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The age-related decline in T-cell function among elderly individuals remains unclear. We thus investigated the interrelationship between T-cell subsets and age to identify the changes in T-cell phenotypes and develop an age prediction model for the elderly population. A total of 127 individuals aged >60 years were divided into three groups (youngest-old group, 61–70 years, n = 34; middle-old group, 71–80 years, n = 53; and oldest-old group, ≥ 81 years, n = 40). The percentage of CD8+CD28− cells (P = 0.001) was highest in the oldest-old group and then followed by the middle-old group, while the youngest-old group was the lowest. Both females and males demonstrated significant decreases in the absolute counts of CD4+CD45RA+ cells (P = 0.020; P = 0.002) and CD8+CD28+ cells (P = 0.015; P = 0.005) with age. Multivariate linear regression showed that the percentage of CD8+CD28− cells (P < 0.001) was an independent predictor of aging after adjusting for sex, body mass index, hospitalization duration, smoking, drinking, chronic medical illness, and medications at admission. In conclusion, our results suggest that aging in elderly individuals is accompanied by a decrease in the counts of T-cell subpopulations. CD8+CD28− cells may be potential targets for elderly individuals in antiaging-related immunosenescence.

Objective: As people get older, the innate and acquired immunity of the elderly are affected, resulting in immunosenescence. Prealbumin (PAB), transferrin (TRF), and albumin (ALB) are commonly used markers to monitor protein energy malnutrition (PEM). However, their relationship with the immune system has not been fully explored. Methods: In our study, a total of 93 subjects (≥65 years) were recruited from Tongji Hospital between January 2015 and February 2017. According to the serum levels of these proteins (PAB, TRF, and ALB), we divided the patients into the high serum protein group and the low serum protein group. Then, we compared the percent expression of lymphocyte subsets between two groups. Results: All the low serum protein groups (PAB, TRF, and ALB) had significant decreases in the percentage of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells and significant increases in the percentage of CD8+ cells, CD8+CD28− cells. PAB, TRF, and ALB levels revealed positive correlations with CD4/CD8 ratio, proportions of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells, and negative correlation with proportions of CD8+ cells, CD8+CD28− cells. Conclusions: This study suggested PAB, TRF, and ALB could be used as immunosenescence indicators. PEM might accelerate the process of immunosenescence in elderly males. [ABSTRACT FROM AUTHOR]

Background: The correlation between impedance cardiography (ICG) and 6 min walk distance (6MWD) in atrial fibrillation (AF) patients remains unknown.Methods: We recruited 49 subjects in the study (21 AF patients and 28 patients without AF) and estimated hemodynamic parameters: cardiac output (CO), stroke volume (SV), stroke volume index (SVI), left stroke work (LSW), left stroke work index (LSWI), stroke systemic vascular resistance (SSVR), stroke systemic vascular resistance index (SSVRI); 6MWD, left ventricle ejection fraction (LVEF), NT-pro brain natriuretic peptide (NT-pro BNP) for the two groups.Results: The AF group have apparently lower CO (2.26 ± 0.14 VS 4.11 ± 0.20 L/min, p = 0.039) and distinctly higher SVR (677.60 ± 69.10 VS 344.41 ± 22.98 dynes/cm(5), p = 0.001), SSVRI (396.97 ± 36.80 VS 199.01 ± 11.72 dynes/cm(5)/m(2), p < 0.001) than the control group. NT-pro BNP (1409.48 ± 239.90 VS 332.59 ± 68.85 pg/ml, p = 0.001) in the AF group was significantly higher than the control group and 6MWD (264.33 ± 14.55 VS 428.79 ± 29.98 m, p < 0.001) in the AF group was lower than the control group. There was no significant difference in LVEF between the two groups (62.67 ± 7.62 % VS 63.93 ± 5.03 %, p = 0.470). Pearson correlation analysis revealed that CO (R = 0.494, p = 0.023), SV (R = 0.633, p = 0.002), LSW (R = 0.615, p = 0.003) and LSWI (R = 0.491, p = 0.024) significantly correlated positively with 6MWD in AF patients.Conclusions: AF patients had lower cardiac output, shorter 6MWD and higher NT-pro BNP than patients with sinus rhythm. The cardiac output measured by impedance cardiography significantly correlated positively with 6MWD in AF patients. [ABSTRACT FROM AUTHOR]

The causal relationship between triglycerides and myocardial infarction (MI) was investigated using Mendelian randomization (MR) studies. Triglycerides were the exposure factor, and MI served as the outcome variable. Inverse variance weighting was used as the main analysis method, MR-Egger, and weight median as other analysis methods for MR analysis. In addition, heterogeneity test, level multivariate analysis, and sensitivity analysis were carried out. Inverse variance weighting results showed that the increase in triglyceride level affected the incidence of MI (OR = 1.287; 95% CI = 1.185-1.398; P = 1.988 × 10-9). Consistently, the results from all 3 methods indicated a statistically significant increase in the risk of MI with higher triglyceride levels (P < .05). The results showed that patients with high triglyceride levels had a higher incidence of MI, suggesting that MI should be prevented in the high triglyceride population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

T-wave alternans (TWA) is a potent arrhythmia substrate under the conditions of acute myocardial ischemia. Abnormal intracellular calcium cycling contributes to the genesis of cardiac alternans. Ryanodine receptor (RyR) is a pivotal Ca 2+ cycling protein central to Ca 2+ signaling in the heart. Here, we investigated the potential role of RyR in cardiac alternans and ventricular arrhythmias in acute myocardial ischemia. Transmembrane action potentials were simultaneously recorded from epicardium and endocardium together with a transmural ECG and isometric contraction force in the arterially perfused left ventricular wedge preparations. Calcium alternans were induced by incremental frequency of field stimulation in rat ventricular myocytes. TWA, mechanical alternans and ventricular arrhythmias were reproducibly induced by rapid pacing in the acute ischemic wedge preparations. Compared with control group, calcium alternans ratio and spontaneous calcium release were increased in acute ischemic myocytes. Verapamil, a phenylalkylamine calcium channel blocker, can successfully abolish spontaneous calcium release, TWA, and ventricular arrhythmias. The inhibition effect of verapamil could be diminished by low concentration of ryanodine (10 nmol/L). However, nifedipine, a dihydropyridine calcium channel blocker, could not block TWA or arrhythmias. Moreover, verapamil, but not nifedipine, significantly decreased ROS production in ischemic myocytes. Collectively, our results indicate that verapamil can significantly inhibit the development of cardiac alternans and ventricular arrhythmias in acute myocardial ischemia, and the mechanism was related to the inhibition of RyR and the protective function to oxidative stress., Competing Interests: None.

Atherosclerosis is an immune-mediated inflammatory process, which acts as the main cause of acute coronary syndrome (ACS). Regulatory CD4+CD25+FOXP3+T cells (Tregs) are thought to play a major role in inhibiting the formation and progression of atherosclerosis. However, the exact role played by Tregs in the pathogenesis of ACS is yet remained unclear. FOXP3 is a key regulator of Treg formation and function. Demethylation at the CpG-rich island of FOXP3 upstream enhancers can alter FOXP3 expression, and may affect Treg function during the development of ACS. This study investigated the immunosuppressive function and methylation status of a FOXP3 upstream enhancer in Tregs in ACS patients. Notably, Tregs from ACS patients exhibited a significantly lower immunosuppressive effect on Teffs. Furthermore, the methylation status of the FOXP3 upstream enhancer was significantly increased in ACS patients. Consistent with these observations, Tregs originated from ACS patients manifested significantly lower levels of FOXP3 mRNA. The immunosuppressive effect of Tregs on Teffs was compromised in ACS patients. Together, our data suggest that examination of the methylation status of the FOXP3 upstream enhancer might be a novel approach to diagnose ACS and to differentiate ACS subtypes.

Objective: Stem cells transplantation is a promising strategy in cardiology. This meta-analysis summarizes the efficacy and safety of stem cells transplantation on top of standard medication on chronic heart failure patients., Methods: The following databases were searched, including Cochrane Library (Issue 4, 2011), PubMed (1980 to 2011), Embase (1990 to 2011), CBM (1978 to 2011), CNKI (1994 to 2011), VIP (1989 to 2011), and WanFang Data (1998 to 2011). Search criteria:studies were screened and the quality was evaluated according to predefined inclusion and exclusion criteria. Intervention measures: the treatment group using stem cell transplantation therapy on top of standard drug treatment, while the control group using standard drug treatments., Results: A total of 31 studies involving 2375 patients were included. The results show that the improvement of LVEDV in the stem cell treatment group is greater than in the control group [SMD = -11.8% (95%CI: -0.223 - 0.013), P = 0.027] and the relative-risk of cardiac events is lower in stem cell treatment group [RR = 0.77 (95%CI: 0.66 - 0.90), P < 0.01] than in control group., Conclusion: Stem cells therapy is effective in improving cardiac remodeling and reducing the relative-risk of cardiac events in patients with chronic heart failure.

Objective: To investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia., Methods: Twenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy., Results: Compared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P < 0.01) and downregulate nonphosphorylated Cx43., Conclusions: LPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.

Objective: To study the Kv1.3 channel expression changes after CD4(+) and subsets CD28(null)/CD28(+)T cells activation in peripheral blood of patients with acute coronary syndrome (ACS)., Methods: CD4(+)T cell in 27 ACS patients and CD4(+)CD28(null)/CD4(+)CD28(+)T cells in 12 out of these 27 ACS patients were isolated from peripheral blood with magnetic cell sorting. The whole-cell Kv1.3 currents for three T cells were recorded with patch-clamp technique before and 72 hours after activation by purified anti-human CD3 Interferon gamma, tumor necrosis factor alpha (TNF-alpha), granzyme B mRNA expression were determined by reverse transcription-PCR before and 72 hours after activation by purified anti-human CD3 in the presence or absence of recombinant Margatoxin (rMgTX, 0.1, 1, 10 nmol/L), a specific Kv1.3 channel blocker., Results: Peak Kv1.3 channel currents of CD4(+), CD4(+)CD28(null), CD4(+)CD28(+)T cells were significantly increased and the mean Kv1.3 channel numbers per cell of these cells were increased by about 90%, 60%, 80% (402 +/- 88 vs. 752 +/- 275, 553 +/- 328 vs. 874 +/- 400, 392 +/- 133 vs. 716 +/- 251, all P < 0.05) after activation compared to baseline values. Baseline CD4(+)CD28(null)T cell numbers were about 40% more than those of CD4(+)CD28(+)T cell (P < 0.05) and were similar after activation (P = 0.102). The mRNA expression of interferon gamma, TNF-alpha and granzyme B were dose-dependently down-regulated by rMgTX., Conclusions: Kv1.3 channels of peripheral CD4(+)T cell and CD28(null)/CD28(+)T cells from ACS patients significantly increased after activation and Kv1.3-specific channel blocker rMgTX could effectively abolish this effect suggesting a potential role of Kv1.3 channel blocker on plaque stabilization in ACS patients.