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  1. Sinniah A, Maniam T, Oei TP, Subramaniam P
    ScientificWorldJournal, 2014;2014:718367.
    PMID: 24672358 DOI: 10.1155/2014/718367
    The aim of this paper is to review the literature on suicide attempts in Malaysia. PsycINFO, PubMed, and Medline databases from 1845 to 2012 and detailed manual search of local official reports from the Ministry of Health and the Malaysian Psychiatric Association and unpublished dissertations from 3 local universities providing postgraduate psychiatric training were included in the current review. A total of 38 studies on suicide attempts in Malaysia were found and reviewed. Twenty-seven (76%) of the studies on suicide attempts were descriptive studies looking at sociodemographic data, psychiatric illnesses, and methods and reasons for suicide attempts. No study has been conducted on treatment and interventions for suicide attempts and the impact of culture was rarely considered. The review showed that in order for researchers, clinicians, and public health policy makers to obtain a better understanding of suicide attempts in Malaysia, more systematic and empirically stringent methodologies and research frameworks need to be used.
  2. Sinniah A, Yazid S, Flower RJ
    Front Pharmacol, 2017;8:827.
    PMID: 29184504 DOI: 10.3389/fphar.2017.00827
    The anti-allergic cromones were originally synthesized in the 1960s by Fisons Plc, and the first drug to emerge from this program, disodium cromoglycate was subsequently marketed for the treatment of asthma and other allergic conditions. Whilst early studies demonstrated that the ability of the cromones to prevent allergic reactions was due to their 'mast cell stabilizing' properties, the exact pharmacological mechanism by which this occurred, remained a mystery. Here, we briefly review the history of these drugs, recount some aspects of their pharmacology, and discuss two new explanations for their unique actions. We further suggest how these findings could be used to predict further uses for the cromones.
  3. Koosha S, Mohamed Z, Sinniah A, Alshawsh MA
    Molecules, 2019 Jul 10;24(14).
    PMID: 31295840 DOI: 10.3390/molecules24142522
    Colon cancer is the third most common type of cancer in the world. Diosmetin (Dis), a natural O-methylated flavone, has been reported to have anti-cancer effects against different types of cancer. Although the mechanisms of action of Dis against several cancer cell lines are well reported, in vivo anti-tumorigenesis properties of this compound are still obscure. Therefore, this study aimed to investigate the anti-tumorigenesis properties of Dis against HCT-116 colon cancer xenografts in nude mice. HCT-116 colon cancer cells were injected in NCr nu/nu nude mice and treatment with Dis was initiated after the tumor volumes reached 100 mm3 and continued for four weeks. On the sacrificing date nude mice treated with 100 mg/kg of Dis showed significant lower tumor volume (264 ± 238.3 mm3) as compared to the untreated group (1428.8 ± 459.6 mm3). Anti-apoptotic Bcl-2 protein was significantly downregulated, while apoptotic protein (Bax) was significantly overexpressed in nude mice treated with 100 mg/kg Dis as compared to untreated mice. In conclusion, our in vivo results indicate that Dis significantly reduces tumor growth rate of HCT-116 colon cancer cells in nude mice at a dose of 100 mg/kg, and has no toxic effects in ICR mice up to 2000 mg/kg.
  4. Ganesan T, Sinniah A, Ibrahim ZA, Chik Z, Alshawsh MA
    Molecules, 2020 Aug 14;25(16).
    PMID: 32823805 DOI: 10.3390/molecules25163700
    Annexin A1 has been extensively investigated as an anti-inflammatory protein, but its role in different types of cancer has not been consolidated in a single systematic review to date. Thus, the aim of this paper is to systematically review and critically analyse 18 studies (in-vivo and in-vitro) to consolidate, in a concerted manner, all the information on differential expression of Annexin A1 in different types of cancer and the role this protein plays in tumorigenesis. Pubmed, Scopus, Web of Science, and ScienceDirect were used for the literature search and the keywords used are "annexin A1," "lipocortin 1," "cancer," "malignancy," "neoplasm," "neoplasia," and "tumor." A total of 1128 articles were retrieved by implementing a standard search strategy subjected to meticulous screening processes and 442 articles were selected for full article screening. A total of 18 articles that adhered to the inclusion criteria were included in the systematic review and these articles possessed low to moderate bias. These studies showed a strong correlation between Annexin A1 expression and cancer progression via modulation of various cancer-associated pathways. Differential expression of Annexin A1 is shown to play a role in cellular proliferation, metastasis, lymphatic invasion, and development of resistance to anti-cancer treatment. Meta-analysis in the future may provide a statistically driven association between Annexin A1 expression and malignancy progression.
  5. Ganesan T, Sinniah A, Chik Z, Alshawsh MA
    Nutrients, 2020 Aug 13;12(8).
    PMID: 32823596 DOI: 10.3390/nu12082430
    Punicalagin (PU), a polyphenol extracted from pomegranate (Punica granatum) husk is proven to have anti-cancer effects on different types of cancer including colorectal cancer (CRC). Its role in modulating endogenous protein as a means of eliciting its anti-cancer effects, however, has not been explored to date. Hence, this study aimed to investigate the role of PU in modulating the interplay between apoptosis and autophagy by regulating Annexin A1 (Anx-A1) expression in HCT 116 colorectal adenocarcinoma cells. In the study, selective cytotoxicity, pro-apoptotic, autophagic and Anx-A1 downregulating properties of PU were shown which indicate therapeutic potential that this polyphenol has against CRC. Autophagy flux analysis via flow cytometry showed significant autophagosomes degradation in treated cells, proving the involvement of autophagy. Proteome profiling of 35 different proteins in the presence and absence of Anx-A1 antagonists in PU-treated cells demonstrated a complex interplay that happens between apoptosis and autophagy that suggests the possible simultaneous induction and inhibition of these two cell death mechanisms by PU. Overall, this study suggests that PU induces autophagy while maintaining basal level of apoptosis as the main mechanisms of cytotoxicity via the modulation of Anx-A1 expression in HCT 116 cells, and thus has a promising translational potential.
  6. Sinniah A, Oei TPS, Maniam T, Subramaniam P
    Psychiatry Res, 2017 08;254:179-189.
    PMID: 28463716 DOI: 10.1016/j.psychres.2017.04.026
    The aim of this study was to investigate the effectiveness of Individual Cognitive Behavior Therapy (ICBT) in treating patients with mood disorders with suicidal ideation. A total of 69 patients (48 females, 21 males) with the diagnoses above were randomly allocated to either the group of Treatment As Usual (TAU)+ICBT (n=33) or the TAU group (n=36). All participants completed the Beck Depression Inventory (BDI), Beck Scale for Suicide Ideation (BSS), Positive and Negative Suicide Ideation Inventory (PANSI), Beck Hopelessness Scale (BHS), and Depression Anxiety Stress Scale-21 (DASS-21). These questionnaires were administered at pre-treatment, midway through treatment (week 4), post-treatment (week 8), and at follow-ups after three months (week 20) and six months (week 32). Factorial ANOVA results showed that the TAU+ICBT patients improved significantly and at faster rate as compared to the TAU group, which showed improvement only from pre to mid treatment on DASS-D and BHS-T measures. The effect size (Cohen's d), for the TAU+ICBT group showed large effect (1.47) for depressive symptoms and suicidal ideation (1.00). These findings suggest that ICBT used in addition to the TAU, was effective in enhancing treatment outcome of patients with unipolar mood disorders as well as, reducing risk for suicide behavior.
  7. Koosha S, Mohamed Z, Sinniah A, Alshawsh MA
    Sci Rep, 2019 03 26;9(1):5148.
    PMID: 30914796 DOI: 10.1038/s41598-019-41685-1
    Diosmetin (Dis) is a bioflavonoid with cytotoxicity properties against variety of cancer cells including hepatocarcinoma, breast and colorectal (CRC) cancer. The exact mechanism by which Dis acts against CRC however, still remains unclear, hence in this study, we investigated the possible molecular mechanisms of Dis in CRC cell line, HCT-116. Here, we monitored the viability of HCT-116 cells in the presence of Dis and investigated the underlying mechanism of Dis against HCT-116 cells at the gene and protein levels using NanoString and proteome profiler array technologies. Findings demonstrated that Dis exhibits greater cytotoxic effects towards HCT-116 CRC cells (IC50 = 3.58 ± 0.58 µg/ml) as compared to the normal colon CCD-841 cells (IC50 = 51.95 ± 0.11 µg/ml). Arrests of the cells in G2/M phase confirms the occurrence of mitotic disruption via Dis. Activation of apoptosis factors such as Fas and Bax at the gene and protein levels along with the release of Cytochrome C from mitochondria and cleavage of Caspase cascades indicate the presence of turbulence as a result of apoptosis induction in Dis-treated cells. Moreover, NF-ƙB translocation was inhibited in Dis-treated cells. Our results indicate that Dis can target HCT-116 cells through the mitotic disruption and apoptosis induction.
  8. Ganesan T, Sinniah A, Ramasamy TS, Alshawsh MA
    Biochem Biophys Res Commun, 2024 Sep 17;725:150202.
    PMID: 38885563 DOI: 10.1016/j.bbrc.2024.150202
    The annexin superfamily protein, Annexin A1, initially recognized for its glucocorticoid-induced phospholipase A2-inhibitory activities, has emerged as a crucial player in diverse cellular processes, including cancer. This review explores the multifaceted roles of Anx-A1 in cancer chemoresistance, an area largely unexplored. Anx-A1's involvement in anti-inflammatory processes, its complex phosphorylation patterns, and its context-dependent switch from anti-to pro-inflammatory in cancer highlights its intricate regulatory mechanisms. Recent studies highlight Anx-A1's paradoxical roles in different cancers, exhibiting both up- and down-regulation in a tissue-specific manner, impacting different hallmark features of cancer. Mechanistically, Anx-A1 modulates drug efflux transporters, influences cancer stem cell populations, DNA damages and participates in epithelial-mesenchymal transition. This review aims to explore Anx-A1's role in chemoresistance-associated pathways across various cancers, elucidating its impact on survival signaling cascades including PI3K/AKT, MAPK/ERK, PKC/JNK/P-gp pathways and NFκ-B signalling. This review also reveals the clinical implications of Anx-A1 dysregulation in treatment response, its potential as a prognostic biomarker, and therapeutic targeting strategies, including the promising Anx-A1 N-terminal mimetic peptide Ac2-26. Understanding Anx-A1's intricate involvement in chemoresistance offers exciting prospects for refining cancer therapies and improving treatment outcomes.
  9. Sinniah A, Oei TP, Chinna K, Shah SA, Maniam T, Subramaniam P
    Front Psychol, 2015;6:1934.
    PMID: 26733920 DOI: 10.3389/fpsyg.2015.01934
    The PANSI is a measure designed to assess the risk and protective factors related to suicidal behaviors. The present study evaluated the psychometric properties and factor structure of the Positive and Negative Suicide Ideation (PANSI) Inventory in a sample of clinical outpatients at a major hospital in Malaysia. In this study, 283 psychiatric patients and 200 medical (non-psychiatric) patients participated. All the patients completed the PANSI and seven other self-report instruments. Confirmative factor analysis supported the 2-factor oblique model. The internal consistency of the two subscales of PANSI-Negative and the PANSI-Positive were 0.93 and 0.84, respectively. In testing construct validity, PANSI showed sizable correlation with the other seven scales. Criterion validity was supported by scores on PANSI which differentiated psychiatric patients from medical patients. Logistic regression analyses showed PANSI can be used to classify the patients into suicidal or non-suicidal. The PANSI is a reliable and valid instrument to measure the severity of suicidal ideation among clinical outpatients in Malaysia.
    Study site: Psychiatric clinic, Medical clinic, Ear, Nose and Throat (ENT) clinic, Ophthalmology clinic and orthopedic clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Scale, Questionnaire and Device: Positive and Negative Suicide Ideation Inventory (PANSI), Depression Anxiety Stress Scale (DASS-21), Reasons for Living Inventory (RFL), Beck Hopelessness Scale (BHS), Provision of Social Relations (PSR), Satisfaction with Life Scale (SWLS), Rosenberg Self Esteem Scale (RSE), The Adult Trait Hope Scale (ATHS)
  10. Cheng KJ, Alshawsh MA, Mejia Mohamed EH, Thavagnanam S, Sinniah A, Ibrahim ZA
    Cell Oncol (Dordr), 2020 Apr;43(2):177-193.
    PMID: 31677065 DOI: 10.1007/s13402-019-00477-5
    BACKGROUND: In recent years, the high mobility group box-1 (HMGB1) protein, a damage-associated molecular pattern (DAMP) molecule, has been found to play multifunctional roles in the pathogenesis of colorectal cancer. Although much attention has been given to the diagnostic and prognostic values of HMGB1 in colorectal cancer, the exact functional roles of the protein as well as the mechanistic pathways involved have remained poorly defined. This systematic review aims to discuss what is currently known about the roles of HMGB1 in colorectal cancer development, growth and progression, and to highlight critical areas for future investigations. To achieve this, the bibliographic databases Pubmed, Scopus, Web of Science and ScienceDirect were systematically screened for articles from inception till June 2018, which address associations of HMGB1 with colorectal cancer.

    CONCLUSIONS: HMGB1 plays multiple roles in promoting the pathogenesis of colorectal cancer, despite a few contradicting studies. HMGB1 may differentially regulate disease-related processes, depending on the redox status of the protein in colorectal cancer. Binding of HMGB1 to various protein partners may alter the impact of HMGB1 on disease progression. As HMGB1 is heavily implicated in the pathogenesis of colorectal cancer, it is crucial to further improve our understanding of the functional roles of HMGB1 not only in colorectal cancer, but ultimately in all types of cancers.

  11. Koosha S, Mohamed Z, Sinniah A, Ibrahim Z, Seyedan A, Alshawsh MA
    Life Sci, 2019 Jul 03.
    PMID: 31278947 DOI: 10.1016/j.lfs.2019.116633
    AIMS: The compound 8-prenylnaringenin (8-PN) is a prenylflavonoid that can be isolated from hops and beer and has anti-cancer properties against breast cancer. The aim of this study is to investigate the anti-proliferative and apoptotic activities of 8-PN against human colon cancer HCT-116 cells.

    MAIN METHODS: Colon cancer HCT-116 cells were treated with 8-PN and subjected to MTT and acridine orange/propidium iodide (AO/PI) staining to investigate the cytotoxicity of 8-PN. Arrest of the cells at different phases of cell cycle was monitored in the presence of 8-PN. Moreover, the apoptotic effects of 8-PN was assessed via annexin V and caspase activity assays and compared to the untreated cells.

    KEY FINDINGS: The findings showed that 8-PN revealed strong inhibitory effect against HCT-116 cells with an IC50 value of 23.83 ± 2.9 μg/ml after 48 h. However, at similar concentrations and experimental time-points, the compound did not show cytotoxic effect to non-cancerous colon cells (CCD-41). Annexin-V assay indicates that 38.5% and 14.4% of HCT-116 cells had entered early and late stages of apoptosis, respectively after exposure of the cells to 8-PN for 48 h. Caspase activity assay illustrates that apoptosis is activated through both intrinsic and extrinsic pathways. Moreover, flow cytometry cell cycle results indicate that treatment with 8-PN significantly arrested the HCT-116 cells at G0/G1 phase.

    SIGNIFICANCE: These findings reveal that 8-PN has anti-proliferative activity against HCT-116 colon cancer cells via induction of intrinsic and extrinsic pathway-mediated apoptosis. Further investigations should be carried out to unravel the mechanistic pathways underlying these activities.

  12. Nik Jaafar NR, Midin M, Mahadevan R, Sinniah A, Rahman AH, Ming W, et al.
    Compr Psychiatry, 2014 Jan;55 Suppl 1:S60-4.
    PMID: 24139853 DOI: 10.1016/j.comppsych.2013.09.002
    OBJECTIVE: Most weight interventions among patients with severe mental illness (SMI) used body mass index (BMI) as outcome measure but excluded waist circumference (WC) although the latter is a stronger predictor of obesity complications. This study aimed to assess a weight-management program consisting of education, exercise and behavioural techniques for patients with SMI using weight parameters including WC as the outcome measures.
    METHODS: A group intervention was carried out as part of psychiatric outpatient community service. It used structured modules on diet, exercise and related topics comprising of education and exercises sessions with a total of 12-week duration. The participants were outpatients with SMI recruited through referrals to the program by the treating doctor. The participants' body weight, BMI and WC were measured at the baseline, fortnightly and at the end of the program.
    RESULTS: A total of 27 patients participated in the program which was carried out in 6 cycles. The pre- and post-intervention comparisons analysis of the weight parameters found a significant reduction in the WC (mean=3.878 cm+5.165, p=0.001) while no significant changes were recorded in body weight and BMI.
    CONCLUSION: Small but significant loss in WC and possibly weight maintenance were achieved using this non-pharmacological intervention. Modest loss in WC may have an impact on reducing the risk of obesity-related health risks.
    Study site: Psychiatric clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  13. Midin M, Razali R, Zamzam R, Fernandez A, Hum LC, Shah SA, et al.
    Int J Ment Health Syst, 2011 May 30;5:14.
    PMID: 21624111 DOI: 10.1186/1752-4458-5-14
    BACKGROUND: Gainful employment is one major area of functioning which is becoming an important goal in psychiatric rehabilitation of patients with schizophrenia. Studies in western countries are pointing to evidence that certain sociodemographic and clinical factors may contribute to employment outcomes in this group of people. However, the area is still largely unexplored in Malaysia. The aim of this study was to examine the sociodemographic, clinical and cognitive correlates of employment status among patients with Schizophrenia.

    METHODS: This was a cross-sectional study. All participants who fulfilled the requirements of the study according to the inclusion and exclusion criteria were enrolled. Study instruments included a demographic data questionnaire, Positive and Negative Symptom Scale (PANSS), Trail Making Tests, Rey's Auditory Verbal Learning Test (RAVLT) and Digit Span. Bivariate analyses were done using chi-square for categorical data and t-test for continuous data and multiple logistic regression analysis was done to identify predictors of employment status.

    RESULTS: A total of 95 participants who fulfilled the inclusion criteria were enrolled into the study. Among the sociodemographic, clinical and cognitive variables studied marital status, educational level, mean scores of negative symptoms, Digit Span and RAVLT and Trail Making Tests were found to show significant association with employment status on bivariate analyses. However, when entered into a logistic regression model, only cognitive variables ie. Trail A and B, Digit Span and RAVLT were significant predictors of employment status.

    CONCLUSIONS: The results from this study support the role of cognitive function, particularly, attention, working memory and executive functioning on attaining and maintaining employment in persons with schizophrenia as measured by the RAVLT, Digit Span and Trail Making Tests. These findings may act as preliminary evidence suggesting the importance of integrating cognitive rehabilitation in the psychosocial rehabilitation program for patients with schizophrenia in Malaysia.

  14. Rampal S, Ganesan T, Sisubalasingam N, Neela VK, Tokgöz MA, Arunasalam A, et al.
    Antibiotics (Basel), 2021 Sep 17;10(9).
    PMID: 34572702 DOI: 10.3390/antibiotics10091120
    BACKGROUND: Necrotizing fasciitis (NF) is a rapidly progressive inflammatory infection of the soft tissue (also known as the fascia) with a secondary necrosis of the subcutaneous tissues, leading to a systemic inflammatory response syndrome (SIRS), shock and eventually death despite the availability of current medical interventions. The clinical management of this condition is associated with a significant amount of morbidity with a high rate of mortality. The prognosis of the disease is affected by multiple factors, which include the virulence of the causative pathogen, local host immunity, local wound factors and empirical antibiotics used. The local trends in the prescription of empirical antibiotics are often based on clinical practice guidelines (CPG), the distribution of the causative microorganism and the cost-effectiveness of the drug. However, there appears to be a paucity of literature on the empirical antibiotic of choice when dealing with necrotizing fasciitis in the clinical setting. This paper will outline common causative microorganisms and current trends of prescription in two tertiary centres in Central Malaysia.

    METHODS: This was a cross-sectional study using retrospective data of patients treated for NF collected from two tertiary care hospitals (Hospital Seremban and Hospital Ampang) in Central Malaysia. A total of 420 NF patients were identified from the five years of retrospective data obtained from the two hospitals.

    RESULTS: The top three empirical antibiotics prescribed are ampicillin + sulbactam (n = 258; 61.4%), clindamycin (n = 55; 13.1%) and ceftazidime (n = 41; 9.8%). The selection of the antibiotic significantly impacts the outcome of NF. The top three causative pathogens for NF are Streptococcus spp. (n = 79; 18.8%), Pseudomonas aeruginosa (n = 61; 14.5%) and Staphylococcus spp. (n = 49; 11.7%). The patients who received antibiotics had 0.779 times lower chances of being amputated. Patients with a lower laboratory risk indicator for necrotizing fasciitis (LRINEC) score had 0.934 times lower chances of being amputated.

    CONCLUSIONS: In this study, the most common empirical antibiotic prescribed was ampicillin + sulbactam followed by clindamycin and ceftazidime. The antibiotics prescribed lower the risk of having an amputation and, hence, a better prognosis of the disease. Broad-spectrum empirical antibiotics following surgical debridement reduce the mortality rate of NF.

  15. Chan LF, Maniam T, Saini SM, Shah SA, Loh SF, Sinniah A, et al.
    Asia Pac Psychiatry, 2013 Apr;5 Suppl 1:123-6.
    PMID: 23857848 DOI: 10.1111/appy.12057
    INTRODUCTION: The aim of this study was to determine the association between sexual abuse, substance abuse and socio-demographic factors with suicidal ideation (SI), plans (SP) and deliberate self-harm (DSH) and propose steps to prevent youth suicidal behavior.
    METHODS: This was a cross-sectional study of 6786 adolescents aged 17-18 years, selected randomly from all Malaysian adolescents to undergo compulsory youth camps located in Selangor, Malaysia (2008-2009). Participants were assessed using self-administered questionnaires developed to reflect the local cultural setting. However, only 4581 subjects were analyzed after excluding incomplete data.
    RESULTS: The rates of SI, SP and DSH were 7.6%, 3.2% and 6.3%, respectively. The multivariable-adjusted odds ratio showed that sexual abuse was associated with SI 1.99 (95% CI: 1.56-2.55), SP 1.57 (95% CI: 1.09-2.27) and DSH 2.26 (95% CI: 1.75-2.94); illicit drug use was associated with SI 4.05 (95% CI: 2.14-7.67), SP 2.62 (95% CI: 1.05-6.53) and DSH 2.06, (95% CI: 1.05-4.04); for alcohol use DSH was 1.34 (95% CI: 1.00-1.79). Being female was associated with all suicidal behaviors: SI 2.51 (95% CI: 1.91-3.30), SP 2.07 (95% CI: 1.39-3.08) and DSH 1.59 (95% CI: 1.19-2.11).
    DISCUSSION: Given the well-founded concern of increasing risk of suicidal behavior among youth, preventive efforts should adopt a more comprehensive approach in dealing with sexual abuse and substance abuse, and their sequelae, especially in girls.
    KEYWORDS: adolescent; risks; sexual abuse; substance abuse; suicidal behavior
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