A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins

Exogenous drugs that are used as antidote against chemotheray, inflammation or viral infection, gets absorbed and interacts reversibly to the major serum transport protein i.e. albumins, upon entering the circulatory system. To have a structural guideline in the rational drug designing and in the synthesis of drugs with greater efficacy, the binding mechanism of an antineoplastic and anti-inflammatory drug Nordihydroguaiaretic acid (NDGA) with human and bovine serum albumins (HSA & BSA) were examined by spectroscopic and computational methods. NDGA binds to site II of HSA with binding constant (K_b) ~10⁵ M^-1 and free energy (ΔG) ~ -7.5 kcal.mol^-1. It also binds at site II of BSA but with lesser binding affinity (K_b) ~10⁵ M^-1 and ΔG ~ -6.5 kcal.mol^-1. The negative value of ΔG, ΔH and ΔS for both the albumins at three different temperatures confirmed that the complex formation process between albumins and NDGA is spontaneous and exothermic. Furthermore, hydrogen bonds and hydrophobic interactions are the main forces involved in complex formation of NDGA with both the albumins as evaluated from fluorescence and molecular docking results. Binding of NDGA to both the albumins alter the conformation and causes minor change in the secondary structure of proteins as indicated by the CD spectra.     

The effect of foetal decapitation on the antenatal development of the enzymes monoamine oxidase and catechol O-methyl transferase in rabbit foetuses

The development of the enzymes monoamine oxidase and catechol O-methyl transferase in rabbit foetuses was studied. The adrenocortical system of the rabbit foetuses was inactivated by hypophysectomy on the 18th day of foetal age. The hypophysectomy of the foetuses by decapitation in utero resulted in marked increases in the activities of the enzymes monoamine oxidase and catechol O-methyl transferase in most of the body organs determined 12 days after the operation. A single administration of adrenocorticotropic hormone or hydrocortisone to the decapitated foetuses reduced the activities of both the enzymes studied in most of the body organs. The results suggest that glucocorticoids present in the circulation of foetal animals act as inhibitory factor for enzymes of catecholamine degradation. The inactivation of glucocorticoidogenesis by removal of the hypophysis takes away this rate-limiting control and highly significant increases in the activities of the enyzmes monoamine oxidase and catechol O-methyl transferase occur.     

Probiotics and their fermented food products are beneficial for health

Probiotics are usually defined as microbial food supplements with beneficial effects on the consumers. Most probiotics fall into the group of organisms' known as lactic acid-producing bacteria and are normally consumed in the form of yogurt, fermented milks or other fermented foods. Some of the beneficial effect of lactic acid bacteria consumption include: (i) improving intestinal tract health; (ii) enhancing the immune system, synthesizing and enhancing the bioavailability of nutrients; (iii) reducing symptoms of lactose intolerance, decreasing the prevalence of allergy in susceptible individuals; and (iv) reducing risk of certain cancers. The mechanisms by which probiotics exert their effects are largely unknown, but may involve modifying gut pH, antagonizing pathogens through production of antimicrobial compounds, competing for pathogen binding and receptor sites as well as for available nutrients and growth factors, stimulating immunomodulatory cells, and producing lactase. Selection criteria, efficacy, food and supplement sources and safety issues around probiotics are reviewed. Recent scientific investigation has supported the important role of probiotics as a part of a healthy diet for human as well as for animals and may be an avenue to provide a safe, cost effective, and 'natural' approach that adds a barrier against microbial infection. This paper presents a review of probiotics in health maintenance and disease prevention.     

Neuro-fuzzy structural classification of proteins for improved protein secondary structure prediction

Fourier transform infrared (FTIR) spectroscopy is a very flexible technique for characterization of protein secondary structure. Measurements can be carried out rapidly in a number of different environments based on only small quantities of proteins. For this technique to become more widely used for protein secondary structure characterization, however, further developments in methods to accurately quantify protein secondary structure are necessary. Here we propose a structural classification of proteins (SCOP) class specialized neural networks architecture combining an adaptive neuro-fuzzy inference system (ANFIS) with SCOP class specialized backpropagation neural networks for improved protein secondary structure prediction. Our study shows that proteins can be accurately classified into two main classes "all alpha proteins" and "all beta proteins" merely based on the amide I band maximum position of their FTIR spectra. ANFIS is employed to perform the classification task to demonstrate the potential of this architecture with moderately complex problems. Based on studies using a reference set of 17 proteins and an evaluation set of 4 proteins, improved predictions were achieved compared to a conventional neural network approach, where structure specialized neural networks are trained based on protein spectra of both "all alpha" and "all beta" proteins. The standard errors of prediction (SEPs) in % structure were improved by 4.05% for helix structure, by 5.91% for sheet structure, by 2.68% for turn structure, and by 2.15% for bend structure. For other structure, an increase of SEP by 2.43% was observed. Those results were confirmed by a "leave-one-out" run with the combined set of 21 FTIR spectra of proteins.     

A molluscan model system in the search for the engram.

A 3-neuron central pattern generator, whose sufficiency and necessity has been directly demonstrated, mediates aerial respiratory behaviour in the pond snail, Lymnaea stagnalis. This behaviour can be operantly conditioned, and this associative learning is consolidated into long-lasting memory. Depending on the operant conditioning training procedure used the learning can be consolidated into intermediate term (ITM) or long-term memory (LTM). ITM persists for only 2-3 h, whilst LTM persists for days to weeks. LTM is dependent on both altered gene activity and new protein synthesis while ITM is only dependent on new protein synthesis. We have now directly established that one of the 3-CPG neurons, RPeD1, is a site of LTM formation and storage. We did this by ablating the soma of RPeD1 and leaving behind a functional primary neurite capable of mediating the necessary synaptic interactions to drive aerial respiratory behaviour by the 3-neuron CPG. However, following soma ablation the neuronal circuit is only capable of mediating learning and ITM. LTM can no longer be demonstrated. However, if RPeD1's soma is ablated after LTM consolidation memory is still present. Thus the soma is not needed for the retention of LTM. Using a similar strategy it may be possible to block forgetting.     

Analysis of Binding Interaction Between Antibacterial Ciprofloxacin and Human Serum Albumin by Spectroscopic Techniques

To develop an efficient method for extracting and purifying the active ingredient, arctiin, from Fructus arctii and to investigate the protective effect of arctiin against glucose-induced rat aortic endothelial cell (RAEC) injury was investigated. Using a L9 (34) orthogonal array and two-step column chromatography (with AB-8 macroporous resin) arctiin extraction was optimized using a reflux method with 70 % ethanol. The RAECs were then treated with different concentrations of arctiin (1, 10, or 100 μg/ml). The effects of arctiin on cell viability in a high glucose medium, malondialdehyde (MDA) levels, and lactate dehydrogenase were measured using commercially available assays. After extraction, the purity of arctiin reached 95.7 %. In rats, arctiin was shown to stimulate the proliferation of RAECs in a high glucose medium in a dose-dependent manner. Exposure of RAECs to high glucose resulted in a significant increase in MDA and release of lactate dehydrogenase. This was accompanied by significant increase in nitric oxide release and expression of antiendothelial nitric oxide synthase. This technique resulted in relatively pure arctiin extraction. Furthermore, the results from this study suggest that arctiin could potentially function as a protector against vascular endothelial cell injury and further investigation is warranted.     

Catalytic transformations with copper-metalated diglycine conjugates

A series of copper-metalated, water-soluble bis-diglycine conjugates were synthesized and characterized through spectroscopic methods. These conjugates were evaluated for the cleavage of phosphodiester substrates, supercoiled plasmid relaxation in the presence of co-oxidants, and for the oxidation of a diphenolic substrate, 2,6-dimethoxyphenol. Appreciable rate enhancements were observed for these reactions and the oxidative nucleolytic cleavage activity and phenol oxidative coupling was presumably manifested via formation of reactive oxygen species.     

Circadian variation in oxidative stress markers in healthy and type II diabetic men

Seven clinically healthy, nondiabetic (ND) and four Type II diabetic (D) men were assessed for circadian rhythms in oxidative “stress markers.” Blood samples were collected at 3h intervals for ∼27 h beginning at 19:00h. Urine samples were collected every 3 h beginning with the 16:00h-19:00h sample. The dark (sleep) phase of the light-dark cycle extended from 22:30h to 06:30h, with brief awakening for sampling at 01:00h and 04:00h. Subjects were offered general hospital meals at 16:30h, 07:30h, and 13:30h (2400 cal in total/24 h). Serum samples were analyzed for uric acid (UA) and nitrite (NO) concentrations, and urine samples were assayed for 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA), and 8-isoprostane (ISP). Data were analyzed statistically both by the population multiple-components method and by the analysis of variance (ANOVA). The 24h mean level of UA and NO was greater in D than in ND subjects (424 vs. 338 μmol/L and 39.2 vs. 12.7 μM, respectively). A significant circadian rhythm in UA (p=0.001) and NO (p=0.048) was evident in ND but not in D (p=0.214 and 0.065). A circadian rhythm (p=0.004, amplitude=8.6 pmol/kgbw/3h urine vol.) was also evident in urine 8-OHdG of ND but not of D. The 24h mean levels of ND and D were comparable (76.8 vs. 65.7 pmol/kgbw/3h urine vol.). No circadian rhythm by population multiple-components was evident in MDA and ISP levels of ND subjects, or in 8-OHdG, MDA, and ISP in D. However, a significant time-effect was demonstrated by ANOVA in all variables and groups. The 24h mean of MDA and ISP in D was significantly greater than in ND (214 vs. 119 nmol/3h urine vol. and 622 vs. 465 ng/3h urine vol.). The peak concentrations of the three oxidative “stress markers” in urine, like those of serum NO, occurred early in the evening in both groups of men. This observation suggests a correlation between increased oxidative damage and increased rate of anabolic-catabolic events as evidenced by similarities in the timing of peak NO production and in parameters relevant to metabolic functions.     

Prevalence and Determinants of the Gender Differentials Risk Factors of Child Deaths in Bangladesh: Evidence from the Bangladesh Demographic and Health Survey, 2011

BackgroundThe number of child deaths is a potential indicator to assess the health condition of a country, and represents a major health challenge in Bangladesh. Although the country has performed exceptionally well in decreasing the mortality rate among children under five over the last few decades, mortality still remains relatively high. The main objective of this study is to identify the prevalence and determinants of the risk factors of child mortality in Bangladesh.MethodsThe data were based on a cross-sectional study collected from the Bangladesh Demographic and Health Survey (BDHS), 2011. The women participants numbered 16,025 from seven divisions of Bangladesh – Rajshahi, Dhaka, Chittagong, Barisal, Khulna, Rangpur and Sylhet. The 𝟀² test and logistic regression model were applied to determine the prevalence and factors associated with child deaths in Bangladesh.ResultsIn 2011, the prevalence of child deaths in Bangladesh for boys and girls was 13.0% and 11.6%, respectively. The results showed that birth interval and birth order were the most important factors associated with child death risks; mothers’ education and socioeconomic status were also significant (males and females). The results also indicated that a higher birth order (7 & more) of child (OR=21.421 & 95%CI=16.879-27.186) with a short birth interval ≤ 2 years was more risky for child mortality, and lower birth order with longer birth interval >2 were significantly associated with child deaths. Other risk factors that affected child deaths in Bangladesh included young mothers of less than 25 years (mothers’ median age (26-36 years): OR=0.670, 95%CI=0.551-0.815), women without education compared to those with secondary and higher education (OR =0 .711 & .628, 95%CI=0.606-0.833 & 0.437-0.903), mothers who perceived their child body size to be larger than average and small size (OR= 1.525 & 1.068, 95%CI=1.221-1.905 & 0.913-1.249), and mothers who delivered their child by non-caesarean (OR= 1.687, 95%CI=1.253-2.272).ConclusionCommunity-based educational programs or awareness programs are required to reduce the child death in Bangladesh, especially for younger women should be increase the birth interval and decrease the birth order. The government should apply the strategies to enhance the socioeconomic conditions, especially in rural areas, increase the awareness program through media and expand schooling, particularly for girls.