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The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.

The cytokine network is the central regulatory system for intercellular communication within the immune system. Its proper function depends on the dynamic balance between pro-inflammatory and anti-inflammatory cytokines. Through complex positive and negative feedback loops, this balance precisely regulates the intensity and duration of immune responses, thereby playing a critical role in both physiological and pathological states. This review systematically summarizes the compositional features and classification framework of the cytokine network, as well as the mechanisms by which it maintain

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a

MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy.

Inhibition of the MDM2/X-p53 interaction is recognized as a potential anti-cancer strategy, including the treatment of glioblastoma (GB). In response to cellular stressors, such as DNA damage, the tumor suppression protein p53 is activated and responds by mediating cellular damage through DNA repair, cell cycle arrest and apoptosis. Hence, p53 activation plays a central role in cell survival and the effectiveness of cancer therapies. Alterations and reduced activity of p53 occur in 25-30% of primary GB tumors, but this number increases drastically to 60-70% in secondary GB. As a result, reacti

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… Within the two major pathways in DNA double-strand break (DSB) repair, p53 interacts with both non-homologous end-joining (NHEJ) proteins as well as with protein RAD51 which plays a major role in homologous recombination (HR), influencing their expression ( 82 , 109 ). …

Интегрин α4β7:: патогенные роли в заболеваниях метаболики и воспаления и в терапии перевода.

Интегрин α4β7 является ключевым рецептором сцепления, который является посредником лимфоцита, движущегося к кишечной слизи через взаимодействие с MAdCAM-1, VCAM-1, и фибронектин, тем самым играя центральную роль в иммунной слежке и мукозаловом иммунитете. Появляющиеся данные расширили его функциональный охват за пределы кишечного гомеостаза, с тем чтобы охватить различные подстрекательские и метаболические заболевания. В настоящем обзоре систематически резюмируются структурные характеристики, взаимодействия лигандов и положения о соответствии α.4β7, с акцентом на патогенную роль в провокационн

Регулярная молекула-а регулирует ответные реакции, связанные с нейтрофильом TH17 в CNS автоиммунитет.

МЯСО И АЙМ: Отталкивающая молекула наведения-А (RGMA) хорошо известна своей ролью в нейро-воспалении и ремонте CNS с помощью Т-образных клеток. Врожденные иммунные взаимодействия, особенно между нейтрофилами и клетками TH17, становятся критическими движущими силами нейроинфламматической патологии в множестве склерозов (MS). Вопрос о том, регулирует ли РГМ эти связанные с нейтрофильом ответы TH17, остается в значительной степени неизвестным. Уточнение этого механизма может выявить новые терапевтические цели для НР. МЕТОДЫ: Уровни сера РГМ, БМП4, нейтрофильная эластаза (NE), IL-17A, и подстрекат

Intrathecal idursulfase-IT in patients with neuronopathic mucopolysaccharidosis II: Results from a phase 2/3 randomized study.

Two-thirds of patients with mucopolysaccharidosis II (MPS II; Hunter syndrome) have cognitive impairment. This phase 2/3, randomized, controlled, open-label, multicenter study (NCT02055118) investigated the effects of intrathecally administered idursulfase-IT on cognitive function in patients with MPS II. Children older than 3 years with MPS II and mild-to-moderate cognitive impairment (assessed by Differential Ability Scales-II [DAS-II], General Conceptual Ability [GCA] score) who had tolerated intravenous idursulfase for at least 4 months were randomly assigned (2:1) to monthly idursulfase-I

Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review.

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous lymphoid malignancy and the most common subtype of non-Hodgkin's lymphoma in adults, with one of the highest mortality rates in most developed areas of the world. More than half of DLBLC patients can be cured with standard R-CHOP regimens, however approximately 30 to 40 % of patients will develop relapsed/refractory disease that remains a major cause of morbidity and mortality due to the limited therapeutic options.Recent advances in gene expression profiling have led to the identification of at least three distinct molecular

Physiological functions and pharmacological targeting of transient receptor potential channels.

Transient receptor potential (TRP) channels represent an extensive and diverse protein family fulfilling salient roles as versatile cellular sensors and effectors. The pivotal role of TRP and related ion channels in sensory processes has been well documented. Over the last few years, a new concept has emerged that TRP proteins control an exceptionally broad spectrum of homeostatic physiological functions such as maintenance of body temperature, blood pressure, transmitter release from neurons, mineral and energy homeostasis, and reproduction. This notion is further supported by more than 20 he

COVID-19 in patients with anemia and haematological malignancies: risk factors, clinical guidelines, and emerging therapeutic approaches.

Extensive research in countries with high sociodemographic indices (SDIs) to date has shown that coronavirus disease 2019 (COVID-19) may be directly associated with more severe outcomes among patients living with haematological disorders and malignancies (HDMs). Because individuals with moderate to severe immunodeficiency are likely to undergo persistent infections, shed virus particles for prolonged periods, and lack an inflammatory or abortive phase, this represents an overall risk of morbidity and mortality from COVID-19. In cases suffering from HDMs, further investigation is needed to achi

Proceedings to the 2020 Online Conference of the Particle Therapy Cooperative Group (PTCOG2020Online): 13-14 September 2020Organized by the Particle Therapy Cooperative Group (PTCOG), this special online meeting featured abstracts and programs that enabled the communication and cross fertilization for which PTCOG meetings are known.

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Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis.

In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of can

Chimeric antigen receptor T-cell therapies related to immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome: Diagnosis, high-risk factors, and management.

AbstractImmune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) is a life-threatening complication of chimeric antigen receptor T cell (CAR-T) therapy. Despite its high mortality rate, IEC-HS remains underrecognized due to overlapping clinical and laboratory features with severe cytokine release syndrome (CRS), leading to delayed diagnosis and suboptimal management. This review systematically analyzes key strategies to distinguish IEC-HS from severe CRS in the literature. The analysis focuses on temporal patterns, such as the delayed onset of IEC-HS after CAR-

The 'speck'-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis.

The NLRP3 inflammasome is an intracellular sensor and an essential component of the innate immune system involved in danger recognition. An important hallmark of inflammasome activation is the formation of a single supramolecular punctum, known as a speck, per cell, which is the site where the pro-inflammatory cytokines IL-1β and IL-18 are converted into their bioactive form. Speck also provides the platform for gasdermin D protein activation, whose N-terminus domain perforates the plasma membrane, allowing the release of mature cytokines alongside with a highly inflammatory form of cell death

Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain.

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates the transcription of many genes that are responsible for the adaptation and survival of tumor cells in hypoxic environments. Over the past few decades, tremendous efforts have been made to comprehensively understand the role of HIF-1 in tumor progression. Based on the pivotal roles of HIF-1 in tumor biology, many HIF-1 inhibitors interrupting expression, stabilization, DNA binding properties, or transcriptional activity have been identified as potential therapeutic agents for various cancers, yet none of these inhi

Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients.

Thyroxine and triiodothyronine (T3) are classical thyroid hormones and with relatively well-understood actions. In contrast, the physiological role of thyroid hormone metabolites, also circulating in the blood, is less well characterized. These molecules, namely, reverse triiodothyronine, 3,5-diiodothyronine, 3-iodothyronamine, tetraiodoacetic acid and triiodoacetic acid, mediate both agonistic (thyromimetic) and antagonistic actions additional to the effects of the classical thyroid hormones. Here, we provide an overview of the main factors influencing thyroid hormone action, and then go on t

Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.

Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells have emerged as a promising modern immunotherapeutic strategy, offering advantages over CAR-T cell therapy due to their innate cytotoxicity, safety profile, and potential for scalable, off-the-shelf allogeneic manufacturing. CAR-NK cells can be generated from multiple sources, with recent clinical studies demonstrating notable efficacy and lack of severe toxicity in hematologic malignancies. Nevertheless, the translation of this success to solid tumors is hampered by limited NK cell persistence, trafficking and infiltration c

The Role of Irisin and Physical Activity in Breast Cancer.

BACKGROUND/AIM: Irisin, a myokine released during physical activity, has been proposed as a mediator of exercise's protective effects against breast cancer (BC). This review underscores the critical role of irisin in mediating the anticancer effects of exercise and its potential application in BC prevention and prognosis. MATERIALS AND METHODS: Studies published up to 2025 were identified in PubMed, Scopus, and Web of Science databases. Data from experimental models, clinical trials, and observational studies were analyzed with emphasis on exercise-induced irisin secretion and its effects on

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… The aforementioned genes are responsible for the homologous recombination-mediated repair of DNA double-strand breaks ( 13 ). Although mutations in the BRCA1/BRCA2 genes affect only 3-5% of BC patients, the risk of developing BC is 10-fold higher in people carrying mutations in these genes. …

Immune Checkpoint Molecules: A Review on Pathways and Immunotherapy Implications.

BackgroundToday, treating cancer patients with monoclonal antibodies (mAbs), by targeting immune checkpoints, is one of the most outstanding immunotherapeutic methods. Immune checkpoints are special molecules having regulatory role in immune system responses. Once these molecules are presented on cancer cells, these cells will be capable of evading the immune system through their own specific pathways. This Evasion can be prevented by counterbalancing immune system responses with immune checkpoints related antibodies.AimsThe current study aimed to highlight immunotherapy and its methods, descr

Биотипные антитела в гематологовых злодеях: атакуют фронтлайн.

С тех пор, как Блинатумомаб утвердился в качестве первого биконкретного антитела (BsAb) в лечении рака, эти иммунодуляторные агенты добились значительного успеха в лимфоидных малигнатах. Через десять лет после предварительного одобрения в рентгеновских условиях блинатумомаб стал частью первой линии индуктивной терапии для пациентов с острой лимфоболической лейкемией (B-ALL). Теперь, six Кроме того, БСАБ имеют разрешение УЛХ на обработку лимфомы В-клеток, не относящихся к Ходжкину, и множественной миеломы (ММ), что позволяет добиться высоких показателей ответов в других сценариях. В лимфоме, эп

Bispecific antibody targets and therapies in multiple myeloma.

Recently, several bispecific antibodies (BsAbs) have been approved for the treatment of relapsed multiple myeloma (MM) after early phase trials in heavily pre-treated patients demonstrated high response rates and impressive progression-free survival with monotherapy. These BsAbs provide crucial treatment options for relapsed patients and challenging decisions for clinicians. Evidence on the optimal patient population, treatment sequence, and duration of these therapeutics is unknown and subject to active investigation. While rates of cytokine release syndrome and neurotoxicity appear to be low