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RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) significantly affects quality of life. We recently cloned synoviolin, a RING-type E3 ubiquitin ligase implicated in the endoplasmic reticulum-associated degradation (ERAD) pathway. Synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of RA. Inhibition of synoviolin activity is a potentially useful therapeutic approach for the treatment of RA. We conducted a high-throughput screen of small molecules to find inhibitors of synoviolin autoubiquitination activity. We identified two classes of small molecules, named LS-101 and

Характеристика повреждений ногой femoris в остеоартрите на различных этапах и эффект акупотомии с помощью ультразвука.

ВВЕДЕНИЕ: Хроническое повреждение мышцы rectus femoris вызывает и усугубляет прогрессирование остеоартрита колена (КОА). Однако характеристики повреждения мышцы rectus femoris в KOA на различных этапах не были в полной мере описаны. Цель этого исследования состояла в том, чтобы проанализировать структуру повреждений мышцы rectus femoris на различных стадиях KOA и изучить механизм, с помощью которого ультразвуковые акупотомические операции могут предотвращать и контролировать KOA. МЕТОДЫ: Ранние, средние и поздние модели кроликов KOA были построены с использованием модифицированного метода Vide

Re-Cellularised Kidney Scaffold for Chikungunya Virus Propagation: A Novel Approach.

BACKGROUND: Re-emerging viral attacks are catastrophic for health and economy. It is crucial to grasp the viral life cycle, replication and mutation policies and attack strategies. It is also absolute to fathom the cost-efficient antiviral remedies earliest possible. METHODS: We propose to use a lab-grown organ (re-cellularized scaffold of sheep kidney) for viral culture and understand its interaction with extra-cellular matrices of the host tissue. RESULTS: Our findings showed that the chikungunya virus (CHIKV) could be better replicated in tissue-engineered bio models than cell culture. A

Bone marrow fibrosis in newly diagnosed multiple myeloma and its correlation with clinicopathological factors.

BACKGROUND: Bone marrow fibrosis (BMF) severely impacts both the quality of life and the efficacy of diagnostic procedures. However, the correlation between BMF and clinicopathological features, cytogenetic changes, and prognosis of newly diagnosed multiple myeloma (NDMM) remains unclear. This study determined the incidence, patient characteristics, and clinical outcomes of patients with NDMM with BMF. METHODS: The clinical data, histological features, and clinical outcomes of patients with NDMM were collected. Reticular fiber staining was performed on the enrolled cases, and the degree of re

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions.

The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors-in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins-not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of

Novel therapeutic approaches for pulmonary fibrosis.

Pulmonary fibrosis represents the end stage of a number of heterogeneous conditions and is, to a greater or lesser degree, the hallmark of the interstitial lung diseases. It is characterized by the excessive deposition of extracellular matrix proteins within the pulmonary interstitium leading to the obliteration of functional alveolar units and in many cases, respiratory failure. While a small number of interstitial lung diseases have known aetiologies, most are idiopathic in nature, and of these, idiopathic pulmonary fibrosis is the most common and carries with it an appalling prognosis - med

Связанные с мукосом инвариантные Т клетки в автоматическом иммунитете, заболеваниях, вызванных иммунной медициной, и заболеваниях дыхательных путей.

Инвариантные клетки, связанные с мукосалом Т (MAIT) — это новый класс врожденных Т клеток, выражающий полуинвариантный рецептор Т-клеток (TCR) и способный распознавать небольшие молекулы, представленные на неполиморфическом белоке MHC 1. Их врожденный фенотип фемориального эффекта, позволяющий секретить провоспалительные цитокины, и их относительное изобилие в человеке означает значительный потенциал для содействия аутоиммунным процессам. Однако, поскольку до недавнего времени клетки MAIT были неизвестны, а конкретные иммунологические инструменты отсутствовали, мало что известно об их роли в б

Genetic factors and management strategies in aortic health: a literature review of inherited aortopathy.

Inherited aortopathies, including Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, are genetic disorders characterized by structural abnormalities of the aorta that predispose individuals to life-threatening complications like aneurysms and dissections. These conditions result from mutations in genes essential for maintaining aortic wall integrity, such as FBN1, TGFBR1, and COL3A1, affecting extracellular matrix components and the transforming growth factor-beta (TGF-β) pathway. Marfan syndrome has a prevalence of approximately 1 in 5000, while Loeys-Dietz syndrome and vascul

The correlation between serum bone metabolism indexes and bone disease and survival in newly diagnosed multiple myeloma patients.

Objective Myeloma-related bone disease (MBD) is one of the most common complications of multiple myeloma (MM). This study aims to investigate the correlation between serum bone metabolism indexes (BMIs), the clinical characteristics and prognosis of newly diagnosed MM (NDMM) patients.MethodsThe serum BMIs of 148 patients with NDMM in a single hematological disease treatment center from April 2014 to December 2019 were analyzed retrospectively, including type I collagen amino terminal elongation peptide (PINP), β-C-terminal telopeptide of type I collagen (β-CTX) and N-terminal osteocalcin (N-MI

Epithelial-Mesenchymal Transition in Cancer: Insights Into Therapeutic Targets and Clinical Implications.

Radiation therapy is a fundamental component of cancer treatment, benefiting 50%-70% of patients by selectively targeting malignant tissues. However, radioresistance remains a significant challenge, often driven by epithelial-mesenchymal transition (EMT). EMT increases cancer invasiveness and metastasis by upregulating mesenchymal markers, including vimentin and N-cadherin, and downregulating epithelial markers, such as E-cadherin. EMT under radiation involves principal signaling pathways, including TGF-β, Wnt/β-catenin, Notch, and ERK, which regulate EMT through transcription factors such as

Генетическое или терапевтическое нарушение траектории подачи сигналов Reelin/Apoer2 улучшает воспалительные результаты артрита.

Ремутатоидный артрит (RA) — хроническое аутоиммунное заболевание, характеризующееся синновальным воспалением, образованием паннуса и постепенным совместным разрушением. Вспыльчивая среда в RA приводит к активации эндотелиальных клеток и к повышению регулирования молекул сцепления, что облегчает проникновение лейкоцитов в синовый. Релин, циркулирующий гликопротеин, ранее связанный с активацией эндотели и вербовкой лейкоцитов для лечения таких заболеваний, как атеросклероз и множественный склероз, стал потенциальным регулятором этих процессов. Однако его роль в патогенезе РА остается слабой. Зде

Совпадение в полном тексте источника
… This result was replicated in three different inflammatory arthritis mouse models, the spontaneous K/BxN mice, the STA induced in C57BL/6J mice with K/BxN serum injection, and the CIA induced in DAB/1 mice by collagen type II immunization. … type II at day 0. …

Nucleic acid aptamers in orthopedic diseases: promising therapeutic agents for bone disorders.

Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging as pivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution of Ligands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA, proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents, including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modificatio

Совпадение в полном тексте источника
… After an eight-week healing period, histomorphological analyses were performed, including safranin-O staining for glycosaminoglycans (GAG) and immunohistochemical staining for collagen type II to evaluate cartilage regeneration. …

Модулирование ренального фиброза: новая роль фактора роста гепатоцитов.

Введение и обоснование фактора роста Hepatocyte (HGF) является многофункциональным белком, связанным с ростом и расширением клеток. Известно, что HGF в значительной степени проявляется в почечной ткани и в ее роли в залечивании ран и распространении тканей. Эта обзорная статья была направлена на изучение патогенеза HGF в почечной фиброзе в дополнение к его связи с взаимосвязанными подстрекательскими заболеваниями, такими, как гипертония и диабет. 2025 - выявление и сопоставление исследований, посвященных взаимосвязи между почечным фиброзом и ГФУ в доклинических и клинических условиях. Полученн

Evolving Paradigms in Chronic Graft-Versus-Host Disease: From Global Immunosuppression to Precision Targeted and Cell-Based Therapies.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment for a range of medical conditions. However, the procedure carries with it a significant risk of chronic graft-versus-host disease (cGVHD), which can have a considerable impact on patients’ quality of life and clinical outcomes. In recent years, there has been a marked shift in treatment strategies for this condition, with greater emphasis being placed on novel targeted therapies and cell therapies that target specific pathways. This shift in approach signifies a more profound comprehension of the pa

Skeletal Site-specific Effects of Zoledronate on in vivo Bone Remodeling and in vitro BMSCs Osteogenic Activity.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been associated with long-term oral or intravenous administration of nitrogen-containing bisphosphonates (BPs). However, the pathogenesis of BRONJ remains unknown, and definitively effective treatment has not yet been established. Bisphosphonate-related osteonecrosis (BRON) tends to occur in maxillofacial bones. Why this occurs is still unclear. Here we show that zoledronate (Zol) treatment suppresses alveolar bone remodeling after tooth typical clinical and radiographic hallmarks of the human BRONJ, whereas enhances peripheral bone q

High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and b

Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value.

Lung cancer is the leading cause of cancer-related death worldwide. Bone metastasis, which usually accompanies severe skeletal-related events, is the most common site for tumor distant dissemination and detected in more than one-third of patients with advanced lung cancer. Biopsy and imaging play critical roles in the diagnosis of bone metastasis; however, these approaches are characterized by evident limitations. Recently, studies regarding potential biomarkers in the serum, urine, and tumor tissue, were performed to predict the bone metastases and prognosis in patients with lung cancer. In t

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and inva

Targeting Oxidative Stress as a Therapeutic Approach for Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by an abnormal reepithelialisation, an excessive tissue remodelling and a progressive fibrosis within the alveolar wall that are not due to infection or cancer. Oxidative stress has been proposed as a key molecular process in pulmonary fibrosis development and different components of the redox system are altered in the cellular actors participating in lung fibrosis. To this respect, several activators of the antioxidant machinery and inhibitors of the oxidant species and pathways have been assayed in precl

Dysregulated TRK signalling is a therapeutic target in CYLD defective tumours.

Individuals with germline mutations in the tumour-suppressor gene CYLD are at high risk of developing disfiguring cutaneous appendageal tumours, the defining tumour being the highly organised cylindroma. Here, we analysed CYLD mutant tumour genomes by array comparative genomic hybridisation and gene expression microarray analysis. CYLD mutant tumours were characterised by an absence of copy-number aberrations apart from LOH chromosome 16q, the genomic location of the CYLD gene. Gene expression profiling of CYLD mutant tumours showed dysregulated tropomyosin kinase (TRK) signalling, with overex