Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney, especially in lung tissue. A growing body of evidence ...suggests that apelin/APJ system is closely related to the development of respiratory diseases. Therefore, in this review, we focus on the role of apelin/APJ system in respiratory diseases, including pulmonary arterial hypertension (PAH), pulmonary embolism (PE), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), obstructive sleep apnoea syndrome (OSAS), non-small cell lung cancer (NSCLC), pulmonary edema, asthma, and chronic obstructive pulmonary diseases. In detail, apelin/APJ system attenuates PAH by activating AMPK-KLF2-eNOS-NO signaling and miR424/503-FGF axis. Also, apelin protects against ALI/ARDS by reducing mitochondrial ROS-triggered oxidative damage, mitochondria apoptosis, and inflammatory responses induced by the activation of NF-κB and NLRP3 inflammasome. Apelin/APJ system also prevents the occurrence of pulmonary edema via activating AKT-NOS3-NO pathway. Moreover, apelin/APJ system accelerates NSCLC cells’ proliferation and migration via triggering ERK1/2–cyclin D1 and PAK1–cofilin signaling, respectively. Additionally, apelin/APJ system may act as a predictor in the development of OSAS and PE. Considering the pleiotropic actions of apelin/APJ system, targeting apelin/APJ system may be a potent therapeutic avenue for respiratory diseases.
Osteoarthritis (OA) affects elderly population worldwide and endoplasmic reticulum (ER) stress is known to be positively correlated with OA development. Previous reports prove the cytoprotective ...effects of baicalin on chondrocytes, whereas the mechanisms are hardly reported. Hence, we aimed to investigate the links between OA, ER stress, and baicalin. Chondrocytes from patients with OA were subjected to H2O2 treatment with or without baicalin pretreatment, and cell viability was assessed via Cell Counting Kit-8. Messenger RNA (mRNA) amounts of apoptosis-related genes (Bax, Bcl-2, and Caspase-3), extracellular matrix (ECM)-related genes (Collange I, Collange II, Aggrecan, and Sox9) and ER stress hallmarks (binding immunoglobulin protein BiP C/EBP homologous protein CHOP) were evaluated via quantitative real-time PCR. Bax, Bcl-2, BiP, and CHOP protein levels were analyzed via Western blot. Baicalin suppressed the changes in cell viability and apoptosis-related gene expressions caused by H2O2. Reactive oxygen species and glutathione/oxidized glutathione assay showed that H2O2 enhanced oxidative stress. Baicalin suppressed H2O2-induced downregulation of mRNA expression of ECM-related genes. Moreover, baicalin reduced H2O2-stimulated increase in oxidative stress and the expression of ER stress hallmarks. Endoplasmic reticulum stress inducer abolished the protective activities, whereas ER stress inhibitor did not exhibit extra protective effects. Baicalin pretreatment protected patient-derived chondrocytes from H2O2 through ER stress inhibition.
The interleukin10 (IL-10) gene polymorphisms have been indicated to be associated with breast cancer (BC) risk, but the findings are still controversial. To derive a more precise evaluation, we ...performed a comprehensive meta-analysis.
A systematic literature search was conducted using PubMed, Embase, CNKI, China biomedical (CBM), and Google Scholar to 29 March 2020. Revman5.3 and Stata 12.0 software analyzed the data, and the strength of the association was identified using the odds ratio (OR) and the corresponding 95% confidence interval (CI).
A total of 23 studies (7,250 cancer cases and 7,675 case-free controls) were included in this meta-analysis. The results show that IL-10 gene polymorphisms were significantly correlated with BC risk based on subgroup analysis by ethnicity. The IL-10 rs1800896 polymorphism was significantly associated with the risk of BC in Asians (G vs. A: OR = 0.78, 95% CI = 0.65-0.95,
= 0.01; GG vs. AA: OR = 0.51, 95% CI = 0.31-0.84,
= 0.007; GA vs. AA: OR = 0.6, 95% CI = 0.44-0.81,
= 0.0009; GG + GA vs. AA: OR = 0.6, 95% CI = 0.45-0.81,
= 0.0007); Moreover, an increased BC risk in Asians were also associated with the IL-10 rs1800872 polymorphism (AA vs CC: OR = 0.74, 95% CI = 0.55-0.99,
= 0.04; A vs C: OR = 0.85, 95% CI = 0.74-0.98,
= 0.03). In addition, The IL-10 rs1800871 (CT vs. TT: OR = 1.8, 95% CI = 1.03-3.13,
= 0.04) and rs1800872 polymorphism (A vs C: OR = 0.65, 95% CI 0.43-0.98,
= 0.04) were associated with BC risk in Caucasians.
Collectively, this meta-analysis demonstrated that IL-10 rs1800896 and rs1800872 (AA vs. CC; A vs. C) polymorphisms significantly increased the risk of BC in Asians, while the rs1800871 and rs1800872 (A vs. C) were associated with the risk of BC in Caucasians. Therefore, this may provide new ideas for predicting and diagnosing BC susceptibility through the detection of IL-10 gene polymorphism.
https://www.crd.york.ac.uk/ PROSPERO, identifier CRD42021266635.
CCCH-type zinc finger proteins comprise a large protein family. Increasing evidence suggests that members of this family are RNA-binding proteins with regulatory functions in mRNA processing. ...Compared with those in animals, functions of CCCH-type zinc finger proteins involved in plant growth and development are poorly understood.
Here, we performed a genome-wide survey of CCCH-type zinc finger genes in maize (Zea mays L.) by describing the gene structure, phylogenetic relationships and chromosomal location of each family member. Promoter sequences and expression profiles of putative stress-responsive members were also investigated. A total of 68 CCCH genes (ZmC3H1-68) were identified in maize and divided into seven groups by phylogenetic analysis. These 68 genes were found to be unevenly distributed on 10 chromosomes with 15 segmental duplication events, suggesting that segmental duplication played a major role in expansion of the maize CCCH family. The Ka/Ks ratios suggested that the duplicated genes of the CCCH family mainly experienced purifying selection with limited functional divergence after duplication events. Twelve maize CCCH genes grouped with other known stress-responsive genes from Arabidopsis were found to contain putative stress-responsive cis-elements in their promoter regions. Seven of these genes chosen for further quantitative real-time PCR analysis showed differential expression patterns among five representative maize tissues and over time in response to abscisic acid and drought treatments.
The results presented in this study provide basic information on maize CCCH proteins and form the foundation for future functional studies of these proteins, especially for those members of which may play important roles in response to abiotic stresses.
The APJ is a class A, rhodopsin-like G protein-coupled receptor (GPCR) with high sequence similarity to the angiotensin receptor AT1. APJ has been shown to be widely expressed in humans tissues, ...including the central nervous system, cardiovascular system, adipocytes and others. APJ plays an important role in the occurrence and development of cardiovascular and metabolic diseases including atherosclerosis (AS), coronary heart disease (CAD), heart failure(HF), pulmonary arterial hypertension (PAH), myocardial hypertrophy and atrial fibrillation, especially hypertension. Previous researchers found that apelin/APJ could induce vasodilation and then reduce blood pressure. Despite APJ is closely associated with many diseases, there are no drugs that can activate or inhibit APJ directly. In the current review, we have summarized recently reported peptides, small molecule agonists and antagonists targeting APJ. Given the role of apelin/APJ in hypertension and other cardiovascular diseases, we believe that the peptides and compounds based on APJ will be developed for treatment of these diseases.
Apelin is an endogenous ligand of the APJ receptor (also known as Aplnr) which is a G protein-coupled receptor 1,2. Elabela (also known as Toddler, ApeLa), which shares little sequence similarity ...with Apelin (Fig. 1), has been identified as a new endogenous ligand for APJ receptor 3. Elabela is encoded by AK092578 gene from a region of the human genome which was previously classified as 'non-coding'. Elabeta is initially translated into a peptide of 54 ami- no acids including a secretory signal peptide. However, its mature form only contains 32 amino acids. The Elabela/Aplnr axis mainly acts in embryonic development compared with Apelin/APJ system which has abundant biological functions in different physiological and pathological processes 4-8. During zebra fish embryogenesis,
Abstract
Background
Bracing and exercise methods were used in scoliosis rehabilitation and proven effective. There was little evidence about the efficacy of insoles on scoliosis.
Objective
This study ...aimed to investigate the effects of 3D personalized insoles on curve magnitude, postural stability, and quality of life (QOL) in moderate adolescent idiopathic scoliosis (AIS) patients.
Methods
Thirty-six volunteers with adolescent idiopathic scoliosis, who had moderate curves (20°-45°), were randomly divided into the experimental and control groups. The control group received traditional rehabilitation with bracing and exercises, and the experimental group received the insole interventions in addition to traditional rehabilitation. The outcome measures were Cobb angle, angle of trunk rotation (ATR), postural stability, and quality of life (Scoliosis Research Society-22 questionnaire). Measurements were conducted at baseline examination, two months and six months.
Results
After two and six months of treatment, the Cobb angle and ATR in both groups were significantly decreased as compared with the baseline (
p
< 0.05), but no significant group difference in Cobb angle and ATR was found in the study (
p
> 0.05). There was a significant difference in the sagittal balance index at six months compared to the control group (
p
< 0.05), and a significant difference in the coronal balance index was observed at six months compared to baseline in the experimental group (
p
< 0.05). Quality of life did not change in either group (
p
> 0.05).
Conclusion
Combining bracing with exercise in patients with moderate AIS is effective. 3D personalized insoles cannot reduce the Cobb angle and angle of trunk rotation of patients with moderate AIS but might have the potential to improve postural stability.
OA imposes a heavy burden on patients and society in that its mechanism is still unclear, and there is a lack of effective targeted therapy other than surgery.
The osteoarthritis dataset GSE55235 was ...downloaded from the GEO database and analyzed for differential genes by limma package, followed by analysis of immune-related modules by xcell immune infiltration combined with the WGCNA method, and macrophage polarization-related genes were downloaded according to the Genecard database, and VennDiagram was used to determine their intersection. These genes were also subjected to gene ontology (GO), disease ontology (DO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Using machine learning, the key osteoarthritis genes were finally screened. Using single gene GSEA and GSVA, we examined the significance of these key gene functions in immune cell and macrophage pathways. Next, we confirmed the correctness of the hub gene expression profile using the GSE55457 dataset and the ROC curve. Finally, we projected TF, miRNA, and possible therapeutic drugs using the miRNet, TargetScanHuman, ENCOR, and NetworkAnalyst databases, as well as Enrichr.
VennDiagram obtained 71 crossover genes for DEGs, WGCNA-immune modules, and Genecards; functional enrichment demonstrated NF-κB, IL-17 signaling pathway play an important role in osteoarthritis-macrophage polarization genes; machine learning finally identified CSF1R, CX3CR1, CEBPB, and TLR7 as hub genes; GSVA analysis showed that CSF1R, CEBPB play essential roles in immune infiltration and macrophage pathway; validation dataset GSE55457 analyzed hub genes were statistically different between osteoarthritis and healthy controls, and the AUC values of ROC for CSF1R, CX3CR1, CEBPB and TLR7 were more outstanding than 0.65.
CSF1R, CEBPB, CX3CR1, and TLR7 are potential diagnostic biomarkers for osteoarthritis, and CSF1R and CEBPB play an important role in regulating macrophage polarization in osteoarthritis progression and are expected to be new drug targets.
•Pioneering bioinformatics approach to study macrophage genes in osteoarthritis.•Breakthrough in analyzing GSE55235 dataset for osteoarthritis.•Identified CSF1R, CX3CR1, CEBPB, TLR7 as diagnostic biomarkers.•Validated hub genes and predicted drugs for osteoarthritis treatment.•Integrated GO, DO, KEGG, and GSEA in osteoarthritis research.
The aim of this study was to investigate the role of apelin in the cell proliferation and autophagy of lung adenocarcin- oma. The over-expression of APJ in lung adenocarcinoma was detected by ...immunohistochemistry, while plasma apelin level in lung cancer patients was measured by enzyme-linked immunosorbent assay. Our findings revealed that apelin-13 significantly increased the phosphorylation of ERK1/2, the expression of cyclin D1, microtubule-associated protein 1 light chain 3A/B (LC3A/B), and beclinl, and con- fwmed that apelin-13 promoted A549 cell proliferation and induced A549 cell autophagy via ERK1/2 signaling. More- over, there are pores on the surface of human lung adeno- carcinoma cell line A549 and apelin-13 causes cell surface smooth and glossy as observed under atomic force micros- copy. These results suggested that ERK1/2 signaling pathway mediates apelin-13-induced lung adenocarcinoma cell proliferation and autophagy. Under our experimental condition, autophagy associated with 3-methyladenine was not involved in cell proliferation.