Betaine ameliorates doxorubicin-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis through the modulation of AMPK/Nrf2/TGF-ß expression.

Doxorubicin (DOX) is a broad-spectrum antibiotic with potent anti-cancer activity. Nevertheless, despite having effective anti-neoplasm activity, its use has been clinically restricted due to its life-threatening side effects, such as cardiotoxicity. It is evident that betaine has anti-oxidant, and anti-inflammatory activity and has several beneficial effects, such as decreasing the amyloid-ß generation, reducing obesity, improving steatosis and fibrosis, and activating AMP-activated protein kinase (AMPK). However, whether betaine could mitigate DOX-induced cardiomyopathy is still unexplored. Cardiomyopathy was induced in male Sprague Dawley rats using DOX (4 mg/kg dose with a cumulative dose of 20 mg/kg, i.p.). Further, betaine (200 and 400 mg/kg) was co-treated with DOX through oral gavage for 28 days. After the completion of the study, several biochemical, oxidative stress parameters, histopathology, western blotting, and qRT-PCR were performed. Betaine treatment significantly reduced CK-MB, LDH, SGOT, and triglyceride levels, which are associated with cardiotoxicity. DOX-induced increased oxidative stress was also mitigated by betaine intervention as the SOD, catalase, MDA, and nitrite levels were restored. The histopathological investigation also confirmed the cardioprotective effect of betaine against DOX-induced cardiomyopathy as the tissue injury was reversed. Further, molecular analysis revealed that betaine suppressed the DOX-induced increased expression of phospho-p53, phospho-p38 MAPK, NF-kB p65, and PINK 1 with an upregulation of AMPK and downregulation of Nrf2 expression. Interestingly, qRT-PCR experiments show that betaine treatment alleviates the DOX-induced increase in inflammatory (TNF-α, NLRP3, and IL-6) and fibrosis (TGF-ß and Acta2) related gene expression, halting the cardiac injury. Interestingly, betaine also improves the mRNA expression of Nrf2, thus modulating the expression of antioxidant proteins and preventing oxidative damage. Here, we provide the first evidence that betaine treatment prevents DOX-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis by regulating AMPK/Nrf2/TGF-ß expression. We believe that betaine can be utilized as a potential novel therapeutic strategy for preventing DOX-induced cardiotoxicity.

Potential of Nano-Engineered Stem Cells in the Treatment of Multiple Sclerosis: A Comprehensive Review.

Multiple sclerosis (MS) is a chronic and degrading autoimmune disorder mainly targeting the central nervous system, leading to progressive neurodegeneration, demyelination, and axonal damage. Current treatment options for MS are limited in efficacy, generally linked to adverse side effects, and do not offer a cure. Stem cell therapies have emerged as a promising therapeutic strategy for MS, potentially promoting remyelination, exerting immunomodulatory effects and protecting against neurodegeneration. Therefore, this review article focussed on the potential of nano-engineering in stem cells as a therapeutic approach for MS, focusing on the synergistic effects of combining stem cell biology with nanotechnology to stimulate the proliferation of oligodendrocytes (OLs) from neural stem cells and OL precursor cells, by manipulating neural signalling pathways-PDGF, BMP, Wnt, Notch and their essential genes such as Sox, bHLH, Nkx. Here we discuss the pathophysiology of MS, the use of various types of stem cells in MS treatment and their mechanisms of action. In the context of nanotechnology, we present an overview of its applications in the medical and research field and discuss different methods and materials used to nano-engineer stem cells, including surface modification, biomaterials and scaffolds, and nanoparticle-based delivery systems. We further elaborate on nano-engineered stem cell techniques, such as nano script, nano-exosome hybrid, nano-topography and their potentials in MS. The article also highlights enhanced homing, engraftment, and survival of nano-engineered stem cells, targeted and controlled release of therapeutic agents, and immunomodulatory and tissue repair effects with their challenges and limitations. This visual illustration depicts the process of utilizing nano-engineering in stem cells and exosomes for the purpose of delivering more accurate and improved treatments for Multiple Sclerosis (MS). This approach targets specifically the creation of oligodendrocytes, the breakdown of which is the primary pathological factor in MS.

Genomic diversity and differentiation of Alu insertion polymorphisms in a native British and four South Asian migrant populations.

BACKGROUND: Alu insertions are bi-allelic and primate-specific, this makes them a useful marker for studying genetic variation, migration patterns, forensic analyses, paternity, and evolutionary heritage; however, specific population studies are limited. AIM: The objective of this study is to document the level and extent of genetic variation at 39 different Alu loci in five populations (British, Indian Punjabi, Indian Gujarati, Pakistani, and Bangladeshi) from the East Midlands region of the UK. Genetic data on migrant populations is currently limited. SUBJECTS AND METHODS: DNA samples (n = 543) were analysed for 39 Alu insertion polymorphisms using specific primers and standard protocols. Data were analysed for population and forensic genetic parameters. RESULTS: All studied Alus were polymorphic in the British White population while South Asian migrant populations had a variable number of loci which were monomorphic. Highest heterozygosities and lowest match probabilities were observed in the British sample, while the Bangladeshi sample had the lowest heterozygosity and higher match probability. CONCLUSION: The analysed Alus insertions (TPA25, Ya5NBC123, Ya5NBC182, Ya5NBC241, and Ya5NBC242) are highly polymorphic and variable among migrant populations. These loci could be useful for population genomic and differentiation studies.

Glucagon-like peptide 1 and fibroblast growth factor-21 in non-alcoholic steatohepatitis: An experimental to clinical perspective.

Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver disease (NAFLD), which slowly progresses toward cirrhosis and finally leads to the development of hepatocellular carcinoma. Obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome are major risk factors contributing to NAFLD. Targeting these risk factors is a rational option for inhibiting NASH progression. In addition, NASH could be treated with therapies that target the metabolic abnormalities causing disease pathogenesis (such as de novo lipogenesis and insulin resistance) as well with medications targeting downstream processes such as cellular damage, apoptosis, inflammation, and fibrosis. Glucagon-like peptide (GLP-1), is an incretin hormone dysregulated in both experimental and clinical NASH, which triggers many signaling pathways including fibroblast growth factor (FGF) that augments NASH pathogenesis. Growing evidence indicates that GLP-1 in concert with FGF-21 plays crucial roles in the conservation of glucose and lipid homeostasis in metabolic disorders. In line, GLP-1 stimulation improves hepatic ballooning, steatosis, and fibrosis in NASH. A recent clinical trial on NASH patients showed that the upregulation of FGF-21 decreases liver fibrosis and hepatic steatosis, thus improving the pathogenesis of NASH. Hence, therapeutic targeting of the GLP-1/FGF axis could be therapeutically beneficial for the remission of NASH. This review outlines the significance of the GLP-1/FGF-21 axis in experimental and clinical NASH and highlights the activity of modulators targeting this axis as potential salutary agents for the treatment of NASH.

Zebrafish as an emerging tool for drug discovery and development for thyroid diseases.

Zebrafish is a useful model for understanding human genetics and diseases and has evolved into a prominent scientific research model. The genetic structure of zebrafish is 70% identical to that of humans. Its small size, low cost, and transparent embryo make it a valuable tool in experimentation. Zebrafish and mammals possess the same molecular mechanism of thyroid organogenesis and development. Thus, thyroid hormone signaling, embryonic development, thyroid-related disorders, and novel genes involved in early thyroid development can all be studied using zebrafish as a model. Here in this review, we emphasize the evolving role of zebrafish as a possible tool for studying the thyroid gland in the context of physiology and pathology. The transcription factors nkx2.1a, pax2a, and hhex which contribute a pivotal role in the differentiation of thyroid primordium are discussed. Further, we have described the role of zebrafish as a model for thyroid cancer, evaluation of defects in thyroid hormone transport, thyroid hormone (TH) metabolism, and as a screening tool to study thyrotoxins. Hence, the present review highlights the role of zebrafish as a novel approach to understand thyroid development and organogenesis.

Emerging role of non-coding RNA in health and disease.

Human diseases have always been a significant turf of concern since the origin of mankind. It is cardinal to know the cause, treatment, and cure for every disease condition. With the advent and advancement in technology, the molecular arena at the microscopic level to study the mechanism, progression, and therapy is more rational and authentic pave than a macroscopic approach. Non-coding RNAs (ncRNAs) have now emerged as indispensable players in the diagnosis, development, and therapeutics of every abnormality concerning physiology, pathology, genetics, epigenetics, oncology, and developmental diseases. This is a comprehensive attempt to collate all the existing and proven strategies, techniques, mechanisms of genetic disorders including Silver Russell Syndrome, Fascio- scapula humeral muscular dystrophy, cardiovascular diseases (atherosclerosis, cardiac fibrosis, hypertension, etc.), neurodegenerative diseases (Spino-cerebral ataxia type 7, Spino-cerebral ataxia type 8, Spinal muscular atrophy, Opitz-Kaveggia syndrome, etc.) cancers (cervix, breast, lung cancer, etc.), and infectious diseases (viral) studied so far. This article encompasses discovery, biogenesis, classification, and evolutionary prospects of the existence of this junk RNA along with the integrated networks involving chromatin remodelling, dosage compensation, genome imprinting, splicing regulation, post-translational regulation and proteomics. In conclusion, all the major human diseases are discussed with a facilitated technology transfer, advancements, loopholes, and tentative future research prospects have also been proposed.

Genetic variation and differentiation among a native British and five migrant South Asian populations of the East Midlands (UK) based on CODIS forensic STR loci.

BACKGROUND: Short Tandem Repeats (STRs) are widely used in population and forensic genetic studies. AIM: The objective of this study was to document the level and extent of genetic variation of the FBI Combined DNA Index System (CODIS) STR loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, D16S539, TH01, TPOX and CSF1PO) in 6 populations (British, Indian (Punjabis and Gujaratis), Pakistani, Bangladeshi and Sri Lankan) of the East Midlands (UK). There is a lack of genetic research on the migrant South Asian populations. SUBJECTS AND METHODS: DNA samples (N = 603) were analysed for 13 autosomal forensic STR loci along with the amelogenin locus following standard protocols. Data were analysed for genetic variation and a range of forensic indices. RESULTS: All loci were polymorphic in all populations with a variable degree of variation. Average observed heterozygosity was highest in Bangladeshi (0.803) and lowest in Punjabi (0.761). FGA locus had the highest power of discrimination (PD) in most populations. CONCLUSION: FGA locus was most polymorphic and discriminatory among migrant populations demonstrating it as the marker with the highest potential in forensic analyses. These results could be useful for population and forensic genomic studies.

Vitamin D receptor (VDR) gene polymorphism and osteoporosis risk in White British men.

In this study, VDR gene ApaI (rs7975232), BsmI (rs 1544410) and TaqI (rs731236) genotypes were compared in men with osteoporosis and male controls. Osteoporosis affects around 20% of all men and overall mortality in the first year after hip fracture is significantly higher in men than women, yet the genetic basis of osteoporosis is less well studied in males. This study consisted of White British males; 69 osteoporosis patients and 122 controls. BMDs at the lumbar spine (vertebrae L1-L4) and hip (femur neck) were measured by dual-energy X-ray absorptiometry (DEXA). The VDR gene ApaI, BsmI and TaqI genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and association analysis was carried out at genotype and haplotype level. Our study suggests that TaqI polymorphism CC genotype frequency is lower in controls and further analysis of genotypes and BMD revealed a significant effect of TaqI polymorphism on Lumbar spine BMD. Two haplotypes (GCC and AAT) were associated with increased osteoporosis risk. In conclusion, VDR gene TaqI polymorphism in recessive mode had a significant effect on lumbar spine BMD within our study. Haplotypes GCC and AAT increase the risk of osteoporosis among White British males.

Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies.

Mitochondria are the powerhouses of the cell and are involved in essential functions of the cell, including ATP production, intracellular Ca2+ regulation, reactive oxygen species production & scavenging, regulation of apoptotic cell death and activation of the caspase family of proteases. Mitochondrial dysfunction and oxidative stress are largely involved in aging, cancer, age-related neurodegenerative and metabolic syndrome. In the last decade, tremendous progress has been made in understanding mitochondrial structure, function and their physiology in metabolic syndromes such as diabetes, obesity, stroke and hypertension, and heart disease. Further, progress has also been made in developing therapeutic strategies, including lifestyle interventions (healthy diet and regular exercise), pharmacological strategies and mitochondria-targeted approaches. These strategies were mainly focused to reduce mitochondrial dysfunction and oxidative stress and to maintain mitochondrial quality in metabolic syndromes. The purpose of our article is to highlight the recent progress on the mitochondrial role in metabolic syndromes and also summarize the progress of mitochondria-targeted molecules as therapeutic targets to treat metabolic syndromes. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy.

Genetic basis of dyslipidemia in disease precipitation of coronary artery disease (CAD) associated type 2 diabetes mellitus (T2DM).

Type 2 diabetes mellitus (T2DM) and its complications are linked to environmental, clinical, and genetic factors. This review analyses the disorders of lipids and their genetics with respect to coronary artery disease (CAD) associated with T2DM. Cell organelles, hepatitis C-virus infection, reactive oxygen species produced in mitochondria, and defective insulin signaling due to the arrest of G1 phase to S phase transition of ß-cells have significant roles in the precipitation of the diseases. Adiponectin is anti-inflammatory and anti-atherosclerotic and improves insulin resistance. Low-density lipoprotein (LDL) is atherosclerotic, and LDL-cholesterol in T2DM is associated with high-cardiovascular risk. Further, LDL cholesterol reduction significantly reduces cardiovascular morbidity and mortality. High-density lipoprotein (HDL) is also anti-atherosclerotic due to HDL associated paraoxonase-1 serum enzyme, which prevents LDL oxidative modifications and the development of CAD. Moreover, elevated apolipoprotein B and apolipoprotein A-I (ApoB/ApoA-I) ratio in plasma is also a risk factor for CAD. LDL receptor, adiponectin, and endocannabinoid receptor-1 genes are independently associated with CAD and T2DM. Polymorphism of Apo E2 (epsilon2) is a positive factor to increase the T2DM risk and Apo E4 (epsilon4) is a negative factor to reduce the disease risk. Taq 1B polymorphism of cholesterol ester transfer protein (CETP) gene contributes to the development of atherosclerosis, whereas haplotypes of APOA5, APOC3, APOC4, and APOC5 genes are in the same cluster and are independently associated with high plasma triglyceride level, CAD and T2DM. In conclusion, because various genes, LDLR, CETP, APOA5, Apo E, Apo B, and Apo A-I, are associated with the precipitation of CAD associated with T2DM, a personalized diet-gene intervention therapy may be advocated to reduce the disease precipitation.

A systematic literature review on the significance of deep learning and machine learning in predicting Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the most prevalent cause of dementia, characterized by a steady decline in mental, behavioral, and social abilities and impairs a person's capacity for independent functioning. It is a fatal neurodegenerative disease primarily affecting older adults. OBJECTIVES: The purpose of this literature review is to investigate various AD detection techniques, datasets, input modalities, algorithms, libraries, and performance evaluation metrics used to determine which model or strategy may provide superior performance. METHOD: The initial search yielded 807 papers, but only 100 research articles were chosen after applying the inclusion-exclusion criteria. This SLR analyzed research items published between January 2019 and December 2022. The ACM, Elsevier, IEEE Xplore Digital Library, PubMed, Springer and Taylor & Francis were systematically searched. The current study considers articles that used Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), APOe4 genotype, Diffusion Tensor Imaging (DTI) and Cerebrospinal Fluid (CSF) biomarkers. The study was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. CONCLUSION: According to the literature survey, most studies (n = 76) used the DL strategy. The datasets used by studies were primarily derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The majority of studies (n = 73) used single-modality neuroimaging data, while the remaining used multi-modal input data. In a multi-modality approach, the combination of MRI and PET scans is commonly preferred. Also, Regarding the algorithm used, Convolution Neural Network (CNN) showed the highest accuracy, 100 %, in classifying AD vs. CN subjects whereas the SVM was the most common ML algorithm, with a maximum accuracy of 99.82 %.

Antibody-drug conjugates in cancer therapy: innovations, challenges, and future directions.

The emergence of antibody-drug conjugates (ADCs) as a potential therapeutic avenue in cancer treatment has garnered significant attention. By combining the selective specificity of monoclonal antibodies with the cytotoxicity of drug molecules, ADCs aim to increase the therapeutic index, selectively targeting cancer cells while minimizing systemic toxicity. Various ADCs have been licensed for clinical usage, with ongoing research paving the way for additional options. However, the manufacture of ADCs faces several challenges. These include identifying suitable target antigens, enhancing antibodies, linkers, and payloads, and managing resistance mechanisms and side effects. This review focuses on the strategies to overcome these hurdles, such as site-specific conjugation techniques, novel antibody formats, and combination therapy. Our focus lies on current advancements in antibody engineering, linker technology, and cytotoxic payloads while addressing the challenges associated with ADC development. Furthermore, we explore the future potential of personalized medicine, leveraging individual patients' molecular profiles, to propel ADC treatments forward. As our understanding of the molecular mechanisms driving cancer progression continues to expand, we anticipate the development of new ADCs that offer more effective and personalized therapeutic options for cancer patients.

Multifaceted role of dynamin-related protein 1 in cardiovascular disease: From mitochondrial fission to therapeutic interventions.

Mitochondria are central to cellular energy production and metabolic regulation, particularly in cardiomyocytes. These organelles constantly undergo cycles of fusion and fission, orchestrated by key proteins like Dynamin-related Protein 1 (Drp-1). This review focuses on the intricate roles of Drp-1 in regulating mitochondrial dynamics, its implications in cardiovascular health, and particularly in myocardial infarction. Drp-1 is not merely a mediator of mitochondrial fission; it also plays pivotal roles in autophagy, mitophagy, apoptosis, and necrosis in cardiac cells. This multifaceted functionality is often modulated through various post-translational alterations, and Drp-1's interaction with intracellular calcium (Ca2 + ) adds another layer of complexity. We also explore the pathological consequences of Drp-1 dysregulation, including increased reactive oxygen species (ROS) production and endothelial dysfunction. Furthermore, this review delves into the potential therapeutic interventions targeting Drp-1 to modulate mitochondrial dynamics and improve cardiovascular outcomes. We highlight recent findings on the interaction between Drp-1 and sirtuin-3 and suggest that understanding this interaction may open new avenues for therapeutically modulating endothelial cells, fibroblasts, and cardiomyocytes. As the cardiovascular system increasingly becomes the focal point of aging and chronic disease research, understanding the nuances of Drp-1's functionality can lead to innovative therapeutic approaches.

Naringin: A flavanone with a multifaceted target against sepsis-associated organ injuries.

BACKGROUND: Sepsis causes multiple organ dysfunctions and raises mortality and morbidity rates through a dysregulated host response to infection. Despite the growing research interest over the last few years, no satisfactory treatment exists. Naringin, a naturally occurring bioflavonoid with vast therapeutic potential in citrus fruits and Chinese herbs, has received much attention for treating sepsis-associated multiple organ dysfunctions. PURPOSE: The review describes preclinical evidence of naringin from 2011 to 2024, particularly emphasizing the mechanism of action mediated by naringin against sepsis-associated specific injuries. The combination therapy, safety profile, drug interactions, recent advancements in formulation, and future perspectives of naringin are also discussed. METHODS: In vivo and in vitro studies focusing on the potential role of naringin and its mechanism of action against sepsis-associated organ injuries were identified and summarised in the present manuscript, which includes contributions from 2011 to 2024. All the articles were extracted from the Medline database using PubMed, Science Direct, and Web of Science with relevant keywords. RESULTS: Research findings revealed that naringin modulates many signaling cascades, such as Rho/ROCK and PPAR/STAT1, PIP3/AKT and KEAP1/Nrf2, and IkB/NF-kB and MAPK/Nrf2/HO-1, to potentially protect against sepsis-induced intestinal, cardiac, and lung injury, respectively. Furthermore, naringin treatment exhibits anti-inflammatory, anti-apoptotic, and antioxidant action against sepsis harm, highlighting naringin's promising effects in septic settings. Naringin could be employed as a treatment against sepsis, based on studies on combination therapy, synergistic effects, and toxicological investigation that show no reported severe side effects. CONCLUSION: Naringin might be a promising therapeutic approach for preventing sepsis-induced multiple organ failure. Naringin should be used alongside other therapeutic therapies with caution despite its great therapeutic potential and lower toxicity. Nonetheless, clinical studies are required to comprehend the therapeutic benefits of naringin against sepsis.

Nutrient-epigenome interactions: Implications for personalized nutrition against aging-associated diseases.

Aging is a multifaceted process involving genetic and environmental interactions often resulting in epigenetic changes, potentially leading to aging-related diseases. Various strategies, like dietary interventions and calorie restrictions, have been employed to modify these epigenetic landscapes. A burgeoning field of interest focuses on the role of microbiota in human health, emphasizing system biology and computational approaches. These methods help decipher the intricate interplay between diet and gut microbiota, facilitating the creation of personalized nutrition strategies. In this review, we analysed the mechanisms related to nutritional interventions while highlighting the influence of dietary strategies, like calorie restriction and intermittent fasting, on microbial composition and function. We explore how gut microbiota affects the efficacy of interventions using tools like multi-omics data integration, network analysis, and machine learning. These tools enable us to pinpoint critical regulatory elements and generate individualized models for dietary responses. Lastly, we emphasize the need for a deeper comprehension of nutrient-epigenome interactions and the potential of personalized nutrition informed by individual genetic and epigenetic profiles. As knowledge and technology advance, dietary epigenetics stands on the cusp of reshaping our strategy against aging and related diseases.

Targeting long non-coding RNAs in cancer therapy using CRISPR-Cas9 technology: A novel paradigm for precision oncology.

Cancer is the second leading cause of death worldwide, despite recent advances in its identification and management. To improve cancer patient diagnosis and care, it is necessary to identify new biomarkers and molecular targets. In recent years, long non-coding RNAs (lncRNAs) have surfaced as important contributors to various cellular activities, with growing proof indicating their substantial role in the genesis, development, and spread of cancer. Their unique expression profiles within specific tissues and their wide-ranging functionalities make lncRNAs excellent candidates for potential therapeutic intervention in cancer management. They are implicated in multiple hallmarks of cancer, such as uncontrolled proliferation, angiogenesis, and immune evasion. This review article explores the innovative application of CRISPR-Cas9 technology in targeting lncRNAs as a cancer therapeutic strategy. The CRISPR-Cas9 system has been widely applied in functional genomics, gene therapy, and cancer research, offering a versatile platform for lncRNA targeting. CRISPR-Cas9-mediated targeting of lncRNAs can be achieved through CRISPR interference, activation or the complete knockout of lncRNA loci. Combining CRISPR-Cas9 technology with high-throughput functional genomics makes it possible to identify lncRNAs critical for the survival of specific cancer subtypes, opening the door for tailored treatments and personalised cancer therapies. CRISPR-Cas9-mediated lncRNA targeting with other cutting-edge cancer therapies, such as immunotherapy and targeted molecular therapeutics can be used to overcome the drug resistance in cancer. The synergy of lncRNA research and CRISPR-Cas9 technology presents immense potential for individualized cancer treatment, offering renewed hope in the battle against this disease.

Therapeutic potential and pharmacological mechanism of visnagin.

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga (L.) Lam (a synonym of Visnaga daucoides Gaertn.) plant, which is used to cure various ailments. Many investigations into the bioactive properties of visnagin have been studied to date. The literature on visnagin demonstrates its biological properties, including anti-inflammatory, anti-diabetic, and beneficial effects in cardiovascular and renal diseases. Moreover, visnagin improves sperm quality parameters, stimulates steroidogenesis, and increases serum gonadotropins and testosterone levels, while decreasing pro-inflammatory cytokines, oxidative damage, genomic instability, and it modulates apoptosis. Thus, visnagin has emerged as an exciting lead for further research, owing to its potential in various unmet clinical needs. The current review summarized its basic structure, pharmacokinetics, and pharmacological effects, focusing on its mechanisms of action. The review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin's safe clinical use. Please cite this article as: Yadav P, Singh SK, Datta S, Verma S, Verma A, Rakshit A, Bali A, Bhatti JS, Khurana A, Navik U. Therapeutic potential and pharmacological mechanism of visnagin. J Integr Med. 2024; Epub ahead of print.

Global Emergence of SARS-CoV2 Infection and Scientific Interventions to Contain its Spread.

The global pandemic caused by COVID-19 posed a significant challenge to public health, necessitating rapid scientific interventions to tackle the spread of infection. The review discusses the key areas of research on COVID-19 including viral genomics, epidemiology, pathogenesis, diagnostics, and therapeutics. The genome sequencing of the virus facilitated the tracking of its evolution, transmission dynamics, and identification of variants. Epidemiological studies have provided insights into disease spread, risk factors, and the impact of public health infrastructure and social distancing measures. Investigations of the viral pathogenesis have elucidated the mechanisms underlying immune responses and severe manifestations including the long-term effects of COVID-19. Overall, the article provides an updated overview of the diagnostic methods developed for SARS-CoV-2 and discusses their strengths, limitations, and appropriate utilization in different clinical and public health settings. Furthermore, therapeutic approaches including antiviral drugs, immunomodulatory therapies, and repurposed medications have been investigated to alleviate disease severity and improve patient outcomes. Through a comprehensive analysis of these scientific efforts, the review provides an overview of the advancements made in understanding and tackling SARS-CoV-2, while underscoring the need for continued research to address the evolving challenges posed by this global health crisis.

In Vitro and In Vivo Investigations of Chromone Derivatives as Potential Multitarget-Directed Ligands: Cognitive Amelioration Utilizing a Scopolamine-Induced Zebrafish Model.

Alzheimer's disease is a complex neurological disorder linked with multiple pathological hallmarks. The interrelation of therapeutic targets assists in the enhancement of cognitive decline through interference with overall neuronal transmission. We have synthesized and screened various chromone derivatives as potential multitarget-directed ligands for the effective treatment of Alzheimer's disease. The synthesized compounds exhibited multipotent activity against AChE, BuChE, MAO-B, and amyloid ß aggregation. Three potent compounds, i.e., VN-3, VN-14, and VN-19 were identified that displayed remarkable activities against different targets. These compounds displayed IC50 values of 80 nM, 2.52 µM, and 140 nM against the AChE enzyme, respectively, and IC50 values of 2.07 µM, 70 nM, and 450 nM against the MAO-B isoform, respectively. VN-3 displayed potent activity against self-induced Aß1-42 aggregation with inhibition of 58.3%. In the ROS inhibition studies, the most potent compounds reduced the intracellular ROS levels up to 80% in SH-SY5Y cells at 25 µM concentration. The compounds were found to be neuroprotective and noncytotoxic even at a concentration of 25 µM against SH-SY5Y cells. In silico studies showed that the compounds were nicely accommodated in the active sites of the receptors along with thermodynamically stable orientations. Compound VN-19 exhibited a balanced multitargeting profile against AChE, BuChE, MAO-B, and Aß1-42 enzymes and was further evaluated for in vivo activities on the scopolamine-induced zebrafish model. VN-19 was found to ameliorate the cognitive decline in zebrafish brains by protecting them against scopolamine-induced neurodegeneration. Thus, VN-3, VN-14, and VN-19 were identified as potent multitarget-directed ligands with a balanced activity profile against different targets and can be developed as therapeutics for AD.

Autophagy and mitophagy as potential therapeutic targets in diabetic heart condition: Harnessing the power of nanotheranostics.

Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition (DHC), which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies. Despite significant progress in reducing mortality rates from cardiovascular diseases (CVDs), heart failure remains a major cause of increased morbidity among diabetic patients. These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components, and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment. While a variety of conventional diagnostic and therapeutic strategies are available, DHC continues to present a significant challenge. Point-of-care diagnostics, supported by nanobiosensing techniques, offer a promising alternative for these complex scenarios. Although conventional medications have been widely used in DHC patients, they raise several concerns regarding various physiological aspects. Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC, offering a promising approach to deliver drugs beyond the limitations of traditional therapies. This article aims to explore the potential connections between autophagy, mitophagy and DHC, while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.