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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Environmental Toxins and Alzheimer's Disease: a Comprehensive Analysis of Pathogenic Mechanisms and Therapeutic Modulation.

Alzheimer's disease is a leading cause of mortality worldwide. Inorganic and organic hazards, susceptibility to harmful metals, pesticides, agrochemicals, and air pollution are major environmental concerns. As merely 5% of AD cases are directly inherited indicating that these environmental factors play a major role in disease development. Long-term exposure to environmental toxins is believed to progress neuropathology, which leads to the development of AD. Numerous in-vitro and in-vivo studies have suggested the harmful impact of environmental toxins at cellular and molecular level. Common mechanisms involved in the toxicity of these environmental pollutants include oxidative stress, neuroinflammation, mitochondrial dysfunction, abnormal tau, and APP processing. Increased expression of GSK-3ß, BACE-1, TNF-α, and pro-apoptotic molecules like caspases is observed upon exposure to these environmental toxins. In addition, the expression of neurotrophins like BDNF and GAP-43 have been found to be reduced as a result of toxicity. Further, modulation of signaling pathways involving PARP-1, PGC-1α, and MAPK/ERK induced by toxins have been reported to contribute in AD pathogenesis. These pathways are a promising target for developing novel AD therapeutics. Drugs like epigallocatechin-gallate, neflamapimod, salsalate, dexmedetomidine, and atabecestat are in different phases of clinical trials targeting the pathways for possible treatment of AD. This review aims to culminate the correlation between environmental toxicants and AD development. We emphasized upon the signaling pathways involved in the progression of the disease and the therapeutics under clinical trial targeting the altered pathways for possible treatment of AD.

Mechanism and recent updates on insulin-related disorders.

Insulin, a small protein with 51 amino acids synthesized by pancreatic ß-cells, is crucial to sustain glucose homeostasis at biochemical and molecular levels. Numerous metabolic dysfunctions are related to insulin-mediated altered glucose homeostasis. One of the significant pathophysiological conditions linked to the insulin associated disorder is diabetes mellitus (DM) (type 1, type 2, and gestational). Insulin resistance (IR) is one of the major underlying causes of metabolic disorders despite its association with several physiological conditions. Metabolic syndrome (MS) is another pathophysiological condition that is associated with IR, hypertension, and obesity. Further, several other pathophysiological disorders/diseases are associated with the insulin malfunctioning, which include polycystic ovary syndrome, neuronal disorders, and cancer. Insulinomas are an uncommon type of pancreatic ß-cell-derived neuroendocrine tumor that makes up 2% of all pancreatic neoplasms. Literature revealed that different biochemical events, molecular signaling pathways, microRNAs, and microbiota act as connecting links between insulin disorder and associated pathophysiology such as DM, insuloma, neurological disorder, MS, and cancer. In this review, we focus on the insulin-related disorders and the underlying mechanisms associated with the pathophysiology.

Advances and challenges in thyroid cancer: The interplay of genetic modulators, targeted therapies, and AI-driven approaches.

Thyroid cancer continues to exhibit a rising incidence globally, predominantly affecting women. Despite stable mortality rates, the unique characteristics of thyroid carcinoma warrant a distinct approach. Differentiated thyroid cancer, comprising most cases, is effectively managed through standard treatments such as thyroidectomy and radioiodine therapy. However, rarer variants, including anaplastic thyroid carcinoma, necessitate specialized interventions, often employing targeted therapies. Although these drugs focus on symptom management, they are not curative. This review delves into the fundamental modulators of thyroid cancers, encompassing genetic, epigenetic, and non-coding RNA factors while exploring their intricate interplay and influence. Epigenetic modifications directly affect the expression of causal genes, while long non-coding RNAs impact the function and expression of micro-RNAs, culminating in tumorigenesis. Additionally, this article provides a concise overview of the advantages and disadvantages associated with pharmacological and non-pharmacological therapeutic interventions in thyroid cancer. Furthermore, with technological advancements, integrating modern software and computing into healthcare and medical practices has become increasingly prevalent. Artificial intelligence and machine learning techniques hold the potential to predict treatment outcomes, analyze data, and develop personalized therapeutic approaches catering to patient specificity. In thyroid cancer, cutting-edge machine learning and deep learning technologies analyze factors such as ultrasonography results for tumor textures and biopsy samples from fine needle aspirations, paving the way for a more accurate and effective therapeutic landscape in the near future.

Current development of 1,2,3-triazole derived potential antimalarial scaffolds: Structure- activity relationship (SAR) and bioactive compounds.

Malaria is among one of the most devastating and deadliest parasitic disease in the world claiming millions of lives every year around the globe. It is a mosquito-borne infectious disease caused by various species of the parasitic protozoan of the genus Plasmodium. The indiscriminate exploitation of the clinically used antimalarial drugs led to the development of various drug-resistant and multidrug-resistant strains of plasmodium which severely reduces the therapeutic effectiveness of most frontline medicines. Therefore, there is urgent need to develop novel structural classes of antimalarial agents acting with unique mechanism of action(s). In this context, design and development of hybrid molecules containing pharmacophoric features of different lead molecules in a single entity represents a unique strategy for the development of next-generation antimalarial drugs. Research efforts by the scientific community over the past few years has led to the identification and development of several heterocyclic small molecules as antimalarial agents with high potency, less toxicity and desired efficacy. Triazole derivatives have become indispensable units in the medicinal chemistry due to their diverse spectrum of biological profiles and many triazole based hybrids and conjugates have demonstrated potential in vitro and in vivo antimalarial activities. The manuscript compiled recent developments in the medicinal chemistry of triazole based small heterocyclic molecules as antimalarial agents and discusses various reported biologically active compounds to lay the groundwork for the rationale design and discovery of triazole based antimalarial compounds. The article emphasised on biological activities, structure activity relationships, and molecular docking studies of various triazole based hybrids with heterocycles such as quinoline, artemisinins, naphthyl, naphthoquinone, etc. as potential antimalarial agents which could act on the dual stage and multi stage of the parasitic life cycle.

Targeting calcium homeostasis and impaired inter-organelle crosstalk as a potential therapeutic approach in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremors, rigidity, and bradykinesia. Current therapeutic strategies for PD are limited and mainly involve symptomatic relief, with no available treatment for the underlying causes of the disease. Therefore, there is a need for new therapeutic approaches that target the underlying pathophysiological mechanisms of PD. Calcium homeostasis is an essential process for maintaining proper cellular function and survival, including neuronal cells. Calcium dysregulation is also observed in various organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes, resulting in organelle dysfunction and impaired inter-organelle communication. The ER, as the primary calcium reservoir, is responsible for folding proteins and maintaining calcium homeostasis, and its dysregulation can lead to protein misfolding and neurodegeneration. The crosstalk between ER and mitochondrial calcium signaling is disrupted in PD, leading to neuronal dysfunction and death. In addition, a lethal network of calcium cytotoxicity utilizes mitochondria, ER and lysosome to destroy neurons. This review article focused on the complex role of calcium dysregulation and its role in aggravating functioning of organelles in PD so as to provide new insight into therapeutic strategies for treating this disease. Targeting dysfunctional organelles, such as the ER and mitochondria and lysosomes and whole network of calcium dyshomeostasis can restore proper calcium homeostasis and improve neuronal function. Additionally targeting calcium dyshomeostasis that arises from miscommunication between several organelles can be targeted so that therapeutic effects of calcium are realised in whole cellular territory.

Targeting dynamin-related protein-1 as a potential therapeutic approach for mitochondrial dysfunction in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease that manifests its pathology through synaptic damage, mitochondrial abnormalities, microRNA deregulation, hormonal imbalance, increased astrocytes & microglia, accumulation of amyloid ß (Aß) and phosphorylated Tau in the brains of AD patients. Despite extensive research, the effective treatment of AD is still unknown. Tau hyperphosphorylation and mitochondrial abnormalities are involved in the loss of synapses, defective axonal transport and cognitive decline in patients with AD. Mitochondrial dysfunction is evidenced by enhanced mitochondrial fragmentation, impaired mitochondrial dynamics, mitochondrial biogenesis and defective mitophagy in AD. Hence, targeting mitochondrial proteins might be a promising therapeutic strategy in treating AD. Recently, dynamin-related protein 1 (Drp1), a mitochondrial fission protein, has gained attention due to its interactions with Aß and hyperphosphorylated Tau, altering mitochondrial morphology, dynamics, and bioenergetics. These interactions affect ATP production in mitochondria. A reduction in Drp1 GTPase activity protects against neurodegeneration in AD models. This article provides a comprehensive overview of Drp1's involvement in oxidative damage, apoptosis, mitophagy, and axonal transport of mitochondria. We also highlighted the interaction of Drp1 with Aß and Tau, which may contribute to AD progression. In conclusion, targeting Drp1 could be a potential therapeutic approach for preventing AD pathology.

Clinical Strategies and Therapeutics for Human Monkeypox Virus: A Revised Perspective on Recent Outbreaks.

An enveloped double-stranded DNA monkeypox virus (MPXV) is a causative agent of the zoonotic viral disease, human monkeypox (HMPX). MPXV belongs to the genus Orthopoxviridae, a family of notorious smallpox viruses, and so it shares similar clinical pathophysiological features. The recent multicountry HMPX outbreak (May 2022 onwards) is recognized as an emerging global public health emergency by the World Health Organization, shunting its endemic status as opined over the past few decades. Re-emergence of HMPX raises concern to reassess the present clinical strategy and therapeutics as its outbreak evolves further. Keeping a check on these developments, here we provide insights into the HMPX epidemiology, pathophysiology, and clinical representation. Weighing on its early prevention, we reviewed the strategies that are being enrolled for HMPX diagnosis. In the line of expanded MPXV prevalence, we further reviewed its clinical management and the diverse employed preventive/therapeutic strategies, including vaccines (JYNNEOS, ACAM2000, VIGIV) and antiviral drugs/inhibitors (Tecovirimat, Cidofovir, Brincidofovir). Taken together, with a revised perspective of HMPX re-emergence, the present report summarizes new knowledge on its prevalence, pathology, and prevention strategies.

Gut microbiota dysbiosis and Huntington's disease: Exploring the gut-brain axis and novel microbiota-based interventions.

Huntington's disease (HD) is a complex progressive neurodegenerative disorder affected by genetic, environmental, and metabolic factors contributing to its pathogenesis. Gut dysbiosis is termed as the alterations of intestinal microbial profile. Emerging research has highlighted the pivotal role of gut dysbiosis in HD, focusing on the gut-brain axis as a novel research parameter in science. This review article provides a comprehensive overview of gut microbiota dysbiosis and its relationship with HD and its pathogenesis along with the future challenges and opportunities. The focuses on the essential mechanisms which link gut dysbiosis to HD pathophysiology including neuroinflammation, immune system dysregulation, altered metabolites composition, and neurotransmitter imbalances. We also explored the impacts of gut dysbiosis on HD onset, severity, and symptoms such as cognitive decline, motor dysfunction, and psychiatric symptoms. Furthermore, we highlight recent advances in therapeutics including microbiota-based therapeutic approaches, including dietary interventions, prebiotics, probiotics, fecal microbiota transplantation, and combination therapies with conventional HD treatments and their applications in managing HD. The future challenges are also highlighted as the heterogeneity of gut microbiota, interindividual variability, establishing causality between gut dysbiosis and HD, identifying optimal therapeutic targets and strategies, and ensuring the long-term safety and efficacy of microbiota-based interventions. This review provides a better understanding of the potential role of gut microbiota in HD pathogenesis and guides the development of novel therapeutic approaches.

Insight into the liver dysfunction in COVID-19 patients: Molecular mechanisms and possible therapeutic strategies.

As of June 2022, more than 530 million people worldwide have become ill with coronavirus disease 2019 (COVID-19). Although COVID-19 is most commonly associated with respiratory distress (severe acute respiratory syndrome), meta-analysis have indicated that liver dysfunction also occurs in patients with severe symptoms. Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensin-converting enzyme receptors. It has also been reported that in some patients with COVID-19, therapeutic strategies, including repurposed drugs (mitifovir, lopinavir/ritonavir, tocilizumab, etc.) triggered liver injury and cholestatic toxicity. Several proven indicators support cytokine storm-induced hepatic damage. Because there are 1.5 billion patients with chronic liver disease worldwide, it becomes imperative to critically evaluate the molecular mechanisms concerning hepatotropism of COVID-19 and identify new potential therapeutics. This review also designated a comprehensive outlook of comorbidities and the impact of lifestyle and genetics in managing patients with COVID-19.