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1.
Ageing Res Rev ; 78: 101635, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35483626

RESUMO

Osteoarthritis (OA), characterized by cartilage erosion, synovium inflammation, and subchondral bone remodeling, is a common joint degenerative disease worldwide. OA pathogenesis is regulated by multiple predisposing factors, including imbalanced matrix metabolism, aberrant inflammatory response, and excessive oxidative stress. Moreover, melatonin has been implicated in development of several degenerative disorders owing to its potent biological functions. With regards to OA, melatonin reportedly promotes synthesis of cartilage matrix, inhibition of chondrocyte apoptosis, attenuation of inflammatory response, and suppression of matrix degradation by regulating the TGF-ß, MAPK, or NF-κB signaling pathways. Notably, melatonin has been associated with amelioration of oxidative damage by restoring the OA-impaired intracellular antioxidant defense system in articular cartilage. Findings from preliminary application of melatonin or melatonin-loaded biomaterials in animal models have affirmed its potential anti-arthritic effects. Herein, we summarize the anti-arthritic effects of melatonin on OA cartilage and demonstrate that melatonin has potential therapeutic efficacy in treating OA.

2.
Ann Transl Med ; 10(6): 273, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35434003

RESUMO

Background: The occurrence of head and neck squamous cell carcinoma (HNSCC) is closely related to the immune system. The integration of traditional treatment methods and immunotherapy will be the future development direction of cancer treatment. But immunotherapy also has its limitations: a lot of basic research is going on, but the translation from basic to clinical is still not enough, and there are still few drugs approved for use.This study aimed to explore the clinical significance of the tumor immune microenvironment in HNSCC. Methods: Six clinically obtained postoperative cases were analyzed using multiplex immunohistochemistry (mIHC) to observe the tumor immune microenvironment and analyze infiltrating immune cells. Correlations between infiltrating immune cells from The Cancer Genome Atlas (TCGA) database and clinicopathological features of 510 HNSCC patients were then analyzed. Kaplan-Meier survival analysis was used to detect the relationship between the expression of different immune cells and the prognosis of HNSCC patients, and univariate and multivariate Cox regression analyses were used to analyze the prognostic factors associated with HNSCC patients. We validated the prognostic and predictive accuracy based on the expression of CD8+ T-cells in an independent group of 510 patients. Results: We detected infiltration of CD8+ T cells, NK cells, and macrophages in patients with laryngeal squamous cell carcinoma by multiplex immunofluorescence. The infiltration of the three types of immune cells in the tumor stroma was significantly higher than in the tumor parenchyma. Our results also showed the infiltration of CD8+ T cells was associated with prognosis, and the COX regression model showed CD8+ T cells were an independent prognostic factor in HNSCC patients. The higher density of infiltrating CD8+ T cells had the better prognosis. In addition, we developed a nomogram for clinical use that integrated the CD8+ T-cells-based classifier and three clinicopathological risk factors to predict the prognosis of HNSCC patients. Conclusions: CD8+ T-cell exhaustion in the tumor microenvironment of HNSCC determines poor prognosis and can be combined with the tumor stage to improve the accuracy of prognosis assessment in HNSCC patients.

4.
Ann Transl Med ; 10(2): 36, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35282057

RESUMO

Background: Articular cartilage-derived progenitor cells (ACPCs) possess the properties of both chondrocytes and bone marrow mesenchymal stem cells (BMSCs). However, the number of ACPCs in articular cartilage is low, and an effective culture system is needed for their expansion. Basic fibroblast growth factor (bFGF) promotes the expansion of chondrocytes and BMSCs, as well as the chondrogenic differentiation of BMSCs. Therefore, the aim of this study was to clarify whether bFGF could be used for in vitro expansion of ACPCs and whether bFGF promoted chondrogenic construction of ACPCs. Methods: We applied the fibronectin adhesion method to sort mice ACPCs and compared the proliferative, osteogenic, and chondrogenic abilities of ACPCs by adding various concentration of bFGF (0, 2, and 5 ng/mL) to the cell culture medium. Then used the best system to construct cartilage with ACPCs in vitro and in vivo. Results: The results indicated that bFGF promoted ACPCs proliferation, inhibited osteogenesis, and promoted chondrogenesis, and that a cell culture system containing 2 ng/mL bFGF was optimal for these effects. ACPCs constructed cartilage using the filtered culture system presented homogeneous cartilaginous histological structure in vitro and in vivo. Conclusions: By applying this cell culture system, homogenous cartilage tissue was constructed in vitro and in vivo by chondrogenic induction, which provides a stable cell expansion culture method for the application of ACPCs in cartilage repair.

5.
J Bone Miner Res ; 37(5): 1056-1072, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35147250

RESUMO

Reactive oxygen species (ROS) are implicated in induction of inflammatory response and cartilage degradation in osteoarthritis (OA). Melatonin has been shown to improve the chondrogenic differentiation and promote cartilage matrix synthesis in mesenchymal stem cells. However, the underlying mechanisms of melatonin-regulated antioxidant activity in OA cartilage are not known. The aim of this study was to explore the effect of melatonin on nuclear factor-erythroid 2-related factor 2 (NRF2), a key antioxidant transcription factor, and its target antioxidant genes in early-stage OA cartilage. Primary chondrocytes were isolated from rats with surgically induced OA. In vitro treatment of melatonin significantly increased cartilage matrix synthesis and upregulated antioxidant enzymes, mainly heme oxygenase 1 (HO-1), while decreasing matrix degradation enzymes and intracellular ROS. In vivo intraarticular injection of melatonin effectively ameliorated cartilage degeneration in an experimental rat OA model. Inhibition of melatonin membrane receptors by Luzindole or 4-P-PDOT reversed the beneficial effects of melatonin on cartilage matrix synthesis, implying that melatonin receptor-mediated pathway is involved in its anti-arthritic effects. Interestingly, melatonin showed no significant effect on the mRNA level of Nrf2 but significantly increased its protein level. Silencing of Nrf2 or HO-1 expression abolished the protective effects of melatonin, as shown by increased ROS levels and matrix degradation enzyme expression. Microarray assays revealed that miR-146a, a predicted target for Nrf2, was significantly upregulated in OA chondrocytes but was markedly reduced by melatonin treatment. Overexpression of miR-146a diminished the protective effects of melatonin by inhibiting NRF2 expression and aggravating OA-induced cartilage degradation. These findings demonstrate that melatonin supports the anabolic metabolism of cartilage matrix in OA chondrocytes by enhancing the protein levels of NRF2 via suppressing miR-146a. Melatonin-mediated activation of the NRF2/HO-1 axis prevents cartilage degeneration and represents a promising therapeutic target for treatment of early-stage OA. © 2022 American Society for Bone and Mineral Research (ASBMR).

6.
J Orthop Res ; 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35072275

RESUMO

The purpose of our study was to investigate the changes in micromorphology and mechanical properties of intervertebral discs degeneration induced by aging and puncture. Normal group (NG), 2 weeks post-puncture degeneration group (PDG) and aging degeneration group (ADG) each included 10 rats. Plain film, magnetic resonance imaging, and histological testing were utilized to assess intervertebral disc degeneration. Atomic force microscope was utilized to analyze the microstructure and elastic modulus of the intervertebral disc, while immunohistochemistry was employed to assess alterations in the cell matrix using collagen I, collagen II, matrix metalloproteinase-3 (MMP-3), and tumour necrosis factor-α (TNF-α). The results showed that the disc height ratio between PDG and ADG decreased. In the PDG and ADG group, histological scores both increased, the gray value of the T2 signal decreased, the proportion of MMP-3 and TNF-positive cells in intervertebral disc tissues was higher (p < 0.05) and the IOD values of COL-2 lower in intervertebral disc tissues (p < 0.05). The elastic modulus of PDG and ADG annulus fibers (AF) increased compared to the NG (p < 0.05); when compared to PDG, the elastic modulus of ADG AF decreased (p < 0.05). The elastic modulus of PDG and ADG collagen increased in the nucleus pulposus (NP, p < 0.05); ADG had a greater AF diameter than NG and PDG (p < 0.05). The results indicated that ADG fiber diameter thickens, and chronic inflammation indicators rise; PDG suffers from severe extracellular matrix loss. The degeneration of the ADG and PDG intervertebral discs is different. The results provide foundation for clinical research.

8.
J Hazard Mater ; 424(Pt B): 127362, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34638075

RESUMO

Development of economic and efficient absorbent for the simultaneous removal of antibiotics and heavy metals is needed. In this study, a three-dimensional porous ultrathin g-C3N4 (UCN) /graphene oxide (GO) hydrogel (UCN-GH) was prepared by co-assembling of UCN and GO nanosheets via the facile hydrothermal reaction. Characterizations indicated that the addition of UCN significantly decreased the reduction of CO and O-CO related groups of GO during the hydrothermal reaction and introduced amine groups on UCN-GH. The UCN-GH exhibited excellent ability on the co-removal of Cu(II) (qmax = 2.0-2.5 mmol g-1) and tetracycline (TC) (qmax = 1.2-3.0 mmol g-1) from water. The adsorption capacities were increased as UCN mass ratio increasing. The mutual effects between Cu(II) and TC were examined through adsorption kinetics and isotherm models. Characterizations and computational chemistry analysis indicated that Cu(II) is apt to coordinate with the amine groups on UCN than with oxygen groups on GO, which accounts for the enhanced adsorption ability of UCN-GH. In the binary system, Cu(II) acts as a bridge between TC and UCN-GH enhanced the removal of TC. The effects of pH and regular salt ions on the removal of Cu(II)/TC were examined. Moreover, the prepared UCN-GH also showed comparable co-adsorption capacities in practical water/wastewater.


Assuntos
Grafite , Poluentes Químicos da Água , Adsorção , Antibacterianos , Cobre , Hidrogéis , Cinética , Tetraciclina , Poluentes Químicos da Água/análise
9.
Poult Sci ; 101(2): 101610, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34936951

RESUMO

In this study, the effects of 5 graded dietary levels (0.025, 0.05, 0.075, 0.1, and 0.125%) of dimethylglycine (DMG) were studied in laying hens during the late laying period (71-78 wk). Graded doses of DMG from 0.025 to 0.125% in the diet produced quadratic positive (P < 0.05) responses in the laying rate, egg-feed ratio, yolk color, grade follicular weight, and the number of large white follicles and linear positive (P < 0.05) responses in average egg weight, and the number of large white follicles. With 0.1% DMG, the laying rate and egg-feed ratio improved (P < 0.05), and the abdominal fat percentage decreased. Considering the laying performance under the conditions used in this study, the best-fit model for the DMG requirements of laying hens was estimated to range from 0.049 to 0.065% DMG during the late laying period based on a regression analysis. The addition of DMG did not affect the total cholesterol (TCH) and triglyceride (TG) contents in the plasma of laying hens; however, it significantly reduced the abdominal fat rate. DMG may change the course of lipid deposition in laying hens during the late laying period. In conclusion, supplementation with DMG can improve the laying rate and follicles development of laying hens.


Assuntos
Ração Animal , Galinhas , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais , Gema de Ovo , Feminino , Óvulo , Sarcosina/análogos & derivados
10.
J Hazard Mater ; 421: 126816, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34396968

RESUMO

Defect and interlayer engineering are considered as two promising strategies to alter the electronic structures of sensing materials for improved gas sensing properties. Herein, ethylene glycol intercalated Al-doped SnS2 (EG-Al-SnS2) featuring Al doping, sulfur (S) vacancies, and an expanded interlayer spacing was prepared and developed as an active NO2 sensing material. Compared to the pristine SnS2 with failure in detecting NO2 at room temperature, the developed EG-Al-SnS2 exhibited a better conductivity, which was beneficial for realizing the room-temperature NO2 sensing. As a result, a high sensing response of 410% toward 2 ppm NO2 was achieved at room temperature by using the 3% EG-Al-SnS2 as the sensing material. Such outstanding sensing performance was attributed to the enhanced electronic interaction of NO2 on the surface of SnS2 induced by the synergistic effect of Al doping, S vacancies, and the expanded interlayer spacing, which is directly revealed by the in-suit measurement based on near-ambient pressure X-ray photoelectronic spectroscopy (NAP-XPS). Furthermore, to identify the role of Al doping, S vacancies, and the expanded interlayer spacing in enhancing the NO2 sensing properties, a series of comparative experiments and theoretical calculations were performed.

12.
BMC Musculoskelet Disord ; 22(1): 945, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772392

RESUMO

BACKGROUND: Postoperative delirium (POD) is widely reported as a common postoperative complication following total joint arthroplasty (TJA) of the hip and knee in elderly patients, leading to many adverse effects. We sought to investigate predictors of delirium after TJA. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched up to 2020 for studies examining POD following TJA in elderly patients. Pooled odds ratio (OR) and mean difference (MD) of those who experienced delirium compared to those who did not were calculated for each variable. The Newcastle-Ottawa Scale (NOS) was used for the study quality evaluation. RESULTS: Fifteen studies with 31 potential factors were included. In the primary analysis, 9 factors were associated with POD, comprising advanced age (MD 3.81; 95% confidence interval (CI) 1.80-5.83), dementia (OR 24.85; 95% CI 7.26-85.02), hypertension (OR 2.26; 95% CI 1.31-3.89), diabetes (OR 2.02; 95% CI 1.15-3.55), stroke (OR 14.61; 95% CI 5.26-40.55), psychiatric illness (OR 2.72; 95% CI 1.45-5.08), use of sedative-hypnotics (OR 6.42; 95% CI 2.53-16.27), lower preoperative levels of hemoglobin (MD - 0.56; 95% CI - 0.89-- 0.22), and lower preoperative mini-mental state examination score (MD - 0.40; 95% CI - 0.69-- 0.12). Twelve studies were included in the systematic review, of which 24 factors were additionally correlated with POD using single studies. CONCLUSIONS: Strategies and interventions should be implemented for the elderly patients receiving TJA surgeries with potential predictors identified in this meta-analysis.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Delírio , Idoso , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Humanos , Razão de Chances , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco
13.
Ann Transl Med ; 9(18): 1443, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733995

RESUMO

BACKGROUND: Increased evidence has indicated that the tumour microenvironment plays an essential in the development, treatment and prognosis of head and neck squamous cell carcinoma (HNSC). Recent studies have indicated CC chemokine receptor 4 (CCR4) plays an essential role in tumor invasion and other adverse biological behavior. This study used data from the Cancer Genome Atlas (TCGA) database to explore the role of CCR4 in HNSC and its clinical significance. METHODS: The gene expression and clinical data of HNSC patients in the TCGA database were extracted. Gene Expression Profiling Interactive Analysis (GEPIA) was used to analyze the expression of CCR4 in tumor and non-tumor tissue. Kaplan-Meier survival analysis was used to analyze the relationship between CCR4 expression and overall survival rate (OS), disease-specific survival (DSS), and progression-free interval (PFI) in HNSC. A logistic regression model was used to analyze the relationships between various clinical factors and CCR4 expression. Gene Set Enrichment Analysis (GSEA) was used to explore the potential role of CCR4 in HNSC. Additionally, we explored the relationship between CCR4 and immune infiltration. RESULTS: The expression of CCR4 in HNSC was not significantly different from that in normal tissue. The expression level of CCR4 in wild-type TP53 was higher than that in mutant TP53. Cox regression analysis showed the expression level of CCR4 was related to the patient's tumor grade and Tumor-Node-Metastasis (TNM) stage. CCR4 expression level is an independent prognostic factor. CCR4 is positively correlated with immune infiltration and immune checkpoints expression levels. The results of GSEA revealed that the high CCR4 expression group genes were enriched in allograft rejection, inflammatory response, IL-6/JAK/STAT3 signaling, interferon gamma response, and KRAS signaling up. Low CCR4 expression group genes were enriched in oxidative phosphorylation, MYC targets v1, DNA repair, reactive oxygen species pathway, and P53 pathway. Further, our study indicated CCR4 can also predict the prognosis of radiotherapy patients. CONCLUSIONS: Our study found that CCR4 was a prognostic marker related to HNSC immune infiltration, and patients with high expression of CCR4 had a better prognosis.

14.
Ann Transl Med ; 9(20): 1554, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790760

RESUMO

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) accounts for 90% of head and neck malignant tumors. As the early symptoms of HNSCC are not obvious, and it is prone to recurrence and metastasis, making the overall survival (OS) rate of patients very low. Existing studies have shown m6A methylation plays a crucial role in various cancers, but it is rarely studied in HNSCC. This study aimed to explore the expression of m6A methylation-related genes in HNSCC and its correlation with prognosis, and to explore its relationship with immune infiltration. METHODS: The gene expression data of HNSCC patient tumor samples (tumor =510) and adjacent normal tissue samples (normal =50) were extracted from The Cancer Genome Atlas (TCGA) database, and the expression characteristics of m6A regulatory factors were described. Kaplan-Meier survival analysis was used to analyze the relationship between m6A regulatory factors and OS and disease-specific survival (DSS). Least absolute shrinkage and selection operator (LASSO) regression was used to construct the m6A regulatory factor-HNSCC risk prediction model. In addition, the relationship between m6A methylation-related genes and tumor immune infiltration were discussed. RESULTS: The differential expression of 20 genes were identified by TCGA, and 18 genes (IGF2BP2, IGF2BP1, IGF2BP3, VIRMA, YTHDF1, YTHDF2, YTHDF3, ZC3H13, METTL14, ALKBH5, METTL3, RBMX, WTAP, YTHDC1, FTO, HNRNPC, HNRNPA2B1, and RBM15) were overexpressed in HNSCC. The survival rate of different gene expression levels was different. The high expression of YTHDC1 and YTHDC2 indicated better OS. Furthermore, for DSS, increased expression of YTHDC2 was also correlated with better clinical outcomes (P<0.05). At the same time, we drew a 3-gene risk score model in the TCGA-HNSCC cohort, and the survival curve showed compared with low-risk patients, high-risk patients had significantly worse OS (P<0.05). Gene enrichment analysis showed EPITHELIAL_MESENCHYMAL_TRANSITIO, MTORC1_SIGNALING, MYC_TARGETS_V1, MYC_TARGETS_V2, MYOGENESIS pathways, high TP53 mutations, and suppressive immunity were related to the high-risk group. The low-risk group was related to ALLOGRAFT_REJECTION, COMPLEMENT, IL6_JAK_STAT3_SIGNALING, INTERFERON_ALPHA_RESPONSE, INTERFERON_GAMMA_RESPONSE pathways, low TP53 mutations, and active immunity. CONCLUSIONS: The m6A methyltransferase-related genes can predict the prognosis of HNSCC and are related to immune infiltration.

16.
Acta Biochim Biophys Sin (Shanghai) ; 53(8): 1017-1026, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34142698

RESUMO

High fatty acid reduces insulin secretion in pancreatic ß-cells and miR-139-5p is increased in diabetic pancreatic tissues and induces islet ß-cell apoptosis. However, to date, there is no study exploring whether or not miR-139-5p is involved in high fatty acid-induced insulin secretion. In the present study, INS-1 cells were exposed to different concentrations (0.1, 0.2, and 0.4 mM) of palmitate for different time periods (12, 24, and 48 h). The expression levels of miR-139-5p and neuronal pentraxin 1 (NPTX1) were evaluated by real-time PCR and western blot analysis. The regulation of NPTX1 by miR-139-5p was examined by luciferase assay. Cell transfection was conducted using Lipo8000 or Lipofectamine RNAiMAX. Potassium or glucose-stimulated insulin secretion levels were used to verify the function of miR-139-5p or NPTX1 in insulin secretion. Insulin secretion levels were detected by radioimmunoassay. We found that miR-139-5p was increased in INS-1 cells stimulated with palmitate. In addition, miR-139-5p was also elevated in islets of high-fat diet-fed mice and db/db mice compared to those in islets of normal diet-fed mice and wild-type mice. Knockdown of miR-139-5p could reverse high fatty acid-induced insulin secretion defects in INS-1 cells. Furthermore, we demonstrated that NPTX1 is a target of miR-139-5p. miR-139-5p mediated palmitate-induced insulin secretion defects by targeting NPTX1. Moreover, palmitate treatment declined the expression of NPTX1 and the NPTX1 expression was also decreased in islets of high-fat diet-fed mice and db/db mice. Impaired NPTX1 expression is involved in fatty acid-induced insulin secretion defects. Collectively, our results illustrate that the induction of ß-cell insulin secretion defects by fatty acids is mediated, at least in part, by miR-139-5p via downregulation of NPTX1 expression.


Assuntos
Proteína C-Reativa/metabolismo , Secreção de Insulina/efeitos dos fármacos , MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Palmitatos/farmacologia , Animais , Proteína C-Reativa/genética , Secreção de Insulina/genética , Masculino , Camundongos , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Ratos
18.
J Hepatol ; 75(5): 1128-1141, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34171432

RESUMO

BACKGROUND & AIMS: Our previous genomic whole-exome sequencing (WES) data identified the key ErbB pathway mutations that play an essential role in regulating the malignancy of gallbladder cancer (GBC). Herein, we tested the hypothesis that individual cellular components of the tumor microenvironment (TME) in GBC function differentially to participate in ErbB pathway mutation-dependent tumor progression. METHODS: We engaged single-cell RNA-sequencing to reveal transcriptomic heterogeneity and intercellular crosstalk from 13 human GBCs and adjacent normal tissues. In addition, we performed WES analysis to reveal the genomic variations related to tumor malignancy. A variety of bulk RNA-sequencing, immunohistochemical staining, immunofluorescence staining and functional experiments were employed to study the difference between tissues with or without ErbB pathway mutations. RESULTS: We identified 16 cell types from a total of 114,927 cells, in which epithelial cells, M2 macrophages, and regulatory T cells were predominant in tumors with ErbB pathway mutations. Furthermore, epithelial cell subtype 1, 2 and 3 were mainly found in adenocarcinoma and subtype 4 was present in adenosquamous carcinoma. The tumors with ErbB pathway mutations harbored larger populations of epithelial cell subtype 1 and 2, and expressed higher levels of secreted midkine (MDK) than tumors without ErbB pathway mutations. Increased MDK resulted in an interaction with its receptor LRP1, which is expressed by tumor-infiltrating macrophages, and promoted immunosuppressive macrophage differentiation. Moreover, the crosstalk between macrophage-secreted CXCL10 and its receptor CXCR3 on regulatory T cells was induced in GBC with ErbB pathway mutations. Elevated MDK was correlated with poor overall survival in patients with GBC. CONCLUSIONS: This study has provided valuable insights into transcriptomic heterogeneity and the global cellular network in the TME, which coordinately functions to promote the progression of GBC with ErbB pathway mutations; thus, unveiling novel cellular and molecular targets for cancer therapy. LAY SUMMARY: We employed single-cell RNA-sequencing and functional assays to uncover the transcriptomic heterogeneity and intercellular crosstalk present in gallbladder cancer. We found that ErbB pathway mutations reduced anti-cancer immunity and led to cancer development. ErbB pathway mutations resulted in immunosuppressive macrophage differentiation and regulatory T cell activation, explaining the reduced anti-cancer immunity and worse overall survival observed in patients with these mutations.


Assuntos
Receptores ErbB/imunologia , Neoplasias da Vesícula Biliar/imunologia , Hospedeiro Imunocomprometido/fisiologia , Midkina/efeitos adversos , Proliferação de Células/genética , China/epidemiologia , Receptores ErbB/antagonistas & inibidores , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/fisiopatologia , Humanos , Midkina/genética , Análise de Sequência de RNA/métodos , Análise de Sequência de RNA/estatística & dados numéricos , Transdução de Sinais/genética , Análise de Célula Única/métodos , Análise de Célula Única/estatística & dados numéricos , Sequenciamento Completo do Exoma/métodos , Sequenciamento Completo do Exoma/estatística & dados numéricos
19.
Cell Death Dis ; 12(5): 483, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986262

RESUMO

Osteoarthritis (OA) is a common articular degenerative disease characterized by loss of cartilage matrix and subchondral bone sclerosis. Kartogenin (KGN) has been reported to improve chondrogenic differentiation of mesenchymal stem cells. However, the therapeutic effect of KGN on OA-induced cartilage degeneration was still unclear. This study aimed to explore the protective effects and underlying mechanisms of KGN on articular cartilage degradation using mice with post-traumatic OA. To mimic the in vivo arthritic environment, in vitro cultured chondrocytes were exposed to interleukin-1ß (IL-1ß). We found that KGN barely affected the cell proliferation of chondrocytes; however, KGN significantly enhanced the synthesis of cartilage matrix components such as type II collagen and aggrecan in a dose-dependent manner. Meanwhile, KGN markedly suppressed the expression of matrix degradation enzymes such as MMP13 and ADAMTS5. In vivo experiments showed that intra-articular administration of KGN ameliorated cartilage degeneration and inhibited subchondral bone sclerosis in an experimental OA mouse model. Molecular biology experiments revealed that KGN modulated intracellular reactive oxygen species in IL-1ß-stimulated chondrocytes by up-regulating nuclear factor erythroid 2-related factor 2 (NRF2), while barely affecting its mRNA expression. Microarray analysis further revealed that IL-1ß significantly up-regulated miR-146a that played a critical role in regulating the protein levels of NRF2. KGN treatment showed a strong inhibitory effect on the expression of miR-146a in IL-1ß-stimulated chondrocytes. Over-expression of miR-146a abolished the anti-arthritic effects of KGN not only by down-regulating the protein levels of NRF2 but also by up-regulating the expression of matrix degradation enzymes. Our findings demonstrate, for the first time, that KGN exerts anti-arthritic effects via activation of the miR-146a-NRF2 axis and KGN is a promising heterocyclic molecule to prevent OA-induced cartilage degeneration.


Assuntos
Anilidas/uso terapêutico , MicroRNAs/metabolismo , Osteoartrite/tratamento farmacológico , Ácidos Ftálicos/uso terapêutico , Anilidas/farmacologia , Animais , Diferenciação Celular , Modelos Animais de Doenças , Progressão da Doença , Humanos , Masculino , Camundongos , Ácidos Ftálicos/farmacologia
20.
Aging Clin Exp Res ; 33(12): 3161-3172, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33913118

RESUMO

OBJECTIVES: Dementia is a common mental disorder that affects the life quality in elders. Recently, emerging studies reported the negative impacts of dementia on prognosis after hip surgeries. However, the integrated and reliable role of dementia in hip surgery is not illustrated. METHODS: We searched the relevant literatures before June 2020 and extracted the data that met the inclusion criteria. The influence of dementia on postoperative walking ability, complications including infection, cardiovascular complications, hip dislocation, delirium, and respiratory complications, and survival rate at different periods were evaluated. Qualitative and quantitative analysis were conducted using Review Manager Version 5.3. RESULTS: The meta-analysis enrolled a total of 30 studies with 1,037,049 patients. The pooled results revealed that there were significant negative impacts of dementia on the recovery of postoperative walking ability, postoperative infection, hip dislocation, delirium and respiratory complications and mortality at different periods. CONCLUSIONS: Dementia is a crucial risk factor for the poor prognosis after hip fracture surgery. Therefore, when making clinical strategies for hip fracture patients with dementia, countermeasures for possible complications should be generated.


Assuntos
Demência , Fraturas do Quadril , Idoso , Fraturas do Quadril/cirurgia , Humanos , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco
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