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  1. Ibrahim MY, Hashim NM, Mohan S, Abdulla MA, Kamalidehghan B, Ghaderian M, et al.
    Drug Des Devel Ther, 2014;8:1629-47.
    PMID: 25302018 DOI: 10.2147/DDDT.S66105
    Cratoxylum arborescens is an equatorial plant belonging to the family Guttiferae. In the current study, α-Mangostin (AM) was isolated and its cell death mechanism was studied. HCS was undertaken to detect the nuclear condensation, mitochondrial membrane potential, cell permeability, and the release of cytochrome c. An investigation for reactive oxygen species formation was conducted using fluorescent analysis. To determine the mechanism of cell death, human apoptosis proteome profiler assay was conducted. In addition, using immunofluorescence and immunoblotting, the levels of Bcl-2-associated X protein (Bax) and B-cell lymphoma (Bcl)-2 proteins were also tested. Caspaces such as 3/7, 8, and 9 were assessed during treatment. Using HCS and Western blot, the contribution of nuclear factor kappa-B (NF-κB) was investigated. AM had showed a selective cytotoxicity toward the cancer cells with no toxicity toward the normal cells even at 30 μg/mL, thereby indicating that AM has the attributes to induce cell death in tumor cells. The treatment of MCF-7 cells with AM prompted apoptosis with cell death-transducing signals. This regulated the mitochondrial membrane potential by down-regulation of Bcl-2 and up-regulation of Bax, thereby causing the release of cytochrome c from the mitochondria into the cytosol. The liberation of cytochrome c activated caspace-9, which, in turn, activated the downstream executioner caspace-3/7 with the cleaved poly (ADP-ribose) polymerase protein, thereby leading to apoptotic alterations. Increase of caspace 8 had showed the involvement of an extrinsic pathway. This type of apoptosis was suggested to occur through both extrinsic and intrinsic pathways and prevention of translocation of NF-κB from the cytoplasm to the nucleus. Our results revealed AM prompt apoptosis of MCF-7 cells through NF-κB, Bax/Bcl-2 and heat shock protein 70 modulation with the contribution of caspaces. Moreover, ingestion of AM at (30 and 60 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that AM is a potentially useful agent for the treatment of breast cancer.
  2. Abdelwahab SI, Abdul AB, Mohan S, Taha MM, Syam S, Ibrahim MY, et al.
    Leuk. Res., 2011 Feb;35(2):268-71.
    PMID: 20708800 DOI: 10.1016/j.leukres.2010.07.025
    Zerumbone (ZER) is a potential anticancer natural compound, isolated from Zingiber zerumbet Smith. In this investigation, the anticancer properties of ZER were evaluated on cancer cells of T-acute lymphoblastic leukemia, CEM-ss. The results showed that ZER has cytotoxic effect against CEM-ss cells with an IC(50) of 8.4 ± 1.9 μg/ml (coefficient of variation < 30%). Comparatively, 5-fluorouracil (positive control), imposed an inhibitory effect on CEM-ss cells with an IC(50) of 1.94 ± 0.06 μg/ml. Scanning electron microscopy (SEM) results revealed abnormalities such as membrane blebbing, holes and cytoplasmic extrusions, all of which are characteristics of apoptosis. In addition, ZER has increased the number of TUNEL-positive stain and the cellular level of caspase-3, the hallmarks of apoptosis, on treated CEM-ss cells. It could be concluded that, ZER was able to produce apoptosis on T-acute lymphoblastic leukemia, CEM-ss. The current findings suggest that ZER might be helpful for improving the usefulness of anticancer agents in the therapy of leukemia.
  3. Mohan S, Abdul AB, Abdelwahab SI, Al-Zubairi AS, Sukari MA, Abdullah R, et al.
    J Ethnopharmacol, 2010 Oct 5;131(3):592-600.
    PMID: 20673794 DOI: 10.1016/j.jep.2010.07.043
    The plant Typhonium flagelliforme (TF), commonly known as 'rodent tuber' in Malaysia, is often used as traditional remedy for cancer, including leukemia.
  4. Salim LZ, Othman R, Abdulla MA, Al-Jashamy K, Ali HM, Hassandarvish P, et al.
    PLoS One, 2014;9(12):e115340.
    PMID: 25531768 DOI: 10.1371/journal.pone.0115340
    BACKGROUND: Thymoquinone is an active ingredient isolated from Nigella sativa (Black Seed). This study aimed to evaluate the in vitro and in vivo anti-leukemic effects of thymoquinone on WEHI-3 cells.

    METHODOLOGY/PRINCIPAL FINDINGS: The cytotoxic effect of thymoquinone was assessed using an MTT assay, while the inhibitory effect of thymoquinone on murine WEHI-3 cell growth was due to the induction of apoptosis, as evidenced by chromatin condensation dye, Hoechst 33342 and acridine orange/propidium iodide fluorescent staining. In addition, Annexin V staining for early apoptosis was performed using flowcytometric analysis. Apoptosis was found to be associated with the cell cycle arrest at the S phase. Expression of Bax, Bcl2 and HSP 70 proteins were observed by western blotting. The effects of thymoquinone on BALB/c mice injected with WEHI-3 cells were indicated by the decrease in the body, spleen and liver weights of the animal, as compared to the control.

    CONCLUSION: Thymoquinone promoted natural killer cell activities. This compound showed high toxicity against WEHI-3 cell line which was confirmed by an increase of the early apoptosis, followed by up-regulation of the anti-apoptotic protein, Bcl2, and down-regulation of the apoptotic protein, Bax. On the other hand, high reduction of the spleen and liver weight, and significant histopathology study of spleen and liver confirmed that thymoquinone inhibited WEHI-3 growth in the BALB/c mice. Results from this study highlight the potential of thymoquinone to be developed as an anti-leukemic agent.

  5. Salim LZ, Mohan S, Othman R, Abdelwahab SI, Kamalidehghan B, Sheikh BY, et al.
    Molecules, 2013 Sep 12;18(9):11219-40.
    PMID: 24036512 DOI: 10.3390/molecules180911219
    There has been a growing interest in naturally occurring compounds from traditional medicine with anti-cancer potential. Nigella sativa (black seed) is one of the most widely studied plants. This annual herb grows in countries bordering the Mediterranean Sea and India. Thymoquinone (TQ) is an active ingredient isolated from Nigella sativa. The anti-cancer effect of TQ, via the induction of apoptosis resulting from mitochondrial dysfunction, was assessed in an acute lymphocyte leukemic cell line (CEMss) with an IC50 of 1.5 µg/mL. A significant increase in chromatin condensation in the cell nucleus was observed using fluorescence analysis. The apoptosis was then confirmed by Annexin V and an increased number of cellular DNA breaks in treated cells were observed as a DNA ladder. Treatment of CEMss cells with TQ encouraged apoptosis with cell death-transducing signals by a down-regulation of Bcl-2 and up-regulation of Bax. Moreover, the significant generation of cellular ROS, HSP70 and activation of caspases 3 and 8 were also observed in the treated cells. The mitochondrial apoptosis was clearly associated with the S phase cell cycle arrest. In conclusion, the results from the current study indicated that TQ could be a promising agent for the treatment of leukemia.
  6. Kunasagran PD, Mokti K, Ibrahim MY, Rahim SSSA, Robinson F, Muyou AJ, et al.
    Korean J Fam Med, 2024 Jan;45(1):3-11.
    PMID: 37848369 DOI: 10.4082/kjfm.23.0084
    The coronavirus disease (COVID-19) pandemic has led to an alarming increase in domestic violence against women owing to lockdown measures and limited access to support services. This article provides insights into the global prevalence of domestic violence, barriers to seeking help, its impact on women and children, and the best practices implemented worldwide. Domestic violence encompasses various forms of abuse; many young women experience partner violence. Barriers to seeking help include fear, financial constraints, lack of awareness of available services, and distrust among stakeholders. The consequences of domestic violence affect the mental health of both mothers and children. Countries have increased shelter funding and developed innovative protocols to reach survivors and address this issue. However, the healthcare sector's involvement in addressing domestic violence has been limited. This review advocates collaboration among healthcare institutions and government bodies. Key recommendations include utilizing telehealth services, implementing comprehensive training programs, establishing effective referral systems, enhancing health education, developing a domestic violence registry, improving the responses of law enforcement and justice systems through healthcare integration, promoting data sharing, and conducting further research. Healthcare systems should recognize domestic violence as a public health concern and detect, prevent, and intervene in cases to support survivors.
  7. Jeffree SM, Mihat O, Lukman KA, Ibrahim MY, Kamaludin F, Hassan MR, et al.
    Asian Pac J Cancer Prev, 2016;17(7):3123-9.
    PMID: 27509940
    BACKGROUND: Cancer is the fourth leading cause of death in Sabah Malaysia with a reported agestandardized incidence rate was 104.9 per 100,000 in 2007. The incidence rate depends on nonmandatory notification in the registry. Underreporting will provide the false picture of cancer control program effectiveness. The present study was to evaluate the performance of the cancer registry system in terms of representativeness, data quality, simplicity, acceptability and timeliness and provision of recommendations for improvement.

    MATERIALS AND METHODS: The evaluation was conducted among key informants in the National Cancer Registry (NCR) and reporting facilities from FebMay 2012 and was based on US CDC guidelines. Representativeness was assessed by matching cancer case in the Health Information System (HIS) and state pathology records with those in NCR. Data quality was measured through case finding and reabstracting of medical records by independent auditors. The reabstracting portion comprised 15 data items. Selfadministered questionnaires were used to assess simplicity and acceptability. Timeliness was measured from date of diagnosis to date of notification received and data dissemination.

    RESULTS: Of 4613 cancer cases reported in HIS, 83.3% were matched with cancer registry. In the state pathology centre, 99.8% was notified to registry. Duplication of notification was 3%. Data completeness calculated for 104 samples was 63.4%. Registrars perceived simplicity in coding diagnosis as moderate. Notification process was moderately acceptable. Median duration of interval 1 was 5.7 months.

    CONCLUSIONS: The performances of registry's attributes are fairly positive in terms of simplicity, case reporting sensitivity, and predictive value positive. It is moderately acceptable, data completeness and inflexible. The usefulness of registry is the area of concern to achieve registry objectives. Timeliness of reporting is within international standard, whereas timeliness to data dissemination was longer up to 4 years. Integration between existing HIS and national registration department will improve data quality.

  8. Naserrudin NA, Jeffree MS, Kaur N, Rahim SSSA, Ibrahim MY
    Int J Environ Res Public Health, 2022 Sep 29;19(19).
    PMID: 36231721 DOI: 10.3390/ijerph191912426
    The most common complication of diabetes mellitus (DM) is diabetic retinopathy (DR). The control of DR risk factors is essential for the effective prevention of DR. There is currently a lack of research to guide DR-related research in Malaysia. This concept paper aimed to review published studies and propose a conceptual framework (CF) as a guide for future research to determine the prevalence of DR and its risk factors across DM patients. After a review of prior research, this study has presented a CF that takes into account these four key elements: the patient's sociodemographic characteristics, comorbidities, complications, and diabetes conditions, namely, the length of the disease and glycaemic control. In the suggested CF, ethnicity was highlighted as a crucial risk factor for DR across lower- to middle-income countries (LMIC) and multiracial countries. In order to guide future studies, scientific guidance is essential. The proposed CF would help future research to conduct scientific research related to DR. Also, the proposed CF was tailored to suit research across LMIC and multiracial countries.
  9. Chin AZ, Avoi R, Atil A, Awang Lukman K, Syed Abdul Rahim SS, Ibrahim MY, et al.
    PLoS One, 2021;16(9):e0257104.
    PMID: 34506556 DOI: 10.1371/journal.pone.0257104
    BACKGROUND: In the Malaysian state of Sabah, P. knowlesi notifications increased from 2% (59/2,741) of total malaria notifications in 2004 to 98% (2030/2,078) in 2017. There was a gap regarding P. knowlesi acquisition risk factors related to practice specifically in working age group. The main objective of this study was to identify the risk factors for acquiring P. knowlesi infection in Sabah among the working age group.

    METHODS AND METHODS: This retrospective population-based case-control study was conducted in Ranau district to assess sociodemographic, behavioural and medical history risk factors using a pretested questionnaire. The data were entered and analyzed using IBM SPSS version 23. Bivariate analysis was conducted using binary logistic regression whereas multivariate analysis was conducted using multivariable logistic regression. We set a statistical significance at p-value less than or equal to 0.05.

    RESULTS: A total of 266 cases and 532 controls were included in the study. Male gender (AOR = 2.71; 95% CI: 1.63-4.50), spending overnight in forest (AOR = 1.92; 95% CI: 1.20-3.06), not using mosquito repellent (AOR = 2.49; 95% CI: 1.36-4.56) and history of previous malaria infection (AOR = 49.34; 95% CI: 39.09-78.32) were found to be independent predictors of P. knowlesi infection.

    CONCLUSIONS: This study showed the need to strengthen the strategies in preventing and controlling P. knowlesi infection specifically in changing the practice of spending overnight in forest and increasing the usage of personal mosquito repellent.

  10. Ibrahim MY, Hashim NM, Dhiyaaldeen SM, Al-Obaidi MMJ, El-Ferjani RM, Adam H, et al.
    Sci Rep, 2020 04 17;10(1):6792.
    PMID: 32303687 DOI: 10.1038/s41598-020-63217-y
    This paper has been retracted.
  11. Abidin A, Awang Lukman K, Sajali H, Syed Abdul Rahim SS, Robinson F, Hassan MR, et al.
    Ann Med Surg (Lond), 2021 Sep;69:102699.
    PMID: 34429955 DOI: 10.1016/j.amsu.2021.102699
    Background: Occupational injuries are among the most important workplace issues. This study aims to determine the safety climate and prevalence of occupational injuries in the small-scale manufacturing industry.

    Methods: A cross-sectional study with ten small scale manufacturers participated accounting for a total of 300 respondents. Data were collected from July to August 2020 using the NOSACQ-50 questionnaire.

    Results: The prevalence of occupational injury for the past 12 months was at 18%. The most often injured body parts were hands and legs while among the most common injury types were open wound, burns and bleeding. The mean NOSACQ-50 scores for all dimensions are good. The associated factors are working hours per week, and compliance to SOP. There are differences in the mean scores of NOSACQ-50 between injured and non-injured workers across all dimensions.

    Conclusion: The safety climate among manufacturing industry employees is at a good level, while the prevalence of occupational injury is relatively low.

  12. Qaiser S, Daud MNM, Ibrahim MY, Gan SH, Rahman MS, Sani MHM, et al.
    Medicine (Baltimore), 2020 May 22;99(21):e20287.
    PMID: 32481309 DOI: 10.1097/MD.0000000000020287
    Unhealthy lifestyle contributes mainly to an increased prevalence of non-communicable diseases including hypertension and cardiovascular diseases tend to increase in Malaysia. These diseases lead to an increased risk of end organ damage and cardiovascular complications. In this study, the prevalence of prehypertension and its associated risk factors among a cohort of university students in Sabah was determined.This is a prospective, cross-sectional study conducted among 365 undergraduate students irrespective of faculties at Universiti Malaysia Sabah (UMS). Standardized and validated World Health Organization (WHO) STEPS questionnaires were used to collect sociodemographic data. Additionally, clinical and anthropometric data were measured and recorded by a trained staff, followed by descriptive and logistic regression analyses.A total of 365 UMS undergraduate students aged 18 years and above participated in the study. The prevalence of prehypertension among university students was high (31%) (95% CI [29.1%, 34.3%]). Well-known risk factors for hypertension including family history of hypertension, reduced sleep duration, reduced physical activity, smoking, being overweight or obese were significantly associated with the risk of developing prehypertension (P 
  13. Ibrahim MY, Hashim NM, Omer FAA, Abubakar MS, Mohammed HA, Salama SM, et al.
    Int J Mol Sci, 2023 Jun 17;24(12).
    PMID: 37373429 DOI: 10.3390/ijms241210283
    In this study, the chemotherapeutic effect of α-mangostin (AM) was assessed in rats injected with LA7 cells. Rats received AM orally at 30 and 60 mg/kg twice a week for 4 weeks. Cancer biomarkers such as CEA and CA 15-3 were significantly lower in AM-treated rats. Histopathological evaluations showed that AM protects the rat mammary gland from the carcinogenic effects of LA7 cells. Interestingly, AM decreased lipid peroxidation and increased antioxidant enzymes when compared to the control. Immunohistochemistry results of the untreated rats showed abundant PCNA and fewer p53-positive cells than AM-treated rats. Using the TUNEL test, AM-treated animals had higher apoptotic cell numbers than those untreated. This report revealed that that AM lessened oxidative stress, suppressed proliferation, and minimized LA7-induced mammary carcinogenesis. Therefore, the current study suggests that AM has significant potential for breast cancer treatment.
  14. Montini Maluda MC, Jelip J, Ibrahim MY, Suleiman M, Jeffree MS, Binti Aziz AF, et al.
    Am J Trop Med Hyg, 2020 08;103(2):864-868.
    PMID: 32524958 DOI: 10.4269/ajtmh.19-0928
    Japanese encephalitis (JE) is endemic in Malaysia. Although JE vaccination is practiced in the neighboring state of Sarawak for a long time, little is known about JE in Sabah state in Borneo. As a result, informed policy formulation for JE in Sabah has not been accomplished. In the present study, we have analyzed JE cases that have been reported to the Sabah State Health Department from 2000 to 2018. A total of 92 JE cases were reported during 19 years, and three-fourths of the cases were attributed to children. The estimated mean incidence for JE cases is 0.161/100,000 population. Japanese encephalitis was predominant in Sabah during June, July, and August, peaking in July. In most cases, pigs were absent within a 400-m radius of the place of residence. We could not establish any relationship between the mapping of JE cases and the number of piggeries in each district. We could not establish a relationship between average rainfall and JE cases, either. We propose the cases reported are possibly showing the tip of an iceberg and continuous surveillance is needed, as JE is a public health challenge in Sabah.
  15. Khataee HR, Ibrahim MY
    IET Nanobiotechnol, 2012 Sep;6(3):87-92.
    PMID: 22894532 DOI: 10.1049/iet-nbt.2011.0062
    Kinesin is a protein-based natural nanomotor that transports molecular cargoes within cells by walking along microtubules. Kinesin nanomotor is considered as a bio-nanoagent which is able to sense the cell through its sensors (i.e. its heads and tail), make the decision internally and perform actions on the cell through its actuator (i.e. its motor domain). The study maps the agent-based architectural model of internal decision-making process of kinesin nanomotor to a machine language using an automata algorithm. The applied automata algorithm receives the internal agent-based architectural model of kinesin nanomotor as a deterministic finite automaton (DFA) model and generates a regular machine language. The generated regular machine language was acceptable by the architectural DFA model of the nanomotor and also in good agreement with its natural behaviour. The internal agent-based architectural model of kinesin nanomotor indicates the degree of autonomy and intelligence of the nanomotor interactions with its cell. Thus, our developed regular machine language can model the degree of autonomy and intelligence of kinesin nanomotor interactions with its cell as a language. Modelling of internal architectures of autonomous and intelligent bio-nanosystems as machine languages can lay the foundation towards the concept of bio-nanoswarms and next phases of the bio-nanorobotic systems development.
  16. Abdelhafez MMA, Ahmed KAM, Ahmed NAM, Ismail MH, Daud MNM, Eldiasty AME, et al.
    Afr J Reprod Health, 2024 Mar 31;28(3):122-129.
    PMID: 38583076 DOI: 10.29063/ajrh2024/v28i3.13
    Menopausal hormone therapy (MHT) is known to increase the risk of venous thromboembolism (VTE), which includes deep vein thrombosis, pulmonary embolism, and less frequently cerebral vein thrombosis, but the absolute risk for a given patient is very low. After starting MHT, the risk of VTE seems to be at its highest, declining to the non-HRT user baseline level of risk after stopping. Whether estrogen-only or estrogen-progestin HRT combination is linked to a similar risk of VTE is unclear from the available evidence. The aim of this study is to evaluate the risks of developing VTE in relation to different types as well as different modes of administration of MHT through a database search including PubMed, MEDLINE, Google Scholar, Cochrane Library, and others in order to provide the women carers with the up-to-date and evidence-based guidelines and recommendations while counseling the post-menopausal women enquiring on use of hormonal therapies either to alleviate the menopausal symptoms or to prevent the long-term sequelae of estrogen deficiency.
  17. Khoo EM, Lee WK, Sararaks S, Abdul Samad A, Liew SM, Cheong AT, et al.
    BMC Fam Pract, 2012 Dec 26;13:127.
    PMID: 23267547 DOI: 10.1186/1471-2296-13-127
    BACKGROUND: Patient safety is vital in patient care. There is a lack of studies on medical errors in primary care settings. The aim of the study is to determine the extent of diagnostic inaccuracies and management errors in public funded primary care clinics.

    METHODS: This was a cross-sectional study conducted in twelve public funded primary care clinics in Malaysia. A total of 1753 medical records were randomly selected in 12 primary care clinics in 2007 and were reviewed by trained family physicians for diagnostic, management and documentation errors, potential errors causing serious harm and likelihood of preventability of such errors.

    RESULTS: The majority of patient encounters (81%) were with medical assistants. Diagnostic errors were present in 3.6% (95% CI: 2.2, 5.0) of medical records and management errors in 53.2% (95% CI: 46.3, 60.2). For management errors, medication errors were present in 41.1% (95% CI: 35.8, 46.4) of records, investigation errors in 21.7% (95% CI: 16.5, 26.8) and decision making errors in 14.5% (95% CI: 10.8, 18.2). A total of 39.9% (95% CI: 33.1, 46.7) of these errors had the potential to cause serious harm. Problems of documentation including illegible handwriting were found in 98.0% (95% CI: 97.0, 99.1) of records. Nearly all errors (93.5%) detected were considered preventable.

    CONCLUSIONS: The occurrence of medical errors was high in primary care clinics particularly with documentation and medication errors. Nearly all were preventable. Remedial intervention addressing completeness of documentation and prescriptions are likely to yield reduction of errors.

  18. Sazali MF, Rahim SSSA, Mohamed MH, Omar A, Pang NTP, Jeffree MS, et al.
    J Public Health Res, 2021 Mar 24;10(3).
    PMID: 33759447 DOI: 10.4081/jphr.2021.2122
    BACKGROUND: COVID-19 related knowledge, attitude and practice plays a major role in determining the readiness of the community to adopt the behavioural change towards recommended preventive measures outlined by public health officials. This study aims to assess the knowledge, attitude, and practice regarding COVID-19 among university students as well as its associated factors.

    METHOD: This is a cross sectional study that was conducted among students in a public university during the early phase of COVID-19 pandemic in Malaysia. An online validated self-administered questionnaire was used to collect the data. Mann-Whitney U and Kruskal Wallis test was used to determine the association between independent variables with knowledge, attitude, and practice score.

    RESULTS: Overall response rate of this study was 92.9 (n=524). Median score of knowledge domain was 78.0 (IQR= ±12.0), median attitude score of 49.0 (IQR= ±5.0), and median practice score of 80.0 (IQR= ±11.0). The mean knowledge, attitude and practice score were significantly higher among diploma holder (vs degree holder, p<0.05), residing in main Kota Kinabalu campus (vs non-KK campus, p<0.001), studying in medical faculty (vs non-medical faculty, p<0.001), and attended COVID-19 education (vs non-attendance; p<0.05).

    CONCLUSION: COVID-19 related knowledge and attitude were below satisfactory level during earlier phase of the pandemic. However, majority of respondents have positive behaviour towards COVID-19 prevention. This highlights the importance of accurate and tailored health education to improve the level of knowledge, attitude and practice of recommended measures to prevent COVID-19 spread.

  19. Ibrahim MY, Mohd Hashim N, Mohan S, Abdulla MA, Abdelwahab SI, Kamalidehghan B, et al.
    Drug Des Devel Ther, 2014;8:2193-211.
    PMID: 25395836 DOI: 10.2147/DDDT.S66574
    BACKGROUND: Cratoxylum arborescens has been used traditionally in Malaysia for the treatment of various ailments.

    METHODS: α-Mangostin (AM) was isolated from C. arborescens and its cell death mechanism was investigated. AM-induced cytotoxicity was observed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Acridine orange/propidium iodide staining and annexin V were used to detect cells in early phases of apoptosis. High-content screening was used to observe the nuclear condensation, cell permeability, mitochondrial membrane potential, and cytochrome c release. The role of caspases-3/7, -8, and -9, reactive oxygen species, Bcl-2 and Bax expression, and cell cycle arrest were also investigated. To determine the role of the central apoptosis-related proteins, a protein array followed by immunoblot analysis was conducted. Moreover, the involvement of nuclear factor-kappa B (NF-κB) was also analyzed.

    RESULTS: Apoptosis was confirmed by the apoptotic cells stained with annexin V and increase in chromatin condensation in nucleus. Treatment of cells with AM promoted cell death-transducing signals that reduced MMP by downregulation of Bcl-2 and upregulation of Bax, triggering cytochrome c release from the mitochondria to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by the executioner caspase-3/7 and then cleaved the PARP protein. Increase of caspase-8 showed the involvement of extrinsic pathway. AM treatment significantly arrested the cells at the S phase (P<0.05) concomitant with an increase in reactive oxygen species. The protein array and Western blotting demonstrated the expression of HSP70. Moreover, AM significantly blocked the induced translocation of NF-κB from cytoplasm to nucleus.

    CONCLUSION: Together, the results demonstrate that the AM isolated from C. arborescens inhibited the proliferation of MDA-MB-231 cells, leading to cell cycle arrest and programmed cell death, which was suggested to occur through both the extrinsic and intrinsic apoptosis pathways with involvement of the NF-κB and HSP70 signaling pathways.

  20. William T, Rahman HA, Jelip J, Ibrahim MY, Menon J, Grigg MJ, et al.
    PLoS Negl Trop Dis, 2013;7(1):e2026.
    PMID: 23359830 DOI: 10.1371/journal.pntd.0002026
    BACKGROUND: The simian parasite Plasmodium knowlesi is a common cause of human malaria in Malaysian Borneo and threatens the prospect of malaria elimination. However, little is known about the emergence of P. knowlesi, particularly in Sabah. We reviewed Sabah Department of Health records to investigate the trend of each malaria species over time.

    METHODS: Reporting of microscopy-diagnosed malaria cases in Sabah is mandatory. We reviewed all available Department of Health malaria notification records from 1992-2011. Notifications of P. malariae and P. knowlesi were considered as a single group due to microscopic near-identity.

    RESULTS: From 1992-2011 total malaria notifications decreased dramatically, with P. falciparum peaking at 33,153 in 1994 and decreasing 55-fold to 605 in 2011, and P. vivax peaking at 15,857 in 1995 and decreasing 25-fold to 628 in 2011. Notifications of P. malariae/P. knowlesi also demonstrated a peak in the mid-1990s (614 in 1994) before decreasing to ≈ 100/year in the late 1990s/early 2000s. However, P. malariae/P. knowlesi notifications increased >10-fold between 2004 (n = 59) and 2011 (n = 703). In 1992 P. falciparum, P. vivax and P. malariae/P. knowlesi monoinfections accounted for 70%, 24% and 1% respectively of malaria notifications, compared to 30%, 31% and 35% in 2011. The increase in P. malariae/P. knowlesi notifications occurred state-wide, appearing to have begun in the southwest and progressed north-easterly.

    CONCLUSIONS: A significant recent increase has occurred in P. knowlesi notifications following reduced transmission of the human Plasmodium species, and this trend threatens malaria elimination. Determination of transmission dynamics and risk factors for knowlesi malaria is required to guide measures to control this rising incidence.

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