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1.
Chem Biol Interact ; 331: 109273, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33002460

RESUMO

Artesunate is a kind of derivative of artemisinin, which possesses potent anti-cancer effect in addition to its anti-malarial property. And autophagy was a highly conserved process, exerting a double-edged effect in cancer cell survival. Besides, apoptosis is a programmed cell death program, crucial to cell homeostasis. However, the relations between autophagy and apoptosis, and the role of artesunate in this interaction have not been elucidated in bladder cancer. In present study, we used human bladder cancer cells (T24 and EJ cell lines) to investigate that how artesunate would influence autophagy and apoptosis processes. We found that artesunate could inhibit the viability, proliferation and migration of bladder cancer cells, as well as induce autophagy in a time and dose dependent manner, in addition, the artesunate induced autophagy subsequently activated cells apoptosis. Furthermore, we pretreated T24 and EJ cells with 3-Methyladenine or Rapamycin to inhibit or promote autophagy, respectively, leading to inhibited or increased apoptosis. Moreover, pretreatment of these cell lines with Acadesine or Dorsomorphin to activate or inhibit the AMPK-mTOR-ULK1 pathway, respectively, also resulting in promotion or suppression in both autophagy and apoptosis. In the upstream, ROS upregulation triggered by ART initiated AMPK-mTOR-ULK1 axis. However, this initiative effect of ROS can be reversed by N-Acetyl-l-cysteine. Therefore, this study indicated that Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 pathway in human bladder cancer cells.

2.
Food Chem Toxicol ; 146: 111803, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035629

RESUMO

This study aimed to investigate the therapeutic effect of curcumin on type 2 diabetes and its underlying mechanisms. A type 2 diabetes mellitus rat model was established by providing high-fat diet and low doses of streptozotocin. Type 2 diabetes mellitus rats were treated with low dose and high dose of curcumin for 8 weeks. The results showed that high-dose curcumin significantly reduced fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase, liver coefficient, and malondialdehyde levels, and BCL2-Associated X expression in the type 2 diabetes mellitus rats. High-dose curcumin increased the levels of liver superoxide dismutase, catalase, and glutathione; as well as the expression of liver B-cell lymphoma-2, phosphatidylinositol 3-kinase, phosphorylated phosphatidylinositol 3-kinase, protein kinase B, and phosphorylated protein kinase B in type 2 diabetes mellitus rats. Furthermore, it ameliorated the histological structure of the liver and pancreas in diabetes mellitus model rats. However, low-dose curcumin had no significant effect on diabetes mellitus model rats. The results suggest that adequate doses of curcumin controls type 2 diabetes mellitus development as well as the mechanism involved in its anti-apoptotic actions and phosphatidylinositol 3-hydroxy kinase/protein kinase B signal pathway regulation in the liver.

3.
J Inorg Biochem ; 212: 111208, 2020 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-33065383

RESUMO

Two new copper(II) complexes, 9-PMAH-Cu (1) and 9-FPMAH-Cu (2), of anthrahydrazone were synthesized and structurally characterized, in which 9-FPMAH (9-(4'-trifluoromethyl)-pyrimidine anthrahydrazone) is the 4'-CF3 derivative of 9-PMAH (9-pyrimidine anthrahydrazone). Both complexes 1 and 2 showed similar intercalative binding modes towards DNA and might compete with the typical DNA intercalator, GelRed, in the same binding site. They could also act as topoisomerase (type I) suppressor to effectively inhibit its activity, in which complex 1 was more effective than 2. The in vitro antitumor screening indicated that complex 1 displayed much higher antiproliferative ability than 2 and cisplatin towards all the tested tumor cell lines. On the other hand, complex 1 also showed high cytotoxicity against human normal liver cell line HL-7702, suggesting it is a potential high cytotoxic antitumor candidate. While it was also suggested that the loss of activity of complex 2 might be due to the presence of 4'-CF3 on the pyrimidine ring. Studies on the cellular level showed that complex 1 could arrest the cell cycle of the most sensitive T-24 cells at G2/M phase and induced cell apoptosis. Complex 1 further showed a significant suppression on the tumor growth on the T-24 tumor xenograft mouse model, but not reduced the body weight. Especially, complex 1 could retain its coordination state in H2O even in the presence of HSA. The results suggests that complex 1 is of enough safety to be considered as a promising anticancer candidate by combining the bioactive Cu(II) and the anthrahydrazone pharmacophore.

4.
Pharmaceuticals (Basel) ; 13(10)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066488

RESUMO

Five novel peptides (LPLF, WLQL, LPSW, VPGLAL, and LVGLPL) bearing dipeptidyl peptidase IV (DPP-IV) inhibitory activities were identified from the gastrointestinal enzymatic hydrolysate of soft-shelled turtle yolk (SSTY) proteins. Peptides were isolated separately using reversed-phase (RP) chromatography in parallel with off-line strong cation exchange (SCX) chromatography followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to determine sequences. Among these peptides, LPSW showed the highest DPP-IV inhibitory activity with an IC50 value of 269.7 ± 15.91 µM. The results of the pre-incubation experiment and the kinetic study of these peptides indicated that WLQL is a true inhibitor and its inhibition toward DPP-IV is of an uncompetitive model, while LPLF, LPSW, and VPGLAL are real-substrates and competitive inhibitors against DPP-IV. The DPP-IV inhibitory peptides derived from SSTY hydrolysate in study are promising in the management of hyperglycemia in Type 2 diabetes.

5.
Nat Commun ; 11(1): 5248, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067419

RESUMO

Cancer has no borders: Generation and analysis of molecular data across multiple centers worldwide is necessary to gain statistically significant clinical insights for the benefit of patients. Here we conceived and standardized a proteotype data generation and analysis workflow enabling distributed data generation and evaluated the quantitative data generated across laboratories of the international Cancer Moonshot consortium. Using harmonized mass spectrometry (MS) instrument platforms and standardized data acquisition procedures, we demonstrate robust, sensitive, and reproducible data generation across eleven international sites on seven consecutive days in a 24/7 operation mode. The data presented from the high-resolution MS1-based quantitative data-independent acquisition (HRMS1-DIA) workflow shows that coordinated proteotype data acquisition is feasible from clinical specimens using such standardized strategies. This work paves the way for the distributed multi-omic digitization of large clinical specimen cohorts across multiple sites as a prerequisite for turning molecular precision medicine into reality.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1534-1538, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067950

RESUMO

OBJECTIVE: To explore the effect of nuclear factor kappa-B (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) on the proliferation and apoptosis of acute leukemia cell HL-60. METHODS: HL-60 cells were cultured with PDTC of 0, 25, 50, 100 µmol/L for 24, 48, 72 h. The inhibition rate of cell proliferation was detected by CCK-8 assay. Cell apoptosis was detected by Hoechst staining. Cell cycle was detected by flow cytometry. The expression of B-cell lymphoma-2 (BCL-2), BCL-2 associated X protein (BAX), cyclinD1, activated cysteinyl aspartate specific proteinase (cleaved caspase 3), cleaved caspase 8 and activation of NF-κB signal pathway related protein was detected by Western blot. RESULTS: After the HL-60 cells were cultured with PDTC of 25, 50, 100 µmol/L for 24, 48, 72 h, the inhibition rate of cell proliferation increased with the enhancement of PDTC concentration at the same time point (r=0.924, P<0.01). At the same PDTC concentration, the inhibition rate of cell proliferation increased with prolonging of time (r=0.952, P<0.01). After HL-60 cell was cultured with PDTC of 25, 50, 100 µmol/L for 48 h, compared with control group, PDTC of 25, 50, 100 µmol/L increased the cell apoptotic rate, arrested cell cycle at G1 phase (P<0.01), the expression of BCL-2, cyclinD1 and p-NF-κB p65 was down-regulated(P<0.05), the expression of BAX, cleaved caspase 3, cleaved caspase 8 was up-regulated(P<0.01). PDTC of 50, 100 µmol/L down-regulated the expression of p-inhibitor of NF-κB (p-IκBα)(P<0.01). CONCLUSION: PDTC can inhibit acute leukemia HL-60 cell proliferation and induce cell apoptosis.

7.
Int J Clin Pract ; : e13760, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068310

RESUMO

INTRODUCTION: Computed tomography (CT) can be effective for the early screening and diagnosis of COVID-19. This study aimed to investigate the distinctive CT characteristics of two stages of the disease (progression and remission). METHODS: We included all COVID-19 patients admitted to Wenzhou Central Hospital from January to February, 2020. Patients underwent multiple chest CT scans at intervals of 3-10 days. CT features were recorded, such as the lesion lobe, distribution characteristics (subpleural, scattered, or diffused), shape of the lesion, maximum size of the lesion, lesion morphology (ground-glass opacity, GGO), and consolidation features. When consolidation was positive, the boundary was identified to determine its clarity. RESULTS: The ratios of some representative features differed between the remission stage and the progression phase, such as round-shape lesion (8.0% vs. 34.4%), GGO (65.0% vs. 87.5%), consolidation (62.0% vs. 31.3%), large cable sign (59.0% vs. 9.4%), and crazy-paving sign (20.0% vs. 50.0%). Using these features, we pooled all the CT data (n = 132) and established a logistic regression model to predict the current development stage. The variables consolidation, boundary feature, large cable sign, and crazy-paving sign were the most significant factors, based on a variable named 'prediction of progression or remission' (PPR) that we constructed. The ROC curve showed that PPR had an AUC of 0.882 (cutoff value = 0.66, sensitivity = 0.75, specificity = 0.875). CONCLUSION: CT characteristics, in particular, round shape, GGO, consolidation, large cable sign, and crazy-paving sign, may increase the recognition of the intrapulmonary development of COVID-19.

8.
Sensors (Basel) ; 20(20)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050320

RESUMO

A novel interactive system for calligraphy called mind calligraphy that reflects the writer's emotions in real time by affective computing and visualization techniques is proposed. Differently from traditional calligraphy, which emphasizes artistic expression, the system is designed to visualize the writer's mental-state changes during writing using audio-visual tools. The writer's mental state is measured with a brain wave machine to yield attention and meditation signals, which are classified next into the four types of emotion, namely, focusing, relaxation, calmness, and anxiety. These emotion types then are represented both by animations and color palettes for by-standing observers to appreciate. Based on conclusions drawn from data collected from on-site observations, surveys via Likert-scale questionnaires, and semi-structured interviews, the proposed system was improved gradually. The participating writers' cognitive, emotional, and behavioral engagements in the system were recorded and analyzed to obtain the following findings: (1) the interactions with the system raise the writer's interest in calligraphy; (2) the proposed system reveals the writer's emotions during the writing process in real time via animations of mixtures of fish swimming and sounds of raindrops, insects, and thunder; (3) the dynamic visualization of the writer's emotion through animations and color-palette displays makes the writer understand better the connection of calligraphy and personal emotions; (4) the real-time audio-visual feedback increases the writer's willingness to continue in calligraphy; and (5) the engagement of the writer in the system with interactions of diversified forms provides the writer with a new experience of calligraphy.

9.
J Cardiol ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33012590

RESUMO

BACKGROUND: Early graft failure can affect the short- and long-term outcomes of patients undergoing coronary bypass grafting surgery (CABG). The aim of our study was to explore the predictive value of transit-time flow measurement (TTFM) parameters for early graft failure (before discharge) after CABG in different coronary territories and calculate the TTFM cut-off values. METHODS: We analyzed a total of 761 grafts (360 patients) that were evaluated by intraoperative TTFM and computed tomography angiography prior to discharge. Logistic model was established to detect the parameters of TTFM to predict early graft failure and receiver operating characteristic curve analysis was used to calculate the cut-off values. RESULTS: The overall early graft failure was 3.5%. The results demonstrated that compared with off-pump CABG, mean graft flow volume was higher (28.0 vs 21.0 mL/min, p = 0.000), but pulse index (PI) (2.3 vs 2.5, p = 0.049) and diastolic flow fraction (DF) (68.0% vs 71.0%, p = 0.001) were lower in on-pump CABGs. DF (73.0% vs 65.5%, p = 0.000) of arterial grafts was higher than that of venous grafts. DF (72.0% vs 62.0%, p = 0.000) in left was higher than that in the right coronary artery territories. The results of multivariate logistic analysis showed that not only in the overall (OR 1.18, 95% CI 1.07-1.30, p = 0.001), but also the left (OR 1.21, 95% CI 1.03-1.41, p = 0.017) and right (OR 1.15, 95% CI 1.03-1.29, p = 0.017) coronary artery target territories, PI was a risk factor for early graft failure and the cut-off value was 3.4, 3.4, and 3.6, respectively. For grafts in left target territories, the results showed that DF (OR 0.94, 95% CI 0.91-0.97, p = 0.000) just in the univariate analysis was a risk factor that affected graft failure. CONCLUSIONS: The overall early graft failure was about 3.5%. High PI value is a risk factor for early graft failure in not only overall grafts but in grafts of different target territories. DF might be more useful for the quality evaluation of grafts in left than in right target territories.

10.
Circ J ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33012748

RESUMO

BACKGROUND: The effect of remote monitoring (RM) in atrial arrhythmia detection, stroke reduction, and anticoagulation therapy remains unknown, particularly for patients with implantable or wearable cardiac devices.Methods and Results:We performed a systematic review and meta-analysis to evaluate the role of RM in atrial arrhythmia detection, stroke reduction and anticoagulation therapeutic intervention. Online databases were queried to include randomized controlled trials comparing detection of atrial arrhythmia and stroke risk between patients undergoing RM and those receiving in-office (IO) follow-up. Outcomes and complications of RM-guided anticoagulation therapy and conventional therapy in patients with atrial fibrillation were also reviewed. A total of 16 studies were included. Compared with patients receiving IO follow-up, patients undergoing RM had a significantly higher detection rate of atrial arrhythmia (risk ratio [RR], 1.363; 95% confidence interval [CI], 1.147-1.619), and a lower risk of stroke (RR, 0.539; 95% CI, 0.301-0.936). The higher rate of atrial arrhythmia was only noted in patients with wearable devices (RR, 4.070; 95% CI, 2.408-6.877), and the lower risk of stroke was only noted in patients with cardiovascular implantable electronic devices (CIED) (RR, 0.513; 95% CI, 0.265-0.996). CONCLUSIONS: RM is effective for atrial arrhythmia detection in patients using wearable devices and for reducing the risk of stroke in patients with CIED.

11.
Cytogenet Genome Res ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022677

RESUMO

The excessive production of inflammatory mediators by vascular endothelial cells (ECs) greatly contributes to the development of atherosclerosis. In this study, we explored the potential effect of lncRNA MALAT1 on endothelial inflammation. First, the EC inflammation model was constructed by treating human umbilical vein ECs (HUVECs) and human coronary artery ECs (HCAECs) with oxidized low-density lipoprotein (ox-LDL), which confirmed the role of MALAT1 in the inflammatory activity. Then MALAT1 was overexpressed in HUVECs and HCAECs, and the levels of inflammatory mediators and nitric oxide (NO) were examined by Western blotting, ELISA, and NO detection assay. The migration ability was confirmed by wound healing assay. The interactions among MALAT1, miR-590, and STAT3 were predicted by bioinformatics analysis and verified by qRT-PCR, Western blotting, or dual-luciferase reporter assay. MALAT1 was upregulated in ECs treated with ox-LDL, and knockdown of MALAT1 significantly inhibited ox-LDL-induced inflammation. MALAT1 overexpression potentiated the inflammatory activities of ECs, including enhanced production of inflammatory cytokines (IL-6, IL-8, and TNF-α) and adhesion molecules (VCAM1 and ICAM1), and decreased NO level and cell migratory ability. Mechanistically, MALAT1 could directly downregulate miR-590, and miR-590 could bind to the 3'-UTR of STAT3 to repress its expression. Additionally, overexpression of MALAT1-mediated inflammation was largely abrogated by the concomitant overexpression of miR-590. miR-590 knockdown activated the inflammatory response, which was reversed by STAT3 inhibition. Thus, MALAT1 serves as a proinflammatory lncRNA in ECs through regulating the miR-590/STAT3 axis, suggesting that MALAT1 may be a promising therapeutic target during the treatment of atherosclerosis.

12.
J Pharm Biomed Anal ; 191: 113611, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-33007733

RESUMO

This manuscript describes a highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of dasotraline in human plasma. Dasotraline and the internal standard (IS) d4-13C4-dasotraline were extracted from the 0.500-mL plasma pre-mixed with 0.20-mL of 0.5 M sodium bicarbonate solution by a 3-mL of hexane containing 0.7 % sec-butyl alcohol. The organic extract, after dried down, was reconstituted in 150 µL acetonitrile containing 0.1 % formic acid. Forty (40) µL of the resulted sample was injected into LC-MS/MS for analysis. Chromatographic separation was on a Betasil Silica column. MS/MS detection was by monitoring m/z 275→159 and 283→160 for dasotraline and IS, respectively. Peak area ratio of analyte/IS was used for constructing calibration curve and calculating sample concentration. The retention time was ∼3.1 min for both dasotraline and IS. The validated linear range was 5-5000 pg/mL with correlation coefficient r ≥ 0.999. Intra-run precision and accuracy were ≤ 7.3 % CV (n = 6) and 94.4-101.0 % of nominals. Inter-run precision and accuracy were ≤ 4.7 % CV (n = 18) and 96.1-99.8 % of nominals. Plasma sample was confirmed stable for 8 cycles of freeze/thaw, 29 h on bench-top, and up to 977 days of storage at both -20 °C and -70 °C. This method was successfully applied to analyze pharmacokinetic (PK) samples from a single ascending dose (SAD) clinical study with healthy subjects. PK results indicated that dasotraline was slowly absorbed (tmax: 10-12 h) and slowly eliminated (terminal elimination half-life, i.e. t1/2: 47-77 h) with dose proportional Cmax but slightly greater than dose proportional AUC with increase of dosed amount.

13.
Radiother Oncol ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039424

RESUMO

PURPOSE: The delineation of the clinical target volume (CTV) is a crucial, laborious and subjective step in cervical cancer radiotherapy. The aim of this study was to propose and evaluate a novel end-to-end convolutional neural network (CNN) for fully automatic and accurate CTV in cervical cancer. METHODS: A total of 237 computed tomography (CT) scans of patients with locally advanced cervical cancer were collected and evaluated. A novel 2.5D CNN network, called DpnUNet, was developed for CTV delineation and further applied for CTV and organ-at-risk (OAR) delineation simultaneously. Comprehensive comparisons and experiments were performed. The mean Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (95HD) and subjective evaluation were used to assess the performance of this method. RESULTS: The mean DSC and 95HD values were 0.86 and 5.34mm for the delineated CTVs. The clinical experts' subjective assessments showed that 90% of the predicted contours were acceptable for clinical usage. The mean DSC and 95HD values were 0.91 and 4.05mm for bladder, 0.85 and 2.16mm for bone marrow, 0.90 and 1.27mm for left femoral head, 0.90 and 1.51mm for right femoral head, 0.82 and 4.29mm for rectum, 0.85 and 4.35mm for bowel bag, 0.82 and 4.96mm for spinal cord respectively. The average delineation time for one patient's CT images was within 15 seconds. CONCLUSION: The experimental results demonstrate that the CTV and OARs delineated for cervical cancer by DpnUNet was in close agreement with the ground truth. DpnUNet could significantly reduce the radiation oncologists' contouring time.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33041238

RESUMO

BACKGROUND: Surgical mobilization of the maxillary segment affects nasal morphology. This study assessed the impact of the type of maxillary mobilization on the three-dimensional (3D) nasal morphometry. METHODS: Pre- and postsurgery cone beam computed tomography-derived facial image datasets of consecutive patients who underwent two-jaw orthognathic surgery were reviewed. Using preoperative 3D facial models as the positional reference of the skeletal framework, 12-month postoperative 3D facial models were classified into four types of maxillary mobilizations (advancement [n = 83], setback [n = 24], intrusion [n = 55], and extrusion [n = 52]) and four types of final maxillary positions (anterosuperior [n = 44], anteroinferior [n = 39], posterosuperior [n = 11], and posteroinferior [n = 13]). Six 3D soft tissue nasal morphometric parameters were measured, with excellent intra- and interexaminer reliability scores (ICC>0.897) for all the measurements. The 3D nasal change for each nasal parameter was computed as the difference between postoperative and preoperative measurement values. RESULTS: The intrusion maxillary mobilization resulted in a significantly (all p<0.05) larger 3D nasal change in terms of alar width, alar base width, and nostril angle parameters, and a smaller change in terms of the nasal tip height parameter than the extrusion maxillary mobilization; however, no significant (all p>0.05) difference was observed between advancement and setback maxillary mobilizations. The anterosuperior and posterosuperior maxillary positions had a significantly (all p<0.05) larger 3D nasal change in terms of the alar base width and nostril angle than the anteroinferior and posteroinferior maxillary positions. CONCLUSION: The type of maxillary mobilization affects the 3D nasal morphometry.

15.
Phytopathology ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044133

RESUMO

The seedlings and fresh fruits of passion fruits are of high value in local and global trade. Fusarium solani is a main disease-causing agents affecting passion fruits. The objectives were to develop Bacillus-based biocontrol agents for the management of fusarium diseases on passion fruits and to investigate their putative control mechanisms. Our studies indicated Bacillus subtilis YBC and 151B1 showed antagonistic activity to F. solani PF7 from passion fruits and inhibited the conidial germination of strain PF7. The application of broth cultures from B. subtilis 151B1 and YBC in SYB medium reduced disease severity of fusarium wilt on the leaves of passion fruits, and enhanced the survival rates of passion fruit seedlings challenged with F. solani PF7. With regard to the putative mechanisms of disease control, the results indicated the treatments consisting of the respective culture filtrates from B. subtilis 151B1 and YBC broths caused aberrant conidial morphology and the loss of cell membrane integrity. Additionally, the treatments caused reductions in mitochondrial membrane potential and interfered with the energy metabolism of F. solani PF7. The treatments also enhanced reactive oxygen species accumulation, and resulted in the externalization of phosphatidylserine, chromatin condensation, and DNA fragmentation, suggesting their functions in triggering apoptotic-like cell death. In conclusion, B. subtilis 151B1 and YBC are potential biocontrol agents for passion fruit disease caused by F. solani. Their control efficacy may result from the produced surfactins to trigger apoptotic-like cell death, reducing the mitochondrial membrane potential and interfering with the energy metabolism of the pathogen.

16.
Reprod Sci ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025530

RESUMO

Premature rupture of membranes (PROM) is usually associated with pregnant and neonatal complications. Most of the PROM cases are caused by ascending asymptomatic genital infection. In China, PROM (15.3%) is more common than spontaneous preterm labor (7.3%) and leads to more adverse pregnancy outcomes. Here, we designed a prospective cohort study to measure the metabolomics changes in vaginal swab samples and explored their potential contribution to PROM. A total of 260 differentially expressed metabolites were identified and further analyzed. In the PROM group, N-acetyl-D-galactosamine and sucrose were downregulated (P = 0.0025, P = 0.0195, respectively), both of which are the upstream metabolites of the glycolysis pathway. Furthermore, estriol 3-sulfate 16-glucuronide (P = 0.0154) and 2-methoxy-17beta-estradiol 3-glucosiduronic acid (P = 0.004), two final metabolites in steroid hormone biosynthesis, were both downregulated in the PROM group. Finally, we found two catechin metabolites (epigallocatechin-7-glucuronide, P = 0.0009; 4'-methyl-epigallocatechin-7-glucuronide, P = 0.01) as well as DL-citrulline (P = 0.0393) were also significantly downregulated in the PROM group compared with the healthy control (HC) group, which are related to important antioxidant and anti-inflammatory activities in the human body. Altogether, metabolite changes in glycolysis, steroid hormone biosynthesis, and antioxidant/anti-inflammatory pathways may contribute to (or be a consequence of) vaginal dysbiosis and PROM. Metabolite pathway analysis is a new and promising approach to further investigate the mechanism of PROM and help prevent its unfavorable pregnant outcomes at a functional level. Trial registration number: ChiCTR2000034721.

17.
Microbiome ; 8(1): 145, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032658

RESUMO

BACKGROUND: Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear. RESULTS: This analysis was based on a Chinese population with 1475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, an undefined genus in the family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features. CONCLUSIONS: These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans. Video Abstract.

19.
Animals (Basel) ; 10(10)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33036420

RESUMO

Semen collection can be achieved via hand penile massage or rectal stimulation using electro-ejaculation methods. Traditional electro-ejaculation procedure applied relatively high voltage of 3-15 volts with a maximum current of 900 mA. However, these manipulations often result in great stress and discomforts in animals. In this study, we showed low-voltage electro-ejaculation procedure using 2-3 volts with a maximum current of 500 mA can efficiently stimulated ejaculations in zoo captive lanyu miniature pigs with a high success rate of 81.3% (13/16). Besides normal semen properties (semen volume, pH, sperm concentration), we demonstrated that low-voltage electro-ejaculation caused less stress in the animals, and sperm cells obtained via low-voltage electro-ejaculation exhibit low abnormality (10.3%), high viability (84.3%), motility (75.7%), progressive motility (63.7%), and acrosome integrity (88%). However, cryopreservation protocol used in the current study requires further optimization, as sperm mitochondrial function was partially compromised during freezing procedures. Taken together, we demonstrated in this study that a low-voltage electro-ejaculation approach can be used to obtain quality sperm cells from zoo captive lanyu miniature pig with less physical stress during electro-ejaculation procedure.

20.
Cancer Commun (Lond) ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038291

RESUMO

BACKGROUND: Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC). However, the epigenetic mechanisms underlying NPC metastasis remains poorly understood. We aimed to find functional genes which regulate the metastasis of NPC and identify therapeutic targets for NPC treatment. METHODS: Bisulfite pyrosequencing was used to analyze zinc finger protein 582 (ZNF582) methylation in NPC tissues and cell lines. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were used to determine the expression of ZNF582. In vitro and in vivo experiments were performed to evaluate the biological function of ZNF582 in NPC. ZNF582-targeting genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) and were confirmed by ChIP-qPCR and luciferase assay. RESULTS: ZNF582 promoter was hypermethylated in NPC, and both the mRNA and protein levels of ZNF582 were down-regulated in NPC tissues and cell lines. The restoration of ZNF582 inhibited NPC migration, invasion, and metastasis, while the knockdown of ZNF582 promoted NPC migration, invasion, and metastasis in vitro and in vivo. ZNF582 directly regulated the transcription and expression of adhesion molecules Nectin-3 and NRXN3. Both Nectin-3 and NRXN3 were identified as functional targets of ZNF582, and the restoration or abrogation of these genes reversed the tumor suppressor effect of ZNF582 in NPC metastasis. CONCLUSIONS: ZNF582 acts as a tumor suppressor gene in NPC by regulating the transcription and expression of adhesion molecules Nectin-3 and NRXN3, which may provide novel therapeutic targets for NPC treatment.

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