Rajiv Gandhi University of Health Sciences

Objective This study integrates network pharmacology, in silico and biological validation to explore the anti-dengue potential of the ethanol extract of Cedrus deodara bark (EECD). Materials and method Cedrus deodara bark was authenticated, shade-dried, defatted using petroleum ether and extracted with ethanol using Soxhlet extraction. Network pharmacology was performed on key phytoconstituents, Cedrol, Himachalol, Widdrol, Deodarin, Kaempferol, Gallic acid, β-Sitosterol using Swiss target prediction, IMPPAT database, while disease genes were retrieved from GeneCards. Overlapping targets were visualized via Cytoscape, and enriched pathways were identified through KEGG and GO analysis.For in silico validation, ADMET profiling was done via SwissADME and Qikprop to access drug-likeness, oral bioavailability, and toxicity. Compounds with favorable properties were docked using Glide module of Schrodinger against both viral (NS5 RdRp, NS3 protease) and host (TNF-α, COX-2 receptor) targets. The ligand-protein complexes were further refined with Prime MM-GBSA to calculate binding free energy (ΔG_bind). Molecular dynamics (MD) simulation using Desmond for 100 ns were conducted to access RMSD, RMSF, protein ligand interactions and structural stability,In vitro anti-dengue activity was evaluated using the MTT assay on DENV-2-infected Vero cells and percentage growth inhibition were determined. Subsequently, in vivo, hydroxyurea-induced thrombocytopenia model in albino rat was used to access hematological parameters including platelet count, RBC, WBC, hemoglobin, PCV, MCV, MCH and MCHC were evaluated along with bone marrow histopathology was also performed post-treatments. Results and Discussion Network pharmacology and pathway analysis revealed the multi-target interactions linked to viral inhibition and immune modulation. Molecular docking results showed binding energies between -9.962 to -10.161 kcal/mol. MD simulations confirmed the stability of key ligand target complexes over 100ns. EECD showed significant cytoprotection in in vitro and normalized hematological balance in thrombocytopenic rats in in vivo. Conclusion Cedrus deodara ethanol extract demonstrates promising anti-dengue activity, further drug development as a plant-based therapeutic candidate. This is the first comprehensive exploration of Cedrus deodara bark against dengue, combining molecular docking, dynamics, and experimental validation.

Corticosteroids have broad anti-inflammatory effects to treat asthma and COPD. They do not alter the disease’s progression, but they do improve the function of lung, symptoms, and quality of life. Additionally, they also reduce the exacerbation of both disorders. In asthma, they reduce mortality, but not in COPD. After penetrating the cytoplasm of the cell, the corticosteroid binds to an inactive glucocorticoid receptor complex. Thus, the activated glucocorticoid receptor attaches to DNA at the glucocorticoid response element sequence, promoting the development of anti-inflammatory proteins (transactivation) and suppressing the transcription and secretion of various proinflammatory cytokines (transrepression). The available corticosteroids differ regarding their therapeutic index and potency. All age groups utilize corticosteroids, but because younger and smaller children can get larger mg/kg doses of corticosteroids than older children, they may be more susceptible to adverse systemic effects. Corticosteroids are most beneficial when taken at low to medium doses. While greater doses may help certain patients, there is little additional improvement shown with them. The benefits of corticosteroids for COPD are more debatable, even though they are the recommended treatment for chronic asthma in people of all ages. When taken as instructed, at low to medium dosages, ICS adverse effects are rare however, the risk increases with greater dosages. Even though many kinds of novel treatments have been invented and analyzed, it is unclear that any of them will take the position of ICSs as the first, long-term controller medication for asthma. However, a better initial control treatment for COPD might be established. This chapter focuses on the role, mechanisms, including glucocorticoid receptor binding and modulation of pro-inflammatory gene expression, steroid resistance, clinical applications, challenges, and limitations of corticosteroids in the management of asthma and COPD.

Background: Type 2 diabetes mellitus (T2DM) is associated with progressive renal dysfunction involving alterations in glomerular filtration, tubular transport, and metabolic homeostasis. Sodium-glucose cotransporter-2 (SGLT-2) and dipeptidyl peptidase-4 (DPP-4) inhibitors exert distinct renal and metabolic effects. The present study compared longitudinal renal biomarker profiles between these treatment groups and interpreted the observed responses in the context of established molecular and genetic pathways involved in renal transport and urate handling. Methods: A 12-month prospective observational cohort study was conducted among patients with T2DM receiving SGLT-2 or DPP-4 inhibitors. Renal parameters, including estimated glomerular filtration rate (eGFR), serum urea, serum creatinine, and serum uric acid, were assessed at baseline and at 3, 6, 9, and 12 months. Changes over time were evaluated using repeated-measures statistical approaches with estimated marginal means, 95% confidence intervals, and post hoc comparisons. The molecular interpretation considered established pathways involving SLC5A2, which encodes SGLT-2, and renal urate transporters including SLC22A12 (URAT1) and SLC2A9 (GLUT9). Results: At baseline, mean eGFR was 94.984 ± 3.146 mL/min/1.73 m² in both groups and decreased to 90.984 ± 3.146 in the SGLT-2 group and 92.984 ± 3.146 in the DPP-4 group at 12 months. Serum urea increased from 16.076 ± 0.235 to 17.001 ± 0.254 mg/dL with SGLT-2 therapy, whereas it decreased from 15.438 ± 0.235 to 15.016 ± 0.254 mg/dL with DPP-4 inhibition. Serum creatinine increased from 0.926 ± 0.006 to 0.966 ± 0.005 mg/dL in the SGLT-2 group, compared with a change from 0.939 ± 0.006 to 0.934 ± 0.005 mg/dL in the DPP-4 group; the time-by-treatment interaction was significant (P < 0.001, partial η² = 0.623). Serum uric acid demonstrated a marked reduction with SGLT 2 treatment, declining from 6.739 ± 0.033 to 5.231 ± 0.029 mg/dL, compared with a smaller reduction from 6.514 ± 0.033 to 6.436 ± 0.029 mg/dL with DPP-4 inhibition. The observed urate response is biologically consistent with modulation of proximal tubular transport mechanisms involving SGLT-2 and urate transport pathways. However, no direct genotyping, gene-expression, or molecular assays were performed. Conclusion: SGLT-2 and DPP-4 inhibitors were associated with distinct longitudinal renal biomarker trajectories over 12 months. The prominent reduction in serum uric acid with SGLT-2 therapy may reflect alterations in proximal tubular glucose-sodium-urate handling, providing a biologically plausible link to pathways involving SLC5A2, SLC22A12, and SLC2A9. These molecular and genetic interpretations should be considered mechanistic rather than direct genetic findings and provide a rationale for future pharmacogenomic and molecular investigations of differential renal responses to glucose-lowering therapies

Introduction: Lumbar disc bulge is a common spinal disorder characterized by the radiating pain and functional disability, often associated with radicular symptoms. Mechanical Diagnosis and Therapy (MDT), commonly known as the McKenzie Technique, is widely used to manage discogenic pain by promoting pain centralization and improving spinal mobility. However, there are limited case-based reports that document the effectiveness of McKenzie techniques in chronic disc bulge conditions. Aim: To evaluate the effectiveness of McKenzie back extension technique in reducing pain and improving functional ability in a patient with chronic lumbar disc bulge. Materials and Methods: A 36-year-old male patient diagnosed with chronic lumbar disc bulge was selected for the case study. The study intervention consisted of McKenzie back extension techniques performed regularly for a duration of seven weeks. The patient was assessed pre- and post- intervention using the Visual Analogue Scale (VAS) for pain and the Oswestry disability index (ODI) for functional disability. Results: At the end of seven weeks, the patient demonstrated significant reduction in pain scores and improvement in functional ability. Pain was centralized from distal region to lumbar spine, and ODI scores indicated marked improvement in daily activities. Conclusion: McKenzie back extension techniques proved effective in reducing pain intensity, centralizing symptoms, and improving functional disability in a patient with chronic lumbar disc bulge. Keywords: McKenzie Back Extension Technique, low back pain, centralization, Visual Analogue Scale, Oswestry Disability Index

Introduction: Thyroid nodules are common endocrine disorders. Fine Needle Aspiration Cytology (FNAC) is widely used as an initial diagnostic tool for evaluating thyroid lesions. Histopathology remains the gold standard for definitive diagnosis. Aim: To study the cytohistopathological correlation of thyroid lesions and evaluate the diagnostic accuracy of FNAC. Materials and Methods: This study included 320 patients presenting with thyroid swelling who underwent FNAC evaluation. Surgical specimens were available in 43 cases and were subjected to histopathological examination. Cytological diagnosis was correlated with histopathological findings and diagnostic indices such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. Results: Out of 43 surgically excised thyroid lesions, 33 cases (76.9%) were benign and 10 cases (23.1%) were malignant on histopathology. FNAC showed high diagnostic performance with sensitivity of 100%, specificity of 99.3%, positive predictive value of 91.6%, negative predictive value of 100%, and overall diagnostic accuracy of 99.35%. Conclusion: FNAC is a highly sensitive and specific diagnostic tool for evaluating thyroid lesions and shows excellent correlation with histopathological findings.