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
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
OBJECTIVES: Atopic dermatitis (AD) is a common allergic disease with potential links to environmental pollutants, including heavy metals. This study investigates the association between co-exposure to cadmium and mercury and AD among Korean children. METHODS: Data from the fourth cycle of the Korean National Environmental Health Survey (KoNEHS) included 736 elementary school students. Urinary cadmium and mercury levels were measured, and their association with lifetime prevalence of AD was analysed using logistic regression, weighted quantile sum (WQS) regression, quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR). Confounders adjusted included age, sex, urinary cotinine, income, and body mass index. Sensitivity analyses used symptomatic AD and AD treatment as outcome variables. RESULTS: Among two metals, only cadmium in the highest tertile showed an odds ratio (OR) of 2.39 (95% CI: 1.12-5.10) compared with lowest tertile, with a significant trend per tertile increase (OR 1.58, 95% CI: 1.08-2.31) in multiple logistic regression. Co-exposure analysis using WQS and QGC revealed significant associations with AD prevalence, with WQS showing an OR of 1.47 (95% CI: 1.18-1.83) and QGC showing an OR of 1.60 (95% CI: 1.20-2.13) per tertile increase of exposure. BKMR indicated a dose-dependent relationship between overall exposure and AD risk. For symptomatic AD, similar trend was found. The treatment status of AD did not show a significant association with either heavy metal. CONCLUSION: This study suggests a significant association between co-exposure to cadmium and mercury and atopic dermatitis, emphasizing the need to consider combined environmental exposures in epidemiological studies.
- MeSH
- atopická dermatitida * epidemiologie chemicky indukované MeSH
- dítě MeSH
- kadmium * moč škodlivé účinky MeSH
- látky znečišťující životní prostředí * moč MeSH
- lidé MeSH
- prevalence MeSH
- rtuť * moč škodlivé účinky MeSH
- studenti statistika a číselné údaje MeSH
- vystavení vlivu životního prostředí * škodlivé účinky statistika a číselné údaje analýza MeSH
- zdravotnické přehledy MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Korejská republika MeSH
BACKGROUND: Duchenne muscular dystrophy (DMD) patients are monitored periodically for cardiac involvement, including cardiac MRI with gadolinium-based contrast agents (GBCA). Texture analysis (TA) offers an alternative approach to assess late gadolinium enhancement (LGE) without relying on GBCA administration, impacting DMD patients' care. The study aimed to evaluate the prognostic value of selected TA features in the LGE assessment of DMD patients. RESULTS: We developed a pipeline to extract TA features of native T1 parametric mapping and evaluated their prognostic value in assessing LGE in DMD patients. For this evaluation, five independent TA features were selected using Boruta to identify relevant features based on their importance, least absolute shrinkage and selection operator (LASSO) to reduce the number of features, and hierarchical clustering to target multicollinearity and identify independent features. Afterward, logistic regression was used to determine the features with better discrimination ability. The independent feature inverse difference moment normalized (IDMN), which measures the pixel values homogeneity in the myocardium, achieved the highest accuracy in classifying LGE (0.857 (0.572-0.982)) and also was significantly associated with changes in the likelihood of LGE in a subgroup of patients with three yearly examinations (estimate: 23.35 (8.7), p-value = 0.008). Data are presented as mean (SD) or median (IQR) for normally and non-normally distributed continuous variables and numbers (percentages) for categorical ones. Variables were compared with the Welch t-test, Wilcoxon rank-sum, and Chi-square tests. A P-value < 0.05 was considered statistically significant. CONCLUSION: IDMN leverages the information native T1 parametric mapping provides, as it can detect changes in the pixel values of LGE images of DMD patients that may reflect myocardial alterations, serving as a supporting tool to reduce GBCA use in their cardiac MRI examinations.
- MeSH
- dítě MeSH
- Duchennova muskulární dystrofie * diagnostické zobrazování patologie MeSH
- gadolinium MeSH
- kontrastní látky MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- mladiství MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Hypokalcemií indukovaná kardiomyopatie je vzácné, avšak závažné onemocnění, náročné z hlediska diagnostiky i léčby. těžká hypokalcemie na podkladě hypoparatyreózy může vyvolat vzácnou, nicméně potenciálně reverzibilní, formu dilatační kardiomyopatie. tato kazuistika popisuje případ 31leté ženy se srdečním selháním vyvolaným hypoparatyreózou po tyreoidektomii. Přes klasickou léčbu srdečního selhání přetrvával u pacientky její závažný stav až do úpravy hypokalcemie. léčba zahrnovala suplementaci kalcia a terapii vedenou podle příslušných doporučených postupů; následně došlo k významnému zlepšení. Proto je pro dosažení zlepšení – pokud byla klasická léčba srdečního selhání neúčinná – naprosto nezbytné monitorovat hodnoty kalcia v séru, zvláště u pacientů s tyreoidektomií v anamnéze. Při léčbě srdečního selhání je třeba být ostražitý a mít neustále na paměti možnou přítomnost hypokalcemie jako reverzibilní příčinu uvedené komplikace.
Hypocalcemia-associated cardiomyopathy, a rare but serious condition, presents challenges in diagnosis and management. Severe hypocalcemia resulting from hypoparathyroidism can precipitate rare yet reversible cases of dilated cardiomyopathy. This case report reported a 31-year-old woman with heart failure precipitated by hypoparathyroidism following thyroidectomy. Despite conventional heart failure treatments, her condition persisted until correction of hypocalcemia. Treatment involved calcium supplementation and guideline-directed heart failure therapy. Significant improvement was observed then. Hence, monitoring serum calcium levels is imperative when conventional heart failure therapies fail to yield improvement, particularly in patients with a history of thyroidectomy. Sustaining clinical awareness and vigilance concerning hypocalcemia is crucial in managing heart failure, considering its possibility as a reversible cause.
- MeSH
- dospělí MeSH
- hypokalcemie * etiologie MeSH
- hypoparatyreóza komplikace MeSH
- kardiomyopatie * diagnóza etiologie komplikace MeSH
- lidé MeSH
- thyroxin aplikace a dávkování MeSH
- tyreoidektomie škodlivé účinky MeSH
- vápník aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: To validate the clinical utility of a previously identified circulating tumor DNA methylation marker (meth-ctDNA) panel for disease detection and survival outcomes, meth-ctDNA markers were compared to PSA levels and PSMA PET/CT findings in men with different stages of prostate cancer (PCa). METHODS: 122 PCa patients who underwent [68Ga]Ga-PSMA-11 PET/CT and plasma sampling (03/2019-08/2021) were analyzed. cfDNA was extracted, and a panel of 8 individual meth-ctDNA markers was queried. PET scans were qualitatively and quantitatively assessed. PSA and meth-ctDNA markers were compared to PET findings, and their relative prognostic value was evaluated. RESULTS: PSA discriminated best between negative and tumor-indicative PET scans in all (AUC 0.77) and hormone-sensitive (hsPC) patients (0.737). In castration-resistant PCa (CRPC), the meth-ctDNA marker KLF8 performed best (AUC 0.824). CHST11 differentiated best between non- and metastatic scans (AUC 0.705) overall, KLF8 best in hsPC and CRPC (AUC 0.662, 0.85). Several meth-ctDNA markers correlated low to moderate with the tumor volume in all (5/8) and CRPC patients (6/8), while PSA levels correlated moderately to strongly with the tumor volume in all groups (all p < 0.001). CRPC overall survival was independently associated with LDAH and PSA (p = 0.0168, p < 0.001). CONCLUSION: The studied meth-ctDNA markers are promising for the minimally-invasive detection and prognostication of CRPC but do not allow for clinical characterization of hsPC. Prospective studies are warranted for their use in therapy response and outcome prediction in CRPC and potential incremental value for PCa monitoring in PSA-low settings.
- MeSH
- cirkulující nádorová DNA genetika krev MeSH
- EDTA analogy a deriváty MeSH
- izotopy gallia * MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA * genetika MeSH
- nádorové biomarkery * genetika krev MeSH
- nádory prostaty rezistentní na kastraci genetika krev diagnostické zobrazování MeSH
- nádory prostaty * genetika krev diagnostické zobrazování MeSH
- PET/CT * metody MeSH
- prognóza MeSH
- prostatický specifický antigen * krev genetika MeSH
- průřezové studie MeSH
- radioizotopy galia * 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
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
