BACKGROUND: Informal caregivers are friends or relative who offer to care for stroke patients after discharge. The care deliveries typically occur without formal training or compensation. The COVID-19 pandemic may increase the level of responsibility of caregivers, resulting in potential negative effects on their overall well-being. METHODS: A cross-sectional study of 94 unpaid informal caregivers of stroke survivors completed an online survey. The stroke caregivers’ burden was measured using the Caregiver Burden Inventory (CBI). Social connection such as social isolation, loneliness and perceived social support was measured using the Lubben Social Network Scale-6 items, UCLA-3 items and Duke Social Support Index (DSSI-11 item), respectively. Sociodemographic data were also collected and analysed. RESULTS: Multiple linear regression analysis revealed that social support (β = -0.34, t = -3.46, p < .001) and loneliness (β = 0.33, t = 3.35, p = .001) significantly predicted the stroke caregivers’ burden. Social support had the major predictive effect, explaining 12% of the variance in caregivers’ burden (R2 = 0.12). Loneliness explained 11% (R2 = 0.11) and 8% (R2 = 0.08) of the variance in developmental and physical burdens, respectively. Social isolation was excluded and not a significant predictor of caregivers’ burden. Caregivers with tertiary education reported significantly higher burden (β = 0.28, t = 2.81, p = .006) than caregivers with secondary education. Education was also a significant predictor of developmental burden (β = 0.25, t = 2.47, p = .016), physical burden (β = 0.29, t = 2.89, p = .005), and emotional burden (β = 0.22, t = 2.12, p = .037). CONCLUSION: The burden experienced by stroke caregivers is linked to their social support, loneliness and educational levels. These findings provide further insight on the role of social support during COVID-19 and its contribution towards caregiver’ burden in an unprecedented time. Interventions that aim to enhance social support for caregivers could help to mitigate this issue and improve their overall well-being.

There is a substantial body of literature that examines health insurance participation among the general population in Malaysia. However, limited attention has been directed to the involvement of healthcare personnel in Malaysia in relation to their participation in health insurance. The primary aim of this research is to examine the impact of sociodemographic factors, attitude, general perceptions, and perceptions regarding health insurance benefits and ease of claims on the participation in personal health insurance among healthcare personnel in a private and a public hospital in Malaysia. This study employed self-administered questionnaires as the primary data collection instrument. The findings of the study indicate a notable disparity with regard to the participation in personal health insurance between gender, professional category, and healthcare sector that the healthcare personnel work in. Whereas there is no statistically significant difference found between age and length of service in relation to participation in personal health insurance among healthcare personnel. Furthermore, a significant and strong positive correlation exists between individuals' attitude, general perceptions, and perceptions of health insurance benefits, and their likelihood of engaging in personal health insurance. Having said that, collaboration among government bodies, healthcare institutions, and insurance providers in Malaysia is crucial to effectively implement programmes, strategies, and initiatives that aim to improve awareness and comprehension among healthcare personnel in Malaysia regarding the significance of personal health insurance. Keywords: Health insurance Participation, Attitude, General Perception, Benefits

Background: University students of the current generation face a plethora of stressors including family, academics, finances and social. Research indicates that academic stressors can affect eating habits in various ways. Students tend to eat an unbalanced meal or have diets consisting of too much starch, sugar and fat. Unbalanced nutrition due to stress can contribute to the development of diseases and impact their cognitive abilities. The prevalence of obesity has been on a rise in Malaysia and the prevalence of overweight and obesity had increased by 80 percent and 70 percent respectively in just under two decades. Objective: This study aims to determine the association of academic stressors and eating behaviours among students in a private university in Kuala Lumpur, Malaysia. Methodology: A cross-sectional quantitative research study was conducted among 183 pre-university students. Students were emailed an online questionnaire after systematic random sampling. The academic stressors of the subjects were assessed using the Academic Stress Questionnaire comprising of four categories of stressors: personal, relating to other people, environmental and scholarly. The Three Eating Factor Questionnaire Revised-18 Items was used to determine the eating behaviours of students which was categorised into: cognitive restraint, uncontrolled eating and emotional eating. Results: The results of this study were significant as there is an evidence of association between academic stressors and eating habits. The increase in academic stressors increases Cognitive Restraint, Uncontrolled Eating, and Emotional Eating. The results of the Pearson Correlation test reveal the mean of academic stressor to be 3.48 and mean of eating behaviour to be 2.23. R- value and p- value are 0.455 and 0.000 respectively. There is a positive correlation and statistically significant difference between both variables. Conclusion: The findings of this study illustrate the need for university initiatives focusing on academic stressors to combat unhealthy eating habits that hamper the wellbeing of students and may progress to disease. This may include revision of curriculum where there is shift away from exam assessments and more towards coursework. Other strategies could include support groups and awareness workshops. Keywords: Academic Stressors, Eating Behaviour, Students

Aims: With the rapid proliferation of data in healthcare it has provided an opportune platform creation of Artificial Intelligence (AI). AI has brought a paradigm shift for healthcare professionals, promising improvement in delivery and quality. This study aims to determine the perception of healthcare personnel on perceived ease of use, perceived usefulness, and subjective norm toward attitude for artificial intelligence acceptance. Methods: This is a cross-sectional single institutional study of employees’ perception of adopting AI in the hospital. The study population is all healthcare personnel of a private hospital. The inclusion criteria include all healthcare personnel involved with clinical management such as doctors, nurses, and others. The survey was conducted using a questionnaire adapted from Technology Acceptance Model and a four-point Likert scale was used for the measurement variables in this study. Data were analysed using IBM Statistical Package for the Social Sciences (SPSS) Version 26. Results: There were 96 respondents. This study started off with three hypotheses but has found that only two hypotheses have been accepted and one hypothesis has been rejected. H2 to H3 perceived usefulness and subjective norm respectively, showed positive relationship between their perception on artificial intelligence acceptance and were accepted However, H1 which was ease of use, was rejected as it did not generate a positive relationship between ease of use on attitude and artificial intelligence acceptance. Conclusion: This study has shown the significant relationship and the importance of ease of use, perceived usefulness, and subjective norm to the acceptance of AI. In the study results, there are determining factor and mostly those with most interaction with the patients and clinical management have a strong acceptance of AI in their practices. Key words: Artificial Intelligence, Acceptance, Healthcare, Healthcare Professionals

Dietary fat when consumed reduces hunger and impairs food intake by eliciting satiety signals and these signals are evoked by entry of triacylglycerol after hydrolization to fatty acids into the small intestine. 1,3-dipalmitoyl-2-oleoyglycerol (POP-), 1,3-distearoyl-2-oleoylglycerol (SOS-) and 1,2,3-triolein (OOO-) type of fats have different melting characteristics that may affect postprandial blood lipids, gut hormone concentrations, insulinemic response and selected cardiovascular disease markers in human volunteers. The main objective of this study is to compare the effects of edible fats with either palmitic acid (16:0) (palm mid-fraction) or stearic acid (18:0) (shea stearin) predominantly at the sn-1 and sn-3 positions on postprandial lipemia and gut hormone concentrations. A randomized, double-blind crossover (3 × 3 arms) orthogonal Latin-square design was used on 36 healthy adults (18 males, 18 females; mean age = 23 years). Each subject received 3 different test muffins (each containing 53 g of test fat) in random order separated by 2 weeks over a 6-week period. The test fats of different melting points were palm mid- fraction (PMF; POP-rich), shea stearin (SS; SOS-rich) and high- oleic sunflower oil (HOSF; OOO-rich) During a postprandial test, each subject was provided with a test muffin plus milkshake (total 3.67 MJ or 876 kcal) in the morning and blood samples were collected at half-hourly intervals until 4.0 hours. No significant difference (p>0.05) was observed between the 3 test meals for postprandial responses in plasma TC, Lp(a), apo(B), NEFA, GLP-1, PYY, ghrelin, VAS, PAI-1, IL-6, TNF-α, glucose, insulin and satiety (VAS scores). Plasma TAG peaked at about 4 hours; levels in the PMF- and HOSF- subjects were significantly higher (p<0.05) compared with SS-subjects after 90 minutes. PMF and HOSF exerted a higher postprandial GIP response (p<0.05) as compared to SS. Plasma C-peptide levels, as a measure of insulinemic response, rose sharply 5.5- folds in all groups, peaking after 90 minutes; levels in the SS group declined at a faster rate (p<0.05) than in the PMF- and HOSF- groups. The POP- and OOO- fats induced similar effects on all the biochemical/physiological outcome measures investigated. In contrast, the SOS- type fat (shea stearin) induced a slower rise (p<0.05) in postprandial TAG and GIP levels and a faster return of plasma C-peptide levels to baseline.

Airborne algae and cyanobacteria (AAC) have received much attention as their occurrence have been documented in several studies, including indoor environment. There has been concern whether AAC can trigger allergic response and thus, they may have ill health effects, especially in relation to sick building syndrome (SBS). There have been very few studies reported on the allergenicity of AAC. The main objective of this study was to assess the allergenic potential of three AAC, namely Scenedesmus sp., Cylindrospermum sp. and Hapalosiphon sp.1, which were isolated from an office building in Kuala Lumpur. The study was based on a mouse model, with the suspension of AAC powder in phosphate buffered saline (PBS) administered via nasal route. Naïve mice were sensitised to 1 mg/mL of AAC for 10 consecutive days during Phase I immunisation. In Phase II immunisation which was given after five resting weeks, the mice were re-challenged with 20 μL of AAC at two concentrations (0.01 and 1 mg/mL) for three consecutive days before they were sacrificed. The immune response was assessed based on white blood cell profiles, quantification of humoural and intracellular expression of IgE, TH2 predominant and inflammatory cytokines and histopathological examination. In general, the three AAC elicited greater immune response in mice challenged with high (1 mg/mL) concentration of AAC than with low (0.01 mg/mL) concentration. In mice challenged with Scenedesmus sp. at both low and high concentrations, there were elevated peripheral eosinophil and monocyte counts. Significantly higher levels of serum IgE (P<0.05) and IFN-γ (P<0.05) compared to negative control were also observed. The data collected 48 h after the last dose of immunisation also indicated possible cause of allergic airway inflammation, a chronic manifestation of respiratory allergy upon nasal exposure to the algal particles. On the other hand, Cylindrospermum sp. and Hapalosiphon sp.1 did not elicit type-1 hypersensitivity as both eosinophil counts and serum IgE levels were not elevated in the sensitised mice. The results suggest that the two airborne cyanobacteria provoked immune response differently. In mice challenged with Cylindrospermum sp. (1 mg/mL), there were elevated serum IL-4 (22.1 pg/mL, P<0.05). However, the increase in peripheral neutrophil counts (9.2%) against Cylindrospermum sp. (1 mg/mL) was not significant when negative control was compared. In comparison, in mice challenged with Hapalosiphon sp.1, there were elevations of serum IL-6 (4.8 pg/mL, P<0.05) yet the observed increase of peripheral lymphocyte counts (9.2%) was not statistically significant. In addition, the elevations in serum IFN-γ levels were highest in mice nasal challenged with Cylindrospermum sp. (71.9 pg/mL, P<0.05), followed by Hapalosiphon sp.1 (50.6 pg/mL, P<0.05). Taken together, the results suggest that nasal exposure to Cylindrospermum sp. and Hapalosiphon sp.1 may provoke inflammatory immune responses in the airway. Further studies are warranted to assess the potential health impact due to the allergenic potential of the AAC, especially with regards to the effect of continual exposure to low concentration of the algal particles over extended period of time.

Background: Since ancient times, Acupuncture was used to treat painful conditions in patient. Currently there is limited research evidence as to whether pregnant women are supportive of acupuncture treatment in maternity services for labour pain management in Malaysia. Objective: To evaluate the perception and acceptance of acupuncture as an alternative, non - pharmacological labour pain management (NPLPM) among antenatal women in a district region, Sandakan, state of Sabah in Malaysia. Method: This is a descriptive, cross-sectional study conducted using a convenient and voluntary sampling method. A total of 201 antenatal women were recruited in the antenatal clinic in a private hospital in Sandakan, Sabah, Malaysia. Data collection tool was a validated, self-administered bilingual questionnaire form consisting of Malay and English language version. All antenatal women regardless of their gestational age, who were attending the antenatal clinic, were included during the study period. The collected data were analysed using SPSS software. Results: 201(100%) respondents had completed and returned the questionnaire form. The study population generally have positive perceptions towards acupuncture. 51.7% of the responders are willing to accept acupuncture as an alternative NPLPM method if available. 35.8% of the responders are in the neutral group and 12 .5% of the responders are not willing to accept acupuncture as an option for their labour pain management. There was a statistically significant difference in acceptance of acupuncture as an alternative NPLPM method among those with and without acupuncture knowledge. Conclusion: About half of the study population are willing to accept acupuncture as a NPLPM method. Introduction of acupuncture for labour pain management can be beneficial and considered especially for woman who refused pharmacological treatment, who has contraindication for labour epidural and in rural region with limited resources. Patients' knowledge, awareness and past experience of acupuncture had a significant effect on acceptance of acupuncture for labour pain management. Keywords Perception, attitudes, knowledge, acupuncture, labour pain, Sabah

Objective: This systematic review aimed to determine the analgesic efficacy and safety of transdermal fentanyl patch as compared to other opioid therapy or placebo in pain management among the patients from different medical condition. Methods: 30 studies (22 randomised controlled trials and eight observational studies) were included for data synthesis, after searching and screening through PubMed, Excerpta Medica database (Embase), International Pharmaceutical Abstracts (IPA), Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Turning Research into Practice (TRiP) databases. Two authors independently screened the articles and assessed the quality of the studies. SIGN checklist and Cochrane Collaboration’s tool were applied to assess the risk of bias in observational and randomized controlled studies. Data on study background, interventions, outcomes measured and outcomes were synthesized into table forms. Results: Pain scores, adverse events and addiction risks were the primary outcomes in this systematic review. Transdermal fentanyl patch showed significant improvement in terms of pain scores when compared to placebo. When fentanyl patch was compared to other opioid treatment, the results were mostly comparable. In terms of adverse events, fentanyl patch and opioid treatment shared similar incidence adverse events with no significant difference. Conclusions: Transdermal fentanyl patch improved pain scores significantly compared to placebo while the opioid efficacy and safety were similar when compared with other opioid therapies. Other than that, the adverse events reported in fentanyl patch group has no statistical significant difference as compared to other opioid treatment. This result showed that transdermal fentanyl patches could be use as an alternative treatment in patients with moderate-to-severe chronic pain and who prefer non-invasive route of administration and much less frequent dosing. However, the outcome on addiction risk is limited.

The achievement of learning goals in laboratory practicals depends on both extrinsic and intrinsic factors, and could be limited by laboratory time, incurred cost, safety, self-efficacy, inadequate prior preparation by learners and different learning styles. Besides, face to face laboratory sessions could be continuously interrupted as seen during the COVID-19 pandemic. Hence, virtual laboratory simulation (vLAB) may be an appropriate e-learning tool to overcome these restrictions. In this study, students' perception about the usefulness of vLAB was determined by using DNA gel electrophoresis and PCR as case examples. The perception of Year 2 and 3 health science undergraduate students’ (N=87) was studied using a questionnaire consisting of 12 items, rated on a 5-point Likert-scale. In addition, students experience and learning from the vLAB was further explored using qualitative analysis. Results showed that all participants perceived vLAB well, with a median score of 4(Agree for all items in the questionnaire. It provides a meaningful learning experience and an authentic environment where students feel safe to practice what they have learnt in lectures. Moreover, vLAB facilitates individualised learning and enhances selfefficacy among students. In conclusion, vLAB prepares students for physical laboratory sessions by activating the prehension dimension of the Kolb’s learning cycle, hence complementing and strengthening the attainments of health sciences laboratory learning goals and outcomes.

The COVID-19 pandemic has had an immense impact on healthcare systems worldwide particularly in terms of infection control measures. Hospital Sungai Buloh has implemented a novel walk-away queuing system for outpatient clinics, namely the iQMS. This system enables infection control via facilitating social distancing whilst waiting for their appointments and affords waiting location flexibility. However, the factors affecting outpatients’ intention to use the iQMS is yet unknown, and this is the subject of this study. The Technology Acceptance Model (TAM), Perceived System Usability and sociodemographic factors were used to study this relationship. This study used a cross-sectional quantitative design utilizing a self-administered questionnaire to obtain data. The questionnaire comprised of sociodemographic factors, Perceived Usefulness, Perceived Ease of Use, Intention to use the iQMS and Perceived System Usability. Two hundred and fifty-four respondents completed the questionnaire, corresponding to a response rate of 87.8%. The questionnaire showed satisfactory construct validity, discriminant validity and reliability. Perceived Usefulness and Perceived Ease of Use had a significant impact on the Intention to use the iQMS, while Perceived System Usability showed a moderate positive relationship with the Perceived Ease of Use. Sociodemographic factors did not influence the Intention to use the iQMS. In conclusion, the Intention to use the iQMS is associated with the Perceived Ease of Use and Perceived Usefulness of the system. Keywords: COVID-19, Queue Management System, Technology Acceptance Model, System Usability Scale

Diabetes mellitus is a chronic metabolic disease and predicted to increase about 366 million cases globally by end of 2030. Type 2 Diabetes is characterized by abnormal insulin secretion followed by inability of beta cells to compensate for insulin resistance. Most individuals diagnosed with diabetes are found to be obese and obesity as well is one of the major risk factors contributing to diabetes. Although modern medicine is used to control blood glucose level in diabetic patients but there is demand for natural products as anti-diabetic agents due to the side effects seen in the current drugs. In this study, we explore Nephelium lappaceum.L’s (or locally known as rambutan rind) ability as an anti-hyperglycemic agent in a type 2 diabetic animal model. The rind of N. lappaceum is found to consist of high antioxidant activity and possess in-vitro anti-hyperglycemic activity. This study is aimed initially to prepare standardised ethanolic extracts of N. lappaceum rind, evaluate toxicity effects in rat model, develop obesity induced type 2 diabetes rat model and finally investigate the anti-glycemic effects of Nephelium lappaceum rind in the diabetic rat model. Ethanolic extraction was followed as previously described to obtain N. lappaceum rind extract. Geraniin being the major bioactive compound in N. lappaceum rind was detected in LC/MS and quantified using HPLC chromatogram method to ensure a standardised sample was prepared. Biological standardisation was also carried out by subjecting the N. lappaceum rind to both alpha glucosidase and alpha amylase assay’s and to establish its in-vitro anti-hyperglycemic activity. Toxicity studies of N. lappaceum rind were carried out in Sprague dawley rats. In the acute toxicity study, rats were given 50mg, 200mg, 1000mg and 2000mg/kg of N.lappaceum rind orally for 14 days whereas in the sub-chronic toxicity study the rats were given a low and high concentration of N. lappaceum rind for 28days (500mg and 2000mg/kg). Type 2 diabetes was seen to develop in the rat model by feeding them with a high fat diet for 12 weeks and injected with 55mg/kg streptozotocin and 210mg/kg nicotinamide. Then, the diabetes induced rats were treated with N. lappaceum rind at 500mg and 2000mg concentrations for 28 days. Positive control rats were treated with 200mg metformin. In this study, we obtained a 41.06% yield of ethanolic extracts from powdered N. lappaceum rind, while geraniin present in the extract was quantified at 33.0 ± 0.2 mg geraniin/g extract. N. lappaceum rind did not show any toxic effect in the rats both during acute and sub-chronic toxicity study. All biochemical analysis, histology of organs, body weight and relative organ weight clearly showed that there were no significant changes in treated rats. Our study also revealed that, the diabetes induced rats treated with 2000mg N. lappaceum showed reduction in blood glucose level and improved insulin levels which were similar to metformin treated group. Pancreas histology revealed that, the group treated with 2000mg of N. lappaceum had a good distribution of healthy islets and the treatment is comparable to the effect of metformin-treated group. Immunohistochemical staining with Glut-4 and PPAR-gamma antibody also markers for regeneration was over expressed in N. lappaceum treated group with large regenerating islets and the effects were similar to metformin-treated group. In conclusion, N. lappaceum rind extract was able to display anti-hyperglycemic activity at a dose of 2000mg/kg without any toxic effects in high fat diabetes-induced rats.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease, where the host immune system attacks the joints. This study used collagen-induced arthritis (CIA) animal model to study the effect of plant-derived antioxidants as the plant-derived antioxidants are known to reduce inflammatory responses in CIA. The aim of the study was to assess the efficacy of ethanol extract from the rind of the rambutan (Nephelium lappaceum) fruit to treat CIA in dark agouti (DA) female rats. Arthritis was induced in DA rats by injecting them with a commercial preparation of collagen from chicken sternal cartilage (4 mg/kg) mixed in complete Freund's adjuvant (CFA). Changes in body weight and joint thickness were monitored every five days from day 0 to 50 of the study. When the signs of arthritis were visible on day 25, the arthritic rats were fed with 300 mg/kg glucosamine or the standardised ethanolic extract (100 or 200 mg/kg) from the rind of the N. lappaceum fruit for 25 days (i.e. until day 50). At autopsy, the sera collected from the animals were tested for C-reactive protein (CRP) and the joints were harvested for histopathology and real-time polymerase chain reaction (qPCR) analysis. iii Both concentrations (100 and 200 mg/kg) of the ethanolic extracts from the rind of the N. lappaceum significantly reduced the arthritis-induced changes in body weight (p<0.05) and paw oedema (p<0.05). There was a significant reduction in the plasma CRP levels (p<0.05) in the treated groups. In addition, a significant reduction (p<0.05) in the arthritis-induced histopathological changes was observed after treatment with the N. lappaceum rind extract. Immunohistochemistry analysis showed that treatment with the N. lappaceum extracts had dose-dependent effects on matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) expression in the joints. There was a minimum of two-fold down regulation (p<0.05) of the TNF-α, COX-2 and NF-κB genes in the joints from arthritic rats treated with the N. lappaceum rind extracts (200 and 100 mg/kg) or glucosamine (300 mg/kg). Treatment with the N. lappaceum rind extracts or glucosamine appear to show regression of RA in the arthritic rats. In conclusion, oral supplementation of standardised ethanolic extract of N. lappaceum rind significantly suppressed pathophysiological, biochemical and histopathological changes induced by collagen administration in the CIA rats. Supplementation with the N. lappaceum extract may be beneficial in preventing the tissue damage and inflammatory conditions in arthritis.

Diminished antioxidant defence or increased production of reactive oxygen species in the biological system can result in oxidative stress which could lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several pro-inflammatory cytokines and mediators. Seaweeds have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties. This study aimed to evaluate the potential of brown (Padina australis and Sargassum polycystum) and green (Caulerpa racemosa) Malaysian seaweeds in inhibiting oxidative stress and neuroinflammation. Anti-oxidative activities of seaweeds were determined by measuring the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical and superoxide anion radical. Production of cytokines and PGE2 was measured using enzyme immunoassay and NO was measured using Griess reagent assay. In addition, cytotoxicity assays were conducted using MTT assay. Hexane extract of S. polycystum exhibited potent DPPH radical scavenging ability (IC50 0.16±0.00 mg/mL) and methanol extract of S. polycystum exhibited potent ABTS radical scavenging ability (IC50 0.85±0.02 mg/mL). Hexane extract of C. racemosa showed the strongest superoxide radical inhibitory effect (IC50 0.39±0.01 mg/mL). All extracts of P. australis, S. polycystum and C. racemosa significantly (P<0.05) reduced the production of PGE2, NO, TNF-α, IL-β and IL-6 in a dose dependent manner. At a concentration of α, IL-1β, IL-6) production and approximately more than 50% of NO production. PGE2 secretion was only suppressed by 20-30%. Isolation and structure elucidation of the seaweed compounds were evaluated using mass spectrometer, 1H and 13C Nuclear Magnetic Resonance Spectrometer. Hexane and dichloromethane extracts of S. polcystum and dichloromethane extract of P. australis afforded the same sterol identified as fucosterol and a pigment identified as pheophytin a. Another pigment identified as 132-hydroxy pheophytin a was isolated from methanol extract of S. polycystum. Hexane, dichloromethane and methanol extract of C. racemosa afforded one alkaloid which was identified as caulerpin. Pheophytin a showed the highest DPPH radical scavenging activity with the lowest IC50 value (0.14±0.01mg/mL). All of the seaweed compounds significantly (P<0.05) inhibited the production of PGE2, NO, TNF-α, IL-β and IL-6 in a dose dependent manner. Caulerpin inhibited 60-70% of cytokines, PGE2 and NO. As a conclusion, this study supports the potential application of these seaweeds for the treatment of AD.

The threat of pathogenic infections has almost been eradicated with the introduction of antibiotic treatment regimes. Unfortunately, the repetitive consumption and increasing doses of antibiotics have led to the manifestation of drug tolerance and resistance in microorganisms due to the natural selection process. As a result of this phenomenon, new antibiotics would need to be developed in order to overcome this tolerance/resistance. In this study, antibacterial effects as a result of the preliminary screening between several commercially available essential oils and beta-lactam antibiotics were investigated on multidrug resistant bacteria followed by the modes of action for resistance reversal capability in some of these essential oils. Out of 35 antibiotic-essential oil pairs tested, four showed synergistic effect (FIC ≤ 0.5) and 31 showed no interaction (FIC > 0.5 – 4.0). The preliminary results obtained highlighted the occurrence of a pronounced synergistic relationship between piperacillin/cinnamon bark oil, piperacillin/lavender oil, piperacillin/peppermint oil as well as meropenem/peppermint oil against Escherichia coli J53 R1 and E. coli J53 pMG309 respectively with FIC index in the range 0.26 – 0.5. The time-kill method was used to evaluate the bactericidal activities of essential oils alone or with antibiotics. A rapid and complete killing of bacteria was observed in piperacillin/peppermint, piperacillin/lavender and meropenem/peppermint combinations within 5 – 10 minutes of exposure time. Piperacillin/cinnamon bark combination showed a complete killing profile after 20 h of exposure. Analysis of the membrane permeability effects of essential oils on treated cultures through their stability against sodium dodecyl sulfate demonstrated that essential oils played a role in disrupting the bacterial cell membrane. The action of essential oils on membrane integrity was also confirmed through the decrease in the negative charge of cell surfaces. In addition, the morphology of cells post-treatment with essential oils alone and in combination with antibiotics showed corrugated surfaces and irregular rod-shaped forms under scanning electron microscopic analysis. The overall study emphasised the potential of peppermint, cinnamon bark and lavender essential oils as potential sources of new multi-targeted antimicrobial products. Reduction in the dosage of antibiotics could be employed as a treatment strategy to combat the onset of antibiotic resistance as well as to decrease its adverse effects.

Breast cancer cells often respond poorly to treatment because of their different subtypes such as low expression of the oestrogen, progesterone and receptor tyrosine-protein kinase erbB-2. Hence, there is a need to identify new molecules for the treatment. Radix Bupleurix contains glucosides, a class of oleanane derivatives called saikosaponins that have been widely used in Traditional Chinese Medicine for over a millennium. There are two main active components in Radix Bupleurix, Saikosaponin A (SSA) and Saikosaponin D (SSD), known to have a wide range of pharmacological actions. This study identifies the anti-cancer effect of SSA and SSD on breast cancer cell lines, MDA-MB-468, MCF7 and T47D. Our findings suggested that SSA and SSD can inhibit the growth of the breast cancer cell line in a dose-response-dependent manner. The IC50 for SSA and SSD ranges between 4.48 μM to 6.97 μM. SSA and SSD can inhibit cell migration and colony formation. Scratch assay results showed a significant area of closure compared to control (p < 0.05) after 120 hours. Furthermore, a combination assay showed no synergistic effect between SSA and SSD. In conclusion, these results suggest that SSA and SSD could be potential molecules for the treatment of breast cancer but further study is required to understand the pathway involved in the anti-cancer effect.

Copper complexes may serve as potential alternatives to platinum-based anticancer agents. By incorporating endogenous metal, such as copper, into metal complexes may reduce toxicity and solve other problems encountered by platinum-based antitumor drugs. A previous study had established that the chiral pairs of ternary copper(II) complex salts, [Cu(phen)(ala)(H2O)]NO3, where ala = alanine, dissociated to yield their respective [Cu(phen)(aa)(H2O)]+ and NO3- ions when dissolved in solution and these species were stable up to more than 24 hours. In this study, two pairs of optically pure chiral [Cu(phen)(ala)(H2O)]X • xH2O, where phen = 1,10-phenanthroline; X = NO3-; ala = L-alanine (L-ala) [LN] and D-alanine (D-ala) [DN]; and X = Cl-; ala = L-ala [LC] and D-ala [DC]; x = number of lattice water molecules, complex salts had been tested on MCF-7 breast cancer cells and its corresponding non-cancer cells, MCF-10A, to investigate the effect of chirality of the alanine and the change in couterion on their anticancer properties and their mechanisms of action. NCI-60 modified MTT assay and morphological study showed that the pairs of chiral ternary copper(II) compounds induced cytostatic and cytotoxic effect in a dose-dependent manner, and there was difference in cell proliferation inhibition on MCF-7 and MCF-10A cells for specific concentration range. The results also showed that chirality did affect their anti-proliferative effect on immortalised MCF-10A but not on cancer cells. However, there were insignificant differences between NO3- and Cl- pairs of the compounds towards MCF-7 and MCF-10A for 48-hour incubation. The ternary copper(II) compounds also induced dose-dependent cell population reduction towards other cancer and non-cancer cell lines, the compounds were selective towards cancer cells over normal cells. Interestingly, human breast carcinoma, MCF-7 was most responsive among the cancer cell lines tested while human hepatocellular carcinoma, HepG2, was the least sensitive towards the ternary copper(II) compounds. The results of screening of [LN] on the NCI panel of 60 human cancer cell lines did show leukaemia was the most resistant and melanoma was the most sensitive. The findings from morphological studies indicated that MCF-7 cells and MCF-10A cells treated with the ternary copper(II) compounds underwent decrease in healthy cells population and cell death by apoptosis. Apoptosis assay using Annexin V-FITC/PI double staining showed that the ternary copper(II) compounds were more selective towards MCF-7 as apoptotic cells in treated MCF-7 cells were more than those in treated immortalised breast MCF-10A cells. Cell cycle data analysis demonstrated that all the compounds suppressed MCF-7 cells growth by accumulate DNA fragments at SubG1 phase. The assay results from using 2’,7’-dicholofluorescein diacetate (DCFH-DA) showed that all the ternary copper(II) compounds induced increase in reactive oxygen species (ROS) in MCF-7 cells with increasing concentration and prolonged exposure (12 to 24 hours) compared to untreated cells. In contrast, the MCF-10A cells, treated under same conditions, showed lower overall ROS generation. The ternary copper(II) compounds induced greater mitochondrial membrane depolarisation in MCF-7 cells than in MCF-10A cells. The effect of all ternary copper(II) compounds on caspase-3/7 activity of MCF-7 cells was no significant for both 12- and 24-hour incubation but they induced distinctive but low increase of caspase-9 activity, especially at 24-hour incubation. In contrast, it was found that treating MCF-10A cells with increasing concentration of each of the ternary copper(II) compounds resulted in activation of both initiator caspase-9 and executor caspase-3/7. These results suggest that apoptosis induction in MCF-10A cells by the above compounds required activation of caspase-3/7 whereas that in MCF-7 did not, thereby implicating activation of different apoptosis pathways. Overall, these findings suggested that ternary copper(II) compounds killed the cancer cells by inducing ROS production, depolarising mitochondrial membrane, and activation of caspase-independent pathway. Therefore, the anticancer properties of the ternary copper(II) compounds involved multiple mode of actions and they also exhibited significant selectivity towards cancer cells rather than non-cancerous cells.

There is an urgent need in search of an insulin-sensitising agent exhibiting good safety, efficacy and tolerability profile for the prevention and treatment of type-2 diabetes mellitus. Catalpol, an iridoid glucoside, is the main bioactive component of Rehmannia glutinosa radix. Catalpol is reported to possess anti-oxidant, neuro-protective and glucose-lowering effects. The work described in this study aimed to examine the effects of catalpol in improving glycaemic control as well as insulin sensitivity in both skeletal muscles and liver of type-2 diabetes mellitus mice. Male C57BL/6N mice aged 5-6 weeks were placed on a high fat diet (60% kcal) for two weeks prior to streptozotocin (50 mg/kg, i.p.) administration for three consecutive days. Group fed with normal chow diet served as the normal control. Four groups of diabetic animals were administered orally with saline, catalpol (100 mg/kg), catalpol (200 mg/kg) or metformin (200 mg/kg) once per day for four consecutive weeks. Treatment of catalpol (200 mg/kg) significantly lowered fasting plasma glucose compared to diabetic control (p < 0.01), along with attenuation of insulin resistance by reducing HOMA-IR index. Catalpol improved insulin sensitivity in skeletal muscles through activating AMPK/SIRT1/PGC-1a pathway. The downstream effect was observed in improved mitochondrial respiration. Administration of catalpol increased the insulin sensitivity in liver by up-regulating PPAR-g and suppressing the expression of gluconeogenic enzymes. Besides, catalpol treatment improved lipid metabolism by regulating plasma adiponectin, plasma triglycerides and liver triglycerides levels. Collectively, catalpol (200 mg/kg) exerted anti-diabetic effects by improving glycaemic control, insulin sensitivity and mitochondrial function in skeletal muscles. Besides, catalpol improved insulin sensitivity in liver and lipid metabolism.

α-Mangostin has been explored by many researchers, and it is effective against bacteria and other microbes such as fungi and mycobacteria. Enterococcus faecalis (E. faecalis), Staphylococcus epidermidis (S. epidermidis), and Candida albicans (C. albicans) are the most prevalent biofilms that induce endodontic flare-ups and secondary infections. This research aimed to formulate and characterize palm oil-in-water based α-Mangostin nanoemulsion (PO-AMNE) endodontic irrigant and test its antimicrobial effectiveness against E. faecalis, S. epidermidis, and C. albicans biofilms with smear layer removal capability. In addition, it was tested for cytotoxicity in Immortalized Oral Kerantinocytes-OKF-6 cells. The optimization of the 0.2% PO-AMNE irrigant was performed using the Box-Behnken statistical design. The optimized 0.2% PO-AMNE irrigant was found to have a particle size of 340.9 nm with 0.246 PDI of the dispersed droplets and zeta potential (mV) of -27.2±0.7 mV. The MIC/mL values showed that 0.2% PO-AMNE (1.22±0.02) was comparable to 2% CHX (1.33±0.01) and 3.25% NaOCl (2.2±0.09) had the least inhibition for E. faecalis. 3.25% NaOCL showed the maximum inhibition on S. epidermidis (0.26±0.05), whereas 0.2% PO-AMNE (1.25±0.0) was comparable to 2% CHX (1.86±0.07). For C. albicans, 2% CHX (8.12±0.12) showed the least inhibition as compared to 0.2% PO-AMNE (1.23±0.02) and 3.25% NaOCl (0.59±0.02). The 0.2% PO-AMNE irrigant was then evaluated for antimicrobial efficacy using colony-forming units (CFU) against E. faecalis, S. epidermidis, and C. albicans biofilms. The 0.2% PO-AMNE was comparable to 3.25% NaOCl and 2% CHX in inhibiting the growth of biofilms. The 0.2% PO-AMNE irrigant was investigated for smear layer removal, and 0.2% POAMNE and 17% EDTA demonstrated comparable efficacy in removing the smear layer with a mean score of p<0.001. Finally, in Immortalized Oral Keratinocytes-OKF-6 cells, 0.2% POAMNE was less cytotoxic compared to 17% EDTA, 3.25% NaOCl, and 2% CHX. The cell viability percentage of 0.2% PO-AMNE after 60 minutes was 32.51%, whereas there was a decrease in the cell viability percentages for 3.25% NaOCl, CHX, and 17% EDTA cell survival of 6.47%, 4.30%, and 4.15%, respectively. Overall, the formulated 0.2% PO-AMNE irrigant may potentially combat endodontic infection-related microbial biofilms. Keywords: α-Mangostin, palm-oil, nanoemulsion, root canal irrigants, antimicrobial, antifungal, smear layer, OKF-6 cells.

Plants have exceptional abilities to produce secondary metabolites that have medicinal value as well as being cytotoxic agents. With the rise of multidrug-resistant strains of bacteria like Vancomycin-resistant Staphylococcus aureus (VRSA) and Methicillin Resistant Staphylococcus aureus (MRSA) has required the discovery of new antimicrobial drug leads. Currently there is not a single chemical entity plant derived antibacterials being used clinically. Malaysia with its abundant biodiversity has many plants which are used in traditional medicine to treat wound infections and with knowledge gathered from ethnobotany lead to this study of the antimicrobial activity of Alternanthera sessilis Red (locally called Hongtyang wu) leaves ethanolic extract on 11 standard microorganisms namely Methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Staphylococcus epidermis, Staphylococcus saprophyticus, Enterococcus fecalis, Bacillus cereus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter iwoffii, Shigella dysenteriae, Aeromonas hydrophilia and Yersinia enterocolitica. In the present study, two microorganisms namely, the gram positive S. aureus and B. cereus exhibited susceptibility to the ethanolic leaves extract using the disk diffusion assay method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were performed using the Resazurin assay (broth microdilution techniques) as described by the Clinical and Laboratory Standards Institute (CLSI). The MIC values were 12.5mg/mL and 0.2mg/mL for B. cereus and S. aureus respectively and A. sessilis Red ethanolic leaves extract killed these 2 types of microorganisms at MBC values of 25mg/mL and 0.4 mg/mL, respectively. The results showed that A. sessilis Red ethanolic leaves extract either modified resistance in B. cereus and S. aureus and/or acted as antibacterial agent by possessing bactericidal or bacteriostatic properties. The leaf extract had potent activity against S. aureus which could be exploited to develop new classes of anti-staphylococcal phytochemical agents which should undergo further microbial specificity, cytotoxic and preclinical in vivo evaluation to determine their development for clinically use.

Although many causes have been suggested, the concept of oxidative stress has often been put forward as one of the important causes of neurodegenerative diseases. Natural antioxidants such as flavonoid polyphenols are essential in protecting neuronal cells from undergoing lipid peroxidation and cell death. The present study was designed to elucidate the antioxidant mechanisms of rutin and isoquercitrin in 6-OHDA induced PC12 rat pheochromocytoma cells. Pre-treatment of PC12 cells with rutin or isoquercitrin markedly (p<0.05) reduced the toxic effects caused by exposure to 6-OHDA as this was found to increase the viability of the PC12 cells. In addition, rutin and isoquercetrin were also found to elevate the levels of the endogenous antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase, catalase as well as glutathione. Rutin and isoquercitrin attenuated lipid peroxidation caused by 6-OHDA with p<0.05. Gene expression study using the qPCR array technique showed rutin suppressed the expression of the Parkin genes such Park 5, Park 7 and pro-apoptotic gene Casp3 gene in the PC12 cells exposed to 6-OHDA whilst isoquercitrin pre-treatment down-regulated expression of the Park 5 and Park 7 genes in these cells. Moreover, pre-treatment with rutin stimulated the expression of the TH gene in the PC12 cells. Tyrosine hydroxylase, the protein coded by the TH gene is crucial for biosynthesis of dopamine. Thus, quercetin glycosides treatment may present a novel approach in improving neurodegenerative diseases, including Parkinson’s (PD) and Alzheimer’s (AD) diseases.