Molecular docking analysis of compounds from Lycopersicon esculentum with the insulin receptor to combat type 2 diabetes

It is known that tomato (Lycopersicon esculentum) contains bioactive compounds to combat type-2 diabetes. Therefore, it is of interest to document data from the molecular docking analysis of compounds from Lycopersicon esculentum with the insulin receptors to combat type-2 diabetes. We report the binding features of cinnamic acid, chlorogenic acid, gallic acid & glucoside with insulin receptors for further consideration.     

Molecular docking analysis of stachydrine and sakuranetin with IL-6 and TNF-α in the context of inflammation

Inflammation is a process triggered by pro-inflammatory cytokines and anti-inflammatory molecules. Therefore, it is of interest to document the anti-inflammatory activity of Stachydrine and Sakuranetin against the inflammatory target proteins IL-6 and TNF-α by using molecular docking analysis. Both compounds showed good binding features with the selected target proteins. Compared to Sakuranetin, the Stachydrine have low binding energy and good hydrogen bond interactions. Hence, data show that Stachydrine possessed high and specific inhibitory activity on tumor necrosis factor-α and interleukin-6.     

Modulation of G protein-coupled adenosine receptors by strategically functionalized agonists and antagonists immobilized on gold nanoparticles

Gold nanoparticles (AuNPs) allow the tuning of pharmacokinetic and pharmacodynamic properties by active or passive targeting of drugs for cancer and other diseases. We have functionalized gold nanoparticles by tethering specific ligands, agonists and antagonists, of adenosine receptors (ARs) to the gold surface as models for cell surface interactions with G protein-coupled receptors (GPCRs). The AuNP conjugates with chain-extended AR ligands alone (PEGylated nucleosides and nonnucleosides, anchored to the Au via thioctic acid) were found to be insoluble in water due to hydrophobic entities in the ligand. Therefore, we added a second, biologically inactive pendant moiety to increase the water solubility, consisting of a PEGylated chain terminating in a carboxylic or phosphate group. The purity and stability of the immobilized biologically active ligand were examined by ultrafiltration and HPLC. Pharmacological receptor binding studies on these GPCR ligand-derivatized AuNPs (2–5 nm in diameter), performed using membranes of mammalian cells stably expressing human A₁, A_2A, and A₃ARs, showed that the desired selectivity was retained with K _i values (nanomolar) of A₃AR agonist 21b and A_2AAR antagonists 24 and 26a of 14 (A₃), 34 (A_2A), and 69 (A_2A), respectively. The corresponding monomers displayed K _i values of 37, 61, and 1,420 nM, respectively. In conclusion, we have synthesized stable, water-soluble AuNP derivatives of tethered A₃ and A_2AAR ligands that retain the biological properties of their monomeric ligands and are intended for therapeutic and imaging applications. This is the first prototypical application to gold carriers of small molecule (nonpeptide) GPCR ligands, which are under investigation for treatment of cancer and inflammatory diseases.     

Mutations in exons 3 and 7 resulting in truncated expression of human ATP6V1B1 gene showing structural variations contributing to poor substrate binding-causative reason for distal renal tubular acidosis with sensorineural deafness

Distal renal tubular acidosis (dRTA) is an autosomal recessive syndrome results defect in either proximal tubule bicarbonate reabsorption or in distal tubule H⁺ secretion and is characterized by severe hyperchloraemic metabolic acidosis in childhood. dRTA is associated with functional variations in the ATP6V1B1 gene encoding β1 subunit of H⁺-ATPase, key membrane transporters for net acid excretion of α-intercalated cells of medullary collecting ducts. In the present study, a 13-year-old male patient suffering with nephropathy and sensorineural deafness was reported in the Department of Nephrology. We predicted improper functioning of ATP6V1B1 gene could be the reason for diseased condition. Therefore, exons 3, 4, and 7 contributing active site of ATP6V1B1 gene was amplified and sequenced (Accession numbers: KF571726, KM222653). The obtained sequences were BLAST searched against the wild type ATP6V1B1 gene which showed novel mutations c.307 A > G, c.308 C > A, c.310 C > G, c.704 T > C, c.705 G > T, c.709 A > G, c.710 A > G, c.714 G > A, c.716 C > A, c.717delC, c.722 C > G, c.728insG, c.741insT, c.753G > C. These mutations resulted in the expression of truncated protein terminating at Lys 209. The mutated ATP6V1B1structure superimposed with wild type showed extensive variations with RMSD 1.336 Å and could not bind to substrate ADP leading to non-functional ATPase. These results conclusively explain these mutations in ATP6V1B1 gene resulted in structural changes causing accumulation of H⁺ ions contributing to dRTA with sensorineural deafness.     

Heregulin-induced epigenetic regulation of the utrophin-A promoter

Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne's muscular dystrophy (DMD) locus. Utrophin is of therapeutic interest since its over-expression can compensate dystrophin's absence. Utrophin is enriched at neuromuscular junctions due to heregulin-mediated utrophin-A promoter activation. We demonstrate that heregulin activated MSK1/2 and phosphorylated histone H3 at serine 10 in cultured C2C12 muscle cells, in an ERK-dependent manner. MSK1/2 inhibition suppressed heregulin-mediated utrophin-A activation. MSK1 over-expression potentiated heregulin-mediated utrophin-A activation and chromatin remodeling at the utrophin-A promoter. These results identify MSK1/2 as key effectors modulating utrophin-A expression as well as identify novel targets for DMD therapy.     

Optical analysis of RE3+ (RE = Nd or Er):B2O3–P2O5–CaF2–ZnO–(Li2O/Na2O/K2O) glasses

Calcium boro fluoro zinc phosphate glasses modified using alkali oxide and doped with Nd³⁺ and Er³⁺ ions with the chemical composition of 69.5 (B₂O₃) + 10 (P₂O₅) + 10 (CaF₂) + 5 (ZnO) + 5 (Na₂O/Li₂O/K₂O) + 0.5 (Er₂O₃/Nd₂O₃) were prepared using a conventional melt quenching technique. The results of X-ray diffraction patterns indicated the amorphous nature of all the prepared glasses. The visible–near-infrared red (NIR) absorption spectra of these glasses were analyzed systematically. The NIR emission spectra of Er³⁺ and Nd³⁺:calcium boro fluoro zinc phosphate glasses showed prominent emission bands at 1536 nm (⁴I_13/2→⁴I_15/2) and 1069 nm (⁴F_3/2→⁴I_11/2) respectively with λ_exci = 514.5 nm (Ar⁺ laser) as the excitation source.     

Incidence of lab-confirmed dengue fever in a pediatric cohort in Delhi,India

BackgroundOur aim was to estimate the overall and age-specific incidence of lab-confirmed dengue fever using ELISA based assays among children 6 months to 15 years in Delhi.MethodsWe enrolled a cohort of 984 children aged 6 months to <14 years in South Delhi and followed-up weekly for fever for 24 months or till 15 completed years of child-age. Households of the enrolled children were geo-tagged. NS1, IgM and IgG assays were conducted using ELISA method to confirm dengue fever in children with ≥3 consecutive days of fever. Molecular typing was done in a subset of NS1 positive cases to identify the circulating serotypes.Principal findingsWe had a total of 1953 person-years (PY) of follow up. Overall, there were 4208 episodes of fever with peaks during June to November. The overall incidence (95%CI) of fever was 215/100 PY (209 to 222). A total of 74/1250 3-day fever episodes were positive for acute dengue fever (NS1 and/or IgM positive). The overall incidence (95%CI) of acute dengue fever was 37.9 (29.8 to 47.6) per 1000 PY; highest among children aged 5 to 10 years (50.4 per 1000 PY, 95% CI 36.5 to 67.8). Spatial autocorrelation analysis suggested a clustering pattern for the dengue fever cases (Moran’s Index 0.35, z-score 1.8, p = 0.06). Dengue PCR was positive in 16 of the 24 specimens tested; DEN 3 was the predominant serotype identified in 15/24 specimens.ConclusionsWe found a high incidence of dengue fever among under 15-year children with clustering of cases in the community. DEN 3 was the most commonly circulating strain encountered. The findings underscore the need for development of affordable pre-vaccination screening strategy as well as newer dengue vaccines for young children while continuing efforts in vector control.