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BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is characterized by articular cartilage degeneration and progressive synovitis. How to effectively inhibit TMJOA in the early stage has been a hot topic in the biomedical field. As a non-invasive physiotherapy, pulsed electromagnetic field (PEMF) treatment has shown great potential in the treatment of osteoarthritis (OA) in extremity joints. OBJECTIVE: This study aims to investigate the biological effect of PEMF intervention on TMJ cartilage degeneration and synovium inflammation at the early stage of TMJOA. METHODS: PEMF (2.0 mT, 15 Hz, 2 h/day) treatment was given to rats in which TMJOA was induced by applying the unilateral anterior crossbite (UAC). Histological and immunohistochemical staining, TUNEL assay, real-time PCR and western blotting assay were performed to detect the changes of the morphology and the expression of pro-inflammatory and degradative factors in condylar cartilage and synovium. RESULTS: Obvious condylar cartilage degeneration, characterized by decreased cartilage thickness, degraded cartilage extracellular matrix, increased expression of pro-inflammatory and degradative factors (TNF-α, IL-1ß, MMP-13, ADAMTS-5, IL-6, MMP-3, MMP-9 and COL-X) and increased chondrocytes death, was observed in UAC group, accompanied by synovium hyperplasia and up-regulation of pro-inflammatory and degradative factors in synovium. PEMF intervention reversed the decreased cartilage thickness at 3 weeks and degraded cartilage extracellular matrix at 6 weeks. Moreover, the up-regulation of pro-inflammatory, degradative and hypertrophyic factors and chondrocytes death in condylar cartilage induced by UAC were inhibited to some extent. In addition, the synovium hyperplasia and the up-regulation of pro-inflammatory and degradative factors in synovium were inhibited at 3 weeks and 6 weeks. CONCLUSIONS: Appropriate PEMF stimulation can reverse the loss of cartilage extracellular matrix, the chondrocytes death, the increased expression of pro-inflammatory and degradative factors in cartilage, the decreased cartilage thickness and synovium inflammation induced by UAC at the early stage of TMJOA to some extent. PEMF stimulation may be a promising method in clinical TMJOA treatment.
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Osteoartrite , Sinovite , Animais , Ratos , Campos Eletromagnéticos , Hiperplasia , Sinovite/terapia , Osteoartrite/terapia , Inflamação , Articulação TemporomandibularRESUMO
BACKGROUND: Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix. OBJECTIVE: This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA). METHODS: Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin-1ß (rrIL-1ß) and SDC4 small interfering RNA (si-SDC4). Anti-SDC4 ectodomain-specific antibodies or IgG were intra-articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4-cKO) and Sdc4flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col-II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays. RESULTS: SDC4 expression was evidently increased in MIA-model animals compared to control groups. rrIL-1ß stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col-II. These effects were reversed by si-SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col-II and ACAN, and a decrease in SDC4, MMP13 and cleaved-CASP3-positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition. CONCLUSIONS: SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA.
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BACKGROUND: Breast cancer is the most common cancer among women in Sweden. Whereas survival for the overall breast cancer population is well-documented, survival of patients with metastatic breast cancer (MBC) is harder to quantify due to the lack of reliable data on disease recurrence in national cancer registers. METHODS: This study used machine learning to classify the total MBC population in Sweden diagnosed between 2009 and 2016 using national registers, with the aim to estimate overall survival (OS). RESULTS: The total population consisted of 13,832 patients-2528 (18.3%) had de novo MBC whereas 11,304 (81.7%) were classed as having a recurrent MBC. Median OS for patients with MBC was found to be 29.8 months 95% confidence interval (CI) [28.9, 30.6]. Hormone-receptor (HR)-positive MBC had a median OS of 37.0 months 95% CI [35.9, 38.3] compared to 9.9 months 95% CI [9.1, 11.0] for patients with HR-negative MBC. CONCLUSION: This study covered the entire MBC population in Sweden during the study time and may serve as a baseline for assessing the effect of new treatment strategies in MBC introduced after the study period.
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Neoplasias da Mama , Neoplasias da Mama/patologia , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Receptor ErbB-2 , Estudos Retrospectivos , Suécia/epidemiologiaRESUMO
BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is characterized by abnormal subchondral bone remodeling and cartilage degeneration. As a non-invasive biophysical technology, pulsed electromagnetic field (PEMF) treatment has been proven to be efficient in promoting osteogenesis. However, the potential bone protective effect and mechanism of PEMF on abnormal subchondral bone remodeling in TMJOA are unknown. METHODS: Unilateral anterior crossbite (UAC) was used to create TMJOA model in rats, and 17ß-estradiol (E2) were injected daily to mimic patients with high-physiological levels of estrogen. Mouse osteoblast-like MC3T3-E1 cells treated with recombinant murine IL-1ß was used to establish inflammatory environment in vitro. The treatment group were subjected to PEMF (2.0mT, 15 Hz, 2 h/d). Micro-CT scanning, histological staining, real-time PCR and western blotting assays were preformed to observe the changes in the subchondral bone. RESULTS: Abnormal resorption of subchondral bone induced by UAC, characterized by decreased bone mineral density, increased osteoclast activity and expression of osteoclast-related factors (RANKL) and down-regulated expression of osteogenesis-related factors (OPG, ALP, Runx2 and OCN) at the early stage, could be reversed by PEMF exposure, which was similar to the effect of estrogen. In addition, PEMF exposure and E2 supplement may have a synergistic effect to some extent. Moreover, PEMF exposure could promote the ALP activity and osteogenic mineralization ability of MC3T3-E1 cells. PEMF promoted the expression of factors related to Wnt/ß-Catenin signal pathway both in vivo and in vitro. CONCLUSIONS: Appropriate PEMF exposure have a protective effect on subchondral bone in TMJOA at early stage, in which canonical Wnt/ß-Catenin pathway may be involved. PEMF may be a promising biophysical approach for early intervention of TMJOA in clinic.
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Campos Eletromagnéticos , Osteoartrite , Ratos , Camundongos , Animais , beta Catenina , Remodelação Óssea , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/patologia , Osteoartrite/patologia , EstrogêniosRESUMO
PURPOSE: Radium-223 is a life-prolonging therapy for castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. However, validated biomarkers for response monitoring are lacking. The study aim was to investigate whether early alkaline phosphatase (ALP) dynamics after the first radium-223 injection can act as surrogate marker for overall survival (OS). METHODS: This retrospective multicenter study included consecutive CRPC patients treated with radium-223. Patients were divided into four subgroups based on baseline ALP level (normal/elevated) and early ALP response, defined as ≥10% ALP decrease after the first radium-223 injection. Primary endpoint was OS among the subgroups. Secondary endpoints included time to first skeletal-related event, time to ALP progression, and treatment completion rate. RESULTS: A total of 180 patients were included for analysis. Median OS was 13.5 months (95% confidence interval 11.5-15.5). Patients with elevated baseline ALP without ALP response after the first injection had significantly worse OS when compared to all other patients (median OS 7.9 months versus 15.7 months, hazard ratio 2.56, 95% confidence interval 1.73-3.80, P < 0.001). Multivariate analysis demonstrated that elevated baseline ALP without ALP response after the first injection, the number of prior systemic therapies, baseline LDH level, and baseline ECOG performance status were prognostic factors of OS. Patients with elevated baseline ALP without ALP response after the first injection had significantly shorter times to ALP progression and first skeletal-related event, and more frequently discontinued radium-223 therapy when compared to other patients. CONCLUSION: Early treatment-induced changes in ALP after one radium-223 injection were associated with OS in metastatic CRPC patients.
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Neoplasias Ósseas , Neoplasias de Próstata Resistentes à Castração , Rádio (Elemento) , Fosfatase Alcalina , Biomarcadores , Neoplasias Ósseas/radioterapia , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/radioterapia , Rádio (Elemento)/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Seizures are common reasons to call an ambulance, and this study aims to analyze the burden of seizures in the prehospital setting based on incidence, hospital admission rate, and costs. METHODS: This was a population-based, cross-sectional analysis of prehospital emergency medical services (EMS) data on suspected seizure cases from the federal state of Hesse, Germany, in 2019. RESULTS: A total of 6534 suspected seizure cases were identified, of which most were those with a known seizure disorder. Incidence rate for epilepsy-related seizures (ES; pediatric epilepsy, first seizure [1stS], seizure with known seizure disorder [SEPI]) was 205.7 per 100,000 inhabitants and incidence rate for pediatric febrile seizures (PFS) was 36.7 per 100,000 inhabitants, corresponding to 171,275 ES and 28,500 PFS (99.3% < 18 years) cases in Germany. A prehospital EMS physician was involved in 40.0% (SEPI) to 54.4% (PFS) of suspected seizure cases. Depending on the type of seizure, 70.7% (SEPI) to 80.9% (1stS) were admitted to hospital for inpatient stay of ≥ 24 h. An additional 4% (PFS) to 16% (1stS) of cases needed immediate intervention at hospital. Prehospital EMS staff needed 8:24 min:s (SD 7:24; n = 5004) after the emergency call to arrive at the scene of the ES and 10:58 min:s (SD 27:39; n = 321) for PFS. ES and PFS cases caused estimated costs of 48.5 and 8.1 million euros for Germany in 2019, respectively, not including hospital treatment-related costs. CONCLUSION: This study identified a high number of suspected seizure-related emergency cases and proportion of patients admitted to hospitals, as well as high associated costs in Germany.
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The coronavirus disease 2019 (COVID-19) has merged as a global health threat since its outbreak in December 2019. Despite widespread recognition, there has been a paucity of studies focusing on the T cell receptor (TCR) bias in adaptive immunity induced by SARS-CoV-2. This research conducted a comparative analysis of the TCR immune repertoire to identify notable αß TCR bias sequences associated with the SARS-CoV-2 virus antigen. The present study encompassed 73 symptomatic COVID-19 patients, categorized as moderate/mild or severe/critical, along with 9 healthy controls. Our findings revealed specific TCR chains prominently utilized by moderate and severe patients, identified as TRAV30-J34-TRBV3-1-J2-7 and TRAV12-3-J6-TRBV28-J1-1, respectively. Additionally, our research explored critical TCR preferences in the bronchoalveolar lavage fluid (BALF) of COVID-19 patients at various disease stages. Indeed, monitoring the dynamics of immune repertoire changes in COVID-19 patients could serve as a crucial biomarker for predicting disease progression and recovery. Furthermore, the study explored TCR bias in both peripheral blood mononuclear cells (PBMCs) and BALF. The most common αß VJ pair observed in BALF was TRAV12-3-J18-TRBV7-6-J2-7. In addition, a comparative analysis with the VDJdb database indicated that the HLA-A*02:01 allele exhibited the widest distribution and highest frequency in COVID-19 patients across different periods. This comprehensive examination provided a global characterization of the TCR immune repertoire in COVID-19 patients, contributing significantly to our understanding of TCR bias induced by SARS-CoV-2.
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COVID-19 , Receptores de Antígenos de Linfócitos T alfa-beta , SARS-CoV-2 , Humanos , COVID-19/imunologia , SARS-CoV-2/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Adulto , Líquido da Lavagem Broncoalveolar/imunologia , Idoso , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Imunidade Adaptativa/imunologia , Índice de Gravidade de DoençaRESUMO
AIM: The Health outcomes and Understanding of MyelomA multi-National Study (HUMANS) was a large-scale, retrospective study conducted across Denmark, Finland and Sweden using linked data from national registries. We describe the characteristics, treatment patterns and clinical outcomes for patients with newly diagnosed multiple myeloma (NDMM) over 2010-2018. METHODS: Patients with NDMM who received MM-specific, first-line treatments, were categorised by treatment (autologous stem cell transplantation [ASCT] or a combination chemotherapy regimen based on bortezomib, lenalidomide or melphalan-prednisolone-thalidomide). RESULTS: 11,023 patients received treatment over 2010-2018. Time between diagnosis and treatment was shortest in Denmark (0.9 months), then Sweden (2.9 months) and Finland (4.6 months). Around one third of patients underwent ASCT. Lenalidomide-based regimens were prescribed to 23-28% of patients in Denmark and Finland, versus 12% in Sweden. Patients receiving lenalidomide had the longest wait for treatment, from 3.2 months (Denmark) to 12.1 months (Sweden). Treatment persistence was highest among patients receiving melphalan-prednisolone-thalidomide (7-8 months) in Finland and Sweden and lowest among those receiving bortezomib (3.5 months) in Finland. Overall survival (OS) was longest among patients with ASCT (7-10 years). Among patients receiving chemotherapy, OS (from diagnosis/treatment initiation), varied between cohorts. In a sensitivity analysis excluding patients with smouldering MM, OS decreased for all; for patients receiving bortezomib or lenalidomide, OS from diagnosis was 40-49 and 27-54 months, respectively. CONCLUSIONS: This population-based study of patients with NDMM receiving first-line MM-specific treatment, provides real-world data on treatment patterns and outcomes to complement data from randomised clinical trials.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/epidemiologia , Lenalidomida , Bortezomib/uso terapêutico , Talidomida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Melfalan , Finlândia/epidemiologia , Estudos Retrospectivos , Suécia/epidemiologia , Dexametasona , Transplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prednisolona/uso terapêutico , Sistema de Registros , Dinamarca/epidemiologiaRESUMO
With ER2319 and B4C powder as feedstocks and additives, respectively, a wire arc additive manufacturing (WAAM) system based on double-pulse melting electrode inert gas shielded welding (DP-MIG) was used to fabricate single-pass multilayer 2319 aluminum alloy. The results showed that, compared with additive manufacturing component without B4C, the addition of which can effectively reduce the grain size (from 43 µm to 25 µm) of the tissue in the deposited layer area and improve its mechanical properties (from 231 MPa to 286 MPa). Meanwhile, the mechanical properties are better in the transverse than in the longitudinal direction. Moreover, the strengthening mechanism of B4C on the mechanical properties of aluminum alloy additive manufacturing mainly includes dispersion strengthening from fine and uniform B4C granular reinforcing phases and fine grain strengthening from the grain refinement of B4C. These findings shed light on the B4C induced grain refinement mechanism and improvement of WAAM 2319 Al alloy.
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OBJECTIVE: To evaluate treatment patterns for ADHD in Sweden. METHOD: Observational retrospective study of patients with ADHD from the Swedish National Patient Register and Prescribed Drug Register, 2018 to 2021. Cross-sectional analyses included incidence, prevalence, and psychiatric comorbidities. Longitudinal analyses (newly diagnosed patients) included medication, treatment lines, duration, time-to-treatment initiation, and switching. RESULTS: Of 243,790 patients, 84.5% received an ADHD medication. Psychiatric comorbidities were common, particularly autism among children, and depression in adults. Most frequent first-/second-line treatments were methylphenidate (MPH; 81.6%) and lisdexamfetamine dimesylate (LDX; 46.0%), respectively. In the second-line, LDX was most frequently prescribed (46.0%), followed by MPH (34.9%), then atomoxetine (7.7%). Median treatment duration was longest for LDX (10.4 months), followed by amphetamine (9.1 months). CONCLUSION: This nationwide registry study provides real-life insights into the current epidemiology of ADHD and the changing treatment landscape for patients in Sweden.
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Adulto , Criança , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Estimulantes do Sistema Nervoso Central/uso terapêutico , Estudos Transversais , Dimesilato de Lisdexanfetamina/uso terapêutico , Metilfenidato/uso terapêutico , Sistema de Registros , Estudos Retrospectivos , Suécia/epidemiologia , Resultado do TratamentoRESUMO
Purpose: Linked health-care registries and high coverage in Nordic countries lend themselves well to epidemiologic research. Given its relatively high incidence in Western Europe, complexity in diagnosis, and challenges in registration, multiple myeloma (MM) was selected to compare registries in Denmark, Finland, and Sweden. Patients and Methods: Data were obtained from four archetypal registries in each country (spanning January 2005-October 2018): National Patient Registry (NPR), Prescribed Drug Registry (PDR), Cancer Registry (CR), and Cause of Death Registry. Patients newly diagnosed with MM who received MM-specific treatment were included. PDR/NPR treatment records were used to assess incident NPR cases. The registration quality of MM-specific drugs in the PDR of each country was also evaluated. Results: In Denmark, only 6% of patients in the NPR were not registered in the CR; in Sweden, it was 16.9%. No systematic differences were identified that could explain this discrepancy. In Denmark, lenalidomide and bortezomib were registered in the NPR with high coverage, but less expensive drugs typically given in combination with bortezomib were not covered in any of the registries. In Finland and Sweden, bortezomib records were not identified in the PDR, but some were in the NPR; other drugs had good coverage in the PDR. Conclusions: The registries evaluated in this study can be used to identify the MM population; however, given the gaps in MM registration in the Finnish and Swedish CRs, Danish registries provide the most comprehensive datasets for research on treatment patterns for MM.
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Constructed wetlands (CWs) are artificial systems that use natural processes to treat wastewater containing organic pollutants. This approach has been widely applied in both developing and developed countries worldwide, providing a cost-effective method for industrial wastewater treatment and the improvement of environmental water quality. However, due to the large organic carbon inputs, CWs is produced in varying amounts of CH4 and have the potential to become an important contributor to global climate change. Subsequently, research on the mitigation of CH4 emissions by CWs is key to achieving sustainable, low-carbon dependency wastewater treatment systems. This review evaluates the current research on CH4 emissions from CWs through bibliometric analysis, summarizing the reported mechanisms of CH4 generation, transfer and oxidation in CWs. Furthermore, the important environmental factors driving CH4 generation in CW systems are summarized, including: temperature, water table position, oxidation reduction potential, and the effects of CW characteristics such as wetland type, plant species composition, substrate type, CW-coupled microbial fuel cell, oxygen supply, available carbon source, and salinity. This review provides guidance and novel perspectives for sustainable and effective CW management, as well as for future studies on CH4 reduction in CWs.
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BACKGROUNDS: Abnormal cartilage calcification is one of the pathological changes of temporomandibular joint (TMJ) osteoarthritis (OA). Recent studies have reported that exosomes can regulate the formation of abnormal calcified nodules in diseases including atherosclerosis and chronic kidney disease. However, the influences of chondrocyte-derived exosomes on abnormal cartilage calcification in TMJ OA are still unclear. METHODS: TMJ OA was induced by unilateral anterior crossbite (UAC) for 4, 8, or 12 weeks in rats to observe abnormal calcification in TMJ condylar cartilage and exosome formation. Concomitantly, GW4869, the inhibitor of exosome formation, was locally injected to the TMJ of rats under stimulation of UAC, while the exosomes extracted from primary condylar chondrocytes stimulated with fluid flow shear stress (FFSS) were locally injected to rats TMJ. RESULTS: Abnormal calcification was enhanced in the degenerative cartilage of TMJ OA in UAC rats, and a large number of exosome-like structures with diameters of 50-150 nm were found in the calcified cartilage together with decreased expression of matrix Gla protein (MGP) and increased expression of CD63, tissue-nonspecific alkaline phosphatase (TNAP) and nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1). After FFSS stimulation, the number of exosomes secreted by chondrocytes and the numbers of calcified nodules were increased in cultured cells, and the protein levels of MGP, TNAP, and NPP1 in exosomes were changed. Inhibition of exosome formation, TNAP, and NPP1 or supplementation with exogenous MGP effectively alleviated FFSS-induced chondrocyte calcification. Local injection of GW4869, the exosome inhibitor, alleviated TMJ OA-related cartilage degeneration and calcification in UAC rats. Local injection of exosomes obtained from chondrocytes stimulated by FFSS to the TMJs of normal rats induced cartilage degeneration and calcification similar to that in TMJ OA. CONCLUSIONS: Abnormal biomechanical loading leads to enhanced formation of chondrocyte-derived exosomes, in which promoters of calcification increased and inhibitors decreased, resulting in accelerating abnormal cartilage calcification in TMJ OA. The inhibition of degenerative chondrocyte-derived exosomes is expected to be a new way to prevent and treat TMJ OA.
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Cartilagem Articular , Exossomos , Osteoartrite , Animais , Cartilagem Articular/patologia , Condrócitos/metabolismo , Exossomos/metabolismo , Osteoartrite/metabolismo , Ratos , Articulação Temporomandibular/metabolismoRESUMO
Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).
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Osteoartrite , Sindecana-4 , Articulação Temporomandibular , Fator de Necrose Tumoral alfa , Animais , Apoptose , Camundongos , Terapia de Alvo Molecular , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoartrite/prevenção & controle , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Sindecana-4/metabolismo , Articulação Temporomandibular/metabolismo , Articulação Temporomandibular/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
As a new type of cell death, necroptosis is initiated by tumor necrosis factor receptor 1(TNFR1), and then activated receptor-interacting protein kinase 1(RIP1) and receptor-interacting protein kinase 3 (RIP3), following by the activation of mixed lineage kinase domain-like protein(MLKL) to deliver cell death signal. When necroptosis happens, damage associated molecular patterns (DAMPs) enter into extracellular area through the ruptured cytomembrane, followed by the disordered tissue hemeostasis. In recent years, many researches showed that necroptosis playimportant roles in a few bone related diseases, such as osteoporosis, osteonecrosis, osteosarcoma, etc. Thus, we try to briefly review the researches in this field.
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Necroptose , Proteínas Quinases , ApoptoseRESUMO
Background: It is unknown whether the rate of psychiatric disorders and cardiovascular disease increases during the diagnostic workup of suspected prostate cancer. Methods: We designed a population-based cohort study including 579 992 men living during 2005-2014 in Skåne, Sweden, according to the Swedish Total Population Register and the Skåne Healthcare Register (SHR). We used the Swedish Cancer Register and the SHR to identify all men with a new diagnosis of prostate cancer (N = 10 996), and all men underwent a prostate biopsy without receiving a cancer diagnosis (biopsy group, N = 20 482) as exposed to a diagnostic workup. Using Poisson regression, we compared the rates of psychiatric disorders and cardiovascular disease during the period before diagnosis or biopsy of exposed men with the corresponding rates of unexposed men. Results: We found an increased rate of psychiatric disorders during the period before diagnosis or biopsy among men with prostate cancer (incidence rate ratio [IRR] = 1.87, 95% confidence interval [CI] = 1.67 to 2.10) and men in the biopsy group (IRR = 2.22, 95% CI = 2.08 to 2.37). The rate of cardiovascular disease increased during the period before diagnosis or biopsy among men with prostate cancer (IRR = 2.22, 95% CI = 2.12 to 2.32) and men in the biopsy group (IRR = 2.56, 95% CI = 2.49 to 2.63). Greater rate increases were noted for a diagnostic workup due to symptoms than due to other reasons. Conclusions: There was an increased risk of psychiatric disorders and cardiovascular disease during the diagnostic workup of suspected prostate cancer regardless of the final cancer diagnosis.
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Doenças Cardiovasculares/epidemiologia , Transtornos Mentais/epidemiologia , Neoplasias da Próstata/diagnóstico , Adulto , Fatores Etários , Idoso , Biópsia/psicologia , Biópsia/estatística & dados numéricos , Estudos de Coortes , Intervalos de Confiança , Humanos , Incidência , Masculino , Distribuição de Poisson , Próstata/patologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/psicologia , Sistema de Registros , Suécia/epidemiologiaRESUMO
Histone methylation is a dynamic process that participates in a diverse array of cellular processes and has been found to associate with cancer. Recently, several histone demethylases have been identified that catalyze the removal of methylation from histone H3 lysine residues. Through bioinformatic and biochemical analysis, we identified JARID1B as a H3K4 demethylase. Overexpression of JARID1B resulted in loss of tri-, di-, and monomethyl H3K4 but did not affect other histone lysine methylations. In vitro biochemical experiments demonstrated that JARID1B directly catalyzes the demethylation. The enzymatic activity requires the JmjC domain and uses Fe(II) and alpha-ketoglutarate as cofactors. Furthermore, we found that JARID1B is up-regulated in prostate cancer tissues, compared with benign prostate samples. We also demonstrated that JARID1B associates with androgen receptor and regulates its transcriptional activity. Thus, we identified JARID1B as a demethylase capable of removing three methyl groups from histone H3 lysine 4 and up-regulated in prostate cancer.
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Proteínas de Ligação a DNA/metabolismo , Dioxigenases/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias da Próstata/enzimologia , Proteínas Repressoras/metabolismo , Linhagem Celular Tumoral , Biologia Computacional , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/genética , Dioxigenases/análise , Dioxigenases/genética , Expressão Gênica , Histonas , Humanos , Histona Desmetilases com o Domínio Jumonji , Lisina/metabolismo , Masculino , Metilação , Proteínas Nucleares/análise , Proteínas Nucleares/genética , Filogenia , Estrutura Terciária de Proteína , Proteínas Repressoras/análise , Proteínas Repressoras/genética , Regulação para CimaRESUMO
Molybdenum disulfide (MoS2), a transition metal dichalcogenide material, possesses great potential in biomedical applications such as chemical/biological sensing, drug/gene delivery, bioimaging, phototherapy, and so on. In particular, monolayer MoS2 has more extensive applications because of its superior physical and chemical properties; for example, it has an ultra-high surface area, is easily modified, and has high biodegradability. It is important to prepare advanced monolayer MoS2 with enhanced energy exchange efficiency (EEE) for the development of MoS2-based nanodevices and therapeutic strategies. In this work, a monolayer MoS2 film was first synthesized through a chemical vapor deposition method, and the surface of MoS2 was further modified via a baking process to develop p-type doping of monolayer MoS2 with high EEE, followed by confirmation by X-ray photoelectron spectroscopy and Raman spectroscopy analysis. The morphology, surface roughness, and layer thickness of monolayer MoS2 before and after baking were thoroughly investigated using atomic force microscopy. The results showed that the surface roughness and layer thickness of monolayer MoS2 modified by baking were obviously increased in comparison with MoS2 without baking, indicating that the surface topography of the monolayer MoS2 film was obviously influenced. Moreover, a photoluminescence spectrum study revealed that p-type doping of monolayer MoS2 displayed much greater photoluminescence ability, which was taken as evidence of higher photothermal conversion efficiency. This study not only developed a novel MoS2 with high EEE for future biomedical applications but also demonstrated that a baking process is a promising way to modify the surface of monolayer MoS2.
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BACKGROUND: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may have a preventive effect against prostate cancer. However, evidence is limited and still controversial, especially considering non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Swedish nationwide population-based cohort study including all long-term (≥180 days) adult male users of aspirin (n = 419,931) or NSAIDs (n = 223,437) followed from the first dispense date until the first cancer diagnosis, death or 31 December 2012, whichever occurred first. The risk of prostate cancer was measured as standardized incidence ratios (SIR) and 95% confidence intervals (CI), assessing duration of use, age and concomitant statins intake, comparing to the general male background population of the same age in Sweden. RESULTS: The overall SIR suggests that maintenance use of aspirin decreases the risk of prostate cancer (SIR = 0.87, 95% CI 0.85-0.88), in particular if used ≥5 years (SIR = 0.31, 95% CI 0.30-0.32). The overall risk was decreased (SIR = 0.87, 95% CI 0.85-0.90) among other NSAIDs users, and again in particular among longer-term users (≥3 years) with SIR = 0.58 (95% CI 0.53-0.63). When statins users were excluded from all aspirin users, there was no remaining association with prostate cancer (SIR = 0.99, 95% CI 0.96-1.02), only if taken ≥5 years (SIR = 0.31, 95% CI 0.29-0.34). For non-aspirin NSAIDs users, the protective effect remained after exclusion of statins users (SIR = 0.92, 95% CI 0.88-0.95). CONCLUSIONS: This population-based cohort study provides evidence for a protective effect of aspirin and other NSAIDs against prostate cancer, in particular for longer durations of use, yet concomitant use of statins strongly influences the risk among aspirin users.