Methylated Flavonols from Amomum koenigii J.F.Gmel. and Their Antimicrobial and Antioxidant ActivitiesRead the full article
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Single-Nucleotide Polymorphisms in XPO5 are Associated with Noise-Induced Hearing Loss in a Chinese Population
Objectives.The purpose of this study was to investigate the correlation between single-nucleotide polymorphism (SNP) in 3′UTR of XPO5 gene and the occurrence of noise-induced hearing loss (NIHL), and to further explore the regulatory mechanism of miRNAs in NIHL on XPO5 gene. Methods.We conducted a case-control study involving 1040 cases and 1060 controls. The effects of SNPs on XPO5 expression were studied by genotyping, real-time polymerase chain reaction (qPCR), cell transfection, and the dual-luciferase reporter assay. Results.We genotyped four SNPs (rs2257082, rs11077, rs7755135, and rs1106841) in the XPO5 gene. The rs2257082 AG/GG carriers have special connection to an increased risk of noise-induced hearing loss compared to the AA carriers. The rs11077TG/GG carriers had a significantly increased association with NIHL susceptibility than the TT carriers. There was a higher risk of NIHL in the XPO5 gene rs7755135 CC carriers than in the TT carriers. No statistically significant correlation was obtained with respect to SNPrs1106841. Functional experiments showed that the rs11077 change might inhibit the interaction between miRNAs (miRNA-4763-5p, miRNA-5002-3p, and miRNA-617) and XPO5, with rs11077G allele resulting in overexpression of XPO5. Conclusion. The genetic polymorphism, rs11077, within XPO5 is associated with the risk of noise-induced hearing loss in a Chinese population.
The Emerging Role of Rab5 in Membrane Receptor Trafficking and Signaling Pathways
Ras analog in brain (Rab) proteins are small guanosine triphosphatases (GTPases) that belong to the Ras-like GTPase superfamily, and they can regulate vesicle trafficking. Rab proteins alternate between an activated (GTP-bound) state and an inactivated (GDP-bound) state. Early endosome marker Rab5 GTPase, a key member of the Rab family, plays a crucial role in endocytosis and membrane transport. The activated-state Rab5 recruits its effectors and regulates the internalization and trafficking of membrane receptors by regulating vesicle fusion and receptor sorting in the early endosomes. In this review, we summarize the role of small Rab GTPases Rab5 in membrane receptor trafficking and the activation of signaling pathways, such as Ras/MAPK and PI3K/Akt, which ultimately affect cell growth, apoptosis, tumorigenesis, and tumor development. This review may provide some insights for our future research and novel therapeutic targets for diseases.
Animal Models of Osteochondral Defect for Testing Biomaterials
The treatment of osteochondral defects (OCD) remains a great challenge in orthopaedics. Tissue engineering holds a good promise for regeneration of OCD. In the light of tissue engineering, it is critical to establish an appropriate animal model to evaluate the degradability, biocompatibility, and interaction of implanted biomaterials with host bone/cartilage tissues for OCD repair in vivo. Currently, model animals that are commonly deployed to create osteochondral lesions range from rats, rabbits, dogs, pigs, goats, and sheep horses to nonhuman primates. It is essential to understand the advantages and disadvantages of each animal model in terms of the accuracy and effectiveness of the experiment. Therefore, this review aims to introduce the common animal models of OCD for testing biomaterials and to discuss their applications in translational research. In addition, we have reviewed surgical protocols for establishing OCD models and biomaterials that promote osteochondral regeneration. For small animals, the non-load-bearing region such as the groove of femoral condyle is commonly chosen for testing degradation, biocompatibility, and interaction of implanted biomaterials with host tissues. For large animals, closer to clinical application, the load-bearing region (medial femoral condyle) is chosen for testing the durability and healing outcome of biomaterials. This review provides an important reference for selecting a suitable animal model for the development of new strategies for osteochondral regeneration.
miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway
Osteoarthritis (OA) is a chronic joint function disorder with characteristics of chondrocytes reduction and extracellular matrix (ECM) components destruction. MicroRNAs (miRNAs) and the SDF-1/CXCR4 axis are essential factors of chondrocyte apoptosis and ECM degeneration. However, very few studies have investigated the correlation between miRNAs and the SDF-1/CXCR4 axis in osteoarthritis so far. Here, through miRNAs microarray and bioinformatics analyses, we identified miR-142-5p as a CXCR4-targeted and dramatically downregulated miRNA in cartilage from OA patients, as well as in SDF-1-induced OA chondrocytes in vitro. In SDF-1-treated primary human OA chondrocytes that were transfected with a miR-142-5p mimic or inhibitor, the expression of CXCR4 was found to be inversely correlated with the expression of miR-142-5p. The dual luciferase reporter assay further verified the target relationship between miR-142-5p and CXCR4. Overexpression of miR-142-5p alleviated OA pathology by suppressing chondrocyte apoptosis, even in CXCR4 overexpressed OA chondrocytes. This was associated with decreased cartilage matrix degradation, reduced cartilage inflammation, and inactivated MAPK signaling pathway. Our study suggests that upregulated expression of CXCR4-targeted miR-142-5p can inhibit apoptosis, inflammation, and matrix catabolism and inactivate the MAPK signaling pathway in OA chondrocytes. Our work provides important insight into targeting miR-142-5p and the SDF-1/CXCR4 axis in OA therapy.
In Vivo Antimalarial Activity of 80% Methanol and Aqueous Bark Extracts of Terminalia brownii Fresen. (Combretaceae) against Plasmodium berghei in Mice
Background. Despite a substantial scientific progress over the past two decades, malaria continues to be a worldwide burden. Evergrowing resistance towards the currently available antimalarial drugs is a challenge to combat malaria. Medicinal plants are a promising source of new drugs to tackle this problem. Thus, the present study aimed at evaluating the antiplasmodial activity of Terminalia brownii in Plasmodium berghei infected mice. Methods. A 4-day suppressive test was employed to evaluate the antimalarial effect of 80% methanol and aqueous bark extracts of T. brownii against P. berghei in Swiss albino mice. Results. The in vivo acute toxicity test indicated that both extracts of T. brownii did not cause mortality. The 4-day early infection test revealed that the 80% methanol and aqueous extracts exhibited a significant inhibition of parasitemia compared to negative control. The maximum level of chemosuppression (60.2%) was exhibited at 400 mg/kg dose of 80% methanol extract. Moreover, the 80% methanol extract showed a significant attenuation of anemia associated with infection in a dose-dependent manner. The aqueous extract, on the other hand, exhibited a percent inhibition of 51.1% at the highest dose (400 mg/kg/day). Conclusion. The present study indicated that hydromethanolic and aqueous bark extracts of T. brownii possess a promising antimalarial activity, with higher effect exhibited by the hydromethanolic extract.
Protein Binding Characteristics of the Principal Green Tea Catechins: A QCM Study Comparing Crude Extract to Pure EGCG
Label-free detection methods such as the quartz crystal microbalance (QCM) are well suited to the analysis of molecular interactions in complex mixtures such as crude botanical extracts. In the present study, the binding characteristics of epigallocatechin gallate (EGCG) and crude green tea extract solutions to bovine serum albumin (BSA) have been investigated. The adsorbed mass levels onto BSA-functionalized surfaces were measured at various solution concentrations. Langmuir and Freundlich isotherms were used to model the adsorption data. The Langmuir isotherm better described the adsorption behavior with correlations of 0.68 and 0.70 for the EGCG and the crude extract solutions, respectively. The better fit of the Langmuir model indicates that adsorption occurs homogeneously and that aggregation is negligible. The mass saturation is estimated to be 58% higher for the crude green tea solution as compared to the pure EGCG solution (7.9 ng/cm2 for green tea and 5 ng/cm2 for EGCG). The increased adsorption for the crude extract indicates that the additional tea chemical constituents are binding to alternate sites on the protein molecule and that competitive binding is a nondominant effect. However, a reduced adsorption rate for the crude extract was also observed, indicating some presence of competitive mechanisms. The results demonstrate the utility of the QCM for the analysis of protein binding in crude mixtures as well as pure compounds.