Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system.

The present letter to the editor is related to the study titled 'Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells'. Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

Prognostic Significance of PD-L1 Expression in Gastric Cancer Patients with Peritoneal Metastasis.

BACKGROUND: Recently, many studies have explored the relationship between the expression of programmed death ligand 1 (PD-L1) and prognosis in gastric cancer, but there is still controversy. Additionally, few studies have specifically investigated the expression of PD-L1 in patients with peritoneal metastasis. METHODS: Immunohistochemistry was used to analyze the expression of PD-L1 in gastric cancer patients with peritoneal metastasis. The combined positive score (CPS) was calculated to evaluate the expression of PD-L1, and the clinicopathological data were analyzed to explore prognostic significance. RESULTS: In total, 147 gastric cancer patients with peritoneal metastasis were enrolled. The negative PD-L1 expression was defined as a CPS < 1, and high PD-L1 expression was defined as a CPS ≥ 10. PD-L1 expression with CPS ≥ 1 and CPS-negative was detected in 67 (45.58%) and 80 (54.42%) patients, respectively. High PD-L1 expression at PD-L1 CPS ≥ 10 was detected in 21(14.29%) patients. The median overall survival (OS) was 18.53 months in the CPS < 10 group and 27.00 months in the CPS ≥ 10 group; the OS difference between the two groups was significant (p = 0.015). Multivariate analysis demonstrated that a poor Eastern Cooperative Oncology Group performance score (ECOG PS) (p = 0.002) and severe peritoneal metastasis (p = 0.033) were significantly associated with poor survival, while palliative chemotherapy (p = 0.002) and high PD-L1 expression (p = 0.008) were independent and significantly favorable prognostic factors. CONCLUSIONS: Our study demonstrated that PD-L1 expression was widely presented in gastric cancer patients with peritoneal metastasis, while a CPS no less than 10 predicted better prognosis.

Effect of Micropillar Array Morphology on Liquid Propagation Coefficient Enhancement.

Roughness on hydrophilic surfaces allows for fast propagation of liquids. In this paper, the hypothesis is tested which theorizes that pillar array structures with nonuniform pillar height levels can enhance wicking rates. In this work, within a unit cell, nonuniform micropillars were arranged with one pillar at constant height, while other shorter pillars were varied in height to study these nonuniform effects. Subsequently, a new microfabrication technique was developed to fabricate a nonuniform pillar array surface. Capillary rising-rate experiments were conducted with water, decane, and ethylene glycol as working liquids to determine the behavior of propagation coefficients that were dependent on pillar morphology. It is found that a nonuniform pillar height structure leads to a separation of layers in the liquid spreading process and the propagation coefficient increases with declining micropillar height for all liquids tested. This indicated a significant enhancement of wicking rates compared to uniform pillar arrays. A theoretical model was subsequently developed to explain and predict the enhancement effect by considering capillary force and viscous resistance of nonuniform pillar structures. The insights and implications from this model thus advance our understanding of the physics of the wicking process and can inform the design of pillar structures with an enhanced wicking propagation coefficient.

Ethnobotanical survey of antifertility medicinal plants in Dali District, Yunnan Province, China.

In recent years, contraceptive medication has been widely used for birth control. It is worth noting that contraceptive medication from botanical source has great potential for clinical use. Yunnan is the province with the most species of plants in China and is known as the "plant kingdom". This study aims to archive herbal remedies traditionally used as antifertility remedies in Dali District, Yunnan Province, P. R. China. The survey was conducted from February 2011 to September 2016 in the population distributed in Dali and the surrounding counties. The data were collected from three groups of practitioners within the study area: therapists using traditional medicines (n = 104), aboriginal families (n = 37), and herbalists in commercial stalls (n = 12), and a total number of 117 plant species were recorded. Among the 117 plant species, 104 of which have been authenticated by a plant taxonomist from the Dali Herbarium. These plants were classified into 98 genera and 54 families, including Leguminosae (12 species), Liliaceae (7 species), Cucurbitaceae, Rosaceae and Rutaceae (5 species, respectively), Malvaceae, Compositae and Euphorbiaceae (4 species, respectively). Our data provides an in-depth delineation of the contraceptive plants used in Dali, which serve as valuable information for the practitioners of traditional Chinese medicine in contraceptive use. In addition, these data also hint that plants from different genus contain contraceptive components, which should be avoided by pregnant women. Future studies are required to identify the active contraceptive components, assess the toxicology, and elucidate the pharmacological mechanism of action.

Expression of MTERF3 gene in breast carcinoma and the relationship with clinicopathological characteristics.

BACKGROUND: Mitochondrial transcription termination factor 3 (MTERF3) is a negative regulator of mitochondrial transcription. It is a modular factor involves in mitochondrial ribosome biogenesis and protein synthesis. However, the association between MTERF3 and breast cancers remains largely unknown. The aim of this study was to investigate the expression of MTERF3 in breast carcinoma and to analyze its clinicopathological significance, and to examine the potential prognostic value of MTERF3 in breast cancer. METHODS: The protein expression levels of MTERF3 in MCF7 (Luminal A), BT-474 (Luminal B), SKBR3 (HER2 overexpression), MDA-MB-468 (Basal like) and MCF10A cell lines were detected by Western blotting. Immunohistochemistry (IHC), Western blotting, and semiquantitative RT-PCR were performed to analyze the protein and mRNA expression levels of MTERF3 in 58 breast cancer tissues and 58 noncancerous breast tissues. The MTERF3 expression data and clinical information from breast cancer patients were downloaded from the TCGA dataset by using the R3.6.1 software. Then the relationship between the expression level of MTERF3 and clinicopathological characteristics and the prognostic value was analyzed. A Cox regression model was performed for the multivariate analysis of the factors that affected the prognosis of breast cancer. The association between the expression levels of MTERF3 and other mitochondrial regulatory genes was analyzed with GEPIA. RESULTS: MTERF3 is upregulated in breast cancer cell lines compared to noncancerous breast cell line. The IHC results showed that the MTERF3 protein was located in the cytoplasm, and the rate of positive expression in breast cancer tissue was significantly upregulated compared with the adjacent normal tissue. The mRNA and protein expression levels of MTERF3 in breast cancer tissues were significantly higher than that in breast tissues. Moreover, the expression of MTERF3 was significantly correlated with ER status, PR status, breast cancer molecular typing, cancer type, histological diagnosis and primary site (P<0.05). Further analysis showed MTERF3 expression was not related to prognosis. Multivariate Cox regression analysis showed that age, metastasis status and tumor type were independent prognostic factors for breast cancer patients. The expression levels of MTERF3 were positively correlated with the TFAM, TFB1M, TFB2M, MTERF1, TEFM and MFN1 genes but negatively correlated with the MTERF4 and PINK1 genes. In addition, the expression levels of MTERF3 were not correlated with the MTERF2 gene. CONCLUSIONS: MTERF3 was significantly upregulated in breast cancer cells and tissues compared with noncancerous cells and tissues. Moreover, the expression level of MTERF3 was correlated with ER status, PR status, breast cancer molecular typing, cancer type, histological diagnosis and primary site. These findings suggested that the upregulation of MTERF3 may be used as a diagnostic and therapeutic target in breast carcinoma.

Insight derived from molecular dynamics simulation into dynamics and molecular motions of cuticle-degrading serine protease Ver112.

Cuticle-degrading serine protease Ver112, which derived from a nematophagous fungus Lecanicillium psalliotae, has been exhibited to have high cuticle-degrading and nematicidal activities. We have performed molecular dynamics (MD) simulation based on the crystal structure of Ver112 to investigate its dynamic properties and large-scale concerted motions. The results indicate that the structural core of Ver112 shows a small fluctuation amplitude, whereas the substrate binding sites, and the regions close to and opposite the substrate binding sites experience significant conformational fluctuations. The large concerted motions obtained from essential dynamics (ED) analysis of MD trajectory can lead to open or close of the substrate binding sites, which are proposed to be linked to the functional properties of Ver112, such as substrate binding, orientation, catalytic, and release. The significant motion in the loop regions that is located opposite the binding sites are considered to play an important role in modulating the dynamics of the substrate binding sites. Furthermore, the bottom of free energy landscape (FEL) of Ver112 are rugged, which is mainly caused by the fluctuations of substrate binding regions and loops located opposite the binding site. In addition, the mechanism underlying the high flexibility and catalytic activity of Ver112 was also discussed. Our simulation study complements the biochemical and structural studies, and provides insight into the dynamics-function relationship of cuticle-degrading serine protease Ver112.

The effects of maternal cigarette smoking on pregnancy outcomes using assisted reproduction technologies: An updated meta-analysis.

There is strong evidence indicating that smoking has negative effects on female reproductive health. Studies to investigate the effects of female smoking on IVF outcomes have been conducted by several research groups, yet the results are controversial. To evaluate the impacts of female smoking on the outcomes of assisted reproduction, a meta-analysis was performed, which included studies published in English up to September 6, 2017 from the MEDLINE, EMBASE, and Cochrane library databases. Twenty-eight studies encompassing 5009 female smokers seeking assisted reproduction and 10,078 non-smokers were used in this meta-analysis. Significant negative outcomes were detected in the female smokers compared with non-smokers including decreases in live birth rate per cycle (OR=0.52, 95% CI 0.37-0.74), in clinical pregnancy rate per cycle (OR 0.59, 95% CI 0.51-0.68), in number of retrieved oocytes (MD=-0.87, 95% CI -1.39 to -0.25), and in average fertilization rate (MD=-4.80, 95% CI -8.49 to -2.02), as well as a significantly increased miscarriage rate per pregnancy (OR=2.48, 95% CI 1.79-3.43). In conclusion, the current meta-analysis provides compelling evidence that female smoking has a significantly negative impact on the outcomes of assisted reproductive technology (ART) and strongly recommends that female smokers will greatly benefit from a smoking cessation before employing ART to become pregnant.

A predictive model for high-quality blastocyst based on blastomere number, fragmentation, and symmetry.

PURPOSE: The aim of this study was to create a predictive model for high-quality blastocyst progression based on the traditional morphology parameters of embryos. METHODS: A total of 1564 embryos from 234 women underwent conventional in vitro fertilization and were involved in the present study. High-quality blastocysts were defined as having a grade of at least 3BB, and all embryos were divided based on the development of high-quality blastocysts (group HQ) or the failure to develop high-quality blastocysts (group NHQ). A retrospective analysis of day-3 embryo parameters, focused on blastomere number, fragmentation, the presence of a vacuole, symmetry, and the presence of multinucleated blastomeres was conducted. RESULTS: All parameters were related to high-quality blastocysts (p < 0001) in t tests, chi-square tests, or Fisher tests. The individual scores for all parameters were determined according to their distributions and corresponding rates of forming high-quality blastocysts. Parameters are indicated by s_bn (blastomere number), s_f (fragmentation), s_pv (presence of a vacuole), s_s (symmetry), and s_MNB (multinucleated blastomeres). Subsequently, univariate and multivariate logistic regression analyses were conducted to explore their relationship. In the multivariate logistic regression analysis, a predictive model was constructed, and a parameter Hc was created based on the s_bn, s_f, and s_s parameters and their corresponding odds ratios. The value of Hc in group HQ was significantly higher than that in group NHQ. A receiver operating characteristic curve was used to test the effectiveness of the model. An area under the curve of 0.790, with a 95% confidence interval of 0.766-0.813, was calculated. A dataset was used to validate the predictive utility of the model. Moreover, another dataset was used to ensure that the model can be applied to predict the implantation of day-3 embryos. CONCLUSIONS: A predictive model for high-quality blastocysts was created based on blastomere number, fragmentation, and symmetry. This model provides novel information on the selection of potential embryos.

Association of the common SNPs in RNF212, STAG3 and RFX2 gene with male infertility with azoospermia in Chinese population.

OBJECTIVE: The aim of this study was to explore the association between the SNP rs4045481 in RNF212 gene, rs1050482 and rs11531577 in STAG3 gene as well as rs2288846 in RFX2 gene and male infertility with azoospermia in Chinese population. STUDY DESIGN: Two hundreds and twenty infertile patients with azoospermia and 248 fertile men were recruited in the present study. The four SNPs investigated were genotyped using polymerase chain reaction and restriction fragment length polymorphism assay. The differences in allelic and genotypic frequencies between patients and controls were evaluated by chi-square test. RESULTS: No significant differences in allele and genotype frequencies of SNP rs1050482 and rs11531577 in STAG3 gene as well as rs2288846 in RFX2 gene between patients with azoospermia and controls were observed. However, the frequencies of allele C(43.6% vs. 34.1%, P = 0.003, OR = 1.498, 95% CI 1.150-1.192) and genotype CC (24.6% vs. 12.0%, P = 0.001, OR = 2.346, 95% CI 1.448-3.858) were significantly higher in patients with azoospermia than those in controls at the rs4045481 locus in RNF212 gene. CONCULUSION: The polymorphism of SNP rs4045481 in RNF212 gene might be associated with azoospermia and genotype CC of this SNP may be a risk factor of azoospermia.

Circulating circular RNA hsa_circ_0001785 acts as a diagnostic biomarker for breast cancer detection.

BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) and characterized by covalently closed loop without 5' and 3' end. Recently, the diagnostic value of circRNAs has received more and more attention. However, the in-depth study about circRNAs diagnosis in breast cancer is still rarely reported. In present study, we try to investigate the circRNAs expression profiles in breast cancer peripheral blood and discover valuable diagnostic biomarkers. METHODS: The expression profiles of circRNAs in plasma specimens were screened from five breast cancer and paired healthy volunteer s. The expression levels of selected candidate circRNAs were detected by RT-PCR. The diagnostic value was performed using receiver operating characteristic (ROC) curve. RESULTS: CircRNAs microarray assay showed that 41 circRNAs were aberrantly expressed with 2 fold change, including 19 up-regulated and 22 down-regulated circRNAs. Among these circRNAs, 3 candidate circRNAs were validated to be significantly dysregulated using RT-PCR, including hsa_circ_0001785, hsa_circ_0108942 and hsa_circ_0068033. In lager study cohort (n=20), ROC curve showed that hsa_circ_0001785 had better diagnostic value (AUC=0.771) than others. Moreover, in further extensive study cohort (n=57), we found that hsa_circ_0001785 plasma had better diagnostic accuracy (AUC=0.784) than CEA (AUC=0.562) and CA15-3 (AUC=0.629). Besides, hsa_circ_0001785 plasma level was closely related to histological grade (P=0.013), TNM stage (P=0.008) and distant metastasis (P=0.016). Furthermore, hsa_circ_0001785 plasma level in postoperative patients (0.283±0.043) was significantly lower than that of preoperative patients (0.109±0.037, P<0.01). CONCLUSION: Our study reveals the aberrant circRNAs expression profiles in breast cancer peripheral blood, and identifies the potential diagnostic value of plasma hsa_circ_0001785, providing a stable biomarkers for the diagnosis and progress of breast cancer.

Association of common SNP rs1136410 in PARP1 gene with the susceptibility to male infertility with oligospermia.

PURPOSE: This study aims to explore possible associations between polymorphisms of common SNP rs1136410 and rS1805405 in PARP1 gene and male infertility with spermatogenesis impairment. METHODS: The polymorphic distributions of SNP rs1136410 and rS1805405 were investigated by polymerase chain reaction and restriction fragment length polymorphism analysis in a Chinese cohort including 371 infertile patients with idiopathic azoospermia or oligospermia and 231 controls. RESULTS: Significant differences in the frequencies of allele and genotype of SNP rs1136410 were observed between patients with oligospermia and controls. The allele C (46.3 % vs. 36.4 %, P = 0.003) and genotype CC (22.6 % vs. 13.4 %, P = 0.014) significantly increased, whereas genotype TT (30 % vs. 40.7 %, P = 0.021) significantly decreased in patients with oligospermia compared with controls at this SNP locus. CONCLUSIONS: These results indicated that genotype CC of SNP rs1136410 may increase the risk of oligosoermia and genotype TT of rs1136410 may have some protective effect from oligospermia, suggesting that the polymorphism of SNP rs1136410 in PARP1 gene may modify the susceptibility to male infertility with oligospermia.

Polymorphism in DNMT1 may modify the susceptibility to oligospermia.

As an important methyltransferase, DNMT1 plays a key role in DNA methylation that is essential for normal spermatogenesis, which suggests that it may be involved in male infertility with spermatogenesis impairment. To explore the relationship between DNMT1 and spermatogenesis impairment, polymorphic distributions of single-nucleotide polymorphisms (SNP) rs16999593, rs2228612 and rs2228611 in DNMT1 were investigated in 342 infertile patients with idiopathic azoospermia or oligospermia and 232 fertile controls in a Chinese population. As a result, no significant differences in allele and genotype frequencies of the three SNP between total patients and controls were observed. However, after stratifying the patients, significant differences in allele and genotype frequencies were detected between oligospermia subgroup and control group. The frequencies of rs16999593 allele A (83.6% versus 77.6%, P=0.033) and genotype AA (69.2% versus 59.0%, P=0.037) and SNP rs2228611 genotype AA (18.4% versus 9.9%, P=0.016) in patients with oligospermia were significantly higher than those in control group. These findings suggest that the polymorphism in DNMT1 might be associated with oligospermia and could modify the susceptibility of oligospermia.