MyMedR

Displaying all 7 publications

Abstract:

Sort:

Fulltext Annexin A1: A Bane or a Boon in Cancer? A Systematic Review

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.
Fulltext Punicalagin Regulates Apoptosis-Autophagy Switch via Modulation of Annexin A1 in Colorectal Cancer

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.
Cracking the code of Annexin A1-mediated chemoresistance

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.
Development of a novel questionnaire to assess knowledge, attitude and practice towards medical disorders in pregnancy among clinicians

Tan TL, Lau Q, Chiew SC, Thanusha, Mahmoud D, Manisha

Med J Malaysia, 2024 Jan;79(1):52-59.
PMID: 38287758

INTRODUCTION: Maternal medicine is important and complex. It focuses on the care of mothers with comorbidities or medical disorders during pregnancy. To date, there are limited tools to assess clinicians' knowledge, attitude and practice (KAP) in this field.
MATERIALS AND METHODS: This study aims to develop and validate a questionnaire measuring the KAP of clinicians towards maternal medicine. Literature reviews, item generation and multiple experts' reviews were conducted during the questionnaire development phase. Convenient sampling was undertaken for this cross-sectional survey. A total of 168 clinicians from one tertiary hospital and three health clinics participated in thepilot testing using the modified questionnaire. In addition, test-retest was performed on 30 participants to examine its reliability, whilst exploratory factor analysis (EFA) was undertaken to determine its construct validity.
RESULTS: This finalised questionnaire contained 36 items with excellent content validity. Pertaining to test-retest reliability, all knowledge domain items showed Kappa values > 0.20, except item K29; attitude domain items overall Cronbach's alpha was 0.787 with corrected item-total correlation > 0.300 and lastly, all items in practice domain achieved intra-class correlation index > 0.700, except P2.5. EFA supported four factor structures, but six items were removed due to the following reasons: cross loading, negative or poor loading factor (< 0.3).
CONCLUSION: Overall, this instrument has an acceptable psychometric property, content validity, internal reliability and construct validity. It is hope that this questionnaire would be validated in other populations and be used in future research to enrich our understanding of clinicians' KAP towards maternal medicine.
Ethnicity influences disease characteristics and symptom severity in allergic rhinitis patients in Malaysia

Amini P, Abdullah M, Seng LS, Karunakaran T, Hani N, Bakar SA, et al.

Int Forum Allergy Rhinol, 2016 Jun;6(6):624-30.
PMID: 26919193 DOI: 10.1002/alr.21442

BACKGROUND: The number of available reports regarding the influence of ethnicity on clinical features of allergic rhinitis (AR), especially disease severity in tropical climates, is limited. We aimed to compare clinical parameters and disease severity in AR patients of different ethnicities.
METHODS: Malay, Chinese, and Indian AR patients (n = 138) with confirmed sensitivity to Dermatophagoides pteronyssinus, Dematophagoides farinae, and Blomia tropicalis were tested for mite-specific immunoglobulin E (sIgE) levels. A detailed questionnaire was used to collect data on nasal symptom score (NSS), ocular symptom score (OSS), sum of symptoms score (SSS), quality of life score (QLS), symptomatic control score (SCS), and total sum of scores (TSS) and correlate the derived data with patients' demography, mite-polysensitivity, and sIgE levels.
RESULTS: AR-related symptoms were most severe in Malays and least in Chinese (p < 0.01). Age (r = 0.516 to 0.673, p < 0.05) and duration of AR (r = 0.635 to 0.726, p < 0.01) correlated positively with severity domains (NSS, SSS, QLS, and TSS) in Chinese. Duration of concurrent allergies was highest in Malays (p < 0.05). Polysensitivity predicted increased sIgE levels in Malays (r = 0.464 to 0.551, p < 0.01) and Indians (r = 0.541 to 0.645, p < 0.05) but affected NSS, SSS, and TSS only in Indians (r = 0.216 to 0.376, p < 0.05). sIgE levels were lowest among Chinese but correlated strongly with NSS, OSS, SSS, and TSS (r = 0408 to 0.898, p < 0.05).
CONCLUSION: Clinical parameters in AR may be influenced by race. Symptoms were most severe among Malays but did not correlate with other variables examined. Although Indian ethnicity did not impact disease severity, duration of concurrent allergies and mite-polysensitivity was associated with more severe disease. Age, duration of disease, and sIgE levels may be useful indicators of disease severity in Chinese.
Evaluating the Intestinal Immunity of Asian Seabass (Lates calcarifer, Bloch 1790) following Field Vaccination Using a Feed-Based Oral Vaccine

Raju T, Manchanayake T, Danial A, Zamri-Saad M, Azmai MNA, Md Yasin IS, et al.

Vaccines (Basel), 2023 Mar 06;11(3).
PMID: 36992186 DOI: 10.3390/vaccines11030602

This study describes the levels of gut lysozyme and IgM, the number, size and density of gut-associated lymphoid tissue (GALT) regions, and the lymphocyte population in Asian seabass following field oral administration of a feed-based vaccine. Fish in a grow-out farm were selected and divided into two groups; Group 1 was vaccinated at week 0, 2, and 6, while Group 2 was not vaccinated. Samplings were done at 2-week intervals when the fish were observed for clinical signs, and gross lesions were recorded. The intestinal tissue and gut lavage fluid were collected. GALT regions (numbers, size, density and population of lymphocytes) were analyzed. Clinical signs such as abnormal swimming pattern and death, and gross lesions including scale loss, ocular opacity, and skin ulceration were observed in both groups. At the end of the study, the incidence rate between both groups were significantly different (p < 0.05). The gut IgM level and lysozyme activity, lymphocyte population, number, size and density of GALT regions of Group 1 were significantly (p < 0.05) higher than Group 2. Therefore, this study concludes that the feed-based vaccine reduces the incidence of vibriosis by stimulating the gut immunity of the vaccinated fish with an enhanced GALT region, specific IgM production against Vibrio harveyi, and lysozyme responses.
Fulltext Local Trends of Antibiotic Prescriptions for Necrotizing Fasciitis Patients in Two Tertiary Care Hospitals in Central Malaysia

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.