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.

Efficacy of Cicuta virosa medicinal preparations against pentylenetetrazole-induced seizures.

Epileptic seizures are characterized by imbalanced inhibition-excitation cycle that triggers biochemical alterations responsible for jeopardized neuronal integrity. Conventional antiepileptic drugs (AEDs) have been the mainstay option for treatment and control; however, symptomatic control and potential to exacerbate the seizure condition calls for viable alternative to these chemical agents. In this context, natural product-based therapies have accrued great interest in recent years due to competent disease management potential and lower associated adversities. Cicuta virosa (CV) is one such herbal remedy that is used in traditional system of medicine against myriad of disorders including epilepsy. Homeopathic medicinal preparations (HMPs) of CV were assessed for their efficacy in pentylenetetrazole (PTZ)-induced acute and kindling models of epilepsy. CV HMPs increased the latency and reduced the duration of tonic-clonic phase in acute model while lowering the kindling score in the kindling model that signified their role in modulating GABAergic neurotransmission and potassium conductance. Kindling-induced impairment of cognition, memory, and motor coordination was ameliorated by the CV HMPs that substantiated their efficacy in imparting sustained neuronal fortification. Furthermore, biochemical evaluation showed attenuated oxidative stress load through reduced lipid peroxidation and strengthened free radical scavenging mechanism. Taken together, CV HMPs exhibited promising results in acute and kindling models and must be further assessed through molecular and epigenomic studies.

Increased stress and altered expression of histone modifying enzymes in brain are associated with aberrant behaviour in vitamin B12 deficient female mice.

A sub-optimal nutritional environment from early life can be envisaged as a stressor that translates into mental health problems in adulthood. After considering (a) the widespread prevalence of vitamin B12 deficiency especially amongst women in developing countries and (b) the importance of vitamin B12 in normal brain function, in this study we have elucidated the behavioural correlates of chronic severe and moderate vitamin B12 deficiency in C57BL/6 mice. Female weanling mice were assigned to three dietary groups: (a) control AIN-76A diet with cellulose as dietary fibre (b) vitamin B12 restricted AIN-76A diet with pectin as dietary fibre (severe deficiency group) and (c) vitamin B12 restricted AIN-76A diet with cellulose as dietary fibre (moderate deficiency group). The mice received these diets throughout pregnancy, lactation and thereafter. Nest-building, maternal care, anxiety and depressive behaviours were evaluated. Oxidative stress, activities of antioxidant enzymes and expression of various histone modifying enzymes in brain were investigated to unravel the probable underlying mechanisms. Our data suggests that both severe and moderate vitamin B12 deficiency induced anxiety and impaired maternal care. However, only severe vitamin B12 deficiency induced depression. Oxidative stress and poor antioxidant defense underlie the deleterious effects of both severe and moderate vitamin B12 deficiency. Altered expression of histone modifying enzymes in the brain of severely deficient mice is suggestive of epigenetic reprogramming. This study suggests that chronic vitamin B12 deficiency leads to behavioural anomalies in female C57BL/6 mice and the severity of these outcomes can be correlated to the level of deficiency.

'Obesageing': Linking obesity & ageing.

Obesity is one of the leading causes of preventable mortalities in many parts of the globe. The rise in geriatric population due to better treatment opportunities has also emerged as a major public health challenge. Both of these health challenges have impacted developed as well as developing countries. Obesity is attributed as a powerful risk factor of a variety of health problems such as cardiovascular diseases, hypertension, type 2 diabetes, dementia, neuropsychiatric diseases and many more. On the other hand, ageing is a natural process involving a gradual decline in physiological functions and is associated with similar co-morbidities as obesity. This review discusses about the commonalities (termed as 'Obesageing') between the pathological phenomenon of obesity and normal physiological process of ageing. A unique rodent model of obesageing has been developed (WNIN/Ob) that has characteristics of morbid obesity as well as premature ageing. Such a novel animal model would facilitate the understanding of the complex interplay of different mechanisms that are common to obesity and ageing and help to devise strategies in future to tackle the growing burden of obesity and ageing.

Epigenomic maintenance through dietary intervention can facilitate DNA repair process to slow down the progress of premature aging.

DNA damage caused by various sources remains one of the most researched topics in the area of aging and neurodegeneration. Increased DNA damage causes premature aging. Aging is plastic and is characterised by the decline in the ability of a cell/organism to maintain genomic stability. Lifespan can be modulated by various interventions like calorie restriction, a balanced diet of macro and micronutrients or supplementation with nutrients/nutrient formulations such as Amalaki rasayana, docosahexaenoic acid, resveratrol, curcumin, etc. Increased levels of DNA damage in the form of double stranded and single stranded breaks are associated with decreased longevity in animal models like WNIN/Ob obese rats. Erroneous DNA repair can result in accumulation of DNA damage products, which in turn result in premature aging disorders such as Hutchinson-Gilford progeria syndrome. Epigenomic studies of the aging process have opened a completely new arena for research and development of drugs and therapeutic agents. We propose here that agents or interventions that can maintain epigenomic stability and facilitate the DNA repair process can slow down the progress of premature aging, if not completely prevent it. © 2016 IUBMB Life, 68(9):717-721, 2016.

Progeria: a rare genetic premature ageing disorder.

Progeria is characterized by clinical features that mimic premature ageing. Although the mutation responsible for this syndrome has been deciphered, the mechanism of its action remains elusive. Progeria research has gained momentum particularly in the last two decades because of the possibility of revealing evidences about the ageing process in normal and other pathophysiological conditions. Various experimental models, both in vivo and in vitro, have been developed in an effort to understand the cellular and molecular basis of a number of clinically heterogeneous rare genetic disorders that come under the umbrella of progeroid syndromes (PSs). As per the latest clinical trial reports, Lonafarnib, a farnesyltranferase inhibitor, is a potent 'drug of hope' for Hutchinson-Gilford progeria syndrome (HGPS) and has been successful in facilitating weight gain and improving cardiovascular and skeletal pathologies in progeroid children. This can be considered as the dawn of a new era in progeria research and thus, an apt time to review the research developments in this area highlighting the molecular aspects, experimental models, promising drugs in trial and their implications to gain a better understanding of PSs.

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.

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.

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.

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.

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.

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.

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.

Xanthogranulomatous Endometritis with calculus formation in setting of prolapsed uterus.

Xanthogranulomatous inflammation is a rare benign inflammatory lesion characterized by sheets of lipid-laden foamy histiocytes. It has been reported in various organs, mainly the kidney and gall bladder. Xanthogranulomatous endometritis (XGE) is sporadic, with only a few cases reported in the English medical literature. Herein, we report a case of xanthogranulomatous endometritis with the formation of stones in a 50-year-old female patient with a prolapsed uterus. Grossly the endometrium was irregular, and the uterine cavity was filled with a yellow friable material, a polypoid growth, and yellowish stones. The microscopy showed sheets of histiocytes with few preserved endometrial glands. In this case, the xanthogranulomatous inflammation may mimic a clear cell carcinoma involving the endometrium and myometrium. One of the important differential diagnoses is malakoplakia. Immunohistochemistry and special stains are helpful in diagnosis.

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.

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.

Olfactory tract transection reveals robust tissue-level plasticity by cellular numbers and neurotrophic factor expression in olfactory bulb.

Nervous system lesions are characterized by the loss of neuronal numbers and types. The neurotrophic factor levels in an injured tissue reflect their potential for regeneration. This hypothesis was investigated in olfactory bulb (OB), where olfactory tract was surgically transected disrupting neuronal migration and turnover. The effects were followed with quantification of mitral cells and three neurotrophic factors mRNA levels for 6 weeks. The neuronal numbers decreased by 3rd- and 4th-week in transected OBs followed by their restoration, comparable with that of controls at 5th- and 6th-week. The endogenous levels of three neurotrophic factors - (brain derived neurotrophic factor, insulin growth factor-1 and fibroblast growth factor-2) using qPCR showed increase at 2nd-week by 136-, 8- and 2-fold respectively. Also, there was a significant increase in specific neurotrophic factors at 5th-week and 6th-weeks. The results propose a temporal link between deployment of neurotrophic factors and the plausible restorative events for mitral cell numbers in OB.