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1.
BMC Musculoskelet Disord ; 25(1): 230, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521939

RESUMO

BACKGROUND: To clarify the value of gait analysis and its consistency with traditional scoring scales for the evaluation of knee joint function after total knee arthroplasty (TKA). METHODS: This study included 25 patients with knee osteoarthritis (KOA) who underwent bilateral TKA, and 25 conditionally matched healthy individuals, categorised into the experimental and control groups, respectively. Patients in the experimental group underwent gait analysis and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) evaluation before and 1 year after TKA. Weight-bearing balance and walking stability were assessed using discrete trends of relevant gait indicators. Pearson's correlation analysis was performed on the gait and WOMAC score data of the experimental group before and after TKA. RESULTS: One year after TKA, patients' gait indices (except gait cycle) were significantly better than before surgery, but significantly worse than that of the control group (P < 0.01). The shape of patients' plantar pressure curves did not return to normal. Additionally, the discrete trend of related gait indicators reflecting weight-bearing balance and walking stability were smaller than before TKA, but still greater than that of the control group. The WOMAC scores of patients 1 year after TKA were significantly lower than those before TKA (P < 0.001), and the efficacy index was > 80%. The WOMAC scores and gait analysis results were significantly correlated before TKA (P < 0.05). CONCLUSIONS: Gait analysis should be used in conjunction with scoring scales to assess joint functions.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/métodos , Articulação do Joelho/cirurgia , Ontário , Universidades , Resultado do Tratamento , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/cirurgia , Marcha
2.
Int Immunopharmacol ; 128: 111475, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38183909

RESUMO

This study aimed to determine whether Thrombospondin-1 (TSP-1) can be used as a biomarker to diagnose early osteoarthritis (OA) and whether it has a chondroprotective effect against OA. We examined TSP-1 expression in cartilage, synovial fluid, and serum at different time points after anterior cruciate ligament transection (ACLT) surgery in rats. Subsequently, TSP-1 was overexpressed or silenced to detect its effects on extracellular matrix (ECM) homeostasis, autophagy level, proliferation and apoptosis in chondrocytes. Adenovirus encoding TSP-1 was injected into the knee joints of ACLT rats to test its effect against OA. Combined with proteomic analysis, the molecular mechanism of TSP-1 in cartilage degeneration was explored. Intra-articular injection of an adenovirus carrying the TSP-1 sequence showed chondroprotective effects against OA. Moreover, TSP-1 expression decreases with OA progression and can effectively promote cartilage proliferation, inhibit apoptosis, and helps to sustain the balance between ECM anabolism and catabolism. Overexpression of TSP-1 also can increase autophagy by upregulating Heat Shock Protein 27 (HSP27, hspb1), thereby enhancing its effect as a stimulator of autophagy. TSP-1 is a hopeful strategy for OA treatment.


Assuntos
Cartilagem Articular , Osteoartrite , Ratos , Animais , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP27/farmacologia , Trombospondina 1/metabolismo , Proteômica , Cartilagem Articular/metabolismo , Osteoartrite/metabolismo , Condrócitos , Autofagia , Modelos Animais de Doenças
3.
BMC Surg ; 23(1): 233, 2023 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-37568124

RESUMO

AIM: To investigate the impacts of breast conservation therapy (BCT) and mastectomy on heart-specific mortality in breast cancer patients. METHODS: Patients with primary breast cancer registered in the Surveillance, Epidemiology, and End Results (SEER) database between Jan 1998 and Dec 2015 were included. Patients were divided into either breast conservation therapy or mastectomy group. To compare mortality caused by heart diseases in breast cancer patients with BCT or mastectomy, univariate and multivariate regression after propensity score matching (PSM) were performed. Kaplan-Meier analysis was also used to evaluate heart-specific survival between two groups. RESULTS: 132,616 patients with breast cancer were enrolled in this study. After PSM, four risk factors including age, race, marital status and types of surgery were identified significantly associated with death from heart diseases. Heart-specific survival analysis further showed that overall, BCT poses a lower risk to heart-specific mortality compared with mastectomy. CONCLUSION: Compared with mastectomy, BCT significantly decreased heart-specific mortality in breast cancer patients.


Assuntos
Neoplasias da Mama , Cardiopatias , Humanos , Feminino , Mastectomia , Neoplasias da Mama/cirurgia , Mastectomia Segmentar/métodos , Análise de Sobrevida
4.
Open Med (Wars) ; 18(1): 20230651, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36896338

RESUMO

Locally advanced breast cancer patients have a poor prognosis; however, the relationship between potential targets and the response to treatment is still unclear. The gene expression profiles of breast cancer patients with stages from IIB to IIIC were downloaded from The Cancer Genome Atlas. We applied weighted gene co-expression network analysis and differentially expressed gene analysis to identify the primary genes involved in treatment response. The disease-free survival between low- and high-expression groups was analyzed using Kaplan-Meier analysis. Gene set enrichment analysis was applied to identify hub genes-related pathways. Additionally, the CIBERSORT algorithm was employed to evaluate the correlation between the hub gene expression and immune cell types. A total of 16 genes were identified to be related to radiotherapy response, and low expression of SVOPL, EDAR, GSTA1, and ABCA13 was associated with poor overall survival and progression-free survival in breast cancer cases. Correlation analysis revealed that the four genes negatively related to some specific immune cell types. The four genes were downregulated in H group compared with the L group. Four hub genes associated with the immune cell infiltration of breast cancer were identified; these genes might be used as a promising biomarker to test the treatment in breast cancer patients.

5.
Front Pharmacol ; 13: 849102, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36133821

RESUMO

Post-traumatic osteoarthritis is a special type of osteoarthritis and a common disease, with few effective treatments available. α2-Macroglobulin (α2M) is important to chondral protection in post-traumatic osteoarthritis. However, its injection into xenogeneic joint cavities involves safety hazards, limiting clinical applications. Exploring serum α2M-enriching strategies and the therapeutic effect and mechanism of α2M-rich serum (α2MRS) autologous joint injection to treat post-traumatic osteoarthritis has significant value. In the present study, a unique filtration process was used to obtain α2MRS from human and mini pig serum. We evaluated the potential of α2MRS in protecting against post-surgery cartilage degeneration. We identify the potential of α2MRS in reducing the expression of inflammatory cytokines and factors that hasten cartilage degeneration in post-operative conditions leading to post-traumatic osteoarthritis. The potential of α2MRS was analyzed in interleukin-1ß induced human chondrocytes and mini pig models. In the chondrocyte model, α2MRS significantly promoted human chondrocyte proliferation and reduced apoptosis and chondrocyte catabolic cytokine gene transcription and secretion. The anterior cruciate ligament autograft reconstruction model of mini pigs was randomized into groups, operated on, and injected with α2MRS or saline. The results showed that α2MRS injection significantly suppressed the levels of inflammatory factors, improved gait, and showed significantly lower cartilage degeneration than the groups that did not receive α2MRS injections. This study highlights the chondroprotective effects of α2MRS, elucidated its potential applications against cartilage degeneration, and could provide a basis for the clinical translation of α2MRS.

6.
Cancer Treat Res Commun ; 32: 100586, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35691256

RESUMO

PURPOSE: To evaluate the impact of post-mastectomy radiation therapy (PMRT) in breast cancer patients with stage T4N0M0. METHOD: Patients diagnosed with breast cancer of T4N0M0 from Jan 2010 to Dec 2015 were extracted from SEER database. Multivariable logistic regression was used to analyze the factors associated with PMRT. Univariate and multivariate COX regression were used to analyze factors that might be associated with breast cancer specific survival (BCSS) and overall survival (OS) of patients. Kaplan-Meier analysis was performed to evaluate BCSS and OS in different subtypes of patients. RESULT: Multivariable logistic regression showed that patients ≥ 71 years were less intend to have PMRT. Multivariate Cox analysis showed that married statue, HR+/Her- and HR+/Her+ subtypes, were independent predictors of improved BCSS and OS, and use of PMRT could improve BCSS and OS . PMRT was beneficial for OS in all subtypes breast cancer patients, but BCSS benefit was observed only in TNBC patients. CONCLUSION: The use of PMRT improves OS in all T4N0M0 patients, but in terms of BCSS, it only beneficial for TNBC patients.


Assuntos
Mastectomia , Neoplasias de Mama Triplo Negativas , Mama/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Programa de SEER
7.
J Inflamm Res ; 15: 3547-3560, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734099

RESUMO

Purpose: To determine the role of histone deacetylase 4 (HDAC4)-controlled chondrocyte hypertrophy in the onset and development of age-related osteoarthritis (OA). Methods: Morphological analysis of human knee cartilages was performed to observe structural changes during cartilage degeneration. HDAC4 expression was deleted in adult aggrecan (Acan)-CreERT2; HDAC4fl/fl transgenic mice. The onset and development of age-related OA were investigated in transgenic and control mice using hematoxylin and eosin (H&E) and Safranin O staining. Furthermore, the progression of ACLT-induced OA following adenovirus-mediated HDAC4 overexpression was explored in rats. The expression levels of genes related to hypertrophy, cartilage matrix and its digestion, and chondrocyte proliferation were investigated using qPCR. Immunohistochemistry (IHC) was used to explore the mechanisms underlying HDAC4-controlled age-related changes in OA progression. Results: In human cartilage, we performed morphological analysis and IHC, the results showed that hypertrophy-related structural changes are related to HDAC4 expression. Age-related OA was detected early (OARSI scores 2.7 at 8-month-old) following HDAC4 deletion in 2-month-old mice. Furthermore, qPCR and IHC results showed changes in hypertrophy-related genes Col10a1, Runx2 and Sox9 in chondrocytes, particularly in the expression of Runt-related transcription factor 2 (Runx2, 13.29±0.99 fold). The expression of the main cartilage matrix-related genes Col2a1 and Acan decreased, that of cartilage matrix digestion-related gene MMP-13 increased, while that of chondrocyte proliferation-related genes PTHrP, Ihh and Gli1 changed. In contrast, rat cartilage's qPCR and IHC results showed opposite outcomes after HDAC4 overexpression. Conclusion: Based on the results above, we concluded that HDAC4 expression regulates the onset and development of age-related OA by controlling chondrocyte hypertrophy. These results may help in the development of early diagnosis and treatment of age-related OA.

8.
J Orthop Surg Res ; 17(1): 152, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264236

RESUMO

BACKGROUND: To compare the gait patterns between posterior cruciate retention and substitution in total knee arthroplasty (TKA). METHODS: Electronic databases including the PubMed, Embase, CINAHL, Web of Science, and Cochrane databases were searched to identify clinical trials investigating posterior cruciate retention versus substitution in TKA. The outcome measurements were the kinematic gait parameters (flexion at heel strike, maximum flexion during loading response, flexion range during loading, minimal flexion at terminal stance, maximal flexion at the swing, and total flexion during the gait cycle), Knee Society Score (KSS), knee flexion, knee extension, and walking speed. Statistical software Review Manager 5.4 and Stata 14.0 were used for data analysis. RESULTS: There were finally 9 studies included in this meta-analysis. The results did not reveal differences between posterior cruciate retention (CR) and posterior cruciate substitution (PS) groups in TKA, in terms of kinematic gait parameters, knee extension, walking speed, and KSS. However, the PS group had a significantly larger knee flexion angle than that in the CR group [weighted mean difference = - 3.20, 95% CI - 6.13 to - 0.28, P = 0.03]. CONCLUSION: Both the posterior cruciate retention and posterior cruciate substitution lead to obvious improvements in patient function and have their advantages in getting a good cup position. The PS design is significantly better on the knee flexion, while there are no statistical differences in kinematic gait parameters and outcome scores between them. This might indicate that surgeons do not necessarily need a PS design to substitute the posterior cruciate ligament during TKA.


Assuntos
Artroplastia do Joelho/métodos , Marcha/fisiologia , Osteoartrite do Joelho/cirurgia , Reconstrução do Ligamento Cruzado Posterior/métodos , Ligamento Cruzado Posterior , Fenômenos Biomecânicos , Humanos , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Prótese do Joelho , Amplitude de Movimento Articular/fisiologia
9.
Asian J Surg ; 45(2): 681-688, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34930653

RESUMO

As the number of fusion levels increases, the complexity of spinal correction surgery also increases. Thus, we conducted this study to determine the safety and efficacy of tranexamic acid (TXA) involving eight or more spinal fusion levels. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) guidelines, a search of the PubMed, Embase, CENTRAL, Web of Science, and ClinicalTrials.gov databases was conducted for relevant studies published prior to May 30, 2019. The primary outcomes, including blood loss and transfusion requirement, and the secondary outcomes, including general indices, postoperative hemoglobin, and coagulation function, were analyzed using Rev Man 5.3.5 software and STATA version 12.0. Eight randomized controlled trials (473 participants) were included in the study. Compared to the control treatments, TXA reduced intraoperative blood loss, total blood loss, transfusion volume, and prothrombin time. There were no significant differences between the TXA and non-TXA groups in transfusion rate, operative time, hospital stay, complications, hemoglobin level, and other coagulation function parameters. In the pediatric subgroup analysis, TXA additionally improved hemoglobin levels, platelet count, and prothrombin time international normalized ratio. The present meta-analysis showed that TXA reduced blood loss and transfusion volume in both adults and children. In pediatric patients, TXA led to a greater benefit in postoperative hemoglobin levels and coagulation function. Intravenous TXA is safe and effective in children with eight or more spinal corrective levels.


Assuntos
Antifibrinolíticos , Ácido Tranexâmico , Adulto , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Criança , Humanos , Coluna Vertebral
10.
Bioengineered ; 13(6): 14489-14502, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-36694467

RESUMO

To determine whether zinc finger protein 521 (Zfp521) has a chondroprotective effect by maintaining extracellular matrix (ECM) homeostasis to attenuate osteoarthritis (OA). In chondrocytes, Zfp521 was overexpressed or silenced to detect its effects on proliferation, apoptosis, and ECM homeostasis. Adenovirus encoding Zfp521 was injected into the knee joints of anterior cruciate ligament transection rats to test its efficacy against OA. Combined with proteomic analysis, the molecular mechanism of Zfp521 in cartilage degeneration was further explored. An intra-articular injection of adenovirus carrying a Zfp521 sequence showed a chondroprotective effect against OA. The molecular mechanism around Zfp521 was classified at the molecular, cellular, histological, and functional levels. It was reported that Zfp521 could effectively promote cartilage proliferation, inhibit apoptosis, and maintain the balance of anabolism and catabolism of ECM. Moreover, it was confirmed that Zfp521 exerted its effect better by upregulating histone deacetylases 4 (HDAC4) in the nucleus and was significantly weakened in the absence of HDAC4 in the nucleus. Overall, Zfp521 better exerts its efficacy against OA by increasing the HDAC4 content in the nucleus, making it a promising strategy for OA treatment.


Assuntos
Cartilagem Articular , Osteoartrite , Ratos , Animais , Proteômica , Cartilagem Articular/patologia , Osteoartrite/metabolismo , Fatores de Transcrição/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Dedos de Zinco
11.
Proc Natl Acad Sci U S A ; 118(33)2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34389675

RESUMO

To identify regulators of triple-negative breast cancer (TNBC), gene expression profiles of malignant parts of TNBC (mTNBC) and normal adjacent (nadj) parts of the same breasts have been compared. We are interested in the roles of estrogen receptor ß (ERß) and the cytochrome P450 family (CYPs) as drivers of TNBC. We examined by RNA sequencing the mTNBC and nadj parts of five women. We found more than a fivefold elevation in mTNBC of genes already known to be expressed in TNBC: BIRC5/survivin, Wnt-10A and -7B, matrix metalloproteinases (MMPs), chemokines, anterior gradient proteins, and lysophosphatidic acid receptor and the known basal characteristics of TNBC, sox10, ROPN1B, and Col9a3. There were two unexpected findings: 1) a strong induction of CYPs involved in activation of fatty acids (CYP4), and in inactivation of calcitriol (CYP24A1) and retinoic acid (CYP26A1); and 2) a marked down-regulation of FOS, FRA1, and JUN, known tethering partners of ERß. ERß is expressed in 20 to 30% of TNBCs and is being evaluated as a target for treating TNBC. We used ERß+ TNBC patient-derived xenografts in mice and found that the ERß agonist LY500703 had no effect on growth or proliferation. Expression of CYPs was confirmed by immunohistochemistry in formalin-fixed and paraffin-embedded (FFPE) TNBC. In TNBC cell lines, the CYP4Z1-catalyzed fatty acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) increased proliferation, while calcitriol decreased proliferation but only after inhibition of CYP24A1. We conclude that CYP-mediated pathways can be drivers of TNBC but that ERß is unlikely to be a tumor suppressor because the absence of its main tethering partners renders ERß functionless on genes involved in proliferation and inflammation.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Receptor beta de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/metabolismo , Proteínas de Anfíbios/genética , Proteínas de Anfíbios/metabolismo , Animais , Benzopiranos/farmacologia , Calcitriol/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Regulação para Baixo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Ácidos Graxos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Camundongos , Neoplasias Experimentais , Distribuição Aleatória , Survivina/genética , Survivina/metabolismo , Transcriptoma , Tretinoína/farmacologia , Neoplasias de Mama Triplo Negativas/genética , Proteínas Wnt/genética , Proteínas Wnt/metabolismo
12.
Int Immunopharmacol ; 99: 107905, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34242997

RESUMO

OBJECTIVE: To determine whether idealized anterior cruciate ligament reconstruction (IACL-R) restores normal gait features, and whether inflammatory factors are involved in the pathogenesisof post-traumatic osteoarthritis (PTOA). METHODS: Fourteen mature female minipigs were allocated to a sham group (n = 7) or an IACL-R group (n = 7). Load asymmetry during gait was recorded using a pressure-sensing walkway measurement system to evaluate the gait features of the right knee joint before and after surgery. Inflammatory factors (including interleukin [IL]-1α, IL-1ß, IL-2, IL-6, IL-8, IL-18, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor) in synovial fluid were measured using Luminex assays before and after surgery. Cartilage integrity and the subchondral bone plate of the right knee were evaluated using histology and imaging at 3 months postoperatively. RESULTS: Swing time and stance time returned to their preoperative values on day 31, while maximum force, contact area, peak force ,and impulse returned to their preoperative values on day 45 after the surgery in the IACL-R group (P = 0.073, 0.053, 0.107, 0.052, 0.152, and 0.059, respectively).Thus, IACL-R restored normal gait. Compared with their preoperative concentrations, all tested inflammatory factors showed significantly increased concentrations in the synovial fluid in the IACL-R group, especially at 3, 7, and 15 days postoperatively. X-ray, computed tomography, magnetic resonance imaging, and histological data showed severe cartilage damage in the IACL-R model. CONCLUSION: IACL-R restored normal gait features but caused significant cartilage damage, indicating that significantly elevated inflammatory factors maybe crucial for the pathogenesis of PTOA.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Osteoartrite do Joelho/terapia , Animais , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Análise da Marcha , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/imunologia , Osteoartrite do Joelho/fisiopatologia , Suínos , Porco Miniatura , Líquido Sinovial/imunologia
13.
Clin Breast Cancer ; 21(5): e512-e517, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33642196

RESUMO

BACKGROUND: B and T lymphocyte attenuator (BTLA), an immunoinhibitory receptor, is shown to suppress the lymphocyte activation. Several studies addressed the relationship between the BTLA rs1982809 polymorphism and the risk of cancer. PATIENTS AND METHODS: To identify the effects of this polymorphism on the risk of breast cancer (BC), this study examined Chinese women from China, Jiangsu Province. This study involved 324 patients with BC and 412 controls. RESULTS: We observed that the BTLA rs1982809 polymorphism elevated the risk of BC. A similar finding was also shown in the subgroups of premenopausal women and those aged < 55 years old. In addition, this polymorphism was correlated with the estrogen receptor status, C-erbB-2 status, Ki-67 status, TNM stage, and tumor size of patients with BC. CONCLUSIONS: Collectively, the BTLA rs1982809 polymorphism shows a significant association with elevated risk and clinical features of BC in Chinese women. Further studies involving other races are urgently needed to replicate these findings.


Assuntos
Povo Asiático/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptores Imunológicos/genética , Adulto , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
14.
Sci Rep ; 9(1): 15762, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673032

RESUMO

Proinflammatory processes in adipose tissue contribute to development of breast cancer and insulin resistance. Crown-like structures (CLS) are histologic hallmarks of the proinflammatory process in adipose tissue. CLS are microscopic foci of dying adipocytes surrounded by macrophages mostly derived from monocytes in blood. Estrogen receptor ß (ERß) is expressed in microglia, macrophages within the central nervous system (CNS), where it evokes an anti-inflammatory response. The present study investigates the function of ERß in macrophages within CLS. We report that even though monocytes in the blood have no detectable levels of ERß, macrophages in CLS do express ERß. In ERß-/- mice, there was a significant increase in the number of CLS in both subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). CLS in these mice were dominated by pro-inflammatory macrophages (M1 macrophages) with higher expression of osteopontin (OPN) and an increase in number of proliferating macrophages. In mice made obese by Western diet, treatment with an ERß selective agonist (LY3201) reduced the number of CLS in both SAT and VAT with downregulation of OPN, activated hypoxia-inducible factor-1α (HIF-1α), proliferation and upregulation prolyl hydroxylase 2 (PHD2), the enzyme which prevents activation of HIF1α, in macrophages. We conclude that ERß expression is induced in macrophages in CLS within adipose tissue where it plays a pivotal role in suppression of CLS. Thus ERß agonists may be used to alleviate CLS-related breast cancer and insulin resistance in adipose tissue.


Assuntos
Tecido Adiposo/metabolismo , Receptor beta de Estrogênio/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Macrófagos/metabolismo , Osteopontina/metabolismo , Tecido Adiposo/patologia , Animais , Receptor beta de Estrogênio/genética , Feminino , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Knockout , Osteopontina/genética
15.
Int Immunopharmacol ; 75: 105752, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31310910

RESUMO

BACKGROUND: Downregulation of histone deacetylase-4 (HDAC4) contributes to cartilage degeneration in osteoarthritis (OA) because it promotes upregulation of runt-related transcription factor-2 (Runx-2) and osteoarthritis-related genes. The effect of HDAC4 upregulation on cartilage damage in OA remains unknown. METHODS: Rat chondrocytes were infected with Ad-GFP or Ad-HDAC4-GFP for 48 h, stimulated with interleukin-1ß (IL-1ß, 10 ng/mL) for 24 h, and then harvested for RT-qPCR. Male Sprague-Dawley rats in 3 groups were given anterior cruciate ligament transection (ACLT) or sham operation, and knee injections with different adenovirus (Ad) vectors at 48 h after surgery and every 3 weeks thereafter: ACLT+Ad-GFP (n = 17); ACLT+Ad-HDAC4-GFP (n = 20); and sham+Ad-GFP (n = 15). Three ACLT-Ad-HDAC4-GFP rats were sacrificed at different times to examine the expression of HDAC4. Two ACLT-Ad-GFP rats and two ACLT-Ad-HDAC4-GFP rats were euthanized at week-2; articular cartilage was harvested and expression of HDAC4 was determined by RT-qPCR. All other rats were euthanized at week-8. Cartilage damage and OA progression was assessed using radiography, fluorescence molecular tomography (FMT), histology, immunohistochemistry (IHC), ELISA, and RT-qPCR. RESULTS: Overexpression of HDAC4 in chondrocytes stimulated by IL-1ß reduced the levels of Runx-2, MMP-13, and Collagen X, but increased the levels of Collagen II and Aggrecan. Upregulation of HDAC4 reduced osteophyte formation and cartilage damage, and increased articular cartilage anabolism. CONCLUSION: HDAC4 attenuated articular cartilage damage by repression of Runx-2, MMP-13, and collagen X and induction of collagen II and ACAN in this rat model of OA. Upregulation of HDAC4 may provide chondroprotection in OA patients.


Assuntos
Adenoviridae/genética , Histona Desacetilases/genética , Osteoartrite , Animais , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Células Cultivadas , Condrócitos/metabolismo , Colágeno/genética , Colágeno/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Progressão da Doença , Interleucina-1beta/farmacologia , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Masculino , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Osteoartrite/genética , Osteoartrite/metabolismo , Osteoartrite/patologia , Ratos Sprague-Dawley , Transdução Genética
16.
Int Immunopharmacol ; 65: 212-220, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30317108

RESUMO

BACKGROUND: It has been noted that anterior cruciate ligament (ACL) injury-induced cartilage degeneration is the key risk factor for post-traumatic osteoarthritis (PTOA). However, whether the cartilage degeneration after ACL injury is caused by inflammation, abnormal biomechanics or both remains largely unknown, as there has been no animal model for separating the two factors so far. METHODS: Eighteen-month-old female mini-pigs were divided into an "idealized" anterior cruciate ligament reconstruction (IACLR) group and a control group (n = 16 limbs per group). Real-time PCR, safranine O staining and indian ink staining were performed to verify whether animal models were successfully established or not. Multiple linear regression analysis was used to evaluate the correlation between levels of the inflammatory factors (including interferon [IFN]-γ, interleukin [IL]-1ß, IL-4, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor [TNF]-α measured by the Luminex method) and changes in cartilage histology (quantified by morphological scoring) after surgery. RESULTS: A significant OA cartilage damage with increased MMP-1, MMP-13 mRNA levels and reduced aggrecan mRNA/protein levels was observed in IACLR groups. As a result, the IACLR gross morphology score was dramatically increased than control. Moreover, IACLR significantly increased the levels of IL-1ß, IL-4, IL-6 and TNF-α in the synovial fluid of the knee. Most importantly, a close relationship was found between IL-1ß, IL-6 and TNF-α concentrations and morphological score of PTOA, respectively. CONCLUSION: These results demonstrated that inflammatory factors are independently responsible for the onset of PTOA.


Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/cirurgia , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Osteoartrite do Joelho/imunologia , Complicações Pós-Operatórias/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Lesões do Ligamento Cruzado Anterior/complicações , Modelos Animais de Doenças , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-6/genética , Osteoartrite do Joelho/etiologia , Suínos , Porco Miniatura , Fator de Necrose Tumoral alfa/genética
17.
J Sci Food Agric ; 94(5): 1000-4, 2014 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-24037944

RESUMO

BACKGROUND: Essential oil of cinnamon (CM) is a potential alternative to chemical fungicides. Thus this work aimed to investigate the possible effects of CM microemulsions on decay developments and qualitative properties of pears. RESULTS: The decay incidence of samples treated with 500 µg L⁻¹ microemulsion was significantly reduced by 18.7% in comparison to that of 500 µg L⁻¹ non-microemulsion after 4 days' storage at 20 °C. In the vapor phase, the CM microemulsion with the lowest concentration had the best control for decay incidence and lesion diameter. The interval between inoculations also influenced decay development. Pears treated with Botrytis cinerea and immediately followed by CM microemulsion showed the lowest decay incidence. Moreover, in the natural decay experiment, the percentage of rotted pears was 3.8% in the CM microemulsion treatment and 5.8% in the control. CM microemulsion delayed the loss of ascorbic acid, yet it had no significant influence on pear qualities such as firmness and color. CONCLUSION: CM microemulsion may be an alternative way to control the gray mold of pears without a negative influence on its qualities.


Assuntos
Botrytis/efeitos dos fármacos , Cinnamomum zeylanicum/química , Conservantes de Alimentos/farmacologia , Frutas/microbiologia , Fungicidas Industriais/farmacologia , Óleos Voláteis/farmacologia , Pyrus/microbiologia , Ácido Ascórbico/análise , Botrytis/crescimento & desenvolvimento , Botrytis/isolamento & purificação , Fenômenos Químicos , China , Emulsões , Conservantes de Alimentos/administração & dosagem , Conservantes de Alimentos/efeitos adversos , Conservantes de Alimentos/química , Qualidade dos Alimentos , Armazenamento de Alimentos , Frutas/química , Frutas/efeitos dos fármacos , Fungicidas Industriais/administração & dosagem , Fungicidas Industriais/efeitos adversos , Fungicidas Industriais/química , Fenômenos Mecânicos , Testes de Sensibilidade Microbiana , Óleos Voláteis/administração & dosagem , Óleos Voláteis/efeitos adversos , Óleos Voláteis/química , Pigmentação/efeitos dos fármacos , Pyrus/química , Pyrus/efeitos dos fármacos , Refrigeração , Fatores de Tempo , Volatilização
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