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Iodine is an essential constituent of thyroid hormone. https://www.selleckchem.com/products/Methazolastone.html Active iodide accumulation in the thyroid is mediated by the sodium iodide symporter (NIS), comprising the first step in thyroid hormone biosynthesis, which relies on the functional expression of NIS on the cell membrane. The retention of NIS expressed in differentiated thyroid cancer (DTC) cells allows further treatment with post-operative radioactive iodine (RAI) therapy. However, compared with normal thyroid tissue, differentiated thyroid tumors usually show a decrease in the active iodide conveyance and NIS is generally retained within the cells, indicating that posttranslational protein transfer to the plasma membrane is abnormal. In recent years, through in vitro studies and studies of patients with DTC, various methods have been tested to increase the transport rate of NIS to the cell membrane and increase the absorption of iodine. An in-depth understanding of the mechanism of NIS transport to the plasma membrane could lead to improvements in RAI therapy. Therefore, in this review, we discuss the current knowledge concerning the post-translational mechanisms that regulate NIS transport to the cell membrane and the current status of redifferentiation therapy for patients with RAI-refractory (RAIR)-DTC.
Successful oral peptide delivery faces two major hurdles low enzymatic stability in the gastro-intestinal lumen and poor intestinal membrane permeability. While lipid-based formulations (LBF) have the potential to overcome these barriers, effective formulation of peptides remains challenging. Lipophilic salt (LS) technology can increase the apparent lipophilicity of peptides, making them more suitable for LBF.
As a model therapeutic peptide, octreotide (OCT) was converted to thedocusate LS (OCT.DoS
), and compared to the commercial acetate salt (OCT.OAc
) in oral absorption studies and related in vitro studies, including parallel artificial membrane permeability assay (PAMPA), Caco-2, in situ intestine perfusion, and simulated digestion in vitro models. The in vivo oral absorption of OCT.DoS
and OCT.OAc
formulated in self-emulsifying drug delivery systems (SEDDS) was studied in rats.
LS formulation improved thesolubility and loading of OCT in LBF excipients and OCT.DoS
in combination with SEDDS showed higher OCT absorption than the acetate comparator in the in vivo studies in rats. The Caco-2 and in situ intestine perfusion models indicated no increases in permeability for OCT.DoS
. However, the in vitro digestion studies showed reduced enzymatic degradation of OCT.DoS
when formulated in the SEDDS formulations. Further in vitro dissociation and release studies suggest that the enhanced bioavailability of OCT from SEDDS-incorporating OCT.DoS
is likely a result of higher partitioning into and prolonged retention within lipid colloid structures.
The combination of LS and LBF enhanced the in vivo oral absorption of OCT primarily via the protective effect of LBF sheltering the peptide from gastrointestinal degradation.
The combination of LS and LBF enhanced the in vivo oral absorption of OCT primarily via the protective effect of LBF sheltering the peptide from gastrointestinal degradation.
Glioblastoma (GBM) is a malignant brain tumor with a poor long-term prognosis due to recurrence from highly resistant GBM cancer stem cells (CSCs), for which the current standard of treatment with temozolomide (TMZ) alone will unlikely produce a viable cure. In addition, CSCs regenerate rapidly and overexpress methyl transferase which overrides the DNA-alkylating mechanism of TMZ, leading to resistance. The objective of this research was to apply the concepts of nanotechnology to develop a multi-drug therapy, TMZ and idasanutlin (RG7388, a potent mouse double minute 2 (MDM2) antagonist), loaded in functionalized nanoparticles (NPs) that target the GBM CSC subpopulation, reduce the cell viability and provide possibility of in vivo preclinical imaging.
Polymer-micellar NPs composed of poly(styrene-b-ethylene oxide) (PS-b-PEO) and poly(lactic-co-glycolic) acid (PLGA) were developed by a double emulsion technique loading TMZ and/or RG7388. The NPs were covalently bound to a 15-nucleotide base-pair CD133 aptamer to target the CD133 antigen expressed on the surfaces of GBM CSCs. For diagnostic functionality, the NPs were labelled with radiotracer Zirconium-89 (
Zr).
NPs maintained size range less than 100nm, a low negative charge and exhibited the ability to target and kill the CSC subpopulation when TMZ and RG7388 were used in combination. The targeting function of CD133 aptamer promoted killing in GBMCSCs providing impetus for further development of targeted nanosystems for localized therapy in future in vivo models.
This work has provided a potential clinical application for targeting GBM CSCs with simultaneous diagnostic imaging.
This work has provided a potential clinical application for targeting GBM CSCs with simultaneous diagnostic imaging.
Cardiovascular diseases are the leading cause of mortality in end-stage renal disease (ESRD) patients, especially those receiving hemodialysis (HD) therapy. HD has many side effects that are related to patients' hearts, such as recurrent myocardial ischemia and global or segmental left-ventricular dysfunction, which is associated with intradialytic hypotension, long-term loss of systolic function, and high incidence of cardiovascular events and death. Systematic exercise training has a beneficial effect on measures of cardiovascular fitness and reducing cardiovascular risk factors in ESRD. Whether there is an acute benefit of exercise during HD on left-ventricular function is not well known. The current study aimed to investigate whether a single bout of hybrid (aerobic and resistance) intradialytic exercise could affect left-ventricular function during HD sessions.
Twenty-one exercise naïve and clinically stable HD patients participated in the study. All participants completed two different HD trials on uld beneficially affect left-ventricular function abnormalities often observed during the HD therapy.
The study is registered at ClinicalTrials.gov (NCT01721551) as a clinical trial.
The study is registered at ClinicalTrials.gov (NCT01721551) as a clinical trial.Beijing, as the capital of China, still has soil pollution problems that cannot be ignored. However, there are few studies on the overall ecological risks of heavy metals in farmland soils in Beijing. This study selected 432 soils and crops heavy metal content data of eight districts in Beijing from academic papers and academic journal papers. In this study, the improved Hakanson method, improved analytic hierarchy process (AHP), and integrated quality impact index (IICQ) comprehensively were used to evaluate the impact of Pb, As, and Cd pollution on the farmland soil environment, and the applicable conditions of these methods were discussed. The results by improved Hakanson method showed that both Pb and As were at the normal ecological risk level, while Cd was the largest contributor to potential ecological risk which accounted for 72.54% of the total risk and is mainly at a moderate ecological risk level. The analysis by improved AHP showed that the average comprehensive index of soil heavy metal pollution in the study area was 0.2317, which was at a light pollution level. The IICQ of soil and agricultural products were between 0 and 1 demonstrating that the soil was clean. In summary, the pollution of heavy metals Pb, As, and Cd in the study area is at a relatively low level, and there is no significant risk to the surrounding environment and human health. IICQ method is suitable for the evaluation of soil heavy metal composition and individual impact and can be more accurately used for the overall ecological evaluation of soil-crop-human health system.This study assessed prophylactic potentials of silymarin against lead-induced hepatorenal toxicity in rats with the respect to its antioxidant and anti-apoptotic activities. Forty male albino rats were distributed into four groups. Control group is provided with distilled water. Lead acetate group was given lead acetate (100 mg/kg bwt) orally for 10 weeks. The third and fourth groups administered silymarin at doses of 50 or 100 mg/kg bwt, respectively, 1 h before administration of lead acetate for 10 weeks. Lead acetate altered liver structure and function that represented by significant elevation of the activities of serum aspartate and alanine aminotransferases and serum levels of urea and creatinine. Hepatic and renal tissues' malondialdehyde concentrations were increased, while reduced glutathione content and superoxide dismutase and catalase activities were reduced in the lead acetate group. Also, lead acetate increased caspase-3 mRNA expression and inhibited alpha-fetoprotein mRNA expression in hepatic tissues, as well as it altered liver and kidney tissues' architectures. In contrast, silymarin ameliorated in a dose dependent mannar the toxic effects of lead acetate on the liver and kidneys through modulation of lead acetate which altered liver and kidney function and structures via reducing lipid oxidation and pathological changes of hepatic and renal tissue structure, improving antioxidant defense system of liver and kidneys, and decreasing pro-apoptotic gene expression in hepatic tissue. This study indicated that silymarin ameliorated lead acetate-induced hepatorenal toxicity via its antioxidant and cytoprotective potentials.Microfiber pollution is one of the recent threats to sustainability. Due to the increased use of synthetic textiles, microplastic fiber release to the environment has increased exponentially. This review aims to analyze the existing literature to identify the potential preventive measures to control microfiber pollution. The review consolidates the findings under the textile properties and laundry product category. The review results show that the use of finer count yarns with filaments and compact structures reduces microfiber shedding. Similarly, mechanical finishes like shearing and raising increase the microfiber release as they damage the fabric structure. A significant increment is noted in microfiber reduction percentage after the chemical (coating) finishing process. In the case of commercial products, the available external laundry filters are reported as more efficient than the in-drum devices in the market. An analysis of the existing regulatory norms showed that very few countries had developed their laws, and no global regulation and standards were found to test microfiber pollution. In the case of laundry filters, though they filter microfiber effectively, they do not prevent it, so it can be a control measure and not a solution for the issue. Out of the review results, it is identified that controlling the textile parameter is the only effective strategy to prevent the microfiber shedding from the synthetic textile. A proper production method and parameter will yield a textile that sheds lesser or no microfiber. However, no detailed research works are found in correlating these parameters together and indicate the potential scope for future research.Many studies report organic carbon stabilization by clay minerals, but the effects of land use and soil type on the properties of humic acids (HAs) are missing. The aim of the paper is to determine the effects of land use and soil types on the characteristics of HAs, which have a considerable influence on organic matter quality. It was hypothesised that the effect of the land use on HAs properties depends on the particular size distribution. The research was performed in three ecosystems agricultural, forest, and meadow, located in Slovakia. From each of them, the samples of 4 soil types were taken Chernozem, Luvisol, Planosol, and Cambisol. The soil samples were assayed for the content of total organic carbon (TOC) and the particle size distribution. HAs were extracted with the Schnitzer method and analysed for the elemental composition, spectrometric parameters in the UV-VIS range, and hydrophilic and hydrophobic properties, and the infrared spectra were produced. The research results have shown that the properties of HAs can be modified by the land use and the scope and that the direction of changes depends on the soil type.
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