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Diverse antitumor effects of ascorbic acid on cancer cells and the tumor microenvironment.

Ascorbic acid has attracted substantial attention for its potential antitumor effects by acting as an antioxidant in vivo and as a cofactor in diverse enzymatic reactions. However, solid proof of its clinical efficacy against cancer and the mechanism behind its effect have not been established. Moreover, cancer forms cancer-specific microenvironments and interacts with various cells, such as cancer-associated fibroblasts (CAFs), to maintain cancer growth and progression; however, the effect of ascorbic acid on the cancer microenvironment is unclear. This review discusses the effects and mechan

Postmenopausal women with osteoarthritis and osteoporosis show different ultrastructural characteristics of trabecular bone of the femoral head.

BackgroundOsteoporosis (OP) and osteoarthritis (OA) are public health diseases affecting the quality of life of the elderly, and bring about a heavy burden to the society and family of patients. It has been debated whether or not there is an inverse relationship between these two disorders.MethodsTo compare the exact difference in bone tissue structure between osteoporosis and osteoarthritis, we observed the ultrastructure of trabecular bone from the femoral heads using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A total of 15 femoral head specimens from post

Advances in materials used for minimally invasive treatment of vertebral compression fractures.

Vertebral compression fractures are becoming increasingly common with aging of the population; minimally invasive materials play an essential role in treating these fractures. However, the unacceptable processing-performance relationships of materials and their poor osteoinductive performance have limited their clinical application. In this review, we describe the advances in materials used for minimally invasive treatment of vertebral compression fractures and enumerate the types of bone cement commonly used in current practice. We also discuss the limitations of the materials themselves, and

Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.

Cancer-associated fibroblasts (CAFs) are functionally diverse stromal regulators that orchestrate tumor progression, metastasis, and therapy resistance through dynamic crosstalk within the tumor microenvironment (TME). Recent advances in single-cell multiomics and spatial transcriptomics have identified conserved CAF subtypes with distinct molecular signatures, spatial distributions, and context-dependent roles, highlighting their dual capacity to promote immunosuppression or restrain tumor growth. However, therapeutic strategies struggle to reconcile this functional duality, hindering clinica

Mobilizing stem cells and inhibition of autoimmunity synergistically modify autoimmune disease to relieve pain: a potential MRG-001 therapy for rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, bone erosion, cartilage destruction, and debilitating pain. Current therapies often fall short in preventing structural damage and restoring immune balance. To address these limitations, we evaluated MRG-001 - a fixed-dose combination of plerixafor (AMD3100) and low-dose tacrolimus (FK506) with reported immunoregulatory and regenerative potential - in preclinical models of RA. METHODS: The therapeutic efficacy of MRG-001 was assessed in collagen-induced arthritis and collag

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

The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art.

Heat shock protein 90 (HSP 90) and its isoforms are a group of homodimeric proteins that regulate several cellular processes, such as the elimination of misfolded proteins, cell development and post-translational modifications of kinase proteins and receptors. Due to its involvement in extracellular matrix (ECM) remodelling, myofibroblast differentiation and apoptosis, HSP 90 has been investigated as a key player in the pathogenesis of lung fibrosis. Idiopathic pulmonary fibrosis (IPF) is the most common and deadly interstitial lung disease, due to the progressive distortion of lung parenchyma

Obesity is associated with suppressed bone turnover: a systematic review and meta-analysis.

BackgroundObesity is an increasingly serious public health issue on a global scale. Although there is increasing research on the relationship between obesity and biochemical markers of bone turnover, this relationship is complex and unclear. We conducted a systematic review and meta-analysis aimed at comparing the concentrations of biochemical markers of bone turnover between individuals with obesity and those with normal-weight.MethodA systematic search was conducted using the PubMed, EMBASE, Web of Science, Cochrane Library, and EBSCO databases from database inception to December 15, 2025. T

CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.

The acronym for the CCN family was recently revised to represent "cellular communication network". These six, small, cysteine-enriched and evolutionarily conserved proteins are secreted matricellular proteins, that convey and modulate intercellular communication by interacting with structural proteins, signalling factors and cell surface receptors. Their role in the development and physiology of musculoskeletal system, constituted by connective tissues where cells are interspersed in the cellular matrix, has been broadly studied. Previous research has highlighted a crucial balance of CCN prote

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… CCN3 counteracts the proliferative potential of CCN2 as it keeps terminally differentiated chondrocytes in a quiescent state and its exogenous administration, overexpression or in vivo supplementation inhibits chondrocyte proliferation and proteoglycan deposition and induces type II collagen, type X … Consistently, the appearance of osteoarthritic-like degeneration is delayed up to 21 weeks in CCN2 knock-in mice: increased cellularity and decreased proteoglycan loss are derived from reduced collagen type X and MMP13 and collagen type I expression in articular chondrocytes (Itoh et al. 2013 ). …

A REVIEW OF SALIVARY BIOMARKERS OF PERIODONTAL DISEASE.

BackgroundPeriodontal disease is a complex multifactorial disease resulting from the interplay amongst microbiota, host immune response (influenced by genetic make-up) and lifestyle factors. The chronic inflammatory nature of the disease results in the destruction of the component of the periodontium. The process of the disease is associated with inflammation, collagen degradation and, bone loss which correlate with clinical features of periodontal disease. The clinical diagnosis of periodontal disease entails clinical examination involving the evaluation of probing depth, bleeding on probing,

Hydrogels-Assisted Cell Engraftment for Repairing the Stroke-Damaged Brain: Chimera or Reality.

The use of advanced biomaterials as a structural and functional support for stem cells-based therapeutic implants has boosted the development of tissue engineering applications in multiple clinical fields. In relation to neurological disorders, we are still far from the clinical reality of restoring normal brain function in neurodegenerative diseases and cerebrovascular disorders. Hydrogel polymers show unique mechanical stiffness properties in the range of living soft tissues such as nervous tissue. Furthermore, the use of these polymers drastically enhances the engraftment of stem cells as w

Spatiotemperal Dynamics of Osteoarthritis: Преобразование значений от стенда до Бедсайда.

Остеоартрит (OA) представляет собой многогранное дегенеративное совместное расстройство, вызванное различными факторами риска, такими, как возраст, механический стресс, воспаление и метаболическое воздействие. Эти элементы способствуют его разнообразным фенотипам и эндотипам, что подчеркивает имманентную сложность болезни. Участие нескольких тканей и их взаимодействие еще больше осложняет расследование ОА. Нынешние ограничения в области технологий пространственного фенотификации в сочетании со сложной сетью многофакторных взаимодействий препятствуют обнаружению надежных ранних диагностических

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… protein; AS : Articular surface; BMP2 : Bone morphogenetic protein 2; CD74 :Cluster of differentiation 74; CHI3L1 : Chitinase 3 like 1; CHI3L2 : Chitinase 3 like 2; CILP : Cartilage intermediate layer protein; COL1A1 : Collagen type I alpha 1 chain; COL1A2: Collagen type I alpha 2 chain; COL10A1 : Collagen … type X alpha 1 chain; COL27A1 : Collagen type XXVII alpha 1 chain; CRTAC1 : Cartilage acidic protein 1; DZ : Deep zone; ECM : Extracellular matrix; ECCs : Effctor chondrocytes; FCs : Fibrocartilaginous chondrocytes; FOSL1 : Fos like 1, AP-1 transcription factor subunit; FRZB : Frizzled related protein …

SOX9 Induces Orbital Fibroblast Activation in Thyroid Eye Disease Via MAPK/ERK1/2 Pathway.

PurposeTo evaluate the expression of sry-box transcription factor 9 (SOX9) in orbital fibroblasts (OFs) of thyroid eye disease (TED) and to find its potential role and underlying mechanism in orbital fibrosis.MethodsOFs were cultured from orbital connective tissues obtained from patients with TED (n = 10) and healthy controls (n = 6). SOX9 was depleted by small interfering RNA or overexpressed through lentivirus transduction in OFs. Fibroblast contractile activity was measured by collagen gel contraction assay and proliferation was examined by EdU assay. Transcriptomic changes were assessed by

MSC-EV therapy for bone/cartilage diseases.

Mesenchymal stromal cells (MSCs) have been utilized in cell therapy for various diseases. Recent studies have demonstrated that extracellular vesicles (EVs) released by MSCs play an important role in their therapeutic activities. EVs contain a variety of bioactive molecules such as proteins, messenger RNAs (mRNAs), and micro RNAs (miRNAs) and modify the function of the recipient cells by transferring these molecules. Despite the promising potential of EV therapy as a substitute for MSC therapy, there are challenges that need to be addressed for the clinical success of EV therapy. EV quality ha

The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8+ T Cell-Orientated Therapy.

The microenvironment in tumors is complicated and is constituted by different cell types and stromal proteins. Among the cell types, the abundance of cancer cells, fibroblasts, and immune cells is high and these cells work as the "Trinity" in promoting tumorigenesis. Although unidirectional or bidirectional crosstalk between two independent cell types has been well characterized, the multi-directional interplays between cancer cells, fibroblasts, and immune cells in vitro and in vivo are still unclear. We summarize recent studies in addressing the interaction of the "Trinity" members in the tu

Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.

Alternative splicing (AS) is the central mechanism of transcriptional regulation and generates diverse splice variants that influence protein structure, function, and intracellular activity. AS plays critical roles in tissue differentiation, organ development, and disease progression. This review focuses on the pivotal roles of AS in bone biology, highlighting its regulatory effects on osteoblasts, osteoclasts, chondrocytes, bone matrix remodeling, and bone remodeling, as well as the involvement of AS-related RNA-binding proteins in these processes. We also emphasize bone-specific AS events an

Update on the role of bone turnover markers in the diagnosis and management of osteoporosis: a consensus paper from The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), International Osteoporosis Foundation (IOF), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

PurposeThe International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis.MethodsEvidence for the re

Targeting strategies for bone diseases: signaling pathways and clinical studies.

Since the proposal of Paul Ehrlich's magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has b

Etodolac improves collagen induced rheumatoid arthritis in rats by inhibiting synovial inflammation, fibrosis and hyperplasia.

Synovial hyperplasia is the main cause of chronic rheumatoid arthritis (RA), but the mechanism of synovial hyperplasia is still unclear. Etodolac (ETD) is a selective COX-2 inhibitor for relieving pain and stiffness in RA, but the disease modifying effect is still lack of evidence. Proteomics method was used to study the differential proteome of synovial tissue in collagen induced arthritis (CIA) in rats. With the help of STRING analysis, the upregulated proteins enriched in the cluster of complement and coagulation cascades and platelet degranulation were highlighted, these proteins with fibr

Whole genome sequencing in adults with clinical hallmarks of hypophosphatasia negative for ALPL variants.

BackgroundHypophosphatasia (HPP) is a rare disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (ALP), encoded by the ALPL gene. The primary objective was to explore novel ALPL variants by whole genome sequencing (WGS) in patients with HPP who previously tested negative by standard methods for ALPL variants. The secondary objective was to search for genes beyond ALPL that may reduce ALP activity or contribute to HPP symptoms.Methods and resultsWGS was performed in 16 patients clinically diagnosed with HPP who had ALP activity below the normal range and tested negativ