Prognostic value of right ventricular free wall strain in patients with sepsis.

Background: Right ventricular systolic dysfunction (RVSD) in patients with sepsis is an area of growing interest, but its prognostic significance remains unclear and additional tools are needed to improve our understanding. Right ventricular free wall strain (RV-FWS) is a relatively new parameter to assess RV function. This study aimed to investigate the potential correlation between impaired RV-FWS and prognostic outcomes in patients with sepsis. Methods: We prospectively assessed right ventricular function in patients with sepsis within the initial 24 h of their hospital admission. RV-FWS, right ventricular global strain (RV-GS), fractional area change (FAC), and tricuspid annular plane systolic excursion (TAPSE) were examined. RVSD was defined as impaired RV-FWS. Moreover, the association between RVSD and 30-day mortality rate was assessed. Results: This study included 89 patients. Among them, 27 (30.3%) succumbed to their illness within 30 days. The nonsurviving patients demonstrated significantly lower absolute RV-FWS (-19.7% ± 2.4% vs. -21.1% ± 2.1%, P = 0.008) and RV-GS (-17.7% ± 1.2% vs. -18.4% ± 1.4%, P = 0.032) values than the surviving patients. However, TAPSE and FAC values were not significantly different between the two groups. The optimal cutoff values for RV-FWS, RV-GS, FAC, and TAPSE were -19.0%, -17.9%, 36.5%, and 1.55 cm, respectively. Kaplan-Meier survival curves revealed that patients with impaired RV-FWS and RV-GS demonstrated lower 30-day survival rates, and the predictive performance of RV-FWS (hazard ratio [HR]: 3.97, 95% confidence interval [CI]: 1.85-8.51, P < 0.001) was slightly higher than FAC and TAPSE. However, multivariable Cox regression analysis revealed no association between impaired RV-FWS and mortality outcomes (HR: 1.85, 95% CI: 0.56-6.14, P = 0.316). Conclusions: Impaired RV-FWS is not associated with short-term mortality outcomes, and RV strain imaging is of limited value in assessing the prognosis of sepsis.

Can prophylactic HPV vaccination reduce the recurrence of cervical lesions after surgery? Review and prospect.

Women with HSIL typically undergo conization/LEEP to remove cervical lesions, but the risk of HSIL lesions returning after surgical treatment remains higher than in the general population. HPV vaccination is essential to prevent cervical cancer. However, the effect of prophylactic HPV vaccination on reducing the risk of recurrent cervical lesions after surgical treatment remains unclear. This review aims to analyze and summarize the latest literature on the role of prophylactic HPV vaccine in reducing the recurrence of cervical lesions after surgery in patients with HSIL, and to review and update the history, efficacy, effectiveness and safety of HPV vaccine, focusing on the current status of global HPV vaccine implementation and obstacles.

Diagnostic Performance and Accuracy of Strain Elastography for BI-RADS Category 4 Lesions among Asian Females.

This work aimed to assess the diagnostic performance of strain elastography (elasticity score) and its accuracy for breast BI-RADS category 4 lesions. Online databases including Cochrane Library, Embase, PubMed, and Web of Science were searched for eligible articles published prior to March 10, 2022. The pooled effect indicators including sensitivity, specificity, positive and negative likelihood ratios (PLR, NLR), the area under the summary receiver operating characteristic (SROC) curve, and diagnostic odds ratio (DOR) were utilised to assess the strain elastography's performance in diagnosing BI-RADS category 4 lesions. Subgroup analyses and meta-regressions were used to explore the potential sources of heterogeneity, and the Deeks' funnel plot asymmetry test was used to detect any publication bias. The literature search yielded 11 studies involving 5028 BI-RADS category 4 lesions (including 1809 malignant lesions). The recruited lesions were all from Asian females. The pooled sensitivity, specificity, PLR, NLR, and DOR with the 95% confidence intervals were 0.68 (0.66-0.71), 0.83 (0.82-0.85), 3.36 (2.45-4.60), 0.32 (0.21-0.49), and 12.11 (7.46-19.65), respectively. The area under the SROC curve was 0.85. No significant publication bias was detected. Taken together, strain elastography had suboptimal sensitivity but desirable specificity for the accurate diagnosis of BI-RADS category 4 lesions among Asian females, which can help avoid unnecessary biopsies and reduce patient anxiety. Key Words: BI-RADS category 4 lesions, Strain elastography, Meta-analysis.

Social and paternal female choice for male MHC genes in golden snub-nosed monkeys (Rhinopithecus roxellana).

Genes of the major histocompatibility complex (MHC) play important roles in vertebrate immunocompetence. MHC genes thus offer females indirect benefits to mate choice through the production of offspring of an optimal MHC genotype. Females may choose males with specific MHC haplotypes, dissimilar MHC genotypes, MHC heterozygous males or MHC-diverse males. We tested these four alternatives for both female social and paternal choice in wild golden snub-nosed monkeys (Rhinopithecus roxellana) by examining overall genetic variability (via microsatellites) and four MHC-genes (DRB1, DRB2, DQA1 and DQB1). Monte Carlo randomization tests showed that MHC dissimilarity was favoured for social choice (males to which females were socially affiliated) and intermediate MHC dissimilarity was favoured in paternal choice (fathers of offspring). No evidence of inbreeding avoidance was found for either social or paternal mates. We found that MHC heterozygotes, higher microsatellite multilocus heterozygosity and higher microsatellites diversity were favoured for social mates, and higher microsatellite diversity was favoured for paternal mates. Independent of male age, we found that the formation of male-female social pairings is significantly predicted by compatibility based on the sharing of MHC haplotypes. However, we found no evidence of independent genetic effects on the duration of male-female social pairings, male social status (achieving OMU leader male status or not), the number of females with which individual leader males paired, the likelihood of potential male-female pairings producing offspring, or whether males fathered offspring or not. Overall, our findings suggest different genetic factors are involved in social and paternal choice in R. roxellana.

Study on mechanical properties and fracture surface characteristics of argillaceous sandstone under different stress paths.

To study the differences in mechanical properties and failure characteristics of underground chambers surrounding rock under different stress conditions, triaxial loading and unloading tests were carried out on argillaceous sandstone. The three-dimensional topography parameters of the fracture surface were obtained by using high-precision three-dimensional topography scanning technology, including six height characteristic parameters and two texture parameters. Compared with the triaxial loading test, the strength, peak strain and residual strength of argillaceous sandstone with the same confining pressure under unloading conditions all decrease, and the stress-strain curve changes from ductility to brittleness. The Mogi-Coulomb strength criterion can better describe the strength properties of argillaceous sandstones than the Mohr-Coulomb and Drucker-Prager strength criteria. Under the unloading condition, the cohesion c decreased by 30.87% and the internal friction angle φ increased by 30.87% compared with the loading condition. The tensile cracks perpendicular to the unloading direction is formed during unloading, resulting in large roughness, dispersion and fluctuation of fracture surface.

Environmental Benefit Assessment of Blended Cement with Modified Granulated Copper Slag.

This study aimed to investigate the environmental impact of modified granulated copper slag (MGCS) utilization in blended cement production at a representative cement plant in China. Sensitivity analysis was performed on the substance inputs, and the life cycle impact assessment (LCIA) model was applied. A detailed comparative analysis was conducted of the environmental impact of cement production in other studies, and ordinary Portland cement production at the same cement plant. Results showed that calcination has the largest contribution impact of all the impact categories, especially in causing global warming (93.67%), which was the most prominent impact category. The life cycle assessment (LCA) result of blended cement was sensitive to the chosen LCIA model and the depletion of limestone and energy. In this study, producing blended cement with MGCS effectively mitigated the environmental impact for all the selected impact categories. Results also show a reduction in abiotic depletion (46.50%) and a slight growth (6.52%) in human toxicity. The adoption of MGCS in blended cement would therefore generally decrease the comprehensive environmental impact of cement, which contributes to the development of sustainable building materials.

Malignant transformation of endometriosis in a laparoscopic trocar site a case report.

BACKGROUND: Malignant transformation of endometriosis is infrequent at the laparoscopic trocar site. Although malignant transformation is uncommon, it must be acknowledged in order to achieve radical resection. CASE PRESENTATION: We report on a 54-year-old woman with trocar site endometriosis 2 years after laparoscopic ovarian endometrial resection. Physical examination revealed a subcutaneous solid tumor with a diameter of 3 cm surrounding the scar of laparoscopic surgery in the right lower abdomen. Transabdominal ultrasonography showed a cystic tumor in the subcutaneous adipose layer of the right lower abdomen. The pathological diagnosis was poorly differentiated endometrioid carcinoma. Hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy were then performed. Histological examination revealed mixed endometrioid carcinoma and clear cell carcinoma. After six cycles of chemotherapy, computed tomography showed no signs of recurrence. CONCLUSIONS: Malignant transformation of laparoscopic endometriosis is very uncommon, and the diagnosis and stage are determined by clinical manifestations and imaging examination. The main therapy methods are radical surgery combined with neoadjuvant chemotherapy and adjuvant radiotherapy. At the same time, reducing iatrogenic abdominal incision implantation is an effective prevention method.

An efficient catalytic method for hydrophosphination of heterocumulenes with diethylzinc as precatalyst without a solvent.

Commercially available compound ZnEt2 acts as an efficient precatalyst for the solvent-free hydrophosphinations of heterocumulenes using Ph2PH as reagent. As far as we knew, this has been not reported in group 12 metal catalyzing reactions. A suggested mechanism of this reaction is explored, and the intermediate [{Ph2PC(NiPr)2}ZnEt]2 is obtained and characterized by a single-crystal X-ray structural analysis.

Low-dose alcohol ameliorated high fat diet-induced anxiety-related behavior via enhancing adiponectin expression and activating the Nrf2 pathway.

Long-term high-fat-diet (HFD)-induced obesity is associated with many comorbidities, such as cognitive impairment and anxiety, which are increasing public health burdens that have gained prevalence in adolescents. Although low-dose alcohol could attenuate the risk of cardiovascular disease, its mechanism on HFD-induced anxiety-related behavior remains not clear. The mice were divided into 4 groups, Control (Con), Alcohol (Alc), HFD and HFD + Alc groups. To verify the effects of low-dose alcohol on HFD-induced anxiety-related behavior, the mice were fed with HFD for 16 weeks. At the beginning of week 13, the HFD-fed mice were administered intragastrically with low-dose alcohol (0.8 g kg-1) for 4 weeks. After 4 weeks of oral administration, low-dose alcohol decreased body weight and Lee's index in HFD-induced obese mice. Moreover, low-dose alcohol alleviated the anxiety-related behaviors of obese mice in the open field test and the elevated plus maze test. The HFD-induced damage to the hippocampus was improved in hematoxylin-eosin staining assay in mice. In addition, low-dose alcohol also suppressed HFD-induced oxidative stress and increased HFD-suppressed adiponectin (APN) expression and nuclear factor erythroid 2-related factor 2 (Nrf2) activation in the hippocampus. Taken together, low-dose alcohol significantly ameliorates HFD-induced obesity, oxidative stress and anxiety-related behavior in mice, which might be related to APN upregulation, Nrf2 activation and related antioxidase expression including SOD1, HO-1, and catalase.

Protocatechuic acid inhibits proliferation, migration and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is a chronic joint inflammatory disease that is closely associated with dysregulation of fibroblast-like synoviocytes (FLSs). Protocatechuic acid (PCA), a phenolic compound of anthocyanins, has been proven to possess anti-inflammatory activity. However, the role of PCA in RA has not been investigated. In the present study, we aimed to explore the effects of PCA on the RA-FLSs. The results showed that PCA suppressed the proliferation, invasion, and migration of RA-FLSs in a dose-dependent manner. PCA treatment also inhibited the expressions of matrix metalloproteinase (MMP)-3 and MMP-13, as well as the secretion of inflammatory cytokines including TNF-α, IL-1ß, IL-6 in RA-FLSs. Moreover, cell apoptosis of RA-FLSs was significantly induced by PCA treatment. PCA was found to repress the activation of NF-κB signalling, which was evidenced by the decreased expression of p-p65 and increased expression of IκBα. Furthermore, PCA significantly decreased the phosphorylation levels of Akt and mTOR in RA-FLSs. In conclusion, the results indicated that PCA exhibited an inhibitory effect on RA-FLSs via inhibiting the NF-κB and Akt/mTOR signalling pathways. These findings supported the concept that PCA might be a therapeutic agent for RA treatment.

MHC-Based Mate Choice in Wild Golden Snub-Nosed Monkeys.

The genes of the major histocompatibility complex (MHC) are an important component of the vertebrate immune system and play a significant role in mate choice in many species. However, it remains unclear whether female mate choice in non-human primates is based on specific functional genes and/or genome-wide genes. The golden snub-nosed monkey (Rhinopithecus roxellana) lives in a multilevel society, which consists of several polygynous one-male-several-female units. Although adult females tend to mainly socialize with one adult male, females often initiate extra-pair copulations with other males resulting in a high proportion of offspring being fathered by extra-pair males. We investigated the effects of adaptive MHC genes and neutral microsatellites on female mate choice in a wild R. roxellana population. We sequenced 54 parent-offspring triads using two MHC class II loci (Rhro-DQA1 and Rhro-DQB1) and 20 microsatellites from 3 years of data. We found that the paternities of offspring were non-randomly associated with male MHC compositions not microsatellite genotypes. Our study showed that the fathers of all infants had significantly less variance for several estimates of genetic similarity to the mothers compared with random males at both MHC loci. Additionally, the MHC diversity of these fathers was significantly higher than random males. We also found support for choice based on specific alleles; compared with random males, Rhro-DQA1∗ 05 and Rhro-DQB1∗ 08 were more common in both the OMU (one-male unit) males and the genetic fathers of offspring. This study provides new evidence for female mate choice for MHC-intermediate dissimilarity (rather than maximal MHC dissimilarity) and highlights the importance of incorporating multiple MHC loci and social structure into studies of MHC-based mate choice in non-human primates.

Potential Drug Targets Against Hepatitis B Virus Based on Both Virus and Host Factors.

BACKGROUND: Hepatitis B is a very harmful and epidemic disease caused by hepatitis B virus (HBV). Although an effective anti-HBV vaccine is available, chronic infection poses still a huge health burden in the whole world. The present anti-HBV drugs including nucleoside analogues and interferonalpha have their limitations without exception. There is no effective drug and therapeutic method that can really and truly cure hepatitis B so far. The variability of HBV genome results in that a significant number of patients develop drug resistance during the long-term use of anti-HBV drugs. Hence, it is urgently needed to discover novel targets and develop new drugs against hepatitis B. OBJECTIVE: The review aims to provide the theory support for designing of the anti-HBV innovative drugs by offering a summary of the current situation of antiviral potential targets. RESULTS AND CONCLUSION: Since HBV is obligate intracellular parasite, and as such it depends on host cellular components and functions to replicate itself. The targeting both virus and host might be a novel therapeutic option for hepatitis B. Accordingly, we analyse the advances in the study of the potential drug targets for anti-HBV infection, focusing on targeting virus genome, on targeting host cellular functions and on targeting virus-host proteins interactions, respectively. Meanwhile, the immune targets against chronic hepatitis B are also emphasized. In short, the review provides a summary of antiviral therapeutic strategies to target virus factors, host factors and immune factors for future designing of the innovative drug against HBV infection.

Pectolinarin inhibits proliferation, induces apoptosis, and suppresses inflammation in rheumatoid arthritis fibroblast-like synoviocytes by inactivating the phosphatidylinositol 3 kinase/protein kinase B pathway.

Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs), a pathological hallmark of rheumatoid arthritis (RA), exhibit the characteristics of tumor cells. The extracts of Cirsium japonicum var. ussuriense have been shown to possess antitumor and anti-inflammatory activities. Our study aimed to investigate the effects of pectolinarin, a flavonoid compound isolated from C. japonicum var. ussuriense, on RA. Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Apoptosis was determined by flow cytometry analysis and Western blot analysis of Bax and Bcl-2 levels. Inflammation was assessed by detecting the expressions and secretion of interleukin (IL)-6 and IL-8 using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The production of nitric oxide (NO) and prostaglandin E2 (PGE2) was also measured. The effects of pectolinarin on the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway were examined by Western blot. We found that pectolinarin significantly inhibited cell viability at 24 and 48 hours in a dose-dependently manner in RA-FLSs. Pectolinarin reduced the apoptotic rate, increased Bax level, and decreased Bcl-2 level in RA-FLSs. Pectolinarin inhibited the messenger RNA expression and secretion of IL-6 and IL-8, as well as the production of PGE2 and NO in RA-FLSs. Furthermore, pectolinarin inactivated the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway in RA-FLSs. Activation of the PI3K/Akt pathway by 740Y-P impaired the effects of pectolinarin on cell viability, apoptosis, and inflammation in RA-FLSs. In conclusion, pectolinarin suppressed cell proliferation and inflammatory response and induced apoptosis in RA-FLSs via inactivation of the PI3K/Akt pathway.

High polymorphism in MHC-DRB genes in golden snub-nosed monkeys reveals balancing selection in small, isolated populations.

BACKGROUND: Maintaining variation in immune genes, such as those of the major histocompatibility complex (MHC), is important for individuals in small, isolated populations to resist pathogens and parasites. The golden snub-nosed monkey (Rhinopithecus roxellana), an endangered primate endemic to China, has experienced a rapid reduction in numbers and severe population fragmentation over recent years. For this study, we measured the DRB diversity among 122 monkeys from three populations in the Qinling Mountains, and estimated the relative importance of different agents of selection in maintaining variation of DRB genes. RESULTS: We identified a total of 19 DRB sequences, in which five alleles were novel. We found high DRB variation in R. roxellana and three branches of evidence suggesting that balancing selection has contributed to maintaining MHC polymorphism over the long term in this species: i) different patterns of both genetic diversity and population differentiation were detected at MHC and neutral markers; ii) an excess of non-synonymous substitutions compared to synonymous substitutions at antigen binding sites, and maximum-likelihood-based random-site models, showed significant positive selection; and iii) phylogenetic analyses revealed a pattern of trans-species evolution for DRB genes. CONCLUSIONS: High levels of DRB diversity in these R. roxellana populations may reflect strong selection pressure in this species. Patterns of genetic diversity and population differentiation, positive selection, as well as trans-species evolution, suggest that pathogen-mediated balancing selection has contributed to maintaining MHC polymorphism in R. roxellana over the long term. This study furthers our understanding of the role pathogen-mediated balancing selection has in maintaining variation in MHC genes in small and fragmented populations of free-ranging vertebrates.

Long non-coding RNA SOX2OT promotes cell proliferation and motility in human ovarian cancer.

Ovarian cancer is one of the most common malignant gynecological cancers. Although conventional chemotherapies have improved the treatment of patients with ovarian cancer, the mortality rate remains high. Hence, it is crucial that the detailed mechanisms that promote ovarian cancer are urgently identified. Therefore, reverse transcription-quantitative polymerase chain reaction was used to reveal the relative transcript levels. Colony formation assay and cell cycle assay were performed in siRNA-treated cells. Transwell assay and western blot assays were also conducted. The results showed that the expression of long non-coding RNA SRY-box 2 overlapping transcript (SOX2OT) was upregulated in clinical ovarian cancer tissues and in cultured ovarian cancer cells (HO-8910 and HO-8910PM). High expression of SOX2OT negatively correlated with the prognosis of patients with ovarian cancer. Knockdown of SOX2OT by specific small interfering RNA against SOX2OT suppressed the colony formation capacity of invasive ovarian cancer cells and resulted in cell cycle arrest in G0/G1 phase. Key cell cycle regulators, cyclin B1 and cell division cycle 25C, were consistently downregulated by the knockdown of SOX2OT. Furthermore, knockdown of SOX2O Tinhibited cell migration, cell invasion and decreased the expression of mesenchymal protein N-cadherin, whereas the expression of epithelial protein E-cadherin was increased in ovarian cancer cells. Overall, SOX2OT expression levels correlated with the prognosis of patients with ovarian cancer, and SOX2OT promoted cell proliferation and motility in ovarian cancer cells. These findings indicated that SOX2OT may serve as a potential therapeutic target in the treatment of ovarian cancer.

Structure Properties and Mechanisms of Action of Naturally Originated Phenolic Acids and Their Derivatives against Human Viral Infections.

BACKGROUND: A great effort has been made to develop efficacious antiviral drugs, but many viral infections are still lack of efficient antiviral therapies so far. The related exploration of natural products to fight viruses has been raised in recent years. Natural compounds with structural diversity and complexity offer a great chance to find new antiviral agents. Particularly, phenolic acids have attracted considerable attention owing to their potent antiviral abilities and unique mechanisms. The aim of this review is to report new discoveries and updates pertaining to antiviral phenolic acids. METHODS: The relevant references on natural phenolic acids were searched. The antiviral phenolic acids were classified according to their structural properties and antiviral types. Meanwhile, the antiviral characteristics and structure-activity relationships of phenolic acids and their derivatives were summarized. RESULTS: The review finds that natural phenolic acids and their derivatives possessed potent inhibitory effects on multiple virus in humans such as human immunodeficiency virus, hepatitis C virus, hepatitis B virus, herpes simplex virus, influenza virus and respiratory syncytial virus. In particular, caffeic acid/gallic acid and their derivatives exhibited outstanding antiviral properties by a variety of modes of action. CONCLUSION: Naturally derived phenolic acids especially caffeic acid/gallic acid and their derivatives may be regarded as novel promising antiviral leads or candidates. Additionally, scarcely any of these compounds has been used as antiviral treatment in clinical practice. Therefore, these phenolic acids with diverse skeletons and mechanisms provide us an excellent resource for finding novel antiviral drugs.

Serum Insulin-Like Growth Factor Axis and the Risk of Pancreatic Cancer: Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate the association between serum concentration of insulin-like growth factor (IGF) and the risk of pancreatic cancer (PaC). METHODS: We identified eligible studies in Medline and EMBASE databases (no reference trials from 2014 to 2016) in addition to the reference lists of original studies and review articles on this topic. A summary of relative risks with 95% confidence intervals (CI) was calculated using a random-effects model. The heterogeneity between studies was assessed using Cochran Q and I² statistics. RESULTS: Ten studies (seven nested case-control studies and three retrospective case-control studies) were selected as they met our inclusion criteria in this meta-analysis. All these studies were published between 1997 and 2013. The current data suggested that serum concentrations of IGF-I, IGF-II and insulin-like growth factor binding protein-3 (IGFBP-3)in addition to the IGF-I/IGFBP-3 ratio were not associated with an increased risk of PaC (Summary relative risks (SRRs) = 0.92, 95% CI: 0.67-1.16 for IGF-I; SRRs = 0.84, 95% CI: 0.54-1.15 for IGF-II; SRRs = 0.93, 95% CI: 0.69-1.17 for IGFBP-3; SRRs = 0.97, 95% CI: 0.71-1.23 for IGF-I/IGFBP-3 ratio). There was no publication bias in the present meta-analysis. CONCLUSION: Serum concentrations of IGF-I, IGF-II, IGFBP-1 and IGFBP-3 as well as the IGF-I/IGFBP-3 ratio were not associated with increased risk of PaC.

Quantitative assessment of the relationship between RASSF1A gene promoter methylation and bladder cancer (PRISMA).

BACKGROUND: Methylation of the Ras-association domain family 1 isoform A (RASSF1A) gene promoter region is thought to participate in the initiation and development of many different cancers. However, in bladder cancer the role of RASSF1A methylation was unclear. To evaluate the relationship between RASSF1A methylation and bladder cancer, a quantitative assessment of an independent meta-analysis was performed. In addition, a DNA methylation microarray database from the cancer genome atlas (TCGA) project was used to validate the results of the meta-analysis. METHODS: We searched published articles from computerized databases, and DNA methylation data were extracted from TCGA project. All data were analyzed by R software. RESULTS: The results of the meta-analysis indicated that the frequency of RASSF1A gene methylation in bladder cancer patients is significantly higher than in healthy controls. The hazard ratio (HR) was 2.24 (95% CI = [1.45; 3.48], P = 0.0003) for overall survival (OS), and the RASSF1A gene promoter methylation status was strongly associated with the TNM stage and differentiation grade of the tumor. The similar results were also found by the data from TCGA project. CONCLUSION: There was a significant relationship between the methylation of the RASSF1A gene promoter and bladder cancer. Therefore, RASSF1A gene promoter methylation will be a potential biomarker for the clinical diagnosis of bladder cancer.

Protective effects of perindopril on d-galactose and aluminum trichloride induced neurotoxicity via the apoptosis of mitochondria-mediated intrinsic pathway in the hippocampus of mice.

Perindopril, an angiotensin converting enzyme inhibitor, has been reported to improve learning and memory in a mouse or rat model of Alzheimer's disease (AD) induced by injection of beta-amyloid protein. However, the exact mechanism of perindopril on the cognitive deficits is not fully understood. Our previous data have indicated that perindopril improves learning and memory in a mouse model of AD induced by D-galactose (D-gal) and aluminum trichloride (AlCl3) via inhibition of acetylcholinesterase activity and oxidative stress. Whether perindopril also inhibit apoptosis to prevent cognitive decline remains unknown in mice. Therefore, the present study explored the protective effects of perindopril in the hippocampus of mice further. Perindopril (0.5 mg/kg/day) was administered intragastrically for 60 days after the mice were given a D-gal (150 mg/kg/day) and AlCl3 (10 mg/kg/day) intraperitoneally for 90 days. Then the expression of Bcl-2, Bax, Fas, FasL, caspase-3, caspase-8 and caspase-9 were analyzed by RT-PCR and western blotting in the hippocampus. Perindopril significantly decreased caspase-3 and caspase-9 activities, and elevated Bcl-2/Bax ratio in the hippocampus. However, the expression of Fas, FasL and caspase-8 did not change in the hippocampus whether treatment with d-gal and AlCl3 or perindopril. Taken together, the above findings indicated that perindopril inhibited apoptosis in the hippocampus may be another mechanism by which perindopril improves learning and memory functions in d-gal and AlCl3 treated mice.