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Fulltext Interleukin-6 and intercellular cell adhesion molecule-1 expression remains elevated in revived live endothelial cells following spaceflight

Muid S, Froemming GR, Ali AM, Nawawi H

Malays J Pathol, 2013 Dec;35(2):165-76.
PMID: 24362480 MyJurnal

The effects of spaceflight on cardiovascular health are not necessarily seen immediately after astronauts have returned but can be delayed. It is important to investigate the long term effects of spaceflight on protein and gene expression of inflammation and endothelial activation as a predictor for the development of atherosclerosis and potential cardiovascular problems. The objectives of this study were to investigate the (a) protein and gene expression of inflammation and endothelial activation, (b) expression of nuclear factor kappa B (NFκB), signal transducer and activator of transcription-3 (STAT-3) and endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVEC) 3 months post-space flight travel compared to ground controls. HUVEC cultured on microcarriers in fluid processing apparatus were flown to the International Space Station (ISS) by the Soyuz TMA-11 rocket. After landing, the cells were detached from microcarriers and recultured in T-25 cm(2) culture flasks (Revived HUVEC). Soluble protein expression of IL-6, TNF-α, ICAM-1, VCAM-1 and e-selectin were measured by ELISA. Gene expression of these markers and in addition NFκB, STAT-3 and eNOS were measured. Spaceflight induced IL-6 and ICAM-1 remain elevated even after 3 months post spaceflight travel and this is mediated via STAT-3 pathway. The downregulation of eNOS expression in revived HUVEC cells suggests a reduced protection of the cells and the surrounding vessels against future insults that may lead to atherosclerosis. It would be crucial to explore preventive measures, in relation to atherosclerosis and its related complications.
Anthraquinones from hedyotis herbacea

Permana D, Lajis NH, Othman AG, Ali AM, Aimi N, Kitajima M, et al.

J Nat Prod, 1999 Oct;62(10):1430-1.
PMID: 10543909

A new anthraquinone, 2-hydroxymethyl-10-hydroxy-1,4-anthraquinone (1), was isolated from Hedyotis herbacea along with three other known derivatives: 1,4-dihydroxy-2-hydroxymethylanthraquinone (2); 2, 3-dimethoxy-9-hydroxy-1,4-anthraquinone; and 1,4-dihydroxy-2, 3-dimethoxyanthraquinone. The structure of 1 was determined based on analysis of its spectroscopic data.
Metabolism of goniothalamin in animal and microbial system

El-Sharkawy S, Yusuf Z, Pihie AH, Ali AM

Boll Chim Farm, 1996 Jan;135(1):35-40.
PMID: 9004738

Of the twenty microorganisms screened for metabolism of goniothalamin only Streptomyces aurofaciens ATCC 10762 and Nocardia species NRRL 5646 produced two metabolites, 3,4-dihydrogoniothalamin and 3,4,7,8 tetrahydrogoniothalamin. The identity of the isolated metabolites were established using TLC, HPLC, MS, IR, and 1H- and 13C-NMR spectroscopy. In addition, the substrate had been transformed into two unknown metabolites by Aspergillus niger ATCC 11394 and Septomyxa affinis ATCC 6737 in low yield. Three of the metabolites were also detected and identified in the urine and blood samples of the goniothalamin-treated Sprague-Dawley rats. The obtained results are in agreement with and support the principle of microbial models of mammalian metabolism.
Screening for the in vitro anti-tumor-promoting activities of edible plants from Malaysia

Murakami A, Ali AM, Mat-Salleh K, Koshimizu K, Ohigashi H

Biosci Biotechnol Biochem, 2000 Jan;64(1):9-16.
PMID: 10705442

A total of 114 methanol extracts from 42 plant families of edible Malaysian plants were screened for their inhibitory activities toward tumor promoter 12-O-hexadecanoylphorbol-13-acetate (HPA)-induced Epstein-Barr virus (EBV) activation in Raji cells. By testing at a concentration of 200 micrograms/ml, 74% of the 114 extracts inhibited EBV activation by 30% or more. This rate is comparable to those observed in the previous tests on edible Thai (60%) and Indonesian (71%) plants, and, importantly, much higher than that (26%) observed for Japanese edible plants. Approximately half of the Malaysian plants did not taxonomically overlap those from the other three countries, suggesting that Malaysian plants, as well as Thai and Indonesian plants, are an exclusive source of effective chemopreventive agents. Further dilution experiments indicated an extract from the leaves of Piper betle L. (Piperaceae) to be one of the most promising species. The high potential of edible Southeast Asian plants for cancer chemoprevention is collectively discussed.
Concurrent And Longitudinal Association Between Glycemic Control And Self Reported Medication Adherence Among Type 2 Diabetes Patients At A Tertiary Care Hospital In Malaysia

Butt M, Ali AM, Bakry MM

Curr Diabetes Rev, 2019;15(5):402-406.
PMID: 30156163 DOI: 10.2174/1573399814666180828152754

BACKGROUND: This study evaluated the association between self-reported adherence with concurrent and subsequent glycemic control amongst type 2 diabetes patients at a tertiary care hospital in Malaysia.
METHODS: Demographic and clinical variables were assessed at baseline, after three and six months in 73 type 2 diabetes patients. Regression analysis, using SPSS, evaluated the concurrent and longitudinal association of medication adherence and glycemic control. Potential confounders of variables were identified using bi-variate correlation analyses.
RESULTS: Concurrent Medication adherence and HbA1c association were significant after adjusting for ethnicity (P = 0.005). For longitudinal observation at 3 months, the association was significant after adjusting for ethnicity (P = 0.016); however, it became non-significant when baseline glycemic control was included in the model (P = 0.28).
CONCLUSION: Easy to administer MALMAS significantly predicted concurrent glycemic control independent of potential confounders. This association persisted in longitudinal observation after 3 months when adjusted for confounders and became non-significant after adjusting for baseline glycemic control.
Computer vision syndrome and dry eye symptoms among breastfeeding women

Subri S, Ali AM, Salleh SN

Med J Malaysia, 2024 Mar;79(Suppl 1):128-133.
PMID: 38555897

INTRODUCTION: Breastfeeding women are susceptible to musculoskeletal symptoms and hormonal changes that can affect the ocular surface. As exposure to visual display units (VDU) that is known to cause symptoms of dry eye and computer vision syndrome (CVS) is increasing worldwide, including among breastfeeding women, it is unknown whether this group of VDU users would experience CVS more than non-breastfeeding women. Therefore, this study aimed to investigate the association between breastfeeding status and symptoms of CVS and dry eye.
MATERIALS AND METHODS: In this cross-sectional study, selfreported CVS and dry eye symptoms were compared between 80 breastfeeding and 72 non-breastfeeding VDU users. Two questionnaires were administered online, which were the CVS-Questionnaire (CVS-Q) and the Ocular Surface Disease Index (OSDI) questionnaire, to evaluate symptoms of CVS and dry eye, respectively. Mann-Whitney test was used to compare CVS and OSDI scores between groups, while correlations between the scores were analyzed using Spearman's test.
RESULT: Results showed that OSDI scores were significantly higher in the non-breastfeeding group (U = 2263, z-score = - 2.276, p = 0.023), indicating more dry eye symptoms experienced by respondents in this group, while no significant group difference was found in terms of CVS scores (U = 2772, z-score = -0.400, p = 0.689). Additionally, no significant association was observed between breastfeeding status and severity of dry eye symptoms as well as CVS symptoms.
CONCLUSION: This study reported the possible benefit of breastfeeding in reducing dry eye symptoms. The CVS symptoms found in the breastfeeding group were possibly due to VDU usage rather than caused by breastfeeding. Public education on preventive measures to reduce the occurrence of CVS symptoms and ocular dryness among VDU users is essential to improve the quality of life.
Fulltext Change in infection control practices and awareness of hospital medical staff in the aftermath of SARS

Loh LC, Chelliah A, Ang TH, Ali AM

Med J Malaysia, 2004 Dec;59(5):659-64.
PMID: 15889569 MyJurnal

Severe Acute Respiratory Syndrome (SARS) epidemic illustrated the crucial role of infection surveillance and control measures in the combat of any highly transmissible disease. We conducted an interview survey of 121 medical staff 145 doctors, 46 staff nurses and 30 medical assistants) in a state hospital in Malaysia three months after the end of SARS epidemic (from October to December 2003). Staff was grouped according to those directly involved in the care of suspected SARS patients [S+ group n=41] and those who were not [S- group; n=80]. On hand washing following sneezing, coughing and touching patients, the proportions of medical staff that reported an increase after the SARS crisis were 22.3%, 16.5% and 45.5% respectively. On wearing masks, gloves, and aprons when meeting potentially infectious patients, the proportions that reported an increase were 39.7%, 47.1% and 32.2% respectively. Significantly more staff in S+ than S- group reported these increases. Sixty percent of staff was aware of changes in hospital infection control policies after SARS; 93.4% was aware of notifying procedures, and 81.8% was aware of whom to notify in the hospital. Regarding infection isolation ward, Infectious Control Nurse and Infection Control Committee Chairman in the hospital, the proportions of staff that could correctly name them were 39.7%, 38.3% and 15.7% respectively. Significantly more in S+ than S- group could do so. However, more than half the staff claimed ignorance on the knowledge of infection isolation ward (56.2%), Infection Control Nurse (57.9%) and Chairman (65.3%). Our findings demonstrated that SARS crisis had some positive impact on the infection control practices and awareness of medical staff especially on those with direct SARS involvement. Implications for future control of infectious diseases are obvious.
Fulltext Response of undergraduate medical students to SARS

Loh LC, Ali AM, Ang TH, Chelliah A

Med J Malaysia, 2004 Aug;59(3):431-2.
PMID: 15727395
Existence of two emm-like "mrp" and "emm" genes in the mga regulon of the Streptococcus pyogenes strain ST4547

Eshaghi M, Ali AM, Jamal F, Yusoff K

J. Biochem. Mol. Biol. Biophys., 2002 Feb;6(1):23-8.
PMID: 12186779

Streptococcus pyogenes ST4547 is an opacity factor negative strain, which has been recently reported as a new emm type from Malaysia. Nucleotide sequencing of the mga regulon of this strain showed the existence of two emm-like genes. The emm gene located upstream of the scpA gene comprises 1305 nucleotides encoding the putative precursor M protein of 435 amino acids in length with an M(r) of 49 kDa. or a predicted mature protein of 394 amino acids with an M(r) of 44.8 kDa. Another gene mrpST4547 was located upstream of the emm gene and downstream of the mga gene. The sequence of this mrp gene comprises 1167 nucleotides encoding a predicted protein of 388 amino acids in length with an M(r) of 42.2 kDa. or a predicted mature protein of 347 amino acids with an M(r) of 37.9 kDa. The mga regulon of strain ST4547 has a mosaic structure comprising segments, which originated from different OF positive and OF negative strains. The sequences flanking the hyper-variable and C repeats of the emmST4547 gene showed high similarity to corresponding regions in the mga regulon of OF positive strains notably M15, M4, M22 and M50. In contrast, the sequence within the hyper-variable and C repeat regions of the emmST4547 gene revealed high similarity to equivalent regions in the OF negative strains. These data indicates that horizontal transfer of emm-like gene could have occurred between OF positive and OF negative strains resulting in architectural divergence in the mga regulon.
Growth and anthraquinone production of Morinda elliptica cell suspension cultures in a stirred-tank bioreactor

Abdullah MA, Ariff AB, Marziah M, Ali AM, Lajis NH

J Agric Food Chem, 2000 Sep;48(9):4432-8.
PMID: 10995375

The effects of medium strategy, number of impellers, aeration mode, and mode of operation on Morinda elliptica cell suspension cultures in a stirred-tank bioreactor are described. A lower number of impellers and continuous aeration contributed toward high cell growth rate, whereas a higher number of impellers reduced cell growth rate, although not anthraquinone yield. The semicontinuous mode could indirectly imitate the larger scale version of production medium strategy and improved anthraquinone production even with 0. 012% (v/v) antifoam addition. Production medium promoted both growth (maximum dry cell weight of 24.6 g/L) and anthraquinone formation (maximum content of 19.5 mg/g of dry cell weight), without any necessity for antifoam addition. Cultures in production medium or with higher growth rate and anthraquinone production were less acidic than cultures in growth medium or with lower growth rate and anthraquinone production. Using the best operating variables, growth of M. elliptica cells (24.6 g/L) and anthraquinone yield (0.25 g/L) were 45% and 140%, respectively, lower than those using a shake flask culture after 12 days of cultivation.
Antimicrobial susceptibility of bifidobacteria

Yazid AM, Ali AM, Shuhaimi M, Kalaivaani V, Rokiah MY, Reezal A

Lett Appl Microbiol, 2000 Jul;31(1):57-62.
PMID: 10886616

Eighteen Bifidobacterium strains were tested for their susceptibility to a range of antimicrobial agents. All the strains tested, including the reference culture Lactobacillus acidophilus CH2, were susceptible to several groups of antimicrobial agents, they were cephalosporin (cefamandole, cefazolin, cefaperazone, cefoxitin), polypeptide (bacitracin), macrolide (erythromycin), penicillin (amoxicillin), phenicol (chloramphenicol) and beta-lactam (imipenem). Fourteen strains were resistant to more than 10 antibiotics. The reference culture was resistant to only three antibiotics. The results showed that bifidobacteria are resistant to a wide range of antimicrobial agents.
Sonochemical synthesis and characterization of Co3O4nanocrystals in the presence of the ionic liquid [EMIM][BF4]

Al-Qirby LM, Radiman S, Siong CW, Ali AM

Ultrason Sonochem, 2017 Sep;38:640-651.
PMID: 27553194 DOI: 10.1016/j.ultsonch.2016.08.016

For the first time, a sonochemical process has been used to synthesis cobalt oxide Co3O4nanoflowers and nanorods morphology in the presence of the ionic liquid 1-Ethyl-3-methylimidazolium tetrafluoroborate [EMIM][BF4] as reaction media and morphology template. Different sonication time periods and different molar ratios of the ionic liquid (IL) were used to investigate their effects on the structural, optical, chemical and magnetic properties of the produced Co3O4nanoparticles. During synthesis process brown powder contains cobalt hydroxide Co(OH)2and cobalt oxyhydroxide (Cobalt hydroxide oxide) CoO(OH) was formed, after calcination in air for 4h at 400°C a black powder of Co3O4nanoparticles was produced. The produced Co3O4nanoparticles properties were characterized by X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), transmission electron microscopy (TEM), FTIR spectroscopy, UV-vis spectroscopy, and Vibrating Sample Magnetometer (VSM). To explain the formation mechanism of Co3O4NPs some investigations were carried on the brown powder before calcination.
Estimating drug-free period using a graphical method: an alternative way to monitor extended-interval dosing of gentamicin therapy

Ab Rahman AF, Md Sahak N, Ali AM

Int J Pharm Pract, 2017 Feb;25(1):75-80.
PMID: 28097717 DOI: 10.1111/ijpp.12336

OBJECTIVES: Published nomograms to monitor extended-interval dosing (EID) gentamicin therapy were based on a fixed dose of 5 or 7 mg/kg. However, the average dose used for EID gentamicin regimen in our setting was about 3 mg/kg per day. We developed a new method of monitoring based on the duration of drug-free period (DFP) in a 24-h dosing interval.
METHODS: Hospitalised adult patients on EID gentamicin were selected. We considered a DFP of between 2 and 8 h as appropriate. Data from two blood samples (2 and 6 h postdose) from each patient were used to estimate the duration of DFP (i.e. DFP method 1). DFP was also calculated for the same patient using an empirically estimated elimination rate constant (Ke ) and the same 6 h postdose concentration value (DFP method 2). Correlation between the two methods was made. An alternative graphical method to estimate DFP was attempted.
KEY FINDINGS: Correlation between Ke and age was favourable (r = -0.453; P = 0.001). Ke derived from this empirical relationship was used to estimate DFP method 2. DFP method 1 correlated well with DFP method 2 (r = 0.742; P
Fulltext Combinatorial Cytotoxic Effects of Gelam Honey and 5-Fluorouracil against Human Adenocarcinoma Colon Cancer HT-29 Cells In Vitro

T-Johari SAT, Hashim F, Ismail WI, Ali AM

Int J Cell Biol, 2019;2019:3059687.
PMID: 30923553 DOI: 10.1155/2019/3059687

Combination of natural products with chemodrugs is becoming a trend in discovering new therapeutics approach for enhancing the cancer treatment process. In the present study, we aimed to investigate the cytotoxic and apoptosis induction of Gelam honey (GH) combined with or without 5-Fluorouracil (5-FU) on HT-29 cells. The cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to assess cytotoxicity. Morphological changes and apoptosis were determined by the inverted microscope, Annexin V-FITC, and DNA fragmentation via flow cytometric analysis, respectively. Our results demonstrate that combined treatment revealed a remarkable and concentration-dependent cytotoxic effect on HT-29 cells in comparison with GH and 5-FU alone. Flow cytometry analysis showed that early apoptosis event was more pronounced in combined treatment. In addition, compared to 5-FU alone, apoptosis of HT-29 cells treated with combinations of GH and 5-FU demonstrated increasing percentages of fragmented DNA. Our results suggest that GH has a synergistic cytotoxic effect with 5-FU in HT-29 cell lines in vitro. Although the actions of the molecular mechanisms are not yet clear, the results reveal that the combination of GH and 5-FU could have the potential as a therapeutic agent.
The use of complementary and alternative medicine (CAM) among cancer patients at a tertiary hospital in Malaysia

Hamed Abdalla MEA, Ali AM, Loong L

Complement Ther Med, 2020 May;50:102343.
PMID: 32444037 DOI: 10.1016/j.ctim.2020.102343

PURPOSE: Complementary and alternative medicine (CAM) use among cancer patients is increasing over the years. Some types of CAM may interact with conventional cancer therapy or may cause serious adverse effects. This study was designed to determine the prevalence of CAM use among cancer patients during cancer therapy and to identify CAM users' characteristics, perception, reasoning, expectation and disclosure of CAM use.
METHOD: This cross-sectional study was conducted between July 2017 to October 2017, on 121 cancer patients in oncology and hematology clinics and daycare of a tertiary hospital in Kuala Lumpur, Malaysia. Study data was collected using a self-administered questionnaire.
RESULTS: The prevalence of CAM use among cancer patients was found to be 61.2 %. Multivariate logistic regression analysis showed that CAM use was associated with change in outlook on life after development of cancer. The most frequently used types of CAM were vitamins and Islamic medical practices. Majority of patients were guided by family and friends' suggestions towards using CAM. Most patients expected CAM to cure their disease. The percentage of patients who disclosed CAM use to the doctors was slightly higher than those who did not disclose CAM use.
CONCLUSION: The use of CAM was found to be remarkably high. Rate of non-disclosure of CAM use was high indicating the need for enhancement of doctor- patient relationship for effective patient's care. Future research is needed with large sample of patients to provide better representation of the population and to help understand patients' beliefs and perception more.
Chemopreventive properties of phytosterols and maslinic acid extracted from Coleus tuberosus in inhibiting the expression of EBV early-antigen in Raji cells

Mooi LY, Wahab NA, Lajis NH, Ali AM

Chem Biodivers, 2010 May;7(5):1267-75.
PMID: 20491082 DOI: 10.1002/cbdv.200900193

Bioassay-guided fractionation of a MeOH extract of tubers of Coleus tuberosus afforded the active anti-tumor-promoting compounds identified as the triterpenoid 2alpha,3beta-dihydroxyolean-12-en-28-oic acid (maslinic acid; CT2) and a phytosterol mixture (CT1). CT1 consists of stigmasterol (32%), beta-sitosterol (40.3%), and campesterol (27.7%) as determined by capillary gas chromatography. CT1 and CT2 showed very strong anti-tumor-promoting activities at IC(50) 0.7 microg/ml and 0.1 microg/ml, respectively, in a convenient, short-term in vitro assay, i.e., the inhibition of Epstein-Barr virus (EBV) activation induced by phorbol 12-myristate 13-acetate (PMA) and sodium butyrate. We report for the first time the anti-tumor-promoting activity of 2alpha,3beta-dihydroxyolean-12-en-28-oic acid and show that a mixture of stigmasterol, beta-sitosterol, and campesterol is more potent than the individual components in inhibiting tumor-promoting activity.
Structural and functional characterisation of HepTH1-5 peptide as a potential hepcidin replacement

Azemin WA, Alias N, Ali AM, Shamsir MS

J Biomol Struct Dyn, 2023 Feb;41(2):681-704.
PMID: 34870559 DOI: 10.1080/07391102.2021.2011415

Hepcidin is a principal regulator of iron homeostasis and its dysregulation has been recognised as a causative factor in cancers and iron disorders. The strategy of manipulating the presence of hepcidin peptide has been used for cancer treatment. However, this has demonstrated poor efficiency and has been short-lived in patients. Many studies reported using minihepcidin therapy as an alternative way to treat hepcidin dysregulation, but this was only applied to non-cancer patients. Highly conserved fish hepcidin protein, HepTH1-5, was investigated to determine its potential use in developing a hepcidin replacement for human hepcidin (Hepc25) and as a therapeutic agent by targeting the tumour suppressor protein, p53, through structure-function analysis. The authors found that HepTH1-5 is stably bound to ferroportin, compared to Hepc25, by triggering the ferroportin internalisation via Lys42 and Lys270 ubiquitination, in a similar manner to the Hepc25 activity. Moreover, the residues Ile24 and Gly24, along with copper and zinc ligands, interacted with similar residues, Lys24 and Asp1 of Hepc25, respectively, showing that those molecules are crucial to the hepcidin replacement strategy. HepTH1-5 interacts with p53 and activates its function through phosphorylation. This finding shows that HepTH1-5 might be involved in the apoptosis signalling pathway upon a DNA damage response. This study will be very helpful for understanding the mechanism of the hepcidin replacement and providing insights into the HepTH1-5 peptide as a new target for hepcidin and cancer therapeutics.Communicated by Ramaswamy H. Sarma.
Fulltext The intervention strategies and service model for pharmacist-led diabetes management: a scoping review

Hassan F, Hatah E, Ali AM, Wen CW

BMC Health Serv Res, 2023 Jan 18;23(1):46.
PMID: 36653832 DOI: 10.1186/s12913-022-08977-1

BACKGROUND: There is increasing intervention activities provided during pharmacist-led diabetes management. Nevertheless, there is an unclear definition of the activities involved during the intervention. Thus, this study aimed to describe the type of intervention strategies and service model provided during pharmacist-led type 2 diabetes management and service outcomes.
METHODS: This study utilized the scoping review methodology of the Joanna Briggs Institute Reviewers' Manual 2015. Articles on pharmacist-led diabetes management focusing on the service content, delivery methods, settings, frequency of appointments, collaborative work with other healthcare providers, and reported outcomes were searched and identified from four electronic databases: Ovid Medline, PubMed, Scopus, and Web of Science from 1990 to October 2020. Relevant medical subject headings and keywords, such as "diabetes," "medication adherence," "blood glucose," "HbA1c," and "pharmacist," were used to identify published articles.
RESULTS: The systematic search retrieved 4,370 articles, of which 61 articles met the inclusion criteria. The types of intervention strategies and delivery methods were identified from the studies based on the description of activities reported in the articles and were tabulated in a summary table.
CONCLUSION: There were variations in the descriptions of intervention strategies, which could be classified into diabetes education, medication review, drug consultation/counseling, clinical intervention, lifestyle adjustment, self-care, peer support, and behavioral intervention. In addition, most studies used a combination of two or more intervention strategy categories when providing services, with no specific pattern between the service model and patient outcomes.
Enhanced QoS Routing Protocol for an Unmanned Ground Vehicle, Based on the ACO Approach

Ali AM, Ngadi MA, Sham R, Al Barazanchi II

Sensors (Basel), 2023 Jan 28;23(3).
PMID: 36772471 DOI: 10.3390/s23031431

Improving models for managing the networks of firefighting unmanned ground vehicles in crowded areas, as a recommendation system (RS), represented a difficult challenge. This challenge comes from the peculiarities of these types of networks. These networks are distinguished by the network coverage area size, frequent network connection failures, and quick network structure changes. The research aims to improve the communication network of self-driving firefighting unmanned ground vehicles by determining the best routing track to the desired fire area. The suggested new model intends to improve the RS regarding the optimum tracking route for firefighting unmanned ground vehicles by employing the ant colony optimization technique. This optimization method represents one of the swarm theories utilized in vehicles ad-hoc networks and social networks. According to the results, the proposed model can enhance the navigation of self-driving firefighting unmanned ground vehicles towards the fire region, allowing firefighting unmanned ground vehicles to take the shortest routes possible, while avoiding closed roads and traffic accidents. This study aids in the control and management of ad-hoc vehicle networks, vehicles of everything, and the internet of things.
In silico analysis prediction of HepTH1-5 as a potential therapeutic agent by targeting tumour suppressor protein networks

Azemin WA, Alias N, Ali AM, Shamsir MS

J Biomol Struct Dyn, 2023 Mar;41(4):1141-1167.
PMID: 34935583 DOI: 10.1080/07391102.2021.2017349

Many studies reported that the activation of tumour suppressor protein, p53 induced the human hepcidin expression. However, its expression decreased when p53 was silenced in human hepatoma cells. Contrary to Tilapia hepcidin TH1-5, HepTH1-5 was previously reported to trigger the p53 activation through the molecular docking approach. The INhibitor of Growth (ING) family members are also shown to directly interact with p53 and promote cell cycle arrest, senescence, apoptosis and participate in DNA replication and DNA damage responses to suppress the tumour initiation and progression. However, the interrelation between INGs and HepTH1-5 remains unknown. Therefore, this study aims to identify the mechanism and their protein interactions using in silico approaches. The finding revealed that HepTH1-5 and its ligands had interacted mostly on hotspot residues of ING proteins which involved in histone modifications via acetylation, phosphorylation, and methylation. This proves that HepTH1-5 might implicate in an apoptosis signalling pathway and preserve the protein structure and function of INGs by reducing the perturbation of histone binding upon oxidative stress response. This study would provide theoretical guidance for the design and experimental studies to decipher the role of HepTH1-5 as a potential therapeutic agent for cancer therapy. Communicated by Ramaswamy H. Sarma.

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