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Abstract
The present study evaluated the neuroprotective and antiepileptic efficacy of ellagic acid (EA) encapsulated in calcium-alginate nanoparticles (Ca2+-ALG NPs) in pentylenetetrazol (PTZ)-induced seizures in male mice. EA was encapsulated in ALG NPs using a nanospray drying method followed by ionotropic crosslinking with Ca2+. Characterization of the developed Ca2+-crosslinked EA-ALG NPs showed spherical, high stability NPs; successful loading of EA within crosslinked ALG NPs; and sustained release of EA. Male Swiss albino mice were divided into ten groups as follows; Group I- (control), Group II (50 mg EA /kg) - (EA), Group III polyethylene glycol (PEG), Group IV EA NPs (50 mg/kg) - (EA NP), Group (50 mg/kg alginate) V void V NPs - (void NPs), Group VI: (37.5 PTZ mg/kg) -(PTZ), Group VII: PTZ and EA – (PTZ-EA). Group VIII: animals received PTZ and PEG concurrently (PTZ-PEG). Group IX; animals received PTZ and void NPs concurrently - (PTZ-void). Group X: animals received PTZ and EA NPs concurrently (PTZ-EA NPs). PTZ was used to induce experimental epilepsy. Ca2+-ALG NPs prevented seizures throughout the experimental period and had a more prominent effect than free EA did. Ca2+-ALG NPs prevented increased glutamate, decreased GABA concentrations and ameliorated increased amyloid-β and homocysteine levels in the serum and brain. Ca2+-EA-ALG NPs were superior to free EA in improving increased IL-6 and TNF-α. Ca2+-ALG NPs ameliorated PTZ-induced oxidative stress, as evidenced by decreased 4HNE levels and enhanced GSH, GR and GPx levels in the brain. These changes were accompanied by amelioration of apoptosis and its regulating proteins, including Cytochrome C, P53, Bax, Bcl2 and caspase-3 and caspase-9, and protected against DNA damage. Histological examination of the hippocampus confirmed that the neuroprotective effect of Ca2+-EA-ALG NPs was superior and more effective than that of free EA.

Abstract

Background
Influenza A virus (IAV) is still a major health threat. The clinical manifestations of this infection are related to immune dysregulation, which causes morbidity and mortality. The usage of traditional medication with immunomodulatory properties against influenza infection has been increased recently. Our previous study showed antiviral activity of quercetin-3-O-α-L-rhamnopyranoside (Q3R) isolated from Rapanea melanophloeos (RM) (L.) Mez (family Myrsinaceae) against H1N1 (A/PR/8/34) infection. This study aimed to confirm the wider range of immunomodulatory effect of Q3R on selective pro- and anti-inflammatory cytokines against IAV in vitro, to evaluate the effect of Q3R on apoptosis pathway in combination with H1N1, also to assess the physical interaction of Q3R with virus glycoproteins and RhoA protein using computational docking.

Methods
MDCK cells were exposed to Q3R and 100CCID50/100 μl of H1N1 in combined treatments (co-, pre- and post-penetration treatments). The treatments were tested for the cytokines evaluation at RNA and protein levels by qPCR and ELISA, respectively. In another set of treatment, apoptosis was examined by detecting RhoA GTPase protein and caspase-3 activity. Molecular docking was used as a tool for evaluation of the potential anti-influenza activity of Q3R.

Results
The expressions of cytokines in both genome and protein levels were significantly affected by Q3R treatment. It was shown that Q3R was much more effective against influenza when it was applied in co-penetration treatment. Q3R in combination with H1N1 increased caspase-3 activity while decreasing RhoA activation. The molecular docking results showed strong binding ability of Q3R with M2 transmembrane, Neuraminidase of 2009 pandemic H1N1, N1 and H1 of PR/8/1934 and Human RhoA proteins, with docking energy of − 10.81, − 10.47, − 9.52, − 9.24 and − 8.78 Kcal/mol, respectively.

Conclusions
Quercetin-3-O-α-L-rhamnopyranoside from RM was significantly effective against influenza infection by immunomodulatory properties, affecting the apoptosis pathway and binding ability to viral receptors M2 transmembrane and Neuraminidase of 2009 pandemic H1N1 and human RhoA cellular protein. Further research will focus on detecting the detailed specific mechanism of Q3R in virus-host interactions.

Keywords
Influenza a virus Quercetin-3-O-α-L-rhamnopyranoside Cytokine Apoptosis Molecular docking

Serum asprosin levels and bariatric surgery outcomes in obese adults

Posted by CY Wang, TA Lin, KH Liu, et al. on 2019-12-18 18:37:00

Abstract
BACKGROUND/OBJECTIVES:
Asprosin is a novel fasting-induced glucogenic and orexigenic protein hormone. The clinical function of asprosin in obesity is currently unknown. This study investigated the association between asprosin abundance and the outcome of bariatric surgery.
SUBJECTS/METHODS:
Patients with body mass index more than 35 kg/m2 were recruited for the Obesity and Clock for Elegant Aging Registry in 2011-2016. Body weight changes, blood sugar, and asprosin were assessed in 117 patients receiving bariatric surgery and 57 non-obese subjects as normal control. Primary outcomes of excess weight loss percentage at 6 months after bariatric surgery were determined at follow-up.
RESULTS:
Asprosin levels were significantly higher in obese patients than in non-obese subjects (2360 ± 5094 vs. 307 ± 832 ng/ml, p < 0.0001). Multivariate analyses showed a significant association of asprosin abundance with excess body weight loss percentage at 6 months after surgery (p < 0.0001). After adjusted for age, sex, smoking, HbA1c, cholesterol, and triglyceride, serum asprosin level was the only independent predictor of 6 months excess weight loss percentage after bariatric surgery. Asprosin levels decreased significantly 6 months after bariatric surgery (162.2 ± 169.1 ng/ml). Furthermore, there was no association between asprosin and serum glucose levels in our study.
CONCLUSION:
This study provides novel evidence that higher asprosin concentrations before bariatric surgery were associated with the weight reduction magnitude at 6 months after surgery. Further studies are warranted to investigate whether asprosin has direct functions to modulate body weight regulation in humans after bariatric surgery.

Decreased Circulating Levels of Asprosin in Obese Children

Posted by WJ Long, XM Xie, CQ Du, et al. on 2019-12-16 19:01:00

Abstract
BACKGROUND:
Circulating asprosin is a newly discovered adipokine that triggers the release of hepatic glucose stores and increases appetite. Asprosin levels are elevated in adult obese men as well as in mice, and reductions in asprosin protect against the hyperinsulinism associated with metabolic syndrome in mice with diet-induced obesity, which indicates a potential therapeutic role of asprosin in obesity and type 2 diabetes.
OBJECTIVES:
Few data on asprosin in children are available, which is why this study aimed to assess concentrations of fasting asprosin, as well as its relationship to parameters of glucose and lipid metabolism, in children.
METHODS:
Data on clinical and metabolic parameters were collected from 40 healthy normal-weight and 47 obese children. Circulating asprosin levels were measured using an ELISA.
RESULTS:
The concentrations of fasting asprosin were lower in the obese children (9.24 ± 4.11 ng/mL) than in the normal-weight controls (12.33 ± 4.18 ng/mL, p < 0.001). When comparing the two groups by sex, both the boys and the girls showed similar trends. In within-group comparison, the asprosin levels were lower in boys than in girls only in the obese group (8.13 ± 4.10 vs. 10.61 ± 3.78 ng/mL, p = 0.013) but not in the control group. Interestingly, asprosin was correlated with ALT after adjusting for age and sex in all participants; in boys, asprosin was correlated with BMI, HOMA-IR, insulin, and HDL after adjusting for age.
CONCLUSIONS:
Concentrations of asprosin were significantly lower in obese children than in normal-weight children, and there was a gender difference in asprosin concentration. Our results suggest a complex role for asprosin in energy metabolism.

The serum level of irisin, but not asprosin, is abnormal in polycystic ovary syndrome patients

Posted by CL Chang, SY Huang, YC Hsu, et al. on 2019-12-10 19:19:00

Abstract
Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, oligo- or anovulation, and/or polycystic ovary. It frequently presents with dyslipidemia and insulin resistance. Recent studies have shown that the white adipose tissue-derived asprosin is elevated in humans with insulin resistance. Because many PCOS patients have a propensity to develop dyslipidemia and/or insulin resistance, asprosin metabolism could be dysregulated in PCOS patients. Accordingly, we investigated serum levels of asprosin, irisin, GIP, androgens, LH, glucose, insulin, and lipids as well as HOMA-IR, QUICKI and ISI Matsuda in a cohort of 444 PCOS patients and 156 controls. Patients were stratified based on metabolic syndrome risk factors (ATPIII [+] and [−] groups), or BMI (overweight and lean groups). The irisin level was significantly correlated with body weight, SBP, DBP, Ferriman–Gallwey score, and levels of TSH, triglycerides, glucose and insulin in the overall population, and was elevated in ATPIII(+) and overweight PCOS patients compared to corresponding controls. By contrast, asprosin levels in PCOS, ATPIII(+), or overweight patients were similar to those of corresponding controls. This finding indicated that the regulation of irisin, but not asprosin, metabolism is abnormal in PCOS patients, and this metabolic characteristic is distinctly different from that of diabetes patients.

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