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

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

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

Possible consequences of early exposure to endocrine disruptors

Endokrini disruptori (ED) egzogene su kemikalije koje mijenjaju funkciju endokrinog sustava, čime dovode do štetnih učinaka na zdravlje životinja i ljudi. U skupinu trajno prisutnih štetnih spojeva ubrajaju se sintetizirani pesticidi, industrijske kemikalije i njihovi nusproizvodi, prirodni mikotoksini i fitoestrogeni. Drugu skupinu ED-a čine proizvodi s kojima se u kontakt dolazi povremeno (proizvodi široke potrošnje, farmaceutski agensi). Štetno djelovanje ED-a ispituje se na životinjama koje obitavaju u prirodi, na laboratorijskim životinjama, staničnim kulturama te u humanim epidemiološkim i kliničkim istraživanjima. Posljedice rane izloženosti ED-u dokazane su u poremećajima reproduktivnog i endokrinog sustava, pojavi metaboličkih poremećaja i bolesti, neurološkim poremećajima. Neke od posljedica prenose se na sljedeće generacije. U ranoj dječjoj dobi važno je otkriti i istražiti indikatore fetalne izloženosti, identificirati skupine velikog i malog rizika izloženosti ED-u, kako bi se mogla provesti prospektivna istraživanja korelacije izloženosti s kliničkim posljedicama tijekom novorođenačkog i dojenačkog razdoblja, djetinjstva i adolescencije.Endocrine disruptors (EDs) are exogenous chemicals that alter the endocrine system function and have adverse effects on animal and human health. Synthesized compounds such as pesticides, industrial chemicals and their by-products, natural mycotoxins and phyto-oestrogens are included in the group of permanently present harmful compounds. The second group contains occasionally used chemicals (personal care products, pharmaceutical agents). The harmful effects of ED are tested in wildlife and laboratory animals, in cell cultures, and in human epidemiological and clinical research. The consequences of early exposure to ED have been demonstrated in disorders of the reproductive and endocrine systems, the occurrence of metabolic disorders and diseases, and neurological disorders. Some of the consequences are passed onto the next generations. In early childhood, it is important to detect and investigate the indicators of foetal exposure to harmful chemicals, to identify high- and low-risk groups for ED exposure, and to conduct prospective studies of the correlation of exposure with clinical outcomes throughout childhood and adolescence