Ashok Kumar Balaraman

Parkinson's Disease (PD) is a progressive neurodegenerative disorder. The existing regimen fails in halting the disease progression. The purpose of this study is to explore the molecules that possess neuroprotection properties and attenuate disease progression. L-carnosine is reported to have antioxidative, anti-inflammatory, and anti-apoptotic properties, hence selected as an experimental compound. In this experiment, a rotenone standard dose was administered as a neurotoxin to induce PD in rats. Treatment groups received a solution of L-carnosine, 200mg/kg and 300mg/kg, through oral gavage for 28 consecutive days concurrently with rotenone. The key symptomatic behavioral parameters that reflect PD were assessed. In addition, evaluation of oxidative homeostasis, extent of Lewy body and Neurofibril tangles formation, and quantitative analysis of dopamine in the striatum were conducted. According to the study, L-carnosine supplementation improved all the assessed behavioral parameters in addition to cellular events. The antioxidant markers- glutathione (GSH), superoxide dismutase (SOD), and catalase showed a significant elevation, whereas the oxidative stress markers- nitrite, malondialdehyde (MDA), and advanced oxidation protein product (AOPP) exhibited suppression. Bielschowsky’s modified silver staining technique showed the reduction of Lewy bodies and neurofibrillary tangles in the L-carnosine-treated rats’ SNpc area. The HPLC data suggested that dopamine quantity was increased in the striatum of L-carnosine-treated rats. Evidence from this study indicates that L-carnosine exhibited considerable neuroprotective properties, suggesting its potential as a therapeutic adjuvant to the existing therapeutics for efficient PD management.

The primary purpose of this review is to explore the green synthesis of silver nanoparticle (AgNP) using natural biomolecules derived from marine sources. This review aims to evaluate the effectiveness of environmentally friendly approaches for synthesizing AgNPs and to examine their potential applications across various fields such as medicine, biotechnology, and environmental remediation. The key research question focuses on understanding how marine biomolecules, including polysaccharides, proteins, enzymes, amino acids, alkaloids, and vitamins, contribute to the formation of AgNPs and how these green-synthesized nanoparticles retain their functional properties. This review systematically examines current literature on the green synthesis of AgNPs, focusing on marine-derived biomolecules such as polysaccharides, proteins, and alkaloids. The methodology includes analyzing green synthesis techniques and comparing them with traditional chemical methods to highlight environmental benefits and overall efficiency. Various marine species, such as seagrass and seaweed, are explored as potent agents in the reduction of silver ions. The findings reveal that green synthesis of AgNPs using marine biomolecules is not only environmentally sustainable but also retains the desirable properties of the nanoparticles, such as antimicrobial, antioxidant, and anticancer activities. Additionally, the green-synthesized AgNPs show significant potential applications in mosquito control, wound healing, and anticancer therapies. Green synthesis of AgNPs using marine sources presents a viable and sustainable alternative to conventional chemical methods, significantly reducing the environmental impact of nanoparticle production while ensuring biocompatibility and functional integrity. This approach holds promise for diverse applications in biomedicine, environmental remediation, and beyond. Further research is recommended to address challenges in scaling up production and commercialization.

Background: Chemoresistance is a significant barrier to combating head and neck cancer, and decoding this resistance can widen the therapeutic application of such chemotherapeutic drugs. This systematic review and meta-analysis explores the influence of microRNA (miRNA) expressions on chemoresistance in head and neck cancers (HNC). The objective is to evaluate the theragnostic effects of microRNA expressions on chemoresistance in HNC patients and investigate the utility of miRNAs as biomarkers and avenues for new therapeutic targets. Methods: We performed a comprehensive bibliographic search that included the SCOPUS, PubMed, and Science Direct bibliographic databases. These searches conformed to a predefined set of search strategies. Following the PRISMA guidelines, inclusion and exclusion criteria were framed upon completing the literature search. The data items extracted were tabulated and collated in MS Excel. This spreadsheet was used to determine the effect size estimation for the theragnostic effects of miRNA expressions on chemoresistance in HNC, the hazard ratio (HR), and 95% confidence intervals (95% CI). The comprehensive meta-analysis was performed using the random effects model. Heterogeneity among the data collected was assessed using the Q test, Tau², I², and Z measures. Publication bias of the included studies was checked using the Egger’s bias indicator test, Orwin and classic fail-safe N test, Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill methods. Results: After collating the data from 23 studies, dysregulation of 34 miRNAs was observed in 2189 people. These data were gathered from 23 studies. Out of the 34 miRNAs considered, 22 were up-regulated, while 12 were down-regulated. The TaqMan transcription kits were the most used miRNA profiling platform, and miR-200c was seen to have a mixed dysregulation. We measured the overall pooled effect estimate of HR to be 1.516 for the various analyzed miRNA at a 95% confidence interval of 1.303–1.765, with a significant p-value. The null hypothesis test’s Z value was 5.377, and the p-value was correspondingly noted to be less than 0.0001. This outcome indicates that the risk of death is determined to be higher in up-regulated groups than in down-regulated groups. Among the 34 miRNAs that were investigated, seven miRNAs were associated with an improved prognosis, especially with the overexpression of these seven miRNAs (miR15b-5p, miR-548b, miR-519d, miR-1278, miR-145, miR-200c, Hsa- miR139-3p). Discussion: The findings reveal that intricate relationships between miRNAs’ expression and chemotherapeutic resistance in HNC are more likely to exist and can be potential therapeutic targets. This review suggests the involvement of specific miRNAs as predictors of chemoresistance and sensitivity in HNC. The examination of the current study results illustrates the significance of miRNA expression as a theragnostic biomarker in medical oncology.

For systemic drug delivery, the buccal region offers an attractive route of drug administration. Salbutamol sulfate is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It's oral bioavailability is ∼40% due to extensive first pass metabolism. Salbutamol sulfate patches were prepared using Eudragit L-100, HPMC, PVA and Carbopol 934 in various proportions and combinations using PEG-400/PG as plasticizers. Patches were laminated on one side with a water impermeable backing layer for unidirectional drug release. The thickness of medicated patches were ranged between 0.23 ± 0.008 and 0.59 ± 0.007 mm and mass varied between 65.23 ± 3.3 and 117.92 ± 4.2 mg. Patches showed an increase in mass and swelling index with PEG-400 when compared with PG. The surface-pH of patches ranged between 6 and 7. Formulations E7 (7.5 mL Eudragit L-100, 15 mL HPMC K4M, 7.5 mL PVA and 2 mL PEG-400), E12 (7.5 mL Eudragit L-100, 7.5 mL PVA, 15 mL Carbopol and 2 mL PEG-400), F7 (7.5 mL Eudragit L-100, 15 mL HPMC K4M, 7.5 mL PVA and 2 mL PG), and F12 (7.5 mL Eudragit L-100, 7.5 mL PVA, 15 mL Carbopol and 2 mL PG) showed high folding endurance. Residence time of the tested patches ranged between 101 and 110 min. The maximum in vitro release was found to be 99.93% over a period of 120 min for formulation F12. Data of in vitro release from patches were fitted to different kinetic models such as Higuchi and Korsmeyer-Peppas models to explain the release profile. Formulations E7 and F7 were best fitted to the non-Fickian, where as formulations E12 and F12 showed Fickian/anomalous drug release. Stability studies indicated that there was no change in the chemical and physical characteristics during the test period.

Abstract: Mucoadhesive buccal patches of Salbutamol Sulphate were prepared using five different polymers (polyvinyl pyrrolidone [PVP]), polyvinyl alcohol [PVA], water soluble chitosan [CHWS], acid soluble chitosan [CHAS], hydroxypropyl methyl cellulose [HPMC]) in various proportions and combinations (CHWS/PVP/HPMC, CHWS/PVA/HPMC, CHAS/PVP/HPMC, and CHAS/PVA/HPMC). A 32 full factorial design was used to design the experiments. A total of 72 patches were prepared. Thickness of the patches ranged between 0.3±0.003 and 0.6±0.009 mm. Mass of the patches were in the range of 68.12±4.6 to 95.52±5.0 mg. Patches showed increased mass whenever PEG -400 was used as plasticizer. The surface pH of patches were acidic to neutral (pH 4-pH 7). Patches showed satisfactory drug loading efficiency (85% to 97%). Eight formulations (C9, C18, C27, C36, D9, D18, D27 and D36)-which showed high folding endurance- were selected for further characterization. Patches with PEG -400 showed higher swelling index when compared to PG. The residence time of the patches ranged between 115 min and 120 min. Formulation C18 showed the maximum in vitro drug release of 101.4 % over a period of 120 min. Formulations D36 and C36 were best fitted to Higuchi model. The remaining formulations were best fitted to the Korsmeyer-Peppas model. Drug permeation was fast and showed the similar profile as that of the in vitro drug release. Patches were stable, during and at the end of the accelerated stability study.