Istine i kontroverze o selenu

Selenium is a trace element, essential in small amounts, but can be toxic in larger amounts. Levels in the body are mainly dependent on the amount of selenium in the diet, which is a function of the selenium content of the soil. Humans and animals require selenium for normal function of more than about 30 known selenoproteins, of which approximately 15 have been purified to allow characterisation of their biological functions. The selenoproteins are comprised of four glutathione peroxidases, three iodothyronine deiodinases, three thioredoxin reductases, selenoprotein P, selenoprotein W and selenophosphate synthetase. Selenium is essential for normal functioning of the immune system and thyroid gland, making selenium an essential element for normal development, growth, metabolism, and defense of the body. Supportive function of selenium in health and disease (male infertility, viral infections, including HIV, cancer, cardiovascular and autoimmune diseases) is documented in great number of clinical examinations. A great number of studies confirm that selenium supplementation play a preventive and therapeutical role in different diseases. Definitive evidence regarding the preventive and therapeutical role of selenium as well as the exact mechanism of its action should be investigated in further studies. Investigations in Croatia indicate a possibility of inadequate selenium status of people in the area.Selen je mikroelement neophodan organizmu u malim količinama, a toksičan u većim količinama. Količina selena u hrani ovisi o količini selena u tlu. Ljudi i životinje trebaju ga za normalno funkcioniranje brojnih procesa. Selen je sastavni dio više od tridesetak poznatih selenoproteina, od kojih su za petnaestak dobro poznata biološka svojstva, primjerice četiri glutation peroksidaze, tri jodtironin dejodinaze, tri tioredoksin reduktaze, selenoprotein P, selenoprotein W i selenofosfat sintetaza. Selen je nužan za normalno funkcioniranje obrambenog sustava i za funkcioniranje tireoidne žlijezde, što znači da je selen esencijalan za normalan razvoj, rast, metabolizam i obranu organizma. Brojna su klinička ispitivanja potvrdila da selen potpomaže u zdravlju i bolesti (muška neplodnost, virusne infekcije, uključujući HIV, karcinom, kardiovaskularne bolesti, autoimune bolesti). Brojne su studije pokazale da suplementacija selena može imati i preventivnu i terapijsku ulogu kod različitih bolesti, ali za konačnu potvrdu kao i točan mehanizam njegova djelovanja nužna su daljnja istraživanja. Istraživanja u Hrvatskoj ukazuju na smanjenu količinu selena u tlu i moguć nedostatan unos selena u ljudski ogranizam

Feroptoza: regulirana stanična smrt

Ferroptosis is a recently identified form of regulated cell death that differs from other known forms of cell death morphologically, biochemically, and genetically. The main properties of ferroptosis are free redox-active iron and consequent iron-dependent peroxidation of polyunsaturated fatty acids in cell membrane phospholipids, which results in the accumulation of lipid-based reactive oxygen species due to loss of glutathione peroxidase 4 activity. Ferroptosis has increasingly been associated with neurodegenerative diseases, carcinogenesis, stroke, intracerebral haemorrhage, traumatic brain injury, and ischemia-reperfusion injury. It has also shown a significant therapeutic potential in the treatment of cancer and other diseases. This review summarises current knowledge about and the mechanisms that regulate ferroptosis.Feroptoza je nedavno identificirani oblik regulirane stanične smrti koji se od ostalih poznatih oblika stanične smrti razlikuje morfološki, biokemijski i genetski. Glavna svojstva feroptoze uključuju slobodno redoks aktivno željezo i posljedičnu, o željezu ovisnu, peroksidaciju polinezasićenih masnih kiselina u fosfolipidima staničnih membrana te gubitak aktivnosti glutation peroksidaze 4, što rezultira akumulacijom lipidnih, reaktivnih kisikovih spojeva. Feroptoza se sve više povezuje s raznim bolestima kao što su neurodegenerativne bolesti, karcinom, moždani udar, intracerebralna krvarenja, traumatične ozljede mozga i ishemijsko-reperfuzijska ozljeda. Također je pokazan značajan terapijski potencijal u liječenju raka i drugih bolesti. Ovaj pregled sažima trenutačne spoznaje i mehanizme koji reguliraju feroptozu

Ferroptosis - a link between iron biology, aging and COVID-19?

Severe form of COVID-19 is more common in the elderly and although it may include a variety of extrapulmonary manifestations, respiratory dysfunction is primarily present, which includes iron dy- shomeostasis. The aging process is characterized by a chronic pro-inflammatory condition of a milder type, and COVID-19 by strong acute inflammation, both resulting in changes in iron metabolism. A new, iron-dependent form of programmed cell death, ferroptosis, is associated with iron dyshomeosta- sis. The main features of ferroptosis include intracellular iron overload, inhibition of the cellular GSH / GPX4 system, and accumulation of lipid reactive compounds. Clinical manifestations of COVID-19 and changes during aging include GSH depletion, GPX4 inactivation, changes in iron metabolism markers as well as markers of enhanced lipid peroxidation. There is therefore a possibility that SARS- CoV-2 may cause feroptotic death of lung cells but also cells of other organs. This review considers the molecular mechanisms of ferroptosis, their relationship to the aging process and the pathogenesis of COVID-19, and the consideration of ferroptosis as a factor linking aging and the pathogenesis of COVID-19

Ferroptosis - a link between iron biology, aging and COVID-19?

Severe form of COVID-19 is more common in the elderly and although it may include a variety of extrapulmonary manifestations, respiratory dysfunction is primarily present, which includes iron dy- shomeostasis. The aging process is characterized by a chronic pro-inflammatory condition of a milder type, and COVID-19 by strong acute inflammation, both resulting in changes in iron metabolism. A new, iron-dependent form of programmed cell death, ferroptosis, is associated with iron dyshomeosta- sis. The main features of ferroptosis include intracellular iron overload, inhibition of the cellular GSH / GPX4 system, and accumulation of lipid reactive compounds. Clinical manifestations of COVID-19 and changes during aging include GSH depletion, GPX4 inactivation, changes in iron metabolism markers as well as markers of enhanced lipid peroxidation. There is therefore a possibility that SARS- CoV-2 may cause feroptotic death of lung cells but also cells of other organs. This review considers the molecular mechanisms of ferroptosis, their relationship to the aging process and the pathogenesis of COVID-19, and the consideration of ferroptosis as a factor linking aging and the pathogenesis of COVID-19

Istine i kontroverze o selenu

Selenium is a trace element, essential in small amounts, but can be toxic in larger amounts. Levels in the body are mainly dependent on the amount of selenium in the diet, which is a function of the selenium content of the soil. Humans and animals require selenium for normal function of more than about 30 known selenoproteins, of which approximately 15 have been purified to allow characterisation of their biological functions. The selenoproteins are comprised of four glutathione peroxidases, three iodothyronine deiodinases, three thioredoxin reductases, selenoprotein P, selenoprotein W and selenophosphate synthetase. Selenium is essential for normal functioning of the immune system and thyroid gland, making selenium an essential element for normal development, growth, metabolism, and defense of the body. Supportive function of selenium in health and disease (male infertility, viral infections, including HIV, cancer, cardiovascular and autoimmune diseases) is documented in great number of clinical examinations. A great number of studies confirm that selenium supplementation play a preventive and therapeutical role in different diseases. Definitive evidence regarding the preventive and therapeutical role of selenium as well as the exact mechanism of its action should be investigated in further studies. Investigations in Croatia indicate a possibility of inadequate selenium status of people in the area.Selen je mikroelement neophodan organizmu u malim količinama, a toksičan u većim količinama. Količina selena u hrani ovisi o količini selena u tlu. Ljudi i životinje trebaju ga za normalno funkcioniranje brojnih procesa. Selen je sastavni dio više od tridesetak poznatih selenoproteina, od kojih su za petnaestak dobro poznata biološka svojstva, primjerice četiri glutation peroksidaze, tri jodtironin dejodinaze, tri tioredoksin reduktaze, selenoprotein P, selenoprotein W i selenofosfat sintetaza. Selen je nužan za normalno funkcioniranje obrambenog sustava i za funkcioniranje tireoidne žlijezde, što znači da je selen esencijalan za normalan razvoj, rast, metabolizam i obranu organizma. Brojna su klinička ispitivanja potvrdila da selen potpomaže u zdravlju i bolesti (muška neplodnost, virusne infekcije, uključujući HIV, karcinom, kardiovaskularne bolesti, autoimune bolesti). Brojne su studije pokazale da suplementacija selena može imati i preventivnu i terapijsku ulogu kod različitih bolesti, ali za konačnu potvrdu kao i točan mehanizam njegova djelovanja nužna su daljnja istraživanja. Istraživanja u Hrvatskoj ukazuju na smanjenu količinu selena u tlu i moguć nedostatan unos selena u ljudski ogranizam

SARS-CoV-2 – a new challenge for laboratory medicine

The new corona virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) causes a disease called COVID-19 (coronavirus disease 2019), that develops mostly in subjects with already impaired immune system function, primarily in the elderly and in individuals with some chronic disease or condition. The reasons for this should be sought in the processes of aging and chronic latent inflammation, i.e. immunosenescence and inflammaging. Laboratory medicine specialists are currently focused on proving the presence of the virus and defining biomarkers that would enable the prediction of disease progression. For now, it has been shown that useful biomarkers can include general biomarkers of inflammation (parameters of complete blood count, C-reactive protein, interleukin-6, procalcitonin), biomarkers of myocardial damage (high sensitivity troponin I/T, B-type natriuretic peptide, and N-terminal B type natriuretic peptide), and vascular biomarkers (D-dimer, prothrombin time, fibrinogen). Their actual diagnostic specificity, sensitivity and predictive value need to be tested on a larger number of subjects. In addition, it is important to find and evaluate specific biomarkers of immunosenescence

DOB I INFEKCIJA VIRUSOM SARS-COV-2

SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2), a novel virus of the beta coronavirus group RNA viruses, is responsible for a zoonotic disease named COVID-19 (coronavirus disease from 2019). The main receptor through which the virus enters the host cell is angiotensin-converting enzyme 2 (ACE2), known as a multifunctional protein. ACE2 expression has been found in oral and nasal mucosa, lungs, adipose tissue, heart, brain, kidneys, vascular tissue, stomach, liver. Upon entry of the virus into the target host cells, two processes are initiated, the host’s immune response and the infl ammatory cascade. As immune (innate and adaptive) and infl ammatory responses change throughout life both qualitatively and quantitatively, both processes are responsible for varying degrees of disease severity depending on the patient’s age. Short-time experience with SARS-CoV-2 infection has shown that: (i) children and adolescents develop the disease with mild symptoms, mainly on upper respiratory airways; (ii) the disease has a more severe course in adult patients with associated chronic diseases such as cardiovascular and renal diseases, chronic respiratory diseases, diabetes, etc.; and (iii) the most severe, often fatal disease occurs in the elderly, due to more pronounced processes of immunosenescence and infl amm-aging.RSARS-CoV-2 (engl. Severe Acute Respiratory Syndrome Coronavirus 2), novi virus iz skupine RNA betakoronavirusa, odgovoran je za zoonotsku bolest nazvanu COVID-19 (bolest uzrokovana koronavirusom iz 2019.). Glavni receptor pomoću kojega virus ulazi u stanicu domaćina je angiotenzin konvertirajući enzim 2 (ACE2), poznat kao multifunkcionalni protein. Receptor ACE2 prisutan je u oralnoj i nosnoj sluznici, plućima, masnom tkivu, srcu, mozgu, bubrezima, vaskularnom tkivu, želucu, jetri. Nakon ulaska virusa u ciljne stanice domaćina pokreću se dva procesa, imunosni odgovor domaćina i upalna kaskada. Budući da se imunosni (urođeni i stečeni) i upalni odgovori tijekom života mijenjaju u kvalitativnom i kvantitativnom smislu, oba procesa su odgovorna za različit stupanj ozbiljnosti bolesti, ovisno o pacijentovoj dobi. Kratkotrajno iskustvo s infekcijom uzrokovanom virusom SARS-CoV-2 pokazalo je da: (i) djeca i adolescenti razvijaju bolest s blagim simptomima, uglavnom na gornjim dišnim putevima; (ii) bolest ima teži tijek u odraslih bolesnika s pridruženim kroničnim bolestima kao što su kardiovaskularne i bubrežne bolesti, kronične respiratorne bolesti, dijabetes i sl.; (iii) najteži, često fatalni oblik pojavljuje se u starijih osoba zbog izraženijih procesa imunosenescencije i upale pri starenju

DOB I INFEKCIJA VIRUSOM SARS-COV-2

SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2), a novel virus of the beta coronavirus group RNA viruses, is responsible for a zoonotic disease named COVID-19 (coronavirus disease from 2019). The main receptor through which the virus enters the host cell is angiotensin-converting enzyme 2 (ACE2), known as a multifunctional protein. ACE2 expression has been found in oral and nasal mucosa, lungs, adipose tissue, heart, brain, kidneys, vascular tissue, stomach, liver. Upon entry of the virus into the target host cells, two processes are initiated, the host’s immune response and the infl ammatory cascade. As immune (innate and adaptive) and infl ammatory responses change throughout life both qualitatively and quantitatively, both processes are responsible for varying degrees of disease severity depending on the patient’s age. Short-time experience with SARS-CoV-2 infection has shown that: (i) children and adolescents develop the disease with mild symptoms, mainly on upper respiratory airways; (ii) the disease has a more severe course in adult patients with associated chronic diseases such as cardiovascular and renal diseases, chronic respiratory diseases, diabetes, etc.; and (iii) the most severe, often fatal disease occurs in the elderly, due to more pronounced processes of immunosenescence and infl amm-aging.RSARS-CoV-2 (engl. Severe Acute Respiratory Syndrome Coronavirus 2), novi virus iz skupine RNA betakoronavirusa, odgovoran je za zoonotsku bolest nazvanu COVID-19 (bolest uzrokovana koronavirusom iz 2019.). Glavni receptor pomoću kojega virus ulazi u stanicu domaćina je angiotenzin konvertirajući enzim 2 (ACE2), poznat kao multifunkcionalni protein. Receptor ACE2 prisutan je u oralnoj i nosnoj sluznici, plućima, masnom tkivu, srcu, mozgu, bubrezima, vaskularnom tkivu, želucu, jetri. Nakon ulaska virusa u ciljne stanice domaćina pokreću se dva procesa, imunosni odgovor domaćina i upalna kaskada. Budući da se imunosni (urođeni i stečeni) i upalni odgovori tijekom života mijenjaju u kvalitativnom i kvantitativnom smislu, oba procesa su odgovorna za različit stupanj ozbiljnosti bolesti, ovisno o pacijentovoj dobi. Kratkotrajno iskustvo s infekcijom uzrokovanom virusom SARS-CoV-2 pokazalo je da: (i) djeca i adolescenti razvijaju bolest s blagim simptomima, uglavnom na gornjim dišnim putevima; (ii) bolest ima teži tijek u odraslih bolesnika s pridruženim kroničnim bolestima kao što su kardiovaskularne i bubrežne bolesti, kronične respiratorne bolesti, dijabetes i sl.; (iii) najteži, često fatalni oblik pojavljuje se u starijih osoba zbog izraženijih procesa imunosenescencije i upale pri starenju

Hallmarks of senescence and aging

The complex process of biological aging, as an intrinsic feature of living beings, is the result of genetic and, to a greater extent, environmental factors and time. For many of the changes taking place in the body during aging, three factors are important: inflammation, immune aging and senescence (cellular aging, biological aging). Senescence is an irreversible form of long-term cell-cycle arrest, caused by excessive intracellular or extracellular stress or damage. The purpose of this cell-cycles arrest is to limit the proliferation of damaged cells, to eliminate accumulated harmful factors and to disable potential malignant cell transformation. As the biological age does not have to be in accordance with the chronological age, it is important to find specific hallmarks and biomarkers that could objectively determine the rate of age of a person. These biomarkers might be a valuable measure of physiological, i.e. biological age. Biomarkers should meet several criteria. For example, they have to predict the rate of aging, monitor a basic process that underlies the aging process, be able to be tested repeatedly without harming the person. In addition, biomarkers have to be indicators of biological processes, pathogenic processes or pharmacological responses to therapeutic intervention. It is considered that the telomere length is the weak biomarker (with poor predictive accuracy), and there is currently no reliable biomarker that meets all the necessary criteria

Starenje, kalorijske restrikcije i kalorijsko restrikcijska mimetrika

In line with the increase in the number of older people in the world, the focus of scientists is directed at examining mechanisms of the aging process as well as establishing strategies/interventions in order to slow down aging and achieve longevity. On preclinical testing models, the most effective strategy for this purpose, as well as for the purpose of delaying age-related diseases, nutritional interven- tion- restriction of calorie (CR) has been demonstrated, but also some alternative forms of calorie restriction. Possible undesirable effects of restriction are still in the testing phase, and it is known that it is generally difficult to implement in humans. Therefore, the new area of research in gerontology has become the discovery and examination of the effects of compounds that mimic the effects of caloric restriction, so called caloric restriction mimetics (CRM). These compounds include numerous compounds of natural origin but also approved medicaments with certain indications. This overview summarizes the latest data on known mechanisms of caloric restriction and more familiar caloric restriction mimetics.U skladu s povećanjem broja starijih ljudi u svijetu, fokus znanstvenika usmjeren je na ispitivanje me- hanizama procesa starenja kao i na uspostavljanje strategija / intervencija kako bi se usporilo starenje i postigla dugovječnost. Na predkliničkim modelima ispitivanja, najučinkovitija strategija za ovu svrhu, kao i za odgađanje bolesti povezanih s dobi, pokazana je prehrambena intervencija - ograničenje kalo- rija, ali i neki alternativni oblici ograničavanja kalorija. Mogući neželjeni učinci restrikcije još su u fazi ispitivanja, a poznato je da je to općenito teško provesti kod ljudi. Stoga je novo područje istraživanja u gerontologiji postalo otkriće i ispitivanje učinaka spojeva koji oponašaju učinke kalorijske restrikci- je, takozvane mimetike kalorijske restrikcije. Ti spojevi uključuju brojne spojeve prirodnog podrijetla, ali i odobrene lijekove s određenim indikacijama. Ovaj pregled sažima najnovije podatke o poznatim mehanizmima kalorijskog ograničenja i poznatijim mimeticima za ograničenje kalorija