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Aldo-keto reductases (ARKs), a group of reductases that rely on nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) to catalyze carbonyl, are widely found in various organisms, which play an important role in the physiological and pathological processes of human. Aldo-keto reductase family 1 member C2 (AKR1C2) as a member of the human ARKs family, can regulate steroid hormones and is abnormally expressed in many cancers. According to whether the tumor can be affected by hormones, we divide malignancies into hormone-dependent and hormone-independent types. Studies have shown that AKR1C2 is involved in regulating tumor invasion, migration, and other malignant phenotypes, eliminating reactive oxygen species (ROS), promoting chemotherapy resistance of tumor cells, and has prognostic value in some cancers. Here, we focus on the role and clinical significance of AKR1C2 in different types of tumors.
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Neoplasias , Humanos , Prognóstico , Aldo-Ceto Redutases/genética , Neoplasias/tratamento farmacológico , Resistência a Medicamentos , Hormônios , Hidroxiesteroide Desidrogenases/genéticaRESUMO
Intestinal ischemia-reperfusion (IIR) often occurs during and following major cardiovascular or gut surgery and causes significant organ including kidney injuries. This study was to investigate the protective effect of intestinal ischemic postconditioning (IPo) on IIR-induced acute kidney injury (AKI) and the underling cellular signaling mechanisms with focus on the Nrf2/HO-1. Adult C57BL/6J mice were subjected to IIR with or without IPo. IIR was established by clamping the superior mesenteric artery (SMA) for 45 minutes followed by 120 minutes reperfusion. Outcome measures were: (i) Intestinal and renal histopathology; (ii) Renal function; (iii) Cellular signaling changes; (iv) Oxidative stress and inflammatory responses. IPo significantly attenuated IIR-induced kidney injury. Furthermore, IPo significantly increased both nuclear Nrf2 and HO-1 expression in the kidney, upregulated autophagic flux, inhibited IIR-induced inflammation and reduced oxidative stress. The protective effect of IPo was abolished by the administration of Nrf2 inhibitor (Brusatol) or Nrf2 siRNA. Conversely, a Nrf2 activator t-BHQ has a similar protective effect to that of IPo. Our data indicate that IPo protects the kidney injury induced by IIR, which was likely mediated through the Nrf2/HO-1 cellular signaling activation.
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Injúria Renal Aguda/prevenção & controle , Autofagia , Heme Oxigenase (Desciclizante)/metabolismo , Intestinos/fisiologia , Pós-Condicionamento Isquêmico/métodos , Fator 2 Relacionado a NF-E2/metabolismo , Traumatismo por Reperfusão/complicações , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Heme Oxigenase (Desciclizante)/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , ReperfusãoRESUMO
BACKGROUND: Concurrent chemoradiotherapy is the common first-line treatment for patients with advanced cervical cancer. However, radioresistance remains a major clinical challenge, which results in recurrence and poor survival. Many studies have shown the potential of Delta-like Ligand 4 (DLL4) as a novel prognostic biomarker and therapeutic target in many solid tumors. Previously, we have found that high DLL4 expression in tumor cells may predict the pelvic lymph node metastasis and poor prognosis in patients with cervical cancer. In our present study, we further studied the effects of DLL4 on the biological behavior and radiosensitivity of cervical cancer cells. METHODS: The expression of DLL4 and epithelial-mesenchymal transition (EMT) phenotype markers in cervical cancer cell lines or tissues were detected using Western blotting, and the expression of DLL4 mRNA in cervical cancer cell lines or tissues was detected using Quantitative real-time PCR. The effect of DLL4 on cell proliferation, migration, and radiosensitivity was evaluated using the CCK8 assay, flow cytometry, Transwell assays for cell invasion and migration, and Immunofluorescence staining in vitro. RESULTS: The expression of DLL4 in radiotherapy-resistant SiHa cells was significantly higher than that in radiotherapy-sensitive Me-180 cells. Furthermore, downregulation of DLL4 enhanced the radiosensitivity of SiHa and Caski cells via the inhibition of cell proliferation, promotion of radiation-induced apoptosis, and inhibition of the DNA damage repair. Moreover, downregulation of DLL4 inhibited the EMT and reduced the proliferation, invasion, and migration ability in SiHa and Caski cells. Consistent with the DLL4 expression in the cell lines, the expression of DLL4 in the tissues of the radioresistant group was also higher than that of the radiosensitive group. CONCLUSIONS: Downregulation of DLL4 inhibited the progression and increased the radiosensitivity in cervical cancer cells by reversing EMT. These results indicated the promising prospect of DLL4 against the radioresistance and metastasis of cervical cancer and its potential as a predictive biomarker for radiosensitivity and prognosis in patients with cervical cancer patients receiving concurrent chemoradiotherapy (cCRT).
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Autophagy is a ubiquitous intracellular process for cellular homeostasis maintenance by recycling damaged protein and organelles. Dysregulation of cardiomyocytes autophagic activity is implicated in various heart diseases. Recent studies had demonstrated that long non-coding RNAs (lncRNAs) played crucial roles on modulation of autophagic activity. In this study, we first established an angiotensin II-induced autophagy model on neonatal rat cardiomyocytes. Western blot assay confirmed that the expression of Beclin 1 and the conversion of soluble LC3-I to lipid bound LC3-II were significantly increased at 12 h after angiotensin II stimulation, but the cardiomyocytes surface area and hypertrophic markers expression had no significant change. Then microarray analysis and real-time PCR were applied to detect differentially expressed lncRNAs during cardiomyocytes autophagy. A total of 1,249 lncRNAs were determined as differentially expressed, including 700 upregulated lncRNAs and 549 downregulated lncRNAs. LncRNAs subgroup analysis showed there were 43 transcribed ultra-conserved noncoding RNAs (T-UCRs) differentially expressed in cardiomyocytes autophagy, of which 26 T-UCRs were upregulated and 17 T-UCRs were downregulated. Bioinformatics analysis further showed that 94 differentially expressed lncRNAs contained potential binding sites of miR-22, a pro-hypertrophic and pro-autophagic microRNA. Therefore, these differentially expressed lncRNAs might play critical roles in cardiomyocytes autophagy. This finding would provide an experimental basis for future investigation on ischemic heart disease.
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Angiotensina II/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , RNA Longo não Codificante/genética , Angiotensina II/genética , Animais , Autofagia/genética , Biologia Computacional , Perfilação da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , TranscriptomaRESUMO
AIMS: As one of the only two isoforms of the eukaryotic initiation factor (EIF)5A family, EIF5A2 plays an important role in tumour progression and prognosis evaluation. The aim of this study was to investigate EIF5A2 expression in International Federation of Gynecology and Obstetrics (FIGO) stage I-II cervical cancer and to evaluate its clinical significance. METHODS AND RESULTS: The mRNA and protein expression levels of EIF5A2 were analysed in 20 tissue samples of FIGO stage I-II cervical cancer and paired surrounding non-tumour cervical tissues by real-time polymerase chain reaction and western blot analysis. Immunohistochemistry was performed to examine EIF5A2 protein expression in paraffin-embedded tissues from 314 patients with cervical cancer. The mRNA and protein expression levels of EIF5A2 were significantly elevated in tumour tissues. The increased EIF5A2 expression was correlated with higher FIGO stage (P < 0.001), deep cervical stromal invasion (P = 0.026), lymphovascular space involvement (P = 0.002), pelvic lymph node metastasis (P < 0.001) and postoperative recurrence (P < 0.001) in patients with cervical cancer. Patients with tumours showing high EIF5A2 expression had a poorer survival time than those with normal EIF5A2 expression, especially the patients with negative pelvic lymph nodes and FIGO stage II. In addition, multivariate Cox analysis showed that high EIF5A2 expression was an independent prognostic factor for overall survival [hazard ratio 1.949; 95% confidence interval (CI) 1.116-3.404; P = 0.019] and disease-free survival (hazard ratio 1.980; 95% CI 1.189-3.297; P = 0.009). CONCLUSIONS: EIF5A2 overexpression may contribute to cancer progression and poor prognosis. Therefore, EIF5A2 could be a novel potential prognostic marker for FIGO stage I-II cervical cancer.
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Biomarcadores Tumorais/metabolismo , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Iniciação de Peptídeos/genética , Prognóstico , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Fator de Iniciação de Tradução Eucariótico 5AAssuntos
Raquianestesia , Infecções por Coronavirus , Hipotensão , Pandemias , Pneumonia Viral , Betacoronavirus , COVID-19 , Cesárea , Feminino , Humanos , Gravidez , SARS-CoV-2RESUMO
To research the influence of Reduning injection on the activity and mRNA expression of cytochrome P450 (CYP450) system in rat liver microsomes. Rat liver microsomes were prepared after a seven-days continuous administration of Reduning injection. An HPLC-MS method was applied to determine the specific metabolites of CYP450 probe substrates in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. The Real-time quantitative polymerase chain reaction (Q-PCR) was applied to determine the mRNA expression levels of CYP450. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13 (P < 0.01), but did not affect CYPlA2; low dose and high dose of Reduning injection had an inhibition trend on the activity of CYP2D2, but did not statistically differ from control group; low dose of Reduning injection significantly induced the activity of CYP3A1 (P < 0.01), high dose of Reduning injection had an induce trend on the activity of CYP3A1, but did not statistically differ from control. At the mRNA level, low and high dose of Reduning injection had an induce trend on the expression of CYP1A2, 2C11, 2D1, 2E1, 3A1, but did not statistically differ from control. Reduning injection significantly induced the activity of CYP2B1. Reduning injection significantly induced the activity of CYP3A1 in mRNA expression and enzyme activity levels, which may result adverse drug reaction after being combined with macrolides antibiotics. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13, 2D2 in enzyme activity levels, when combined with other drugs, it should be fully taken into account of the possible drug-drug interaction in order to avoid adverse side effects.
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Sistema Enzimático do Citocromo P-450/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Microssomos Hepáticos/efeitos dos fármacos , Animais , Injeções , Isoenzimas/metabolismo , Masculino , Microssomos Hepáticos/enzimologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: This study aimed to evaluate the accuracy of surgical outcomes in free iliac crest mandibular reconstructions that were carried out with virtual surgical plans and rapid prototyping templates. METHODS: This study evaluated eight patients who underwent mandibular osteotomy and reconstruction with free iliac crest grafts using virtual surgical planning and designed guiding templates. Operations were performed using the prefabricated guiding templates. Postoperative three-dimensional computer models were overlaid and compared with the preoperatively designed models in the same coordinate system. RESULTS: Compared to the virtual osteotomy, the mean error of distance of the actual mandibular osteotomy was 2.06 ± 0.86 mm. When compared to the virtual harvested grafts, the mean error volume of the actual harvested grafts was 1412.22 ± 439.24 mm3 (9.12% ± 2.84%). The mean error between the volume of the actual harvested grafts and the shaped grafts was 2094.35 ± 929.12 mm3 (12.40% ± 5.50%). CONCLUSIONS: The use of computer-aided rapid prototyping templates for virtual surgical planning appears to positively influence the accuracy of mandibular reconstruction.
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Ameloblastoma/cirurgia , Transplante Ósseo , Desenho Assistido por Computador , Ílio/transplante , Neoplasias Mandibulares/cirurgia , Osteotomia , Procedimentos de Cirurgia Plástica , Adulto , Ameloblastoma/patologia , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Neoplasias Mandibulares/patologia , Pessoa de Meia-Idade , Prognóstico , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
In this study, the characteristics of the nitride-based blue light-emitting diode (LED) without an electron-blocking layer (EBL) are analyzed numerically. The emission spectra, carrier concentrations in the quantum wells (QWs), energy band diagrams, electrostatic fields, and internal quantum efficiency (IQE) are investigated. The simulation results indicate that the LED without an EBL has a better hole-injection efficiency and smaller electrostatic fields in its active region over the conventional LED with an AlGaN EBL. The simulation results also show that the LED without an EBL has severe efficiency droop. However, when the special designed p-type doped InGaN QW barriers are used, the efficiency droop is markedly improved and the electroluminescence (EL) emission intensity is greatly enhanced which is due to the improvement of the hole uniformity in the active region and small electron leakage.
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Desenho Assistido por Computador , Índio/química , Iluminação/instrumentação , Modelos Teóricos , Semicondutores , Cor , Simulação por Computador , Transporte de Elétrons , Desenho de Equipamento , Análise de Falha de Equipamento , Luz , Espalhamento de RadiaçãoRESUMO
BACKGROUND: Primary ciliary dyskinesia (PCD) is an uncommon and genetically diverse condition. According to reports, most patients had more than 50 visits before being diagnosed with PCD, and the age at diagnosis was mostly in preschool, with an average age of about (10.9 ± 14.4) years old. CCNO is a pathogenic gene that regulates the cell cycle, and its mutation is linked to the uncommon human genetic disorder PCD. Although the prevalence of the CCNO mutation is regarded to be exceptionally low, new reports of this mutation have increased in comparison to prior ones. PCD patients with CCNO are rare, and the incidence rate is no more than 2% in whole PCD patients. CASE SUMMARY: Here, we report a case of a young Chinese woman diagnosed with PCD, who was found to carry the CCNO gene by whole exon gene sequencing. In this case, a young non-smoking Chinese female exhibiting recurrent cough and sputum at birth. Chest computed tomography (CT) showed bronchiectasis with infection, and sinus CT showed chronic sinusitis. However, the patient had no visceral transposition and no history of infertility. Under electron microscope, it was found that cilia were short and reduced in number, and no power arm of cilia was observed. Whole exon sequencing analysis of the genome of the patient showed that the patient carried CCNO pathogenic gene, exon c.303C>A nonsense mutation and c.248_252dup frameshift mutation. Her clinical symptoms and CT images were improved after two months of treatment with aerosol inhalation and oral azithromycin. CONCLUSION: The results showed that CCNO is an important cause of PCD. More mutant genes that may contribute to genetically diverse disorders like PCD have been discovered as sequencing technology has advanced. Furthermore, the increase of genetic information makes it easier to diagnose uncommon diseases in clinical practice.
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[This corrects the article DOI: 10.3389/fphar.2020.584177.].
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Fentanyl-induced cough (FIC) often occurs after intravenous bolus administration of fentanyl analogs during induction of general anesthesia and analgesia procedure. The cough is generally benign, but sometimes it causes undesirable side effects, including elevated intra-abdominal, intracranial or intraocular pressure. Therefore, understanding the related mechanisms and influencing factors are of great significance to prevent and treat the cough. This paper reviews the molecular mechanism, influencing factors and preventive administration of FIC, focusing on the efficacy and side effects of various drugs in inhibiting FIC to provide some medical reference for anesthesiologists.
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BACKGROUND: To evaluate the dosimetric parameters of different bone marrow sparing strategies and radiotherapy technologies and determine the optimal strategy to reduce hematologic toxicity associated with concurrent chemoradiation (cCRT) for cervical cancer. METHODS: A total of 15 patients with Federation International of Gynecology and Obsterics (FIGO) Stage IIB cervical cancer treated with cCRT were re-planned for bone marrow (BM)-sparing plans. First, we determined the optimal BM sparing strategy for intensity modulated radiotherapy (IMRT), including a BMS-IMRT plan that used total BM sparing (IMRT-BM) as the dose-volume constraint, and another plan used os coxae (OC) and lumbosacral spine (LS) sparing (IMRT-LS+OC) to compare the plan without BM-sparing (IMRT-N). Then, we determined the optimal technology for the BMS-IMRT, including fixed-field IMRT (FF-IMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (HT). The conformity and homogeneity of PTV, exposure volume of OARs, and efficiency of radiation delivery were analyzed. RESULTS: Compared with the IMRT-N group, the average volume of BM that received ≥10, ≥20, ≥30, and ≥40 Gy decreased significantly in both two BM-sparing groups, especially in the IMRT-LS+OC group, meanwhile, two BMS-IMRT plans exhibited the similar effect on PTV coverage and other organs at risk (OARs) sparing. Among three common IMRT techniques in clinic, HT was significantly less effective than VMAT and FF-IMRT in the aspect of BM-Sparing. Additionally, VMAT exhibited more efficient radiation delivery. CONCLUSION: We recommend the use of VMAT with OC and LS as separate dose-volume constraints in cervical cancer patients aiming at reducing hematologic toxicity associated with cCRT, especially in developing countries.
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Numerous studies have reported that diabetes is associated with an increased susceptibility to cardiac ischemia reperfusion injury; however, the mechanism underlying the role of diabetes during intestinal ischemiareperfusion (IIR) has yet to be elucidated. The present study evaluated the intestinal pathological alterations and possible underlying mechanisms in a mouse model of type 1 diabetes mellitus with IIR. The effects of diabetes were investigated by assessing the histopathology, oxidative stress, inflammatory cytokine levels in intestine tissues and blood plasma, and protein expression levels of phosphatase and tensin homologinduced putative kinase (PINK1), Parkin and the ratio of light chain 3B (LC3B) II/I. The results demonstrated that diabetes increased the Chiu's intestinal injury score, concentration of interleukin (IL)1ß, IL6 and tumor necrosis factor (TNF)α, and levels of oxidative stress. Furthermore, the alterations were more pronounced in the diabetes with IIR group. The expression levels of PINK1 and Parkin, as well as the ratio of LC3BII/I, were significantly upregulated in the IIR group compared with the Sham group. Diabetes activated PINK1 and Parkin, and increased the expression of LC3BII. Furthermore, transmission electron microscopy revealed that mitochondrial destruction and the number of autophagosomes was increased in the diabetic groups compared with the nondiabetic groups. Collectively, the results of the present study suggest that diabetes increased intestinal vulnerability to IIR by enhancing inflammation and oxidative stress. Furthermore, IIR was associated with overactivation of mitochondrial autophagy; therefore, the increased vulnerability to IIRinduced intestine damage due to diabetes may be associated with PINK1/Parkinregulated mitochondrial autophagy.
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Diabetes Mellitus Experimental/complicações , Intestinos/lesões , Mitocôndrias/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Mitofagia , Estresse Oxidativo , Proteínas Quinases/metabolismo , Traumatismo por Reperfusão/etiologia , Estreptozocina , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIMS: Ischemic postconditioning (IPO) has a strong protective effect against intestinal ischemia-reperfusion (IIR) injury that is partly related to autophagy. However, the precise mechanisms involved are unknown. METHODS: C57BL/6J mice were subjected to unilateral IIR with or without IPO. After 45 min ischemia and 120 min reperfusion, intestinal tissues and blood were collected for examination. HE staining and Chiu's score were used to evaluate pathologic injury. We test markers of intestinal barrier function and oxidative stress. Finally, we used WB to detect the expression of key proteins of autophagy and the Akt/GSK-3ß/Nrf2 pathway. RESULTS: IPO significantly attenuated IIR injury. Expression levels of LC3 II/I, Beclin-1, and p62 were altered during IIR, indicating that IPO enhanced autophagy. IPO also activated Akt, inhibited GSK-3ß/Nrf2 pathway. CONCLUSION: Our study indicates that IPO can ameliorate IIR injury by evoking autophagy, activating Akt, inactivating GSK-3ß, and activating Nrf2. These findings may provide novel insights for the alleviation of IIR injury.ß/Nrf2 pathway.
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Glicogênio Sintase Quinase 3 beta/metabolismo , Pós-Condicionamento Isquêmico/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/terapia , Animais , Autofagia , Masculino , Camundongos , Estresse OxidativoRESUMO
OBJECTIVE: Investigate the influences of human beta-defensinl (hbetaD1) on the replication and expression of HPV18 in Hela cell. METHODS: Gene transfection: mediated by Fugen HD, hbetaD1/psectag plasmid was transfected to Hela cell [hbetaD1/psectag : liposome complexes (hbetaD1/psectag : lip)group], and control groups [psectag : liposome complexes(psectag : lip) group and blank group) were also established. After transfection, the expression of the target gene in Hela cell was investigated by the method of immunocytochemistry. 48 h and 72 h after the transfection, the change of the copy number of HPV18 DNA in Hela cell was investigated respectively by the quantitative fluorescent PCR method, and the change of the HPV18 E6 mRNA in Hela cell was evaluated by the semiquantitative RT-PCR. RESULTS: 48 h and 72 h after the transfection of hbetaD1/psectag plasmid to Hela cell, hbetaD1 was expressed in both of the two groups, and the latter showed a tendency of stronger expression. Compared with the control groups, the copy number of HPV18 DNA in Hela cell in the hbetaD1/psectag : lip group increased at 48 h and decreased at 72 h after the transfection, but the change was not statistically significant. 48 h after the transfection, compared with the control groups, the expression of HPV18 E6 mRNA in Hela cell in the hbetaD1/psectag : lip group changed a little; and 72 h after the transfection, the expression level of HPV18 E6 mRNA decreased significantly (P < 0.05). CONCLUSION: hbetaD1 displayed an inhibitory effect to the expression of HPV18 mRNA in Hela cell in a concentration-dependent pattern, but no significant effect on the duplication of HPV18 DNA.
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Proteínas de Ligação a DNA/metabolismo , Papillomavirus Humano 18/fisiologia , Proteínas Oncogênicas Virais/metabolismo , Neoplasias do Colo do Útero/virologia , Replicação Viral/efeitos dos fármacos , beta-Defensinas/farmacologia , DNA Viral/metabolismo , Proteínas de Ligação a DNA/genética , Feminino , Células HeLa , Humanos , Proteínas Oncogênicas Virais/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Parrotia subaequalis is an endangered palaeoendemic tree from disjunct montane sites in eastern China. Due to the lack of effective genomic resources, the genetic diversity and population structure of this endangered species are not clearly understood. In this study, we conducted paired-end shotgun sequencing (2 × 125 bp) of genomic DNA for two individuals of P. subaequalis on the Illumina HiSeq platform. Based on the resulting sequences, we have successfully assembled the complete chloroplast genome of P. subaequalis, as well as identified the polymorphic chloroplast microsatellites (cpSSRs), nuclear microsatellites (nSSRs) and mutational hotspots of chloroplast. Ten polymorphic cpSSR loci and 12 polymorphic nSSR loci were used to genotype 96 individuals of P. subaequalis from six populations to estimate genetic diversity and population structure. Our results revealed that P. subaequalis exhibited abundant genetic diversity (e.g., cpSSRs: Hcp = 0.862; nSSRs: HT = 0.559) and high genetic differentiation (e.g., cpSSRs: RST = 0.652; nSSRs: RST = 0.331), and characterized by a low pollen-to-seed migration ratio (r ≈ 1.78). These genetic patterns are attributable to its long evolutionary histories and low levels of contemporary inter-population gene flow by pollen and seed. In addition, lack of isolation-by-distance pattern and strong population genetic structuring in both marker systems, suggests that long-term isolation and/or habitat fragmentation as well as genetic drift may have also contributed to the geographic differentiation of P. subaequalis. Therefore, long-term habitat protection is the most important methods to prevent further loss of genetic variation and a decrease in effective population size. Furthermore, both cpSSRs and nSSRs revealed that P. subaequalis populations consisted of three genetic clusters, which should be considered as separated conservation units.
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AIM: To investigate the association between endogenous gene expression and growth regulation including proliferation and apoptosis induced by transforming growth factor-beta1 (TGF-beta1) in human gastric cancer (GC) cells. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the main components of the TGF-beta1/Smads signal pathway in human poorly differentiated GC cell line BGC-823. Localization of Smad proteins was also determined using immunofluorescence. Then, the BGC-823 cells were cultured in the presence or absence of TGF-beta1 (10 ng/mL) for 24 and 48 h, and the effects of TGF-beta1 on proliferation and apoptosis were measured by cell growth curve and flow cytometry (FCM) analysis. The ultrastructural features of BGC-823 cells with or without TGF-beta1 treatment were observed under transmission electron microscope. The apoptotic cells were visualized by means of the terminal deoxynucleotidyl transferase (TdT)-mediated dTUP in situ nick end-labeling (TUNEL) method. Meanwhile, the expression levels of endogenous p15, p21 and Smad7 mRNA and the corresponding proteins in the cells were detected at 1, 2 and 3 h after culture in the presence or absence of TGF-beta1 (10 ng/mL) by semi-quantitative RT-PCR and Western blot, respectively. RESULTS: The TGF-beta1/Smad signaling was found to be intact and functional in BGC-823 cells. The growth curve revealed the most evident inhibition of cell proliferation by TGF-beta1 at 48 h, and FCM assay showed G1 arrest accompanied with apoptosis induced by TGF-beta1. The typical morphological changes of apoptosis were observed in cells exposed to TGF-beta1. The apoptosis index (AI) in TGF-beta1-treated cells was significantly higher than that in the untreated controls (10.7+/-1.3% vs 0.32+/-0.06%, P<0.01). The levels of p15, p21 and Smad7 mRNA and corresponding proteins in cells were significantly up-regulated at 1 h, but gradually returned to basal levels at 3 h following TGF-beta1 (10 ng/mL) treatment. CONCLUSION: TGF-beta1 affects both proliferation and apoptosis of GC cells through the regulation of p15 and p21, and induces transient expression of Smad 7 as a negative feedback modulation of TGF-beta1 signal. Our results suggest a novel functional role of p21 as an accelerant of TGF-beta1-mediated apoptosis in GC cells.
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Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Gástricas/genética , Fator de Crescimento Transformador beta/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Proteínas de Ciclo Celular/genética , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p15 , Inibidor de Quinase Dependente de Ciclina p21 , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteína Smad7 , Transativadores/genética , Transativadores/metabolismo , Fator de Crescimento Transformador beta1 , Proteínas Supressoras de Tumor/genética , Regulação para Cima/efeitos dos fármacosRESUMO
OBJECTIVE: To determine the reliability of the fetal abdominal circumference (FAC) measured by ultrasound as a predictor of birth weight. METHODS: FAC was measured by ultrasound within 0-7 days of delivery and the birth weight were followed in 1475 pregnant women. Statistics analysis was carried out to determine the relationship between FAC and birth weight. RESULTS: Ultrasound measurement of FAC had a linear relation with birth weight, and the correlation coefficient was 0.85. Among the fetuses with FAC < 34 cm, no newborn had a weight more than 4000 g; the macrosomia rate was only 1.1% when FAC was between 34-34.9 cm. Among the fetuses with FAC between 35-35.9 cm, the average birth weight was (3691 +/- 277) g, the macrosomia rate was 14.6%; when FAC was between 36-36.9 cm, the average birth weight was (3957 +/- 256) g, the macrosomia rate was 51.0%. The macrosomia rate was 84.4% with FAC between 37-37.9 cm. When FAC > or = 38 cm the macrosomia rate was 100%. The cesarean section rate for the newborn weighing between 4000-4500 g was 71.4%, and for the fetuses weighing > or = 4500 g the cesarean section rate was 93.8%, which was significantly higher than that of fetuses weighing less than 4000 g. Only one baby who weighed 4350 g had shoulder dystocia with Erb's palsy and clavicle fracture, but recovered 2 months later. CONCLUSIONS: FAC measured by ultrasound can help to evaluate the birth weight. It is useful in screening macrosomia and avoiding shoulder dystocia.
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Abdome/anatomia & histologia , Peso ao Nascer , Ultrassonografia Pré-Natal , Abdome/diagnóstico por imagem , Tamanho Corporal , Feminino , Macrossomia Fetal/diagnóstico por imagem , Peso Fetal , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Terceiro Trimestre da GravidezRESUMO
To assess the role of microsatellite instability(MSI) on chromosome 19 in the carcinogenesis of gastric cancer. 26 microsatellite markers on chromosome 19 were amplified by Fluorescence-Labelled Primers Multiplex PCR in 44 paired gastric cancer tissues for MSI. The amplified fragments ran in PAGE gel by ABI 377 sequencer and the gel images were analyzed by GeneScan and Genotyper. Meanwhile, MSI of four of all microsatellite sites were also analyzed using PCR-SSLP-silver stain method. MSI was observed in 22 of 26(84.62%) microsatellite sites. D19S402 showed the highest frequency(22.73%). The total frequency of MSI was 8.3%. In 44 gastric cancer samples, 34(77.27%) cases showed MSI at one or more than one site. MSI, as a possible mechanism of carcinogenesis, might play an important role in human primary gastric cancer. MSI detections will become an integral part of the routine classification of all gastrointestinal tumors in the very near future.