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Nrf2-Независимое антивоспалительное воздействие диметилфумарата: проблемы и перспективы развития электрофильных Nrf2 активаторов нейродегенеративных заболеваний.

Связанный с NF-E2 путь 2 (Nrf2)-антиоксидантный элемент реакции (ARE) является потенциальной терапевтической целью для заболеваний центральной нервной системы. В настоящем обзоре подчеркивается роль окислительного стресса и нейронного воспаления в нейродегенеративных заболеваниях с уделением особого внимания терапевтическому потенциалу таких активаторов Nrf2, как диметилфумарат (ДМФ). ДМФ, первоначально применяемый для лечения псориаза, продемонстрировал эффективность при множественном склерозе и метаболизируется до монометила фумарата, что может оказывать значительное терапевтическое воздейст

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… In 1959, Schweckendiek, a physician, self-administered fumaric acid, a compound that serves as an intermediate in the citric acid cycle, in an attempt to alleviate his psoriasis symptoms [ 33 ]. …

Generation and characterization of mAb 61H9 against junctional adhesion molecule-a with potent antitumor activity.

Junctional adhesion molecule-A (JAM-A) is an adhesion molecule that exists on the surface of certain types of cells, including white blood cells, endothelial cells, and dendritic cells. In this study, the cDNA sequences of JAM-A-Fc were chemically synthesized with optimization for mammalian expression. Afterward, we analyzed JAM-A protein expression through transient transfection in HEK293 cell lines. Mice were immunized with JAM-A-Fc protein, and hybridoma was prepared by fusing myeloma cells and mouse spleen cells. Antibodies were purified from the hybridoma supernatant and four monoclonal s

Contemporary Perspectives on the Warburg Effect Inhibition in Cancer Therapy.

In the 1920s, Otto Warburg observed the phenomenon of altered glucose metabolism in cancer cells. Although the initial hypothesis suggested that the alteration resulted from mitochondrial damage, multiple studies of the subject revealed a precise, multistage process rather than a random pattern. The phenomenon of aerobic glycolysis emerges not only from mitochondrial abnormalities common in cancer cells, but also results from metabolic reprogramming beneficial for their sustenance. The Warburg effect enables metabolic adaptation of cancer cells to grow and proliferate, simultaneously enabling

NAT10 Regulates LPS-Induced Inflammation via Stabilization of N4-Acetylated PTX3 mRNA in Human Dental Pulp Stem Cells.

Severe dental pulp inflammation can lead to tissue lysis and destruction, underscoring the necessity for effective treatment of pulpitis. N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification has recently emerged as a key regulator in inflammatory processes. However, whether NAT10 affects the inflammatory response in human dental pulp stem cells (hDPSCs) remains unelucidated. In this study, elevated NAT10 expression was observed in pulpitis tissues and LPS-stimulated hDPSCs. Knockdown of NAT10 led to reduced inflammatory gene expression and lower reactive oxygen species

Sheng-Jiang Powder Alleviates Th17/Treg Immune Imadium of Experimental Autoimune Encephalomyelitis путем регулирования метаболизма жирных кислот.

Множественный склероз (MS) является одной из главных причин инвалидности среди молодежи, и иммунный дисбаланс между клеткой Т 17 (Th17) и клетками регулирования Т (Tregs) играет решающую роль в ее патогенезе. В настоящее время лечение MS в значительной степени зависит от иммунодепрессивных препаратов или глюкокортикоидов, которые часто имеют побочные эффекты и недостатки в эффективности. Порошок Шэн Цзян (SJP) — традиционная китайская медицина — продемонстрировал антивоспалительные эффекты и может предложить новый терапевтический вариант для MS.АИМ: Цель этого исследования заключалась в изучен

Metabolic features of myeloma cells in the context of bone microenvironment: Implication for the pathophysiology and clinic of myeloma bone disease.

Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of malignant plasma cells (PCs) into the bone marrow (BM). The complex interaction between the BM microenvironment and MM PCs can lead to severe impairment of bone remodeling. Indeed, the BM microenvironment exerts a critical role in the survival of malignant PCs. Growing evidence indicates that MM cells have several metabolic features including enhanced glycolysis and an increase in lactate production through the upregulation of glucose transporters and enzymes. More recently, it has been reported that MM ce

Post-transplant cyclophosphamide-induced cardiotoxicity: A comprehensive review.

Cyclophosphamide-induced cardiotoxicity, associated with its toxic metabolite acrolein, is a significant concern and unresolved issue, especially when cyclophosphamide is administrated in high doses. However, cardiotoxicity following low-dose cyclophosphamide has been also documented, especially in post-hematopoietic stem cell transplantation (post-HSCT) settings. Despite the involvement of multiple signaling pathways in cyclophosphamide-induced cardiomyopathy, the exact underlying mechanisms remain to be fully elucidated. This review outlines the current challenges of cyclophosphamide therapy

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… The Influence of Oxygen Tension and Glycolytic and Citric Acid Cycle Substrates in Acroleininduced Cellular Injury in the Differentiated H9c2 Cardiac Cell Model [dissertation]. University of South Florida; 2016. 17. Barnett S, Errington J, Sludden J, Jamieson D, Poinsignon V, Paci A, et al. …

Glutamine and cancer: metabolism, immune microenvironment, and therapeutic targets.

Glutamine is the most abundant amino acid in human serum, and it can provide carbon and nitrogen for biosynthesis, which is crucial for proliferating cells. Moreover, it is widely known that glutamine metabolism is reprogrammed in cancer cells. Many cancer cells undergo metabolic reprogramming targeting glutamine, increasing its uptake to meet their rapid proliferation demands. An increasing amount of study is being done on the particular glutamine metabolic pathways in cancer cells.Further investigation into the function of glutamine in immune cells is warranted given the critical role these

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… Entry of glucose- and glutamine-derived carbons into the citric acid cycle supports early steps of HIV-1 infection in CD4 T cells. Nat Metab. 2019;1(7):717–30. 10.1038/s42255-019-0084-1. 57. Ma G, et al. …

Окисляющий стресс и воспаление в патогенезе неврологических расстройств: механизмы и последствия.

Нейрозащита — это активный подход к защите нервной системы, включая мозг, спинной мозг и периферийные нервы, путем предотвращения или ограничения повреждения нервных клеток и других компонентов. Она защищает центральную нервную систему от повреждений от острых и прогрессивных нейродегенеративных расстройств. Окисляющий стресс, дисбаланс между естественными механизмами защиты тела и образованием реактивных видов кислорода, имеет решающее значение для развития неврологических расстройств. Из-за высокой скорости метаболизма и потребления кислорода мозг особенно уязвим к окисляющему стрессу. Чрезм

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… Biochemical analysis of postmortem AD brains revealed impaired citric acid cycle enzyme function, correlated with clinical status, and linked to reduced brain metabolism 121 . In NDDs, mitochondrial dysfunction is a significant concern. …

Hypercalcemia of Malignancy: An Update on Pathogenesis and Management.

Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechani

Potential of Lycii Radicis Cortex as an Ameliorative Agent for Skeletal Muscle Atrophy.

Lycii Radicis Cortex (LRC) is a traditional medicine in East Asia with various beneficial effects, including antioxidant, anti-inflammatory, anti-tumor, anti-diabetic, and anti-depressant properties. However, its potential effects on skeletal muscle atrophy have not been studied. In this study, the protective effects of LRC extract (LRCE) on dexamethasone (DEX)-induced muscle atrophy were investigated in C2C12 myotubes and mice. We evaluated the effect of LRCE on improving muscle atrophy using a variety of methods, including immunofluorescence staining, quantitative polymerase chain reaction (

Rosmarinic Acid and Related Dietary Supplements: Potential Applications in the Prevention and Treatment of Cancer.

Cancer constitutes a severe threat to human health and quality of life and is one of the most significant causes of morbidity and mortality worldwide. Natural dietary products have drawn substantial attention in cancer treatment and prevention due to their availability and absence of toxicity. Rosmarinic acid (RA) is known for its excellent antioxidant properties and is safe and effective in preventing and inhibiting tumors. This review summarizes recent publications on culture techniques, extraction processes, and anti-tumor applications of RA-enriched dietary supplements. We discuss techniqu

Properties of Approved Antitumour Chinese Herbal Medicines: Integrating Evidence and Tradition.

The properties and meridian affinities of Chinese herbal medicine are closely associated with their therapeutic efficacy. This review focuses on approved antitumour Chinese medicines listed in the Pharmacopoeia of the People's Republic of China (2020 Edition, Volume I), highlighting their key components. Statistical methods were used to analyse the properties, flavours and channel tropisms of antitumour traditional Chinese medicine (TCM), including both proprietary formulations and commercially available individual herbs. Distinctive patterns were identified by comparing herb profiles with con

Energy metabolism in health and diseases.

Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, exten

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… Associated pathways consist of interconnected processes, such as glycolysis, the citric acid cycle (Krebs cycle), and OXPHOS, which are tightly regulated by enzymes and metabolic intermediates. …

Iron in the Tumor Microenvironment-Connecting the Dots.

Iron metabolism and tumor biology are intimately linked. Iron facilitates the production of oxygen radicals, which may either result in iron-induced cell death, ferroptosis, or contribute to mutagenicity and malignant transformation. Once transformed, malignant cells require high amounts of iron for proliferation. In addition, iron has multiple regulatory effects on the immune system, thus affecting tumor surveillance by immune cells. For these reasons, inconsiderate iron supplementation in cancer patients has the potential of worsening disease course and outcome. On the other hand, chronic im

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… In addition, cellular iron availability impacts on mitochondrial respiration, ATP (for adenosine triphosphate) and mitochondrial radical formation, but also controls cellular metabolism and aerobic glycolysis via its regulatory effects on citric acid cycle enzymes ( 7 , 8 ). … Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation . Biochim Biophys Acta ( 1999 ) 1413 : 99 – 107 . 10556622 10.1016/s0005-2728(99)00088-2 8. Volani C Doerrier C Demetz E Haschka D Paglia G Lavdas AA . …

Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran.

Gastrointestinal cancers are a major global health challenge, with high mortality rates. This study investigated the anti-cancer activities of 30 monomers extracted from Morus alba L. (mulberry) against gastrointestinal cancers. Toxicological assessments revealed that most of the compounds, particularly immunotoxicity, exhibit some level of toxicity, but it is generally not life-threatening under normal conditions. Among these components, Sanggenol L, Sanggenon C, Kuwanon H, 3'-Geranyl-3-prenyl-5,7,2',4'-tetrahydroxyflavone, Morusinol, Mulberrin, Moracin P, Kuwanon E, and Kuwanon A demonstrate

Piperine: From Green Extraction to Clinical Translation-A Review.

BACKGROUND: Piperine has diverse pharmacological and bioenhancing activities, but poor aqueous solubility, variable exposure, interaction liability, and discontinuity across production, formulation, and clinical evaluation limit translation. This review integrates these frequently separated stages. METHODS: A structured narrative PubMed search covered English-language studies published from 1 January 2021 to 27 April 2026, supplemented by ClinicalTrials.gov records checked through 13 June 2026, backward citation searching, and selected earlier seminal studies. Evidence was synthesized by expe

Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve.

To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration of bortezomib and a well-established "chronic" schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in the

Биоразлагаемый электроспун PLGA Nanofibers-Encapsolated Trichinella Sphiralis Antigens защищает от повторного использования экспериментального аутоиммунного энцефаломилита и связанного с ним микробиота дисбиоз.

ЦЕЛЬ: " Тричинелла спиралис " создала сложные механизмы иммуномодуляции при посредничестве экскременто-секретарских продуктов (ESL1), которые позволяют ей выжить в принимающей стране. Следовательно, антигены ESL1 обладают прекрасным потенциалом для лечения аутоиммунных заболеваний, таких, как множественный склероз (MS). Однако вопрос о том, могут ли своевременные контролируемые поставки антигенов ESL1 в vivo, как и в случае естественных инфекций, повысить его терапевтический потенциал в отношении MS, до сих пор неизвестен.Для этого мы ввели антигены ESL1 в полихлорированные (лактидно

Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma.

The proteasome is crucial for the degradation of intracellular proteins and plays an important role in mediating a number of cell survival and progression events by controlling the levels of key regulatory proteins such as cyclins and caspases in both normal and tumor cells. However, compared to normal cells, cancer cells are more dependent on the ubiquitin proteasome pathway (UPP) due to the accumulation of proteins in response to uncontrolled gene transcription, allowing proteasome to become a potent therapeutic target for human cancers such as multiple myeloma (MM). Up to date, three protea