Atherosclerosis is a complex pathology that involves several factors in its development, like oxidative stress, inflammation, hyperlipidemia, platelet aggregation and thrombus formation. Several drugs and therapeutic approaches have been developed to handle these aspects of atherosclerosis. However, some of these treatments can be costly and have undesirable side effects. Many constituents of mushrooms have been shown to have potential anti-atherosclerotic effects in several in vitro and in vivo studies. Recently, the possible mechanisms in which they exert these effects have also been elucidated. In this review, some of the research focusing on mushrooms and their potential anti-atherosclerotic effects are examined. Many mushroom species exhibited anti-oxidative, anti-inflammatory and hypolipidemic effects that can potentially attenuate the progression of atherosclerosis, either through their isolated compounds or use of crude extracts. More studies are focused on the effect that mushrooms have on gene expressions that are involved in oxidative stress, inflammation, and hyperlipidemia. These studies could provide us with a better understanding on the mechanisms in which the consumption of mushrooms could exert their possible anti-atherosclerotic effects. Further research needs to be done to uncover other possible mechanisms that are affected by mushroom use.
Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC(50) values of ≤ 20.0 µg/mL. Hexane extract of P. watsonii was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1→PW-10). PW-4→PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1→PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC(50) values ranged from 0.66-0.83 µg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs.
Species of Phyllanthus have traditionally been used for hundreds of years for treating many ailments including diabetes, anemia, bronchitis and hepatitis. The present study aims to investigate the cytotoxic and apoptotic effects of methanol (PWM), hexane (PWH) and ethyl acetate (PWE) extracts from the leaves of the endemic plant Phyllanthus watsonii Airy Shaw (Phyllanthaceae) on MCF-7 human breast cancer cells. We observed that the PWM, PWH and PWE extracts were cytotoxic and selectively inhibited the growth and proliferation of MCF-7 cells compared to untreated control in a dose dependent manner with an IC(50) of 12.7 ± 4.65, 7.9 ± 0.60 and 7.7 ± 0.29 μg/ml, respectively. However, the extracts were not toxic at these concentrations to normal human lung fibroblast MRC-5 cells. Cell death induced by PWM, PWH and PWE extracts were mainly due to apoptosis which was characterized by apoptotic morphological changes and a nuclear DNA fragmentation. Caspase-3 activation following P. watsonii extracts treatment was also evident for apoptotic cell death which was preceded by an S phase cell cycle perturbation. The results suggested that the cytotoxic activity of P. watsonii extracts was related to an early event of cell cycle perturbation and a later event of apoptosis. Hence, P. watsonii displays potential to be further exploited in the discovery and development of new anticancer agents.
Spinal tuberculosis is not common in the paediatric age group. Initial clinical features are often vague and non specific until the disease progresses to later stages. We highlight the diagnostic difficulties and management challenges of a complicated extradural tuberculoma with neurological deficits in a very young girl.
Montney Formation (MF) source rock located in northeastern British Columbia (BC), Canada, was analyzed to determine its depositional conditions and organic matter source input other than to determine their level of thermal maturity. The high total sulfur (TS) (2.23-20.86 wt.%) and good to very good total organic carbon (TOC) content (0.3-5.87 wt.%) in the analyzed samples give good evidence that the deposition of MF source rock was in a marine environment under reducing conditions. A mixed marine-terrestrial derived organic matter (OM) for the Montney source rock that was deposited in a marine dysoxic environment is deduced from the composition and distribution of different biomarker traces. Thus, the previous result is supported by the high short-chain n-alkanes ratio, accompanied by carbon preference index (CPI) around unity, high concentration of tricyclic terpanes, high C24 tricyclic/C24 tetracyclic, hopane/sterane ratios ranging from low to moderate, as well as the relationship between regular sterane compositions. During deposition of the MF source rock, it can be noticed that more land organic materials this was deduced according to the high waxiness index. From maturity ratios of Ts/(Ts + Tm), C32 22S/(22S + 22R) homohopane, moretane/hopane and 20S/(20S + 20R) and ββ/(ββ + αα) C29 it can give a conclusion that the source rock is mature to postmature of hydrocarbon generation.
This paper reports on the vinca alkaloid produced by a novel Nigrospora sphaerica isolated from Catharanthus roseus. Through liquid chromatography-mass spectrometry (LCMS), only the crude mycelia extract of this fungus was positive for determination of vinblastine. This vinca alkaloid was then purified by using high-performance liquid chromatography (HPLC) and tested for cytotoxicity activity using MTT assays. The breast cell line cancer (MDA-MB 231) was treated with a purified vinblastine which was intracellulary produced by N. sphaerica. The purified vinblastine from extracted leaf of C. roseus was used as a standard comparison. A positive result with a value of half maximal inhibitory concentration (IC50 ) of > 32 μg ml-1 was observed compared with standard (IC50 ) of 350 μg ml-1 only. It showed that a vinblastine produced by N. sphaerica has a high cytotoxicity activity even though the concentration of vinblastine produced by this endophytic fungus was only 0.868 μg ml-1 .
A polysaccharide fraction from Solanum nigrum, SN-ppF3 was shown previously to have an immunomodulatory activity where it could possibly be used to enhance the host immune response in fighting cancer. The non-toxic SN-ppF3 was fed orally to breast tumor bearing-mice with concentrations of 250 and 500mg/kg for 10days. During the treatment period, size of the tumor and weight of the mice were monitored. At the end of the treatment, blood, tumor, spleen and thymus were harvested for physiological and immunological analyses. After the treatment, the tumor volume and tumor weight were significantly inhibited by 65% and 40%, respectively. Based on the histological observation, the treatment of SN-ppF3 resulted in the disruption of tumor cells morphology. The increase in infiltrating T cells, NK cells and macrophages were observed in tumor tissues of the treated mice, which partly explained the higher apoptosis tumor cells observed in the treated mice. Moreover, the level of TNF-α, IFN-γ and IL-4 were elevated, while the level of IL-6 was decreased significantly, in serum of the treated mice. These results suggested that tumor suppression mechanisms observed in SN-ppF3-treated mice were most probably due through enhancing the host immune response.
Here, we announce the draft genome sequence of a Candida parapsilosis clinical isolate (USM039K) recovered from a patient with catheter-related bloodstream infection (CRBSI). The genome size is 12,860,016 bp long, with 188 scaffolds, a G+C content of 38.65%, and 5,467 genes.
Winged bean seed (WBS) is an underutilized tropical crop. The current study evaluates its potential to reduce blood pressure (BP) in spontaneously hypertensive rats and finds that it reduces BP significantly, in a dose-dependent manner. Five peptides with the sequences, RGVFPCLK, TQLDLPTQ, EPALVP, MRSVVT and DMKP, have been characterized in terms of their stability against ACE via in vitro and in silico modelling. All peptides exhibited IC50 values between 0.019 and 6.885 mM and various inhibitory modes, including substrate, prodrug and true inhibitor modes. The toxicity status of non-Current Good Manufacturing Practice (non-CGMP) peptides is evaluated and the results show that such peptides are toxic, and thus are not suitable to be tested in animals, particularly in repeated-dose studies. In short, WBS hydrolysate demonstrated in vitro ACE inhibitory properties and in vivo blood pressure lowering efficacy in rat models, fostering its potential as a functional food ingredient. Non-CGMP grade peptides are toxic and unfit for testing in animal models.
Poly(glycolide-co-caprolactone) (PGCL) has become a novice to the bioresorbable suture owing to the synergistic properties taken from the homo-polyglycolide (PGA) and polycaprolactone (PCL) such as excellent bioresorption and flexibility. In addition to under conventional monotonic loading, the understanding of mechanical responses of PGCL copolymers under complex loading conditions such as cyclic and stress relaxation is crucial for its application as a surgical suture. Consequently, the present work focuses on evaluating the mechanical responses of PGCL sutures under monotonic, cyclic, and stress relaxation loading conditions. Under monotonic loading, the stress-strain behavior of the PGCL suture was found to be non-linear with noticeable strain-rate dependence. Under cyclic loading, inelastic responses including stress-softening, hysteresis and permanent set were observed. During cyclic loading, both stress-softening and hysteresis were found to increase with the maximum strain. In multi-step stress relaxation, the PGCL sutures were observed to exhibit a strong viscoelastic response. In an attempt to describe the relationship between the stress-relaxation and strain-induced crystallization (SIC) occurring during the loading and relaxation processes, a schematic illustration of the conformational change of polymer chains in PGCL sutures was proposed in this work. Results showed that SIC was dependent on the strain level as well as the loading and relaxation durations. The inelastic phenomena observed in PGCL sutures can be thus correlated to the combined effect of stress relaxation and SIC.
Stone fish is an under-utilized sea cucumber with many health benefits. Hydrolysates with strong ACE-inhibitory effects were generated from stone fish protein under the optimum conditions of hydrolysis using bromelain and fractionated based on hydrophobicity and isoelectric properties of the constituent peptides. Five novel peptide sequences with molecular weight (mw) < 1000 daltons (Da) were identified using LC-MS/MS. The peptides including Ala-Leu-Gly-Pro-Gln-Phe-Tyr (794.44 Da), Lys-Val-Pro-Pro-Lys-Ala (638.88 Da), Leu-Ala-Pro-Pro-Thr-Met (628.85 Da), Glu-Val-Leu-Ile-Gln (600.77 Da) and Glu-His-Pro-Val-Leu (593.74 Da) were evaluated for ACE-inhibitory activity and showed IC50 values of 0.012 mM, 0.980 mM, 1.310 mM, 1.440 mM and 1.680 mM, respectively. The ACE-inhibitory effects of the peptides were further verified using molecular docking study. The docking results demonstrated that the peptides exhibit their effect mainly via hydrogen and electrostatic bond interactions with ACE. These findings provide evidence about stone fish as a valuable source of raw materials for the manufacture of antihypertensive peptides that can be incorporated to enhance therapeutic relevance and commercial significance of formulated functional foods.
Congenital Adrenal Hyperplasia (CAH) is primarily caused by mutations in genes responsible to produce enzymes involved in the synthesis of cortisol, aldosterone, or both. This study aims to determine the prevalence, sociodemographic distributions, and clinical factors associated with CAH in the Malaysian population. This retrospective study reviewed laboratory records of 17-hydroxyprogesterone (17OHP) test requests received at the Institute for Medical Research, Kuala Lumpur from January 2021 to December 2021. Descriptive statistics were employed for most variables, and logistic regression analysis was conducted to determine factors associated with CAH. The dataset included a total of 775 patients (64.2%) from 1,207 test requests screened. The prevalence of newly diagnosed CAH in the year 2021 was 13.5% (n=105). The majority were Malays (15.1%), neonates (13.8%), and females (45.7%). Higher baseline 17-OHP (cOR:1.31, 95% CI:1.19, 1.45), unknown gender at birth (cOR:7.82, 95% CI:2.86, 21.37), and neonatal age group at presentation (cOR:29.3, 95% CI:12.07, 71.03) independently predict CAH. The high prevalence of CAH in our region has been speculated to be due to the cultural consanguinity norms, resulting in genetic aberrations. CAH may manifest as ambiguous genitalia, particularly in females, due to the overproduction of androgens in-utero, resulting in atypical genitalia, necessitating thorough investigation. To the best of our knowledge, the data presented are the latest report on CAH prevalence, distribution, and description of positive CAH cases in the Malaysian population. These findings are essential for further public health planning to improve the diagnostic capacity and clinical management of CAH.
The One Health concept was initiated to promote the integration of human, animal, and environmental ecosystems into healthcare to ensure effective control and the sustainable governance of multifaceted health matters. Climate change, deforestation, and rigorous farming disrupt the environment, which serves as the natural habitat for many animals and microbes, increasing the likelihood of disease transmission between humans and animals. Melioidosis (neglected tropical diseases) and glanders are of humans and animals caused by the gram-negative bacteria Burkholderia pseudomallei and its close relative Burkholderia mallei, respectively. In Malaysia, although melioidosis is endemic, it is not a notifiable disease. Hence, the true prevalence of melioidosis in Malaysia is unknown and varies in different regions of the country, with reported hotspots associated with agriculture-related activities. To date, no incidence of human glanders has been reported in Malaysia, although occupational exposure for equine handlers and veterinary professionals remains a concern. Additionally, antibiotics are widely used in the healthcare and veterinary sectors to treat or prevent B. pseudomallei and B. mallei infections, leading to the emergence of resistance in B. pseudomallei. Lack of surveillance, research, assessment, and management of glanders and melioidosis is a major issue in Malaysia. Proper assessment systems and cross-discipline cooperation are vital to recognize and manage both diseases. Experts and practitioners from clinical and veterinary disciplines, environmentalists, law enforcement, policymakers, researchers, local communities, and other experts need to communicate, collaborate, and coordinate activities to fill the knowledge gap on glanders and melioidosis to reduce morbidity and mortality rates in the country. This review aims to define the organizational and functional characteristics of One Health surveillance approaches for glanders and melioidosis from a Malaysian perspective.
INTRODUCTION: The lack of evidence that proves the benefit of traditional and complementary medicines (T & CM) in treating chronic medical conditions does not deter its usage among patients worldwide. Prevalence of usage among post-stroke patients in Malaysia especially is unknown. This study aims to determine the prevalence, practice and perception of T & CM use among stroke survivors attending an outpatient rehabilitation program in a teaching hospital.
METHODS: A cross-sectional study was conducted among 104 post stroke patients attending an outpatient rehabilitation program. A structured self-administered questionnaire was used to collect data on sociodemographic and clinical profile of patients, as well as types of therapy used and perception on T & CM usage. Descriptive analysis was done, and bivariate analysis was used to determine associations between categorical data.
RESULTS: Mean age of patients was 62 years (SD 12.2), 54% were Chinese and 75% of the patients had ischaemic stroke. Mean age of T & CM users was younger compared to non- T & CM users (61 years vs. 66 years, p=0.04). Two-thirds (66%) of patients admitted to concurrent T & CM usage while attending conventional post stroke rehabilitation. Acupuncture (40.4%), massage (40.4%) and traditional Chinese medicine (11.5%) were the most common T & CM used. Positive perception was recorded in terms of ability of T & CM usage to relieve post stroke symptoms (68%), and it was safe to use because it was made from 'natural sources'. Negative perception recorded: T & CM caused significant adverse effects (57.6%) and was not safe to be used in combination with other conventional medicines (62.5%).
CONCLUSIONS: Concurrent T & CM usage among post-stroke patients attending structured outpatient rehabilitation program is widely practised especially acupuncture, massage and traditional Chinese medicines. Overall the perception towards its use is favourable.
Study site: Medical Rehabilitation Services Department, Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Neat waste plastic oil (WPO) application as a fuel in engines reduces BTE and increases deleterious emissions of CO, UHC, NOx, and smoke due to the presence of insufficient oxygen and unbreakable hydrocarbon chains in WPO. Present investigation was performed to evaluate the impact of ZnO nanoparticles on the performance and emission characteristics of a diesel engine operated with the waste plastic oil (WPO20) blend. The objective of doping ZnO nanoparticles with WPO20 was to enhance the oxidation reaction and heat transfer rate between fuel droplets during combustion, which aids in completing the combustion. The sol-gel technique was adopted to successfully synthesize the ZnO nanoparticles using zinc acetate (Zn(CH3CO2)2.2H2O) and sodium hydroxide (NaOH) precursors. The structure and morphology of resulted particles were studied by XRD and FESEM tests. Both results indicate the stable formation of ZnO, and exhibit the crystallinity nature, spherical surface, and size consistency. The synthesized ZnO nanoparticles were infused in WPO20 blend in the amounts of 50, 100, and 150 ppm with the aid of the ultrasonication technique. Engine test was conducted with diesel fuel, WPO20 blend, and nano-infused fuels at a constant speed of 1500 rpm under various loads. The disparities in performance and emission characteristics were examined and compared with pure diesel fuel. The findings demonstrated that adding nanoparticles to WPO20 significantly lowers the smoke, CO, UHC, and NOx emissions and simultaneously improves the BTE and decreases the BSFC of the diesel engine. Optimum results were obtained for 100 ppm concentration of ZnO nanoparticles. Reduction of smoke by 11.86%, CO by 5.7%, UHC by 28%, and NOx by 14.93%, along with the enhancement of BTE by 2.47%, were noticed at maximum load with 100 ppm particles. Based on the test results, it is concluded that ZnO nanoparticles can be used as a suitable additive in WPO blends to improve the overall engine characteristics. Further scope of the present work is to study the effect of organic nanoparticles with WPO on engine behaviour, the detailed combustion of nanoparticles infused WPO, and the nanoparticles doped WPO on engine wear and corrosion.
In the battle against tuberculosis (TB), plasticity of the Mycobacterium tuberculosis genome is believed to contribute to the pathogen's virulence and drug resistance. Here, we report 10 draft genome sequences of clinical M. tuberculosis isolated in Malaysia as the basis for understanding the genome plasticity of the M. tuberculosis isolates.
Multidrug-resistant (MDR) or extensively drug-resistant (XDR) Tuberculosis (TB) is a major challenge to global TB control. Therefore, accurate tracing of in-country MDR-TB transmission are crucial for the development of optimal TB management strategies. This study aimed to investigate the diversity of MTBC in Nigeria. The lineage and drug-resistance patterns of the clinical MTBC isolates of TB patients in Southwestern region of Nigeria were determined using the WGS approach. The phenotypic DST of the isolates was determined for nine anti-TB drugs. The sequencing achieved average genome coverage of 65.99X. The most represented lineages were L4 (n = 52, 83%), L1 (n = 8, 12%), L2 (n = 2, 3%) and L5 (n = 1, 2%), suggesting a diversified MTB population. In term of detection of M/XDR-TB, while mutations in katG and rpoB genes are the strong predictors for the presence of M/XDR-TB, the current study also found the lack of good genetic markers for drug resistance amongst the MTBC in Nigeria which may pose greater problems on local tuberculosis management efforts. This high-resolution molecular epidemiological data provides valuable insights into the mechanistic for M/XDR TB in Lagos, Nigeria.
The Ministry of Health Malaysia aims to fully replace liquid-based cytology (LBC) with Human Papillomavirus (HPV) tests and increase the screening coverage from a baseline of 25% to 40% by 2023, followed by a 10% yearly increment until 70% coverage. This transition requires proper planning, including the number of tests needed and budget allocation. This study aims to simulate different transition strategies involving the shift from LBC to HPV testing with expanded screening coverage to predict their impact on cervical cancer elimination in Malaysia. A system dynamics model was developed to simulate the transition from LBC to HPV testing and HPV vaccination coverage in Malaysia. The dynamic model utilised local epidemiological data, published research, and expert opinion when data was unavailable. The simulation showed that a combination of high HPV vaccination coverage and transitioning fully to five-yearly HPV testing by 2030, coupled with a 70% screening uptake by 2040, would accelerate cancer elimination in Malaysia by 18 years with an estimated screening cost of MYR1.81 billion equivalent to USD 411 millions compared to the baseline of using LBC as the primary screening method (MYR1.39 billion, USD 315 millions). Sustained, it would lead to averting 6,000 new cancer cases by 2070. Alternatively, conducting HPV screenings twice before age 50 would advance cervical cancer elimination by 14 years and prevent approximately 1000 new cases by 2070, with an estimated cost of MYR1.13 billion equivalent to USD 257 millions. A delay in achieving the full transition prolonged the elimination more than a delay in increasing the screening coverage. In all scenarios, yearly vaccination of 90% of girls age 13 is crucial to achieving elimination. In the Malaysian context, where HPV vaccination coverage has reached considerable levels, the evidence advocates for a full transition from LBC to HPV testing, ideally by 2030. While expanding screening coverage remains a critical factor in this endeavour, the findings unequivocally endorse prioritising the transition process. Trial registration: Trial registration number: NMRR ID-22-00187-DJU.