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1.
Cancer Res ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822496

RESUMO

T cell acute lymphoblastic leukemia (T-ALL) is a type of aggressive leukemia with inferior prognosis. While activating mutations of NOTCH1 are observed in most T-ALL cases, these mutations alone are not sufficient to drive the full development of T-ALL. ß-Arrestins (ARRBs) are versatile and multifunctional adapter proteins that regulate diverse cellular functions, including promoting the development of cancer. However, the role of ARRBs in T-ALL have largely remained elusive. In this study, we showed that ARRB1 is expressed at low levels in assayed T-ALL clinical samples and cell lines. Exogenous ARRB1 expression inhibited T-ALL proliferation and improved the survival of T-ALL xenograft animals. ARRB1 facilitated NOTCH1 ubiquitination and degradation through interactions with NOTCH1 and DTX1. Mechanistically, the oncogenic microRNA (oncomiR) miR-223 targeted the 3'-UTR of ARRB1 (BUTR) and inhibited its expression in T-ALL. Furthermore, overexpression of the ARRB1-derived miR-223 sponge BUTR suppressed T-ALL cell proliferation and induced apoptosis. Collectively, these results demonstrate that ARRB1 acts as a tumor suppressor in T-ALL by promoting NOTCH1 degradation, which is inhibited by elevated miR-223, suggesting that ARRB1 may serve as a valid drug target in the development of novel T-ALL therapeutics.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31874254

RESUMO

BACKGROUND AND AIMS: Claudin 7 (Cldn7) is a tight junction (TJ) membrane protein located at the apical TJ and basolateral side of intestinal epithelial cells. Deletion of Cldn7 by gene-targeting leads to the inflammatory bowel disease (IBD)-like phenotype in mice, which includes weight loss, diarrhea, mucosa ulceration, and severe intestinal epithelial damage. In this study, we test our hypothesis that Cldn7 plays a critical role in regulating intestinal crypt stem cell functions. METHODS: Gene expression microarray, qRT-PCR, in situ hybridization, histological examinations, immunoblotting, 3D organoid culture, and various treatments to rescue Cldn7-deficient organoid defects were conducted using global Cldn7 knockout (gKO) mice and inducible, conditional Cldn7 knockout (cKO) mice. RESULTS: Gene-deletion of Cldn7 in intestines displayed significant alteration of expression profiles with striking downregulation of intestinal crypt stem cell markers such as Olfm4, dislocated proliferative cells, and disrupted epithelial cell differentiation. In addition, the isolated Cldn7-deficient crypts where the stem cells reside were either unable to survive at all or formed defective spheroids, highlighting the functional impairment of crypt stem cells in the absence of Cldn7. Remarkably, the Cldn7 expressing organoids with buddings underwent rapid cell degeneration within days after turning off Cldn7 expression in the culture. We identified that activation of Wnt/ß-catenin signaling rescued the organoid defects caused by Cldn7 deletion. CONCLUSIONS: In this study, we demonstrate for the first time that Cldn7 is indispensable in controlling Wnt/ß-catenin signaling-dependent intestinal epithelial stem cell survival, self-renewal and cell differentiation. This study could open a door to study roles of TJ proteins in stem cell regulations in other tissues and organs.

3.
Math Biosci Eng ; 16(6): 6962-6974, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31698598

RESUMO

To investigate effect of the number of deviators, the tension method, and the tendon profile on the flexural behaviour of reinforcement concrete (RC) T-beams strengthened with externally prestressed tendons, seven identical RC T-beams strengthened with external prestressing tendons were tested under four-point loading. Of these, one beam was ordinary RC beam without strengthening, another six beams were classified into three groups termed G1, G2 and G3. Two beams in G1 had identical straight external tendons with a different number of deviators, two beams in G2 had identical V shape external tendons with different tension method, and two beams in G3 had identical U shape external tendons with different tension method. The failure mode, deflection, strain, load carrying capacity and ductility of the specimens under loading were recorded and analyzed. Test results indicated that strengthening with external prestressing tendons is a very effective method to improve the load carrying capacity and stiffness of the RC beam. Provision of two deviators at the loading points led to satisfactory service load behavior (deflection, cracking, and concrete strain) and a higher load carrying capacity compared to the case where one deviator or no deviators were provided. In addition, tension method of the external tendon nearly had no effect on the load carrying capacity and mechanical behaviour of the RC beams.

4.
Int J Neurosci ; : 1-9, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31516040

RESUMO

Purpose: Evidence has shown that propofol may cause widespread apoptotic neurodegeneration. Hypoxic preconditioning has been demonstrated to provide neuroprotection and brain recovery from both acute and chronic neurodegeneration in several cellular and animal models. However, the mechanism has not been well elucidated. Therefore, the present study was designed to investigate the expression of glucose transporters (GLUT1 and GLUT3) and mitochondrial division and fusion (Drp1 and Mfn2) proteins in rats exposed to hypoxic preconditioning to attenuate propofol neurotoxicity. Methods: Propofol (100 mg/kg) was given to 7-day-old Sprague-Dawley rats; in some rats, hypoxic preconditioning was administered before intraperitoneal propofol injection by subjecting rats to five cycles of 10 min of hypoxia (8% O2) and 10 min of normoxia (21% O2). Then, the rats were allowed to breathe room air for 2 h. Neuronal mitochondrial morphology was observed by transmission electron microscopy. ATP content was detected using an ATP assay kit. The expression levels of GLUT1, GLUT3, pDrp1, Drp1 and Mfn2 were detected by Western blot, and the expression levels of GLUT1 and GLUT3 were further examined by immunohistochemistry. Results: Propofol damaged mitochondria, and decreased ATP content and GLUT3 and pDrp1 protein expression. However, our results suggested that hypoxic preconditioning could attenuate propofol neurotoxicity by reducing mitochondrial damage and increasing ATP content and pDrp1, GLUT1 and GLUT3 protein expression. Conclusion: Hypoxic preconditioning reduced propofol-induced damage in the hippocampus of neonatal rats by attenuating the increase in mitochondrial division and decrease in GLUT3 expression.

5.
Int J Mol Sci ; 20(15)2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31382627

RESUMO

Claudin-7 knockout (CLDN7-/-) mice display renal salt wasting and dehydration phenotypes. To address the role of CLDN7 in kidneys, we established collecting duct (CD) cell lines from CLDN7+/+ and CLDN7-/- mouse kidneys. We found that deletion of CLDN7 increased the transepithelial resistance (TER) and decreased the paracellular permeability for Cl- and Na+ in CLDN7-/- CD cells. Inhibition of transcellular Cl- and Na+ channels has no significant effect on TER or dilution potentials. Current-voltage curves were linear in both CLDN7+/+ and CLDN7-/- CD cells, indicating that the ion flux was through the paracellular pathway. The impairment of Cl- and Na+ permeability phenotype can be rescued by CLDN7 re-expression. We also found that WNK4 (its mutations lead to hypertension) expression, but not WNK1, was significantly increased in CLDN7-/- CD cell lines as well as in primary CLDN7-/- CD cells, suggesting that the expression of WNK4 was modulated by CLDN7. In addition, deletion of CLDN7 upregulated the expression level of the apical epithelial sodium channel (ENaC), indicating a potential cross-talk between paracellular and transcellular transport systems. This study demonstrates that CLDN7 plays an important role in salt balance in renal CD cells and modulating WNK4 and ENaC expression levels that are vital in controlling salt-sensitive hypertension.

6.
Chaos ; 29(7): 073112, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31370402

RESUMO

In this paper, the reliable synchronization of oscillatory power networks with different topologies is investigated by presenting two simple control strategies, namely, phase feedback control and frequency feedback control. The power networks are modeled by the coupled second-order Kuramoto oscillators that represent both consumers and generators. Through the simulations on the power networks with control, it is found that both the proposed control strategies can effectively enhance the synchronizability of the power networks, except for the case when the frequency feedback strategy is adopted for a coupled power network with the WS structure. In this case, it is observed that the critical coupling strength reaches the smallest value when the feedback control strength is equal to one and a sudden drop of order parameter occurs as the control strength further increases. This work provides innovative ideas for constructing a cost-effective power system.

7.
World J Gastroenterol ; 25(25): 3231-3241, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31333314

RESUMO

BACKGROUND: Barrett's esophagus (BE) is a pre-malignant condition associated with the development of esophageal adenocarcinoma. The prevalence of BE in the general populations of Asian countries ranges from 0.06% to 1%. However, with lifestyle changes in Asian countries and adoption of western customs, the prevalence of BE might have increased. AIM: To determine the current prevalence of BE in Taiwan, and to investigate risk factors predicting the presence of BE. METHODS: This retrospective study was conducted at the Health Evaluation Center of Kaohsiung Veterans General Hospital in Taiwan. Between January 2015 and December 2015, 3385 subjects undergoing routine esophagogastroduodenoscopy examinations as part of a health check-up at the Health Evaluation Center were included. Patient characteristics and endoscopic findings were carefully reviewed. Lesions with endoscopic findings consistent with BE awaiting histological evaluation were judged as endoscopically suspected esophageal metaplasia (ESEM). BE was defined based on extension of the columnar epithelium ≥ 1 cm above the gastroesophageal junction and was confirmed based on the presence of specialized intestinal metaplasia (IM) in the metaplastic esophageal epithelium. Clinical factors of subjects with BE and subjects without BE were compared, and the risk factors predicting BE were analyzed. RESULTS: A total of 3385 subjects (mean age, 51.29 ± 11.42 years; 57.1% male) were included in the study, and 89 among them were confirmed to have IM and presence of goblet cells via biopsy examination. The majority of these individuals were classified as short segment BE (n = 85). The overall prevalence of BE was 2.6%. Multivariate analysis disclosed that old age [odds ratio (OR) = 1.033; 95% confidence interval (CI): 1.012-1.055; P = 0.002], male gender (OR = 2.106; 95%CI: 1.145-3.872; P = 0.017), ingestion of tea (OR = 1.695; 95%CI: 1.043-2.754; P = 0.033), and presence of hiatal hernia (OR = 3.037; 95%CI: 1.765-5.225; P < 0.001) were significant risk factors predicting BE. The independent risk factor for the presence of IM in ESEM lesions was old age alone (OR = 1.029; 95%CI: 1.006-1.053; P = 0.014). CONCLUSION: Current prevalence of BE among the general population in Taiwan is 2.6%. Old age, male gender, ingestion of tea and hiatal hernia are significant risk factors for BE.

8.
Therap Adv Gastroenterol ; 12: 1756284819853115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31210784

RESUMO

Background: Barrett's esophagus (BE) is a premalignant condition with increased incidence worldwide both in old and young individuals. However, the role of certain potential risk factors remains unclear in young adults (< 50 years). We aimed to determine the risk factors of BE in young adults. Methods: A total of 4943 young adults who underwent upper gastrointestinal endoscopy at our health check-up center were enrolled. The diagnosis of BE was based on histological confirmation. We analyzed demographic factors, laboratory data, potential risk factors such as smoking, alcohol consumption, presence of gastroesophageal reflux disease (GERD) symptoms, and metabolic syndrome for the risk of BE by using binary logistic regression analysis. Results: The prevalence of BE was 1.8% (88/4943). Male sex, the presence of GERD symptoms, and smoking were three significant risk factors related to BE. Furthermore, participants who had smoked for 10 pack-years or more had increased risk of BE with dose-dependent phenomenon (p trend < 0.001). The proportion of BE in male participants with both GERD symptoms and a smoking history of 10 pack-years or more was as high as 10.3% (16/155). Conclusions: Significant risk factors of BE in young adults are male sex, the presence of GERD symptoms, and smoking. The risk also increases with an increase in cumulative exposure to smoking.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 777-784, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204931

RESUMO

OBJECTIVE: To investigate the effect of ß-arrestin1 gene on senescence of T-ALL cells and its possible mechanism. METHODS: The bone marrow specimens of T-ALL patients and controls were collected, the expression of ß-arrestin1 and ß-arrestin1 in the T-ALL patients was detected by RT-PCR and Western blot, respectively, and the relation of ß-arrestin1 expression with the clinical pathologic characteristics and the prognosis of T-ALL patients was analyzed statistically. The stable Jurkat cell line with knocked down or overexpressed ß-arrestin1 was constructed, the CCK method was used to detect the Jurkat cell number, the ß-gal staining was used to analyze the effect of ß-arrestin1 on senescence of Jurkat cells, the cross analysis of RNA-Seg data and KEGG data was performed for screening the possible signaling pathway, and Western blot was performed for varifying the key sites of signaling pathway. RESULTS: The ß-arrestin1 expression in specimens of T-ALL patients decreased (P<0.01), moreover the ß-arrestin1 expression negatively related with peripheral blood cell number (r=-0.601), the blasts in peripheral blood (r=-0.516) and extramedullary infiltration (r=-0.359), while positively related with the response to chemotherapy (r=0.393). The detection of stable Jurkat cell line with knocked-down and overexpressed ß-arrestin1 found that the ß-arrestin 1 could decrease the Jurkat cell number and accelarate the senescence of Jurkat cells (P<0.05). The cross analysis of RNA-Seg data and KEGG data showed that the senescence of T-ALL cells may be regulated via RAS-P16-PRb-E2F1 by ß-arrestin 1. Western bolt confirmed that ß-arrestin1 promoted the expression of Ras and p16, and decreased the expression of pRB and E2F1 (P<0.05). CONCLUSIONS: ß-arrestin1 accelerates the senescence of Jurkat cells via Ras-p16-pRb-E2F1, and delays the progression in T-ALL, which may provide a new hypothesis for the pathogenesis of T-ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , beta-Arrestina 1/genética , Senescência Celular , Humanos , Células Jurkat , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico
10.
J Gastroenterol Hepatol ; 34(11): 1968-1976, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31115933

RESUMO

BACKGROUND AND AIMS: Anti-Helicobacter pylori therapy may lead to the growth of pathogenic or antibiotic-resistant bacteria in the gut. The study aimed to investigate the short-term and long-term impacts of H. pylori eradication with reverse hybrid therapy on the components and macrolide resistance of the gut microbiota. METHODS: Helicobacter pylori-related gastritis patients were administered a 14-day reverse hybrid therapy. Fecal samples were collected before treatment and at the end of week 2, week 8, and week 48. The V3-V4 region of the bacterial 16S rRNA gene in fecal specimens was amplified by polymerase chain reaction and sequenced on Illumina MiSeq platform. Additionally, amplification of erm(B) gene (encoding erythromycin resistance methylase) was performed. RESULTS: Reverse hybrid therapy resulted in decreased relative abundances of Firmicutes (from 62.0% to 30.7%; P < 0.001) and Actinobacteria (from 3.4% to 0.6%; 0.032) at the end of therapy. In contrast, the relative abundance of Proteobacteria increased from 10.2% to 49.1% (0.002). These microbiota alterations did not persist but returned to the initial levels at week 8 and week 48. The amount of erm(B) gene in fecal specimens was comparable with the pretreatment level at week 2 but increased at week 8 (0.025) and then returned to the pretreatment level by week 48. CONCLUSIONS: Helicobacter pylori eradication with reverse hybrid therapy can lead to short-term gut dysbiosis. The amount of erm(B) gene in the stool increased transiently after treatment and returned to the pretreatment level at 1-year post-treatment.

11.
Clin Transl Gastroenterol ; 10(5): 1-8, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31082856

RESUMO

OBJECTIVES: Some metabolic factors and noninvasive markers, including fatty liver index (FLI), are used to predict nonalcoholic fatty liver disease (NAFLD) in obese patients. Despite the increasing prevalence of NAFLD in lean patients (lean-NAFLD), the risk factors and predictors are not well determined in this population. We investigated factors associated with lean-NAFLD and validated their predictive ability. METHODS: From 9,293 examinees who underwent routine health checkups, we enrolled 4,000, aged ≥20 years, with a body mass index <24 kg/m in our lean-NAFLD study population. NAFLD diagnoses were made according to the patients' histories, laboratory values, and sonographic criteria. Clinical variables, serum sugar, lipid, and liver profiles were evaluated using multiple logistic regression analysis. The predictive ability and optimal cutoff values for NAFLD were determined according to the area under the receiver operating characteristic curve. RESULTS: Overall, 18.5% (n = 740) of the lean population had NAFLD. Male sex, body mass index, body fat mass, fasting plasma glucose, uric acid, alanine aminotransferase, triglyceride, and FLI values were associated with NAFLD. FLI had the best discriminative ability to predict lean-NAFLD compared to the other biochemical markers. We further used the Youden index test and found an optimum cut-off value for FLI of 15 with the highest discriminant ability than other values. DISCUSSION: The prevalence of lean-NAFLD was not low. FLI was superior to other predictors including sex, liver function, and other metabolic factors, in the prediction of lean-NAFLD. FLI may be considered an easy to use, noninvasive marker to screen for lean-NAFLD.

12.
Oncol Lett ; 17(3): 2890-2896, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30854065

RESUMO

Claudins are a family of tight junction proteins, and serve important roles in epithelial barrier, selective ion transports and cancer metastasis. Although the exact role of claudin-7 in human lung cancer has not been completely elucidated, recent clinical studies have demonstrated that claudin-7 is associated with the survival of patients with lung cancer. Our previous studies have demonstrated that claudin-7 forms a protein complex with integrin ß1 in human lung cancer cells. The knockdown (KD) of claudin-7 by short hairpin RNA (shRNA) reduced integrin ß1 expression and increased the cell proliferative rate, whereas claudin-7 re-expression in the KD cells decreased the cell proliferation. It is unknown as to whether claudin-7 and integrin ß1 regulate cell proliferation and invasion synergistically or independently. In the present study, it was observed that ectopic expression of integrin ß1 in claudin-7 KD lung cancer cells did not reduce the cell proliferation. However, integrin ß1-transfected cells migrated more effectively in wound healing and cell invasion assays and were more adhesive in a cell attachment assay when compared with those of claudin-7 KD cells. This indicates that claudin-7 controls cell proliferation, while cell attachment and motility were regulated partially through integrin ß1. Additionally, claudin-7 overexpression in claudin-7 KD cells resulted in an improved ability to attach to the surface of cell culture plates and a higher expression of focal adhesion proteins when compared with claudin-7 non-KD control cells, which supports the role of claudin-7 in cell adhesion and motility. Taken together, these data suggest that claudin-7 regulates cell motility through integrin ß1, providing additional insight into the roles of claudins in carcinogenesis and cancer cell metastasis.

13.
Cancer Biol Ther ; 20(6): 740-749, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30849276

RESUMO

Cdc42 is a member of the Rho family of small GTPases that are at the crossroads of major oncogenic signaling pathways involved in both lung and prostate cancers. However, the therapeutic potential of Cdc42 regulation is still unclear due to the lack of pharmacological tools. Herein, we report that ZCL367 is a bona fide Cdc42 inhibitor that suppressed cancer development and ZCL278 can act as a partial Cdc42 agonist. In lung cancer cell lines with varying EGFR and Ras mutations as well as both androgen-independent and androgen-dependent prostate cancer cell lines, ZCL367 impeded cell cycle progression, reduced proliferation, and suppressed migration. ZCL367 decreased Cdc42-intersectin interactions and reduced Cdc42-mediated filopodia formation. ZCL367 showed increased potency and selectivity for Cdc42 when compared to Rac1 and RhoA. ZCL367 reduced A549 tumorigenesis in a xenograft mouse model. Altogether, ZCL367 is a selective Cdc42 inhibitor and an excellent candidate for lead compound optimization for further anticancer studies.

14.
Sci Total Environ ; 653: 758-764, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30759601

RESUMO

This study investigated the water resource potential for bioenergy production from sweet sorghum (Sorghum bicolor (L.)) in Northern China according to the distribution of water resources, climate conditions and the total water consumption of bioenergy based on sweet sorghum, which consisted of blue water, green water and grey water. At a case study site in Inner Mongolia, simulation with a plant phenological model was used to determine whether sweet sorghum could reach the harvestable stage for sugar juice production. The blue water in the agricultural phase was estimated according to the potential crop evapotranspiration (ETc), the drought sensitivity of sweet sorghum in different stages and the precipitation during the growing season. The results showed that the irrigation water was significantly different among the districts, ranging from 730 to 5500 m3/ha and 2060 to 6680 m3/ha for early-maturing and late-maturing varieties, respectively. To avoid the water pressure level to be exacerbated and the severe reallocation of water resources resulting in negative effects on other sectors, the maximal annual water withdrawal was set to not surpass the upper threshold of water stress level of 40%. That makes the maximum area for the production of sweet sorghum cannot exceed 1.95 × 104 ha, representing only 0.24% of the total marginal land area in Inner Mongolia. However, the economic benefits of bioenergy production from sweet sorghum would be negative due to the high labour input. Therefore, not only the availability of marginal land, the climate conditions and local water resources but also the improvement of mechanisation and agricultural production techniques should be considered to attain the sustainable development of bioenergy production and address global energy and environmental crises.


Assuntos
Irrigação Agrícola , Biocombustíveis/análise , Sorghum/crescimento & desenvolvimento , Recursos Hídricos/provisão & distribução , Biomassa , China
15.
Med Sci Monit ; 24: 8849-8859, 2018 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-30524119

RESUMO

BACKGROUND Intensity-modulated radiotherapy (IMRT) is the standard treatment for patients with nasopharyngeal cancer (NPC). However, the dose-volume criteria for adjacent anatomically normal organs at risk (OARs) remain controversial. The aim of this study was to evaluate the effects of higher than conventional doses of static and dynamic IMRT on the locoregional control of NPC, patient survival, and brainstem radiation toxicity. MATERIAL AND METHODS Patients (n=186) with stage III and stage IVa NPC underwent high-dose static and dynamic IMRT treatment (68-76.96 Gy) with or without chemotherapy for 34-57 days. Overall survival (OS), the presence of distant metastases, and brainstem toxicity were assessed. One-year, three-year, and five-year follow-up was performed. RESULTS High-dose IMRT alone or in combination with chemotherapy resulted in a 100% objective response rate and significantly improved OS rates, with one-year, three-year, and five-year OS rates of 94.1%, 89.8%, and 88.2%, respectively. The local recurrence rate (17.6%), and distant metastasis to the lung, liver, and bone (17.2%), and mortality (n=22) were reduced. Chemotherapy was the only factor that was significantly correlated with patient survival. Brainstem toxicity was reduced in patients treated with static IMRT (0.07%) and dynamic IMRT (0.08%). There were 26 additional factors that were not found to significantly affect brainstem toxicity. CONCLUSIONS High-dose static or dynamic IMRT combined with chemotherapy improved survival and reduces distal metastasis with a very low occurrence of brainstem toxicity in patients with locally advanced NPC. These findings might provide therapeutic guidance for clinicians when planning optimal dose-volume IMRT parameters.


Assuntos
Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Tronco Encefálico/patologia , Tronco Encefálico/efeitos da radiação , Quimiorradioterapia/métodos , Quimiorradioterapia/mortalidade , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/mortalidade , Análise de Sobrevida , Taxa de Sobrevida
16.
Exp Ther Med ; 16(6): 5390-5393, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30542500

RESUMO

The present study examined the effectiveness of the method of inversing the distal clavicle anatomic locking plate to treat medial-end clavicle fractures. This involved retrospectively analyzing six cases of medial-end clavicle fractures treated using the method of inversing the distal clavicle anatomic locking plate between September 2013 and December 2015. These cases included five men and one woman with an average age of 46.3±10.6 years old and a range of 24-66 years old. Among these cases, one was type A, two were type C, and three were type D, based on the Throckmorton type classification. All patients had fresh closed fractures, which were caused by direct injury. A regular postoperative follow-up was performed and the therapeutic efficacy was evaluated systematically with reference to the Rockwood and Disability of the Arm, Shoulder and Hand (DASH) score standards. All six cases had a follow-up visit, which was between 10 and 14 months with an average of 12.0±2.2 months. All patients exhibited osseous healing and functional recovery without incision infection, nerve vascular injury, chest injury, fracture nonunion, or other complications. According to the Rockwood and DASH score standards, evaluation of the curative effect showed that five cases were excellent and one case was good, and the associated rate for achieving good or excellent outcomes was 100%. All of the DASH scores were <10. These results indicated that the effect of the treatment of medial-end clavicle fractures by the method of inversing the distal clavicle anatomic locking plate was reliable, and the functional recovery of patients was good, making this method worthy of clinical promotion.

17.
BMC Pediatr ; 18(1): 372, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482190

RESUMO

BACKGROUND: Necrotizing enterocolitis (NEC) is a leading cause of death in preterm infants. Neonates weighing <1500 grams are at the highest risk for acquiring NEC, with a prevalence of nearly 7-10%, mortality up to 30%, and several long-term complications among survivors. Despite advancements in neonatal medicine, this disease remains a challenge to treat. The aim of this study is to investigate the effect of NEC on gut epithelial tight junctions and its barrier function using a NEC mouse model. METHODS: Three-day old C57BL/6 mouse pups were fed with Esbilac formula every 3 hours and then subjected to hypoxia twice daily followed by cold stress. Dam fed pups from the same litters served as controls. Pups were observed and sacrificed 96 hours after the treatments and intestines were removed for experiments. The successful induction of NEC was confirmed by histopathology. Changes in tight junction proteins in NEC intestines were studied by western blotting and immunofluorescent microscopy using specific protein markers. The gut leakage in NEC was visualized using biotin tracer molecules. RESULTS: Our study results demonstrate that we induced NEC in >50% of experimental pups, pups lost nearly 40% of weight and their intestines showed gross changes and microscopic changes associated with NEC. There were inflammatory changes with loss of tight junction barrier function and disruption of tight junction claudin proteins in the intestines of NEC mouse model. We have demonstrated for the first time that NEC intestines develop increased leakiness as visualized by biotin tracer leakage. CONCLUSIONS: NEC leads to breakdown of epithelial barrier due to changes in tight junction proteins with increased leakiness which may explain the transmigration of microbes and microbial products from the gut lumen into the blood stream leading to sepsis like signs clinically witnessed.


Assuntos
Permeabilidade Capilar/fisiologia , Enterocolite Necrosante/patologia , Enterocolite Necrosante/fisiopatologia , Mucosa Intestinal/irrigação sanguínea , Junções Íntimas/patologia , Animais , Claudinas/sangue , Modelos Animais de Doenças , Mediadores da Inflamação/sangue , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos C57BL
18.
Ying Yong Sheng Tai Xue Bao ; 29(7): 2111-2120, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30039647

RESUMO

Three monitoring plots were established in the Yangming Mountains mossy dwarf forest concentration zone in the Yangmingshan National Nature Reserve in Hunan Province in 2005. The changes of species composition and diversity during 2005-2016 were analyzed from species numerical characteristics, species importance value, diameter class structure, height structure, and species diversity. The results showed that from 2005 to 2016, the individual number for ≥1.0 cm diameter at ground height (DGH) in tree layer decreased by 30.9%. Viburnum dilatatum decreased greatest with 98.6%, and Rhododendron fortunei decreased least with 1.8%. Species richness was increased, and evenness was decreased. Except for R. fortunei, the importance values of all the species decreased significantly after ten years, indicating that R. fortunei was the dominant species in the dwarf forest. The diameter-class distribution of species in the dwarf forest was arranged at 1 cm level. The density of small-diameter (1 cm≤DGH<6 cm) species was higher, but that of medium-diameter (6 cm≤DGH<15 cm) and large-diameter (15 cm≤DGH) was lower. The diameter-class distribution of R. fortunei exhibited a reversed 'J' shape, and the height of community increased from 2005 to 2016, indicating the population had a stable and well-developing trend. The other species were poorly renewed and their diameter-class structure was irregular. Generally, the Patrick and Menhinick richness indices and the Simpson index were increased, and the Shannon and Pielou indices were decreased during the ten years.


Assuntos
Biodiversidade , Briófitas , Florestas , China , Ecossistema , Árvores
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(3): 261-267, 2018 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-29643030

RESUMO

OBJECTIVE: To explore the key genes in T-cell acute lymphoblastic leukemia (T-ALL) using bioinformatics method to better understand the pathogenic mechanisms of T-ALL. METHODS: The gene expression profiles of GSE14317 were obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) in T-ALL were analyzed using R package Limma. The online analysis tool DAVID was used to perform the functional and pathway enrichment analysis. The protein-protein interaction network was constructed by STRING and visualized by Cytoscape. Based on the JASPAR database, the transcription factors (TFs) of the hub genes were obtained. RT-PCR was used to test the mRNA expression level of the key genes. RESULTS: A total of 1443 DEGs were identified, including 800 up-regulated genes and 643 down-regulated genes. These DEGs were significantly enriched in the cell cycle, hematopoietic cell lineage, cytokine-cytokine receptor interaction and T cell receptor signaling pathway. The top 10 hub genes identified from the PPI networks included CDK1, PIK3R1, CCNB1, CCNA2, CDC20, JUN, GNG11, PLK1, PCNA and CCNB2, which were enriched in chemokine signaling pathway, ubiquition mediated proteolysis and cell cycle. In the TF-target gene network, 42 differentially expressed TFs were identified, among which ELF5, HIC2 and MEISI had binding sites with 9 of the candidate hub genes. RT-PCR showed that the mRNA expression level of all the candidate hub genes except for GNG11 were consistent with the gene expression profiles. CONCLUSION: The hub genes CDK1, PIK3R1, CCNB1, CCNA2, CDC20, JUN, PLK1, PCNA, CCNB2, ELF5, HIC2 and MEISI participate in the occurrence of T-ALL. Our finding provides new insights into the pathogenesis of T-ALL.


Assuntos
Perfilação da Expressão Gênica , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Biologia Computacional , Regulação Leucêmica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Transdução de Sinais , Fatores de Transcrição/genética
20.
Dig Dis Sci ; 63(5): 1200-1209, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29488037

RESUMO

BACKGROUND: As a potential tumor suppressor gene, Claudin-7 (Cldn7), which is a component of tight junctions, may play an important role in colorectal cancer occurrence and development. AIMS: To generate a knockout mouse model of inducible conditional Cldn7 in the intestine and analyze the phenotype of the mice after induction with tamoxifen. METHODS: We constructed Cldn7-flox transgenic mice and crossed them with Villin-CreERT2 mice. The Cldn7 inducible conditional knockout mice appeared normal and were well developed at birth. We induced Cldn7 gene deletion by injecting different dosages of tamoxifen into the mice and then conducted a further phenotypic analysis. RESULTS: After induction for 5 days in succession at a dose of 200 µl tamoxifen in sunflower oil at 10 mg/ml per mouse every time, the mice appeared dehydrated, had a lower temperature, and displayed inactivity or death. The results of hematoxylin-eosin staining showed that the intestines of the Cldn7 inducible conditional knockout mice had severe intestinal defects that included epithelial cell sloughing, necrosis, inflammation and hyperplasia. Owing to the death of ICKO mice, we adjusted the dose of tamoxifen to a dose of 100 µl in sunflower oil at 10 mg/ml per mouse (aged more than 8 weeks old) every 4 days. And we could induce atypical hyperplasia and adenoma in the intestine. Immunofluorescent staining indicated that the intestinal epithelial structure was destroyed. Electron microscopy experimental analysis indicated that the intercellular gap along the basolateral membrane of Cldn7 inducible conditional knockout mice in the intestine was increased and that contact between the cells and matrix was loosened. CONCLUSIONS: We generated a model of intestinal Cldn7 inducible conditional knockout mice. Intestinal Cldn7 deletion induced by tamoxifen initiated inflammation and hyperplasia in mice.


Assuntos
Claudinas/genética , Modelos Animais de Doenças , Enterite/genética , Deleção de Genes , Intestino Delgado/patologia , Camundongos Knockout/genética , Adenoma/induzido quimicamente , Adenoma/diagnóstico por imagem , Adenoma/genética , Adenoma/patologia , Animais , Western Blotting , Enterite/induzido quimicamente , Enterite/diagnóstico por imagem , Enterite/patologia , Feminino , Hiperplasia/induzido quimicamente , Hiperplasia/diagnóstico por imagem , Hiperplasia/genética , Hiperplasia/patologia , Imuno-Histoquímica , Neoplasias Intestinais/induzido quimicamente , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Intestino Delgado/diagnóstico por imagem , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Fenótipo , Tamoxifeno/administração & dosagem , Junções Íntimas/patologia
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