Proteomic analysis of plasma proteins from patients with cardiac rupture after acute myocardial infarction using TMT-based quantitative proteomics approach.

BACKGROUND: Cardiac rupture (CR) is a rare but catastrophic mechanical complication of acute myocardial infarction (AMI) that seriously threatens human health. However, the reliable biomarkers for clinical diagnosis and the underlying signaling pathways insights of CR has yet to be elucidated. METHODS: In the present study, a quantitative approach with tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry was used to characterize the differential protein expression profiles of patients with CR. Plasma samples were collected from patients with CR (n = 37), patients with AMI (n = 47), and healthy controls (n = 47). Candidate proteins were selected for validation by multiple reaction monitoring (MRM) and enzyme-linked immunosorbent assay (ELISA). RESULTS: In total, 1208 proteins were quantified and 958 differentially expressed proteins (DEPs) were identified. The difference in the expression levels of the DEPs was more noticeable between the CR and Con groups than between the AMI and Con groups. Bioinformatics analysis showed most of the DEPs to be involved in numerous crucial biological processes and signaling pathways, such as RNA transport, ribosome, proteasome, and protein processing in the endoplasmic reticulum, as well as necroptosis and leukocyte transendothelial migration, which might play essential roles in the complex pathological processes associated with CR. MRM analysis confirmed the accuracy of the proteomic analysis results. Four proteins i.e., C-reactive protein (CRP), heat shock protein beta-1 (HSPB1), vinculin (VINC) and growth/differentiation factor 15 (GDF15), were further validated via ELISA. By receiver operating characteristic (ROC) analysis, combinations of these four proteins distinguished CR patients from AMI patients with a high area under the curve (AUC) value (0.895, 95% CI, 0.802-0.988, p < 0.001). CONCLUSIONS: Our study highlights the value of comprehensive proteomic characterization for identifying plasma proteome changes in patients with CR. This pilot study could serve as a valid foundation and initiation point for elucidation of the mechanisms of CR, which might aid in identifying effective diagnostic biomarkers in the future.

A fluorescence-based immunochromatographic assay using quantum dot-encapsulated nanoparticles for the rapid and sensitive detection of fetuin-B.

Coronary artery disease (CAD) is the leading cause of death worldwide. Earlier detection of CAD improves treatment outcomes and secondary prevention. The circulating fetuin-B protein is considered to be a promising biomarker for the early detection of CAD. However, a facile and reliable clinical test for fetuin-B is still lacking. Herein, we describe a reliable fluorescent biosensor for detecting fetuin-B in plasma that combines quantum dots-doped polystyrene nanoparticles with an immunochromatographic assay strip (QNPs-ICAS). The QNPs served as detection signals in the QNPs-ICAS sensor system, which was based on a double-antibody sandwich structure. Under optimum experimental conditions, the biosensor exhibited a broad linear range of 1-200 ng mL-1 and a low detection limit of 0.299 ng mL-1. Furthermore, the proposed immunosensor demonstrated high sensitivity, satisfactory selectivity, good reproducibility, and excellent recovery. Finally, the performance and applicability of our QNPs-based ICAS system were validated in clinical samples using a commercial ELISA kit with excellent correlations (r = 0.98451, n = 116). To conclude, the proposed sensor served as a rapid, sensitive, and accurate method for detecting fetuin-B in actual clinical samples, thereby demonstrating its potential for preliminary CAD screening and diagnosis.

Prevalence of risk factors associated with rupture of abdominal aortic aneurysm (AAA): a single center retrospective study.

Background: Abdominal aortic aneurysm (AAA) is a severe cardiovascular disease. The mortality rate for an AAA rupture is very high. Understanding the risk factors for AAA rupture would help AAA management, but little is known about these risk factors in the Chinese population. Methods: This retrospective study included patients that were diagnosed with AAA during the last 5 years in a large national hospital in southern China. AAA patients were divided into a rupture and non-rupture group. Clinical data were extracted from the hospital medical record system. Clinical features were compared between the rupture and non-rupture groups. The associations between potential risk factors and rupture risk were evaluated using a multivariate logistic regression analysis. Results: A total of 337 AAA patients were included for analysis in the present study. AAA diameter was significantly larger, and high-sensitivity C-reactive protein (hs-CRP) and serum creatinine levels were both significantly higher in AAA rupture patients. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels were significantly lower in AAA rupture patients. After adjustment, the multivariate logistic analysis found that AAA diameter and hs-CRP were independently positively associated with AAA rupture, and HDL-C level was adversely associated with AAA rupture. Conclusions: Our data suggests that larger AAA diameter and higher hs-CRP level are associated with a higher risk of AAA rupture, and higher HDL-C level is associated with a lower risk of AAA rupture. The results of this study may be helpful for the management of AAA patients in southern China.

USP10 regulates macrophage inflammation responses via stabilizing NEMO in LPS-induced sepsis.

BACKGROUND: Sepsis is a systemic inflammatory response syndrome characterized by persistent inflammation and immunosuppression, leading to septic shock and multiple organ dysfunctions. Ubiquitin-specific peptidase 10 (USP10), a deubiquitinase enzyme, plays a vital role in cancer and arterial restenosis, but its involvement in sepsis is unknown. OBJECTIVE: In this study, we investigated the significance of USP10 in lipopolysaccharide (LPS)-stimulated macrophages and its biological roles in LPS-induced sepsis. METHODS: Lipopolysaccharides (LPS) were used to establish sepsis models in vivo and in vitro. We use western blot to identify USP10 expression in macrophages. Spautin-1 and USP10-siRNA were utilized for USP10 inhibition. ELISA assays were used to assess for TNF-α and IL-6 in vitro and in vivo. Nuclear and cytoplasmic protein extraction and Confocal microscopy were applied to verify the translocation of NF-κB. Mechanically, co-immunoprecipitation and rescue experiments were used to validate the regulation of USP10 and NEMO. RESULTS: In macrophages, we found that LPS induced USP10 upregulation. The inhibition or knockdown of USP10 reduced the pro-inflammatory cytokines TNF-α and IL-6 and suppressed LPS-induced NF-κB activation by regulating the translocation of NF-κB. Furthermore, we found that NEMO, the regulatory subunit NF-κB essential modulator, was essential for the regulation of LPS-induced inflammation by USP10 in macrophages. NEMO protein evidently interacted with USP10, whereby USP10 inhibition accelerated the degradation of NEMO. Suppressing USP10 significantly attenuated inflammatory responses and improved the survival rate in LPS-induced sepsis mice. CONCLUSIONS: Overall, USP10 was shown to regulate inflammatory responses by stabilizing the NEMO protein, which may be a potential therapeutic target for sepsis-induced lung injury.

Navigation and closed-loop control of magnetic microrobot in plant vein mimic environment.

In recent years, research on the manipulation and control of microrobot has gradually matured. In order to improve the intelligence of microrobots, navigation study also becomes an important research topic. In practice, microrobots could be disturbed by the flowing liquid when it moves in a microfluidic environment. As a result, the actual trajectory of microrobots will deviate from the intended one. In this paper, firstly, different algorithms for the navigation of microrobots in a simulated plant leaf vein environment are investigated. According to the simulation results, RRT*-Connect is then selected as the path planning algorithm with a relatively better performance. Based on the pre-planned trajectory, a fuzzy PID controller is further designed for precise trajectory tracking, which can effectively eliminate the random disturbance caused by micro-fluid flow during the motion and make it quickly recover to a stable movement state.

Colorimetry-Based Phosphate Measurement for Polymerase Elongation.

DNA detection, which includes the measurement of variants in sequences or the presence of certain genes, is widely used in research and clinical diagnosis. Both require DNA-dependent DNA polymerase-catalyzed strand extension. Currently, these techniques rely heavily on the instruments used to visualize the results. This study introduced a simple and direct colorimetric method to measure polymerase-directed elongation. First, pyrophosphate (PPi), a by-product of strand extension, is converted into phosphate (Pi). Phosphate levels were measured using either Mo-Sb or BIOMOL Green reagent. This study showed that this colorimetry can distinguish single-base variants and detect PCR products in preset stringent conditions, implicating the potential value of this strategy to detect DNA.

Saliency-CCE: Exploiting colour contextual extractor and saliency-based biomedical image segmentation.

Biomedical image segmentation is one critical component in computer-aided system diagnosis. However, various non-automatic segmentation methods are usually designed to segment target objects with single-task driven, ignoring the potential contribution of multi-task, such as the salient object detection (SOD) task and the image segmentation task. In this paper, we propose a novel dual-task framework for white blood cell (WBC) and skin lesion (SL) saliency detection and segmentation in biomedical images, called Saliency-CCE. Saliency-CCE consists of a preprocessing of hair removal for skin lesions images, a novel colour contextual extractor (CCE) module for the SOD task and an improved adaptive threshold (AT) paradigm for the image segmentation task. In the SOD task, we perform the CCE module to extract hand-crafted features through a novel colour channel volume (CCV) block and a novel colour activation mapping (CAM) block. We first exploit the CCV block to generate a target object's region of interest (ROI). After that, we employ the CAM block to yield a refined salient map as the final salient map from the extracted ROI. We propose a novel adaptive threshold (AT) strategy in the segmentation task to automatically segment the WBC and SL from the final salient map. We evaluate our proposed Saliency-CCE on the ISIC-2016, the ISIC-2017, and the SCISC datasets, which outperform representative state-of-the-art SOD and biomedical image segmentation approaches. Our code is available at https://github.com/zxg3017/Saliency-CCE.

Association of serum laboratory parameters with periprocedural myocardial infarction after a primary percutaneous coronary intervention.

BACKGROUND: Periprocedural myocardial infarction (PMI) is one of the mortality-related complications of percutaneous coronary intervention (PCI) and significantly affects short- and long-term adverse outcomes and immediate cardiovascular events. Our present study aimed to evaluate the association of preprocedural serum laboratory parameters and PMI in patients who received primary PCI and attempted to provide detailed data on the predictors of PCI-related PMI. METHODS: A total of 1184 consecutive coronary artery disease (CAD) patients who received primary and elective PCI between July 2015 and June 2017 were included and divided into control group and PMI group. The data of serum laboratory parameters were collected from the electronic database of Meizhou People's Hospital. RESULTS: The results indicated that preprocedural fasting blood glucose were higher in PMI group compared with the control group (p < .001). Patients with prior hyperlipidemia were more likely to have experienced PCI-related PMI (p = .018) and the preprocedural level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, apolipoprotein B (Apo B), and LDL-C/high density lipoprotein cholesterol (HDL-C) were significantly enhanced in PMI group (p < .001). Multivariate regression analysis revealed that preprocedural fasting blood glucose > 6.11 mmol/L (p < .001, OR = 1.949, 95% CI: 1.444-2.630) and LDL-C levels ≥130 mg/dL (p = .005, OR = 1.941, 95% CI: 1.217-3.098) independently predicted PCI-related PMI. CONCLUSION: Our results indicated preprocedural fasting blood glucose >6.11 mmol/L and LDL-C levels ≥130 mg/dL may be useful predictors for PCI-related PMI. The study may provide a detailed data on the predictors of PCI-related PMI.

Clinical, epidemiological, and drug resistance insights into HIV-positive patients in Meizhou, China.

The acquired immunodeficiency syndrome (AIDS) epidemic, resulting from human immunodeficiency virus (HIV) infection, exhibits distinct regional characteristics. This study undertakes a retrospective analysis of the epidemiological and clinical features of 195 HIV-positive cases in Meizhou, China, from May 1, 2018 to December 31, 2019. Western blotting (WB) confirmed and assessed these cases. Notably, the majority of cases emanated from socio-economic groups with comparatively lower levels of education, with 80% being male. Strikingly, 90% of the cases were found to be in the middle to late stages of infection based on CD4+ T cell counts. Among the 30 different serum antibody profiles examined, reactivity with seven bands (p24, p31, gp41, p51, p66, gp120, and gp160) emerged as the most commonly observed WB pattern. The absence of specific bands, specifically p55 (17.44%), p39 (32.31%), and p17 (25.64%) were most frequent, with the detection frequency of p17 bands significantly reduced among cases in the AIDS and middle stages. An analysis of drug resistance genotypes indicated that, despite viral mutations conferring resistance to certain reverse transcriptase inhibitors, the first-line treatment regimen remained effective for patients in Meizhou. Notably, mutations resistant to protease inhibitors were infrequent (2.7%), suggesting that incorporating protease inhibitors into the treatment regimen may enhance therapeutic outcomes for local patients. These findings provide essential insights into the specific epidemiological patterns, serum antibody profiles, and drug resistance genotypes of HIV-infected patients in Meizhou. Significantly, this research contributes to the formulation of future treatment strategies tailored to the local context.

Effects of APOE gene ε4 allele on serum lipid profiles and risk of cardiovascular disease and tumorigenesis in southern Chinese population.

BACKGROUND: Human apolipoprotein E (APOE) polymorphisms are attributable to the presence of three common alleles, namely, ε2, ε3, and ε4, which generate six genotypes, viz, E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4. APOE polymorphisms are associated with all types of tumors and cardiovascular diseases (CVD). However, the relationship between the type of APOE polymorphisms and tumorigenesis remains debatable. Therefore, we aimed to investigate the role of APOE polymorphisms on the tumor with or without CVD in southern China. METHODS: A total of 1438 participants were categorized into 4 groups: 409 patients with tumor, 369 patients with CVD, 338 patients with both tumor and CVD, and 322 controls. APOE polymorphisms were determined by genotyping assay. The factors influencing tumor patients with or without CVD were also analyzed by logistic regression analysis. RESULTS: The present study involved different types of solid tumors. Lung cancer was the most common cancer (20.2%, 151/747), followed by colorectal (17%, 127/747), esophageal (9.8%, 73/747), and liver (8.7%, 65/747) cancers. E3/E3 was the most frequent genotype, and ɛ3 was the greatest allele frequency in our study population. The frequencies of the E3/E3, E3/E4, E2/E3, E2/E4, E4/E4, and E2/E2 genotypes in tumor patients were 76.97% (575/747), 14.19% (106/747), 6.83% (51/747), 1.2% (9/747), 0.4% (3/747), and 0.4% (3/747), respectively. Tumor patients carrying ε3 with or without CVD showed higher levels of TG, TC, and LDL-C and lower levels of HDL-C compared to the controls carrying ε3. On the other hand, the tumor patients carrying ε4 with or without CVD showed higher levels of TG and LDL-C and lower levels of HDL-C (all P < 0.05). The frequency of APOE ε4 allele and the E3/E4 genotype was relatively greater in tumor or CVD patients (P < 0.001). In addition, ε4 allele acted as an independent risk factor for tumor patients group (P = 0.037, adjusted OR = 1.92, 95% CI 1.04-3.55) and tumor + CVD patients group (P = 0.012, adjusted OR = 2.53, 95% CI 1.22-5.23). CONCLUSIONS: Individuals carrying ε4 are at a higher risk of tumor with or without CVD, and APOE polymorphisms affect the serum lipid profiles.

Clinical study of factors associated with pregnancy outcomes in pregnant women with systemic lupus erythematosus in the southern China.

Objectives: This study aims to estimate predicted factors for maternal and fetal outcomes in Hakka pregnant women with systemic lupus erythematosus (SLE) in the southern China. Patients and methods: Between June 2014 and February 2020, we retrospectively analyzed the data of a total of 123 singleton pregnant women with SLE (mean age: 27.1±4.1 years; range, 19 to 39 years) who were referred to our rheumatology clinic. Demographic, clinical, and laboratory data of the patients were recorded. Adverse pregnancy outcomes (APOs) were assessed. Results: Multivariate logistic regression analysis revealed that preeclampsia was associated with the increased odds of APOs (odds ratios [OR]=9.538, 95% confidence interval [CI]: 2.055-44.271, p=0.004), premature birth (OR=14.289, 95% CI: 3.596-56.777, p<0.001) and low birth weight (OR=8.275, 95% CI: 2.117-32.345, p=0.002). Anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody positivity was the predictor of APOs (OR=2.165, 95% CI: 1.034-4.532, p=0.040), premature birth (OR=2.849, 95% CI: 1.220-6.657, p=0.016) and pregnancy loss (OR=3.004, 95% CI: 1.086-8.305, p=0.034). The use of hydroxychloroquine and prednisone was associated with the decreased odds of APOs (OR=0.412, 95% CI: 0.198-0.860, p=0.018) and pregnancy loss (OR=0.304, 95% CI: 0.111-0.831, p=0.020). Conclusion: Our study results indicate that preeclampsia, anti-dsDNA antibody positivity, and the use of hydroxychloroquine and prednisone are independent predictors of pregnancy outcomes.

Plasma Proteome Profiling of Patients With In-stent Restenosis by Tandem Mass Tag-Based Quantitative Proteomics Approach.

Background: Despite the widespread application of new drug-eluting stents, a considerable portion of patients experience in-stent restenosis (ISR). To date, the pathophysiologic mechanisms of ISR remain poorly understood. Methods: In this study, we collected plasma samples from ISR patients (n = 29) and non-ISR patients (n = 36) after drug-eluting stent implantation, as well as from healthy controls (HCs) (n = 32). Our goal was to investigate differences in plasma protein profiles using tandem mass tag (TMT) labeling coupled with liquid chromatography and tandem mass spectrometry. The proteomic data were validated by enzyme-linked immunosorbent assay (ELISA). Bioinformatic analyses were conducted to analyze potential pathways and protein-protein interaction (PPI) involved in ISR. Results: A total of 1,696 proteins were identified, of which 278 differed in protein abundance between non-ISR and HCs, 497 between ISR and HCs, and 387 between ISR and non-ISR, respectively. Bioinformatic analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and PPI, further demonstrated that differentially abundant proteins between ISR and non-ISR are involved in several crucial biological processes and signaling pathways, such as focal adhesion, platelet activation, Rap1 signaling, regulation of actin cytoskeleton, and cholesterol metabolism. Among the identified differentially abundant proteins in ISR, 170 were increased in abundance relative to both non-ISR patients and HCs. Some of these proteins were identified to have critical functions for atherosclerosis development and might be involved in ISR pathology. Among these proteins, 3 proteins with increased abundance including fetuin-B, apolipoprotein C-III (APOC3), and cholesteryl ester transfer protein (CETP) were confirmed by ELISA. Conclusions: This is the first study provided a comprehensive proteomic profile to understand ISR pathology, which may help identify early diagnostic biomarkers and therapeutic targets.

Association of ALDH2 rs671 and MTHFR rs1801133 polymorphisms with hypertension among Hakka people in Southern China.

BACKGROUND: Genetic factors play an important role in susceptibility to hypertension. Herein, the association between acetaldehyde dehydrogenase 2 (ALDH2) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hypertension was analyzed among Hakka population in southern China. METHODS: A total of 3057 hypertensive patients and 2215 controls were enrolled. The ALDH2 rs671 and MTHFR rs1801133 genotyping were analyzed using gene chip. Relevant information and medical records of these subjects were collected. RESULTS: Hypertensive patients with ALDH2 rs671 G/A heterozygous had lower systolic blood pressure (SBP) than other genotypes (P < 0.001), while hypertensive patients with A allele had lower diastolic blood pressure (DBP) than patients with G allele (P < 0.001). The level of plasma homocysteine (Hcy) in patients with MTHFR CC, CT and TT genotypes showed an increasing trend (P < 0.001). The ALDH2 G/A genotype in the co-dominant model (adjusted OR 1.251, 95% CI 1.024-1.528, P = 0.028) and ALDH2 A/A genotype in the recessive model (adjusted OR 1.221, 95% CI 1.008-1.478, P = 0.041) were significant risk factors for the presence of hypertension. The MTHFR C/T genotype in the co-dominant model (adjusted OR 1.307, 95% CI 1.039-1.643, P = 0.022) and MTHFR C/T and T/T genotypes in the dominant model (adjusted OR 1.281, 95% CI 1.146-1.430, P < 0.001) were significant risk factors for the presence of hypertension. Further, logistic regression analysis showed that age, smoking, alcohol consumption, hyperhomocysteinemia, and high level of serum TG, Apo-A1, Apo-B were significant risks for hypertension. CONCLUSIONS: In summary, ALDH2 rs671 G/A, A/A genotypes and MTHFR rs1801133 C/T, T/T genotypes may be risk factors for hypertension in this Chinese Hakka population.

The Features of BRCA1 and BRCA2 Germline Mutations in Hakka Ovarian Cancer Patients: BRCA1 C.536 A>T Maybe a Founder Mutation in This Population.

Objective: To investigate the frequencies of BRCA1 and BRCA2 mutations in Chinese Hakka patients with ovarian cancer. Methods: The protein coding regions and exon intron boundary regions of the BRCA gene were sequenced using genomic DNA isolated from the lymphocytes of patients with next-generation sequencing. The patients' family history and clinical records were collected. Results: A total of 195 patients with ovarian cancer were included in the study, and 52 distinct variants of the BRCA gene were identified. It was found that 64 patients (64/195, 32.8%) had BRCA gene mutations, including 32 patients (50.0%) with BRCA1 mutation, 27 patients (42.2%) with BRCA2 mutation, and 5 patients (7.8%) with both mutations. Furthermore, 22 pathogenic mutations were detected in 26 patients, 2 likely pathogenic variants in 2 patients, 12 variants of uncertain significance in 20 patients, and 16 likely benign variants in 24 patients. The mutations were mainly found to occur in exons 8, 14, and 17 of BRCA1 and exons 10, 11, 14, and 15 of BRCA2. The results showed that the BRCA genes possess different mutation hotspots in different ethnic groups. In addition, recurrent mutations were noted in many patients. BRCA1 c.536 A>T, considered a founder mutation, was identified in 10 patients (15.63%, 10/64), followed by BRCA1 c.2635 G>T (6.25%, 4/64) and BRCA2 c.2566 T>C (6.25%, 4/64). Conclusion: The BRCA1 c.536 A>T could be considered to be a founder mutation in this ovarian cancer population. This recurrent BRCA1 mutation has rarely been observed in other ethnic groups. Our findings are expected to provide valuable data for clinical consultation and for designing individualized treatment for ovarian cancer.

Inducible co-stimulator inhibits lipid phagocytosis of human aortic smooth muscle cells by down-regulating CD36 expression.

BACKGROUND: To explore the potential mechanism of inducible co-stimulator (ICOS) inhibition of lipid phagocytosis in human aortic smooth muscle cells (HASMCs). METHODS: Excess Dil (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate)-labeled oxidized low-density lipoprotein (ox-LDL) was used to induce HASMCs to form a foam cell model; HASMCs were cultured together with ICOS-overexpressed JurKat (JK-ICOS) cells or recombinant human ICOS protein (rICOS protein) to be stimulated, and a confocal laser microscope was used to observe the lipid phagocytosis of HASMCs. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot, and immunofluorescence staining were used to detect the expression of the lipid phagocytic receptor, cluster of differentiation 36 (CD36) in HASMCs. RESULTS: The uptake of Dil ox-LDL by HASMCs was concentration-dependent, and excessive Dil ox-LDL uptake led to lipid accumulation in HASMCs. Pretreatment with JK-ICOS cells or rICOS protein for HASMCs 48 hours reduced Dil ox-LDL-induced lipid accumulation. Compared with HASMCs co-cultured with empty lentiviral JurKat (JK-EV) cells, the messenger RNA (mRNA) and protein expressions of CD36 in HASMCs co-cultured with JK-ICOS cells were significantly down-regulated. The results of immunofluorescence staining showed that co-culturing with JK-ICOS cells could down-regulate ox-LDL-induced expression of CD36 in HASMCs, but JK-EV cells could not. Similarly, the results of qPCR, western blot, and immunofluorescence staining showed that rICOS protein could down-regulate the ox-LDL-induced expression of CD36 in HASMCs, but this down-regulation was not as significant as that in JK-ICOS cells. CONCLUSIONS: ICOS could inhibit the lipid phagocytosis of HASMCs by down-regulating the expression of CD36, suggesting a potential anti-atherosclerosis (anti-AS) mechanism of ICOS, and preventing ox-LDL-induced formation of myogenic foam cells.

Tanshinone IIA and its derivative activate thermogenesis in adipocytes and induce "beiging" of white adipose tissue.

Tanshinone IIA (TAN2A) is a major active ingredient of Salvia miltiorrhiza used in traditional Chinese medicine and tanshinone 20 (TAN20) is a derivative of TAN2A. In this study, we examined the effects of TAN2A and TAN20 on adipogenesis, lipid metabolism, and thermogenesis. Our experiments showed that both TAN2A and TAN20 increased mitochondria content in adipose tissue, enhanced energy expenditure, reduced body weight, and improved insulin sensitivity and metabolic homeostasis in obese and diabetic mouse models. We demonstrated that TAN20 can facilitate the transformation from white to beige adipose tissue, as well as activate brown adipose tissue. In uncoupling protein 1 (UCP1) knockout mouse model, the effects of TAN2A and TAN20 on body weight and glucose tolerance were not observed, suggesting that such effects were UCP1 dependent. Furthermore, we found that TAN2A and TAN20 increased the expression of UCP1 and other thermogenic genes in adipocytes through AMPK-PGC-1α signaling pathway. Our findings indicate that TAN2A and its derivative TAN20 are potential interesting energy expenditure regulators and may be implicated in treatment of obesity and other metabolic disorders.

Incidence and risk factors of in-stent restenosis after percutaneous coronary intervention in patients from southern China.

BACKGROUND: In-stent restenosis (ISR) remains a challenge for coronary artery disease (CAD) patients who undergo percutaneous coronary intervention (PCI) with stents, and risk factors for ISR are controversial. This study aimed to investigate the incidence and risk factors of ISR in patients from southern China. METHODS: In this retrospective study, patients diagnosed as acute coronary syndromes (ACS) and underwent successful PCI with drug-eluting stent (DES) and conducted a follow-up coronary angiography in Center for Cardiovascular Diseases of Meizhou People's Hospital at the period of January 1st, 2016 to January 1st, 2021 were included for analysis. The clinical and angiographic factors were compared between patients in ISR ( +) and ISR (-) groups. The association between variables and ISR was evaluated by multivariate logistic regression model. RESULT: A total of 341 ACS patients who had been installed at least 1 stent were included in this study. The follow-up time was 34.2 ± 17.2 months. During the follow-up period, 62 (18.2%) patients experienced ISR, and the average time for ISR was 32.8 months; the incidence of ISR for left main coronary artery, left anterior descending coronary artery, left circumflex artery coronary artery and right coronary artery were 6.7%, 20.9%, 19.4% and 14.4%, respectively; left ventricular ejection fraction (LVEF), stent number, stent type, statin therapy, antiplatelet therapy were significantly different between patients in ISR ( +) and ISR (-) group. Multivariate logistic analysis suggested that LVEF and stent number were significantly correlated with ISR. CONCLUSION: Our study revealed the incidence and risk factors of ISR in patients from southern China. Our data suggested that LVEF and stent number were independent risk factors associated with ISR.

Characterization of the B cell receptor repertoire of patients with acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) is a complex cardiovascular disease whose development involves the dysregulation of adaptive immune responses. Though it has been proven that T cells associate with inflammation in the development of ACS, the function of B cells in disease remains unclear. OBJECTIVE: The aim of this study was to reveal the diversity of the B cell receptor (BCR) repertoire of patients with ACS. METHODS: We conducted a pilot study to sequence the immune repertoire of peripheral blood mononuclear cells (PBMCs) from patients with ACS, including acute myocardial infarction (AMI) and unstable angina (UA), and quantitatively characterized BCR repertoires by bioinformatics analysis. RESULTS: We found that patients with AMI and UA had lower BCR repertoire diversity compared with controls with normal coronary arteries (NCA). Lower percentages of productive unique BCR nt sequences and higher percentages of top 200 unique BCR sequences were identified in AMI and UA patients than NCA controls. Patients had various preferential usage of V and J genes from B cell clones in accordance with the disease severity of coronary arteries. AMI patients had distinct CDR3 amino acids, and their frequency differed among patients with ACS. CONCLUSIONS: Our results indicate that differential BCR signatures represent an imprint of distinct repertoires among ACS patients. This study thereby opens up the prospect of studying disease-relevant B cells to better understand and treat ACS.