The Potential of Mitochondrial Therapeutics in the Treatment of Oxidative Stress and Inflammation in Aging.

Mitochondria are central to cellular energy production, and their dysfunction is a major contributor to oxidative stress and chronic inflammation, pivotal factors in aging, and related diseases. With aging, mitochondrial efficiency declines, leading to an increase in ROS and persistent inflammatory responses. Therapeutic interventions targeting mitochondrial health show promise in mitigating these detrimental effects. Antioxidants such as MitoQ and MitoVitE, and supplements like coenzyme Q10 and NAD + precursors, have demonstrated potential in reducing oxidative stress. Additionally, gene therapy aimed at enhancing mitochondrial function, alongside lifestyle modifications such as regular exercise and caloric restriction can ameliorate age-related mitochondrial decline. Exercise not only boosts mitochondrial biogenesis but also improves mitophagy. Enhancing mitophagy is a key strategy to prevent the accumulation of dysfunctional mitochondria, which is crucial for cellular homeostasis and longevity. Pharmacological agents like sulforaphane, SS-31, and resveratrol indirectly promote mitochondrial biogenesis and improve cellular resistance to oxidative damage. The exploration of mitochondrial therapeutics, including emerging techniques like mitochondrial transplantation, offers significant avenues for extending health span and combating age-related diseases. However, translating these findings into clinical practice requires overcoming challenges in precisely targeting dysfunctional mitochondria and optimizing delivery mechanisms for therapeutic agents. Continued research is essential to refine these approaches and fully understand the interplay between mitochondrial dynamics and aging.

Advancing the understanding of diabetic encephalopathy through unravelling pathogenesis and exploring future treatment perspectives.

Diabetic encephalopathy (DE), a significant micro-complication of diabetes, manifests as neurochemical, structural, behavioral, and cognitive alterations. This condition is especially dangerous for the elderly because aging raises the risk of neurodegenerative disorders and cognitive impairment, both of which can be made worse by diabetes. Despite its severity, diagnosis of this disease is challenging, and there is a paucity of information on its pathogenesis. The pivotal roles of various cellular pathways, activated or influenced by hyperglycemia, insulin sensitivity, amyloid accumulation, tau hyperphosphorylation, brain vasculopathy, neuroinflammation, and oxidative stress, are widely recognized for contributing to the potential causes of diabetic encephalopathy. We also reviewed current pharmacological strategies for DE encompassing a comprehensive approach targeting metabolic dysregulations and neurological manifestations. Antioxidant-based therapies hold promise in mitigating oxidative stress-induced neuronal damage, while anti-diabetic drugs offer neuroprotective effects through diverse mechanisms, including modulation of insulin signaling pathways and neuroinflammation. Additionally, tissue engineering and nanomedicine-based approaches present innovative strategies for targeted drug delivery and regenerative therapies for DE. Despite significant progress, challenges remain in translating these therapeutic interventions into clinical practice, including long-term safety, scalability, and regulatory approval. Further research is warranted to optimize these approaches and address remaining gaps in the management of DE and associated neurodegenerative disorders.

Exploring advancements in early detection of Alzheimer's disease with molecular assays and animal models.

Alzheimer's Disease (AD) is a challenging neurodegenerative condition, with overwhelming implications for affected individuals and healthcare systems worldwide. Animal models have played a crucial role in studying AD pathogenesis and testing therapeutic interventions. Remarkably, studies on the genetic factors affecting AD risk, such as APOE and TREM2, have provided valuable insights into disease mechanisms. Early diagnosis has emerged as a crucial factor in effective AD management, as demonstrated by clinical studies emphasizing the benefits of initiating treatment at early stages. Novel diagnostic technologies, including RNA sequencing of microglia, offer promising avenues for early detection and monitoring of AD progression. Therapeutic strategies remain to evolve, with a focus on targeting amyloid beta (Aß) and tau pathology. Advances in animal models, such as APP-KI mice, and the advancement of anti-Aß drugs signify progress towards more effective treatments. Therapeutically, the focus has shifted towards intricate approaches targeting multiple pathological pathways simultaneously. Strategies aimed at reducing Aß plaque accumulation, inhibiting tau hyperphosphorylation, and modulating neuroinflammation are actively being explored, both in preclinical models and clinical trials. While challenges continue in developing validated animal models and translating preclinical findings to clinical success, the continuing efforts in understanding AD at molecular, cellular, and clinical levels offer hope for improved management and eventual prevention of this devastating disease.

Neurological insights into brain-targeted cancer therapy and bioinspired microrobots.

Cancer, a multifaceted and pernicious disease, continuously challenges medicine, requiring innovative treatments. Brain cancers pose unique and daunting challenges due to the intricacies of the central nervous system and the blood-brain barrier. In this era of precision medicine, the convergence of neurology, oncology, and cutting-edge technology has given birth to a promising avenue - targeted cancer therapy. Furthermore, bioinspired microrobots have emerged as an ingenious approach to drug delivery, enabling precision and control in cancer treatment. This Keynote review explores the intricate web of neurological insights into brain-targeted cancer therapy and the paradigm-shifting world of bioinspired microrobots. It serves as a critical and comprehensive overview of these evolving fields, aiming to underscore their integration and potential for revolutionary cancer treatments.

Challenges and Solutions for Better Management of Side Effects in Geriatric Oncology.

This editorial discusses the difficulties encountered in the management of cancer among the geriatric population. Although cancer research has made substantial advancements, treatments frequently fail to consider the long-lasting consequences and adverse effects on elderly people. We advocate for enhanced geriatric oncology care, embodying enhanced evaluation techniques, the incorporation of complementary therapies, and the utilisation of wearable technologies for remote surveillance. Additionally, we suggest modifying future clinical trials to take into account the cognitive well-being of senior individuals. Implementing these modifications would greatly enhance cancer treatment for geriatric cancer patients.

Recent Advances in Drug Delivery Systems Targeting Insulin Signalling for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of neurofibrillary tangles and amyloid-ß plaques. Recent research has unveiled the pivotal role of insulin signaling dysfunction in the pathogenesis of AD. Insulin, once thought to be unrelated to brain function, has emerged as a crucial factor in neuronal survival, synaptic plasticity, and cognitive processes. Insulin and the downstream insulin signaling molecules are found mainly in the hippocampus and cortex. Some molecules responsible for dysfunction in insulin signaling are GSK-3ß, Akt, PI3K, and IRS. Irregularities in insulin signaling or insulin resistance may arise from changes in the phosphorylation levels of key molecules, which can be influenced by both stimulation and inactivity. This, in turn, is believed to be a crucial factor contributing to the development of AD, which is characterized by oxidative stress, neuroinflammation, and other pathological hallmarks. Furthermore, this route is known to be indirectly influenced by Nrf2, NF-κB, and the caspases. This mini-review delves into the intricate relationship between insulin signaling and AD, exploring how disruptions in this pathway contribute to disease progression. Moreover, we examine recent advances in drug delivery systems designed to target insulin signaling for AD treatment. From oral insulin delivery to innovative nanoparticle approaches and intranasal administration, these strategies hold promise in mitigating the impact of insulin resistance on AD. This review consolidates current knowledge to shed light on the potential of these interventions as targeted therapeutic options for AD.

Psychedelics for alzheimer's disease-related dementia: Unveiling therapeutic possibilities and pathways.

Psychedelics have traditionally been used for spiritual and recreational purposes, but recent developments in psychotherapy have highlighted their potential as therapeutic agents. These compounds, which act as potent 5-hydroxytryptamine (5HT) agonists, have been recognized for their ability to enhance neural plasticity through the activation of the serotoninergic and glutamatergic systems. However, the implications of these findings for the treatment of neurodegenerative disorders, particularly dementia, have not been fully explored. In recent years, studies have revealed the modulatory and beneficial effects of psychedelics in the context of dementia, specifically Alzheimer's disease (AD)-related dementia, which lacks a definitive cure. Psychedelics such as N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and Psilocybin have shown potential in mitigating the effects of this debilitating disease. These compounds not only target neurotransmitter imbalances but also act at the molecular level to modulate signalling pathways in AD, including the brain-derived neurotrophic factor signalling pathway and the subsequent activation of mammalian target of rapamycin and other autophagy regulators. Therefore, the controlled and dose-dependent administration of psychedelics represents a novel therapeutic intervention worth exploring and considering for the development of drugs for the treatment of AD-related dementia. In this article, we critically examined the literature that sheds light on the therapeutic possibilities and pathways of psychedelics for AD-related dementia. While this emerging field of research holds great promise, further studies are necessary to elucidate the long-term safety, efficacy, and optimal treatment protocols. Ultimately, the integration of psychedelics into the current treatment paradigm may provide a transformative approach for addressing the unmet needs of individuals living with AD-related dementia and their caregivers.

Harnessing the power of biological macromolecules in hydrogels for controlled drug release in the central nervous system: A review.

Hydrogels have immense potential in revolutionizing central nervous system (CNS) drug delivery, improving outcomes for neurological disorders. They serve as promising tools for controlled drug delivery to the CNS. Available hydrogel types include natural macromolecules (e.g., chitosan, hyaluronic acid, alginate), as well as hybrid hydrogels combining natural and synthetic polymers. Each type offers distinct advantages in terms of biocompatibility, mechanical properties, and drug release kinetics. Design and engineering considerations encompass hydrogel composition, crosslinking density, porosity, and strategies for targeted drug delivery. The review emphasizes factors affecting drug release profiles, such as hydrogel properties and formulation parameters. CNS drug delivery applications of hydrogels span a wide range of therapeutics, including small molecules, proteins and peptides, and nucleic acids. However, challenges like limited biodegradability, clearance, and effective CNS delivery persist. Incorporating 3D bioprinting technology with hydrogel-based CNS drug delivery holds the promise of highly personalized and precisely controlled therapeutic interventions for neurological disorders. The review explores emerging technologies like 3D bioprinting and nanotechnology as opportunities for enhanced precision and effectiveness in hydrogel-based CNS drug delivery. Continued research, collaboration, and technological advancements are vital for translating hydrogel-based therapies into clinical practice, benefiting patients with CNS disorders. This comprehensive review article delves into hydrogels for CNS drug delivery, addressing their types, design principles, applications, challenges, and opportunities for clinical translation.

Ketamine as a therapeutic agent in major depressive disorder and posttraumatic stress disorder: Potential medicinal and deleterious effects.

Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are the most common causes of emotional distress that impair an individual's quality of life. MDD is a chronic mental illness that affects 300 million people across the world. Clinical manifestations of MDD include fatigue, loss of interest in routine tasks, psychomotor agitation, impaired ability to focus, suicidal ideation, hypersomnolence, altered psychosocial functioning, and appetite loss. Individuals with depression also demonstrate a reduced behavioral response while experiencing pleasure, a symptom known as anhedonia. Like MDD, PTSD is a prevalent and debilitating psychiatric disorder resulting from a traumatic incident such as sexual assault, war, severe accident, or natural disaster. Symptoms such as recalling event phases, hypervigilance, irritability, and anhedonia are common in PTSD. Both MDD and PTSD pose enormous socioeconomic burdens across the globe. The search for effective treatment with minimal side effects is still ongoing. Ketamine is known for its anesthetic and analgesic properties. Psychedelic and psychotropic effects of ketamine have been found on the nervous system, which highlights its toxicity. In this article, the effectiveness of ketamine as a potential therapeutic for PTSD and MDD along with its mechanisms of action, clinical trials, and possible side effects have been discussed.

A Comprehensive Review of Emerging Trends and Innovative Therapies in Epilepsy Management.

Epilepsy is a complex neurological disorder affecting millions worldwide, with a substantial number of patients facing drug-resistant epilepsy. This comprehensive review explores innovative therapies for epilepsy management, focusing on their principles, clinical evidence, and potential applications. Traditional antiseizure medications (ASMs) form the cornerstone of epilepsy treatment, but their limitations necessitate alternative approaches. The review delves into cutting-edge therapies such as responsive neurostimulation (RNS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), highlighting their mechanisms of action and promising clinical outcomes. Additionally, the potential of gene therapies and optogenetics in epilepsy research is discussed, revealing groundbreaking findings that shed light on seizure mechanisms. Insights into cannabidiol (CBD) and the ketogenic diet as adjunctive therapies further broaden the spectrum of epilepsy management. Challenges in achieving seizure control with traditional therapies, including treatment resistance and individual variability, are addressed. The importance of staying updated with emerging trends in epilepsy management is emphasized, along with the hope for improved therapeutic options. Future research directions, such as combining therapies, AI applications, and non-invasive optogenetics, hold promise for personalized and effective epilepsy treatment. As the field advances, collaboration among researchers of natural and synthetic biochemistry, clinicians from different streams and various forms of medicine, and patients will drive progress toward better seizure control and a higher quality of life for individuals living with epilepsy.

From sleep to cancer to neurodegenerative disease: the crucial role of Hsp70 in maintaining cellular homeostasis and potential therapeutic implications.

Sleep is a fundamental process essential for reparatory and restorative mechanisms in all organisms. Recent research has linked sleep to various pathological conditions, including cancer and neurodegeneration, which are associated with various molecular changes in different cellular environments. Despite the potential significance of various molecules, the HSPA1A or Hsp70 protein, which has possible connections with sleep and different neuropsychological and pathological disorders, has been explored the least. This paper explores the potential for manipulating and discovering drugs related to the Hsp70 protein to alleviate sleep problems and improve the prognosis for various other health issues. This paper discusses the critical role of Hsp70 in cancer, neurodegeneration, apoptosis, sleep, and its regulation at the structural level through allosteric mechanisms and different substrates. The significant impact of Hsp70's connection to various conditions suggests that existing sleep medicine could be used to improve such conditions, leading to improved outcomes, minimized research costs, and a new direction for current research. Overall, this paper highlights the potential of Hsp70 protein as a key therapeutic target for developing new drugs for the treatment of sleep disorders, cancer, neurodegeneration, and other related pathological conditions. Further research into the molecular mechanisms of Hsp70 regulation and its interactions with other cellular pathways is necessary to develop targeted treatments for these conditions.Communicated by Ramaswamy H. Sarma.

Chitosan Nanoparticles-Based Cancer Drug Delivery: Application and Challenges.

Chitin is the second most abundant biopolymer consisting of N-acetylglucosamine units and is primarily derived from the shells of marine crustaceans and the cell walls of organisms (such as bacteria, fungi, and algae). Being a biopolymer, its materialistic properties, such as biodegradability, and biocompatibility, make it a suitable choice for biomedical applications. Similarly, its deacetylated derivative, chitosan, exhibits similar biocompatibility and biodegradability properties, making it a suitable support material for biomedical applications. Furthermore, it has intrinsic material properties such as antioxidant, antibacterial, and antitumor. Population studies have projected nearly 12 million cancer patients across the globe, where most will be suffering from solid tumors. One of the shortcomings of potent anticancer drugs is finding a suitable cellular delivery material or system. Therefore, identifying new drug carriers to achieve effective anticancer therapy is becoming essential. This paper focuses on the strategies implemented using chitin and chitosan biopolymers in drug delivery for cancer treatment.

Plausible Role of Stem Cell Types for Treating and Understanding the Pathophysiology of Depression.

Major Depressive Disorder (MDD), colloquially known as depression, is a debilitating condition affecting an estimated 3.8% of the population globally, of which 5.0% are adults and 5.7% are above the age of 60. MDD is differentiated from common mood changes and short-lived emotional responses due to subtle alterations in gray and white matter, including the frontal lobe, hippocampus, temporal lobe, thalamus, striatum, and amygdala. It can be detrimental to a person's overall health if it occurs with moderate or severe intensity. It can render a person suffering terribly to perform inadequately in their personal, professional, and social lives. Depression, at its peak, can lead to suicidal thoughts and ideation. Antidepressants manage clinical depression and function by modulating the serotonin, norepinephrine, and dopamine neurotransmitter levels in the brain. Patients with MDD positively respond to antidepressants, but 10-30% do not recuperate or have a partial response accompanied by poor life quality, suicidal ideation, self-injurious behavior, and an increased relapse rate. Recent research shows that mesenchymal stem cells and iPSCs may be responsible for lowering depression by producing more neurons with increased cortical connections. This narrative review discusses the plausible functions of various stem cell types in treating and understanding depression pathophysiology.

Therapeutics for the Management of Cytokine Release Syndrome in COVID-19.

Coronavirus disease (COVID-19) is the greatest pandemic of this era and has affected more than 10 million people across 213 nations. However, the etiology, management, and treatment of COVID-19 remain unknown. A better understanding of the novel virus would help in developing accurate diagnostic methods and efficacious drugs for the treatment of patients of all age groups. To control the pandemic urgently, many drugs are being repurposed and several clinical trials are in progress for the same. As cytokine storm has been observed to be one of the common mechanisms of immune response in COVID-19 patients, several drugs are under trials to control the cytokine storm. In this review, we discuss the different categories of drugs in clinical trials for the management of cytokine storms in COVID-19 patients. Hitherto, several promising candidates such as IL-1 and IL-6 inhibitors have failed to display efficacy in the trials. Only corticosteroid therapy has shown benefit so far, albeit limited to patients on ventilator support. Thus, it is crucial to seek novel strategies to combat hyperinflammation and increase survival in COVID-19 afflicted patients.

Navigating the Commonality of Healthcare Failures: COVID-19 and Conflict Zones.

The weaknesses of healthcare systems have been sharply revealed amid the instability of the COVID-19 pandemic and the ongoing conflicts across the borders of different countries. One thing unites these two crises that appear to be separate: the incapacity of healthcare systems to provide for the most basic human requirements in emergency situations. With an emphasis on the roles of the United Nations and the World Health Organisation, we look into the similarities between healthcare failures in COVID-19 and conflict zones in this Editorial and offer possible solutions to improve the circumstances.