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We report herein anti-proliferation effects of 4-arylthiosemicarbazides, with a cyclopentane substitution at N1 position, on highly virulent RH strain of Toxoplasma gondii. Among them, the highest in vitro anti-Toxoplasma activity was found with the meta-iodo derivative. Further experiments demonstrated inhibitory effects of thiosemicarbazides on tyrosinase (Tyr) activity, and good correlation was found between percentage of Tyr inhibition and IC50Tg. To confirm the concept that thiosemicarbazides are able to disrupt tyrosine metabolism in Toxoplasma tachyzoites, the most potent Tyr inhibitors were tested for their efficacy of T. gondii growth inhibition. All of them significantly reduced the number of tachyzoites in the parasitophorous vacuoles (PVs) compared to untreated cells, as well as inhibited tachyzoites growth by impeding cell division. Collectively, these results indicate that compounds with the thiosemicarbazide scaffold are able to disrupt tyrosine metabolism in Toxoplasma tachyzoites by deregulation of their crucial enzyme tyrosine hydroxylase (TyrH).The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.Purpose Bearing partially or fully metallic passive implants represents an exclusion criterion for patients undergoing a magnetic hyperthermia procedure, but there are no specific studies backing this restrictive decision. This work assesses how the secondary magnetic field generated at the surface of two common types of prostheses affects the safety and efficiency of magnetic hyperthermia treatments of localized tumors. The paper also proposes the combination of a multi-criteria decision analysis and a graphical representation of calculated data as an initial screening during the preclinical risk assessment for each patient.Materials and methods Heating of a hip joint and a dental implant during the treatment of prostate, colorectal and head and neck tumors have been assessed considering different external field conditions and exposure times. The Maxwell equations including the secondary field produced by metallic prostheses have been solved numerically in a discretized computable human model. The heat excharostheses at initial stages of treatment, since recommended thermal thresholds are soon surpassed for higher field intensities. However, it has also been found that under some operational conditions the typical safety rule of staying below or attain a maximum temperature increase or SAR value is met.Conclusion The current exclusion criterion for implant-bearing patients in magnetic hyperthermia should be revised, since it may be too restrictive for a range of the typical field conditions used. Systematic in silico treatment planning using the proposed methodology after a well-focused diagnostic procedure can aid the clinical staff to find the appropriate limits for a safe treatment window. In the treatment of patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI), it is unclear which combination of antithrombotic drugs is preferable and which is the optimal duration of treatment. The authors review the available evidence in this area resulting from single studies and meta-analyses. In the absence of direct head-to-head comparisons between different non-vitamin K oral anticoagulants (NOAC), the authors review the available studies with NOACS in these patients and derived indirect comparisons. In patients with AF who undergo PCI, a dual antithrombotic strategy which includes a NOAC plus single antiplatelet therapy with a P2Y12 inhibitor (preferably clopidogrel) should be considered as the preferred treatment option in most cases. Oral anticoagulation associated with dual antiplatelet therapy (triple antithrombotic therapy) should be offered for no longer than 30days to patients with very high thrombotic and low hemorrhagic risk. It is unclear whether theestablish the best patient-tailored approach in this complex scenario.Sulfites are commonly used as a preservative and antioxidant additives in the food industry. Sulfites are absorbed by the gastrointestinal tract and distributed essentially to all body tissues. Although sulfites have been believed to be safe food additives, some studies have shown that they exhibit adverse effects in various tissues. OD36 In this study, we examined the cytotoxic effect of sodium sulfite (Na2SO3) against rat gastric mucosal cells (RGM1) and further investigated its underlying molecular mechanism. We demonstrated that exposure to Na2SO3 exerts significant cytotoxicity in RGM1 cells through induction of oxidative stress. Exposure of RGM1 cells to Na2SO3 caused a significant formation of protein carbonyls and 8-hydroxy-2'-deoxyguanosine, major oxidative stress markers, with a concomitant accumulation of carbonylated protein-related aggregates. Furthermore, we found that incubation of lysozyme with Na2SO3 evokes protein carbonylation and aggregation via the metal ion-catalyzed free radical formation derived from Na2SO3. Our results suggest that Na2SO3 might lead to gastric tissue injury via induction of oxidative stress by the formation of Na2SO3-related free radicals.In this paper, a set of 3-methylquniazolinone derivatives were designed, synthesised, and studied the preliminary structure-activity relationship for antiproliferative activities. All target compounds performed significantly inhibitory effects against wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) and tumour cells (A431, A549, MCF-7, and NCI-H1975). In particular, compound 4d 3-fluoro-N-(4-((3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)methoxy)phenyl)benzamide showed higher antiproliferative activities against all tumour cells than Gefitinib (IC50 of 3.48, 2.55, 0.87 and 6.42 μM, respectively). Furthermore, compound 4d could induce apoptosis of MCF-7 cells and arrest in G2/M phase at the tested concentration. Molecular docking and ADMET studies showed that compound 4d could closely form many hydrogen bonds with EGFRwt-TK. Therefore, compound 4d is potential to develop as novel anti-cancer drug.

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