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1.
Anticancer Res ; 40(5): 2475-2479, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366391

RESUMO

BACKGROUND/AIM: Matrix-producing breast carcinoma (MPBC) is a rare and usually aggressive triple-negative breast cancer (TNBC). In the present report, we determined the drug sensitivity for a triple-negative MPBC using a patient-derived orthotopic xenograft (PDOX) model. MATERIALS AND METHODS: The PDOX model was established in the left 2nd mammary by surgical orthotopic implantation (SOI). MPBC PDOX models were randomized into 4 groups (6 mice per group) when the tumor volume became 80 mm3: G1, control group; G2, cisplatinum group [intraperitoneal (i.p.) injection, weekly, for 2 weeks]; G3, paclitaxel group (i.p., weekly, for 2 weeks); G4, eribulin group [intravenous (i.v.) injection, weekly, for 2 weeks]. All mice were sacrificed on day 15. Tumor volume and body weight were measured one time per week. RESULTS: The MPBC PDOX model was resistant to cisplatinum (p=0.800). Paclitaxel suppressed tumor growth compared to the control group (p=0.009). However, only eribulin regressed the tumor (p=0.001). CONCLUSION: Eribulin has clinical potential for triple-negative MPBC patients.


Assuntos
Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Furanos/farmacologia , Cetonas/farmacologia , Neoplasias de Mama Triplo Negativas/patologia , Animais , Biomarcadores Tumorais , Cisplatino/uso terapêutico , Modelos Animais de Doenças , Feminino , Furanos/uso terapêutico , Humanos , Cetonas/uso terapêutico , Camundongos , Paclitaxel/farmacologia , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/etiologia , Neoplasias de Mama Triplo Negativas/metabolismo , Carga Tumoral/efeitos dos fármacos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Anticancer Res ; 40(5): 2481-2485, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366392

RESUMO

BACKGROUND/AIM: In the present study, the breast cancer patient-derived orthotopic xenograft (PDOX) model was used to identify an effective drug for a highly aggressive triple negative breast cancer (TNBC). MATERIALS AND METHODS: The TNBC tumor from a patient was implanted in the right 4th inguinal mammary fat pad of nude mice to establish a PDOX model. Three weeks later, 19 mice were randomized into the untreated-control group (n=10) and the eribulin treatment group (n=9, eribulin, 0.3 mg/kg, i.p., day 1). RESULTS: On day 8, eribulin significantly inhibited tumor volume compared to the control group (p<0.01). Eribulin regressed tumors in 3 mice (33.3%) and apparently eradicated them in 6 mice (66.7%). At day 14, tumor regrowth was observed in 2 mice of the eribulin group, which was undetectable on day 8. However, 44.4% (4 out of 9) of the mice in the eribulin group were tumor-free on day 14. CONCLUSION: A single low-dose eribulin was efficacious on a highly aggressive TNBC. The breast cancer PDOX model can be used to identify highly effective drugs for TNBC.


Assuntos
Antineoplásicos/administração & dosagem , Furanos/administração & dosagem , Cetonas/administração & dosagem , Neoplasias de Mama Triplo Negativas/patologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Histocitoquímica , Humanos , Camundongos , Metástase Neoplásica , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/etiologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Anticancer Res ; 40(5): 2509-2514, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366395

RESUMO

BACKGROUND/AIM: Matrix-producing breast carcinoma (MPBC) is a rare and usually aggressive triple-negative breast cancer (TNBC). In this study, we determined drug sensitivity for a triple-negative MPBC, without BRCA mutations, in a patient-derived orthotopic xenograft (PDOX) model. MATERIALS AND METHODS: The MPBC PDOX model was established in the left 2nd mammary gland of nude mouse by implantation of the patient tumor using surgical orthotopic implantation (SOI). We randomized MPBC PDOX mice into 5 groups (n=5 mice/per treatment group) when the tumor volume reached 80 mm3: G1, control-no treatment; G2, bevacizumab [intra-peritoneal (i.p.), weekly, for 2 weeks]; G3, vinorelbine (i.p., weekly, for 2 weeks); G4, olaparib (oral., daily, for 2 weeks); G5, eribulin [intravenous (i.v.), weekly, for 2 weeks]. The mice in each treatment group were sacrificed on day 15. Tumor volume and body weight were measured once/week. RESULTS: The MPBC PDOX model was resistant to olaparib (p=0.22). The MPBC PDOX model treated with bevacizumab and vinorelbine showed significantly suppressed tumor growth compared to the untreated group (p=0.005 and 0.002, respectively). However, only eribulin regressed the tumor (p=0.0001). Eribulin was more effective than olaparib (p=0.0001), bevacizumab (p=0.0025) and vinorelbine (p=0.0061). CONCLUSION: Eribulin has clinical potential as treatment for triple-negative MPBC patients that are resistant to a PARP inhibitor such as olaparib.


Assuntos
Bevacizumab/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Furanos/farmacologia , Cetonas/farmacologia , Ftalazinas/farmacologia , Piperazinas/farmacologia , Neoplasias de Mama Triplo Negativas/patologia , Vinorelbina/farmacologia , Adulto , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
4.
In Vivo ; 34(3): 973-978, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32354882

RESUMO

BACKGROUND/AIM: We have recently shown that oral recombinant methionase (o-rMETase) prevents obesity in mice on a high-fat (HF) diet. The present study aimed to determine if o-rMETase can inhibit the onset of diabetes in mice on a HF diet. MATERIALS AND METHODS: The mice on a HF diet were divided into two groups: 1) HF+phosphate buffered saline (PBS) group; 2) HF+o-rMETase group. RESULTS: The blood glucose level in the HF+PBS group increased to average of 201 mg/dl during the experimental period of 8 weeks. In contrast, the blood glucose level in the HF+o-rMETase group maintained an average of 126 mg/dl (p<0.01, HF+PBS vs. HF+o-rMETase). The glucose tolerance test showed a significant increase in tolerance in the HF+o-rMETase group at 120 min after glucose injection compared to the HF+PBS group (p=0.04). Visceral adipose tissue was significantly less in the HF+o-rMETase group than the HF+PBS group (p=0.05). There was no difference in insulin levels, cholesterol or triglycerides between the HF+PBS and HF+o-rMETase groups. CONCLUSION: o-rMETase inhibited the onset of diabetes as well as prevented obesity on a high-fat diet, offering a possibility of a new and easy-to-use alternative to severe dieting or insulin injections.

5.
In Vivo ; 34(3): 979-984, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32354883

RESUMO

BACKGROUND/AIM: We have recently shown that oral recombinant methionase (o-rMETase) prevents obesity and diabetes onset in mice on a high-fat (HF) diet. The present study aimed to determine if o-rMETase can inhibit the onset of nonalcoholic fatty liver disease (NAFLD) onset in mice on a high-fat diet. MATERIALS AND METHODS: Male C57BL/6J mice in the control group were fed a normal-fat diet (NFD) (+6.5% fat), and other mice were fed a high-fat (HF) diet (+34.3% fat). Then, the mice on the HF diet were divided into two dietary groups: i) HF+phosphate buffered saline (PBS) group, and ii) HF+o-rMETase group. RESULT: The fatty change score in the livers of mice treated with HF+PBS increased to an average of 2.6 during the experimental period of 8 weeks. In contrast, the fatty change in the livers of mice on the HF+o-rMETase group had an average score of 0.92 (p=0.04, HF+PBS vs HF+o-rMETase). CONCLUSION: o-rMETase inhibited the onset of NAFLD as well as prevented obesity and the onset of diabetes on a high-fat diet, offering a possibility of a new paradigm to prevent liver cirrhosis or liver cancer via NAFLD.

6.
Rev Sci Instrum ; 91(4): 044701, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357711

RESUMO

Conventional thermionic microwave and radio frequency (RF) guns can offer high average beam current, which is important for synchrotron light and terahertz (THz) radiation source facilities, as well as for industrial applications. For example, the Advanced Photon Source at Argonne National Laboratory is a national synchrotron-radiation light source research facility that utilizes thermionic RF guns. However, these existing thermionic guns are bulky, difficult to handle and install, easily detuned, very sensitive to thermal expansion, and due for a major upgrade and replacement. In this paper, we present the design of a new, more stable, and reliable gun with optimized electromagnetic performance, improved thermal engineering, and a more robust cathode mounting technique, which is a critical step to improve the performance of existing and future light sources, industrial accelerators, and electron beam-driven THz sources. We will also present a fabricated gun prototype and show results of high-power and beam tests.

7.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(5): 519-522, 2020 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-32388952

RESUMO

Objective: To explore the impacts on birth situation associated with birth policy adaption in monitoring area of birth defect population in Zhejiang province. Methods: Data were obtained from hospital-based birth defect surveillance system in Zhejiang Province. The surveillance population was childbearing women living in Nanhu of Jiaxing and Fenghua of Ningbo no less than 1 year. We divided data into three groups as "only child" (Jan, 2012-Sep, 2013), "privileged second child" (Jan, 2015-Sep, 2016) and "universal second child" (Jan, 2017-Sep, 2018) according to birth policy adaption. The differences of maternal age distribution in different birth policy periods were compared by using Kruskal-Wallis test. The changing trend of the proportion of parturient in different birth policy periods was analyzed by using Trend χ(2) test. Unconditional logistic regression model was used to analyze the relationship between birth policy and adverse perinatal outcomes. Results: During "only child" , " privileged second child" and "universal second child" period, the number of childbearing women was 12 557, 14 097 and 15 509, respectively, with an increase of 12.3% and 10.0% over previous periods. Maternal ages [M (P(25), P(75))] were [27 (25, 30)], [28 (26, 31)] and [28 (26, 32)] years old. The proportion of multipara in each period was 19.5%, 35.7% and 45.8%, showing an increased trend (P<0.001). The incidence of adverse perinatal outcomes was lowest in the "only child" period (8.7%) and highest in the "universal second child" period (11.1%). Unconditional logistic regression model showed that after adjusting for age, compared with the "only child" period, the risk of premature birth [OR values (95%CI) were 1.20(1.08-1.33) and 1.08 (1.02-1.13), respectively] and birth defects [OR values (95%CI) were 1.33(1.13-1.55) and 1.29 (1.20-1.39), respectively] increased in "privileged second child" and "universal second child" period. The risk of macro infants decreased significantly [OR values(95%CI) were 0.87 (0.80-0.96) and 0.91 (0.87-0.95), respectively], and the risk of perinatal death changed insignificantly [OR values (95%CI) were 0.78 (0.53-1.15) and 0.84 (0.69-1.02), respectively]. Conclusion: According to population based surveillance in two regions in Zhejiang, the proportion of women with advanced age, the proportion of multipara , the risks of birth defects increased with birth policy adaption.

8.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(5): 581-585, 2020 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-32388964

RESUMO

Early life adversity is a risk factor for many diseases, but the related mechanism is not clear. Some research clues suggest that early life adversity is related to biological aging, and at present, the more recognized biological aging index is telomere length. Therefore, exploring the relationship between early life adversity and telomere length is of great significance to reveal the related mechanism of adversity. Through a review of previous literature, this paper discusses the possible effects of different adversity types, exposure time and research design on the relationship between early life adversity and telomere length, so as to provide a basis for the intervention of early life adversity.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32438493

RESUMO

OBJECTIVES: To develop and validate a nomogram based on fetal nuchal translucency (NT) and ultrasonographic facial markers for the screening of trisomy 21 in the first-trimester of pregnancy. METHODS: This was a retrospective case-control study using stored 2D midsagittal fetal profile images captured at 11+0 to 13+6 weeks' gestation. Our database was used to identify 302 cases of trisomy 21 pregnancies and 322 euploid pregnancies. For each case, the maternal age and ultrasonographic facial markers were investigated. Least absolute shrinkage and selection operator (LASSO) method and multivariable analysis were used to select the discriminative markers automatically. Logistic regression was used to develop a model (LASSO-model) based on the selected markers to screen for trisomy 21 in the first-trimester of pregnancy. Furthermore, 60 cases were randomly selected as a retest set to evaluate the model's robustness. The predictive performance of the model of fetal NT and maternal age, the model of all markers of this study and the LASSO-model for the screening of trisomy 21 was assessed using area under receiver operating characteristic (ROC) curve (AUC). A nomogram was developed as an individualized tool to predict patient-specific probability for trisomy 21, which is a more intuitive presentation of the LASSO-model. The performance of the nomogram was assessed using C-index and calibration curve. RESULTS: Eight markers were incorporated into the LASSO-model, including fetal NT, prenasal thickness-to-nasal bone length ratio, facial profile line, frontomaxillary facial angle, frontonasal facial angle, mandibulomaxillary facial angle, maxilla-nasion-mandible angle, and d2 (distance between the anterior edge of the prefrontal skin and the mandibulomaxillary line) (all P-values <0.05). The AUCs of the LASSO-model for the screening of trisomy 21 were 0.983 (95% CI: 0.971-0.994) and 0.979 (95% CI: 0.966-0.993) in the training and the validation sets, respectively, which were higher than the AUCs of all eight individual ultrasonographic markers included in the LASSO-model. The AUC of the LASSO-model in the retest set was 0.997 (95% CI: 0.990-1.000), which showed the good robustness of LASSO-model. The AUC of the LASSO-model was significantly higher than the AUC of the model based on fetal NT and maternal age in both the training and the validation sets. The nomogram of LASSO-model showed a good discrimination of trisomy 21 with C-indexes of 0.983 in the training set and 0.981 in the validation set. CONCLUSION: This study has presented an individualized nomogram, which incorporates the fetal NT and a series of ultrasonographic facial profile markers selected by the LASSO-method and multivariable analysis. It can potentially be utilized as a convenient and effective tool for the screening of trisomy 21 in the first-trimester of pregnancy. This article is protected by copyright. All rights reserved.

10.
Eur Rev Med Pharmacol Sci ; 24(9): 4940-4953, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32432757

RESUMO

OBJECTIVE: Long non-coding RNA taurine upregulated gene 1 (lncRNA TUG1) has been demonstrated to promote malignant phenotypes and Adriamycin resistance in acute myeloid leukemia (AML) cells. However, the function and mechanism of TUG1 in cytarabine (Ara-C) sensitivity in AML remain unclear. PATIENTS AND METHODS: Levels of TUG1, microRNA (miR)-655-3p or cyclin D1 (CCND1) mRNA were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation activity and apoptosis were analyzed using cell counting kit-8 (CCK-8) or flow cytometry, respectively. Western blot was utilized to detect the protein levels of Ki-67, B-cell lymphoma-2-associated X protein (Bax), and CCND1. The interaction between miR-655-3p and TUG1 or CCND1 was confirmed by Dual-Luciferase reporter and pull-down assay. RESULTS: TUG1 and CCND1 were higher expressed, while miR-655-3p was lower expressed in AML cells compared with that in normal cells. Higher expression levels of TUG1 or CCND1, and lower expression levels of miR-655-3p both notably reversed Ara-C-induced proliferation inhibition and apoptosis promotion in AML cells. TUG1 was a sponge of miR-655-3p, and TUG1 knockdown enhanced the sensitivity of AML cells to Ara-C by regulating miR-655-3p. MiR-655-3p directly targeted CCND1, and CCND1 overexpression attenuated miR-655-3p restoration-mediated reinforcement of Ara-C sensitivity in AML cells. Besides that, TUG1 up-regulated CCND1 expression via miR-655-3p. CONCLUSIONS: TUG1 weakened the sensitivity of AML cells to Ara-C by up-regulating CCND1 via miR-655-3p, suggesting a new insight into the chemotherapy of AML.

11.
J Biol Regul Homeost Agents ; 34(1): 69-82, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392921

RESUMO

Baicalin has been used in China to treat inflammation-related diseases, such as inflammation-induced acute kidney injury (AKI). However, the specific mechanism of baicalin remains unclear. To observe the protective effects of baicalin on lipopolysaccharide (LPS)-induced inflammatory injury of renal tubular epithelial cells (HK-2 cells) and to explore its protective mechanism. LPS (1 mg/L) was used to induce an HK-2 cell inflammatory injury model in vitro. The cells were divided into seven groups: the normal control group, LPS-induced group, LPS plus 5 µmol/L baicalin treatment group, LPS plus 15 µmol/L baicalin treatment group, LPS plus 25 µmol/L baicalin treatment group, LPS plus 50 µmol/L baicalin treatment group, and LPS plus 75 µmol/L baicalin treatment group. 3-(4,5-dimethyl-2-thiazolyl)-2,5- diphenyl-2-H-tetrazolium bromide (MTT) assay was employed for detecting the relative survival rate of HK-2 cells. Enzyme-linked immunosorbent assay was used for detecting the levels of inflammatory factors, including interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α). Moreover, the expression of inducible nitric oxide synthase (iNOS); cyclooxygenase-2 (COX-2); nuclear factor kB65 (NF-κB65); phosphorylated NF-κB inhibitory protein-α (p-IκB-α); NF-κB inhibitory protein (IκB); human thioredoxin interacting protein (TXNIP); and human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) were determined by Western blot analysis. The expression levels of NLRP3 and TXNIP mRNA and miR-223-3p were determined by RT-PCR. Results found that the relative survival rate of HK-2 cells treated with different baicalin concentrations was significantly increased (P<0.05) and the levels of the inflammatory factors IL-6, IL-1ß, and TNF-α were significantly decreased (P<0.05) compared with those of the LPS-induced group. The expression levels of the inflammatory proteins inducible nitric oxide synthase and cyclooxygenase-2 and the genes expressions of TXNIP and NLRP3 were significantly decreased in the cells (P<0.05), while the expression level of miR-223- 3p was significantly increased (P<0.05). These changes were induced in a dose-dependent manner. The results suggest that baicalin significantly inhibited the expression of inflammation-related proteins and alleviated LPS-induced inflammatory injury in HK-2 cells. The mechanism may be associated with the inhibition of activation of the TXNIP/NLRP3 inflammatory pathway, which might be mediated by increased expression of miR-223-3p. Thus, NLRP3 is a regulatory target of miR-223-3p.

12.
Zhonghua Wai Ke Za Zhi ; 58(5): 356-362, 2020 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-32393002

RESUMO

Objective: To examine the short and long-term clinical outcomes of total arterial coronary artery bypass grafting. Methods: Clinic data of 208 patients with left main and multiple vessel coronary artery disease and undertaken total arterial coronary artery bypass grafting from February 2009 to December 2019 in Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine were analyzed retrospectively. There were 188 males and 20 females with an age of (54.7±10.7) years (range: 32 to 79 years). The harvest of arterial conduits and grafting strategies were depended upon the individual patient characteristics and surgeon's experience. Left internal thoracic artery (LITA) was applied in 207 cases, right internal thoracic artery (RITA) in 38 cases (bilateral internal thoracic artery (BITA) in 37 cases), and radial artery (RA) in 187 cases (188 grafts). The graft number per case was 2.6±0.7 (range: 2 to 4). Surgical procedures was completed with off-pump technique in 98.1% patients (204/208). Subgroup analysis was carried out between subgroup BITA (n=37) and subgroup SITA (single ITA+RA) (n=171). The t test, χ(2) test or Fisher exact test were used to compare the clinic characteristics between the two subgroups. The Kaplan-Meier curve was used to estimate the rate of late mortality, major adverse cardiac cerebrovascular event (MACCE), and target vessel revascularization (TVR). A Cox proportional hazards model was used to identify the independent prognosis factors of late mortality. Results: The overall mortality within 30 days postoperatively was 1.4%(3/208). The incidences of perioperative MACCE, re-operation for bleeding and deep sternal wound infection (DSWI) were 1.9%(4/208), 0.5%(1/208) and 1.4%(3/208), respectively. Perioperative myocardial infarction and TVR were not observed. There was no significant difference of 30-day mortality, MACCE, bleeding and DSWI between subgroup BITA and SITA+RA (all P>0.05). In a follow-up period of (5.4±2.8)years (range: 0.2 to 10.9 years), the incidence of all-cause mortality at 1-, 5- and 10-year was 2.3%, 3.4% and 6.9%, respectively. The incidence of MACCE was 3.9%,11.2% and 28.5%, respectively. The rate of TVR was 0.4%, 3.7% and 11.9%, respectively. Age>65 was an independent prognosis factor of late mortality (HR=1.125, 95% CI:1.050 to 1.205, P<0.01). Conclusions: Total arterial coronary bypass grafting is safe and achievable with proper patient selection and surgical strategies. It significantly decreases the risks of late mortality and repeated revascularization.

13.
Eur Rev Med Pharmacol Sci ; 24(7): 3509-3516, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32329824

RESUMO

OBJECTIVE: To explore the effects of micro ribonucleic acid (miR)-32 on the proliferation and apoptosis of myeloma cells, and to verify whether it exerts its function by targeting phosphatase and tensin homolog deleted on chromosome ten (PTEN). PATIENTS AND METHODS: The differentially expressed miRNAs were screened in healthy people and myeloma patients. The myeloma U266 cells transfected with negative control (NC) were used as control group, those transfected with miR-32 inhibitor as transfection group, and those transfected with miR-32 inhibitor and treated with PTEN inhibitor SF1670 as the transfection + inhibitor group. Then, the cell proliferation and apoptosis in each group were detected using the 5-Ethynyl-2'-deoxyuridine (EdU) kit and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, respectively. Finally, the expressions of apoptosis-related proteins B-cell lymphoma-2 (Bcl-2), Bcl-2 homologous antagonist/killer (Bak), caspase-9, and survivin were detected. RESULTS: The expressions of some miRNAs and genes in myeloma patients were significantly different from those in healthy people. In myeloma patients, miR-32, miR-126, miR-123, and miR-183 were significantly highly expressed, while miR-5, miR-76, and miR-50 were remarkably lowly expressed. After myeloma U266 cells were transfected with the miR-32 inhibitor, the expression of miR-32 markedly declined. In addition, the mRNA expression of PTEN in myeloma cells rose after transfection with the miR-32 inhibitor, and declined after addition of the PTEN inhibitor SF1670, which were consistent with the results of Western blotting. Besides, the proliferation ability of myeloma cells was evidently weakened after transfection with the miR-32 inhibitor, while it was restored to a certain extent after addition of the PTEN inhibitor SF1670. Moreover, the number of apoptotic myeloma cells was remarkably larger after transfection with the miR-32 inhibitor, while it was remarkably smaller after addition of the PTEN inhibitor SF1670. The expressions of pro-apoptotic proteins Bak and caspase-9 in myeloma cells were significantly increased after transfection with the miR-32 inhibitor (p<0.05), and significantly decreased after addition of the PTEN inhibitor SF1670, while the expressions of anti-apoptotic proteins Bcl-2 and survivin were opposite to those of Bak and caspase-9. CONCLUSIONS: MiR-32 targeting PTEN will have certain effects on the proliferation and apoptosis of myeloma cells.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32277496

RESUMO

BACKGROUND: Hyperthermia upregulates DNAJA4, a member of heat shock proteins (HSPs) 40 family, in human keratinocytes and HPV-infected tissue. DNAJA4 deficiency enhances growth arrest induced by hyperthermia. Clusterin (CLU) and phosphorylated ERK (p-ERK) play a role in regulating cell proliferation and apoptosis, under environmental stress. OBJECTIVES: To examine the downstream molecules and signalling pathways of DNAJA4 and assess their roles in cell cycle and apoptosis of keratinocytes in response to hyperthermia. METHODS: Wild-type and DNAJA4-knockout (KO) HaCaT cells were exposed to either 44 °C (hyperthermia) or 37 °C (control) for 30 min. The expression levels of CLU and p-ERK were determined by RT-PCR and Western blotting. RNAi and PD98059 were used to inhibit the expression of CLU and p-ERK, respectively. Cell viability, cell cycle and apoptosis were analysed by MTS assay and flow cytometry. Fresh biopsy samples of human normal foreskin or condyloma acuminatum (CA) were utilized to examine the expression of CLU and p-ERK after ex vivo culture at 44 °C. RESULTS: The expression of CLU and p-ERK was significantly increased by hyperthermia treatment at 44 °C in HaCaT cells, foreskin and HPV-infected tissues. In HaCaT cells subjected to hyperthermia, DNAJA4 deficiency further augmented the expression of CLU and p-ERK. CLU deficiency enhanced the p-ERK expression. Hyperthermia-induced CLU and p-ERK exerted protective roles mainly through inhibiting apoptosis and maintaining cell cycle, respectively. CONCLUSIONS: In keratinocytes, CLU and p-ERK are induced by hyperthermia, an effect which can be further enhanced by DNAJA4 deficiency. CLU deficiency also increases p-ERK expression. Both CLU and p-ERK are critical protective factors of human keratinocytes from hyperthermia-induced injury.

15.
J Phys Condens Matter ; 32(31): 315702, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32235052

RESUMO

Topological semimetals (TSMs) present intriguing quantum states and have attracted much attention in recent years because of exhibiting various anomalous magneto-transport phenomena. Theoretical prediction shows that some novel phenomena, such as negative magnetoresistance (MR) and the planar Hall effect (PHE), originate from the chiral anomaly in TSMs. In this work, high-field (33 T) Shubnikov-de Haas (SdH) oscillations are obtained to reveal the topology of PtSn4. Giant PHE and anisotropic magnetoresistance (AMR) are observed in Dirac node arcs of semimetal PtSn4. First, a non-zero transverse voltage can be acquired while tilting the in-plane magnetic field. Moreover, the amplitude of PHE sharply increases at T * ∼ 50 K with decreasing temperature, which is suggested to be related to the Fermi surface reconstruction observed in PtSn4. Subsequently, the field-dependent amplitudes of the PHE show an abnormal behavior around 50 K, which is thought to stem from the complex correlation between the chiral charge and electric one in PtSn4 driving the system into different coupling states due to the complicated band structure. On the other hand, the relative AMR is negative and up to -98% at 8.5 T. Our work proves that the PHE measurements are a convincing transport fingerprint feature to confirm the chiral anomaly in TSMs.

16.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(4): 514-519, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32344474

RESUMO

Objective: To investigate the influence of the prevalence and co-prevalence of risk factors for metabolic syndrome on the scores of different levels of metabolic syndrome in people receiving physical examination in Urumqi. Methods: Using the 2017 Xinjiang Health Examination Database, a total of 175 927 people from 7 districts and 1 county in Urumqi were selected as subjects. Face-to-face survey and body measurements were used to collect cardiovascular risk factors and metabolic syndrome scores. Metabolic syndrome scores were used. For the 0-5 points at 6 levels, χ(2), χ(2) trend test, correlation analysis of ordered variable Kendall's tau-b, and logistic regression analysis of ordered results were used to analyze the influence of prevalence and co-prevalence of behavioral risk factors on the MS scores. Results: The percentages of 6 metabolic syndrome scores in the sample population were 23.82%, 27.87%, 22.41%, 16.03%, 8.02%, and 1.85%, respectively. The scores of metabolic syndrome were different in different age groups, ethnic groups, groups with different drinking rates, and groups with different dietary types, with the differences all significant (P<0.05).The MS score in men increased with the increase of oil/salt rate and excessive drinking rate (P<0.01). The score in women increased with the increase of the current smoking rate, oil/salt rate, and increased with the decrease of physical activity (P≤0.01). There was no significant difference in the distribution of regular drinking rates between different score groups (P>0.05). The scores of metabolic syndrome increased with the increase of risk factors (P<0.05). Ordered results logistic analysis found that in the men with ≥3 risk factors and the metabolic syndrome score was 1.15 (1.06-1.26) times higher than that in the men without risk factor, as well as in women with 2 risk factors and≥3 risk factors. The metabolic syndrome scores were 1.38 (1.22-1.55), 2.02 (1.53-2.66) times higher than those in the women without risk factors. Conclusions: The physical examination group in Urumqi, the more the metabolic syndrome disease behavior risk factors clustered, the higher the metabolic syndrome score was. Therefore, comprehensive intervention measures should be taken to control the different forms of metabolic syndrome to prevent the occurrence and progress of the disease.

17.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(4): 562-566, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32344483

RESUMO

Objective: To understand the pathogens and molecular-epidemiologic characteristics of viral meningo-encephalitis in Zhejiang province during 2002 to 2018. Methods: All the samples were collected from suspected patients admitted to the hospitals under the monitoring program. Of the total samples, 2 173 were cerebrospinal fluids while the other 455 were stool specimens. Cerebrospinal fluid (CSF) samples were subject to real-time qPCR for the detection of Human enterovirus (HEV), Mumps virus (MuV), Herpes simplex virus (HSV), Cytomegalovirus (CMV) and Japanese encephalitis virus (JEV). Stool sample were subject to real-time qPCR for HEV. ELISA was used to detect the IgM antibodies in CSF, in the 5 kinds of virus mentioned above. VP1 genes from all RNA-positive specimen were amplified, sequenced, for typing and for evolution analysis. Results: 871 (40.1%) of the 2 173 samples were detected as HEV nucleic acid positive during 2002 to 2018. 654 (38.1%) of the 1 718 CSF sample were HEV nucleic acid positive while 217 (47.7%) of the 455 stool sample were HEV nucleic acid positive. Among the total positive nucleic acid sample, 670 of them were VP1 sequence positive, including 5 HEV-A and 665 HEV-B. There were 23 HEV serotypes, including Coxsackievirus (CV) CVA4, CVA6, CVA9, CVA10, CVB1-5, Echovirus (EchoV; E) E3, E4, E6,E7, E9, E11, E14, E16, E18, E21, E25, E30, E33 and EV-71. The top three serotypes went to E30, E6 and CVB5. These three serotypes presented enhanced viral activity in every several years. 795 CSF samples were detected as virus nucleic acid positive, including 374 HEV, 6 MuV, 5 HSV and 5 CMV, from 2012 to 2015 and in 2018. 5 kinds of IgM antibodies were detected simultaneously in 368 CSF samples, including 2 HEV positive, 6 JEV positive and 1 MuV positive for 5 viruses, respectively. Except for EV-71, there were 517 EchoV and 152 CV viruses presented, with the ratio of 3.4∶1. These two kinds of viruses alternately changed for each predominant epidemic strains in every 3-5 years. Based on VP1, results from the phylogenetic tree showed that HEV from Zhejiang province clustered into HEV-A and HEV-B clades respectively. E30 developed both h and i sub-genotypes. Conclusions: HEV-B seemed the main pathogen for viral meningo-encephalitis in Zhejiang province. Ratio of positive detection on EchoV was significantly higher than that on CV. These two kinds of virus alternately presented changing tendency in every several years. Predominant epidemic strains E30, CVB5 and E6 were presenting enhanced viral activity, also in every several years. High correlation was found in both HEV viral activity from the surveillance sites and in time line of the viral meningo-encephalitis outbreaks.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32276116

RESUMO

OBJECTIVE: To evaluate a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and compare it with RT-PCR. METHODS: We designed primers specific to the orf1ab and S genes of SARS-CoV-2. Total viral RNA was extracted using the QIAamp Viral RNA Mini Kit. We optimized the RT-LAMP assay, and evaluated it for its sensitivity and specificity of detection using real-time turbidity monitoring and visual observation. RESULTS: The primer sets orf1ab-4 and S-123 amplified the genes in the shortest times, the mean (±SD) times were 18 ± 1.32 min and 20 ± 1.80 min, respectively, and 63°C was the optimum reaction temperature. The sensitivities were 2 × 101 copies and 2 × 102 copies per reaction with primer sets orf1ab-4 and S-123, respectively. This assay showed no cross-reactivity with 60 other respiratory pathogens. To describe the availability of this method in clinical diagnosis, we collected 130 specimens from patients with clinically suspected SARS-CoV-2 infection. Among them, 58 were confirmed to be positive and 72 were negative by RT-LAMP. The sensitivity was 100% (95% CI 92.3%-100%), specificity 100% (95% CI 93.7%-100%). This assay detected SARS-CoV-2 in a mean (±SD) time of 26.28 ± 4.48 min and the results can be identified with visual observation. CONCLUSION: These results demonstrate that we developed a rapid, simple, specific and sensitive RT-LAMP assay for SARS-CoV-2 detection among clinical samples. It will be a powerful tool for SARS-CoV-2 identification, and for monitoring suspected patients, close contacts and high-risk groups.

19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(3): 343-348, 2020 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-32294832

RESUMO

Objective: To understand the actual needs for the pre-exposure prophylaxis (PrEP) for HIV infection and the factors hindering PrEP utilization in men who have sex with men (MSM). Methods: Participants were recruited by using MSM social application software Blued 6.5.0 and through MSM peer referral, sample size was 600. An electronic questionnaire survey was conducted anonymously with guidance of investigators via "Questionnaire Star" platform. The contents of the survey included demographic characteristics of the participants, the awareness of PrEP related knowledge, willingness and concerns about using PrEP, actual need for PrEP and self-efficacy of using PrEP. Results: A total of 622 MSM completed the survey, of whom 56.4% (351/622) and 4.3% (27/622) ever heard of and received PrEP, respectively. The need assessment of PrEP showed that 67.2% (418/622) of the participants had actual needs for PrEP and 21.2% (132/622) used PrEP with good self-efficacy. Structural equation modeling analysis showed that the awareness of PrEP related knowledge and concerning about PrEP utilization in MSM played a direct positive role in their self-efficiency of using PrEP, and the effect coefficients were 0.08 and 0.13, respectively. MSM self-discrimination indirectly affected the self-efficiency of using PrEP through concerns about PrEP use, the effect coefficient was 0.035. The result of generalized linear mixed model analysis demonstrated that the utilization of PrEP can improve the self-efficacy of using PrEP (OR=5.55), which increased by 0.14 times and 0.07 times with the increase of 1 score of the awareness of PrEP related knowledge and concern about using PrEP respectively. In addition, this survey found that in the participants, the main concerns about using PrEP were side effects, HIV prevention effect and its expense, accounting for 61.1% (380/622), 60.1% (374/622) and 53.2% (331/622), respectively. Most participants hoped to obtain PrEP services from CDC, MSM social organization and internet, accounting for 75.6% (470/622), 65.4% (407/622), and 63.8% (397/622), respectively. Conclusions: MSM showed difference of high need but low utilization of PrEP services. Low awareness of PrEP related knowledge, concerns about the prevention effect, side effects and expense of PrEP as well as self-discrimination were the factors hindering the use of PrEP in MSM. It is necessary to establish a suitable PrEP service model to meet the needs for PrEP in MSM.

20.
Animal ; : 1-9, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32295654

RESUMO

Beef cattle are often fed high-concentrate diet (HCD) to achieve high growth rate. However, HCD feeding is strongly associated with metabolic disorders. Mild acid treatment of grains in HCD with 1% hydrochloric acid (HA) followed by neutralization with sodium bicarbonate (SB) might modify rumen fermentation patterns and microbiota, thereby decreasing the negative effects of HCD. This study was thus aimed to investigate the effects of treatment of corn with 1% HA and subsequent neutralization with SB on rumen fermentation and microbiota, inflammatory response and growth performance in beef cattle fed HCD. Eighteen beef cattle were randomly allocated to three groups and each group was fed different diets: low-concentrate diet (LCD) (concentrate : forage = 40 : 60), HCD (concentrate : forage = 60 : 40) or HCD based on treated corn (HCDT) with the same concentrate to forage ratio as the HCD. The corn in the HCDT was steeped in 1% HA (wt/wt) for 48 h and neutralized with SB after HA treatment. The animal trial lasted for 42 days with an adaptation period of 7 days. At the end of the trial, rumen fluid samples were collected for measuring ruminal pH values, short-chain fatty acids, endotoxin (or lipopolysaccharide, LPS) and bacterial microbiota. Plasma samples were collected at the end of the trial to determine the concentrations of plasma LPS, proinflammatory cytokines and acute phase proteins (APPs). The results showed that compared with the LCD, feeding the HCD had better growth performance due to a shift in the ruminal fermentation pattern from acetate towards propionate, butyrate and valerate. However, the HCD decreased ruminal pH and increased ruminal LPS release and the concentrations of plasma proinflammatory cytokines and APPs. Furthermore, feeding the HCD reduced bacterial richness and diversity in the rumen. Treatment of corn increased resistant starch (RS) content. Compared with the HCD, feeding the HCDT reduced ruminal LPS and improved ruminal bacterial microbiota, resulting in decreased inflammation and improved growth performance. In conclusion, although the HCD had better growth performance than the LCD, feeding the HCD promoted the pH reduction and the LPS release in the rumen, disturbed the ruminal bacterial stability and increased inflammatory response. Treatment of corn with HA in combination with subsequent SB neutralization increased the RS content and helped counter the negative effects of feeding HCD to beef steers.

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