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Background: Polyethylene glycol interferon alpha (PEG-IFN-α) is the most frequently used pharmacotherapeutic approach in patients infected with hepatitis B virus (HBV). Numerous studies have reported that interleukin-28B (IL-28B) genetic polymorphisms are related to the therapeutic efficacy of PEG-IFN-α, but the results are inconsistent. The present meta-analysis aimed to analyze the association between IL-28B genetic polymorphisms and the prognosis of patients with chronic hepatitis B (CHB) treated with PEG-IFN-α to inform clinical practice. Methods: PubMed, EBSCO, and Scopus databases were searched for relevant literature published before February 30, 2021. We calculated the crude odds ratios (ORs) with 95% confidence intervals (CIs) of the cited articles. A total of 2510 patients with CHB treated with PEG-IFN-α in 13 clinical cohort studies were analyzed. Results: The overall analysis demonstrated a potential association between IL-28B genetic polymorphisms and response to PEG-IFN-α; however, the association was not statistically significant. Furthermore, the subgroup analysis revealed that among patients with HBeAg-negative CHB, the rs12979860 CC genotype and rs8099917 TT genotype were associated with more significant treatment response to PEG-IFN-α (CC vs. non-CC: OR 2.78, 95% CI 1.00-7.76, I 2 = 83%; TT vs. non-TT: OR 2.16, 95% CI 1.35-3.48, I 2 = 0%). Among Asian patients with CHB, the rs12979860 CC genotype was associated with a more significant treatment response to PEG-IFN (CC vs. non-CC: OR 1.88, 95% CI 1.18-2.99, I 2 = 0%). Conclusion: This meta-analysis revealed that the IL-28B rs12979860 CC genotype and rs8099917 TT genotype indicated a better treatment response than non-CC and non-TT genotypes for PEG-IFN-α in patients with CHB.
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The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.
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Adulto , Humanos , Masculino , Astenozoospermia/virologia , COVID-19/fisiopatologia , China , Hormônios Esteroides Gonadais/sangue , Progesterona/sangue , Prolactina/sangue , SARS-CoV-2 , Sêmen/fisiologia , Análise do Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides/fisiologia , Fatores de TempoRESUMO
Objective:To analyze the relationship between the AXIN2 gene promoter methylation status in breast cancer tissues with the breast cancer-related risk factors, clinicopathological characteristics and the mRNA expression of AXIN2 gene.Methods:The breast cancer tissues and adjacent tissues of 84 breast cancer patients were taken to detect the AXIN2 gene promoter methylation status and the AXIN2 mRNA expression. We used different concentrations of methyltransferase inhibitors 5-Azacytidine (5 -Aza) to treat human breast cancer ZR-75-1 cells, and collected the breast cancer-related risk factors and clinicopathological characteristics.Results:The positive rate of methylation of AXIN2 gene promoter in breast cancer tissues (40.5%) was significantly higher than that of adjacent tissues (19.0%) ( χ2=10.401, P=0.001) . The positive rate of AXIN2 methylation was related to the age at first delivery ( χ2=5.467, P=0.019) and a history of induced abortion ( χ2=8.372, P=0.006) ; the positive rate of AXIN2 methylation was related to lymph node metastasis ( χ2=5.338, P=0.021) , ER expression status ( χ2=9.141, P=0.002) and PR expression status ( χ2=6.918, P=0.009) . In addition, the relative expression of AXIN2 gene mRNA in breast cancer tissues (0.22 ± 0.03) was significantly lower than that in adjacent tissues (0.46 ± 0.06) ( t=3.527, P<0.001) . The relative mRNA expression of the methylation-positive breast cancer tissues (0.13 ± 0.02) was significantly lower than that of the methylation-negative breast cancer tissues (0.29 ± 0.04) ( t=3.616, P<0.001) . After ZR-75-1 cells treated with 5-Aza, the relative expression of AXIN2 gene mRNA increased significantly ( t=3.824, P<0.001) . Conclusion:DNA methylation in the promoter region of the AXIN2 gene is related to the pathogenesis of breast cancer, and has certain clinical application value.
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Objective:To explore the influencing factors of uterine myometrial and parauterine venous plexus reflux during transvaginal four-dimensional contrast-enhanced hysterosalpingography, which will help reduce and avoid the occurrence of reflux and improve the accuracy of diagnosis.Methods:A total of 306 infertile patients who underwent transvaginal four-dimensional contrast-enhanced hysterosalpingograph from June 2016 to June 2017 in the Third Affiliated Hospital of Guangzhou Medical University were retrospectively enrolled. The ultrasonographic characteristics were reviewed and the correlations between reflux and endometrial thickness, days after menstruation, intrauterine operation history and patency of fallopian tube were analyzed.Results:The incidence of countercurrent during four-dimensional contrast-enhanced hysterosalpingography was 14.71%. The chi-square test showed that the endometrial thickness and the days after menstruation had statistically significant effects on the incidence of reflux ( P=0.031 and <0.001, respectively). There were no statistically significant effects of intrauterine operation history and patency of the fallopian tube on the incidence of reflux ( P=0.610, 0.137). Logistic regression analysis showed that the incidence of reflux was associated with endometrial thickness ( B=-1.171, P<0.001) and the days after menstruation ( B=0.439, P=0.015). Conclusions:Transvaginal ultrasound measurement of endometrial thickness before angiography and selection of appropriate examination time according to the menstrual cycle can effectively reduce the incidence of reflux, and adverse reactions, and improve the accuracy of four-dimensional contrast-enhanced hysterosalpingography.
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<p><b>BACKGROUND</b>Tenascin-x, an extracellular matrix glycoprotein exclusively expressed in fibroblasts, can mediate fibrosis in the presence of collagen. Therefore, we have investigated its potential role in facilitating myocardial fibrosis and cardiac remodeling via the transforming growth factor-β1 and peroxisome proliferator-activated receptor γ (TGFβ(1)-PPARγ) pathway in alcoholic cardiomyopathy (ACM).</p><p><b>METHODS</b>Experimental animals were divided into control (group A) and tenascin-x knock-out groups (group B) receiving alcohol. Six months post treatment, cardiac ejections fraction (EF), fractional shortening (FS), left ventricle end-diastole internal diameter (LVEDd) and collagen column fraction (CVF) were observed. Tenascin-x, smad-3, TGFβ(1), smad-7 and PPARγ protein expression levels were detected by Western blotting.</p><p><b>RESULTS</b>Six months post treatment, EF and FS values were higher in group B than in group A (P < 0.05 and P < 0.01, respectively), while LVEDd and CVF were lower in group B (P < 0.05 and P < 0.01, respectively). Tenascin-x, smad-3 and TGFβ(1) protein expression levels were higher in group A, while smad-7 and PPARγ levels were lower than in group B (P < 0.01), as measured by immunohistochemistry and Western blotting. Tenascin-x protein expression was negatively correlated with EF, FS, smad-7 and PPARγ, and positively correlated with LVEDd, CVF, smad-3, and TGFβ(1) (P < 0.001).</p><p><b>CONCLUSION</b>Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGFβ(1) and downregulation of PPARγ.</p>
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Animais , Camundongos , Ratos , Western Blotting , Cardiomiopatia Alcoólica , Metabolismo , Imuno-Histoquímica , Microscopia Eletrônica , Miocárdio , Metabolismo , PPAR gama , Metabolismo , Proteína Smad3 , Metabolismo , Proteína Smad7 , Metabolismo , Tenascina , Metabolismo , Fator de Crescimento Transformador beta1 , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To evaluate the effects of valsartan and carnitine on cardiomyocyte Calpain-1 and Bcl-xl expressions of dogs with chronic alcohol intake-induced cardiomyopathy.</p><p><b>METHODS</b>Dogs were randomly assigned into 4 groups (n = 7 each): (1) alcohol fed (free access to 5%, 1(st) week; 10% 2(nd) week; 500 ml 25% bolus plus free access to 5% from 3 to 24 weeks, A); (2) alcohol + valsartan (5 mg×kg(-1)×d(-1), B); (3) alcohol + carnitine (300 mg×kg(-1)×d(-1), C); (4) Control (D). After six months, all animals were assessed for left ventricular (LV) function by echocardiography. The Bad and Bcl-xl protein expressions were evaluated by immunohistochemistry. The expression of Calpain-1 protein was determined with Western blot. Myocardial morphology was quantified on HE stained slices and under electron microscopy. The terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) was performed for apoptosis analysis.</p><p><b>RESULTS</b>Compared with group D, LVEDD and LVESD were significantly increased while EF and FS significantly decreased in group A. In alcohol fed group, expressions of Bad and Calpain-1 protein were significantly increased while Bcl-xl protein expression was downregulated, all changes could be significantly attenuated by intervention with valsartan and carnitine (all P < 0.05).</p><p><b>CONCLUSION</b>These data suggest that alcohol could promote cardiac myocyte apoptosis, reduce cardiac function and aggravate myocardial remodeling which valsartan and carnitine could reduce alcoholic cardiomyopathy by downregulating Calpain-1 and Bad protein expression and upregulating expression of Bcl-xl protein.</p>
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Animais , Cães , Apoptose , Calpaína , Metabolismo , Cardiomiopatia Alcoólica , Metabolismo , Patologia , Carnitina , Farmacologia , Modelos Animais de Doenças , Miócitos Cardíacos , Metabolismo , Tetrazóis , Farmacologia , Valina , Farmacologia , Valsartana , Proteína de Morte Celular Associada a bcl , Metabolismo , Proteína bcl-X , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To develop an efficient non-viral gene delivery system in order to transfer CDKN1B gene efficiently into lung and liver carcinoma cells.</p><p><b>METHODS</b>A recombinant plasmid composed of CDKN1B sequence and EYFP as reporter gene was constructed and identified. The recombinant DNA was then formulated the lipids-polycation-DNA complexes(LPDs) with protamine sulfate. Several kinds of lung and liver carcinoma cells were transfected by means of LPDs. The physicochemical properties of LPDs were investigated using PCS method and TEM, respectively. The expression of EYFP in A549 cells was observed under fluorescent microscope and evaluated by flow cytometry analysis. Finally, the production of CDKN1B protein in transfected LLC, Chang and 7721 cells was identified by Western blot analysis.</p><p><b>RESULTS</b>The average diameter of the LPDs were 167 nm with the polydispersity index of 0.35. The average zeta potential of LPDs was +32.6 mV. LPDs look like a sunken sphere. The fluoresent microscope picture clearly indicated the expression of EYFP in A549 cells. The flow cytometry result showed that the transfection efficiency of LPDs in A549 cells was comparable with that of LipofectAMINE, the positive control. Western blot analysis confirmed the production of CDKN1B protein in LLC, Chang and 7721 cells transfected with LPDs, while no CDKN1B protein was detected in cells transfected with naked DNA.</p><p><b>CONCLUSION</b>The construction of the recombinant plasmid is successful. LPDs can deliver the recombinant plasmid to lung carcinoma cells and liver carcinoma cells with high efficiency. Therefore, this kind of gene delivery system has the potential uses for the treatment of lung and liver cancer.</p>