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Quantification and local density estimation of radiation-induced reactive oxygen species (ROS) were described focusing on our recent and related studies. Charged particle radiation, i.e. heavy-ion beams, are currently utilized for medical treatment. Differences in ROS generation properties between photon and charged particle radiation may lead to differences in the quality of radiation. Radiation-induced generation of ROS in water was quantified using several different approaches to electron paramagnetic resonance (EPR) techniques. Two different densities of localized hydroxyl radical (•OH) generation, i.e. milli-molar and molar levels, were described. Yields of sparse •OH decreased with increasing linear energy transfer (LET), the yield total •OH was not affected by LET. In the high-density, molar level, •OH environment, •OH can react and directly make hydrogen peroxide (H2O2), and then possible to form a high-density H2O2 cluster. The amount of total oxidation reactions caused by oxidative ROS, such as •OH and hydroperoxyl radial (HO2•), was decreased with increasing LET. Possibilities of the sequential reactions were discussed based on the initial localized density at the generated site. Water-induced ROS have been well investigated. However, little is known about radiation-induced free radical generation in lipidic conditions. Radio-chemistry to understand the sequential radio-biological effects is still under development.Candida parapsilosis is a leading cause of invasive mycoses and the major cause of nosocomial fungaemia amongst low and very low birth weight neonates. However, the molecular and physiological characteristics of this fungus remain understudied. To advance our knowledge about the pathobiology of this pathogen, we sought to develop and validate an effective method for chemical transformation of C. parapsilosis. Chemical transformation is the primary procedure for introducing foreign DNA into Candida yeast as it requires no special equipment, although its performance efficacy drops rapidly when the size of the transforming DNA increases. To define optimal conditions for chemical transformation in C. parapsilosis, we selected a leucine auxotroph laboratory strain. We identified optimal cell density for transformation, incubation times, inclusion of specific enhancing chemicals, and size and amounts of DNA fragments that resulted in maximized transformation efficiency. We determined that the inclusion of dimethyl sulfoxide was beneficial, but dithiothreitol pretreatment reduced colony recovery. As a result, the modified protocol led to a 20-55-fold increase in transformation efficiency, depending on the size of the transforming fragment. We validated the modified methodology with prototrophic isolates and demonstrated that the new approach resulted in the recovery of significantly more transformants in 5 of 6 isolates. Additionally, we identified a medium in which transformation competent yeast cells could safely be maintained at -80°C for up to 6 weeks that reduces laboratory work and shortens the overall procedure. These modifications will significantly aid further investigations into the genetic basis for virulence in C. parapsilosis.Human brain and intestinal microbes reportedly maintain a constant bidirectional connection through diverse neural, endocrine, immune, and metabolic pathways. Increasing evidence indicates that this communication system, referred to as microbiota-gut-brain axis, enables the gut microbes to influence several aspects of brain function and behavior, including hypothalamic-pituitary-adrenal (HPA) axis stress responses, and on the other hand, stress can affect gut microbiota. However, the role of gut microbiota in the HPA axis functioning in humans remains to be specified especially in early life. This study aimed at identifying the potential link between the cortisol stress response and the gut microbiota at the age of 2.5 months. Fecal microbiota profiles were acquired by 16S rRNA gene sequencing, while salivary cortisol responses after an exposure to a mild acute stressor represented the HPA axis reactivity. We observed that a blunted cortisol stress response was weakly associated with a diverse gut microbiota diversity at the age of 2.5 months. Gut microbiota composition was not associated with cortisol stress responsiveness, but rather with covariates, i.e. factors that influence gut microbiota composition and colonization.LAY SUMMARYThis exploratory study aimed at identifying possible links between cortisol stress responses and fecal microbiota composition in early infancy. In a well-characterized study population of 2.5-month-old infants, we observed that an attenuated cortisol stress responsiveness after a mild stressor was weakly associated with a diverse fecal microbiota. Our results suggest that the gut microbiota composition is associated with environmental factors, such as delivery mode and number of siblings, rather than with cortisol stress responsiveness, in this age group.The interaction of thiazine dye methylene blue (MB) with Calf thymus DNA and human blood serum albumin (HSA) has been studied. MB was revealed to stabilize the native structure of DNA and HSA, since the melting temperature of the complexes is shifted to higher values in relation to that of both macromolecules in pure state. It was also revealed that the absorption and fluorescence spectra of the MB-DNA complexes change significantly, while those of MB-albumin complexes do not change noticeably. Analysis of the obtained data allows to conclude that MB binds to DNA by two modes, including intercalation and electrostatic mechanisms. In the case of HSA, the main binding mode of MB, conditioning the stabilization of the protein native structure, is the electrostatic mechanism.Communicated by Ramaswamy H. Sarma.Peptic ulcer disease (PUD) is a common condition that is induced by acid and pepsin causing lesions in the mucosa of the duodenum and stomach. The pathogenesis of PUD is a many-sided scenario, which involves an imbalance between protective factors, such as prostaglandins, blood flow, and cell renewal, and aggressive ones, like alcohol abuse, smoking, Helicobacter pylori colonisation, and the use of non-steroidal anti-inflammatory drugs. The standard oral treatment is well established; however, several problems can decrease the success of this therapy, such as drug degradation in the gastric environment, low oral bioavailability, and lack of vectorisation to the target site. In this way, the use of strategies to improve the effectiveness of these conventional drugs becomes interesting. Currently, the use of drug delivery systems is being explored as an option to improve the drug therapy limitations, such as antimicrobial resistance, low bioavailability, molecule degradation in an acid environment, and low concentration of the drug at the site of action. This article provides a review of oral drug delivery systems looking for improving the treatment of PUD.Green tea extract (GTE) improves exercise outcomes and reduces obesity. However, case studies indicate contradictory physiology regarding liver function and toxicity. We studied the effect of two different decaffeinated GTE (dGTE) products, from a non-commercial (dGTE1) and commercial (dGTE2) supplier, on hepatocyte function using the human cell model, HepG2. dGTE1 was protective against hydrogen peroxide (H2O2)-induced apoptosis and cell death by attenuating oxidative stress pathways. Conversely, dGTE2 increased cellular and mitochondrial oxidative stress and apoptosis. A bioavailability study with dGTE showed the major catechin in GTE, EGCG, reached 0.263 µg·ml-1. In vitro, at this concentration, EGCG mimicked the protective effect of dGTE1. GC/MS analysis identified steric acid and higher levels of palmitic acid in dGTE2 versus dGTE1 supplements. We demonstrate the significant biological differences between two GTE supplements which may have potential implications for manufacturers and consumers to be aware of the biological effects of supplementation.
This study aimed to estimate the cost-utility of stereotactic body radiotherapy (SBRT) plus cetuximab for patients with previously irradiated recurrent squamous cell carcinoma of the head and neck.
We constructed a Markov health-state transition model to simulate costs and clinical outcomes of recurrent squamous cell carcinoma of the head and neck. Model parameters were derived from the published literature and the National Health Insurance Administration reimbursement price list. Incremental cost-effectiveness ratio and the net monetary benefit were calculated from a health payer perspective. The impact of uncertainty was modeled with one-way and probabilistic sensitivity analyses.
In the base-case, SBRT plus cetuximab compared to SBRT alone resulted in an ICER of NT$ 840,455 per QALY gained. In the one-way sensitivity analysis, the utility of progression-free state for patients treated with SBRT plus cetuximab or SBRT alone and the cost of progression-free survival for SBRT+Cet were the most sensitive parameters in the model. Probabilistic sensitivity analysis showed that the probability of cost-effectiveness at a willingness-to-pay threshold of NT$ 2,252,340 per QALY was 100% for SBRT plus cetuximab but 0% for SBRT alone.
This study showed that SBRT+Cet was cost-effective and benefited patients with previously irradiated rSCCHN.
This study showed that SBRT+Cet was cost-effective and benefited patients with previously irradiated rSCCHN.Objective Although biologic agents are used in Takayasu arteritis (TAK), corticosteroids are still the mainstay of treatment. This study aimed to investigate the feasible maintenance dose of prednisolone (PSL) in the biologic therapy era.Method We enrolled 93 patients with TAK who satisfied the criteria of the American College of Rheumatology and visited our department from 2008 to 2018. The clinical characteristics and PSL dose of the patients were retrospectively evaluated.Results The mean ± sd maintenance dose of PSL was 5.0 ± 3.0 mg/day. In patients having TAK for > 20 years, PSL discontinuation and drug-free status were achieved in 27.2% and 18%, respectively. Although tapering the PSL dose to 10 mg/day was achieved within 12 months, tapering to 5 mg/day required 10 years. Relapse significantly interfered with the PSL dose reduction. check details The clinical characteristics of patients with relapse included a lower rate of combination therapy using immunosuppressants. Moreover, biologics were used in > 60% of patients with relapse. Tapering of PSL was significantly possible in patients receiving biologics and additional relapse was observed in 6.3% and 50% of patients with and without biologics, respectively. Such PSL-sparing effect enabled the reduction of the median PSL dose from 10 to 5 mg/day. Steroid discontinuation was achieved in some patients.Conclusions The use of biologics significantly reduced the PSL dose in relapsed patients. A PSL dose of ≤ 5 mg/day is a feasible target for TAK, especially when biologic agents are used. Nevertheless, corticosteroid discontinuation may also be the target in some patients.Cancer is a broad term used to describe a group of diseases that have more than 270 types. Today, due to the suffering of patients from the side effects of existing methods in the treatment of cancer such as chemotherapy and radiotherapy, the employment of targeted methods in the treatment of this disease has been received much consideration. In recent years, nanoparticles have revolutionized in the treatment of many diseases such as cancer. Among these nanoparticles, liposomes are more considerable. Active targeted liposomes show an important role in the selective action of the drug on cancer cells. Until now, a variety of anti-cancer agents have been reported for targeted delivery to cancer cells using liposomes. The results of in vitro and studies in vivo have been shown that selective action of the targeted liposomes is increased with reduced side effects and toxicity compared with free drugs or non-targeted liposomes. This systematic review expresses the reports of this type of drug delivery system. Search terms were searched through several online databases including PubMed, Scopus, and Science Direct from 1990 to 2019 and the quality evaluation was performed.
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