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Unravelling Osteoporosis: Key Genes and Potential Therapies.

Osteoporosis is a metabolic bone disease characterised by decreased bone mass and increased fracture risk, especially in aging women. Current treatments have limitations and side effects, prompting the need for novel therapeutic targets. Using Mendelian randomisation (MR) on the basis of GWAS data from the FinnGen consortium, we identified druggable genes associated with osteoporosis. Transcriptomic profiling, single-cell RNA sequencing (scRNA-seq) and immune infiltration analysis were employed to explore gene expression patterns and immune relevance. Gene set enrichment analysis and gene set

Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.

Bone and joint-related diseases, including osteoarthritis (OA), rheumatoid arthritis (RA), and bone tumors, pose significant health challenges due to their debilitating effects on the musculoskeletal system. 14-3-3 proteins, a family of conserved regulatory molecules, play a critical role in the pathology of these diseases. This review discusses the intricate structure and multifunctionality of 14-3-3 proteins, their regulation of signaling pathways, and their interactions with other proteins. We underscore the significance of 14-3-3 proteins in the regulation of osteoblasts, osteoclasts, chon

Cellular and Molecular Mechanisms Associating Obesity to Bone Loss.

Obesity is an alarming disease that favors the upset of other illnesses and enhances mortality. It is spreading fast worldwide may affect more than 1 billion people by 2030. The imbalance between excessive food ingestion and less energy expenditure leads to pathological adipose tissue expansion, characterized by increased production of proinflammatory mediators with harmful interferences in the whole organism. Bone tissue is one of those target tissues in obesity. Bone is a mineralized connective tissue that is constantly renewed to maintain its mechanical properties. Osteoblasts are responsib

Progress in high-throughput screening for drug and material discovery in orthopedic diseases: a literature review.

Orthopedic diseases are referred to as a series of conditions affecting the normal structure and function of the skeletal system. With a wide variety of types and a year-by-year increasing incidence, they have a severe impact on patients' quality of life. Traditional research has made relatively significant progress in understanding the pathogenesis and treating orthopedic diseases, however, it remains constrained by limitations such as low-throughput experimentation, and difficulty in mimicking the complex bone microenvironment. In recent years, high-throughput screening (HTS) technology has

Pulmonary hypertension in patients with multiple myeloma: A comprehensive review.

Multiple myeloma (MM) is a common hematological malignancy resulting from clonal proliferation of plasma cells and is defined by criteria set forth by the international myeloma working group. Pulmonary hypertension (PH) is defined by an elevated mean pulmonary artery pressure >20 mmHg measured during right heart catheterization. Echocardiography-diagnosed PH is relatively common in patients with MM and has been associated with increased mortality, morbidity, and poor stem cell transplant outcomes. PH in patients with MM (PH-MM) is usually multifactorial in origin. MM disease-specific factors,

Совпадение в полном тексте источника
… In anemia of multiple myeloma, hepcidin is induced by increased bone morphogenetic protein 2. Blood. 116:3635–44. 10.1182/blood-2010-03 43. Metivier F, Marchais SJ, Guerin AP, Pannier B, London GM. Pathophysiology of anaemia: focus on the heart and blood vessels. …

Minimally Invasive Spinal Stabilization Using Fluoroscopic-Guided Percutaneous Screws as a Form of Palliative Surgery in Patients with Spinal Metastasis.

STUDY DESIGN: Prospective cohort study. PURPOSE: To report the outcome of 50 patients with spinal metastases treated with minimally invasive stabilization (MISt) using fluoroscopic guided percutaneous pedicle screws with/without minimally invasive decompression. OVERVIEW OF LITERATURE: The advent of minimally invasive percutaneous pedicle screw stabilization system has revolutionized the treatment of spinal metastasis. METHODS: Between 2008 and 2013, 50 cases of spinal metastasis with pathological fracture(s) with/without neurology deficit were treated by MISt at our institution. The patien

Current progress and mechanisms of bone metastasis in lung cancer: a narrative review.

Lung cancer is a kind of malignant tumor with rapid progression and poor prognosis. Distant metastasis has been the main cause of mortality among lung cancer patients. Bone is one of the most common sites. Among all lung cancer patients with bone metastasis, most of them are osteolytic metastasis. Some serious clinical consequences like bone pain, pathological fractures, spinal instability, spinal cord compression and hypercalcemia occur as well. Since the severity of bone metastasis in lung cancer, it is undoubtedly necessary to know how lung cancer spread to bone, how can we diagnose it and

Активаторы Nrf2 для лечения редких заболеваний, связанных с перегрузкой железа: от скамейки до кровати.

Железная перегрузка и связанные с ней окислительные повреждения наблюдаются во многих редких болезнях в результате мутации генов, связанных с гомеостазом железа. Будучи основным регулятором реакции на клеточную антиоксидантную реакцию, Nrf2 может также снизить системный и клеточный уровень железа путем регулирования генов и путей, связанных с железом, что делает Nrf2 очень хорошими инициаторами для лечения нарушений, связанных с перегрузкой железа. К числу успешных примеров относится клиническое использование омавельоксолона для атаксии Фридрейха и диметилфумарата для повторного излучающего мн

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.

The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. Wnt proteins are secreted, lipid-modified signaling molecules that activate the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. Cellular behaviors such as proliferation, differentiation, maturation, and proper body-axis specification are carried out by the canonical pathway, which is the best characterized of the known Wnt signaling paths. Wnt signaling has emerged as an important factor in stem cell biology and is

Терапевтический потенциал моделей Purmorphamine через болезни.

Purmorphamine (PUR) — тройная субституция пурина, которая выборочно активирует сгущенный рецептор, тем самым инициируя Sonic Hedgehog (Shhh) сигнализирующий путь, имеющий решающее значение для эмбриональной модели, нейронной спецификации и регенерации тканей в различных системах различных органов. Регулирование сигнала " Шш " причастно к дегенеративным заболеваниям, однако терапевтические меры, направленные на этот путь, по-прежнему ограничены. PUR демонстрирует широкую терапевтическую эффективность различных моделей предклинических заболеваний путем активации как транскрипции с помо

Inhibiting KCNMA1-AS1 promotes osteogenic differentiation of HBMSCs via miR-1303/cochlin axis.

OBJECTIVE: Osteoporosis is a progressive systemic skeletal disorder. Multiple profiling studies have contributed to characterizing biomarkers and therapeutic targets for osteoporosis. However, due to the limitation of the platform of miRNA sequencing, only a part of miRNA can be sequenced based on one platform. MATERIALS AND METHODS: In this study, we performed miRNA sequencing in osteoporosis bone samples based on a novel platform Illumina Hiseq 2500. Bioinformatics analysis was performed to construct osteoporosis-related competing endogenous RNA (ceRNA) networks. Gene interference and osteo

Inflammaging in periodontal, periapical, and malignancy-associated disease: drivers of alveolar bone loss and repair.

BACKGROUND: Aging significantly impacts bone metabolism through altered osteoblast/osteoclast dynamics, reduced stem cell regeneration, and chronic inflammaging. This narrative review explores how these age-related changes influence alveolar bone loss and regeneration in the oral cavity. METHODS: The review investigates key mechanisms-including immunosenescence and inflammasome activation-across three specific pathological contexts: (1) periodontitis, (2) periapical bone resorption, and (3) malignancy-associated osteolysis. Preclinical and clinical evidence were integrated to analyze the bone

Mesenchymal stem cells in the treatment of osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory. Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multi-potentia

Chloroquine Restores eNOS Signaling in Shunt Endothelial Cells via Inhibiting eNOS Uncoupling.

Pulmonary arterial hypertension (PAH) is characterized by increased lung vascular stiffness and impaired vessel relaxation, primarily due to reduced nitric oxide (NO) production in endothelial cells. Recent studies indicate that chloroquine, an autophagy inhibitor, may help lower pulmonary arterial pressure and enhance lung vascular function. This study investigates the mechanisms underlying the chloroquine-mediated restoration of NO bioavailability in endothelial cells derived from aortopulmonary shunt lambs, a relevant model for congenital heart defect (CHD)-associated PAH. We found that NO

A Borate-Based Bioactive Glass Advances Wound Healing in Non-Healing Wagner Grade 1 Diabetic Foot Ulcers: A Randomised Controlled Clinical Trial.

A novel advanced synthetic bioactive glass matrix was studied in patients with non-healing diabetic foot ulcers (DFUs). Bioactive glasses can be constructed to be biocompatible, with water-soluble materials in multiple geometries including fibre scaffolds that mimic the 3D architecture of a fibrin clot. In this trial, chronic, Wagner Grade 1 DFUs were randomised to receive borate-based bioactive glass Fibre Matrix (BBGFM) plus standard of care (SOC) therapy for 12 weeks or SOC alone. The primary study endpoint was the proportion of subjects that obtained complete wound closure at 12 weeks. Sec

Advances in the research on myokine-driven regulation of bone metabolism.

The traditional view posits that bones and muscles interact primarily through mechanical coupling. However, recent studies have revealed that myokines, proteins secreted by skeletal muscle cells, play a crucial role in the regulation of bone metabolism. Myokines are widely involved in bone metabolism, influencing bone resorption and formation by interacting with factors related to bone cell secretion or influencing bone metabolic pathways. Here, we review the research progress on the myokine regulation of bone metabolism, discuss the mechanism of myokine regulation of bone metabolism, explore

Cancer metastasis to the bone: Mechanisms and animal models (Review).

The majority of cancer-related deaths result from tumor metastasis, with bone metastasis occurring in almost all types of malignant tumors. Understanding the mechanism by which tumors metastasize to bone is critical for the identification of novel therapeutic targets. A large amount of research has been carried out using animal models, and these models have been crucial in advancing the fundamental understanding of cancer. However, current models are limited; although they can mimic specific stages of the metastatic process, they are not able to replicate the entire process from tumorigenesis

Beyond boundaries: unraveling innovative approaches to combat bone-metastatic cancers.

Evidence demonstrated that bones, liver, and lungs are the most common metastasis sites in some human malignancies, especially in prostate and breast cancers. Bone is the third most frequent target for spreading tumor cells among these organs and tissues. Patients with bone-metastatic cancers face a grim prognosis characterized by short median survival time. Current treatments have proven insufficient, as they can only inhibit metastasis or tumor progression within the bone tissues rather than providing a curative solution. Gaining a more profound comprehension of the interplay between tumor c

Molecular mechanisms and clinical management of cancer bone metastasis.

As one of the most common metastatic sites of malignancies, bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish. The fenestrated capillaries in the bone, bone matrix, and bone cells, including osteoblasts and osteoclasts, together maintain the homeostasis of the bone microenvironment. In contrast, tumor-derived factors act on bone components, leading to subsequent bone resorption or excessive bone formation. The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases. In this review, we summarize the curr

Latest Advancements in the Management of H3K27M-Mutant Diffuse Intrinsic Pontine Glioma: A Narrative Review.

Despite recent advancements in radiotherapy for Diffuse Intrinsic Pontine Glioma (DIPG), the prognosis of this disease remains poor, highlighting the need for new treatment strategies to improve outcomes. Adding stereotactic biopsy to the diagnostic process for children with DIPG has been crucial in improving the management of this disease. Indeed, the discovery of the H3K27M mutation as a key driver of DIPG has led to the development of new drugs that are more effective than traditional ones. These include nimotuzumab (an anti-EGFR drug) and vinorelbine (a semisynthetic vinca alkaloid) in com