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Mitochondrial Kv1.3 Channels as Target for Treatment of Multiple Myeloma.

Despite several new developments in the treatment of multiple myeloma, all available therapies are only palliative without curative potential and all patients ultimately relapse. Thus, novel therapeutic options are urgently required to prolong survival of or to even cure myeloma. Here, we show that multiple myeloma cells express the potassium channel Kv1.3 in their mitochondria. The mitochondrial Kv1.3 inhibitors PAPTP and PCARBTP are efficient against two tested human multiple myeloma cell lines (L-363 and RPMI-8226) and against ex vivo cultured, patient-derived myeloma cells, while healthy b

Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.

The development of brain metastasis is a major cause of significantly reduced survival in breast cancer patients. The initiation and progression of breast cancer brain metastasis (BCBM) involve multiple distinct molecular pathways and reprogramming of the tumor microenvironment (TME). This review systematically summarizes key mechanisms underlying BCBM, including epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and the spatiotemporal dynamics of metabolic reprogramming regulated by critical signaling pathways during brain colonization. In particular, we highlight

Natural bioactive molecules and chemotherapeutics synergism for enhanced cancer therapy.

BACKGROUND: Chemotherapy remains a foundation of cancer care but is limited by multidrug resistance, systemic toxicities, and suboptimal selectivity, prompting interest in adjunctive strategies that improve efficacy and tolerability without adding significant burden to patients or healthcare systems. AIMS/OBJECTIVES: This review highlights evidence on natural bioactive compounds, including polyphenols, alkaloids, terpenoids, and fungal metabolites, as adjuvants to standard chemotherapeutics, with objectives to: first, delineate mechanisms by which these agents enhance cytotoxic efficacy and o

Dendritic cell biology and its role in tumor immunotherapy.

As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4+ and CD8+ T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovere

Целенаправленная деградация белка разрушает ненаркомные цели, чтобы обратить вспять иммунное уклонение и терапию устойчивости к раку.

Таргетированная деградация белков (ТД) использует эндогенные протеолитические системы — систему убиквина и протеасомы и лизосомальные пути — для селективного удаления белков, вызывающих болезни, которые не реагируют на традиционное ингибирование. В онкологической иммунотерапии ТД разрушает критические иммунодепрессивные узлы в экзоцитоплазматическом, мембранном и цитоплазматическом компартментах, перепрограммируя микросреду опухоли от иммунологически «холодной» к «горячей» состоянию. Эта статья рассматривает молекулярные принципы инженерии бифункциональных деградаторов и обобщает клинические д

Sp3 улучшила экспериментальный аутоиммунный энцефаломиэлит, спровоцировав Socs3 в клетках Th17.

ВВЕДЕНИЕ: Хотя считается, что хронические подстрекательские и дегенеративные заболевания центральной нервной системы поддерживаются аутоиммунными клетками ТТ17, основополагающие механизмы остаются в основном неисследованными. Недавние исследования и наши исследования показали, что Sp3 был заблокирован в нескольких склерозах (MS) и экспериментальном аутоиммунном энцефаломиелите (EAE). Вместе с тем остается неясным, почему в нем ничего не говорится и как он регулирует дифференциацию клеток TH17 в MS. ЦЕЛИ: Данное исследование было направлено на изучение воздействия Сп3 на ТХ17 в клетках EAE и ле

Астроглиальная модуляция синаптической функции в недемилинированной коре головного мозга зависит от сигнала MyD88 в модели токсичного обезвоживания.

Прогрессивный неврологический спад в множественном склерозе связан с аксонной потерей и синаптической дисфункцией в недемилинированном нормальном сером веществе (NAGM) и занимает видное место в мозжечке. В отличие от ранних стадий заболеваний, когда синаптическая и нейро-аксональная патология коррелирует с масштабами инфильтрации клеток Т, для прогрессивных MS была предложена важная роль врожденной иммунной системы. Вместе с тем конкретный вклад микроглии и астроцитов в синаптическую патологию мозгового мозга в НГММ - независимо от адаптивной реакции Т клеток - по-прежнему в значительной степе

The biogenesis and biological function of PIWI-interacting RNA in cancer.

Small non-coding RNAs (ncRNAs) are vital regulators of biological activities, and aberrant levels of small ncRNAs are commonly found in precancerous lesions and cancer. PIWI-interacting RNAs (piRNAs) are a novel type of small ncRNA initially discovered in germ cells that have a specific length (24-31 nucleotides), bind to PIWI proteins, and show 2'-O-methyl modification at the 3'-end. Numerous studies have revealed that piRNAs can play important roles in tumorigenesis via multiple biological regulatory mechanisms, including silencing transcriptional and posttranscriptional gene processes and a

Преодоление препятствий: развитие клеточной терапии в области аутоиммунной борьбы с заболеваниями.

Аутоиммунные заболевания возникают в результате дисрегламента в иммунной системе, что приводит к агрессивному нападению на ткани самого организма. Патогенез этих условий является многофакторным, охватывающим сложные взаимосвязи между генетическими предрасположениями, экологическими детерминантами и гормональными колебаниями. Диапазон аутоиммунных заболеваний является широким и оказывает воздействие на множество систем органов, при этом можно привести такие примечательные примеры, как ревматуидный артрит (RA), системный волчан (SLE), множественный склероз (MS), псориаз и витилиго. Несмотря на з

Совпадение в полном тексте источника
… The IRF5 gene plays a role in the immune response, and several SNPs (rs4728142, rs2004640, rs1744583) and small insertions/deletions in the IRF5 gene or regulatory regions have been validated to independently cause SLE, MS and RA by altering gene expression, splicing, and RNA stability ( 46 ) These findings …

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018) : Washington, D.C., USA. 7-11 November 2018.

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33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018) : Washington, D.C., USA. 7-11 November 2018.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Dynamic Evolution of the Tumor Immune Microenvironment in Malignant Tumors and Emerging Therapeutic Paradigms.

Cancer is more than just a collection of tumor cells. The complex tumor system, including the tumor immune microenvironment (TIME), is continually changing. Tumor cells are in constant communication with all stromal elements (e.g., fibroblasts, endothelial cells, and extracellular matrix) and immune effector cells (e.g., T cells, B cells, natural killer cells, dendritic cells, macrophages, and myeloid-derived suppressor cells). Together, these intricate interactions among cell and molecular signaling pathways collectively drive tumor growth, tumor invasion, and metastasis and significantly aff

Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells.

: Lesions with driver mutations, including atypical nevi and seborrheic keratoses, are very common in dermatology, and are prone to senescence. The molecular events that prevent senescent lesions from becoming malignant are not well understood. We have developed a model of vascular proliferation using a temperaturesensitive, large T antigen and oncogenic HRas. By elevating the temperature to 39 °C, we can turn off large T antigen and study the molecular events in cells with the Ras driver mutation. To assess the signaling events associated with the switch from a proliferative to a nonprolifera

Effects of human umbilical cord mesenchymal stem cells derived from exosomes on migration ability of endometrial glandular epithelial cells.

The present study aimed to investigate the effects of human umbilical cord mesenchymal stem cells (Huc‑MSCs)‑derived exosomes on the migratory abilities of endometrial glandular epithelial cells, and to evaluate the underlying mechanism from the perspective of epithelial‑mesenchymal transition (EMT). Huc‑MSCs were prepared from human umbilical cord, and eutopic endometrial glandular epithelial cells were isolated from patients with endometriosis. The exosomes derived from Huc‑MSCs (Huc‑MSCs‑exo) were prepared using an exosome extraction kit. The endometrial glandular epithelial cells were rand

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

Effect of Autologous Stem Cell Transplantation Combined with Modified VTD Regimen on Elderly Patients with Multiple Myeloma and Its Influence on miRNA Cytokines.

ObjectiveTo explore the effect of autologous stem cell transplantation combined with modified VTD regimen on elderly patients with multiple myeloma and its influence on miRNA cytokines.MethodsThe data of 42 elderly patients with multiple myeloma who were treated in our hospital from May 2010 to June 2018 were retrospectively analyzed, and they were divided into the combined group (autologous stem cell transplantation combined with improved VTD scheme, n = 25) and the control group (improved VTD scheme, n = 17) according to different treatment schemes, and the clinical efficacy of the two group

Biomarker-Driven Approaches to Bone Metastases: From Molecular Mechanisms to Clinical Applications.

Bone metastases represent a critical complication in oncology, frequently indicating advanced malignancy and substantially reducing patient quality of life. This review provides a comprehensive analysis of the complex interactions between tumor cells and the bone microenvironment, emphasizing the relevance of the "seed and soil" hypothesis, the RANK/RANKL/OPG signaling axis, and Wnt signaling pathways that collectively drive metastatic progression. The molecular and cellular mechanisms underlying the formation of osteolytic and osteoblastic lesions are examined in detail, with a particular foc

The landscape and trajectory of global CRISPR therapeutics.

With the first regulatory approval in 2023 of a CRISPR-based therapy for sickle cell disease followed by the recent demonstration of an accelerated, personalized CRISPR treatment for congenital severe carbamoyl-phosphate synthetase 1 deficiency, CRISPR-Cas9 genome editing has progressed from a laboratory technology into a clinical reality in just over a decade. While enthusiasm for deploying CRISPR-Cas9 to treat a range of human genetic diseases continues to grow, broad clinical application remains constrained due to technical, regulatory, manufacturing and economic challenges. Here, scientist

The Cancer Antioxidant Regulation System in Therapeutic Resistance.

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cancer cells adeptly maintain elevated levels of both ROS and antioxidants through a process termed "redox reprogramming". This balance optimizes the proliferative influence of ROS while simultaneously reducing the potential for ROS to cause damage to the cell. In some cases, the adapted antioxidant machinery can hamper the efficacy of treatments for neoplastic diseases, representing a significant facet of the resistance mechanisms ob

Отличительные стратегии распознавания tRNA, используемые гомологической семьей редактирующих доменов, предотвращают неправильный перевод.

Ошибки в синтезе белка из-за пропускания аминокислот с tRNA ставят под угрозу жизнеспособность клеток. Было описано несколько контрольно-пропускных пунктов для предотвращения образования Ala- и Cys-tRNA(Pro), в том числе специально для Ala редактируемый домен (INS) большинства бактериальных проли-тринских синтезаторов (PRS) и автономный однодомный INS homolog, YbaK, который очищает Cys-tRNA(Pro) в транс. Во многих видах, где у ПРОРС нет домена INS, за редактирование Ala-tRNA(ProXp-ala) отвечает другой однодомный белок, похожий на INS. Хотя аминокислотная специфичность этих доменов редактирован