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Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update.

In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biolo

A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.

Emerging evidence in cancer neuroscience has established a reciprocal bidirectional loop between neural signaling and tumor metabolism as a central driver of malignant progression. This review critically evaluates bidirectional neuro-metabolic symbiosis and its profound implications for overcoming treatment refractoriness. We first analyzed the anterograde mechanism, in which peripheral nerve terminals and systemic endocrine factors impose distinct metabolic dependencies on malignant and stromal cell populations. By forcing alterations in nutrient utilization pathways, these neural cues create

Структурное и механистическое профилирование модулятуры Hurr1 vidofludimus позволяет проектировать лиганд на основе структуры.

В центре биомедицинских исследований находится фактор нейрозащиты, связанный с ядерным рецептором 1 (Nurr1, NR4A2) для его многообещающей нейрозащитной роли в болезни Паркинсона, болезни Альцгеймера и множественном склерозе. Его деятельность может контролироваться лигандами, предлагающими доступ к фармакологической модуляции Hurr1. Вместе с тем связующие эпитопы и механизмы молекулярной активации синтетических активаторов Hurr1 по-прежнему остаются труднодостижимыми, но имеют важное значение для продвижения к новым лекарствам лигандов Hurr1. Здесь мы охарактеризовали диссоциацию Hurr1 димера и

Amyloidosis with Cardiac Involvement: Identification, Characterization, and Management.

Purpose of reviewAmyloidosis is a protein deposition disease whereby a variety of precursor proteins form insoluble fibrils that deposit in tissues, causing organ dysfunction and, many times, death. Accurate characterization of the disease based on the nature of the precursor protein, organ involvement, and extent of disease is paramount to guide management. Cardiac amyloidosis is critical to understand because of its impact on prognosis and new treatment options available.Recent findingsNew imaging methods have proven to be considerably valuable in the identification of cardiac amyloid infilt

Ammonium metabolism rewiring in the prostate cancer microenvironment: Mechanisms and clinical prospects.

Ammonium metabolism represents a critically understudied yet pivotal driver of prostate tumorigenesis and tumor microenvironment (TME) remodeling. The interplay between tumor metabolic reprogramming and the tumor microenvironment has emerged as a critical frontier in oncology research. While previous studies on prostate cancer metabolism have predominantly focused on lipid metabolism and the Warburg effect, the role of ammonium metabolism, particularly the urea cycle in tumor immune regulation remains insufficiently explored. This metabolic reprogramming constitutes a central node connecting c

DNA Damaging Drugs

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Assessment of circulating proteins in thyroid cancer: Proteome-wide Mendelian randomization and colocalization analysis.

The causality between circulating proteins and thyroid cancer (TC) remains unclear. We employed five large-scale circulating proteomic genome-wide association studies (GWASs) with up to 100,000 participants and a TC meta-GWAS (nCase = 3,418, nControl = 292,703) to conduct proteome-wide Mendelian randomization (MR) and Bayesian colocalization analysis. Protein and gene expressions were validated in thyroid tissue. Through MR analysis, we identified 26 circulating proteins with a putative causal relationship with TCs, among which NANS protein passed multiple corrections (P BH = 3.28e-5, 0.05/1,5

Совпадение в полном тексте источника
… In the Gene Ontology (GO) enrichment analysis, these proteins were involved in several biological processes (BPs), including the biosynthesis of dicarboxylic acids, proteoglycan metabolism, and chondroitin sulfate metabolism. …

Иммунотерапия при помощи модуляции кишечного микробиота в множестве склерозов и ассоциации с диетологической и клинической реакцией - эффект диметилфуматовой терапии.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Накопление данных подтверждает ту роль, которую микробиота играет в здравоохранении и болезнях, в том числе в многократном склерозе (МС). Как наркотики MS влияют на микробиоту и является ли это частью их способа действия, пока неизвестно. ЦЕЛИ: Оценка воздействия диметилфумарата (ДМП) на кишечник микробиота и того, связана ли микробиота с клинической реакцией или неблагоприятными явлениями (АЭ) с ДМФ или с диетой. DESIGN: когортное исследование наблюдений, в котором микробиота 45 больные с повторной эмиссией MS до начала работы DMF и после этого 6 месяцев психотерапии ДМ

Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.

Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, H

Exploring the Molecular Mechanisms by Which DEHP Promotes the Occurrence and Progression of Kidney Stones Based on Network Toxicology and Experimental Validation.

BACKGROUND: The global burden of kidney stones is increasing, while di(2-ethylhexyl) phthalate (DEHP), a widespread plasticizer and endocrine-disrupting pollutant, has been implicated as a potential environmental risk factor. This study investigated the mechanisms by which DEHP may aggravate calcium oxalate kidney stones through network toxicology, computational analyses, and experimental validation. METHODS: DEHP- and kidney stone-related targets were retrieved from six databases. Shared targets were analyzed using protein-protein interaction networks and Gene Ontology and Kyoto Encyclopedia

Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as Drivers of Neoplastic Change.

The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states-cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic glycolysis". Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic acids and lipids. To date, several molec

Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.

Acylation modification plays a crucial role in tumor progression through altering protein homeostasis and localization. However, a comprehensive summary of these processes is lacking. Protein acylation modifications are comprehensively summarized and categorized based on the amino acids that are modified. This review focuses on modifications of the lysine (acetylation, succinylation, crotonylation, malonylation, and glutarylation) and cysteine (myristoylation and palmitoylation) groups. The key enzymes involved in the occurrence and erasure of different modifications, as well as their effects

Микроаэробный маленький белок от теплового шока способствует ризобию лимуминозараму/Писуму симбиозу и взаимодействует с широким диапазоном бактерироидных белков.

Во время создания симбиоза с бобовыми растениями ризобия подвергается воздействию враждебной физической и химической микроокружающей среды, к которой требуется адаптация. Протеины реакции на стресс, включая небольшие белки от теплового удара (SHSP), ранее, как было установлено, дифференцировались в бактерироидах, индуцируемых ризобием лимуминозарум бv. viciae UPM791 в различных хост-узлах. В ходе этой работы мы провели функциональный анализ зависящих от принимающей стороны SHSP RLV_1399. Рlv_1399- Исключенный штамм мутантов был нарушен в симбиотических свойствах гороха, но не чечевиц. Выражени

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… Bacteroids express the nitrogenase enzyme converting N 2 to ammonia that is secreted to the plant for amino acid synthesis and, in return, the plant provides carbon sources and energy in the form of dicarboxylic acids ( 2 ). …

The Onco-Nephrology Field: The Role of Personalized Chemotherapy to Prevent Kidney Damage.

In recent years, the onco-nephrology field has acquired a relevant role in internal medicine due to the growing number of cases of renal dysfunction that have been observed in cancer patients. This clinical complication can be induced by the tumor itself (for example, due to obstructive phenomena affecting the excretory tract or by neoplastic dissemination) or by chemotherapy, as it is potentially nephrotoxic. Kidney damage can manifest as acute kidney injury or represent a worsening of pre-existing chronic kidney disease. In cancer patients, physicians should try to set preventive strategies

Drug-Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics.

Cannabidiol (CBD) is an easily accessible and affordable Marijuana (Cannabis sativa L.) plant derivative with an extensive history of medical use spanning thousands of years. Interest in the therapeutic potential of CBD has increased in recent years, including its anti-tumour properties in various cancer models. In addition to the direct anticancer effects of CBD, preclinical research on numerous cannabinoids, including CBD, has highlighted their potential use in: (i) attenuating chemotherapy-induced adverse effects and (ii) enhancing the efficacy of some anticancer drugs. Therefore, CBD is ga

Inhibition of Cxcr4 chemokine receptor signaling improves habituation learning in a zebrafish model of neurofibromatosis.

Neurofibromatosis type 1 (NF1) is a neurogenetic disorder caused by loss-of-function mutations in the gene neurofibromin 1 (NF1). NF1 encodes neurofibromin, a multifunctional tumor-suppressing protein that regulates Ras, cAMP and dopamine signaling. NF1 predisposes patients to a wide range of symptoms, including peripheral nerve tumors, brain tumors and cognitive dysfunction. Despite considerable work using animal models to investigate the role of neurofibromin in behavior, translating research into treatment for NF1-associated cognitive dysfunction has not yet been successful. Here, we provid

Chemotherapy-induced acute kidney injury: epidemiology, pathophysiology, and therapeutic approaches.

Despite significant advancements in oncology, conventional chemotherapy remains the primary treatment for diverse malignancies. Acute kidney injury (AKI) stands out as one of the most prevalent and severe adverse effects associated with these cytotoxic agents. While platinum compounds are well-known for their nephrotoxic potential, other drugs including antimetabolites, alkylating agents, and antitumor antibiotics are also associated. The onset of AKI poses substantial risks, including heightened morbidity and mortality rates, prolonged hospital stays, treatment interruptions, and the need for

Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications.

Curcumin, a yellow polyphenolic pigment from the Curcuma longa L. (turmeric) rhizome, has been used for centuries for culinary and food coloring purposes, and as an ingredient for various medicinal preparations, widely used in Ayurveda and Chinese medicine. In recent decades, their biological activities have been extensively studied. Thus, this review aims to offer an in-depth discussion of curcumin applications for food and biotechnological industries, and on health promotion and disease prevention, with particular emphasis on its antioxidant, anti-inflammatory, neuroprotective, anticancer, h

Pharmacomicrobiomics in precision cancer therapy: bench to bedside.

The burgeoning field of pharmacomicrobiomics offers promising insights into the intricate interplay between the microbiome and cancer, shaping responses to diverse treatment modalities. This review aims to analyze the molecular mechanisms underlying interactions between distinct microbiota types and cancer, as well as their influence on treatment outcomes. We explore how the microbiome impacts antitumor immunity, and response to chemotherapy, immunotherapy, and radiation therapy, unveiling its multifaceted roles in cancer progression and therapy resistance. Moreover, we discuss the challenges

FDA-Approved Drugs Containing Amide Functionality in the Last Five Years (2021-2025): Pharmaceutical Use, Trends and Synthetic Approaches.

The amide functional group remains a cornerstone of medicinal chemistry, serving as an indispensable scaffold in the design of modern therapeutics. This review presents an analysis of FDA-approved drugs (small molecules and peptides with MW ®), amides form the structural backbone of peptidomimetics, enabling high-affinity binding to a viral protease. In precision oncology, as seen with adagrasib (Krazati®), the amide acts as a critical, metabolically stable linker that positions a covalent warhead for selective inhibition of a mutant kinase. This analysis underscores that amide's unique combin