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Adjunctive use of superoxidized solution in chest wall necrotizing soft tissue infection

Tata MD, Kwan KC, Abdul-Razak MR, Paramalingam S, Yeen WC

Ann Thorac Surg, 2009 May;87(5):1613-4.
PMID: 19379926 DOI: 10.1016/j.athoracsur.2008.10.019

A 39-year-old Indian man presented with necrotizing soft tissue infection of his right forearm and previously undiagnosed diabetes mellitus. The infection progressively worsened to involve his right lateral chest wall despite multiple debridements and systemic antibiotics. His right arm was eventually disarticulated along with wide debridement of the surrounding tissue. Aggressive wound debridement, mechanical scrubbing, and irrigation were then initiated every 8 hours. A superoxidized solution was later introduced as a wound irrigant and dressing agent. The large defect was suitable for split-thickness skin grafting after 16 days of a strict wound management routine with the superoxidized solution.
Fulltext Accumulation and risk assessment of heavy metals employing species sensitivity distributions in Linggi River, Negeri Sembilan, Malaysia

Razak MR, Aris AZ, Zakaria NAC, Wee SY, Ismail NAH

Ecotoxicol Environ Saf, 2021 Mar 15;211:111905.
PMID: 33453636 DOI: 10.1016/j.ecoenv.2021.111905

The constant increase of heavy metals into the aqueous environment has become a contemporary global issue of concern to government authorities and the public. The study assesses the concentration, distribution, and risk assessment of heavy metals in freshwater from the Linggi River, Negeri Sembilan, Malaysia. Species sensitivity distribution (SSD) was utilised to calculate the cumulative probability distribution of toxicity from heavy metals. The aquatic organism's toxicity data obtained from the ECOTOXicology knowledgebase (ECOTOX) was used to estimate the predictive non-effects concentration (PNEC). The decreasing sequence of hazardous concentration (HC5) was manganese > aluminium > copper > lead > arsenic > cadmium > nickel > zinc > selenium, respectively. The highest heavy metal concentration was iron with a mean value of 45.77 μg L-1, followed by manganese (14.41 μg L-1) and aluminium (11.72 μg L-1). The mean heavy metal pollution index (HPI) value in this study is 11.52, implying low-level heavy metal pollutions in Linggi River. The risk quotient (RQ) approaches were applied to assess the potential risk of heavy metals. The RQ shows a medium risk of aluminium (RQm = 0.1125) and zinc (RQm = 0.1262); a low risk of arsenic (RQm = 0.0122) and manganese (RQm = 0.0687); and a negligible risk of cadmium (RQm = 0.0085), copper (RQm = 0.0054), nickel (RQm = 0.0054), lead (RQm = 0.0016) and selenium (RQm = 0.0012). The output of this study produces comprehensive pollution risk, thus provides insights for the legislators regarding exposure management and mitigation.
Occurrence, abundance, and distribution of microplastics pollution: an evidence in surface tropical water of Klang River estuary, Malaysia

Zaki MRM, Ying PX, Zainuddin AH, Razak MR, Aris AZ

Environ Geochem Health, 2021 Sep;43(9):3733-3748.
PMID: 33712970 DOI: 10.1007/s10653-021-00872-8

Microplastics have been considered as contaminants of emerging concern due to ubiquity in the environment; however, the occurrence of microplastics in river estuaries is scarcely investigated. The Klang River estuary is an important ecosystem that receives various contaminants from urbanised, highly populated areas and the busiest maritime centre in Selangor, Malaysia. This study investigates the abundance and characteristics of microplastics in surface water of the Klang River estuary. The abundance of microplastics ranged from 0.5 to 4.5 particles L-1 with a mean abundance of 2.47 particles L-1. There is no correlation between the abundance of microplastics and physicochemical properties, while there is a strong correlation between salinity and conductivity. The microplastics were characterised with a stereomicroscope and attenuated total reflection-Fourier transform infrared spectroscopy to analyse size, shape, colour, and polymer composition. The microplastics in the surface water were predominantly in the 300-1000 μm size class, followed by > 1000 μm and
Iminodiacetic acid modified kenaf fiber for waste water treatment

Razak MR, Yusof NA, Haron MJ, Ibrahim N, Mohammad F, Kamaruzaman S, et al.

Int J Biol Macromol, 2018 Jun;112:754-760.
PMID: 29428390 DOI: 10.1016/j.ijbiomac.2018.02.035

In the present study, iminodiacetic acid (IDA)-modified kenaf fiber, K-IDA formed by the chemical modification of plant kenaf biomass was tested for its efficacy as a sorbent material towards the purification of waste water. The K-IDA fiber was first characterized by the instrumental techniques like Fourier transform infrared (FTIR) analysis, elemental analysis (CHNSO), and scanning electron microscopy (SEM). On testing for the biosorption, we found that the K-IDA has an increment in the adsorption of Cu2+ ions as compared against the untreated fiber. The Cu2+ ions adsorption onto K-IDA fits very well with the Langmuir model and the adsorption maximum achieved to be 91.74mg/g. Further, the adsorption kinetics observed to be pseudo second-order kinetics model and the Cu2+ ions adsorption is a spontaneous endothermic process. The desorption study indicates a highest percentage of Cu2+ of 97.59% from K-IDA under 1M HCl solution against H2SO4 (72.59%) and HNO3 (68.66%). The reusability study indicates that the efficiency did not change much until the 4th cycle and also providing enough evidence for the engagement of our biodegradable K-IDA fiber towards the removal of Cu2+ ions in real-time waste water samples obtained from the electroplating and wood treatment industries.
Fulltext Apolipoprotein Eε4: A Biomarker for Executive Dysfunction among Parkinson's Disease Patients with Mild Cognitive Impairment

Samat NA, Abdul Murad NA, Mohamad K, Abdul Razak MR, Mohamed Ibrahim N

Front Neurosci, 2017;11:712.
PMID: 29326545 DOI: 10.3389/fnins.2017.00712

Background: Cognitive impairment is prevalent in Parkinson's disease (PD), affecting 15-20% of patients at diagnosis. α-synuclein expression and genetic polymorphisms of Apolipoprotein E (ApoE) have been associated with the presence of cognitive impairment in PD although data have been inconsistent. Objectives: To determine the prevalence of cognitive impairment in patients with PD using Montreal Cognitive Assessment (MoCA), Comprehensive Trail Making Test (CTMT) and Parkinson's disease-cognitive rating scale (PDCRS), and its association with plasma α-synuclein and ApoE genetic polymorphisms. Methods: This was across-sectional study involving 46 PD patients. Patients were evaluated using Montreal cognitive assessment test (MoCA), and detailed neuropsychological tests. The Parkinson's disease cognitive rating scale (PDCRS) was used for cognitive function and comprehensive trail making test (CTMT) for executive function. Blood was drawn for plasma α-synuclein measurements and ApoE genetic analysis. ApoE polymorphism was detected using MutaGELAPoE from ImmunDiagnostik. Plasma α-synuclein was detected using the ELISA Technique (USCN Life Science Inc.) according to the standard protocol. Results: Based on MoCA, 26 (56.5%) patients had mild cognitive impairment (PD-MCI) and 20 (43.5%) had normal cognition (PD-NC). Based on the PDCRS, 18 (39.1%) had normal cognition (PDCRS-NC), 17 (37%) had mild cognitive impairment (PDCRS-MCI), and 11 (23.9%) had dementia (PDCRS-PDD). In the PDCRS-MCI group, 5 (25%) patients were from PD-NC group and all PDCRS-PDD patients were from PD-MCI group. CTMT scores were significantly different between patients with MCI and normal cognition on MoCA (p = 0.003). Twenty one patients (72.4%) with executive dysfunction were from the PD-MCI group; 17 (77.3%) with severe executive dysfunction and 4 (57.1%) had mild to moderate executive dysfunction. There were no differences in the plasma α-synuclein concentration between the presence or types of cognitive impairment based on MoCA, PDCRS, and CTMT. TheApoEe4 allele carrier frequency was significantly higher in patients with executive dysfunction (p = 0.014). Conclusion: MCI was prevalent in our PD population. PDCRS appeared to be more discriminatory in detecting MCI and PDD than MoCA. Plasma α-synuclein level was not associated with presence nor type of cognitive impairment, but the ApoEe4 allele carrier status was significantly associated with executive dysfunction in PD.
Fulltext Assessment of RNA extraction protocols from cladocerans

Razak MR, Aris AZ, Md Yusoff F, Yusof ZNB, Kim SD, Kim KW

PLoS One, 2022;17(4):e0264989.
PMID: 35472091 DOI: 10.1371/journal.pone.0264989

The usage of cladocerans as non-model organisms in ecotoxicological and risk assessment studies has intensified in recent years due to their ecological importance in aquatic ecosystems. The molecular assessment such as gene expression analysis has been introduced in ecotoxicological and risk assessment to link the expression of specific genes to a biological process in the cladocerans. The validity and accuracy of gene expression analysis depends on the quantity, quality and integrity of extracted ribonucleic acid (RNA) of the sample. However, the standard methods of RNA extraction from the cladocerans are still lacking. This study evaluates the extraction of RNA from tropical freshwater cladocerans Moina micrura using two methods: the phenol-chloroform extraction method (QIAzol) and a column-based kit (Qiagen Micro Kit). Glycogen was introduced in both approaches to enhance the recovery of extracted RNA and the extracted RNA was characterised using spectrophotometric analysis (NanoDrop), capillary electrophoresis (Bioanalyzer). Then, the extracted RNA was analysed with reverse transcription polymerase chain reaction (RT-PCR) to validate the RNA extraction method towards downstream gene expression analysis. The results indicate that the column-based kit is most suitable for the extraction of RNA from M. micrura, with the quantity (RNA concentration = 26.90 ± 6.89 ng/μl), quality (A260:230 = 1.95 ± 0.15, A280:230 = 1.85 ± 0.09) and integrity (RNA integrity number, RIN = 7.20 ± 0.16). The RT-PCR analysis shows that the method successfully amplified both alpha tubulin and actin gene at 33-35 cycles (i.e. Ct = 32.64 to 33.48). The results demonstrate that the addition of glycogen is only suitable for the phenol-chloroform extraction method. RNA extraction with high and comprehensive quality control assessment will increase the accuracy and reliability of downstream gene expression, thus providing more ecotoxicological data at the molecular biological level on other freshwater zooplankton species.
Occurrence, distribution, and ecological risk of bisphenol analogues in marine ecosystem of urbanized coast and estuary

Zainuddin AH, Roslan MQJ, Razak MR, Yusoff FM, Haron DEM, Aris AZ

Mar Pollut Bull, 2023 Jul;192:115019.
PMID: 37201347 DOI: 10.1016/j.marpolbul.2023.115019

Bisphenol analogues are prevalent globally because of rampant usage and imprecise processing techniques, prompting alerts about environmental and health hazards. The method employed in this study by solid phase extraction (SPE) and liquid chromatography-tandem quadrupole mass spectrometer (LC-MS/MS) for both quantification and qualitative analysis of the bisphenol compounds in the surface water samples. The coastal and estuarine surface water of Port Dickson and Lukut ranges from 1.32 ng/L to 1890.51 ng/L of bisphenol analogues. BPF mean concentration at 1143.88 ng/L is the highest, followed by BPA and BPS at 59.01 ng/L and 10.96 ng/L, respectively. Based on RQm for bisphenol analogues, the highest for BPF at 2.49 (RQ > 1, high risk), followed by BPS at 0.12 (0.1
De Novo Transcriptomic and Life-History Responses of Moina Micrura Under Stress Environment Conditions

Razak MR, Aris AZ, Yusoff FM, Yusof ZNB, Kim SD, Kim KW

Mar Biotechnol (NY), 2023 Jun;25(3):473-487.
PMID: 37310522 DOI: 10.1007/s10126-023-10220-9

Moina micrura represents a promising model species for ecological and ecotoxicological investigations in tropical freshwater ecosystems. Illumina NovaSeq™ 6000 sequencing was employed in this study to analyze M. micrura across three distinct developmental stages: juvenile, adult, and male. Current study successfully annotated 51,547 unigenes (73.11%) derived from seven (7) different databases. A total of 554 genes were found to be significantly upregulated, while 452 genes showed significant downregulation between juvenile and male. Moreover, 1001 genes were upregulated, whereas 830 genes exhibited downregulation between the adult and male. Analysis of differentially expressed genes revealed upregulation of chitin, cuticle, myosin (MYO), mitogen-activated protein kinases (MAPK), fibrillin (FBN), cytochrome (CYP), glutathione s-transferase (GST), vitellogenin (VTG), acetylcholinesterase (AChE), and transforming growth factor beta (TGFB) under unfavorable environmental conditions (male), as compared to favorable environmental conditions (juveniles and adults). These alterations in gene expression significantly impact the phenological and life-history traits of M. micrura. Furthermore, the upregulation of hemoglobin (HMB), doublesex (DSX), juvenile hormone analogs (JHA), heat shock protein (HSP), and methyltransferase (METT) genes in males initiates the sex-switching effects observed in M. micrura. These findings hold substantial value for researchers interested in determining M. micrura sequences for future investigations of gene expression and comparative reproductive genome analysis within the Moina genus and cladoceran families.
Fulltext Effect of selected local medicinal plants on the asexual blood stage of chloroquine resistant Plasmodium falciparum

Mohd Abd Razak MR, Afzan A, Ali R, Amir Jalaluddin NF, Wasiman MI, Shiekh Zahari SH, et al.

BMC Complement Altern Med, 2014;14:492.
PMID: 25510573 DOI: 10.1186/1472-6882-14-492

The development of resistant to current antimalarial drugs is a major challenge in achieving malaria elimination status in many countries. Therefore there is a need for new antimalarial drugs. Medicinal plants have always been the major source for the search of new antimalarial drugs. The aim of this study was to screen selected Malaysian medicinal plants for their antiplasmodial properties.
Occurrence and distribution of endocrine-disrupting chemicals in mariculture fish and the human health implications

Ismail NAH, Aris AZ, Wee SY, Nasir HM, Razak MR, Kamarulzaman NH, et al.

Food Chem, 2021 May 30;345:128806.
PMID: 33352402 DOI: 10.1016/j.foodchem.2020.128806

The presence and distribution of endocrine-disrupting chemicals (EDCs) in the mariculture fish from Pulau Kukup, Johor of Malaysia have been studied along with the impact on human health. Six different species of mariculture fish were collected, due to their high consumption in the Asian region-especially Malaysia, to assess their levels of EDCs. The highest concentration of EDCs detected in the muscle was dexamethasone (2.37-15.84 ng/g) and (0.77-13.41 ng/g), in the liver was dexamethasone (<2.54-43.56 ng/g) and progesterone (2.23-9.78 ng/g), and in the reproductive organ are dexamethasone (<2.54-37.23 ng/g) and caffeine (0.21-18.92 ng/g). The human health risk assessment in the current study suggested that there is no potential risk to the consumer because the hazard index was below 1 (HI
Development of a single-run liquid chromatography-mass spectrometry analysis for the detection of 11 multiclass contaminants of emerging concern using a direct filtration method

Razak MR, Aris AZ, Sukatis FF, Zaki MRM, Zainuddin AH, Haron DEM, et al.

J Sep Sci, 2023 Jan;46(1):e2200282.
PMID: 36337037 DOI: 10.1002/jssc.202200282

In toxicological analysis, the analytical validation method is important to assess the exact risk of contaminants of emerging concern in the environment. Syringe filters are mainly used to remove impurities from sample solutions. However, the loss of analyte to the syringe filter could be considerable, causing an underestimate of the analyte concentrations. The current study develops and validates simultaneous liquid chromatography-mass spectrometry analysis using a direct filtration method to detect four groups of contaminants of emerging concern. The adsorption of the analyte onto three different matrices and six types of syringe filters is reported. The lowest adsorption of analytes was observed in methanol (16.72%), followed by deionized water (48.19%) and filtered surface lake water (48.94%). Irrespective of the type of the matrices, the lowest average adsorption by the syringe filter was observed in the 0.45 μm polypropylene membrane (15.15%), followed by the 0.20 μm polypropylene membrane (16.10%), the 0.20 μm regenerated cellulose (16.15%), the 0.20 μm polytetrafluoroethylene membrane (47.38%), the 0.45 μm nylon membrane (64.87%) and the 0.20 μm nylon membrane (71.30%). In conclusion, the recommended syringe filter membranes for contaminants of emerging concern analysis are polypropylene membranes and regenerated cellulose, regardless of the matrix used.
Acute toxicity and risk assessment of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) in tropical cladocerans Moina micrura

Razak MR, Aris AZ, Zainuddin AH, Yusoff FM, Balia Yusof ZN, Kim SD, et al.

Chemosphere, 2023 Feb;313:137377.
PMID: 36457264 DOI: 10.1016/j.chemosphere.2022.137377

Per- and polyfluoroalkyl substances (PFAS) are gaining worldwide attention because of their toxicity, bioaccumulative and resistance to biological degradation in the environment. PFAS can be categorised into endocrine disrupting chemicals (EDCs) and identified as possible carcinogenic agents for the aquatic ecosystem and humans. Despite this, only a few studies have been conducted on the aquatic toxicity of PFAS, particularly in invertebrate species such as zooplankton. This study evaluated the acute toxicity of two main PFAS, perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS), by using freshwater cladocerans (Moina micrura) as bioindicators. This study aimed to assess the adverse effects at different levels of organisations such as organ (heart size and heart rate), individual (individual size and mortality) and population (lethal concentration, LC50). PFOA was shown to be more hazardous than PFOS, with the LC50 values (confidence interval) of 474.7 (350.4-644.5) μg L-1 and 549.6 (407.2-743.9) μg L-1, respectively. As the concentrations of PFOS and PFOA increased, there were declines in individual size and heart rate as compared to the control group. The values of PNECs acquired by using the AF method (PNECAF) for PFOA and PFOS were 0.4747 and 0.5496 μg L-1, respectively. Meanwhile, the PNEC values obtained using the SSD method (PNECSSD) were 1077.0 μg L-1 (PFOA) and 172.5 μg L-1 (PFOS). PNECAF is more protective and conservative compared to PNECSSD. The findings of this study have significant implications for PFOS and PFOA risk assessment in aquatic environments. Thus, it will aid freshwater sustainability and safeguard the human dependency on water resources.
Risk assessment of bisphenol analogues towards mortality, heart rate and stress-mediated gene expression in cladocerans Moina micrura

Razak MR, Aris AZ, Yusoff FM, Yusof ZNB, Abidin AAZ, Kim SD, et al.

Environ Geochem Health, 2023 Jun;45(6):3567-3583.
PMID: 36450975 DOI: 10.1007/s10653-022-01442-2

Bisphenol A (BPA) is a well-known endocrine-disrupting compound that causes several toxic effects on human and aquatic organisms. The restriction of BPA in several applications has increased the substituted toxic chemicals such as bisphenol F (BPF) and bisphenol S (BPS). A native tropical freshwater cladoceran, Moina micrura, was used as a bioindicator to assess the adverse effects of bisphenol analogues at molecular, organ, individual and population levels. Bisphenol analogues significantly upregulated the expressions of stress-related genes, which are the haemoglobin and glutathione S-transferase genes, but the sex determination genes such as doublesex and juvenile hormone analogue genes were not significantly different. The results show that bisphenol analogues affect the heart rate and mortality rate of M. micrura. The 48-h lethal concentration (LC50) values based on acute toxicity for BPA, BPF and BPS were 611.6 µg L-1, 632.0 µg L-1 and 819.1 µg L-1, respectively. The order of toxicity based on the LC50 and predictive non-effect concentration values were as follows: BPA > BPF > BPS. Furthermore, the incorporated method combining the responses throughout the organisation levels can comprehensively interpret the toxic effects of bisphenol analogues, thus providing further understanding of the toxicity mechanisms. Moreover, the output of this study produces a comprehensive ecotoxicity assessment, which provides insights for the legislators regarding exposure management and mitigation of bisphenol analogues in riverine ecosystems.
Inhibitory effect of food-functioned phytochemicals on dysregulated inflammatory pathways triggered by SARS-CoV-2: a mechanistic review

Jantan I, Norahmad NA, Yuandani, Haque MA, Mohamed-Hussein ZA, Mohd Abd Razak MR, et al.

Crit Rev Food Sci Nutr, 2024 Apr 15.
PMID: 38619217 DOI: 10.1080/10408398.2024.2341266

Inflammatory cascades of the dysregulated inflammatory pathways in COVID-19 can cause excessive production of pro-inflammatory cytokines and chemokines leading to cytokine storm syndrome (CSS). The molecular cascades involved in the pathways may be targeted for discovery of new anti-inflammatory agents. Many plant extracts have been used clinically in the management of COVID-19, however, their immunosuppressive activities were mainly investigated based on in silico activity. Dietary flavonoids of the extracts such as quercetin, luteolin, kaempferol, naringenin, isorhamnetin, baicalein, wogonin, and rutin were commonly identified as responsible for their inhibitory effects. The present review critically analyzes the anti-inflammatory effects and mechanisms of phytochemicals, including dietary compounds against cytokine storm (CS) and hyperinflammation via inhibition of the altered inflammatory pathways triggered by SARS-CoV-2, published since the emergence of COVID-19 in December 2019. Only a few phytochemicals, mainly dietary compounds such as nanocurcumin, melatonin, quercetin, 6-shagoal, kaempferol, resveratrol, andrographolide, and colchicine have been investigated either in in silico or preliminary clinical studies to evaluate their anti-inflammatory effects against COVID-19. Sufficient pre-clinical studies on safety and efficacy of anti-inflammatory effects of the phytochemicals must be performed prior to proper clinical studies to develop them into therapeutic adjuvants in the prevention and treatmemt of COVID-19 symptoms.
Fulltext Genetic Diversity of Plasmodium falciparum Populations in Malaria Declining Areas of Sabah, East Malaysia

Mohd Abd Razak MR, Sastu UR, Norahmad NA, Abdul-Karim A, Muhammad A, Muniandy PK, et al.

PLoS One, 2016;11(3):e0152415.
PMID: 27023787 DOI: 10.1371/journal.pone.0152415

Malaysia has a national goal to eliminate malaria by 2020. Understanding the genetic diversity of malaria parasites in residual transmission foci can provide invaluable information which may inform the intervention strategies used to reach elimination targets. This study was conducted to determine the genetic diversity level of P. falciparum isolates in malaria residual foci areas of Sabah. Malaria active case detection was conducted in Kalabakan and Kota Marudu. All individuals in the study sites were screened for malaria infection by rapid diagnostic test. Blood from P. falciparum-infected individuals were collected on filter paper prior to DNA extraction. Genotyping was performed using merozoite surface protein-1 (MSP-1), merozoite surface protein-2 (MSP-2), glutamate rich protein (GLURP) and 10 neutral microsatellite loci markers. The size of alleles, multiplicity of infection (MOI), mean number of alleles (Na), expected heterozygosity (He), linkage disequilibrium (LD) and genetic differentiation (FST) were determined. In Kalabakan, the MSP-1 and MSP-2 alleles were predominantly K1 and FC27 family types, respectively. The GLURP genotype VI (751-800 bp) was predominant. The MOI for MSP-1 and MSP-2 were 1.65 and 1.20, respectively. The Na per microsatellite locus was 1.70. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.17, 0.37, 0.70 and 0.33, respectively. In Kota Marudu, the MSP-1 and MSP-2 alleles were predominantly MAD20 and 3D7 family types, respectively. The GLURP genotype IV (651-700 bp) was predominant. The MOI for both MSP-1 and MSP-2 was 1.05. The Na per microsatellite locus was 3.60. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.24, 0.25, 0.69 and 0.30, respectively. A significant LD was observed in Kalabakan (0.495, p<0.01) and Kota Marudu P. falciparum populations (0.601, p<0.01). High genetic differentiation between Kalabakan and Kota Marudu P. falciparum populations was observed (FST = 0.532). The genetic data from the present study highlighted the limited diversity and contrasting genetic pattern of P. falciparum populations in the malaria declining areas of Sabah.
Fulltext Immunomodulatory Activities of Carica papaya L. Leaf Juice in a Non-Lethal, Symptomatic Dengue Mouse Model

Mohd Abd Razak MR, Norahmad NA, Md Jelas NH, Afzan A, Mohmad Misnan N, Mat Ripen A, et al.

Pathogens, 2021 Apr 21;10(5).
PMID: 33919457 DOI: 10.3390/pathogens10050501

The role of Carica papaya L. leaf juice in immune dysregulation caused by dengue virus infection remains unclear. This study aimed to investigate the immunomodulatory activities of the freeze-dried C. papaya leaf juice (FCPLJ) on AG129 mice infected with a clinical DENV-2 (DMOF015) isolate. The infected AG129 mice were orally treated with 500 and 1000 mg/kg/day of FCPLJ, for three days. Platelet, leukocyte, lymphocyte and neutrophil counts were microscopically determined. The level of plasma proinflammatory cytokines was measured by multiplex immunoassay. The levels of intracellular cytokines and viral RNA were determined by RT-qPCR technique. The results showed that the FCPLJ treatment increased the total white blood cell and neutrophil counts in the infected mice. The FCPLJ treatment decreased the level of GM-CSF, GRO-alpha, IL-1 beta, IL-6, MCP-1 and MIP-1 beta in the plasma of the infected mice. The intracellular IL-6 and viral RNA levels in the liver of infected mice were decreased by the FCPLJ treatment. In conclusion, this study supports the potential immunomodulatory role of the FCPLJ in a non-lethal, symptomatic dengue mouse model. Further studies on the action mechanism of the C. papaya leaf juice and its possible use as adjunctive dengue immunotherapy are warranted.
Fulltext Preliminary study on the expression of endothelial cell biology related genes in the liver of dengue virus infected mice treated with Carica papaya leaf juice

Mohd Abd Razak MR, Norahmad NA, Md Jelas NH, Jusoh B, Muhammad A, Mohmad Misnan N, et al.

BMC Res Notes, 2019 Apr 03;12(1):206.
PMID: 30944031 DOI: 10.1186/s13104-019-4242-z

OBJECTIVE: The purpose of this study was to profile and identify the endothelial cell biology related genes that are affected by dengue virus infection in the liver tissue of AG129 mice, with and without Carica papaya leaf juice treatment.
RESULTS: The dengue fever mouse model was established by intraperitoneal inoculation of dengue virus, New Guinea C strain at 2 × 106 PFU. Daily oral administration of 1000 mg/kg freeze-dried C. papaya leaf juice (FCPLJ) was done starting from day 1 to day 3 post infection. The RNA was extracted from liver tissues harvested on day 4 post infection. The expression levels of 84 genes related to mouse endothelial cell biology were determined by qRT-PCR technique. Dengue virus infection upregulated 15 genes and downregulated two genes in the liver of AG129 mice. The FCPLJ treatment upregulated monocyte chemoattractant protein 1 and downregulated intercellular adhesion molecule 1, integrin beta 3 and fibronectin 1 genes during dengue virus infection. The data showed the potential effect of FCPLJ treatment on the expression profile of endothelial cell biology related genes in the liver of dengue virus infected-AG129 mice. Further proteomic studies are needed to determine the functional roles of the genes affected by FCPLJ treatment.
Fulltext Synthesis, Molecular Docking, and Antimalarial Activity of Hybrid 4-Aminoquinoline-pyrano[2,3-c]pyrazole Derivatives

Shamsuddin MA, Ali AH, Zakaria NH, Mohammat MF, Hamzah AS, Shaameri Z, et al.

Pharmaceuticals (Basel), 2021 Nov 17;14(11).
PMID: 34832956 DOI: 10.3390/ph14111174

Widespread resistance of Plasmodium falciparum to current artemisinin-based combination therapies necessitate the discovery of new medicines. Pharmacophoric hybridization has become an alternative for drug resistance that lowers the risk of drug-drug adverse interactions. In this study, we synthesized a new series of hybrids by covalently linking the scaffolds of pyrano[2,3-c]pyrazole with 4-aminoquinoline via an ethyl linker. All synthesized hybrid molecules were evaluated through in vitro screenings against chloroquine-resistant (K1) and -sensitive (3D7) P. falciparum strains, respectively. Data from in vitro assessments showed that hybrid 4b displayed significant antiplasmodial activities against the 3D7 strain (EC50 = 0.0130 ± 0.0002 μM) and the K1 strain (EC50 = 0.02 ± 0.01 μM), with low cytotoxic effect against Vero mammalian cells. The high selectivity index value on the 3D7 strain (SI > 1000) and the K1 strain (SI > 800) and the low resistance index value from compound 4b suggested that the pharmacological effects of this compound were due to selective inhibition on the 3D7 and K1 strains. Molecular docking analysis also showed that 4b recorded the highest binding energy on P. falciparum lactate dehydrogenase. Thus, P. falciparum lactate dehydrogenase is considered a potential molecular target for the synthesized compound.
Fulltext LC-MS/MS-QTOF dataset of compounds detected in kelulut honey of the stingless bees, Heterotrigona itama and Tetrigona binghami from Kuantan, Pahang, Malaysia

Ismail CMKH, Khong NMH, Ahmad A, Mokhtar KI, Lestari W, Mustafa Alahmad BE, et al.

Data Brief, 2023 Aug;49:109409.
PMID: 37520655 DOI: 10.1016/j.dib.2023.109409

Honey is a sustainable nutritious substance which has been incorporated into the human diet since ancient times for its health and remedial benefits. Stingless bee honey or kelulut honey (KH) is well-known in Malaysia and has received high demand in the market due to its distinctive unique flavour. Its composition, colour, and flavour are majorly affected by the geographical location, floral source, climate, as well as the bee species. This data article presents the nontargeted metabolite profiling of the extracts of KH of Heterotrigona itama and Tetrigona binghami bee species. The KH was collected from three nests in Kuantan, Pahang, which is situated in the east coast of Peninsular Malaysia. The extracts were prepared using sugaring-out assisted liquid-liquid extraction (SULLE) method and the Liquid Chromatography-Tandem Mass Spectrometry with Quadrupole Time-of-Flight, operated in the negative ion mode, was used to identify compounds in the extracts. The data processing revealed the presence of 35 known compounds in the KH1 extract by Heterotrigona itama collected from Bukit Kuin, 38 compounds in the KH2 extract by H. itama collected from Indera Mahkota, whilst 50 known compounds were present in KH3 extract by Tetrigona binghami species from Indera Mahkota. This data article contains the m/z values, retention times, and the METLIN database search hit identities of the compounds and their respective classes.
Fulltext Data on LC-MS profile of Brucea javanica (L.) Merr. and the NMR data of its major indole alkaloids

Mohd Yousof NSA, Mohmad Misnan N, Abdul Karim AH, Zainol M, Mohd Abd Razak MR, Md Jelas NH, et al.

Data Brief, 2024 Feb;52:109895.
PMID: 38161655 DOI: 10.1016/j.dib.2023.109895

This article presents two types of phytochemical data obtained from Brucea javanica (L.) Merr. roots, a medicinal plant belonging to the Simaroubaceae family. The high-resolution LC-MS dataset comprised the chemical profile of dichloromethane extract, which was utilised to annotate 35 chemical constituents. For annotations, the measured spectral data were compared with the in-silico spectral data generated from 920 molecular structures previously reported in Simaroubaceae. Indole alkaloids, quassinoids, aliphatics and lignan were the chemical groups identified in the root extract. The second dataset provides NMR spectra (1H, 13C, COSY, HMQC and HMBC) for the six indole alkaloids previously detected in LC-MS analysis and isolated through centrifugal partition chromatography. The chemical structures of all compounds were confirmed based on NMR data as bruceolline J (compound 7), canthin-6-one-N-oxide (compound 10), bruceolline E (compound 15), 5-methoxycanthin-6-one (compound 16), canthin-6-one (compound 20), and 1‑hydroxy-11-methoxycanthin-6-one (compound 22). This phytochemical data was generated to support an ongoing anti-cancer and anti-dengue study.

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