Uloga polinezasićenih masnih kiselina u inflamaciji

Low-grade systemic inflammation is at the base of the most chronic non-communicable diseases, which are reaching epidemic proportions worldwide. Key players in the regulation of inflammation are n-6 and n-3 polyunsaturated fatty acids (PUFAs), in particular arachidonic acid (n-6) and eicosapentaenoic acid (n-3). They are precursors of eicosanoids - signaling molecules involved in modulating the intensity and duration of inflammatory responses. Eicosanoids derived from n-6 PUFAs have proinflammatory actions, while those derived from n-3 PUFAs act anti-inflammatory. Therefore, dietary intake of n-6 and n-3 PUFAs, as well as their ratio, could markedly affect the pathogenesis and manifestation of many chronic diseases associated with low-grade inflammation. This review will focus on the relationship between dietary PUFAs and inflammation, with reference to PUFAs status in plasma phospholipids in Serbian population.U osnovi većine hroničnih nezaraznih bolesti, koje širom sveta dostižu epidemijske razmere, leži 'tiha' inflamacija. Ključni igrač u regulaciji inflamacije su polinezasićene masne kiseline (PNMK) n-6 i n-3 familije, posebno arahidonska (n-6) i eikozapentaenska kiselina (n-3). One su prekursori eikozanoida - signalnih molekula koji su uključeni u intenzitet i trajanje inflamatornog odgovora. Eikozanoidi poreklom od n-6 PNMK deluju proinflamatorno, dok oni poreklom od n-3 PNMK imaju anti-inflamatorno dejstvo. Zbog toga dijetarni unos n-6 i n-3 PNMK, kao i njihov odnos, može značajno da utiče na patogenezu i manifestaciju mnogih hroničnih oboljenja koja su povezana sa 'tihom' inflamacijom. Ovaj pregledni rad se bavi vezom između unosa PNMK i inflamacije, sa osvrtom na status n-3 i n-6 masnih kiselina u fosfolipidima plazme u populaciji u Srbiji

Crosstalk between dietary patterns, obesity and nonalcoholic fatty liver disease

The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising worldwide, paralleling the epidemic of obesity. The liver is a key organ for the metabolism of proteins, fats and carbohydrates. Various types of fats and carbohydrates in isocaloric diets differently influence fat accumulation in the liver parenchyma. Therefore, nutrition can manage hepatic and cardiometabolic complications of NAFLD. Even moderately reduced caloric intake, which leads to a weight loss of 5%-10% of initial body weight, is effective in improving liver steatosis and surrogate markers of liver disease status. Among dietary patterns, the Mediterranean diet mostly prevents the onset of NAFLD. Furthermore, this diet is also the most recommended for the treatment of NAFLD patients. However, clinical trials based on the dietary interventions in NAFLD patients are sparse. Since there are only a few studies examining dietary interventions in clinically advanced stages of NAFLD, such as active and fibrotic steatohepatitis, the optimal diet for patients in these stages of the disease must still be determined. In this narrative review, we aimed to critically summarize the associations between different dietary patterns, obesity and prevention/risk for NAFLD, to describe specific dietary interventions’ impacts on liver steatosis in adults with NAFLD and to provide an updated overview of dietary recommendations that clinicians potentially need to apply in their daily practice

Role of Corticosteroids in Drug-Induced Liver Injury. A Systematic Review

Introduction: Apart from cessation of the implicated agent leading to drug-induced liver injury (DILI), there is no standard therapy for DILI. Corticosteroids have been used in DILI, although their efficacy is unclear. Published data showed either beneficial effects or no improvement associated with steroid therapy. The aim of the current study was to perform a systematic review of the role of corticosteroids in the treatment of DILI. Methods: A search was performed in PubMed, searching for the terms: “corticosteroids” and “drug-induced liver injury”. Observation studies were included, but case reports excluded. Results: A total of 24 papers were retrieved. Most of these were observational studies on the effects of corticosteroids in moderate/severe DILI (n = 8), reports on the corticosteroid treatment in patients with drug-induced autoimmune hepatitis (DI-AIH) (n = 5), and effects of corticosteroids in drug-induced fulminant acute liver failure (ALF, n = 2). Furthermore, treatment of corticosteroids in patients with liver injury due to check point inhibitors (CPIs) was addressed in nine studies. In moderate/severe DILI, six out of eight studies suggested steroid treatment to be beneficial, whereas two studies showed negative results. All five observational studies on the effects of corticosteroids in DI-AIH showed good therapeutic response with rapid and long lasting effects after discontinuation of corticosteroids and without evidence of relapse. Steroid therapy was not associated with improved overall survival in patients with drug-induced fulminant ALF. CPIs-induced liver injury was found to improve spontaneously in 33–50% without corticosteroids, and the rate of patients who were treated responded to steroids in 33–100% (mean 72%). Conclusions: The majority of studies analyzing the effects of corticosteroids in moderate/severe DILI have demonstrated beneficial effects. However, this was not the case in drug-induced fulminant ALF. Patients with DI-AIH had an excellent response to corticosteroids. The majority of those with CPIs-induced liver injury responded to corticosteroids; however, patients without treatment usually recovered spontaneously. The observational design and comparison with historical controls in these studies makes it very difficult to draw conclusions on the efficacy of corticosteroids in DILI. Therefore, there is a strong need for a randomized controlled trial to properly assess the role of corticosteroids in DILI

Biological aspects of application of nanomaterials in tissue engineering

Millions of patients worldwide need surgery to repair or replace tissue that has been damaged through trauma or disease. To solve the problem of lost tissue, a major emphasis of tissue engineering (TE) is on tissue regeneration. Stem cells and highly porous biomaterials used as cell carriers (scaffolds) have an essential role in the production of new tissue by TE. The cellular component is important for the generation and establishment of the extracellular matrix, while a scaffold is necessary to determine the shape of the newly formed tissue and facilitate migration of cells into the desired location, as well as their growth and differentiation. This review describes the types, characteristics and classification of stem cells. Furthermore, it includes functional features of cell carriers - biocompatibility, biodegradability and mechanical properties of biomaterials used in developing state-of-the-an scaffolds for TE applications, as well as suitability for different tissues. Moreover, it explains the importance of nanotechnology and defines the challenges and the purpose of future research in this rapidly advancing field

Liver disease and COVID-19: The link with oxidative stress, antioxidants and nutrition

Varying degrees of liver injuries have been reported in patients infected with the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). In general, oxidative stress is actively involved in initiation and progression of liver damage. The liver metabolizes various compounds that produce free radicals. Maintaining the oxidative/antioxidative balance is important in coronavirus disease 2019 (COVID-19) patients. Antioxidant vitamins, essential trace elements and food compounds, such as polyphenols, appear to be promising agents, with effects in oxidative burst. Deficiency of these nutrients suppresses immune function and increases susceptibility to COVID-19. Daily micronutrient intake is necessary to support anti-inflammatory and antioxidative effects but for immune function may be higher than current recommended dietary intake. Antioxidant supplements (βcarotene, vitamin A, vitamin C, vitamin E, and selenium) could have a potential role in patients with liver damage. Available evidence suggests that supplementing the diet with a combination of micronutrients may help to optimize immune function and reduce the risk of infection. Clinical trials based on the associations of diet and SARS-CoV-2 infection are lacking. Unfortunately, it is not possible to definitively determine the dose, route of administration and best timing to intervene with antioxidants in COVID-19 patients because clinical trials are still ongoing. Until then, hopefully, this review will enable clinicians to understand the impact of micronutrient dietary intake and liver status assessment in COVID-19 patients

Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU145 human prostate cancer cells

Gamma-irradiation (gamma-IR) is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of Co-60 gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD), specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P lt 0.001) antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control) to 49% (IR cells), with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death

Polinezasićene masne kiseline u zdravlju i bolesti

Polyunsaturated fatty acids (PUFAs) are necessary for overall health. Two PUFAs families, n-6 and n-3 fatty acids, are physiologically and metabolically distinct. The proportion of PUFAs in serum and erythrocyte phospholipids, which depends on endogenous metabolism controlled by genetic polymorphisms and dietary intake, is an important determinant of both health and disease. Both n-3 and n-6 PUFAs are processed to powerful promoters of eicosanoids synthesis at the cyclooxygenase and lipoxygenase level. Evidence from observational and intervention studies suggest that n-3 PUFAs are cardio-protective, perhaps through their anti-inflammatory, anti-arrhythmic, lipid-low­ering and antihypertensive effects. In contrast, dietary n-6 PUFAs have pro-inflammatory effects. Low n-3 and elevated n-6 PUFAs levels were found in patients with cancer on different sites. The present review focuses on current knowledge related to PUFAs intake and status in health and disease, with reference to the Serbian population.Polinezasićene masne kiseline (PMK) su neophodne za normalno funkcionisanje organizma. Dve PMK familije, n-6 i n-3 masne kiseline se fiziološki i metabolički razlikuju. Udeo PMK u fosfolipidima seruma i eritrocita je važan pokazatelj zdravlja i bolesti, i zavisi od endogenog metabolizma, koji je kontrolisan genetskim polimorfizmom, i unosa hrane. I n-6 i n-3 PMK su prekursori za sintezu eikozanoida na ciklooksigenaznom i lipooksigenaznom nivou. Opservacione i interventne studije ukazuju da n-3 PMK imaju kardioprotektivni efekat, delujući anti-inflamatorno, anti-aritmogeno, hipolipidemično i antihipertenzivno. Nasuprot tome, smatra se da n-6 PMK imaju pro-inflamatorno dejstvo. Nizak nivo n-3 i povišen udeo n-6 PMK je pokazan kod pacijenata sa različitim tipovima maligniteta. U okviru ovog rada dat je pregled najnovijih saznanja o dijetarnom unosu i biomarkerima statusa PMK u promociji zdravlja i prevenciji bolesti, sa posebnim osvrtom na rezultate u našoj populaciji

Efekat dugotrajnog napornog vežbanja na masnokiselinski profil fosfolipida plazme kod rukometaša

Background/Aim. Consensus on the exercise effect on the fatty acid metabolism has not been reached, and probably depends on the type of sports (aerobic, anaerobic or mixed). The aim of this study was to investigate effect of long-term handball training on the body composition, lipid profile and the plasma phospholipid fatty acid composition in female and male younger players. Methods. Seventeen female and 15 male active handball players, aged 16-20 years, who competed at the national/international level, were enrolled in the study. A control group was established from healthy, sedentary individuals (13 females and 19 males, aged 17-21 years), comparable to the athletes in terms of age, sex and body mass index. Results. In both groups of handball players a higher percentage of palmitoleic acid and alpha linolenic acid (18:3, n-3), were found and lower percentage of oleic acid and docosahexaenoic acid (22:6, n-3), when compared with corresponding control group. On the other hand, the lower level of stearic acid and estimated activity of plasma elongase was detected in female players than in sedentary women. Furthermore, higher proportion of linoleic acid (18:2, n-6), n-6 polyunsaturated fatty acids (PUFA) and total PUFA was found only in female players in comparison to the control group. Conclusion. The observed differences between handball players and sedentary individuals showed that handball training influenced lipid and fatty acid metabolism. Follow-up of these changes could indicate potential need for supplementation or nutritional intervention in young handball players.Uvod/Cilj. Konsenzus o uticaju treniranja na metabolizam masnih kiselina nije postignut, a taj uticaj verovatno zavisi od tipa sporta - aerobno, anaerobno ili mešovito vežbanje. Cilj ove studije bio je da se ispita efekat dugotrajnog, aktivnog treniranja rukometa na telesnu kompoziciju, profil lipida i masnih kiselina fosfolipida plazme kod mlađih kategorija rukometaša oba pola. Metode. U studiju je bilo uključeno 17 devojaka i 15 mladića, starosne dobi od 16 do 20 godina koji treniraju rukomet i takmiče se na nacionalnom i internacionalnom nivou. Kontrolnu grupu činilo je 13 devojaka i 19 mladića starosti od 17 do 21 godine, koji su bili uporedivi sa sportistima po godinama, polu i indeksu telesne mase. Rezultati. Procenat palmitoleinske i alfa-linolenske kiseline (18:3, n-3) bio značajno viši, dok je procenat oleinske i dokozaheksaenske kiseline (22:6, n-3) bio značajno niži u fosfolipidima plazme kod obe grupe sportista u odnosu na kontrolnu grupu. Sa druge strane, niži nivo stearinske kiseline i procenjene aktivnosti elongaze, ali i visok nivo linolne kiseline (18:2, n-6), ukupnih n-6 masnih kiselina, kao i ukupnih polinezasićenih masnih kiselina, utvrđen je kod rukometašica u odnosu na ispitanice iz kontrolne grupe, dok u grupi muškaraca nisu utvrđene takve razlike. Zaključak. Utvrđene razlike između rukometaša i rukometašica, sa jedne strane, i kontrolne grupe, sa druge strane, ukazale su na to da treniranje rukometa utiče na metabolizam lipida i masnih kiselina. Praćenje tih promena moglo bi ukazati na moguću potrebu za suplementacijom kod mladih rukometaša i rukometašica

Lipid Peroxidation and Antioxidant Supplementation in Neurodegenerative Diseases: A Review of Human Studies

Being characterized by progressive and severe damage in neuronal cells, neurodegenerative diseases (NDDs) are the major cause of disability and morbidity in the elderly, imposing a significant economic and social burden. As major components of the central nervous system, lipids play important roles in neural health and pathology. Disturbed lipid metabolism, particularly lipid peroxidation (LPO), is associated with the development of many NDDs, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), all of which show elevated levels of LPO products and LPO-modified proteins. Thus, the inhibition of neuronal oxidation might slow the progression and reduce the severity of NDD; natural antioxidants, such as polyphenols and antioxidant vitamins, seem to be the most promising agents. Here, we summarize current literature data that were derived from human studies on the effect of natural polyphenols and vitamins A, C, and E supplementation in patients with AD, PD, and ALS. Although these compounds may reduce the severity and slow the progression of NDD, research gaps remain in antioxidants supplementation in AD, PD, and ALS patients, which indicates that further human studies applying antioxidant supplementation in different forms of NDDs are urgently needed

Neuroinflammation in Autism and Supplementation Based on Omega-3 Polyunsaturated Fatty Acids: A Narrative Review

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction across multiple contexts and restricted, repetitive patterns of behavior, interests and activities. The maternal status of polyunsaturated fatty acids (PUFA) regulates microglial activity and neuroinflammatory pathways during a child’s brain development. In children with ASD, the metabolism of PUFA is thought to be deficient or abnormal, leading to increased production of proinflammatory cytokines, increased oxidative stress and an imbalance in the formation and action of neurotransmitters. In addition, nutritional deficits in omega-3 PUFA may affect gut microbiota and contribute to ASD by the gut–brain axis. The aim of this study was to review the possible role of neuroinflammation in ASD development and the effect of omega-3 PUFA supplementation in children with ASD. Due to a wide heterogeneity across RCTs, no definitive conclusion about omega-3 PUFA effects in ASD can be drawn. Supplementation with PUFA could be considered as one of the aspects in regulating the biological status of the organism and could provide added value to standard medical and psychological interventions for reducing behavioral deficits