BACKGROUND: Vitamin D is a hormone regulating not only calcium and phosphate homeostasis but also, at the same time, exerting many other extraskeletal functions via genomic effects (gene transcription) and probably by non-genomic effects as well. Availability is ensured by dietary intake of its precursors and by de novo production via sunlight. Yet, vitamin D deficiency and insufficiency are very common across the globe and are connected to many pathophysiological states, for example, diabetes mellitus, allergies, autoimmune diseases, pregnancy complications, and recently have also been associated with worse COVID-19 clinical outcomes. SUMMARY: In this review, we summarize current knowledge about vitamin D metabolism in general, its role in diabetes mellitus (mainly type 2) and diabetic complications (mainly diabetic kidney disease), and potential therapeutic perspectives including vitamin D signalling as a druggable target. Key Messages: Vitamin D is not only a vitamin but also a hormone involved in many physiological processes. Its insufficiency or deficiency can lead to many pathological states.

• Klíčová slova
• Diabetes mellitus, Diabetic kidney disease, Sodium-glucose linked co-transporter 2 inhibitors, Vitamin D,
• MeSH
• COVID-19 metabolismus   MeSH
• diabetes mellitus farmakoterapie   etiologie   metabolismus   patofyziologie   MeSH
• diabetické nefropatie farmakoterapie   etiologie   metabolismus   patofyziologie   MeSH
• lidé MeSH
• nedostatek vitaminu D komplikace   farmakoterapie   metabolismus   patofyziologie   MeSH
• signální transdukce účinky léků   MeSH
• vitamin D metabolismus   terapeutické užití   MeSH
• vitaminy metabolismus   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• vitamin D MeSH
• vitaminy MeSH

Thyroid nodules are a very frequent pathology among common population. Despite the vast majority of them are of benign origin, the incidence of thyroid cancer is currently rather rising. Although there are several risk factors of thyroid cancer and several clinical, ultrasound, biochemical and molecular diagnostic markers, the exact mechanisms of thyroid oncogenesis and the linkage between thyroid nodule ultrasound appearance and its biological character remain unclear. While ionizing radiation is the only one well-known risk factor for thyroid cancer, the significance of some others remains unclear. The aim of our review was to discuss some not completely known pathophysiological mechanisms involved in thyroid oncogenesis as hypothyroidism, mutations of genes regulating cell proliferation, thyroid autoimmunity and pregnancy and to describe pathophysiological background of some ultrasound markers of thyroid cancer (size, echogenicity, vascularization, calcifications and stiffness). Better knowledge in this field is crucial for development of novel diagnostic techniques and therapeutic approaches. For example, the analysis of BRAF, RAS and other mutations in cytological samples may help to distinction between follicular thyroid carcinoma and follicular thyroid adenoma and may significantly decrease the number of unnecessary surgery among patients with thyroid nodules. Alternatively, the different malign cells growth, angiogenesis, destructions of thyroid follicles, reparative changes, growth retardation, fibrosis and increased interstitial fluid pressure implicate the typical ultrasound appearance of papillary thyroid cancer (hypoechogenicity, irregular vascularization, microcalcifications, stiffness) which is essential to catch the suspicious nodules on the basis of their ultrasound appearance among large amount of benign nodules.

• MeSH
• genetická predispozice k nemoci MeSH
• lidé MeSH
• nádorová transformace buněk * genetika   metabolismus   patologie   MeSH
• nádory štítné žlázy diagnostické zobrazování   etiologie   metabolismus   patologie   patofyziologie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• rizikové faktory MeSH
• signální transdukce MeSH
• ultrasonografie MeSH
• uzle štítné žlázy diagnostické zobrazování   etiologie   metabolismus   patologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The metabolic pathways that contribute to maintain serum calcium concentration in narrow physiological range include the bone remodeling process, intestinal absorption and renal tubule resorption. Dysbalance in these regulations may lead to hyper- or hypocalcemia. Hypercalcemia is a potentionally life-threatening and relatively common clinical problem, which is mostly associated with hyperparathyroidism and/or malignant diseases (90 %). Scarce causes of hypercalcemia involve renal failure, kidney transplantation, endocrinopathies, granulomatous diseases, and the long-term treatment with some pharmaceuticals (vitamin D, retinoic acid, lithium). Genetic causes of hypercalcemia involve familial hypocalciuric hypercalcemia associated with an inactivation mutation in the calcium sensing receptor gene and/or a mutation in the CYP24A1 gene. Furthermore, hypercalcemia accompanying primary hyperparathyroidism, which develops as part of multiple endocrine neoplasia (MEN1 and MEN2), is also genetically determined. In this review mechanisms of hypercalcemia are discussed. The objective of this article is a review of hypercalcemia obtained from a Medline bibliographic search.

• MeSH
• hyperkalcemie krev   genetika   patofyziologie   MeSH
• hyperparatyreóza krev   genetika   patofyziologie   MeSH
• lidé MeSH
• mutace genetika   MeSH
• vápník krev   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• vápník MeSH

New neurophysiological insights into the natural behaviour of dystonia, obtained during the successful botulinum toxin A (BoNT) treatment of the disorder, have urged the inclusion of sensory (and particularly somatosensory) mechanisms into the pathophysiological background of dystonia. Muscle spindles play a pivotal role in the generation of dystonic movements. Abnormal behaviour in the muscle spindles that generates an irregular proprioceptive input via the group-IA afferents may result in abnormal cortical excitability and intracortical inhibition in dystonia. The aim of this article is to support our hypothesis that dystonic movement is at the end of an impaired function of somatosensory pathways and analysers, which, in turn, may be hinged on the abnormality of sensorimotor integration, that is, brain plasticity. BoNT treatment can potentially modulate this plasticity mechanism and is probably the seminal cause of the sustained effect of the subsequent BoNT-treatment sessions and the long-term alleviation of symptoms of dystonia.

• MeSH
• botulotoxiny farmakologie   terapeutické užití   MeSH
• dystonie farmakoterapie   patofyziologie   MeSH
• lidé MeSH
• nervosvalová vřeténka účinky léků   fyziologie   MeSH
• propriocepce účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• botulotoxiny MeSH

Thiamine deficiency (TD) results in lactate acidosis, which is associated with neurodegeneration. The aim of this study was to investigate this alteration in primary rat brain endothelia. Spectrophotometric analysis of culture media revealed that only a higher concentration of pyrithiamine, which accelerates the intracellular blocking of thiamine, significantly elevated the lactate level and lactate dehydrogenase activity within 7 days. The medium without pyrithiamine and with a thiamine concentration comparable to pathophysiological plasma levels mildly reduced only the activity of transketolase. This suggests that significant metabolic changes may not occur at the early phase of TD in cerebral capillary cells, while anaerobic glycolysis in capillaries may be mediated during late stage/chronic TD.

• MeSH
• endoteliální buňky metabolismus   MeSH
• energetický metabolismus * MeSH
• glukosa metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• kyselina mléčná metabolismus   MeSH
• mikrocirkulace metabolismus   MeSH
• mozek MeSH
• nedostatek thiaminu metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukosa MeSH
• kyselina mléčná MeSH

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging.

• Klíčová slova
• cell metabolism, immune senescence, immunometabolism, inflammaging, senolytic drugs, senomorphic drugs,
• MeSH
• chronická nemoc MeSH
• chronická obstrukční plicní nemoc metabolismus   farmakoterapie   imunologie   MeSH
• lidé MeSH
• metabolické sítě a dráhy * MeSH
• plicní nemoci etiologie   farmakoterapie   metabolismus   imunologie   MeSH
• stárnutí buněk * účinky léků   MeSH
• stárnutí imunologie   metabolismus   MeSH
• zánět metabolismus   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Mequindox (MEQ) is a synthetic antimicrobial agent of quinoxaline-1,4-dioxide group (QdNOs). The liver is regarded as the toxicity target of QdNOs, and the role of N → O group-associated various toxicities mediated by QdNOs is well recognized. However, the mechanism underlying the in vivo effects of MEQ on the liver, and whether the metabolic pathway of MEQ is altered in response to the pathophysiological conditions still remain unclear. We now provide evidence that MEQ triggers oxidative damage in the liver. Moreover, using LC/MS-ITTOF analysis, two metabolites of MEQ were detected in the liver, which directly confirms the potential connection between N → O group reduction metabolism of MEQ and liver toxicity. The gender difference in MEQ-induced oxidative stress might be due to adrenal toxicity and the generation of M4 (2-isoethanol 1-desoxymequindox). Furthermore, up-regulation of the MAPK and Nrf2-Keap1 family and phase II detoxifying enzymes (HO-1, GCLC and NQO1) were also observed. The present study demonstrated for the first time the protein peroxidation and a proposal metabolic pathway after chronic exposure of MEQ, and illustrated that the MAPK, Nrf2-Keap1 and NF-кB signaling pathways, as well as the altered metabolism of MEQ, were involved in oxidative toxicity mediated by MEQ in vivo.

• MeSH
• antiinfekční látky aplikace a dávkování   farmakokinetika   toxicita   MeSH
• chinoxaliny aplikace a dávkování   farmakokinetika   toxicita   MeSH
• faktor 2 související s NF-E2 metabolismus   MeSH
• játra účinky léků   metabolismus   MeSH
• KEAP-1 metabolismus   MeSH
• MAP kinasový signální systém * MeSH
• myši MeSH
• oxidace-redukce MeSH
• oxidační stres * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiinfekční látky MeSH
• chinoxaliny MeSH
• faktor 2 související s NF-E2 MeSH
• KEAP-1 MeSH
• Keap1 protein, mouse MeSH Prohlížeč
• Mequindox MeSH Prohlížeč
• Nfe2l2 protein, mouse MeSH Prohlížeč

Inflammation is among the core causatives of male infertility. Despite male infertility being a serious global issue, "bits and pieces" of its complex etiopathology still remain missing. During inflammation, levels of proinflammatory mediators in the male reproductive tract are greater than usual. According to epidemiological research, in numerous cases of male infertility, patients suffer from acute or chronic inflammation of the genitourinary tract which typically occurs without symptoms. Inflammatory responses in the male genital system are inextricably linked to oxidative stress (OS). OS is detrimental to male fertility parameters as it causes oxidative damage to reproductive cells and intracellular components. Multifarious male infertility causative factors pave the way for impairing male reproductive functions via the common mechanisms of OS and inflammation, both of which are interlinked pathophysiological processes, and the occurrence of any one of them induces the other. Both processes may be simultaneously found in the pathogenesis of male infertility. Thus, the present article aims to explain the role of inflammation and OS in male infertility in detail, as well as to show the mechanistic pathways that link causative factors of male reproductive tract inflammation, OS induction, and oxidant-sensitive cellular cascades leading to male infertility.

• Klíčová slova
• cytokines, inflammation, male infertility, oxidative stress, reactive oxygen species,
• MeSH
• cytokiny metabolismus   MeSH
• infertilita patofyziologie   MeSH
• lidé MeSH
• mužské pohlavní orgány metabolismus   MeSH
• oxidační stres genetika   fyziologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• zánět metabolismus   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• reaktivní formy kyslíku MeSH

Oxidative stress is a pathological process related to not only animal kingdom but also plants. Regarding oxidative stress in plants, heavy metals are frequently discussed as causative stimuli with relevance to ecology. Because heavy metals have broad technological importance, they can easily contaminate the environment. Much of previous effort regarding the harmful impact of the heavy metals was given to their toxicology in the animals and humans. Their implication in plant pathogeneses is less known and remains underestimated.The current paper summarizes basic facts about heavy metals, their distribution in soil, mobility, accumulation by plants, and initiation of oxidative stress including the decline in basal metabolism. The both actual and frontier studies in the field are summarized and discussed. The major pathophysiological pathways are introduced as well and link between heavy metals toxicity and their ability to initiate an oxidative damage is provided. Mobility and bioaccessibility of the metals is also considered as key factors in their impact on oxidative stress development in the plant. The metals like lead, mercury, copper, cadmium, iron, zinc, nickel, vanadium are depicted in the text.Heavy metals appear to be significant contributors to pathological processes in the plants and oxidative stress is probably an important contributor to the effect. The most sensitive plant species are enlisted and discussed in this review. The facts presented here outline next effort to investigate pathological processes in the plants.

• Klíčová slova
• Contamination, Heavy metals, Oxidative damage, Oxidative stress, Pathophysiological pathways, Plants,
• MeSH
• biologická dostupnost MeSH
• cukry metabolismus   MeSH
• druhová specificita MeSH
• oxidační stres účinky léků   MeSH
• rostliny metabolismus   MeSH
• těžké kovy metabolismus   toxicita   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cukry MeSH
• těžké kovy MeSH

Adenosine and cAMP are potent modulators of immune-triggered cytokine production. Their effects overlap with regard to the inhibition of the pro-inflammatory cytokines TNF-alpha, IFN-gamma, IL-12, and the stimulation of production of the major anti-inflammatory cytokine IL-10. They may tentatively be considered to be upregulators of the production of Th2 cytokines (IL-10, IL-6), but downregulators of the production of Th1 cytokines (IL-2 and IFN-gamma). Cytokines produced in common by Th0, Th1 and Th2 cells are affected as well, although the low quantity and heterogeneity of the contemporary experimental data do not allow unambiguous conclusions to be drawn. Nevertheless, IL-3, IL-4, MIP-1alpha/beta and GM-CSF have usually been found to be inhibited, IL-5 stimulated, while IL-1 remains largely unaffected by adenosine or cAMP. These effects, and in particular the inhibition of TNF-alpha and stimulation of IL-10 expression, might be of therapeutic value in a variety of pathophysiological conditions.

• MeSH
• adenosin metabolismus   MeSH
• AMP cyklický metabolismus   MeSH
• cytokiny biosyntéza   MeSH
• lidé MeSH
• zpětná vazba MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• adenosin MeSH
• AMP cyklický MeSH
• cytokiny MeSH