OBJECTIVE: Prepregnancy optimization of cardiovascular function may reduce the risk of pre-eclampsia. We aimed to assess the feasibility and effect of preconception cardiovascular monitoring, exercise, and beetroot juice on cardiovascular parameters in women planning to conceive. DESIGN AND METHOD: Prospective single-site, open-label, randomized controlled trial. Thirty-two women, aged 18-45 years, were allocated into one of four arms (1 : 1 : 1 : 1): exercise, beetroot juice, exercise plus beetroot juice and no intervention for 12 weeks. Blood pressure (BP) was measured at home daily. Cardiac output ( CO ) and total peripheral resistance (TPR) were assessed via bio-impedance. RESULTS: Twenty-nine out of 32 (91%) participants completed the study. Adherence to daily BP and weight measurements were 81% and 78%, respectively ( n = 29). Eight out of 15 (53%) of participants did not drink all the provided beetroot juice because of forgetfulness and taste. After 12 weeks, exercise was associated with a reduction in standing TPR (-278 ± 0.272 dynes s cm -5 , P < 0.05), and an increase in standing CO (+0.88 ± 0.71 l/min, P < 0.05). Exercise and beetroot juice together was associated with a reduction in standing DBP ( 7 ± 6 mmHg, P < 0.05), and an increase in standing CO (+0.49 ± 0.66 l/min, P < 0.05). The control group showed a reduction in standing TPR ( 313 ± 387 dynes s cm -5 ) and standing DBP ( 8 ± 5mmHg). All groups gained weight. CONCLUSION: Exercise and beetroot juice in combination showed a signal towards improving cardiovascular parameters. The control group showed improvements, indicating that home measurement devices and regular recording of parameters are interventions in themselves. Nevertheless, interventions before pregnancy to improve cardiovascular parameters may alter the occurrence of hypertensive conditions during pregnancy and require further investigation in adequately powered studies.
- MeSH
- cvičení fyziologie MeSH
- dusičnany * MeSH
- dvojitá slepá metoda MeSH
- hypertenze * MeSH
- krevní tlak MeSH
- lidé MeSH
- potravní doplňky MeSH
- prospektivní studie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- cisplatina MeSH
- cystektomie MeSH
- invazivní růst nádoru MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- močový měchýř * chirurgie MeSH
- nádory močového měchýře * farmakoterapie MeSH
- neoadjuvantní terapie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system. The first-line defense mechanism is the most efficient and involves antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). This line of defense plays an irreplaceable role in the dismutation of superoxide radicals (O2•-) and hydrogen peroxide (H2O2). The removal of superoxide radicals by SOD prevents the formation of the much more damaging peroxynitrite ONOO- (O2•- + NO• → ONOO-) and maintains the physiologically relevant level of nitric oxide (NO•), an important molecule in neurotransmission, inflammation, and vasodilation. The second-line antioxidant defense pathway involves exogenous diet-derived small-molecule antioxidants. The third-line antioxidant defense is ensured by the repair or removal of oxidized proteins and other biomolecules by a variety of enzyme systems. This review briefly discusses the endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) and exogenous (e.g., smoking, radiation, drugs, pollution) sources of ROS (superoxide radical, hydrogen peroxide, hydroxyl radical, peroxyl radical, hypochlorous acid, peroxynitrite). Attention has been given to the first-line antioxidant defense system provided by SOD, CAT, and GPx. The chemical and molecular mechanisms of antioxidant enzymes, enzyme-related diseases (cancer, cardiovascular, lung, metabolic, and neurological diseases), and the role of enzymes (e.g., GPx4) in cellular processes such as ferroptosis are discussed. Potential therapeutic applications of enzyme mimics and recent progress in metal-based (copper, iron, cobalt, molybdenum, cerium) and nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) are also discussed. Moreover, attention has been given to the mechanisms of action of low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids (e.g., β-carotene, lycopene, lutein), flavonoids (e.g., quercetin, anthocyanins, epicatechin), and glutathione (GSH)), the activation of transcription factors such as Nrf2, and the protection against chronic diseases. Given that there is a discrepancy between preclinical and clinical studies, approaches that may result in greater pharmacological and clinical success of low-molecular-weight antioxidant therapies are also subject to discussion.
- MeSH
- anthokyaniny metabolismus farmakologie MeSH
- antioxidancia * farmakologie metabolismus MeSH
- chronická nemoc MeSH
- kyselina peroxydusitá farmakologie MeSH
- lidé MeSH
- nádory * MeSH
- oxid dusnatý MeSH
- oxidační stres MeSH
- peroxid vodíku MeSH
- reaktivní formy kyslíku metabolismus MeSH
- superoxiddismutasa metabolismus MeSH
- superoxidy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
I-Motifs (iM) are non-canonical DNA structures potentially forming in the accessible, single-stranded, cytosine-rich genomic regions with regulatory roles. Chromatin, protein interactions, and intracellular properties seem to govern iM formation at sites with i-motif formation propensity (iMFPS) in human cells, yet their specific contributions remain unclear. Using in-cell NMR with oligonucleotide iMFPS models, we monitor iM-associated structural equilibria in asynchronous and cell cycle-synchronized HeLa cells at 37 °C. Our findings show that iMFPS displaying pHT < 7 under reference in vitro conditions occur predominantly in unfolded states in cells, while those with pHT > 7 appear as a mix of folded and unfolded states depending on the cell cycle phase. Comparing these results with previous data obtained using an iM-specific antibody (iMab) reveals that cell cycle-dependent iM formation has a dual origin, and iM formation concerns only a tiny fraction (possibly 1%) of genomic sites with iM formation propensity. We propose a comprehensive model aligning observations from iMab and in-cell NMR and enabling the identification of iMFPS capable of adopting iM structures under physiological conditions in living human cells. Our results suggest that many iMFPS may have biological roles linked to their unfolded states.
- MeSH
- azidy * MeSH
- benzazepiny * MeSH
- DNA MeSH
- HeLa buňky MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- protilátky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Navzdory klesající incidenci a účinné prevenci představuje karcinom hrdla dělohy v České republice nadále veliký společenský a medicínský problém. Ročně se v naší zemi diagnostikuje více než 700 případů zhoubného onemocnění hrdla dělohy, přičemž asi 300 pacientek ročně tomuto onemocnění podlehne. Mezioborová spolupráce, zkušenosti jednotlivých aplikujících odborníků (lékařů, sester, medicínských fyziků a asistentů atd.), moderní přístrojové vybavení i dostupnost inovativních léků mají obrovský dopad na stále se zlepšující prognózu našich pacientek. Přehledový článek sumarizuje aktuální postupy a doporučení v nechirurgické léčbě karcinomu hrdla dělohy.
Cervical cancer remains a significant social and medical problem in the Czech Republic despite a decrease in incidence and effective prevention measures. Every year, over 700 cases of malignant cervix disease are diagnosed in the country, and about 300 patients die from the disease. However, interdisciplinary cooperation, the expertise of individual healthcare professionals (such as doctors, nurses, medical physicists, and assistants), modern equipment, and the availability of innovative drugs have contributed to an improving prognosis for patients. This review article highlights the current procedures and recommendations for non-surgical treatment of cervical cancer.
Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether l-citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (n = 11) or OTC (n = 13) deficiency, 25% did not receive l-citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, p = 0.8 and OTC, p = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (p = 0.67). Regression analysis showed no correlation between l-citrulline substitution and failure to thrive (p = 0.611) or neurological outcome (p = 0.701). Peak ammonia had a significant effect on mental impairment (p = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with l-citrulline substitution.
- MeSH
- amoniak metabolismus MeSH
- arginin terapeutické užití MeSH
- citrulin MeSH
- hyperamonemie * farmakoterapie MeSH
- karbamoylfosfát metabolismus terapeutické užití MeSH
- karbamoylfosfátsynthasa (amoniak) metabolismus MeSH
- lidé MeSH
- nemoc z nedostatku ornithinkarbamoyltransferázy * chirurgie MeSH
- ornithinkarbamoyltransferasa MeSH
- retrospektivní studie MeSH
- transplantace jater * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
The unique potential of fullerene C60 for various biological applications has ignited significant interest. However, its inherent non-polarity poses a critical challenge for its effective integration within biological systems. This study delves into the intricate physicochemical characteristics of the innovative [C60 + NO] complex using density functional theory and time-dependent density functional theory. The computational analyses encompass molecular charge, surface electrostatic potential, and dipole moment evaluations. Impressively, the dipole moment of the [C60 + NO] complex significantly increases to 12.92 D. Meticulous surface analysis reveals a subtle interplay between molecular structures, indicating weak interactions. The analysis of the absorption spectrum unveils a noteworthy red-shift of 200 nm subsequent to complex formation. To elucidate the electron transfer mechanisms, we explore photo-induced electron transfer through CAM-B3LYP. This exploration elucidates intricate pathways governing electron transfer, with complementary insights gleaned from Marcus theory's outputs, especially the Gibbs free energy of electron transfer. Changes in the physicochemical properties of approaching C60 and NO molecules reveal interesting results compared to separate molecules. These findings resonate profoundly in the context of potential biological and pharmaceutical utilization. With implications for the biomedical area, the outcomes linked to the [C60 + NO] complex kindle optimism for pioneering biomedical applications.
Inducible NO synthase (NOS II) was proposed to play an important role in salt resistance of Dahl salt-resistant (SR/Jr) rats. Its chronic inhibition by specific inhibitors was accompanied by blood pressure (BP) elevation in animals subjected to high salt intake. The aim of our study was to evaluate 1) whether such inhibitors affect BP and/or its particular components (sympathetic tone and NO-dependent vasodilation) only under the conditions of high salt intake, and 2) whether similar BP effects are elicited after systemic or intracerebroventricular (icv) application of these inhibitors. Wistar rats fed Altromin diet (0.45 % NaCl) and SR/Jr rats fed either a low-salt (LS, 0.3 % NaCl) or a high-salt (HS, 4 % NaCl) diet were studied. Aminoguanidine (AMG) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) were used as NOS II inhibitors. BP and its responses to acute blockade of renin-angiotensin system (captopril), sympathetic nervous system (pentolinium) and NO synthase (L-NAME) were measured in conscious cannulated rats. There were no significant changes of BP or its components in either Wistar rats or SR/Jr rats subjected to chronic inhibition of NOS II by peroral aminoguanidine administration (50 mg/kg/day for 4 weeks). This was true for SR/Jr rats fed either LS or HS diets. Furthermore, we have studied BP effects of chronic icv administration of both NOS II inhibitors in SR/Jr rats fed HS diet, but we failed to find any BP changes elicited by such treatment. In conclusion, inducible NO synthase does not participate in the resistance of SR/Jr rats to hypertensive effects of excess salt intake.
- MeSH
- chlorid sodný MeSH
- hypertenze * chemicky indukované MeSH
- krevní tlak fyziologie MeSH
- krysa rodu rattus MeSH
- kuchyňská sůl * MeSH
- oxid dusnatý MeSH
- potkani inbrední Dahl MeSH
- potkani Wistar MeSH
- synthasa oxidu dusnatého, typ II MeSH
- synthasa oxidu dusnatého MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Spruce wood and Typha (wetland plant) derived biochars pyrolyzed at 350 °C and 600 °C were tested for their sorption affinity for organic pollutants (diclofenac, methylparaben, benzotriazole and sodium 1-decanesulfonate) and nutrients (nitrate, ammonium, phosphate and boron) commonly found in greywater. Batch and column studies combined with molecular dynamics modelling determined the sorption capacity, kinetics, and described the underlying mechanisms. The spruce biochar (600 °C) exhibited the highest sorption capacity mainly for the tested organics. The dynamic test performed for spruce biochar (600 °C) showed that the magnitude of desorption was low, and the desorbed amount ranged between 3 and 11 %. Molecular dynamics modelling (a computational tool for elucidating molecular-level interactions) indicated that the increased sorption of nitrate and boron on spruce biochar (600 °C) could be attributed to hydrophobic interactions. The molecular dynamics shows that predominant adsorption of organic pollutants was governed by π-π stacking, with a minor role of hydrogen-bonding on the biochar surface. In summary, higher pyrolysis temperature biochar yielded greater adsorption capacity greywater borne contaminants and the reaction temperature (10-34 °C) and presence of anionic surfactant had a limited effect on the adsorption of organic pollutants, suggesting efficacious application of biochar in general for greywater treatment in nature-based systems.
V rámci paliativní léčby cholangiocelulárního karcinomu byla donedávna široce využívána chemoterapie, zejména režimy cisplatina + gemcitabin a FOLFOX. V poslední době došlo k výraznému rozšíření možností léčby cholangiocelulárního karcinomu se specifickými mutacemi – u nádorů s fúzí genu FGFR byla prokázána účinnost tyrosinkinázového inhibitoru FGFR1–3 pemigatinibu, u nádorů s aktivační mutací IDH1 byl účinný ivosidenib a u HER2-pozitivních nádorů byl pozorován přínos anti-HER2 léčby (pertuzumab + trastuzumab, zanidatamab). Ukazuje se rovněž, že část pacientů s pokročilým cholangiocelulárním adenokarcinomem by mohla být úspěšně léčena checkpoint inhibitory (CPI): v této souvislosti přinesla robustní data studie TOPAZ-1, ve které vedlo přidání CPI durvalumabu k chemoterapii cisplatina + gemcitabin k signifikantnímu prodloužení přežití bez progrese i celkového přežití pacientů, aniž by přitom došlo k významnějšímu nárůstu toxicity léčby.
Until recently, chemotherapy has been widely used in the palliative treatment of cholangiocellular carcinoma, especially cisplatin + gemcitabine and FOLFOX regimens. Lately, there has been a significant expansion of treatment options for cholangiocellular carcinoma with specific mutations – in tumours with the FGFR gene fusion, efficacy of the FGFR1–3 tyrosine kinase inhibitor pemigatinib has been shown, in tumours with activating IDH1 mutations, ivosidenib has been beneficial, and in HER2-positive tumours, the efficacy of anti-HER2 therapy (pertuzumab + trastuzumab, zanidatamab) has been observed. It also seems, that a proportion of patients with advanced cholangiocellular adenocarcinoma could be successfully treated with checkpoint inhibitors (CPIs): in this context, the TOPAZ-1 trial provided robust data, in which the addition of the CPI durvalumab to cisplatin + gemcitabine chemotherapy led to a significant increase in progressionfree survival as well as overall survival of the patients, without a marked increase in treatment toxicity.
- MeSH
- cholangiokarcinom * farmakoterapie MeSH
- cisplatina farmakologie terapeutické užití MeSH
- gemcitabin farmakologie terapeutické užití MeSH
- lidé MeSH
- monoklonální protilátky farmakologie terapeutické užití MeSH
- protokoly antitumorózní kombinované chemoterapie MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
