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Dodson Graves opublikował 1 rok, 8 miesięcy temu
Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8-17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8-17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.Hydrogen is a clean fuel and an abundant renewable energy resource. In recent years, huge scientific attention has been invested to invent suitable materials for its safe storage. Conducting polymers has been extensively investigated as a potential hydrogen storage and fuel cell membrane due to the low cost, ease of synthesis and processability to achieve the desired morphological and microstructural architecture, ease of doping and composite formation, chemical stability and functional properties. The review presents the recent progress in the direction of material selection, modification to achieve appropriate morphology and adsorbent properties, chemical and thermal stabilities. Polyaniline is the most explored material for hydrogen storage. Polypyrrole and polythiophene has also been explored to some extent. Activated carbons derived from conducting polymers have shown the highest specific surface area and significant storage. This review also covers recent advances in the field of proton conducting solid polymer electrolyte membranes in fuel cells application. This review focuses on the basic structure, synthesis and working mechanisms of the polymer materials and critically discusses their relative merits.Background HIV poses a threat to global health. With effective treatment options available, education and testing strategies are essential in preventing transmission. Text messaging is an effective tool for health promotion and can be used to target higher risk populations. This study reports on the design, delivery and testing of a mobile text messaging SMS intervention for HIV prevention and awareness, aimed at adults in the construction industry and delivered during the COVID-19 pandemic. Method Participants were recruited at Test@Work workplace health promotion events (21 sites, n = 464 employees), including health checks with HIV testing. Message development was based on a participatory design and included a focus group (n = 9) and message fidelity testing (n = 291) with assessment of intervention uptake, reach, acceptability, and engagement. Barriers to HIV testing were identified and mapped to the COM-B behavioural model. 23 one-way push SMS messages (19 included short web links) were generated and fidest. Conclusions SMS messaging for HIV prevention and awareness is acceptable to adults in the construction industry, has high uptake, low attrition and good engagement with message content, when delivered during a global pandemic. Data collection methods may need refinement for audience, and effect of COVID-19 on results is yet to be understood.HJURP is a key factor for CENP-A deposition and maintenance in centromeres. The role of mis-regulation of histone chaperones in cancer initiation and progression has been studied. However, its role in colorectal cancer is still unclear. In this study, we aimed to evaluate the expression of HJURP in 162 colorectal cancer tissue. To investigate the function of HJURP in the colorectal cancer cell, we suppressed HJURP expression by siRNA and confirmed proliferation, migration, invasion, and anchorage independent of colony forming ability. The association between HJURP expression levels and clinicopathological factors was evaluated in 162 CRC tissues using immunohistochemistry. The overall survival rate in patients of HJURP high expression was higher than those in HJURP low expression in CRC. Suppressing HJURP expression decreased cellular proliferation, invasion, and migration in four CRC cell lines HT29, HCT116, SW480, SW620 in vitro study. Our findings revealed that the knockdown of HJURP suppressed the proliferation, migration, invasion, and tumorigenicity in CRC cells. Due to its strong association with CRC, HJURP could be a potential prognostic biomarker and a novel target for drug discovery.The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert pleiotropic effects on cardiac cell biology which are not yet fully understood. Here we tested whether statin treatment affects resident endogenous cardiac stem/progenitor cell (CSC) activation in vitro and in vivo after myocardial infarction (MI). Statins (Rosuvastatin, Simvastatin and Pravastatin) significantly increased CSC expansion in vitro as measured by both BrdU incorporation and cell growth curve. Additionally, statins increased CSC clonal expansion and cardiosphere formation. The effects of statins on CSC growth and differentiation depended on Akt phosphorylation. Twenty-eight days after myocardial infarction by permanent coronary ligation in rats, the number of endogenous CSCs in the infarct border zone was significantly increased by Rosuvastatin-treatment as compared to untreated controls. Additionally, commitment of the activated CSCs into the myogenic lineage (c-kitpos/Gata4pos CSCs) was increased by Rosuvastatin administration. Accordingly, Rosuvastatin fostered new cardiomyocyte formation after MI. Finally, Rosuvastatin treatment reversed the cardiomyogenic defects of CSCs in c-kit haploinsufficient mice, increasing new cardiomyocyte formation by endogenous CSCs in these mice after myocardial infarction. In summary, statins, by sustaining Akt activation, foster CSC growth and differentiation in vitro and in vivo. The activation and differentiation of the endogenous CSC pool and consequent new myocyte formation by statins improve myocardial remodeling after coronary occlusion in rodents. Similar effects might contribute to the beneficial effects of statins on human cardiovascular diseases.
Bariatric surgery is a widely used treatment for morbid obesity. Prediction of postoperative weight loss currently relies on prediction models, which mostly overestimate patients’ weight loss. Data about the influence of Non-alcoholic fatty liver disease (NAFLD) on early postoperative weight loss are scarce.
This prospective, single-center cohort study included 143 patients receiving laparoscopic gastric bypass surgery (One Anastomosis-Mini Gastric Bypass (OAGB-MGB) or Roux-en-Y Gastric Bypass (RYGB)). Liver biopsies were acquired at surgery. NAFLD activity score (NAS) assigned patients to „No NAFLD”, „NAFL” or „NASH”. Follow up data were collected at 3, 6 and 12 months.
In total, 49.7% of patients had NASH, while 41.3% had NAFL. Compared with the No NAFLD group, NAFL and NASH showed higher body-mass-index (BMI) at follow-up (6 months 31.0 kg/m
vs. 36.8 kg/m
and 36.1 kg/m
, 12 months 27.0 kg/m
vs. 34.4 and 32.8 kg/m
) and lower percentage of total body weight loss (%TBWL) (6 months 27.1% vs. 23.3% and 24.4%; 12 months 38.5% vs. 30.1 and 32.6%). Linear regression of NAS points significantly predicts percentage of excessive weight loss (%EWL) after 6 months (Cologne-weight-loss-prediction-score).
Histopathological presence of NAFLD might lead to inferior postoperative weight reduction after gastric bypass surgery. The mechanisms underlying this observation should be further studied.
Histopathological presence of NAFLD might lead to inferior postoperative weight reduction after gastric bypass surgery. The mechanisms underlying this observation should be further studied.An overwhelming flood of misinformation is accompanying the pandemic of COVID-19. Fake news and conspiracy theories are so prevalent that the World Health Organization started as early as February 2020 to use the term „infodemic”. This paper is focused on the assessment of the prevalence of beliefs in conspiracy theories related to COVID-19 in Polish society. The association of support for conspiracy theories with sociodemographic variables, health literacy (HL) and eHealth literacy (eHL) was studied. The analysis reported here was based on the data from an online survey of a representative sample (n = 1002) of the adult population of Polish Internet users. The multivariate linear regression for the COVID-19-related conspiracy belief score (CCBS) and logistic regression models for the support of individual conspiracy theories was developed. The percentage of supporters of particular conspiracy theories in the study sample ranged from 43% to 56%. The CCBS was significantly associated with age, education level, vocational status and both HL and eHL. However, it was lower for persons with higher HL (regression coefficient (B) = -0.04, p less then 0.001) but higher for those with higher eHL (B = 0.04, p = 0.038). The most influential predictors of CCBS were age (standardised regression coefficient (β) = -0.21) and education level (β from 0.08 to 0.16 for respondents with lower education levels and those with master’s degrees). In conclusion, younger persons rather than older, those with a lower rather than with a higher level of education, employees rather than students and persons with lower rather than higher HL were more likely to believe the conspiracy theories. Surprisingly, contrary to expectations, higher eHL was significantly associated with greater belief in such theories.In fish, sperm motility activation is one of the most essential procedures for fertilization. Previous studies have mainly focused on the external environmental effects and intracellular signals in sperm activation; however, little is known about the metabolic process of sperm motility activation in fish. In the present study, using ricefield eel (Monopterus albus) sperm as a model, metabonomics was used to analyze the metabolic mechanism of the sperm motility activation in fish. Firstly, 529 metabolites were identified in the sperm of ricefield eel, which were clustered into the organic acids, amino acids, nucleotides, benzene, and carbohydrates, respectively. Among them, the most abundant metabolites in sperm were L-phenylalanine, DL-leucine, L-leucine, lysolecithin choline 180, L-tryptophan, adenine, hypoxanthine, 7-Methylguanine, shikimic acid, and L-tyrosine. Secondly, compared to pre-activated sperm, the level of S-sulfo-L-cysteine and L-asparagine were both increased in the post-activated sperm. Ninety-two metabolites were decreased in the post-activated sperm, including quinic acid, acetylsalicylic acid, 7,8-dihydro L-biopterin, citric acid, glycylphenylalanine, and dihydrotachysterol (DHT). Finally, basing on the pathway analysis, we found that the changed metabolites in sperm motility activation were mainly clustered into energy metabolism and anti-oxidative stress. Fish sperm motility activation would be accompanied by the release of a large amount of energy, which might damage the genetic material of sperm. Thus, the anti-oxidative stress function is a critical process to maintain the normal physiological function of sperm.


