Sepantronium Bromide (YM155), A Small Molecule Survivin Inhibitor,Promotes Apoptosis by Induction of Oxidative Stress,Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study

Neurochemical Research - Cuprizone (cup) model targets oligodendrocytes (OLGs) degeneration and is frequently used for the mechanistic understanding of de- and remyelination. Improperly, this...     

Chemical composition and antifungal efficacy of five essential oils against Calonectria pseudonaviculata,the causal agent of boxwood blight: an in vitro study

Recent epidemics of box (boxwood) blight caused by the fungus Calonectria pseudonaviculata in Hyrcanian forests led to the search for eco-friendly fungicides. Essential oils (EOs) of medicinal plants undoubtedly have been highlighted as a new therapeutic approach. In this study, EOs from Cuminum cyminum, Lavandula angustifolia, Thymus daenensis, Trachyspermum copticum and Hyssopus officinalis were evaluated for their inhibitory activities against C. pseudonaviculata Cy-08 in vitro. Quantitative and qualitative composition variations of the EOs were also analysed by GC–MS. Based on the high inhibitory efficacy and low related EC₅₀, MFC and MIC values, T. copticum, L. angustifolia and Th. daenensis EOs can be mentioned as those providing extraordinary efficacy against Cy-08, respectively. Major chemical components of T. copticum, L. angustifolia and Th. daenensis EOs were thymol, linalyl acetate and thymol, respectively. Thymol and linalyl acetate may be the most effective compounds against C. pseudonaviculata.     

Trends in Cardiovascular Disease Risk Factors in People with and without Diabetes Mellitus: A Middle Eastern Cohort Study

Aims/Hypothesis

To investigate secular trends in cardiovascular disease (CVD) risk factors during a decade of follow-up in a Middle Eastern cohort, and to compare observed trends between diabetic and non-diabetic populations.

Methods

In a population of 6181 participants (2622 males and 3559 females), diabetes status and CVD risk factors were evaluated in 4 study phases from 1999–2011. 1045 subjects had type 2 diabetes mellitus at baseline and 5136 participants were diabetes-free. To examine the trends of CVD risk factors, generalized estimation equation models were constructed. The interaction between the diabetes status and each phase of the study was checked in a separate model.

Results

During the follow-up period diabetic females significantly gained better control of their blood pressure, serum low density lipoprotein cholesterol and general and central obesity measures compared to non-diabetic counterparts, although 60% of them had high BP and 64% had high serum LDL-C levels till the end of the study. Diabetic males however, experienced significantly better control on their serum LDL-C and general and central obesity measures compared to their non-diabetic controls; but 24% of them were still smoker, 63% had high BP and 60% had high serum LDL-C levels at the end of the follow-up (all Ps _interaction <0.05). Use of lipid-lowering and antihypertensive medications increased consistently in both diabetic and non-diabetic populations.

Conclusions/Interpretation

Although CVD risk factors have been controlled to some extent among diabetic population in Iran, still high numbers of people with diabetes have uncontrolled CVD risk factors that prompt more attention.     

Method to assemble and integrate biochemical pathways into the chloroplast genome of Chlamydomonas reinhardtii

Recombinant protein expression in the chloroplasts of green algae has recently become more routine; however, the heterologous expression of multiple proteins or complete biosynthetic pathways remains a significant challenge. Here, we show that a modified DNA Assembler approach can be used to rapidly assemble multiple‐gene biosynthetic pathways in yeast and then integrate these assembled pathways at a site‐specific location in the chloroplast genome of the microalgal species Chlamydomonas reinhardtii. As a proof of concept, this method was used to successfully integrate and functionally express up to three reporter proteins (AphA6, AadA, and GFP) in the chloroplast of C. reinhardtii. An analysis of the relative gene expression of the engineered strains showed significant differences in the mRNA expression levels of the reporter genes and thus highlights the importance of proper promoter/untranslated region selection when constructing a target pathway. This new method represents a useful genetic tool in the construction and integration of complex biochemical pathways into the chloroplast genome of microalgae and should aid current efforts to engineer algae for biofuels production and other desirable natural products. Biotechnol. Bioeng. 2012; 109: 2896–2903. © 2012 Wiley Periodicals, Inc.     

Electrochemical investigations of tau protein phosphorylations and interactions with pin1

Phosphorylation of Tau by the protein kinase GSK-3β was monitored by electrochemical impedance spectroscopy of immobilized Tau on gold surfaces. As a result of Tau phosphorylation, the film resistance decreases significantly due to conformational changes and reorganization of the immobilized phosphorylated Tau (pTau) protein, which in turn enables the interactions of pTau with the peptidyl-prolyl cis/trans isomerase, Pin1. Interactions are specific to phospho-Ser (pSer) and phospho-Thr (pThr) residues of pTau. Impedance changes occurred as a function of pTau?Pin1 interactions and are related to the amount of Pin1 bound, which resulted in an increase of the charge-transfer resistance, R(CT) . Our results clearly indicate that the isomerase Pin1 interacts favorably with pSer/pThr-Pro residues in Tau, but does not bind non-phosphorylated Tau or phospho-Tyr residues in Tau films. Our study demonstrates the utility of electrochemical impedance studies to probe protein modifications and biomolecular interactions.     

Neuroprotective Effect of Decalepis hamiltonii in Paraquat-Induced Neurotoxicity in Drosophila melanogaster: Biochemical and Behavioral Evidences

In this paper, we have demonstrated for the first time, the antioxidant and neuroprotective effects of Decalepis hamiltonii (Dh) root extract against paraquat (PQ)-induced oxidative stress and neurotoxicity in Drosophila melanogaster. Exposure of adult D. melanogaster (Oregon K) to PQ induced oxidative stress as evidenced by glutathione depletion, lipid peroxidation and enhanced activities of antioxidant enzymes such as catalase, superoxide dismutase as well as elevated levels of acetylcholine esterase. Pretreatment of flies by feeding with Dh extract (0.1, 0.5 %) for 14 days boosted the activities of antioxidant enzymes and prevented the PQ-induced oxidative stress. Dietary feeding of Dh extract prior to PQ exposure showed a lower incidence of mortality and enhanced motor activities of flies in a negative geotaxis assay; both suggesting the neuroprotective potential of Dh. Based on the results, we contemplate that the roots of Dh might prevent and ameliorate the human diseases caused by oxidative stress. The neuroprotective action of Dh can be attributed to the antioxidant constituents while the precise mechanism of its action needs further investigations.     

Biochemical responses as early and reliable biomarkers of organophosphate and carbamate pesticides intoxication: A systematic literature review

Inhibition of cholinesterase (ChE) activity has been long considered as the main diagnostic method of organophosphate (OP) and carbamate pesticides poisoning; however, it has been shown that ChE activity may also be altered due to exposure to other non-organophosphorus toxicants and variety of different medical conditions. Hence, to avoid misdiagnosis, we aimed to systematically review available documents to look for additional biomarkers of OP and carbamate poisoning. The electronic databases in addition to Google scholar were searched for eligible articles on March 2022 using “organophosphate,” “carbamate,” and “biomarker” including all their similar terms. After collecting the relevant documents, the data were extracted and described qualitatively. In total, data of 66 articles from 51 human and 15 animal studies were extracted. Findings demonstrated that enzymes such as β-glucuronidase, neuropathy target esterase, amylase, and lipase, in addition to hematological indicators such as CBC, CRP, lactate dehydrogenase, and CPK have high sensitivity and accuracy in the diagnosis of OP poisoning. Findings suggest that using various markers for diagnosis of OP intoxication is helpful for appropriate management, and early identifying the patients at risk of death. The suggested biomarkers also help to avoid misdiagnosis of OP poisoning with other similar conditions.     

Exploration,antifungal and antiaflatoxigenic activity of halophilic bacteria communities from saline soils of Howze-Soltan playa in Iran

In the present study, halophilic bacteria communities were explored in saline soils of Howze-Soltan playa in Iran with special attention to their biological activity against an aflatoxigenic Aspergillus parasiticus NRRL 2999. Halophilic bacteria were isolated from a total of 20 saline soils using specific culture media and identified by 16S rRNA sequencing in neighbor-joining tree analysis. Antifungal and antiaflatoxigenic activities of the bacteria were screened by a nor-mutant A. parasiticus NRRL 2999 using visual agar plate assay and confirmed by high-performance liquid chromatography. Among a total of 177 halophilic bacteria belonging to 11 genera, 121 isolates (68.3%) inhibited A. parasiticus growth and/or aflatoxin production. The most potent inhibitory bacteria of the genera Bacillus, Paenibacillus and Staphylococcus were distributed in three main phylogenetic clusters as evidenced by 16S rRNA sequence analysis. A. parasiticus growth was inhibited by 0.7–92.7%, while AFB₁ and AFG₁ productions were suppressed by 15.1–98.9 and 57.0–99.6%, respectively. Taken together, halophilic bacteria identified in this study may be considered as potential sources of novel bioactive metabolites as well as promising candidates to develop new biocontrol agents for managing toxigenic fungi growth and subsequent aflatoxin contamination of food and feed in practice.