Acupuncture at "Die E acupoint" alleviates inflammatory reaction via inhibiting TLR4/MyD88/NF-κB signaling in rats with allergic rhinitis. / 基于Tollæ ·å—ä½“4/é«“æ ·åˆ†åŒ–å› å­88/æ ¸è½¬å½•å› å­κB信号通路探讨针刺"è¶è ­ç©´"æ”¹å–„å˜åº”æ€§é¼»ç‚Žå¤§é¼ å ç–«ç‚Žæ€§ååº”çš„æœºåˆ¶.

OBJECTIVES: To observe effects of acupuncture at "Die E acupoint" on the protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB), transcription factor T-bet (T-bet), and GATA-binding protein-3 (GATA-3) in the nasal mucosa and the serum contents of related inflammatory cytokines in rats with allergic rhinitis, so as to explore the mechanism of acupuncture in treating allergic rhinitis. METHODS: Twenty-four healthy SD rats were randomly divided into blank, model, acupuncture, and sham acupuncture groups, with 6 rats in each group. The rat model of allergic rhinitis was established by using ovalbumin induction. The rats in the acupuncture group received bilateral acupuncture at the "Die E acupoint" with a depth of 15-20 mm, while the rats in the sham acupuncture group received only sham acupuncture (light and shallow acupunture of the skin at the "Die E acupoint" ). Both interventions were performed once daily for a total of 6 days. Behavioral scores of rats in each group were recorded. Pathological changes of nasal mucosa were observed by H.E. staining. Serum contents of IgE, ovalbumin-specific IgE (OVA-sIgE), interferon(IFN)-γ, interleukin(IL)-4, IL-10 and IL-17 were measured by ELISA and the protein expression levels of T-bet, GATA-3, TLR4, MyD88 and NF-κB p65 in the nasal mucosa were detected by Western blot. RESULTS: After modeling, compared with the blank group, rats in the model group showed increased behavioral scores, serum IgE, OVA-sIgE, IL-4, and IL-17 contents, and nasal mucosal GATA-3, TLR4, MyD88, and NF-κB p65 protein expression levels (P<0.05), whereas the contents of serum IFN-γ, IL-10 and the protein expression level of T-bet in the nasal mucosa were decreased (P<0.05). Comparison between the EA and model groups showed that acupuncture intervention can decrease the behavioral scores of rats with allergic rhinitis, the contents of serum IgE, OVA-sIgE, IL-4, IL-17, and the protein expression levels of GATA-3, TLR4, MyD88, and NF-κB p65 in the nasal mucosa (P<0.05), and up-regulate the contents of serum IFN-γ, IL-10, and the nasal mucosal T-bet protein expression level. Sham acupuncture did not have a significant modulating effect on the above indicators. Inflammatory infiltration of nasal mucosa was seen in the model group and sham acupuncture, and the inflammatory reaction was milder in the acupuncture group. CONCLUSIONS: Acupuncture at "Die E acupoint" can alleviate the symptoms of allergic rhinitis and suppress the inflammation of nasal mucosa in rats, which may be related to inhibiting the TLR4/MyD88/NF-κB signaling and balancing the levels of cytokines of Th1/Th2 and Treg/Th17, and T-bet/GATA-3.

Association of ambient ozone exposure and greenness exposure with hemorrhagic stroke mortality at different times: A cohort study in Shandong Province, China.

Evidence on the association between long-term ozone exposure and greenness exposure and hemorrhagic stroke (HS) is limited, with mixed results. One potential source of this inconsistency is the difference in exposure time metrics. This study aimed to investigate the association between long-term exposure to ambient ozone, greenness, and mortality from HS using exposure metrics at different times. We also examined whether greenness exposure modified the relationship between ozone exposure and mortality due to HS. The study population consisted of 45771 participants aged ≥40 y residing in 20 counties in Shandong Province who were followed up from 2013 to 2019. Ozone exposure metrics (annual mean and warm season) and the normalized difference a measure of greenness exposure, were calculated. The relationship between environmental exposures (ozone and greenness exposures) and mortality from HS was assessed using time-dependent Cox proportional hazards models, and the modification of greenness exposure was examined using stratified analysis with interaction terms. The person-years at the end of follow-up were 90,663. With full adjustments, the risk of death from hemorrhagic stroke increased by 5% per interquartile range increase in warm season ozone [hazard ratio =1.05; 95 % confidence interval: 1.01-1.08]. No clear association was observed between annual ozone and mortality HS. Both the annual and summer NDVI were found to reduce the risk of HS mortality. The relationships were influenced by age, sex, and residence (urban or rural). Furthermore, greenness exposure was shown to have a modifying effect on the relationship between ozone exposure and the occurrence of HS mortality (P for interaction = 0.001). Long-term exposure to warm season O3 was positively associated with HS mortality, while greenness exposure was inversely associated with HS mortality. Greenness exposure may mitigate the negative effects of warm season ozone exposure on HS mortality.

Identification of a novel compound heterozygous pathogenic variant in MYO7A causing Usher syndrome type IB in a Chinese patient: a case report.

Herein, we report the clinical and genetic features of a patient with Usher syndrome type IB to improve our collective understanding of the disorder. The patient was a teenaged boy with congenital profound hearing loss, progressive visual loss, and vestibular hypoplasia; his parents were phenotypically normal. His pure tone audiometry hearing thresholds were 100 dB at all frequencies, and distortion product otoacoustic emission was not elicited at any frequencies in either ear. Moreover, an auditory brainstem response test at 100 dB normal hearing level revealed no relevant response waves, and a caloric test showed vestibular hypoplasia. Fundus examination revealed retinitis pigmentosa and a reduced visual field. The use of high-throughput sequencing technology to screen the patient's family lineage for deafness-related genes revealed that the patient carried a compound heterozygous pathogenic variant of MYO7A: c.541C > T and c.6364delG. This pathogenic variant has not previously been reported. Our findings may provide a basis for genetic counseling, effective treatment, and/or gene therapy for Usher syndrome.

Effects of greenness in university campuses on test anxiety among Chinese university students during COVID-19 lockdowns: a correlational and mediation analysis.

The purpose of this study is to investigate the correlations of greenness exposure with test anxiety among university students during COVID-19 lockdowns and to explore their mechanisms. We conducted a cross-sectional study with 2609 university students in Anhui and Shandong provinces, China. We assessed perceived campus greenness using a five-point Likert scale for quality, visibility, abundance, usage, and accessibility. Objective greenness was estimated via average normalised difference vegetation index (NDVI) in 1,000-, 1,500-, and 2,000-m radius zones around each of the campuses. A generalised linear mixed model examined the associations between greenness and test anxiety and to evaluate the mediation effects of physical activity, body mass index (BMI), and air pollution. Results showed that higher NDVI1500-m correlated with lower test anxiety (OR = 0.871; 95% CI: 0.851, 0.891), physical activity may partially mediate this association. Increased campus greenness may alleviate test anxiety among Chinese university students.

Association of greenness with the disease burden of lower respiratory infections and mediation effects of air pollution and heat: a global ecological study.

Exposure to greenness is increasingly linked to beneficial health outcomes, but the associations between greenness and the disease burden of lower respiratory infections (LRIs) are unclear. We used the normalized difference vegetation index (NDVI) and the leaf area index (LAI) to measure greenness and incidence, death, and disability-adjusted life years (DALYs) due to LRIs to represent the disease burden of LRIs. We applied a generalized linear mixed model to evaluate the association between greenness and LRI disease burden and performed a stratified analysis, after adjusting for covariates. Additionally, we assessed the potential mediating effects of fine particulate matter (PM2.5), ozone (O3), nitrogen dioxide (NO2), and heat on the association between greenness and the disease burden of LRIs. In the adjusted model, one 0.1 unit increase of NDVI and 0.5 increase in LAI were significantly inversely associated with incidence, death, and DALYs due to LRIs, respectively. Greenness was negatively correlated with the disease burden of LRIs across 15-65 age group, both sexes, and low SDI groups. PM2.5, O3, and heat mediated the effects of greenness on the disease burden of LRIs. Greenness was significantly negatively associated with the disease burden of LRIs, possibly by reducing exposure to air pollution and heat.

Postmortem biochemical analysis of soluble ST2 in the pericardial fluid of patients with sudden cardiac death caused by ischemic heart disease: a pilot study.

Soluble growth stimulation expressed gene 2 protein (sST2) is a myocardial protein induced by biomechanical stress. sST2 is widely present in the serum of patients with heart failure and is recommended as an important indicator to predict adverse outcomes in these patients. However, no postmortem biochemical analysis of sST2 in forensic practice has been reported. The present pilot study aimed to investigate the expression of sST2 in the pericardial fluid of patients with sudden cardiac death (SCD) caused by ischemic heart disease (IHD). In addition, to explore the relationship of sST2 with CK-MB, cTnT, and NT-proBNP, which have been proven to be auxiliary biomarkers for the diagnosis of SCD, we analyzed CK-MB, cTnT, NT-proBNP, and sST2 levels in twenty-one pericardial fluid samples from the Center of Forensic Investigation, China Medical University, with a Roche cobas e 411 electrochemiluminescence automatic immunoassay system and ST2/IL-33R Valukine™ enzyme-linked immunosorbent assay kit. The levels of sST2 in the pericardial fluid of patients with SCD caused by IHD were significantly increased (P < 0.01) and positively correlated with CK-MB and NT-proBNP (P < 0.0001). Receiver operating characteristic curve analysis indicated that the combined measurement of sST2 and NT-proBNP has a higher diagnostic value for SCD caused by IHD than the measurement of either indicator alone. This study preliminarily demonstrated that sST2 in the pericardial fluid was significantly increased in patients with SCD caused by IHD and might be used as a novel auxiliary biomarker for postmortem diagnosis of SCD in forensic practice.

Exercise Preconditioning Ameliorates Cognitive Impairment in Mice with Ischemic Stroke by Alleviating Inflammation and Modulating Gut Microbiota.

Several studies have demonstrated that exercise preconditioning is an effective means of alleviating poststroke cognitive impairment (PSCI). Mechanisms of regulating cognitive function have not been fully elucidated. Herein, the present study is aimed at exploring the effect of the microbiota-gut-inflammasome-brain axis in the process of exercise preconditioning moderating cognitive impairment after ischemic stroke. We observed that exercise preconditioning decreased infarct size, reduced the degree of neuronal damage, and alleviated cognitive impairment in mice with ischemic stroke. In addition, exercise preconditioning also reduced the expression of inflammatory cytokines, as well as NLRP3, Caspase-1, IL-18, and IL-1ß protein expressions. Ischemic stroke could downregulate the abundance of Roseburia while increasing the abundance of the Helicobacter at the level of genus. As a comparison, exercise preconditioning increased the abundance of the Lactobacillus, which was beneficial for mice at the genus level. In conclusion, exercise preconditioning can improve cognitive dysfunction after ischemic stroke through alleviating inflammation and regulating the composition and diversity of the gut microbiota, which might provide a new strategy for the prevention of PSCI.

Myocardial Injury Caused by Chronic Alcohol Exposure-A Pilot Study Based on Proteomics.

Chronic alcohol exposure can cause myocardial degenerative diseases, manifested as cardiac insufficiency, arrhythmia, etc. These are defined as alcoholic cardiomyopathy (ACM). Alcohol-mediated myocardial injury has previously been studied through metabolomics, and it has been proved to be involved in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway concerning unsaturated fatty acids biosynthesis and oxidative phosphorylation, which tentatively explored the mechanism of ACM induced by chronic drinking. To further study alcohol-induced myocardial injury, myocardial specimens from a previously successfully established mouse model of ACM were subjected to histological, echocardiographic, and proteomic analyses, and validated by real-time quantitative polymerase chain reaction (qPCR). Results of histopathology and echocardiography showed the hypertrophy of cardiomyocytes, the dilation of ventricles, and decreased cardiac function. Proteomic results, available via ProteomeXchange with identifier PXD032949, revealed 56 differentially expressed proteins (DEPs) were identified, which have the potential to be involved in the KEGG pathway related to fatty acid biosynthesis disorders, lipid metabolism disorders, oxidative stress, and, ultimately, in the development of dilated cardiomyopathy (DCM). The present study further elucidates the underlying effects of myocardial injury due to chronic alcohol intake, laying a foundation for further studies to clarify the potential mechanisms of ACM.

City-level greenness exposure is associated with COVID-19 incidence in China.

Accumulating studies have suggested an important role of environmental factors (e.g. air pollutants) on the occurrence and development of coronavirus disease 2019 (COVID-19). Evidence concerning the relationship of greenness on COVID-19 is still limited. This study aimed to assess the association between greenness and COVID-19 incidence in 266 Chinese cities. A total of 12,377 confirmed COVID-19 cases were identified through February 29th, 2020. We used the average normalized difference vegetation index (NDVI) during January and February 2020 from MOD13A2 product, to represent the city-level greenness exposure. A generalized linear mixed-effects model was used to estimate the association between NDVI exposure and COVID-19 incidence using COVID-19 cases as the outcome. We evaluated whether the association was modified by population density, GDP per capita, and urbanization rate, and was mediated by air pollutants. We also performed a series of sensitivity analyses to discuss the robustness of our results. Per 0.1 unit increment in NDVI was negatively associated with COVID-19 incidence (IRR: 0.921, 95% CI: 0.898, 0.944) after adjustment for confounders. Associations with COVID-19 incidence were stronger in cities with lower population density, lower GDP per capita, and lower urbanization rate. We failed to detect any mediation effect of air pollutants on the association between NDVI and COVID-19 incidence. Sensitivity analyses also indicated consistent estimates. In conclusion, our study suggested a beneficial association between city-level greenness and COVID-19 incidence. We could not establish which mechanisms may explain this relationship.

Fatal methanol poisoning with different clinical and autopsy findings: Case report and literature review.

Methanol poisoning is responsible for high morbidity and mortality, and the elevated concentration of methanol in the body is the major criteria for forensic diagnosis of methanol poisoning. However, in cases with lower methanol concentrations, diagnosis is mainly dependent on highly variable postmortem manifestations.Herein, we report a fatal methanol poisoning cases that two subjects ingested the same amount of methanol simultaneously, yet the subject one presented only non-specific gastrointestinal and mild central nervous system symptoms, while the other subject exhibited typical toxic manifestations with the exception of visual compromise. In autopsy, subject number 1 did not show typical pathological changes caused by methanol poisoning, except for the elevated levels of methanol in body fluids. On the contrary, bilateral basal ganglia hemorrhage and necrosis caused by methanol-induced brain lesion was observed in case number 2. Due to the complex and multifactorial process of methanol intoxication, many factors, including comprehensive autopsy, quantitative detection of methanol and formic acid, and genotype analysis, participate in its metabolism and toxicity, and can impact the clinical symptoms, prognosis and postmortem manifestations. Therefore, a combination of multiple diagnosis methods may more accurately contribute to the forensic diagnosis of methanol poisoning and should be tailored on an individual basis. This case report also reviews forensic diagnosis literature on methanol poisoning to provide a reference for forensic pathologists.

Association Analyses of SNAP25, HNMT, FCHSD1, and DBH Single-Nucleotide Polymorphisms with Parkinson's Disease in a Northern Chinese Population.

PURPOSE: Sequencing potentially causal and susceptible genes and genome-wide association studies in samples from Parkinson's disease (PD) patients has revealed several related loci. The genes for synaptosome-associated protein of 25 kDa (SNAP25), histamine-N-methyltransferase (HNMT), FCH and double SH3 domains 1 (FCHSD1) and dopamine ß-hydroxylase (DBH) are candidate loci and have not been studied in a northern Chinese population. We explored the genetic distribution of four single-nucleotide polymorphisms (rs3746544, rs11558538, rs456998, rs129882) located on SNAP25, HNMT, FCHSD1 and DBH, respectively. PATIENTS AND METHODS: A total of 330 patients with sporadic PD and 332 healthy controls (HCs) were recruited from a northern Chinese population. Polymerase chain reaction restriction fragment length polymorphism was used to genotype these four SNPs. RESULTS: After statistical analyses and correction of the genotyping results, the mutant-allele T in rs456998 of FCHSD1 was found to be significantly related to reducing the PD risk (P = 0.029, OR = 0.754, 95% CI = 0.586-0.971, power = 0.591). However, rs3746544, rs11558538, and rs129882 did not show an association with PD. CONCLUSION: FCHSD1 rs456998 may have a protective role in PD in a northern Chinese population, but more studies are needed to support this suggestion.

A Pilot Metabolomic Study on Myocardial Injury Caused by Chronic Alcohol Consumption-Alcoholic Cardiomyopathy.

Chronic alcohol consumption leads to myocardial injury, ventricle dilation, and cardiac dysfunction, which is defined as alcoholic cardiomyopathy (ACM). To explore the induced myocardial injury and underlying mechanism of ACM, the Liber-DeCarli liquid diet was used to establish an animal model of ACM and histopathology, echocardiography, molecular biology, and metabolomics were employed. Hematoxylin-eosin and Masson's trichrome staining revealed disordered myocardial structure and local fibrosis in the ACM group. Echocardiography revealed thinning wall and dilation of the left ventricle and decreased cardiac function in the ACM group, with increased serum levels of brain natriuretic peptide (BNP) and expression of myocardial BNP mRNA measured through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (PCR), respectively. Through metabolomic analysis of myocardium specimens, 297 differentially expressed metabolites were identified which were involved in KEGG pathways related to the biosynthesis of unsaturated fatty acids, vitamin digestion and absorption, oxidative phosphorylation, pentose phosphate, and purine and pyrimidine metabolism. The present study demonstrated chronic alcohol consumption caused disordered cardiomyocyte structure, thinning and dilation of the left ventricle, and decreased cardiac function. Metabolomic analysis of myocardium specimens and KEGG enrichment analysis further demonstrated that several differentially expressed metabolites and pathways were involved in the ACM group, which suggests potential causes of myocardial injury due to chronic alcohol exposure and provides insight for further research elucidating the underlying mechanisms of ACM.

Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis.

The prevention and diagnosis of sudden cardiac death (SCD) are among the most important keystones and challenges in clinical and forensic practice. However, the diagnostic value of the current biomarkers remains unresolved issues. Therefore, novel diagnostic biomarkers are urgently required to identify patients with early-stage cardiovascular diseases (CVD), and to assist in the postmortem diagnosis of SCD cases without typical cardiac damage. An increasing number of studies show that circular RNAs (circRNAs) have stable expressions in myocardial tissue, and their time- and tissue-specific expression levels might reflect the pathophysiological status of the heart, which makes them potential CVD biomarkers. In this article, we briefly introduced the biogenesis and functional characteristics of circRNAs. Moreover, we described the roles of circRNAs in multiple SCD-related diseases, including coronary artery disease (CAD), myocardial ischemia or infarction, arrhythmia, cardiomyopathy, and myocarditis, and discussed the application prospects and challenges of circRNAs as a novel biomarker in the clinical and forensic diagnosis of SCD.

CircSLC8A1 and circNFIX can be used as auxiliary diagnostic markers for sudden cardiac death caused by acute ischemic heart disease.

Sudden cardiac death (SCD) caused by acute ischemic heart disease (IHD) is a major cause of sudden death worldwide. Circular RNAs (circRNAs) are abundant in the heart and play important roles in cardiovascular diseases, but the role of circRNAs as biomarkers in the forensic diagnosis of SCD caused by acute IHD remains poorly characterized. To investigate the potential of two heart-enriched circRNAs, circNFIX and circSLC8A1, we explored the expression of these two circRNAs in different kinds of commonly used IHD models, and further verified their expressions in forensic autopsy cases. The results from both the IHD rat and H9c2 cell models revealed that circSlc8a1 level was upregulated, while the circNfix level was elevated in the early stage of ischemia and subsequently downregulated. The time-dependent expression patterns of the two circRNAs suggested their potential as SCD biomarkers. In autopsy cases, the results showed that the expression of these two circRNAs in the myocardium with acute IHD-related SCDs corresponded to the observations in the ischemic models. Further analysis related to myocardial ischemia indicated that circSLC8A1 showed high sensitivity and specificity for myocardial infarction and was positively correlated with creatine kinase MB in pericardial fluid. Downregulated circNFIX level could indicate the ischemic myocardial damage, and it was negatively correlated with the coronary artery stenosis grade. The combination of circSLC8A1 and circNFIX had better performance to discriminate IHD-related SCDs. The results suggested that circSLC8A1 and circNFIX may be used as auxiliary diagnostic markers for SCD caused by acute IHD in forensic medicine.

The Estimation of Postmortem Serum Urea via the Ultrafiltration of Hemolyzed Blood.

Postmortem serum urea has been demonstrated as an objective indicator for the forensic diagnosis of cause of death. However, samples used in postmortem biochemical analysis are always affected by hemolysis. To investigate whether hemolysis affects the biochemical analysis of urea and to explore the feasibility of using ultrafiltration to process hemolyzed blood samples, three different levels of hemolyzed blood samples were used to assess the influence of hemolysis on postmortem biochemical analysis of urea, and two ultrafiltration methods were used to process the hemolyzed blood samples. Bias% was used to assess the interference of hemolysis. Our results showed that heavy hemolysis had a significant influence on the biochemical analysis of urea. Both ultrafiltration methods in the present study could significantly reduce the interference of hemolysis, with the |bias%| of methods A and B decreasing from 69.74% ± 99.14% to 12.18% ± 7.23% and 10.77% ± 8.09%, respectively, compared to the original serum. After regression correction, there was no significant difference between the urea concentration in the ultrafiltrates of the two ultrafiltration methods and that in the original serum, which suggested that the postmortem serum urea concentration could be estimated by the corrected urea concentration in the ultrafiltrate. The current study also provided possible pretreatment methods for postmortem biochemical analysis of other biomarkers in hemolyzed blood samples of forensic practice.

Systematic sequence analysis of the FUT3 gene identifies 11 novel alleles in the Sindhi and Punjabi populations from Pakistan.

The FUT3 (Lewis) gene is responsible for the expression of Lewis fucosyltransferase, which is required for the synthesis of the structural determinants of both Lewisa and Lewisb specificity. These factors play an important role not only in clinical but also in medico-legal investigations. The gene sequence is highly polymorphic and ethnically specific. In the current study, we performed systematic sequence analysis of the coding region of FUT3 by DNA sequencing to investigate the genetic variations of FUT3 and the molecular basis of the Lewis phenotype in the Sindhi and Punjabi populations of Pakistan. Twenty-three point mutations were observed, including 7 unreported mutations, among which two missense mutations (490 G > A and 959 T > C) were predicted to be deleterious to enzyme activity by software assessment. In total, we observed 24 Lewis alleles, including 11 novel ones. However, all unreported missense mutations were present in Lewis-negative alleles confirmed previously. According to genotypic data, the Lewis-negative phenotypic frequencies were 11.5% and 22.93% in the Sindhi and Punjabi ethnic groups, respectively. Moreover, we found that le202,314 and le59,1067 were predominant among Lewis-negative alleles, while the frequency of le59,1067 in the Punjabi population was significantly higher than that in the Sindhi population. In summary, our study revealed that there is a relatively high degree of sequence variation of the Lewis gene in Pakistani populations and provided the first genetic data on FUT3 in these two ethnic groups from Pakistan. The allele types and their frequencies showed that these ethnic groups exhibit more Caucasian components.

The Expression of BNP, ET-1, and TGF-ß1 in Myocardium of Rats with Ventricular Arrhythmias.

Ventricular arrhythmia (VA) is a major component of sudden cardiac death (SCD). To investigate the expression of brain natriuretic peptide (BNP), endothelin-1 (ET-1), and transforming growth factor-beta 1 (TGF-ß1) during VA, we established a rat model of VA induced by BaCl2 solution through a microinjector pump. PD142893 (ET-1 receptor blocker) and SB431542 (TGF-ß1 receptor type I blocker) were used to explore the effect of ET-1 and TGF-ß1 on BNP expression in the myocardium after VA. BNP, ET-1, and TGF-ß1 in rat myocardium were assayed by western blot and immunohistochemical staining for proteins, and real-time quantitative polymerase chain reaction for mRNAs. We found increased expression of BNP and ET-1 in rat myocardium that was associated with the duration of VA. However, TGF-ß1 protein expression remained unchanged. Such early increases in BNP and ET-1 may be attributed to fatal arrhythmias associated with SCD, suggesting these may be novel biomarkers of this disease. After intraperitoneal injection of PD142893 and SB431542, respectively, BNP was downregulated in the myocardium of the left ventricle; however, this was abrogated by co-application of the two inhibitors. These results suggested that both ET-1 and TGF-ß1, by specifically binding to their receptors, might be involved in the myocardial synthesis of BNP during VA in vivo.

Differential expression of B-type natriuretic peptide between left and right ventricles, with particular regard to sudden cardiac death.

The aim of the present study was to investigate the differential expression of B­type natriuretic peptide (BNP) between the left and right ventricle (RV) in sudden cardiac death (SCD). A total of 26 forensic autopsy cases of sudden death (survival time <30 min, postmortem interval <48 h or frozen within 6 h following death) in the present institute were examined. The cases consisted of acute ischemic heart disease (AIHD, n=15) with/without apparent myocardial necrosis as a sign of infarction (acute myocardial infarction, n=6; ischemic heart disease, IHD, n=9), and arrhythmogenic right ventricular cardiomyopathy (ARVC/D, n=5), in addition to traffic accidents and high falls without any pre existing heart disease as control (C, total n=6). BNP was investigated in all cases by the colloidal gold method, hematoxylin­eosin staining, immunohistochemistry (IHC) and the molecular pathological method. The IHC results demonstrated that a positive BNP immunostaining was detected in all groups; however, there was no difference between different causes of death. Pericardial N­terminal (NT)­proBNP concentration was significantly increased in deaths resulting from AIHD and ARVC/D compared with control group. The relative quantification of BNP mRNA demonstrated that relative expression levels of BNP mRNA were significantly increased in the left ventricle (LV) in the AIHD group, and in the RV of the ARVC/D group. The relative quantification difference and ratio of BNP mRNA between LV and RV demonstrated a significantly greater value in the AIHD group compared with control group. BNP mRNA in myocardium and NT­proBNP concentration in pericardial fluid were elevated in SCD patients, and left ventricular dysfunction predominated in AIHD patients, whereas right ventricular dysfunction predominated in ARVC/D patients. The results of the present study suggest the possible use of molecular pathology of BNP for the determination of terminal cardiac function in SCD and analysis of its fatal mechanism in forensic practice.

The Expression of B-Type Natriuretic Peptide After CaCl2-Induced Arrhythmias in Rats.

To investigate the patterns of B-type natriuretic peptide (BNP) expression after arrhythmia, BNP was assessed at different time points (0 minute, 10 minutes, 30 minutes, 1 hour, 3 hours, and 6 hours) in CaCl2-induced arrhythmia in rats through various methods such as immunohistochemistry, Western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Immunohistochemistry results showed that the expression of BNP in the endocardium was higher than that in the epicardium in rats undergoing sustained arrhythmias. The BNP-to-GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratios determined by Western blotting analysis revealed no change at 0 minute but increased at 10 minutes and reached the first peak (0.48 [0.03]) at 30 minutes. After a brief decline, the second peak was observed at 6 hours (0.54 [0.03]). Similar patterns of BNP messenger RNA expression were also observed by quantitative real-time polymerase chain reaction. The plasma BNP concentrations did not change after initial bouts of cardiac arrhythmias but significantly increased 30 minutes after CaCl2 injections. The results demonstrate that arrhythmia causes an elevation of BNP in the myocardium and blood, and BNP messenger RNA increases in initial arrhythmia while its protein in myocardium and plasma does not; however, both of them were elevated after sustained arrhythmia. Such an elevated BNP expression, which is directly related to the severity and duration of the arrhythmias, may suggest the existence of fatal arrhythmia in sudden cardiac death.