Spáčil, Roman*
Dotaz
Zobrazit nápovědu
... Věcná práva (§ 976–1474) / Jiří Spáčil a kol. 2013. xv, 1260 s. -- IV. ... ... Dědické právo (§ 1475-1720) / Roman Fiala, Ljubomír Drápal a kol. 2015. xi, 633 s. -- V. ...
Velké komentáře
1. vyd. 6 sv. ; 25 cm
Znovuzačlenění rodinného práva do nového ObčZ v duchu evropských kontinentálních tradic přináší především změnu formální systematiky a také nutnost pracovat s celým kodexem. To předpokládá znalost nejen obecné části, ale i porozumění celkové koncepci a obsahu mnoha institutů zakotvených v dalších částech zákoníku.
- Konspekt
- Soukromé právo
- NLK Obory
- právo, zákonodárství
- NLK Publikační typ
- komentáře
Background: One of the severely debilitating and fatal subtypes of hemorrhagic stroke is intracerebral hemorrhage (ICH), which lacks an adequate cure at present. The Zhilong Huoxue Tongyu (ZLHXTY) capsule has been utilized effectively since last decade to treat ICH, in some provinces of China but the scientific basis for its mechanism is lacking. Purpose: To investigate the neuroprotective role of ZLHXTY capsules for ICH-induced oxidative injury through the regulation of redox imbalance with the Nrf2 signaling pathway. Methods: Autologous blood injection model of ICH in C57BL/6J mice was employed. Three treatment groups received ZLHXTY once daily through oral gavage at doses 0.35 g/kg, 0.7 g/kg, and 1.4 g/kg, started after 2 h and continued for 72 h of ICH induction. The neurological outcome was measured using a balance beam test. Serum was tested for inflammatory markers IL-1β, IL-6, and TNF-α through ELISA, oxidative stress through hydrogen peroxide content assay, and antioxidant status by total antioxidant capacity (T-AOC) assay. Nuclear extract from brain tissue was assayed for Nrf2 transcriptional factor activity. RT-qPCR was performed for Nfe2l2, Sod1, Hmox1, Nqo1, and Mgst1; and Western blotting for determination of protein expression of Nrf2, p62, Pp62, Keap, HO1, and NQO1. Fluoro-jade C staining was also used to examine neuronal damage. Results: ZLHXTY capsule treatment following ICH demonstrated a protective effect against oxidative brain injury. Neurological scoring showed improvement in behavioral outcomes. ELISA-based identification demonstrated a significant decline in the expression of serum inflammatory markers. Hydrogen peroxide content in serum was found to be reduced. The total antioxidant capacity was also reduced in serum, but the ZLHXTY extract showed a concentration-dependent increase in T-AOC speculating at its intrinsic antioxidant potential. Nrf2 transcriptional factor activity, mRNA and protein expression analyses revealed normalization of Nrf2 and its downstream targets, which were previously elevated as a result of oxidative stress induced by ICH. Neuronal damage was also reduced markedly after ZLHXTY treatment as revealed by Fluoro-jade C staining. Conclusion: ZLHXTY capsules possess an intrinsic antioxidant potential that can modulate the ICH-induced redox imbalance in the brain as revealed by the normalization of Nrf2 and its downstream antioxidant targets.
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIM: Zhilong Huoxue Tongyu (ZL) capsule is a classical traditional Chinese medicine (TCM) with satisfactory curative effects. Endothelial cell (EC) dysfunction plays an important role during myocardial fibrosis (MF). But the therapeutic effect of ZL capsule on EC dysfunction remains unknown in the development of MF. This study aims to investigate the effect of ZL capsule on EC dysfunction during MF in vivo. EXPERIMENTAL PROCEDURE: The model of MF is established in vivo by injecting isoproterenol for 14 days, simultaneously, we examined the therapeutic effect of ZL capsule on MF in vivo. An integrative approach combining biomarker examination, echocardiography and myocardial fibrosis condition using Hematoxylin-eosin staining, Masson staining, and Sirius red staining were performed to assess the efficacy of ZL capsule against MF. Subsequently, comprehensive immunofluorescence staining was performed to evaluate the therapeutic effect of ZL capsule on EC dysfunction. RESULTS AND CONCLUSION: Prior to experiments, analysis of the published single-cell sequencing data was performed and it was discovered that EC dysfunction plays an important role. Further pharmacological results showed that ZL capsule could alleviate fibrosis injury and collagen fiber deposition. The mechanism investigation results showed that the endothelial-to-mesenchymal transition (EndMT) and MHC class-II (MHC-II) expression in EC were improved. In addition, ZL capsule can attenuate the inflammatory response during MF by intervening the activation of CD4+T cell mediated by EC. For the first time, we provided evidence that ZL capsule could improve MF by alleviating EC dysfunction via the regulation of EndMT and expression of MHC-II. TAXONOMY CLASSIFICATION BY EVISE: Myocardial fibrosis, Chinese Herbal Medicine, Traditional Medicine, Endothelium, dysfunction, Endothelial-to-mesenchymal transition.
- Publikační typ
- časopisecké články MeSH
It is becoming increasingly clear that the communities of microorganisms that populate the surfaces exposed to the external environment, termed microbiota, are key players in the regulation of pathogen-host cross talk affecting the onset as well as the outcome of infectious diseases. We have performed a multicenter, prospective, observational study in which nasal and oropharyngeal swabs were collected for microbiota predicting the risk of invasive fungal infections (IFIs) in patients with hematological malignancies. Here, we demonstrate that the nasal and oropharyngeal microbiota are different, although similar characteristics differentiate high-risk from low-risk samples at both sites. Indeed, similar to previously published results on the oropharyngeal microbiota, high-risk samples in the nose were characterized by low diversity, a loss of beneficial bacteria, and an expansion of potentially pathogenic taxa, in the presence of reduced levels of tryptophan (Trp). At variance with oropharyngeal samples, however, low Trp levels were associated with defective host-derived kynurenine production, suggesting reduced tolerance mechanisms at the nasal mucosal surface. This was accompanied by reduced levels of the chemokine interleukin-8 (IL-8), likely associated with a reduced recruitment of neutrophils and impaired fungal clearance. Thus, the nasal and pharyngeal microbiomes of hematological patients provide complementary information that could improve predictive tools for the risk of IFI in hematological patients.
The ability to predict invasive fungal infections (IFI) in patients with hematological malignancies is fundamental for successful therapy. Although gut dysbiosis is known to occur in hematological patients, whether airway dysbiosis also contributes to the risk of IFI has not been investigated. Nasal and oropharyngeal swabs were collected for functional microbiota characterization in 173 patients with hematological malignancies recruited in a multicenter, prospective, observational study and stratified according to the risk of developing IFI. A lower microbial richness and evenness were found in the pharyngeal microbiota of high-risk patients that were associated with a distinct taxonomic and metabolic profile. A murine model of IFI provided biologic plausibility for the finding that loss of protective anaerobes, such as Clostridiales and Bacteroidetes, along with an apparent restricted availability of tryptophan, is causally linked to the risk of IFI in hematologic patients and indicates avenues for antimicrobial stewardship and metabolic reequilibrium in IFI.
- MeSH
- antifungální látky farmakologie terapeutické užití MeSH
- farynx mikrobiologie MeSH
- hematologické nádory komplikace MeSH
- hodnocení rizik MeSH
- krevní nemoci komplikace MeSH
- lidé MeSH
- metagenom MeSH
- metagenomika metody MeSH
- mikrobiota * MeSH
- modely nemocí na zvířatech MeSH
- mykózy diagnóza farmakoterapie etiologie MeSH
- myši MeSH
- pneumonie diagnóza farmakoterapie etiologie MeSH
- rizikové faktory MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
Indoleamine 2,3-dioxygenases (IDOs) degrade l-tryptophan to kynurenines and drive the de novo synthesis of nicotinamide adenine dinucleotide. Unsurprisingly, various invertebrates, vertebrates, and even fungi produce IDO. In mammals, IDO1 also serves as a homeostatic regulator, modulating immune response to infection via local tryptophan deprivation, active catabolite production, and non-enzymatic cell signaling. Whether fungal Idos have pleiotropic functions that impact on host-fungal physiology is unclear. Here, we show that Aspergillus fumigatus possesses three ido genes that are expressed under conditions of hypoxia or tryptophan abundance. Loss of these genes results in increased fungal pathogenicity and inflammation in a mouse model of aspergillosis, driven by an alternative tryptophan degradation pathway to indole derivatives and the host aryl hydrocarbon receptor. Fungal tryptophan metabolic pathways thus cooperate with the host xenobiotic response to shape host-microbe interactions in local tissue microenvironments.
- MeSH
- významné osobnosti MeSH
- Publikační typ
- biografie MeSH
- O autorovi
- Kölbel, František, 1933-2016 Autorita
- Bojar, Martin, 1947- Autorita
- Bytešník, Jan, 1947- Autorita
- Čerbák, Roman, 1933-2018 Autorita
- Češka, Richard, 1957- Autorita
- Horký, Karel, 1933-2016 Autorita
- Niederle, Petr, 1944-2008 Autorita
- Spáčil, Jiří, 1939- Autorita
- Staněk, Vladimír, 1933- Autorita
- Stolz, Ivo, 1932- Autorita
- Šimon, Jaroslav, 1930-2009 Autorita
- Widimský, Jiří, 1925-2020 Autorita
- Widimský, Petr, 1954- Autorita
1. elektronické vydání 1 online zdroj (252 stran)
Co může otec udělat pro to, aby jeho dva synové vykročili do života tou správnou nohou? Inženýr Spáčil má jasno. Nachystá pro ně náročnou zkoušku odolnosti v odlehlé horské chalupě. Ovšem navzdory jeho smělému plánu není nouze o komické situace a při čtení se proto skvěle pobavíte!; Humoristický román o jednom ne zcela hladce běžícím otcovském plánu na zocelení dvou změkčilých synků. Co může správný otec udělat pro to, aby jeho dva školou povinní kluci vykročili do života tou správnou nohou? Inženýr Spáčil má v tomto směru jasno. Jako obdivovatel drsných horolezců pro ně nachystá náročnou zkoušku odolnosti v odlehlé horské chalupě, samozřejmě bez mobilů a jiných vymožeností. Ovšem jeho smělý plán přeměnit zhýčkané synky v budoucí chlapy naráží na nečekané a mnohdy kuriózní překážky. O komické situace tak rozhodně není nouze.