Anuradha Mishra

Introduction: Dopaminergic neuronal loss, mitochondrial dysfunction, oxidative stress, and neurotransmitter imbalance are the hallmarks of Parkinson's Disease (PD), a progressive neurodegenerative disorder. Despite their established antioxidant and neuroprotective qualities, the mechanistic significance of Juglans regia L. and Cardiospermum halicacabum L. in Parkinson's disease remains unclear, especially in the context of extract-based treatment approaches. Methods: Drug-likeness and ADMET properties were evaluated with SwissADME and ADMETlab 3.0, respectively. SwissTargetPrediction was used to predict potential targets of selected phytoconstituents, whereas gene sets associated with Parkinson's disease were mined from Dis- GeNET and GeneCards. Venn analysis was performed to identify overlapping targets for drugs, followed by Protein-Protein Interaction (PPI) network construction using STRING and topological analysis in Cytoscape. Gene Ontology (GO) and KEGG pathway enrichment analysis were performed using DAVID 2021, then a Bioactive Compound-Target-Pathway (BA-TAR-PATH) network was constructed. Molecular docking based on AutoDock Vina was used to predict the binding affinity between the protein and ligand for the top 10 hits; then, molecular dynamics simulation using GROMACS was applied to assess the stability of the protein-ligand complexes. Result: Phytochemical characterization by HPTLC, FTIR, HPLC, and ESI-MS supported the presence of flavonoids, phenolic compounds, tannins, and lipid-associated constituents in the combined extract. Target prediction yielded 355 related compounds and 30 PD-associated genes, identifying five overlapping targets (ACHE, DRD2, MAOB, COMT, and SLC6A3). Molecular docking revealed favourable binding interactions, particularly quercetin-ACHE (-11.4 kcal/mol), while molecular dynamics simulations supported the stability of selected protein-ligand complexes. Discussion: Network analysis highlighted MAOB, COMT, and SLC6A3 as key hub genes. GO and KEGG analyses revealed significant enrichment of dopaminergic synapse, neuroactive ligand– receptor signalling, and Parkinson disease pathways. Molecular docking demonstrated stable binding interactions, notably quercetin-ACHE (-11.4 kcal/mol), supporting the therapeutic relevance of flavonoids. Conclusion: Based on the above findings, we propose that both J. regia kernel and C. halicacabum seed extracts may contain phytoconstituents that interact with various PD-related targets and pathways linked to dopaminergic neurotransmission and oxidative stress. This extractanchored network pharmacology approach presents a mechanism-related framework to facilitate follow-up experiments targeting specific bioactive constituents and molecular targets. At the same time, the results come exclusively from computational analyses and should be treated as hypothesis-generating. In vitro, in vivo, and pharmacokinetic studies need to be performed to validate the biological activity and therapeutic relevance experimentally.

Purpose of review: Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by degeneration of spinal motor neurons due to loss of SMN1 gene function, with disease severity influenced by SMN2 copy number. This review aims to summarize the current understanding of SMA pathogenesis, diagnostic approaches, and the evolving landscape of SMN-dependent therapeutic strategies, including antisense oligonucleotide therapy, small molecule splicing modifiers, and gene replacement therapy, while highlighting implications for clinical outcomes and early intervention. Sources of information: A systematic literature search was conducted across the databases of Gene Reviews, PubMed, Brain Sciences, Science Direct, and the search engine Google Scholar to identify studies on SMA. Relevant studies addressing SMN1/SMN2 mechanisms, clinical types, and current SMN-enhancing therapies were screened. Published evidence relating to SMA epidemiology in India, Japan, and the global population was examined alongside data on FDA-approved treatments. Eligible studies meeting these criteria were included in the review. Key findings: SMA results from biallelic SMN1 disruption, leading to insufficient SMN protein for motor neuron survival. SMN2 copy number predicts disease phenotype. Advances in molecular biology have produced three disease-modifying treatments that increase SMN protein or replace SMN1 function. Adjunct therapies targeting muscle function show early but limited benefits. Conclusion: Early newborn screening, carrier detection, and timely intervention are expected to significantly improve SMA incidence, presentation, and prognosis. Despite progress with gene replacement and SMN2 -modifying therapies, further research is needed to optimize outcomes and assess long-term effectiveness.

Background: Parkinson's disease (PD) is a progressive neurodegenerative illness characterized by loss of dopaminergic neurons and misfolded α-synuclein aggregation. The pathophysiology of PD involves the interplay of oxidative stress, neuroinflammation, and genetic variables. This review provides an overview of the ways oxidative stress and neuroinflammation interact with genetic and epigenetic pathways in PD, as well as how omics technologies have aided in the identification of biomarkers that can be targeted by treatments. Methodology: This study was conducted as a narrative review. Using terms such as "Parkinson's disease," "oxidative stress," "neuroinflammation," "biomarkers," "genetics," and "omics," a literature search was conducted in PubMed, Web of Science, and Scopus for research published between January 2012 and December 2025. Studies pertinent to PD-related molecular processes and biomarkers were included after articles were filtered based on titles and abstracts; non- English publications were eliminated. Result: According to recent research, oxidative stress and inflammation create a positive feedback loop that promotes neuronal death. The genes SNCA, LRRK2, and PINK1 have been associated with impaired mitochondria and mitophagy. PD-related RNA alterations, DNA methylation changes, and dysregulated miRNAs were discovered using omics approaches such as transcriptomics, epigenomics, and epitranscriptomics. BDNF, 8-OHdG, DJ-1, and phosphorylated α- synuclein are potential biomarkers for disease monitoring and diagnosis. Discussion: In PD, oxidative stress and neuroinflammation work in combination with genetic, epigenetic, and epitranscriptomic dysregulation to cause dopaminergic neurodegeneration. This highlights the importance of multi-omics integration for identifying reliable biomarkers and disease- modifying therapeutic targets. Conclusion: Precision medicine is facilitated by an integrative, multi-omics-driven strategy that improves our understanding of the molecular pathophysiology of PD. Future research should focus on validating biomarkers, conducting longitudinal studies, and translating molecular discoveries into personalized treatments.

Introduction: The emergence and proliferation of microorganisms resistant to conventional antimicrobial agents represent one of the most significant threats to global public health. Certain pathogens have evolved resistance to multiple classes of antibiotics, including those considered last-resort therapies, leading to increased morbidity, mortality, and treatment complexity. The growing incidence of Antimicrobial Resistance (AMR) has rendered many standard treatments ineffective, prolonging the duration of illness, elevating healthcare costs, and increasing the risk of fatal outcomes. Methods: Multidrug Resistance (MDR) is now widespread among diverse infectious agents, including bacteria, fungi, viruses, and parasites, contributing to the global burden of infectious diseases. These MDR organisms, often referred to as “superbugs,” present a formidable challenge to modern medicine. Results: Although resistance can occur naturally, factors such as inappropriate use of antimicrobial agents, suboptimal infection control practices, and inadequate sanitation significantly accelerate its development and dissemination. Discussion: The present findings emphasize the growing global challenge of Antimicrobial Resistance (AMR), which has emerged as one of the most pressing threats to public health. The widespread occurrence of Multidrug Resistance (MDR) across bacteria, fungi, viruses, and parasites reflects the alarming adaptability of microorganisms and their ability to undermine even last-resort therapies. This has serious clinical implications, as infections caused by MDR organisms are associated with prolonged illness, increased mortality, and greater healthcare costs. Conclusion: In response to this pressing issue, the present study aims to investigate and identify potential therapeutic strategies effective against multidrug-resistant bacterial pathogens.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, underscoring the urgent need for novel therapeutic approaches beyond standard treatments. Nanovaccines are a revolutionary platform in cancer immunotherapy, providing improved antigen delivery, enhanced immune activation, and targeted tumor targeting. This review critically discusses the promise of nanovaccines in HCC therapy, specifically focusing on their ability to induce strong antitumor immune responses while avoiding systemic toxicity. Key nanoplatforms such as lipid-based nanoparticles, polymeric carriers, and dendrimers are explained in detail to describe their mechanisms for encapsulating adjuvants and tumor-associated antigens to enhance immunogenicity. Further, we explain underlying mechanisms of action such as antigen cross-presentation, T-cell activation, and regulating the tumor microenvironment for immune evasion in HCC. Possible future directions in preclinical and clinical research and issues involving large-scale manufacturing and deployment are discussed, including combinatorial approaches using immune checkpoint inhibitors. This paper emphasizes the potentially transformative role of nanovaccines in the therapeutic regimen of HCC. It offers critical feedback on how their efficacy, safety, and translatability can be maximized for designing the next generation of cancer immunotherapies. Graphical abstract

Neurodegenerative disorders are distinguished by the progressive loss of neurons and synapses in the brain, and currently available treatments are limited with more side effects. Piper nigrum, referred to as black pepper, has been traditionally used in various medicinal applications, and is reported to have antioxidant, anti-inflammatory, and neuroprotective properties. This study investigated the phytochemical profile and pharmacological potential of the ethanolic extract of Piper nigrum. The analysis of Phytochemicals revealed the presence of alkaloids, triterpenoids, and phenols, with LC-MS/MS identification confirming major constituents including Piperine, Guineensine, and Caffeic acid. In-silico analysis suggested moderate biological activity for Piperine and Guineensine, particularly in interaction with GPCRs, while Caffeic acid exhibited neuroprotective properties. Physicochemical characterization indicated favorable properties for gastrointestinal absorption and blood-brain barrier permeability in Piperine and Guineensine. Docking studies revealed promising binding affinities against NADPH oxidase enzyme. These findings highlight the pharmacological potential of Piper nigrum constituents, suggesting their utility in neuroprotection and inflammatory conditions. Further research is warranted to validate their therapeutic efficacy and safety profiles.

Inflammation is a fundamental immunological response to external stimuli or damage caused by pathogens. Inflammatory disorders can be categorized to acute or chronic joint diseases. Rheumatoid arthritis (RA) is classified as an inflammatory disorder, whereas osteoarthritis (OA) does not exhibit overt inflammatory characteristics compared to those of RA; however, certain inflammatory cytokines and episodic inflammation have been implicated in the progression of OA. This review enumerates how biological factors trigger the activation of Inflammasomes followed by series of inter-related processes. Latest literature revealed the management of arthritis requires comprehensive and multidimensional strategies. Although plethora of conventional anti-arthritic agents have been utilized to alleviate the manifestations of arthritis. Yet, their efficacy and tolerability may be compromised with human health while reviewing the documented adverse effects. Hence, an urgent priority is to investigate complementary and alternative therapeutic modalities, specifically traditional medicine, medicinal flora, and their associated phytochemicals. These demonstrate considerable anti-inflammatory properties with diminished adverse effects on human health. The current review aims to consolidate information regarding such promising medicinal plants and naturally occurring bioactive compounds that exhibit anti-inflammatory effects against arthritis, as evidenced by various in vitro, in vivo, and other preclinical as well as clinical investigations, thereby aiding researchers in the development of phytomedicinal therapies for arthritis.

Pattern Recognition Receptors (PRRs), particularly Toll-like Receptors (TLRs), are pivotal in the innate immune system for recognizing Pathogen-associated Molecular Patterns (PAMPs) and initiating inflammatory responses. TLRs, characterized by their transmembrane structure, Leucine-rich Repeat (LRR) ectodomain, and Toll/Interleukin-1 Receptor (TIR) domains, detect a diverse range of microbial and endogenous ligands through MyD88- and TRIFdependent pathways. This engagement activates downstream signaling cascades involving key mediators such as Nuclear Factor Kappa B (NF-κB), Mitogen-activated Protein (MAP) kinases, and Interferon Regulatory Factors (IRFs), which orchestrate pro-inflammatory cytokine production and immune responses. TLRs are not only implicated in various pathologies like multiple sclerosis, rheumatoid arthritis, and atherosclerosis but also show potential in diagnosing and preventing infectious diseases like dengue fever and periodontal disease. Recent advancements reveal their dual role as both agonists and antagonists in enhancing vaccine responses and developing novel cancer immunotherapies. This review provides a comprehensive synthesis of recent research and patents on TLRs, emphasizing novel therapeutic strategies and targeted delivery systems for biomedical applications. The future scope of TLR research is explored, with a focus on how TLR-targeted therapies could transform the management of inflammatory and immune-mediated disorders.

Amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disease characterized by motor symptoms, and cognitive impairment. The complexity in treating ALS arises from genetic and environmental factors, contributing to the gradual decline of lower and upper motor neurons. The anticipated pharmaceutical market valuation for ALS is projected to reach $1,038.94 million by 2032. This projection underscores the escalating impact of ALS on global healthcare systems. ALS prevalence is expected to surge to 376,674 cases by 2040. In 2022, India ranked among the top 3 Asian-Pacific nations, while North America dominated the global ALS market. Ongoing investigations explore the potential of neuroprotective drugs like riluzole and edaravone in ALS treatment. Recently approved drugs, Relyvrio (sodium phenylbutyrate and taurursodiol) and Tofersen (Qalsody) have completed the trials, and others are currently undergoing extensive clinical trials. Continuous research and exploration of therapeutic avenues, including gene therapy and neuroprotective treatments, are imperative to address the challenges posed by ALS and other neurodegenerative diseases. Traditional Chinese medicine (TCM) approaches and clinical trials are being explored for treating ALS symptoms, targeting neuroinflammation, oxidative damage, and muscle weakness, showcasing the potential benefits of integrating traditional and modern approaches in ALS management.