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Publikace se zaměřuje na biomedicínské využití uhlíkových nanomateriálů a jejich toxicitu a zdravotní rizika. Určeno odborné veřejnosti.
- MeSH
- nanostruktury MeSH
- nanotechnologie MeSH
- noxy MeSH
- otrava MeSH
- testy toxicity MeSH
- uhlík MeSH
- vystavení vlivu životního prostředí MeSH
- Konspekt
- Nauka o materiálu
- NLK Obory
- technika
- biomedicínské inženýrství
- toxikologie
- NLK Publikační typ
- kolektivní monografie
Introduction: Olive (Olea uropeae) is a traditional plant containing oleuropein and hydroxytyrosol, which are useful and used empirically for treating diabetes mellitus.Objective: To review the potential of oleuropein and hydroxytyrosol as an evidence base for diabetes potential treatment and safety.Methods: This chapter summarizes several studies available on Pubmed and Google Scholar regarding the characteristic method and extraction method as well as the effectiveness and toxicity of oleuropein and hydroxytyrosol in vitro and in vivo.Result: Oleuropein and hydroxytyrosol are effective antihyperglycemics for treating T2D. They can reduce body weight, basal glycemia, and insulin resistance by stopping the liver from making glucose and stopping the body from absorbing glucose. Several studies have shown that both isolates can control glycemic levels equivalent to free fatty acids and are safe to use.Conclusion: Oleuropein and hydroxytyrosol are extracted by several methods and can be used as potential anti-diabetics with obesity risk factors. Evidence shows that both isolates are safe for both acute and chronic use.
- Klíčová slova
- oleuropein, hydroxytyrosol,
- MeSH
- diabetes mellitus 2. typu farmakoterapie metabolismus MeSH
- hypoglykemika * farmakologie terapeutické užití MeSH
- inzulinová rezistence MeSH
- iridoidy farmakologie terapeutické užití MeSH
- lidé MeSH
- Olea * fyziologie MeSH
- rostlinné extrakty * farmakologie terapeutické užití MeSH
- testy toxicity metody MeSH
- Check Tag
- lidé MeSH
Částice atmosférického aerosolu jsou celosvětově považovány za významné zdravotní riziko. Přestože přesné mechanismy toxicity aerosolu stále nejsou plně známy, několik studií uvádí, že generování reaktivních sloučenin kyslíku je jedním z hlavních mechanismů, který je zodpovědný za chronické i akutní zdravotní problémy. Z tohoto důvodu byl oxidativní potenciál (OP), definovaný jako schopnost aerosolu generovat reaktivní sloučeniny kyslíku, navržen jako relevantní parametr pro hodnocení toxicity aerosolu. Tento článek popisuje různé acelulární in vitro metody stanovení OP a vliv chemického složení a velikosti aerosolu na OP.
Atmospheric aerosol particles are considered to be a significant health risk worldwide. Although the exact mechanisms of aerosol toxicity are still not fully understood, several studies report that the generation of reactive oxygen species (ROS) is one of the main mechanisms responsible for chronic and acute health problems. For this reason, oxidative potential (OP) which is defined as the ability of an aerosol to generate ROS, has been proposed as a relevant parameter for assessing aerosol toxicity. This article describes different acellular in vitro methods to determine OP and the influence of chemical composition and aerosol size on OP.
- Klíčová slova
- oxidativní potenciál,
- MeSH
- aerosoly * škodlivé účinky MeSH
- atmosféra analýza chemie MeSH
- lidé MeSH
- oxidační stres * MeSH
- techniky in vitro MeSH
- testy toxicity * metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
OBJECTIVES: Cluster of differentiation 38 (CD38) is a key target on multiple myeloma (MM) cells. This multi-centre, Phase 1, single-agent study (NCT04000282) investigated SAR442085, a novel fragment crystallisable (Fc)-modified anti-CD38 monoclonal antibody (mAb), with enhanced affinity towards Fc-gamma receptor on effector cells in patients with relapsed and/or refractory (RR) MM. METHODS: This study comprised two parts: Part-A (dose-escalation involving anti-CD38 mAb pre-treated and naïve patients) and Part-B (dose expansion). Primary endpoints were maximum tolerated dose and recommended Phase 2 dose (RP2D). RESULTS: Thirty-seven heavily pre-treated patients were treated in Part A. Part-B (dose-expansion) was not studied. Seven dose-limiting toxicities were reported at DL3, DL5, DL6, and DL7. RP2D was determined to be 5-7·5 mg/kg. Most common treatment-emergent adverse events were infusion-related reactions in 70·3% (26/37) patients. Grade ≥3 thrombocytopenia was reported in 48·6% (18/37). Overall response rate was 70% in anti-CD38 mAb naïve and 4% in anti-CD38 pre-treated patients, with a median progression-free survival of 7·62 (95%CI: 2·858; not calculable) months and 2·79 (95%CI: 1·150; 4·172) months and, respectively. CONCLUSIONS: The efficacy of SAR442085 was promising in anti-CD38 mAb naïve patients but did not extend to the larger cohort of anti-CD38 mAb pre-treated patients. This observation, along with transient high-grade thrombocytopenia, could potentially limit its clinical use.
- MeSH
- antigeny CD38 antagonisté a inhibitory imunologie MeSH
- chemorezistence MeSH
- dospělí MeSH
- humanizované monoklonální protilátky aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- maximální tolerovaná dávka MeSH
- mnohočetný myelom * farmakoterapie mortalita MeSH
- monoklonální protilátky aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- recidiva MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
- multicentrická studie MeSH
- MeSH
- antagonista receptoru pro interleukin 1 terapeutické užití MeSH
- B-lymfocyty patologie účinky léků MeSH
- biomarkery farmakologické MeSH
- chimerické antigenní receptory * účinky léků MeSH
- lymfohistiocytóza hemofagocytární diagnóza farmakoterapie patofyziologie MeSH
- monitorování fyziologických funkcí MeSH
- nežádoucí účinky léčiv MeSH
- premedikace metody MeSH
- receptory interleukinu-6 antagonisté a inhibitory MeSH
- sekundární prevence metody MeSH
- syndrom uvolnění cytokinů chemicky indukované farmakoterapie prevence a kontrola MeSH
- testy toxicity MeSH
- vakcinace MeSH
- Publikační typ
- novinové články MeSH
In the present review we addressed the determination of DNA damage induced by small-molecule carcinogens, considered their persistence in DNA and mutagenicity in in vitro and in vivo systems over a period of 30 years. The review spans from the investigation of the role of DNA damage in the cascade of chemical carcinogenesis. In the nineties, this concept evolved into the biomonitoring studies comprising multiple biomarkers that not only reflected DNA/chromosomal damage, but also the potential of the organism for biotransformation/elimination of various xenobiotics. Since first years of the new millennium, dynamic system of DNA repair and host susceptibility factors started to appear in studies and a considerable knowledge has been accumulated on carcinogens and their role in carcinogenesis. It was understood that the final biological links bridging the arising DNA damage and cancer onset remain to be elucidated. In further years the community of scientists learnt that cancer is a multifactorial disease evolving over several decades of individual ́s life. Moreover, DNA damage and DNA repair are inseparable players also in treatment of malignant diseases, but affect substantially other processes, such as degeneration. Functional monitoring of DNA repair pathways and DNA damage response may cast some light on above aspects. Very little is currently known about the relationship between telomere homeostasis and DNA damage formation and repair. DNA damage/repair in genomic and mitochondrial DNA and crosstalk between these two entities emerge as a new interesting topic.
- MeSH
- DNA MeSH
- karcinogeneze genetika MeSH
- karcinogeny MeSH
- kometový test MeSH
- lidé MeSH
- oprava DNA MeSH
- poškození DNA MeSH
- pracovní expozice * MeSH
- xenobiotika * toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The proper course and reproducibility of diagnostic techniques depend on narrowly defined reaction conditions, including the reaction pH. Nevertheless, numerous assays are affected by an inaccurately defined reaction pH. Buffers are sometimes suggested for use outside their useful pH ranges, which complicates the reproducibility of results because the buffering capacity is insufficient to retain the disclosed pH. Here, we focus on the comet assay lysis buffer. Comet assay is broadly used for quantifying DNA breaks in eukaryotic cells. The most widespread comet assay protocols employ lysis of the cells before electrophoresis in a buffer containing Triton X-100, a high concentration of NaCl, sodium sarcosinate, EDTA, and Tris, with some modifications. However, nearly all researchers report that they use Tris buffer at pH 10, and some report the pH of the Tris additive alone. Alternatively, others report the pH of the final lysis buffer. However, the lysis solution used in the comet assay is buffered at a pH outside the useful range of Tris. Tris-based buffers have a useful pH range of 7.0 - 9.0. The buffer composed of 10 mM Tris has pKa 8.10 at 25°C and 8.69 at 4°C. The cell lysis conditions used in nearly all modifications of comet assay protocols remain imprecise and uncritically employed. Despite the pH of the lysis buffer likely has negligible effect on the detection of DNA breaks, precise lysis conditions are highly important for the use of comet assay in the detection of base modifications, which are often unstable and sensitive to pH.
- MeSH
- DNA * MeSH
- kometový test metody MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- poškození DNA * MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
MAP/microtubule affinity-regulating kinases (MARKs) were recently identified as potential drug targets for Alzheimer's disease (AD) due to their role in pathological hyperphosphorylation of tau protein. Hyperphosphorylated tau has decreased affinity for microtubule binding, impairing their stability and associated functions. Destabilization of microtubules in neuronal cells leads to neurodegeneration, and microtubule-unbound tau forms neurofibrillary tangles, one of the primary hallmarks of AD. Many phosphorylation sites of tau protein have been identified, but phosphorylation at Ser262, which occurs in early stages of AD, plays a vital role in the pathological hyperphosphorylation of tau. It has been found that Ser262 is phosphorylated by MARK4, which is currently an intensively studied target for treating Alzheimer's disease and other neurodegenerative diseases. Our present study aimed to develop a high throughput compatible assay to directly detect MARK enzymatic activity using echoacoustic transfer and MALDI-TOF mass spectrometer. We optimized the assay for all four isoforms of MARK and validated its use for identifying potential inhibitors by the screening of 1280 compounds from the LOPAC®1280 International (Library Of Pharmacologically Active Compounds). Six MARK4 inhibitors with IC50 < 1 μM were identified. To demonstrate their therapeutic potential, active compounds were further tested for MARK4 selectivity and ability to cross the blood-brain barrier. Lastly, the molecular docking with the most active inhibitors to predict their interaction with MARK4 was performed.
- MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- fosforylace fyziologie MeSH
- hematoencefalická bariéra metabolismus MeSH
- inhibiční koncentrace 50 MeSH
- mikrotubuly metabolismus MeSH
- protein-serin-threoninkinasy antagonisté a inhibitory MeSH
- proteiny tau metabolismus MeSH
- simulace molekulového dockingu MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice metody MeSH
- Publikační typ
- časopisecké články MeSH
Radioterapie je základní léčebnou modalitou v terapii jak časného stadia, tak lokálně pokročilého nemalobuněčného karcinomu plic (NSCLC), může však být velice technicky náročným procesem díky blízkosti kritických orgánů. Použití protonové terapie otevírá možnosti využití fyzikální výhody charakteristického Braggova peaku, který umožňuje navýšit dávku do cílového objemu při významnějším šetření normální okolní tkáně a tím v konečném důsledku i zvýšení lokální kontroly a celkového přežití při zachování kvality života redukcí toxicity související s léčbou.
Radiation therapy is an essential component of treatment for early stages and also for locally advanced non-small cell lung cancer (NSCLC), but can be technically challenging because of the proximity of lung tumors to nearby critical organs. Using proton therapy offers the potential for further advantages because of the unique depth-dose characteristics of the particles (Bragg peak), which can allow higher dose escalation to tumors with greater sparing of normal tissues, with the ultimate goal of improving local tumor control and survival while preserving quality of life by reducing treatment-related toxicity.
Cucurbit[n]urils are macrocyclic compounds capable of forming host-guest complexes with different molecules. In this study, we focused on cucurbit[7]uril (CB[7]) safety and pharmacokinetics. We investigated CB[7] cytotocixity in human renal cells ACHN using the xCELLigence system. We also determined maximum tolerated doses (MTD) and no observed adverse effect levels (NOAEL) after intramuscular (i.m.), intraperitoneal (i.p.), and intragastric (i.g.) administration in mice using clinical observation, blood biochemistry, and histopathology. At NOAELs, we studied its pharmacokinetics in plasma and kidneys. Finally, we performed a 7 day repeated-dose toxicity study at 50% of NOAEL after i.p. administration, assaying CB[7] concentration in plasma, brain, kidney, and liver; we also assessed the liver and kidney histopathology. In vitro, CB[7] did not show toxicity up to 0.94 mg/mL. MTDs in vivo were set at 300, 350, and 600 mg/kg, and NOAEL were established at 150, 100, and 300 mg/kg after i.m., i.p., and i.g. administration, respectively. Parenteral administration produced tissue damage mainly to the kidney, while i.g. administration caused only minor liver damage. Parenteral CB[7] administration led to fast elimination from blood, accompanied with kidney accumulation; absorption from the gastrointestinal tract was minimal. Short repeated i.p. administration was well tolerated. After initial CB[7] accumulation in blood and kidney, the concentrations stabilised and decreased during the experiment. Approximately 3.6% of animals showed signs of nephrotoxicity. Although CB[7] appears to be a promising molecule, nephrotoxicity may be the most critical drawback of its parenteral use, because the kidney represents the main organ of its elimination.
