OBJECTIVE: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the production of pro-inflammatory mediators.
METHOD: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay.
RESULTS: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators.
CONCLUSIONS: These findings provided evidence that PS root extracts confer neuroprotection against Aβ- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer's disease (AD).
METHODS: This is a cross-sectional study in which patients receiving IV alteplase in Hospital Universiti Sains Malaysia, from January 2017 to April 2020 were recruited. Demographical data, National Institutes of Health Stroke Scale (NIHSS) scores, door-to-needle time were recorded. Modified Rankin scale (mRS) scores were evaluated at 90 days after initial therapy. Good and poor functional outcomes were defined as 0-2 and 3-6, respectively.
RESULTS: A total of 30 patients were included in the study with a mean age of 59±11.47 years old. 76.7% of them were male and the rest were female. From the study, onset-toneedle time was 197.47±51.74 minutes, whereas door-toneedle time was 120.93±53.63 minutes. Seventeen (56.3%) patients achieved a favourable score of 0-2 on the mRS at 90 days after treatment. Haemorrhagic transformation occurred in eight (26.7%) of the patients with a mortality rate of 13.3%.
CONCLUSION: 56.7% of our patients showed improvement in the mRS at 90 days post thrombolysis for AIS. Higher baseline NIHSS scores and diabetes mellitus were associated with poorer functional outcomes after thrombolysis.
MATERIALS AND METHODS: The inhibitory effects of hexane (LHXN), dichloromethane (LDCM), ethyl acetate (LEA) and methanol (LMEOH) extracts from leaves of PS on Aβ-induced production and mRNA expression of pro-inflammatory mediators in BV-2 microglial cells were assessed using colorimetric assay with Griess reagent, ELISA kit and real-time RT-PCR respectively. Subsequently, MTT reduction assay was used to evaluate the neuroprotective effects of PS leaf extracts against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y neuroblastoma cells. The levels of tau proteins phosphorylated at threonine 231 (pT231) and total tau proteins (T-tau) were determined using ELISA kits.
RESULTS: Polar extracts of PS leaves (LEA and LMEOH) reduced the Aβ-induced secretion of pro-inflammatory cytokines (IL-1β and TNF-α) in BV-2 cells by downregulating the mRNA expressions of pro-inflammatory cytokines. The inhibition of nitric oxide (NO) production could be due to the free radical scavenging activity of the extracts. In addition, conditioned media from Aβ-induced BV-2 cells pre-treated with LEA and LMEOH protected SH-SY5Y cells against microglia-mediated neurotoxicity. Further mechanistic study suggested that the neuroprotective effects were associated with the downregulation of phosphorylated tau proteins.
CONCLUSIONS: The present study suggests that polar extracts of PS leaves confer neuroprotection against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y cells by attenuating tau hyperphosphorylation through their anti-inflammatory actions and could be a potential therapeutic agent for Alzheimer's disease.
BIOLOGICAL SIGNIFICANCE: This study reveals the compositional details of the venom proteome of Pakistani spectacled cobra (Naja naja). The protein subtypes, proteoforms, and relative abundances of individual proteins were comprehensively revealed in this study, following a venom decomplexing proteomic approach. The Pakistani cobra venom is unique among the rest of the N. naja venom composition reported thus far, as it contains a high abundance of alpha-neurotoxins (predominated by long neurotoxins); these are highly potent post-synaptic neuromuscular blockers that cause paralysis and are principal toxins that account for the high lethality of the venom (LD50=0.2μg/g in mice). In contrast, previous reports showed that the N. naja venoms of India and Sri Lanka had a lower content of neurotoxins and a relatively higher value of LD50. The Pakistani cobra venom demonstrated sufficient immunoreactivity toward three antivenom products manufactured outside Pakistan (including the Indian product VINS), however the potency of antigen binding was the highest toward Naja kaouthia monovalent antivenom, a heterologous antivenom raised against a long neurotoxin-predominated venom of the Thai monocled cobra. From the practical standpoint, the findings indicate that the treatment of N. naja envenomation in Pakistan may be improved by the production of a locale-specific antivenom, in which the antivenom produced contains more antibodies that can target and react more specifically with the highly abundant lethal neurotoxins in the Pakistani N. naja venom.
DESIGN/METHODOLOGY/APPROACH: Current research is a descriptive-correlational quantitative survey to determine teachers' psychological status, e-teaching competencies and working motivation during Movement Control Order (MCO) to contain the Covid-19 pandemic. The study sample consists of 595 secondary school teachers selected via convenient sampling. Quantitative data are collected from an online survey through the questionnaires with demographic, psychological status (stress, anxiety and depression), e-teaching competencies (teaching, monitoring and evaluation) and teaching motivation developed by the researchers were distributed during the MCO period. SPSS 25 is applied, Statistical measures such as Cronbach's alpha, means, percentage and standard deviation were employed to analyze the data to obtain the value of the school teachers' psychological status, e-teaching competencies and teaching motivation. Consequently, a Pearson correlation table was created to show the analysis of the school teachers' psychological status and competencies in e-teaching.
FINDINGS: This finding indicated that the teachers' psychological factors in stress, anxiety and depressed are moderate, the teachers' competencies in e-teaching is moderate as well as teachers' working motivations is also the moderate level. However, the highest mean value was found among the variables, this is revealed that despite the challenges during the Covid-19 outbreak, teachers showed positive and strong motivation in conducting e-teaching. Additionally, the result showed a negative relationship between psychological status and e-teaching competencies (-0.286, p < 0.01), as well as reported a negative relationship between dimension of psychological status and competencies in e-teaching.
LIMITATION & RECOMMENDATIONS: This study has its limitations. This study is included only Selangor teachers and given that the information obtained from the study was gather from secondary schools, the generalizability might be limited. future research may consider expanding the scope from secondary schools to primary schools' teachers and then to university lecturers. Perhaps the scope is expanding, so more information could be obtaining and help researchers understand the teachers' competencies in e-teaching, psychological status and work motivation.
METHOD: Data between 1996 to 2015 from a population-based cancer registry in Sarawak Malaysia was analyzed. Crude incidence rates and age-standardized rates (ASR) were calculated and compared between ethnic groups and locations (administrative division) and Joinpoint regression analysis was done to analyze trends.
RESULT: A total of 3643 cases of NPC were recorded with male to female ratio of 2.5:1. Annualised age-standardized incidence rates able 2) for men is 13.2 cases per 100,000 population (95% CI: 12.6, 13.7) and for women is 5.3 cases per 100,000 population (95% CI: 5.0, 5.6). The highest incidence rates were reported among the Bidayuh population and it ranks among the highest in the world. Trend analysis noted an overall reduction of cases, with a significant decrease between 1996 and 2003 (annual percentage reduction of incidence by 3.9%). Analysis of individual ethnic groups also shows a general reduction with exception of Iban males showing an average 5.48 per cent case increase between 2009 to 2015, though not statistically significant.
CONCLUSION: Comparing the incidences with other registries, the Bidayuh population in Sarawak remained among the highest in the world and warrants close attention for early screening and prevention strategies.
METHODS: A cross-sectional survey was conducted among the coaches and athletes in Malaysia. Data were collected using a convenience sampling approach over a 6-month period. The study was carried out in two phases using two independent samples of coaches and athletes to assess the construct validity and internal consistency of the Malay version of the CART-Q. The CART-Q consisted of 11 items measuring three constructs: i) closeness (four items), ii) commitment (three items) and iii) complementarity (four items). In phase 1, the subjects consisted of 211 coaches (21 years old-65 years old) from both sexes and from individual and team sports, ranging from levels 1 to 5. In phase 2, the subjects consisted of 362 athletes (12 years old-39 years old), also from both sexes and from individual and team sports. The statistical analyses performed included confirmatory factor analysis (CFA) to validate the translated version scale, composite reliability (CR), average variance extracted (AVE) and internal consistency (Cronbach's alpha).
RESULTS: In phase 1, the sample of coaches, with 190 males (90.0%) and 21 females (10.0%), had a mean age of 38.6 (SD = 8.74) years old. The major sport type was archery (19.0%). The CFA revealed adequate fit indices with all 11 items retained (root mean square error of approximation [RMSEA] = 0.059, comparative fit index [CFI] = 0.964, Tucker and Lewis Index [TLI] = 0.950, standardised root mean square residual [SRMR] = 0.037). The CR values were closeness = 0.874, commitment = 0.566 and complementarity = 0.757. The AVE values were closeness = 0.357, commitment = 0.194 and complementarity = 0.275. The Cronbach's alpha values were closeness = 0.867, commitment = 0.553 and complementarity = 0.794. In phase 2, the sample of athletes, with 175 males (48.1%) and 189 females (51.9%), had a mean age of 20.2 (SD = 3.35) years old. The major sport type was archery (11.5%). The CFA revealed satisfactory fit indices with all 11 items retained (RMSEA = 0.092, CFI = 0.948, TLI = 0.924, SRMR =.038). The CR values were closeness = 0.893, commitment = 0.786 and complementarity = 0.949. The AVE values were closeness = 0.401, commitment = 0.253 and complementarity = 0.418. The Cronbach's alpha values were closeness = 0.900, commitment = 0.772 and complementarity = 0.900.
CONCLUSION: Overall, the study findings supported the conclusion that the Malay version of the CART-Q has adequate psychometric properties to assess the perceptions of coaches and athletes regarding their relationship.
OBJECTIVE: The present study aimed to investigate neuroprotective properties of PS against Aβ-induced neurotoxicity and to evaluate its potential mechanism of action.
METHODS: Neuroprotective effects of hexane (HXN), dichloromethane (DCM), ethyl acetate (EA) and methanol (MEOH) extracts from leaves (L) and roots (R) of PS against Aβ-induced neurotoxicity were investigated in SH-SY5Y human neuroblastoma cells. Cells were pre-treated with PS for 24 h followed by 24 h of induction with Aβ. The neuroprotective effects of PS were studied using cell viability and cellular reactive oxygen species (ROS) assays. The levels of extracellular Aβ and tau proteins phosphorylated at threonine 231 (pT231) were determined. Gene and protein expressions were assessed using qRT-PCR analyses and western blot analyses, respectively.
RESULTS: Hexane extracts of PS (LHXN and RHXN) protected SH-SY5Y cells against Aβ-induced neurotoxicity, and decreased levels of extracellular Aβ and phosphorylated tau (pT231). Although extracts of PS inhibited Aβ-induced ROS production, it was unlikely that neuroprotective effects were simply due to the anti-oxidant capacity of PS. Further, mechanistic study suggested that the neuroprotective effects of PS might be due to its capability to regulate amyloidogenesis through the downregulation of BACE and APP.
CONCLUSION: These findings suggest that hexane extracts of PS confer neuroprotection against Aβ- induced neurotoxicity in SH-SY5Y cells by attenuating amyloidogenesis and tau hyperphosphorylation. Due to its neuroprotective properties, PS might be a potential therapeutic agent for Alzheimer's disease.