As one of the seven National Institutes of Pharmaceutical Education and Research (NIPERs) it is granted the Institute of National Importance status. It offers 2-year MS (Pharm.) programmes and doctoral programmes in pharmaceutical sciences. On 2016 Institute pact with Sanofi India to promote academic excellence and research in the areas of pharmaceuticals and consumer healthcare products, to cater to the current and future needs of the pharmaceutical industry.
Aging, a complex physiological and molecular process, has undergone significant changes, of which gut microbiome composition has surfaced as an important key in the maintenance of neurological health. Recent studies have revealed the significant impact of age-related gut dysbiosis in the induction of neuroinflammation, metabolic syndrome, disruptions in gut-brain axis, and age-related neurological decline. Although significant studies have revealed the impact of the microbiome-gut-brain axis in individual neurological diseases, an aging-focused holistic synthesis has not yet been adequately developed. This review provides a critical assessment of the involvement of age-related dysbiosis of gut microbiota in the development and progression of neurological disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and cognitive aging of the elderly, and to focus on age-related microbial patterns and mechanisms of dysbiosis related to neurological aging, including inflammation and immune system dysregulation, metabolic changes, oxidative stress, barrier dysfunction, and gut-brain communication through enteroendocrine, enteric neural, and vagal mechanisms, and to emphasize disease-specific and common microbial patterns of dysbiosis and beneficial and harmful microbial roles in aging diseases. This review assesses some of the latest promising therapies aimed at the microbiota, such as probiotics, prebiotics, dietary therapies, fecal microbiota transplantation, as well as pharmacological therapies, and critically discusses their limitations in terms of interindividual variability and their generalisation and applicability. Focusing on mechanistic, comparative, and translation aspects, this review offers a comprehensive approach to neurological aging due to gut microbiota and identifies gaps for future precision microbiome-based interventions.
Liver disease is a severe health issue that is alarmingly common throughout the world. The current investigation sought to evaluate and compare two veterinary formulations—Dozliv Forte-P (Treatment group 1) and Dozliv Forte-P Ultra (Treatment group 2)—for their hepatoprotective potential in a carbon tetrachloride (CCl₄)-induced liver injury model. Hepatoprotective properties of both the treatment groups were evaluated in Wistar albino rats at a dosage of 0.25 ml/kg/day per os (p.o.). The level of protection was assessed by identifying the marker enzymes (SGOT, SGPT). Additionally, to assess antioxidant activity, the effects of the treatment groups on glutathione (GSH), catalase (CAT), nitrite level, and lipid peroxidation (LPO) have been estimated in liver homogenates. The biochemical markers, such as SGOT (serum glutamate-oxaloacetate transaminase) and SGPT (serum glutamate-pyruvate transaminase), which were increased by carbon tetrachloride (CCl4) intoxication, significantly decreased in the animal groups receiving Dozliv Forte-P, Dozliv Forte-P Ultra, and Silymarin. Hepatic antioxidant enzyme levels, including GSH and catalase, dropped following CCl4 injection, and hepatic lipid peroxidation and nitrite level increased. Therapy with Treatment group 1, Treatment group 2, and Silymarin restored normal levels of these liver antioxidant enzymes. The biochemical results were corroborated by histological investigations, and Dozliv Forte-P and Dozliv Forte-P Ultra therapies successfully demonstrated hepatoprotective potential in rats. Additionally, both Dozliv Forte-P and Dozliv Forte-P Ultra significantly decreased the CCl₄ group’s activity; but Dozliv Forte-P Ultra’s effects were more pronounced, demonstrating greater hepatoprotective efficacy.
Vitiligo is a chronic autoimmune skin disease characterized by the selective destruction of melanocytes, resulting in depigmented macules and patches. Tofacitinib citrate (TC), a Janus kinase 1/3 (JAK1/3) inhibitor, has emerged as a capable therapeutic agent for vitiligo therapy; however, its oral administration is associated with systemic side effects. Therefore, in the present investigation, tofacitinib citrate-loaded functional nanostructured lipid carriers (TC-F-NLCs) enriched with perillyl alcohol were scaled up using the hot emulsification technique under the framework of face-centered central composite design. Next, TC-F-NLCs were assessed for particle size (133.8 +/- 1.99 nm), polydispersity index (PDI; 0.219 +/- 0.008), zeta (zeta) potential (-29.6 +/- 1.17 mV), entrapment efficiency (89.2 +/- 0.03 %), and surface topography. Later, TC-F-NLCs were transformed into tofacitinib citrate-loaded functional nanostructured lipid carriers amalgamated gel (TC-F-NLCs-Gel). TC-F-NLCs-Gel demonstrated a 4.4-fold increment in skin deposition compared to conventional tofacitinib citrate ointment. The therapeutic efficacy of TC-F-NLCs-Gel was assessed in validated experimental vitiligo induced by 40 % w/w monobenzone ointment in C57BL/6 male mice. TC-F-NLCs-Gel revealed enhanced melanogenic potential through elevated melanin synthesis, along with diminished reactive oxygen species (ROS) and nitric oxide (NoX) levels. Moreover, TC-F-NLCs-Gel also suppressed pro-inflammatory cytokine mRNA expressions (JAK1, JAK3, IL-6, IFN-gamma, and IL-1 beta) in experimental vitiligo significantly (One-way ANOVA test, P-### < 0.001), higher than functional nanostructured lipid carriers enriched with perillyl alcohol amalgamated gel (F-NLCs-Gel) used as a placebo. Thus, the additive efficacy offered by TC-F-NLCs-Gel enriched with perillyl alcohol in promoting re-pigmentation in experimental vitiligo may be attributed to the inhibition of the JAK/STAT pathway, in addition to the attenuation of oxidative stress markers. Hence, TC-F-NLCs-Gel may be a potential candidate for translating into a clinically viable nanopharmaceutical product.
A facile one-pot annulation method for the synthesis of diverse bioactive thiazole/benzothiazole-based isoquinolin-1(2H)-one frameworks was accomplished. This approach involves the Ullman-type coupling of halo-substituted phenyl thiazolamides with various alkyl cyanoacetates employing copper (II) chloride as sustainable catalyst and water as co-solvent. Further, in silico studies were revealed the compound's selectivity towards kinase inhibition. Eventually, these derivatives were evaluated for their in vitro cytotoxicity against various cancer cell lines such as MCF-7, HCT-116, A549, HEPG-2, and HEK-293 (normal cell line). Among them, compound 3h has displayed significant cytotoxicity with an IC50 value of 7.75 ± 0.37 μM on HCT-116 cell line. Next, the compound 3h has also ability to induce apoptosis, which is examined through various staining assays like AO/EtBr, JC-1, and ROS. An ADP Glo kinase kit is utilised to evaluate the kinase inhibitory activity with most potent compound 3h, and showed an IC50 value of 1.94 μM, which is comparable to that of the standard drug sunitinib (IC50 of 400 nM). Finally, this straightforward one-pot annulation protocol is amenable in the generation of a library of new thiazole/benzothiazole-based heterocyclic compounds as potential cytotoxic and VEGFR-2 inhibitors in cancer drug discovery.
Nucleic acid-based diagnostics play a crucial role in early and accurate disease detection. However, conventional extraction approaches are expensive, time-consuming, and require complex instrumentation and skilled personnel, which restricts their use in resource-limited settings. To develop and evaluate a simple, low-cost, and equipment-free paper-based microfluidic cassette device for rapid extraction of nucleic acids (DNA and RNA) from biological samples. A paper-plastic cassette was fabricated by laminating filter paper or glass fibre substrates between thermally bonded plastic sheets. The system was tested using Klebsiella pneumoniae (DNA) and HeLa cells (RNA) with different lysis buffer formulations. Extracted nucleic acids were quantified using a Qubit fluorimeter and assessed by gel electrophoresis and PCR amplification. Results were compared with standard commercial extraction kits. Among tested substrates, LF1 combined with lysis buffers 2, 4, and 5 yielded the highest quality DNA and RNA with 260/280 absorbance ratios of approximately 1.8 (DNA) and 2.0 (RNA). The nucleic acid yields were comparable to commercial kits, and the extracted material was suitable for direct downstream applications, including PCR. The developed paper-plastic cassette enables rapid, affordable, and equipment-free extraction of nucleic acids. This platform shows strong potential for point-of-care molecular diagnostics, particularly in low-resource and decentralized healthcare settings.
