Current Pharmaceutical Design - Volume 29, Issue 41, 2023

The cochlear structure is highly complex and specific, and its development is regulated by multiple signaling pathways. Abnormalities in cochlear development can lead to different degrees of loss of function. Hair cells (HCs), which are difficult to regenerate in the mature mammalian cochlea, are susceptible to damage from noise and ototoxic drugs, and damage to HCs can cause hearing loss to varying degrees. Notch, a classical developmental signaling molecule, has been shown to be closely associated with embryonic cochlear development and plays an important role in HC regeneration in mammals, suggesting that the Notch signaling pathway may be a potential therapeutic target for cochlear development and hearing impairment due to HC damage. In recent years, the important role of the Notch signaling pathway in the cochlea has received increasing attention. In this paper, we review the role of Notch signaling in cochlear development and HC regeneration, with the aim of providing new research ideas for the prevention and treatment of related diseases.

This review highlights the relationships between gastrointestinal microorganisms and the brain. The gut microbiota communicates with the central nervous system through nervous, endocrine, and immune signalling mechanisms. Our brain can modulate the gut microbiota structure and function through the autonomic nervous system, and possibly through neurotransmitters which directly act on bacterial gene expression. In this context, oxidative stress is one the main factors involved in the dysregulation of the gut-brain axis and consequently in neurodegenerative disorders. Several factors influence the susceptibility to oxidative stress by altering the antioxidant status or free oxygen radical generation. Amongst these, of interest is alcohol, a commonly used substance which can negatively influence the central nervous system and gut microbiota, with a key role in the development of neurodegenerative disorder. The role of "psychobiotics" as a novel contrast strategy for preventing and treating disorders caused due to alcohol use and abuse has been investigated.

Cancer is one of life's most difficult difficulties and a severe health risk everywhere. Except for haematological malignancies, it is characterized by unchecked cell growth and a lack of cell death, which results in an aberrant tissue mass or tumour. Vascularization promotes tumor growth, which eventually aids metastasis and migration to other parts of the body, ultimately resulting in death. The genetic material of the cells is harmed or mutated by environmental or inherited influences, which results in cancer. Presently, anti-neoplastic medications (chemotherapy, hormone, and biological therapies) are the treatment of choice for metastatic cancers, whilst surgery and radiotherapy are the mainstays for local and non-metastatic tumors. Regrettably, chemotherapy disturbs healthy cells with rapid proliferation, such as those in the gastrointestinal tract and hair follicles, leading to the typical side effects of chemotherapy. Finding new, efficient, targeted therapies based on modifications in the molecular biology of tumor cells is essential because current chemotherapeutic medications are harmful and can cause the development of multidrug resistance. These new targeted therapies, which are gaining popularity as demonstrated by the FDA-approved targeted cancer drugs in recent years, enter molecules directly into tumor cells, diminishing the adverse reactions. A form of cancer treatment known as targeted therapy goes after the proteins that regulate how cancer cells proliferate, divide, and disseminate. Most patients with specific cancers, such as chronic myelogenous leukemia (commonly known as CML), will have a target for a particular medicine, allowing them to be treated with that drug. Nonetheless, the tumor must typically be examined to determine whether it includes drug targets.

Introduction: The current article reviews the latest information on epidemiology, clinical features, diagnosis, recent advancements in clinical management, current therapeutic novelties, and the prevention of migraines. In a narrative review, all studies as per developed MeSH terms published until February 2023, excluding those irrelevant, were identified through a PubMed literature search.Methods: Overall, migraine affects more than a billion people annually and is one of the most common neurological illnesses. A wide range of comorbidities is associated with migraines, including stress and sleep disturbances. To lower the worldwide burden of migraine, comprehensive efforts are required to develop and enhance migraine treatment, which is supported by informed healthcare policy. Numerous migraine therapies have been successful, but not all patients benefit from them.Results: CGRP pathway-targeted therapy demonstrates the importance of translating mechanistic understanding into effective treatment. In this review, we discuss clinical features, diagnosis, and recently approved drugs, as well as a number of potential therapeutic targets, including pituitary adenylate cyclase-activating polypeptide (PACAP), adenosine, opioid receptors, potassium channels, transient receptor potential ion channels (TRP), and acid-sensing ion channels (ASIC).Conclusion: In addition to providing more treatment options for improved clinical care, a better understanding of these mechanisms facilitates the discovery of novel therapeutic targets.

Introduction: Renal cancer ranks 10^th in the mortality structure of the Russian Federation. The introduction of checkpoint inhibitors has changed the paradigm of treatment of patients with malignant neoplasms.Method: Data from clinical trials have shown good progression-free median and median overall survival. Each cancer center has been accumulating its own experience in treating patients with renal cell cancer by applying modern target drugs and immunotherapy. Result: In routine clinical practice, oncologists do not get the results that have been demonstrated in clinical trials when evaluating the effectiveness of the therapy. Conclusion: In this single-center clinical study, we discuss the results of using nivolumab as mono-therapy and the combination of nivolumab with ipilimumab in metastatic renal parenchyma cancer patients.

Introduction: In the present study, we aimed to investigate the extraction and identification of the potential phytochemicals from the Methanolic Extract of Dryopteris ramosa (MEDR) using GC-MS profiling for validating the traditional uses of MEDR its efficacy in inflammations by using in-vitro, in-vivo and in silico approaches in anti-inflammatory models.Methods: GC-MS analysis confirmed the presence of a total of 59 phytochemical compounds. The human red blood cells (HRBC) membrane stabilization assay and heat-induced hemolysis method were used as in-vitro anti-inflammatory activity of the extract. The in-vivo analysis was carried out through the Xylene-induced mice ear oedema method. It was found that MEDR at a concentration of 20 μg, 30 μg, and 40 μg showed 35.45%, 36.01%, and 36.33% protection to HRBC in a hypotonic solution, respectively. At the same time, standard Diclofenac at 30 μg showed 45.31% protection of HRBC in a hypotonic solution.Results: The extract showed inhibition of 25.32%, 26.53%, and 33.31% cell membrane lysis at heating at 20 μg, 30 μg, and 40 μg, respectively. In comparison, standard Diclofenac at 30 μg showed 50.49% inhibition of denaturation to heat. Methanolic extract of the plant exhibited momentous inhibition in xylene-induced ear oedema in mice treated with 30 μg extract were 47.2%, 63.4%, and 78.8%, while inhibition in mice ear oedema treated with 60 μg extract was 34.7%, 43.05%, 63.21% and reduction in ear thickness of standard drug were 57.3%, 59.54%, 60.42% recorded at the duration of 1, 4 and 24 hours of inflammation. Molecular docking and simulations were performed to validate the anti-inflammatory role of the phytochemicals that revealed five potential phytochemicals i.e. Stigmasterol,22,23dihydro, Heptadecane,8methyl, Pimaricacid, Germacrene and 1,3Cyclohexadiene,_5(1,5dimethyl4hexenyl)-2methyl which revealed potential or significant inhibitory effects on cyclooxygenase-2 (COX-2), tumour necrosis factor (TNF-α), and interleukin (IL-6) in the docking analysis.Conclusion: The outcome of the study signifies that MEDR can offer a new prospect in the discovery of a harmonizing and alternative therapy for inflammatory disease conditions.