OBJECTIVE: Transgenic mice with fluorescent protein (FP) reporters take full advantage of new in vivo imaging technologies. Therefore, we generated a TRPC5- and a TRPA1-reporter mouse based on FP C-terminal fusion, providing us with better alternatives for studying the physiology, interaction and coeffectors of these two TRP channels at the cellular and tissue level. METHODS: We generated transgenic constructs of the murine TRPC5- and TRPA1-gene with a 3*GGGGS linker and C-terminal fusion to mCherry and mTagBFP, respectively. We microinjected zygotes to generate reporter mice. Reporter mice were examined for visible fluorescence in trigeminal ganglia with two-photon microscopy, immunohistochemistry and calcium imaging. RESULTS: Both TRPC5-mCherry and TRPA1-mTagBFP knock-in mouse models were successful at the DNA and RNA level. However, at the protein level, TRPC5 resulted in no mCherry fluorescence. In contrast, sensory neurons derived from the TRPA1-reporter mice exhibited visible mTag-BFP fluorescence, although TRPA1 had apparently lost its ion channel function. CONCLUSIONS: Creating transgenic mice with a TRP channel tagged at the C-terminus with a FP requires detailed investigation of the structural and functional consequences in a given cellular context and fine-tuning the design of specific constructs for a given TRP channel subtype. Different degrees of functional impairment of TRPA1 and TRPC5 constructs suggest a specific importance of the distal C-terminus for the regulation of these two channels in trigeminal neurons.
- MeSH
- červený fluorescenční protein MeSH
- ganglion trigeminale metabolismus MeSH
- genový knockin * MeSH
- kationtové kanály TRPC * genetika metabolismus MeSH
- kationtový kanál TRPA1 * genetika metabolismus MeSH
- luminescentní proteiny * genetika metabolismus MeSH
- myši transgenní * MeSH
- myši MeSH
- rekombinantní fúzní proteiny metabolismus genetika MeSH
- vápník metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Nitrogen, phosphorus, and potassium are the three most essential micronutrients which play major roles in plant survivability by being a structural or non-structural component of the cell. Plants acquire these nutrients from soil in the fixed (NO3 ̄, NH4+) and solubilized forms (K+, H2PO4- and HPO42-). In soil, the fixed and solubilized forms of nutrients are unavailable or available in bare minimum amounts; therefore, agrochemicals were introduced. Agrochemicals, mined from the deposits or chemically prepared, have been widely used in the agricultural farms over the decades for the sake of higher production of the crops. The excessive use of agrochemicals has been found to be deleterious for humans, as well as the environment. In the environment, agrochemical usage resulted in soil acidification, disturbance of microbial ecology, and eutrophication of aquatic and terrestrial ecosystems. A solution to such devastating agro-input was found to be substituted by macronutrients-availing microbiomes. Macronutrients-availing microbiomes solubilize and fix the insoluble form of nutrients and convert them into soluble forms without causing any significant harm to the environment. Microbes convert the insoluble form to the soluble form of macronutrients (nitrogen, phosphorus, and potassium) through different mechanisms such as fixation, solubilization, and chelation. The microbiomes having capability of fixing and solubilizing nutrients contain some specific genes which have been reported in diverse microbial species surviving in different niches. In the present review, the biodiversity, mechanism of action, and genomics of different macronutrients-availing microbiomes are presented.
- MeSH
- Bacteria * metabolismus genetika klasifikace MeSH
- biodiverzita * MeSH
- biotechnologie * MeSH
- draslík metabolismus MeSH
- dusík metabolismus MeSH
- fosfor metabolismus MeSH
- mikrobiota * MeSH
- půda chemie MeSH
- půdní mikrobiologie MeSH
- zemědělské plodiny MeSH
- zemědělství MeSH
- živiny * metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Heavy metals are naturally occurring components of the Earth's crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO·), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O2·-), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO-). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer's and Parkinson's diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.
- MeSH
- antioxidancia metabolismus MeSH
- bioakumulace MeSH
- látky znečišťující životní prostředí toxicita MeSH
- lidé MeSH
- oxidační stres * účinky léků MeSH
- těžké kovy * toxicita MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Yeasts are unicellular fungi that occur in a wide range of ecological niches, where they perform numerous functions. Furthermore, these microorganisms are used in industrial processes, food production, and bioremediation. Understanding the physiological and adaptive characteristics of yeasts is of great importance from ecological, biotechnological, and industrial perspectives. In this context, we evaluated the abilities to assimilate and ferment different carbon sources, to produce extracellular hydrolytic enzymes, and to tolerate salt stress, heavy metal stress, and UV-C radiation of two isolates of Eremothecium coryli, isolated from Momordica indica fruits. The two isolates were molecularly identified based on sequencing of the 18S-ITS1-5.8S-ITS2 region. Our isolates were able to assimilate nine carbon sources (dextrose, galactose, mannose, cellobiose, lactose, maltose, sucrose, melezitose, and pectin) and ferment three (glucose, maltose, and sucrose). The highest values of cellular dry weight were observed in the sugars maltose, sucrose, and melezitose. We observed the presence of hyphae and pseudohyphae in all assimilated carbon sources. The two isolates were also capable of producing amylase, catalase, pectinase, and proteases, with the highest values of enzymatic activity found in amylase. Furthermore, the two isolates were able to grow in media supplemented with copper, iron, manganese, nickel, and zinc and to tolerate saline stress in media supplemented with 5% NaCl. However, we observed a decrease in CFU at higher concentrations of these metals and NaCl. We also observed morphological changes in the presence of metals, which include changes in cell shape and cellular dimorphisms. The isolates were sensitive to UV-C radiation in the shortest exposure time (1 min). Our findings reinforce the importance of endophytic yeasts for biotechnological and industrial applications and also help to understand how these microorganisms respond to environmental variations caused by human activities.
- MeSH
- endofyty * izolace a purifikace genetika metabolismus fyziologie klasifikace účinky záření MeSH
- fermentace MeSH
- fylogeneze MeSH
- fyziologický stres * MeSH
- metabolismus sacharidů * MeSH
- ovoce * mikrobiologie MeSH
- Saccharomycetales * izolace a purifikace genetika fyziologie metabolismus účinky záření klasifikace MeSH
- těžké kovy toxicita MeSH
- ultrafialové záření MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: To develop a gadolinium-free MRI-based diagnosis prediction decision tree (DPDT) for adult-type diffuse gliomas and to assess the added value of gadolinium-based contrast agent (GBCA) enhanced images. MATERIALS AND METHODS: This study included preoperative grade 2-4 adult-type diffuse gliomas (World Health Organization 2021) scanned between 2010 and 2021. The DPDT, incorporating eleven GBCA-free MRI features, was developed using 18% of the dataset based on consensus readings. Diagnosis predictions involved grade (grade 2 vs. grade 3/4) and molecular status (isocitrate dehydrogenase (IDH) and 1p/19q). GBCA-free diagnosis was predicted using DPDT, while GBCA-enhanced diagnosis included post-contrast images. The accuracy of these predictions was assessed by three raters with varying experience levels in neuroradiology using the test dataset. Agreement analyses were applied to evaluate the prediction performance/reproducibility. RESULTS: The test dataset included 303 patients (age (SD): 56.7 (14.2) years, female/male: 114/189, low-grade/high-grade: 54/249, IDH-mutant/wildtype: 82/221, 1p/19q-codeleted/intact: 34/269). Per-rater GBCA-free predictions achieved ≥ 0.85 (95%-CI: 0.80-0.88) accuracy for grade and ≥ 0.75 (95%-CI: 0.70-0.80) for molecular status, while GBCA-enhanced predictions reached ≥ 0.87 (95%-CI: 0.82-0.90) and ≥ 0.77 (95%-CI: 0.71-0.81), respectively. No accuracy difference was observed between GBCA-free and GBCA-enhanced predictions. Group inter-rater agreement was moderate for GBCA-free (0.56 (95%-CI: 0.46-0.66)) and substantial for GBCA-enhanced grade prediction (0.68 (95%-CI: 0.58-0.78), p = 0.008), while substantial for both GBCA-free (0.75 (95%-CI: 0.69-0.80) and GBCA-enhanced (0.77 (95%-CI: 0.71-0.82), p = 0.51) molecular status predictions. CONCLUSION: The proposed GBCA-free diagnosis prediction decision tree performed well, with GBCA-enhanced images adding little to the preoperative diagnostic accuracy of adult-type diffuse gliomas. KEY POINTS: Question Given health and environmental concerns, is there a gadolinium-free imaging protocol to preoperatively evaluate gliomas comparable to the gadolinium-enhanced standard practice? Findings The proposed gadolinium-free diagnosis prediction decision tree for adult-type diffuse gliomas performed well, and gadolinium-enhanced MRI demonstrated only limited improvement in diagnostic accuracy. Clinical relevance Even inexperienced raters effectively classified adult-type diffuse gliomas using the gadolinium-free diagnosis prediction decision tree, which, until further validation, can be used alongside gadolinium-enhanced images to respect standard practice, despite this study showing that gadolinium-enhanced images hardly improved diagnostic accuracy.
- MeSH
- dospělí MeSH
- gadolinium MeSH
- gliom * diagnostické zobrazování MeSH
- kontrastní látky * MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- nádory mozku * diagnostické zobrazování MeSH
- prediktivní hodnota testů MeSH
- reprodukovatelnost výsledků MeSH
- rozhodovací stromy * MeSH
- senioři MeSH
- stupeň nádoru * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
With the advent rise is in urbanization and industrialization, heavy metals (HMs) such as lead (Pb) and cadmium (Cd) contamination have increased considerably. It is among the most recalcitrant pollutants majorly affecting the biotic and abiotic components of the ecosystem like human well-being, animals, soil health, crop productivity, and diversity of prokaryotes (bacteria) and eukaryotes (plants, fungi, and algae). At higher concentrations, these metals are toxic for their growth and pose a significant environmental threat, necessitating innovative and sustainable remediation strategies. Bacteria exhibit diverse mechanisms to cope with HM exposure, including biosorption, chelation, and efflux mechanism, while fungi contribute through mycorrhizal associations and hyphal networks. Algae, especially microalgae, demonstrate effective biosorption and bioaccumulation capacities. Plants, as phytoremediators, hyperaccumulate metals, providing a nature-based approach for soil reclamation. Integration of these biological agents in combination presents opportunities for enhanced remediation efficiency. This comprehensive review aims to provide insights into joint action of prokaryotic and eukaryotic interactions in the management of HM stress in the environment.
- MeSH
- Bacteria * metabolismus účinky léků MeSH
- biodegradace * MeSH
- Eukaryota metabolismus účinky léků MeSH
- houby metabolismus MeSH
- kadmium * metabolismus toxicita MeSH
- látky znečišťující půdu * metabolismus MeSH
- olovo * metabolismus toxicita MeSH
- rostliny mikrobiologie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Účel studie: Radiosynoviortéza (RSO), dříve též nazývána slovem radiosynovektomie (RS), je metoda zaměřená na léčbu bolesti a otoku kloubů způsobených synovitidou u artritid a dekompenzovaných artróz prostřednictvím lokální aplikace beta zářičů. Zářením vyvolaná povrchová nekróza části buněk v synoviální membráně ve svém výsledku může zmírnit bolest, snížit otoky a zlepšit funkci kloubů. Materiál a metoda: V období 2013–2024 bylo RSO léčeno celkem 436 pacientů, z toho 291 pro otok kolenního kloubu vzniklý v důsledku dekompenzované artrózy a 172 kvůli artritidě. Kolenní kloub byl RSO ošetřen 268krát a malé a střední klouby 50krát. Používalo se yttrium u kolenních kloubů, rhenium u středních nebo erbium u malých kloubů. Samotný zákrok spočíval v punkci kloubu a odsátí případného kloubního výpotku, následné aplikaci radiofarmaka a imobilizaci kloubu po dobu 2–3 dnů. Výsledky: K hodnocení klinického efektu RSO jsme vybrali aplikace v letech 2022 a 2023. V roce 2022 bylo provedeno 45 ošetření a v roce 2023 dalších 26. Po jednom roce bylo 61 % pacientů s léčbou kolenních kloubů zcela spokojeno, přičemž uváděli zmenšení otoku a zlepšení rozsahu pohybu. U pacientů léčených s malými a středně velkými klouby se celkové zlepšení objevilo u 57 % z nich. Někteří zaznamenali recidivující výpotek menšího objemu nebo jen částečné zlepšení. Závěr: Radiosynoviortéza je účinná léčba otoků a bolesti kloubů způsobených synovitidou s pozitivními výsledky jak u kolenních, tak i menších kloubů, což je doloženo jak objektivními, tak subjektivními zlepšeními.
Purpose of the study: Radiosynoviorthesis (RSO), previously also called radiosynovectomy (RS), is a method focused on the treatment of joint pain and swelling caused by synovitis in arthritis and decompensated osteoarthrosis using beta emitters. Radiation-induced surface necrosis of part of the cells in the synovial membrane can, as a result, relieve pain, reduce swelling, and improve joint function. Material and method: Between 2013-2024, 436 patients were treated with RSO, primarily for knee joint swelling due to decompensated osteoarthrosis (291 patients) and arthritis (172 patients). RSO was performed on the knee (268 cases) and on small/medium joints (50 cases), using yttrium for knee joints, rhenium for medium joins or erbium for small joints. The procedure involved puncture of the joint and suction of any joint effusion, injecting the radioactive isotope, and subsequently immobilizing the joint for 2–3 days. Results: We selected treatments in 2022 and 2023 to evaluate the clinical effect of RSO. In 2022, 45 treatments were performed, and in 2023 another 26. One year post-treatment, 61 % of patients with knee joint involvement were fully satisfied, reporting reduced swelling and improved range of motion. Among patients treated for small and medium-sized joints, 57 % experienced overall improvement. Some patients observed recurring effusions of smaller volume or only partial improvement. Conclusion: Radiosynoviorthesis is an effective treatment for joint swelling and pain caused by synovitis, with positive outcomes seen in knee as well as smaller joints. Both objective and subjective assessments confirmed significant benefits.
- Klíčová slova
- radiosynoviortéza,
- MeSH
- artritida diagnostické zobrazování radioterapie MeSH
- erbium aplikace a dávkování terapeutické užití MeSH
- injekce intraartikulární MeSH
- klinické zkoušky jako téma MeSH
- osteoartróza diagnostické zobrazování radioterapie MeSH
- radiofarmaka * aplikace a dávkování terapeutické užití MeSH
- radioizotopy ytria aplikace a dávkování terapeutické užití MeSH
- rhenium aplikace a dávkování terapeutické užití MeSH
- synovitida * diagnostické zobrazování radioterapie MeSH
Hyponatremia is a crucial complication of therapy with thiazide diuretics. This study compares the epidemiological and biochemical profiles and hospital course of patients using hydrochlorothiazide (HCTZ), indapamide (INDA), and chlorthalidone (CTD) admitted with thiazide-associated hyponatremia (TAH). Data were obtained retrospectively from the hospital's digital registries. The epidemiological and biochemical parameters between the HCTZ, INDA, and CTD groups were compared. The correlation between dose and biochemical parameters in each group was performed. The thiazide groups without diuretic co-medication were compared (HCTZ vs. INDA), and the correlation between dose and biochemical parameters in each group was examined. A comparison of the HCTZ (n = 135), INDA (n = 125), and CTD (n = 27) groups identified differences in serum potassium (s-K; p = 0.03). The hyponatremia correction rate was slower in the CTD group at 96 h after admission (p < 0.001). After the exclusion of diuretic co-medication, the HCTZ group (n = 64/135) showed a higher prevalence of ARBs, s-K (both p < 0.001), and a lower median (IQR) equipotent dose (12.5 (o) mg vs. 2.5 (1.2) mg), prevalence of ACE-I (p < 0.001), and eGFR (p = 0.03), when compared to the INDA group (n = 109/125). In conclusion, except for s-K, we observed no significant difference in biochemical and epidemiological profiles between HCTZ, INDA, and CTD. After excluding the influence of other diuretics, we observed higher s-K in the HCTZ group compared to the INDA group, potentially explained by the lower equipotent dose of HCTZ. The CTD group showed a statistically significant trend of slower hyponatremia correction.
- MeSH
- antihypertenziva škodlivé účinky MeSH
- chlorthalidon * škodlivé účinky terapeutické užití aplikace a dávkování MeSH
- diuretika škodlivé účinky MeSH
- draslík krev MeSH
- hydrochlorthiazid * škodlivé účinky terapeutické užití aplikace a dávkování MeSH
- hypertenze * farmakoterapie MeSH
- hyponatremie * chemicky indukované epidemiologie krev MeSH
- indapamid * škodlivé účinky terapeutické užití aplikace a dávkování MeSH
- inhibitory symportérů pro chlorid sodný škodlivé účinky MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- MeSH
- estetika stomatologická MeSH
- implantace zubů metody MeSH
- informovaný souhlas pacienta MeSH
- lidé středního věku MeSH
- lidé MeSH
- malokluze chirurgie MeSH
- pacientova volba MeSH
- zirkonium MeSH
- zubní implantáty jednotlivých zubů * MeSH
- zubní korunky MeSH
- zubní náhrada ve spojení s implantáty metody MeSH
- zubní protéza - design metody MeSH
- zubní protéza - oprava * metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
