Biofilm formation is an effective survival strategy of plant-associated microorganisms in hostile environments, so the application of biofilm-forming and exopolysaccharide (EPS)-producing beneficial microbes to plants has received more attention in recent years. This study examined the ability of biofilm and EPS production of Bacillus subtilis and Bacillus thuringiensis strains under different NaCl concentrations (0, 50, 100, 200, and 400 mmol/L), pH values (5.5, 6.5, 7.5, and 8.5), and phosphate levels (0, 25, 50, and 100 mmol/L at 0 and 400 mmol/L NaCl). B. subtilis BS2 and B. thuringiensis BS6/BS7 strains significantly increased biofilm formation in a similar pattern to EPS production under salt stress. B. subtilis BS2/BS3 enhanced biofilm production at slightly acidic pH with a lower EPS production but the other strains formed considerably more amount of biofilm and EPS at alkaline pH. Interestingly, higher levels of phosphate substantially decreased biofilm and EPS production at 0 mmol/L NaCl but increased biofilm formation at 400 mmol/L salt concentration. Overall, contrary to phosphate, salt and pH differently influenced biofilm and EPS production by Bacillus strains. EPS production contributed to biofilm formation to some extent under all the conditions tested. Some Bacillus strains produced more abundant biofilm under salt and pH stress, indicating their potential to form in vivo biofilms in rhizosphere and on plants, particularly under unfavorable conditions.
- MeSH
- Bacillus subtilis fyziologie metabolismus účinky léků MeSH
- Bacillus thuringiensis fyziologie účinky léků MeSH
- bakteriální polysacharidy * metabolismus biosyntéza MeSH
- biofilmy * účinky léků růst a vývoj MeSH
- chlorid sodný * farmakologie metabolismus MeSH
- fosfáty * metabolismus farmakologie MeSH
- koncentrace vodíkových iontů 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
The innate immune response represents the first-line of defense against invading pathogens. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been implicated in various aspects of innate immune function, which involves respiratory bursts and inflammasome activation. These reactive species widely distributed within the cellular environment are short-lived intermediates that play a vital role in cellular signaling and proliferation and are likely to depend on their subcellular site of formation. NADPH oxidase complex of phagocytes is known to generate superoxide anion radical (O2•-) that functions as a precursor for antimicrobial hydrogen peroxide (H2O2) production, and H2O2 is utilized by myeloperoxidase (MPO) to generate hypochlorous acid (HOCl) that mediates pathogen killing. H2O2 modulates the expression of redox-responsive transcriptional factors, namely NF-kB, NRF2, and HIF-1, thereby mediating redox-based epigenetic modification. Survival and function of immune cells are under redox control and depend on intracellular and extracellular levels of ROS/RNS. The current review focuses on redox factors involved in the activation of immune response and the role of ROS in oxidative modification of proteins in macrophage polarization and neutrophil function.
Chloride Intracellular Channel (CLIC) family members uniquely transition between soluble and membrane-associated conformations. Despite decades of extensive functional and structural studies, CLICs' function as ion channels remains debated, rendering our understanding of their physiological role incomplete. Here, we expose the function of CLIC5 as a fusogen. We demonstrate that purified CLIC5 directly interacts with the membrane and induces fusion, as reflected by increased liposomal diameter and lipid and content mixing between liposomes. Moreover, we show that this activity is facilitated by acidic pH, a known trigger for CLICs' transition to a membrane-associated conformation, and that increased exposure of the hydrophobic inter-domain interface is crucial for this process. Finally, mutation of a conserved hydrophobic interfacial residue diminishes the fusogenic activity of CLIC5 in vitro and impairs excretory canal extension in C. elegans in vivo. Together, our results unravel the long-sought physiological role of these enigmatic proteins.
- MeSH
- Caenorhabditis elegans * genetika metabolismus MeSH
- chloridové kanály metabolismus MeSH
- chloridy * metabolismus MeSH
- liposomy MeSH
- zvířata MeSH
- Check Tag
- zvířata 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.
BACKGROUND: Several studies explored the interdependence between Paco2 and bicarbonate during respiratory acid-base derangements. The authors aimed to reframe the bicarbonate adaptation to respiratory disorders according to the physical-chemical approach, hypothesizing that (1) bicarbonate concentration during respiratory derangements is associated with strong ion difference; and (2) during acute respiratory disorders, strong ion difference changes are not associated with standard base excess. METHODS: This is an individual participant data meta-analysis from multiple canine and human experiments published up to April 29, 2021. Studies testing the effect of acute or chronic respiratory derangements and reporting the variations of Paco2, bicarbonate, and electrolytes were analyzed. Strong ion difference and standard base excess were calculated. RESULTS: Eleven studies were included. Paco2 ranged between 21 and 142 mmHg, while bicarbonate and strong ion difference ranged between 12.3 and 43.8 mM, and 32.6 and 60.0 mEq/l, respectively. Bicarbonate changes were linearly associated with the strong ion difference variation in acute and chronic respiratory derangement (β-coefficient, 1.2; 95% CI, 1.2 to 1.3; P < 0.001). In the acute setting, sodium variations justified approximately 80% of strong ion difference change, while a similar percentage of chloride variation was responsible for chronic adaptations. In the acute setting, strong ion difference variation was not associated with standard base excess changes (β-coefficient, -0.02; 95% CI, -0.11 to 0.07; P = 0.719), while a positive linear association was present in chronic studies (β-coefficient, 1.04; 95% CI, 0.84 to 1.24; P < 0.001). CONCLUSIONS: The bicarbonate adaptation that follows primary respiratory alterations is associated with variations of strong ion difference. In the acute phase, the variation in strong ion difference is mainly due to sodium variations and is not paralleled by modifications of standard base excess. In the chronic setting, strong ion difference changes are due to chloride variations and are mirrored by standard base excess.
- MeSH
- acidobazická rovnováha * MeSH
- chloridy farmakologie MeSH
- hydrogenuhličitany * MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- psi MeSH
- sodík farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
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
Fonticins are phage tail-like bacteriocins produced by the Gram-negative bacterium Pragia fontium from the family Budviciaceae. This bacterium produces contractile-type particles that adsorb on the surface of sensitive bacteria and penetrate the cell wall, probably during contraction, in a way similar to the type VI secretion system. We characterized the pore-forming activity of fonticins using both living cells and in vitro model membranes. Using a potassium leakage assay, we show that fonticins are able to permeabilize sensitive cells. On black lipid membranes, single-pore conductance is about 0.78 nS in 1 M NaCl and appears to be linearly dependent on the increasing molar strength of NaCl solution, which is a property of considerably large pores. In agreement with these findings, fonticins are not ion selective for Na+, K+, and Cl-. Polyethylene glycol 3350 (PEG 3350) molecules of about 3.5 nm in diameter can enter the fonticin pore lumen, whereas the larger molecules cannot pass the pore. The size of fonticin pores was confirmed by transmission electron microscopy. The terminal membrane-piercing complex of the fonticin tube probably creates a selective barrier restricting passage of macromolecules. IMPORTANCE Phage tail-like bacteriocins are now the subject of research as potent antibacterial agents due to their narrow host specificity and single-hit mode of action. In this work, we focused on the structure and mode of action of fonticins. According to some theories, related particles were initially adapted for passage of double-stranded DNA (dsDNA) molecules, but fonticins changed their function during the evolution; they are able to form large pores through the bacterial envelope of Gram-negative bacteria. As various pore-forming proteins are extensively used for nanopore sequencing and stochastic sensing, we decided to investigate the pore-forming properties of fonticin protein complexes on artificial lipid membranes. Our research revealed remarkable structural properties of these particles that may have a potential application as a nanodevice.
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
Two cationic [Cu2(L1-2)2](ClO4)2 (1, 2), and four neutral doubly bridged-phenoxido-copper(II) complexes [Cu2(L3-4)2] (3, 4) and [Cu2(L5-6)2(H2O)]‧2H2O (5, 6) as well as 1D polymeric catena-[Cu(L7)] (7), where HL1-2 and H2L3-7 represent tripodal tetradentate pyridyl or aliphatic-amino groups based 2,4-disubstituted phenolates, were synthesized and thoroughly characterized by various spectroscopic methods and single crystal X-ray analysis. The molecular structures of the complexes exhibited diverse geometrical environments around the central Cu(II) atoms. The in vitro antiproliferative activity of the isolated complexes and selected parent free ligands were screened against some human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, MCF-7). The most promising cytotoxicity against cancer cells were obtained for 1-6, while complex 6 was found as the best performing as compared to the reference drug cisplatin. The cytotoxicity study of complex 6 was therefore extended to wider variety of cancer cell lines (HOS, A549, PANC-1, CaCo2, HeLa) and results revealed its significant cytotoxicity on all investigated human cancer cells. The cell uptake study showed that cytotoxicity of 6 (3 μM concentration and 24 h of incubation) against A2780 cells was almost independent from the intracellular levels of copper. The effect of complexes 4, 6 and 7 on cell cycle of A2780 cells indicates that the mechanism of action in these complexes is not only different from that of cisplatin but also different among them. Complex 7 was able to induce apoptosis in A2780 cells, while complexes 4 and 6 did not and on the other hand, they showed considerable effect on autophagy induction and there are some clues that these complexes were able to induce cuproptosis in A2780 cells.
- MeSH
- antitumorózní látky * farmakologie chemie MeSH
- Caco-2 buňky MeSH
- cisplatina MeSH
- komplexní sloučeniny * farmakologie chemie MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- ligandy MeSH
- měď chemie MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- nádory vaječníků * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
