Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.698
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-31568257

RESUMO

BACKGROUND: With the advancement of endoscopic technology, laparoscopic liver resection has become the standard procedure for left lateral segmentectomy. The aim of this study was to compare perioperative and oncological outcomes between laparoscopic and open left lateral segmentectomy for hepatocellular carcinoma (HCC) >5 cm. PATIENTS AND METHODS: A total of 66 patients underwent left lateral segmentectomy for HCC (>5 cm) during the period spanning between 2013 and 2015. To overcome selection bias, 1:3 match using propensity score-matched analysis was performed between laparoscopic and open liver resection. RESULTS: Relatively smaller tumor size (6.0 vs. 7.0 cm; P=0.030) and more frequent incidence of complete tumor capsule (93.3% vs. 58.8%; P=0.013) were observed in the laparoscopic group compared with the open group before matching. Although the longer operation time (195 vs. 150 min; P=0.022) was consumed in the laparoscopic procedure after matching, the laparoscopic group had shorter postoperative hospital stay (6 vs. 7 d; P=0.002) and less blood loss volume (50 vs. 100 mL; P=0.022). The Pringle maneuver for hepatic inflow occlusion was more likely to be applied in patients who underwent open surgery. The incidence of postoperative complication seemed to be lower in the laparoscopic group (6.7%) compared with that in the open group (11.8%) before matching. On the basis of propensity score-matched analysis, the complication rates were comparable between the 2 groups (7.1% vs. 6.7%, P=0.953). No difference in the 1-year and 3-year overall and recurrence-free survival rates was found between the laparoscopic and open groups. CONCLUSION: Laparoscopic left lateral segmentectomy for large HCC patients showed better perioperative outcomes and equivalent oncologic outcomes as the open procedure, providing evidence for considering as a standard laparoscopic practice through careful selection.

2.
Environ Toxicol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566298

RESUMO

Galangin, a natural flavonol, has anti-inflammatory and antioxidative potential. However, the cytoprotective effects of galangin against oxidative-induced aging in human fibroblasts have not been well studied. IGF-1 signaling pathway is associated with the control of aging and longevity in human. The goal of this study was to investigate the effects of galangin on human skin fibroblast HS68 cells under H2 O2 exposure to induce aging. In this study, we demonstrate that galangin could decrease the levels of pro-inflammatory proteins and enhanced collagen formation through promoting the IGF-1R pathway. Furthermore, aging markers such as senescence-associated ß-galactosidase p53, p21Cip1/WAF1 , and p16INK4A were upregulated under H2 O2 exposure and galangin could reverse its effects. Taken together, these data indicated that anti-inflammatory and antiaging activities of galangin may be mediated through the IGF-1R signaling pathway. These findings may provide the evidence for galangin to develop as an antiwrinkle product on human skin.

3.
Infect Dis Poverty ; 8(1): 79, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31581953

RESUMO

BACKGROUND: The China-Gates TB project Phase II implemented case-based payment reform in three Chinese counties in 2014, designed specifically for patients diagnosed with Tuberculosis (TB). This study aimed to examine the changes in utilization and expenses of outpatient services before and after the reform implementation, among TB patients in the three counties in China. METHODS: We collected quantitative data using surveys in 2013 (baseline year) and 2015 (final year). We used outpatient hospital records to measure service utilization and medical expenses of TB patients. We conducted qualitative interviews with local health authorities, officers of health insurance agencies, and hospital managers (n = 18). We utilized three focus group discussions with hospital staff and TB doctors and nurses. The χ2 tests and Mann-Whitney U tests were used to analyse quantitative data, and the thematic analysis using a framework approach was applied to analyse qualitative data. RESULTS: Dantu and Yangzhong counties enacted TB-specific case-based payment method in 2014. Jurong County maintained global budget payment but raised the reimbursement rate for TB care. Compared to the baseline, the percentage of TB patients in Dantu and Yangzhong with eight or above outpatient visits increased from 7.5 to 55.1% and from 22.1 to 53.1% in the final survey, respectively. Jurong experienced the opposite trend, decreasing from 63.0 to 9.8%. In the final survey, the total outpatient expenses per patient during a full treatment course in Dantu (RMB 2939.7) and Yangzhong (RMB 2520.6) were significantly higher than those in the baseline (RMB 690.4 and RMB 1001.5, respectively), while the total outpatient expenses in Jurong decreased significantly (RMB 1976.0 in the baseline and RMB 660.8 in the final survey). Health insurance agencies in Dantu and Yangzhong did not approve the original design with outpatient and inpatient expenses packaged together, revealed by qualitative interviews. Furthermore, staff at designated hospitals misunderstood that health insurance agencies would only reimburse actual expenses. Many TB doctors complained about their reduced salary, which might be due to decreased hospital revenue generated from TB care after the payment method reform. CONCLUSIONS: The intended effect on cost containment of case-based payment was not evident in Dantu and Yangzhong. In Jurong, where the global budget payment system maintained with the reimbursement rate enhanced, we found an effect on cost containment, but the quality of TB care might be compromised. The TB-specific case-based payment method could be redesigned to combine payment on outpatient and inpatient expenses and to set an appropriate payment standard for TB care during a full treatment course. Local health insurance agencies have to provide explicit explanations on the payment method. TB care providers should be provided with proper incentives. Monitoring and evluaiton on the quality of TB care should be undertaken at regular intervals.

4.
J Bone Miner Metab ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31583541

RESUMO

INTRODUCTION: The aim of this study was to develop an algorithm to identify high-risk populations of fragility fractures in Taiwan. MATERIALS AND METHODS: A total of 16,539 postmenopausal women and men (age ≥ 50 years) were identified from the Taiwan Osteoporosis Survey database. Using the Taiwan FRAX® tool, the 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) and the individual intervention threshold (IIT) of each participant were calculated. Subjects with either a probability above the IIT or those with MOF ≥ 20% or HF ≥ 9% were included as group A. Subjects with a bone mineral density (BMD) T-score at femoral neck based on healthy subjects of ≤ - 2.5 were included in group B. We tested several cutoff points for MOF and HF so that the number of patients in group A and group B were similar. A novel country-specific hybrid intervention threshold along with an algorithm was generated to identify high fracture risk individuals. RESULTS: 3173 (19.2%) and 3129 (18.9%) participants were categorized to groups A and B, respectively. Participants in group B had a significantly lower BMD (p < 0.001), but clinical characteristics, especially the 10-year probability of MOF (p < 0.001) or HF (p < 0.001), were significantly worse in group A. We found the algorithm generated from the hybrid intervention threshold is practical. CONCLUSION: The strategy of generating an algorithm for fracture prevention by novel hybrid intervention threshold is more efficient as it identifies patients with a higher risk of fragility fracture and could be a template for other country-specific policies.

5.
6.
Asian J Androl ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31603140

RESUMO

The first-line treatment options for high-risk prostate cancer (PCa) are definitive external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT) and radical prostatectomy (RP) with or without adjuvant therapies. However, few randomized trials have compared the survival outcomes of these two treatments. To systematically evaluate the survival outcomes of high-risk PCa patients treated with EBRT- or RP-based therapy, a comprehensive and up-to-date meta-analysis was performed. A systematic online search was conducted for randomized or observational studies that investigated biochemical relapse-free survival (bRFS), cancer-specific survival (CSS), and/or overall survival (OS), in relation to the use of RP or EBRT in patients with high-risk PCa. The summary hazard ratios (HRs) were estimated under the random effects models. We identified heterogeneity between studies using Q tests and measured it using I2 statistics. We evaluated publication bias using funnel plots and Egger's regression asymmetry tests. Seventeen studies (including one randomized controlled trial [RCT]) of low risk of bias were selected and up to 9504 patients were pooled. When comparing EBRT-based treatment with RP-based treatment, the pooled HRs for bRFS, CSS, and OS were 0.40 (95% confidence interval [CI]: 0.24-0.67), 1.36 (95% CI: 0.94-1.97), and 1.39 (95% CI: 1.18-1.62), respectively. Better OS for RP-based treatment and better bRFS for EBRT-based treatment have been identified, and there was no significant difference in CSS between the two treatments. RP-based treatment is recommended for high-risk PCa patients who value long-term survival, and EBRT-based treatment might be a promising alternative for elderly patients.

7.
Endocr Relat Cancer ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593922

RESUMO

Environmental phenols and phthalates are common ingredients in personal care products and some have been implicated in breast cancer progression. We have previously identified genes differentially expressed in response to low-dose exposure to diethyl phthalate (DEP) and methyl paraben (MPB) in a rat model. Herein we explore if these genes are associated with breast cancer mortality in humans. STUDY DESIGN: We profiled MPB- and DEP- responsive genes in tumors by NanoString from a population-based cohort of 606 women with first primary breast cancer among whom 119 breast cancer-specific deaths occurred within 15+ years of follow-up. For each gene, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results were validated in two publicly available datasets. RESULTS: From 107 DEP- and 77 MPB-responsive genes profiled, 44 and 30 genes, respectively, were significantly associated with breast cancer-specific mortality. Some top DEP-responsive genes are novel for breast cancer mortality, such as ABHD14B [for high-vs-low expression, HR 0.36, 95% CI: 0.2-0.5] and TMC4 [HR 0.37, 95% CI: 0.3-0.5]; top hits for MPB (SLC40A1 [HR 0.37, 95% CI: 0.3-0.5] and NTN4 [HR 0.39, 95% CI: 0.3-0.6]) are well-known predictors of breast cancer survival. PLEKHA6 was another novel survival predictor, sensitive to hormonal receptor status (HR 0.5, 95% CI 0.3-0.9 for hormonal receptor-positive and HR 3.2, 95% CI 1.7-6.2 for -negative group). CONCLUSIONS: Tumor expression of DEP- and MPB-responsive genes is associated with breast cancer mortality, supporting that exposure to these chemicals may influence the progression of breast cancer.

8.
Nano Lett ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596096

RESUMO

Nanomedicines have been demonstrated as promising strategies for cancer therapy due to the advantages in pharmacokinetics and drug targeting delivery to tumor tissues. However, creation of delivery platforms able to intrinsically and spatially optimize drug cellular uptake during entire delivering process remain challenging. To address this challenge, here we report on tumor microenvironment-adaptable self-assembly (TMAS) of pentapeptides regulated by the pH-sensitive cis-trans isomerization of 4-amino-proline (Amp) amide bonds for enhanced drug delivery and photodynamic therapeutic (PDT) efficacy. We found that decreasing solution pH led to the cis  trans isomerization of Amp amide bonds, thus promoting reversible self-assembly of pentapeptide FF-Amp-FF (AmpF) into superhelices and nanoparticles upon alternating exposure to neutral and mild acidic conditions. Co-assembly of peptide AmpF with its derivative containing a photosensitizer Chlorin e6 (AmpF-C) allows for creation of TMAS systems undergoing a morphological transition adaptable to the pH gradient present in cellular uptake pathway. Ex vivo studies revealed that TMAS nanomedicines prolonged circulation in animal body and improved accumulation at tumor sites compared to morphological persistent nanomedicines. In addition to the optimized cellular uptake, the morphological transition of TMAS into nanofibers in cytoplasm caused an enhanced intracellular ROS level compared to nanoparticle counterparts, thus leading to a lower half lethal dose value for cancer cells. The combined advantages of TMAS eventually allowed in vivo PDT therapy for significant inhibition of tumor growth, thus demonstrating the improved drug delivery efficiency and therapeutic efficacy of TMAS systems towards new-generation nanomedicines.

9.
Kidney Blood Press Res ; : 1-12, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31487717

RESUMO

BACKGROUND/AIMS: Stress-induced cell senescence, which contributes to cell cycle arrest and is independent of age, plays an important role in chronic kidney disease (CKD) progression. DcR2, as a senescent marker, exclusively expressed in senescent tubular epithelia. The objective of this study was to examine whether urinary DcR2 (uDcR2) could be a potential biomarker for tubulointerstitial fibrosis (TIF) in patients with immunoglobulin A nephropathy (IgAN). METHODS: This study included 210 IgAN patients and 80 healthy volunteers, with uDcR2 levels measured using enzyme-linked immunosorbent assay. We examined the relationship among uDcR2/Cr levels, renal function, and pathological parameters, using regression analysis to identify risk factors for TIF and the area under the curve (AUC) approach to predict TIF. Renal DcR2 expression was quantified by immunohistochemistry. Co-expression of DcR2 with fibrotic markers (α-smooth muscle actin [α-SMA], collagen III) was analyzed by confocal microscopy. RESULTS: Levels of uDcR2/Cr were significantly higher in IgAN patients and in those with more severe TIF, compared with healthy controls. Serum DcR2 levels were similar across groups. The proportion of IgAN patients with stages 1-2 CKD and T0 was highest among those with uDcR2/Cr <130 ng/g. In contrast, the majority of those with uDcR2/Cr >201 ng/g had stages 4-5 CKD and T2. Levels of uDcR2/Cr were positively associated with urinary albumin to creatinine ratio (ACR), urinary N-acetyl-ß-D-glucosaminidase (uNAG)/Cr, and TIF scores and negatively associated with estimated glomerular filtration rate (eGFR). uDcR2/Cr, uNAG, ACR, and eGFR were independent predictors for TIF, with AUC of 0.907 for uDcR2/Cr. This AUC value was higher than that observed for eGFR, uNAG/Cr, or ACR. The sensitivity and specificity of uDcR2/Cr in predicting TIF were 87.0 and 80.5%, respectively. Moreover, uDcR2/Cr levels were positively associated with the percentage of renal DcR2 expression. Renal DcR2 co-localized with α-SMA and collagen III in the kidneys of IgAN patients. CONCLUSIONS: Levels of uDcR2/Cr were closely associated with the severity of TIF and renal function parameters. uDcR2/Cr represents a potential biomarker for predicting TIF in IgAN patients.

11.
Mol Genet Genomics ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31489484

RESUMO

Regulatory factors function by modulating a variety of cascade mechanisms in cells. RBM4 is a multifunctional RNA-binding protein in post-transcriptional gene regulation. Cytoplasmic RBM4 interacts with Ago2 to regulate inflammatory responses by affecting mRNA decay and cap-dependent translation. However, it is unclear whether RBM4 functions in inflammation regulation by its splicing factor role. Here, the cell biology, gene expression profile and alternative splicing pattern of HeLa cells with RBM4 overexpression (RBM-OE) were compared with the control. The results showed that RBM4-OE inhibited proliferation. RBM4-OE extensively affects the transcriptional level of genes involved in cell surface receptor signalling pathway, inflammatory responses and the response to lipopolysaccharide. RBM4 broadly regulated the alternative splicing of hundreds of genes with functions of protein binding, helicase activity, DNA binding and transcription co-activator. RBM4-regulated splicing of these genes plays an important role in apoptotic process and gene transcription regulation. As an example, exon inclusion of TNIP1 mediated by RBM4 affects the expression of its targets in inflammatory pathways. These results indicated that RBM4 can mediate the inflammatory response via splicing regulation, which adds to the understanding of the critical role of RBM4 in cancer complicated by inflammation. In conclusion, this study indicated a mechanism in which the dysregulation of alternative splicing can influence cellular biology and lead to various immune-related diseases.

12.
Chin J Nat Med ; 17(7): 490-497, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31514980

RESUMO

Current study systematically investigated the interaction of two alkaloids, anisodine and monocrotaline, with organic cation transporter OCT1, 2, 3, MATE1 and MATE2-K by using in vitro stably transfected HEK293 cells. Both anisodine and monocrotaline inhibited the OCTs and MATE transporters. The lowest IC50 was 12.9 µmol·L-1 of anisodine on OCT1 and the highest was 1.8 mmol·L-1 of monocrotaline on OCT2. Anisodine was a substrate of OCT2 (Km = 13.3 ± 2.6 µmol·L-1 and Vmax = 286.8 ± 53.6 pmol/mg protein/min). Monocrotaline was determined to be a substrate of both OCT1 (Km = 109.1 ± 17.8 µmol·L-1, Vmax = 576.5 ± 87.5 pmol/mg protein/min) and OCT2 (Km = 64.7 ± 14.8 µmol·L-1, Vmax = 180.7 ± 22.0 pmol/mg protein/min), other than OCT3 and MATE transporters. The results indicated that OCT2 may be important for renal elimination of anisodine and OCT1 was responsible for monocrotaline uptake into liver. However neither MATE1 nor MATE2-K could facilitate transcellular transport of anisodine and monocrotaline. Accumulation of these drugs in the organs with high OCT1 expression (liver) and OCT2 expression (kidney) may be expected.

13.
Int J Mol Med ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31545417

RESUMO

Previously, a ubiquinol­cytochrome c reductase binding protein (UQCRB) homolog was identified in the house dust mite (HDM) species Dermatophagoides farinae (Der f) as a major allergen. In the present study, the immunodominant immunoglobulin E (IgE) epitope of the protein Der f 24 was investigated. Analysis of the homologous amino acid (aa) sequences in Der f and human UQCRB was performed. Four different recombinant Der f 24 and hybrid proteins formed by integrating Der f and human UQCRB sequences were expressed in Escherichia coli, purified using Ni­NTA resins, and IgE­binding activity was determined using IgE­western blotting and enzyme­linked immunosorbent assay (ELISA) experiments. IgE epitopes were further identified by IgE­dot blotting and IgE­ELISA with synthetic polypeptides and HDM­allergic sera. Three­dimensional (3D) structural modeling was used to analyze the position of the immunodominant IgE epitope. The amino acid sequence homology between Der f 24 and the human UQCRB protein was determined to be 39.34%. IgE­ELISA and western blot analysis showed that all of the Der f­human UQCRB hybrid proteins generated, except for the one lacking 59 residues of the N­terminal region of Der f 24, were bound by allergic serum IgE. A synthetic polypeptide consisting of 32 residues of the N­terminal reacted with IgEs from HDM­allergic sera and could be used to generate high titer specific IgG or specific IgE antibodies in immunized mice. The 32­aa N­terminal region of Der f 24 was localized to a structural protrusion, which may facilitate specific IgE­binding. These results indicate that the immunodominant IgE epitope of Der f 24 is located mainly in a 32­residue region of the N­terminus. These findings may inform the mechanisms of HDM allergy sensitization and allergy immunotherapy development.

14.
J Formos Med Assoc ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31477483

RESUMO

BACKGROUND/PURPOSE: Birth defects (BDs) are main causes of mortality and disability in infants and children. The aims of this study were to analyze the prevalence, types and risk factors of BDs in Taiwan. METHODS: Data of all births (including live and stillbirths), types, characteristics, and associated risk factors of BDs were obtained from the National Birth Registry and National Health Insurance Research Data base in Taiwan between 2005 and 2014. Birth defects were coded according to International Classification of Diseases 9th Revision-Clinical Modification codes 740-759. RESULTS: A total of 55,299 infants were diagnosed as having BDs among 2,033,004 births. The prevalence of BDs was 271.66 per 10,000 births. The prevalence of BDs did not change significantly between 2005 and 2014, there was a higher birth rate and lower BDs in 2012 (year of dragon) in Taiwan. The most common type of BDs was cardiovascular abnormalities, and ventricular septal defect was the most common disease. Extreme maternal age (<18 years or ≧30 years), preterm, and low birth weight were associated with BDs. Maternal diseases associated with BDs included hypertension, cardiovascular diseases, renal diseases, genitourinary infections, anemia, mental disorders, and diabetes mellitus. CONCLUSION: The prevalence of BDs was 271.66 per 10,000 births. The most common types of BDs were cardiovascular abnormalities. If we can reduce maternal chronic diseases, we will decrease the prevalence of BDs.

16.
J Pharm Biomed Anal ; 177: 112837, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31493746

RESUMO

The ambiguity of dose-effect relationship of many traditional Chinese medicines (TCMs) has always influenced their rational use in TCM clinic. Rhubarb, a preferred representative of cathartic TCM, is currently widely used that results in a diversity of its dosage. The aim of this study was to use an integrated metabolomics strategy to simultaneously reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats. Six doses of rhubarb (0.135, 0.27, 0.81, 1.35, 4.05, and 8.1 g/kg) were examined to elucidate the laxative and fire-purging effects by pathological sections and UPLC-Q-TOF/MSE. The results showed that there existed serious lesions in the stomach and colon of model rats. And conditions were basically improved to some extent in rhubarb-treated groups. Through relative distance calculation based on metabolomics score plots, it suggested that the effective dose threshold (EC20-EC80 range) of rhubarb was from 0.31 to 4.5 g/kg (corresponding to 3.44-50.00 g in the clinic) in rat serum and 0.29-2.1 g/kg (corresponding to 3.22-23.33 g in the clinic) in feces. Then, 33 potential biomarkers were identified in total. Functional pathway analysis revealed that the alterations of these biomarkers were associated with 15 metabolic pathways, mainly including arachidonic acid metabolism, glycerophospholipid metabolism, steroid biosynthesis, primary bile acid biosynthesis and sphingolipid metabolism. Of note, different doses of rhubarb could alleviate endogenous disorders to varying degrees through regulating multiple perturbed pathways to the normal state, which might be in a dose-dependent manner and involved in therapeutic mechanisms. To sum up, integrated serum and fecal metabolomics obtained that rhubarb ranging from 0.31 to 2.1 g/kg is safe and effective for constipation treatment. Also, our findings showed that the robust metabolomics techniques would be promising to be more accurately used in the dose-effect studies of complex TCM, and to clarify syndrome pathogenesis and action mechanisms in Chinese medicine.

17.
PLoS One ; 14(9): e0222522, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31527921

RESUMO

PURPOSE: In a retrospective cohort study, we report the current epidemiology of patients with multiple myeloma (MM) and analyze the real-world clinical outcomes of bortezomib-based therapy. MATERIALS AND METHODS: This retrospective study was mainly designed to evaluate the characteristics, treatment outcomes, and prognostic factors of patients with MM who received bortezomib-based therapy. We identified 5,726 patients in Taiwan with MM newly diagnosed between 2007 and 2015. Confidential data from the National Health Insurance Research Database (NHIRD) was used under strict guidelines, as it was made available in an electronic format for research purposes. In addition, we analyzed 96 patients who have been diagnosed with MM and were treated at the Tri-Service General Hospital (TSGH) between January 1, 2002, and December 31, 2018. RESULTS: Patients receiving first-line treatment with bortezomib had longer overall survival (OS) compared to those who received non-first-line treatment (p<0.001). In addition, the statistically lowest risk of mortality was when patients received first-line bortezomib followed by an autologous hematopoietic stem cell transplant (adjusted hazard ratio = 0.39, p<0.001). In the TSGH study, the patients were enrolled between January 1, 2002, and December 31, 2018, with an initial diagnosis of MM; there were 96 individuals treated with bortezomib. There was no statistically significant difference in the OS or progression-free survival (PFS) according to the gender, myeloma type, International Staging System stage, or treatment regimen. There was a significant difference in the PFS in patients receiving first-line bortezomib treatment with transplantation compared to those without transplantation (p = 0.021). CONCLUSIONS: Bortezomib as a first-line treatment extended the OS in four-year mortality tracking and lowered the mortality risk according to the NHIRD analysis. In the TSGH analysis, the results indicated that the initial conditions of patients with MM have a lower influence on the OS and PFS after bortezomib-based therapy was administered.

18.
Parasite ; 26: 58, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31535970

RESUMO

Toxoplasma gondii infection is prevalent in humans and animals worldwide. In this study, recombinant eukaryotic expression plasmids (pVAX-GRA24, pVAX-GRA25 and pVAX-MIC6) were constructed, and then injected into Kunming mice intramuscularly, as cocktailed plasmids or as single-gene plasmids. We evaluated immune protective responses by detecting the titer of antibodies and cytokine production of IFN-γ, IL-2, IL-4, IL-10, IL-12 and IL-23, the percentages of the subclasses of T lymphocytes, as well as the records of the survival time and cyst decrement in the brain of the mouse model after challenge with the T. gondii RH and Pru strains, respectively. Compared with the control groups, antibody and cytokine production were significantly increased, while the survival times of mice in all immunized groups were also prolonged, and the number of T. gondii cysts in their brains were decreased significantly (29.03% for pVAX-GRA24; 40.88% for pVAX-GRA25; 37.70% for pVAX-MIC6; 48.06% for pVAX-GRA24 + pVAX-GRA25; and 55.37% for pVAX-GRA24 + pVAX-GRA25 + pVAX-MIC6). The mouse group immunized with the three-gene cocktail (TgGRA24 + TgGRA25 + TgMIC6) had better performance in each detection index than the mouse groups immunized with the two-gene cocktail of TgGRA24 + TgGRA25, which was better than that in the group immunized with the single gene vaccine of TgGRA24, TgMIC6 or TgGRA25. In conclusion, TgGRA24 or TgGRA25 may be good vaccine candidates against T. gondii infection, but the three-gene cocktail of TgGRA24, TgMIC6 and TgGRA25 may induce the strongest protective immunity. Further studies of multi-antigenic DNA vaccines or cocktailed vaccines against T. gondii infection are necessary.

19.
World J Gastroenterol ; 25(34): 5197-5209, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31558867

RESUMO

BACKGROUND: Colorectal high-grade neuroendocrine neoplasms (HGNENs) are rare and constitute less than 1% of all colorectal malignancies. Based on their morphological differentiation and proliferation identity, these neoplasms present heterogeneous clinicopathologic features. Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial. AIM: To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy. METHODS: This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019. The clinicopathologic characteristics and follow-up data were carefully collected from their medical records, outpatient reexaminations, and telephone interviews. A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease. RESULTS: According to the latest recommendations for the classification and nomenclature of colorectal HGNENs, 61 (84.7%) patients in our cohort had poorly differentiated neoplasms, which were categorized as high-grade neuroendocrine carcinomas (HGNECs), and the remaining 11 (15.3%) patients had well differentiated neoplasms, which were categorized as high-grade neuroendocrine tumors (HGNETs). Most of the neoplasms (63.9%) were located at the rectum. More than half of the patients (51.4%) presented with distant metastasis at the date of diagnosis. All patients were followed for a median duration of 15.5 mo. In the entire cohort, the median survival time was 31 mo, and the 3-year and 5-year survival rates were 44.3% and 36.3%, respectively. Both the univariate and multivariate analyses demonstrated that increasing age, HGNEC type, and distant metastasis were risk factors for poor clinical outcomes. CONCLUSION: Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes. However, patients with younger age, good morphological differentiation, and without metastatic disease can have a relatively favorable prognosis.

20.
BMC Cancer ; 19(1): 926, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533668

RESUMO

BACKGROUND: Reproductive characteristics are well-established risk factors for breast cancer, but the underlying mechanisms are not fully resolved. We hypothesized that altered DNA methylation, measured in tumor tissue, could act in concert with reproductive factors to impact breast carcinogenesis. METHODS: Among a population-based sample of women newly diagnosed with first primary breast cancer, reproductive history was assessed using a life-course calendar approach in an interviewer-administered questionnaire. Methylation-specific polymerase chain reaction and Methyl Light assays were used to assess gene promotor methylation status (methylated vs. unmethylated) for 13 breast cancer-related genes in archived breast tumor tissue. We used case-case unconditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations with age at menarche and parity (among 855 women), and age at first birth and lactation (among a subset of 736 parous women) in association with methylation status. RESULTS: Age at first birth > 27 years, compared with < 23 years, was associated with lower odds of methylation of CDH1 (OR = 0.44, 95% CI = 0.20-0.99) and TWIST1 (OR = 0.48, 95% CI = 0.28-0.82), and higher odds of methylation of BRCA1 (OR = 1.63, 95% CI = 1.14-2.35). Any vs. no lactation was associated with higher odds of methylation of the PGR gene promoter (OR = 1.59, 95% CI = 1.01-2.49). No associations were noted for parity and methylation in any of the genes assayed. CONCLUSIONS: Our findings indicate that age at first birth, lactation and, perhaps age at menarche, are associated with gene promoter methylation in breast cancer, and should be confirmed in larger studies with robust gene coverage.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA