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Fulltext Platelet Transcriptome-based approaches in the fight against dengue and other diseases

Suppiah, J., Sakinah, S., Chan, S.Y., Wong, Y.P., Subbiah, S.K., Chee, H.Y., et al.

Pertanika Journal of Science & Technology, 2018;26(3):933-946.
MyJurnal

Human platelets are anucleate cells that lack in deoxyribonucleic acid (DNA), thus hampering genomic study on them. However, the presence of their own messenger ribonucleic acid (mRNA) transcript allows functional study via the transcriptome approach. Transcriptome not only allows profiling of platelet but also aids in studying gene regulation in virus infections and other diseases that have an impact on platelets. Some viruses are known to affect the platelet either by causing a reduction or destruction. Dengue virus is one of the most postulated virus having such effect and frequently linked to platelet reduction. The transcriptome approach has a pivotal role in providing a deeper insight to link certain diseases and their effect on platelets. This review critically discusses role of platelet in dengue and other viral diseases of public health relevance, with a specific focus on the methods currently used in platelet transcriptome profiling.
Racial disparity in the prevalence of thyroid disorder during pregnancy

Sakinah SO, Khalid BA, Aishah AB

Ann Acad Med Singap, 1993 Jul;22(4):563-6.
PMID: 8257059

A study to determine the prevalence of goitre and abnormal thyroid status during pregnancy in Malaysian women was conducted. Two hundred and three women (Malay = 85, Chinese = 47 and Indian = 71) in the third trimester and with no known thyroid disease were studied. There was a marked racial disparity in the prevalence of goitre: Indian 61%, Malay 28% and Chinese 29% (p = 0.001). The serum thyrotropic hormone (TSH) was significantly higher in Indians (median: 1.36 uIU/ml) compared to Malays (1.14 uIU/ml, p = 0.009). The serum albumin was also significantly lower in Indians (mean +/- sd; 36.12 +/- 3.9 mmol/l) compared to Malays (39.3 +/- 4.8 mmol/l) or Chinese (39.1 +/- 5.2) (p < 0.001). Thyroid antibody was detected in 14.6% of these women with no significant racial difference in its prevalence. Three women were found to be thyrotoxic but none were hypothyroid. This study found a high prevalence of goitre among the pregnant Indian women, probably related to the protein malnutrition state. The high prevalence of positive thyroid antibody in our population indicates that a high percentage of women are at risk of developing postpartum thyroiditis.
Fulltext Painful thyroiditis in postpartum period

Sakinah SO, Sharifah NA, Yusoff K

Med J Malaysia, 1993 Mar;48(1):83-5.
PMID: 8341177

Destructive thyroiditis commonly occurs during the postpartum period, with a prevalence rate of 5% to 16%, and is mainly due to postpartum autoimmune thyroiditis (PPT) and, very rarely, to subacute thyroiditis. The thyroiditis is similar to Hashimoto's thyroiditis and is generally painless in nature, although cases with painful thyroiditis have been described. We report a case of painful destructive thyroiditis occurring during the postpartum period, which was clinically and biochemically indistinguishable from the variant of painful PPT or subacute thyroiditis. Fine needle aspiration cytology showed multi-nucleated giant cells diagnostic of subacute thyroiditis.
Regulation of p53-, Bcl-2- and caspase-dependent signaling pathway in xanthorrhizol-induced apoptosis of HepG2 hepatoma cells

Handayani T, Sakinah S, Nallappan M, Pihie AH

Anticancer Res, 2007 Mar-Apr;27(2):965-71.
PMID: 17465228

Xanthorrhizol is a sesquiterpenoid compound extracted from the rhizome of Curcuma xanthorrhiza. This study investigated the antiproliferative effect and the mechanism of action of xanthorrhizol on human hepatoma cells, HepG2, and the mode of cell death. An antiproliferative assay using methylene blue staining revealed that xanthorrhizol inhibited the proliferation of the HepG2 cells with a 50% inhibition of cell growth (IC50) value of 4.17 +/- 0.053 microg/ml. The antiproliferative activity of xanthorrhizol was due to apoptosis induced in the HepG2 cells and not necrosis, which was confirmed by the Tdt-mediated dUTP nick end labeling (TUNEL) assay. The xanthorrhizol-treated HepG2 cells showed typical apoptotic morphology such as DNA fragmentation, cell shrinkage and elongated lamellipodia. The apoptosis mediated by xanthorrhizol in the HepG2 cells was associated with the activation of tumor suppressor p53 and down-regulation of antiapoptotic Bcl-2 protein expression, but not Bax. The levels of Bcl-2 protein expression decreased 24-h after treatment with xanthorrhizol and remained lower than controls throughout the experiment, resulting in a shift in the Bax to Bcl-2 ratio thus favouring apoptosis. The processing of the initiator procaspase-9 was detected. Caspase-3 was also found to be activated, but not caspase-7. Xanthorrhizol exerts antiproliferative effects on HepG2 cells by inducing apoptosis via the mitochondrial pathway.
Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio

Sakinah SA, Handayani ST, Hawariah LP

Cancer Cell Int, 2007;7:4.
PMID: 17407577

Zerumbone is a cytotoxic component isolated from Zingiber zerumbet Smith, a herbal plant which is also known as lempoyang. This new anticancer bioactive compound from Z. zerumbet was investigated for its activity and mechanism in human liver cancer cell lines.
Fulltext Iodine content in drinking water not an important determinant of endemic goitre

Osman A, Khalida M, Azman AB, Jamil R, Tan TT, Wu LL, et al.

Asia Pac J Clin Nutr, 1993 Sep;2(3):115-8.
PMID: 24352141

The prevalence of goitre was determined in several communities in rural parts of Pahang. Urine specimens were collected randomly among the participants. Drinking water from various sources such as river and spring, and water from gravity feed systems was also collected to determine the iodine content by using the ashing method. The results were compared to that of Kuala Lumpur City. lt was found that the prevalence of goitre in rural areas was between 20 and 70% depending on village, ethnic group, age and gender. The interior parts of the jungle where Aborigines lived was moderately endemic with goitre prevalence of goitre more than 20% and urinary iodine content 2.0-5.0 μg I/dl). A nearby Malay traditional village which was studied had mild endemia (prevalence 10-30% and urinary iodine content 5.0-10.0 μg I/dl) while a Felda Malay resettlement scheme and Kuala Lumpur City did not have endemic goitre. Endemic goitre in rural areas was associated with low iodine content in drinking water. Even though Kuala Lumpur had low iodine content in its drinking water there was no endemic goitre, indicating that other factors were more important.
Leptospirosis: Molecular trial path and immunopathogenesis correlated with dengue, malaria and mimetic hemorrhagic infections

Priya SP, Sakinah S, Sharmilah K, Hamat RA, Sekawi Z, Higuchi A, et al.

Acta Trop, 2017 Dec;176:206-223.
PMID: 28823908 DOI: 10.1016/j.actatropica.2017.08.007

Immuno-pathogenesis of leptospirosis can be recounted well by following its trail path from entry to exit, while inducing disastrous damages in various tissues of the host. Dysregulated, inappropriate and excessive immune responses are unanimously blamed in fatal leptospirosis. The inherent abilities of the pathogen and inabilities of the host were debated targeting the severity of the disease. Hemorrhagic manifestation through various mechanisms leading to a fatal end is observed when this disease is unattended. The similar vascular destructions and hemorrhage manifestations are noted in infections with different microbes in endemic areas. The simultaneous infection in a host with more than one pathogen or parasite is referred as the coinfection. Notably, common endemic infections such as leptospirosis, dengue, chikungunya, and malaria, harbor favorable environments to flourish in similar climates, which is aggregated with stagnated water and aggravated with the poor personal and environmental hygiene of the inhabitants. These factors aid the spread of pathogens and parasites to humans and potential vectors, eventually leading to outbreaks of public health relevance. Malaria, dengue and chikungunya need mosquitoes as vectors, in contrast with leptospirosis, which directly invades human, although the environmental bacterial load is maintained through other mammals, such as rodents. The more complicating issue is that infections by different pathogens exhibiting similar symptoms but require different treatment management. The current review explores different pathogens expressing specific surface proteins and their ability to bind with array of host proteins with or without immune response to enter into the host tissues and their ability to evade the host immune responses to invade and their affinity to certain tissues leading to the common squeal of hemorrhage. Furthermore, at the host level, the increased susceptibility and inability of the host to arrest the pathogens' and parasites' spread in different tissues, various cytokines accumulated to eradicate the microorganisms and their cellular interactions, the antibody dependent defense and the susceptibility of individual organs bringing the manifestation of the diseases were explored. Lastly, we provided a discussion on the immune trail path of pathogenesis from entry to exit to narrate the similarities and dissimilarities among various hemorrhagic fevers mentioned above, in order to outline future possibilities of prevention, diagnosis, and treatment of coinfections, with special reference to endemic areas.
Experience of a rapid access falls and syncope service at a teaching hospital in Kuala Lumpur

Gan SY, Saedon NI, Sukanya S, Fairuz NHA, Sakinah SMN, Fatin NIAH, et al.

Med J Malaysia, 2017 08;72(4):203-208.
PMID: 28889130 MyJurnal

No abstract available.
Seroprevalence of leptospiral antibodies among market workers and food handlers in the central state of Malaysia

Samsudin S, Sakinah SNS, Malina O, Norliza BA, Noh MA, Fairuz A, et al.

Trop Med Int Health, 2018 03;23(3):327-333.
PMID: 29356240 DOI: 10.1111/tmi.13033

OBJECTIVE: The high prevalence of leptospirosis in humans is of great public health concern, particularly in tropical and subtropical regions. This study aimed to determine the seroprevalence of leptospiral antibodies and distribution of serovars, and to assess the usefulness of enzyme-linked immunosorbent assay (ELISA) as a screening method for leptospiral antibodies in a high-risk healthy community.
METHODS: Cross-sectional study of 231 market workers and food handlers in wet markets and food premises from two localities in central Malaysia. Respondents' background information was obtained using a questionnaire. Serum samples were tested for leptospiral antibodies using ELISA and microscopic agglutination test (MAT).
RESULTS: Seroprevalence of leptospirosis among healthy workers was 46.3%. Detection of seropositivity was higher by MAT (46%) than ELISA (15%). We observed high seropositivity among local workers (49%), food handlers (49.5%), females (60.8%) and those aged 34 years and older (46.3%). Local strain LEP175 was the predominant serovar, followed by WHO strain Patoc.
CONCLUSION: Overall seroprevalence among healthy food handlers and market workers was high in this study. The workplace places susceptible individuals at risk of leptospirosis.
Micro-anatomical changes in major blood vessel caused by dengue virus (serotype 2) infection

Priya SP, Sakinah S, Ling MP, Chee HY, Higuchi A, Hamat RA, et al.

Acta Trop, 2017 Jul;171:213-219.
PMID: 28427958 DOI: 10.1016/j.actatropica.2017.04.010

Dengue virus (DENV) has emerged as a major economic concern in developing countries, with 2.5 billion people believed to be at risk. Vascular endothelial cells (ECs) lining the circulatory system from heart to end vessels perform crucial functions in the human body, by aiding gas exchange in lungs, gaseous, nutritional and its waste exchange in all tissues, including the blood brain barrier, filtration of fluid in the glomeruli, neutrophil recruitment, hormone trafficking, as well as maintenance of blood vessel tone and hemostasis. These functions can be deregulated during DENV infection. In this study, BALB/c mice infected with DENV serotype 2 were analyzed histologically for changes in major blood vessels in response to DENV infection. In the uninfected mouse model, blood vessels showed normal architecture with intact endothelial monolayer, tunica media, and tunica adventitia. In the infected mouse model, DENV distorted the endothelium lining and disturbed the smooth muscle, elastic laminae and their supporting tissues causing vascular structural disarrangement. This may explain the severe pathological illness in DENV-infected individuals. The overall DENV-induced damages on the endothelial and it's supporting tissues and the dysregulated immune reactions initiated by the host were discussed.
Impact of dengue virus (serotype DENV-2) infection on liver of BALB/c mice: A histopathological analysis

Sakinah S, Priya SP, Kumari S, Amira F, K P, Alsaeedy H, et al.

Tissue Cell, 2017 Feb;49(1):86-94.
PMID: 28034555 DOI: 10.1016/j.tice.2016.11.005

In this research, we characterized the histopathological impact of dengue virus (serotype DENV-2) infection in livers of BALB/c mice. The mice were infected with different doses of DENV-2 via intraperitoneal injection and liver tissues were processed for histological analyses and variation was documented. In the BALB/c mouse model, typical liver tissues showed regular hepatocyte architecture, with normal endothelial cells surrounding sinusoid capillary. Based on histopathological observations, the liver sections of BALB/c mice infected by DENV-2 exhibited a loss of cell integrity, with a widening of the sinusoidal spaces. There were marked increases in the infiltration of mononuclear cells. The areas of hemorrhage and micro- and macrovesicular steatosis were noted. Necrosis and apoptosis were abundantly present. The hallmark of viral infection, i.e., cytopathic effects, included intracellular edema and vacuole formation, cumulatively led to sinusoidal and lobular collapse in the liver. The histopathological studies on autopsy specimens of fatal human DENV cases are important to shed light on tissue damage for preventive and treatment modalities, in order to manage future DENV infections. In this framework, the method present here on BALB/c mouse model may be used to study not only the effects of infections by other DENV serotypes, but also to investigate the effects of novel drugs, such as recently developed nano-formulations, and the relative recovery ability with intact immune functions of host.
Fulltext Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury

Sakinah S, Priya SP, Mok PL, Munisvaradass R, Teh SW, Sun Z, et al.

Front Cell Dev Biol, 2021;9:637270.
PMID: 34291043 DOI: 10.3389/fcell.2021.637270

Extensive clinical efforts have been made to control the severity of dengue diseases; however, the dengue morbidity and mortality have not declined. Dengue virus (DENV) can infect and cause systemic damage in many organs, resulting in organ failure. Here, we present a novel report showing a tailored stem-cell-based therapy that can aid in viral clearance and rescue liver cells from further damage during dengue infection. We administered a combination of hematopoietic stem cells and endothelial progenitor cells in a DENV-infected BALB/c mouse model and found that delivery of this cell cocktail had improved their liver functions, confirmed by hematology, histopathology, and next-generation sequencing. These stem and progenitor cells can differentiate into target cells and repair the damaged tissues. In addition, the regime can regulate endothelial proliferation and permeability, modulate inflammatory reactions, enhance extracellular matrix production and angiogenesis, and secrete an array of growth factors to create an enhanced milieu for cell reparation. No previous study has been published on the treatment of dengue infection using stem cells combination. In conclusion, dengue-induced liver damage was rescued by administration of stem cell therapy, with less apoptosis and improved repair and regeneration in the dengue mouse model.
Corrigendum: Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury

Sakinah S, Priya SP, Mok PL, Munisvaradass R, Teh SW, Sun Z, et al.

Front Cell Dev Biol, 2021;9:800659.
PMID: 35178398 DOI: 10.3389/fcell.2021.800659

[This corrects the article DOI: 10.3389/fcell.2021.637270.].
Fulltext Efficiency of newly formulated camptothecin with β-cyclodextrin-EDTA-Fe3O4 nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug

Krishnan P, Rajan M, Kumari S, Sakinah S, Priya SP, Amira F, et al.

Sci Rep, 2017 09 08;7(1):10962.
PMID: 28887536 DOI: 10.1038/s41598-017-09140-1

Camptothecin (CPT) is an anti-cancer drug that effectively treats various cancers, including colon cancer. However, poor solubility and other drawbacks have restricted its chemotherapeutic potential. To overcome these restrictions, CPT was encapsulated in CEF (cyclodextrin-EDTA-FE3O4), a composite nanoparticle of magnetic iron oxide (Fe3O4), and β-cyclodextrin was cross-linked with ethylenediaminetetraacetic acid (EDTA). This formulation improved CPT's solubility and bioavailability for cancer cells. The use of magnetically responsive anti-cancer formulation is highly advantageous in cancer chemotherapy. The chemical characterisation of CPT-CEF was studied here. The ability of this nano-compound to induce apoptosis in HT29 colon cancer cells and A549 lung cancer cells was evaluated. The dose-dependent cytotoxicity of CPT-CEF was shown using MTT. Propidium iodide and Annexin V staining, mitochondrial membrane depolarisation (JC-1 dye), and caspase-3 activity were assayed to detect apoptosis in CPT-CEF-treated cancer cells. Cell cycle analysis also showed G1 phase arrest, which indicated possible synergistic effects of the nano-carrier. These study results show that CPT-CEF causes a dose-dependent cell viability reduction in HT29 and A549 cells and induces apoptosis in colon cancer cells via caspase-3 activation. These data strongly suggest that CPT could be used as a major nanocarrier for CPT to effectively treat colon cancer.
3D modelling of the pathogenic Leptospira protein LipL32: A bioinformatics approach

Kumaran SK, Bakar MFA, Mohd-Padil H, Mat-Sharani S, Sakinah S, Poorani K, et al.

Acta Trop, 2017 Dec;176:433-439.
PMID: 28941729 DOI: 10.1016/j.actatropica.2017.09.011

Leptospirosis is a widespread zoonotic disease caused by pathogenic Leptospira species (Leptospiraceae). LipL32 is an abundant lipoprotein from the outer membrane proteins (OMPs) group, highly conserved among pathogenic and intermediate Leptospira species. Several studies used LipL32 as a specific gene to identify the presence of leptospires. This research was aimed to study the characteristics of LipL32 protein gene code, to fill the knowledge gap concerning the most appropriate gene that can be used as antigen to detect the Leptospira. Here, we investigated the features of LipL32 in fourteen Leptospira pathogenic strains based on comparative analyses of their primary, secondary structures and 3D modeling using a bioinformatics approach. Furthermore, the physicochemical properties of LipL32 in different strains were studied, shedding light on the identity of signal peptides, as well as on the secondary and tertiary structure of the LipL32 protein, supported by 3D modelling assays. The results showed that the LipL32 gene was present in all the fourteen pathogenic Leptospira strains used in this study, with limited diversity in terms of sequence conservation, hydrophobic group, hydrophilic group and number of turns (random coil). Overall, these results add basic knowledge to the characteristics of LipL32 protein, contributing to the identification of potential antigen candidates in future research, in order to ensure prompt and reliable detection of pathogenic Leptospira species.

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