ProFun: A web server for functional enrichment analysis of parasitic protozoan genes.

BACKGROUND: The initial step to interpreting putative biological functions from comparative multi-omics studies usually starts from a differential expressed gene list followed by functional enrichment analysis (FEA). However, most FEA packages are designed exclusively for humans and model organisms. Although parasitic protozoan is the most important pathogen in the tropics, no FEA package is available for protozoan functional (ProFun) enrichment analysis. To speed up comparative multi-omics research on parasitic protozoans, we constructed ProFun, a web-based, user-friendly platform for the research community. METHODS: ProFun utilizes the Docker container, ShinyProxy, and R Shiny to construct a scalable web service with load-balancing infrastructure. We have integrated a series of visual analytic functions, in-house scripts, and custom-made annotation packages to create three analytical modules for 40 protozoan species: (1) Gene Overlaps; (2) Over-representation Analysis (ORA); (3) Gene Set Enrichment Analysis (GSEA). RESULTS: We have established ProFun, a web server for functional enrichment analysis of differentially expressed genes. FEA becomes as simple as pasting a list of gene IDs into the textbox of our website. Users can customize enrichment parameters and results with just one click. The intuitive web interface and publication-ready charts enable users to reveal meaningful biological events and pinpoint potential targets for further studies. CONCLUSION: ProFun is the first web application that enables gene functional enrichment analysis of parasitic protozoans. In addition to supporting FEA analysis, ProFun also allows the comparison of FEA results across complicated experimental designs. ProFun is freely available at http://dalek.cgu.edu.tw:8080/app/profun.

Universal cutoff for tumor mutational burden in predicting the efficacy of anti-PD-(L)1 therapy for advanced cancers.

Background: The US Food and Drug Administration (FDA)'s tumor-agnostic approval of pembrolizumab in high tumor mutational burden (TMB-high, i.e., TMB≥10 mut/Mb) cases, based on the data from KEYNOTE-158, has raised considerable concerns among the immuno-oncology community. This study aims to statistically infer the optimal universal cutoff in defining TMB-high that is predictive of the efficacy of anti-PD-(L) 1 therapy in advanced solid tumors. Methods: We integrated MSK-IMPACT TMB data from a public cohort and the objective response rate (ORR) for anti-PD-(L) 1 monotherapy across diverse cancer types in published trials. The optimal TMB cutoff was determined by varying the universal cutoff to define TMB-high across cancer types and examining the cancer-level correlation between objective response rate and the proportion of TMB-high cases. The utility of this cutoff in predicting overall survival (OS) benefits from anti-PD-(L) 1 therapy was then evaluated in a validation cohort of advanced cancers with coupled MSK-IMPACT TMB and OS data. In silico analysis of whole-exome sequencing data from The Cancer Genome Atlas was further employed to assess the generalizability of the identified cutoff among panels comprising several hundred genes. Results: The cancer type-level analysis identified 10 mut/Mb as the optimal cutoff for MSK-IMPACT in defining TMB-high, with the corresponding TMB-high (TMB≥10 mut/Mb) percentage strongly correlated with ORR for PD-(L) 1 blockade across cancer types [correlation coefficient, 0.72 (95% CI, 0.45-0.88)]. This cutoff was also the optimum in defining TMB-high (via MSK-IMPACT) when predicting OS benefits from anti-PD-(L) 1 therapy in the validation cohort. In this cohort, TMB≥10 mut/Mb was associated with significantly improved OS (hazard ratio, 0.58 [95% CI, 0.48-0.71]; p < 0.001). Moreover, in silico analyses revealed excellent agreement of TMB≥10 mut/Mb cases between MSK-IMPACT and the FDA-approved panels and between MSK-IMPACT and various randomly sampled panels. Conclusion: Our study demonstrates that 10 mut/Mb is the optimal, universal cutoff for TMB-high that guides the clinical application of anti-PD-(L) 1 therapy for advanced solid tumors. It also provides rigorous evidence beyond KEYNOTE-158 for the utility of TMB≥10 mut/Mb in predicting the efficacy of PD-(L) 1 blockade in broader settings, which could help to mitigate the challenges in embracing the tumor-agnostic approval of pembrolizumab in TMB-high cases.

Exogenous gibberellin delays maturation in persimmon fruit through transcriptional activators and repressors.

As the harvest season of most fruit is concentrated, fruit maturation manipulation is essential for the fresh fruit industry to prolong sales time. Gibberellin (GA), an important phytohormone necessary for plant growth and development, has also shown a substantial regulatory effect on fruit maturation; however, its regulatory mechanisms remain inconclusive. In this research, preharvest GA3 treatment effectively delayed fruit maturation in several persimmon (Diospyros kaki) cultivars. Among the proteins encoded by differentially expressed genes, 2 transcriptional activators (NAC TRANSCRIPTION FACTOR DkNAC24 and ETHYLENE RESPONSIVE FACTOR DkERF38) and a repressor (MYB-LIKE TRANSCRIPTION FACTOR DkMYB22) were direct regulators of GERANYLGERANYL DIPHOSPHATE SYNTHASE DkGGPS1, LYSINE HISTIDINE TRANSPORTER DkLHT1, and FRUCTOSE-BISPHOSPHATE ALDOLASE DkFBA1, respectively, resulting in the inhibition of carotenoid synthesis, outward transport of an ethylene precursor, and consumption of fructose and glucose. Thus, the present study not only provides a practical method to prolong the persimmon fruit maturation period in various cultivars but also provides insights into the regulatory mechanisms of GA on multiple aspects of fruit quality formation at the transcriptional regulation level.

Comparative analysis of cystic biliary atresia and choledochal cysts.

Objective: Cystic biliary atresia (CBA) is a rare and peculiar type of biliary atresia (BA) that is easily confused with infantile choledochal cysts (CCs). This study explored information for early CBA diagnosis and treatment. Method: The authors retrospectively analyzed the clinical data of 32 children with hilar cysts from January 2013 to May 2021. According to the diagnosis, they were divided into the CBA (n = 12) and CC (n = 20) groups. Patient features, biochemical indexes, preoperative ultrasound characteristics, cholangiography features, and intraoperative findings were analyzed and compared between the two groups. Results: The alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin levels in the CBA group were higher than in the CCs group (P < 0.05). Additionally, B-mode ultrasound showed a cystic mass in front of the hepatic hilum, and the cyst size was much smaller in the CBA group compared with the CC group (2.2 ± 1.3 cm vs. 6.0 ± 2.2 cm, P < 0.001). Among all of the parameters, cyst width was the most accurate for identifying CBA and CCs. A cutoff value of 2.5 cm (area under the curve, 0.98, P < 0.001) showed 90.9% sensitivity and 95% specificity for cyst size. Conclusion: For children with early-onset severe jaundice, and if the width of the cystic mass was ≤2.5 cm, a diagnosis of CBA was highly likely. Early cholangiography and surgical treatment are necessary for the effective treatment of these infants.

Targeting the Epithelial-to-Mesenchymal Transition in Cancer Stem Cells for a Better Clinical Outcome of Glioma.

Glioma is one of the most common malignant tumors of the central nervous system with a poor prognosis at present due to lack of effective treatment options. Its initiation, migration, and multipotency are affected by cancer stem cell's transition. Previous studies imply that changes in the cancer stem cells can affect the malignant differentiation of the tumor. We found that the epithelial-to-mesenchymal transition (EMT)-related regulatory pathway is an important target for tumor therapy. In this review, we discuss the transition factor of EMT and 3 specific pathways that affect the EMT of cancer stem cells during tumor development. We conclude that targeting the EMT process of cancer stem cells can be a feasible approach in the treatment of glioma.

Energy Requirement of Patients Undergoing Hemodialysis: A Cross-Sectional Study in Multiple Centers.

BACKGROUND: Energy requirements must be estimated before nutritional care can be provided for patients undergoing hemodialysis (HD). However, the recommended caloric intake for patients has not been conclusively determined because of insufficiently large sample sizes. METHOD: This cross-sectional observational study recruited patients undergoing long-term HD from multiple centers as well as people in the general population without chronic kidney disease. People from both groups were matched by sex and age. Resting energy expenditure (REE) was estimated using an indirect calorimeter. Two commonly used equations for estimating REE and daily energy requirement recommended by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) were chosen. RESULTS: This study had 154 HD patients and 33 matched HD-control group pairs. Age (r = -0.36, p < 0.01) and dry body weight after dialysis (r = -0.36, p < 0.01) and dry body weight after dialysis (. CONCLUSIONS: Age and dry body weight are the main factors affecting the energy expenditure of HD patients. Furthermore, predicting the energy expenditure of HD patients by measuring the energy expenditure of their sedentary counterparts in the general population with the same sex, age range, and weight may yield better results than using traditional equations for predicting TEE. In East Asian populations, the TEE values were 32 and 30 kcal/kg dry weight for those aged <65 and ≥65 years, respectively. Future prospective cohort studies with larger sample sizes are needed.

Identification of cross-talk between m6A and 5mC regulators associated with onco-immunogenic features and prognosis across 33 cancer types.

Methylation of RNA and DNA, notably in the forms of N6-methyladenosine (m6A) and 5-methylcytosine (5mC) respectively, plays crucial roles in diverse biological processes. Currently, there is a lack of knowledge regarding the cross-talk between m6A and 5mC regulators. Thus, we systematically performed a pan-cancer genomic analysis by depicting the molecular correlations between m6A and 5mC regulators across ~ 11,000 subjects representing 33 cancer types. For the first time, we identified cross-talk between m6A and 5mC methylation at the multiomic level. Then, we further established m6A/5mC epigenetic module eigengenes by combining hub m6A/5mC regulators and informed a comprehensive epigenetic state. The model reflected status of the tumor-immune-stromal microenvironment and was able to predict patient survival in the majority of cancer types. Our results lay a solid foundation for epigenetic regulation in human cancer and pave a new road for related therapeutic targets.

Maximum Somatic Allele Frequency in Combination With Blood-Based Tumor Mutational Burden to Predict the Efficacy of Atezolizumab in Advanced Non-small Cell Lung Cancer: A Pooled Analysis of the Randomized POPLAR and OAK Studies.

Background: Blood-based tumor mutational burden (bTMB) was recently found to be suboptimal in predicting overall survival (OS) benefits of atezolizumab over docetaxel among patients with advanced non-small cell lung cancer (NSCLC). The maximum somatic allele frequency (MSAF) is an indicator of the proportion of tumor-derived plasma DNA, which could affect the concordance between bTMB and tissue-based TMB. Therefore, we aimed to evaluate the utility of MSAF, alone or in combination with bTMB, to identify NSCLC patients with or without survival benefit from atezolizumab over docetaxel. Methods: We analyzed the individual patient-level data from the randomized POPLAR and OAK studies. The bTMB and MSAF were derived from the pre-treatment blood-based genomic data. Results: In both the bTMB-high (i.e., bTMB ≥ 13) and bTMB-low subgroups, atezolizumab significantly improved OS compared with docetaxel (hazard ratio [HR] = 0.43 [95% CI, 0.29-0.65], P < 0.001 and HR = 0.73 [95% CI, 0.61-0.87], P < 0.001, respectively). Among patients with a low MSAF (i.e., MSAF < 10.3%), OS significantly favored atezolizumab (HR = 0.59 [95% CI, 0.48-0.72], P < 0.001), whereas OS with atezolizumab was similar to that with docetaxel in the MSAF-high subgroup (HR = 0.91 [95% CI, 0.68-1.20], P = 0.500; interaction test P = 0.017). Among patients from the bTMB-low and MSAF-high subgroup, OS was numerically worse with atezolizumab than with docetaxel (HR = 1.06 [95% CI, 0.78-1.45], P = 0.710); in contrast, OS was significantly improved with atezolizumab compared with docetaxel in those with either a high bTMB or low MSAF (HR = 0.57 [95% CI, 0.47-0.69], P < 0.001; interaction test P < 0.001). Consistent findings were obtained for progression-free survival data. Conclusions: MSAF alone or in combination with bTMB can effectively distinguish patients with or without survival benefit from atezolizumab compared with docetaxel. MSAF and the combined bTMB-MSAF classification may become practical predictive markers for atezolizumab in advanced NSCLC.

Proposal of a modified American Joint Committee on Cancer staging scheme for resectable pancreatic ductal adenocarcinoma with a lymph node ratio-based N classification: A retrospective cohort study.

The recently launched 8th edition of the American Joint Committee on Cancer (AJCC) staging scheme for pancreatic ductal adenocarcinoma (PDAC) did not account for the impact of the total examined lymph node count on prognostic accuracy. In this population-based cohort study, we proposed a modified AJCC staging scheme by incorporating a lymph node ratio (LNR)-based N classification for patients with resectable PDAC.We analyzed 8615 patients with resectable PDAC from the Surveillance, Epidemiology, and End Results database between 2004 and 2013. The optimal cut-off points for LNR were identified by recursive partitioning, and an LNR-based N classification was designed accordingly.The LNR-based N classification could further stratify patients with the 8th AJCC N1 and N2 disease into subgroups with significantly different overall survival (P < .001 for both). By replacing the 8th AJCC N classification with the corresponding LNR-based N classification, we further proposed a modified AJCC staging scheme. The modified AJCC staging outperformed the 8th AJCC staging in terms of the discriminatory capacity measured by the concordance index and Akaike information criterion, and the prognostic homogeneity assessed by using the likelihood ratio chi-squared test and stratified survival analysis.Replacing the 8th AJCC N classification with the LNR-based N classification can improve the prognostic performance of the 8th AJCC staging scheme for PDAC.

Equipping the 8th Edition American Joint Committee on Cancer Staging for Gastric Cancer with the 15-Node Minimum: a Population-Based Study Using Recursive Partitioning Analysis.

BAKCGROUND: The recently proposed 8th American Joint Committee on Cancer (AJCC) staging for gastric cancer (GC) did not include the evaluated lymph node (ELN) count as a prognostic indicator. In this study, we performed recursive partitioning analysis (RPA) to objectively combine the 15-ELN threshold and 8th AJCC stage to refine the staging for GC. METHODS: We analyzed 19,018 patients with non-metastatic GC from the Surveillance, Epidemiology, and End Results database. The dataset was randomly divided into training and validation sets. RESULTS: For each 8th AJCC stage, survival was significantly better for patients with ≥15 ELNs versus those with <15 ELNs (P < 0.001 for all). RPA divided non-metastatic GC into seven stages: RPA-IA (8th AJCC IA with ≥15 ELNs), RPA-IB (IA with <15 ELNs and IB/IIA with ≥15 ELNs), RPA-IIA (IB with <15 ELNs and IIB with ≥15 ELNs), RPA-IIB (IIA with <15 ELNs and IIIA with ≥15 ELNs), RPA-IIIA (IIB with <15 ELNs), RPA-IIIB (IIIA with <15 ELNs and IIIB ≥15 ELNs), and RPA-IIIC (IIIB with <15 ELNs and IIIC). The corresponding 5-year survival rates were 84.1, 70.3, 52.8, 41.4, 32.9, 21.7, and 10.2%, respectively (P < 0.001 for all pairwise comparisons). The RPA staging outperformed the 8th AJCC staging in terms of discrimination and homogeneity among the SEER training and validation sets, as well as an independent Chinese cohort. CONCLUSION: By equipping the 8th AJCC stage with the 15-ELN threshold, the proposed RPA staging is superior to the 8th AJCC staging without overcomplicating.

Equipping the American Joint Committee on Cancer staging for resectable pancreatic ductal adenocarcinoma with tumor grade: a recursive partitioning analysis.

Previous studies of pancreatic ductal adenocarcinoma (PDAC) have demonstrated that the addition of tumor grade to the 7th American Joint Committee on Cancer (AJCC) staging can provide improved prognostication and that the recently proposed 8th edition AJCC staging exhibited superior reproducibility to the 7th edition in resectable PDAC. Thus, we aimed to combine tumor grade and 8th AJCC stage to develop a refined staging scheme for resectable PDAC. We analyzed 7719 patients with resectable PDAC from the 2004-2012 Surveillance, Epidemiology, and End Results database. We performed recursive partitioning analysis (RPA) to objectively incorporate tumor grade with 8th AJCC stage into a novel staging system. The performance of the proposed RPA staging was assessed against the 8th AJCC staging in terms of discriminatory ability and prognostic homogeneity. For each 8th AJCC stage, survival was significantly worse for high-grade versus low-grade tumors. RPA divided resectable PDAC into five stages: RPA-IA (low-grade T1N0), RPA-IB (high-grade T1N0 or low-grade T2N0), RPA-IIA (high-grade T2N0 or low-grade T3N0/T1-T3N1), RPA-IIB (high-grade T3N0/T1-T3N1 or low-grade T1-T3N2), and RPA-III (high-grade T1-T3N2; median survival: 42, 26, 19, 15, and 12 months, respectively; P < 0.001). The RPA staging outperformed the 8th AJCC classifications in terms of discrimination (concordance index, 0.585 versus 0.565; P < 0.001) and prognostic homogeneity. Tumor grade can provide additional prognostic information to the 8th AJCC staging. The proposed RPA staging is a superior risk-stratified tool to the 8th AJCC staging and is not substantially more complex.

Ratio of C-Reactive Protein to Albumin Predicts Muscle Mass in Adult Patients Undergoing Hemodialysis.

Recent studies have indicated that the ratio of C-reactive protein to albumin (CRP-Alb ratio) is associated with clinical outcomes in patients with disease. We examined the predictive value of this ratio in patients undergoing hemodialysis (HD). In this cross-sectional study, 91 eligible adult HD patients were analyzed, and the correlation between the CRP-Alb ratio and skeletal muscle mass normalized for body weight (SMM/wt; estimated using a bioelectrical impedance analyzer) was investigated. The mean age of the study participants was 54.9 ± 6.6 years (ranging from 27 to 64 years); 43 (47.2%) were men. The mean values for the SMM/wt were 39.1% ± 5.4%. The CRP-Alb ratio was found to be negatively correlated with SMM/wt (r = -0.33, P = 0.002) and creatinine (r = -0.20, P = 0.056). All the univariate significant and nonsignificant relevant covariates were selected for multivariable stepwise regression analysis. We determined that the homeostasis model assessment-estimated insulin resistance and CRP-Alb ratio were independent risk determinants for SMM/wt (ßHOMA-IR = -0.18 and ßCRP-Alb ratio = -3.84, adjusted R2 = 0.32). This study indicated that the CRP-Alb ratio may help clinicians in predicting muscle mass in adult patients undergoing HD.

Ratio of dietary ω-3 and ω-6 fatty acids-independent determinants of muscle mass-in hemodialysis patients with diabetes.

OBJECTIVE: ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are essential nutrients in the human diet and possibly affect muscle mass. We evaluated the association between the dietary ratios of ω-3 and ω-6 PUFAs and muscle mass, indicated as skeletal muscle mass (SMM) and appendicular skeletal muscle mass (ASM), in patients with diabetes undergoing hemodialysis (HD). METHODS: In this cross-sectional study, data on 69 patients with diabetes who underwent standard HD therapy were analyzed. For estimating muscle mass, anthropometric and bioelectrical impedance analyses were conducted following dialysis. In addition, routine laboratory and 3-d dietary data were obtained. The adequate intake (AI) cut-off for ω-3 PUFAs was 1.6 g/d and 1.1 g/d for male and female patients, respectively. RESULTS: The average age of the participants was 63.0 ± 10.4 y. The mean ratios of ω-3/ω-6 PUFA intake, ω-6/ω-3 PUFA intake, SMM, and ASM of the patients were 0.13 ± 0.07, 9.4 ± 6.4, 24.6 ± 5.4 kg, and 18.3 ± 4.6 kg, respectively. Patients who had AI of ω-3 PUFAs had significantly higher SMM and ASM than did their counterparts. Linear and stepwise multivariable adjustment analyses revealed that insulin resistance and the ω-6/ω-3 PUFA ratio were the independent deleterious determinants of ASM normalized to height in HD patients. CONCLUSIONS: Patients with AI of ω-3 PUFAs had total-body SMM and ASM that were more appropriate. A higher dietary ratio of ω-6/ω-3 PUFAs was associated with reduced muscle mass in HD patients.

Ratio of Dietary n-6/n-3 Polyunsaturated Fatty Acids Independently Related to Muscle Mass Decline in Hemodialysis Patients.

BACKGROUND: n-3 polyunsaturated fatty acids (PUFAs) might be useful nutritional strategy for treating patients with sarcopenia. We evaluated the effect of the intake of dietary n-3 PUFAs on the skeletal muscle mass (SMM), appendicular skeletal muscle mass (ASM), and its determinants in patients receiving standard hemodialysis (HD) treatment for the management of end stage renal disease. METHODS: In this cross-sectional study, data of 111 HD patients were analyzed. Anthropometric and bioelectrical impedance measurements used to estimate the muscle mass were performed the day of dialysis immediately after the dialysis session. Routine laboratory and 3-day dietary data were also collected. The cutoff value of adequate intake (AI) for both n-3 PUFAs and alpha-linolenic acid (ALA) was 1.6 g/day and 1.1 g/day for men and women, respectively. RESULTS: The mean age, mean dietary n-3 PUFAs intake, ALA intake, ratio of n-6/n-3 PUFAs intake, SMM, and ASM of patients were 61.4 ± 10.4 years, 2.0 ± 1.3 g/day, 1.5 ± 1.0 g/day, 9.5 ± 6.7 g/day, 23.9 ± 5.5 kg, and 17.5 ± 4.5 kg, respectively. A higher SMM and ASM significantly observed in patients who achieved an AI of n-3 PUFAs. Similar trends appeared to be observed among those patients who achieved the AI of ALA, but the difference was not significantly, except for ASM (P = 0.047). No relevant differences in demographics, laboratory and nutritional parameters were observed, regardless of whether the patients achieved an AI of n-3 PUFAs. Multivariate analysis showed that the BMI and equilibrated Kt/V were independent determinants of the muscle mass. Moreover, the ratio of n-6/n-3 PUFAs was an independent risk determinant of reduced ASM in HD patients. CONCLUSION: Patients with an AI of n-3 PUFAs had better total-body SMM and ASM. A higher dietary ratio of n-6/n-3 PUFAs seemed to be associated with a reduced muscle mass in HD patients.

Association of Processed Meat Intake with Hypertension Risk in Hemodialysis Patients: A Cross-Sectional Study.

In this cross-sectional study, we hypothesized that hemodialysis patients consuming greater processed meat is associated with hypertension risk, which can be partly explained by the high sodium content in processed meat. From September 2013 to May 2014, one hundred and four patients requiring chronic hemodialysis treatment were recruited from hemodialysis centers. Data on systolic blood pressure and diastolic blood pressure before receiving dialysis, and 3-day dietary records of the recruited patients were collected. HD patients with systolic and diastolic blood pressures greater than140 mmHg and higher than 90 mmHg, respectively, were considered hypertension risk. Protein foods were divided into 4 categories: red meat, white meat, soybeans, and processed meat (e.g., sausage and ham). In a model adjusted for energy intake and hypertension history, additional servings of processed meats was positively associated to systolic blood pressure >140 mmHg (odds ratio [95% confidence interval]: 2.1 [1.0-4.3]), and diastolic blood pressure > 90 mmHg (odds ratio: 2.5 [1.2-5.5]). After adjustment for dietary sodium contents or body mass index (BMI), most associations were substantially attenuated and were no longer significant. In systolic blood pressure greater than140 mmHg, one serving per day of red meats (ß = -1.22, P < .05) and white meats (ß = -0. 75, P = .05) was associated with a reduced risk compared with one serving per day of processed meats. Similarly, compared with one serving per day of processed meat, a reduced risk of diastolic blood pressure higher than 90 mmHg was associated with one serving per day of red meat (ß = -1. 59, P < .05), white meat (ß = -0. 62, P < .05). Thus, in these hemodialysis patients, intake of processed meat is significantly positively associated with higher blood pressure risk, and both sodium contents in processed meat and BMI significantly contributes to this association.

InGaN working electrodes with assisted bias generated from GaAs solar cells for efficient water splitting.

Hydrogen generation through water splitting by n-InGaN working electrodes with bias generated from GaAs solar cell was studied. Instead of using an external bias provided by power supply, a GaAs-based solar cell was used as the driving force to increase the rate of hydrogen production. The water-splitting system was tuned using different approaches to set the operating points to the maximum power point of the GaAs solar cell. The approaches included changing the electrolytes, varying the light intensity, and introducing the immersed ITO ohmic contacts on the working electrodes. As a result, the hybrid system comprising both InGaN-based working electrodes and GaAs solar cells operating under concentrated illumination could possibly facilitate efficient water splitting.

Myocardium and microvessel endothelium apoptosis at day 7 following reperfused acute myocardial infarction.

OBJECTIVES: This study was to investigate the salvaged myocardial and microvascular endothelial cells apoptosis at the first week of reperfused acute myocardial infarction (AMI). METHODS: Sixteen mini swines (20-30 kg) were randomly assigned to the sham-operated group and the AMI group. The acute myocardial infarction and reperfusion model was created, and pathologic myocardial tissue was collected at day 7 following left anterior descending coronary artery reperfusion, and detected by transmission electron microscope, in situ cell apoptosis detection (TUNEL method), Real-time Quantitative Polymerase Chain Reaction and Western blot. RESULTS: In the AMI group, the infarcted area showed the myolysis, fibroblast and injuried endothelial cells under transmission electron microscope. The infarcted area had higher apoptotic index of microvascular endothelial cells than the marginal area, the normal area, and the sham-operated area (all P<0.05). Fas and Bax mRNA expressions in the infarcted area were higher than those in the marginal area, the normal area, and the sham-operated area (all P<0.05), and both protein overexpressions and Bcl-2 low expression in the infarcted and marginal areas compared with the normal area and the sham-operated area. CONCLUSIONS: The overexpressions of Fas and Bax or the low expression of Bcl-2 in the infarcted and marginal heart tissue may play an important role in the acceleration of myocardial and endothelial apoptosis at 7th day following reperfused acute myocardial infarction.