Displaying publications 1 - 20 of 86 in total

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  1. Bakar AF, Alitheen NB, Keong YS, Hamid M, Ali SA, Ali AM
    Hybridoma (Larchmt), 2009 Jun;28(3):199-203.
    PMID: 19519247 DOI: 10.1089/hyb.2007.0531
    Hybridoma clone C3A8, which is a fusion product between splenic lymphocytes of Balb/c mice immunized with MCF7 breast carcinoma cells and SP2/0 myelomas, was produced and characterized. A stable clone that secreted IgM monoclonal antibody (MAb) with kappa light chain was obtained through limiting dilutions. Cell-ELISA screening, flow cytometry analysis, and immunofluorescence staining revealed that the MAb C3A8 had bound specifically and strongly to MCF7 and HT29 but cross reacted weakly or not on HeLa cell line. The MAb C3A8 reacted positively with paraffin-embedded tissues of human breast and colon cancers but there were no positive reactions on normal tissues. Western blot analysis showed the MAb recognized a 55 kDa protein, which was present in the extract of MCF7 and HT29 cell lines. Our results demonstrated that MAb C3A8 could be used for basic and clinical research of breast and colon cancers.
  2. Ramli Hamid MT, Ab Mumin N, Abdul Hamid S, Ahmad Saman MS, Rahmat K
    Clin Radiol, 2024 Jan 10.
    PMID: 38267349 DOI: 10.1016/j.crad.2023.12.016
    AIM: To compare the diagnostic performance of abbreviated breast magnetic resonance (AB-MR) imaging (MRI) and digital breast tomosynthesis (DBT) for breast cancer detection in Malaysian women with dense breasts, using histopathology as the reference standard.

    MATERIALS AND METHODS: This was a single-centre cross-sectional study of 115 women with American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BIRADS) breast density C and D on DBT with breast lesions who underwent AB-MR from June 2018 to December 2021. AB-MR was performed on a 3 T MRI system with an imaging protocol consisting of three sequences: axial T1 fat-saturated unenhanced; axial first contrast-enhanced; and subtracted first contrast-enhanced with maximum intensity projection (MIP). DBT and AB-MR images were evaluated by two radiologists blinded to the histopathology and patient outcomes. Diagnostic accuracy (sensitivity, specificity, positive predictive value [PPV] and negative predictive value [NPV]) was assessed.

    RESULT: Of the 115 women, the mean age was 50.6 years. There were 48 (41.7%) Malay, 54 (47%) Chinese, and 12 (10.4%) Indian women. The majority (n=87, 75.7%) were from the diagnostic population. Sixty-one (53.1%) were premenopausal and 54 (46.9%) postmenopausal. Seventy-eight (72.4%) had an increased risk of developing breast cancer. Ninety-one (79.1%) women had density C and 24 (20.9%) had density D. There were 164 histopathology-proven lesions; 69 (42.1%) were malignant and 95 (57.9%) were benign. There were 62.8% (n=103/164) lesions detected at DBT. All the malignant lesions 100% (n=69) and 35.7% (n=34) of benign lesions were detected. Of the 61 lesions that were not detected, 46 (75.4%) were in density C, and 15 (24.6%) were in density D. The sensitivity, specificity, PPV, and NPV for DBT were 98.5%, 34.6%, 66.3%, and 94.7%, respectively. There were 65.2% (n=107/164) lesions detected on AB-MR, with 98.6% (n=68) malignant and 41.1% (39) benign lesions detected. The sensitivity, specificity, PPV, and NPV for AB-MR were 98.5%, 43.9%, 67.2%, and 96.2%, respectively. One malignant lesion (0.6%), which was a low-grade ductal carcinoma in-situ (DCIS), was missed on AB-MR.

    CONCLUSION: The present findings suggest that both DBT and AB-MR have comparable effectiveness as an imaging method for detecting breast cancer and have high NPV for low-risk lesions in women with dense breasts.

  3. D'Cruz F, Samsudin AT, Hamid MS, Abraham T
    Med J Malaysia, 1990 Jun;45(2):123-30.
    PMID: 2152016
    A prospective study of acute nephritis in children was conducted at the Universiti Sains Malaysia Hospital, Kubang Kerian between July 1987 and June 1988. One hundred and twenty four children were admitted with acute glomerulonephritis. The aim of the study was to determine the clinical pattern of the nephritis as well as its aetiology. The majority of our patients came from the lower socio-economic group and 54% of the families had incomes below the poverty line. Preceding skin infection was much more common than throat infection. The children showed a high incidence of complications: severe hypertension (43.6%), hypertensive encephalopathy (11.3%), clinical pulmonary oedema (36.3%), severe azotaemia (10.5%), and prolonged gross haematuria (13.7%). By using immunologic indices such as ASOT, anti-DNase B and complement 3, it was concluded that 121 of the 124 patients had post-streptococcal nephritis.
  4. Zakaria NF, Hamid M, Khayat ME
    Nutrients, 2021 Jun 29;13(7).
    PMID: 34209599 DOI: 10.3390/nu13072229
    Amino acids are needed for general bodily function and well-being. Despite their importance, augmentation in their serum concentration is closely related to metabolic disorder, insulin resistance (IR), or worse, diabetes mellitus. Essential amino acids such as the branched-chain amino acids (BCAAs) have been heavily studied as a plausible biomarker or even a cause of IR. Although there is a long list of benefits, in subjects with abnormal amino acids profiles, some amino acids are correlated with a higher risk of IR. Metabolic dysfunction, upregulation of the mammalian target of the rapamycin (mTOR) pathway, the gut microbiome, 3-hydroxyisobutyrate, inflammation, and the collusion of G-protein coupled receptors (GPCRs) are among the indicators and causes of metabolic disorders generating from amino acids that contribute to IR and the onset of type 2 diabetes mellitus (T2DM). This review summarizes the current understanding of the true involvement of amino acids with IR. Additionally, the involvement of GPCRs in IR will be further discussed in this review.
  5. Hamid MF, Idroas MY, Ishak MZ, Zainal Alauddin ZA, Miskam MA, Abdullah MK
    Biomed Res Int, 2016;2016:1679734.
    PMID: 27419127 DOI: 10.1155/2016/1679734
    Torrefaction process of biomass material is essential in converting them into biofuel with improved calorific value and physical strength. However, the production of torrefied biomass is loose, powdery, and nonuniform. One method of upgrading this material to improve their handling and combustion properties is by densification into briquettes of higher density than the original bulk density of the material. The effects of critical parameters of briquetting process that includes the type of biomass material used for torrefaction and briquetting, densification temperature, and composition of binder for torrefied biomass are studied and characterized. Starch is used as a binder in the study. The results showed that the briquette of torrefied rubber seed kernel (RSK) is better than torrefied palm oil shell (POS) in both calorific value and compressive strength. The best quality of briquettes is yielded from torrefied RSK at the ambient temperature of briquetting process with the composition of 60% water and 5% binder. The maximum compressive load for the briquettes of torrefied RSK is 141 N and the calorific value is 16 MJ/kg. Based on the economic evaluation analysis, the return of investment (ROI) for the mass production of both RSK and POS briquettes is estimated in 2-year period and the annual profit after payback was approximately 107,428.6 USD.
  6. Ahmed U, Manzoor M, Qureshi S, Mazhar M, Fatima A, Aurangzeb S, et al.
    Acta Trop, 2023 Mar;239:106824.
    PMID: 36610529 DOI: 10.1016/j.actatropica.2023.106824
    Pathogenic A. castellanii and N. fowleri are opportunistic free-living amoebae. Acanthamoeba spp. are the causative agents of granulomatous amebic encephalitis (GAE) and amebic keratitis (AK), whereas Naegleria fowleri causes a very rare but severe brain infection called primary amebic meningoencephalitis (PAM). Acridinone is an important heterocyclic scaffold and both synthetic and naturally occurring derivatives have shown various valuable biological properties. In the present study, ten synthetic Acridinone derivatives (I-X) were synthesized and assessed against both amoebae for anti-amoebic and cysticidal activities in vitro. In addition, excystation, encystation, cytotoxicity, host cell pathogenicity was also performed in-vitro. Furthermore, molecular docking studies of these compounds with three cathepsin B paralogous enzymes of N. fowleri were performed in order to predict the possible docking mode with pathogen. Compound VII showed potent anti-amoebic activity against A. castellanii with IC50 53.46 µg/mL, while compound IX showed strong activity against N. fowleri in vitro with IC50 72.41 µg/mL. Compounds II and VII showed a significant inhibition of phenotypic alteration of A. castellanii, while compound VIII significantly inhibited N. fowleri cysts. Cytotoxicity assessment showed that these compounds caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 µg/mL, while also effectively reduced the cytopathogenicity of Acanthamoeba to HaCaT cells. Moreover, Cathepsin B protease was investigated in-silico as a new molecular therapeutic target for these compounds. All compounds showed potential interactions with the catalytic residues. These results showed that acridine-9(10H)-one derivatives, in particular compounds II, VII, VIII and IX hold promise in the development of therapeutic agents against these free-living amoebae.
  7. Syed Najmuddin SU, Romli MF, Hamid M, Alitheen NB, Nik Abd Rahman NM
    BMC Complement Altern Med, 2016 Aug 24;16(1):311.
    PMID: 27558166 DOI: 10.1186/s12906-016-1290-y
    Annona muricata Linn which comes from Annonaceae family possesses many therapeutic benefits as reported in previous studies and to no surprise, it has been used in many cultures to treat various ailments including headaches, insomnia, and rheumatism to even treating cancer. However, Annona muricata Linn obtained from different cultivation area does not necessarily offer the same therapeutic effects towards breast cancer (in regards to its bioactive compound production). In this study, anti-proliferative and anti-cancer effects of Annona muricata crude extract (AMCE) on breast cancer cell lines were evaluated.
  8. Khoo LT, Abas F, Abdullah JO, Mohd Tohit ER, Hamid M
    PMID: 24987430 DOI: 10.1155/2014/614273
    Melastoma malabathricum Linn. is a perennial traditional medicine plants that grows abundantly throughout Asian countries. In this study, M. malabathricum Linn. leaf hot water crude extract with anticoagulant activity was purified through solid phase extraction cartridge and examined for the bioactive chemical constituents on blood coagulation reaction. The SPE purified fractions were, respectively, designated as F1, F2, F3, and F4, and each was subjected to the activated partial thromboplastin time (APTT) anticoagulant assay. Active anticoagulant fractions (F1, F2, and F3) were subjected to chemical characterisation evaluation. Besides, neutral sugar for carbohydrate part was also examined. F1, F2, and F3 were found to significantly prolong the anticoagulant activities in the following order, F1 > F2 > F3, in a dose dependent manner. In addition, carbohydrate, hexuronic acid, and polyphenolic moiety were measured for the active anticoagulant fractions (F1, F2, and F3). The characterisation of chemical constituents revealed that all these three fractions contained acidic polysaccharides (rhamnogalacturonan, homogalacturonan, and rhamnose hexose-pectic type polysaccharide) and polyphenolics. Hence, it was concluded that the presence of high hexuronic acids and polysaccharides, as well as polyphenolics in traditional medicinal plant, M. malabathricum, played a role in prolonging blood clotting in the intrinsic pathway.
  9. Ishak NA, Ismail M, Hamid M, Ahmad Z, Abd Ghafar SA
    PMID: 23762147 DOI: 10.1155/2013/601838
    Curculigo latifolia fruit is used as alternative sweetener while root is used as alternative treatment for diuretic and urinary problems. The antidiabetic and hypolipidemic activities of C. latifolia fruit:root aqueous extract in high fat diet (HFD) and 40 mg streptozotocin (STZ) induced diabetic rats through expression of genes involved in glucose and lipid metabolisms were investigated. Diabetic rats were treated with C. latifolia fruit:root extract for 4 weeks. Plasma glucose, insulin, adiponectin, lipid profiles, alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), urea, and creatinine levels were measured before and after treatments. Regulations of selected genes involved in glucose and lipid metabolisms were determined. Results showed the significant (P < 0.05) increase in body weight, high density lipoprotein (HDL), insulin, and adiponectin levels and decreased glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), urea, creatinine, ALT, and GGT levels in diabetic rats after 4 weeks treatment. Furthermore, C. latifolia fruit:root extract significantly increased the expression of IRS-1, IGF-1, GLUT4, PPAR α , PPAR γ , AdipoR1, AdipoR2, leptin, LPL, and lipase genes in adipose and muscle tissues in diabetic rats. These results suggest that C. latifolia fruit:root extract exerts antidiabetic and hypolipidemic effects through altering regulation genes in glucose and lipid metabolisms in diabetic rats.
  10. Mohd Dom NS, Yahaya N, Adam Z, Nik Abd Rahman NMA, Hamid M
    PMID: 32831872 DOI: 10.1155/2020/6374632
    The present study aimed to evaluate the potential of standardized methanolic extracts from seven Ficus deltoidea varieties in inhibiting the formation of AGEs, protein oxidation, and their antioxidant effects. The antiglycation activity was analyzed based on the inhibition of AGEs, fructosamine, and thiol groups level followed by the inhibition of protein carbonyl formation. The antioxidant activity (DPPH radical scavenging activity and reducing power assay) and total phenolic contents were evaluated. After 28 days of induction, all varieties of Ficus deltoidea extracts significantly restrained the formation of fluorescence AGEs by 4.55-5.14 fold. The extracts also reduced the fructosamine levels by 47.0-86.5%, increased the thiol group levels by 64.3-83.7%, and inhibited the formation of protein carbonyl by 1.36-1.76 fold. DPPH radical scavenging activity showed an IC50 value of 66.81-288.04 μg/ml and reducing power activity depicted at 0.02-0.24 μg/ml. The extent of phenolic compounds present in the extracts ranged from 70.90 to 299.78 mg·GAE/g. Apart from that, correlation studies between the activities were observed. This study revealed that seven varieties of Ficus deltoidea have the potential to inhibit AGEs formation and possess antioxidant activity that might be attributed to the presence of phenolic compounds.
  11. Khoo HE, Azlan A, Nurulhuda MH, Ismail A, Abas F, Hamid M, et al.
    PMID: 24368926 DOI: 10.1155/2013/434057
    This study aimed to determine anthocyanins and their antioxidative and cardioprotective properties in defatted dabai parts. Anthocyanins in crude extracts and extract fractions of defatted dabai peel and pericarp were quantified using UHPLC, while their antioxidant capacity and oxidative stress inhibition ability were evaluated by using DPPH and CUPRAC assays as well as linoleic acid oxidation system, hemoglobin oxidation, and PARP-1 inhibition ELISA. Cardioprotective effect of the defatted dabai peel extract was evaluated using hypercholesterolemic-induced New Zealand white rabbits. Six anthocyanins were detected in the defatted dabai peel, with the highest antioxidant capacities and oxidative stress inhibition effect compared to the other part. The defatted dabai peel extract has also inhibited lipid peroxidation (plasma MDA) and elevated cellular antioxidant enzymes (SOD and GPx) in the tested animal model. Major anthocyanin (cyanidin-3-glucoside) and other anthocyanins (pelargonidin-3-glucoside, malvidin-3-glucoside, cyanidin-3-galactoside, cyanidin-3-arabinoside, and peonidin-3-glucoside) detected in the defatted dabai peel are potential future nutraceuticals with promising medicinal properties.
  12. Nik Abd Rahman NMA, Nurliyana MY, Afiqah MNFNN, Osman MA, Hamid M, Lila MAM
    BMC Complement Altern Med, 2019 Nov 29;19(1):340.
    PMID: 31783838 DOI: 10.1186/s12906-019-2757-4
    BACKGROUND: Clinacanthus nutans Lindau (C. nutans) is a species of in Acanthaceae family and primarily used in South East Asian countries. C. nutans is well known as Sabah snake grass in Malaysia, and its leaves have diverse medicinal potential in conventional applications, including cancer treatments. On the basis of literature search, there is less conclusive evidence of the involvement of phytochemical constituents in breast cancer, in particular, animal tumor models. The current study aimed to determine the antitumor and antioxidant activities of C. nutans extract in 4 T1 tumor-bearing mice.

    METHODS: C. nutans leaves were subjected to methanol extraction and divided into two different concentrations, 200 mg/kg (low-dose) and 1000 mg/kg (high-dose). The antitumor effects of C. nutans extracts were assessed using bone marrow smearing, clonogenic, and splenocyte immunotype analyses. In addition, hematoxylin and eosin, tumor weight and tumor volume profiles also used to indicate apoptosis appearance. Serum cytokine levels were examined using ELISA assay. In addition, nitric oxide assay reflecting antioxidant activity was performed.

    RESULTS: From the results obtained, the methanol extract of C. nutans leaves at 200 mg/kg (P 

  13. Ali AM, Mackeen MM, Intan-Safinar I, Hamid M, Lajis NH, el-Sharkawy SH, et al.
    J Ethnopharmacol, 1996 Sep;53(3):165-9.
    PMID: 8887024
  14. Ujang Z, Ng KS, Tg Hamzah TH, Roger P, Ismail MR, Shahabudin SM, et al.
    Water Sci Technol, 2007;56(9):103-8.
    PMID: 18025737
    A pilot scale membrane plant was constructed and monitored in Shah Alam, Malaysia for municipal wastewater reclamation for industrial application purposes. The aim of this study was to verify its suitability under the local conditions and environmental constraints for secondary wastewater reclamation. Immersed-type crossflow microfiltration (IMF) was selected as the pretreatment step before reverse osmosis filtration. Secondary wastewater after chlorine contact tank was selected as feed water. The results indicated that the membrane system is capable of producing a filtrate meeting the requirements of both WHO drinking water standards and Malaysian Effluent Standard A. With the application of an automatic backwash process, IMF performed well in hydraulic performance with low fouling rate being achieved. The investigations showed also that chemical cleaning is still needed because of some irreversible fouling by microorganisms always remains. RO treatment with IMF pretreatment process was significantly applicable for wastewater reuse purposes and promised good hydraulic performance.
  15. Ajdari Z, Ebrahimpour A, Abdul Manan M, Hamid M, Mohamad R, Ariff AB
    J Biomed Biotechnol, 2011;2011:426168.
    PMID: 22190851 DOI: 10.1155/2011/426168
    Monacolins, as natural statins, form a class of fungal secondary metabolites and act as the specific inhibitors of HMG-CoA reductase. The interest in using the fermented products as the natural source of monacolins, instead of statin drugs, is increasing enormously with its increasing demand. In this study, the fermented products were produced by Monascus purpureus FTC5391 using submerged and solid state fermentations. Two commercial Monascus-fermented products were also evaluated for comparison. Improved methods of monacolins extraction and identification were developed for the assessment of monacolins in the fermented products. Methanol and ethanol were found to be the most favorable solvents for monacolins extraction due to their ability to extract higher amount of monacolin K and higher numbers of monacolin derivatives. Problem related to false-positive results during monacolins identification was solved by adding monacolin lactonization step in the assessment method. Using this improved method, monacolin derivatives were not detected in all Monascus-fermented products tested in this study, suggesting that their hypocholesterolemic effects may be due to other compounds other than monacolins.
  16. Vadivelu RK, Yeap SK, Ali AM, Hamid M, Alitheen NB
    PMID: 23056140 DOI: 10.1155/2012/251362
    Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC) is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC(50) of 3.8 μg/mL significantly (P < 0.05). Nevertheless, betulinic acid exhibited G(1) cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24 h of treatment. In conclusion, betulinic acid induced G(1) cell cycle arrest and dose-dependent DNA damage on VSMC.
  17. Khoo LT, Abdullah JO, Abas F, Tohit ER, Hamid M
    Molecules, 2015 Feb 24;20(3):3697-715.
    PMID: 25719740 DOI: 10.3390/molecules20033697
    The aims of this study were to examine the bioactive component(s) responsible for the anticoagulant activity of M. malabathricum Linn. leaf hot water crude extract via bioassay-guided fractionation and to evaluate the effect of bioactive component(s) on the intrinsic blood coagulation pathway. The active anticoagulant fraction of F3 was subjected to a series of chromatographic separation and spectroscopic analyses. Furthermore, the effect of the bioactive component(s) on the intrinsic blood coagulation pathway was studied through immediate and time incubation mixing studies. Through Activated Partial Thromboplastin Time (APTT) assay-guided fractionation, Subfraction B was considered the most potent anticoagulant fraction. Characterisation of Subfraction B indicated that anticoagulant activity could partly be due to the presence of cinnamic acid and a cinnamic acid derivative. APTT assays for both the immediate and time incubation mixing were corrected back into normal clotting time range (35.4-56.3 s). In conclusion, cinnamic acid and cinnamic acid derivative from Subfraction B were the first such compounds to be discovered from M. malabathricum Linn. leaf hot water crude extract that possess anticoagulant activity. This active anticoagulant Subfraction B prolonged blood clotting time by causing factor(s) deficiency in the intrinsic blood coagulation pathway.
  18. Kwan Z, Yeoh CA, Mohd Affandi A, Alias FA, Hamid M, Baharum N, et al.
    Med J Malaysia, 2015 Oct;70(5):273-7.
    PMID: 26556114
    BACKGROUND: Patients with severe psoriasis, namely those requiring phototherapy or systemic treatment, have an increased risk of death. The aim of this study was to determine the prevalence, aetiology and risk factors for mortality among adult patients aged 18 years and above with psoriasis in Malaysia.

    METHODS: This was a retrospective study involving adult patients notified by dermatologists to the Malaysian Psoriasis Registry between July 2007 and December 2013. Data were cross-checked against the National Death Registry. Patients certified dead were identified and the cause of death was analysed. Multivariate analysis using multiple logistic regression were conducted on potential factors associated with higher risk of mortality.

    RESULTS: A total of 419 deaths were identified among the 9775 patients notified. There were four significant risk factors for higher mortality: age>40 years (age 41-60 years old, Odds Ratio (OR) 2.70, 95%CI 1.75, 4.18; age>60 years OR 7.46, 95%CI 4.62, 12.02), male gender (OR 1.72, 95%CI 1.33,2.22), severe psoriasis with body surface area (BSA) >10% (OR 1.52, 95%CI 1.19, 1.96) and presence of at least one cardiovascular co-morbidity (OR 1.67, 95% CI 1.30, 2.14). Among the 301 patients with verifiable causes of death, the leading causes were infection (33.9%), cardiovascular disease (33.6%) and malignancy (15.9%).

    CONCLUSION: Infection was the leading cause of death among psoriasis patients in Malaysia. Although cardiovascular diseases are well-known to cause significant morbidity and mortality among psoriasis patients, the role of infections and malignancy should not be overlooked.

  19. Ahmad Aufa Z, Hassan FA, Ismail A, Mohd Yusof BN, Hamid M
    J Agric Food Chem, 2014 Mar 5;62(9):2077-84.
    PMID: 24499380 DOI: 10.1021/jf403481p
    Underutilized vegetables are currently studied not only for their nutrient values but also for their health-promoting components for protection against chronic diseases. The present study was performed to evaluate chemical compositions and antioxidant properties of underutilized vegetable palm hearts, namely, lalis (Plectocomiopsis geminiflora) and pantu (Eugeissona insignis). Additionally, the vegetable extracts were evaluated for their activities in the inhibition of digestive enzymes and effects on insulin secretion using BRIN BD11 pancreatic cell lines. Both vegetables contain valuable sources of dietary fiber, potassium, and zinc. For the first time, the phenolic compounds of the vegetables were identified and quantified using HPLC-DAD and LC-ESI-MS. Appreciable amounts of chlorogenic acid were found in the studied vegetables. The sample extracts exhibited potential antioxidant capacities through chemical and biological in vitro assays. High inhibition of α-amylase activity (>50%) was found from the extracts. Thus, it was suggested the vegetable consumption could fulfill the nutrient requirements among local communities.
  20. Ninyio NN, Ho KL, Yong CY, Chee HY, Hamid M, Ong HK, et al.
    Int J Mol Sci, 2021 Feb 15;22(4).
    PMID: 33672018 DOI: 10.3390/ijms22041922
    Hepatitis B is a major global health challenge. In the absence of an effective treatment for the disease, hepatitis B vaccines provide protection against the viral infection. However, some individuals do not have positive immune responses after being vaccinated with the hepatitis B vaccines available in the market. Thus, it is important to develop a more protective vaccine. Previously, we showed that hepatitis B virus (HBV) 'a' determinant (aD) displayed on the prawn nodavirus capsid (Nc) and expressed in Spodoptera frugiperda (Sf9) cells (namely, Nc-aD-Sf9) self-assembled into virus-like particles (VLPs). Immunisation of BALB/c mice with the Nc-aD-Sf9 VLPs showed significant induction of humoral, cellular and memory B-cell immunity. In the present study, the biophysical properties of the Nc-aD-Sf9 VLPs were studied using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the antigenicity of the Nc-aD-Sf9 VLPs, and multiplex ELISA was employed to quantify the cytokine response induced by the VLPs administered intramuscularly into BALB/c mice (n = 8). CD spectroscopy of Nc-aD-Sf9 VLPs showed that the secondary structure of the VLPs predominantly consisted of beta (β)-sheets (44.8%), and they were thermally stable up to ~52 °C. ELISA revealed that the aD epitope of the VLPs was significantly antigenic to anti-HBV surface antigen (HBsAg) antibodies. In addition, multiplex ELISA of serum samples from the vaccinated mice showed a significant induction (p < 0.001) of IFN-γ, IL-4, IL-5, IL-6, IL-10, and IL-12p70. This cytokine profile is indicative of natural killer cell, macrophage, dendritic cell and cytotoxic T-lymphocyte activities, which suggests a prophylactic innate and adaptive cellular immune response mediated by Nc-aD-Sf9 VLPs. Interestingly, Nc-aD-Sf9 induced a more robust release of the aforementioned cytokines than that of Nc-aD VLPs produced in Escherichia coli and a commercially used hepatitis B vaccine. Overall, Nc-aD-Sf9 VLPs are thermally stable and significantly antigenic, demonstrating their potential as an HBV vaccine candidate.
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