Publications by authors named "Muhammad Fazril Mohamad Razif"

6 Publications

  • Page 1 of 1

Antioxidant and Cytotoxic Effects and Identification of Bioactive Proteins Using Shotgun Proteomic Analysis.

Food Technol Biotechnol 2021 Jun;59(2):201-208

Medicinal Mushroom Research Group, Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

Research Background: a highly valued medicinal fungus, is close to extinction due to overexploitation. Successful cultivation of fruiting body (OCS02®) shows that the cultivar has a promising nutritional value and numerous bioactive compounds. Antioxidant and antiproliferative properties and biologically active proteins of the OCS02® are investigated for possible development into nutraceuticals.

Experimental Approach: The chemical composition of the OCS02® cold water extract was determined, and the antioxidant activities were examined using ferric reducing, DPPH and O scavenging assays. Tetrazolium dye (MTT) cytotoxic assay was performed to assess the antiproliferative activity of the extract. Bioactive proteins in the active fraction of the extract were identified using liquid chromatography (LC) and tandem-mass spectrometry (MS/MS).

Results And Conclusions: The OCS02® extract exhibited strong O scavenging (expressed as Trolox equivalents (18.4±1.1) mol/g) and potent cytotoxic activities against adenocarcinomic human alveolar basal epithelial (A549) cells (IC=(58.2±6.8) µg/mL). High molecular mass polysaccharides, proteins and protein-polysaccharide complexes could have contributed to the antioxidant and cytotoxic selectivity of the OCS02®. LC-MS/MS analysis identified several potential cytotoxic proteases and an oxalate decarboxylase protein which may exhibit protection effects on kidneys.

Novelty And Scientific Contributions: The findings demonstrate the potential of OCS02® to be developed into functional food due to its promising superoxide anion radical scavenging capacity, cytotoxic effect and presence of biopharmaceutically active proteins.
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http://dx.doi.org/10.17113/ftb.59.02.21.7151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284113PMC
June 2021

Proteasomal degradation of p130 facilitate cell cycle deregulation and impairment of cellular differentiation in high-risk Human Papillomavirus 16 and 18 E7 transfected cells.

Mol Biol Rep 2021 Jun 24;48(6):5121-5133. Epub 2021 Jun 24.

Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.

The High-Risk Human Papillomaviruses (HR-HPVs) 16 and 18 are known to cause cervical cancer, which is primarily attributed to E6 and E7 oncoproteins. In addition, recent studies have focused on the vital role of the p130 pocket protein as an oncosuppressor to limit the expression of E2F transcription factors required for cell cycle progression. In view of this, the current study was conducted to investigate the mechanism by which transfection with HPV16/18 E7 leads to the deregulation of the host cell cycle, altering the localisation of p130, and expression of differentiation genes in Human Keratinocytes (HaCaT) cells. Co-immunoprecipitation, Western blot analysis, immunofluorescence microscopy, flow cytometry, quantitative-Polymerase Chain Reaction (qPCR), and the inhibition of p130 by MG132 inhibitor were employed to investigate the loss of p130 and its disruption in HPV 16/18 E7-transfected HaCaT cells. The HPV16- and HPV18-transformed cells, known as CaSki and HeLa, respectively, were also used to complement the ectopic expressions of E7 in HaCaT cells. Normal keratinocytes displayed higher level of p130 expression than HPV-transformed cells. In addition, the immunofluorescence analysis revealed that both HPV 16/18 E7-transfected HaCaT and HPV-transformed cells exhibited higher level of cytoplasmic p130 compared to nuclear p130. A significant increase in the number of S/G2 phase cells in HPV-transformed cells was also recorded since E7 has been shown to stimulate proliferation through the deactivation of Retinoblastoma Protein (pRB)-dependent G1/S checkpoint. Furthermore, the findings recorded the down-regulation of keratinocyte differentiation markers, namely p130, keratin10, and involucrin. The proteasomal degradation of the exported p130 confirmed the cellular localisation pattern of p130, which was commonly observed in cancerous cells. The findings provide strong evidence that the localisation of nuclear p130 nuclear was disrupted by HPV16/18 E7 led to the deregulation of the cell cycle and the impairment of cellular differentiation ultimately lead to cellular transformation.
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http://dx.doi.org/10.1007/s11033-021-06509-4DOI Listing
June 2021

Immunomodulatory Properties of Water-Soluble Polysaccharides Extracted from the Fruiting Body of Chinese Caterpillar Mushroom, Ophiocordyceps sinensis Cultivar OCS02® (Ascomycetes).

Int J Med Mushrooms 2020 ;22(10):967-977

Medicinal Mushroom Research Group (MMRG), Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Center for Natural Products Research and Drug Discovery (CENAR), University of Malaya, Kuala Lumpur, Malaysia; University of Malaya Centre for Proteomics Research (UMCPR), University of Malaya, Kuala Lumpur, Malaysia.

Ophiocordyceps sinensis (=Cordyceps sinensis) has been known for its various medicinal properties, in particular immunomodulatory activities associated with its polysaccharides. In this study, the fruiting body of O. sinensis cultivar OCS02® was investigated for its chemical composition and monosaccharide profile. Cold water extract (CWE) obtained from this fruiting body was fractionated by molecular weight (MW) into high (HMW), medium (MMW), and low (LMW) fractions. Polysaccharides in the extract and fractions were identified as heteroglycans containing mostly glucose and mannose with small amounts of galactose, fucose, arabinose, and xylose. The immunomodulatory potential of these heteroglycans was evaluated by induction of cytokine/chemokine secretion using murine macrophage RAW 264.7. All treatments showed significant modulation of IL-6, IL-9, MIP-2, and TIMP-1, especially for CWE, HMW, and MMW, which might be due to their high ratios of glucose and the presence of protein. Further investigation on the structure-function relationship of these fruiting body polysaccharide fractions is needed to delineate the underlying mechanism of their immunomodulatory effect both in vitro and in vivo.
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http://dx.doi.org/10.1615/IntJMedMushrooms.2020036351DOI Listing
July 2021

The Immunomodulating Properties of Tiger Milk Medicinal Mushroom, Lignosus rhinocerus TM02® Cultivar (Agaricomycetes) and Its Associated Carbohydrate Composition.

Int J Med Mushrooms 2020 ;22(8):803-814

Medicinal Mushroom Research Group (MMRG), Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Center for Natural Products Research and Drug Discovery (CENAR), University of Malaya, Kuala Lumpur, Malaysia; University of Malaya Centre for Proteomics Research (UMCPR), University of Malaya, Kuala Lumpur, Malaysia.

Natural compounds found in Lignosus rhinocerus like polysaccharides and polysaccharide-protein complexes have the capabilities to modulate the immune system. It possesses antitumor and anti-inflammatory properties and is commonly used in Southeast Asia and Southern China to alleviate illness. To investigate its immunomodulating properties, composition of polysaccharides and the expression of cytokines/chemokines from L. rhinocerus (TM02®) cultivar treated RAW 264.7 were explored. It was revealed, CWE contains linear polysaccharides with 1,4-linkages and rhinoprolycan fraction (HMW & MMW) possesses 1,4-Glcp and 1,6-Glcp backbone and branched chain (1,3,6-Glcp, 1,4,6-Glcp, 1,3,6-Glcp, 1,2,4,6-Glcp). Cytokines profile showed upregulation from CWE (IL-5: 12.078 ± 1.225), HMW (IL-6: 7.297 ± 0.338; TIMP-1: 3.358 ± 0.200), MMW (IL-5: 15.412 ± 5.823; TIMP-1: 1.747 ± 0.053), and LMW (MIP-2: 3.495 ± 0.416; TIMP-1: 7.573 ± 0.088) and possible involvement of NF-κB and MAPK signaling pathway. Further in vivo studies are needed to fully understand the immunomodulatory effects of TM02®.
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http://dx.doi.org/10.1615/IntJMedMushrooms.2020035658DOI Listing
July 2021

Leptin and soluble leptin receptor in association with gestational diabetes: a prospective case-control study.

Arch Gynecol Obstet 2018 03 21;297(3):797-803. Epub 2017 Dec 21.

Department of Pathology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.

Purpose: To assess the association of serum leptin and its receptor (SLeptinR) with the risk of gestational diabetes mellitus (GDM) and to evaluate the longitudinal circulation of these peptides in pregnancy.

Methods: This study consisted of 53 subjects diagnosed with GDM and 43 normal glucose tolerance (NGT) pregnant women. Serum leptin and SLeptinR were measured at 24-28 weeks, prior and after delivery, and post-puerperium.

Results: Lower levels of leptin and SLeptinR were observed in GDM compared to NGT. Leptin [OR 0.97 (95% CI 0.94-1.0)] and SLeptinR [OR 0.86 (95% CI 0.79-0.93]) were inversely associated with GDM. Participants in the lowest tertile for leptin and SLeptinR had a 2.8-fold (95% CI 1.0-7.6) and a 5.7-fold (95% CI 1.9-17.3) higher risk of developing GDM compared with the highest tertile, respectively. These relationships were attenuated after adjustment for covariates. In both the groups, peak leptin was observed at 24-28 weeks, decreasing continuously during pregnancy (p > 0.05) and after delivery (p < 0.017). SLeptinR level increased (p < 0.001) during pregnancy and decreased (p < 0.005) after delivery in GDM, however, levels remained the same in NGT. In GDM, leptin and SLeptinR was positively and inversely correlated with BMI and HOMA-IR at 24-28 weeks and post-puerperium, respectively. The cord levels of both leptin and SLeptinR were lower than maternal levels. There were no significant differences in serum cord leptin and SLeptinR levels between the groups.

Conclusion: Leptin and SLeptinR are independently and inversely associated with GDM. Lower levels of these peptides may play an important role in the pathophysiology of GDM and pre-diabetic state in post-puerperium.
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http://dx.doi.org/10.1007/s00404-017-4617-0DOI Listing
March 2018

Subversion of immunoproteasome subunit expression in dengue virus serotype 2-infected HepG2 cells.

Rev Soc Bras Med Trop 2017 Jan-Feb;50(1):99-103

Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Introduction:: Infection with all serotypes of dengue virus (DV) results in augmented antigen presentation by MHC class I molecules. However, the upregulation of immunoproteasome subunits only results from infection with two serotypes. This study aims to elucidate changes in the expression of immunoproteasome subunits resulting from infection with DV, particularly DV serotype 2 (DV2).

Methods:: HepG2 cells were grown in various culture milieu. Total cellular RNA and proteins were extracted and quantified.

Results:: Results demonstrated sequestration of immunoproteasome subunits LMP2 and LMP7 in DV2-infected cells.

Conclusions:: This study provides insights into the mechanisms underlying immune evasion by DV.
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http://dx.doi.org/10.1590/0037-8682-0207-2016DOI Listing
May 2017
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