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2.
Sci Rep ; 11(1): 11615, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34079035

RESUMO

This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between 2008 and 2017. Patients were stratified into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors suffered higher rates of hypotension (P < 0.001), shock (P < 0.001) and kidney injury (P = 0.001) than survivors did. Kaplan-Meier analysis indicated that patients with shock suffered lower cumulative survival than did patients without shock (log-rank test, P < 0.001). In a multivariate-Cox-regression model, shock was a significant predictor of mortality after intoxication (odds ratio 18.182, 95% confidence interval 2.045-166.667, P = 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively.

3.
Int Immunopharmacol ; 97: 107826, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34091114

RESUMO

PURPOSE: Treatment options for recurrent glioblastoma (rGBM) remain scarce, which may be due to the limited understanding of its molecular characteristics. METHODS: Based on gene expression profiling, the infiltration scores of 26 immune cell types were calculated using gene set variation analysis. The differences between rGBM and other cancer subtypes were estimated to characterize the specific immune characteristics of rGBM, and the prognostic value of immune cells in rGBM was estimated using univariate and multivariate Cox analysis. Subgroup analyses and Kaplan-Meier analyses were performed to identify whether CD8 T-cell infiltration could be useful in selecting treatment options for rGBM patients. RESULTS: We found that rGBM patients were associated with enrichment of activated CD8 T cells, and high CD8 T-cell infiltration was associated with superior overall survival. Patients exhibiting high CD8 T-cell infiltration who received treatment with bevacizumab and lomustine combination therapy experienced a significant benefit in overall survival and progression-free survival, whereas patients with low CD8 T-cell infiltration did not experience such a benefit. CD8 T cells remained an independent prognostic factor in multivariate analyses (cohort 1: hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.316-0.945, P = 0.031; cohort 3: HR = 0.615, 95% CI: 0.387-0.978, P = 0.040) after adjusting for clinicopathological and molecular factors. CONCLUSIONS: Activated CD8 T-cells is a promising biomarker for predicting overall survival in rGBM patients and could be used for assisting treatment selection.

4.
Int J Med Sci ; 18(12): 2521-2531, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104083

RESUMO

Developing treatment strategies for triple-negative breast cancer (TNBC) has become an important clinical challenge. Currently, taxane-based chemotherapy is one of the standard treatments for TNBC. However, determining the key factor of taxane-resistance is urgently in need for clinical treatment for breast cancer. We used GEO data to generate paclitaxel resistance in two basal-like TNBC cell lines (SUM149 and MDA-MB-468). Seventy-one common upregulated differentially expressed genes (DEGs) and 11 downregulated DEGs were found to be related to paclitaxel resistance. By constructing protein-protein interactions, 28 hub proteins with a degree cutoff criterion of ≥1 were found. Nine hub genes (COL4A6, COL4A5, IL6, PDGFA, LPAR1, FYB, IL20, IL18R1 and INHBA) are involved in important signaling pathways. We found that upregulated PDGFA and downregulated COL4A6 were significantly associated with an insensitive response to neoadjuvant paclitaxel-based therapy. A Kaplan-Meier plot was created to check the prognostic values of 11 hub DEGs in terms of recurrence-free survival. High expressions of PDGFA and LAMB3 were correlated with poor recurrence-free survival, while low levels of FYB, IL18R1, and RASGRP1 indicated poorer relapse-free survival. Our results suggest that PDGFA, COL4A6, LPAR1, FYB, COL4A5, and RASGRP1 might be candidate target genes for taxane-based therapy in basal-like TNBC.

5.
Clin Cancer Res ; 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078650

RESUMO

PURPOSE: Patient derived xenografts (PDXs) are a research tool for studying cancer biology and drug response phenotypes. While engraftment rates are higher for tumors with more aggressive characteristics, it is uncertain whether engraftment is prognostic for cancer recurrence. EXPERIMENTAL DESIGN: In a prospective study of breast cancer patients treated with neoadjuvant chemotherapy (NAC) with taxane+/-trastuzumab followed by anthracycline-based chemotherapy, we report the association between breast cancer events and PDX engraftment using tumors derived from treatment naïve (pre-NAC biopsies from 113 patients) and treatment resistant (post-NAC at surgery from 34 patients). Gray's test was used to assess whether the cumulative incidence of a breast cancer event differs with respect to either pre-NAC PDX engraftment or post-NAC PDX engraftment. RESULTS: With a median follow up of 5.7 years, the cumulative incidence of breast cancer relapse did not differ significantly according to pre-NAC PDX engraftment (5-year rate: 13.6% versus 13.4%; p=0.89). However, the incidence of a breast event was greater for patients with post-NAC PDX engraftment (5-year rate: 50.0% versus 19.6%), but this did not achieve significance (p=0.11). CONCLUSIONS: In treatment-naive breast cancer receiving standard NAC, PDX engraftment was not prognostic for breast cancer recurrence. Further study is needed to establish whether PDX engraftment in the treatment-resistant setting is prognostic for cancer recurrence.

6.
J Agric Food Chem ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34060828

RESUMO

Daily intake of tea has been known to relate to a low risk of depression. In this study, we report that a special variety of tea in China, Camellia assamica var. kucha (kucha), possesses antidepressant effects but with less adverse effects as compared to traditional tea Camellia sinensis. This action of kucha is related to its high amount of theacrine, a purine alkaloid structurally similar to caffeine. We investigated the antidepressant-like effects and mechanisms of theacrine in chronic water immersion restraint stress and chronic unpredictable mild stress mice models. PC12 cells and primary hippocampal neural stem cells were treated with stress hormone corticosterone (CORT) to reveal the potential antidepression mechanism of theacrine from the perspective of adult hippocampus neurogenesis. Results of behavioral and neurotransmitter analysis showed that intragastric administration of theacrine significantly counteracted chronic stress-induced depression-like disorders and abnormal 5-hydroxytryptamine (5-HT) metabolism with less central excitability. Further investigation from both in vivo and in vitro experiments indicated that the antidepressant mechanism of theacrine was associated with promoting adult hippocampal neurogenesis, via the modulation of the phosphodiesterase-4 (PDE4)/cyclic adenosine monophosphate (cAMP)/cAMP response-element binding (CREB)/brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway. Collectively, our findings could promote the prevalence of kucha as a common beverage with uses for health care and contribute to the development of theacrine as a potential novel antidepressant medicine.

8.
Biomed Pharmacother ; 140: 111692, 2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-34004511

RESUMO

Piezo-type mechanosensitive ion channel component 1 (Piezo1) is a mechanosensitive ion channel protein that is evolutionarily conserved and multifunctional. It plays an important role as an oncogenic mediator in several malignant tumors. It mediates the proliferation, migration, and invasion of a variety of cancer cells through various mechanisms. Multiple studies have shown that the expression of Piezo1 is related to the clinical characteristics of senescence and cancer patients, making Piezo1 useful as a new biomarker for the diagnosis and prognosis of a variety of human cancers. Manipulating the expression or function of Piezo1 is a potential therapeutic strategy for different diseases. Piezo1 may be a promising tumor biomarker and therapeutic target. Here we review the biological function, mechanism of action, and potential clinical significance of Piezo1 in oncogenesis and progression.

9.
Transl Oncol ; 14(8): 101127, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34020370

RESUMO

PURPOSE: To develop a nomogram for predicting the prognosis of T1 esophageal squamous cell carcinoma (ESCC) patients with positive lymph node. METHODS: T1 ESCC patients with lymph node metastasis diagnosed between 2010 and 2015 were selected from the Surveillance, Epidemiology, and Final Results (SEER) database. The entire cohort was randomly divided in the ratio of 7:3 into a training group (n=457) and validation group (n=192), respectively. Prognostic factors were identified by univariate and multivariate Cox regression models. Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve were used to evaluate the discrimination and calibration of the nomogram. The accuracy and clinical net benefit of the nomogram compared with the 7th AJCC staging system were evaluated using net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). RESULTS: The nomogram consisted of eight factors: insurance, T stage, summary stage, primary site, radiation code, chemotherapy, surgery, and radiation sequence with surgery. In the training and validation cohorts, the AUCs exceeded 0.700, and the C-index scores were 0.749 and 0.751, respectively, indicating that the nomogram had good discrimination. The consistency between the survival probability predicted by the nomogram and the actual observed probability was indicated by the calibration curve in the training and validation cohorts. For NRI>0 and IDI>0, the predictive power of the nomogram was more accurate than that of the 7th AJCC staging system. Furthermore, the DCA curve indicated that the nomogram achieved better clinical utility than the traditional system. CONCLUSIONS: Unlike the 7th AJCC staging system, the developed and validated nomogram can help clinical staff to more accurately, personally and comprehensively predict the 1-year and 3-year OS probability of T1 ESCC patients with lymph node metastasis.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34013735

RESUMO

Thermally activated delayed fluorescence (TADF) emitters have aroused considerable attention, particularly for their great potential in organic light-emitting diodes (OLEDs). In typical TADF molecules, intramolecular charge transfer (CT) between electron-donor (D) and electron-acceptor (A) moieties is the dominant transition. Actually, CT transitions can possibly occur between different molecules as well. Herein, we used a nonconjugated triptycene (TPE) moiety to space D and A moieties and developed two novel emitters tBuDMAC-TPE-TRZ and tBuDMAC-TPE-TTR to explore the roles of intra- and intermolecular CT transitions. Along with weak intramolecular CT transitions, intermolecular CT transitions are dominant for tBuDMAC-TPE-TRZ and tBuDMAC-TPE-TTR neat films. Particularly, tBuDMAC-TPE-TRZ showed a high maximum external quantum efficiency of 10.0% in a nondoped solution-processed OLED, which was evidently higher than that of a corresponding 10 wt % tBuDMAC-TPE-TRZ-doped OLED with 4,4',4″-tris(carbazol-9-yl)triphenylamine (TCTA) as the host matrix. The results prove that intermolecular CT transitions indeed participate in the CT transition process in these systems and they are helpful to enhance the electroluminescence performance of emitting systems with weak intramolecular CT transitions.

11.
Adv Sci (Weinh) ; : e2100503, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34014610

RESUMO

Great success in 2D van der Waals (vdW) heterostructures based photodetectors is obtained owing to the unique electronic and optoelectronic properties of 2D materials. Performance of photodetectors based 2D vdW heterojunctions at atomic scale is more sensitive to the nanointerface of the heterojunction than conventional bulk heterojunction. Here, a nanoengineered heterostructure for the first-time demonstration of a nanointerface using an inserted graphene layer between black phosphorus (BP) and InSe which inhibits interlayer recombination and greatly improves photodetection performances is presented. In addition, a transition of the transport characteristics of the device is induced by graphene, from diffusion motion of minority carriers to drift motion of majority carriers. These two reasons together with an internal photoemission effect make the BP/G/InSe-based photodetector have ultrahigh specific detectivity at room temperature. The results demonstrate that high-performance vdW heterostructure photodetectors can be achieved through simple structural manipulation of the heterojunction interface on nanoscale.

12.
Ecotoxicol Environ Saf ; 218: 112289, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33940442

RESUMO

Perfluoroalkyl substances (PFASs) in source water is of growing concern for its adverse effects on human health and wildlife as well. The Yangtze River is the vital drinking water source in Jiangsu Province of China, but little attention has been paid on PFASs. The occurrence, spatial distribution and temporal trend of PFASs in 21 water sources along the Jiangsu section of the Yangtze River was investigated with sampling from 2018 to 2020. Moreover, health risk of PFASs was assessed by estimated intake dose and derived tolerable intake dose, while ecological risk was assessed by selected effect concentration and environmental exposure. PFASs concentrations in source water ranged from 12.0 to 128 ng/L, with perfluorooctanoic acid (PFOA) as the dominated congener. Fluorine chemical industry lead to a great increase of perfluorohexanoic acid (PFHxA) in its nearest water source. The estimated daily intake of PFASs through drinking was 0.54 and 0.82 ng/kg bw/day for adults and children. The major health risk was from perfluorooctane sulfonate (PFOS) and PFOA for their toxicity on liver, reproduction, development and immunity, with the maximum hazard quotient of 0.029 and 0.043 for adults and children in the worst scenario. The ecological risks from PFASs on nine species groups ranged from 2.7 × 10-10 to 5.2. PFOA and Perfluorobutane sulfonate (PFBS) were causing significant risk on wildlife, particularly on worms, mussels, and fish, which may further influence the structure and processes in the foodweb. Overall, PFASs, especially PFOS, PFOA and PFBS, induced considerable risk on human health and aquatic species in some hotspot area. It would be necessary to include them into monitoring in China and develop standards for different protection purposes.

13.
J Immunother Cancer ; 9(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34006632

RESUMO

BACKGROUND: Immunotherapies may prolong the survival of patients with small-cell lung cancer (SCLC) to some extent. The role of forkhead box protein P3 (FOXP3) in tumor microenvironment (TME) remains controversial. We aimed to examine FOXP3-related expression characteristics and prognostic values and to develop a clinically relevant predictive system for SCLC. METHODS: We enrolled 102 patients with histologically confirmed SCLC at stages I-III. Through immunohistochemistry, we determined the expression pattern of FOXP3 and its association with other immune biomarkers. By machine learning and statistical analysis, we constructed effective immune risk score models. Furthermore, we examined FOXP3-related enrichment pathways and TME traits in distinct cohorts. RESULTS: In SCLC, FOXP3 level was significantly associated with status of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), CD4, CD8, and CD3 (p=0.002, p=0.001, p=0.002, p=0.030, and p<0.001). High FOXP3 expression showed longer relapse-free survival (RFS) than the low-level group (41.200 months, 95% CI 26.937 to 55.463, vs 14.000 months, 95% CI 8.133 to 19.867; p=0.008). For tumor-infiltrating lymphocytes (TILs), subgroup analysis demonstrated FOXP3 and PD-1, PD-L1, lymphocyte activation gene-3, CD3, CD4, or CD8 double positive were significantly correlated with longer RFS. We further performed importance evaluation for immune biomarkers, constructed an immune risk score incorporating the top three important biomarkers, FOXP3, TIL PD-L1, and CD8, and found their independently prognostic role to predict SCLC relapse. Better predictive performance was achieved in this immune risk model compared with single-indicator-based or two-indicator-based prediction systems (area under the curve 0.715 vs 0.312-0.711). Then, relapse prediction system integrating clinical staging and immune risk score was established, which performed well in different cohorts. High FOXP3-related genes were enriched in several immune-related pathways, and the close relationships of interleukin-2, CD28, basic excision repair genes MUTYH, POLD1, POLD2, and oxidative phosphorylation related gene cytochrome c oxidase subunit 8A with FOXP3 expression were revealed. Moreover, we found low-immune risk score group had statistically higher activated CD4+ memory T cells (p=0.014) and plasma cells (p=0.049) than the high-risk group. The heterogeneity of tumor-infiltrating immune cells might represent a promising feature for risk prediction in SCLC. CONCLUSION: FOXP3 interacts closely with immune biomarkers on tumor-infiltrating cells in TME. This study highlighted the crucial prognostic value and promising clinical applications of FOXP3 in SCLC.

14.
Nat Commun ; 12(1): 2540, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953163

RESUMO

Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. To map the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyze 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and present the large scale, single cell resolution profiles of advanced NSCLCs. In addition to cell types described in previous single cell studies of early stage lung cancer, we are able to identify rare cell types in tumors such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also reveals a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Microambiente Tumoral/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Células Epiteliais , Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Humanos , Pulmão/patologia , Células Th17 , Transcriptoma
15.
Med Sci Monit Basic Res ; 27: e930887, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33972493

RESUMO

BACKGROUND The aim of this study was to determine the effect of kangfuxin liquid (KFXL) on inflammatory response, and its underlying mechanism in treating acute ulcerative colitis (UC) in mice induced by dextran sulfate sodium (DSS). MATERIAL AND METHODS Mice were provided drinking water containing DSS (3%) for 7 days to induce acute enteritis. The mice were divided into 6 groups: a control group, a DSS-induced (vehicle) group, a sulfasalazine (SASP) group, and low-, medium-, and high-dose kangfuxin liquid groups. Disease activity index (DAI), colon mucosa damage index (CMDI), histopathological score (HS), and organ index were monitored daily. The levels of interleukin-1ß (IL-1ß), interleukin-10 (IL-10) in serum and interleukin-17 (IL-17) and epidermal growth factor (EGF) in colon tissue were assessed by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to assess the changes of T lymphocyte subsets in spleens of mice to evaluate the therapeutic effect of drugs on acute UC in mice. RESULTS Different doses of kangfuxin liquid reduced the DAI, CMDI, and HS scores (P<0.01 or P<0.05) of acute UC mice, reduced the level of IL-1ß and IL-17 in serum, increased the expression of IL-10 in serum and EGF in colon tissue, increased the number of CD3⁺ T cells, and decreased the level of CD4⁺ T cells and the ratio of CD4⁺/CD8⁺. CONCLUSIONS Kangfuxin liquid has a therapeutic effect on DSS-induced acute UC in mice, and its mechanism of action may be associated with regulating immune function and reducing intestinal inflammatory response.

16.
Int J Med Sci ; 18(11): 2251-2261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967600

RESUMO

Colorectal cancer (CRC) is a worldwide health problem. Glucose-regulated protein 94 (GRP94) is known as an important endoplasmic reticulum-stress response protein that shows correlation with aggressive cancer behavior. However, the role of GRP94 in CRC is still unclear. Our results showed that silencing GRP94 (GRP94-KD) reduced cell proliferation, invasion and migration of CRC cells and suppressed tumorigenesis in the xenograft mouse model. Rescue assay showed that ETV1 overexpression reversed the effect of GRP94 on cell proliferation and migration. In the molecular mechanism, we found that knockdown of GRP94 inhibited the level of MAPK pathway, including ERK/p-ERK, JNK/p-JNK, and p38/p-p38 signals. Cyclooxygenase-2 and epithelial-mesenchymal transformation biomarkers, such as N-cadherin, vimentin, and ß-catenin were suppressed in GRP94 knockdown cells. Treatment of specific inhibitors of MAPK pathway showed that ERK/p-ERK, and p38/p-p38 inhibitors significantly influenced ETV1 expression as compared to JNK/p-JNK inhibitor. Our results indicated that silencing GRP94 repressed the ability of EMT process, cancer cell proliferation, metastasis, and CRC tumorigenesis. Therefore, GRP94 may play an important role in CRC by regulating ETV1 and MAPK pathway.

17.
Immunol Res ; 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33988814

RESUMO

The p38 mitogen-activated protein kinase (MAPK) pathway is an important intracellular signalling pathway that leads to increased expression of pro-inflammatory mediators. Our previous studies have shown that the p38 MAPK pathway was changed in the acute renal injury (ARI) in acute pancreatitis in late pregnancy (APIP), whereas the role of p38 MAPK in APIP-induced ARI has been poorly understood. The present study was undertaken to investigate the participation of the p38 MAPK signalling pathway and the protective effect of SB203580, an inhibitor of p38 MAPK in ARI in APIP. Twenty-four late-gestation SD rats were randomly assigned to four groups: the normal group (N), sham-operated group (SO), acute necrotizing pancreatitis (ANP) group, and p38 MAPK inhibitor (SB203580) treatment group (T). The results showed that serum amylase, lipase, urea, and creatinine levels of p38 inhibitor of T groups were markedly lower than the ANP groups. Additionally, the expression of phosphorylated p38 and myeloperoxidase (MPO), tumour necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, nuclear factor kappa-B (NF-κB), caspase-3, and terminal deoxynucleotidyl TUNEL-positive cells was markedly lower in the T group than in the ANP group. Our results suggest that SB203580 can inhibit renal injury by inhibiting the P38 MAPK signalling pathway and blocking the inflammatory responses in APIP.

18.
Chem Biol Interact ; 344: 109529, 2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34029542

RESUMO

Ganoderic acid A (GAA), one of the major triterpenoid components extracted from Ganoderma mushroom has been shown to possess numerous important pharmacological activities. The present study was aimed to investigate the mechanisms of GAA on carbon tetrachloride (CCl4)-induced kidney inflammation, fibrosis and oxidative stress in mice. The male mice were treated with 25 and 50 mg/mg GAA after stimulated with CCl4. Our results showed that GAA improved renal damage by decreasing the serum levels of creatinine, urea, uric acid and alleviating kidney fibrosis. GAA ameliorated CCl4-induced indices of inflammation. GAA suppressed oxidative stress by regulating the glutathione antioxidant system and the thioredoxin antioxidant system. GAA increased the activations of thioredoxin reductase (TrxR), Trx, GSH, SOD, GPx. Furthermore, GAA supplementation inhibited the JAK and STAT3 pathway. GAA inhibited the activations of RhoA, ROCK, NF-κB, TGF-ß and Smad3. Thus, this study demonstrated that GAA possesses immune-protective properties through regulating the Trx/TrxR, JAK2/STAT3 and RhoA/ROCK pathways.

19.
Stem Cell Res Ther ; 12(1): 307, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051865

RESUMO

BACKGROUND: The stem cells of the stem cell banks have prominent problems for insufficient sources, easy contamination, unstable biological characteristics after serial subcultivations, and high cost. METHODS: After collecting the construction processes of the existing stem cell banks and suggestions from authoritative experts in the past 10 years, 230 reference principles were obtained, and finally, the principles of "5C" for the establishment of modern standardized stem cell banks were summarized, and their related applications on the management of sports injuries were reviewed as well. RESULTS: The basic principles of "5C" for the establishment of modern standardized stem cell banks include (1) principle of informed consent, (2) confidentiality principle, (3) conformity principle, (4) contamination-free principle, and (5) commonweal principle. The applications of stem cells on repairs, reconstructions, and regenerations of sports injuries were also reviewed, especially in tissue-engineered cartilage, tissue-engineered meniscus, and tissue-engineered ligament. CONCLUSIONS: The proposal of the basic principles of "5C" is conducive to relevant stem cell researchers and clinical medical experts to build modern stem cell banks in a more standardized and efficient manner while avoiding some major mistakes or problems that may occur in the future. On this basis, stem cells from stem cell banks would be increasingly used in the management of sports injuries. More importantly, these days, getting stem cell samples are difficult in a short time, and such banks with proper legal consent may help the scientific community.

20.
Biomed Res Int ; 2021: 6699910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937412

RESUMO

Cartilage injury of the knee joint is very common. Due to the limited self-healing ability of articular cartilage, osteoarthritis is very likely to occur if left untreated. Bone marrow mesenchymal stem cells (BMMSCs) are widely used in the study of cartilage injury due to their low immunity and good amplification ability, but they still have disadvantages, such as heterogeneous undifferentiated cells. MicroRNAs can regulate the chondrogenic differentiation ability of MSCs by inhibiting or promoting mRNA translation and degradation. In this research, we primarily investigated the effect of microRNA-210-3p (miR-210-3p) on chondrogenic and adipogenic differentiation of BMMSCs in vitro. Our results demonstrate that miR-210-3p promoted chondrogenic differentiation and inhibited adipogenic differentiation of rat BMMSCs, which was related to the HIF-3α signalling pathway. Additionally, miR-210-3p promotes mRNA and protein levels of the chondrogenic expression genes COLII and SOX9 and inhibits mRNA and protein levels of the adipogenic expression genes PPARγ and LPL. Thus, miR-210-3p combined with BMMSCs is a candidate for future clinical applications in cartilage regeneration and could represent a promising new therapeutic target for OA.


Assuntos
Adipogenia/genética , Condrogênese/genética , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Masculino , MicroRNAs/genética , Modelos Biológicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Fatores de Transcrição/genética
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