👤 Asim Pervaiz

Metabolic dysfunction-associated steatotic liver disease (MASLD) primarily results from dysregulated lipid metabolism in hepatocytes. However, the mechanisms governing hepatic lipid metabolism remain incompletely understood. Our preliminary experiments demonstrated elevated expression of R-spondin 2 (RSPO2), a matricellular protein, in steatotic livers. Therefore, we investigated the role of RSPO2 in MASLD and potential underlying mechanisms. Comprehensive RSPO2 expression was significantly increased in steatotic livers of high-fat diet-fed wild-type ( These findings identify RSPO2 as a key suppressor of hepatic steatosis and fibrosis, and highlight its potential as a therapeutic target for MASLD. Given the hepatic/extrahepatic complications associated with MASLD (metabolic dysfunction-associated steatotic liver disease) and its high prevalence, it is crucial to decipher the precise molecular mechanisms regulating its pathogenesis to identify novel druggable targets. In this study, we demonstrate for the first time that hepatocyte RSPO2 plays a protective role against hepatic steatosis, fibrosis, and inflammation. Show less

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, driven by the accumulation of amyloid-beta plaques and neurofibrillary tangles. It involves the dysfunction of key enzymes such as Acetylcholinesterase (AChE) and β-secretase (BACE1), making them critical targets for therapeutic intervention. In this study we investigated an in-house library of 820 secondary metabolites obtained from Ayurvedic plants against AChE and BACE1 with the aim to discover novel leads for AD. Virtual screening resulted in 15 ligands, mostly belonging to the ursane-type or dammarene-type triterpene saponins of Centella asiatica, reestablishing the potency of this plant in drug discovery against AD. The binding affinities were further verified by molecular dynamics (MD) simulation trajectories, including root mean square fluctuations (RMSF), root mean square deviation (RMSD), hydrogen bonding analysis, Coulomb interaction calculation, Lennard-Jones interactions, and the total interaction energy. Moreover, extensive Principal Component Analysis (PCA) and Gibbs free energy landscape were performed. Our results demonstrated three compounds, namely (S)-eriodictyol 7-O-(6-β-O-trans-p-coumaroyl)-β-d-glucopyranoside, sitoindoside-X and 1,5-di-o-caffeoyl quinic acid as more effective in treating AD due to their comparable drug-like properties. Drug-likeness, structural chemistry, pharmacophore, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis support their potential for future drug development. To establish the effectiveness of these lead compounds against AD, additional experimental testing should be performed. Show less

Colon cancer is reported as third most prevalent malignancy worldwide, while sericin being an antioxidant, is now used in biomedical applications due to its biochemical characteristics and has shown potential efficacy to treat colon cancer. Sericin was isolated by the degumming process followed by the characterization by using FTIR, UV, XRD, and SEM techniques to confirm the successful synthesis of SAgNPs and SChiAgNPs. The male Balb C mice were then divided into 13 groups. Group 1: Control, Group 2: DMH (20 mg/kg) (injected (IP) thrice a week for 14 weeks). Groups 3,4,5: Sericin (S) (100 mg/kg), Sericin silver nanoparticles (SAgNPs) (100 mg/kg), and Sericin Chitosan silver nanoparticles (SChiAgNPs) (100 mg/kg) were given orally for 14 weeks respectively. Groups 6,7,8,9 were considered as preventive groups and were given DMH (IP) + 5-FU (IP), DMH(IP) + S (orally), DMH (IP) + SAgNPs (orally), DMH (IP) + SChiAgNPs (orally) respectively for the period of 14 weeks Groups 10,11,12,13 were considered as treatment groups and were given 5-FU (5 mg/kg) (IP), (S) (100 mg/kg) (orally), (SAgNPs) (100 mg/kg) (orally), (SChiAgNPs) (100 mg/kg) (orally) for a period of first 7 weeks after 7 weeks of DMH administration (IP). After 14 weeks period study, blood samples and colon tissue were used for the analysis of biochemical markers i.e., CEA, CA19-9, TIMP-1, and IL-6, IL-8, IL-27, SOD, CAT, GR, GSH, GST, MDA and MMP-7 via ELISA and histopathological analysis. The UV absorption peaks obtained at 435 and 463 nm indicated the formation of SAgNPs and SChiAgNPs formation respectively. FTIR spectra peaks obtained, indicate NH stretching of primary and secondary amine group), (NH stretching of amine salt) (N=C=S stretching of thiocyanate compound), (CC stretching of alkene), (NO stretching of nitro compound), (SO stretching of sulfonyl chloride), (CN stretching of amine) and (C-O-O stretching) for sericin, SAgNPs, and SChiAgNPs, confirming, the presence of theses functional groups. The XRD pattern revealed that SAgNPs and SChiAgNPs had structure crystalline structures. EDX characterization peaks for SAgNPs indicated the presence of silver along with other elements including; calcium, oxygen carbon, while EDX characterization peaks for SChiAgNPs indicated the presence of silver along with other elements including; oxygen, carbon, sodium, phosphorus, Sulphur and chlorine. SEM analysis showed that SAgNPs are of spherical shape, while the SChiAgNPs displayed the rectangular shape. The results for biomarker analysis indicated significantly elevated levels of CEA, CA19-9, TIMP-1, IL-6, IL-8, IL-27, MDA, and MMP-7 in DMH treated group (p ≤ 0.001) which were decreased significantly in SChiAg(T) (p ≤ 0.001). In contrast, levels of SOD, GR, GSH, CAT and GST were reduced significantly in DMH treated group, which were increased significantly in SChiAg(T) (p ≤ 0.001). The histopathological analysis of proximal and distal parts of colon tissue of the DMH-treated group showed low-grade dysplasia (LGD), and high-grade dysplasia (HGD) while SChiAgNPs improved the histopathological changes induced by DMH. The findings suggest that Sericin Chitosan conjugated silver nanoparticles showed their efficacy against DMH-induced colon cancer, making a potential future in the anticancer research field. Show less