Interplay between Ca2+ cycling and mitochondrial permeability transition pores promotes reperfusion-induced injury of cardiac myocytes

Uncontrolled release of Ca(2+) from the sarcoplasmic reticulum (SR) contributes to the reperfusion-induced cardiomyocyte injury, e.g. hypercontracture and necrosis. To find out the underlying cellular mechanisms of this phenomenon, we investigated whether the opening of mitochondrial permeability transition pores (MPTP), resulting in ATP depletion and reactive oxygen species (ROS) formation, may be involved. For this purpose, isolated cardiac myocytes from adult rats were subjected to simulated ischemia and reperfusion. MPTP opening was detected by calcein release and by monitoring the ΔΨ(m). Fura-2 was used to monitor cytosolic [Ca(2+)](i) or mitochondrial calcium [Ca(2+)](m), after quenching the cytosolic compartment with MnCl(2). Mitochondrial ROS [ROS](m) production was detected with MitoSOX Red and mag-fura-2 was used to monitor Mg(2+) concentration, which reflects changes in cellular ATP. Necrosis was determined by propidium iodide staining. Reperfusion led to a calcein release from mitochondria, ΔΨ(m) collapse and disturbance of ATP recovery. Simultaneously, Ca(2+) oscillations occurred, [Ca(2+)](m) and [ROS](m) increased, cells developed hypercontracture and underwent necrosis. Inhibition of the SR-driven Ca(2+) cycling with thapsigargine or ryanodine prevented mitochondrial dysfunction, ROS formation and MPTP opening. Suppression of the mitochondrial Ca(2+) uptake (Ru360) or MPTP (cyclosporine A) significantly attenuated Ca(2+) cycling, hypercontracture and necrosis. ROS scavengers (2-mercaptopropionyl glycine or N-acetylcysteine) had no effect on these parameters, but reduced [ROS](m). In conclusion, MPTP opening occurs early during reperfusion and is due to the Ca(2+) oscillations originating primarily from the SR and supported by MPTP. The interplay between Ca(2+) cycling and MPTP promotes the reperfusion-induced cardiomyocyte hypercontracture and necrosis. Mitochondrial ROS formation is a result rather than a cause of MPTP opening.     

VO(acac)(2)/H(2)O(2)/NaI: a mild and efficient combination for the cleavage of dithioacetal derivatives of sugars

A wide variety of dithioacetal derivatives of sugars can be cleaved easily into the corresponding open-chain aldehydo sugars using an efficient combination of VO(acac)₂/H₂O₂/NaI at 0–5 °C. Some of the salient features of this protocol are mild reaction conditions, good yields, short reaction times, easy work-up procedures, and non-involvement of toxic chemicals.     

Molecular identification and characterization of a new type of bovine enterovirus

Bovine enteroviruses belong to the family Picornaviridae. Little is known about their pathogenic potential; however, they cause asymptomatic infections in cattle and are excreted in feces. In the present study, viruses isolated from environmental samples were sequenced. According to phylogenetic analyses and standard picornavirus nomenclature, these isolates constitute a new type of bovine enterovirus serogroup A.     

First genetic evidence for the presence of the rumen fluke Paramphistomum epiclitum in Pakistan

More than 70 species of the Superfamily Paramphistomoidea, have been identified in ruminants in different parts of the world. Most are pathogenic, causing amphistomosis. Adult flukes within this family have a predilection for the forestomach (rumen) or bile duct of the liver, where they may cause epithelial damage. Identification of adult Paramphistomum, Calicophoron, Gastrothylax and Fischoederius at the species level based on morphology requires specialised expertise, whereas molecular genetic marker analysis is more precise and transferable. In the present study, we performed molecular characterisation of twenty seven adult flukes collected from the forestomachs of buffalo, cattle and goats in the Punjab province of Pakistan. PCR and sequencing of the ITS-2 rDNA region revealed a single haplotype in all cases. Phylogenetic comparison of P. epiclitum ITS2-rDNA sequences with those from other Paramphistomum, Calicophoron, Gastrothylax and Fischoederius species was performed to assess within and between species variation and validate the use of ITS-2 rDNA as a robust species-specific marker for P. epiclitum identification. This work provides a validated species-specific marker of P. epiclitum and the first report of this parasite species from Pakistan. The results of this study also have implications for the diagnosis and control of rumen flukes in the region and the need for accurate species identification to understand parasite distribution and population genetics.     

NutriTRAILomics in prostate cancer: time to have two strings to one’s bow

The astonishing development of broad genomics and proteomics tools have catalyzed a new era in both therapeutic interventions and nutrition in prostate cancer. The terms pharmacogenomics and nutrigenomics have been derived out of their genetic forbears as large-scale genomics technologies have been established in the last decade. It is unquestionable that rationale of both disciplines is to individualize or personalize medicine and food and nutrition, and eventually health, by tailoring the drug or the food to the individual genotype. The purpose of this review is to significantly inspect results from current research concerning the mechanisms of action of phytonutrients and potential effects on prostate cancer. Substantial emerging data supports the synergistic adiministration of nutraceuticals with TRAIL in prostate cancer progression to circumvent TRAIL refractoriness. Nonetheless, developing novel scientific methods for discovery, validation, characterization and standardization of these multicomponent phyto-therapeutics is vital to their recognition into mainstream medicine. The key to interpret a personalized response is a greater comprehension of nutrigenomics, proteomics and metabolomics.     

Sulphur application improves the growth, seed yield and oil quality of canola

Sulphur (S) nutrition is very important for harvesting potential seed and oil yield of rapeseed. This study evaluated response of foliage applied thiourea on the performance of two canola cultivars Shiralee and Dunkeld. Sulphur was applied to soil (40 kg ha^?1) or foliage (500 and 1,000 mg L^?1) at rosette, bud initiation and flowering stages using elemental S or thiourea as source, respectively; no S application was taken as control. Among all the treatments, soil application of S improved the crop growth, yield and oil quality in both cultivars and was followed by foliar application of thiourea at 1,000 mg L^?1 compared with no application. Soil applied S and foliar thiourea (1,000 mg L^?1) delayed the flowering and maturity. Soil and foliar applied S significantly improved leaf area index, crop growth rate, net assimilation rate and chlorophyll contents. Plant height, number of branches, siliqua per plant, seed number per siliqua, 1,000-seed weight, biological and seed yield were also increased by soil applied S and foliage applied thiourea (1,000 mg L^?1). Nonetheless, improvement in harvest index, seed oil, protein and glucosinolate contents was only observed from foliage applied thiourea (1,000 mg L^?1). Response of cv. Shiralee to sulphur application was better than cv. Dunkeld. In conclusion, foliar applied thiourea (1,000 mg L^?1) can have potential to improve growth, yield and oil quality in canola and can be economically viable and attractive alternative source.