YKL-40 Knockdown Decreases Oxidative Stress Damage in Ovarian Granulosa Cells.

Background: Oxidative stress has been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). To develop novel antioxidant drugs, it is necessary to explore the key regulatory molecules involved in oxidative stress in PCOS. Plasma YKL-40 levels are elevated in patients with PCOS; however, its role remains unclear. Methods: The follicular fluids of 20 women with PCOS and 12 control subjects with normal ovarian function were collected, and YKL-40 in follicular fluids was measured by enzyme-linked immunosorbent assay. A letrozole-induced PCOS rat model was established and the expression level of YKL-40 in the ovaries was detected by immunohistochemistry. KGN cells were treated with H2O2 to generate an ovarian granulosa cell (OGC) model of oxidative stress. The siRNA was transfected into the cells for knockdown. The effect of YKL-40 knockdown on H2O2-treated KGN cells was evaluated by measuring proliferation, apoptosis, activities of T-SOD, GSH-Px, and CAT, levels of MDA, IL-1ß, IL-6, IL-8, and TNF-α, and the PI3K/AKT/NF-κB signaling pathway. Results: YKL-40 levels were elevated in the follicular fluids of women with PCOS compared with control subjects with normal ovarian function. The expression level of YKL-40 in the ovaries of rats with PCOS is obviously higher than that in the ovaries of the control group rats. H2O2 treatment enhanced YKL-40 mRNA expression and protein secretion. YKL-40 knockdown enhanced cell proliferation and antioxidant capacity while decreasing apoptosis and inflammatory factor levels in KGN cells following H2O2 treatment. The knockdown activated the PI3K/AKT signaling pathway and suppressed NF-κB nuclear translocation from the cytoplasm. Conclusion: YKL-40 levels were elevated in the follicular fluids of women with PCOS and the ovaries of rats with PCOS. YKL-40 expression can be induced by oxidative stress, and YKL-40 knockdown can decrease oxidative stress damage in OGCs.

Oxidative Transformation of Nafion-Related Fluorinated Ether Sulfonates: Comparison with Legacy PFAS Structures and Opportunities of Acidic Persulfate Digestion for PFAS Precursor Analysis.

The total oxidizable precursor (TOP) assay has been extensively used for detecting PFAS pollutants that do not have analytical standards. It uses hydroxyl radicals (HO•) from the heat activation of persulfate under alkaline pH to convert H-containing precursors to perfluoroalkyl carboxylates (PFCAs) for target analysis. However, the current TOP assay oxidation method does not apply to emerging PFAS because (i) many structures do not contain C-H bonds for HO• attack and (ii) the transformation products are not necessarily PFCAs. In this study, we explored the use of classic acidic persulfate digestion, which generates sulfate radicals (SO4-•), to extend the capability of the TOP assay. We examined the oxidation of Nafion-related ether sulfonates that contain C-H or -COO-, characterized the oxidation products, and quantified the F atom balance. The SO4-• oxidation greatly expanded the scope of oxidizable precursors. The transformation was initiated by decarboxylation, followed by various spontaneous steps, such as HF elimination and ester hydrolysis. We further compared the oxidation of legacy fluorotelomers using SO4-• versus HO•. The results suggest novel product distribution patterns, depending on the functional group and oxidant dose. The general trends and strategies were also validated by analyzing a mixture of 100000- or 10000-fold diluted aqueous film-forming foam (containing various fluorotelomer surfactants and organics) and a spiked Nafion precursor. Therefore, (1) the combined use of SO4-• and HO• oxidation, (2) the expanded list of standard chemicals, and (3) further elucidation of SO4-• oxidation mechanisms will provide more critical information to probe emerging PFAS pollutants.

LncRNA LINC01503 aggravates the progression of cervical cancer through sponging miR-342-3p to mediate FXYD3 expression.

Cervical cancer (CC), an aggressive malignancy, has a high risk of relapse and death, mainly occurring in females. Accumulating investigations have confirmed the critical role of long noncoding RNAs (lncRNAs) in diverse cancers. LncRNA LINC01503 has been reported as an oncogene in several cancers. Nonetheless, its role and molecular mechanism in CC have not been explored. In the present study, we found that FXYD3 expression was considerably up-regulated in CC tissues and cells. Moreover, FXYD3 deficiency conspicuously hampered cell proliferation and migration while facilitated cell apoptosis in CC cells. Subsequently, molecular mechanism experiments implied that FXYD3 was a downstream target gene of miR-342-3p, and FXYD3 expression was reversely mediated by miR-342-3p. Moreover, we discovered that LINC01503 acted as the endogenous sponge for miR-342-3p. Besides, LINC01503 negatively regulated miR-342-3p expression and positively regulated FXYD3 expression in CC. Rescue assays revealed that LINC01503 depletion-induced repression on CC progression could be partly recovered by miR-342-3p inhibition, and then the co-transfection of sh-FXYD3#1 rescued this effect. Conclusively, LINC01503 aggravated CC progression through sponging miR-342-3p to mediate FXYD3 expression, providing promising therapeutic targets for CC patients.

MiR-1258 promotes the apoptosis of cervical cancer cells by regulating the E2F1/P53 signaling pathway.

OBJECTIVE: Cervical cancer is the most common malignant tumor in gynaecology with high mortality. MiRNA has been reported to regulate cell biological processes in cervical cancer. This study aimed to explore the expression of miR-1258 and role of miR-1258 by targeting E2F1 in cervical cancer cells. METHODS: The expression of miR-1258 and E2F1 in cervical cancer cells and transfection effects was determined by RT-qPCR analysis. The expression of E2F1, MMP2, MMP7, MMP9, Bcl2, Bax, cleaved caspase3, caspase3, KI67, p-AKT, cyclinD1, CDK2, P53 and AKT in cervical cancer cells was detected by western blot analysis. The proliferation, invasion, migration and apoptosis were respectively analyzed by CCK-8 assay, transwell assay, wound healing assay and flow cytometry analysis. E2F1 was a potential target of miR-1258, which demonstrated by a dual-luciferase reporter assay. RESULTS: miR-1258 expression was decreased while E2F1 expression was increased in cervical cancer cells. MiR-1258 overexpression could down-regulate the E2F1 expression. Overexpression of miR-1258 inhibited the proliferation, invasion and migration and promoted the apoptosis of cervical cancer cells by AKT and P53 signal pathway. And, Overexpression of miR-1258 also suppressed the tumor growth by AKT and P53 signal pathway. Overexpression of E2F1 reduced the inhibition effects of miR-1258 in cervical cancer. CONCLUSION: Taken together, miR-1258 overexpression exerts its inhibition effects on the proliferation, invasion and migration and promotion effects on the apoptosis of cervical cancer cells by targeting the E2F1, which might provide new ideas for clinical treatment of cervical cancer.

Efficacy of orthodontic and orthognathic treatment for oral and maxillofacial deformities.

BACKGROUND: This study aims to assess the efficacy and safety of orthodontic and orthognathic treatment (OOT) for patients with oral and maxillofacial deformities (OMDF) systematically. METHODS: This study will comprehensively search Cochrane Library, PubMed, EMBASE, Scopus, Web of Science, PsycINFO, Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from their inceptions to the July 1, 2019. Grey literature will be explored via searching dissertations, Google scholar and conference abstracts. Two team members will independently perform all citations, data extraction, and methodological quality. We will also utilize RevMan 5.3 Software for statistical analysis. RESULTS: This study will provide high quality evidence of OOT for OMDF. The primary outcomes consist of number of patients cured; proportion of patients healed; and time to complete healing within trial period. Secondary outcomes include quality of life (often assessed as any relevant scales, such as 36-Item Short Form Survey), costs, and complications. CONCLUSION: This study will provide evidence for judging whether OOT is effective treatment for OMDF. SYSTEMATIC REVIEW REGISTRATION: CRD42019144610.

Endovascular graft exclusion for treating Stanford type B acute aortic dissection in aged population.

The aim of this study was to investigate the efficiency of endovascular graft exclusion for treating Stanford type B acute aortic dissection (AAD) in aged population.Forty-six consecutive patients aged ≥65 years with Stanford type B AAD underwent endovascular therapy in Tianjin Chest Hospital between 2010and 2015 were included in this study. All patients received echocardiography, contrast-enhanced CT, hepatic and renal functions tests, and the blood and urine routine examinations. After the procedure, annual review of the whole aortic computed tomography (CT) was performed for all patients before discharge, as well as 3 months, 6 months and12 months after surgery. All patients were followed up until December, 2015. The outcomes of the whole aortic CT and survival rate were analyzed.Five patients (10.87%) died. Among the 5 cases, 2 showed perioperative death induced by cerebral infarction, 1 died because of newly developed AD 8 months after surgery, and 2 died because of acute myocardial infarction (n = 1) and renal/cardiac failure (n = 1). The other 41 patients (89.13%) were symptom-free with satisfactory conditions.Endovascular stent-graft placement was effective for treating the senior patients with Stanford type B AAD.

[Klf10 silencing inhibited mechanical force induced osteogenic differentiation of human periodontal ligament cells].

PURPOSE: To investigate the effect of Klf10 silence on human periodontal ligament cells (HPDLCs) under mechanical force. METHODS: HPDLCs were isolated and transfected with Klf10 siRNA, and then exposed to centrifugal force for 6 h at 631 r/min. Purmorphamine, an hedgehog signaling pathway agonist, was used for intervention. The activity of alkaline phosphatase (ALP) was detected by ELISA. RT-PCR and Western blot were performed to detect the mRNA and protein expression of Klf10, Runt related transcription factor 2 (Runx2), osteopontin (OPN) and osteocalcin (OCN). The protein expression of glioma associated oncogene homolog 1 (Gli1) and patched-1 (PTCH1) was detected by Western blot. SPSS 20.0 software package was used to analyze the data. RESULTS: Mechanical force increased mRNA and protein level of Klf10, Runx2, OPN and OCN, and elevated ALP activity significantly (P<0.05). Mechanical force also upregulated the protein expression of GLI1 and Ptch1 significantly (P<0.05). Compared with the control group, Klf10 siRNA transfection significantly decreased mRNA and protein level of Klf10 (P<0.05). Klf10 siRNA significantly inhibited the activity of ALP, and downregulated mRNA and protein expression of Runx2, OPN and OCN (P<0.05). Moreover, Klf10 siRNA significantly inhibited protein expression of GLI1 and Ptch1 (P<0.05), and purmorphamine obviously inhibited the effect of Klf10 siRNA (P<0.05). CONCLUSIONS: Klf10 silencing could inhibit bone differentiation of human periodontal ligament cells under mechanical force, which may be through regulation of hedgehog signaling pathway.

Vitamin D receptor genetic variants are associated with chemotherapy response and prognosis in patients with advanced non-small-cell lung cancer.

BACKGROUND: The aim of this study was to explore the association between vitamin D receptor (VDR) genetic polymorphisms and platinum-based chemotherapy response as well as the prognosis of non-small-cell lung cancer (NSCLC) in a Chinese cohort. PATIENTS AND METHODS: Seven hundred fifty-five patients with advanced NSCLC (stage III [A + B] or stage IV) were enrolled. Platinum-based chemotherapy was given to each patient with NSCLC, and the therapeutic effect was evaluated. The VDR polymorphisms were genotyped. RESULTS: Three hundred twenty-one (42.5%) patients responded to chemotherapy (complete response [CR] or partial response [PR]) and 434 (57.5%) patients were nonresponders (stable disease [SD] or progressive disease [PD]). The genotypic and allelic frequencies of FokI, BsmI, and TaqI were not significantly different between chemotherapy responders and nonresponders. However, the genotypic and allelic frequencies of ApaI thymine (T) > guanine (G) were significantly different between the responders and nonresponders. Multivariate logistic regression analysis showed that GG genotype carriers of ApaI T > G had a higher chance of being responders. The ApaI T > G polymorphisms affected mean overall survival (OS). The GG genotype carriers of ApaI polymorphisms had a longer mean OS compared with TT carriers. Multivariate Cox regression analyses showed that ApaI T > G was significantly associated with OS. CONCLUSION: We found that there was an effect of ApaI T > G polymorphisms of the VDR gene on the chemotherapy response in patients with NSCLC, as well as a prognostic role of the VDR gene polymorphisms in Chinese patients with advanced NSCLC.

Association between the NBS1 Glu185Gln polymorphism and lung cancer risk: a systemic review and meta-analysis.

Nijmegen Breakage Syndrome protein 1 (NBS1) is one of the most important DNA repair proteins playing important roles in maintaining the genomic stability of NDA. Previous studies regarding the association between NBS1 8360G>C (Glu185Gln) polymorphism and lung cancer reported conflicting results. To derive a more precise estimation of this association, a systemic review and meta-analysis was performed. We performed a meta-analysis using eligible case-control studies to summarize the data on the association between the NBS1 Glu185Gln polymorphism and lung cancer risk. Odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CIs) were pooled to assess the association between NBS1 Glu185Gln polymorphism and lung cancer risk. Six case-control studies with a total of 2,348 lung cancer cases and 2,401 controls without canner were included into the meta-analysis. Overall, there was an association between NBS1 Glu185Gln polymorphism and lung cancer risk under the dominant comparison model (fixed-effects OR GluGln/GlnGln vs. GluGlu = 1.21, 95 % CI 1.07-1.37, P = 0.002, I (2) = 8.1 %). Subgroup analysis by race suggested a significant association between NBS1 Glu185Gln polymorphism and lung cancer risk in Asians (fixed-effects OR GluGlnGlnGln vs. GluGlu = 1.22, 95 % CI 1.06-1.41, P = 0.005) but not in Caucasians (fixed-effects OR GluGlnGlnGln vs. GluGlu = 1.17, 95 % CI 0.91-1.50, P = 0.220). This meta-analysis supports that there is an association between NBS1 Glu185Gln polymorphism and lung cancer risk. More studies are needed to further verify this association.

The association between MTHFR 677C>T polymorphism and cervical cancer: evidence from a meta-analysis.

BACKGROUND: MTHFR 677C>T polymorphism is a genetic alteration in an enzyme involved in folate metabolism, but its effect on host susceptibility to cervical cancer is still uncertain. The aim of this study was to investigate the association between MTHFR 677C>T polymorphism and cervical cancer by performing a meta-analysis. METHODS: Pubmed, Embase, Web of Science, and the Chinese Biomedical Database (CBM) databases were searched for case-control studies investigating the association between MTHFR 677C>T polymorphism and cervical cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess this possible association. RESULTS: 11 studies with a total of 1898 cervical cancer cases and 2678 controls were included. Meta-analyses of a total 11 studies showed no association between MTHFR 677C>T polymorphism and cervical cancer using all five genetic models (All P values>0.05). However, subgroup analyses showed the odds of the homozygous TT genotype were much less in cervical cancer cases than in controls in Europeans, which implied an association between the homozygous TT genotype and cervical cancer in Europeans (For TT versus CC, fixed-effects OR=0.65, 95%CI 0.45-0.93, P=0.020, I2=0.0%). The odds for the homozygous TT genotype were greater in cervical cancer cases than in controls in East Asians, which also implied an association between the homozygous TT genotype and cervical cancer in East Asians (For TT versus CC, random-effects OR=1.66, 95%CI 1.05-2.62, P=0.029, I2=52.6%; For TT versus CT/CC, random-effects OR=1.55, 95%CI 1.09-2.22, P=0.016, I2=42.4%). Both subgroup analyses and meta-regression analyses suggested ethnicity was the major source of heterogeneity. Publication bias was not evident. CONCLUSIONS: This meta-analysis supports an association between MTHFR 677C>T polymorphism and cervical cancer, and the effect of this association may be race specific. Further studies with large sample sizes and careful design are needed to identify this association more comprehensively.

[Effects of heparin and anticardiolipin antibodies positive serum from patients with recurrent pregnancy loss on proliferation of BeWo cells].

OBJECTIVE: To investigate the effects of anticardiolipin antibodies positive serum from patients with recurrent pregnancy loss on the proliferation of BeWo cells as well as the modulation of heparin on the growth of BeWo cell. METHODS: Thirty patients with recurrent pregnancy loss whose anticardiolipin antibodies were positive and thirty healthy women with a history of term delivery were selected. Their sera were separately added to BeWo cell culture systems which contained either heparin or not. After 24 hours, the PCNA and 490 nm A value were detected by immunofluorescence and methyl thiazolyl tetrazolium (MTT), and the proliferation of BeWo cell was evaluated. RESULTS: In the culture systems with heparin and normal serum, normal serum, heparin and serum with positive autoantibody, serum with positive autoantibody, the mean fluorescence gray scale values of PCNA were 34.8 +/- 3.1, 33.8 +/- 1.8, 33.4 +/- 2.2 and 25.1 +/- 2.3, the 490 nm A values were 0.0560 +/- 0.0033, 0.0535 +/- 0.0024, 0.0524 +/- 0.0027 and 0.0350 +/- 0.0040, respectively. CONCLUSIONS: The serum with anticardiolipin antibodies from patients with recurrent pregnancy loss can influence the prospective potency of BeWo cell, inhibit cell proliferation in vitro. Through this direct effect on biological behaviour of the trophoblastic cell, it will lead to recurrent pregnancy loss, whereas heparin can increase the ratio of pregnancy by reversing such effects in those patients.