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Метаболизм триптофана в области диагностических и внегигиенических заболеваний: механизмы, клинические последствия и терапевтические перспективы.

Метаболизм триптофана (Trp) лежит на пересечении питания, микробиотики кишечника, мукосовой иммунологии и системных процессов воспаления, которые играют ключевую роль во многих желудочно-кишечных и внекишечных заболеваниях. Трап представляет собой важнейшую аминокислоту, получаемую с помощью рациона питания. Помимо своей роли в синтезе белка, он метаболизируется по трем основным направлениям: кинуреньиновый путь, серотонин/мелатонин, и микробный метаболизм в кишечнике, ведущий к индолу и связанным с ним производным. Кинуренинский путь представляет собой основной путь деградации Trp и тесно свя

Цереброспинная жидкость и сывороточные биомаркеры в идиопатической внутричерепной гипертонии: систематический обзор.

ЦЕЛЬ: Это исследование было направлено на систематический анализ литературы по растворимым биомаркерам у взрослых с идиопатической внутричерепной гипертонией (МИГ). КОЛИЧЕСТВО: Идиопатическая внутричерепная гипертония представляет собой многофакторное расстройство, характеризующееся повышенным внутричерепным давлением без какой-либо явной причины. Хотя она в первую очередь затрагивает женщин репродуктивного возраста с избыточным весом, ее патогенез по-прежнему не до конца изучен. Симптомы включают головную боль и визуальные нарушения, вызванные папилледомой. Все большее внимание уделяется раст

Бенефициарное воздействие Омега-3 Жировых кислот на ожирение и связанные с ним метаболические и хронические воспаленные заболевания.

Известно, что омега-3 полинунасыщенные жирные кислоты (N-3 PUFA) помогают решить проблему воспаления посредством создания антивоспалительных эйкосаноидов и специализированных посредников по восстановлению, включая резолвинов, защитных сооружений и мареинов. Благодаря привязке к рецептору GPR120/FFAR4 они оказывают благоприятное воздействие в результате фосфолипидной реконструкции мембраны, повреждения воспалительных сигнальных молекул, последующего ингибирования NF-ИВ и воспаления активации, а также уменьшения окислительного стресса. Ожирение, хроническое воспалительное заболевание, которое пр

Medication-Related Osteonecrosis of the Jaw: Successful Medical Management of Complex Maxillary Alveolus with Sinus Involvement.

Medication-related osteonecrosis of the jaw (MRONJ) in cancer patients presents a considerable challenge in management. Current management is primarily based on interventions in a limited number of cases assessing a single approach. Medical management typically is reported to include antimicrobial therapy with or without surgery. Advances in the understanding of pathogenesis have led to the investigation of additional medical interventions for early-stage necrosis. We present 3 patients with advanced-stage MRONJ of the maxilla using combined medical modalities including antimicrobial therapy,

Roadmap for new practitioners to navigate the multiple myeloma landscape.

Multiple myeloma (MM) is a blood cancer in which monoclonal plasma cells cause end organ damage resulting in hypercalcemia, renal failure, anemia, and bone lesions. MM is considered incurable, however, recent advances in treatment have improved survival. Historically, MM has been treated with immunomodulatory drugs (IMiDs), proteosome inhibitors (PIs), and corticosteroids. While newer therapeutic approaches such as monoclonal antibodies and cellular therapies have broadened the treatment horizon, the selection and sequencing of these therapies has become more complex. This review aims to help

pIL6-TRAIL-engineered umbilical cord mesenchymal/stromal stem cells are highly cytotoxic for myeloma cells both in vitro and in vivo.

BackgroundMesenchymal/stromal stem cells (MSCs) are favorably regarded in anti-cancer cytotherapies for their spontaneous chemotaxis toward inflammatory and tumor environments associated with an intrinsic cytotoxicity against tumor cells. Placenta-derived or TRAIL-engineered adipose MSCs have been shown to exert anti-tumor activity in both in-vitro and in-vivo models of multiple myeloma (MM) while TRAIL-transduced umbilical cord (UC)-MSCs appear efficient inducers of apoptosis in a few solid tumors. However, apoptosis is not selective for cancer cells since specific TRAIL receptors are also ex

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… Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment. Cytotherapy. 2010;12:615–25. doi: 10.3109/14653241003631815. 14. Krasikova LS, Karshieva SS, Cheglakov IB, Belyavsky AA. …

Биполярное расстройство у людей с множественным склерозом: обновленный систематический обзор и метаанализ.

Множественный склероз (MS) — аутоиммунное расстройство, характеризующееся провокационным демиэлированием внутри центральной нервной системы. Она является второй причиной тяжелой инвалидности и низкого качества жизни среди молодежи. Предыдущие исследования свидетельствуют о значительных различиях в распространенности и риске биполярного расстройства (БД) среди людей, имеющих МЗС, что свидетельствует о необходимости проведения всеобъемлющего анализа для получения надежных оценок. В рамках этого обзора было предложено изучить общую распространенность БД в ПВМС и взаимосвязь между БД и МЗ. МЕТОДЫ:

The potential of dibenzazepine carboxamides in cancer therapy.

Cancer is a leading cause of mortality worldwide, with most conventional treatments lacking efficacy and having significant challenges like drug resistance. Finding new molecules is quite challenging in terms of cost, time and setbacks. Hence, drug repurposing is considered sensible for skipping the long process of drug development. Dibenzazepine carboxamides, as traditional anticonvulsants, primarily function by blocking voltage-gated sodium channels, which not only mitigate seizures but also influence mood disorders through modulation of serotonin and dopamine. Recent studies have uncovered

Modulation of Lonp1 Activity by Small Compounds.

The Lon protease homolog 1 (LONP1) is an ATP-dependent mitochondrial protease essential for maintaining proteostasis, bioenergetics, and cellular homeostasis. LONP1 plays a pivotal role in protein quality control, mitochondrial DNA maintenance, and oxidative phosphorylation system (OXPHOS) regulation, particularly under stress conditions. Dysregulation of LONP1 has been implicated in various pathologies, including cancer, metabolic disorders, and reproductive diseases, positioning it as a promising pharmacological target. This review examines compounds that modulate LONP1 activity, categorizin

Study of Liposomes Containing Extract from the Leaves of Protium heptaphyllum (Aubl.) March in Animals Submitted to a Mutagenic Model Induced by Cyclophosphamide.

Cyclophosphamide (CPA) is an alkylating agent used as a chemotherapy agent in the treatment of cancer, but it has immunosuppressive effects. Protium heptaphyllum (P. heptaphyllum) is a plant rich in triterpenes and flavonoids, with some bioactive and therapeutic properties presented in the literature. Thus, the present study aimed to investigate the chemoprotective potential of P. heptaphyllum extract inserted into liposomes against oxidative damage chemically induced by CPA. Male Swiss mice received 1.5 mg/kg of P. heptaphyllum liposomes as a pre-treatment for 14 consecutive days (via gavage)

The Impact of NLRP3 Activation on Hematopoietic Stem Cell Transplantation.

NLR family pyrin domain-containing 3 (NLRP3) is an intracellular protein that after recognizing a broad spectrum of stressors, such as microbial motifs and endogenous danger signals, promotes the activation and release of the pro-inflammatory cytokines IL-1β and IL-18, thus playing an essential role in the innate immune response. Several blood cell types, including macrophages, dendritic cells, and hematopoietic stem and progenitor cells (HSPCs), express NLRP3, where it has been implicated in various physiological and pathological processes. For example, NLRP3 participates in the development a

The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.

The cGAS-STING pathway acts as a critical molecular hub connecting genomic instability with cellular senescence. Functioning as a key regulator of the innate immune system, this pathway detects aberrant cytoplasmic DNA to activate downstream inflammatory responses, thereby playing a pivotal role in aging-related diseases. This review systematically explores the core mechanisms by which the cGAS-STING pathway regulates cellular senescence, emphasizing its role in triggering senescence through the recognition of DNA damage signals (e.g., oxidative stress, telomere dysfunction) and promoting para

A Comprehensive Evaluation of CAR-T Cell Gene Therapy, Tracing its Revolutionary Clinical Breakthroughs and Advancements Towards Next-Generation Engineering.

BACKGROUND: CAR-T cell gene therapy has advanced from an experimental concept to a standard curative treatment for selected hematologic malignancies. Substantial clinical evidence has established CAR-T therapy as a cornerstone for relapsed/refractory B-cell malignancies and multiple myeloma, demonstrating durable, long-term remissions. In 2025, the U.S. Food and Drug Administration (FDA) eliminated the Risk Evaluation and Mitigation Strategy (REMS) requirement, reflecting improved clinical management of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome

Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities.

The interleukin 23 (IL-23) is a key pro-inflammatory cytokine in the development of chronic inflammatory diseases, such as psoriasis, inflammatory bowel diseases, multiple sclerosis, or rheumatoid arthritis. The pathological consequences of excessive IL-23 signaling have been linked to its ability to promote the production of inflammatory mediators, such as IL-17, IL-22, granulocyte-macrophage colony-stimulating (GM-CSF), or the tumor necrosis factor (TNFα) by target populations, mainly Th17 and IL-17-secreting TCRγδ cells (Tγδ17). Due to their pivotal role in inflammatory diseases, IL-23 and

Decoding Waldenström Macroglobulinemia Through Genomics, Epigenomics and Cellular Interactions

Waldenström macroglobulinemia is a rare lymphoplasmacytic malignancy characterized by bone marrow infiltration and monoclonal immunoglobulin M production. Despite its indolent clinical course, the disease exhibits considerable biological complexity driven by recurrent genetic alterations, dysregulated signaling pathways, and a supportive bone marrow microenvironment. The identification of MYD88 and CXCR4 mutations has significantly advanced understanding of disease pathogenesis, clonal evolution, and treatment response. Additional insights from cytogenetic, epigenetic, and microRNA studies hav

Polypharmacology: new drugs in 2023-2024.

Polypharmacology is an emerging approach to drug design and development that involves the use of multi-target-directed ligands (MTDLs), agents capable of interacting with multiple biological targets simultaneously. The effective treatment of chronic and multifactorial conditions, driven by the dysregulation of multiple interconnected pathways, such as cancer, autoimmune and metabolic disorders, cardiovascular and neurodegenerative diseases, is one of the most substantial challenges in contemporary pharmacology. 'Traditional' single-target-based treatment frequently shows limited effectiveness,

Selected Abstracts from the 13th Annual Meeting of the Clinical Immunology Society: 2022 Annual Meeting: Immune Deficiency and Dysregulation North American Conference

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Antibodies to watch in 2018.

The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016. As of December 1, 2017, nine antibody

Cancer Cells Exploit Notch Signaling to Redefine a Supportive Cytokine Milieu.

Notch signaling is a well-known key player in the communication between adjacent cells during organ development, when it controls several processes involved in cell differentiation. Notch-mediated communication may occur through the interaction of Notch receptors with ligands on adjacent cells or by a paracrine/endocrine fashion, through soluble molecules that can mediate the communication between cells at distant sites. Dysregulation of Notch pathway causes a number of disorders, including cancer. Notch hyperactivation may be caused by mutations of Notch-related genes, dysregulated upstream p

Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.

Background: Bone metastasis is a frequent and debilitating complication of advanced cancer, particularly in breast and prostate cancer, and is driven by complex interactions among tumor cells, bone-resident cells, immune populations, vascular components, and the extracellular matrix. Within this specialized microenvironment, proteoglycans have emerged as key molecular regulators of tumor-bone crosstalk, matrix remodeling, metastatic niche formation, dormancy, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies pu