👤 JoJo Hai

Interleukin-27 (IL-27) in the pleural fluid has gained significant attention as a diagnostic biomarker for tuberculous pleural effusion (TPE); however, considerable variability exists across available studies. This systematic review and meta-analysis aimed to determine the diagnostic accuracy of IL-27 in identifying TPE. In addition, we also compared the diagnostic accuracy of IL-27 and adenosine deaminase (ADA) with a head-to-head meta-analysis. We searched the PubMed and Web of Science databases to identify diagnostic test accuracy studies evaluating the accuracy of IL-27 for diagnosing TPE. The last search date was September 2025. We extracted data from the eligible studies and constructed a two-by-two table with true positives (TP), false positives (FP), true negatives (FN), and false negatives (FN). The QUADAS-2 tool was used to assess the quality of eligible studies. A bivariate model was applied to pool sensitivity and specificity, and a summary receiver operating characteristic (sROC) curve with the area under the curve (AUC) was generated to estimate the overall diagnostic accuracy of IL-27 and ADA. A Deeks funnel plot asymmetry test was used to evaluate publication bias. Nine studies encompassing ten cohorts were included, involving 1573 patients (429 with TPE and 1144 with non-TPE). The reported AUCs for IL-27 ranged from approximately 0.73 to 0.99 across eligible studies. The pooled sensitivity and specificity were 0.94 (95% CI, 0.83-0.98) and 0.96 (95% CI, 0.89-0.98), respectively. The AUC for sROC was 0.99 (95% CI, 0.97-0.99). The pooled positive likelihood ratio was 21.97 (95% CI, 7.95-60.69), the negative likelihood ratio was 0.07 (95% CI, 0.02-0.18), and the diagnostic odds ratio (DOR) was 329 (95% CI, 72-1506). Significant heterogeneity was observed in both sensitivity (I IL-27 is a promising diagnostic marker for TPE, and its diagnostic accuracy is comparable to that of ADA. IL-27 should be used as a complementary diagnostic marker to ADA for TPE. Show less

Lead (Pb) exposure poses significant health risks, particularly in neurodegenerative diseases such as Alzheimer's disease (AD). This study investigates the neuroprotective effects of pea peptide (PP4) on PC12 cells exposed to Pb. Using Cell Counting Kit-8 (CCK-8), pretreatment with PP4 at 50 and 200 µM concentrations significantly improved cell viability compared to Pb-only treated cells (P < 0.05), indicating a protective effect. Moreover, Pb exposure led to increased Amyloid Precursor Protein (APP) expression at 10 and 20 µM after 24 h (P < 0.05), while β-site amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) levels were elevated across all concentrations tested (P < 0.05). We established that PP4 can mitigate Pb-induced cytotoxicity and reduce the expression of APP and BACE1 by activating the Phosphoinositide 3-kinase / Protein Kinase (PI3K/AKT) signaling pathway. This study highlights the potential of PP4 as a therapeutic agent in preventing neurotoxic damage associated with lead exposure, suggesting a novel approach for the management of AD. Show less

The metabolic reprogramming of macrophages is a potential therapeutic strategy for sepsis treatment, but the mechanism underlying this reprogramming remains unclear. Since glycolysis can drive macrophage phenotype switching, the rate-limiting enzymes in glycolysis may be key to treating sepsis. Here, we found that, compared with other isoenzymes, the expression of 6-phosphofructokinase, muscle type (PFKM) was the most upregulated in monocytes from septic patients. Recombinant thrombomodulin (rTM) treatment downregulated the protein expression of PFKM in macrophages. Both rTM treatment and Pfkm knockout protected mice from sepsis and reduced the production of the proinflammatory cytokines IL-1β, IL-6, TNF-α, and IL-27, whereas PFKM overexpression increased the production of these cytokines. Mechanistically, rTM treatment inhibited glycolysis in macrophages by decreasing PFKM expression in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. HIF-1α overexpression increased methyltransferase-like 3 (METTL3) expression, elevated the m Show less

The locus coeruleus (LC), enriched in vesicular glutamate transporter 2 (VGlut2) neurons, is a potential homeostasis-regulating hub. However, the identity of melanocortin-4 receptor (MC4R) neurons in the paraventricular nucleus (PVN) of the hypothalamus, PVN Show less

Bile acid metabolites have been increasingly recognized as pleiotropic signaling molecules that regulate cardiovascular functions, but their role in mesenchymal stromal cells (MSC)-based therapy has never been investigated. It is found that overexpression of farnesoid X receptor (FXR), a main receptor for bile acids, improves the retention and cardioprotection of adipose tissue-derived MSC (ADSC) administered by intramyocardial injection in mice with myocardial infarction (MI), which shows enhanced antiapoptotic, proangiogenic, and antifibrotic effects. RNA sequencing, LC-MS/MS, and loss-of-function studies reveal that FXR overexpression promotes ADSC paracrine angiogenesis via Angptl4. FXR overexpression improves ADSC survival in vivo but fails in vitro. By performing bile acid-targeted metabolomics using ischemic heart tissue, 19 bile acids are identified. Among them, cholic acid and deoxycholic acid significantly increase Angptl4 secretion from ADSC overexpressing FXR and further improve their proangiogenic capability. Moreover, ADSC overexpressing FXR shows significantly lower apoptosis by upregulating Nqo-1 expression only in the presence of FXR ligands. Retinoid X receptor α is identified as a coactivator of FXR. It is first demonstrated that there is a bile acid pool in the myocardial microenvironment. Targeting the bile acid-FXR axis may be a novel strategy for improving the curative effect of MSC-based therapy for MI. Show less

Few intravenously administered mesenchymal stromal cells (MSCs) engraft to the injured myocardium, thereby limiting their therapeutic efficacy for the treatment of ischemic heart injury. Here, it is found that irisin pretreatment increases the cardiac homing of adipose tissue-derived MSCs (ADSCs) administered by single and multiple intravenous injections to mice with MI/R by more than fivefold, which subsequently increases their antiapoptotic, proangiogenic, and antifibrotic effects in rats and mice that underwent MI/R. RNA sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis, and loss-of-function studies identified CSF2RB as a cytokine receptor that facilitates the chemotaxis of irisin-treated ADSCs in the presence of CSF2, a chemokine that is significantly upregulated in the ischemic heart. Cardiac-specific CSF2 knockdown blocked the cardiac homing and cardioprotection abilities of intravenously injected irisin-treated ADSCs in mice subjected to MI/R. Moreover, irisin pretreatment reduced the apoptosis of hydrogen peroxide-induced ADSCs and increased the paracrine proangiogenic effect of ADSCs. ERK1/2-SOD2, and ERK1/2-ANGPTL4 are responsible for the antiapoptotic and paracrine angiogenic effects of irisin-treated ADSCs, respectively. Integrin αV/β5 is identified as the irisin receptor in ADSCs. These results provide compelling evidence that irisin pretreatment can be an effective means to optimize intravenously delivered MSCs as therapy for ischemic heart injury. Show less

Melanocortin-4 receptors (MC4Rs) are key regulators of energy homeostasis and adipose deposition in the central nervous system. Considering that MC4R expression regions and function-related research mainly focus on the paraventricular nucleus (PVN), little is known about their distribution throughout the mouse brain, although its messenger RNA distribution has been analyzed in the rat. Therefore, MC4R protein localization in mouse neurons was the focus of this study. MC4R protein distribution was assessed in mice through immunofluorescence and Western blotting. MC4R was differentially expressed throughout the arcuate nucleus (ARC), nucleus of the solitary tract (NTS), raphe pallidus (RPa), medial cerebellar nucleus, intermediolateral nucleus, and brainstem. The highest MC4R protein levels were found in the ARC and ventromedial hypothalamic nucleus, while they were significantly lower in the parabrachial nucleus and NTS. The lowest MC4R protein levels were found in the PVN; there was no difference in the protein levels between the area postrema and RPa. These data provide a basic characterization of MC4R-expressing neurons and protein distribution in the mouse brain and may aid further research on its role in energy homeostasis. Show less

Amylin, a pancreatic hormone cosecreted with insulin, exerts important anorexic and weight-loss effects. Melanocortin 4 receptor (MC4R) signalling plays a critical role in energy homeostasis; however, its role on amylin-dependent regulation of food intake and adaptive thermogenesis of interscapular brown adipose tissue (IBAT) are unclear. In this study, we examined the effects of amylin on food intake and thermogenesis on IBAT via the MC4R pathway in mice. Acute food consumption and thermogenesis in IBAT were measured in male wild-type (WT) and MC4R-deficient mice following intraperitoneal injection of amylin and SHU9119, an MC3R/4R antagonist, to determine the role of the central melanocortin system on the hypothalamus and IBAT. Amylin (50 μg/kg) suppressed feeding and stimulated thermogenesis on IBAT via activation of the MC4R system in mice. Pharmacological blockade of MC4R using SHU9119 (50 μg/kg) attenuated amylin-induced inhibition of feeding and stimulation of thermogenesis in IBAT. No changes were observed when SHU9119 was injected alone. Moreover, amylin significantly increased MC4R expression and c-Fos neuronal signals in the arcuate nucleus and significantly increased acetyl-CoA carboxylase (ACC) phosphorylation in the hypothalamus and IBAT and uncoupling protein-1 (UCP1) expression in the IBAT of WT mice via the MC4R pathway. The melanocortin system was involved in amylin-induced suppression of food intake and activation of thermogenesis in both the hypothalamus and IBAT via modulation of ACC phosphorylation and UCP1 expression. Show less

Targeted next generation sequencing of gene panels has become a popular tool for the genetic diagnosis of hypertrophic (HCM) and dilated cardiomyopathy (DCM). However, it is uncertain whether the use of Whole Exome Sequencing (WES) represents a more effective approach for diagnosis of cases with HCM and DCM. In this study, we performed indirect comparisons of the coverage and diagnostic yield of WES on genes and variants related to HCM and DCM versus 4 different commercial gene panels using 40 HCM and DCM patients, assuming perfect coverage in those panels. We identified 6 pathogenic or likely pathogenic among 14 HCM patients (diagnostic yield 43%). 3 pathogenic or likely pathogenic were found among the 26 DCM patients (diagnostic yield 12%). The coverage was similar to that of four existing commercial gene panels due to the clustering of mutation within MYH7, MYBPC3, TPM1, TNT2, and TTN. Moreover, the coverage of WES appeared inadequate for TNNI3 and PLN. We conclude that most of the pathogenic variants for HCM and DCM can be found within a small number of genes which were covered by all the commercial gene panels, and the application of WES did not increase diagnostic yield. Show less

Fibroblast growth factor 21 (FGF21) is increasingly recognized as an important metabolic regulator of glucose homeostasis. Here, we conducted an exome-chip association analysis by genotyping 5,169 Chinese individuals from a community-based cohort and two clinic-based cohorts. A custom Asian exome-chip was used to detect genetic determinants influencing circulating FGF21 levels. Single-variant association analysis interrogating 70,444 single nucleotide polymorphisms identified a novel locus, Show less