Advances in the Study of Plant-Derived Vesicle-Like Nanoparticles in Inflammatory Diseases.

All humans are universally affected by inflammatory diseases, and there is an urgent need to identify new anti-inflammatory drugs with good therapeutic benefits and minimal side effects to the organism. Recently, it has been found that plant-derived vesicle-like nanoparticles (PDVLNs) have good biocompatibility, with their active ingredients exhibiting good therapeutic effects on inflammation. They can also be used as drug carriers for targeted delivery of anti-inflammatory drugs. Therefore, PDVLNs represent a popular research area for novel anti-inflammatory drugs. This paper details the origin, biological functions, isolation and purification, and identification of PDVLNs, as well as the therapeutic effects of their intrinsic bioactive components on inflammatory diseases. It also introduces their targets as drug carriers to facilitate the development and application of PDVLNs anti-inflammatory drugs.

Phenotypic Variation in Flower Color and Morphology in the Gerbera (Gerbera hybrida) F1 Hybrid Population and Their Association with EST-SSR Markers.

Gerbera (Gerbera hybrida) is a widely cultivated ornamental plant. However, its genetic improvement is limited by the lack of genetic analysis and molecular markers for traits. In this study, we analyzed the phenotypic and genotypic variation of 140 F1 progeny from two gerbera varieties with different flower types and colors. We evaluated the flower's morphology, color, and pigment content of the F1 population and performed cluster principal component analysis (PCA) and correlation analysis. The results showed that the main ornamental traits of the hybrid progeny varied greatly. The segregation ratios of single and double flowers and ligulate and split ray florets were both 1:1. The flower colors of the F1 progeny were mainly red and purple-red, similar to the male parent's color. Furthermore, we conducted a genetic analysis of the hybrid progeny using EST-SSR markers and performed association analysis with phenotypic traits. We identified 2, 2, 3, 1, and 2 loci to be associated with peduncle length (PL), ray floret length (RFL), and outer ray floret; the level of apex relative to the top of involucre (LAI); outer corolla lips (OCL); and the b* of ray floret color, respectively. Our results reveal the genetic patterns of important ornamental traits and provide a theoretical basis and practical tools for gerbera genetic breeding.

Circular RNA Hsa_circ_0006766 targets microRNA miR-4739 to regulate osteogenic differentiation of human bone marrow mesenchymal stem cells.

Circular RNAs (circRNAs) are emerging as important regulators in bone metabolism, which is mediated by microRNA (miRNA) sponges. However, it is not clear how circRNA regulates osteogenic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs).Therefore, based on the previous circRNA chip results, hsa_circ_0006766, which is differentially expressed in the osteogenic differentiation of hBM-MSCs, was screened out, and bioinformatics analysis was performed to predict potential target miRNAs. During osteogenic differentiation of hBM-MSCs, hsa_circ_0006766 and its target miRNAs (miR-4739, miR-619-5p, miR-5787, miR-7851-3p, and miR-3192-5p) were detected by quantitative Real Time-PCR (qRT-PCR). Target gene prediction for the differentially expressed target miRNAs was performed, and target genes were validated by dual-luciferase reporter gene assay and qRT-PCR. It is shown that hsa_circ_0006766 was up-regulated and miR-4739 was down-regulated during osteogenic differentiation of hBM-MSCs.Moreover, the target gene Notch2 was predicted to be highly expressed during osteogenic differentiation. And dual-luciferase assay proved that Notch2 was the gene targeting to miR-4739. Taken together, our finding confirmed that hsa_circ_0006766 may act as a major regulatory part in osteogenic differentiation of hBM-MSCs via an hsa_circ_0006766-miR-4739-Notch2 regulatory axis. Accordingly, hsa_circ_0006766 may affect the development of osteoporosis and may thus become a therapeutic target.

Exosomal CA125 as A Promising Biomarker for Ovarian Cancer Diagnosis.

The main diagnostic indicators of ovarian cancer (OC), including carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4), show good sensitivity and poor specificity or vice versa. This study investigated changes in CA125 and HE4 expression and their correlation in serum-derived exosomes of 55 patients with OC (OC group), 33 patients with malignant tumors (non-OC group), and 55 normal controls (NC group). We compared serum and exosomal CA125 and HE4 levels to determine whether their contents in exosomes were elevated. We also compared the diagnostic efficacy of serum HE4, serum CA125, exosomal CA125, and serum HE4+exosomal CA125 in OC using the receiver operating characteristic (ROC) curve. CA125 levels in serum-derived exosomes in all groups significantly increased (P < 0.0001) compared with serum CA125 levels. HE4 was undetected in exosomes. The ROC curve showed the following values: serum CA125: 0.9093 (area), 87.27% (sensitivity), and 90.91% (specificity); serum HE4: 0.9302, 83.64%, and 94.55%; exosomal CA125: 0.9755, 94.55%, and 92.73%; and serum HE4+exosomal CA125: 0.9861, 96.36%, and 92.73%. In conclusion, CA125 can be detected at higher levels in exosomes than in serum, significantly improving OC diagnosis sensitivity. The serum HE4+exosomal CA125 combination significantly improves OC diagnostic efficiency.

PD-1 mRNA expression in peripheral blood mononuclear cells as a biomarker for different stages of primary gouty arthritis.

There is currently a lack of biomarkers to assist the diagnosis and prediction of primary gouty arthritis (PG). Therefore, we evaluated the clinical value of programmed cell death protein 1 (PD-1) mRNA expression in peripheral blood mononuclear cells (PBMCs) of patients with PG. This study included 36 patients with acute phase PG (APPG), 48 with non-acute phase PG (NAPPG), 42 with asymptomatic hyperuricemia (AH) and 79 normal controls (NCs). PD-1 mRNA expression levels were detected by qRT-PCR. PD-1 mRNA expression was statistically analysed by ANOVA or t tests, while correlations between PD-1 mRNA and clinical variables were assessed using Pearson correlation tests. Receiver operator characteristic (ROC) curve analysis was used to evaluate the diagnostic value of PD-1 in different PG stages. PD-1 mRNA expression was significantly lower in patients with APPG than that in NAPPG, AH and NCs (P < 0.01). Correlation analysis revealed that PD-1 mRNA levels correlated negatively with T-score (r = -0.209, P < 0.01). ROC curve analysis showed that serum uric acid (SUA), PD-1 mRNA and both combined displayed higher diagnostic value in patients with PG, NAPPG and APPG compared to that in NCs and patients with non-PG arthritis (NPG). Moreover, ROC curve analysis showed that SUA and PD-1 mRNA had good diagnostic value in APPG, with the greatest diagnostic power when combined. PD-1 mRNA could be a clinical auxiliary diagnostic biomarker for APPG, and the combined use of PD-1 mRNA and SUA is better than that of SUA alone.

Potential diagnostic value of PD-1 in peripheral blood mononuclear cells of postmenopausal osteoporosis patients.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is an estrogen deficiency-induced skeletal disorder. Bone mineral density (BMD) testing is the gold standard for diagnosing osteoporosis. However, its sensitivity for fracture risk assessment is low. Programmed cell death protein 1 (PD-1) is a key immune checkpoint molecule implicated in the pathophysiology of bone remodeling, but its role in osteoporosis has not yet been explored. Thus, this study aimed to assess the expression and diagnostic utility of PD-1 in PMOP. METHODS: A total of 56 patients with PMOP and 37 postmenopausal healthy controls (NC) were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll density gradient centrifugation, and PD-1 expression was measured by quantitative polymerase chain reaction (qPCR). Pearson's correlation test was performed to explore the associations between PD-1 level and clinical variables, while receiver operating characteristic (ROC) curve analysis was used to evaluate the potential diagnostic value of PD-1 in patients with PMOP. RESULTS: We found that PD-1 level was significantly upregulated in the PBMCs of PMOP patients than those of NC (P = .016). PD-1 expression was positively correlated with C-reactive protein (CRP) levels. ROC curve analysis showed that PD-1 had certain diagnostic value for PMOP (area under the curve = 0.65, standard error = 0.06, 95% confidence interval [0.53,0.76], P = .016), with a sensitivity and specificity of 44.64% and 81.08%, respectively. CONCLUSION: Programmed cell death protein 1 is significantly upregulated in the PBMCs of PMOP patients and has certain diagnostic value for PMOP.

Hsa_Circ_0001275: A Potential Novel Diagnostic Biomarker for Postmenopausal Osteoporosis.

BACKGROUND/AIMS: Circular RNAs (circRNAs) serve as potential diagnostic biomarkers. In this study, we aimed to identify a potential biomarker from peripheral blood mononuclear cells (PBMCs) of patients with postmenopausal osteoporosis (PMOP). METHODS: CircRNA expression in PBMCs from three pairs of samples from PMOP patients and controls was initially detected by circRNA microarray. The changes in selected circRNAs in PBMCs from 28 PMOP patients and 21 age- and sex-matched controls were confirmed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Next, samples from 30 PMOP patients and 20 controls were used for further verification. Pearson correlation test was performed to assess the correlation between circRNAs and clinical variables. The area under the receiver operator characteristic (ROC) curve was calculated to evaluate the diagnostic value. RESULTS: Six differentially expressed circRNAs were identified by chip microarray analysis, of which only hsa_circ_0001275 showed consistency and statistical significance in qRT-PCR. The correlation analysis between age, body weight, height, WBC, lymphocyte and monocyte count, bone density, T-score, ß-CROSSL, OSTEOC, and TP1NP showed that hsa_circ_0001275 was negatively correlated with T-score. ROC curves showed that hsa_circ_0001275 has significant diagnostic value in PMOP (AUC=0.759, P< 0.001). CONCLUSION: This study suggests that hsa_circ_0001275 may serve as a potential diagnostic biomarker for PMOP.

A common variant in pre-miR-146 is associated with coronary artery disease risk and its mature miRNA expression.

miRNAs are small non-coding RNAs that play an important role in numerous physiological processes. Common single nucleotide polymorphisms (SNPs) in pre-miRNAs may change their property through altering miRNAs expression and/or maturation, resulting in diverse functional consequences. To date, the role of genetic variants in pre-miRNAs on coronary artery disease (CAD) risk remains poorly understood. Here we aimed to evaluate the influence of three common SNPs in pre-miRNAs (miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, miR-499 rs3746444 T>C) on individual susceptibility to CAD in a Chinese population of 295 CAD patients and 283 controls. Genotyping was performed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. In a logistic regression analysis, we detected an association of rs2910164 in pre-miR-146a with the CAD risk; compared with the GG homozygotes, the GC heterozygotes [odds ratio (OR)=1.89, 95% confidence interval (CI)=1.06-3.36, P=0.029] and the CC homozygotes (OR=1.83, 95% CI=1.01-3.32, P=0.046) genotype were statistically significantly associated with the increased risk for CADs. As we used further genotype association models, we found a similar trend of the association in recessive model (OR=1.86, 95% CI=1.09-3.19, P=0.023). We also found that the genotypes of miR-146a rs2910164 were associated with its mature miRNA expression by analyzing 23 PBMC samples from CAD patients. Individuals carrying rs11614913 GC or CC genotypes showed 3.2-fold higher expression compared to GG genotype carriers (P<0.05). We observed no association of the other two SNPs in miR-196a2 (rs11614913) and miR-499 (rs3746444) with the CAD incidence. Our data provide the first evidence that the miR-146a rs2910164 polymorphism is associated with increased risk of CAD in Chinese Han population, which may be through influencing the expression levels of the miRNA.