Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.351
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Dev Comp Immunol ; 103: 103513, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31585194

RESUMO

Adrenergic receptors (ARs) are members of the G-protein-coupled receptor superfamily that can be categorized into αARs and ßARs. The specific function of ARs in teleost monocytes/macrophages (MO/MФ) remains unknown. We determined the cDNA sequence of ARs from ayu (Plecoglossus altivelis; PaαAR and PaßAR). Sequence comparisons showed that PaαAR was most closely related to the αAR of the Japanese flounder and Nile tilapia, while PaßAR was most closely related to the ßAR of Atlantic salmon. The AR transcripts were mainly expressed in the spleen, and their expression was altered in various tissues upon infection with Vibrio anguillarum. PaαAR and PaßAR proteins were upregulated in MO/MФ after infection, and PaßAR knockdown resulted in a pro-inflammatory status in ayu MO/MФ upon V. anguillarum infection and lowered the phagocytic activity of MO/MФ. Our results indicate that PaßAR plays the role of an anti-inflammatory mediator in the immune response of ayu against bacterial infection.

2.
Chemosphere ; 239: 124702, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31520979

RESUMO

Restoration of submerged macrophytes is widely applied to counteract eutrophication in shallow lakes. However, proliferation and accumulation of filamentous algae (possessing free-floating and periphytic life forms) hamper growth of submerged macrophytes. Here, we explored factors triggering the excessive proliferation of filamentous algae during lake restoration using field investigations and laboratory experiments. Results showed that, compared with free-floating Oscillatoria sp. (FO), periphytic Oscillatoria sp. (PO) showed faster growth rate, greater photosynthetic capacities and higher phosphorus (P) affinity. Therefore, PO was physiologically competitively superior to FO under low P concentration and improved light conditions. And proliferation of filamentous algae was mainly manifested in periphytic life form. Besides, field results showed that density of filamentous algae in water column might be related to substrate types. Some macrophyte (Ceratophyllum oryzetorum and Potamogeton crispus) might provide proper substrates for proliferation of filamentous algae. Further physiological experiments found that Oscillatoria showed specific eco-physiological responses to different macrophyte species. Hydrilla verticillata and C. oryzetorum promoted growth and photosynthetic activity of Oscillatoria, while Potamogeton malaianus inhibited growth and P uptake of PO. Myriophyllum spicatum exhibited no impact on growth of Oscillatoria. Our results revealed the intrinsic (physiological differences between free-floating and periphytic life forms of filamentous algae) and extrinsic (different macrophytes) factors affect the proliferation of filamentous algae, which are important for guidance on planting of submerged macrophytes during lake restoration.

3.
J Med Chem ; 62(22): 10352-10361, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31689116

RESUMO

Described herein is a new approach to mitigate CYP3A4 induction. In this unconventional approach, a fine-tuning of the dihedral angle between the C4 phenyl and the dihydropyrimidine core of the heteroaryldihydropyrimidine (HAP) class of capsid inhibitors successfully altered the structure-activity-relationships (SARs) of the unwanted CYP3A4 induction and the desired HBV capsid inhibition to more favorable values. This eventually led to the discovery of a new capsid inhibitor with significantly reduced CYP3A4 induction, excellent anti-HBV activity, favorable preclinical PK/PD profiles, and no early safety flags.

4.
Cancer Med ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774249

RESUMO

PURPOSE: To investigate the clinical characteristics of nasopharyngeal carcinoma (NPC) and a concomitant hepatitis B virus (HBV) infection, as well as the potential effects of HBV infection and antiviral therapy on prognosis. METHODS: We conducted a retrospective chart review of all NPC patients from December 2010 to December 2014. After collecting medical records and conducting follow-ups on patients, a total of 876 eligible NPC patients were included. For each patient, medical records were reviewed. Factors predictive of outcome were compared using the log-rank test and Cox regression analysis. RESULTS: Among the 876 participants, 106 (12.1%) patients were HBV-infected patients. The hepatitis B surface antigen-positive [HBsAg(+)] group had a lower CD4+ T cell count than the HBsAg(-) group (P = .048). Among patients with stage I/II NPC, 5-year overall survival (OS), disease-free survival (DFS), relapse-free survival, and distant metastasis-free survival (DMFS) of the HBsAg(+) group were 82.5%, 70.7%, 87.7%, and 76.6%, respectively, whereas those of the HBsAg(-) group were 91.4%, 86.0%, 93.8%, and 92.1%, respectively. Statistically significant differences in OS, DFS, and DMFS existed between both groups (P = .017, .018, and .004, respectively). The multivariate analysis indicated that HBsAg status and N stage are independent risk factors affecting OS, DFS, and DMFS of NPC patients. A statistically significant difference in 5-year DMFS existed between the antivirus (90.0%) and no-antivirus groups (70.0%) (P = .043). CONCLUSIONS: Hepatitis B virus infection is an independent risk factor for early stage NPC, which may be associated with its reduced immune functions compared to the HBsAg(-) group. Anti-HBV treatment may improve the prognosis of HBV-infected NPC patients.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31775283

RESUMO

OBJECTIVES: Evidence of school-based physical activity (PA) on academic performance in children and adolescents was inconsistent, especially in high school students who face a high academic burden. In this study, we tested the efficacy of a strengthened physical education (PE) program on academic outcomes in Shanghai. METHODS: A quasi-experimental design was conducted to investigate the effect of strengthened PE on academic scores by calculating the grade-cohort difference before and after the intervention. PE curriculum switched from traditional short duration (40 minutes) general fitness training to long duration (90 minutes) specialized sports (e.g., football, aerobics). A total of 460 high school students (236 pre-intervention and 224 post-intervention) were enrolled in grade 10 and followed for two and three semesters. The academic outcome was assessed by district-standardized test scores. A difference-in-difference approach was employed. RESULTS: After two semesters, the standardized Chinese language scores and English language scores for the post intervention group were increased by 0.61 SD (95% confidence interval (CI): 0.44, 0.78, p < 0.001) and 0.28 SD (95% CI: 0.09, 0.47, p = 0.01). However, the standardized math scores for the post intervention group were decreased in girls. After three semesters, standardized Chinese language scores for the post intervention group were increased by 0.27 SD (95% CI: 0.06, 0.48, p = 0.01). Math scores and English language scores decreased by 0.18 SD (95% CI: -0.36, -0.01, p = 0.04) and 0.23 SD (95% CI: -0.38, -0.09, p = 0.00), respectively. CONCLUSION: A school-based physical education program had mixed effects on academic scores in high school students.

6.
Bioinformatics ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722369

RESUMO

MOTIVATION: Systematic and comprehensive analysis of protein subcellular location as a critical part of proteomics ("location proteomics") has been studied for many years, but annotating protein subcellular locations and understanding variation of the location patterns across various cell types and states is still challenging. RESULTS: In this work, we used immunohistochemistry images from the Human Protein Atlas as the source of subcellular location information, and built classification models for the complex protein spatial distribution in normal and cancerous tissues. The models can automatically estimate the fractions of protein in different subcellular locations, and can help to quantify the changes of protein distribution from normal to cancer tissues. In addition, we examined the extent to which different annotated protein pathways and complexes showed similarity in the locations of their member proteins, and then predicted new potential proteins for these networks. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

7.
BMC Genomics ; 20(1): 854, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31726987

RESUMO

BACKGROUND: The ureagenesis plays a central role in the homeostatic control of nitrogen metabolism. This process occurs in the liver, the key metabolic organ in the maintenance of energy homeostasis in the body. To date, the understanding of the influencing factors and regulators of ureagenesis in ruminants is still poor. The aim of this study was to investigate the relationship between energy metabolism and ureagenesis and detect the direct regulators of ureagenesis in the liver by using RNA-seq technology. RESULTS: Eighteen four-month-old male goats were divided into two groups randomly and received a diet containing 10% (LNFC group, n = 9) or 30% non-fiber carbohydrate (MNFC group, n = 9), respectively, for four weeks. The global gene expression analysis of liver samples showed that, compared with a LNFC diet, the MNFC diet promoted the expression of genes required for synthesis of fatty acid and glycerol, whereas it suppressed those related to fatty acid oxidation, gluconeogenesis from amino acids and ureagenesis. Additionally, gene expression for rate-limiting enzymes of ureagenesis were highly correlated to the gene expression of key enzymes of both fatty acid synthesis and glycerol synthesis (Spearman correlation coefficient > 0.8 and p < 0.05). In the differentially expressed signaling pathways related to the endocrine system, the MNFC diet activated the insulin and PPAR signaling pathway, whereas it suppressed the leptin-JAK/STAT signaling pathway, compared with the LNFC diet. Reverse transcription quantitative PCR analyses of 40 differentially expressed genes confirmed the RNA-seq results (R2 = 0.78). CONCLUSION: Our study indicated that a dietary NFC-induced increase of energy supply promoted lipid anabolism and decreased ureagenesis in the caprine liver. By combining our results with previously published reports, insulin signaling can be suggested to play the dominant role in the coordinated control of hepatic energy metabolism and ureagenesis.

8.
Drug Des Devel Ther ; 13: 3669-3682, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695334

RESUMO

Purpose: The lack of effective therapies mandates the development of new treatment strategies for vascular dementia (VaD). G protein-coupled receptor 124 (GPR124) may be a therapeutic target for angiogenesis-related diseases of CNS, including VaD. The GCPF peptide is a truncated and screened fragment of the GPR124 extracellular domain. The potential use of GCPF for VaD treatment, angiogenesis and targeting of integrin αvß3 are evaluated. Methods and results: First, the in vivo results indicated that the GCPF peptide could decrease mean escape latency and increase platform crossing times in BCCAO rats. Second, the in vitro and ex vivo results indicated that the GCPF peptide was an active angiogenic peptide and could promote hCMEC/D3 cell migration and adhesion to ECM molecules. Third, in silico analyses predicted that GCPF could specifically interact with integrin αvß3; the ∆G of GCPF binding to the binding pocket was -16.402 KJ/mol. The molecular characteristics indicated that highly hydrophilic GCPF with a pI of 11.70 had a short half-life in mammals (~1 hr). Finally, the ELISA experiments indicated that low dissociation constant (Kd= 2.412±0.455 nM) corresponds to the high affinity of GCPF for integrin αvß3. Conclusion: The data indicate that adhesion of GCPF immobilized on ECM surface to endothelial cells via integrin αvß3 modulates cellular functions to promote angiogenesis and improve cognitive function. This is the first report to prove that GCPF, a novel octapeptide, may be an effective strategy for VaD therapy.

9.
J Pharm Biomed Anal ; : 112974, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31767224

RESUMO

Cicadae Periostracum, which is derived from the slough of Cicadidae insects, is a commonly used crude drug in traditional Chinese medicine (TCM). As specified in Chinese Pharmacopoeia, Cryptotympana atrata (CA) is the only official species of this crude drug. However, the slough of other three species, i.e., Auritibicen flammatus (AF), Cryptotympana mandrina (CM) and Platypleura kaempferi (PK), have been also used as the origins of Cicadae Periostracum in Chinese herbal market, although whether the quality of these four origins is consistent or not is still unknown. In present study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was employed to qualitatively and quantitatively compare the chemical profiles of the four origins. Totally, 34 N-acetyldopamine polymers were identified from the four origins, including 4 N-acetyldopamine dimers, 11 N-acetyldopamine trimers, 10 N-acetyldopamine tetramers, and 9 N-acetyldopamine pentamers. AF, CM and PK had similar chemical profiles with that of CA. The contents and compositional ratio of the four types of polymers in CA, AF and CM were consistent with each other, but significantly lower or different in PK. All these results suggested that AF and CM might be considered as the potential resources of Cicadae Periostracum concerning their consistent holistic quality, whereas whether PK could be used as potential origin of Cicadae Periostracum or not need further evaluation for their different compositional ratios and contents of the four types of N-acetyldopamine polymers. This is the first study on chemical profiling and comparison of N-acetyldopamine polymers in four origins of Cicadae Periostracum, which is beneficial for potential resources utilization and quality standard improvement of Cicadae Periostracum.

10.
Environ Monit Assess ; 191(12): 719, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31691166

RESUMO

Phytoplankton species composition has long been recognized to be structured by environmental filtering, but our knowledge of patterns of spatial dissimilarity congruence between the phytoplankton community and environmental divers is rather limited. Specifically, a study on whether there are specific temporal properties that could be more related to spatial dissimilarity remains to be seen. We examined the extent to how spatial dissimilarity changed with seasonal succession by measuring ß-diversity in phytoplankton communities in Lake Erhai (from January 2012 to December 2014 at 15 sampling sites) as a function of different period conditions (high-density period and low-density period). We found that congruences of spatial dissimilarity in algal communities over time were neither stable in time nor showed a seasonal pattern. The spatial dissimilarity congruence between the phytoplankton community and dissolved inorganic phosphorus (DIP) concentration followed exponential decay patterns, and this congruence was led by algal cell density. This result implies that species and functions of phytoplankton are specialized, and DIP concentration drastically increases in high-density periods than in low-density periods. This means that DIP enrichment is related to the loss of algal diversity and functions and the increase of algal biomass in eutrophic lakes.

11.
Org Lett ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31725307

RESUMO

The construction of chiral multiple-substituted cyclohexanes motifs is a challenging topic in organic synthesis. By the combination of desymmetrization and remote stereocontrol, a ruthenium-catalyzed transfer hydrogenative desymmetrization of 2,2,5-trisubstituted 1,3-cyclohexanediones has been successfully developed for the construction of chiral multiple-substituted cyclohexanes with high enantioselectivity and diastereoselectivity. When an ester group was introduced to the two-position, a hydrogenative desymmetrization/transesterification cascade occurred, affording the bicyclic lactones bearing three stereocenters, including two discrete stereocenters and one quaternary stereogenic center, with high enantioselectivity. The products are the multiple-substituted chiral cyclohexanes bearing the hydroxyl and carbonyl functional groups, which provide a new opportunity for further precise elaboration.

12.
Endocr J ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31685721

RESUMO

Ectopic parathyroid adenomas (PAs) can occur in numerous locations and are thought to be the cause of a significant portion of failed primary surgery for hyperparathyroidism. PA is a rare cause of hoarseness, which may be harbingers of a malignant process. Here, we describe an unusual case of an ectopic PA in the carotid sheath presenting as unilateral vocal cord paralysis (VCP). A 49-year-old lady presented with a 1-week history of hoarseness, irritating cough and shortness of breath. Fibreoptic laryngoscopy revealed left VCP. Ultrasound and computed tomography of the neck demonstrated a mass in the carotid sheath. Laboratory investigations revealed hypercalcemia (3.10 mmol/L), hypophosphatemia (0.81 mmol/L) and elevated intact parathyroid hormone (iPTH) level (381.6 pg/mL), despite of a negative 99mTc-sestamibi scan. After more rigorous tests, the ectopic tumor adjacent to the left vagus nerve was successfully resected, with subsequent histopathological confirmation of PA. The patient eventually got a normal iPTH level and serum calcium postoperatively, and regular voice function was also regained 4 months after surgery. This case emphasizes the importance of broad differential diagnosis and thorough workup. Although most patients with PA present with hypercalcemia, this disease entity also need to be considered in the differentials of neck masses and VCP.

13.
Surg Endosc ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595400

RESUMO

BACKGROUND: Ureteral injury is an intractable complication in gynecological cancer surgeries. Identifying risk factors can ensure safety of the ureters intraoperatively. A narrow pelvis is known to exert extra difficulties in pelvic surgeries. However, whether pelvic dimension can affect the risk of ureteral injury in gynecological cancer surgeries is poorly understood. We aimed to evaluate the association between pelvic dimension and the risk of ureteral injury during gynecological cancer surgeries. METHODS: All patients who had undergone gynecological cancer surgeries were searched from January 2011 to July 2017. We included patients with ureteral injury who had available data of abdominal and pelvic computed tomography for measuring pelvic dimensions. Multivariate condition logistic analysis was used to identify the risk factors independently correlated with ureteral injury in gynecological cancer surgeries. RESULTS: A total of 43 cases with 86 controls were included in this study. We discovered that a longer anteroposterior diameter of the mid-pelvis (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.13, P = 0.019) and a shorter transverse diameter of the mid-pelvis (OR 0.92, 95% CI 0.86-0.98, P = 0.013) were associated with ureteral injury in gynecological cancer surgeries. In laparoscopic analysis, a longer anteroposterior diameter of the mid-pelvis (OR 1.11, 95% CI 1.00-1.24, P = 0.041) was a risk factor for ureteral injury. In the analysis of open surgery, a longer transverse diameter of the mid-pelvis (OR 0.79, 95% CI 0.66-0.93, P = 0.006) was a protective factor for ureteral injury. CONCLUSIONS: This study demonstrated that mid-pelvis dimensions were associated with ureteral injury, but the observed differences were too small. In addition, pelvic inlet dimensions did not appear to relate with ureteral injury. Thus, these pelvimetry measures could not be beneficial in assessing the risk of ureteral injury in gynecological cancer surgeries.

14.
Int Wound J ; 16(6): 1533-1544, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606950

RESUMO

Pressure injuries (PIs) have now become a common complication of the elderly patients. Some studies have observed that pressure injuries may increase mortality, but this area of evidence has not been evaluated and summarised. The aim of this study was to compare the mortality of patients with pressure injuries and those without pressure injuries. A meta-analysis of observational studies was performed. PubMed, Cochrane Library, Embase, and Web of Science were searched up to April 2019. Studies about mortality among the elderly patients with and without pressure injuries were included. Methodological quality was assessed by the Newcastle-Ottawa Scale (NOS). The fixed effect or random effect model was determined by the test of heterogeneity. The subgroup analysis was performed based on the pressure injuries stages, the region, and the type of study design. The meta-regression analysis was performed to investigate the relationship between the mortality and patients' enrolled year, average age, the incidence of pressure injuries, and gender ratio. The sensitivity analysis was used to explore the impact of an individual study by excluding one at a time. The hazard ratio (HR) and 95% confidence intervals (CIs) in terms of the comparison of two groups were extracted for meta-analysis. A survival curve between two groups by individual patient-level was drew. Eight studies with 5523 elderly patients were included in the analysis. Follow-up periods for the included studies ranged from about 0.5 to 3 years. The elderly patients who complicated with pressure injuries had a higher risk of death. The pooled HR was 1.78 (95% CI 1.46-2.16). A funnel plot showed no publication bias. Further subgroup analysis showed that HR values for the patient stage 3 to 4 pressure injuries (HR:2.41; 95% CI:1.08-5.37) were higher than stage 1-4 and 2-4 pressure injuries (HR: 1.66; 95% CI: 1.35-2.05; HR: 1.74; 95% CI: 1.16-2.60). The meta-regression analysis found that patients' enrolled year, average age, the incidence of pressure injuries, and gender ratio were not the sources of heterogeneity. Sensitivity analyses showed that the outcomes of the study did not change after removing the Onder's article. The survival curve at the individual patient-level also indicated that patients complicated with pressure injuries significantly increased the risk of death (HR: 1.958; 95% CI: 1.79-2.14) in elderly patients. Our meta-analysis indicated that patients complicated with pressure injuries are estimated to have a two times higher risk on mortality compared with patients without pressure injuries during the 3 years follow-up period. Particular attention should be given to the elderly patients who are at higher risk for mortality.

15.
Int J Chron Obstruct Pulmon Dis ; 14: 2291-2304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31631999

RESUMO

Purpose: Pulmonary rehabilitation (PR) is essential to manage patients with COPD. The aim of this study was to investigate the appropriate intensity of PR exercise training for patients with moderate-to-severe COPD. Patients and methods: A prospective multicenter randomized controlled trial was conducted from January 2014 to October 2018. The subjects were randomly assigned to three groups with different intensities of PR, according to their maximum oxygen uptake percentage determined by cardiopulmonary exercise testing. After 20 weeks of exercise training, the effects of low-, moderate-, and high-intensity exercise interventions on patients were compared to determine the most appropriate PR prescription. Results: For patients with moderate COPD, all the measured parameters were significantly improved in the moderate- and high-intensity PR groups (P<0.01), while there was no significant difference in the frequency of acute exacerbations and the mMRC questionnaire after 20 weeks of PR exercise in the low-intensity PR group. For patients with severe COPD, all variables were also improved in the high-intensity PR group (P<0.05), while the mean differences of pre- and post-PR were lower than those in patients with moderate COPD. Moreover, the Hamilton Anxiety Scale and body mass index showed no significant difference in low-intensity PR group (P>0.05). Conclusion: High-intensity PR exercise is helpful for patients with moderate to severe COPD. Moderate COPD patients need to receive intensive PR training; the improvement degrees from PR intervention were higher than those of the severe COPD patients. For patients with severe COPD, high-intensity PR exercise may be more beneficial if patients can tolerate it.

16.
Int J Gynecol Cancer ; 29(8): 1280-1284, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570543

RESUMO

INTRODUCTION: The solute carrier family 12 member 5 (SLC12A5) gene is playing a putative oncogenic role in colorectal carcinoma. However, the status of SLC12A5 amplification and expression in ovarian carcinoma and its potential clinical and/or prognostic significance has not yet been investigated. METHODS: In the present study, semi-quantitative staining and fluorescence in situ hybridization were used to investigate SLC12A5 protein expression and gene amplification levels. Samples were obtained from archival, formalin-fixed, paraffin-embedded pathological specimens consisting of 30 normal ovaries, 30 ovarian cystadenomas, 30 borderline ovarian tumors, and 147 invasive ovarian carcinomas. SLC12A5 immunohistochemical staining results, pathological parameters, and patient prognosis were then evaluated using various statistical models. Patient survival rate was also assessed using receiver-operator curve analysis. RESULTS: Our results revealed no SLC12A5 protein overexpression in normal ovaries. However, 7% of cystadenomas had SLC12A5 protein overexpression along with 17% of borderline tumors and 37% of ovarian carcinomas (P<0.01). Amplification of SLC12A5 was detected in 10.3% of ovarian carcinomas. Further correlational analyses showed that SLC12A5 protein overexpression in ovarian carcinomas was significantly associated with ascending histological grade, pT/pN/pM status, as well as FIGO stage (P<0.05). A subsequent univariate survival analysis of our ovarian carcinoma cohorts resulted in a significant association between SLC12A5 protein overexpression and decreased patient survival (44.3 and 85.9 months for high and low SLC12A5 protein expression, respectively; P<0.001). Importantly, additional multivariate analysis revealed that SLC12A5 protein expression was a significant, independent prognostic factor for overall survival in ovarian carcinoma patients (P=0.003). CONCLUSIONS: Collectively, these findings support the conclusion that SLC12A5 protein overexpression could indicate an invasive and/or aggressive phenotype of ovarian carcinoma. Future work will need to investigate whether SLC12A5 protein can serve as an independent prognostic molecular marker in patients with ovarian carcinoma.

18.
iScience ; 20: 265-277, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31605942

RESUMO

MicroRNAs (miRNAs) play crucial roles in biological processes involved in diseases. The associations between diseases and protein-coding genes (PCGs) have been well investigated, and miRNAs interact with PCGs to trigger them to be functional. We present a computational method, DimiG, to infer miRNA-associated diseases using a semi-supervised Graph Convolutional Network model (GCN). DimiG uses a multi-label framework to integrate PCG-PCG interactions, PCG-miRNA interactions, PCG-disease associations, and tissue expression profiles. DimiG is trained on disease-PCG associations and an interaction network using a GCN, which is further used to score associations between diseases and miRNAs. We evaluate DimiG on a benchmark set from verified disease-miRNA associations. Our results demonstrate that DimiG outperforms the best unsupervised method and is comparable to two supervised methods. Three case studies of prostate cancer, lung cancer, and inflammatory bowel disease further demonstrate the efficacy of DimiG, where top miRNAs predicted by DimiG are supported by literature.

19.
Chin J Nat Med ; 17(8): 591-599, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472896

RESUMO

Whitmania pigra has been used as a traditional Chinese medicine (TCM) for promoting blood circulation, alleviating blood coagulation, activating meridians and relieving stasis for several hundred years. However, the therapeutic components of this species, especially proteins and peptides were poorly exploited. Until now only a few of them were obtained by using chromatographic isolation and purification. In recent decade, transcriptome techniques were rapidly developed, and have been used to fully reveal the functional components of many animal venoms. In the present study, the cDNA of the salivary gland of Whitmania pigra was sequenced by illumina and the transcriptome was assembled by using Trinity. The proteome were analysed by LC-MS/MS. Based on the data of the transcriptome and the proteome, a potential antiplatelet protein named pigrin was found. Pigrin was cloned and expressed using P. pastoris GS115. The antiplatelet andantithrombotic bioactivities of pigrin were tested by using aggregometer and the rat arterio-venous shunt thrombosis model, respectively. Thebleeding time of pigrin was measured by a mice tail cutting method. The docking of pigrin and protease-activated receptor 1 (PAR1) or collagen were conducted using the ZDOCK Server. Pigrin was able to selectively inhibit platelet aggregation stimulated by PAR1 agonist and collagen. Pigrin attenuated thrombotic formation in vivo in rat, while did not prolong bleeding time at its effective dosage. There are significant differences in the key residues participating in binding of Pigrin-Collagen complex from Pigrin-PAR1 complex. In conclusion,a novel PAR1 inhibitor pigrin was found from the leech Whitmania pigra. This study helped to elucidate the mechanism of the leech for the treatment of cardiovascular disorder.

20.
J Exp Clin Cancer Res ; 38(1): 396, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500650

RESUMO

Hepatocellular carcinoma (HCC) ranks the most common primary liver malignancy and the third leading cause of tumor-related mortality worldwide. Unfortunately, despite advances in HCC treatment, less than 40% of HCC patients are eligible for potentially curative therapies. Recently, cancer immunotherapy has emerged as one of the most promising approaches for cancer treatment. It has been proven therapeutically effective in many types of solid tumors, such as non-small cell lung cancer and melanoma. As an inflammation-associated tumor, it's well-evidenced that the immunosuppressive microenvironment of HCC can promote immune tolerance and evasion by various mechanisms. Triggering more vigorous HCC-specific immune response represents a novel strategy for its management. Pre-clinical and clinical investigations have revealed that various immunotherapies might extend current options for needed HCC treatment. In this review, we provide the recent progress on HCC immunology from both basic and clinical perspectives, and discuss potential advances and challenges of immunotherapy in HCC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA