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Emergence of Cancer-Associated Fibroblasts as an Indispensable Cellular Player in Bone Metastasis Process.

Bone metastasis is frequently complicated in patients with advanced solid cancers such as breast, prostate and lung cancers, and impairs patients' quality of life and prognosis. At the first step of bone metastasis, cancer cells adhere to the endothelium in bone marrow and survive in a dormant state by utilizing hematopoietic niches present therein. Once a dormant stage is disturbed, cancer cells grow through the interaction with various bone marrow resident cells, particularly osteoclasts and osteoblasts. Consequently, osteoclast activation is a hallmark of bone metastasis. As a consequence,

Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report.

We identified a rare heterozygous germline loss-of-function variant in the tumor necrosis factor receptor-associated factor 2 (TRAF2) in a young adult patient diagnosed with medulloblastoma. This variant is located within the TRAF-C domain of the E3 ubiquitin ligase protein and is predicted to diminish the binding affinity of TRAF2 to upstream receptors and associated adaptor proteins. Integrative genomics revealed a biallelic loss of TRAF2 via partial copy-neutral loss-of-heterozygosity of 9q in the medulloblastoma genome. We further performed comparative analysis with an in-house cohort of 2

Oxygen targets in critically ill patients: from pathophysiology to population enrichment strategies.

Oxygen supplementation is widely used to enhance oxygen delivery and to treat or prevent hypoxia; however, it requires careful management to avoid the harmful effects of excessive oxygen exposure. Both hyperoxia (inspiratory oxygen fraction exceeding 0.21) and hyperoxemia (arterial oxygen tension oxygen partial pressure [PaO2] > 100 mmHg) can contribute to lung injury, promote systemic vasoconstriction, and increase the production of reactive oxygen species, which can impair macromolecular and cellular functions. Conversely, in certain situations, hyperoxemia may provide benefits, such as hemo

E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.

Therapy resistance in gastrointestinal tumors remains a critical challenge in clinical oncology, severely compromising therapeutic efficacy and long-term patient survival. E3 ubiquitin ligases, as core enzymes involved in the protein ubiquitination process, have been demonstrated to play indispensable roles in regulating key biological processes in tumor cells, including DNA damage repair, cell cycle progression, apoptosis, cancer stem cell maintenance, and immune evasion. Additionally, E3 ligases are key regulators of resistance to multiple anticancer strategies, such as chemotherapy, radioth

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… Employing Cullin as a molecular scaffold, CRLs recruit substrate receptors (e.g., F-box proteins, SOCS box proteins) via their C-terminal regions while binding RING proteins (RBX1/2) at the N-terminus, thereby assembling diverse ubiquitination pathways such as SCF and CRL2-VHL complexes ( 79 ). …

Functional SARS-CoV-2-specific T cells of donor origin in allogeneic stem cell transplant recipients of a T-cell-replete infusion: A prospective observational study.

In the current post-pandemic era, recipients of an allogeneic hematopoietic stem cell transplant (HCT) deserve special attention. In these vulnerable patients, vaccine effectiveness is reduced by post-transplant immune-suppressive therapy; consequently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) is often associated with elevated morbidity and mortality. Characterizing SARS-CoV-2 adaptive immunity transfer from immune donors to HCT recipients in the context of immunosuppression will help identify optimal timing and vaccination strategies that can provide ade

Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).

Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT parameters, key signaling axes, major effector cells, organ‑specific contexts and clinical translation. It describes how the cyclic GMP‑AMP synthase/stimulator of interferon genes (STING)/IFN‑I, NF‑κB and TGF‑β pathways coordinate immune activation and immune suppression after irradiation. It then summarizes macrophage‑centered regulatory circuits and chemokine axes, including C‑

Artificial intelligence in immunotherapy: revolutionizing diagnostic and therapeutic applications in cancer and autoimmune diseases.

Artificial intelligence (AI) is increasingly advancing precision immunotherapy by integrating high-dimensional biomedical data to support diagnosis, treatment selection, and longitudinal monitoring in both cancer and autoimmune diseases. This review summarizes AI applications in biomarker discovery, prediction of immune checkpoint inhibitor (ICI) response and toxicity, neoantigen prioritization, CAR-T cell optimization, and therapeutic antibody engineering. In oncology, multimodal models combining multi-omics, medical imaging, and clinical variables improve patient stratification and non-invas

Терапевтический потенциал зубных мезенхимальных стволовых клеток в сравнении с мезенхимальными стволовыми клетками из других источников: систематический обзор исследований животных.

ЦЕНТРАЛЬНАЯ терапия на основе стволовых клеток, являющаяся одной из важнейших областей регенеративной медицины, направлена на совершенствование механизмов ремонта тела (d) путем стимулирования, модуляции и регулирования внутренних стволовых клеток или пополнения пулов клеток, способствуя тем самым развитию гомеостаза и регенерации тканей и предлагая перспективное лечение многочисленных системных заболеваний. В настоящем систематическом обзоре содержится всеобъемлющее резюме исследований животных, в ходе которых изучается эффективность зубоврачебных мезенхимальных стволовых клеток (НКЦ) в лечен

Identifying Patients With Asymptomatic Hyperparathyroidism by Serum Calcium and Vitamin D Screening in West Bengal, India.

BACKGROUND: Primary hyperparathyroidism (PHPT) is the leading cause of hypercalcemia, with solitary parathyroid adenoma responsible for most cases. Many patients with hyperparathyroidism remain asymptomatic, but early detection and parathyroidectomy can prevent complications such as nephrolithiasis, pancreatitis, and bone and kidney disorders. This study emphasizes the importance of screening for asymptomatic hyperparathyroidism to enable timely intervention. METHODS: Serum calcium and Vitamin D3 levels were screened in 6000 outpatients between March 2021 and September 2022. Patients with kno

Recent Progress of CircRNAs in Hematological Malignancies.

Circular RNAs (circRNAs) are now recognized as key regulators in the epigenetic control of genetic expression, being involved in a wide range of cellular activities such as proliferation, differentiation, and apoptosis. Their unique closed-loop structure endows them with stability and resistance to exonuclease degradation, making them not only key regulatory molecules within the cell but also promising biomarkers for disease diagnosis and prognosis, particularly in hematological malignancies. This review comprehensively explores the role of circRNAs in the pathogenesis, progression, and therap

Feline infectious peritonitis.

The article discusses feline infectious peritonitis (FIP), an important disease frequently seen in veterinary practice. FIP causes many problems to the veterinarian as it can be difficult to definitively diagnose the disease, as there is no effective treatment, and as prophylactic interventions are not very successful. Although intense research has created a lot of new knowledge about this disease in the last years, there are still many unanswered questions. The objective of this article is to review recent knowledge and to increase understanding of the complex pathogenesis of FIP.

Выявляется стабильная устойчивая донора диких голубей для многих доминирующих видов брухидов в Индии.

Выявление стабильных и устойчивых источников представляет собой экологически благоприятную и устойчивую стратегию борьбы с насекомыми. Sixty-eight Присоединения диких голубей систематически проверялись three Преобладающие виды брухидов (Callosobruchus analis, C. chinensis, C. maculatus) с использованием высокопроизводительного скринингового трубопровода в Канпуре, Индия, 2021 в адрес 2024. Классификация устойчивости основывается на повреждении семян и индексе уязвимости. Four Присоединения к ринкосии брактета неизменно демонстрировали конвергентное и полное сопротивление в отношении различных

Development of novel gene signatures for the risk stratification of prognosis and diagnostic prediction of osteosarcoma patients using bioinformatics analysis.

BackgroundOsteosarcoma (OS) is a common malignant bone cancer in children and teenagers that originates from osteoblast cells. Although many biomarkers have been reported in OS, they have not improved the prognosis of this disease. This study sought to identify effective biomarkers for the early diagnosis and prognosis of OS using a comprehensive bioinformatics analysis.MethodsOS-associated microRNAs (miRNAs) were screened in the Human microRNA Disease Database (HMDD). The differentially expressed genes (DEGs) related to OS were screened using 3 data sets (GSE16088, GSE36001, and GSE56001) fro

Bridging the gap: ferroptosis of immune cells in the tumor microenvironment.

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly recognized as a pivotal immunomodulatory mechanism within the tumor microenvironment (TME). Beyond its well-established role in tumor cell elimination, emerging evidence reveals that immune cell subsets exhibit distinct susceptibility to ferroptosis, with profound consequences for antitumor immunity. This review systematically delineates the dual and cell-type-specific roles of ferroptosis across innate and adaptive immune populations: while ferroptosis-mediated depletion of immunosuppress

Enzimatic Paradox of Yeast Arginil-tRNA Synthetase: Исключительная передача Аргинина, контролируемая гибким механизмом признания tRNA.

Детерминанты идентичности необходимы для точного признания переноса РНК синтетиками аминоачил-тРНА. На сегодняшний день аргининские детерминанты в дрожжах сачаромице были выявлены исключительно in vitro и только на ограниченном числе изоприятцев trNA Arginin. В нынешнем исследовании мы выступаем за полный клеточный подход и расширяем исследования аргининских детерминант до всех four TRNA Arg изо-приемники. В более конкретном плане эта работа позволяет проанализировать актуальность нуклеотидов ТРНА на месте. 20, 35 и 36 в реакции дрожжей на аргинилацию. Мы построили 21 мутантов мутагенезом, упр

Von Hippel-Lindau Disease: Current Challenges and Future Prospects.

Understanding of molecular mechanisms of tumor growth has an increasing impact on the development of diagnostics and targeted therapy of human neoplasia. In this review, we summarize the current knowledge on molecular mechanisms and their clinical implications in von Hippel-Lindau (VHL) disease. This autosomal dominant tumor syndrome usually manifests in young adulthood and predisposes affected patients to the development of benign and malignant tumors of different organ systems mainly including the nervous system and internal organs. A consequent screening and timely preventive treatment of l

Множественный склероз: то, что мы узнали и можем узнать из электронной микроскопии.

Множественный склероз (MS) — воспалительное нейродегенеративное заболевание, характеризующееся возникновением демиелинированных повреждений в центральной нервной системе. Повреждения MS могут подвергаться воспоминанию, временно смягчая симптомы, но по мере развития болезни воспроизводство становится менее эффективным. Помимо повреждений, нормальные появляющиеся ткани мозга имеют тонкие изменения, потенциально указывающие на более широкую диффузную патологию и/или повышенную подверженность воздействию повреждений. Патология MS варьируется между повреждениями серых и белых веществ и их нормальны

Тип общей генетической и нейроиммунной архитектуры 1 диабет с нейрокогнитивными признаками.

Тип 1 диабет, особенно в детстве, ассоциируется с изменяющимися нейрокогнитивными признаками, однако основные биологические механизмы неясны. Здесь мы интегрируем результаты общегеномной ассоциации с одноклеточных эпигеномических профилей и показываем этот тип 1 Наследственность диабета обогащается доступным хроматином клеток мозга человека, в первую очередь микроглией, через нейроразвитие до взрослого возраста. Анализ генетической корреляции, скорректированный по методу Bonferroni, показывает отрицательную корреляцию типа 1 диабет с интеллектом, исполнительными функциями и биполярным расстрой

Inhibiting of TACC3 Promotes Cell Proliferation, Cell Invasion and the EMT Pathway in Breast Cancer.

Accumulating evidences indicate that transforming acidic coiled-coil 3 (TACC3) is a tumor-related gene, was highly expressed in a variety of human cancers, which is involved in cancer development. However, the potential role of TACC3 in breast cancer remains largely unknown. In the present study, we found that TACC3 was highly-expressed in breast cancer tissues, and its level was positively correlated with the clinical features of breast cancer patients. Specifically, TACC3 expression was significantly associated with the estrogen receptor (ER), progesterone receptor (PR), human epidermal grow

Activated Ras as a Therapeutic Target: Constraints on Directly Targeting Ras Isoforms and Wild-Type versus Mutated Proteins.

The ability to selectively and directly target activated Ras would provide immense utility for treatment of the numerous cancers that are driven by oncogenic Ras mutations. Patients with disorders driven by overactivated wild-type Ras proteins, such as type 1 neurofibromatosis, might also benefit from progress made in that context. Activated Ras is an extremely challenging direct drug target due to the inherent difficulties in disrupting the protein:protein interactions that underlie its activation and function. Major investments have been made to target Ras through indirect routes. Inhibition