Discovery of small molecule human FPR1 receptor antagonists

The identification of two novel series of formyl peptide receptor 1 (FPR1) antagonists are reported, represented by methionine benzimidazole 6 and diamide 7. Both series specifically inhibited the binding of labelled fMLF to hrFPR1 and selectively antagonized FPR1 function in human neutrophils, making them useful in vitro validation tools for the target.     

Microbial production and industrial applications of keratinases: an overview

Massive production of keratinaceous byproducts in the form of agricultural and industrial wastes throughout the world necessitates its justified utilization. Chemical treatment of keratin waste is proclaimed as an eco-destructive approach by various researchers since it generates secondary pollutants. Microbial degradation of keratin waste is an emerging and eco-friendly approach and offers dual benefits, i.e., treatment of recalcitrant pollutant (keratin) and procurement of a commercially important enzyme (keratinase). This review summarizes the potential utility of some bacterial and fungal species for the production of keratinase using a variety of keratinaceous wastes as growth substrates. The application of microbial keratinases in waste management; animal feed, detergent, and fertilizer manufacturing; and leather, cosmetic, and pharmaceutical industries is also abridged in this review.     

Contrasting effects of maize residue,coal gas residue and their biochars on nutrient mineralization,enzyme activities and CO2 emissions in sandy loess soil

Mismanagement of crop straw and coal gas residue threatens the atmosphere and the economy. Nevertheless, thermal-pyrolysis is an option for management that turns bio-waste into biochar; its viability and adoption by the public as soil amendments is dependent on the agronomic and environmental values compared between biochar and the raw materials. We undertook a 60-day short-term analysis to assess the impact of various wastes and biochars, as well as inorganic nutrients (N), on carbon dioxide (CO₂) fluxes, soil enzyme activities, soil fertility status, and microbial activities. There were eight treatments of soil amendments: without an amendment (CK), Nutrients (N), straw + nutrients (S+N), straw biochar + nutrients (SB+N), coal gas residue + nutrients (C+N), coal gas residue biochar + nutrients (CB+N), straw + straw biochar + nutrients (S+SB+N) and coal gas residue waste + coal gas residue biochar + nutrients (C+ CB +N). The results indicated that soil EC, pH, nitrate N (NO₃^–- N), SOC, TN and available K were significantly (p < 0.05) increased coal gas residue biochar and combined with coal fly ash as compared to maize straw biochar and combined with maize straw and N treatments. The higher concentrations of soil MBC and MBN activities were increased in the maize straw application, while higher soil enzyme activity such as, invertase, urease and catalase were enhanced in the coal fly ash derived biochar treatments. The higher cumulative CO₂ emissions were recorded in the combined applications of maize straw and its biochar as well as coal gas residue and its biochar treatment. Our study concludes, that maize straw and coal fly ash wastes were converted into biochar product could be a feasible substitute way of discarding, since land amendment and decreased CO₂ fluxes and positive changes in soil microbial, and chemical properties, and can be confirmed under long-term conditions for reduction of economical and environment issues.     

An improved synthesis of 6β-hydroxy-5β-pregnane-3,20-dione

6β-Hydroxy-5β-pregnane-3,20-dione, formerly prepared by a hydroboration method, has been obtained in greatly improved yield by a simpler irradiation-hydrogenation procedure.     

Drug targeting: anti-HSV-1 activity of mannosylated polymer-bound 9-(2-phosphonylmethoxyethyl)adenine

The antiviral drug, 9-(2-phosphonylmethoxyethyl) adenine (PMEA) was linked to a synthetic and neutral polymer bearing mannosyl residues to allow its internalization by macrophages via membrane lectins. PMEA bound to the mannosylated polymer was more efficient in vitro than free PMEA in preventing lysis of human macrophages by herpes virus.     

Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: insight into chemobrain

Adriamycin (ADR) is a chemotherapeutic agent useful in treating various cancers. ADR is a quinone-containing anthracycline chemotherapeutic and is known to produce reactive oxygen species (ROS) in heart. Application of this drug can have serious side effects in various tissues, including brain, apart from the known cardiotoxic side effects, which limit the successful use of this drug in treatment of cancer. Neurons treated with ADR demonstrate significant protein oxidation and lipid peroxidation. Patients under treatment with this drug often complain of forgetfulness, lack of concentration, dizziness (collectively called somnolence or sometimes called chemobrain). In this study, we tested the hypothesis that ADR induces oxidative stress in brain. Accordingly, we examined the in vivo levels of brain protein oxidation and lipid peroxidation induced by i.p. injection of ADR. We also measured levels of the multidrug resistance-associated protein (MRP1) in brain isolated from ADR- or saline-injected mice. MRP1 mediates ATP-dependent export of cytotoxic organic anions, glutathione S-conjugates and sulphates. The current results demonstrated a significant increase in levels of protein oxidation and lipid peroxidation and increased expression of MRP1 in brain isolated from mice, 72 h post i.p injection of ADR. These results are discussed with reference to potential use of this redox cycling chemotheraputic agent in the treatement of cancer and its chemobrain side effect in brain.     

Ferulic acid ethyl ester as a potential therapy in neurodegenerative disorders

Oxidative stress is involved in the onset, progression and pathogenesis of a number of diseases including neurodegenerative diseases. It is critical to develop a pharmacological approach to combat oxidative stress which may reduce the risk of diseases and help in promoting healthy life. In an attempt to reduce the side effects associated with allopathic medicines a number of studies are now focusing on developing treatment regimens from naturally occurring plant products. In this review, the protective role of ferulic acid (4-hydroxy-3-methoxycinnamic acid) (FA), a naturally occurring antioxidant compound found in fruit, some vegetables, and grains, and its ethyl ester derivative are discussed with respect to neurodegeneration. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.     

Occupational Attainment as a Marker of Cognitive Reserve in Multiple Sclerosis

Cognitive dysfunction affects half of MS patients. Although brain atrophy generally yields the most robust MRI correlations with cognition, significant variance in cognition between individual MS patients remains unexplained. Recently, markers of cognitive reserve such as premorbid intelligence have emerged as important predictors of neuropsychological performance in MS. In the present study, we aimed to extend the cognitive reserve construct by examining the potential contribution of occupational attainment to cognitive decline in MS patients. Brain atrophy, estimated premorbid IQ, and occupational attainment were assessed in 72 MS patients. The Minimal Assessment of Cognitive Functioning in MS was used to evaluate indices of information processing speed, memory, and executive function. Results showed that occupational attainment was a significant predictor of information processing speed, memory, and executive function in hierarchical linear regressions after accounting for brain atrophy and premorbid IQ. These data suggest that MS patients with low occupational attainment fare worse cognitively than those with high occupational attainment after controlling for brain atrophy and premorbid IQ. Occupation, like premorbid IQ, therefore may make an independent contribution to cognitive outcome in MS. Information regarding an individual''s occupation is easily acquired and may serve as a useful proxy for cognitive reserve in clinical settings.     

CuO nanoparticles significantly influence in vitro culture,steviol glycosides,and antioxidant activities of <Emphasis Type="Italic">Stevia rebaudiana</Emphasis> Bertoni

Copper oxide (CuO) nanoparticles (NPs) synthesized through co-precipitation method were employed in MS media during in vitro culture of Stevia rebaudiana. Physiological characteristics, production of steviol glycosides, and antioxidative parameters were investigated in regenerated plants. CuO NPs had crystalline monoclinic cubic cuprous oxides with average size 47 nm. The NPs were applied at 0, 0.1, 1.0, 10, 100 and 1000 mg/L in MS media for direct organogenesis of S. rebaudiana from nodal segments. Shoot organogenesis was found highest (88.5%) at 10 mg/L CuO and average shoot length, mean number of shoot per explant, and fresh weight were also found significantly higher at the same concentration. High performance liquid chromatography (HPLC) illustrated significant rise of bioactive major steviol glycosides (rebaudioside A and stevioside) at 10 mg/L CuO NPs in MS media. The oxidative stress produced by CuO nanoparticles on S. rebaudiana was affirmed by antioxidant activities i.e. total antioxidant activity (TAC), total reducing power (TRP) and 2,2-diphenyl-1-picryl hydrazyl (DPPH)-free radical scavenging activity. The oxidative stress generated by NPs involved production of antioxidative molecules total phenolic content (TPC), total flavonoid content (TFC) depending on NPs concentration. The study concludes that copper oxide nanoparticles functions as a stimulator of bioactive components productions, and can be employed in in vitro batch cultures.