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Fulltext Over-the-Counter Breast Cancer Classification Using Machine Learning and Patient Registration Records

Hanis TM, Ruhaiyem NIR, Arifin WN, Haron J, Wan Abdul Rahman WF, Abdullah R, et al.

Diagnostics (Basel), 2022 Nov 16;12(11).
PMID: 36428886 DOI: 10.3390/diagnostics12112826

This study aims to determine the feasibility of machine learning (ML) and patient registration record to be utilised to develop an over-the-counter (OTC) screening model for breast cancer risk estimation. Data were retrospectively collected from women who came to the Hospital Universiti Sains Malaysia, Malaysia for breast-related problems. Eight ML models were used: k-nearest neighbour (kNN), elastic-net logistic regression, multivariate adaptive regression splines, artificial neural network, partial least square, random forest, support vector machine (SVM), and extreme gradient boosting. Features utilised for the development of the screening models were limited to information in the patient registration form. The final model was evaluated in terms of performance across a mammographic density. Additionally, the feature importance of the final model was assessed using the model agnostic approach. kNN had the highest Youden J index, precision, and PR-AUC, while SVM had the highest F2 score. The kNN model was selected as the final model. The model had a balanced performance in terms of sensitivity, specificity, and PR-AUC across the mammographic density groups. The most important feature was the age at examination. In conclusion, this study showed that ML and patient registration information are feasible to be used as the OTC screening model for breast cancer.
Fulltext The transmission modes and sources of COVID-19: A systematic review

Rahman HS, Aziz MS, Hussein RH, Othman HH, Salih Omer SH, Khalid ES, et al.

Int J Surg Open, 2020;26:125-136.
PMID: 34568614 DOI: 10.1016/j.ijso.2020.08.017

The current rampant coronavirus infection in humans, commonly known as COVID-19, a pandemic that may cause mortality in humans, has been declared a global emergency by the World Health Organization (WHO). The morbidity and mortality rates due to the pandemic are increasing rapidly worldwide, with the USA most affected by the disease. The source COVID-19 is not absolutely clear; however, the disease may be transmitted by either by COVID-19-positive individuals or from a contaminated environment. In this review, we focused on how the COVID-19 virus is transmitted in the community. An extensive literature search was conducted using specific keywords and criteria. Based on the published report, it is concluded that COVID-19 is primarily transmitted human-to-human via oral and respiratory aerosols and droplets with the virus-contaminated environment play a lesser role in the propagation of disease. Healthcare providers and the elderly with comorbidities are especially susceptible to the infection.
Fulltext Cyclophilin A as a target in the treatment of cytomegalovirus infections

A Abdullah A, Abdullah R, A Nazariah Z, N Balakrishnan K, Firdaus J Abdullah F, A Bala J, et al.

Antivir Chem Chemother, 2018;26:2040206618811413.
PMID: 30449131 DOI: 10.1177/2040206618811413

BACKGROUND: Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity.
METHODS: Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins.
RESULTS: Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug.
CONCLUSION: Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.
Fulltext Plasticized Sodium-Ion Conducting PVA Based Polymer Electrolyte for Electrochemical Energy Storage-EEC Modeling, Transport Properties, and Charge-Discharge Characteristics

Aziz SB, Nofal MM, Abdulwahid RT, O Ghareeb H, Dannoun EMA, M Abdullah R, et al.

Polymers (Basel), 2021 Mar 05;13(5).
PMID: 33807956 DOI: 10.3390/polym13050803

This report presents the preparation of plasticized sodium ion-conducting polymer electrolytes based on polyvinyl alcohol (PVA)via solution cast technique. The prepared plasticized polymer electrolytes were utilized in the device fabrication of electrical double-layer capacitors (EDLCs). On an assembly EDLC system, cyclic voltammetry (CV), electrical impedance spectroscopy (EIS), linear sweep voltammetry (LSV), transfer number measurement (TNM) and charge-discharging responses were performed. The influence of plasticization on polymer electrolytes was investigated in terms of electrochemical properties applying EIS and TNM. The EIS was fitted with electrical equivalent circuit (EEC) models and ion transport parameters were estimated with the highest conductivity of 1.17 × 10-3 S cm-1 was recorded. The CV and charge-discharging responses were used to evaluate the capacitance and the equivalent series resistance (ESR), respectively. The ESR of the highest conductive sample was found to be 91.2 Ω at the first cycle, with the decomposition voltage of 2.12 V. The TNM measurement has shown the dominancy of ions with tion = 0.982 for the highest conducting sample. The absence of redox peaks was proved via CV, indicating the charge storing process that comprised ion accumulation at the interfacial region. The fabricated EDLC device is stable for up to 400 cycles. At the first cycle, a high specific capacitance of 169 F/g, an energy density of 19 Wh/kg, and a power density of 600 W/kg were obtained.
Fulltext An Overview of In Vitro, In Vivo, and Computational Techniques for Cancer-Associated Angiogenesis Studies

Rahman HS, Tan BL, Othman HH, Chartrand MS, Pathak Y, Mohan S, et al.

Biomed Res Int, 2020;2020:8857428.
PMID: 33381591 DOI: 10.1155/2020/8857428

Angiogenesis is a crucial area in scientific research because it involves many important physiological and pathological processes. Indeed, angiogenesis is critical for normal physiological processes, including wound healing and embryonic development, as well as being a component of many disorders, such as rheumatoid arthritis, obesity, and diabetic retinopathies. Investigations of angiogenic mechanisms require assays that can activate the critical steps of angiogenesis as well as provide a tool for assessing the efficacy of therapeutic agents. Thus, angiogenesis assays are key tools for studying the mechanisms of angiogenesis and identifying the potential therapeutic strategies to modulate neovascularization. However, the regulation of angiogenesis is highly complex and not fully understood. Difficulties in assessing the regulators of angiogenic response have necessitated the development of an alternative approach. In this paper, we review the standard models for the study of tumor angiogenesis on the macroscopic scale that include in vitro, in vivo, and computational models. We also highlight the differences in several modeling approaches and describe key advances in understanding the computational models that contributed to the knowledge base of the field.
Fulltext Induction of Apoptosis in MCF-7 Cells via Oxidative Stress Generation, Mitochondria-Dependent and Caspase-Independent Pathway by Ethyl Acetate Extract of Dillenia suffruticosa and Its Chemical Profile

Tor YS, Yazan LS, Foo JB, Wibowo A, Ismail N, Cheah YK, et al.

PLoS One, 2015;10(6):e0127441.
PMID: 26047480 DOI: 10.1371/journal.pone.0127441

Dillenia suffruticosa, which is locally known as Simpoh air, has been traditionally used to treat cancerous growth. The ethyl acetate extract of D. suffruticosa (EADs) has been shown to induce apoptosis in MCF-7 breast cancer cells in our previous study. The present study aimed to elucidate the molecular mechanisms involved in EADs-induced apoptosis and to identify the major compounds in the extract. EADs was found to promote oxidative stress in MCF-7 cells that led to cell death because the pre-treatment with antioxidants α-tocopherol and ascorbic acid significantly reduced the cytotoxicity of the extract (P<0.05). DCFH-DA assay revealed that treatment with EADs attenuated the generation of intracellular ROS. Apoptosis induced by EADs was not inhibited by the use of caspase-inhibitor Z-VAD-FMK, suggesting that the cell death is caspase-independent. The use of JC-1 dye reflected that EADs caused disruption in the mitochondrial membrane potential. The related molecular pathways involved in EADs-induced apoptosis were determined by GeXP multiplex system and Western blot analysis. EADs is postulated to induce cell cycle arrest that is p53- and p21-dependent based on the upregulated expression of p53 and p21 (P<0.05). The expression of Bax was upregulated with downregulation of Bcl-2 following treatment with EADs. The elevated Bax/Bcl-2 ratio and the depolarization of mitochondrial membrane potential suggest that EADs-induced apoptosis is mitochondria-dependent. The expression of oxidative stress-related AKT, p-AKT, ERK, and p-ERK was downregulated with upregulation of JNK and p-JNK. The data indicate that induction of oxidative-stress related apoptosis by EADs was mediated by inhibition of AKT and ERK, and activation of JNK. The isolation of compounds in EADs was carried out using column chromatography and elucidated using the nuclear resonance magnetic analysis producing a total of six compounds including 3-epimaslinic acid, kaempferol, kaempferide, protocatechuic acid, gallic acid and β-sitosterol-3-O-β-D-glucopyranoside. The cytotoxicity of the isolated compounds was determined using MTT assay. Gallic acid was found to be most cytotoxic against MCF-7 cell line compared to others, with IC50 of 36 ± 1.7 μg/mL (P<0.05). In summary, EADs generated oxidative stress, induced cell cycle arrest and apoptosis in MCF-7 cells by regulating numerous genes and proteins that are involved in the apoptotic signal transduction pathway. Therefore, EADs has the potential to be developed as an anti-cancer agent against breast cancer.
Fulltext Study of heavy metal levels among farmers of Muda Agricultural Development Authority, Malaysia

Ghazali AR, Abdul Razak NE, Othman MS, Othman H, Ishak I, Lubis SH, et al.

J Environ Public Health, 2012;2012:758349.
PMID: 22536276 DOI: 10.1155/2012/758349

Heavy metals, particularly cadmium, lead, and arsenic, constitute a significant potential threat to human health. This study was conducted to determine the levels of cadmium, lead, and arsenic in nail samples from farmers at Muda Agricultural Development Authority (MADA), Kedah, Malaysia, and evaluate factors that can contribute to their accumulations. A total of 116 farmers participated in this study. Inductively coupled plasma mass spectrometry (ICP-MS) was used to analyze concentration of heavy metals in the nail samples and questionnaires were given to participants to get demographic, health status, and their agricultural activities data. In this paper, the level of heavy metals was within the normal range and varies according to demographic factors. We found that there were significant correlations between working period with level of lead and arsenic (r=0.315 and r=0.242, resp., P<0.01) and age with lead level (r=0.175, P<0.05). Our findings suggested that agricultural activities could contribute to the accumulation of heavy metals in farmers. Hence, the control of environmental levels of and human exposure to these metals to prevent adverse health effects is still an important public health issue.
Dentatin isolated from Clausena excavata induces apoptosis in MCF-7 cells through the intrinsic pathway with involvement of NF-κB signalling and G0/G1 cell cycle arrest: a bioassay-guided approach

Arbab IA, Abdul AB, Sukari MA, Abdullah R, Syam S, Kamalidehghan B, et al.

J Ethnopharmacol, 2013 Jan 9;145(1):343-54.
PMID: 23178663 DOI: 10.1016/j.jep.2012.11.020

Clausena excavata Burm. f. has been used in folk medicines in eastern Thailand for the treatment of cancer.
Induction of cell cycle arrest and apoptosis by betulinic acid-rich fraction from Dillenia suffruticosa root in MCF-7 cells involved p53/p21 and mitochondrial signalling pathway

Foo JB, Saiful Yazan L, Tor YS, Wibowo A, Ismail N, How CW, et al.

J Ethnopharmacol, 2015 May 26;166:270-8.
PMID: 25797115 DOI: 10.1016/j.jep.2015.03.039

Dillenia suffruticosa (Family: Dilleniaceae) or commonly known as "Simpoh air" in Malaysia, is traditionally used for treatment of cancerous growth including breast cancer.
Fulltext Pharmacokinetics and Biodistribution of Thymoquinone-loaded Nanostructured Lipid Carrier After Oral and Intravenous Administration into Rats

Zakarial Ansar FH, Latifah SY, Wan Kamal WHB, Khong KC, Ng Y, Foong JN, et al.

Int J Nanomedicine, 2020;15:7703-7717.
PMID: 33116496 DOI: 10.2147/IJN.S262395

Background: Thymoquinone (TQ), an active compound isolated from Nigella sativa, has been proven to exhibit various biological properties such as antioxidant. Although oral delivery of TQ is valuable, it is limited by poor oral bioavailability and low solubility. Recently, TQ-loaded nanostructured lipid carrier (TQ-NLC) was formulated with the aim of overcoming the limitations. TQ-NLC was successfully synthesized by the high-pressure homogenization method with remarkable physiochemical properties whereby the particle size is less than 100 nm, improved encapsulation efficiency and is stable up to 24 months of storage. Nevertheless, the pharmacokinetics and biodistribution of TQ-NLC have not been studied. This study determined the bioavailability of oral and intravenous administration of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) in rats and its distribution to organs.
Materials and Methods: TQ-NLC was radiolabeled with technetium-99m before the administration to the rats. The biodistribution and pharmacokinetics parameters were then evaluated at various time points. The rats were imaged at time intervals and the percentage of the injected dose/gram (%ID/g) in blood and each organ was analyzed.
Results: Oral administration of TQ-NLC exhibited greater relative bioavailability compared to intravenous administration. It is postulated that the movement of TQ-NLC through the intestinal lymphatic system bypasses the first metabolism and therefore enhances the relative bioavailability. However, oral administration has a slower absorption rate compared to intravenous administration where the AUC0-∞ was 4.539 times lower than the latter.
Conclusion: TQ-NLC had better absorption when administered intravenously compared to oral administration. However, oral administration showed greater bioavailability compared to the intravenous route. This study provides the pharmacokinetics and biodistribution profile of TQ-NLC in vivo which is useful to assist researchers in clinical use.
Constructions of expression vectors of polyhydroxybutyrate-co-hydroxyvalerate (PHBV) and transient expression of transgenes in immature oil palm embryos

Ariffin N, Abdullah R, Rashdan Muad M, Lourdes J, Emran NA, Ismail MR, et al.

Plasmid, 2011 Sep;66(3):136-43.
PMID: 21827784 DOI: 10.1016/j.plasmid.2011.07.002

Polyhydroxybutyrate-co-hydroxyvalerate (PHBV) is a polyhydroxyalkanoate (PHA) bioplastic group with thermoplastic properties is thus high in quality and can be degradable. PHBV can be produced by bacteria, but the process is not economically competitive with polymers produced from petrochemicals. To overcome this problem, research on transgenic plants has been carried out as one of the solutions to produce PHBV in economically sound alternative manner. Four different genes encoded with the enzymes necessary to catalyze PHBV are bktB, phaB, phaC and tdcB. All the genes came with modified CaMV 35S promoters (except for the tdcB gene, which was promoted by the native CaMV 35S promoter), nos terminator sequences and plastid sequences in order to target the genes into the plastids. Subcloning resulted in the generation of two different orientations of the tdcB, pLMIN (left) and pRMIN (right), both 17.557 and 19.967 kb in sizes. Both plasmids were transformed in immature embryos (IE) of oil palm via Agrobacterium tumefaciens. Assays of GUS were performed on one-week-old calli and 90% of the calli turned completely blue. This preliminary test showed positive results of integration. Six-months-old calli were harvested and RNA of the calli were isolated. RT-PCR was used to confirm the transient expression of PHBV transgenes in the calli. The bands were 258, 260, 315 and 200 bp in size for bktB, phaB, phaC and tdcB transgenes respectively. The data obtained showed that the bktB, phaB, phaC and tdcB genes were successfully integrated and expressed in the oil palm genome.
M2/ANXA5 haplotype as a predisposition factor in Malay women and couples experiencing recurrent spontaneous abortion: a pilot study

Thean Hock T, Bogdanova N, Kai Cheen A, Kathirgamanathan S, Bin Abdullah R, Mohd Yusoff N, et al.

Reprod Biomed Online, 2015 Apr;30(4):434-9.
PMID: 25682309 DOI: 10.1016/j.rbmo.2014.12.014

Recurrent spontaneous abortion (RSA) is a prevalent condition among the Malay population of Malaysia, where carriage risk of conventional hereditary thrombophilia factors has been generally ruled out. The contribution of M2/ANXA5, a common haplotype in the annexin A5 gene promoter, was evalauted for RSA in Malay. Seventy-seven women who had experienced two or more unexplained RSA and 41 available male partners were selected for study, with 360 population controls recruited from healthy Malay individuals. Incidence of M2 carriage and odds ratios were calculated between control and patient groups, and clinically defined subgroups and RSA risk was evaluated. M2/ANXA5, found in 42.2% of the general Malay population, was associated with greater risks for women with primary and secondary RSA with early (gestational week 5-15) losses. The risk was somewhat higher in Malay couples when both partners were carriers and a trend of higher prevalence was seen for the male partners patients who had experienced RSA. M2 carriage seems to be a risk factor with unusually high incidence in Malay women and couples with primary and secondary RSA with 'early' spontaneous abortions. The associated male partner risk confirms the proposed role of M2/ANXA5 as a genetic trait impeding embryonic anticoagulation.
Clausenidin Induces Caspase 8-Dependent Apoptosis and Suppresses Production of VEGF in Liver Cancer Cells

Waziri PM, Abdullah R, Rosli R, Omar AR, Abdul AB, Kassim NK, et al.

Asian Pac J Cancer Prev, 2018 Apr 25;19(4):917-922.
PMID: 29693341

Clausena excavata Burm f. is used by traditional healers to treat cancer patients in South East Asia. The use of the
plant and its compounds is based on Asian folklore with little or no scientific evidence supporting the therapeutic efficacy
The current study aimed to determine the effect of pure clausenidin isolated from C. excavata on caspase-8-induced cell
death as well as angiogenesis in the HepG2 hepatocellular carcinoma cell line. Caspase-8 and extrinsic death receptor
protein expression was determined using spectrophotometry and protein profile arrays, respectively. Ultrastructural
analysis of clausenidin-treated cells was conducted using transmission electron microscopy. In addition, anti-angiogenic
effects of clausenidin were investigated by Western blot analysis. Clausenidin significantly (p<0.05) increased the
activity of caspase-8 and expression of protein components of the death inducing signaling complex (DISC) in HepG2
cells. Ultrastructural analysis of the clausenidin-treated HepG2 cells revealed morphological abnormalities typical of
apoptosis. Furthermore, clausenidin significantly (p<0.05) decreased the expression of vascular endothelial growth
factor (VEGF). Therefore, clausenidin is a potential anti-angiogenic agent which may induce apoptosis of hepatocellular
carcinoma cells.
Fulltext Thymoquinone loaded in nanostructured lipid carrier showed enhanced anticancer activity in 4T1 tumor-bearing mice

Ong YS, Saiful Yazan L, Ng WK, Abdullah R, Mustapha NM, Sapuan S, et al.

Nanomedicine (Lond), 2018 07;13(13):1567-1582.
PMID: 30028248 DOI: 10.2217/nnm-2017-0322

AIM: To investigate the enhancement of anticancer activity of thymoquinone (TQ) by the use of nanostructured lipid carrier (NLC) in 4T1 tumor-bearing female BALB/c mice.
MATERIAL & METHODS: TQ was incorporated into NLC (TQNLC) by using high pressure homogenization. TQNLC and TQ were orally administered to the mice.
RESULTS & CONCLUSION: TQNLC and TQ are potential chemotherapeutic drugs as they exhibited anticancer activity. The use of NLC as a carrier has enhanced the therapeutic property of TQ by increasing the survival rate of mice. The antimetastasis effect of TQNLC and TQ to the lungs was evidence by downregulation of MMP-2. TQNLC and TQ induced apoptosis via modulation of Bcl-2 and caspase-8 in the intrinsic apoptotic pathway.
Hepatitis Screening and Treatment Campaign in Malaysia-Validation of Low-cost Point of Care Screening Tests and Nucleic Acid Tests for Hepatitis B and C

Radzi Ah M, S Tan S, Mohamed R, Jaya F, K S, C Aun A, et al.

Euroasian J Hepatogastroenterol, 2019 02 01;8(2):101-107.
PMID: 30828549 DOI: 10.5005/jp-journals-10018-1273

Background: Two major challenges in implementing budget-constrained Hepatitis screening and treatment campaign in Malaysia are the availability of low-cost point of care tests (POCT) and nucleic acid tests (NAT) for hepatitis C virus ribonucleic acid (HCV RNA) and hepatitis B virus dioxyribo nucleic acid (HBV DNA). We evaluated the performance of these tests in this study.
Methods: We conducted a cross-sectional study to evaluate the diagnostic performance of four POCT brands at 12 sites in Malaysia. We assessed the sensitivity and specificity of the POCTs for the detection of HBsAg and anti-HCV in a finger-stick capillary or venepuncture whole-blood samples compared with test results from lab-based enzyme immunoassay (EIA) or chemi-luminescence immunoassay (CLIA) assay as the reference standard. We also conducted a cross-sectional study on 30 to 139 serum specimen panel to evaluate the diagnostic performance of a low-cost in-house Applied Biosystem®TaqMan real-time polymerase chain reaction (PCR) assay (ABS) for the detection of HCV RNA and HBV DNA, compare with Roche Cobas® Ampliprep/TaqMan assay (COBAS).
Results: Between March and December 2017, we enroll 295 participants for the evaluation of POCT for HBsAg and another 307 participants for POCT anti-HCV evaluation. Three of the four POCT brands dropped out of evaluation early on account of sub-optimal sensitivity. The sensitivity of the remaining POCT for HBsAg was 95.2%and specificity 100%, while the POCT for anti-HCV has a sensitivity of 98.1% and specificity 100%.Hepatitis B virus dioxyribo nucleic acid and HCV RNA concentrations detected by the ABS were systematically higher than those measured by COBAS (mean bias +0.10 and +0.17 log10 IU/mL respectively). The 95% limits of agreement between the two assays are -1.28 to 1.47 log10 IU/mL for HBV DNA and -0.41 to 0.75 log10 IU/mL for HCV RNA.
Conclusion: We found adequate evidence for the diagnostic validity of a low-cost POCT for anti-HCV and HBsAg, as well as for an in-house nucleic acid tests (NAT), to provide support for their broader use in our Hepatitis screening and treatment campaign.
Abbreviations: ABS: Applied Biosystem®TaqMan real-time PCR assay, CI: Confidence interval, CLD: Chronic liver disease, CLIA: Chemi-luminescence immunoassay, COBAS: Roche Cobas® Ampliprep/ TaqMan assay, DAA: Direct Acting Anti-Viral drugs, EIA: Enzyme immunoassay, HBV: Hepatitis B virus, HCV: Hepatitis C virus, HFPM: Hepatitis Free Pahang Malaysia, LOA: Limits of agreement, LOD: Limit of detection, MOH: Ministry of Health, Malaysia, NAT: Nucleic Acid Tests, POCT: Point of Care Tests, SD: Standard deviation, WHO: World Health OrganizationHow to cite this article: Radzi AHM, Tan SS, Mohamed R, Jaya F, Senamjit K, Aun AC, Kutty GA, Wong HS, Abdullah R, Seman MR, Mahtab MA, Morad Z, Lim TO. Hepatitis Screening and Treatment Campaign in Malaysia-Validation of Low-cost Point of Care Screening Tests and Nucleic Acid Tests for Hepatitis B and C. Euroasian J Hepatogastroenterol, 2018;8(2):101-107.
Fulltext Radiosensitization Effects by Bismuth Oxide Nanoparticles in Combination with Cisplatin for High Dose Rate Brachytherapy

Sisin NNT, Abdul Razak K, Zainal Abidin S, Che Mat NF, Abdullah R, Ab Rashid R, et al.

Int J Nanomedicine, 2019;14:9941-9954.
PMID: 31908451 DOI: 10.2147/IJN.S228919

Purpose: The aim of this study was to investigate the potential of the synergetic triple therapeutic combination encompassing bismuth oxide nanoparticles (BiONPs), cisplatin (Cis), and high dose rate (HDR) brachytherapy with Ir-192 source in breast cancer and normal fibroblast cell line.
Methods: In vitro models of breast cancer cell lines (MCF-7, MDA-MB-231) and normal fibroblast cell line (NIH/3T3) were employed. Cellular localization and cytotoxicity studies were conducted prior to inspection on the radiosensitization effects and generation of reactive oxygen species (ROS) on three proposed radiosensitizers: BiONPs, Cis, and BiONPs-Cis combination (BC). The optimal, non-cytotoxic concentration of BiONPs (0.5 mM) and the 25% inhibitory concentration of Cis (1.30 µM) were applied. The radiosensitization effects were evaluated by using a 0.38 MeV Iridium-192 HDR brachytherapy source over a prescribed dose range of 0 Gy to 4 Gy.
Results: The cellular localization of BiONPs was visualized by light microscopy and accumulation of the BiONPs within the vicinity of the nuclear membrane was observed. Quantification of the sensitization enhancement ratio extrapolated from the survival curves indicates radiosensitization effects for MCF-7 and MDA-MB-231 when treated with BiONPs, Cis, and BC. However, NIH/3T3 cells exhibited contradictive behavior as it only reacted towards the BC combination. Nonetheless, the MCF-7 cell line loaded with BC shows the highest SER of 4.29. ROS production analysis, on the other hand, shows that Cis and BC radiosensitizers generated the highest free radicals in comparison to BiONPs alone.
Conclusion: A BiONPs-Cis combination was unveiled as a novel approach that offers promising radiosensitization enhancement that will increase the efficiency of tumor control while preserving the normal tissue at a reduced dose. This data is the first precedent to prove the synergetic implication of BiONPs, Cis, and HDR brachytherapy that will be beneficial for future chemoradiotherapy strategies in cancer care.
Fulltext Physicochemical characterization, cytotoxic effect and toxicity evaluation of nanostructured lipid carrier loaded with eucalyptol

Izham MNM, Hussin Y, Rahim NFC, Aziz MNM, Yeap SK, Rahman HS, et al.

BMC Complement Med Ther, 2021 Oct 07;21(1):254.
PMID: 34620132 DOI: 10.1186/s12906-021-03422-y

BACKGROUND: Eucalyptol is an active compound of eucalyptus essential oil and was reported to have many medical attributes including cytotoxic effect on breast cancer cells. However, it has low solubility in aqueous solutions which limits its bioavailability and cytotoxic efficiency. In this study, nanostructured lipid carrier loaded with eucalyptol (NLC-Eu) was formulated and characterized and the cytotoxic effect of NLC-Eu towards breast cancer cell lines was determined. In addition, its toxicity in animal model, BALB/c mice was also incorporated into this study to validate the safety of NLC-Eu.
METHODS: Eucalyptol, a monoterpene oxide active, was used to formulate the NLC-Eu by using high pressure homogenization technique. The physicochemical characterization of NLC-Eu was performed to assess its morphology, particle size, polydispersity index, and zeta potential. The in vitro cytotoxic effects of this encapsulated eucalyptol on human (MDA MB-231) and murine (4 T1) breast cancer cell lines were determined using the MTT assay. Additionally, acridine orange/propidium iodide assay was conducted on the NLC-Eu treated MDA MB-231 cells. The in vivo sub-chronic toxicity of the prepared NLC-Eu was investigated using an in vivo BALB/c mice model.
RESULTS: As a result, the light, translucent, milky-colored NLC-Eu showed particle size of 71.800 ± 2.144 nm, poly-dispersity index of 0.258 ± 0.003, and zeta potential of - 2.927 ± 0.163 mV. Furthermore, the TEM results of NLC-Eu displayed irregular round to spherical morphology with narrow size distribution and relatively uniformed particles. The drug loading capacity and entrapment efficiency of NLC-Eu were 4.99 and 90.93%, respectively. Furthermore, NLC-Eu exhibited cytotoxic effects on both, human and mice, breast cancer cells with IC50 values of 10.00 ± 4.81 μg/mL and 17.70 ± 0.57 μg/mL, respectively at 72 h. NLC-Eu also induced apoptosis on the MDA MB-231 cells. In the sub-chronic toxicity study, all of the studied mice did not show any signs of toxicity, abnormality or mortality. Besides that, no significant changes were observed in the body weight, internal organ index, hepatic and renal histopathology, serum biochemistry, nitric oxide and malondialdehyde contents.
CONCLUSIONS: This study suggests that the well-characterized NLC-Eu offers a safe and promising carrier system which has cytotoxic effect on breast cancer cell lines.
Potential serum biomarkers associated with mild and severe leptospirosis infection: A cohort study in the Malaysian population

Tan XT, Amran FB, Thayan R, Ahmad N, Jaafar R, Haron R, et al.

Electrophoresis, 2017 09;38(17):2141-2149.
PMID: 28524240 DOI: 10.1002/elps.201600471

Leptospirosis is an emerging zoonotic infectious disease in Malaysia. The symptoms of leptospirosis vary from mild nonspecific flu-like illness to a severe condition which is usually associated with serious complication and fatality. To study the protein expression profile of mild and severe leptospirosis, 15 paired sera were collected from the patients who were mildly infected and following that progressed to severe stage. The proteome profiles of mild and severe cases were studied using 2DE analysis in combination with LC-MS/MS. The expression of proteins that were significantly different and had a fold difference of at least 2 had been identified and then validated using Western blot. Our study demonstrated apolipoprotein A-I (APOA-I), serum amyloid A (SAA), transferrin (TF), haptoglobin (HP) and transthyretin (TTR) have significantly different expression between mild and severe leptospirosis. The Ingenuity Pathway Analysis software suggested the expression of these five proteins were modulated by acute phase response signaling pathway. Besides that, a functional network of lipid metabolism, molecular transport and small molecule biochemistry that interconnects these five proteins with interactomes also had been predicted by this software. In conclusion, this finding supports the potential of these five proteins to be the biomarkers for mild and severe human leptospirosis.
Respiratory carriage of hypervirulent Klebsiella pneumoniae by indigenous populations of Malaysia

Das S, Pandey AK, Morris DE, Anderson R, Lim V, Wie CC, et al.

BMC Genomics, 2024 Apr 17;25(1):381.
PMID: 38632538 DOI: 10.1186/s12864-024-10276-4

Klebsiella pneumoniae is a Gram-negative Enterobacteriaceae that is classified by the World Health Organisation (WHO) as a Priority One ESKAPE pathogen. South and Southeast Asian countries are regions where both healthcare associated infections (HAI) and community acquired infections (CAI) due to extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant K. pneumoniae (CRKp) are of concern. As K. pneumoniae can also exist as a harmless commensal, the spread of resistance genotypes requires epidemiological vigilance. However there has been no significant study of carriage isolates from healthy individuals, particularly in Southeast Asia, and specially Malaysia. Here we describe the genomic analysis of respiratory isolates of K. pneumoniae obtained from Orang Ulu and Orang Asli communities in Malaysian Borneo and Peninsular Malaysia respectively. The majority of isolates were K. pneumoniae species complex (KpSC) 1 K. pneumoniae (n = 53, 89.8%). Four Klebsiella variicola subsp. variicola (KpSC3) and two Klebsiella quasipneumoniae subsp. similipneumoniae (KpSC4) were also found. It was discovered that 30.2% (n = 16) of the KpSC1 isolates were ST23, 11.3% (n = 6) were of ST65, 7.5% (n = 4) were ST13, and 13.2% (n = 7) were ST86. Only eight of the KpSC1 isolates encoded ESBL, but importantly not carbapenemase. Thirteen of the KpSC1 isolates carried yersiniabactin, colibactin and aerobactin, all of which harboured the rmpADC locus and are therefore characterised as hypervirulent. Co-carriage of multiple strains was minimal. In conclusion, most isolates were KpSC1, ST23, one of the most common sequence types and previously found in cases of K. pneumoniae infection. A proportion were hypervirulent (hvKp) however antibiotic resistance was low.
Fulltext The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells

Etti IC, Abdullah R, Kadir A, Hashim NM, Yeap SK, Imam MU, et al.

PLoS One, 2017;12(8):e0182357.
PMID: 28771532 DOI: 10.1371/journal.pone.0182357

Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer.

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