Tarpdavenport8584

At 200 μg/ml concentration, no differences in cellular uptake and cytotoxicity were observed between TiO2 NPs and Ti(Sm)O2 NPs in both A549 and DU145 cells. However, the combination of Ti(Sm)O2 NPs and X-rays elicited higher cytotoxic effect and ROS generation in the cells than that with TiO2 NPs and X-rays. LY-188011 in vivo The CT numbers of Ti(Sm)O2 NPs were systematically higher than that of TiO2 NPs. Conclusions The Ti(Sm)O2 NPs increased the dose enhancement of MV X-ray beams than that elicited by TiO2 NPs. Samarium improved the efficiency of TiO2 NPs as potential radiosensitising agent.The aim of this study was to evaluate the dosimetric effect of continuous motion monitoring based localization (Calypso, Varian Medical Systems), gating and intrafraction motion correction in prostate SBRT. Delivered doses were modelled by reconstructing motion inclusive dose distributions for different localization strategies. Actually delivered dose (strategy A) utilized initial Calypso localization, CBCT and additional pre-treatment motion correction by kV-imaging and Calypso, and gating during the irradiation. The effect of gating was investigated by simulating non-gated treatments (strategy B). Additionally, non-gated and single image-guided (CBCT) localization was simulated (strategy C). A total of 308 fractions from 22 patients were reconstructed. The dosimetric effect was evaluated by comparing motion inclusive target and risk organ dose-volume parameters to planned values. Motion induced dose deficits were seen mainly in PTV and CTV to PTV margin regions, whereas CTV dose deficits were small in all strategies mean ± SD difference in CTVD99% was -0.3 ± 0.4%, -0.4 ± 0.6% and -0.7 ± 1.2% in strategies A, B and C, respectively. Largest dose deficits were seen in individual fractions for strategy C (maximum dose reductions were -29.0% and -7.1% for PTVD95% and CTVD99%, respectively). The benefit of gating was minor, if additional motion correction was applied immediately prior to irradiation. Continuous motion monitoring based localization and motion correction ensured the target coverage and minimized the OAR exposure for every fraction and is recommended to use in prostate SBRT. The study is part of clinical trial NCT02319239.Approximately fifty percent of premenopausal women who smoke cigarettes or on nicotine replacement therapy are also on hormonal contraceptives, especially oral estrogen-progestin. Oral estrogen-progestin therapy has been reported to promote insulin resistance (IR) which causes lipid influx into non-adipose tissue and impairs Na+/K+ -ATPase activity, especially in the heart and kidney. However, the effects of nicotine on excess lipid and altered Na+/K+ -ATPase activity associated with the use of estrogen-progestin therapy have not been fully elucidated. This study therefore aimed at investigating the effect of nicotine on cardiac and renal lipid influx and Na+/K+ -ATPase activity during estrogen-progestin therapy. Twenty-four female Wistar rats grouped into 4 (n = 6/group) received (p.o.) vehicle, nicotine (1.0 mg/kg) with or without estrogen-progestin steroids (1.0 μg ethinyl estradiol and 5.0 μg levonorgestrel) and estrogen-progestin only daily for 6 weeks. Data showed that estrogen-progestin treatment or nicotine exposure caused IR, hyperinsulinemia, increased cardiac and renal uric acid, malondialdehyde, triglyceride, glycogen synthase kinase-3, plasminogen activator inhibitor-1, reduced bilirubin and circulating estradiol. Estrogen-progestin treatment led to decreased cardiac Na+/K+-ATPase activity while nicotine did not alter Na+/K+-ATPase activity but increased plasma and tissue cotinine. Renal Na+/K+-ATPase activity was not altered by the treatments. However, all these alterations were reversed following combined administration of oral estrogen-progestin therapy and nicotine. The present study therefore demonstrates that oral estrogen-progestin therapy and nicotine exposure synergistically prevents IR-linked cardio-renotoxicity with corresponding improvement in cardiac and renal lipid accumulation, oxidative stress, inflammation and Na+/K+-ATPase activity.Endoplasmic reticulum stress (ERS), mutual crosstalk between autophagy and apoptosis-related signaling pathway, plays an important role in the process of acute liver injury (ALI). The present study was to investigate the effects and underlying mechanisms of Asiatic acid from Potentilla chinensis (AAPC) on ALI. The model of ALI in mice was induced by administration with Lipopolysaccharide/D-Galactosamine (LPS/D-GalN). The effects of AAPC on hepatic pathology and hepatocyte apoptosis were observed by hematoxylin-eosin (H&E) staining and TUNEL staining. Serum transaminases activities were measured using an automated biochemical analyzer. Moreover, ERS and autophagy were induced in LO2 cells, respectively. Cell cycle and apoptosis were analyzed using flow cytometry. In addition, ERS and autophagy-related pathways were detected in vivo and in vitro. The results showed that AAPC significantly ameliorated LPS/D-GalN-induced ALI in mice, as evidenced by the improvement of liver pathology and the decrease in serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activities. Moreover, AAPC pre-treatment markedly inhibited thapsigargin-induced cell apoptosis, accompanied by cell cycle arrest at S/G1 phase in LO2 cells. AAPC notably inhibited the activation of the PERK/ATF6 and IRE1 pathway, alleviating the extent of ERS. Additionally, AAPC significantly promoted autophagy, as evidenced by the increase in the formation of autophagic vacuoles and the number of autophagosomes as well as the increased expressions of LC3II/I, Beclin-1, Atg5 and Atg7. In summary, our results indicate that AAPC significantly ameliorates ALI by inhibiting the ERS pathway and promoting hepatocyte autophagy.ALOX12 encodes arachidonic acid 12-lipoxygenase that acts on different polyunsaturated fatty acid substrates to produce biologically active lipid mediators including eicosanes and lipoxins. ALOX12 protein plays an important role in inflammation and oxidation, while abnormal DNA methylation and genetic variants of ALOX12 are associated with various human diseases and pathological phenotypes, such as cardiovascular disease, diabetes, neurodegenerative diseases, respiratory system disease, cancer, infection, etc. Here, this article reviews the mechanisms by which ALOX12 participates in related diseases, which will provide systematic knowledge for future ALOX12 related studies.Aberrant scar formation, which includes keloid and hypertrophic scars, is associated with a pathological disorganized wound healing process with chronic inflammation. The TGF-β/Smad signaling pathway is the most canonical pathway through which the formation of collagen in the fibroblasts and myofibroblasts is regulated. Sustained activation of the TGF-β/Smad signaling pathway results in the long-term overactivation of fibroblasts and myofibroblasts, which is necessary for the excessive collagen formation in aberrant scars. There are two categories of therapeutic strategies that aim to target the TGF-β/Smad signaling pathway in fibroblasts and myofibroblasts to interfere with their cellular functions and reduce cell proliferation. The first therapeutic strategy includes medications, and the second strategy is composed of genetic and cellular therapeutics. Therefore, the focus of this review is to critically evaluate these two main therapeutic strategies that target the TGF-β/Smad pathway to attenuate abnormal skin scar formation.Chemotherapy with a single chemotherapeutic agent or a combined chemotherapeutic regimen is the clinically standardized treatment for almost all human cancers. Upregulated expression of cyclooxygenase (COX)-2, also known as prostaglandin-endoperoxide synthase (PTGS), is associated with human carcinogenesis and cancer progression and COX-2 inhibitors show antitumor activity in different human cancers. Thus, a combination of chemotherapeutic agents with COX-2 inhibitors has been shown to improve therapeutic effects on human cancers. This review discusses and summarizes recent advances in cancer control and treatment using various antineoplastic drugs combined with COX-2 inhibitors. These combinations showed synergistic antitumor effects. At the gene level, COX-2 inhibitors can reduce inflammatory factors thereby regulating macrophage recruitment for activating the antitumor immune microenvironment; downregulating vascular endothelial growth factor (VEGF) to inhibit tumor angiogenesis; and inhibiting the PI3K/Akt signaling pathway to induce tumor cell apoptosis. In addition, such a combination can reduce toxicity and chemoresistance and enhance radiosensitivity, although COX-2 inhibitors-related cardiotoxicity may potentially affect its use. Further in-depth investigation of these drug combinations is needed to maximize antitumor efficacy and minimize the side effects.Purpose This study aims to compare the neurocognitive outcome in term infants who were treated using phenobarbital (PB) and levetiracetam (LEV) monotherapy for neonatal clinical seizures. Methods Term infants who were treated using PB or LEV monotherapy as the first-line anti-epileptic treatment for neonatal clinical seizures and followed-up in a pediatric neurology outpatient clinic were enrolled in this study. link2 Neurodevelopmental outcome assessments were carried out using the Bayley Scales of Infant Development, third edition (BSID-III), including cognitive, receptive language, expressive language, fine motor and gross motor subscales. Results The study group consisted of 62 infants who received monotherapy with PB monotherapy (n = 22) and LEV (n = 40). The mean duration of monotherapy treatment was 8 ± 6 months. There was no statistically significant difference between PB and LEV monotherapy groups concerning each outcome parameter on the BSID-III. There was also no statistically significant difference between PB and LEV monotherapy subgroups excluding the infants with neurodevelopmental impairment with a BSID-III scale score less then 7 or a composite score less then 85. Conclusion Our findings suggest that both LEV and PB therapy can be equally safe as monotherapy for neonatal clinical seizures for the neurodevelopmental outcome assessment with BSID-III.Purpose Ramadan fasting represents a challenge for both Muslim patients with epilepsy (MPWE) as well as their treating neurologists who aim to minimize the risk of fasting-related seizures. Several factors may contribute to the risk of fasting-related seizures such as the half-life of antiepileptic drugs (AEDs), seizure control before Ramadan, and sleep fragmentation. The aim of this work was to investigate these factors. Methods An observational prospective study included all MPWE who completed Ramadan fasting in 2019, about 16 h per day for 30 days. They were assessed regarding seizure control, AEDs, and sleep alterations using The Pittsburgh Sleep Quality Index. link3 Results The study included 430 MPWE. The majority of patients (75.58%) completed Ramadan fasting without breakthrough seizures. Patients achieved successful Ramadan fasting were significantly younger, had shorter disease duration, longer periods of seizure freedom before Ramadan, more efficient and longer sleep hours. There was no significant difference between patients receiving monotherapy regimens with short versus intermediate long t½.