Pectin-based cinnamon essential oil Pickering emulsion film with two-sided differential wettability: A major role in the spatial distribution of microdroplets.

Pickering emulsions have attracted much attention as a novel emulsifying technology. This research to explore Zein-Citrus pectin nanoparticles stabilized cinnamon essential oil (CEO) Pickering emulsion (ZCCPEs) for constructing Pickering emulsion edible film (PEF). Unlike traditional research, which focuses on antibacterial and antioxidant activities, our research examined the physical properties of PEF, specifically changes in wettability. The results show that PEF has better transparency and tensile strength than the pectin alone direct emulsion film (PAEF), and the spatial distribution of Pickering emulsion droplets gives different wettability on both sides of PEF. The partially hydrophobic upside has important application value in food packaging. At the same time, the PEF is biodegradable and environmentally non-polluting. The edible film loaded with essential oils, developed based on the Pickering stabilization mechanism in this study, possesses several desirable characteristics for potential used as bioactive packaging films in food applications.

Hepatocyte growth factor is protective in early stage but bone-destructive in late stage of experimental periodontitis.

BACKGROUND AND OBJECTIVE: Clinical studies found high levels of hepatocyte growth factor (HGF) expression in patients with periodontitis. Studies suggest that HGF plays an important role in periodontitis, is involved in inflammation, and modulates alveolar bone integrity in periodontitis. This study aims to investigate the effects and mechanisms of HGF in the progression of experimental periodontitis. METHODS: We used silk thread ligation to induce periodontitis in HGF-overexpressing transgenic (HGF-Tg) and wild-type C57BL/6J mice. The effects of HGF overexpression on alveolar bone destruction were assessed by microcomputed tomography imaging at baseline and on days 7, 14, 21, and 28. We analyzed the cytokines (IL-6 and TNF-α) and lymphocytes in periodontitis tissues by enzyme-linked immunosorbent assay and flow cytometry. The effects of HGF on alveolar bone destruction were further tested by quantifying the systemic bone metabolism markers CTXI and PINP and by RNA sequencing for the signaling pathways involved in bone destruction. Western blotting and immunohistochemistry were performed to further elucidate the involved signaling pathways. RESULTS: We found that experimental periodontitis increased HGF production in periodontitis tissues; however, the effects of HGF overexpression were inconsistent with disease progression. In the early stage of periodontitis, periodontal inflammation and alveolar bone destruction were significantly lower in HGF-Tg mice than in wild-type mice. In the late stage, HGF-Tg mice showed higher inflammatory responses and progressively aggravated bone destruction with continued stimulation of inflammation. We identified the IL-17/RANKL/TRAF6 pathway as a signaling pathway involved in the HGF effects on the progression of periodontitis. CONCLUSION: HGF plays divergent effects in the progression of experimental periodontitis and accelerates osteoclastic activity and bone destruction in the late stage of inflammation.

Sea bass protein-polyphenol complex stabilized high internal phase of algal oil Pickering emulsions to stabilize astaxanthin for 3D food printing.

The protective effect of sea bass protein (SBP)-(-)-epigallocatechin-3-gallate (EGCG) covalent complex-stabilized high internal phase (algal oil) Pickering emulsions (HIPPEs) on astaxanthin and algal oils was demonstrated in this study. The SBP-EGCG complex with better wettability and antioxidant activity was formed by the free radical-induced reaction to stabilize HIPPEs. Our results show that the SBP-EGCG complex formed dense particle shells surrounding the oil droplets, and the shells were crosslinked with the complex in the continuous phase to produce a network structure. The rheological analysis demonstrated that the SBP-EGCG complex endowed HIPPEs with high viscoelasticity, high thixotropic recovery, and good thermal stability, which were beneficial for three-dimensional (3D) printing applications. HIPPEs stabilized by SBP-EGCG complex were applied to improve the stability and bioaccessibility of astaxanthin and to delay algal oil lipid oxidation. The HIPPEs might become a food-grade 3D printing material served as a delivery system for functional foods.

m6A methyltransferase METTL3 inhibits endometriosis by regulating alternative splicing of MIR17HG.

In brief: Inflammation and abnormal immune response are the key processes in the development of endometriosis (EMs), and m6A modification can regulate the inflammatory response. This study reveals that METTL3-mediated N6-methyladenosine (m6A) modification plays an important role in EMs. Abstract: m6A modification is largely involved in the development of different diseases. This study intended to investigate the implication of m6A methylation transferase methyltransferase like 3 (METTL3) in EMs. EMs- and m6A-related mRNAs and long non-coding RNAs were identified through bioinformatics analysis. Next, EM mouse models established by endometrial autotransplantation and mouse endometrial stromal cell (mESC) were prepared and treated with oe-METTL3 or sh-MIR17HG for pinpointing the in vitro and in vivo effects of METTL3 on EMs in relation to MIR17HG through the determination of mESC biological processes as well as estradiol (E2) and related lipoprotein levels. We demonstrated that METTL3 and MIR17HG were downregulated in the EMs mouse model. Overexpression of METTL3 suppressed the proliferation, migration, and invasion of mESCs. In addition, METTL3 enhanced the expression of MIR17HG through m6A modification. Moreover, METTL3 could inhibit the E2 level and alter related lipoprotein levels in EMs mice through the upregulation of MIR17HG. The present study highlighted that the m6A methylation transferase METTL3 prevents EMs progression by upregulating MIR17HG expression.

The effect of sperm DNA fragmentation on in vitro fertilization outcomes of unexplained infertility

Abstract Background Infertility is caused by heterogeneous risks, but most of them are unexplained. The sperm DNA Fragmentation Index (DFI) was increasingly acknowledged as a parameter for the evaluation of male infertility. This study aimed to investigate the association between sperm DFI and laboratory and clinical outcomes in a population with unexplained infertility. Methods The clinical data of an infertile population was collected for the selection of reproductive patients with unexplained infertility. The authors classified the patients with normal sperm parameters in a control group (DFI < 25%) and an observation group (DFI ≥ 25%) and compared the difference in basal characteristics, laboratory, and clinical outcomes between the two groups. The authors conducted a correlation analysis to examine the relationship between DFI and the number of D3 good-quality embryos, as well as the clinical pregnancy rate and live birth rate. A total of 176 cases were enrolled in the retrospective study. Results The observation group (n = 88) showed advanced male age, lower sperm concentration, progressive motility, and morphology assessment than the control group. In addition, lower No. of D3 good-quality embryos, clinical pregnancy rate, and the live birth rate were shown in the observation group. A negative correlation between the DFI and No. of D3 good-quality embryos (rs = -0.347, p < 0.001) or live birth rate (rs = -0.185, p = 0.028) was shown. Conclusions Sperm DFI was a good indicator for the prediction of D3 good-quality embryos in unexplained infertility couples, but it did not provide sufficient information regarding clinical pregnancy outcome but live pregnancy outcome.

Effects of exercise interventions on cancer-related fatigue in breast cancer patients: an overview of systematic reviews.

OBJECTIVE: This overview of systematic reviews aims to critically appraise and consolidate evidence from current systematic reviews (SRs)/meta-analyses on the effects of exercise interventions on cancer-related fatigue (CRF) in breast cancer patients. METHODS: SRs/meta-analyses that explored the effects of exercise interventions on CRF in breast cancer patients compared with the routine methods of treatment and care were retrieved from nine databases. The methodological quality of the included SRs was appraised using A MeaSurement Tool to Assess systematic Reviews II (AMSTAR II). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to calculate the grading of outcomes in the included SRs. The exercise type, frequency, duration, and inclusion/absence of supervision were further evaluated with subgroup analyses. The Stata 16.0 software was utilized for data analysis. RESULTS: Twenty-nine reviews were included. The overall methodological quality and level of evidence of the included reviews were unsatisfactory, with only three reviews rated as high methodological quality and no review identified as high-quality evidence. Moderate certainty evidence indicated that exercise could improve fatigue in breast cancer patients (SMD = - 0.40 [95%CI - 0.58, - 0.22]; P = 0.0001). Subgroup analysis based on the types of exercise showed that yoga (SMD = - 0.30 [95%CI - 0.56, - 0.05]; I2 = 28.7%) and aerobic exercise (SMD = - 0.29 [95%CI - 0.56, - 0.02]; I2 = 16%) had a significantly better effect on CRF in breast cancer patients; exercising for over 6 months (SMD = - 0.88 [95%CI - 1.59, - 0.17]; I2 = 42.7%; P = 0.0001), three times per week (SMD = - 0.77 [95%CI - 1.04, - 0.05]; I2 = 0%; P = 0.0001), and for 30 to 60 min per session (SMD = - 0.81 [95%CI - 1.15, - 0.47]; I2 = 42.3%; P = 0.0001) can contribute to a moderate improvement of CRF. Supervised exercise (SMD = - 0.48 [95%CI - 0.77, - 0.18]; I2 = 87%; P = 0.001) was shown to relieve CRF. CONCLUSION: Exercise played a favorable role in alleviating CRF in breast cancer. Yoga was recommended as a promising exercise modality for CRF management in the majority of the included studies. Exercising for at least three times per week with 30 to 60 min per session could be recommended as a suitable dosage for achieving improvement in CRF. Supervised exercise was found to be more effective in alleviating CRF than unsupervised exercise. More rigorously designed clinical studies are needed to specify the exact exercise type, duration, frequency, and intensity to have an optimal effect on CRF in breast cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: CRD42020219866.

Correlation between impaired hemodynamic response and cardiopulmonary fitness in middle-aged type 2 diabetes mellitus patients: a case-control study.

PURPOSE: Impaired cardiorespiratory fitness (CRF) is a predictor of mortality in patients with type 2 diabetes mellitus (T2DM). It is still not known how the exercise hemodynamic response correlates with CRF. The purpose was to assess the correlation between hemodynamic changes and CRF in middle-aged patients with T2DM. METHODS: After 1:1 matching by age and sex, 139 T2DM patients and 139 non-T2DM controls who completed the exercise treadmill test were included. Maximal aerobic capacity (VO2max), exercise-induced changes in heart rate (ΔHR), systolic blood pressure (ΔSBP), diastolic blood pressure (ΔDBP), and rate-pressure product (ΔRPP) were measured. HRR1 was calculated as the maximum heart rate minus the heart rate after 1 min of rest. RESULTS: Compared to the control population, T2DM patients had decreased ΔHR (87 (77, 97) v 93 (84, 104) bpm, p < 0.05), ΔRPP (3833.64 ± 1670.34 v 4381.16 ± 1587.78 bpm∙mmHg, p < 0.05), HRR1 (21 (14, 27) v 21 (17, 27) bpm, p < 0.05), and VO2max (32.76 ± 5.63 v 34.68 ± 5.70 ml/kg/min, p < 0.05). Multiple linear regression analysis showed that ΔHR and HRR1, yielded a positive correlation with VO2max in T2DM patients (ß = 0.325, P < 0.001; ß = 0.173, P = 0.01). CONCLUSION: The presence of impaired hemodynamic response and VO2max in middle-aged T2DM patients and the association of impaired ΔHR, HRR1, and VO2max may indicate a physiological pathway of impaired CRF, and our results support the need for cardiorespiratory screening and individualized treatment of middle-aged T2DM patients.

A Risk Score Model Incorporating Three m6A RNA Methylation Regulators and a Related Network of miRNAs-m6A Regulators-m6A Target Genes to Predict the Prognosis of Patients With Ovarian Cancer.

Ovarian cancer (OC) is the leading cause of cancer-related death among all gynecological tumors. N6-methyladenosine (m6A)-related regulators play essential roles in various tumors, including OC. However, the expression of m6A RNA methylation regulators and the related regulatory network in OC and their correlations with prognosis remain largely unknown. In the current study, we obtained the genome datasets of OC from GDC and GTEx database and analyzed the mRNA levels of 21 key m6A regulators in OC and normal human ovarian tissues. The expression levels of 7 m6A regulators were lower in both the OC tissues and the high-stage group. Notably, the 5-year survival rate of patients with OC presenting low VIRMA expression or high HNRNPA2B1 expression was higher than that of the controls. Next, a risk score model based on the three selected m6A regulators (VIRMA, IGF2BP1, and HNRNPA2B1) was built by performing a LASSO regression analysis, and the moderate accuracy of the risk score model to predict the prognosis of patients with OC was examined by performing ROC curve, nomogram, and univariate and multivariate Cox regression analyses. In addition, a regulatory network of miRNAs-m6A regulators-m6A target genes, including 2 miRNAs, 3 m6A regulators, and 47 mRNAs, was constructed, and one of the pathways, namely, miR-196b-5p-IGF2BP1-PTEN, was initially validated based on bioinformatic analysis and assay verification. These results demonstrated that the risk score model composed of three m6A RNA methylation regulators and the related network of miRNAs-m6A regulators-m6A target genes is valuable for predicting the prognosis of patients with OC, and these molecules may serve as potential biomarkers or therapeutic targets in the future.

Preparation and characterization of glycosylated protein nanoparticles for astaxanthin mitochondria targeting delivery.

Novel mitochondria targeting nanocarriers were prepared using triphenylphosphonium bromide (TPP)-modified whey protein isolate (WPI)-dextran (DX) conjugates by self-assembly method for astaxanthin mitochondria targeting delivery. The nanocarriers of astaxanthin-loaded WPI-DX and astaxanthin-loaded TPP-WPI-DX were 135.26 and 193.64 nm, respectively, which exhibited a spherical structure and good dispersibility. The mitochondria targeting nanocarriers had good stability in the stimulated blood fluid. In vitro experiments indicated that the TPP-modified nanocarriers could effectively realize lysosomes escape, and specifically accumulate in the cell mitochondria. Simultaneously, the astaxanthin-loaded nanocarriers could significantly reduce reactive oxygen species generation produced from hydrogen peroxide, protect the normal levels of the mitochondrial membrane potential, and dramatically promote the vitality of leukemia cells in mouse macrophage (RAW 264.7) cells. The present study highlights the promising application of mitochondria targeting nanocarriers for enhanced delivery of astaxanthin.

The LINC00922 aggravates ovarian cancer progression via sponging miR-361-3p.

BACKGROUND: Long noncoding RNA (lncRNA) LINC00922 has been reported to promote tumorigenesis of lung and breast cancer. However, the functions and mechanisms of LINC00922 in ovarian cancer (OC) remain unclarified. The current study aims to clarify the detailed functions and underlying mechanisms of LINC00922 in the progression of OC. METHODS: LINC00922 expression in OC tissues and cells was identified by a comprehensive strategy of data miming, computational biology and quantitative real-time polymerase chain reaction (RT-qPCR) experiment. In vitro CCK-8, wound healing, transwell invasion, western blotting and in vivo tumorigenesis assays LINC00922 were conducted to evaluate the functions of LINC00992. Subsequently, bioinformatics technology and dual luciferase reporter assay were performed to confirm the between miR-361-3p and LINC00922 or CLDN1. Finally, rescue experiments were performed to confirm whether LINC00922 effect functions of OC cells through regulation of miR-361-3p. RESULTS: LINC00922 was significantly upregulated in OC tissues and cell lines, which is significantly positively corelated with the poor prognosis of patients with OC. LINC00922 knockdown inhibited proliferation and tumorigenesis of OC cells in vitro and vivo. In addition, LINC00922 knockdown suppressed migration, invasion, and EMT of OC cells in vitro. Mechanically, LINC00922 could competitively bind with miR-361-3p to relieve the repressive effect of miR-361-3p on its target gene CLDN1 in OC cells. In addition, silencing miR-361-3p promoted OC cell proliferation, migration, invasion, EMT and Wnt/ß-catenin signaling, while LINC00922 knockdown inhibited Wnt/ß-catenin signaling by upregulating miR-361-3p. Rescue experiments revealed that LINC00922 knockdown inhibited OC cell proliferation, migration, invasion and EMT by regulating miR-361-3p. CONCLUSION: This study suggested that LINC00922 could competitively bind with miR-361-3p to promote the CLDN1 expression and activate Wnt/ß-catenin signaling in OC progression, which providing a promising therapeutically target for OC.

RPL34-AS1-induced RPL34 inhibits cervical cancer cell tumorigenesis via the MDM2-P53 pathway.

Ribosomal proteins (RPs) are important components of ribosomes and related to the occurrence and development of tumors. However, little is known about the effects of the RP network on cervical cancer (CC). In this study, we screened differentially expressed RPL34 in CC by high-throughput quantitative proteome assay. We found that RPL34 acted as a tumor suppressor and was downregulated in CC and inhibited the proliferation, migration, and invasion abilities of CC cells. Next, we verified that RPL34 regulated the CC through the MDM2-P53 pathway by using Act D medicine, MDM2 inhibitor, and a series of western blotting（WB）assays. Moreover, an antisense lncRNA, RPL34-AS1, regulated the expression of RPL34 and participated in the tumorigenesis of CC. RPL34 can reverse the effect of RPL34-AS1 in CC cells. Finally, by RNA-binding protein immunoprecipitation (RIP) assay we found that eukaryotic initiation factor 4A3 (EIF4A3), which binds to RPL34-AS1, regulated RPL34-AS1 expression in CC. Therefore, our findings indicate that RPL34-AS1-induced RPL34 inhibits CC cell proliferation, invasion, and metastasis through modulation of the MDM2-P53 signaling pathway, which provides a meaningful target for the early diagnosis and treatment of CC.

Cost Impact of a Pharmacist-Driven Medication Reconciliation Program during Transitions to Long-Term Care and Retirement Homes.

The current provincial funding model in Ontario, Canada, does not offer dedicated funding to drive medication reconciliation (MedRec) programs during transitions into long-term care and retirement homes. This economic analysis aimed to estimate potential cost savings attributed to hospitalizations averted and decreases in polypharmacy by a MedRec program from a healthcare payer perspective. From a pool of 6,678 pharmacist recommendations, a limited sample of recommendations targeting specific medication-related adverse events showed potential savings of $622.35 per patient from hospital admissions avoided and of $1,414.52 per patient per year from medication discontinuations. Pharmacist-driven MedRec, conducted virtually, delivers substantial healthcare savings.

Neuropilin-1 is associated with the prognosis of cervical cancer in Henan Chinese population.

Objective: Neuropilin-1 has been reported to be a valuable diagnostic biomarker in patients with cervical intraepithelial neoplasia (CIN) and early cervical cancer. The aim of this study was to investigate the association between Neuropilin-1 and the prognosis of cervical cancer in Henan Chinese population. Methods: Tissues were collected in The Third Affiliated Hospital of Zhengzhou University between 2010 and 2012, determining the level and expression of Neuropilin-1 in different cervical lesions by immunohistochemistry. The cell proliferation assay, wound-healing assays and Transwell assay were performed to explore the ability of proliferation, migration and invasion for Hela and Caski cells after NRP-1 was knocked down by shRNA transfection. Western blotting was performed to investigate the role of NRP-1 in endothelial-to-mesenchymal transition (EndMT). Tumor xenografts model was used to evaluate the effect of NRP-1 on the tumor growth. Results: The expression of NRP-1 was upregulated in the tumor tissues compared with the CIN and normal tissues (P<0.0001). The overall survival time of the high NRP-1 expression group was significantly shorter than that of the low NRP-1 expression group (P<0.0001); NRP-1-depleted cells had dramatically lower rate of proliferation, migration and invasion compared to control cells (all P<0.05). Depletion of NRP-1 significantly suppressed the growth of CaSki xenograft tumor in nude mice. Conclusions: The current study demonstrated that NRP-1 expression is significantly correlated with the progression of CC. Notably, high NRP-1 expression is correlated with a poorer survival in patients with CC, and has been shown to be an independent prognostic factor.

MicroRNA let­7d­5p rescues ovarian cancer cell apoptosis and restores chemosensitivity by regulating the p53 signaling pathway via HMGA1.

Ovarian cancer (OC) is the gynecological malignancy type with the highest mortality rate in females. The regulatory effect of microRNAs (miRs) on their target genes serves a key role in tumor development. Therefore, in the present study, whether miR let­7d­5p targeting high mobility group A1 (HMGA1) regulated biological characteristics and chemosensitivity of OC cells by mediating the p53 signaling pathway was investigated. The let­7d­5p level was detected in OC tissues and adjacent normal tissues, followed by detection in OC cell lines SKOV3, A2780, OVCAR­3 and CaOV3, and human normal ovarian epithelial cell line (IOSE­80), in order to select the OC cell line for the following experiments. Subsequently, OC cells were treated with the let­7d­5p mimic, siHMGA1 and Tenovin­1. The targeting association between let­7d­5p and HMGA1 was then examined, and the OC cell viability, migration, cycle and apoptosis were evaluated. Subsequently, the chemosensitivity of OC cells to cisplatin was verified. Finally, expression levels of let­7d­5p, HMGA1, p21, B­cell lymphoma­2 (Bcl­2)­associated X (Bax), p27, p53 wild­type (p53wt), p53 mutated (p53mut), proliferating cell nuclear antigen (PCNA), cyclin­dependent kinase 2 (CDK2), matrix metallopeptidase (MMP)2, MMP9 and Bcl­2 were determined. As demonstrated in the results, let­7d­5p expression was low in OC tissues and had an increased reduction in the OVCAR­3 cell line. HMGA1 was confirmed as a target of let­7d­5p, and its expression was also silenced by let­7d­5p. let­7d­5p repressed OC cell viability, migration, cell cycle progression and apoptosis, while it promoted the chemosensitivity of OC cells to cisplatin by targeting HMGA1. The expression of let­7d­5p, p21, Bax, p27 and p53wt was increased, while that of HMGA1, p53mut, PCNA, CDK2, MMP2, MMP9 and Bcl­2 was reduced following cell transfection. The results in the present study provided evidence that let­7d­5p may suppress proliferation, and facilitate apoptosis and cisplatin chemosensitivity of OC cells by silencing HMGA1 via the p53 signaling pathway.

CP­31398 attenuates endometrial cancer cell invasion, metastasis and resistance to apoptosis by downregulating MDM2 expression.

Endometrial cancer (EC) is one of the most common malignancies of the female reproductive system, and metastasis is a major cause of mortality. In this study, we aimed to explore the role of CP­31398 in the migration, invasion and apoptosis of EC cells by its regulation of the expression of the murine double minute 2 (MDM2) gene. For this purpose, EC tissues and adjacent normal tissues were collected, and the positive expression rate of MDM2 in these tissues was assessed. Subsequently, the cellular 50% inhibitory concentration (IC50) of CP­31398 was measured. The EC RL95­2 and KLE cell lines had a higher MDM2 expression and were thus selected for use in subsequent experiments. The EC cells were then treated with CP­31398 (2 µg/ml), and were transfected with siRNA against MDM2 or an MDM2 overexpression plasmid in order to examine the effects of CP­31398 and MDM2 on EC cell activities. The expression of p53, p21, Bad, Bax, B­cell lymphoma­2 (Bcl­2), cytochrome c (Cyt­c), caspase­3, Cox­2, matrix metalloproteinase (MMP)­2 and MMP­9 was measured to further confirm the effects of CP­31398 on cell migration, invasion and apoptosis. Our results indicated that MDM2 was highly expressed in EC tissues. Notably, EC cell viability decreased with the increasing concentrations of CP­31398. The EC cells treated with CP­31398 or siRNA against MDM2 exhibited an increased apoptosis and a suppressed migration and invasion, corresponding to an increased expression of p53, p21, Bad, Bax, Cyt­c and caspase­3, as well as to a decreased expression of Bcl­2, Cox­2, MMP­2 and MMP­9. Moreover, treatment with CP­31398 and siRNA against MDM2 further enhanced these effects. Taken together, the findings of this study indicate that the CP­31398­mediated downregulation of MDM2 may suppress EC progression via its inhibitory role in EC cell migration, invasion and resistance to apoptosis. Therefore, treatment with CP­31398 may prove to be possible therapeutic strategy for EC.

Effects of shRNA-mediated silencing of PSMA7 on cell proliferation and vascular endothelial growth factor expression via the ubiquitin-proteasome pathway in cervical cancer.

This study aims to evaluate the effects of PSMA7 silencing on cervical cancer (CC) cell proliferation and vascular endothelial growth factor (VEGF) expression through the ubiquitin-proteasome pathway. CC tissues (n = 43) and normal tissues (n = 27) were first collected from patients. Human CC cell line (SiHa) and human normal cervical epithelial cells (H8) were obtained and classified into the normal, blank, negative control (NC), PSMA7-shRNA1, and PSMA7-shRNA2 groups, respectively. In situ hybridization was used to detect the expressions of wild-type and mutant p53 proteins. Immunofluorescence assay was carried out to test the activity of 20S proteasomes. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were both performed to determine the expressions of PSMA7, ubiquitin, P27, P53, and VEGF in sample tissues and cells. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to analyze cell proliferation rates, and flow cytometry was used to analyze the cell cycle and the apoptotic rate. Compared with normal tissues, CC tissues showed increased expression levels of PSMA7, ubiquitin, p53, VEGF as well as increased activity of 20S proteasomes but exhibited a decrease in p27 expression. Compared with the blank and NC groups, the PSMA7-shRNA1 and PSMA7-shRNA2 groups all had decreased expression levels of PSMA7, ubiquitin, p53, and VEGF as well as decreased cell proliferation, 20S proteasomes activity, and cell number in the S phase, increased p27 expression, cell apoptosis and cell number in the G0/G1 phase. Our study demonstrated that PSMA7 silencing can suppress CC cell proliferation and VEGF expression in addition to promoting cell apoptosis through inhibiting the UPP signaling pathway.

Role of CXCL12-CXCR4 axis in ovarian cancer metastasis and CXCL12-CXCR4 blockade with AMD3100 suppresses tumor cell migration and invasion in vitro.

Ovarian cancer (OC) is a lethal gynecologic tumor, which brings its mortality to the head. CXCL12 and its receptor chemokine receptor 4 ( CXCR4) have been found to be highly expressed in OC and contribute to the disease progression by affecting tumor cell proliferation and invasion. Here, in this study, we aim to explore whether the blockade of CXCL12-CXCR4 axis with AMD3100 (a selective CXCR4 antagonist) has effects on the progression of OC. On the basis of the gene expression omnibus database of OC gene expression chips, the OC differentially expressed genes were screened by microarray analysis. OC (nonmetastatic and metastatic) and normal ovarian tissues were collected to determine the expressions of CXCL12 and CXCR4. A series of AMD3100, shRNA against CXCR4, and pCNS-CXCR4 were introduced to treat CAOV3 cells with the highest CXCR4 was assessed. Cell viability, apoptosis, migration, and invasion were all evaluated. The microarray analysis screened out the differential expression of CXCL12-CXCR4 in OC. CXCL12 and CXCR4 expressions were increased in OC tissues, particularly in the metastatic OC tissues. Downregulation of CXCR4 by AMD3100 or shRNA was observed to have a critical role in inhibiting cell proliferation, migration, and invasion of the CAOV3 OC cell line while promoting cell apoptosis. Overexpressed CXCR4 brought significantly promoting effects on the proliferation and invasiveness of OC cells. These results reinforce that the blockade of CXCL12-CXCR4 axis with AMD3100 inhibits the growth of OC cells. The antitumor role of the inhibition of CXCL12-CXCR4 axis offers a preclinical validation of CXCL12-CXCR4 axis as a therapeutic target in OC.

HOXC6 gene silencing inhibits epithelial-mesenchymal transition and cell viability through the TGF-ß/smad signaling pathway in cervical carcinoma cells.

BACKGROUND: Homeobox C6 (HOXC6) plays a part in malignant progression of some tumors. However, the expression of HOXC6 and its clinical significance remains unclear in cervical carcinoma (CC). The purpose of this study is to verify the effects of HOXC6 gene silencing on CC through the TGF-ß/smad signaling pathway. METHODS: CC tissues and corresponding paracancerous tissues were collected from CC patients with involvement of a series of HOXC6-siRNA, HA-HOXC6 and the TGF-ß/smad pathway antagonist. HOXC6 expression was analyzed in six CC cell lines (C-33A, HeLa, CaSki, SiHa, ME-180, and HCC-94) by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The mRNA and protein expression of HOXC6, TGF-ß1, TGF-ß RII, smad4, smad7, E-cadherin, N-cadherin, Vimentin, ki-67, proliferating cell nuclear antigen (PCNA), p27, and Cyclin D1 were determined by RT-qPCR and western blot analysis. Cell proliferation, apoptosis and cell cycle were detected by MTT assay and flow cytometry, respectively. RESULTS: Higher positive expression rate of HOXC6 protein was observed in CC tissues and HOXC6 was related to TNM stage, lymphatic metastasis, cancer types, primary lesion diameter, and histological grade of CC. Silencing HOXC6 inhibited epithelial-mesenchymal transition (EMT) (shown as decreased N-cadherin and Vimentin, and increased E-cadherin) through the inactivation of the TGF-ß/smad signaling pathway. HOXC6 gene silencing hindered cell proliferation and accelerated cell apoptosis of CC cells. Furthermore, the effect of HOXC6 silencing was enhanced when the TGF-ß/smad signaling pathway was suppressed. CONCLUSION: The results reveal that HOXC6 gene silencing may inhibit EMT event and cell viability in CC through the inhibition of the activation of TGF-ß/smad signaling pathway.

Investigation of single-dose thoracic paravertebral analgesia for postoperative pain control after thoracoscopic lobectomy - A randomized controlled trial.

BACKGROUND: Thoracoscopic lobectomy is less painful than normal thoracotomy, but pain management is still an issue in the postoperative period. Thoracic epidural analgesia (TEA) is considered as the gold standard for post-thoracotomy pain control, but is associated with numerous risks. METHODS: A total of 114 patients undergoing thoracoscopic lobectomy were randomly divided into three groups. Patients in the PVB-R group received a single-dose 0.5% ropivacaine paravertebral block (PVB), combined with patient-controlled intravenous analgesia (PCIA) after extubation during the 48-h postoperative period; those in the PVB-RD group received a single-dose 0.5% ropivacaine and dexmedetomidine (1 µg/kg) PVB, combined with the same PCIA scheme; and those in the TEA group received intraoperative thoracic epidural anesthesia with 0.5% ropivacaine, and a single dose of epidural morphine (0.03 mg/kg) after extubation combined with the same PCIA scheme. The dose and first time of postoperative analgesia, verbal rating score (VRS), change in catecholamine, cortisol and cytokine levels, change in hemodynamic parameters, and side effects during the postoperative period were recorded. RESULTS: Compared to the PVB-R group, the dose of postoperative analgesia and VRS were lower and the first time of postoperative analgesia were longer in the PVB-RD and TEA group. Patients in the PVB-RD group had a lower incidence of side effects compared to those in the TEA group. CONCLUSIONS: Single-dose 0.5% ropivacaine combined with dexmedetomidine (1 µg/kg) PVB provides satisfactory postoperative pain control after thoracoscopic lobectomy, and can reduce the incidence of postoperative side effects.

Robotic radical hysterectomy is superior to laparoscopic radical hysterectomy and open radical hysterectomy in the treatment of cervical cancer.

OBJECTIVE: Cervical cancer (CC) continues to be a global burden for women, with higher incidence and mortality rates reported annually. Many countries have witnessed a dramatic reduction in the prevalence of CC due to widely accessed robotic radical hysterectomy (RRH). This network meta-analysis aims to compare intraoperative and postoperative outcomes in way of RRH, laparoscopic radical hysterectomy (LTH) and open radical hysterectomy (ORH) in the treatment of early-stage CC. METHODS: A comprehensive search of PubMed, Cochrane Library and EMBASE databases was performed from inception to June 2016. Clinical controlled trials (CCTs) of above three hysterectomies in the treatment of early-stage CC were included in this study. Direct and indirect evidence were incorporated for calculating values of weighted mean difference (WMD) or odds ratio (OR), and drawing the surface under the cumulative ranking curve (SUCRA). RESULTS: Seventeen 17 CCTs were ultimately enrolled in this network meta-analysis. The network meta-analysis showed that patients treated by RRH and LRH had lower estimated blood loss compared to patients treated by ORH (WMD = -399.52, 95% CI = -600.64~-204.78; WMD = -277.86, 95%CI = -430.84 ~ -126.07, respectively). Patients treated by RRH and LRH had less hospital stay (days) than those by ORH (WMD = -3.49, 95% CI = -5.79~-1.24; WMD = -3.26, 95% CI = -5.04~-1.44, respectively). Compared with ORH, patients treated with RRH had lower postoperative complications (OR = 0.21, 95%CI = 0.08~0.65). Furthermore, the SUCRA value of three radical hysterectomies showed that patients receiving RRH illustrated better conditions on intraoperative blood loss, operation time, the number of resected lymph nodes, length of hospital stay and intraoperative and postoperative complications, while patients receiving ORH demonstrated relatively poorer conditions. CONCLUSION: The results of this meta-analysis confirmed that early-stage CC patients treated by RRH were superior to patients treated by LRH and ORH in intraoperative blood loss, length of hospital stay and intraoperative and postoperative complications, and RRH might be regarded as a safe and effective therapeutic procedure for the management of CC.