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  • Ottesen posted an update 9 months ago

    Intravenous infusion of high dose (>10 g) vitamin C (IVC) is a common alternative cancer therapy. IVC results in millimolar levels of circulating ascorbate, which is proposed to generate cytotoxic quantities of H2O2 in the presence of transition metal ions. In this study we report on the in vitro and in vivo effects of millimolar ascorbate on erythrocytes. Addition of ascorbate to whole blood increased erythrocyte intracellular ascorbate approximately 35-fold. Within 10 min of ascorbate addition, we detected increased oxidation of erythrocyte peroxiredoxin 2 (Prx2), a major thiol antioxidant protein and a sensitive marker of H2O2 production. Up to 50% of Prx2 was present in the oxidised form after 60 min. The presence of extracellular catalase, removal of plasma or the addition of a metal chelator did not prevent ascorbate-induced Prx2 oxidation, suggesting that the H2O2 responsible for Prx2 oxidation was generated within the erythrocyte. Ascorbate is known to increase the rate of haemoglobin autoxidation and H2O2 production. Through spectral monitoring of oxidised haemoglobin we estimated a generation rate of 15 μM H2O2/min inside erythrocytes. We also investigated changes in erythrocyte ascorbate concentration and Prx2 oxidation following IVC infusion in a cohort of patients with cancer. Plasma ascorbate levels ranged from 7.8 to 35 mM immediately post infusion, while erythrocyte ascorbate levels reached 1.5-3.4 mM 4 h after beginning infusion. Transient oxidation of erythrocyte Prx2 was observed. We conclude that erythrocytes accumulate ascorbate during IVC infusion, providing a significant reservoir of ascorbate, and this ascorbate increases H2O2 generation within the cells. The consequence of increased erythrocyte Prx2 oxidation warrants further investigation.Surgical site infection (SSI) is associated with increased morbidity, cost and mortality in human medicine and with increased morbidity and cost in veterinary medicine. The aim of this study was to evaluate risk factors for SSI development after clean surgical procedures in dogs, treated at both first opinion clinics as well as referral hospitals. 1550 dogs scored 1 or 2 according to the American Society of Anesthesiologists (ASA), that underwent clean surgical procedures at 103 clinics located in Northern and Central Europe were included in the study. Data regarding the surgical procedure, surgery time use of perioperative antimicrobial prophylaxis (AMP), surgery type, intraoperative hypothermia, and the use of surgical implants were recorded according to predefined protocols. Active 30-day SSI surveillance was performed. A random effects logistic regression model was used to evaluate the association between the perioperative variables and SSI development. SSI was detected in 85/1550 dogs (5.5%); 25 occurred in the 500 orthopedic/neurosurgery procedures (5.0%), and 60 in the 1050 soft tissue procedures (5.7%). A total of 1524 dogs were included in the final multivariable model. Increased surgery time was the only variable associated with an increased risk of SSI. No association between the other risk factors evaluated in the study and SSI occurrence was detected. Efforts must therefore be made to keep the surgery time as short as possible. Orthopedic and neurosurgical procedures including those where an implant is placed should not automatically be regarded as high-risk procedures benefiting from perioperative AMP.Heterosis has been widely applied in watermelon breeding, because of the higher resistance and yield of hybrid. As the basis of heterosis utilization, genic male sterility (GMS) is an important tool for facilitating hybrid seed production, while the detailed mechanism in watermelon is still largely unknown. Here, we report a spontaneous mutant Se18 exhibited complete male sterility due to the uniquely multilayered tapetum and the un-meiotic pollen mother cells during pollen development. Using TMT based quantitative proteomic analyses, a total of 348 differentially abundant proteins (DAPs) were detected with the overwhelming majority down-regulated in mutant Se18. By analyzing the putative orthologs/homologs of Arabidopsis GMS related genes, the biosynthesis and transport of sporopollenin and tryphine precursors were predictably altered in mutant compared to its sibling wild type. this website Moreover, the general phenylpropanoid pathway as well as its related metabolisms was also expectably impaired in mutant, coincidentTMT based proteomic analyses. Referring to functionally characterized GMS related genes, the genetic pathway DYT1-TDF1-AMS-MS188-MS1 regulating tapetum development, together with some downstream targets, were considerably altered in mutant Se18. Moreover, enrichment analyses illustrated the general phenylpropanoid related metabolisms, as well as the biosynthesis and transport of sporopollenin and tryphine precursors, were significantly disrupted in defective anther development. Collectively, the proposed regulatory networks in watermelon not only contribute to a better understanding of molecular mechanisms underlying male sterility, but also provide valuable GMS related candidates for future researches.Parkinson’s disease (PD) is a complicated neurodegenerative disease attributed to multifactorial changes. However, its pathological mechanism remains undetermined. Accumulating evidence has revealed the emerging functions of gut microbiota and microbial metabolites, which can affect both the enteric nervous system and the central nervous system via the microbiota-gut-brain axis. Accordingly, intestinal dysbiosis might be closely associated with PD. This review explores alterations to gut microbiota, correlations with clinical manifestations of PD, and briefly probes the underlying mechanisms. Next, the highly controversial roles of microbial metabolites including short-chain fatty acids (SCFAs), H2 and H2S are discussed. Finally, the pros and cons of the current treatments for PD, including those targeting microbiota, are assessed. Advancements in research techniques, further studies on levels of specific strains and longitudinal prospective clinical trials are urgently needed for the identification of early diagnostic markers and the development of novel therapeutic approaches for PD.

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