A comprehensive review on the pharmacological role of gut microbiome in neurodegenerative disorders: potential therapeutic targets.

Neurological disorders, including Alzheimer and Parkinson's, pose significant challenges to public health due to their complex etiologies and limited treatment options. Recent advances in research have highlighted the intricate bidirectional communication between the gut microbiome and the central nervous system (CNS), revealing a potential therapeutic avenue for neurological disorders. Thus, this review aims to summarize the current understanding of the pharmacological role of gut microbiome in neurological disorders. Mounting evidence suggests that the gut microbiome plays a crucial role in modulating CNS function through various mechanisms, including the production of neurotransmitters, neuroactive metabolites, and immune system modulation. Dysbiosis, characterized by alterations in gut microbial composition and function, has been observed in many neurological disorders, indicating a potential causative or contributory role. Pharmacological interventions targeting the gut microbiome have emerged as promising therapeutic strategies for neurological disorders. Probiotics, prebiotics, antibiotics, and microbial metabolite-based interventions have shown beneficial effects in animal models and some human studies. These interventions aim to restore microbial homeostasis, enhance microbial diversity, and promote the production of beneficial metabolites. However, several challenges remain, including the need for standardized protocols, identification of specific microbial signatures associated with different neurological disorders, and understanding the precise mechanisms underlying gut-brain communication. Further research is necessary to unravel the intricate interactions between the gut microbiome and the CNS and to develop targeted pharmacological interventions for neurological disorders.

Obesity and Depression: Common Link and Possible Targets.

Depression is among the main causes of disability, and its protracted manifestations could make it even harder to treat metabolic diseases. Obesity is linked to episodes of depression, which is closely correlated to abdominal adiposity and impaired food quality. The present review is aimed at studying possible links between obesity and depression along with targets to disrupt it. Research output in Pubmed and Scopus were referred for writing this manuscript. Obesity and depression are related, with the greater propensity of depressed people to gain weight, resulting in poor dietary decisions and a sedentary lifestyle. Adipokines, which include adiponectin, resistin, and leptin are secretory products of the adipose tissue. These adipokines are now being studied to learn more about the connection underlying obesity and depression. Ghrelin, a gut hormone, controls both obesity and depression. Additionally, elevated ghrelin levels result in anxiolytic and antidepressant-like effects. The gut microbiota influences the metabolic functionalities of a person, like caloric processing from indigestible nutritional compounds and storage in fatty tissue, that exposes an individual to obesity, and gut microorganisms might connect to the CNS through interconnecting pathways, including neurological, endocrine, and immunological signalling systems. The alteration of brain activity caused by gut bacteria has been related to depressive episodes. Monoamines, including dopamine, serotonin, and norepinephrine, have been widely believed to have a function in emotions and appetite control. Emotional signals stimulate arcuate neurons in the hypothalamus that are directly implicated in mood regulation and eating. The peptide hormone GLP-1(glucagon-like peptide- 1) seems to have a beneficial role as a medical regulator of defective neuroinflammation, neurogenesis, synaptic dysfunction, and neurotransmitter secretion discrepancy in the depressive brain. The gut microbiota might have its action in mood and cognition regulation, in addition to its traditional involvement in GI function regulation. This review addressed the concept that obesity-related low-grade mild inflammation in the brain contributes to chronic depression and cognitive impairments.

Herbal Interactions with Cardiac Medications: A Comprehensive Review of Potential Interactions between Herbal Drugs and Commonly Prescribed Cardiac Medications.

BACKGROUND: The concomitant use of herbal remedies in conjunction with conventional cardiac medications has increased significantly in recent years, primarily due to improvements in the quality standards of herbal medicines and the pervasive belief that natural products pose no harm to the human body. Contrary to this belief, multiple phytoconstituents found in herbal products have the potential to interact with conventional cardiac drugs, potentially resulting in severe adverse effects.

Objective: This review aimed to elucidate the intricacies of these interactions highlighting herbal medications that interact with established pharmaceuticals used for the treatment of cardiovascular disorders. Moreover, the review draws attention to safety concerns and preventative steps that should be taken by patients and medical professionals.. This endeavor is vital to avert adverse events stemming from such interactions.

Methods: Our approach entailed a comprehensive literature review employing keywords such as "mechanisms of herb-drug interactions," "herbal medications," and "cardiovascular disorders." The drugs presented in this review were selected based on their popularity among the general population, frequency of their employability, and potential to manifest drug interactions. We sourced pertinent information from reputable databases, including PubMed, Scopus, and Elsevier.

Results: Heart or blood vessel disorders are referred to as cardiovascular diseases (CVDs), which include conditions such as heart failure, stroke, hypertensive heart disease, and peripheral arterial disease. The primary underlying factor for the development of CVDs is dyslipidemia, which can be treated with classical antihyperlipidemic drugs such as statins, ezetimibe, and PCSK9-inhibitors. The use of herbal remedies is often unregulated, and there is a lack of scientific evidence supporting their use, particularly in the management of heart failure. Patients may not disclose their use of herbal remedies to health care practitioners, which can result in potential harm.

Conclusion: Uncontrolled dyslipidemia leads to hypercholesterolemia, which can result in atherosclerotic plaques and blocked arteries and veins. Herbal remedies and botanical products are also used to prevent or treat illnesses, and many prescription pharmaceuticals are made from plant compounds. Herbal remedies are often preferred because of the belief that they are safe and have no potential to cause harm. However, there is insufficient scientific data to support the use of herbal remedies, especially when treating heart disease. Using herbal remedies in conjunction with medicinal pharmaceuticals may result in unfavorable effects.

A Systematic Review of Herbal Interventions for the Management of Cardiovascular Diseases.

BACKGROUND: Cardiovascular diseases represent a significant global health burden, necessitating diverse approaches for effective management. Herbal interventions have gained attention as potential adjuncts or alternatives to conventional therapies due to their perceived safety and therapeutic potential. This structured abstract provides a comprehensive review of herbal interventions for the management of CVDs, summarising key findings, mechanisms of action, and clinical implications. OBJECTIVE: This systematic review aims to evaluate the impact of various herbal interventions employed for managing cardiovascular diseases. METHOD: We conducted an extensive literature search across electronic databases, including PubMed, Scopus, and Web of Science, from inception to 2022. Studies were included if they investigated the use of herbal remedies for preventing or treating CVDs. Data extraction and synthesis focused on botanical sources, active compounds, mechanisms of action, and clinical outcomes. RESULT: Numerous herbal interventions have demonstrated promising cardiovascular benefits. A number of medicinal herbs well identified to treat CVD are Moringaoleifera, Ginseng, Ginkgo biloba, Celosia argentea, Gongronematrifolium, Gynostemmapentaphyllum, Bombaxceiba, Gentianalutea, Allium sativum, Crataegusspp, Curcuma longa, Camellia sinensis, and Zingiberofficinale. Mechanistic insights reveal that herbal interventions often target multiple pathways involved in CVD pathogenesis. These mechanisms encompass anti-inflammatory, antioxidant, anti-thrombotic, anti-hypertensive, and lipid-lowering effects. Additionally, some herbs enhance endothelial function, promote nitric oxide production, and exert vasodilatory effects, contributing to improved cardiovascular health. Clinical studies have provided evidence of the efficacy of certain herbal interventions in reducing CVD risk factors and improving patient outcomes. However, more rigorous, large-scale clinical trials are needed to establish their long-term safety and effectiveness. It is crucial to consider potential herb-drug interactions and standardise dosages for reliable therapeutic outcomes. CONCLUSION: This comprehensive review highlights the potential of herbal interventions as valuable adjuncts or alternatives for managing cardiovascular diseases. Herbal remedies offer diverse mechanisms of action, targeting key CVD risk factors and pathways. While promising, their clinical utility warrants further investigation through well-designed trials to establish their safety and efficacy, paving the way for integrated approaches to cardiovascular disease management. Healthcare providers and patients should engage in informed discussions about the use of herbal interventions alongside conventional therapies in the context of CVD prevention and treatment.

Revolutionizing pediatric neuroblastoma treatment: unraveling new molecular targets for precision interventions.

Neuroblastoma (NB) is the most frequent solid tumor in pediatric cases, contributing to around 15% of childhood cancer-related deaths. The wide-ranging genetic, morphological, and clinical diversity within NB complicates the success of current treatment methods. Acquiring an in-depth understanding of genetic alterations implicated in the development of NB is essential for creating safer and more efficient therapies for this severe condition. Several molecular signatures are being studied as potential targets for developing new treatments for NB patients. In this article, we have examined the molecular factors and genetic irregularities, including those within insulin gene enhancer binding protein 1 (ISL1), dihydropyrimidinase-like 3 (DPYSL3), receptor tyrosine kinase-like orphan receptor 1 (ROR1) and murine double minute 2-tumor protein 53 (MDM2-P53) that play an essential role in the development of NB. A thorough summary of the molecular targeted treatments currently being studied in pre-clinical and clinical trials has been described. Recent studies of immunotherapeutic agents used in NB are also studied in this article. Moreover, we explore potential future directions to discover new targets and treatments to enhance existing therapies and ultimately improve treatment outcomes and survival rates for NB patients.

Potential role of oxytocin in the regulation of memories and treatment of memory disorders.

Oxytocin (OXT) is an "affiliative" hormone or neurohormone or neuropeptide consists of nine amino acids, synthesized in magnocellular neurons of paraventricular (PVN) and supraoptic nuclei (SON) of hypothalamus. OXT receptors are widely distributed in various region of brain and OXT has been shown to regulate various social and nonsocial behavior. Hippocampus is the main region which regulates the learning and memory. Hippocampus particularly regulates the acquisition of new memories and retention of acquired memories. OXT has been shown to regulate the synaptic plasticity, neurogenesis, and consolidation of memories. Further, findings from both preclinical and clinical studies have suggested that the OXT treatment improves performance in memory related task. Various trials have suggested the positive impact of intranasal OXT in the dementia patients. However, these studies are limited in number. In the present study authors have highlighted the role of OXT in the formation and retrieval of memories. Further, the study demonstrated the outcome of OXT treatment in various memory and related disorders.

Potential Applications of Mitochondrial Therapy with a Focus on Parkinson's Disease and Mitochondrial Transplantation.

Purpose: Both aging and neurodegenerative illnesses are thought to be influenced by mitochondrial malfunction and free radical formation. Deformities of the energy metabolism, mitochondrial genome polymorphisms, nuclear DNA genetic abnormalities associated with mitochondria, modifications of mitochondrial fusion or fission, variations in shape and size, variations in transit, modified mobility of mitochondria, transcription defects, and the emergence of misfolded proteins associated with mitochondria are all linked to Parkinson's disease. Methods: This review is a condensed compilation of data from research that has been published between the years of 2014 and 2022, using search engines like Google Scholar, PubMed, and Scopus. Results: Mitochondrial transplantation is a one-of-a-kind treatment for mitochondrial diseases and deficits in mitochondrial biogenesis. The replacement of malfunctioning mitochondria with transplanted viable mitochondria using innovative methodologies has shown promising outcomes as a cure for Parkinson's, involving tissue sparing coupled with enhanced energy generation and lower oxidative damage. Numerous mitochondria-targeted therapies, including mitochondrial gene therapy, redox therapy, and others, have been investigated for their effectiveness and potency. Conclusion: The development of innovative therapeutics for mitochondria-directed treatments in Parkinson's disease may be aided by optimizing mitochondrial dynamics. Many neurological diseases have been studied in animal and cellular models, and it has been found that mitochondrial maintenance can slow the death of neuronal cells. It has been hypothesized that drug therapies for neurodegenerative diseases that focus on mitochondrial dysfunction will help to delay the onset of neuronal dysfunction.

Predictive Modelling in pharmacokinetics: from in-silico simulations to personalized medicine.

INTRODUCTION: Pharmacokinetic parameters assessment is a critical aspect of drug discovery and development, yet challenges persist due to limited training data. Despite advancements in machine learning and in-silico predictions, scarcity of data hampers accurate prediction of drug candidates' pharmacokinetic properties. AREAS COVERED: The study highlights current developments in human pharmacokinetic prediction, talks about attempts to apply synthetic approaches for molecular design, and searches several databases, including Scopus, PubMed, Web of Science, and Google Scholar. The article stresses importance of rigorous analysis of machine learning model performance in assessing progress and explores molecular modeling (MM) techniques, descriptors, and mathematical approaches. Transitioning to clinical drug development, article highlights AI (Artificial Intelligence) based computer models optimizing trial design, patient selection, dosing strategies, and biomarker identification. In-silico models, including molecular interactomes and virtual patients, predict drug performance across diverse profiles, underlining the need to align model results with clinical studies for reliability. Specialized training for human specialists in navigating predictive models is deemed critical. Pharmacogenomics, integral to personalized medicine, utilizes predictive modeling to anticipate patient responses, contributing to more efficient healthcare system. Challenges in realizing potential of predictive modeling, including ethical considerations and data privacy concerns, are acknowledged. EXPERT OPINION: AI models are crucial in drug development, optimizing trials, patient selection, dosing, and biomarker identification and hold promise for streamlining clinical investigations.

Exploring the pathophysiological influence of heme oxygenase-1 on neuroinflammation and depression: A study of phytotherapeutic-based modulation.

BACKGROUND: The heme oxygenase (HO) system plays a significant role in neuroprotection and reduction of neuroinflammation and neurodegeneration. The system, via isoforms HO-1 and HO-2, regulates cellular redox balance. HO-1, an antioxidant defense enzyme, is highlighted due to its association with depression, characterized by heightened neuroinflammation and impaired oxidative stress responses. METHODOLOGY: We observed the pathophysiology of HO-1 and phytochemicals as its modulator. We explored Science Direct, Scopus, and PubMed for a comprehensive literature review. Bibliometric and temporal trend analysis were done using VOSviewer. RESULTS: Several phytochemicals can potentially alleviate neuroinflammation and oxidative stress-induced depressive symptoms. These effects result from inhibiting the MAPK and NK-κB pathways - both implicated in the overproduction of pro-inflammatory factors - and from the upregulation of HO-1 expression mediated by Nrf2. Bibliometric and temporal trend analysis further validates these associations. CONCLUSION: In summary, our findings suggest that antidepressant agents can mitigate neuroinflammation and depressive disorder pathogenesis via the upregulation of HO-1 expression. These agents suppress pro-inflammatory mediators and depressive-like symptoms, demonstrating that HO-1 plays a significant role in the neuroinflammatory process and the development of depression.

Phyto-pharmacological Potential of Aegle marmelos (L.) for Neurological Disorders: Progress and Prospects.

BACKGROUND: Aegle marmelos, an Indian plant, has been extensively utilized by the people of the Indian subcontinent over about 5000 years. The leaves, bark, roots, and fruits, including seeds, are widely used to cure a variety of diseases in the Indian traditional system of medicine, Ayurveda, along with numerous folk medicines. By revealing the existence of significant bioactive chemicals, modern research has effectively substantiated the therapeutic effects of bael. OBJECTIVE: The objective of this study was to review the literature regarding A. marmelos geographical distribution, morphology, therapeutic benefits, and phytochemicals found in the bael leaves, fruits, and other parts of the plant that offer a wide range of pharmacological applications in neurological disorders. METHODOLOGY: A thorough literature search was conducted using five computerized databases, such as PubMed, Google Scholar, ScienceDirect, Elsevier, and Wiley Online Library (WOL), by using standard keywords "A. marmelos," "Geographical distribution," "Morphological description," "Ethnobotanical Uses," "Phytoconstituents" and "Neuroprotective activities" for review papers published between 1975 and 2023. A small number of earlier review articles focused on phyto-pharmacological potential of Aegle marmelos (L.) for neurological disorders. RESULTS: According to some research, Aegle marmelos extracts potentially have neuroprotective benefits. This is due to its capacity to alter cellular mechanisms that cause neuronal damage. CONCLUSION: Neurodegenerative illnesses usually induce permanent neuronal network loss overall the brain along with the spinal cord (CNS), resulting in chronic functional impairments. The review summarizes the multiple aspects and processes of A. marmelos extract and its components in several models of neurodegenerative diseases such as anxiety, epilepsy, depression, Parkinson's disease, Alzheimer's disease, and others. MDA, nitrite, TNF-, and IL-6 levels were dramatically elevated, whereas glutathione levels were significantly lowered in the hippocampus of STZ-treated rats. Furthermore, STZ-treated rats showed a substantial drop in catalase activity and an increase in AChE activity, indicating cholinergic hypofunction and neuronal injury. The neuroprotective ability of A. marmelos against STZ-induced oxidative stress and cognitive loss in rats suggests that it has therapeutic relevance in Alzheimer's disease (AD).

Revisiting the Mitochondrial Function and Communication in Neurodegenerative Diseases.

Neurodegenerative disorders are distinguished by the progressive loss of anatomically or physiologically relevant neural systems. Atypical mitochondrial morphology and metabolic malfunction are found in many neurodegenerative disorders. Alteration in mitochondrial function can occur as a result of aberrant mitochondrial DNA, altered nuclear enzymes that interact with mitochondria actively or passively, or due to unexplained reasons. Mitochondria are intimately linked to the Endoplasmic reticulum (ER), and ER-mitochondrial communication governs several of the physiological functions and procedures that are disrupted in neurodegenerative disorders. Numerous researchers have associated these disorders with ER-mitochondrial interaction disturbance. In addition, aberrant mitochondrial DNA mutation and increased ROS production resulting in ionic imbalance and leading to functional and structural alterations in the brain as well as cellular damage may have an essential role in disease progression via mitochondrial malfunction. In this review, we explored the evidence highlighting the role of mitochondrial alterations in neurodegenerative pathways in most serious ailments, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD).

Therapeutic potential of vasopressin in the treatment of neurological disorders.

Vasopressin (VP) is a nonapeptide made of nine amino acids synthesized by the hypothalamus and released by the pituitary gland. VP acts as a neurohormone, neuropeptide and neuromodulator and plays an important role in the regulation of water balance, osmolarity, blood pressure, body temperature, stress response, emotional challenges, etc. Traditionally VP is known to regulate the osmolarity and tonicity. VP and its receptors are widely expressed in the various region of the brain including cortex, hippocampus, basal forebrain, amygdala, etc. VP has been shown to modulate the behavior, stress response, circadian rhythm, cerebral blood flow, learning and memory, etc. The potential role of VP in the regulation of these neurological functions have suggested the therapeutic importance of VP and its analogues in the management of neurological disorders. Further, different VP analogues have been developed across the world with different pharmacotherapeutic potential. In the present work authors highlighted the therapeutic potential of VP and its analogues in the treatment and management of various neurological disorders.

Targeting the vivid facets of apolipoproteins as a cardiovascular risk factor in rheumatoid arthritis.

Mostly, cardiovascular diseases are blamed for casualties in rheumatoid arthritis (RA) patients. Customarily, dyslipidemia is probably the most prevalent underlying cause of untimely demise in people suffering from RA as it hastens the expansion of atherosclerosis. The engagement of inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), etc., is crucial in the progression and proliferation of both RA and abnormal lipid parameters. Thus, lipid abnormalities should be monitored frequently in patients with both primary and advanced RA stages. An advanced lipid profile examination, i.e., direct role of apolipoproteins associated with various lipid molecules is a more dependable approach for better understanding of the disease and selecting suitable therapeutic targets. Therefore, studying their apolipoproteins is more relevant than assessing RA patients' altered lipid profile levels. Among the various apolipoprotein classes, Apo A1 and Apo B are primarily being focused. In addition, it also addresses how calculating Apo B:Apo A1 ratio can aid in analyzing the disease's risk. The marketed therapies available to control lipid abnormalities are associated with many other risk factors. Hence, directly targeting Apo A1 and Apo B would provide a better and safer option.

SMAC Mimetics for the Treatment of Lung Carcinoma: Present Development and Future Prospects.

BACKGROUND: Uncontrolled cell growth and proliferation, which originate from lung tissue often lead to lung carcinoma and are more likely due to smoking as well as inhaled environmental toxins. It is widely recognized that tumour cells evade the ability of natural programmed death (apoptosis) and facilitates tumour progression and metastasis. Therefore investigating and targeting the apoptosis pathway is being utilized as one of the best approaches for decades. OBJECTIVE: This review describes the emergence of SMAC mimetic drugs as a treatment approach, its possibilities to synergize the response along with current limitations as well as future perspective therapy for lung cancer. METHOD: Articles were analysed using search engines and databases namely Pubmed and Scopus. RESULT: Under cancerous circumstances, the level of Inhibitor of Apoptosis Proteins (IAPs) gets elevated, which suppresses the pathway of programmed cell death, plus supports the proliferation of lung cancer. As it is a major apoptosis regulator, natural drugs that imitate the IAP antagonistic response like SMAC mimetic agents/Diablo have been identified to trigger cell death. SMAC i.e. second mitochondria activators of caspases is a molecule produced by mitochondria, stimulates apoptosis by neutralizing/inhibiting IAP and prevents its potential responsible for the activation of caspases. Various preclinical data have proven that these agents elicit the death of lung tumour cells. Apart from inducing apoptosis, these also sensitize the cancer cells toward other effective anticancer approaches like chemo, radio, or immunotherapies. There are many SMAC mimetic agents such as birinapant, BV-6, LCL161, and JP 1201, which have been identified for diagnosis as well as treatment purposes in lung cancer and are also under clinical investigation. CONCLUSION: SMAC mimetics acts in a restorative way in the prevention of lung cancer.

A Systemic Review on Nutraceutical Supplements used in the Management of Osteoarthritis.

Osteoarthritis (OA) is a progressive degenerative joint disease. It basically impairs the structural integrity of articulate cartilage and imbalances the catabolic and anabolic signals in the joint. A degenerative disease is characterized by swelling, pain, and joint stiffness. The treatment and management of osteoarthritis are based on analgesic and anti-inflammatory agents, whereas the exact cause of OA is not known yet. The negative effects of synthetic medications have led to a daily rise in the usage of nutraceuticals and dietary supplements. Clinicians are aware of these treatments, and they also recommend nutraceuticals in addition to the currently preferred therapy. Many in-vitro and in-vivo experiments have been performed in past years to evaluate the function of these on osteoarthritis. The collection of articles was published on search engines like PubMed, Scopus, Google Scholar, ResearchGate, and ScienceDirect. The evaluation covers every potential nutraceutical utilized in osteoarthritis, together with its supporting data and mode of action. The present review discusses nutraceuticals, including devil's claw, vitamin D, boswellic acid, capsaicin, ginger, curcumin, krill oil, ginger, and avocado/soybean unsaponifiable.

Current Landscape of Gene Therapy for the Treatment of Cardiovascular Disorders.

Cardiovascular disorders (CVD) are the primary cause of death worldwide. Multiple factors have been accepted to cause cardiovascular diseases; among them, smoking, physical inactivity, unhealthy eating habits, age, and family history are flag-bearers. Individuals at risk of developing CVD are suggested to make drastic habitual changes as the primary intervention to prevent CVD; however, over time, the disease is bound to worsen. This is when secondary interventions come into play, including antihypertensive, anti-lipidemic, anti-anginal, and inotropic drugs. These drugs usually undergo surgical intervention in patients with a much higher risk of heart failure. These therapeutic agents increase the survival rate, decrease the severity of symptoms and the discomfort that comes with them, and increase the overall quality of life. However, most individuals succumb to this disease. None of these treatments address the molecular mechanism of the disease and hence are unable to halt the pathological worsening of the disease. Gene therapy offers a more efficient, potent, and important novel approach to counter the disease, as it has the potential to permanently eradicate the disease from the patients and even in the upcoming generations. However, this therapy is associated with significant risks and ethical considerations that pose noteworthy resistance. In this review, we discuss various methods of gene therapy for cardiovascular disorders and address the ethical conundrum surrounding it.

An Insight into the Pathogenesis of Diabetic Cardiomyopathy Along with the Novel Potential Therapeutic Approaches.

BACKGROUND: The existence of aberrant myocardial activity and function in the exclusion of those other cardiovascular events, such as atherosclerosis, hypertension, and severe valve disease, is known as diabetic cardiomyopathy. Diabetes patients are much more prone to death from cardiovascular illnesses than from any other cause, and they also have a 2-5 fold higher likelihood of acquiring cardiac failure and other complications. OBJECTIVE: In this review, the pathophysiology of diabetic cardiomyopathy is discussed, with an emphasis on the molecular and cellular irregularities that arise as the condition progresses, as well as existing and prospective future treatments. METHOD: The literature for this topic was researched utilizing Google Scholar as a search engine. Before compiling the review article, several research and review publications from various publishers, including Bentham Science, Nature, Frontiers, and Elsevier, were investigated. RESULT: The abnormal cardiac remodelling, marked by left ventricular concentric thickening and interstitial fibrosis contributing to diastolic impairment, is mediated by hyperglycemia, and insulin sensitivity. The pathophysiology of diabetic cardiomyopathy has been linked to altered biochemical parameters, decreased calcium regulation and energy production, enhanced oxidative damage and inflammation, and a build-up of advanced glycation end products. CONCLUSION: Antihyperglycemic medications are essential for managing diabetes because they successfully lower microvascular problems. GLP-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors have now been proven to benefit heart health by having a direct impact on the cardiomyocyte. To cure and avoid diabetic cardiomyopathy new medicines are being researched, including miRNA and stem cell therapies.

Understanding the promising role of antibody drug conjugates in breast and ovarian cancer.

A nascent category of anticancer therapeutic drugs called antibody-drug conjugates (ADCs) relate selectivity of aimed therapy using chemotherapeutic medicines with high cytotoxic power. Progressive linker technology led to the advancement of more efficacious and safer treatments. It offers neoteric as well as encouraging therapeutic strategies for treating cancer. ADCs selectively administer a medication by targeting antigens which are abundantly articulated on the membrane surface of tumor cells. Tumor-specific antigens are differently expressed in breast and ovarian cancers and can be utilized to direct ADCs. Compared to conventional chemotherapeutic drugs, this approach enables optimal tumor targeting while minimizing systemic damage. A cleavable linker improves the ADCs because it allows the toxic payload to be distributed to nearby cells that do not express the target protein, operating on assorted tumors with dissimilar cell aggregation. Presently fifteen ADCs are being studied in breast and ovarian carcinoma preclinically, and assortment of few have already undergone promising early-phase clinical trial testing. Furthermore, Phase I and II studies are investigating a wide variety of ADCs, and preliminary findings are encouraging. An expanding sum of ADCs will probably become feasible therapeutic choices as solo agents or in conjunction with chemotherapeutic agents. This review accentuates the most recent preclinical findings, pharmacodynamics, and upcoming applications of ADCs in breast and ovarian carcinoma.

Phytochemicals and Their Potential Mechanisms Against Insulin Resistance.

Insulin's inception dates back to 1921 and was unveiled through a momentous revelation. Diabetes is a dangerous, long-term disease in which the body fails to generate enough insulin or utilize the insulin it creates adequately. This causes hyperglycemia, a state of high blood sugar levels, which can even put a person into a coma if not managed. Activation of the insulin receptor corresponds to two crucial metabolic functions, i.e., uptake of glucose and storage of glycogen. Type 2 diabetes mellitus (T2DM) exists as one of the most challenging medical conditions in the 21st century. The sedentary lifestyle and declining quality of food products have contributed to the rapid development of metabolic disorders. Hence, there is an urgent need to lay some reliable, significant molecules and modalities of treatment to combat and manage this epidemic. In this review, we have made an attempt to identify and enlist the major phytoconstituents along with the associated sources and existing mechanisms against insulin resistance. The conducted study may offer potential sustainable solutions for developing and formulating scientifically validated molecules and phytoconstituents as formulations for the management of this metabolic disorder.

Recent Development in the Search for Epidermal Growth Factor Receptor (EGFR) Inhibitors based on the Indole Pharmacophore.

The signal transduction and cell proliferation are regulated by the epidermal growth factor receptor. The proliferation of tumor cells, apoptosis, invasion, and angiogenesis is inhibited by the epidermal growth factor receptor. Thus, breast cancer, non-small cell lung cancer, cervical cancer, glioma, and bladder cancer can be treated by targeting the epidermal growth factor receptor. Although third-generation epidermal growth factor receptor inhibitors are potent drugs, patients exhibit drug resistance after treatment. Thus, the search for new drugs is being continued. Among the different potent epidermal growth factor receptor inhibitors, we have reviewed the indole-based inhibitors. We have discussed the structure-activity relationship of the compounds with the active sites of the epidermal growth factor receptor receptors, their synthesis, and molecular docking studies.