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  1. Jaganathan R, Ravindran R, Dhanasekaran S
    Can J Diabetes, 2018 Aug;42(4):446-456.e1.
    PMID: 29229313 DOI: 10.1016/j.jcjd.2017.10.040
    Adipose tissue is an enormously active endocrine organ, secreting various hormones, such as adiponectin, leptin, resistin and visfatin, together with classical cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). All these adipocytokines play significant roles in the regulation of energy metabolism, glucose and lipid metabolism, reproduction, cardiovascular function and immunity. Adipocytokines are significantly regulated by nutritional status and can directly influence other organ systems, including brain, liver and skeletal muscle. Adiponectin plays a key role as an anti-inflammatory hormone. Upregulated expression of resistin, vaspin, apelin and TNF-α plays a significant role in induction of insulin resistance linked with obesity and type 2 diabetes. Ghrelin, the circulating peptide, has been found to stimulate appetite and regulate energy balance. Thus, it can be considered 1 of the candidate genes for obesity and type 2 diabetes. Omentin is a novel adipokine produced by visceral adipose tissue. Circulating levels of omentin are decreased in insulin-resistant states, for example, in obesity and diabetes. IL-6 plays a vital role in regulating the accumulation of lipids intramyocardially. Based on the biologic relevance of these adipocytokines, they can no longer be considered as energy storage sites alone but must also be considered in metabolic control. Hence, the present review summarizes the regulatory roles of adipocytokines in diabetes linked with obesity.
  2. Nagrani T, Kumar S, Haq MA, Dhanasekaran S, Gajjar S, Patel C, et al.
    Cureus, 2023 Oct;15(10):e46909.
    PMID: 37841989 DOI: 10.7759/cureus.46909
    Background Ridge preservation became a crucial dental health issue and strategy to keep away from ridge defacement after post-tooth loss. The recent scientific evolution of platelet-rich fibrin (PRF) comprises a parenteral formulation of PRF. The combined allograft for socket preservation gives benefits. In this study, bone allografts, demineralized freeze-dried bone allografts (DFDBA) and freeze-dried bone allografts (FDBA) are used in a 30:70 ratio alone or in combination with injectable PRF (I-PRF) for socket preservation. Methods This study is a radiographic and histological examination conducted on 60 participants aged between 19-65 years. Participating patients agreed voluntarily that they would not bear any fixed prosthesis for the next nine months and plan for implanted teeth placement, including multi-rooted mandibular molars denticles. Both groups received atraumatic extraction; then, the socket was preserved with bone allograft alone in the control group and bone allograft mixed with I-PRF, forming sticky bone, in the experimental group. Clinical, radiological, and histological assessments were taken at the inception stage, three months, six months, and nine months. A multivariate regression model and a generalized estimating equation (GEE) model were used to analyse the effects of these changes on outcomes. Results In all the parameters, the test group indicated a good amount of bone growth with increasing intervals of time for bone height radiographically with statistically significant difference present (p<0.05) and histologically after nine months when socket site grafted with bone graft in combination with I-PRF. Conclusion This study's results demonstrated that I-PRF possesses the potential to regenerate and heal in the tooth-extracted socket. This study further recommends the implementation of I-PRF in safeguarding and conserving the raised rim of the tooth. Future research should take place on the osteogenic capability of I-PRF in more comprehensive ridge accession surgical procedures and additional expanding and improving capacities in periodontal reconstruction.
  3. Nagaraj B, Sivasubramanian A, Musthafa SA, Muhammad S, Anilkumar AK, Munuswamy-Ramanujam G, et al.
    Free Radic Biol Med, 2024 Oct 10;225:925-932.
    PMID: 39393554 DOI: 10.1016/j.freeradbiomed.2024.10.275
    3-deoxycaryoptinol (Clerodin) is a clerodane diterpene isolated from the leaves of Clerodendrum infortunatum. The present research investigates the anticancer therapeutic efficacy of clerodin in human monocytic leukemic (THP-1) cells for the first time. In vitro assay using THP-1 cells showed the cytotoxic ability of clerodin. Further, Annexin-V(FITC)/PI and intracellular ROS (DCFDA) assays carried out using flow cytometry, and confocal laser scanning microscopy confirmed the apoptotic potential of clerodin. Moreover, the Western blot was used to detect mitochondrial apoptosis of THP-1 cells. RT-PCR, ELISA, and Western blot analysis clearly indicated that clerodin significantly increased the expression of pro-apoptotic marker caspase-3 in THP-1 cells. clerodin also selectively targeted the G2/M phase of THP-1 cells, a key feature for anticancer molecules. Importantly, the clerodin did not exhibit cytotoxicity against human peripheral blood cells. These properties of clerodin make it a potential chemotherapeutic agent that can selectively induce apoptosis in leukemia-like cancer cells.
  4. Subramanian S, Duraipandian C, Alsayari A, Ramachawolran G, Wong LS, Sekar M, et al.
    Front Pharmacol, 2023;14:1096905.
    PMID: 36817128 DOI: 10.3389/fphar.2023.1096905
    Background: Dodonaea viscosa Jacq. (D. viscosa) belongs to the family of Sapindaceae, commonly known as "Sinatha," and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds. Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds. Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group (p < 0.01). Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds.
  5. Dhanasekaran S, Selvadoss PP, Manoharan SS, Jeyabalan S, Yaraguppi DA, Choudhury AA, et al.
    Cell Biochem Biophys, 2024 Jul 23.
    PMID: 39042185 DOI: 10.1007/s12013-024-01359-w
    Chronic hepatitis caused by the hepatitis C virus (HCV) is closely linked with the advancement of liver disease. The research hypothesis suggests that the NS5B enzyme (non-structural 5B protein) of HCV plays a pivotal role in facilitating viral replication within host cells. Hence, the objective of the present investigation is to identify the binding interactions between the structurally diverse phytotherapeutics and those of the catalytic residue of the target NS5B polymerase protein. Results of our docking simulations reveal that compounds such as arjunolic acid, sesamin, arjungenin, astragalin, piperic acid, piperidine, piperine, acalyphin, adhatodine, amyrin, anisotine, apigenin, cuminaldehyde, and curcumin exhibit a maximum of three interactions with the catalytic residues (Asp 220, Asp 318, and Asp 319) present on the Hepatitis C virus NS5B polymerase of HCV. Molecular dynamic simulation, particularly focusing on the best binding lead compound, arjunolic acid (-8.78 kcal/mol), was further extensively analyzed using RMSD, RMSF, Rg, and SASA techniques. The results of the MD simulation confirm that the NS5B-arjunolic acid complex becomes increasingly stable from 20 to 100 ns. The orientation of both arjunolic acid and sofosbuvir triphosphate (standard) within the active site was investigated through DCCM, PCA, and FEL analysis, indicating highly stable interactions of the lead arjunolic acid with the catalytic region of the NS5B enzyme. The findings of our current investigation suggest that bioactive therapeutics like arjunolic acid could serve as promising candidates for limiting the NS5B polymerase activity of the hepatitis C virus, offering hope for the future of HCV treatment.
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