Evaluation of neuroprotective properties of two synthetic prenylated xanthone analogues against paraquat and 6- hydroxydopamine toxicity in human neuroblastoma SHSY5Y cells

Purpose: To investigate whether two synthetic prenylated xanthone analogues - 1,3,6,8-tetrahydroxy- 9H-xanthen-9-one (SX1) and 1,3,6-trihydroxy-2-(3-methylbut-2-enyl)-9H-xanthen-9-one (SX2) - are potential candidates for neuroprotection against paraquat- and 6-hydroxydopamine (OHDA)-induced human neuroblastoma SH-SY5Y cell death.Methods: SH-SY5Y cells were treated with SX1 and SX2, and the maximum non-toxic dose (MNTD) were obtained by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MTT assay was also used to assess the ability of MNTD and half MNTD (HMNTD) doses of SX1 and SX2 to protect against the neurotoxicity of 200 μM paraquat and 100 μM 6-OHDA. Intracellular ROS production by SHSY5Y cells treated or untreated with SX1 or SX2 was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay.Results: SX1 and SX2 MNTDs at concentrations of 1850 nM and 105 nM, respectively, did not significantly (p > 0.05) provide neuroprotection against paraquat-induced SH-SY5Y cell death. Only SX2 MNTD and HMNTD significantly (p < 0.05) protected SH-SH5Y cells against 6-OHDA-induced cell death by 10 and 17 % improved cell viability. Although intracellular ROS production was significantly attenuated by SX1 HMNTD and MNTD, this did not improve cell viability against paraquat-induced cell death.Conclusion: These results reveal that SX2 confers neuroprotection on 6-OHDA-induced SH-SY5Y neurotoxicity. Further investigations to elucidate the detailed molecular mechanisms of neuroprotection by SX2 are warranted.Keywords: Prenylation, Xanthone derivatives, Neuroprotection, Paraquat, Dopamine, Neurotoxicity, Human neuroblastoma SH-SY5Y cell, 6-Hydroxydopamin

Phylogenetic characterization of genes encoding for viral envelope glycoprotein (ORF5) and nucleocapsid protein (ORF7) of porcine reproductive & respiratory syndrome virus found in Malaysia in 2013 and 2014

Background: Porcine reproductive and respiratory syndrome (PRRS) is one of the most expensive diseases of modern swine production & results in annual economic losses and cost the industry over 600 million USD in U.S. alone and billions of dollars worldwide. Two atypical PRRS cases were observed in 2013 and 2014 characterized by late-term abortion, fever and sudden increase in sow mortality which persisted for a prolonged period of time. Methods: Lungs, lymph nodes and other samples were collected for disease investigation. Sequencing of the viral envelope glycoprotein (ORF5) and nucleocapsid protein (ORF7) of PRRSV was done using the BigDye Terminator v3. 1 cycle sequencing kit chemistry. The phylogenetic tree was constructed by using the Maximum Likelihood method, generated by Mega 6.06®. Results: Analysis of the ORF5 and ORF7 showed high degree of sequence homology to PRRSV parent vaccine strain VR-2332, RespPRRSV and other mutant/chimeric virus strains. Conclusions: Our study suggests that recombination events between vaccine strains and field isolates may contribute to PRRSV virulence in the field

Safety assessment of tocotrienol supplementation in subjects with metabolic syndrome: a randomised control trial

Previous studies have reported that tocotrienols (T3) possess many distinct properties such as antioxidant, cardioprotective, neuroprotective, anti-cancer, anti-inflammatory and anti-angiogenic, which are beneficial for the improvement of human health. However, there is limited data available on the safety assessment of T3 compared to tocopherols (T). A randomised, double-blinded, cross-over and placebo-controlled human clinical trial was conducted to determine the safety and tolerance of T3 supplementation in 31 subjects with metabolic syndrome. The subjects were supplemented with tocotrienol-rich fraction (TRF) 200 mg or placebo capsules twice daily for two weeks followed by a post-intervention visit. Results showed that T3 supplementation had no significant adverse effect on the red blood cell (RBC), white blood cell (WBC) and platelet counts between TRF (5.10 ± 0.78 × 1012 litre-1, 7.35 ± 1.59 × 109 litre-1, 279.45 ± 73.86 × 109 litre-1, respectively) and placebo interventions (5.13 ± 0.76 × 1012 litre-1, 7.25 ± 1.95 × 109 litre-1, 267.45 ± 68.72 × 109 litre-1, respectively). Measures of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT)) and albumin did not differ between TRF (25.68 ± 10.72 IU litre-1, 38.26 ± 24.74 IU litre-1, 43.61 ± 2.26 g litre-1, respectively) and placebo interventions (27.39 ± 16.44 IU litre-1, 42.23 ± 33.58 IU litre-1, 43.68 ± 2.15 g litre-1, respectively). This study indicated that supplementation with T3 at the dosage of 400 mg per day for 14 days did not induce haematoxicity and hepatotoxicity in subjects with metabolic syndrome

Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19

COVID-19 severity is associated with cytokine levels and lymphopenia, but the role of immune cell subsets is not well understood. Here the authors immunophenotype whole blood samples from 54 COVID-19 patients and find that the immature neutrophil-to-VD2 T-cell ratio is associated with severe COVID-19

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Bioactivities and chemical constituents of several ferns in Malaysia, with emphasis on Blechnum orientale Linn.

In the preliminary study to find new and natural sources of antioxidant, tyrosinase inhibition and antibacterial compounds, methanolic extracts from fifteen fern species were investigated. The total phenolic content (TPC) was determined using the Folin-Ciocalteau method and the antioxidant capacities were measured using the DPPH radical scavenging, ferric reducing power (FRP), metal ion chelating power and β–carotene bleaching (BCB) assays. Five fern species that possessed strong DPPH radical scavenging activity, FRP and BCB activity were Blechnum orientale L., Cyathea latebrosa (Wall. Ex. Hook) Copel, Cibotium barometz (L.) J. Sm., Drynaria quercifolia (L.) J. Sm. and Dicranopteris linearis (Burm.) Underwood var. linearis. Strong ion chelating activity was shown by Pteris vittata L. and Pteris venulosa Bl. Moderate tyrosinase inhibition activity was found in B. orientale and C. latebrosa, while antibacterial activities were exhibited by B. orientale, D. linearis and C. barometz. Five solvent extracts of B. orientale (BO) and C. barometz (CB) were prepared by suspending the respective methanolic crude extracts in water and successively extracting with petroleum ether, chloroform, ethyl acetate and butanol. HPLC and LC-MS analyses identified rutin, chlorogenic acid, kaempferol, caffeic acid, apigenin-7,4-diglucoside, luteolin-7-rutinoside and luteolin triglycoside in BO, while rutin and esculin were found in CB. Bioactivities investigations showed that the ethyl acetate- (BOeaf), butanol- (BObutf) and water- (BOwatf) soluble extracts possessed strong radical scavenging (IC50 8.6-13.0 µg/mL), antibacterial activity against Bacillus cereus, Micrococcus luteus, methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and Stapylococcus epidermidis (minimum bactericidal concentration MBC 15.6-250 µg/mL) and selective cytotoxic activity against human colon cancer cells HT29 (IC50 27.5-42.9 µg/mL). Tyrosinase inhibition activities were strongest in BOeaf (70% at 2.5 mg/mL) and BOwatf (51%). The water extract (BOwatf) was found to be safe (i.e. low toxicity) for oral consumption following an oral acute toxicity study. The traditional usage of BO in wound healing was verified in an in vivo study using the water extract, as revealed by the significant wound size reduction, mean epithelisation time and the increased collagen synthesis in the 2% extract-treated group, compared with those of the vehicle-group. A polymeric proanthocyanidin (condensed tannins) and a flavan-3-ol were isolated from the active solvent extracts of BO. Spectroscopic analyses showed that the proanthocyanidin was a heterogeneous polymer possessing epicatechin subunits with 2-12 degree of polymerization and co-existing with minor units of epiafzelechin and epigallocatechin at C4-C8 interflavanoid linkages. Bioactivity studies recorded strong radical scavenging activity (IC50 5.6 ± 0.1 µg/mL), bactericidal activity and selective cytotoxicity towards colon cancer cells HT29 (IC50 7.0 ± 0.3 µg/mL). Further studies were conducted to assess the cytotoxic potential and apoptosis induction effects on HT29. Cell death was found to be time and dose dependent. The induction of apoptosis was confirmed using fluorescence microscopy, FITC-Annexin V staining coupled with flow cytometry, caspase colorimetric assays and western blot analyses. The molecular mechanism underlying the apoptosis in the extract-treated HT29 cells involved caspases -3, -6 and -8. These results provided the first evidence of the apoptotic induction capability of the proanthocyanidins of B. orientale via an extrinsic-mediated pathway. The flavan-3-ol isolated was characterized as 4β-carboxymethyl-(-)-epicatechin which possessed antioxidant potential (IC50 14.66 ± 0.29 µM) comparable to that of ascorbic acid. The overall results indicate the promising potential of the proanthocyanidins of B. orientale as a natural therapeutic source to treat oxidative related medical health problems, for the chemotherapy of colon cancer and a source of bactericidal agent

ORIGINAL ARTICLE Associated Factors of Sleep Quality and Behavior among Students of Two Tertiary Institutions in Northern Malaysia

The objective of the study was to investigate the associated factors of sleep quality and behavior among Malaysian tertiary students. The response rate to the questionnaire study was 41.0%. 1,118 students (M = 486, F = 632; mean age = 20.06 ± 1.53 years) were recruited from Universiti and Kolej Tunku Abdul Rahman (Perak campuses) who completed a sleep quality and behavior questionnaire based o

Antioxidant, antibacterial and tyrosinase inhibiting activities of extracts from Myristica fragrans Houtt

Aims: To evaluate the antioxidant, antibacterial and tyrosinase inhibiting activities of the methanolic extracts of the leaf and fruit pericarp from Myristica fragrans. Study Design: In vitro assays. Place and Duration of Study: School of Biosciences, Taylor’s University (Jan – December 2013) Methodology: Total phenolic content (TPC) was assessed using Folin-Ciocalteu’s method. The antioxidant activity was evaluated via radical scavenging against 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric ion reducing power (FRP) and ferrous ion chelating (FIC). Antibacterial activity was assessed using disc diffusion on four Gram-positve bacteria: M. luteus, E. faecalis, S. aureus, B. cereus and three Gram-negative bacteria: P. aeruginosa, E. coli and K. pneumoniae, followed by determination of minimum inhibitory concentration and minimum bactericidal concentration using broth dilution assays. Tyrosinase inhibiting activity was assessed using L-3,4-dihydroxyphenylalanine, L-DOPA as the substrate. Results: The methanolic leaf extracts exhibited significantly higher TPC 2712-2779 mg gallic acidequivalent/100 g in contrast to that obtained from the pericarp. The leaf extracts also exhibited significantly stronger DPPH radical scavenging activity (2962-3787 mg ascorbic acid equivalent/100 g), ferric reducing activity (1383-1653 mg gallic acid equivalent/100 g) and chelating activity, as compared to the pericarp extracts. Leaf extracts were effective against all Gram-positve bacteria tested: M. luteus, E. faecalis, S. aureus, B. cereus (minimum inhibitory concentration 250-500 μg/mL; minimum bactericidal concentration 250-500 μg/mL). Studies on the tyrosinase inhibiting properties for applications in preventing food browning or treating hyperpigmentation disorders, showed significantly stronger activities exhibited by the leaf extracts (80-81%) as compared to that shown by pericarp (27-31%). Conclusion: The present results suggest that nutmeg leaf could be employed as a natural antioxidant, antibacterial and tyrosinase inhibiting agent for applications in pharmaceuticals or in functional foods