Detecting G protein-coupled receptor complexes in postmortem human brain with proximity ligation assay and a Bayesian classifier

Despite the controversy regarding the existence and physiological relevance of class A G protein-coupled receptor dimerization, there is substantial evidence for functional interactions between the dopamine D2 receptor (D2R) and the adenosine A2A receptor (A2AR). A2AR-D2R complexes have been detected in rodent brains by proximity ligation assay; however, their existence in the human brain has not been demonstrated. In this study, we used Brightfield proximity ligation assay, combined with a systematic sampling and a parameter-free naive Bayesian classifier, and demonstrated proximity between the D2R and the A2AR in the adult human ventral striatum, consistent with their colocalization within complexes and the possible existence of D2R-A2AR heteromers. These methods are applicable to the relative quantification of proximity of two proteins, as well as the expression levels of individual proteins

Gender-Specific and U-Shaped Relationship Between Serum Uric Acid and All-Cause Mortality Among Chinese Older Adults: A National Population-Based Longitudinal Study

Objectives: This study aimed to prospectively investigate gender-specific relationship between hyperuricemia and all-cause mortality among Chinese older adults.Methods: The study was based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2008–2018, a prospective nationwide cohort of older adults in China. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for all-cause mortality. Restricted cubic splines (RCS) were conducted to explore the dose-response relationship between SUA levels and all-cause mortality.Results: For older women, compared to the participants in the third quartile of SUA level, those in the highest quartile of SUA was associated with significantly higher risk of all-cause mortality in the fully adjusted model (HR: 1.41, 95% CI: 1.03–1.92). No significant associations between SUA levels and all-cause mortality were observed in older men. The present study further found a U-shaped non-linear relationship between SUA levels and all-cause mortality in both sexes of older population (P for non-linear <0.05).Conclusions: This study provided prospective epidemiological evidence for the predictive role of SUA on all-cause mortality among the Chinese aging population over 10 years of follow-up, while revealing considerable gender-related differences

Detecting G protein-coupled receptor complexes in postmortem human brain with proximity ligation assay and a Bayesian classifier

Despite the controversy regarding the existence and physiological relevance of class A G protein-coupled receptor dimerization, there is substantial evidence for functional interactions between the dopamine D2 receptor (D2R) and the adenosine A2A receptor (A2AR). A2AR-D2R complexes have been detected in rodent brains by proximity ligation assay; however, their existence in the human brain has not been demonstrated. In this study, we used Brightfield proximity ligation assay, combined with a systematic sampling and a parameter-free naive Bayesian classifier, and demonstrated proximity between the D2R and the A2AR in the adult human ventral striatum, consistent with their colocalization within complexes and the possible existence of D2R-A2AR heteromers. These methods are applicable to the relative quantification of proximity of two proteins, as well as the expression levels of individual proteins.METHOD SUMMARY : Brightfield proximity ligation assay was used to assess the expression of G protein-coupled receptors and their proximity in postmortem adult human brains. A novel automated machine learning method (Bayesian optimized PLA signal sorting) was developed to automatically quantify Brightfield proximity ligation assay data

Hypomethylation of ABCG1 in peripheral blood as a potential marker for the detection of coronary heart disease

Abstract Background Novel molecular biomarkers for the risk assessment and early detection of coronary heart disease (CHD) are urgently needed for disease prevention. Altered methylation of ATP-binding cassette subfamily G member 1 (ABCG1) has been implicated in CHD but was mostly studied in Caucasians. Exploring the potential relationship between ABCG1 methylation in blood and CHD among the Chinese population would yield valuable insights. Methods Peripheral blood samples were obtained from a case–control study (287 CHD patients vs. 277 controls) and a prospective nested case–control study (171 CHD patients and 197 matched controls). DNA extraction and bisulfite-specific PCR amplification techniques were employed for sample processing. Quantitative assessment of methylation levels was conducted using mass spectrometry. Statistical analyses involved the utilization of logistic regression and nonparametric tests. Results We found hypomethylation of ABCG1 in whole blood was associated with the risk of CHD in both studies, which was enhanced in heart failure (HF) patients, female and younger subjects. When combined with baseline characteristics, altered ABCG1 methylation showed improved predictive effect for differentiating CHD cases, ischemic cardiomyopathy (ICM) cases, younger than 60 years CHD cases, and female CHD cases from healthy controls (area under the curve (AUC) = 0.68, 0.71, 0.74, and 0.73, respectively). Conclusions We demonstrated a robust link between ABCG1 hypomethylation in whole blood and CHD risk in the Chinese population and provided novel evidence indicating that aberrant ABCG1 methylation in peripheral blood can serve as an early detection biomarker for CHD patients

Molecular imaging of HER2 expression in breast cancer patients using a novel peptide-based tracer 99mTc-HP-Ark2: a pilot study

Abstract Background Due to the temporal and spatial heterogeneity of human epidermal growth factor receptor 2 (HER2) expression in breast tumors, immunohistochemistry (IHC) cannot accurately reflect the HER2 status in real time, which may cause misguided treatment decisions. HER2-specific imaging can noninvasively determine HER2 status in primary and metastatic tumors. In this study, HER2 expression in breast cancer patients was determined in vivo by SPECT/CT of 99mTc-HP-Ark2, comparing with PET/CT of 18F-FDG lesion by lesion. Methods A novel HER2-targeted peptide probe 99mTc-HP-Ark2 was constructed. Biodistribution and nanoScan SPECT/CT imaging were performed in mice models. The correlation between the quantified tumor uptake and HER2 expression in tumor cells was analyzed. In the pilot clinical study, a total of 34 breast cancer patients (mean age ± SD: 49 ± 10 y) suspected of having breast cancer according to mammography or ultrasonography were recruited at Peking Union Medical College Hospital, and 99mTc-HP-Ark2 SPECT/CT and 18F-FDG PET/CT were carried out with IHC and fluorescence in situ hybridization as validation. Results Small animal SPECT/CT of 99mTc-HP-Ark2 clearly identified tumors with different HER2 expression. The quantified tumor uptake and tumor HER2 expression showed a significant linear correlation (r = 0.932, P < 0.01). Among the 36 primary lesions in the 34 patients, when IHC (2 +) or IHC (3 +) was used as the positive evaluation criterion, 99mTc-HP-Ark2 SPECT/CT imaging with a tumor-to-background ratio of 1.44 as the cutoff value reflected the HER2 status with sensitivity of 89.5% (17/19), specificity of 88.2% (15/17) and accuracy of 88.9% (32/36), while the 18F-FDG PET/CT showed sensitivity of 78.9% (15/19), specificity of 70.6% (12/17) and accuracy of 75.0% (27/36). In particular, 100% of IHC (3 +) tumors were all identified by 99mTc-HP-Ark2 SPECT/CT imaging. Conclusion 99mTc-HP-Ark2 SPECT/CT can provide a specific, noninvasive evaluation of HER2 expression in breast cancer, showing great potential to guide HER2-targeted therapies in clinical practice. ClinicalTrials.gov Trial registration: NCT04267900. Registered 11th February 2020. Retrospectively registered, https://www.clinicaltrials.gov/ct2/results?pg=1&load=cart&id=NCT04267900

Psychosocial Problems and Condomless Anal Sex among Transgender Women in Two Cities of China: Study Based on the Syndemic Framework

Studies examining the association between psychosocial problems and condomless anal sex (CAS) among transgender women (TGW) are rare. In this study, close attention was paid to the effect of co-occurring psychosocial problems on sexual risk behaviors. A cross-sectional study, including 247 TGW, was conducted in Kunming and Shenyang, China. The prevalence of condomless anal sex among TGW in the previous 6 months was 30.8%. Most of the psychosocial factors were associated with one another in bivariate logistic regression models. Low self-esteem (ORm = 2.99, 95% CI = 1.25&ndash;7.18), sexual compulsivity (ORm = 2.13, 95% CI = 1.13&ndash;4.00), and intimate partner violence (ORm = 2.21, 95% CI = 1.19&ndash;4.11) were discovered to be related to condomless anal sex in the multivariate regression model. No significant interactive effects of the syndemic factors on condomless anal sex were detected. More programmatic and effective HIV prevention interventions targeting psychosocial problems are required to reduce HIV infection within the population

Blood lipid levels and all-cause mortality in older adults: the Chinese Longitudinal Healthy Longevity Survey 2008-2018

OBJECTIVES Proper blood lipid levels are essential for survival in older adults, but inconsistent relationships have been reported between blood lipids and all-cause mortality in the elderly. METHODS This retrospective longitudinal study analyzed data from 1,067 Chinese older adults enrolled in the Chinese Longitudinal Healthy Longevity Survey collected in 2008 and followed up until death or December 31, 2018. The outcome was all-cause mortality. Multivariate Cox regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with stratification by age (60-80, 80-100, or ≥100 years) for further analysis. The survival probability according to lipid profile quartiles was calculated using Kaplan-Meier curves and the log-rank test. RESULTS The participants’ mean age was 84.84 years, and 57.0% were female. In total, 578 individuals died, and 277 were lost to follow-up. The mean total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were higher among those who died than among those who survived. Participants in the second HDL-C quartile and the highest LDL-C and triglyceride (TG) quartiles had 28% higher, 23% lower, and 49% lower risks of all-cause mortality, respectively. After further adjustment, the associations remained except for HDL-C, and additional associations were observed between all-cause mortality and the third TC and LDL-C quartiles and the second TG quartile (HR, 1.44; 95% CI, 1.01 to 2.06; HR, 0.68; 95% CI, 0.49 to 0.94; HR, 0.79; 95% CI, 0.62 to 0.99, respectively). CONCLUSIONS Older adults should maintain an LDL-C level of 1.91-2.47 mmol/L and a TG level of no less than 1.66 mmol/L