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Fulltext In vitro antibacterial properties of etlingera elatior flower extracts against acne-inducing bacteria: propionibacterium acnes and staphylococcus aureus.

Nurul Saidah D, Salwani I, Rabiatul Adawiyah U, Nurul ‘Adani, Mohd Hilmi AB, Mohd Khairi Z

IIUM Medical Journal Malaysia, 2019;18(3):128-135.
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Acne is a common skin disorder and is generally caused by Propionibacterium acnesand Staphylococcus aureus. Etlingera elatior flower extract is known to have antibacterial properties however, the properties against these bacteria have not been extensively reported. Thus, this study aimed to investigate the antibacterial properties of the flower extract against these bacteria. Materials and Methods: The flower extract was subjected to sequential extraction using three different solvent polarities; n-Hexane, dichloromethane (DCM) and ethanol. The antibacterial properties were evaluated using the disc diffusion and broth dilution assays techniques by determining the inhibition zone diameter, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Total phenolic acids (TPC) and flavonoids contents (TFC) were estimated using Folin-Ciocalteu and aluminium-chloride colorimetric assay respectively. Morphological changes of the treated bacteria were studied using scanning electron microscope (SEM). Results:DCM flower extract showed the highest antibacterial properties against P. acnes; at 25 mg/ml it had the widest inhibition zone (11.39 ± 0.45 mm) and the lowest MIC (6.25 mg/mL) and MBC (12.5 mg/mL). The ethanolic flower extract had the highest antibacterial properties against S. aureus; at 50 mg/ml the inhibition zone was 6.21 ± 0.25 mm and the MIC and MBC were both 12.5 mg/mL. Ethanolic extracts had the highest TPC (966.304 ± 114.08 mg GAE/g) and TFC (796.33 ± 65.78 mg QE/g). There was significant morphological changes of the treated bacteria observed under SEM. Conclusion:E. elatior flower extracts exhibited antibacterial properties against acne-inducing bacteria.
A Bilayer Engineered Skin Substitute for Wound Repair in an Irradiation-Impeded Healing Model on Rat

Mohd Hilmi AB, Hassan A, Halim AS

Adv Wound Care (New Rochelle), 2015 May 1;4(5):312-320.
PMID: 26005597

Objective: An engineered skin substitute is produced to accelerate wound healing by increasing the mechanical strength of the skin wound via high production of collagen bundles. During the remodeling stage of wound healing, collagen deposition is the most important event. The collagen deposition process may be altered by nutritional deficiency, diabetes mellitus, microbial infection, or radiation exposure, leading to impaired healing. This study describes the fabrication of an engineered bilayer skin substitute and evaluates its effectiveness for the production of collagen bundles in an impaired healing model. Approach: Rats were exposed to 10 Gy of radiation. Two months postirradiation, the wounds were excised and treated with one of three skin replacement products: bilayer engineered skin substitutes, chitosan skin templates, or duoderm(©). The collagen deposition was analyzed by hematoxylin and eosin staining. Results: On day 21 postwound, the irradiated wounds displayed increased collagen bundle deposition after treatment using bilayer engineered skin substitutes (3.4±0.25) and chitosan skin templates (3.2±0.58) compared with duoderm (2.0±0.63). Innovation: We provide the first report on the fabrication of bilayer engineered skin substitutes using high density human dermal fibroblasts cocultured with HFSCs on chitosan skin templates. Conclusion: The high density of fibroblasts significantly increases the penetration of cells into chitosan skin templates, contributing to the fabrication of bilayer engineered skin substitute.
Fulltext Vital roles of stem cells and biomaterials in skin tissue engineering

Mohd Hilmi AB, Halim AS

World J Stem Cells, 2015 Mar 26;7(2):428-36.
PMID: 25815126 DOI: 10.4252/wjsc.v7.i2.428

Tissue engineering essentially refers to technology for growing new human tissue and is distinct from regenerative medicine. Currently, pieces of skin are already being fabricated for clinical use and many other tissue types may be fabricated in the future. Tissue engineering was first defined in 1987 by the United States National Science Foundation which critically discussed the future targets of bioengineering research and its consequences. The principles of tissue engineering are to initiate cell cultures in vitro, grow them on scaffolds in situ and transplant the composite into a recipient in vivo. From the beginning, scaffolds have been necessary in tissue engineering applications. Regardless, the latest technology has redirected established approaches by omitting scaffolds. Currently, scientists from diverse research institutes are engineering skin without scaffolds. Due to their advantageous properties, stem cells have robustly transformed the tissue engineering field as part of an engineered bilayered skin substitute that will later be discussed in detail. Additionally, utilizing biomaterials or skin replacement products in skin tissue engineering as strategy to successfully direct cell proliferation and differentiation as well as to optimize the safety of handling during grafting is beneficial. This approach has also led to the cells' application in developing the novel skin substitute that will be briefly explained in this review.
Fulltext Effect of Non-hydrogen Peroxide on Antibacterial Activity of Malaysian Meliponini Honey against Staphylococcus aureus

Jibril FI, Mohd Hilmi AB, Aliyu S

J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S831-S835.
PMID: 33828385 DOI: 10.4103/jpbs.JPBS_280_19

Introduction: Stingless bee is an insect that belongs to the family Apidae. Its name is based on its disability of stinging. It has a high product of Meliponini honey and propolis by which are commonly referred to as stingless bee honey and stingless bee propolis. Meliponini honey is one of the crucial natural sources and has the potential to kill infectious microorganisms. Previous studies have proved that the antibacterial activity of natural honey was an effect of hydrogen peroxide, a substance contained in the honey. However, these claims were contradicting with too many studies.
Objective: Therefore, this study aimed to identify the antibacterial activity of Malaysian Meliponini honey which contained non-hydrogen peroxide against Staphylococcus aureus, an opportunistic microbial.
Materials and Methods: Meliponini honey was used as an antibacterial agent for the treatment of S. aureus in agar well diffusion assay. An amplex red hydrogen peroxide kit was used to identify the hydrogen peroxide in the honey sample. Meanwhile, non-hydrogen peroxide activity was performed by using honey-catalase treated.
Results: For the first time, we found that hydrogen peroxide was absent in all Meliponini honey samples. Meliponini honey has higher antibacterial activity (13.30 ± 0.56mm) compared to Apis honey (9.03 ± 0.22mm) in agar well diffusion assay.
Discussion: Non-hydrogen peroxide in Meliponini honey is a bioactive compound and beneficial to kill the microbial infection.
Conclusion: Antibacterial activity of Malaysian Meliponini honey is directly contributed by non-hydrogen peroxide.
Fulltext Chitosan dermal substitute and chitosan skin substitute contribute to accelerated full-thickness wound healing in irradiated rats

Mohd Hilmi AB, Halim AS, Jaafar H, Asiah AB, Hassan A

Biomed Res Int, 2013;2013:795458.
PMID: 24324974 DOI: 10.1155/2013/795458

Wounds with full-thickness skin loss are commonly managed by skin grafting. In the absence of a graft, reepithelialization is imperfect and leads to increased scar formation. Biomaterials can alter wound healing so that it produces more regenerative tissue and fewer scars. This current study use the new chitosan based biomaterial in full-thickness wound with impaired healing on rat model. Wounds were evaluated after being treated with a chitosan dermal substitute, a chitosan skin substitute, or duoderm CGF. Wounds treated with the chitosan skin substitute showed the most re-epithelialization (33.2 ± 2.8%), longest epithelial tongue (1.62 ± 0.13 mm), and shortest migratory tongue distance (7.11 ± 0.25 mm). The scar size of wounds treated with the chitosan dermal substitute (0.13 ± 0.02 cm) and chitosan skin substitute (0.16 ± 0.05 cm) were significantly decreased (P < 0.05) compared with duoderm (0.45 ± 0.11 cm). Human leukocyte antigen (HLA) expression on days 7, 14, and 21 revealed the presence of human hair follicle stem cells and fibroblasts that were incorporated into and surviving in the irradiated wound. We have proven that a chitosan dermal substitute and chitosan skin substitute are suitable for wound healing in full-thickness wounds that are impaired due to radiation.
Fulltext Pseudomonas Aeruginosa and Streptococcus Pyogenes Exposed to Malaysian Trigona Honey In Vitro Demonstrated Downregulation of Virulence Factor

A Al-Kafaween M, Mohd Hilmi AB, A Nagi Al-Jamal H, A Elsahoryi N, Jaffar N, Khairi Zahri M

Iran J Biotechnol, 2020 Oct;18(4):e2542.
PMID: 34056021 DOI: 10.30498/IJB.2020.2542

Background: Honey has been known as a traditional medicine for centuries with its antibacterial properties. It is considered one of the most enduring substances used in wound management.
Objectives: This study aimed to: (i) evaluate the effects of Malaysian Trigona honey on bacterial structure and (ii) assess the anti-virulence potential of this honey by examining their impacts on the expression of selected genes (involved in stress survival and biofilm formation) in a test organism.
Materials and Methods: Trigona honey's impacts on the bacterial structure (cell morphology) and the expression profiles of select Pseudomonas Aeruginosa and Streptococcus Pyogenes genes were examined using scanning electron microscopy (SEM) and real-time PCR (RT-qPCR) analysis, respectively.
Results: SEM showed that the decreased cell density deformed, disrupted, and damaged cells for both bacteria. RT-qPCR showed that the expression of fleN, fleQ, and fleR genes of P.aeruginosa were decreased, 4.26-fold, 3.80-fold and 2.66- fold respectively. In addition, scpA, ftsY, and emm13 of S.pyogenes were decreased, 2.87-fold, 3.24-fold, and 4.65-fold respectively.
Conclusion: Our results indicate that Trigona honey may be an effective inhibitor and virulence modulator of P. aeruginosa and S. pyogenes via multiple molecular targets. This deduction needs to be investigated in vivo.
Memory Enhancing and Neurogenesis Activity of Honey Bee Venom in the Symptoms of Amnesia: Using Rats with Amnesia-like Alzheimer's Disease as a Model

Khleifat KM, Al-Tawarah NM, Al-Kafaween MA, Al-Ksasbeh W, Qaralleh H, Alqaraleh M, et al.

Curr Alzheimer Res, 2023;20(3):190-201.
PMID: 37317907 DOI: 10.2174/1567205020666230614143027

BACKGROUND/OBJECTIVE: Alzheimer's disease (AD) is mainly characterized by amnesia that affects millions of people worldwide. This study aims to explore the effectiveness capacities of bee venom (BV) for the enhancement of the memory process in a rat model with amnesia-like AD.
METHODS: The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively.
RESULTS: During the nootropic phase, treatment groups demonstrated a significant (P < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant (P < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant (P < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group (P < 0.05) in a dose-dependent manner.
CONCLUSION: This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed.