Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Eriodictyol attenuates doxorubicin-induced nephropathy by activating the AMPK/Nrf2 signalling pathway

Doxorubicin (DOX), an anthracycline chemotherapy, plays a prominent role in the treatment of various cancers. Unfortunately, its nephrotoxic effects limit its dosing and expose cancer survivors to increased morbidity and mortality. This study examined the nephroprotective effects of eriodictyol, a natural polyphenolic flavanone, in DOX-treated rats and the molecular pathways involved. Forty adult rats were divided into five groups (8/group): Control; eriodictyol (20 mg/kg/day); DOX (2.5 mg/kg, twice/week); DOX + Eriodictyol; and DOX + Eriodictyol + Compound C (CC), an AMPK inhibitor (0.2 mg/kg/day). Experiments continued for 21 days. Eriodictyol administration in DOX-treated rats reduced their fasting glucose levels and increased food intake, final body weight, and kidney weight, improved kidney function, prevented glomerular and tubular damage, and reduced collagen deposition and renal TGF-β1 mRNA levels. Furthermore, eriodictyol reduced their renal levels of Bax, caspase-3, and cytochrome-c; and enhanced the levels of Bcl2. Noticeably, in the kidneys of both controls and DOX-treated rats, eriodictyol increased levels of phosphorylated-AMPK(Thr172) but not AMPK mRNA nor protein levels. Also, in the same two groups, eriodictyol increased mRNA and nuclear Nrf2 levels, and levels of glutathione, superoxide dismutase, catalase, and hemeoxygenase-1, but reduced the levels of malonaldehyde, TNF-α, and mRNA, total, and nuclear levels of NF-κB. All the detected nephroprotective effects and improvements in the levels of markers of oxidation and inflammation were prevented by coadministration of CC. In conclusion, the coadministration of eriodictyol and DOX alleviates DOX-induced renal damage. In renal tissues, eriodictyol is an AMPK activator and its nephroprotective antioxidant and anti-inflammatory effects are AMPK-dependent

Phyto-Synthesis, Characterization, and In Vitro Antibacterial Activity of Silver Nanoparticles Using Various Plant Extracts

Aloe vera, Mentha arvensis (mint), Coriandrum sativum (coriander), and Cymbopogon citratus (lemongrass) leaf extracts were used to synthesize stable silver nanoparticles (Ag-NPs) by green chemistry. UV–vis spectrophotometry, X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX) spectroscopy techniques were used to characterize these biosynthesized nanoparticles. The data indicated that the silver nanoparticles were successfully synthesized, and the narrower particle size distribution was at 10–22 nm by maintaining a specific pH. As a short-term post-sowing treatment, Ag-NP solutions of different sizes (10 and 50 ppm) were introduced to mung bean seedlings, and the overall increase in plant growth was found to be more pronounced at 50 ppm concentration. The antibacterial activity of Ag-NPs was also investigated by disc diffusion test, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) test. The zones of inhibition (ZOI) were shown by Escherichia coli (E. coli) (1.9, 2.1, 1.7, and 2 mm), followed by Staphylococcus aureus (S. aureus) (1.8, 1.7, 1.6, and 1.9 mm), against coriander, mint, Aloe vera, and lemongrass, respectively. MIC and MBC values of E. coli, and S. aureus ranged from 7 to 8 µg/mL. Overall, this study demonstrates that Ag-NPs exhibit a strong antimicrobial activity and thus might be developed as a new type of antimicrobial agent for the treatment of bacterial infection