Úvod: V důsledku metabolických dějů dochází v živých strukturách k endogenní produkci chemiluminiscence, kterou také označujeme jako biologickou autochemiluminiscenci (BAL). Generování BAL je úzce spojeno s oxidačními procesy, tvorbou volných radikálů a obecně oxidačně-redukční homeostázou zkoumaného biologického materiálu. BAL byla již dříve studována v savčích buněčných modelech a tkáních. Doposud ovšem nebyl tento jev popsán v případě struktur zubní tkáně. Kromě endogenně generované BAL lze BAL indukovat i exogenně, a to jak fyzikálními (UV záření, mechanické poškození, teplo), tak i chemickými (oxidační činidla, např. H2O2) a biotickými (patogeny) faktory. Metodika: V předložené práci byla zkoumána endogenně produkovaná i exogenně indukovaná BAL v povrchových a vnitřních strukturách semiretinovaných a retinovaných třetích molárů, které byly indikovány k extrakci zubním lékařem pro jejich nevhodné uložení v čelisti u dvou pacientů (žena, 21 let, muž, 22 let). Detekce BAL byla provedena po mechanickém odstranění zubního plaku rotačním kartáčkem. Pomocí piezoelektrické pily byly připraveny podélné řezy vedené tak, aby došlo k odhalení všech vnitřních částí zubu. Takto připravené vzorky – celého vnitřního řezu a vnější části celého zubu – byly podrobeny detekci BAL ve světlotěsné komoře za použití fotonásobičového modulu. Následně byly vzorky ošetřeny roztokem oxidačního činidla 3% H2O2 a redukčního činidla 10 mM TCEP (tris(karboxyethyl)fosfin). Výsledky: U obou vzorků zubu bylo prokázáno, že produkují BAL. Produkce endogenní chemiluminiscence byla pozorována ve vnitřních strukturách zubu (18 600 pulzů/600 s), která byla přibližně 2,7krát vyšší než BAL detekovaná na povrchových strukturách zubu (6 900 pulzů/600 s). Po ošetření H2O2 došlo k významnému (až 14násobnému) nárůstu BAL pro vnitřní struktury zubu ve srovnání s bazální intenzitou endogenně produkované BAL. Aplikace TCEP (negativní kontrola) vedla k mírnému potlačení produkce BAL. Závěr: Výsledky této pilotní studie ukazují, že BAL může být produkována nejenom měkkými tkáněmi, ale i tvrdou zubní tkání. Získané výsledky by mohly být využity k výzkumu metabolické aktivity a reaktivity vnitřních i vnějších částí zubu, a to především v kontextu výzkumu oxidačněredukční homeostázy. Detekce BAL by také mohla být aplikována pro vývoj nových zobrazovacích technik.
Introduction: As a result of metabolic processes, the endogenous production of chemiluminescence occurs in living biological structures, which we also refer to as biological autochemiluminescence (BAL). The generation of BAL is closely connected with oxidation processes, the formation of free radicals, and in general the redox homeostasis of the investigated biological material. BAL has previously been studied in mammalian cells and tissues. So far, however, this phenomenon has not been described in dental tissue structures. In addition to endogenously generated BAL, BAL can be exogenously induced by physical (UV radiation, mechanical damage, heat), chemical (oxidizing agents, e.g. H2O2) or biotic (pathogens) factors. Methods: Endogenously and exogenously induced BAL were investigated on the surface and internal structures of semi-impacted and impacted third molars, which were indicated for extraction by a dentist due to their inappropriate placement in the jaw in two patients (a 21-year-old woman and a 22-year-old man). BAL detection was performed with samples after dental plaque was mechanically removed with a rotating brush. Using a piezosurgery unit with a saw headpiece, longitudinal sections were made to reveal all internal parts of the tooth. The samples prepared in this way – the entire internal section and the external part of the entire tooth – were subjected to BAL detection in a dark chamber using H7360-01 PMT photomultiplier. Subsequently, the samples were treated with a solution of the oxidizing agent 3% H2O2 or the reducing agent 10 mM TCEP (tris(carboxyethyl)phosphine). Results: Both tooth samples were shown to produce BAL. Endogenous chemiluminescence production was observed in the internal structures of the tooth (18,600 counts/600 s), which was 2.7-fold higher than the BAL detected on the tooth outer surfaces (6,900 counts/600 s). After H2O2 treatment, there was a significant (up to 14-fold) increase in BAL for internal tooth structures compared to the basal intensity of endogenously produced BAL. The application of TCEP (negative control) resulted in a residual suppression of BAL production. Conclusion: The results of this pilot study show that BAL can be produced not only by soft tissues but also by hard dental tissue. The obtained results could be used for further research of the metabolic activity and reactivity of the inner and outer parts of the tooth, especially in the context of redox biology research. BAL detection could also be applied in the development of new imaging techniques.
Olfactory sensitivity to odorant molecules is a complex biological function influenced by both endogenous factors, such as genetic background and physiological state, and exogenous factors, such as environmental conditions. In animals, this vital ability is mediated by olfactory sensory neurons (OSNs), which are distributed across several specialized olfactory subsystems depending on the species. Using the phosphorylation of the ribosomal protein S6 (rpS6) in OSNs following sensory stimulation, we developed an ex vivo assay allowing the simultaneous conditioning and odorant stimulation of different mouse olfactory subsystems, including the main olfactory epithelium, the vomeronasal organ, and the Grueneberg ganglion. This approach enabled us to observe odorant-induced neuronal activity within the different olfactory subsystems and to demonstrate the impact of environmental conditioning, such as temperature variations, on olfactory sensitivity, specifically in the Grueneberg ganglion. We further applied our rpS6-based assay to the human olfactory system and demonstrated its feasibility. Our findings show that analyzing rpS6 signal intensity is a robust and highly reproducible indicator of neuronal activity across various olfactory systems, while avoiding stress and some experimental limitations associated with in vivo exposure. The potential extension of this assay to other conditioning paradigms and olfactory systems, as well as its application to other animal species, including human olfactory diagnostics, is also discussed.
- MeSH
- Smell physiology MeSH
- Olfactory Mucosa metabolism MeSH
- Olfactory Receptor Neurons * metabolism physiology MeSH
- Phosphorylation MeSH
- Humans MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Odorants analysis MeSH
- Ribosomal Protein S6 * metabolism MeSH
- Vomeronasal Organ metabolism physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system. The first-line defense mechanism is the most efficient and involves antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). This line of defense plays an irreplaceable role in the dismutation of superoxide radicals (O2•-) and hydrogen peroxide (H2O2). The removal of superoxide radicals by SOD prevents the formation of the much more damaging peroxynitrite ONOO- (O2•- + NO• → ONOO-) and maintains the physiologically relevant level of nitric oxide (NO•), an important molecule in neurotransmission, inflammation, and vasodilation. The second-line antioxidant defense pathway involves exogenous diet-derived small-molecule antioxidants. The third-line antioxidant defense is ensured by the repair or removal of oxidized proteins and other biomolecules by a variety of enzyme systems. This review briefly discusses the endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) and exogenous (e.g., smoking, radiation, drugs, pollution) sources of ROS (superoxide radical, hydrogen peroxide, hydroxyl radical, peroxyl radical, hypochlorous acid, peroxynitrite). Attention has been given to the first-line antioxidant defense system provided by SOD, CAT, and GPx. The chemical and molecular mechanisms of antioxidant enzymes, enzyme-related diseases (cancer, cardiovascular, lung, metabolic, and neurological diseases), and the role of enzymes (e.g., GPx4) in cellular processes such as ferroptosis are discussed. Potential therapeutic applications of enzyme mimics and recent progress in metal-based (copper, iron, cobalt, molybdenum, cerium) and nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) are also discussed. Moreover, attention has been given to the mechanisms of action of low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids (e.g., β-carotene, lycopene, lutein), flavonoids (e.g., quercetin, anthocyanins, epicatechin), and glutathione (GSH)), the activation of transcription factors such as Nrf2, and the protection against chronic diseases. Given that there is a discrepancy between preclinical and clinical studies, approaches that may result in greater pharmacological and clinical success of low-molecular-weight antioxidant therapies are also subject to discussion.
- MeSH
- Anthocyanins metabolism pharmacology MeSH
- Antioxidants * pharmacology metabolism MeSH
- Chronic Disease MeSH
- Peroxynitrous Acid pharmacology MeSH
- Humans MeSH
- Neoplasms * MeSH
- Nitric Oxide MeSH
- Oxidative Stress MeSH
- Hydrogen Peroxide MeSH
- Reactive Oxygen Species metabolism MeSH
- Superoxide Dismutase metabolism MeSH
- Superoxides MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Skin plays an important role in protection, metabolism, thermoregulation, sensation, and excretion whilst being consistently exposed to environmental aggression, including biotic and abiotic stresses. During the generation of oxidative stress in the skin, the epidermal and dermal cells are generally regarded as the most affected regions. The participation of reactive oxygen species (ROS) as a result of environmental fluctuations has been experimentally proven by several researchers and is well known to contribute to ultra-weak photon emission via the oxidation of biomolecules (lipids, proteins, and nucleic acids). More recently, ultra-weak photon emission detection techniques have been introduced to investigate the conditions of oxidative stress in various living systems in in vivo, ex vivo and in vitro studies. Research into two-dimensional photon imaging is drawing growing attention because of its application as a non-invasive tool. We monitored spontaneous and stress-induced ultra-weak photon emission under the exogenous application of a Fenton reagent. The results showed a marked difference in the ultra-weak photon emission. Overall, these results suggest that triplet carbonyl (3C=O∗) and singlet oxygen (1O2) are the final emitters. Furthermore, the formation of oxidatively modified protein adducts and protein carbonyl formation upon treatment with hydrogen peroxide (H2O2) were observed using an immunoblotting assay. The results from this study broaden our understanding of the mechanism of the generation of ROS in skin layers and the formation/contribution of various excited species can be used as tools to determine the physiological state of the organism.
Alzheimerova choroba (AD) je nejčastější příčinou demence a významně se podílí na celkové morbiditě a mortalitě v populaci, zejména u seniorů. AD rozdělujeme na geneticky podmíněnou a sporadickou, které se liší etiopatogenezí, četností výskytu i průběhem. Sporadická forma AD představuje 99 % případů onemocnění. Její etiologie je komplexní a do velké míry zůstává neobjasněna; pravděpodobně se jedná o souhru mnoha endogenních a exogenních faktorů. V práci je podán základní přehled hypotéz vysvětlujících vznik a progresi AD s důrazem na nejrozšířenější amyloidovou hypotézu, která za klíčový faktor považuje nepřiměřenou tvorbu nebo nedostatečné odstraňování toxických forem amyloidových peptidů z amyloidového prekurzorového proteinu. Další teorie vzniku AD se přiklánějí k primární- mu působení jiných činitelů, např. tau proteinu, nepřiměřeného působení některých mediátorů, metabolických, neurovaskulárních, zánětlivých, infekčních a jiných faktorů. Práce také shrnuje některé kontroverzní závěry o patofyziologii choroby, které patrně pramení z obecné aplikace poznatků získaných výzkumem rozdílných forem choroby a přímé translace výsledků výzkumu na experimentálních modelech AD na lidské onemocnění. Navzdory obrovskému pokroku ve výzkumu AD nebyla dosud nalezena kauzální léčba.
Alzheimer's disease (AD) is the most common cause of dementia and contributes significantly to overall morbidity and mortality in the population. Despite the global and social importance of AD and dementia, despite extensive research, the etiopathogenetic mechanisms associated with AD have not yet been fully elucidated. The disease can be divided into early onset or familial AD and sporadic or late onset AD, which differ in etiopathogenesis, prevalence, course, and genetic predisposition. The sporadic form of AD represents 99% of cases of the disease. Its etiology is complex and largely unclear; it probably results from an interplay of many endogenous and exogenous factors. The present article provides a basic overview of hypotheses explaining the origin and progress of AD with emphasis on the most common amyloid hypothesis regarding excessive synthesis or insufficient clearance of toxic forms of amyloid peptides as the key factor of AD pathophysiology. Other theories tend to explain AD development by the primary impact of other factors, such as tau protein, the inappropriate effects of some neurotransmitters, metabolic, neurovascular, inflammatory, infectious, and other factors. The article also summarizes some controversial conclusions on the pathophysiology of the disease, which probably stem from the general application of knowledge gained in the research on different forms of the disease and direct translation of research results on experimental models of AD to human disease. Despite enormous advances in AD research, causal treatment of this devastating disease has not yet been found.
- Keywords
- hypotézy vzniku nemoci, amyloidová hypotéza, mitochondriální hypotéza,
- MeSH
- Alzheimer Disease * history etiology physiopathology MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Recently, we demonstrated that chronic blockade of the renin-angiotensin system (RAS) lowered the blood pressure (BP) of adult Ren-2 transgenic rats (TGR) mainly through the attenuation of central sympathoexcitation. However, the participation of central and peripheral mechanisms in the development of high BP in immature TGR remains unclear. In the present study, 6-week-old heterozygous TGR males were chronically treated with intracerebroventricular (ICV) or intraperitoneal (IP) infusions of the AT1 receptor inhibitor losartan (1 or 2 mg/kg/day) for 4 weeks. The influence of these treatments on sympathetic- and angiotensin II-dependent BP components (BP response to pentolinium or captopril, respectively) as well as on BP response to exogenous angiotensin II were determined to evaluate the participation of central and peripheral RAS in hypertension development. Chronic IP losartan administration (1 or 2 mg/kg/day) lowered the BP of immature TGR by reducing both sympathetic and angiotensin II-dependent BP components. The central action of IP-administered losartan was indicated by a reduced BP response to acute ICV angiotensin II injection. Chronic ICV administration of a lower losartan dose (1 mg/kg/day) reduced only the sympathetic BP component, whereas a higher ICV administered dose (2 mg/kg/day) was required to influence the angiotensin II-dependent BP component. Accordingly, chronic ICV losartan administration of 2 mg/kg/day (but not 1 mg/kg/day) attenuated the BP response to acute intravenous angiotensin II application. In conclusion, central sympathoexcitation seems to play an important role in hypertension development in immature TGR. Central sympathoexcitation is highly susceptible to inhibition by low doses of RAS-blocking agents, whereas higher doses also affect peripheral angiotensin II-dependent vasoconstriction.
- MeSH
- Angiotensin II * MeSH
- Hypertension * MeSH
- Blood Pressure physiology MeSH
- Rats MeSH
- Losartan pharmacology therapeutic use MeSH
- Rats, Transgenic MeSH
- Renin-Angiotensin System MeSH
- Renin metabolism MeSH
- Vasoconstriction MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The analysis of volatile organic compounds (VOCs) can provide important clinical information (entirely non-invasively); however, the exact extent to which VOCs from human skin can be signatures of health and disease is unknown. This systematic review summarises the published literature concerning the methodology, application, and volatile profiles of skin VOC studies. An online literature search was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis, to identify human skin VOC studies using untargeted mass spectrometry (MS) methods. The principal outcome was chemically verified VOCs detected from the skin. Each VOC was cross-referenced using the CAS number against the Human Metabolome and KEGG databases to evaluate biological origins. A total of 29 studies identified 822 skin VOCs from 935 participants. Skin VOCs were commonly sampled from the hand (n = 9) or forearm (n = 7) using an absorbent patch (n = 15) with analysis by gas chromatography MS (n = 23). Twenty-two studies profiled the skin VOCs of healthy subjects, demonstrating a volatolome consisting of aldehydes (18%), carboxylic acids (12%), alkanes (12%), fatty alcohols (9%), ketones (7%), benzenes and derivatives (6%), alkenes (2%), and menthane monoterpenoids (2%). Of the VOCs identified, 13% had putative endogenous origins, 46% had tentative exogenous origins, and 40% were metabolites from mixed metabolic pathways. This review has comprehensively profiled the human skin volatolome, demonstrating the presence of a distinct VOC signature of healthy skin, which can be used as a reference for future researchers seeking to unlock the clinical potential of skin volatolomics. As significant proportions of identified VOCs have putative exogenous origins, strategies to minimise their presence through methodological refinements and identifying confounding compounds are discussed.
- Publication type
- Journal Article MeSH
- Review MeSH
Albumin je protein, který tvoří hlavní část celkového obsahu plazmatických proteinů. Má mnoho fyziologických funkcí, je zásadním modulátorem onkotického tlaku, ale podílí se také na transportu některých endogenních i exogenních látek. Koncentrace albuminu tak ovlivňuje i účinnost některých léků či senzitivitu na jejich působení. Albumin je také důležitým markerem stavu výživy organismu. Pokles koncentrace albuminu může mít mnoho příčin. Hypoalbuminemie může mít závažné následky, včetně zvýšení mortality, morbidity a délky pobytu na lůžku intenzivní péče. Hypoalbuminemie může vyžadovat korekci. Aplikace albuminu je možná jen v určitých indikacích a má svá pravidla. Při podávání albuminu je nutné mít na paměti i ekonomické aspekty.
Albumin is a protein that forms a major part of the total plasma protein content. It has many physiological functions. This one is an essential modulator of the oncotic pressure, but also involves the transport of some endogenous and exogenous substances. Albumin level also affects the effectiveness of some drugs or their sensitivity. Albumin is also the important marker of the body's nutritional status. Decreased albumin level can have many causes. Hypoalbuminemia can have serious consequences, including increased mortality, morbidity, and length of stay in the intensive care unit. Hypalbuminemia may require correction. Albumin application is possible only in certain indications and has its rules. Economic aspects must also be borne in mind when administering albumin.
- MeSH
- Albumins * administration & dosage physiology metabolism therapeutic use MeSH
- Hypoalbuminemia etiology therapy MeSH
- Humans MeSH
- Solutions administration & dosage therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Mycobacteria are a unique group of microorganisms. They are characterised by exceptional adaptability and durability. They are capable of colonisation and survival even in very unfavourable conditions. In addition to the well-known obligate human pathogens, Mycobacterium tuberculosis and M. leprae, more than 200 other species have been described. Most of them form a natural part of the microflora of the external environment and thrive in aquatic and soil environments especially. For many of the mycobacterial species associated with human disease, their natural source has not yet been identified. From an ecological point of view, mycobacteria are saprophytes, and their application in human and animal diseases is opportunistic. Most cases of human disease from saprophytic mycobacteria occur in immunocompromised individuals. This adaptability and resilience to environmental pressures makes treatment of mycobacterial diseases (most often sapronoses and less often zoonoses) and permanent eradication of mycobacteria from the environment very difficult. Saprophytic mycobacterial diseases (sapronoses) are chronic and recurrent due to the fact of repeated endogenous or exogenous re-exposure. Therefore, knowledge regarding their occurrence in soil and dust would aid in the prevention of saprophytic mycobacterioses. In conjunction, their presence and ecological significance in the environment can be revealed.
- Publication type
- Journal Article MeSH
- Review MeSH
Diabetes mellitus (zejména diabetes mellitus 2. typu) a kolorektální karcinom jsou v naší populaci relativně častými onemocněními. Tyto jednotky zároveň sdílejí některé společné rizikové faktory, jako je např. obezita, nedostatek fyzické aktivity a hyperinzulinemie. Dostupná data ukazují, že pacienti s diabetem mají zvýšené riziko výskytu kolorektálního adenomu a karcinomu, zvýšené riziko výskytu kolorektálního karcinomu v nižším věku, jakož i zvýšené riziko recidivy a zvýšenou mortalitu při karcinomu kolorekta. Článek předkládá aktuální pohled na vztah diabetu a kolorektálního karcinomu s důrazem na informace podstatné pro klinickou praxi, zejména na screening kolorektálního karcinomu a režimová doporučení pro pacienty s diabetem.
Diabetes mellitus (type 2 diabetes in particular) and colorectal carcinoma are relatively frequent diseases in our population. At the same time, these units share some common risk factors, for example obesity, lack of physical activity and hyperinsulinemia. Available data show patients with diabetes have increased risk of colorectal adenoma and carcinoma, increased risk of colorectal carcinoma at a lower age, as well as increased risk of relapse and increased mortality with colorectal cancer. The aim of this article is to point out the relationship between diabetes and colorectal carcinoma, with emphasis on the information important for clinical practice, particularly the screening of colorectal carcinoma and lifestyle recommendations for patients with diabetes. Therefore, we offer an overview of the important available publications which consider this topic.
