Immune signature and phagocytosis of circulating DC subsets in healthy adults during aging.

Dendritic cells (DC) play a pivotal role in the onset and progression of immunosenescence-associated diseases, serving as a link between innate and adaptive immunity. Thus, there is a need to establish reference ranges for DC subset levels in healthy adults and investigate the potential impact of age on DC subset levels and phagocytic activity. Single-platform multi-color flow cytometry was performed to assess the proportions of circulating conventional type 1 DC (cDC1), conventional type 2 DC (cDC2), and plasmacytoid DC (pDC), as well as the percentages of CD80, CD86, CD83, PD-L1, and CD32 in cDC1, cDC2, and pDC. Reference ranges were established based on age and gender, and the percentage of circulating DC subsets in different age groups was compared. In addition, circulating DC were enriched using a magnetic bead sorting kit and co-cultured with polystyrene (PS) beads, categorized by age groups, followed by the evaluation of PS bead phagocytosis using light microscopy and flow cytometry. The results indicated that the percentages of circulating cDC1, cDC2, and CD32+cDC2 decreased with age (P < 0.05) and revealed age-related impairment in phagocytic percentage of cDC2 (P < 0.05). These findings provide a deeper understanding of the impact of age on the phenotype and phagocytic activity of DC subsets, shedding light on their role and function in immunosenescence.

Myocardial Ischemia/Reperfusion Injury: Mechanism and Targeted Treatment for Ferroptosis.

Myocardial ischemia/reperfusion injury (MIRI) is a pathophysiological process connected to the onset of numerous heart disorders. The pathogenesis of MIRI is complex, and it mainly involves calcium overload, classic oxidative stress, mitochondrial disorder, inflammation, microvascular disorder, and cell death. The clinical treatment options for MIRI are presently constrained, making it imperative to develop new treatment modalities. Recent studies have demonstrated that ferroptosis is the main cause of MIRI. Ferroptosis is a new type of regulated iron-dependent cell death whose mechanism and targeted therapy are anticipated to be novel therapeutic techniques for MIRI. Herein, the primary mechanism underlying ferroptosis (the 3 major metabolic routes involving iron, amino acids, and lipids, and in MIRI, the specific mechanism and therapeutic target of ferroptosis) are discussed to determine the potential therapeutic approach for MIRI.

The DC-T cell axis is an effective target for the treatment of non-small cell lung cancer.

The dendritic cell (DC)-T cell axis is a bridge that connects innate and adaptive immunities. The initial immune response against tumors is mainly induced by mature antigen-presenting DCs. Enhancing the crosstalk between DCs and T cells may be an effective approach to improve the immune response to non-small cell lung cancer (NSCLC). In this article, a review was made of the interaction between DCs and T cells in the treatment of NSCLC and how this interaction affects the treatment outcome.

Prognostic significance of blood-based PD-L1 analysis in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis.

BACKGROUND: The main types of PD-L1 in the blood include soluble PD-L1 (sPD-L1), exosomal PD-L1 (exoPD-L1), and PD-L1 in circulating tumor cells (CTCs). However, the predictive and prognostic values of these three indicators in patients with non-small cell lung cancer (NSCLC) undergoing immune checkpoint inhibitor (ICI) therapy are unclear, warranting a systematic meta-analysis. METHODS: A systematic literature search was performed in the PubMed, Cochrane Library, and Embase databases. The pooled hazard ratio (HR) and 95% confidence interval (CI) values were extracted from the included studies to investigate the correlation between the three PD-L1 indicators and overall survival (OS) or progression-free survival (PFS). The Newcastle-Ottawa Scale (NOS) was used to examine the quality of the included studies. Subgroup analyses were employed to investigate the heterogeneity. The publication bias of the included studies was assessed using Begg's and Egger's tests. P < 0.05 was regarded as significantly different. RESULTS: The pooled results revealed that high pre-treatment sPD-L1 levels were significantly associated with inferior OS (HR = 2.32, 95% CI = 1.68-3.18, P < 0.001) and PFS (HR = 2.52, 95% CI = 1.72-3.68, P < 0.001). However, dynamic changes in sPD-L1 after immunotherapy were not statistically significant for OS (HR = 1.46, 95% CI = 0.65-3.26, P > 0.05) or PFS (HR = 1.62, 95% CI = 0.92-2.86, P > 0.05). Meanwhile, the upregulated pre-treatment exoPD-L1 levels were significantly associated with poor PFS (HR = 4.44, 95% CI = 2.87-6.89, P < 0.001), whereas the post-treatment dynamic upregulation of exoPD-L1 was significantly correlated with superior PFS (HR = 0.36, 95% CI = 0.24-0.54, P < 0.001) and OS (HR = 0.20, 95% CI = 0.07-0.53, P < 0.001). For PD-L1 in CTCs, the pooled results indicated that PD-L1 expression in CTCs was not significantly correlated with OS (HR = 0.75, 95% CI = 0.49-1.13, P = 0.170) and PFS (HR = 0.79, 95% CI = 0.59-1.06, P = 0.12). CONCLUSIONS: Blood-based PD-L1 analysis is a potential strategy for predicting treatment efficacy and prognosis in patients with cancer.

Sacubitril/valsartan: research progress of multi-channel therapy for cardiorenal syndrome.

Cardiorenal syndrome (CRS) results from complex interaction between heart and kidneys, inducing simultaneous acute or chronic dysfunction of these organs. Although its incidence rate is increasing with higher mortality in patients, effective clinical treatment drugs are currently not available. The literature suggests that renin-angiotensin-aldosterone system (RAAS) and diuretic natriuretic peptide (NP) system run through CRS. Drugs only targeting the RAAS and NPs systems are not effective. Sacubitril/valsartan contains two agents (sacubitril and valsartan) that can regulate RAAS and NPs simultaneously. In the 2017 American College of Cardiology/American Heart Association/American Heart Failure (HF) ssociation (ACC/AHA/HFSA) guideline, sacubitril/valsartan was recommended as standard therapy for HF patients. The latest research shows that Combined levosimendan and Sacubitril/Valsartan markets are protected the heart and kidney against cardiovascular syndrome in rat. However, fewer studies have reported its therapeutic efficacy in CRS treatment, and their results are inconclusive. Therefore, based on RAAS and NPs as CRS biomarkers, this paper summarizes possible pathophysiological mechanisms and preliminary clinical application effects of sacubitril/valsartan in the prevention and treatment of CRS. This will provide a pharmacological justification for expanding sacubitril/valsartan use to the treatment of CRS.

NLRP3 inflammasome as a novel therapeutic target for heart failure.

Heart failure (HF) is a leading cause of mortality worldwide. The pathogenesis of HF is complex and has not yet been fully elucidated, which has slowed drug development and long-term treatments. Inflammasome-mediated responses occur during the progression of HF. It has been reported that energy metabolism and metabolites of intestinal flora are also involved in the process of HF, and they interact with each other to promote the progression of HF. NLR family pyrin domain containing 3 (NLRP3) inflammasome may be a key target in the relationship between inflammation-mediated energy metabolism and metabolites of intestinal flora. Elucidating the relationship among the above three factors may help to identify new molecular targets for the prevention and treatment of HF and ultimately affect the course of HF. In this study, we systematically summarize evidence regarding the relationship among NLRP3 inflammasome, energy metabolism, intestinal microflora metabolites, and inflammation, as well as highlight advantages of NLRP3 inflammasome in treating HF.

Shengmai Yin formula exerts cardioprotective effects on rats with chronic heart failure via regulating Linoleic Acid metabolism.

The objective of this study was to investigate the protective effects of Shengmai Yin(SMY) on rats with chronic heart failure(CHF).Sprague-Dawley rats were used to establish a CHF animal model via ligation of the left anterior descending branch of the coronary artery and exhaustive swimming.Echocardiography, serum biochemical indicators and histopathology were used to evaluate the pharmacodynamics of SMY in CHF rats.UPLC-Q-TOF/MS analysis based on serum was performed to identify the potential metabolites in the pathological process of CHF. Metabolic pathway analysis was carried out to elucidate the metabolic network associated with SMY treatment of CHF.Moreover,quantitative real-time PCR (qRT-PCR), Western blotting (WB), and Enzyme-linked immunosorbent assay (ELISA) were used to measure the RNA and protein expression levels in related pathways. Results revealed that SMY significantly restored the cardiac function of CHF rats, reduced the serum biochemical indicators, and alleviated cardiac histological damage. Metabolomics analysis shows that the therapeutic effect of SMY for CHF involves 14 biomarkers and 8 metabolic pathways, especially linoleic acid pathway, to be influenced, which implied the potential mechanism of SMY in treating CHF. Two key indicators Lipoxygenase arachidonic acid 15 lipoxygenase (ALOX15) and Cytochrome P450 1A2(CYP1A2) of linoleic acid metabolism pathway were verified by RT-PCR, WB and ELISA. Verification result showed that compared with the model group, expression levels of ALOX15 and CYP1A2 in SMY group were lower. In conclusion, SMY has cardioprotective effect on chronic heart failure rats, and its mechanism may be related to linoleic acid metabolism pathway.

Apoptosis detection: a purpose-dependent approach selection.

Apoptosis is closely associated with many diseases. Detection of apoptosis can be achieved by morphology, biochemistry, molecular biology, immunology, and other techniques. However, as technologies are increasingly used for the detection of apoptosis, many researchers are confused about how to choose a suitable method to detect apoptosis. Selection of a suitable detection method for apoptosis will help clinical diagnosis and prevention of diseases. This article reviews the selection of optimal apoptosis-detection methods based on research purposes and technique principles.