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1.
Anim Genet ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34807998

RESUMO

miRNAs are a class of hairpin-derived RNAs, 21-24 nucleotides in length, which are involved in a range of biological processes. The bta-miR-2285 family has over 40 members spanning the entire bovine genome. We previously found that bta-miR-2285o-3p was highly expressed in yak heart and lung when compared with cattle, which prompted us to investigate its potential function in high-altitude adaptation of yaks. In this study, we detected wide-spread high expression of bta-miR-2285o-3p in yak tissues. Further experiments revealed that the protein tyrosine phosphatase receptor type M (PTPRM) gene was the host gene of bta-miR-2285o-3p and that two linked SNPs in bta-mir-2285o precursor affected the biogenesis of mature miRNA (bta-miR-2285o-3p). Functional analysis in vitro indicated that bta-miR-2285o-3p attenuated hypoxia-induced apoptosis by targeting very low-density lipoprotein receptor (VLDLR), phosphatase and tensin homolog (PTEN) and caspase-3. Expression level analysis in vivo revealed the high negative Pearson's correlation between bta-miR-2285o-3p and caspase3 in yak, highlighting the potential important roles of bta-miR-2285o-3p in yak high-altitude adaptation. Our study provides a typical model for deciphering the function of miRNAs in environmental adaptation.

2.
Zhonghua Xue Ye Xue Za Zhi ; 42(10): 807-813, 2021 Oct 14.
Artigo em Chinês | MEDLINE | ID: mdl-34788919

RESUMO

Objective: To elucidate the clinical characteristics of bloodstream infection in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in our hospital and improves the survival of transplant patients with bloodstream infection. Methods: Two hundred and ten patients with allo-HSCT from the Department of Hematology were retrospectively analyzed between October 2014 and September 2019. Pathogen distribution, drug resistance, risk factors, and outcomes were investigated in 49 allo-HSCT patients with bloodstream infections. Results: Forty-nine of 210 patients with allo-HSCT had bloodstream infection, and 59 pathogenic microorganisms were identified, mainly Gram-negative bacteria (67.8%) , of which E. coli had the highest incidence (23.7%) , CRO accounted for 42.5%, and Grampositive bacteria accounted for 23.7% (without vancomycin or linezolid-resistant strain) . Additionally, fungi accounted for 8.5%. Univariate analysis suggested that the risk factors of bloodstream infection were gender, pretransplant disease status, and conditioning regimen. In contrast, multivariate analysis showed that bloodstream infection was mainly related to conditioning regimens. Further grouping results showed that 77.6% of patients with neutropenia had bloodstream infections, and 22.4% of patients with non-neutropenia had bloodstream infections; 81.0% of patients with active infections before transplantation had bloodstream infections, while bloodstream infection occurred in 16.9% of patients without active infection. Survival analysis showed that long-term survival of patients with bloodstream infection is shorter than that of patients without bloodstream infection and long-term survival of patients with CRO infection is shorter than that of patients without CRO infection. The survival of patients with neutropenia longer than 14 d is shorter than that of patients with neutropenia shorter than 14 d. Furthermore, there is no correlation between whether there is an active infection before transplantation and whether they are in a neutropenic state at the time of infection and survival. Conclusion: Our results suggest that effective prevention of bloodstream infections from drug-resistant bacteria, particularly CRO, shortening the duration of neutropenia, eradication of potential infections before transplantation, and patient-adaptive conditioning could reduce transplant-related mortality and improve prognosis.


Assuntos
Bacteriemia , Transplante de Células-Tronco Hematopoéticas , Sepse , Bactérias , Resistência a Medicamentos , Escherichia coli , Humanos , Estudos Retrospectivos , Fatores de Risco
4.
Zhonghua Fu Chan Ke Za Zhi ; 56(8): 545-553, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34420286

RESUMO

Objective: To study the risk factors of adverse pregnancy outcomes for induced abortion of cesarean scar pregnancy in midtrimester. Methods: A national multicenter retrospective study was conducted. A total of 154 singletons pregnant women with cesarean scar pregnancy during the second trimester induced abortion by various reasons in 12 tertiary A hospitals were selected, their pregnant outcomes were observed and the risk factors of serious adverse outcomes were analyzed with univariate and multivariate logstic regression; the role of ultrasound and MRI in predicting placenta accreta and severe adverse outcomes was evaluated, the effectiveness of uterine artery embolization (UAE) in preventing hemorrhage in pregnant women with and without placenta accreta was compared. Results: Among 154 subjects, the rate of placenta accreta was 42.2% (65/154), the rate of postpartum hemorrhage≥1 000 ml was 39.0% (60/154), the rate of hysterectomy was 14.9% (23/154), the rate of uterine rupture was 0.6% (1/154). The risk factor of postpartum hemorrhage≥1 000 ml and hysterectomy was placenta accreta (P<0.01). For each increase in the number of parity, the risk of placenta accreta increased 2.385 times (95%CI: 1.046-5.439; P=0.039); and the risk of placenta accreta decreased with increasing ultrasound measurement of scar myometrium thickness (OR=0.033, 95%CI: 0.001-0.762; P=0.033). The amount of postpartum hemorrhage and hysterectomy rate in the group with placenta accreta diagnosed by ultrasound combined with MRI were not significantly different from those in the group with placenta accreta diagnosed by ultrasound only or MRI only (all P>0.05). For pregnant women with placenta accreta, there were no significant difference in the amount of bleeding and hysterectomy rate between the UAE group [median: 1 300 ml; 34% (16/47)] and the non-embolization group (all P>0.05); in pregnant women without placenta accreta, the amount of bleeding in the UAE group was lower than that in the non-embolization group (median: 100 vs 600 ml; P<0.01), but there was no significant difference in hysterectomy rate [2% (1/56) vs 9% (3/33); P>0.05]. Conclusions: (1) Placenta accreta is the only risk factor of postpartum hemorrhage≥1 000 ml with hysterectomy for induced abortion of cesarean scar pregnancy in midtrimester; multi-parity and ultrasound measurement of scar myometrium thickness are risk factors for placenta accreta. (2) The technique of using ultrasound and MRI in predicting placenta accreta of cesarean scar pregnancy needs to be improved. (3) It is necessary to discuss of UAE in preventing postpartum hemorrhage for induced abortion of cesarean scar pregnancy in midtrimester.


Assuntos
Placenta Acreta , Embolização da Artéria Uterina , Cicatriz , Feminino , Humanos , Placenta Acreta/diagnóstico por imagem , Placenta Acreta/epidemiologia , Gravidez , Segundo Trimestre da Gravidez , Estudos Retrospectivos
5.
Toxicol Appl Pharmacol ; 426: 115647, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34271065

RESUMO

Acrolein, an electrophilic α,ß-unsaturated aldehyde, is present in foods and beverages, and is a product of incomplete combustion, and thus, reaches high ppm levels in tobacco smoke and structural fires. Exposure to acrolein is linked with cardiopulmonary toxicity and cardiovascular disease risk. The hypothesis of this study is the direct effects of acrolein in isolated murine blood vessels (aorta and superior mesenteric artery, SMA) are transient receptor potential ankyrin-1 (TRPA1) dependent. Using isometric myography, isolated aorta and SMA were exposed to increasing levels of acrolein. Acrolein inhibited phenylephrine (PE)-induced contractions (approximately 90%) in aorta and SMA of male and female mice in a concentration-dependent (0.01-100 µM) manner. The major metabolite of acrolein, 3-hydroxypropylmercapturic acid (3HPMA), also relaxed PE-precontracted SMA. As the SMA was 20× more sensitive to acrolein than aorta (SMA EC50 0.8 ± 0.2 µM; aorta EC50 > 29.4 ± 4.4 µM), the mechanisms of acrolein-induced relaxation were studied in SMA. The potency of acrolein-induced relaxation was inhibited significantly by: 1) mechanically-impaired endothelium; 2) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME); 3) guanylyl cyclase (GC) inhibitor (ODQ); and, 4) a TRPA1 antagonist (A967079). TRPA1 positive immunofluorescence was present in the endothelium. Compared with other known TRPA1 agonists, including allyl isothiocyanate (AITC), cinnamaldehyde, crotonaldehyde, and formaldehyde, acrolein stimulated a more potent TRPA1-dependent relaxation. Acrolein, at high concentration [100 µM], induced tension oscillations (spasms) independent of TRPA1 in precontracted SMA but not in aorta. In conclusion, acrolein is vasorelaxant at low levels (physiological) yet vasotoxic at high levels (toxicological).


Assuntos
Acetilcisteína/análogos & derivados , Acroleína/farmacologia , Aorta Torácica/efeitos dos fármacos , Artéria Mesentérica Superior/efeitos dos fármacos , Canal de Cátion TRPA1/fisiologia , Acetilcisteína/sangue , Acetilcisteína/farmacologia , Acroleína/sangue , Animais , Aorta Torácica/fisiologia , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/fisiologia , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/fisiologia , Masculino , Artéria Mesentérica Superior/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Canal de Cátion TRPA1/genética
7.
Zhonghua Fu Chan Ke Za Zhi ; 56(6): 393-400, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34154314

RESUMO

Objective: To identify the factors associated with long-term survival and guide the decision for primary surgery in patients with advanced high-grade serous ovarian cancer(HGSOC). Methods: In this case-control study, clinical parameters, including surgical and non-surgical associated factors, were collected and compared between the patients with short-term (<2 years) and long-term (>5 years) survival who all underwent primary debulking surgery (PDS) followed by carboplatin and paclitaxel chemotherapy from January 2004 to December 2016. Univariate analysis was examined by chi-square test and multivariate analysis was performed by logistic regression analysis. Results: There were 95 cases long-term survival (LTS group) and 77 cases short-term survival (STS group) in 698 newly diagnosed HGSOC patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅲc and Ⅳ who met include and exclude criteria. (1) Univariate analysis showed that the proportion of complete cytoreduction with no visible residual disease (R0) at PDS and platinum sensitivity in LTS group were significantly higher than those in STS group (P<0.01). The surgical complexity score (SCS), the preoperative serum CA125 level and the ascites volume in the LTS group were significantly lower than those of the STS group (all P<0.05). In the LTS group, the preoperative incidence of lesions in retrograde peritoneum of the bladder, serosal and mesangial membrane of the small intestine, upper abdominal peritoneum and liver parenchyma were significantly lower than those in the STS group (all P<0.05). Multivariate logistic regression analysis showed that platinum sensitivity (OR=0.016, 95%CI: 0.004-0.063, P<0.01), ascites volume >500 ml (OR=3.193, 95%CI: 1.285-7.930, P=0.012), and SCS ≥8 (OR=17.433, 95%CI: 2.281-133.25, P=0.003) were independent factors affecting long-term survival (P>0.05). (2) Totally 37 of 95 in long-term survival and 16 of 77 in short-term survival achieved R0 cytoreduction at PDS. Univariate analysis showed that preoperative serum CA125 level, preoperative lesion score, preoperative lesion (DS) score, ascites volume, platinum sensitivity,and SCS were significantly correlated with the R0 PDS (all P<0.05). Multivariate analysis showed that ascites volume >500 ml (OR=5.199, 95%CI: 2.015-13.409, P=0.001), DS >2 (OR=15.264, 95%CI: 5.843-39.874, P<0.01) and SCS ≥4 (OR=4.176, 95%CI: 1.618-10.777, P=0.003) were independent factors associated with R0 cytoreduction. In patients with DS ≤2 or SCS <4, but not those with DS >2 or SCS ≥4, R0 cytoreduction was significantly associated with long-term survival. Conclusion: The intrinsic biology of tumor is the factor influencing long-term survival of advanced HGSOC patients, and those who present with wide intraperitoneal metastases and need to remove multiple organs may not benefit from R0 cytoreduction.


Assuntos
Neoplasias Ovarianas , Carboplatina , Estudos de Casos e Controles , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Paclitaxel , Estudos Retrospectivos
8.
Hum Reprod ; 36(6): 1691-1701, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-33860322

RESUMO

STUDY QUESTION: What is the true incidence of chromosomal mosaicism in embryos analyzed by preimplantation genetic testing (PGT). SUMMARY ANSWER: The true incidence of chromosomal mosaicism is much lower than we usually surmise. WHAT IS KNOWN ALREADY: In recent years, contemporary methods for chromosome analysis, along with the biopsy of more than one cell, have given rise to an increased rate of chromosomal mosaicism detection after preimplantation genetic testing for aneuploidy. However, the exorbitant incidence of mosaicism represents a dilemma and imposes restrictions on the application of PGT treatment. Concern has been raised about the possibility that the incidence of chromosomal mosaicism is overestimated and quite a few of the results are false-positive errors. However, studies verifying the diagnosis of chromosomal mosaicism and assessing the true incidence of chromosomal mosaicism are limited. STUDY DESIGN, SIZE, DURATION: A total of 1719 blastocysts from 380 patients who underwent PGT treatment were retrospectively analyzed to evaluate the typical incidence of mosaicism. Then 101 embryos donated by 70 couples were re-biopsied and dissected into three portions if available: trophectoderm (TE), inner cell mass (ICM), and the remaining portions. All the portions were tested using next-generation sequencing (NGS), and the results were compared to the original diagnosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: The setting for this study was a university-affiliated center with an in-house PGT laboratory. All samples were amplified with multiple annealing and looping-based amplification cycles (MALBACs) and the NGS was carried out on a Life Technologies Ion Proton platform. MAIN RESULTS AND THE ROLE OF CHANCE: A clinical TE biopsy revealed an incidence of 11.9% for diploid-aneuploid mosaicism (DAM), 17.3% for aneuploid mosaicism (AM) and 29.1% in total. After rebiopsy, 94.1% whole-chromosome aneuploidies and 82.8% segmental-chromosome aneuploidies were confirmed in the embryos. As for the mosaic errors, only 32 (31.7%) out of 101 embryos presented with uniform chromosomal aberrations in agreement with the original biopsy results, 15 (14.8%) embryos presented with de novo chromosomal aberrations, and 54 (53.5%) embryos showed a euploid profile in all portions. Among the 32 uniform embryos, the true mosaicism was confirmed in only 4 cases, where a reciprocal chromosomal aberration was identified; 14 embryos presented with identical mosaicism, providing the moderate evidence for true mosaicism; and 14 embryos displayed uniform full aneuploidies in all portions of embryo, revealing a high-grade mosaicism or a false-negative diagnosis. Logistical regression analysis revealed that the concordance rate with ICM was associated with the type and level of mosaicism. The concordance rate of segmental-chromosome mosaicism was significantly lower than whole-chromosome mosaicism (adjusted Odds Ratio (aOR): 5.137 (1.061, 24.876), P = 0.042) and compared to DAM, the concordance rate of AM was significantly higher (aOR: 6.546 (1.354, 31.655), P = 0.019). The concordance rate also increased with increasing levels of mosaicism (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: This study was limited by a small sample size and the use of a single whole-genome amplification (WGA) method and NGS platform. These findings are only applicable to samples subjected to MALBAC amplification and Ion Proton platform, and studies involving larger sample sizes and multiple WGA methods and NGS platforms are required to prove our findings. WIDER IMPLICATIONS OF THE FINDINGS: TE biopsy is reliable to detect whole-chromosome aneuploidies, but the ability to diagnose mosaicism is doubtful. More attention should be paid to false-positive and false-negative errors in NGS-based PGT, especially for laboratories using less stringent criteria for mosaicism classification (i.e. 20-80%), which might be subject to a much higher false-positive mosaicism rate in the practice. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key R&D Program of China (No. 2016YFC1000206-5) and the National Natural Science Foundation of China (No. 81701509). TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Diagnóstico Pré-Implantação , Aneuploidia , Biópsia , Blastocisto , China , Feminino , Testes Genéticos , Humanos , Incidência , Mosaicismo , Gravidez , Estudos Retrospectivos
9.
J Endocrinol Invest ; 44(12): 2645-2654, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33860453

RESUMO

PURPOSE: Whether Tsukushi (TSK) can protect against high-fat diet (HFD)-induced obesity and improve glucose metabolism remains controversial. Serum levels of TSK in the population have not been reported until now. We assessed the association among TSK level, TSKU genotype, and metabolic traits in humans. METHODS: Associations between serum TSK levels and metabolic traits were assessed in 144 Han Chinese individuals. Loci in the TSKU gene region were further genotyped in 11,022 individuals. The association between the loci and serum TSK level was evaluated using the additive genetic model. The association between the loci and their metabolic traits in humans were also verified. RESULTS: Lower TSK levels were observed in obese subjects than in control subjects (median and interquartile range 17.78:12.07-23.28 vs. 23.81:12.54-34.56, P < 0.05). However, in obese subjects, TSK was positively associated with BMI (ß ± SE: 0.63 ± 0.31, P = 0.049), visceral fat area (ß ± SE: 12.15 ± 5.94, P = 0.011), and deterioration of glucose metabolism. We found that rs11236956 was associated with TSK level in obese subjects (ß 95% CI 0.17, 0.07-0.26; P = 0.0007). There was also a significant association between rs11236956 and metabolic traits in our population. CONCLUSIONS: Our findings showed that serum TSK levels were associated with metabolic disorders in obese subjects. We also identified rs11236956 to be associated with serum TSK levels in obese subjects and with metabolic disorders in the total population.

10.
Zhonghua Yu Fang Yi Xue Za Zhi ; 55(3): 346-352, 2021 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-33730826

RESUMO

Objective: To analyze the results of liver cancer screening for urban residents in Zhejiang Province from 2013 to 2018 and explore the influencing factors of the detection rate. Methods: From September 2013 to August 2019, six urban communities in Hangzhou (Jianggan District and Gongshu District), Ningbo (Haishu District, Yinzhou District and Jiangbei District), and Quzhou (Kecheng District) were selected as study sites. All permanent residents aged 40-74 (with local household registration and living in the local area for more than 3 years) were selected as the research subjects by using cluster sampling method. Patients with confirmed cancers and other serious medical and surgical diseases were excluded. A total of 166 293 research subjects were included. Basic demographic characteristics and risk factors of subjects were obtained through questionnaire surveys. The cancer risk assessment system was used to evaluate the liver cancer risk of subjects. Clinical screening participation and screening results for subjects at high risk of liver cancer were obtained from participating hospitals. The high-risk rate of liver cancer, clinical screening rate, detection rate of positive lesions, and detection rate of suspected liver cancer were analyzed. Poisson regression was used to analyze the influencing factors of detection rate. Results: The age of 166 293 subjects was (56.01±8.40) years, of which 41.36% (68 777) were males. A total of 23 765 high-risk subjects for liver cancer were screened (the high-risk rate was 14.29%). Among them, a total of 12 375 subjects participated in clinical screening for liver cancer, with a screening rate of 52.07% (12 375/23 765). A total of 297 cases of positive lesions were detected and the detection rate was 2.40% (297/12 375). A total of 8 cases of suspected liver cancer were detected, with a detection rate of 0.06% (8/12 375). The results of multivariate Poisson regression model analysis showed that compared with men, people who never smoked, never ate pickled food, had low oil content, and had no history of hepatobiliary disease, female, people who were smoking or had smoked, sometimes ate pickled food, ate higher oil content, and had a history of hepatobiliary disease had a higher detection rate of positive lesions. The incidence rate ratio (IRR) (95%CI) values were 1.98 (1.45-2.70), 2.23 (1.61-3.09)/2.08 (1.31-3.28), 1.82 (1.22-2.70), 1.44 (1.08-1.91), and 1.45 (1.05-2.00), respectively. Compared with those aged from 40 to 49 years old and without HBsAg test, the IRR (95%CI) of suspected liver cancer in people aged 70 to 74 years old and HBsAg positive were 16.30 (1.32-200.74) and 6.43 (1.24-33.22), respectively. Conclusion: The urban cancer early diagnosis and early treatment project in Zhejiang Province has good compliance in clinical screening of liver cancer. Abdominal ultrasound examination and serum alpha-fetoprotein detection are helpful to detect liver cancer and its precancerous lesions in the high-risk population of liver cancer.


Assuntos
Detecção Precoce de Câncer , Neoplasias Hepáticas , Adulto , Idoso , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Fatores de Risco , População Urbana
11.
Eur Rev Med Pharmacol Sci ; 25(3): 1600-1611, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33629329

RESUMO

OBJECTIVE: In a previous study, we reported that transplantation of bone mesenchymal stem cells (BMSCs) significantly attenuated liver damage in a mouse autoimmune hepatitis (AIH) model. Moreover, expression of the LIM domain protein, LMO7, correlated positively with the invasive capacity of hepatoma cells. However, whether LMO7 plays a role in inflammation and fibrosis of AIH remains unknown. This investigation aimed to explore the effect of BMSC transplantation on LMO7 and the role of LMO7 in hepatic fibrosis. MATERIALS AND METHODS: S100-induced murine AIH and LPS-induced hepatocyte injury models were successfully established. Three doses of BMSCs were injected into AIH mice via the tail vein. LPS-treated AML12 cells were co-cultured with BMSCs in vitro. Small interfering (si) LMO7 RNA and T5224 (a specific inhibitor of AP-1) were used to demonstrate the relationship between LMO7-AP1-transforming growth factor (TGF)-ß. RESULTS: Pathological examination and serum alanine and aspartate aminotransferase levels indicated that liver damage was notably ameliorated in the BMSC-treated mice. LMO7 level was upregulated, while AP-1 and TGF-ß levels were downregulated upon intervention with BMSCs. AP-1 expression was upregulated in the siLMO7 group, whereas TGF-ß level was downregulated in the T5224 group when compared to those in the control group. CONCLUSIONS: BMSC transplantation significantly limits liver fibrosis and upregulates the expression of LMO7. LMO7 inhibits the TGF-ß pathway by inhibiting AP-1. This implies that BMSCs are a potential means of treating liver fibrosis. This approach has important implications for the treatment of AIH and other fibrotic diseases.


Assuntos
Hepatite Autoimune/metabolismo , Proteínas com Domínio LIM/metabolismo , Cirrose Hepática/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fator de Transcrição AP-1/metabolismo , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Hepatite Autoimune/patologia , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(2): 184-192, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33624590

RESUMO

OBJECTIVE: To investigate the role of the differential piRNA NU13 derived from piwil2-induced cancer stem-like cells (piwil2-iCSCs) in regulating biological behaviors of Wilms tumor cells (G401). OBJECTIVE: The expressions of piRNA NU13 and NOP56 were detected in Wilms tumor cell line G401 using RT-qPCR. G401 cells were transfected with piRNA NU13 mimics and inhibitor for its over-expression and inhibition, and the transfection efficiency was verified with RT-qPCR. The changes in proliferation of G401 cells after transfection were detected using CCK8 assay, and cell apoptosis was analyzed using flow cytometry. Wound healing assay and Transwell assay were performed to examine the changes in migration and invasion abilities of the transfected cells. The binding of NOP56 and piRNA NU13 was detected using dual luciferase experiment. The protein expressions of MMP2, MMP9, BAX, Bcl2, and NOP56 in the cells were detected with Western blotting. OBJECTIVE: RTqPCR showed that the expression of piRNA NU13 decreased significantly in human Wilms tumor G401 cells as compared with that in renal tubular epithelial cell line HK2 (P < 0.05), and NOP56 was highly expressed in G401 cells and Wilms tumor tissues (P < 0.05). Over-expression of piRNA NU13 significantly suppressed the proliferation, migration and invasion of G401 cells, promoted cell apoptosis (P < 0.05), inhibited the expression of MMP2, MMP9 and Bcl2, and enhanced the expression of BAX (P < 0.05). The results of dual luciferase experiment showed that piRNA NU13 did not bind to NOP56 directly but regulated the expression of NOP56 in an indirect manner. OBJECTIVE: piRNA NU13 is down-regulated and NOP56 is highly expressed in Wilms tumor. piNU13 may regulate the expression of NOP56 indirectly to inhibit the proliferation, migration and invasion and promote apoptosis of Wilms tumor cells in vitro.


Assuntos
Neoplasias Renais , MicroRNAs , Tumor de Wilms , Proteínas Argonauta , Movimento Celular , Proliferação de Células , Humanos , Neoplasias Renais/genética , Invasividade Neoplásica , Proteínas Nucleares/metabolismo , RNA Interferente Pequeno/genética , Tumor de Wilms/genética
15.
Mol Ther ; 29(1): 275-290, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33002420

RESUMO

Urothelial carcinoma (UC) is the predominant form of bladder cancer. Significant molecular heterogeneity caused by diverse molecular alterations brings about large variations in the response to treatment in UC. An improved understanding of the genetic mechanisms underlying the development and progression of UC is essential. Through deep analysis of next-generation sequencing data of 99 UC patients, we found that 18% of cases had recurrent somatic mutations in zinc finger protein gene zinc finger protein 83 (ZNF83). ZNF83 mutations were correlated with poor prognosis of UC. We also found a hotspot mutation, p.E293V, in the evolutionarily well-conserved region of ZNF83. ZNF83-E293V increased tumor growth and reduced the apoptosis of UC cells compared to wild-type ZNF83 both in vitro and in mice xenografted tumors. ZNF83-E293V activated nuclear factor κB (NF-κB) more potently than did the wild-type protein owing to its decreased transcriptional repression for S100A8. The NF-κB inhibitors could pharmacologically block the tumor growth in mice engrafted with ZNF83-E293V-transfected UC cells. These findings provide a mechanistic insight and a potential therapeutic strategy for UC, which established a foundation for using the ZNF83-E293V mutation as a predictive biomarker of therapeutic response from NF-κB inhibitors.


Assuntos
Alelos , Calgranulina A/genética , Fatores de Transcrição Kruppel-Like/genética , Mutação , NF-kappa B/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Biomarcadores Tumorais , Calgranulina A/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Transdução de Sinais , Neoplasias da Bexiga Urinária/patologia
16.
Clin Transl Oncol ; 23(7): 1292-1303, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33210236

RESUMO

BACKGROUND: Breast cancer (BRCA) is a malignant cancer that threatened the life of female with unsatisfactory prognosis. The aim of this study was to identify prognostic nuclear receptors (NRs) signature of BRCA. METHODS: BRCA patient samples were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Consensus clustering analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis were performed to evaluate, select NRs as prognostic factors and build Risk Score model. GSEA analysis was explored to check signaling differences between High- and Low-Risk group. Nomogram model basing on age and Risk Score was established to predict the 1-, 3- and 5-year survival. Model performance was assessed by a time-dependent receiver operating characteristic (ROC) curve and calibration plot. CIBERSORT, ESTIMATE and TIMER algorithm were introduced to evaluate the immune landscape. RESULTS: NR3C1, NR4A3, THRA, RXRG, NR2F6, NR1D2 and RORB were optimized as a prognostic signature for BRCA. This seven-NR-based Risk Score could effectively predict overall survival status. The area under the curve (AUC) of 1-, 3- and 5-year overall survival are 0.702, 0.734 and 0.722 in TCGA training cohort, and 0.630, 0.721 and 0.823 in GEO validation cohort, respectively. Calibration plot demonstrated satisfactory agreement between predictive and observed outcomes. Nomogram model worked well on predicting survival probabilities. Multiple cancer-related pathways were highly enriched in High-Risk group. High- and Low-Risk groups showed significant differed immune cell infiltration. There exists an obvious connection between Risk Score and immune checkpoints LAG3, PD1 and TIM3. CONCLUSION: The seven-NR-based Risk Score represents a promising signature for estimating overall survival in patients with BRCA, and is correlated with the immune microenvironment.

17.
J Endocrinol Invest ; 44(6): 1193-1207, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32979189

RESUMO

AIM: Diabetic retinopathy (DR) is a chronic disease causing health and economic burdens on individuals and society. Thus, this study is conducted to figure out the mechanisms of bone marrow mesenchymal stem cells (BMSCs)-induced exosomal microRNA-486-3p (miR-486-3p) in DR. METHODS: The putative miR-486-3p binding sites to 3'untranslated region of Toll-like receptor 4 (TLR4) was verified by luciferase reporter assay. High glucose (HG)-treated Muller cells were transfected with miR-486-3p or TLR4-related oligonucleotides and plasmids to explore theirs functions in DR. Additionally, HG-treated Muller cells were co-cultured with BMSC-derived exosomes, exosomes collected from BMSCs that had been transfected with miR-486-3p or TLR4-related oligonucleotides and plasmids to explore their functions in DR. MiR-486-3p, TLR4 and nuclear factor-kappaB (NF-κB) expression, angiogenesis-related factors, oxidative stress factors, viability and apoptosis in HG-treated Muller cells were detected by RT-qPCR, western blot analysis, ELISA, MTT assay and flow cytometry, respectively. RESULTS: MiR-486-3p was poorly expressed while TLR4 and NF-κB were highly expressed in HG-treated Muller cells. TLR4 was a target of miR-486-3p. Upregulating miR-486-3p or down-regulating TLR4 inhibited oxidative stress, inflammation and apoptosis, and promoted proliferation of HG-treated Muller cells. Meanwhile, BMSC-derived exosomes inhibited oxidative stress, inflammation and apoptosis, and promoted proliferation of HG-treated Muller cells. Restoring miR-486-3p further enhanced, while up-regulating TLR4 reversed, the improvement of exosomes treatment. CONCLUSION: Our study highlights that up-regulation of miR-486-3p induced by BMSC-derived exosomes played a protective role in DR mice via TLR4/NF-κB axis repression.

18.
Clin Microbiol Infect ; 27(4): 597-602, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32553880

RESUMO

OBJECTIVES: Bedaquiline treatment significantly improves multidrug-resistant tuberculosis (MDR-TB) patient treatment outcomes. However, safety and efficacy data are lacking for bedaquiline used with background regimens to treat Chinese TB patients. Here, we describe our initial clinical experience for bedaquiline treatment of a large multicentre cohort of MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patients in China. METHODS: Patients (177) received 24-week bedaquiline treatment combined with personalized anti-TB drug background regimens. As primary efficacy endpoints, times to initial sputum culture conversion were measured. RESULTS: Of 177 MDR-TB patients completing the 24-week treatment course, sputum culture conversion occurred for 151/177 (85.3%), while 26 had unfavourable outcomes, including 3/177 (1.7%) deaths and 23/177 (13.0%) non-responders at treatment completion. The median time to sputum culture conversion was 4 (interquartile range 2-8) weeks. Conversion rates were 33/39 (84.6%, 95% confidence interval (CI) 73.3-95.9) for MDR-TB patients, 47/56 (83.9%, 95% CI 74.3-93.6) for pre-XDR-TB patients and 71/82 (86.6%, 95% CI 79.2-94.0) for XDR-TB patients. Multivariate analysis demonstrated that patients with low body mass index (odds ratio 7.356; 95% CI 2.652-20.401) were at significantly high risk of unfavourable outcomes, with serious adverse events noted in 15 (8.5%) patients, including six with corrected QT interval (QTc) prolongation times (>500 ms). CONCLUSION: Bedaquiline, when included in background regimens for treatment of MDR-TB and XDR-TB patients in China, was safe and associated with a high rate of culture conversion.


Assuntos
Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Antituberculosos/administração & dosagem , China/epidemiologia , Diarilquinolinas/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
J Endocrinol Invest ; 44(2): 287-296, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32474764

RESUMO

OBJECTIVES: To evaluate the effect of peri-prostatic adipose tissue (PPAT) measurements using preoperative MRI on the prediction of prostate cancer (PCa) aggressiveness in men undergoing radical prostatectomy (RP). METHODS: We performed a retrospective study on 179 consecutive patients receiving RP from June 2016 to October 2018. Clinical characteristics were collected. PPAT measurements including peri-prostatic fat area (PPFA) and peri-prostatic fat area to prostate area (PA) ratio (PPFA/PA) were calculated by MRI. Multivariable logistic regression analysis was performed to identify independent predictors of PCa lymph node metastasis (LNM). The predictive performance was estimated through ROC curves. Nomograms were created based on the predictors. RESULTS: Pathologic Gleason score positively correlated with digital rectal examination (DRE), PSA, PPFA/PA, P504S, and Ki-67 (all P < 0.05). ROC curves revealed that high PPFA and high PPFA/PA were associated with LNM (both P < 0.05). Multivariate analysis revealed that high PPFA/PA, pathologic Gleason score, pT stage, and Ki-67 were independently predictive of LNM. The nomograms were created and the C-index was 0.945. CONCLUSIONS: PPFA/PA is an independent predictor for LNM along with Gleason score, pT stage, and Ki-67. PPFA/PA may help predict LNM in men undergoing RP, thus providing adjunctive information for therapeutic strategy and prognosis.


Assuntos
Tecido Adiposo/patologia , Imageamento por Ressonância Magnética/métodos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
20.
Insect Mol Biol ; 30(3): 241-252, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33368728

RESUMO

In Drosophila melanogaster, ecdysis triggering hormone (ETH) is the key factor triggering ecdysis behaviour and promoting trachea clearance. However, whether ETH plays the dual roles in non-dipteran insects is unknown. In this survey, we found that Ldeth mRNA levels were positively correlated with circulating 20-hydroxyecdysone (20E) titers in Leptinotarsa decemlineata. Ingestion of an ecdysteroid agonist halofenozide or 20E stimulated the transcription of Ldeth, whereas RNA interference (RNAi) of ecdysteroidogenesis (LdPTTH or LdSHD) or 20E signalling (LdEcR, LdUSP or LdFTZ-F1) genes inhibited the expression, indicating ETH acts downstream of 20E. RNAi of Ldeth at the final instar stage impaired pupation. More than 80% of the Ldeth-depleted beetles remained as prepupae, completely wrapped in the old larval cuticles. These prepupae became withered, dried and darkened gradually, and finally died in soil. The remaining Ldeth hypomorphs pupated and emerged as abnormal adults, bearing smaller and wrinkle elytrum and hindwing. Moreover, the tracheae in the Ldeth hypomorphs were full of liquid. We accordingly proposed that the failure of trachea clearance disenabled air-swallowing after pupa-adult ecdysis and impacted wing expansion. Our results suggest that ETH plays the dual roles, initiation of ecdysis and motivation of trachea clearance, in a coleopteran.


Assuntos
Benzoatos/administração & dosagem , Besouros/crescimento & desenvolvimento , Ecdisterona/administração & dosagem , Hidrazinas/administração & dosagem , Muda/fisiologia , Interferência de RNA , Animais , Ecdisterona/antagonistas & inibidores , Inseticidas/administração & dosagem , Larva/crescimento & desenvolvimento , Pupa/crescimento & desenvolvimento
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