integrative Bioscience and Biotechnology, Sejong University, Gwangjin-gu, Seoul, 05006, Republic of Korea; 3Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of KoreaCorrespondence: Jong-Hoon KimCollege of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 79 Gobong-ro, Iksan-city, Jeollabuk-Do, 54596, Republic of KoreaEmail jhkim1@jbnu.ac.krPurpose: The pathogenesis of osteoarthritis (OA) is characterized by joint degeneration. The pro-inflammatory cytokine interleukin (IL)-1β plays a vital role in the pathogenesis of OA by stimulation of specific signaling pathways like NF-κB, PI3K/Akt, and MAPKs pathways. The catabolic role of growth factors in the OA may be inhibited cytokine-activated pathogen. The purpose of this study was to investigate the potential effects of insulin-like growth factor-1 (IGF-1) on IL-1β-induced apoptosis in rabbit chondrocytes in vitro and in an in vivo rabbit knee OA model.Methods: In the present study, the OA developed in chondrocyte with the treatment of IL-1β and articular cartilage ruptures by removal of cartilage from the rabbit knee femoral condyle. After IGF-1 treatment, immunohistochemistry and qRT-PCR were identified OA expression with changes in MMPs (matrix metalloproteinases). The production of ROS (intracellular reactive oxygen species) in the OA was detected by flow cytometry. Further, the disease progression was microscopically investigated and pathophysiological changes were analyzed using histology. The NF-κB, PI3K/Akt and P38 (MAPK) specific pathways that are associated with disease progression were also checked using the Western blot technique.Results: The expression of MMPs and various apoptotic markers are down-regulated following administration of IGF-1 in a dose-dependent fashion while significantly up-regulation of TIMP-1. The results showed that higher levels of ROS were observed upon treatment of chondrocytes and chondral OA with IL-1β. Collectively, our results indicated that IGF-1 protected NF-κB pathway by suppression of PI3K/Akt and MAPKs specific pathways. Furthermore, the macroscopic and pathological investigation showed that it has a chondroprotective effect by the formation of hyaline cartilage.Conclusion: Our results indicate a protective effect of IGF-1 against OA pathogenesis by inhibition of NF-κB signaling via regulation of the MAPK and PI3K/Akt signaling pathways and prevention of apoptosis by suppression of ROS production.Keywords: insulin-like growth factor-1, chondrocyte, cartilage development, osteoarthritis, rabbit

Manik Chandra Shill,1 Asim Kumar Bepari,1 Mahi Khan,1 Zarin Tasneem,1 Tania Ahmed,1 Md Asif Hasan,1 Md Jahir Alam,1 Murad Hossain,1 Md Ashrafur Rahman,1 Shazid Md Sharker,1 Masum Shahriar,2 Ghazi Muhammad Sayedur Rahman,1 Hasan Mahmud Reza1 1Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka, 1229, Bangladesh; 2Department of Pharmacy, Jahangirnagar University, Savar, BangladeshCorrespondence: Manik Chandra Shill; Hasan Mahmud RezaDepartment of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka, 1229, BangladeshEmail manik.shill@northsouth.edu; hasan.reza@northsouth.eduIntroduction: Hypoglycemia in diabetes mellitus (DM) correlates with hepatic impairment, nephropathy, lipid abnormalities, and oxidative stress and subsequently complicates the disease pathogenesis. Medicinal plants have been used for the management of diabetes since ancient times. In this study, we explored the potentials of Colocasia affinis (CA), a plant known to possess anti-allergic and anti-inflammatory activities, as a remedy for diabetes and related complications.Methods: We induced diabetes in rats using a single intraperitoneal dose (65 mg/kg) of streptozotocin (STZ). We next treated the rats with an ethanolic extract of leaves of CA to reveal its antidiabetic and organ-protective potentials. Biomarkers of diabetes, inflammation, and oxidative stress were measured using biochemical and histopathological analysis. We also performed molecular docking for three major phytochemicals (kaempferol, myricetin, and rosmarinic acid) of CA.Results: Oral administration of the CA leaves extract at 250 mg/kg and 500 mg/kg doses decreased blood glucose level significantly (p< 0.05) in STZ-induced diabetic rats. The extract also considerably attenuated plasma HbA1c levels and normalized blood lipids, glycogen, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Additionally, treatment with the extract improved kidney complications by decreasing serum creatinine and blood urea nitrogen (BUN) levels. Furthermore, CA leaves extract normalized nitric oxide (NO) and advance oxidative protein products (AOPP) in diabetic rats. The extract also showed significant improvement of the antioxidant enzymes glutathione dismutase (GSH) and superoxide dismutase (SOD) at a dose of 500 mg/kg. Besides, histological investigation demonstrated attenuation of inflammation of the vital organs, including the liver and the kidney. In silico studies revealed that three major phytochemicals (kaempferol, myricetin, and rosmarinic acid) of the ethanolic extract of leaves of CA can inhibit several molecular targets of diabetes and inflammation.Conclusion: Collectively, our results demonstrated the therapeutic potentials of CA for the mitigation of diabetes and diabetic complications.Keywords: diabetes mellitus, Colocasia affinis, antidiabetic potentials, vital organs protection, oxidative stress markers

Md Jahangir Alam,1 Ozair Alam,1 Suroor Ahmad Khan,1 Mohd Javed Naim,1 Mohammad Islamuddin,2 Girdhar Singh Deora3 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, 2Parasite Immunology Laboratory, Department of Biotechnology, Faculty of Science, Jamia Hamdard, New Delhi, 3Institute of Life Sciences, University of Hyderabad, Hyderabad, India Abstract: This article reports on the design, synthesis, and pharmacological activity of a new series of hybrid pyrazole analogues: 5a–5u. Among the series 5a–5u, the compounds 5u and 5s exhibited potent anti-inflammatory activity of 80.63% and 78.09% and inhibition of 80.87% and 76.56% compared with the standard drug ibuprofen, which showed 81.32% and 79.23% inhibition after 3 and 4 hours, respectively. On the basis of in vivo studies, 12 compounds were selected for assessment of their in vitro inhibitory action against COX1/2 and TNFα. The compounds 5u and 5s showed high COX2-inhibitory activity, with half-maximal inhibitory concentrations of 1.79 and 2.51 µM and selectivity index values of 72.73 and 65.75, respectively, comparable to celecoxib (selectivity index =78.06). These selected compounds were also tested for TNFα, cytotoxicity, and ulcerogenicity. Docking studies were also carried out to determine possible interactions of the potent compounds (5u and 5s), which also showed high docking scores of -12.907 and -12.24 compared to celecoxib, with a -9.924 docking score. These selective COX2 inhibitors were docked into the active site of COX2, and showed the same orientation and binding mode to that of celecoxib (selective COX2 inhibitor). Docking studies also showed that the SO2NH2 of 5u and 5s is inserted deep inside the selective pocket of the COX2-active site and formed a hydrogen-bond interaction with His90, Arg513, Phe518, Ser353, Gln192, and Ile517, which was further validated by superimposed docked pose with celecoxib. Keywords: anti-inflammatory activity, analgesic activity, selective COX2 inhibition, TNFα inhibition, molecular docking studies, pyrazole

We study balanced circle packings and circle-contact representations for planar graphs, where the ratio of the largest circle’s diameter to the smallest circle’s diameter is polynomial in the number of circles. We provide a number of positive and negative results for the existence of such balanced configurations.