Naringenin protects AlCl3/D-galactose induced neurotoxicity in rat model of AD via attenuation of acetylcholinesterase levels and inhibition of oxidative stress

Currently prescribed medications for the treatment of Alzheimer\u27s disease (AD) that are based on acetylcholinesterase inhibition only offer symptomatic relief but do not provide protection against neurodegeneration. There appear to be an intense need for the development of therapeutic strategies that not only improve brain functions but also prevent neurodegeneration. The oxidative stress is one of the main causative factors of AD. Various antioxidants are being investigated to prevent neurodegeneration in AD. The objective of this study was to investigate the neuroprotective effects of naringenin (NAR) against AlCl3+D-gal induced AD-like symptoms in an animal model. Rats were orally pre-treated with NAR (50 mg/kg) for two weeks and then exposed to AlCl3+D-gal (150 mg/kg + 300 mg/kg) intraperitoneally for one week to develop AD-like symptoms. The standard drug, donepezil (DPZ) was used as a stimulator of cholinergic activity. Our results showed that NAR pre-treatment significantly protected AD-like behavioral disturbances in rats. In DPZ group, rats showed improved cognitive and cholinergic functions but the neuropsychiatric functions were not completely improved and showed marked histopathological alterations. However, NAR not only prevented AlCl3+D-gal induced AD-like symptoms but also significantly prevented neuropsychiatric dysfunctions in rats. Results of present study suggest that NAR may play a role in enhancing neuroprotective and cognition functions and it can potentially be considered as a neuroprotective compound for therapeutic management of AD in the future

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Effects of ultrasonic processing on the quality properties of fortified yogurt

This study evaluated the effect of ultrasonic processing on functional yogurts fortified with banana-resistant starch (BRS) and green papaya powder (GPP). Ultrasonication technology (80% amplitude, 8 min at 20 kHz frequency) was utilized as an alternative to conventional thermal treatment (85 °C, 30 min) to improve functional yogurts' physical and textural properties. A total of 6 set-type yogurt groups were prepared by ultrasonication (UT) and conventional treatment (CT). Based on the textural studies and correlation (Pearson’s) plots, fortified and UT samples were more stiff, firm, sticky, adhesive, and viscous (least elastic) compared to the CT samples. All of the tested yogurts maintained a remarkable number of viable colony counts (≥7.23 log CFU/mL) during the storage. Ultrasonication significantly (p < 0.05) changed the L, a*, and b* color values. The ultrasonic processing reduced whey syneresis and improved the water-holding capacity in fresh and stored yogurts. Further, it retained the fatty acid profile of fortified yogurts. However, ultrasonication negatively affected, i.e., reduced the total polyphenol content and antioxidant activity of yogurts as compared to the conventionally (thermal) treated counterparts. Overall, ultrasound technology can be a potential alternative to thermal treatment for the improved quality and safety of fortified yogurts

Characterization of Green and Yellow Papaya (<i>Carica papaya</i>) for Anti-Diabetic Activity in Liver and Myoblast Cells and Wound-Healing Activity in Fibroblast Cells

Obesity and diabetes, often characterized as “metabolic syndrome”, have been recognized as two of the most important public health issues worldwide. The objective of the present research was to evaluate green and yellow papaya for anti-oxidation and anti-diabetic properties. Leaves, skin, pulp, and seed samples from papayas were freeze-dried and then extracted in water or 80% methanol. The extracts were used to determine total polyphenolic content and anti-oxidation activities, and to determine biological activities, including glucose uptake, Glut-2 expression, triglyceride reduction, and wound-healing activity. Our data demonstrated that methanol and water extracts of green and yellow papaya have similar concentrations of polyphenols in skin (10–20 mg/g dry powder), leaf (25–30 mg/g dry powder), and pulp (1–3 mg/g dry powder) fractions. However, both methanol and water extracts of seeds from yellow papaya have substantially higher concentrations of polyphenols compared to green papaya. Both water and methanol extracts of yellow papaya exhibited higher anti-oxidation activity compared to green papaya in skin (50–60%), pulp (200–300%), and seeds (10–800%). Old leaves also showed greater anti-oxidation activity (30–40%) compared to new leaves. Pulp extracts from both yellow and green papaya stimulated greater glucose uptake, but only pulp from green papaya stimulated glucose uptake in muscle cells. Similarly, pulp extract stimulated glucose transporter Glut-2 expression in liver cells. The skin, pulp, and seeds of green or yellow papaya showed triglyceride-lowering activity in liver cells by 60–80%, but samples taken from yellow papaya had a more potent effect. Seeds from both green and yellow papaya significantly stimulated the migration of fibroblasts in the wounded area by 2–2.5-fold compared to the untreated control. Consistent with these data, seeds from both green and yellow papaya also significantly stimulated collagen synthesis in fibroblast cells by almost 3-fold. In conclusion, our data indicate that different parts of papaya produce stimulatory effects on glucose uptake, Glut-2 expression, TG reduction, and wound-healing activities. This study concludes that different parts of the papaya can be beneficial for preventing diabetes and diabetes-related wound healing

Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus Communis on Inflammatory Response in Mouse Macrophages

(1) Introduction: Reactive oxygen species (ROS) and nitric oxide (NO) are key signaling molecules that play important roles in the progression of inflammatory disorders. The objective of this study was to explore the use of myrtucommuacetalone-1 (MCA-1), as a novel compound of natural origin and a potential anti-inflammatory agent. (2) Methodology: The anti-inflammatory potential of MCA-1, which was isolated from Myrthus communis Linn, was determined by assaying superoxide, hydrogen peroxide, and nitric oxide production in macrophages. Furthermore, the effects of the compound were analyzed via phosphorylation and translocation of the transcription factor NF kappa B, which is a key regulator of iNOS activation. The effect of MCA-1 on the inducible nitric oxide synthase (iNOS) enzyme was also examined using in silico docking studies. The anticancer potential for MCA-1 was evaluated with an MTT cytotoxic assay. (3) Results: In stimulated macrophages, MCA-1 inhibited superoxide production by 48%, hydrogen peroxide by 53%, and nitric oxide (NO) with an IC50 of &lt;1 &micro;g/mL. MCA-1 also showed a very strong binding pattern within the active site of the inducible nitric oxide synthase enzyme. Furthermore, 25 &micro;g/mL of MCA-1 inhibited inducible nitric oxide synthase expression and abolished transcription factor (NF&kappa;B) phosphorylation and translocation to the nucleus. Cytotoxicity analyses of MCA-1 on 3T3 mouse fibroblasts, CC1 liver cell line, J774.2, macrophages and MDBK bovine kidney epithelial cell, yielded IC50 values of 6.53 &plusmn; 1.2, 4.6 &plusmn; 0.7, 5 &plusmn; 0.8, and 4.6 &plusmn; 0.7, &micro;g/mL, respectively. (4) Conclusion: Our results suggest that MCA-1, a major phloroglucinol-type compound, shows strong anti-inflammatory activity and has a potential to be a leading therapeutic agent in the future

Poster # 503 Factors determining outcome of hematopoietic cell transplantation in patients with acute lymphoblastic leukemia at King Faisal specialist hospital and research center, Riyadh, Saudi Arabia

Background: Hematopoietic cell transplantation (HCT) is used as a viable treatment option for Acute Lymphoblastic Leukemia (ALL) whose disease demonstrates dismal prognosis with chemotherapy.Objectives: Determining factors that affect outcome after HCT.Design/Method: Records of 82 patients with ALL who underwent HCT (2005–2011) were reviewed after approval from institution review board. Data extracted included those related to clinical characteristics of the patients and their outcome.Results: Forty five patients were male (54.80%). Median age at HCT was 7.46 years (range 0.98–14.31), median time to HCT after diagnosis was 12.56 months. Ten patients were below the age of one year (12%). All patients were in complete remission (CR) at the time of HCT. 40 patients were in CR1, 35 in CR2 and 7 in CR3 at the time of HCT. In 83 transplants, 64 patients received HCT from HLA-identical related donors and 19 from other donors (1 or 2 antigens mismatch cord blood [CB] or one antigen mismatch sibling or related bone marrow [BM]). Stem cell source was BM in 65(78%) and CB in 18(22%). All patients were given myeloablative conditioning regimen. Overall (OS) in our patients was 58.8% and event free survival(EFS) was 54.3%. Median follow-up time for the cohort was 47.2 ± 4.3 months (95%CI: 38.7–55.6) .49 patients were alive with a median follow-up time of 47.2 months (Min: 6.1, Max: 109.9). 17 patients survived for more than 5 years (Min: 61.4, Max: 109.9) months. The cumulative incidence of acute GVHD was 4.8 ± 2.3 and of chronic GVHD was 8.9 ± 3.2. Median time to ANC and platelet recovery was 17 days (range 12–43) and 28 days (range 15–98) respectively. One patient acquired CMV infection after transplant. No one developed VOD, Hemorrhagic cystitis or other complication. Patient\u27s age at HCT and gender, donor‘s HLA status and gender, source of transplant and CR status at HCT did not significantly affect the probability of OS and EFS.Conclusion: Our results show a favorable outcome to HCT for ALL patients comparable to published data, and no single factor was associated with superior outcome. OS and EFS in cord blood recipient graft is similar to BM recipient graft

Walnut supplementation reverses the scopolamine-induced memory impairment by restoration of cholinergic function via mitigating oxidative stress in rats: A potential therapeutic intervention for age related neurodegenerative disorders

The brain is highly susceptible to the damaging effects of oxidative reactive species. The free radicals which are produced as a consequence of aerobic respiration can cause cumulative oxygen damage which may lead to age-related neurodegeneration. Scopolamine, the anti-muscarinic agent, induces amnesia and oxidative stress similar to that observed in the older age. Studies suggest that antioxidants derived from plant products may provide protection against oxidative stress. Therefore, the present study was designed to investigate the attenuation of scopolamine-induced memory impairment and oxidative stress by walnut supplementation in rats. Rats in test group were administrated with walnut suspension (400 mg/kg/day) for four weeks. Both control and walnut-treated rats were then divided into saline and scopolamine-treated groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg dissolved in saline) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM), and novel object recognition task (NOR) followed by estimation of regional acetylcholine levels and acetylcholinesterase activity. In the next phase, brain oxidative status was determined by assaying lipid peroxidation, and measuring superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Results showed that scopolamine-treatment impaired memory function, caused cholinergic dysfunction, and induced oxidative stress in rats compared to that saline-treated controls. These impairments were significantly restored by pre-administration of walnut. This study demonstrates that antioxidant properties of walnut may provide augmented effects on cholinergic function by reducing oxidative stress and thus improving memory performance