JSS Academy of Higher Education & Research

Kamrul-Hasan A.B., Borozan S., Fernandez C.J., Dutta D., Nagendra L., Pappachan J.M.

Aims/Background Data from randomized controlled trials (RCTs) comparing the efficacy and safety of thrice-weekly insulin degludec (IDeg 3TW) versus once-daily insulin glargine (IGlar OD) in patients with type 2 diabetes mellitus (T2DM) are scarce and not uniform. Moreover, no systematic review and meta-analysis (SRM) is available for such a comparison. This SRM aimed to compare the effectiveness and safety of IDeg 3TW versus IGlar OD in the available RCTs in T2DM. Methods Electronic databases and registers, which include MEDLINE (via PubMed), Scopus, Cochrane Central Register, and ClinicalTrials.gov, were searched for RCTs conducted among T2DM subjects with IDeg 3TW as intervention and IGlar OD as control from inception to 30 July 2024. The primary outcome was glycated haemoglobin (HbA1c) reduction from baseline; secondary outcomes were the changes in other glycemic parameters and adverse events (AEs). RevMan web was used to conduct meta-analysis using random-effects models. Outcomes were presented as mean difference (MD), odds ratio (OR), or risk ratio (RR) with 95% confidence intervals (CIs). Results Three RCTs (N = 1171) with study durations ranging from 16–26 weeks and minimal risk of bias were included. IDeg 3TW was less effective than IGlar OD in HbA1c reduction (MD 0.27%, 95% CI [0.14, 0.39], p < 0.0001), reduction in mean nine-point self-monitored capillary blood glucose profile (MD 0.45 mmol/L, 95% CI [0.22, 0.67], p < 0.0001), and HbA1c reduction <7% (OR 0.69, 95% [0.53, 0.89], p = 0.005). IDeg 3TW outperformed IGlar OD regarding the mean daily insulin dose (MD –0.07 U, 95% CI [–0.13, –0.01], p = 0.02). However, both groups achieved comparable fasting plasma glucose reduction (MD 0.37 mmol/L, 95% [–0.19, 0.93], p = 0.19), changes in body weight (MD 0.04 kg, 95% CI [–0.46, 0.55], p = 0.86), and overall physical (MD 0.21, 95% CI [–0.62, 1.04], p = 0.62) and mental health scores (MD –0.02, 95% CI [–1.05, 1.01], p = 0.97). The risks for confirmed hypoglycemia (RR 1.16, 95% CI [0.83, 1.62], p = 0.38), nocturnal hypoglycemia (RR 1.18, 95% CI [0.49, 2.84], p = 0.71), any AEs (RR 1.04, 95% CI [0.84, 1.30], p = 0.71), serious AEs (RR 1.43, 95% CI [0.77, 2.65], p = 0.25), and injection-site reactions (RR 1.29, 95% CI [0.56, 2.96], p = 0.55) were identical in the two groups. Conclusion In short-term follow-up, IDeg 3TW was less effective than IGlar OD in glycaemic control; however, their safety profile was comparable. Larger multicenter RCTs comparing the overall benefit-risk ratio are necessary for appropriate clinical practice decisions. Systematic Review Registeration PROSPERO: CRD42024593493 .

Chand J., Fanai H.L., Ahmad S.F., Al‐Mazroua H.A., Emran T.B.

ABSTRACTTriple‐negative breast cancer is highly aggressive, with limited treatment options and high resistance to existing therapies. Liriodenine, a natural alkaloid, shows potential as an anticancer agent, but its therapeutic mechanisms require further investigation. This study aimed to explore liriodenine's potential as a multi‐target therapeutic agent for breast cancer. Molecular docking and dynamics simulations were conducted to assess liriodenine's interactions with key targets. Functional enrichment and pathway analyses were used to identify its involvement in critical processes such as cell proliferation, survival, and metastasis. Liriodenine exhibited strong binding affinity and stable interactions with epidermal growth factor receptors and modulated pathways such as PI3K‐Akt, JAK‐STAT, and angiogenesis. It targeted multiple breast cancer‐related proteins, including mTOR, STAT3, and SRC, critical in tumor growth, immune evasion, and metastasis. Liriodenine shows promise as a multi‐target agent for breast cancer therapy, with potential enhanced by structural optimization and the integration of computational and experimental approaches to improve specificity, bioavailability, efficacy, and safety. Overall, the current study provides a compelling rational for further preclinical validations to establish liriodenine's as a promising natural compound for breast cancer treatment, suggesting further in vitro and in vivo evaluation to identify antiproliferative and apoptosis activity.

Paramakrishnan N., Raadhika K., Elayaperumal S., Sivamani Y., Paramaswaran Y., Siang L.J., Venkata Rathina Kumar T., Lim K.G., Ramesh M., Muthuraman A.

Trigeminal neuralgia is a chronic pain disorder due to neuronal damage. The present study was designed to investigate the effect of 7,8-dimethoxy coumarin (DMC) in a rat model of trigeminal neuralgia. The neuropathic pain was induced by the single endoneural injection of tumor necrosis factor-alpha (TNF-α; 0.1 μL: stock 10 pg/mL) in the rat trigeminal nerve. The DMC (100 and 200 mg/kg) and carbamazepine (100 mg/kg) were administered orally for 10 consecutive days from the 5th day of TNF-α injection. The battery of behavioral tests, i.e., acetone drop and Von Frey filament test, was performed to assess the degree of thermal and mechanical allodynia on 0, 1st, 7th, and 14th days. In addition, the biochemical tests, i.e., total protein, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and TNF-α, were also performed in trigeminal nerve tissue. Furthermore, TNF-α-induced neuronal histopathological changes were also evaluated by the eosin and hematoxylin staining method. The administration of DMC was shown to demonstrate the significant (p < 0.05) reversal of TNF-α-induced percentage reduction of thermal and mechanical sensitivity, along with a rise in TBARS and TNF-α and a decrease in GSH levels. Further, DMC also attenuates the histopathological changes. It may be concluded that DMC may be a potential therapeutic agent for the management of trigeminal neuralgia disorders.

Archana S.S., Abdul Khader M., N P., Dharwadkar S., Prashant A., Nagendra L., Ramu V.

17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency is a rare autosomal recessive disorder that impairs testosterone synthesis, leading to undervirilisation in 46,XY individuals. An individual in their early 20s, raised as female, developed male secondary sexual characteristics at puberty. Evaluation revealed a 46,XY karyotype. Hormonal and genetic analyses confirmed the diagnosis of 17β-HSD3 deficiency, showing the homozygous HSD17B3 mutation and a decreased testosterone-to-androstenedione ratio. Despite identifying as male, the patient opted against gender-affirming therapy, citing cultural and financial constraints as reasons for disinterest in further management. This reluctance emphasises the challenges of managing rare disorders of sex development (DSD) in resource-limited countries like India, compounded by limited awareness, social stigma and inadequate access to gender-affirming care. Psychosocial counselling was initiated to address gender dysphoria and educate the patient on long-term risks, including malignancy. However, the patient disengaged from follow-up discussions. This case highlights the importance of multidisciplinary care and societal support in addressing the needs of individuals with DSD.

Chand J., Fanai H.L., Ahmad S.F., Attia S.M., Emran T.B.

AbstractBreast cancer is driven by complex oncogenic mechanisms, including aberrant signaling pathways and genetic mutations. Current therapies often face limitations, such as drug resistance and adverse effects, necessitating the identification of novel therapeutic agents. Protopine, known for its anticancer properties in other malignancies, remains unexplored for breast cancer. This study investigates the therapeutic potential of protopine in breast cancer by examining its effects on critical molecular targets and signaling pathways involved in tumor progression and metastasis through computational pharmacological approaches. Breast cancer‐associated targets were identified, and protopine's binding affinity for PIK3CA was evaluated using molecular docking and molecular dynamics simulations. Binding stability and dynamics were assessed using RMSD, hydrogen bonding analysis, and MM‐PBSA energy calculations. Protopine exhibited multitargeted activity, interacting with 17 breast cancer‐associated targets, including PIK3CA, CHEK1, and CDK2. It modulated critical pathways such as PI3K‐Akt, JAK‐STAT, and VEGF, disrupting processes like cell proliferation and angiogenesis. Molecular docking showed strong binding affinity for PIK3CA (−9.2 kcal/mol), while molecular dynamics confirmed stable binding with favorable free energy (−6.71 ± 0.64 kcal/mol). Protopine demonstrated significant therapeutic promise as a multitargeted agent, modulating key oncogenic pathways and providing the potential to overcome resistance and improve breast cancer therapies.

Senthilnathan R., Das N., Ismail A., Borade R.R., Subbappa A., Anand L.S.

ABSTRACT Objective: This study evaluated the ability of Fibro-Gide® and Mucoderm® collagen matrices to stimulate fibroblast proliferation. Materials and Methods: The study tested two collagen matrices, Mucoderm® and Fibro-Gide®, on human gingival fibroblasts. Surface roughness, cell viability, and collagen quantities were measured using profilometers and ELISA. Results: Fibro-Gide® outperformed Mucoderm® in terms of surface roughness (2.75 μm) and cell survival, while ELISA findings showed a greater collagen type and a higher optical density (0.920 OD). Conclusion: Fibro-Gide® showed better fibroblast proliferation and extracellular matrix production, indicating promise for tissue regeneration and remodeling in periodontal and peri-implant applications, while Mucoderm® remains viable.

Kondaveeti D., Badvel J.K., Rayana S., Thommandru S., Chandra R., Yerrakula G., Gollamudi S., Konganti B.N., Pennepalli S.T., Yanda S., Mahasamudram Sreehari S., Chatragadda P.

Anaemia refers to the common blood disorder that affects around one-third of the world's population. Infection risk is raised due to a lack of knowledge about anaemia. The aim of the study: The aim of the study is to examine patient knowledge, attitude, practice, and prescription trends regarding anaemia among patients. Also, to identify a correlation between haemoglobin levels and KAP score among patients. Materials and methods: A prospective observational study was carried out in 133 in-patients admitted to SVIMS Hospital, General Medicine department diagnosed with anaemia for 6 months. Patient data were gathered through a review of their medical case records to evaluate prescribing patterns, while a structured and validated questionnaire was used to conduct face-to-face interviews with the patients, aiming to assess their knowledge, attitudes, and practices regarding anaemia. Results: Males comprised 38 (29%) and females 95 (71%). For microcytic hypochromic anaemia, Tablet. Ferrous fumarate with tablet folic acid and Inj. Eldervit were prescribed 64 times. Vitamins and folic acid (23 prescriptions). KAP scores were linked to haemoglobin. Hb levels were inversely connected with patients' knowledge scores (p < 0.05). Highly conclusive, patients' attitude assessments and Hb levels were positively correlated (p < 0.05). Practice score and Hb levels correlated positively (p < 0.05). Conclusions: According to this study, anaemic individuals' medicine prescription behaviours should be monitored. Anaemia awareness should be enhanced

Shetty S.K., Saran T., Prakash S.

Roychowdhury P., Prajapati G.K., Singh R., Gurunath P., C R., Kuppuswamy G., De A.

Background: Ulcerative colitis (UC) is a chronic inflammatory condition associated with the colon and rectum, often predisposing individuals to inflammatory bowel disease-related colorectal cancer (IBD-CRC). Current therapeutic options for UC, including corticosteroids and immunosuppressive drugs, pose significant side effects. Punica granatum peel powder (PPPG), a traditional herbal remedy in Ayurveda medicine for colitis, exhibits promising therapeutic effects with a favorable safety profile. Objectives: This study aims to explore the therapeutic potential and mechanism of action of a modified PPPG formulation in UC treatment. Methods: Using NCM460 cells and an acetic acid-induced UC murine model, the efficacy of modified PPPG was evaluated. Results: Therapy with modified PPPG significantly improved UC-associated symptoms, such as improvements in body weight, colon length, and disease activity index, as validated by histological examination. Transcriptomic sequencing identified downregulation of the IL-6/STAT3 signaling pathway and reduced inflammatory markers like p-NF-κB, IL-1β, and NLRP3 on PPPG therapy. Conclusions: These findings suggest that modified PPPG holds promise as a novel therapeutic strategy for UC intervention, targeting key inflammatory pathways implicated in UC pathogenesis and potentially mitigating the risk of IBD-CRC.

Gupta S., Nagar L., Singla M., - S., Singh S., Gupta G., Bhojraj S., Syed R.U., Alshammari A.D., Alshammari M.D., Alshammari N.N., Alshammari A.N., Alhaidan E.M.

Background: This research explored the antimicrobial, antifungal, and in vivo anticandidal activities of two herbal extracts: Ocimum basilicum (HEOB) and Ocimum sanctum (HEOS). Additionally, the study analyzed the phytochemical components of these extracts. Aim: To examine the efficacy of HEOB and HEOS extracts in terms of their antimicrobial, antifungal, and anti-candidal activities and analyze their phytochemical composition, antioxidant potential, and immunomodulatory properties in vivo. Methods: Dried flowers and leaves from Ocimum basilicum and Ocimum sanctum were extracted using a cold maceration process with a 1:1 ethanol-water solution. Phytochemical analysis followed established protocols, and the total phenolic and flavonoid contents were measured using colourimetric methods. HPLC was used to determine the concentrations of specific compounds, including rosmarinic acid, rutin, eugenol, and quercetin. Antioxidant activity, specifically nitric oxide (NO) scavenging and antimicrobial properties, was assessed in vitro using the cup plate method. In vivo studies were conducted on immunocompromised mice with systemic candidiasis, treated with plant extracts at 200 and 400 mg/kg or with ketoconazole as a control. Survival rates, tissue histology, and leukocyte counts were evaluated, and statistical analysis was performed using ANOVA. Results: HEOB and HEOS extracts possess strong antimicrobial and antioxidant activities, largely due to flavonoids such as rutin, quercetin, rosmarinic acid and eugenol. In vivo experiments revealed that both extracts effectively reduced fungal load, increased survival rates, and alleviated immunosuppression in mice with systemic candidiasis. The extracts also exhibited significant immunomodulatory properties by boosting cellmediated immune responses. At higher concentrations, the antifungal performance of HEOB and HEOS was similar to that of ketoconazole. result: HEOB and HEOS extracts possess strong antimicrobial and antioxidant activities, largely due to phenolic compounds and flavonoids such as eugenol, rosmarinic acid, quercetin, and rutin. In vivo experiments revealed that both extracts effectively reduced fungal load, increased survival rates, and alleviated immunosuppression in mice with systemic candidiasis. The extracts also exhibited significant immunomodulatory properties by boosting cell-mediated immune responses. At higher concentrations, the antifungal performance of HEOB and HEOS was similar to that of ketoconazole. Conclusion: HEOB and HEOS exhibited strong antibacterial, antifungal, and anticandidal properties, showing significant effectiveness in treating systemic candidiasis. Their immunomodulatory effects and ability to boost cell-mediated immunity make these extracts promising options for addressing systemic candidiasis, particularly in individuals with weakened immune systems. This research offers valuable insights and sets the stage for future investigations into the treatment of oral and vaginal candidiasis.

Saravanan T., Selvinthanuja C., Jubie S., Kathiravan M.K., Thilagavathy R., Ravichandran V., Prabha T.

Background: The thiazole nucleus serves as a bioactive synthetic scaffold in drug design and discovery due to its diverse pharmacological activities. It was discovered that many types of thiazole derivatives, including those with one, two, or three substitutions, five- or six-membered heterocycles, fused rings, and thiazole-derived Schiff bases, hydrazinyl derivatives, amides, chalcones, and bis-thiazoles, can fight cancer. Thus, the structural diversity of thiazole nuclei makes it one of the significant areas of research in the pharmaceutical field. Objective: We would like to elaborate on the recent literature available on the antiproliferative property of molecules bearing 1,3-thiazole nuclei. Methods: This review summarises the anticancer potency of thiazole derivatives collected from recently available scientific literature. We extracted the information from online data-bases like PubMed, Scopus, and Web of Science using relevant keywords from 2016 to the present. We discuss the current state of thiazole derivatives and highlight the most promising compounds. We also describe how they work and what their half-maximum inhibitory con-centration (IC50) is. Results: Based on our extensive literature review, we found that thiazole derivatives exhibit anticancer activity through their ability to induce apoptosis in cancer cells, mitochondrial membrane disruption by blocking signalling pathways such as Akt, NFkB, PI3K, and Src/Abl, and inhibition of proteins responsible for cell growth. Moreover, thiazole-protein interactions essential for cancer inhibition are predominantly regulated by hydrogen bonding, supported by the sulphur and nitrogen atoms in the thiazole molecule, which effectively interacts with the amino acids serine, tyrosine, and glutamine. π–π stacking and π–cation interactions involv-ing aromatic amino acids such as tryptophan, tyrosine, and phenylalanine, along with hydro-phobic effects and van der Waals forces, play a crucial role in thiazole–protein interactions. These interactions dictate binding affinity and efficacy, measured through thermodynamic characteristics such as Binding Constant (Kb), Dissociation Constant (Kd), and Gibbs free energy (ΔG). Comprehending these features is essential for the development of effective thia-zole-based anticancer pharmaceuticals. Conclusion: This cumulative information is enough to give new ideas for the rational drug design of thiazole-based derivatives and could be pursued as a promising lead in the future for the management of cancer threats.

Prathyusha P., Nihaa J., Vinutha R., Ranugha P., Srilakshmi N., Veeranna S., Kanthraj G.R.

Background Point counting serial image index (PCSI) is a scoring method used to assess the area and severity of melasma. Double tracing and the inability to assess scattered pigmentation are its limitations. Objectives To propose modifications to PCSI, the Box counting serial image index (BCSI) was compared and validated with PCSI. Methods In BCSI, a preset grid was placed, and serial images were captured. One speck of pigmentation was counted as one box. The area involved and time taken were recorded by the principal investigator and coinvestigator using BCSI and PCSI methods, respectively. The intensity of the pigmentation was recorded on a scale of 0-5. Melasma score = Area x Intensity of pigmentation. The difference in the total scores and time taken were analysed. Results A significant decrease (p<0.0003) in the total scores between baseline and first follow-up and baseline and second follow-up was observed in both methods. Similarly to PCSI, BCSI was found to be sensitive to changes over time with treatment (p<0.0003). These p values were recalculated using Bonferroni corrections. The mean time taken by PCSI was significantly higher than BCSI (p < 0.0003). Limitations Grid placement over bony prominences and interference of facial hair. Conclusion BCSI overcomes the limitations of PCSI by directly capturing images and it is easy and rapid.

Sankova M.V., Nikolenko V.N., Bolotskaia A.A., Oganesyan M.V., Rizaeva N.A., Sankov A.V., Zharikova T.S., Pontes-Silva A., Beeraka N.M., P.R. H.V., Y. P.R., Kandula D.K., Gurupadayya B., Zharikov Y.O.

Background: The human intestine is continuously exposed to a variety of aggressive agents, including food antigens, xenobiotics, numerous pathogenic microorganisms, metabolic products, and toxins. Consequently, it has developed a specialized system for protection against these adverse factors. Objective: This study aims to investigate the biochemical compounds synthesized by Paneth cells and their mechanisms of action to develop new therapeutic approaches for gastroenterological diseases. Methods: We conducted a systematic review, excluding a comprehensive meta-analysis, of the current scientific literature sourced from electronic libraries (CyberLeninka, e-Library.ru, and Cochrane Library), search engines (Google Scholar, Embase, and Global Health), and scientific databases (Elsevier, Medline, PubMed-NCBI, and Scopus). Following PRISMA guidelines, a total of 104 articles were initially selected based on defined inclusion and exclusion criteria. After careful evaluation, 63 articles were included in this study. Results: Our findings indicate that Paneth cells play a crucial role in regulating small intestine homeostasis by secreting numerous biologically active molecules. A key feature of these cells is their ability to recognize soluble microbial products via pattern recognition receptors and respond by releasing a variety of antimicrobial peptides and enzymes. These secretions contribute to the formation of a biochemical barrier that prevents pathogen adhesion and translocation. Paneth cells are integral to immunological protection, maintaining protective inflammatory responses under both normal and pathological conditions. Additionally, they regulate the division, growth, and differentiation of intestinal stem cells, ensuring proper enterocyte localization. Paneth cells also aid digestive processes through enzyme secretion and are the only epithelial cells capable of eliminating activated autoreactive lymphocytes and abnormal enterocytes. Conclusion: Paneth cells are unique epithelial cells that, through the synthesis of numerous biologically active molecules, control the timely regeneration of the intestinal epithelium, maintain a healthy microbiota, and prevent infectious, autoimmune, and cancerous diseases. Understanding their role in these processes is crucial for developing new therapies for gastroenterological diseases.

Singh V., VishnoI M., Verma N., Maurya M., Kumar V., Bharat N., Bansal A.

Hybrid composites offer advantages over single composites due to their superior properties and ease of processing. In this research, the mechanical and surface characterization of a hybrid composite based on AA6063 was carried out, reinforced with 5 wt.% Silicon Carbide and varying concentrations of Erbium Oxide at 0, 2, 4, and 6 wt.%, fabricated using the stir casting technique. The composite with 4 wt.% Er 2 O 3 exhibited the highest tensile strength of 134 MPa and a maximum hardness of 58 HV, representing improvements of 17.16% and 24.14%, respectively, over the unreinforced alloy. Cavitation erosion resistance also improved significantly, with a mass loss reduction of 74.2%, from 26.29 g (AA6063) to 6.78 g in the optimized composite. These enhancements were attributed to refined microstructure, reduced porosity, and improved reinforcement dispersion, as confirmed through SEM, XRD, and EDAX analyses. Overall, the study underscores the potential of Er 2 O 3 -SiC-reinforced AA6063 composites in structural and erosive environments.

Gupta S., Sharma B.B., Pathak P.K., Prakash V., Chawda S., Sharma S.