Chlorogenic acid prevents hepatotoxicity in arsenic-treated mice: role of oxidative stress and apoptosis

Molecular Biology Reports - Arsenic is a potent and toxic heavy metal found in the environment that causes health problems, including liver disease, in humans and animals. Chlorogenic acid (CA) is...     

Biochemical study on modifying role of variants of leptin gene and its receptor on serum leptin levels in breast cancer

Molecular Biology Reports - The leptin is discharged from breast adipose tissue and is overexpressed in breast cancer (BC). Conflicting relation of leptin with BC was reported. We investigated this...     

Association between vitamin D receptor (FokI) genetic variant rs2228570 and iron profile in hemodialysis patients

Iron deficiency is a common etiology of anemia that causes suboptimal response to erythropoietin therapy in hemodialysis (HD) patients. This study investigated the association between vitamin D receptor (VDR) genetic variant (FokI) rs2228570 with iron indices (serum iron, transferrin, transferrin saturation, and ferritin). Sixty adequately hemodialyzed patients subdivided into two groups; 31 patients with transferrin saturation (TSAT)?<?20% and 29 with TSAT?>?20% who received I.V sodium ferric gluconate, calcium, and vitamin D. Sixty normal healthy were selected as the control group.. VDR genetic variant (SNP rs2228570) was genotyped in all subjects using PCR/RFLP. HD patients showed a higher frequency of rs2228570 FF genotype (38.3%) than controls (31.7%). The frequency of ff genotype and f allele in patients (8.4 and 35% respectively) were significantly lower than controls (25 and 46.7% respectively). Allele model (f vs. F): OR 0.721, 95% CI 0.521–0.998, P?=?0.049. While (ff vs. FF): OR 0.452, 95% CI 0.223–0.917, P = 0.028. The distribution of Ff?+?ff genotypes in HD cases with TSAT?>?20% was higher than in HD cases with TSAT?<?20%, Dominant model (Ff +ff vs FF): OR 2.753, 95% CI 1.902–3.409, P?=?0.048. f allele showed lower frequency in low TSAT group than high TSAT group (27.4 vs. 43.1%) with significant P value (P?=?0.042) with allele model (f vs. F): OR 2.012, 95% CI 1.923–4.226, P?=?0.042. Fok-1 ff, Ff?+?ff genotypes were significantly associated with TSAT?>?20% with a protective effect against low TSAT in HD patients.

     

Luteolin protects against lead acetate-induced nephrotoxicity through antioxidant,anti-inflammatory,anti-apoptotic,and Nrf2/HO-1 signaling pathways

Molecular Biology Reports - Lead (Pb) is one of the most common heavy metal pollutants affecting living organisms. It induces nephrotoxicity with significant alterations in renal structure and...     

Intraspecific Diversity and Taxonomy of Emmonsia crescens

Mycopathologia - Emmonsia crescens is known as an environmental pathogen causing adiaspiromycosis in small rodents. As the generic name Emmonsia is no longer available for this species, its...     

Biophysical insights into the binding characteristics of bovine serum albumin with dipyridamole and the influence of molecular interaction with β cyclodextrin

Abstract

The binding characteristic of anti-platelet drug dipyridamole has been investigated with a transport protein, serum albumin. A multi-spectroscopic approach has been employed, and the results were well supported by in silico molecular docking and simulation studies. The fluorescence quenching of serum albumin at three different temperatures revealed that the mechanism involved is static and the binding constant of the interaction was found to be of the order of 10⁴ M^?1. The reaction was found to be spontaneous and involved hydrophobic interactions. Synchronous, 3D fluorescence and CD spectroscopy indicated a change in conformation of bovine serum albumin (BSA) on interaction with DP. Using site-selective markers, the binding site of DP was found to be in subdomain IB. Molecular docking studies further corroborated these results. Molecular dynamic (MD) simulations showed lower RMSD values on interaction, suggesting the existence of a stable complex between DP and BSA. Furthermore, since β-Cyclodextrin (βCD) is used to improve the solubility of DP in ophthalmic solutions, therefore, the effect of (βCD) on the interaction of BSA and DP was also studied, and it was found that in the presence of βCD, the binding constant for BSA-DP interaction decreased. The present study is an attempt to characterize the transport of DP and to improve its bioavailability, consequently helping in dosage design to achieve optimum therapeutic levels.

Communicated by Ramaswamy H. Sarma     

Apoptosis detection via automated algorithms to analyze biomarker translocation in reporter cells

Rapid, efficient, and robust quantitative analyses of dynamic apoptotic events are essential in a high-throughput screening workflow. Currently used methods have several bottlenecks, specifically, limitations in available fluorophores for downstream assays and misinterpretation of statistical image data analysis. In this study, we developed cytochrome-C (Cyt-C) and caspase-3/-8 reporter cell lines using lung (PC9) and breast (T47D) cancer cells, and characterized them from the response to apoptotic stimuli. In these two reporter cell lines, the spatial fluorescent signal translocation patterns served as reporters of activations of apoptotic events, such as Cyt-C release and caspase-3/-8 activation. We also developed a vision-based, tunable, automated algorithm in MATLAB to implement the robust and accurate analysis of signal translocation in single or multiple cells. Construction of the reporter cell lines allows live monitoring of apoptotic events without the need for any other dyes or fixatives. Our algorithmic implementation forgoes the use of simple image statistics for more robust analytics. Our optimized algorithm can achieve a precision greater than 90% and a sensitivity higher than 85%. Combining our automated algorithm with reporter cells bearing a single-color dye/fluorophore, we expect our approach to become an integral component in the high-throughput drug screening workflow.     

Assessing the effect of zooprophylaxis on zoonotic cutaneous leishmaniasis transmission: A system dynamics approach

Capturing or diverting the disease carrying vector from humans can reduce the transmission of vector borne diseases such as leishmaniasis. The use of animals that act as dead-end hosts to relieve the vector (sandfly) bites on humans is called zooprophylaxis. However, as the number of blood meal providers especially domestic animals increases, the sandflies enhanced availability of blood meals will improve its number and survival, thereby countering the impact of diverting bites from humans. Thus, the transmission model exhibits the structure of a feedback loop characterizing complex dynamic systems. In order to rigorously assess the effect of zooprophylaxis, we propose a system dynamic model for zoonotic cutaneous leishmaniasis transmission with 3 blood-meal hosts: domestic animals, humans, and a reservoir (rodents). In this context, a simulation study of the proposed model with a follow-up period of 1000 days was performed.     

Carboxyl terminal domain basic amino acids of mycobacterial topoisomerase I bind DNA to promote strand passage

Bacterial DNA topoisomerase I (topoI) carries out relaxation of negatively supercoiled DNA through a series of orchestrated steps, DNA binding, cleavage, strand passage and religation. The N-terminal domain (NTD) of the type IA topoisomerases harbor DNA cleavage and religation activities, but the carboxyl terminal domain (CTD) is highly diverse. Most of these enzymes contain a varied number of Zn²⁺ finger motifs in the CTD. The Zn²⁺ finger motifs were found to be essential in Escherichia coli topoI but dispensable in the Thermotoga maritima enzyme. Although, the CTD of mycobacterial topoI lacks Zn²⁺ fingers, it is indispensable for the DNA relaxation activity of the enzyme. The divergent CTD harbors three stretches of basic amino acids needed for the strand passage step of the reaction as demonstrated by a new assay. We also show that the basic amino acids constitute an independent DNA-binding site apart from the NTD and assist the simultaneous binding of two molecules of DNA to the enzyme, as required during the catalytic step. Although the NTD binds to DNA in a site-specific fashion to carry out DNA cleavage and religation, the basic residues in CTD bind to non-scissile DNA in a sequence-independent manner to promote the crucial strand passage step during DNA relaxation. The loss of Zn²⁺ fingers from the mycobacterial topoI could be associated with Zn²⁺ export and homeostasis.     

Yield loss of faba bean (Vicia faba) due to chocolate spot (Botrytis fabae) in sole and mixed cropping systems in Ethiopia

Two field experiments were conducted during 2004 and 2005 cropping seasons at Adet Agricultural Research Center, Ethiopia to assess yield losses caused by chocolate spot(Botrytis fabae) of faba bean in sole and mixed cropping systems using two cultivars. Cropping systems were sole faba bean (FB), faba bean mixed with field pea (FB: FP), barley (FB: BA) and maize (FB: MA). Mancozeb was sprayed at the rate of 2.5 kg a.i/ha at 7-, 14- and 21-day interval to generate different levels of chocolate spot disease in all the four cropping systems, and unsprayed control was also included. The treatments were arranged in a randomised complete block design (RCBD) with four replications. FB: MA mixed cropping significantly reduced disease severity and the area under disease progress curve (AUDPC) and increased faba bean grain yield. The highest faba bean grain yield among the three mixed croppings under different spray schedules was obtained from FB: MA mixed cropping in both 2004 and 2005 (2.56 and 3.74 t/ha, respectively) cropping seasons. There were highly significant yield differences (P < 0.05) among the spray intervals of mancozeb in both seasons. The highest grain yield (4.9 t/h) was recorded from the 7-day spray interval in 2005. The unsprayed faba bean had a lower grain yield (1.9 t/ha in 2004 and 2.3 t/ha in 2005) compared to the sprayed plots. The highest relative yield loss (67.5%) was calculated in 2005 from FB: FP mixed cropping in unsprayed plots. The relative yield losses in the unsprayed plots were in the range of 35.8–41.5% in 2004 and 52.6–67.5% in the 2005 cropping season. Severity and AUDPC were inversely correlated with faba bean grain yield. Significant differences were recorded in the 100-seed weight and days to maturity (DM). The unsprayed plots had shorter DM ranging from 126 to 128.5 day (except FB: MA mixed cropping) in 2004 and 122–123.9 days in 2005. In the sprayed plots DM was relatively longer than the unsprayed plots. A higher seed weight was recorded in the sole FB (56 g) and FB: MA (55 g) mixed cropping, and the lowest value of 100-seed weight was recorded from FB: FP (53 g) mixed cropping. The productivity of the mixed cropping evaluated by land equivalent ratio (LER) exceeded that of sole cropping. Faba bean grain yield was highly influenced by the severity of chocolate spot. The disease affects the DM, forcing early maturing of the plants.