Effects of Cu2O nanoparticles on the kinetic characteristics of rapid chlorophyll fluorescence induction and related genes in wheat seedlings.

Metal nanoparticles could be accumulated in soils, which threatens the ecological stability of crops. Investigating the effects of cuprous oxide nanoparticles (Cu2O-NPs) on photosystem Ⅱ (PSⅡ) of wheat seedling leaves holds considerable importance in comprehending the implications of Cu2O-NPs on crop photosynthesis. Following the hydroponic method, we investigated the effects of 0, 10, 50, 100, and 200 mg·L-1 Cu2O-NPs on chlorophyll fluorescence induction kinetics and photosynthetic-related genes in wheat seedlings of "Zhoumai 18". The results showed that, with the increases of Cu2O-NPs concentrations, chlorophyll contents in wheat leaves decreased, and the standardization of the OJIP curve showed a clearly K-phase (ΔK＞0). Cu2O-NPs stress increased the parameters of active PSⅡ reaction centers, including the absorption flux per active RC (ABS/RC), the trapping flux per active RC (TRo/RC), the electron transport flux per active RC (ETo/RC), and the dissipation flux per active RC (DIo/RC). Cu2O-NPs stress decreased the parameters of PSⅡ energy distribution ratio including the maximum quantum yield of PSⅡ (φPo), the quantum yield of electron transport from QA (φEo), and the probability that a trapped exciton moved an electron further than QA (Ψo), while increased the quantum ratio for heat dissipation (φDo). Moreover, there was a decrease in photosynthetic quantum yield Y(Ⅱ), photochemical quenching coefficient (qP), net photosynthetic rate (Pn), stomatal conductance (gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) of leaves with the increases of Cu2O-NPs concentration. Under Cu2O-NPs stress, the expression levels of genes which included PSⅡ genes (PsbD, PsbP, Lhcb1), Rubisco large subunit genes (RbcL), cytochrome b6/f complex genes (PetD, Rieske), and ATP synthase genes (AtpA, AtpB, AtpE, AtpI) were downregulated. These results indicated that Cu2O-NPs stress altered the activity and structure of PSⅡ in wheat seedlings, affected the activity of PSⅡ reaction centers, performance parameters of PSⅡ donor and acceptor sides. PSⅡ related genes were downregulated and exhibited significant concentration effects.

Integrated proteogenomic characterization reveals an imbalanced hepatocellular carcinoma microenvironment after incomplete radiofrequency ablation.

BACKGROUND: Efforts to precisely assess tumor-specific T-cell immune responses still face major challenges, and the potential molecular mechanisms mediating hepatocellular carcinoma (HCC) microenvironment imbalance after incomplete radiofrequency ablation (iRFA) are unclear. This study aimed to provide further insight into the integrated transcriptomic and proteogenomic landscape and identify a new target involved in HCC progression following iRFA. METHODS: Peripheral blood and matched tissue samples were collected from 10 RFA-treated HCC patients. Multiplex immunostaining and flow cytometry were used to assess local and systemic immune responses. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were explored via transcriptomic and proteogenomic analyses. Proteinase-3 (PRTN3) was identified in these analyses. And then, the ability of PRTN3 to predict overall survival (OS) was assessed in 70 HCC patients with early recurrence after RFA. In vitro CCK-8, wound healing and transwell assays were conducted to observe interactions between Kupffer cells (KCs) and HCC cells induced by PRTN3. The protein levels of multiple oncogenic factors and signaling pathway components were detected by western blotting. A xenograft mouse model was built to observe the tumorigenic effect of PRTN3 overexpression on HCC. RESULTS: Multiplex immunostaining revealed no immediate significant change in local immune cell counts in periablational tumor tissues after 30 min of iRFA. Flow cytometry showed significantly increased levels of CD4+ T cells, CD4+CD8+ T cells, and CD4+CD25+CD127- Tregs and significantly decreased the levels of CD16+CD56+ natural killer cells on day 5 after cRFA (p < 0.05). Transcriptomics and proteomics revealed 389 DEGs and 20 DEPs. Pathway analysis showed that the DEP-DEGs were mainly enriched in the immunoinflammatory response, cancer progression and metabolic processes. Among the DEP-DEGs, PRTN3 was persistently upregulated and closely associated with the OS of patients with early recurrent HCC following RFA. PRTN3 expressed in KCs may affect the migration and invasion of heat stress-treated HCC cells. PRTN3 promotes tumor growth via multiple oncogenic factors and the PI3K/AKT and P38/ERK signaling pathways. CONCLUSIONS: This study provides a comprehensive overview of the immune response and transcriptomic and proteogenomic landscapes of the HCC milieu induced by iRFA, revealing that PRTN3 promotes HCC progression after iRFA. TRIAL REGISTRATION: ChiCTR2200055606, http://www.chictr.org.cn/showproj.aspx?proj=32588 .

Unraveling the Emerging Niche Role of Hepatic Stellate Cell-derived Exosomes in Liver Diseases.

Hepatic stellate cells (HSCs) play an essential role in various liver diseases, and exosomes are critical mediators of intercellular communication in local and distant microenvironments. Cellular crosstalk between HSCs and surrounding multiple tissue-resident cells promotes or inhibits the activation of HSCs. Substantial evidence has revealed that HSC-derived exosomes are involved in the occurrence and development of liver diseases through the regulation of retinoid metabolism, lipid metabolism, glucose metabolism, protein metabolism, and mitochondrial metabolism. HSC-derived exosomes are underpinned by vehicle molecules, such as mRNAs and microRNAs, that function in, and significantly affect, the processes of various liver diseases, such as acute liver injury, alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, fibrosis, and cancer. As such, numerous exosomes derived from HSCs or HSC-associated exosomes have attracted attention because of their biological roles and translational applications as potential targets for therapeutic targets. Herein, we review the pathophysiological and metabolic processes associated with HSC-derived exosomes, their roles in various liver diseases and their potential clinical application.

Associations of executive function and age of first use of methamphetamine with methamphetamine relapse.

Background and aims: Methamphetamine (MA) is a psychostimulant associated with a high relapse rate among patients with MA use disorder (MUD). Long-term use of MA is associated with mental disorders, executive dysfunction, aggressive behaviors, and impulsivity among patients with MUD. However, identifying which factors may be more closely associated with relapse has not been investigated. Thus, we aimed to investigate the psychological factors and the history of MA use that may influence MA relapse. Methods: This cross-sectional study included 168 male MUD patients (MUD group) and 65 healthy male residents (control group). Each patient was evaluated with self-report measures of executive dysfunction, psychopathological symptoms, impulsiveness, aggressiveness, and history of MA use. Data were analyzed with t-tests, analyses of variance, and correlation and regression analyses. Results: The MUD group reported greater executive dysfunction, psychopathological symptoms, impulsivity, and aggression than the control group. Lower age of first MA use was associated both with having relapsed one or more times and with having relapsed two or more times; greater executive dysfunction was associated only with having relapsed two or more times. Conclusion: Patients with MUD reported worse executive function and mental health. Current results also suggest that lower age of first MA use may influence relapse rate in general, while executive dysfunction may influence repeated relapse in particular. The present results add to the literature concerning factors that may increase the risk of relapse in individuals with MUD.

Predictive Role of Executive Function in the Efficacy of Intermittent Theta Burst Transcranial Magnetic Stimulation Modalities for Treating Methamphetamine Use Disorder-A Randomized Clinical Trial.

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment. Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls. Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively. Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR2100046954.

Sex Difference of Ribosome in Stroke-Induced Peripheral Immunosuppression by Integrated Bioinformatics Analysis.

Ischemic stroke (IS) greatly threatens human health resulting in high mortality and substantial loss of function. Recent studies have shown that the outcome of IS has sex specific, but its mechanism is still unclear. This study is aimed at identifying the sexually dimorphic to peripheral immune response in IS progression, predicting potential prognostic biomarkers that can lead to sex-specific outcome, and revealing potential treatment targets. Gene expression dataset GSE37587, including 68 peripheral whole blood samples which were collected within 24 hours from known onset of symptom and again at 24-48 hours after onset (20 women and 14 men), was downloaded from the Gene Expression Omnibus (GEO) datasets. First, using Bioconductor R package, two kinds of differentially expressed genes (DEGs) (nonsex-specific- and sex-specific-DEGs) were screened by follow-up (24-48 hours) vs. baseline (24 hours). 30 nonsex-specific DEGs (1 upregulated and 29 downregulated), 79 female-specific DEGs (25 upregulated and 54 downregulated), and none of male-specific DEGs were obtained finally. Second, bioinformatics analysis of female-specific DEGs was performed. Gene Ontology (GO) functional annotation analysis shows that DEGs were mainly enriched in translational initiation, cytosolic ribosome, and structural constituent of ribosome. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis shows that the top 6 enrichment pathways are ribosome, nuclear factor--kappa B (NF-kappa B) signaling pathway, apoptosis, mineral absorption, nonalcoholic fatty liver disease, and pertussis. Three functional modules were clustered in the protein-protein interaction (PPI) network of DEGs. The top 10 key genes of the PPI network constructed were selected, including RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2. Sex difference of ribosome in stroke-induced peripheral immunosuppression may be the potential mechanism of sex disparities in outcome after IS, and women are more likely to have stroke-induced immunosuppression. RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2 may be novel prognostic biomarkers and potential therapeutic targets for IS.

Clinical Application Values of Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratios in Multiple Cancers.

BACKGROUND: As the mechanism of systemic inflammatory response in the course of cancer progression is gradually revealed, research has begun to focus on the two indictors of neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) which may be associated with clinical disease development, treatment, and prognosis in patients who are undergoing surgery, chemotherapy, targeted therapy, and immunotherapy. We aim to define the clinical application values of those two biomarkers in multiple cancers. METHODS: PubMed and Web of Science are used to perform the systematic literature research. Related articles and references were identified for analyzing the association of between NLR and PLR with treatment outcome, as well as progression of cancers. RESULTS: NLR and PLR are convenient, easy to calculate, economical, and practical biomarkers, effectively predicting treatment outcome and risk of death based on inflammatory cells. Elevated NLR and PLR are significantly in line with worse clinical pathological characteristics, deeper invasiveness, more lymph node metastasis and advanced TNM stage. A significant association was observed that high NLR and PLR predict poor overall survival and disease-free survival. CONCLUSIONS: NLR and PLR can be used as available biomarkers in prognostic survival and formulation of treatment strategy of multiple cancers.

Development and validation of a RNA binding protein-associated prognostic model for lung adenocarcinoma.

RNA binding proteins (RBPs) dysregulation have been reported in various malignant tumors and associated with the occurrence and development of cancer. However, the role of RBPs in lung adenocarcinoma (LUAD) is poorly understood. We downloaded the RNA sequencing data of LUAD from the Cancer Genome Atlas (TCGA) database and determined the differently expressed RBPs between normal and cancer tissues. The study then systemically investigated the expression and prognostic value of these RBPs by a series of bioinformatics analysis. A total of 223 differently expressed RBPs were identified, including 101 up-regulated and 122 down-regulated RBPs. Eight RBPs (IGF2BP1, IFIT1B, PABPC1, TLR8, GAPDH, PIWIL4, RNPC3, and ZC3H12C) were identified as prognosis related hub gene and used to construct a prognostic model. Further analysis indicated that the patients in the high-risk subgroup had poor overall survival(OS) compared to those in low-risk subgroup based on the model. The area under the curve of the time-dependent receiver operator characteristic curve of the prognostic model are 0.775 in TCGA cohort and 0.814 in GSE31210 cohort, confirming a good prognostic model. We also established a nomogram based on eight RBPs mRNA and internal validation in the TCGA cohort, which displayed a favorable discriminating ability for lung adenocarcinoma.

[Oxidative Stress and DNA Damage Induced by DEP Exposure in Earthworms].

Diethyl phthalate (DEP) is a plastic additive that entered the soil environment due to the extensive use of plastic products. However, its toxicity to soil animals and the associated toxicity mechanism were not completely understood. Eisenia foetida was selected as the research object and exposed to simulated contaminated soil with different concentrations of DEP. Antioxidant enzyme activity, reactive oxygen species (ROS) content, Glutathione-S-Transferase (GST) activity, Malondialdehyde (MDA) content and amount of DNA damage in the earthworms were used as evaluation parameters for the study. The results showed that under DEP stress, the activities of antioxidant enzymes, GST and ROS in earthworms changed and resulted in gene damage. Under the stress of 0.1-50 mg·kg-1 DEP exposure during the 28 d experiment, the level of ROS increased and there was a "dose-effect" relationship. Excessive ROS gave rise to an increase of MDA content in the body from lipid peroxidation. Under the combined action of ROS and MDA, DNA in the body cavity of earthworm was damaged and there was also a "dose-effect" relationship between the degree of damage and the concentration of DEP. In summary, DEP may cause a certain degree of damage to organisms, with damage to the DNA of earthworms representing fairly strong eco-toxicological effects. Therefore, adequate attention should be paid to DEP disposal.

Chinese medicine as complementary therapy for female infertility.

Chinese medicine (CM) has been used in clinical treatment for thousands of years in China, Japan, Korea, and other countries. CM is at present attracting many attentions around the world for reproductive health care and disease prevention, including treatment of female infertility. This review focuses on the CM treatment for female infertility patients, and supplies a summary on the efficacy, safety, and mechanism of some Chinese herbal medicines, herbal medicine-derived active compounds, and acupuncture. A large number of researches have reported that CM could alleviate or even cure female infertility by regulating hormone, improving reproductive outcome of in vivo fertilization, affecting embryonic implantation, curing polycystic ovarian syndrome, endometriosis, pelvic inflammatory disease, relieving mental stress, and regulating immune system. Meanwhile, a few studies claimed that there was little adverse reaction of CM in randomized controlled trials. However, up to present there is a lack of adequate evidences with molecular mechanistic researches and randomized controlled trials to prove the CM as an effective and safe treatment for infertility. Thus, utility of CM as a complementary medicine will be a feasible method to improve the outcome of female infertility treatment.

Application of TiO2-organobentonite modified by cetyltrimethylammonium chloride photocatalyst and polyaluminum chloride coagulant for pretreatment of aging landfill leachate.

This study investigated the treatment performance for aging leachate containing refractory organic pollutants by TiO2-organobentonite photocatalyst combined with polyaluminum chloride (PAC) coagulant. TiO2 was immobilized on organobentonite granules as a supporter modified by cetyltrimethylammonium chloride (CTAC). The prepared catalysts were characterized by ESEM, FTIR, and XRD analysis, which showed that TiO2-organobentonite catalyst had uniform coating of TiO2 on support. Chemical oxygen demand (COD) and NH3-N removal rates by combination of TiO2-CTAC2.0 photocatalysis and PAC coagulation were evaluated, optimized, and compared to that by either treatment alone, with respect to TiO2-CTAC2.0 dose, photocatalytic contact time, pH, and PAC dose. Furthermore, higher removal rates (COD 80 %; NH3-N 46 %) were achieved by response surface methodology (RSM) when TiO2-CTAC2.0 photocatalysis was followed by PAC coagulation at optimized conditions. The optimized experimental conditions were TiO2-CTAC2.0 dosage of 5.09 g/L, at pH 5.53, photocatalytic contact time for 180 min, and PAC dosage of 1062 mg/L.

An updated systematic review of the evolution of ALPPS and evaluation of its advantages and disadvantages in accordance with current evidence.

The main obstacle to achieving an R0 resection after a major hepatectomy is inability to preserve an adequate future liver remnant (FLR) to avoid postoperative liver failure (PLF). Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel technique for resecting tumors that were previously considered unresectable, and this technique results in a vast increase in the volume of the FLR in a short period of time. However, this technique continues to provoke heated debate because of its high mortality and morbidity.The evolution of ALPPS and its advantages and disadvantages have been systematically reviewed and evaluated in accordance with current evidence. Electronic databases (PubMed and Medline) were searched for potentially relevant articles from January 2007 to January 2016.ALPPS has evolved into various modified forms. Some of these modified techniques have reduced the difficulty of the procedure and enhanced its safety. Current evidence indicates that the advantages of ALPPS are rapid hypertrophy of the FLR, the feasibility of the procedure, and a higher rate of R0 resection in comparison to other techniques. However, ALPPS is associated with worse major complications, more deaths, and early tumor recurrence.Hepatobiliary surgeons should carefully consider whether to perform ALPPS. Some modified forms of ALPPS have reduced the mortality and morbidity of the procedure, but they cannot be recommended over the original procedure currently. Portal vein embolization (PVE) is still the procedure of choice for patients with a tumor-free FLR, and ALPPS could be used as a salvage procedure when PVE fails. More persuasive evidence needs to be assembled to determine whether ALPPS or two-stage hepatectomy (TSH) is better for patients with a tumor involving the FLR. Evidence with regard to long-term oncological outcomes is still limited. More meticulous comparative studies and studies of the 5-year survival rate of ALPPS could ultimately help to determine the usefulness of ALPPS. Indications and patient selection for the procedure need to be determined.

Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma.

The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV). According to recommendations by the World Health Organization guidelines for HBV/HCV, alpha-fetoprotein (AFP) testing and abdominal ultrasound should be performed in routine surveillance of HCC every 6 mo for high-risk patients. These examinations have also been recommended worldwide by many other HCC guidelines over the past few decades. In recent years, however, the role of AFP in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by the American Association for the Study of Liver Diseases in 2010, the European Association for the Study of the Liver in 2012, and the National Comprehensive Cancer Network in 2014. Other biomarkers, including the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin, Dickkopf-1, midkine, and microRNA, are being studied in this regard. Furthermore, increasing attention has focused on the clinical utility of biomarkers as pre-treatment predictors for tumor recurrence and as post-treatment monitors. Serum and tissue-based biomarkers and genomics may aid in the diagnosis of HCC, determination of patient prognosis, and selection of appropriate treatment. However, further studies are needed to better characterize the accuracy and potential role of these approaches in clinical practice.

Combination of cathodic reduction with adsorption for accelerated removal of Cr(VI) through reticulated vitreous carbon electrodes modified with sulfuric acid-glycine co-doped polyaniline.

Improving the reduction kinetics is crucial in the electroreduction process of Cr(VI). In this study, we developed a novel adsorption-electroreduction system for accelerated removal of Cr(VI) by employing reticulated vitreous carbon electrode modified with sulfuric acid-glycine co-doped polyaniline (RVC/PANI-SA-GLY). Firstly, response surface methodology confirmed the optimum polymerization condition of co-doped polyaniline for modifying electrodes (Aniline, sulfuric acid and glycine, respectively, of 0.2 mol/L, 0.85 mol/L, 0.93 mol/L) when untraditional dopant glycine was added. Subsequently, RVC/PANI-SA-GLY showed higher Cr(VI) removal percentages in electroreduction experiments over RVC electrode modified with sulfuric acid doped polyaniline (RVC/PANI-SA) and bare RVC electrode. In contrast to RVC/PANI-SA, the improvement by RVC/PANI-SA-GLY was more significant and especially obvious at more negative potential, lower initial Cr(VI) concentration, relatively less acidic solution and higher current densities, best achieving 7.84% higher removal efficiency with entire Cr(VI) eliminated after 900 s. Current efficiencies were likewise enhanced by RVC/PANI-SA-GLY under quite negative potentials. Fourier transform infrared (FTIR) and energy dispersive spectrometer (EDS) analysis revealed a possible adsorption-reduction mechanism of RVC/PANI-SA-GLY, which greatly contributed to the faster reduction kinetics and was probably relative to the absorption between protonated amine groups of glycine and HCrO4(-). Eventually, the stability of RVC/PANI-SA-GLY was proven relatively satisfactory.

[The mRNA expression of BRCA1, ERCC1, TUBB3, PRR13 genes and their relationship with clinical chemosensitivity in primary epithelial ovarian cancer].

OBJECTIVE: To evaluate the expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA and their relationship with clinical chemosensitivity in primary ovarian cancer, and to assess the predictive value of joint detection of both BRCA1 and ERCC1 genes for the treatment of primary ovarian cancer. METHODS: Primary epithelial ovarian tumor samples were collected from 46 patients who underwent cytoreductive surgery. Real-time quantitative PCR was used to analyze the relative expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA in those cases. The correlation of clinical chemosensitivity and the test results was statistically analyzed. The efficacy of the joint prediction of clinical chemosensitivity by combining the two drug resistance gene detection was evaluated. RESULTS: The BRCA1 mRNA relative expression logarithm in the clinical-resistant group was 0.673±2.143, and clinical-sensitive group -1.436±2.594 (P=0.008). The ERCC1 mRNA relative expression logarithm in the clinical-resistant group was -0.529±1.982 and clinical-sensitive group -3.188±2.601 (P=0.001). BRCA1 and ERCC1 expression level is negatively correlated with platinum-based chemosensitivity. The PRR13 expressions in the two groups were not significantly different (P=0.074), and the TUBB3 expressions between the two groups were also not significantly different (P=0.619). When the intercept point value BRCA1 mRNA expression logarithm was -0.6, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 73.3%, 75.0%, 84.6% and 60.0%, respectively, with the best comprehensive assessment. When the intercept point value of ERCC1 mRNA expression logarithm was -1, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 80.0%, 68.8%, 82.8% and 64.7%, respectively, with the best comprehensive assessment. The combination detection of BRCA1 and ERCC1 can improve the chemotherapeutic sensitivity, specificity, positive predictive value and negative predictive value to 86.7%, 68.8%, 83.9% and 73.3%, respectively. CONCLUSIONS: BRCA1 and ERCC1 mRNA expression has a negative correlation with the clinical sensitivity of platinum-based chemotherapy. Combination detection of the two drug-resistance associated genes can improve the predictive efficacy of ovarian cancer chemosensitivity and beneficial to individual treatment of ovarian cancer.

[Predicting clinical chemo-sensitivity of primary ovarian cancer using adenosine triphosphate-tumor chemosensitivity assay combined with detection of drug resistance genes].

OBJECTIVE: To predict clinical chemotherapy sensitivity of primary ovarian cancer by jointing adenosine triphosphate (ATP)-tumor chemo-sensitivity assay (TCA) method in vitro and detection of drug resistance genes, provide reference for clinical treatment. METHODS: Forty-seven primary epithelial ovarian tumor samples were collected from the patients who received cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissue were tested for their sensitivity to carboplatin (CBP), cisplatin (DDP), paclitaxel (PTX) and CBP + PTX using ATP-TCA method in vitro; at same time, real-time quantitative PCR was used to analysis BRCA1 and ERCC1 mRNA relative expression in forty-six specimens (1 frozen tumor samples mRNA were not detected due to serious degradation). The relationship between ATP-TCA test results, clinical indicators, and the effectiveness of the joint prediction on clinical chemo-sensitivity by combining these two methods were statistically analyzed using chi-square test. RESULTS: (1) The results showns that three programs of DDP, CBP and PTX + CBP were significantly related with clinical results (P < 0.05) in vitro, in which the compliance rate in PTX + CBP program was the highest 83% (39/47), and the predictive sensitivity, predictive specificity, positive predictive value, negative predictive value and predictive accurate rate were 90%, 71%, 84% and 80%, respectively. PTX + CBP combined in vitro test results was also related with residual tumor size and neoadjuvant chemotherapy, which was more prone to drug resistance with residual tumor larger than 2 cm (P = 0.023) and with neoadjuvant chemotherapy (P = 0.011). (2) BRCA1 mRNA expression levels in the clinical-resistant group and the clinical-sensitive group was 0.673 ± 2.143 and -1.436 ± 2.594 (P = 0.008), ERCC1 mRNA expression levels in the clinical-resistant group and the clinical-sensitive group was -0.529 ± 1.982 and -3.188 ± 2.601 (P = 0.001). There were also significant correlation among the expression levels of BRCA1, ERCC1 mRNA and clinical efficacy (P < 0.01). (3) ATP-TCA and detection of drug resistance genes combined to predict the clinical application of PTX + CBP resistance may occur in 8/9 cases. CONCLUSIONS: ATP-TCA may be an ideal method of in vitro drug sensitivity testing method, which could effectively predict clinical chemotherapy sensitivity. Combination of the drug-resistant associated genes detection method and the ATP-TCA method can increase the predictive effectiveness of ovarian cancer chemosensitivity and guide individual chemotherapy of ovarian cancer.

Embryonic ectoderm development protein is regulated by microRNAs in human neural tube defects.

OBJECTIVE: The objective of the study was to investigate the expression and regulation of polycomb group (PcG) proteins in human neural tube defects (NTDs). STUDY DESIGN: PcG proteins in human NTD fetuses and age-matched controls were detected by Western blot. The relation between PcG proteins and microribonucleic acids was predicted and confirmed by the bioinformatics method, real-time polymerase chain reaction (PCR), dual-luciferase activity assay, and Western blot. The trimethyl condition of histone H3 Lys27 (H3K27) was detected by immunohistochemical and immunofluorescence. RESULTS: Embryonic ectoderm development protein (EED) was differentially detected in placenta, cerebral cortex, and spinal cord from NTDs and age-matched controls. MiR-30b can interact with 3'-untranslated region (UTR) of Eed and regulate endogenous EED expression in neural tissues. In addition, we found an inverse relationship between the miR-30b expression and the amount of trimethyl H3K27. CONCLUSION: Differential expression of EED exists in the nerves system in human NTDs and that is regulated by miR-30b.

Temporal and spatial regulation of miR-320 in the uterus during embryo implantation in the rat.

The implantation process is complex, requiring reciprocal interactions between implantation-competent blastocysts and the receptive uterus. There were reports to show that some microRNAs (miRNAs) may play a key role during embryo implantation in mouse. However, the miR-320 expression profiles in the rat uterus during peri-implantation are unknown. In the present study, we found that the expression level of miR-320 was lower on day 5 of gestation (g.d. 5) in rats than g.d.3 and g.d.4 and restored gradually from g.d.6. MiR-320 was specifically localized in glandular and luminal epithelia and decidua. The expression of miR-320 was not significantly different in the pseudopregnant uterus and decreased in the uteri of rats subjected to activation of delayed implantation. Artificial decidualization and treatment with progesterone increased the miR-320 expression. Thus, miR-320 was differentially expressed in the rat uterus during implantation. The expression level was affected by active blastocysts and decidualization during the window of implantation. Steroid hormones, progesterone stimulated miR-320 expression.

[Application of ATP-tumor chemosensitivity assay in recurrent epithelial ovarian cancer].

OBJECTIVE: To explore the value of adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in individualized treatment of recurrent epithelial ovarian cancer (REOC), and to evaluate the correlation between the in vitro chemosensitivity assay and clinical drug sensitivity. METHODS: Sixty-nine REOC specimens were tested by ATP-TCA assay retrospectively. The patients were divided into strong sensitive, moderate sensitively and resistant groups according to the ATP-TCA assay results. The clinical results were evaluated according to imaging and serum CA125 analysis. The correlation between in vitro ATP-TCA assay and clinical outcome was statistically analyzed by χ(2) test. The progression free survival (PFS) and overall survival (OS) of each group were analyzed using Kaplan-Meier method. RESULTS: The results of ATP-TCA assay had significant correlation with clinical outcome. The clinical chemotherapy outcome became better with increased drug sensitivity in vitro (χ(2) = 9.066, P = 0.004). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate for ATP-TCA method to predict the clinical chemotherapy sensitivity of REOC were 87.5%, 45.9%, 58.3%, 80.9% and 65.2%, respectively. The mean PFS of strong sensitive group, moderately sensitive group and resistant group were 187.1 days, 195.0 days and 60.3 days, respectively. The mean OS were 476.7, 335.7 and 237.5 days, respectively, following the start of TCA-directed therapy. The PFS and OS of the two sensitivity groups in vitro were significantly longer than that of the in vitro-resistant group (P < 0.01). CONCLUSION: The results of ATP-TCA assay are well correlated with clinical treatment responses. The assay may be an important and useful method for individualized chemotherapy for recurrent ovarian cancer.