DIETARY ADMINISTRATION OF ETHANOL AND METHANOL EXTRACTS OF Withania somnifera ROOT STIMULATES INNATE IMMUNITY, PHYSIOLOGICAL PARAMETERS AND GROWTH IN NILE TILAPIA Oreochromis niloticus

U istraživanju je procijenjena učinkovitost etanola i metanolnih ekstrakata korijena ljekovite biljke Withania somnifera na imunostimulativna svojstva i rast Nilsketilapije Oreochromis niloticus. Korijeni Withanie ekstrahirani su vodom, etanolom, metanolom, metilenkloridom, heksanom i sukcesivnim metanolom. Izmjereni su sadržaji fenola i flavonoida te antiradikalna aktivnost svih ekstrakata. Nakon toga, izvršena je hranidba nilske tilapije (n=126) hranom koja je sadržavala različite koncentracije (0, 0,3, 0,5 i 0,7 g kg-1 hrane) etanola i metanolnih ekstrakata korijena W. somnifera tijekom 30 dana kroz 3 ponavljanja. Pri usporedbi s kontrolnom hranidbom, ribe hranjene hranom obogaćenom biljnim ekstraktom indicirale suznačajno bolje (P <0,05) imunološke, hematološke i biokemijske pokazatelje te parametre rasta. Riba hranjena hranom koja sadrži ekstrakt etanola u koncentraciji od 0,7g kg-1 imala je najveće imunološke (fagocitna aktivnost, aktivnost respiratornog praska, lizozim u serumu, ukupni protein, ukupni imunoglobulin), hematološke (ukupna crvena krvna zrnca, hemoglobin, hematokrit, ukupnobijelih krvnih zrnaca, limfocita) i biokemijske (smanjena aktivnost glutationa, glutation-reduktaza) pokazatelje te najviše parametre rasta (masa, prirast, specifičnu stopurasta). Prema rezultatima, istraživani biljni ekstrakt može djelovati kao sredstvo za uklanjanje slobodnih radikala u ribljim tkivima te posjeduje sposobnost zaštite tkiva,pritom povećavajući zdravlje riba.Efficacy of ethanol and methanol extracts of medicinal herb Withania somnifera roots was evaluated in Nile tilapia Oreochromis niloticus on immunostimulation and growth. Withania roots were extracted with water, ethanol, methanol, methylene chloride, hexane, successive methanol. Phenol, flavonoid content and antiradical activity of all the extracts weremeasured. Ethanol extract showed the highest phenol, flavonoid content and antiradical activity followed by methanol extract. Subsequently, Nile tilapia (n = 126) were fed diets containing different concentrations (0.0, 0.3, 0.5 and 0.7 g kg-1 feed) of ethanol and methanol extracts of W. somnifera roots for 30 days (3 replicates). Fish fed plant extract fortified diets showed significantly better (P<0.05) immunological, haematological, biochemical and growth parameters compared to the fish fed control diet. Fish fed dietcontaining ethanol extract at the concentration of 0.7 g kg-1 feed showed the highest immunological (phagocytotic activity, respiratory burst activity, serum lysozyme, total protein, total immunoglobulin), haematological (total red blood cells, haemoglobin, hematocrit, total white blood cells, lymphocyte), biochemical (reduced glutathione, glutathione reductase activity) and growth (final weight, weight gain, daily weight gain, specific growth rate) parameters. The plant extract might act as potent free radical scavenger in fish tissues and have tissue protecting ability, thus increasingfish health

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Melatonin ameliorates H2O2-induced oxidative stress through modulation of Erk/Akt/NFkB pathway

Abstract Background Improper control on reactive oxygen species (ROS) elimination process and formation of free radicals causes tissue dysfunction. Pineal hormone melatonin is considered a potent regulator of such oxidative damage in different vertebrates. Aim of the current communication is to evaluate the levels of oxidative stress and ROS induced damage, and amelioration of oxidative status through melatonin induced activation of signaling pathways. Hepatocytes were isolated from adult Labeo rohita and exposed to H2O2 at three different doses (12.5, 25 and 50 µM) to observe peroxide induced damage in fish hepatocytes. Melatonin (25, 50 and 100 μg/ml) was administered against the highest dose of H2O2. Enzymatic and non-enzymatic antioxidants such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) was measured spectrophotometrically. Expression level of heat shock proteins (HSP70 and HSP90), HSPs-associated signaling molecules (Akt, ERK, cytosolic and nuclear NFkB), and melatonin receptor was also measured by western blotting analysis. Results H2O2 induced oxidative stress significantly altered (P < 0.05) MDA and GSH level, SOD and CAT activity, and up regulated HSP70 and HSP90 expression in carp hepatocytes. Signaling proteins exhibited differential modulation as revealed from their expression patterns in H2O2-exposed fish hepatocytes, in comparison with control hepatocytes. Melatonin treatment of H2O2-stressed fish hepatocytes restored basal cellular oxidative status in a dose dependent manner. Melatonin was observed to be inducer of signaling process by modulation of signaling molecules and melatonin receptor. Conclusions The results suggest that exogenous melatonin at the concentration of 100 µg/ml is required to improve oxidative status of the H2O2-stressed fish hepatocytes. In H2O2 exposed hepatocytes, melatonin modulates expression of HSP70 and HSP90 that enable the hepatocytes to become stress tolerant and survive by altering the actions of ERK, Akt, cytosolic and nuclear NFkB in the signal transduction pathways. Study also confirms that melatonin could act through melatonin receptor coupled to ERK/Akt signaling pathways. This understanding of the mechanism by which melatonin regulates oxidative status in the stressed hepatocytes may initiate the development of novel strategies for hepatic disease therapy in future