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The Multifaceted Nature of GLP-1: Molecular Mechanisms and Signaling Pathways in Metabolic and Neurodegenerative Diseases.

The aim of this article is to present the current state of knowledge regarding the use of GLP-1 agonists in the treatment of type 2 diabetes, obesity, and other potential clinical indications, including neurodegenerative conditions. The article describes the characteristics of the diseases discussed, with particular emphasis on the pathophysiological mechanisms and the impact of metabolic disorders on the course of the diseases. In addition, the specific role of GLP-1 receptor agonists and their mechanisms of action leading to improved clinical outcomes were discussed, including their impact o

Chronic pruritus: a narrative review.

Chronic pruritus encompasses a manifestation of several cutaneous, allergic, infectious, neurological, psychological, and systemic conditions, whose etiological investigation and therapeutic strategy can be challenging. This comprehensive review aims to enhance the understanding of pruritus by highlighting important elements in its pathogenesis, including keratinocytes, Merkel cells and mast cells, nerve fibers, histaminergic and nonhistaminergic pathways, and the interaction of itch signals with the central nervous system. Diagnostic evaluation of chronic pruritus may require a meticulous app

Pain Management in Patients with Multiple Myeloma: An Update.

Most patients with multiple myeloma (MM) suffer from chronic pain at every stage of the natural disease process. This review focuses on the most common causes of chronic pain in MM patients: (1) pain from myeloma bone disease (MBD); (2) chemotherapy-induced peripheral neuropathy as a possible consequence of proteasome inhibitor therapy (i.e., bortezomib-induced); (3) post-herpetic neuralgia as a possible complication of varicella zoster virus reactivation because of post-transplantation immunodepression; and (4) pain in cancer survivors, with increasing numbers due to the success of antiblasti

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

Male Lower Urinary Tract Dysfunction: An Underrepresented Endpoint in Toxicology Research.

Lower urinary tract dysfunction (LUTD) is nearly ubiquitous in men of advancing age and exerts substantial physical, mental, social, and financial costs to society. While a large body of research is focused on the molecular, genetic, and epigenetic underpinnings of the disease, little research has been dedicated to the influence of environmental chemicals on disease initiation, progression, or severity. Despite a few recent studies indicating a potential developmental origin of male LUTD linked to chemical exposures in the womb, it remains a grossly understudied endpoint in toxicology research

Epigenetic Dysregulation in Neurodegeneration: The Role of Histone Deacetylases and Emerging Inhibitor Strategies.

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are characterized by complex pathologies with progressive neurodegeneration, protein misfolding, oxidative stress, and persistent inflammation. Recent findings indicate the pivotal involvement of epigenetic disruption, particularly aberrant histone deacetylase (HDAC) activity, in disease initiation and progression. In the current review, we systematically discuss the mechanistic function of HDACs across all classes (I, IIa, IIb, III, and IV) in neurodegenerative disease mechanis

Unveiling the Role of CCL3: A Driver of CIPN in Colon Cancer Patients?

Cancer neuroscience is an emerging field revealing how malignancies interact with the nervous system to shape disease progression and symptom burden. In colorectal cancer (CRC), increasing evidence suggests a direct interplay between tumor cells and peripheral sensory neurons, contributing not only to cancer progression but also to chemotherapy-induced side effects such as peripheral neuropathy. Chemokines, particularly CCL3, appear to be key players in this bidirectional communication. This literature review aims to critically examine the role of CCL3 in CRC and chemotherapy-induced periphera

Neurotropin alleviates rat osteocarcinoma pain via P2X3 receptor activation in the midbrain periaqueductal gray.

ObjectivesClinically effective analgesia treatment for patients afflicted with osteocarcinoma lessens the intensity of pain. The midbrain periaqueductal gray (PAG) plays a critical role in pain modulation, and activation of P2X3 receptors in this region mediates pain processing. Neurotropin is a small molecule drug used for analgesic treatment of a number of chronic pain conditions. The present study aims at determining whether P2X3 receptor activation in PAG is responsible for the analgesic effect of neurotropin in rats with osteocarcinoma pain.Materials and methodsThe tibia of female Sprague

Diagnosis and Management of Chronic Pruritus: An Expert Consensus Review.

The aim of this study is to formulate the best clinical practice in the diagnosis and management of chronic pruritus (CP). We searched PubMed, EMBASE, Scopus, Web of Science, and the WHO's regional databases, for studies on "Diagnosis and management of chronic pruritus" from January 1, 2014, to July 31, 2015. We included programmatic reports and hand-searched references of published reviews and articles. Two independent reviewers screened articles and extracted data. We screened 87 of 95 studies that contained qualitative data. Avoid: Dry climate, heat, alcohol compress, ice packs, frequent ba

Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies.

Lysophosphatidic acid (LPA) is an abundant bioactive phospholipid, with multiple functions both in development and in pathological conditions. Here, we review the literature about the differential signaling of LPA through its specific receptors, which makes this lipid a versatile signaling molecule. This differential signaling is important for understanding how this molecule can have such diverse effects during central nervous system development and angiogenesis; and also, how it can act as a powerful mediator of pathological conditions, such as neuropathic pain, neurodegenerative diseases, an

Drug Repurposing of New Treatments for Neuroendocrine Tumors.

Drug repurposing or drug repositioning is the process of identifying new therapeutic uses for approved or investigational drugs beyond the original treatment indication. The discovery of new drugs for cancer therapy needs this cost-effective and time-saving alternative strategy to traditional drug development for a rapid clinical translation in Phase II/III studies, especially for unmet medical needs and rare diseases. Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms arising from cells of the neuroendocrine system that, though often indolent, can be aggressive and metas

Advancing Brain Health Naturally: β-Caryophyllene and Xanthohumol as Neuroprotective Agents.

Neurodegenerative diseases (NDDs) represent a class of incurable and progressive disorders characterized by the gradual degeneration of the structure and function of the nervous system, particularly the brain and spinal cord. A range of innovative therapeutic approaches is currently under investigation, such as stem cell-based therapies, gene-editing platforms such as CRISPR, and immunotherapies directed at pathogenic proteins. Moreover, phytochemicals such as β-caryophyllene and xanthohumol have demonstrated significant neuroprotective potential in preclinical models. These natural agents exe

Plasma cell targeting with the anti-CD38 antibody daratumumab in myalgic encephalomyelitis/chronic fatigue syndrome-a clinical pilot study.

BackgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) entails low quality of life for patients and massive societal costs. There is an urgent need for elucidation of disease mechanisms and for rational treatment. Our working hypothesis is that ME/CFS in a subgroup of patients is associated with functional autoantibodies emerging after an infection, and that plasma-cell depletion with transient reductions in serum immunoglobulins will have a beneficial effect on patients' symptoms.ObjectiveTo evaluate feasibility and toxicity of plasma-cell targeting treatment using the subcutan

Autoantibodies as Biomarker and Therapeutic Target in Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disorder characterized by immune dysregulation evoking the pathophysiological triad of inflammation, fibrosis and vasculopathy. In SSc, several alterations in the B-cell compartment have been described, leading to polyclonal B-cell hyperreactivity, hypergammaglobulinemia and autoantibody production. Autoreactive B cells and autoantibodies promote and maintain pathologic mechanisms. In addition, autoantibodies in SSc are important biomarkers for predicting clinical phenotype and disease progression. Autoreactive B cells and autoantibodies rep

Естественные соединения серы в состоянии психического здоровья и неврологических расстройств: наблюдения и исследования.

За прошедшие годы глобальное бремя неврологических и психических расстройств значительно возросло, в результате чего они стали одной из наиболее серьезных проблем и вызовов для здоровья человека. В рамках новых методов лечения от болезней и болезней все больше внимания уделяется вопросам питания и здравоохранения. Питание серы, главным образом полученное из различных природных источников, играет решающую роль в многочисленных физиологических процессах, включая функцию мозга. В настоящем обзоре содержится обзор химического состава ряда естественных источников таких богатых серой веществ, как из

Колокольчик коерулус на перекрестке воспаления и нейродегенерации в множестве склерозов.

Множественный склероз (MS) все чаще признается в качестве системного расстройства, включающего повреждения серой материи, разрыв сети и нейропсихиатрические симптомы наряду с демиелинацией. В этих рамках Colus coeruleus (LC), являющийся основным источником норадреналина (NA) в центральной нервной системе, появляется в качестве надежного центра регулирования в рамках распределенной моноаминергической сети. Основные элементы: С помощью ЛК формируется микроглиальная и астроцитическая реактивность, окислительный стресс, митохондриальная функция, дифференциация олигодендроцитов и устойчивость мозго

Oral Graft-Versus-Host Disease: A Pictorial Review and a Guide for Dental Practitioners.

IntroductionGraft-versus-host disease (GVHD) is a complication of haematopoietic stem cell transplantation (HSCT). GVHD may also develop following solid transplants or blood transfusions if white blood cells are transferred. GVHD affects multiple organs, including the oral tissues.ObjectiveThis pictorial review provides a background of GVHD to dental practitioners, describes the most common oral manifestations of GVHD and highlights the main treatment modifications needed to deliver dental care to patients with GVHD.MethodsA narrative review enhanced with clinical photographs.ResultsAcute GVHD

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… Pharmacological stimulation may be achieved with cholinergic agonists, such as pilocarpine (5–10 mg, three or four times daily) and cevimeline (15–30 mg, two or three times daily). 53 Electrical stimulation has also been studied in patients with oral cGVHD. 54 An important component in the management …

Repositioning of drugs for Parkinson's disease and pharmaceutical nanotechnology tools for their optimization.

Parkinson's disease (PD) significantly affects patients' quality of life and represents a high economic burden for health systems. Given the lack of safe and effective treatments for PD, drug repositioning seeks to offer new medication alternatives, reducing research time and costs compared to the traditional drug development strategy. This review aimed to collect evidence of drugs proposed as candidates to be reused in PD and identify those with the potential to be reformulated into nanocarriers to optimize future repositioning trials. We conducted a detailed search in PubMed, Web of Science,

Cancer cachexia--pathophysiology and management.

About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Cachexia can have a profound impact on quality of life, symptom burden, and a patient's sense of dignity. It is a very serious complication, as weight loss during cancer treatment is associated with more chemotherapy-related side effects, fewer completed cycles of chemotherapy, and decreased survival rates. Numerous cytokines have been postulated to play a role in the etiology of cancer cachexia. Cytokines can elicit effects that mimic leptin signaling a

Pulmonary hypertension and the potential of 'drug' repurposing: A case for African medicinal plants.

AbstractPulmonary hypertension (PH) is a haemodynamic disorder in which elevated blood pressure in the pulmonary circulation is caused by abnormal vascular tone. Despite advances in treatment, PH mortality remains high, and drug repurposing has been proposed as a mitigating approach. This article reviews the studies that have investigated drug repurposing as a viable option for PH. We provide an overview of PH and highlight pharmaceutical drugs with repurposing potential, based on limited evidence of their mechanisms of action. Moreover, studies have demonstrated the benefits of medicinal plan