The role of protein arginine methyltransferase 7 in human developmentally arrested embryos cultured in vitro.

Human embryos of in vitro fertilization (IVF) are often susceptible to developmental arrest, which greatly reduces the efficiency of IVF treatment. In recent years, it has been found that protein arginine methyltransferase 7 (PRMT7) plays an important role in the process of early embryonic development. However, not much is known about the relationship between PRMT7 and developmentally arrested embryos. The role of PRMT7 in developmentally arrested embryos was thus investigated in this study. Discarded human embryos from IVF were collected for experimental materials. Quantitative real-time polymerase chain reaction (qRT-PCR) and confocal analyses were used to identify PRMT7 mRNA and protein levels in early embryos at different developmental stages, as well as changes in the methylation levels of H4R3me2s. Additionally, PRMT7 was knocked down in the developmentally arrested embryos to observe the further development of these embryos. Our results demonstrated that PRMT7 mRNA and protein levels in arrested embryos were significantly increased compared with those in control embryos; meanwhile, the methylation levels of H4R3me2s in arrested embryos were also increased significantly. Knockdown of PRMT7 could rescue partially developmentally arrested embryos, and even individual developmentally arrested embryos could develop into blastocysts. In conclusion, over-expression of PRMT7 disrupts the early embryo development process, leading to early embryos developmental arrest, but these developmentally arrested defects could be partially rescued by knockdown of the PRMT7 protein.

Procalcitonin (PCT) Improves the Accuracy and Sensitivity of Dyspnea, Eosinopenia, Consolidation, Acidemia and Atrial Fibrillation (DECAF) Score in Predicting AECOPD Patients Admission to ICU.

BACKGROUND: The score of Dyspnea, Eosinopenia, Consolidation, Acidemia and Atrial Fibrillation (DECAF) can be used to predict the in-hospital mortality of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). It is worth noting that the DECAF score is the first scoring standard combining biomarkers and clinical variables. The application of biomarkers is helpful for improving the accuracy of the scoring system. In recent years, more and more reports and studies paid attentions to procalcitonin (PCT) in respiratory infectious diseases and its clinical value has attracted increasing attention. The study aimed at investigating the effectiveness of the DECAF score combined with PCT in predicting admission of AECOPD patients to intensive care unit (ICU). METHODS: We conducted a retrospective study. We analyzed data from 171 non-immune individuals over the age of 40 in this study. All patients received blood routine measurement and DECAF score calculation on admission. The primary outcome used to assess the probability of an AECOPD patient was who would get a bed in general ward or ICU. Receiver operating characteristic curves (ROC) are used to assess the sensitivity and specificity of PCT, WBC, creatinine, and DECAF scores in predicting the risk of admissions to the ICU of COPD patients. We combined PCT, WBC, and creatinine with DECAF scores, observing the sensitivity and specificity of the different combinations in predicting COPD patients with regard to who should be admitted to ICU. RESULTS: After analyzing the data from 171 patients, we found that the probability of entering the ICU was 21.05% (36/171). The area under curve (AUC) of PCT, WBC, creatinine, and DECAF score in individually predicting the probability of entering the ICU of AECOPD patients were 0.71 (95% CI 0.61 - 0.81), 0.64 (95% CI 0.52 - 0.75), 0.74 (95% CI 0.63 - 0.84), and 0.88 (95% CI 0.81 - 0.94), respectively, with statistically significant differences (p = 0.00). The sensitivities of PCT, WBC, creatinine and DECAF scores were 0.61, 0.61, 0.56, and 0.91, respectively. The specificities of PCT, WBC, creatinine, and DECAF scores were 0.76, 0.67, 0.88 and 0.74, respectively. The AUC of Combination 1 (PCT&DECAF scores), Combination 2 (WBC&DECAF scores), and Combination 3 (creatinine&DECAF scores) for predicting AECOPD patients entering the ICU was 0.92 (95% CI 0.86 - 0.97), 0.89 (95% CI 0.84 - 0.94), and 0.91 (95% CI 0.85 - 0.96), respectively, with statistically significant differences (p = 0.00); the sensitivities were 0.92, 0.86, and 0.94, respectively, and the specificities were 0.97, 0.78, and 0.74, respectively. CONCLUSIONS: Procalcitonin improves the accuracy and sensitivity of the DECAF score in predicting the probability of AECOPD patients entering the ICU, and PCT was superior to other indexes to improve the sensitivity and specificity of the DECAF score.

Diverse Fibrosis Architecture and Premature Stimulation Facilitate Initiation of Reentrant Activity Following Chronic Atrial Fibrillation.

INTRODUCTION: Patients with paroxysmal atrial fibrillation (AF) often transition between sinus rhythm and AF. For AF to initiate there must be both a trigger and a substrate that facilitates reentrant activity. This trigger is often caused by a premature atrial contraction or focal activations within the atrium. We hypothesize that specific architectures of fibrosis alter local conduction to enable AF. METHODS AND RESULTS: Control goats (n = 13) and goats in chronic AF (for an average of 6 months, n = 6) had a high-density electrode plaque placed on the LA appendage. Conduction patterns following a premature atrial contraction, caused by an electrical stimulation, were quantified to determine regions of conduction slowing. These regions were compared to architecture, either diffuse fibrosis or regions of obstructive fibrosis, and overall fibrosis levels as determined by histology from the mapped region. The chronic AF goats had more obstructive fibrosis than the controls (17.5 ± 8.0 fibers/mm(2) vs. 8.6 ± 3.0 fibers/mm(2)). Conduction velocity of the AF goats was significantly slowed compared to the control goats in the transverse direction (0.40 ± 0.04 m/s vs. 0.53 ± 0.15 m/s) but not in the longitudinal direction (0.70 ± 0.27 m/s vs. 0.76 ± 0.18 m/s). CONCLUSIONS: AF-induced atrial remodeling leads to increased obstructive fibrosis and conduction velocity slowing transverse to fiber orientation following premature stimuli. The decrease in conduction velocity causes a decrease in the cardiac wavelength, and increases the likelihood of reentry and AF onset.

Jump Performance and Its Relationship with Lower Body Joint Kinetics and Kinematics in Children with Cerebral Palsy.

PURPOSE: The aim was to quantify jump performance in children with cerebral palsy (CP) and determine if the expected deficit is related to their lower body joint kinetics and kinematics. METHODS: Twenty-four ambulatory ( n = 17 level I and 7 level II in the Gross Motor Function Classification System) children with spastic CP ( n = 13 unilateral and 11 bilateral) and 24 age-, sex-, and race-matched typically developing controls were studied. Jump height and peak power and range of motion at the hip, knee, and ankle of the more affected limb in children with CP and the nondominant limb in controls were assessed during a countermovement jump using three-dimensional motion capture and a force platform. RESULTS: Compared with controls, children with CP had lower jump height (33%, Cohen's d ( d ) = 1.217), peak power at the knee (39%, d = 1.013) and ankle (46%, d = 1.687), and range of motion at the hip (32%, d = 1.180), knee (39%, d = 2.067), and ankle (46%, d = 3.195; all P < 0.001). Jump height was positively related to hip, knee, and ankle power and range of motion in children with CP ( rs range = 0.474-0.613, P < 0.05), and hip and ankle power and knee and ankle range of motion in controls ( rs range = 0.458-0.630, P < 0.05). The group difference in jump height was no longer detected when ankle joint power, ankle range of motion, or knee range of motion was statistically controlled ( P > 0.15). CONCLUSIONS: Jump performance is compromised in children with CP and is associated with low power generation and range of motion in the lower limb, especially at the ankle.

Drug repositioning of disulfiram induces endometrioid epithelial ovarian cancer cell death via the both apoptosis and cuproptosis pathways.

Various therapeutic strategies have been developed to overcome ovarian cancer. However, the prognoses resulting from these strategies are still unclear. In the present work, we screened 54 small molecule compounds approved by the FDA to identify novel agents that could inhibit the viability of human epithelial ovarian cancer cells. Among these, we identified disulfiram (DSF), an old alcohol-abuse drug, as a potential inducer of cell death in ovarian cancer. Mechanistically, DSF treatment significantly reduced the expression of the anti-apoptosis marker B-cell lymphoma/leukemia-2 (Bcl-2) and increase the expression of the apoptotic molecules Bcl2 associated X (Bax) and cleaved caspase-3 to promote human epithelial ovarian cancer cell apoptosis. Furthermore, DSF is a newly identified effective copper ionophore, thus the combination of DSF and copper was used to reduce ovarian cancer viability than DSF single treatment. Combination treatment with DSF and copper also led to the reduced expression of ferredoxin 1 and loss of Fe-S cluster proteins (biomarkers of cuproptosis). In vivo, DSF and copper gluconate significantly decreased the tumor volume and increased the survival rate in a murine ovarian cancer xenograft model. Thus, the role of DSF revealed its potential for used as a viable therapeutic agent for the ovarian cancer.

Outcomes of Microcatheter-Assisted Trabeculotomy for Glaucoma Associated With Sturge-Weber Syndrome and Phakomatosis Pigmentovascularis.

PURPOSE: To evaluate mid-term efficacy and safety of ab externo Microcatheter-assisted trabeculotomy (MAT) for early-onset glaucoma associated with Sturge-Weber syndrome (SWS) and phakomatosis pigmentovascularis (PPV). DESIGN: Retrospective, non-comparative, interventional case series. METHODS: Medical records of consecutive SWS- or PPV-associated glaucoma patients who had undergone ab externo MAT between August 2017 and April 2020 at Beijing Children's Hospital were reviewed. Success was defined as an intraocular pressure (IOP) of <21 mmHg with (qualified success) or without (complete success) the use of antiglaucoma medication. RESULTS: Overall, 13 eyes (12 patients) with SWS and 9 eyes (8 patients) with PPV were included, with a mean age of 12.8 ± 15.8 months at the time of surgery and a mean follow-up time of 39.5 ±10.4 months. Both the SWS (26.5 ± 5.3 mmHg at baseline vs 16.5 ± 5.0 mmHg at the last visit; P < .001) and PPV (29.2 ± 7.5 mmHg vs 23.4 ± 4.7 mmHg; P = .014) subsets achieved a statistically significant fall in IOP following surgery. The Kaplan-Meier survival rate of complete (qualified) success after 42 months was 76.2% (87.5%) and 22.2% (40.0%) for eyes with SWS and PPV, respectively. Complications were minimal. Phakomatosis pigmentovascularis was associated with worse surgical outcomes. CONCLUSIONS: Ab externo MAT is an effective and safe treatment for early-onset glaucoma associated with SWS, but a gradual increase in IOP over time was noted in some patients. Ab externo MAT has limited efficacy for early-onset glaucoma associated with PPV in the mid-term.

Shugan Jieyu capsule improve sleep and emotional disorder in coronavirus disease 2019 convalescence patients: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of the Shugan Jieyu capsule on improving sleep and emotional disorder during Coronavirus disease 2019 (COVID-19) convalescence. METHODS: We conducted a randomized, double-blind, placebo-controlled trial, and recruit 200 COVID-19 convalescence patients and then divide the subjects into two groups respectively: the experimental group ( 100) and the control group ( 100). Patients in the control group were given doses as a placebo, while those in the experimental group were given Shugan Jieyu capsule. The investigators mainly observed the differences between the two groups before and after treatment in terms of the rate of reduction and the rate of efficiency in Hamilton Depression Scale (HAMD-17) total scores from baseline, and recorded the scores of Hamilton Anxiety Scale (HAMA), Patient Health Questionnaire-15 (PHQ-15), Insomnia Severity Index (ISI) and Treatment Emergent Symptom Scale at 2 week, the 4 week and the 6 week respectively after treatment, and compared the differences between the groups. And the occurrence of adverse events was recorded. RESULTS: After 6-week treatment, there were statistically significant differences in the rate of reduction as well as efficiency in HAMD-17 scores, HAMA Total Scores, PHQ-15 Score, ISI Score from baseline in the experimental group and control group (< 0.05). There were 4 adverse events in the experimental group and 1 in the control group. CONCLUSION: Shugan Jieyu capsule could significantly improve sleep and emotional disorder in patients during COVID-19 convalescence.

Regulatory control of high levels of carotenoid accumulation in potato tubers.

Potato (Solanum tuberosum L.) tubers contain a wide range of carotenoid contents. To decipher the key factors controlling carotenoid levels in tubers, four potato lines (Atlantic, Désirée, 91E22 and POR03) were examined by a combination of biochemical, molecular and genomics approaches. These lines contained incremental levels of carotenoids, which were found to be associated with enhanced capacity of carotenoid biosynthesis as evident from norflurazon treatment. Microarray analysis of high and low carotenoid lines (POR03 versus Atlantic) revealed 381 genes that showed significantly differential expression. The carotenoid metabolic pathway genes ß-carotene hydroxylase 2 (BCH2) and ß-carotene hydroxylase 1 (BCH1), along with zeaxanthin epoxidase (ZEP), and carotenoid cleavage dioxygenase 1A (CCD1A) were among the most highly differentially expressed genes. The transcript levels of BCH2 and BCH1 were lowest in Atlantic and highest in POR03, whereas those of ZEP and CCD1A were high in low carotenoid lines and low in high carotenoid lines. The high expression of BCH2 in POR03 line was associated with enhanced response to sugars. Our results indicate that high levels of carotenoid accumulation in potato tubers were due to an increased metabolic flux into carotenoid biosynthetic pathway, as well as the differential expression of carotenoid metabolic genes.

Ankle-Knee Initial Contact Angle and Latency to Maximum Angle are Affected by Prolonged Run.

The initial contact and midstance angles may influence injury risk. Previous literature has not assessed these angles under the influence of new footwear for a non-exhaustive prolonged run or the relationship between the angles. To assess lower extremity kinematic changes and the relationship between kinematic parameters at initial contact and midstance with prolonged running under the influence of different types of footwear. Twelve experienced, recreational runners (6 male; 6 female; 24.8 ± 8.4 years; 70.5 ± 9.3 kg; 174.1 ± 9.7 cm) ran for 31 minutes at a self-selected pace for three testing sessions wearing maximalist, habitual, and minimalist shoes. Sixteen anatomical retroreflective markers and seven tracking clusters were placed on the participants' lower extremities. Kinematic data were collected every five minutes beginning at minute one. Initial contact angle (IC), maximum angle (MAX) during midstance, and latency (Tmax) between IC and MAX were calculated for the ankle and knee joints in the frontal and sagittal planes. No significant differences were observed between footwear. Rearfoot inversion (F3,33 = 9.72, p < .001) and knee flexion (F6,66 = 5.34, p < .001) at IC increased over time. No significant differences were detected for MAX over time. Tmax for dorsiflexion (F6,66 = 10.26, p < .001), rearfoot eversion, (F6,66 = 7.84, p < .001) and knee flexion (F6,66 = 11.76, p < .001) increased over time. Maximum eversion during midstance is related to the angle at initial contact, and regardless of footwear type, IC and Tmax increased over the duration of the run. No differences in the ankle and knee sagittal or frontal plane kinematics between minimalist, habitual, and maximalist footwear were observed During a self-paced run.

Lack of the Histone Methyltransferase Gene Ash2 Results in the Loss of Citrinin Production in Monascus purpureus.

ABSTRACT: Absent, small, or homeotic discs 2 (Ash2), a histone H3K4 methyltransferase complex, has been implicated in the control of hyphal development and secondary metabolism in many kinds of filamentous fungi. We constructed an Ash2 deletion mutant (ΔAsh2) by using an Agrobacterium-mediated gene knockout method to investigate the function of the Ash2 gene in the mold Monascus purpureus. Lack of the Ash2 gene resulted in the formation of a lower colony phenotype with fluffy aerial hyphae that autolyzed as the colony grew on potato dextrose agar at 30°C. The production of pigments and the number of conidia were significantly lower in the ΔAsh2 than in the wild type. Citrinin production by the ΔAsh2 was not detected during 15 days of fermentation. Relative expression levels of secondary metabolite regulatory genes PigR and CTNR, secondary metabolite synthesizing genes PKSPT and CTN, key genes of mitogen-activated protein kinase pathway Spk1 and its downstream gene mam2, the conidium development control gene BrlA, and global regulatory genes LaeA and VeA were detected by the quantitative real-time PCR. These results indicate that the Ash2 gene is involved in conidial germination, pigment production, and citrinin production and plays a key role in development and secondary metabolism in M. purpureus.

Fumonisin B1 Inhibits Endoplasmic Reticulum Stress Associated-apoptosis After FoscanPDT Combined with C6-Pyridinium Ceramide or Fenretinide.

BACKGROUND/AIM: Combining an anticancer agent fenretinide (HPR) or C6-pyridinium ceramide (LCL29) with Foscan-mediated photodynamic therapy (FoscanPDT) is expected to augment anticancer benefits of each substance. We showed that treatment with FoscanPDT+HPR enhanced accumulation of C16-dihydroceramide, and that fumonisin B1 (FB), an inhibitor of ceramide synthase, counteracted caspase-3 activation and colony-forming ability of head and neck squamous cell carcinoma (HNSCC) cells. Because cancer cells appear to be more susceptible to increased levels of the endoplasmic reticulum (ER) stress than normal cells, herein we tested the hypothesis that FoscanPDT combined with HPR or LCL29 induces FB-sensitive ER stress-associated apoptosis that affects cell survival. MATERIALS AND METHODS: Using an HNSCC cell line, we determined: cell survival by clonogenic assay, caspase-3 activity by spectrofluorometry, the expression of the ER markers BiP and CHOP by quantitative real-time polymerase chain reaction and western immunoblotting, and sphingolipid levels by mass spectrometry. RESULTS: Similar to HPR+FoscanPDT, LCL29+FoscanPDT induced enhanced loss of clonogenicity and caspase-3 activation, that were both inhibited by FB. Our additional pharmacological evidence showed that the enhanced loss of clonogenicity after the combined treatments was singlet oxygen-, ER stress- and apoptosis-dependent. The combined treatments induced enhanced, FB-sensitive, up-regulation of BiP and CHOP, as well as enhanced accumulation of sphingolipids. CONCLUSION: Our data suggest that enhanced clonogenic cell killing after the combined treatments is dependent on oxidative- and ER-stress, apoptosis, and FB-sensitive sphingolipid production, and should help develop more effective mechanism-based therapeutic strategies.

PREDICTIVE MODELING OF HOSPITAL READMISSION RATES USING ELECTRONIC MEDICAL RECORD-WIDE MACHINE LEARNING: A CASE-STUDY USING MOUNT SINAI HEART FAILURE COHORT.

Reduction of preventable hospital readmissions that result from chronic or acute conditions like stroke, heart failure, myocardial infarction and pneumonia remains a significant challenge for improving the outcomes and decreasing the cost of healthcare delivery in the United States. Patient readmission rates are relatively high for conditions like heart failure (HF) despite the implementation of high-quality healthcare delivery operation guidelines created by regulatory authorities. Multiple predictive models are currently available to evaluate potential 30-day readmission rates of patients. Most of these models are hypothesis driven and repetitively assess the predictive abilities of the same set of biomarkers as predictive features. In this manuscript, we discuss our attempt to develop a data-driven, electronic-medical record-wide (EMR-wide) feature selection approach and subsequent machine learning to predict readmission probabilities. We have assessed a large repertoire of variables from electronic medical records of heart failure patients in a single center. The cohort included 1,068 patients with 178 patients were readmitted within a 30-day interval (16.66% readmission rate). A total of 4,205 variables were extracted from EMR including diagnosis codes (n=1,763), medications (n=1,028), laboratory measurements (n=846), surgical procedures (n=564) and vital signs (n=4). We designed a multistep modeling strategy using the Naïve Bayes algorithm. In the first step, we created individual models to classify the cases (readmitted) and controls (non-readmitted). In the second step, features contributing to predictive risk from independent models were combined into a composite model using a correlation-based feature selection (CFS) method. All models were trained and tested using a 5-fold cross-validation method, with 70% of the cohort used for training and the remaining 30% for testing. Compared to existing predictive models for HF readmission rates (AUCs in the range of 0.6-0.7), results from our EMR-wide predictive model (AUC=0.78; Accuracy=83.19%) and phenome-wide feature selection strategies are encouraging and reveal the utility of such datadriven machine learning. Fine tuning of the model, replication using multi-center cohorts and prospective clinical trial to evaluate the clinical utility would help the adoption of the model as a clinical decision system for evaluating readmission status.

Expression and clinical significance of Oct-4 and E-cad in non-small-cell lung cancer.

Non-small-lung cancer (NSCLC) is a common malignant tumor and is a leading cause of cancer mortality. Tumor stem cells are associated with tumor pathogenesis and development as well as invastion and metastasis. In the present study, the expression and correlation of tumor stem cell markers, octamer-binding transcription factor 4 (Oct-4) and E-cadherin (E-cad) in NSCLC and normal lung tissue were investigated. Additionally, the molecular mechanisms of invasion and metastasis of NSCLC were assessed. The expression of Oct-4 and E-cad was examined in 65 pathologically diagnosed cases of NSCLC using immunohistochemistry. The correlation between Oct-4 and E-cad, as well as the association with pathological grade and clinical staging were also analyzed. Fifteen cases of normal lung tissues served as the control. The positive expression of Oct-4 and abnormal expression of E-cad was higher in the NSCLC tissue compared to the normal lung tissue, and increased as NSCLC malignancy increased. The differences in each grade each stage were statistically significant (P<0.05). A correlation was identified between the abnormal expression of Oct-4 and E-cad (P<0.05, coefficient of contingency C=0.439). In conclusion, the expression of Oct-4 promoted the epithelial-mesenchymal transition in lung cancer.

Retroperitoneal laparoscopic management of a solitary extramedullary plasmacytoma associated with human immunodeficiency virus infection: A case report.

Extramedullary plasmacytoma (EMP) is a rare malignant tumor that is characterized by a malignant plasma cell neoplasm. Such neoplasms in human immunodeficiency virus (HIV)-infected patients are extremely rare. To the best of our knowledge, the present study describes the first case of a solitary adrenal EMP in a patient with HIV. A 35-year-old male who had been diagnosed with HIV 3 months previously presented with a 2-week history of intermittent right flank pain. Abdominal computed tomography revealed a soft-tissue density mass in the right adrenal gland area. The patient subsequently underwent a retroperitoneal laparoscopic adrenalectomy. Post-operative pathological diagnosis revealed a solitary EMP. Although the patient refused to undergo post-operative radiotherapy and chemotherapy, no recurrence was detected after 2 years of follow-up. The present case illustrates the fact that this rare type of solitary EMP associated with acquired immune deficiency syndrome (AIDS) can occur in the adrenal glands, and that retroperitoneal laparoscopic resection of the tumor may be a good method to manage this condition. In addition, although rare, solitary EMP should be considered in the differential diagnosis of an adrenal mass in HIV-infected patients.

Dyslipidemia in patients with systemic lupus erythematosus: Association with disease activity and B-type natriuretic peptide levels.

The aim of the present study was to evaluate the association between the levels of lipids and B-type natriuretic peptide (BNP) in systemic lupus erythematosus (SLE) patients with heart failure (HF). A total of 46 patients with active SLE and 40 healthy, age-matched control subjects were studied. BNP was measured by an immunofluorescence assay in fresh plasma. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apolipoprotein (Apo) B, ApoA-I and lipoprotein(a) were assessed. Compared with the control subjects, HDL-C and ApoA-I levels were considerably decreased and TG level increased markedly from SLE patients. The average concentration of HDL-C and ApoA-I in the SLE group with HF was significantly reduced compared to those patients without HF. The results showed that the levels of HDL-C and ApoA-I in SLE patients were negatively correlated with BNP. Disease activity was associated with the TC and TG levels. The present data indicated the presence of a cardiovascular (CV) risk in active SLE with high disease activity, which was demonstrated by the high frequency of dyslipidemia and higher BNP concentrations. Therefore, dyslipoproteinemia may underlie some of the increased risk for CV disease and HF in patients with SLE.

Successful treatment of cardiac electrical storm in dilated cardiomyopathy using esmolol: A case report.

The present study reports a case of electrical storm occurring in a 43-year-old woman with dilated cardiomyopathy. The patient suffered from a cardiac electrical storm, with 98 episodes of ventricular tachycardia rapidly degenerating to ventricular fibrillation in hospital. The patient was converted with a total of 120 defibrillations. Recurrent ventricular tachycardia/fibrillation was initiated by premature ventricular beats. The patient did not respond to the use of amiodaronum. However, the administration of esmolol stabilized the patient's heart rhythm. A moderate dose of the ß-blocker esmolol, administered as an 0.5-mg intravenous bolus injection followed by an infusion at a rate of 0.15 mg/kg/min, inhibited the recurrence of ventricular fibrillation and normalized the electrocardiographic pattern. The results suggest that esmolol may be able to improve the survival rate of patients with electrical storm in dilated cardiomyopathy and should be considered as a primary therapy in the management of cardiac electrical storms.

Integration and bioinformatics analysis of DNA-methylated genes associated with drug resistance in ovarian cancer.

The main obstacle to the successful treatment of ovarian cancer is the development of drug resistance to combined chemotherapy. Among all the factors associated with drug resistance, DNA methylation apparently plays a critical role. In this study, we performed an integrative analysis of the 26 DNA-methylated genes associated with drug resistance in ovarian cancer, and the genes were further evaluated by comprehensive bioinformatics analysis including gene/protein interaction, biological process enrichment and annotation. The results from the protein interaction analyses revealed that at least 20 of these 26 methylated genes are present in the protein interaction network, indicating that they interact with each other, have a correlation in function, and may participate as a whole in the regulation of ovarian cancer drug resistance. There is a direct interaction between the phosphatase and tensin homolog (PTEN) gene and at least half of the other genes, indicating that PTEN may possess core regulatory functions among these genes. Biological process enrichment and annotation demonstrated that most of these methylated genes were significantly associated with apoptosis, which is possibly an essential way for these genes to be involved in the regulation of multidrug resistance in ovarian cancer. In addition, a comprehensive analysis of clinical factors revealed that the methylation level of genes that are associated with the regulation of drug resistance in ovarian cancer was significantly correlated with the prognosis of ovarian cancer. Overall, this study preliminarily explains the potential correlation between the genes with DNA methylation and drug resistance in ovarian cancer. This finding has significance for our understanding of the regulation of resistant ovarian cancer by methylated genes, the treatment of ovarian cancer, and improvement of the prognosis of ovarian cancer.

Fat-1 gene inhibits human oral squamous carcinoma cell proliferation through downregulation of ß-catenin signaling pathways.

The ω-3 fatty acid desaturase (fat-1) gene encodes the enzyme that converts ω-6 polyunsaturated fatty acids (PUFAs) to ω-3 PUFAs. Numerous studies have suggested that the ratio of ω-6/ω-3 PUFAs has an impact on tumorigenesis. To investigate the biological function of the fat-1 gene in human oral squamous cell carcinoma (OSCC), the fat-1 gene was introduced into OSCC cells by transfection. The uptake of the gene was confirmed by reverse transcription-polymerase chain reaction and analyzed using gas chromatography. The antitumor effects and mechanisms of the fat-1 gene were evaluated by studying cell survival and tumor growth in vitro and in vivo. Gas chromatography results revealed that the cells transfected with the fat-1 gene had a higher ω-3/ω-6 PUFA ratio than cells transfected with the control vector. An MTT and DNA fragmentation assay indicated that the presence of the fat-1 gene in vitro significantly decreased OSCC cell proliferation and significantly increased the rate of apoptosis. Similar antitumor effects of the fat-1 gene were also observed in vivo. Immunohistochemistry analysis confirmed that Tca8113 cell tumors displayed a significant reduction in cell growth and cell survival following the introduction of the fat-1 gene. The current study suggests that the inhibitory effect of the fat-1 gene on tumor growth may be a result of a reduction in the expression of the tumor survival protein ß-catenin. The results also support the theory that the ratio of ω-3/ω-6 PUFAs has an impact on OSCC tumor growth. The findings of the study provide notable molecular insight into the theory suggesting that ω-3 PUFAs are an intermediate for the chemoprevention and treatment of human OSCC.

Human lymphatic endothelial cells contribute to epithelial ovarian carcinoma metastasis by promoting lymphangiogenesis and tumour cell invasion.

The microenvironment of a tumour is an important factor in ovarian cancer metastasis. The present study aimed to simulate the in vivo microenvironment of an ovarian carcinoma using a co-culture system consisting of human lymphatic endothelial cells (HLECs) and human ovarian carcinoma cells with directional high lymphatic metastasis (SKOV3-PM4s) in order to investigate the role of both cell types in ovarian carcinoma metastasis. The SKOV3-PM4s cultured in the HLEC-conditioned medium exhibited increased numbers of pseudopodia and mitotic figures, proliferated at a faster rate and exhibited enhanced invasion and migratory abilities. Furthermore, the HLECs cultured in SKOV3-PM4-conditioned medium exhibited significant morphological alterations and vacuolisation of the cytoplasm, as well as increased invasion, migratory and tube forming abilities. In addition, spontaneous fusion of the SKOV3-PM4s and HLECs was observed in the co-culture system using laser confocal microscopy. The gelatin zymography assay demonstrated that matrix metalloproteinase-2, which was downregulated in the SKOV3-PM4s, was upregulated in the co-culture system. The results of the present study suggested that the invasion ability of the SKOV3-PM4s was increased in the in vitro co-culture system of SKOV3-PM4 and HLECs. Therefore, alterations in the cell microenvironment may represent a novel strategy for ovarian cancer therapy.

Fentanyl inhibits the progression of human gastric carcinoma MGC-803 cells by modulating NF-κB-dependent gene expression in vivo.

Fentanyl is widely used to treat acute and chronic pain. Previous in vitro studies by the present authors demonstrated that fentanyl inhibits the progression of the MGC-803 human gastric carcinoma cell line by affecting apoptosis-related genes, including nuclear factor-kappa B (NF-κB) and phosphatase and tensin homolog. In the present study, the effects of fentanyl on NF-κB-dependent gene expression were investigated in vivo. Nude mice were inoculated with an MGC-803 cell suspension, and mice that developed subcutaneous tumors measuring >1.0×1.0 cm were selected for study. Mice were administered intraperitoneal injections of fentanyl (0.05 mg/kg, group F1; 0.1 mg/kg, group F2; 0.2 mg/kg, group F3; and 0.4 mg/kg, group F4) for 14 consecutive days. Non-fentanyl-treated mice (group C) and normal saline-treated mice (group N) served as the control groups. Tumor growth was monitored by calculating the time-shift of the growth curve. Morphological changes were also observed using microscopy. The expression of NF-κB, B-cell lymphoma-2 (Bcl-2), B-cell associated X protein (Bax), vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) in the subcutaneous tumor tissue was also analyzed by reverse transcription-polymerase chain reaction and western blot analysis, and confirmed using immunohistochemistry. The relative tumor volumes of groups F1, F2, F3 and F4 were significantly reduced compared with groups C and N. Furthermore, subcutaneous tumor cells exhibited nuclear swelling, chromatin condensation, reduced chromatin and nuclear fragmentation in the F1, F2, F3 and F4 groups. The number of NF-κB+, Bcl-2+, VEGF-A+ and MMP-9+ subcutaneous tumor cells was reduced, whereas the number of Bax+ cells was increased in the F1, F2, F3 and F4 groups. Additionally, in these groups, tumor expression of NF-κB, Bcl-2, VEGF-A and MMP-9 transcripts and proteins was downregulated, while Bax messenger RNA and protein expression levels were upregulated. The results revealed that fentanyl inhibits the growth of subcutaneous human gastric carcinoma tumors in mice. Therefore, it could be hypothesized that this antineoplastic activity may result from the inhibition of NF-κB activation, suppression of downstream VEGF-A and MMP-9 expression, and normalization of the pro-apoptotic Bax/Bcl-2 ratio.