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1.
Medicina (Kaunas) ; 60(10)2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39459456

RESUMO

Background: Minimally invasive plate osteosynthesis (MIPO) for clavicular shaft fracture yields favorable functional outcomes and results in less surgery-related soft tissue injury than other techniques. Anterior chest and shoulder skin numbness, a common complication after open reduction and plate fixation, is related to injury to the supraclavicular nerves. We propose MIPO combined with a mini-open approach without fluoroscopy for nerve preservation to minimize the risk of postoperative numbness compared with traditional open plating without nerve preservation. Methods: A total of 59 patients were retrospectively identified, with a follow-up period of 6 months. Thirty-two patients underwent MIPO with mini-open and nerve preservation technique (MIPO group), and 27 patients underwent traditional open plating without nerve preservation (open group). Constant-Murley shoulder outcome score, operation time, wound length, skin numbness, and number of implant removals were compared between the groups. Results: The MIPO group had significantly lower rates of anterior chest and shoulder skin numbness than the open group (MIPO: 12.5% vs. open: 55.6%; p < 0.001). Operation time was significantly longer in the MIPO group than in the open group (MIPO: 109.38 ± 18.83 vs. open: 81.48 ± 18.85; p < 0.001). Wound length was significantly shorter in the MIPO group than in the open group (MIPO: 4.73 ± 0.79 vs. open: 9.76 ± 1.64; p < 0.001). Both groups had similarly excellent Constant-Murley shoulder scores. There were significantly fewer implant removals in the MIPO group than in the open group (MIPO: 6.3% vs. open: 25.9%; p = 0.036). Neither group experienced any infection, implant failure, or nonunion. Conclusions: Our technique combining MIPO with the mini-open approach and supraclavicular nerve preservation yields a lower incidence of skin numbness than traditional open plating without nerve preservation.


Assuntos
Placas Ósseas , Clavícula , Fixação Interna de Fraturas , Fraturas Ósseas , Hipestesia , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias , Humanos , Clavícula/lesões , Clavícula/cirurgia , Masculino , Feminino , Adulto , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/efeitos adversos , Hipestesia/prevenção & controle , Hipestesia/etiologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Fraturas Ósseas/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Resultado do Tratamento
2.
Arch Osteoporos ; 19(1): 97, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39404970

RESUMO

Brief rationale: Zoledronic acid treatment against osteoporosis is limited by APR. Main result: Combination therapy (hydrocortisone plus non-steroidal anti-inflammatory drugs, acetaminophen, and prednisolone) reduced intolerable APR levels and provided complete symptom relief in most patients. Significance of the paper: Combination therapy can enhance patient outcomes in osteoporosis management. PURPOSE: Osteoporosis is a common condition associated with high morbidity rates, often requiring treatment with bisphosphonates such as zoledronic acid. However, the persistence to zoledronic acid infusion is commonly limited by acute phase response (APR). This retrospective study aimed to evaluate the efficacy of a novel combination therapy in preventing APR symptoms. METHODS: A retrospective case-control study was conducted on 931 patients who received their first zoledronic acid infusion between 2011 and 2021. We evaluated the efficacy of combination therapy comprising a single dose of hydrocortisone prior to the infusion and a 3-d oral regimen of non-steroidal anti-inflammatory drugs, acetaminophen, and prednisolone following the infusion. Patients were divided into protocol (receiving combination therapy) and control groups (without treatment). Baseline characteristics, APR incidence, and the efficacy of symptom control were compared between groups using Fisher's exact test and Student's t-test. RESULTS: There was no difference in APR incidence between the protocol (n = 507) and control group (n = 407; p = 0.1442). However, the protocol group exhibited lower intolerable APR levels (3.72% vs. 16.71%; p < 0.0001) and complete symptom relief in 96.28% of cases. CONCLUSION: The combination therapy protocol effectively reduced intolerable APR and relieved symptoms in most patients following zoledronic acid infusion. This study highlights the importance of proactive management strategies for APR and emphasizes the potential of combination therapy in alleviating APR symptoms and reducing the occurrence of severe APR in patients undergoing osteoporosis management.


Assuntos
Acetaminofen , Reação de Fase Aguda , Anti-Inflamatórios não Esteroides , Conservadores da Densidade Óssea , Quimioterapia Combinada , Hidrocortisona , Osteoporose , Prednisolona , Ácido Zoledrônico , Humanos , Ácido Zoledrônico/uso terapêutico , Ácido Zoledrônico/administração & dosagem , Feminino , Masculino , Estudos Retrospectivos , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Acetaminofen/administração & dosagem , Acetaminofen/uso terapêutico , Pessoa de Meia-Idade , Estudos de Casos e Controles , Osteoporose/tratamento farmacológico , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Hidrocortisona/uso terapêutico , Hidrocortisona/administração & dosagem , Idoso de 80 Anos ou mais , Resultado do Tratamento
3.
Int J Mol Sci ; 25(16)2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39201457

RESUMO

Uremic toxins cause bone disorders in patients with chronic kidney disease (CKD). These disorders are characterized by low turnover osteodystrophy and impaired bone formation in the early stages of CKD. Evidence indicates that the aryl hydrocarbon receptor (AhR) mediates signals that suppress early osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). However, whether the AhR mediates the effects of indoxyl sulfate (IS), a uremic toxin, on BMSC osteogenesis remains unclear. We investigated whether IS affects osteogenesis through the AhR/Hes1 pathway. Expression levels of osteogenesis genes (Runx2, Bmp2, Alp, and Oc), AhR, and Hes1 were measured in mouse BMSCs (D1 cells). At concentrations of 2-50 µM, IS significantly reduced mineralization, particularly in the early stages of BMSC osteogenesis. Furthermore, IS significantly downregulated the expression of Runx2, Bmp2, Oc, and Alp. Notably, this downregulation could be prevented using an AhR antagonist and through Ahr knockdown. Mechanistically, IS induced the expression of Hes1 through AhR signaling, thereby suppressing the transcription of Runx2 and Bmp2. Our findings suggest that IS inhibits early osteogenesis of BMSCs through the AhR/Hes1 pathway, thus suppressing the transcription of Runx2 and Bmp2. Our findings may guide new therapeutic strategies against CKD-related bone disorders.


Assuntos
Indicã , Células-Tronco Mesenquimais , Osteogênese , Receptores de Hidrocarboneto Arílico , Transdução de Sinais , Fatores de Transcrição HES-1 , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Osteogênese/efeitos dos fármacos , Camundongos , Fatores de Transcrição HES-1/metabolismo , Fatores de Transcrição HES-1/genética , Transdução de Sinais/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 2/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos
4.
Amino Acids ; 56(1): 43, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935136

RESUMO

Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis.


Assuntos
Diferenciação Celular , Eflornitina , Osteoblastos , Osteoclastos , Osteogênese , Poliaminas , Animais , Camundongos , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Ratos , Humanos , Diferenciação Celular/efeitos dos fármacos , Eflornitina/farmacologia , Feminino , Poliaminas/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Células RAW 264.7 , Ovariectomia , Ratos Sprague-Dawley , Espermidina/farmacologia
5.
Mol Nutr Food Res ; 68(14): e2300685, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38860356

RESUMO

SCOPE: Kaempferol (KMP), a bioactive flavonoid compound found in fruits and vegetables, contributes to human health in many ways but little is known about its relationship with muscle mass. The effect of KMP on C2C12 myoblast differentiation and the mechanisms that might underlie that effect are studied. METHODS AND RESULTS: This study finds that KMP (1, 10 µM) increases the migration and differentiation of C2C12 myoblasts in vitro. Studying the possible mechanism underlying its effect on migration, the study finds that KMP activates Integrin Subunit Beta 1 (ITGB1) in C2C12 myoblasts, increasing p-FAK (Tyr398) and its downstream cell division cycle 42 (CDC42), a protein previously associated with cell migration. Regarding differentiation, KMP upregulates the expression of myosin heavy chain (MHC) and activates IGF1/AKT/mTOR/P70S6K. Interestingly, pretreatment with an AKT inhibitor (LY294002) and siRNA knockdown of IGF1R leads to a decrease in cell differentiation, suggesting that IGF1/AKT activation is required for KMP to induce C2C12 myoblast differentiation. CONCLUSION: Together, the findings suggest that KMP enhances the migration and differentiation of C2C12 myoblasts through the ITG1B/FAK/paxillin and IGF1R/AKT/mTOR pathways. Thus, KMP supplementation might potentially be used to prevent or delay age-related loss of muscle mass and help maintain muscle health.


Assuntos
Diferenciação Celular , Movimento Celular , Integrina beta1 , Quempferóis , Mioblastos , Paxilina , Proteínas Proto-Oncogênicas c-akt , Receptor IGF Tipo 1 , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Quempferóis/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Diferenciação Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Integrina beta1/metabolismo , Paxilina/metabolismo , Linhagem Celular , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 1/genética , Quinase 1 de Adesão Focal/metabolismo , Quinase 1 de Adesão Focal/genética
6.
J Clin Med ; 13(10)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38792280

RESUMO

Background: The comparison between the mini-midvastus (mini-MV) and mini-parapatellar (mini-MPP) approach in total knee arthroplasty (TKA) remains a subject of debate. The present study compared quadriceps activation, pain levels, and clinical outcomes between the two approaches; quadricep activation was assessed using surface electromyography (sEMG). Methods: This retrospective cross-sectional study comprised a total of 78 patients aged between 50 and 85 years with primary osteoarthritis. Patients were divided into a mini-MV (n = 38) group and a mini-MPP (n = 40) group according to the surgical approach. Results: The two groups exhibited no significant differences in sEMG for the vastus medialis (VM) or rectus femoris (RF) at the follow-up time points, with the exception that the mini-MV group exhibited superior strength of RF during extensions at the 2-week follow-up. However, the mini-MPP group had superior Western Ontario and McMaster Universities Index (WOMAC) total and function scores at the 2- and 6-week follow-ups. The mini-MPP group also had superior WOMAC stiffness scores at the 2-week follow-up. The two groups did not differ significantly in terms of pain levels or morphine consumption. Conclusions: The sEMG data of quadriceps muscle would not differ significantly between the mini-MV and mini-MPP approaches for TKA. Moreover, the mini-MPP approach may yield superior WOMAC scores when compared with the mini-MV approach.

7.
Curr Issues Mol Biol ; 46(5): 4403-4416, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38785535

RESUMO

Acute pancreatitis (AP) is characterized by elevated intracellular Ca2+ concentrations, mitochondrial dysfunction, and oxidative stress in pancreatic acinar cells. Algal oil (AO) has demonstrated antioxidant and anti-inflammatory properties. This study aims to explore the effects of algal oil on the microenvironment of AP. Rat pancreatic acinar AR42J cells were pretreated with AO containing 0, 50, 100, or 150 µM of docosahexaenoic acid (DHA) 2 h prior to AP induction using sodium taurocholate (STC). After 1 h of STC treatment, AR42J cells exhibited a significant increase in intracellular Ca2+ concentration and the production of amylase, lipase, reactive oxygen species, and pro-inflammatory mediators, including tumor necrosis factor-α and interleukin-6. These STC-induced increases were markedly reduced in cells pretreated with AO. In comparison to cells without AO, those treated with a high dose of AO before STC exposure demonstrated a significant increase in mitochondrial membrane potential and a decrease in lipid peroxidation. Furthermore, STC-activated nuclear factor kappa-B (NF-κB) was attenuated in AO-pretreated cells, as evidenced by a significant decrease in activated NF-κB. In conclusion, AO may prevent damage to pancreatic acinar cells by alleviating intracellular Ca2+ overload, mitigating mitochondrial dysfunction, reducing oxidative stress, and attenuating NF-κB-targeted inflammation.

8.
Osteoporos Sarcopenia ; 10(1): 3-10, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38690538

RESUMO

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

9.
Korean J Radiol ; 24(12): 1249-1259, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38016684

RESUMO

OBJECTIVE: This study aimed to evaluate the clinical outcomes and cost-effectiveness of dual-energy X-ray absorptiometry (DXA) for osteoporosis screening. MATERIALS AND METHODS: Eligible patients who had and had not undergone DXA screening were identified from among those aged 50 years or older at Kaohsiung Veterans General Hospital, Taiwan. Age, sex, screening year (index year), and Charlson comorbidity index of the DXA and non-DXA groups were matched using inverse probability of treatment weighting (IPTW) for propensity score analysis. For cost-effectiveness analysis, a societal perspective, 1-year cycle length, 20-year time horizon, and discount rate of 2% per year for both effectiveness and costs were adopted in the incremental cost-effectiveness (ICER) model. RESULTS: The outcome analysis included 10337 patients (female:male, 63.8%:36.2%) who were screened for osteoporosis in southern Taiwan between January 1, 2012, and December 31, 2021. The DXA group had significantly better outcomes than the non-DXA group in terms of fragility fractures (7.6% vs. 12.5%, P < 0.001) and mortality (0.6% vs. 4.3%, P < 0.001). The DXA screening strategy gained an ICER of US$ -2794 per quality-adjusted life year (QALY) relative to the non-DXA at the willingness-to-pay threshold of US$ 33004 (Taiwan's per capita gross domestic product). The ICER after stratifying by ages of 50-59, 60-69, 70-79, and ≥ 80 years were US$ -17815, US$ -26862, US$ -28981, and US$ -34816 per QALY, respectively. CONCLUSION: Using DXA to screen adults aged 50 years or older for osteoporosis resulted in a reduced incidence of fragility fractures, lower mortality rate, and reduced total costs. Screening for osteoporosis is a cost-saving strategy and its effectiveness increases with age. However, caution is needed when generalizing these cost-effectiveness results to all older populations because the study population consisted mainly of women.


Assuntos
Osteoporose , Humanos , Feminino , Masculino , Absorciometria de Fóton , Análise Custo-Benefício , Osteoporose/diagnóstico por imagem , Programas de Rastreamento/métodos , Análise de Custo-Efetividade
10.
Sci Rep ; 13(1): 19534, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37945626

RESUMO

Previously, the discrimination of collagen types I and II was successfully achieved using peptide pitch angle and anisotropic parameter methods. However, these methods require fitting polarization second harmonic generation (SHG) pixel-wise information into generic mathematical models, revealing inconsistencies in categorizing collagen type I and II blend hydrogels. In this study, a ResNet approach based on multipolarization SHG imaging is proposed for the categorization and regression of collagen type I and II blend hydrogels at 0%, 25%, 50%, 75%, and 100% type II, without the need for prior time-consuming model fitting. A ResNet model, pretrained on 18 progressive polarization SHG images at 10° intervals for each percentage, categorizes the five blended collagen hydrogels with a mean absolute error (MAE) of 0.021, while the model pretrained on nonpolarization images exhibited 0.083 MAE. Moreover, the pretrained models can also generally regress the blend hydrogels at 20%, 40%, 60%, and 80% type II. In conclusion, the multipolarization SHG image-based ResNet analysis demonstrates the potential for an automated approach using deep learning to extract valuable information from the collagen matrix.


Assuntos
Colágeno Tipo I , Hidrogéis , Colágeno , Diagnóstico por Imagem , Processamento de Imagem Assistida por Computador
11.
J Biol Eng ; 17(1): 74, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012588

RESUMO

Reconstruction of severe osteochondral defects in articular cartilage and subchondral trabecular bone remains a challenging problem. The well-integrated bilayer osteochondral graft design expects to be guided the chondrogenic and osteogenic differentiation for stem cells and provides a promising solution for osteochondral tissue repair in this study. The subchondral bone scaffold approach is based on the developed finer and denser 3D ß-tricalcium phosphate (ß-TCP) bioceramic scaffold process, which is made using a digital light processing (DLP) technology and the novel photocurable negative thermo-responsive (NTR) bioceramic slurry. Then, the concave-top disc sintered 3D-printed bioceramic incorporates the human adipose-derived stem cells (hADSCs) laden photo-cured hybrid biohydrogel (HG + 0.5AFnSi) comprised of hyaluronic acid methacryloyl (HAMA), gelatin methacryloyl (GelMA), and 0.5% (w/v) acrylate-functionalized nano-silica (AFnSi) crosslinker. The 3D ß-TCP bioceramic compartment is used to provide essential mechanical support for cartilage regeneration in the long term and slow biodegradation. However, the apparent density and compressive strength of the 3D ß-TCP bioceramics can be obtained for ~ 94.8% theoretical density and 11.38 ± 1.72 MPa, respectively. In addition, the in vivo results demonstrated that the hADSC + HG + 0.5AFnSi/3D ß-TCP of the bilayer osteochondral graft showed a much better osteochondral defect repair outcome in a rabbit model. The other word, the subchondral bone scaffold of 3D ß-TCP bioceramic could accelerate the bone formation and integration with the adjacent host cancellous tissue at 12 weeks after surgery. And then, a thicker cartilage layer with a smooth surface and uniformly aligned chondrocytes were observed by providing enough steady mechanical support of the 3D ß-TCP bioceramic scaffold.

13.
Int J Mol Sci ; 24(17)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37686220

RESUMO

Osteoarthritis (OA) is the most common age-related degenerative joint disease. Inflammaging, linking inflammation and aging, is found in senescent cells with the secretions of matrix-degrading proteins and proinflammatory cytokines. The senescence-associated secretory phenotype (SASP) plays a very important role in OA progression. However, there remains no effective way to suppress OA progression, especially by suppressing inflammaging and/or the chondrocyte SASP. Recent studies have shown that exosomes derived from hypoxia-cultured BMSCs can regenerate cartilage in OA animal models. Some reports have further indicated that exosomes secreted from MSCs contribute to the efficacy of MSC therapy in OA. However, whether hypoxia-cultured ADSC-secreted exosomes (hypoxia-ADSC-Exos) can alleviate the chondrocyte SASP or OA progression remains unclear. Accordingly, we hypothesized that hypoxia-ADSC-Exos have a beneficial effect on the normal functions of human articular chondrocytes (HACs), can attenuate the SASP of OA-like HACs in vitro, and further suppress OA progression in rats. Hypoxia-ADSC-Exos were derived from ADSCs cultured in 1% O2 and 10% de-Exo-FBS for 48 h. The molecular and cell biological effects of hypoxia-ADSC-Exos were tested on IL1-ß-induced HACs as OA-like HACs in vitro, and the efficacy of OA treatment was tested in ACLT-induced OA rats. The results showed that hypoxia-ADSC-Exos had the best effect on GAG formation in normal HACs rather than those cultured in normoxia or hypoxia plus 2% de-Exo-FBS. We further found that hypoxia-ADSC-Exos alleviated the harmful effect in OA-like HACs by decreasing markers of normal cartilage (GAG and type II collagen) and increasing markers of fibrous or degenerative cartilage (type I or X collagen), matrix degradation enzymes (MMP13 and ADAMT5), and inflammatory cytokines (TNFα and IL-6). More importantly, intra-articular treatment with hypoxia-ADSC-Exos suppressed OA progression, as evidenced by the weight-bearing function test and cartilage GAG quantification in ACLT rats. Moreover, through NGS and bioinformatic analysis, seven potential miRNAs were found in hypoxia-ADSC-Exos, which may contribute to regulating cellular oxidative stress and attenuating cell senescence. In summary, we demonstrated that hypoxia-ADSC-Exos, carrying potent miRNAs, not only improve normal HAC function but also alleviate HAC inflammaging and OA progression. The results suggest that hypoxia-ADSC-Exo treatment may offer another strategy for future OA therapy.


Assuntos
Exossomos , MicroRNAs , Osteoartrite , Humanos , Animais , Ratos , Condrócitos , Osteoartrite/etiologia , Osteoartrite/terapia , MicroRNAs/genética , Citocinas , Hipóxia , Células-Tronco
14.
J Clin Endocrinol Metab ; 109(1): e200-e208, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37526298

RESUMO

CONTEXT: Despite prevalent anti-osteoporosis medication (AOM) switching in real-world osteoporosis management, few studies have evaluated the impact of persistent AOM treatment, allowing for AOM switching, on the risk of subsequent fracture. OBJECTIVE: We examined the association between persistence in AOM and subsequent fractures, allowing for medication switching among patients with osteoporotic fractures. METHODS: This retrospective cohort study used Taiwan National Health Insurance claims data to select patients who initiated AOM between 2013 and 2016. Treatment persistence was defined as use of any AOM on a given day of interest with a 45-day grace period. Medication switch was allowed for persistence if remaining on treatment. AOMs with long-lasting inhibition of bone resorption (zoledronate and denosumab) were categorized as high-potency; others as low-potency. Multivariate Cox models were used to evaluate risk of subsequent fractures ≥3 months after initiating AOM. RESULTS: A total of 119 473 patients were included (mean [SD] follow-up 46.4 [15.6] months), and 26.8% switched from the index AOM. Within 1 year, 52% remained persistent with AOM. Compared to patients with persistent AOM, those not persistent had higher risk of subsequent hip (adjusted hazard ratio [aHR] = 1.31; 95% CI, 1.21-1.42), vertebral (aHR = 1.17; 95% CI, 1.13-1.22), and radius fractures (aHR = 1.16; 95% CI, 1.08-1.25). Patients with persistent AOM who switched from high- to low-potency AOM had higher risk of subsequent vertebral fractures than those with persistent AOM and no potency switch (aHR = 1.28; 95% CI, 1.02-1.60). CONCLUSION: Patients with non-persistent AOM had higher risk of subsequent fractures than persistent users when allowing AOM switch. Switching AOM potency may influence the risk of subsequent vertebral fractures and warrants further investigation.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Fraturas por Osteoporose/induzido quimicamente , Fraturas por Osteoporose/epidemiologia , Conservadores da Densidade Óssea/efeitos adversos , Estudos Retrospectivos , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/complicações
17.
Int J Mol Sci ; 24(11)2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37298473

RESUMO

Osteoarthritis (OA) is a prevalent form of arthritis that affects over 32.5 million adults worldwide, causing significant cartilage damage and disability. Unfortunately, there are currently no effective treatments for OA, highlighting the need for novel therapeutic approaches. Thrombomodulin (TM), a glycoprotein expressed by chondrocytes and other cell types, has an unknown role in OA. Here, we investigated the function of TM in chondrocytes and OA using various methods, including recombinant TM (rTM), transgenic mice lacking the TM lectin-like domain (TMLeD/LeD), and a microRNA (miRNA) antagomir that increased TM expression. Results showed that chondrocyte-expressed TM and soluble TM [sTM, like recombinant TM domain 1 to 3 (rTMD123)] enhanced cell growth and migration, blocked interleukin-1ß (IL-1ß)-mediated signaling and protected against knee function and bone integrity loss in an anterior cruciate ligament transection (ACLT)-induced mouse model of OA. Conversely, TMLeD/LeD mice exhibited accelerated knee function loss, while treatment with rTMD123 protected against cartilage loss even one-week post-surgery. The administration of an miRNA antagomir (miR-up-TM) also increased TM expression and protected against cartilage damage in the OA model. These findings suggested that chondrocyte TM plays a crucial role in counteracting OA, and miR-up-TM may represent a promising therapeutic approach to protect against cartilage-related disorders.


Assuntos
Cartilagem Articular , MicroRNAs , Osteoartrite , Camundongos , Animais , Condrócitos/metabolismo , Trombomodulina/metabolismo , Antagomirs/metabolismo , Cartilagem Articular/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/genética , Osteoartrite/metabolismo , MicroRNAs/metabolismo , Interleucina-1beta/metabolismo
18.
J Formos Med Assoc ; 122 Suppl 1: S82-S91, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37353444

RESUMO

BACKGROUND: Previous epidemiological researchers have used various algorithms to identify a second hip fracture; however, there has been no validation of these algorithms to date. This study aimed to verify existing algorithms for identifying second hip fracture under the International Classification of Diseases diagnostic coding systems. Furthermore, we examined the validity of two newly proposed algorithms that integrated the concept of periprosthetic fractures and laterality of the ICD-10 coding system. METHODS: Claims data of patients hospitalized for hip fracture from National Taiwan University Hospitals between 2007 and 2020 were retrieved. Hip fracture was confirmed by 2 orthopaedic surgeons with medical records and imaging data as gold standards. The validity of 9 existing and 2 newly proposed algorithms for identifying second hip fracture was evaluated. RESULTS: The positive predictive value (PPV) range between 84% and 90% in existing algorithms for identifying second hip fractures. Noteworthy, the longer time interval for discrimination resulted in slightly increased PPV (from 87% to 90%), while decreased sensitivity noticeably (from 87% to 72%). When considering the information about periprosthetic fracture, the PPV increased to 91% without diminished sensitivity. The PPV of the newly proposed ICD-10-specific algorithm was 100%. CONCLUSION: Algorithms integrated clinical insights of periprosthetic fractures and laterality concept of ICD-10 coding system provided satisfactory validity and help precisely define second hip fracture in future database research.


Assuntos
Fraturas do Quadril , Fraturas Periprotéticas , Humanos , Taiwan/epidemiologia , Fraturas do Quadril/diagnóstico , Fraturas do Quadril/epidemiologia , Prontuários Médicos , Algoritmos
19.
Biomedicines ; 11(3)2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36979841

RESUMO

Preeclampsia (PE) occurs in women pregnant for more than 20 weeks with de novo hypertension and proteinuria, and is a devastating disease in maternal-fetal medicine. Cytokine tumor necrosis factor (TNF)-α may play a key role in the pathogenesis of PE. We conducted this study to investigate the regulatory regions of the TNF genes, by investigating two promoter polymorphisms, TNFA-308G/A (rs1800629) and -238G/A (rs361525), known to influence TNF expression, and their relationship to PE. An observational, monocentric, case-control study was conducted. We retrospectively collected 74 cases of severe PE and 119 pregnant women without PE as control. Polymerase chain reaction (PCR) was carried out for allele analysis. Higher A allele in women with PE was found in rs1800629 but not rs361525. In this study, we first found that polymorphism at the position -308, but not -238, in the promoter region of the TNF-α gene can contribute to severe PE in Taiwanese Han populations. The results of our study are totally different to previous Iranian studies, but have some similarity to a previous UK study. Further studies are required to confirm the roles of rs1800629 and rs361525 in PE with circulating TNF-α in PE.

20.
J Formos Med Assoc ; 122 Suppl 1: S4-S13, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36781371

RESUMO

Osteoporosis greatly increases the risk of fractures. Osteoporotic fractures negatively impact quality of life, increase the burden of care, and increase mortality. Taiwan is an area with a high prevalence of osteoporosis. This updated summary of guidelines has been developed by experts of the Taiwan Osteoporosis Association with the intention of reducing the risks of osteoporotic fractures and improving the quality of care for patients with osteoporosis. The updated guidelines compile the latest evidence to provide clinicians and other healthcare professionals with practical recommendations for the prevention, diagnosis, and management of osteoporosis under clinical settings in Taiwan.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Fraturas por Osteoporose , Humanos , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/epidemiologia , Taiwan/epidemiologia , Qualidade de Vida , Osteoporose/complicações , Osteoporose/diagnóstico , Osteoporose/prevenção & controle , Prevenção Secundária , Conservadores da Densidade Óssea/uso terapêutico
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