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Oxidative Stress: Signaling Pathways, Biological Functions, and Disease.

The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single-organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan-organ di

Наследственная оптическая нейропатия Лебера и множественный склероз: совпадение между митохондриальной болезнью и нейроинфламмацией.

Хотя Множественный склероз (MS) и наследственная оптическая нейропатия Лебера (LHON) имеют различные патофизиологические механизмы, они оба являются нейродегенеративными условиями, связанными с дисфункцией митохондриала. MS — аутоиммунная болезнь, которая характеризуется обезвоживанием и нейроинфламмацией; и LHON — митохондриальное расстройство, в основном воздействующее на зрительные нервы, приводящее к серьезной потере зрения. Проведенные в последнее время исследования свидетельствуют о сосуществовании этих двух условий, особенно у женщин, и позволяют предположить, что митохондриальные вариа

Окисляющий стресс как терапевтическая цель в амиотропическом боковом склерозе: возможности и ограничения.

Амиотропический боковой склероз (ALS), известный также как болезнь моторных нейронов (MND) и болезнь Лу Гехрига, характеризуется потерей нижних моторных нейронов в спинном мозге и верхних моторных нейронов в коре головного мозга. Ввиду сложного и многофакторного характера различных факторов и механизмов риска, связанных с механическим нейронным дегенерацией, патологические механизмы БАС не в полной мере понимаются. Окисляющий стресс one из известных причин патогенез АБС. Это наблюдалось у пациентов, а также у клеточных и животных моделей и, как известно, вызывало митохондриальную дисфункцию и

Osteoporosis: Current and Emerging Therapies Targeted to Immunological Checkpoints.

Osteoporosis is a skeletal pathology characterized by compromised bone strength leading to increased risk of fracture, mainly the spine and hip fractures. Osteoporosis affects more than 200 million people worldwide and because of the skeletal fractures it causes, represents a major cause of morbidity, disability and mortality in older people. Recently, the new discoveries of osteoimmunology have clarified many of the pathogenetic mechanisms of osteoporosis, helping to identify new immunological targets for its treatment opening the way for new and effective therapies with biological drugs. Cur

Inhibition of insulin-like growth factor receptor/AKT/mammalian target of rapamycin axis targets colorectal cancer stem cells by attenuating mevalonate-isoprenoid pathway in vitro and in vivo.

We observed a co-upregulation of the insulin-like growth factor receptor (IGF-1R)/AKT/mammalian target of rapamycin (mTOR) [InAT] axis and the mevalonate-isoprenoid biosynthesis (MIB) pathways in colorectal cancer stem cells (CSCs) in an unbiased approach. Hence, we hypothesized that the InAT axis might regulate the MIB pathway to govern colorectal CSCs growth. Stimulation (IGF-1) or inhibition (IGF-1R depletion and pharmacological inhibition of IGF-1R/mTOR) of the InAT axis produced induction or attenuation of CSC growth as well as expression of CSC markers and self-renewal factors respective

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… Hydroxymethylglutaryl coenzyme A reductase (HMGCR), the rate limiting enzyme of the MIB pathway, induced neoplastic transformation of MCF 10A mammary epithelial as well as promoted the growth of transformed MCF7 breast cancer cells [ 19 ], highlighting the importance of the MIB pathway in carcinogenesis … Abbreviations eIF-4E-binding protein 1 Antibiotic-Antimycotic liquid Acetyl Coenzyme A Protein kinase B Prominin-1/Cluster of differentiation133 Cluster of differentiation 44 Myc proto-oncogene protein Colorectal cancer stem cells C-X-C chemokine receptor type 4 doublecortin and CaM kinase-like …

Никотинамид Аденин динуклеотид дополняет Cuprizone испытуемые многочисленные поведенческие изменения в C57BL/6J Mice.

ЦЕЛЬ: Изучение вопроса о том, может ли добавка никотинамида аденина динуклеотида (NAD+) улучшить поведенческие изменения в модели мыши, опьяненной мышью. МЕТОДЫ: Six- Неделю назад мыши C57BL/6J были разделены на three группы: two еда 0.2% cuprizone chow (cuprizone и cuprizone + NAD+ группы), а другая группа получила нормальную грызуновую (контрольную группу) 4 недель. Мыши в чашезоне + NAD+ группа получили 250 мг/кг/сут NAD+ interperitononyly один раз в день, в то время как другие мыши получали засос одновременно. Были проведены поведенческие тесты на пространственное воспоминание (Моррисский

Drug Repurposing in Veterinary Oncology: Myth or Reality?

Drug repurposing, that is, the identification of new therapeutic indications for existing medications, has been shown to be a cost-effective and time-efficient alternative to de novo drug development. This review provides a comprehensive overview of repurposed drugs in veterinary oncology, describing their mechanisms of action, current evidence of clinical benefit, and translational relevance. The therapeutic agents discussed include non-steroidal anti-inflammatory drugs (e.g., piroxicam), metabolic modulators (e.g., metformin), anti-parasitic drugs (e.g., fenbendazole), immunomodulators (e.g.

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… Statins Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, are primarily cholesterol-lowering agents, but exhibit pleiotropic effects, including antiproliferative, pro-apoptotic, and anti-invasive properties in tumour cells in vitro [ 13 ]. … monophosphate–activated protein kinase; AT1R, angiotensin II type 1 receptor; COX, cyclooxygenase; CRBN, cereblon; CSC, cancer stem cell; CR: complete response; DFI, disease-free interval; EMT, epithelial–mesenchymal transition; FGF2, fibroblast growth factor 2; GI, gastrointestinal; HMG-CoA, 3-hydroxy-3-methylglutaryl-coenzyme …

Curcumin Formulations for Better Bioavailability: What We Learned from Clinical Trials Thus Far?

Curcumin has been credited with a wide spectrum of pharmacological properties for the prevention and treatment of several chronic diseases such as arthritis, autoimmune diseases, cancer, cardiovascular diseases, diabetes, hemoglobinopathies, hypertension, infectious diseases, inflammation, metabolic syndrome, neurological diseases, obesity, and skin diseases. However, due to its weak solubility and bioavailability, it has limited potential as an oral medication. Numerous factors including low water solubility, poor intestinal permeability, instability at alkaline pH, and fast metabolism contri

The Effect of Myc Inhibition Combined with the Synergistic Effect of Photothermal, Photodynamic and Radiotherapy in Tumor Treatment.

Photothermal therapy, photodynamic therapy, and radiotherapy offer the potential for precise tumor ablation with minimal adverse reactions. Myc is an oncogene that plays a critical role in cell growth and tumor development by regulating processes such as cell proliferation, differentiation, apoptosis, and metabolism. It is widely expressed in human cancers and is recognized as one of the potential targets for cancer therapy. Recent studies on the mechanism of Myc suggest that inhibiting its expression can delay cancer onset and progression. With the development of medical technology, photother

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

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… Acetyl-coenzyme A carboxylase: Crucial metabolic enzyme and attractive target for drug discovery. Cell. Mol. Life Sci. 2005;62:1784–1803. doi: 10.1007/s00018-005-5121-4. 44. Milgraum L.Z., Witters L.A., Pasternack G.R., Kuhajda F.P. … Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res. 2000;60:213–218. 51. Wang C., Xu C., Sun M., Luo D., Liao D.F., Cao D. …

Osteonecrosis of the jaws in patients treated with bisphosphonates.

The literature describes an increasing presence of bisphosphonate-induced osteonecrosis of the jaws (ONJ), characterized by the exposure for over 8 weeks of necrotic bone in the maxillofacial region, after bisphosphonate therapy, in the absence of prior maxillary radiotherapy. The present literature review examines the etiopathogenesis, risk factors, clinical forms, diagnosis, treatment and prevention of bisphosphonate-induced ONJ. In addition, a review is made of all the series involving over 15 patients diagnosed with this disorder between 1 January 2011 and 15 May 2011. A PubMed-Medline sea

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… Bisphosphonates inhibit the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. Once bound to bone, they prevent bone resorption mediated by osteoclasts, and stimulate apoptosis of these cells. …

Causes, clinical findings and therapeutic options in chylomicronemia syndrome, a special form of hypertriglyceridemia.

The prevalence of hypertriglyceridemia has been increasing worldwide. Attention is drawn to the fact that the frequency of a special hypertriglyceridemia entity, named chylomicronemia syndrome, is variable among its different forms. The monogenic form, termed familial chylomicronemia syndrome, is rare, occuring in 1 in every 1 million persons. On the other hand, the prevalence of the polygenic form of chylomicronemia syndrome is around 1:600. On the basis of the genetical alterations, other factors, such as obesity, alcohol consumption, uncontrolled diabetes mellitus and certain drugs may sign

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… Statins Inhibiting the hepatic hydroxymethylglutaryl-coenzyme A (HMGCoA) reductase, statins promote the uptake of LDL particles from the circulation. However, no significant impact on LDL concentration was observed in primary CS [ 101 ]. … Diacylglycerol O-acyltransferase 1 Deoxyribonucleic acid Eicosapentaenoic acid Familial chylomicronemia syndrome Familiar hypercholesterolemia Familial partial lipodystrophy Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 High-density lipoprotein Hydroxymethylglutaryl-coenzyme …

Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer.

Cannabis sativa L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present in Cannabis sativa L., namely, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different

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… The synthesis of the former part occurs via the polyketide pathway by the stepwise condensation of three malonyl-Coenzyme A molecules with hexanoyl-Coenzyme A, in order to yield olivetolic acid [ 18 ]. …

Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia.

While the understanding of the genomic aberrations that underpin chronic and acute myeloid leukaemia (CML and AML) has allowed the development of therapies for these diseases, limitations remain. These become apparent when looking at the frequency of treatment resistance leading to disease relapse in leukaemia patients. Key questions regarding the fundamental biology of the leukaemic cells, such as their metabolic dependencies, are still unresolved. Even though a majority of leukaemic cells are killed during initial treatment, persistent leukaemic stem cells (LSCs) and therapy-resistant cells

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… In turn, for the TCA cycle to function, it needs a steady supply of oxaloacetate and acetyl coenzyme A (acetyl-CoA) [ 38 ]. Importantly, cells can synthesise acetyl-CoA from three main sources: carbohydrates, lipids, and proteins, following different catabolic pathways. … Electrons are donated by NADH to complex I and by FADH 2 to complex II, then transferred to coenzyme Q, to complex III, to cytochrome c and finally to complex IV. …

Acupuncture combined with methylcobalamin for the treatment of chemotherapy-induced peripheral neuropathy in patients with multiple myeloma.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) seriously affects the quality of life of patients with multiple myeloma (MM) as well as the response rate to chemotherapy. Acupuncture has a potential role in the treatment of CIPN, but at present there have been no randomized clinical research studies to analyze the effectiveness of acupuncture for the treatment of CIPN, particularly in MM patients. METHODS: The MM patients (104 individuals) who met the inclusion criteria were randomly assigned into a solely methylcobalamin therapy group (500 μg intramuscular methylcobalamin injec

Comparison of the prophylactic use of ibandronate and its use in early-stage osteonecrosis in rats with steroid-induced osteonecrosis of the femoral head.

OBJECTIVES: The aim of this study was to investigate the effects of ibandronate before and after the onset of osteonecrosis in rats with steroid-induced osteonecrosis of the femoral head. MATERIALS AND METHODS: A total of 24 female Sprague-Dawley rats were used in this study. Three groups were formed with eight rats in each group. The first group was the prophylactic group that received ibandronate treatment before and after the onset of osteonecrosis (Group PT). The second group received ibandronate treatment three weeks after the development of osteonecrosis (Group TAO). The third group was

Keyword Index for Volume 110

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Keyword Index for Volume 90

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… 137 Cs- γ rays 48 [ 18 F]FETA 2232 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) 620 2D gel electrophoresis 1955 2D-DIGE 173 2-methoxyoestradiol 932 2-methoxyoestradiol- bis- sulphamate 932 2-nitroimidazole 2232 3 H-thymidine 48 3-hydroxy-3-methylglutaryl coenzyme A inhibitors …

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases.

Iridoids, which have beneficial health properties, include a wide group of cyclopentane [c] pyran monoterpenoids present in plants and insects. The cleavage of the cyclopentane ring leads to secoiridoids. Mainly, secoiridoids have shown a variety of pharmacological effects including anti-diabetic, antioxidant, anti-inflammatory, immunosuppressive, neuroprotective, anti-cancer, and anti-obesity, which increase the interest of studying these types of bioactive compounds in depth. Secoiridoids are thoroughly distributed in several families of plants such as Oleaceae, Valerianaceae, Gentianaceae a

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… A large number of studies highlighted the antioxidant properties of these compounds including their abilities to promote the activity of ROS-detoxifying enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR) and glutathione S-transferase (GST), to compete with coenzyme … They found that an OL diet showed an increase of oxygen consumption, fat oxidation, and myocardial β-hydroxyacyl coenzyme A dehydrogenase activity and a reduction in the levels of lipid hydroperoxide and up-regulation of antioxidant enzyme confirmed that OL improved myocardial oxidative stress in standard-fed …

Изменения лакта и лактилации в неврологических расстройствах.

Значительное внимание стало уделяться изучению изменений в лактилации различных целевых органов как в области здравоохранения, так и в области болезней. Многие жизненно важные процессы и начало болезней связаны не только с избытком белков, но и в первую очередь регулируются различными посттрансляционными изменениями белков. Лактат, который раньше считался лишь побочным продуктом анаэробного метаболизма, превратился в важнейшую энергетическую субстрату и сигнализирующую молекулу, связанную как с физиологическими, так и патологическими процессами в нервной системе. Кроме того, в недавних исследо

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… Additionally, lactate can be transformed into lactyl-CoA, which participates in the lactylation of histones within nucleosomes and non-histone proteins located in the cytoplasm and mitochondria. α-KG: Alpha-ketoglutarate; ATP: adenosine triphosphate; CoA: coenzyme A; NAD + : nicotinamide adenine dinucleotide … Additionally, Zhu et al. (2024) demonstrated that ACSS2 functions as a lactate coenzyme A synthetase, facilitating the conversion of lactate into acetyl-CoA. …