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Osteoprotegerin and receptor activator of NF-kappaB ligand as biomarkers for bone resorption-related disorders.

Osteoclastic bone diseases represent a significant health burden, especially in an aging population, due to imbalances in bone homeostasis that result in postmenopausal osteoporosis, inflammatory arthritis, malignancy-induced bone disease and secondary metabolic conditions, which result in fragility fractures, disability and death. Although advances in imaging and pharmacology have enhanced management, existing diagnostic strategies have poor sensitivity in detecting early-stage pathological changes or fracture risk. The NF-kappaB/receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin

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… Ann Rheum Dis. 2016;75:1187–1195. doi: 10.1136/annrheumdis-2014-207137. 100. Goldring S, Gravallese E. Adverse effects of rheumatoid arthritis on bone remodeling. Arthritis Res Ther. 2004;6:38. 101. Schett G, Gravallese E. Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. …

The Role of the Ubiquitin System in Eye Diseases.

The ubiquitin-proteasome system (UPS) is a fundamental process that regulates various biological functions, including immune response, cell cycle, oxidative stress, migration, and cellular proliferation. This system is responsible for the degradation of proteins, while proteasomes play a significant role in mechanisms involved in health and human diseases. The participation of the UPS in immune response is particularly relevant, leading to the involvement of immunoproteasomes. This specialized proteasome is involved in the processing and presentation of antigenic peptides, making it crucial fo

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… Rheum. Dis. 2015;74:1302–1310. doi: 10.1136/annrheumdis-2013-204584. 86. Nättinen J., Jylhä A., Aapola U., Mäkinen P., Beuerman R., Pietilä J., Vaajanen A., Uusitalo H. Age-associated changes in human tear proteome. Clin. Proteomics. 2019;16:11. doi: 10.1186/s12014-019-9233-5. 87. …

Prevalence of symptomatic toxicities for novel therapies in adult oncology trials: a scoping review.

BackgroundPatients' self-report of their symptoms can provide important data for the evaluation of treatment benefit and tolerability of oncology drugs. Contemporary treatment approaches, including immunotherapy and molecular targeted therapies, have unique toxicities based on their novel mechanisms of action. This scoping review aimed to summarize evidence from existing reviews and clinical practice guidelines to examine the type and prevalence of toxicities including symptomatic adverse events (sympAEs) for adult cancer patients to inform clinical care and therapeutic trials.MethodsA systema

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… | GI: hepatitis (5%-30%), pancreatitis (4%), colitis (10%-35%) Resp: pneumonitis/interstitial lung disease (2%-4%) CV: cardiac toxicity (<5%) Skin: cutaneous AEs (>50%) Neuro: neurotoxicity (1%-5%), myasthenia gravis-like syndrome Vision: ocular toxicity (<1%) Pain: inflammatory arthritis (5%-10%) Rheum …

Anti-B Cell Strategy in Nephrotic Syndrome: Beyond Rituximab.

Nephrotic syndrome (NS) is a complex kidney disorder characterized by profound proteinuria, hypoalbuminemia, hyperlipidemia, and edema, significantly impacting patients' quality of life. While corticosteroids and calcineurin inhibitors (CNIs) have traditionally been the primary treatments, B cell-targeted therapies, especially the anti-CD20 monoclonal antibody rituximab, have transformed the management of steroid-dependent and multidrug-resistant NS (MRNS). Rituximab has demonstrated efficacy in reducing relapse rates and steroid dependence by depleting CD20+ B cells, which play a pivotal role

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… Rheum. Dis. 2025 84 106 114 10.1136/ard-2024-226142 39874224 46. Reddy V.R. Pepper R.J. Shah K. Cambridge G. Henderson S.R. Klein C. Kell L. Taylor S.J. Isenberg D.A. Cragg M.S. …

Dose-escalation studies of mesenchymal stromal cell therapy for decompensated liver cirrhosis: phase Ia/Ib results and immune modulation insights.

Decompensated liver cirrhosis (DLC) is characterized by severe liver dysfunction and immune dysregulation, posing significant treatment challenges. Mesenchymal stromal cell (MSC) therapy has shown promise in DLC treatment, but the optimal dosing strategies and dose-dependent therapeutic mechanisms in humans remain unclear, limiting its clinical application. We conducted sequential Phase Ia/Ib trials using a single-arm, dose-escalation design to evaluate the safety and tolerability of MSC therapy in DLC patients while also exploring its immunomodulatory effects and gathering preliminary therape

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… Rheum. Dis. 69 , 1423–1429 (2010). 38. Piano, S., Bunchorntavakul, C., Marciano, S. & Rajender Reddy, K. Infections in cirrhosis. Lancet Gastroenterol. Hepatol. 9 , 745–757 (2024). 39. Giacomini, C., Graneli, C., Hicks, R. & Dazzi, F. …

Оценка двунаправленных причинно-следственных последствий болезни Альцгеймера в различных условиях: систематический обзор и мета-анализ Мендельских исследований в области рандомизации.

В этом исследовании проводится систематическая оценка и мета-анализ менделианских случайных исследований причинно-следственной связи между болезнью Альцгеймера (АБ) и системными заболеваниями. Мы искали five - базы данных, оценка качества исследований и получение данных. Болезни были классифицированы с использованием ICD-11, и метаанализ был проведен с RevMan 5.4. Всего 56 В ходе исследований были выявлены генетические связи между уязвимостью и системными заболеваниями. В частности, генетические прокси для бедра остеоартрита (OR = 0.80; p = 0.007) и ревматоидный артрит (OR = 0.97; p = 0.004) б

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This study systematically evaluates and meta-analyzes Mendelian randomization studies on the bidirectional causal relationship between Alzhe … y and systemic diseases. Notably, genetic proxies for hip osteoarthritis (OR = 0.80; p = 0.007) and rheumatoid arthritis (OR = 0.97; p = 0.004) were inversely associated with AD risk, while gout (OR = 1.02; p = 0.049) showed a positive association. Genetic liability to depression (OR = 1.03; p = 0.001) elevated AD risk, and AD genetic risk increased sus …

Regorafenib Attenuates Osteoclasts Differentiation by Inhibiting the NF-κB, NFAT, ERK, and p38 Signaling Pathways.

Osteolytic diseases such as osteoporosis and neoplastic bone metastases are caused by the excessive activation of osteoclasts. Inhibiting the excessive activation of osteoclasts is a crucial strategy for treating osteolytic diseases. This study investigated the roles and mechanisms of regorafenib, a tyrosine kinase inhibitor, on osteoclasts and osteolytic diseases. We first identified the potential targets and mechanisms of regorafenib on osteoclast-related osteolytic diseases using network pharmacological analysis and molecular docking techniques. Then, we verified its role and mechanism on o

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… Rheum. Dis. 2023 , 26 ( 4 ), 718 – 726 . 10.1111/1756-185X.14627 . 36808837 Heilmann T. ; Rumpf A. L. ; Roscher M. ; Tietgen M. ; Will O. ; Gerle M. ; Damm T. ; Borzikowsky C. ; Maass N. ; Glüer C. C. ; et al. …

Network Pharmacology Approaches Used to Identify Therapeutic Molecules for Chronic Venous Disease Based on Potential miRNA Biomarkers.

Chronic venous disease (CVD) is a prevalent condition in adults, significantly affecting the global elderly population, with a higher incidence in women than in men. The modulation of gene expression through microRNA (miRNA) partly regulated the development of cardiovascular disease (CVD). Previous research identified a functional analysis of seven genes (CDS2, HDAC5, PPP6R2, PRRC2B, TBC1D22A, WNK1, and PABPC3) as targets of miRNAs related to CVD. In this context, miRNAs emerge as essential candidates for CVD diagnosis, representing novel molecular and biological knowledge. This work aims to i

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… Down-regulation of microRNA-34a* in rheumatoid arthritis synovial fibroblasts promotes apoptosis resistance Arthritis Rheum. 2012 64 1771 1779 10.1002/art.34334 22161761 98. Ducasse E. Giannakakis K. Speziale F. Midy D. Sbarigia E. Baste J.C. Faraggiana T. …

Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients.

Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone regeneration arise. To determine the appropriate amount of bone to be removed, preoperative imaging techniques such as bone and CT scans are employed. To prevent local recurrence, the current standard of care suggests maintaining bony and soft tissue margins from 3 to 7 cm beyond the tumor. The amount

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… Arthritis Rheum. 2009;60:813–823. doi: 10.1002/art.24330. 82. Todeschi M.R., El Backly R., Capelli C., Daga A., Patrone E., Introna M., Cancedda R., Mastrogiacomo M. …

Bone Metabolism Effects of Medical Therapy in Advanced Renal Cell Carcinoma.

The medical therapy of advanced renal cell carcinoma (RCC) is based on the use of targeted therapies, such as tyrosine kinase inhibitors (TKI) and immune-checkpoint inhibitors (ICI). These therapies are characterized by multiple endocrine adverse events, but the effect on the bone is still less known. Relatively few case reports or small case series have been specifically focused on TKI and ICI effects on bone metabolism. However, the importance to consider these possible side effects is easily intuitable because the bone is one of the most frequent metastatic sites of RCC. Among TKI used in R

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… Rheum. Dis. 2010;69:284–290. doi: 10.1136/ard.2008.104786. 121. Harmer D., Falank C., Reagan M.R. Interleukin-6 interweaves the bone marrow microenvironment, bone loss, and multiple myeloma. Front. Endocrinol. 2018;9:788. doi: 10.3389/fendo.2018.00788. 122. …

Mesenchymal stem cells: A new therapeutic tool for chronic kidney disease.

Chronic kidney disease (CKD) has a major impact on public health, which could progress to end-stage kidney disease (ESRD) and consume many medical resources. Currently, the treatment for CKD has many flaws, so more effective treatment tools are urgently required for CKD. Mesenchymal stem cells (MSCs) are primitive cells with self-renewal and proliferation capacity and differentiation potential. Extensive preclinical and clinical data has shown that cell-based therapies using MSCs can modulate immunity, inhibit inflammatory factors, and improve renal function in CKD, suggesting that MSCs have t

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… Rheum. Dis. 76, 1436–1439. 10.1136/annrheumdis-2017-211073 Docherty N. G., O'Sullivan O. E., Healy D. A., Fitzpatrick J. M., Watson R. W. (2006). Evidence that inhibition of tubular cell apoptosis protects against renal damage and development of fibrosis following ureteric obstruction. Am. J. …

Exosomes: A new option for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These ca

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… Int J Rheum Dis . 2018 ; 21 : 1659 – 69 . 30345646 10.1111/1756-185X.13346 [63] Fu M Fang L Xiang X . Microarray analysis of circRNAs sequencing profile in exosomes derived from bone marrow mesenchymal stem cells in postmenopausal osteoporosis patients. …

Osteoprotective Roles of Green Tea Catechins.

Osteoporosis is the second most common disease only secondary to cardiovascular disease, with the risk of fracture increasing with age. Osteoporosis is caused by an imbalance between osteoblastogenesis and osteoclastogenesis processes. Osteoclastogenesis may be enhanced, osteoblastogenesis may be reduced, or both may be evident. Inflammation and high reactive oxygen enhance osteoclastogenesis while reducing osteoblastogenesis by inducing osteoblast apoptosis and suppressing osteoblastic proliferation and differentiation. Catechins, the main polyphenols found in green tea with potent anti-oxida

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… . (−)-Epigallocatechin-3-gallate suppresses osteoclast differentiation and ameliorates experimental arthritis in mice Arthritis Rheum. 2008 58 2012 2018 10.1002/art.23594 18576345 58. Lee J.H. Jin H. Shim H.E. Kim H.N. Ha H. Lee Z.H. …

Diagnosis and treatment of cardiac amyloidosis: an interdisciplinary consensus statement.

The prevalence and significance of cardiac amyloidosis have been considerably underestimated in the past; however, the number of patients diagnosed with cardiac amyloidosis has increased significantly recently due to growing awareness of the disease, improved diagnostic capabilities and demographic trends. Specific therapies that improve patient prognosis have become available for certain types of cardiac amyloidosis. Thus, the earliest possible referral of patients with suspicion of cardiac amyloidosis to an experienced center is crucial to ensure rapid diagnosis, early initiation of treatmen

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… Arthritis Rheum. 1989;32:1474–1476. doi: 10.1002/anr.1780321119. 38. Auer-Grumbach M, et al. Hereditary ATTR amyloidosis in Austria: prevalence and epidemiological hot spots. J Clin Med. 2020;9(7):2234. doi: 10.3390/jcm9072234. 39. Saraiva MJ. …

Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation.

Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft

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… Ann Rheum Dis (2010) 69:241–8. 10.1136/ard.2008.101881 40. Azevedo RI, Minskaia E, Fernandes-Platzgummer A, Vieira AIS, da Silva CL, Cabral JMS, et al. Mesenchymal stromal cells induce regulatory T cells via epigenetic conversion of human conventional CD4 T cells in vitro. …

Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities.

Subcutaneous delivery of biotherapeutics has become a valuable alternative to intravenous administration across many disease areas. Although … , treatment settings, administration volumes, and injection devices. We focus on biotherapeutics in rheumatoid arthritis (RA), immunoglobulin-replacement therapy in primary immunodeficiency (PI), beta interferons in multiple sclerosis (MS), and monoclonal antibodies (mAbs) in oncology. While most subcutaneous biotherapeutics in RA, PI, and MS are self-a …

Pomalidomide mitigates neuronal loss, neuroinflammation, and behavioral impairments induced by traumatic brain injury in rat.

BACKGROUND: Traumatic brain injury (TBI) is a global health concern that typically causes emotional disturbances and cognitive dysfunction. Secondary pathologies following TBI may be associated with chronic neurodegenerative disorders and an enhanced likelihood of developing dementia-like disease in later life. There are currently no approved drugs for mitigating the acute or chronic effects of TBI. METHODS: The effects of the drug pomalidomide (Pom), an FDA-approved immunomodulatory agent, were evaluated in a rat model of moderate to severe TBI induced by controlled cortical impact. Post-TBI

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… Ann Rheum Dis. 2012;71(11):1895–9. doi: 10.1136/annrheumdis-2012-201784. 81. US Food and Drug Administration. Guidance for industry. Estimating the maximum safe. Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy. …

DNA-hydrolysing activity of IgG antibodies from the sera of patients with schizophrenia.

It is believed that damage to the membranes of brain cells of schizophrenia (SCZ) patients induces the formation of autoantigens and autoantibodies. Nevertheless, the importance of immunological changes leading to the loss of tolerance to self-antigens in the genesis of SCZ has not been established. The MALDI mass spectra of the IgG light chains of 20 healthy donors were relatively homogeneous and characterized by one peak with only one maximum. In contrast to the healthy donors, the MALDI mass spectra of IgG light chains corresponding to 20 SCZ patients demonstrated, similarly to 20 autoimmun

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… Arthritis Rheum . 25 , 1271 – 1277 . ( doi:10.1002/art.1780251101 ) 7138600 10.1002/art.1780251101 51 American College of Rheumatology. 1982 Revised criteria for classification of systemic lupus erythematosus. …

Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists' arsenal.

Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of dist

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… between lymphangiogenic signalling and prostaglandin biology: a missing link in the metastatic pathway Oncotarget 2012 3 8 893 906 23097685 10.18632/oncotarget.593 PMC3478465 18 Baigent C Patrono C Selective cyclooxygenase 2 inhibitors, aspirin, and cardiovascular disease: a reappraisal Arthritis Rheum …

Co-inhibition of NF-κB and JNK is synergistic in TNF-expressing human AML.

Leukemic stem cells (LSCs) isolated from acute myeloid leukemia (AML) patients are more sensitive to nuclear factor κB (NF-κB) inhibition-induced cell death when compared with hematopoietic stem and progenitor cells (HSPCs) in in vitro culture. However, inadequate anti-leukemic activity of NF-κB inhibition in vivo suggests the presence of additional survival/proliferative signals that can compensate for NF-κB inhibition. AML subtypes M3, M4, and M5 cells produce endogenous tumor necrosis factor α (TNF). Although stimulating HSPC with TNF promotes necroptosis and apoptosis, similar treatment wi

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… Rheum. Dis. 70 : i104 – i108 10.1136/ard.2010.140145 21339211 Günther C. Martini E. Wittkopf N. Amann K. Weigmann B. Neumann H. Waldner M.J. Hedrick S.M. Tenzer S. Neurath M.F. Becker C. 2011 Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis . …