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Apoptosis and (in) Pain-Potential Clinical Implications.

The deregulation of apoptosis is involved in the development of several pathologies, and recent evidence suggests that apoptosis may be involved in chronic pain, namely in neuropathic pain. Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system; however, the details of the molecular mechanisms have not yet been fully elucidated. Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect signals released by injured tissues and respond to these damage signals. TRP channels are similar to the

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… In contrast, there is a decrease in inhibitory transmission due to a reduction of Gamma-Aminobutyric Acid (GABA) release or death of GABAergic neurons [ 26 ]. …

Карвацоль Ойл как нейропоохранный агент: обзор дизайна исследований и последних достижений.

Нейродегенеративные заболевания в основном воспринимаются как болезни стареющего населения, однако сегодня в день эти заболевания представляют угрозу для населения всех возрастных групп, несмотря на значительное улучшение качества жизни. Согласно сообщениям, почти все основные масла (ЭО) обладают определенными нейрозащитными способностями и на протяжении столетий использовались в качестве добавок к хорошему психическому здоровью. Этот обзор свидетельствует о терапевтическом потенциале одного такого монотерпенового фенола, карвакрула (CV), который может быть использован в качестве основного тер

Analgesic Alkaloids Derived From Traditional Chinese Medicine in Pain Management.

Chronic pain is one of the most prevalent health problems. The establishment of chronic pain is complex. Current medication for chronic pain mainly dependent on anticonvulsants, tricyclic antidepressants and opioidergic drugs. However, they have limited therapeutic efficacy, and some even with severe side effects. We turned our interest into alkaloids separated from traditional Chinese medicine (TCM), that usually act on multiple drug targets. In this article, we introduced the best-studied analgesic alkaloids derived from TCM, including tetrahydropalmatine, aloperine, oxysophocarpine, matrine

ASENT 2022 Annual Meeting.

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Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms.

Peripheral neurologic complications are frequent adverse events during oncologic treatments and often lead to dose reduction, administration delays with time elongation of the therapeutic plan and, not least, worsening of patients' quality of life. Experience skills are required to recognize symptoms and clinical evidences and the collaboration between different health professionals, in particular oncologists and hospital pharmacists, grants a correct management of this undesirable occurrence. Some classes of drugs (platinates, vinca alkaloids, taxanes) typically develop this kind of side effe

Morphine-3-glucuronide upregulates PD-L1 expression via TLR4 and promotes the immune escape of non-small cell lung cancer.

ObjectivePatients with cancer pain are highly dependent on morphine analgesia, but studies have shown a negative correlation between morphine demand and patient outcomes. The long-term use of morphine may result in abnormally elevated serum morphine-3-glucuronide (M3G) levels. Hence, the effects of M3G on tumor progression are worth studying.MethodsThe effects of M3G on PD-L1 expressions in human non-small cell lung cancer (NSCLC) cell lines were first evaluated. Activation of TLR4 downstream pathways after M3G treatment was then determined by Western blot. The effects of M3G on human cytotoxi

Drugs and Epigenetic Molecular Functions. A Pharmacological Data Scientometric Analysis.

Interactions of drugs with the classical epigenetic mechanism of DNA methylation or histone modification are increasingly being elucidated mechanistically and used to develop novel classes of epigenetic therapeutics. A data science approach is used to synthesize current knowledge on the pharmacological implications of epigenetic regulation of gene expression. Computer-aided knowledge discovery for epigenetic implications of current approved or investigational drugs was performed by querying information from multiple publicly available gold-standard sources to (i) identify enzymes involved in c

Serum Onconeural Antibodies in Dogs and Cats for Early Diagnosis of Cancer.

Cancer is one of the leading causes of death in dogs and cats worldwide, and effective early detection techniques and reliable therapies are still lacking. Given the high demand for early cancer detection and differentiation in veterinary diagnostics, we developed and validated a new diagnostic approach to assess onconeural antibodies, also known as high-risk antibodies, in dog and cat blood serum samples. We determined the presence of systemic onconeural/high-risk (ONHR) antibodies, their suitability for early cancer diagnostics, and the feasibility of differentiating various malignancies. Ou

Sacubitril/Valsartan Ameliorates Crizotinib-Induced Cardiotoxicity in Mice.

BackgroundLung cancer is one of the major cause of death globally. Crizotinib is a first-line drug used in treating non-small-cell lung cancer (NSCLC). However, the pathophysiological mechanisms underlying its cardiotoxicity are unknown. This study investigated the mechanisms of crizotinib-induced cardiotoxicity and explored whether this toxicity can be prevented by the angiotensin receptor/neprilysin inhibitor sacubitril/valsartan.MethodsMale C57BL/6 mice were randomly divided into three groups: control, crizotinib (40 mg ⋅ kg - 1 ⋅ d - 1 for four weeks), and crizotinib + sacubitril/valsartan

Student Summer Research Awards - SSRAAbstracts of the SSRA September 2022 meeting, UCD School of Medicine.

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Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk.

Cancer neuroscience is an emerging field that investigates the intricate relationship between the nervous system and cancer, gaining increasing recognition for its importance. The central nervous system governs the development of the nervous system and directly affects brain tumors, and the peripheral nervous system (PNS) shapes the tumor microenvironment (TME) of peripheral tumors. Both systems are crucial in cancer initiation and progression, with recent studies revealing a more intricate role of the PNS within the TME. Tumors not only invade nerves but also persuade them through remodeling

Amyloid Proteins and Peripheral Neuropathy.

Painful peripheral neuropathy affects millions of people worldwide. Peripheral neuropathy develops in patients with various diseases, including rare familial or acquired amyloid polyneuropathies, as well as some common diseases, including type 2 diabetes mellitus and several chronic inflammatory diseases. Intriguingly, these diseases share a histopathological feature-deposits of amyloid-forming proteins in tissues. Amyloid-forming proteins may cause tissue dysregulation and damage, including damage to nerves, and may be a common cause of neuropathy in these, and potentially other, diseases. He

Autonomic control of ventricular function in health and disease: current state of the art.

PurposeCardiac autonomic dysfunction is one of the main pillars of cardiovascular pathophysiology. The purpose of this review is to provide an overview of the current state of the art on the pathological remodeling that occurs within the autonomic nervous system with cardiac injury and available neuromodulatory therapies for autonomic dysfunction in heart failure.MethodsData from peer-reviewed publications on autonomic function in health and after cardiac injury are reviewed. The role of and evidence behind various neuromodulatory therapies both in preclinical investigation and in-use in clini

Посттрансляционные изменения в нейроиммунных клетках во время нейроинфламмации: комплексные сети регулирования и терапевтические возможности.

Нейроинфламмация представляет собой общий патологический механизм, лежащий в основе широкого спектра нарушений центральной нервной системы (КНС), включая нейродегенеративные расстройства (НДД), ишемический инсульт (ИС), травматическое повреждение мозга (ТБИ) и демиелионирующие заболевания, такие как множественный склероз (МС). Этот процесс начинается с организованной реакции микроглий, астроцитов, олигодендроцитов, нейронов, эндотелиальных клеток головного мозга и проникновения в периферийные иммунные клетки. Нейроинфламмация может облегчить ремонт тканей или, наоборот, увековечить хроническое

From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients' outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs hav

Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases.

There have been magnificent advancements in the understanding of molecular mechanisms of chronic diseases over the past several years, but these diseases continue to be a considerable cause of death worldwide. Most of the approved medications available for the prevention and treatment of these diseases target only a single gene/protein/pathway and are known to cause severe side effects and are less effective than they are anticipated. Consequently, the development of finer therapeutics that outshine the existing ones is far-reaching. Natural compounds have enormous applications in curbing seve

Invited Lectures : Overviews Purinergic signalling: past, present and future.

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Highlighting recent achievements to advance more effective cancer immunotherapy.

From 17 to 19th October 2024, the XXI Italian Network for Bio-Immunotherapy of Tumors Meeting (NIBIT) took place in Palermo, in the marvelous historical location of Teatro Politeama, under the auspices of the Italian Association of Medical Oncology (AIOM), Italian Association of Cancer Research (AIRC), Fondazione Pezcoller, Italian Alliance against Cancer (ACC), Italian Lymphoma Foundation (FIL), Grazia Focacci Foundation and Melagioco Foundation. The conference covered a spectrum of topics ranging from target discovery to therapeutic advances in immuno-oncology, bringing world-renowned expert

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

Химерический антигенный рецептор T-клеточная терапия в нейроиммунных болезнях: механистическое обоснование, клинический опыт и проблемы с переводом.

Нейроиммунные заболевания представляют собой разнородную группу расстройств, при которых клетки В, плазменные удары, плазменные клетки, автоантитела и Т клетки поразному влияют на повреждение тканей. Хотя биологика B-клеток улучшила контроль за заболеваниями, некоторые пациенты по-прежнему сталкиваются с реанимацией, рецидивом после лечения или кумулятивной неврологической инвалидностью. Химерическая антигенная рецепторная T-клетка (CAR-T-клетка) является средством достижения более глубокого и потенциально устойчивого истощения определенных патогенных иммунных клеток. Этот описательный обзор в