ORCID Profile
0000-0001-8342-5183
Current Organisation
Universiti Malaya
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Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000452895
Abstract: b i Background: /i /b Khat ( i Catha edulis /i ) is a plant that is deeply rooted in the cultural life of East African and Southwestern Arabian populations. Prevalent traditional beliefs about khat are that the plant has an effect on appetite and body weight. b i Summary: /i /b This review assesses the accumulated evidences on the mutual influence of monoamines, hormones and neuropeptides that are linked to obesity. A few anti-obesity drugs that exert their mechanisms of action through monoamines are briefly discussed to support the notion of monoamines being a critical target of drug discovery for new anti-obesity drugs. Subsequently, the review provides a comprehensive overview of central dopamine and serotonin changes that are associated with the use of khat or its alkaloids. Then, all the studies on khat that describe physical, biochemical and hormonal changes are summarised and discussed in depth. b i Conclusion: /i /b The reviewed studies provide relatively acceptable evidence that different khat extracts or cathinone produces changes in terms of weight, fat mass, appetite, lipid biochemistry and hormonal levels. These changes are more pronounced at higher doses and long durations of intervention. The most suggested mechanism of these changes is the central action that produces changes in the physiology of dopamine and serotonin. Nonetheless, there are a number of variations in the study design, including species, doses and durations of intervention, which makes it difficult to arrive at a final conclusion about khat regarding obesity, and further studies are necessary in the future to overcome these limitations.
Publisher: MDPI AG
Date: 13-08-2020
DOI: 10.3390/NU12082430
Abstract: 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.
Publisher: MDPI AG
Date: 14-08-2020
DOI: 10.3390/MOLECULES25163700
Abstract: 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.
Publisher: BMJ
Date: 08-2020
DOI: 10.1136/BMJOPEN-2020-038128
Abstract: Colorectal cancer is one of the leading causes of cancer-related morbidity worldwide and it has been reported to be associated with poor lifestyle habits which include excess tobacco and alcohol intake as well as genetics and age factors. Probiotics such as the lactic acid bacteria and Bifidobacterium as well as probiotic containing foods (kombucha, kefir, miso etc) have received lots of attention as anticancer agents for prevention and treatment. The effects of the administration of probiotics to patients with colorectal cancer is the primary goal of this systematic review. The overall aim is to assess how the use of probiotics in patients with colorectal cancer helps in the management of colorectal cancer and its effect on the ersity of gut microbiota. The final systematic review will provide a comprehensive evidence base for the use and efficacy of probiotics in patient with colorectal cancer care. The systematic review, will be conducted by extensively searching different databases such as PubMed, Web of Science, Scopus, Wiley and ProQuest to identify randomised controlled trials (with no time frame) which relate to the administration of probiotics to patients with colorectal cancer. The search strategy will include words like colorectal cancer, probiotics, Bifidobacterium , clinical trials etc. A systematic search of databases was performed between 17 and 20 January 2020. Two reviewers will independently review the studies and also search the reference lists of the eligible studies to obtain more references. Data will be extracted from the eligible studies using standardised data extraction form. After assessing the risk of bias, qualitative analysis will be used to synthesise the systematic review. This is a protocol for a systematic review therefore, it doesn’t require any ethics approval. We intend to disseminate the protocol in a peer reviewed journal.
Publisher: Oxford University Press (OUP)
Date: 24-05-2021
Abstract: Colorectal cancer (CRC) is a leading cause of cancer deaths. Recently, much attention has been given to the microbiome and probiotics as preventive and therapeutic approaches to CRC and the mechanisms involved. To interpret the findings of randomized controlled trials (RCTs) of probiotics relative to patients with CRC and to outline challenges of and future directions for using probiotics in the management and prevention of CRC. Web of Science, PubMed, ProQuest, Wile,y and Scopus databases were searched systematically from January 17–20, 2020, in accordance with PRISMA guidelines. Primacy RCTs that reported the effects of administration to patients with CRC of a probiotic vs a placebo were eligible to be included. The studies were screened and selected independently by 2 authors on the basis of prespecified inclusion and exclusion criteria. The data extraction and risk-of-bias assessment were also performed independently by 2 authors. A total of 23 RCTs were eligible for inclusion. Probiotics supplementation in patients with CRC improved their quality of life, enhanced gut microbiota ersity, reduced postoperative infection complications, and inhibited pro-inflammatory cytokine production. The use of certain probiotics in patients with CRC also reduced the side effects of chemotherapy, improved the outcomes of surgery, shortened hospital stays, and decreased the risk of death. Bifidobacteria and Lactobacillus were the common probiotics used across all studies. Probiotics have beneficial effects in patients with CRC regardless of the stage of cancer. There is an opportunity for probiotics to be used in mainstream health care as a therapy in the fight against CRC, especially in early stages however, larger clinical trialsof selected or a cocktail of probiotics are needed to confirm the efficacy, dosage, and interactions with chemotherapeutics agents. PROSPERO registration no. CRD42020166865.
Publisher: Springer Science and Business Media LLC
Date: 29-09-2022
DOI: 10.1007/S00204-022-03382-3
Abstract: With more than 80 cytochrome P450 (CYP) encoding genes found in the nematode Caenorhabditis elegans (C. elegans), the cyp35 genes are one of the important genes involved in many biological processes such as fatty acid synthesis and storage, xenobiotic stress response, dauer and eggshell formation, and xenobiotic metabolism. The C. elegans CYP35 subfamily consisted of A, B, C, and D, which have the closest homolog to human CYP2 family. C. elegans homologs could answer part of the hunt for human disease genes. This review aims to provide an overview of CYP35 in C. elegans and their human homologs, to explore the roles of CYP35 in various C. elegans biological processes, and how the genes of cyp35 upregulation or downregulation are influenced by biological processes, upon exposure to xenobiotics or changes in diet and environment. The C. elegans CYP35 gene expression could be upregulated by heavy metals, pesticides, anti-parasitic and anti-chemotherapeutic agents, polycyclic aromatic hydrocarbons (PAHs), nanoparticles, drugs, and organic chemical compounds. Among the cyp35 genes, cyp-35A2 is involved in most of the C. elegans biological processes regulation. Further venture of cyp35 genes, the closest homolog of CYP2 which is the largest family of human CYPs, may have the power to locate cyps gene targets, discovery of novel therapeutic strategies, and possibly a successful medical regime to combat obesity, cancers, and cyps gene-related diseases.
Publisher: Springer Science and Business Media LLC
Date: 11-2019
DOI: 10.1007/S13402-019-00477-5
Abstract: 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. 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.
Publisher: Elsevier BV
Date: 2022
Publisher: Wiley
Date: 17-05-2022
Publisher: Springer Science and Business Media LLC
Date: 17-07-2023
Publisher: MDPI
Date: 31-05-2021
Publisher: Elsevier BV
Date: 11-2022
Publisher: Springer Science and Business Media LLC
Date: 10-10-2018
DOI: 10.1007/S13318-018-0518-2
Abstract: A significant number of people worldwide consume khat on daily basis. Long term of khat chewing has shown negative impact on several organ systems. It is likely that these people are co-administered khat preparations and conventional medication, which may lead to khat-drug interactions. This study aimed to reveal the inhibitory potencies of khat ethanol extract (KEE) and its major active ingredient (cathinone) on human cytochrome P450 (CYP) 2C9, CYP2D6, and CYP3A4 enzymes activities, which are collectively responsible for metabolizing 70-80% clinically used drugs. In vitro fluorescence-based enzyme assays were developed and the CYP enzyme activities were quantified in the presence and absence of KEE and cathinone employing Vivid KEE inhibited human CYP2C9, CYP2D6, and CYP3A4 enzyme activities with IC Khat-drug interactions are possible due to administration of clinical drugs metabolized by CYP2C9/CYP2D6/CYP3A4 together with khat chewing. Further in vivo studies are required to confirm our findings and identify the causative constituents of these inhibitory effects.
Publisher: MDPI AG
Date: 13-05-2022
DOI: 10.3390/BIOMEDICINES10051128
Abstract: Faecalibacterium prausnitzii is one of the most abundant commensals of gut microbiota that is not commonly administered as a probiotic supplement. Being one of the gut’s major butyrate-producing bacteria, its clinical significance and uses are on the rise and it has been shown to have anti-inflammatory and gut microbiota-modulating properties in the treatment of inflammatory bowel illness, Crohn’s disease, and colorectal cancer. Colorectal cancer (CRC) is a silent killer disease that has become one of the leading causes of cancer-related death worldwide. This study aimed to evaluate the anti-tumorigenic and antiproliferative role of F. prausnitzii as well as to study its effects on the ersity of gut microbiota in rats. Findings showed that F. prausnitzii probiotic significantly reduced the colonic aberrant crypt foci frequency and formation in Azoxymethane (AOM)-induced CRC in rats. In addition, the administration of F. prausnitzii lowered the lipid peroxidation levels in the colon tissues. For in vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, the cell-free supernatant of F. prausnitzii suppressed the growth of HCT116 colorectal cancer cells in a time/dose-dependent manner. 16S rRNA gene sequencing using rat stool s les showed that the administration of F. prausnitzii modulated the gut microbiota of the rats and enhanced its ersity. Hence, these findings suggest that F. prausnitzii as a probiotic supplement can be used in CRC prevention and management however, more studies are warranted to understand its cellular and molecular mechanisms of action.
Publisher: SAGE Publications
Date: 04-06-2022
DOI: 10.1177/10915818221103790
Abstract: Cathine is the stable form of cathinone, the major active compound found in khat ( Catha edulis Forsk) plant. Khat was found to inhibit major phase I drug metabolizing cytochrome P450 (CYP) enzyme activities in vitro and in vivo. With the upsurge of khat consumption and the potential use of cathine to combat obesity, efforts should be channelled into understanding potential cathine-drug interactions, which have been rather limited. The present study aimed to assess CYPs activity and inhibition by cathine in a high-throughput in vitro fluorescence-based enzyme assay and molecular docking analysis to identify how cathine interacts within various CYPs’ active sites. The half maximal inhibitory concentration (IC 50 ) values of cathine determined for CYP2A6 and CYP3A4 were 80 and 90 μM, while CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP2J2 and CYP3A5 showed no significant inhibition. Furthermore, in K i analysis, the Lineweaver-Burk plots depicted non-competitive mixed inhibition of cathine on both CYP2A6 and CYP3A4 with K i value of 63 and 100 μM, respectively. Cathine showed negligible time-dependent inhibition on CYPs. Further, molecular docking studies showed that cathine was bound to CYP2A6 via hydrophobic, hydrogen and π-stacking interactions and formed hydrophobic and hydrogen bonds with active site residues in CYP3A4. Both molecular docking prediction and in vitro outcome are in agreement, granting more detailed insights for predicting CYPs metabolism besides the possible cathine-drug interactions. Cathine-drug interactions may occur with concomitant consumption of khat or cathine-containing products with medications metabolized by CYP2A6 and CYP3A4.
Publisher: MDPI AG
Date: 05-01-2023
Abstract: Polyethylene glycol (PEG) coated Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) for cancer treatment are biocompatible, nonimmunogenic and accumulate in tumour sites due to the enhanced permeability and retention (EPR). Doxorubicin (DOX) is a potent but cardiotoxic anticancer agent. Hyaluronic acid (HA) occurs naturally in the extra-cellar matrix and binds to CD44 receptors which are overexpressed in cancer metastasis, proven to be characteristic of cancer stem cells and responsible for multidrug resistance. In this study, an athymic mice model of breast cancer metastasis was developed using red fluorescent protein (RFP)-labelled triple negative cancer cells. The animals were ided into four treatment groups (Control, HA-PEG-PLGA nanoparticles, PEG-PLGA nanoparticles, and Free DOX). The tumour size growth was assessed until day 25 when animals were sacrificed. Mice treated with HA-PEG-PLGA NPs inhibited tumour growth. The tumour growth at day 25 (118% ± 13.0) was significantly (p 0.05) less than PEG-PLGA NPs (376% ± 590 and control (826% ± 970). Fluorescent microscopy revealed that HA-PEG-PLGA NPs had significantly (p 0.05) less metastasis in liver, spleen, colon, and lungs as compared to control and to Free DOX groups. The efficacy of HA-PEG-PLGA NPs was proven in vivo. Further pharmacokinetic and toxicity studies are required for this formulation to be ready for clinical research.
Publisher: MDPI AG
Date: 29-04-2023
DOI: 10.3390/IJMS24098080
Abstract: Colorectal cancer (CRC) accounts for 10% of all cancer diagnoses and cancer-related deaths worldwide. Over the past two decades, several studies have demonstrated the clinical benefits of probiotic supplementation and some studies have shown that certain probiotics can modulate immunity and strengthen gut microbiota ersity. This study aims to assess the impact of the Propionibacterium freudenreichii (PF) probiotic against CRC induced by azoxymethane (AOM), and to investigate its effects on gut microbiota ersity in rats, as well as to evaluate the anti-proliferative activities of PF in HCT116 CRC cells. This experiment was performed using four groups of SD rats: normal control, AOM group, PF group (1 × 109 CFU/mL), and standard drug control (5-fluorouracil, 35 mg/kg). Methylene blue staining of colon tissues showed that the administration of PF significantly reduced the formation of colonic aberrant crypt foci (ACF) compared to the AOM control group. In addition, treated rats had lower levels of malondialdehyde in their colon tissue homogenates, indicating that lipid peroxidation was suppressed by PF supplementation. Furthermore, 16S rRNA gene analysis revealed that probiotic treatment enhanced the ersity of gut microbiota in rats. In vitro study showed that the viability of HCT116 cells was inhibited by the probiotic cell-free supernatant with an IC50 value of 13.3 ± 0.133. In conclusion, these results reveal that consuming PF as probiotic supplements modulates gut microbiota, inhibits the carcinogenic effects of AOM, and exerts anti-proliferative activity against CRC cells. Further studies are required to elucidate the role of PF on the immune response during the development and growth of CRC.
No related grants have been discovered for Mohammed Alshawsh.