Pentoxifylline administration changes protein expression profile of coronary artery disease patients

Increased level of inflammatory mediators plays a central role in the features of coronary artery diseases. As pentoxifylline could suppress the inflammatory process and has shown some promising beneficial effects in inflammatory diseases, we evaluated the effect of two months pentoxifylline administration in proteome of PBMCs of patients with coronary artery disease (CAD). A randomized placebo-controlled study was used. Fourteen CAD patients were randomized to 2 months of pentoxifyline treatment (1200 mg/day) (n = 7) or placebo treatment (n = 7). Blood samples were obtained before and after treatment. A comparative 2 dimensional gel electrophoresis was performed, and gels were silver-stained. Differentially expressed protein spots were detected and were identified by MALDI-TOF spectrometry. Six differentially expressed proteins were identified as HSP70, PPIA and α-Enolase, (all up-regulated) S100-A9, PIMT and β-5 tubulin (all down-regulated), most of which had previously been shown to play a potential role in the pathogenesis of atherosclerosis. As the blood mononuclear cell proteome responds to pentoxifylline with changes in a number of atherosclerosis-relevant proteins, it seems that pentoxifylline could be a good choice for future studies for prevention of cardiovascular events.     

Plant Spatial Pattern Predicts Hillslope Runoff and Erosion in a Semiarid Mediterranean Landscape

Abstract The importance of the spatial pattern of vegetation for hydrological behavior in semiarid environments is widely acknowledged. However, there is little empirical work testing the hypothetical covariation between vegetation spatial structure and hillslope water and sediment fluxes. We evaluated the relationships between vegetation structural attributes (spatial pattern, functional diversity), soil surface properties (crust, stone, plant, and ground cover, and particle size distribution) and hillslope hydrologic functioning in a semiarid Mediterranean landscape; in particular, we tested whether decreasing patch density or coarsening plant spatial pattern would increase runoff and sediment yield at the hillslope scale. Runoff and sediment yield were measured over a 45-month period on nine 8 × 2-m plots that varied in vegetation type and spatial pattern. We grouped vegetation into functional types and derived plant spatial pattern attributes from field plot maps processed through a GIS system. We found that there was an inverse relationship between patch density and runoff, and that both runoff and sediment yields increased as the spatial pattern of vegetation coarsened. Vegetation pattern attributes and plant functional diversity were better related to runoff and sediment yield than soil surface properties. However, a significant relationship was found between physical crust cover and plant spatial pattern. Our results present empirical evidence for the direct relationship between the hydrologic functioning of semiarid lands and both the spatial pattern and the functional diversity of perennial vegetation, and suggest that plant spatial pattern, physical crust cover, and functional diversity may be linked through feedback mechanisms.     

Novel group-based QSAR and combinatorial design of CK-1δ inhibitors as neuroprotective agents

Background

Tar DNA binding protein 43 (TDP-43) hyperphosphorylation, caused by Casein kinase 1 (CK-1) protein isoforms, is associated with the onset and progression of Amyotrophic Lateral Sclerosis (ALS). Among the reported isoforms and splice variants of CK-1 protein superfamily, CK-1δ is known to phosphorylate different serine and threonine sites on TDP-43 protein in vitro and thus qualifies as a potential target for ALS treatment.

Results

The developed GQSAR (group based quantitative structure activity relationship) model displayed satisfactory statistical parameters for the dataset of experimentally reported N-Benzothiazolyl-2-Phenyl Acetamide derivatives. A combinatorial library of molecules was also generated and the activities were predicted using the statistically sound GQSAR model. Compounds with higher predicted inhibitory activity were screened against CK-1δ that resulted in to the potential novel leads for CK-1δ inhibition.

Conclusions

In this study, a robust fragment based QSAR model was developed on a congeneric set of experimentally reported molecules and using combinatorial library approach, a series of molecules were generated from which we report two top scoring, CK-1δ inhibitors i.e., CHC (6-benzyl-2-cyclopropyl-4-{[(4-cyclopropyl-6-ethyl-1,3-benzothiazol-2-yl)carbamoyl]methyl}j-3-fluorophenyl hydrogen carbonate) and DHC (6-benzyl-4-{[(4-cyclopropyl-6-ethyl-1,3-benzothiazol-2-yl)carbamoyl]methyl}-2-(decahydronaphthalen-1-yl)-3-hydroxyphenyl hydrogen carbonate) with binding energy of ?6.11 and ?6.01 kcal/mol, respectively.

     

Association between IGF‐1 levels ranges and all‐cause mortality: A meta‐analysis

The association between IGF‐1 levels and mortality in humans is complex with low levels being associated with both low and high mortality. The present meta‐analysis investigates this complex relationship between IGF‐1 and all‐cause mortality in prospective cohort studies. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, and Cochrane Library up to September 2019. Published studies were eligible for the meta‐analysis if they had a prospective cohort design, a hazard ratio (HR) and 95% confidence interval (CI) for two or more categories of IGF‐1 and were conducted among adults. A random‐effects model with a restricted maximum likelihood heterogeneity variance estimator was used to find combined HRs for all‐cause mortality. Nineteen studies involving 30,876 participants were included. Meta‐analysis of the 19 eligible studies showed that with respect to the low IGF‐1 category, higher IGF‐1 was not associated with increased risk of all‐cause mortality (HR = 0.84, 95% CI = 0.68–1.05). Dose–response analysis revealed a U‐shaped relation between IGF‐1 and mortality HR. Pooled results comparing low vs. middle IGF‐1 showed a significant increase of all‐cause mortality (HR = 1.33, 95% CI = 1.14–1.57), as well as comparing high vs. middle IGF‐1 categories (HR = 1.23, 95% CI = 1.06–1.44). Finally, we provide data on the association between IGF‐1 levels and the intake of proteins, carbohydrates, certain vitamins/minerals, and specific foods. Both high and low levels of IGF‐1 increase mortality risk, with a specific 120–160 ng/ml range being associated with the lowest mortality. These findings can explain the apparent controversy related to the association between IGF‐1 levels and mortality.     

Effects of Systemic Nicotine,Alcohol or Their Combination on Cholinergic Markers in the Frontal Cortex and Hippocampus of Rat

Acute alcohol (Alc) intoxication has been shown to decrease choline acetyltransferase (ChAT) in the rat brain. The present study extends that finding by examining the effects of nicotine (Nic), Alc, and their combination on ChAT and acetylcholinesterase (AChE) in the frontal cortex and hippocampus of rat. The samples were collected at 30 and 120 min after intraperitoneal administration of saline (0.9%, control), Nic (1 mg/kg), Alc (1 g/kg), and Nic + Alc and analyzed by RT-PCR, Western blot and colorimetry. Alc alone considerably reduced ChAT mRNA expression, whereas Nic alone decreased AChE mRNA expression. In contrast, Nic + Alc exposure had resulted in no significant change in the parameters. These findings are consistent with the results of the Western blot and AChE activity analysis. The results, therefore, indicate that Nic and Alc alone may interact with the central cholinergic system. This interactive effect may contribute to a frequent association of tobacco and Alc consumption.     

Distribution and health risk assessment of heavy metals in soil surrounding a lead and zinc smelting plant in Zanjan,Iran

One of the problematic issues in soil pollution studies is heavy metal particles which are produced by mines and smelting units and spread through wind action and/or runoff. Pollution and health risk assessment of cadmium, lead, zinc, copper, and nickel in soil around the lead and zinc smelting factory was carried out in Zanjan City, Iran. Contamination factor (Cf), pollution load index (PLI), geoaccumulation index (Igeo), hazard quotient (HQ), hazard index (HI), and carcinogenic risk were pollution and human health risk assessment metrics in this study. Based on the Iranian soil guideline value, soil samples in the studied areas were contaminated the least by copper and nickel and the most by cadmium. PLI results showed that soils near the production line were heavily or extremely heavily polluted. The results of Cf and Igeo showed that lead and zinc were the most important contaminants. Health risk assessment indicated that lead and cadmium in soil were the main contaminants, which pose both carcinogenic and non-carcinogenic risks to human health; carcinogenic risk levels were unacceptably high (above 1 × 10^?4). It can be concluded that mining and smelting activities degrade soil quality in this region and the soil pollution might be extended to farming areas.     

Prevalence of Escherichia coli strains resistance to antibiotics in wound infections and raw milk

Antibiotic-resistant Escherichia coli strains including extended-spectrum β-lactamase (ESBL) isolates are globally widespread in medical, food, and environmental sources. Some of these strains are considered the most pathogenic bacteria in humans. The present work examined the predominance of antibiotic resistance in E. coli strains in wound infections comparing with E. coli strains isolated from a raw milk as a potential source of those strains. The wound infections included abdomen, anus, arm, back, buttock, chest, foot, hand, head, leg, lung, mouth, neck, penis, thigh, toe, and vagina infections. In total, 161 and 153 isolates identified as E. coli were obtained from wound infections and raw milk, respectively. A Vitek 2 system innovated by bioMérieux, France was applied to perform the identification and susceptibility tests. The E. coli isolates that have ability to produce ESBL were detected by an ESBL panel and NO45 card (bioMérieux). Over half of the E. coli were from abdomen, back, and buttock wound infections. More than 50%of the E. coli isolates obtained from wound infections were resistant to cefazolin, ampicillin, cefuroxime, ciprofloxacin, mezlocillin, moxifloxacin, piperacillin, and tetracycline; 70% of the isolates from wound infections and 0% of the isolates from raw milk were E. coli isolates produced ESBL. The data showed that the strains resistance to multi-antibiotic and produced ESBL are more widespread among wound infections than in raw milk.     

cDNA cloning and mapping of the human creatine kinase M gene to 19q13

We describe the first isolation of a human creatine kinase M cDNA clone and its mapping of the gene to human chromosome 19. A human creatine kinase M cDNA clone, pJN2CK-M, harboring a 1,160-bp insert, was isolated by colony hybridization with a previously sequenced chicken creatine kinase M cDNA probe. The human cDNA was used as a probe in Southern transfers of TaqI-digested genomic DNA from mouse/human somatic-cell hybrids to localize the human creatine kinase-M gene to chromosome 19. In situ hybridization of the tritiated cDNA probe to metaphase chromosomes of peripheral blood lymphocytes from normal males revealed significant labeling to chromosome 19. These two independent methodologies assign the human creatine kinase-M gene to chromosome 19. Since greater than 69% of the grains of chromosome 19 label band q13, the human creatine kinase-M gene has been mapped to 19q13. On the basis of high-resolution G-banding, the predominant labeling site was 19q13.2-q13.3.     

Polyamines and Somatic Embryogenesis in Carrot. III. Effects of Methylglyoxal bis(guanylhydrazone)

The effects of methylglyoxal bis(guanylhydrazone) (MGBG) onsomatic embryogenesis, titres of cellular polyamines and 1-aminocyclopropane-l-carboxylicacid, and the activity of arginine decarboxylase (ADC) werestudied using suspension cultures of carrot (Daucus carota L.).Whereas MGBG (0.1–0.5 mM) significantly inhibited thecellular levels of spermidine and spermine, putrescine levelswere higher in the treated tissue. MGBG also promoted ACC levelsin the cells. The activity of ADC was inhibited in the presenceof MGBG. Somatic embryogenesis in the auxin-free medium wascompletely inhibited by MGBG. The effects of MGBG on somaticembryogenesis were reversed by 0.1–0.2 mM spermidine butnot by spermine. These results are consistent with the suggestionthat an interaction between ethylene and polyamine bio-syntheticpathways through competition for the common precursor, S-adenosylmethionine,plays an important role in the development of somatic embryosin carrot cell cultures. ¹Scientific Contribution Number 1649 from the New HampshireAgricultural Experiment Station. This research was supportedby NSF Grant No. DCB-8615945, Central University Research Funds,UNH, and NHAES Project H-233 ²Present address: Nancy S. Papa, In Vitron Corporation, 4649LeBourget Drive, St. Louis, MO 63134, U.S.A. ³Present address: Dr. A. Jamal Khan, Department of Plant Science,College of Agriculture, Sultan Qaboos University, P.O. Box-32484,Al-Khod, Muscat, Sultanate of Oman (Received September 17, 1990; Accepted January 21, 1991)     

Changes in brown-adipose-tissue mitochondrial processes in streptozotocin-diabetes.

Yeast glucose-6-phosphate dehydrogenase was inhibited by low NADPH concentrations in cell-free extracts, and de-inhibited by GSSG; extensive dialysis of the crude extract did not diminish the GSSG effect. Immunoprecipitation of glutathione reductase abolished the de-inhibition of glucose-6-phosphate dehydrogenase by GSSG. Purified glucose-6-phosphate dehydrogenase was inhibited by NADPH but not de-inhibited by GSSG, and upon addition of pure glutathione reductase GSSG completely de-inhibited the glucose-6-phosphate dehydrogenase.