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Facile engineering of aptamer-coupled silk fibroin encapsulated myogenic gold nanocomposites: investigation of antiproliferative activity and apoptosis induction

Elayappan PK, Kandasamy K, Sasikumar V, Bharathi M, Hirad AH, Alarfaj AA, et al.

Biotechnol Lett, 2024 Apr 27.
PMID: 38676857 DOI: 10.1007/s10529-024-03491-2

Nanocomposites selectively induce cancer cell death, holding potential for precise liver cancer treatment breakthroughs. This study assessed the cytotoxicity of gold nanocomposites (Au NCs) enclosed within silk fibroin (SF), aptamer (Ap), and the myogenic Talaromyces purpureogenus (TP) against a human liver cancer cell (HepG2). The ultimate product, Ap-SF-TP@Au NCs, results from a three-step process. This process involves the myogenic synthesis of TP@Au NCs derived from TP mycelial extract, encapsulation of SF on TP@Au NCs (SF-TP@Au NCs), and the conjugation of Ap within SF-TP@Au NCs. The synthesized NCs are analyzed by various characteristic techniques. Ap-SF-TP@Au NCs induced potential cell death in HepG2 cells but exhibited no cytotoxicity in non-cancerous cells (NIH3T3). The morphological changes in cells were examined through various biochemical staining methods. Thus, Ap-SF-TP@Au NCs emerge as a promising nanocomposite for treating diverse cancer cells.
Facile construction of gefitinib-loaded zeolitic imidazolate framework nanocomposites for the treatment of different lung cancer cells

Aiyasamy K, Ramasamy M, Hirad AH, Arulselvan P, Jaganathan R, Suriyaprakash J, et al.

Biotechnol Appl Biochem, 2024 Apr 09.
PMID: 38594878 DOI: 10.1002/bab.2585

Gefitinib (GET) is a revolutionary targeted treatment inhibiting the epidermal growth factor receptor's tyrosine kinase action by competitively inhibiting the ATP binding site. In preclinical trials, several lung cancer cell lines and xenografts have demonstrated potential activity with GET. Response rates neared 25% in preclinical trials for non-small cell lung cancer. Here, we describe the one-pot synthesis of GET@ZIF-8 nanocomposites (NCs) in pure water, encapsulating zeolitic imidazolate framework 8 (ZIF-8). This method developed NCs with consistent morphology and a loading efficiency of 9%, resulting in a loading capacity of 20 wt%. Cell proliferation assay assessed the anticancer effect of GET@ZIF-8 NCs on A549 and H1299 cells. The different biochemical staining (Calcein-AM and PI and 4',6-Diamidino-2-phenylindole nuclear staining) assays assessed the cell death and morphological examination. Additionally, the mode of apoptosis was evaluated by mitochondrial membrane potential (∆ψm) and reactive oxygen species. Therefore, the study concludes that GET@ZIF-8 NCs are pledged to treat lung cancer cells.
Fulltext Therapeutic strategy of biological macromolecules based natural bioactive compounds of diabetes mellitus and future perspectives: A systematic review

Shahzad N, Alzahrani AR, Aziz Ibrahim IA, Shahid I, Alanazi IM, Falemban AH, et al.

Heliyon, 2024 Jan 30;10(2):e24207.
PMID: 38298622 DOI: 10.1016/j.heliyon.2024.e24207

High blood glucose levels are a hallmark of the metabolic syndrome known as diabetes mellitus. More than 600 million people will have diabetes by 2045 as the global prevalence of the disease continues to rise. Contemporary antidiabetic drugs reduce hyperglycemia and its consequences. However, these drugs come with undesirable side effects, so it's encouraging that research into plant extracts and bioactive substances with antidiabetic characteristics is on the rise. Natural remedies are preferable to conventional anti-diabetic drugs since they are safer for the body, more affordable and have fewer potential adverse effects. Biological macromolecules such as liposomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles, nanoemulsions and metallic nanoparticles are explored in this review. Current drug restrictions have been addressed, and the effectiveness of plant-based antidiabetic therapies has enhanced the merits of these methods. Plant extracts' loading capacity and the carriers' stability are the primary obstacles in developing plant-based nanocarriers. Hydrophilic, hydrophobic, and amphiphilic drugs are covered, and a brief overview of the amphipathic features of liposomes, phospholipids, and lipid nanocarriers is provided. Metallic nanoparticles' benefits and attendant risks are highlighted to emphasize their efficiency in treating hyperglycemia. Researchers interested in the potential of nanoparticles loaded with plant extracts as antidiabetic therapeutics may find the current helpful review.
Fulltext Synthesis and Characterization of Graphene Oxide/Polyethylene Glycol/Folic Acid/Brucine Nanocomposites and Their Anticancer Activity on HepG2 Cells

Ibrahim IAA, Alzahrani AR, Alanazi IM, Shahzad N, Shahid I, Falemban AH, et al.

Int J Nanomedicine, 2024;19:1109-1124.
PMID: 38344441 DOI: 10.2147/IJN.S445206

BACKGROUND: Liver cancer is the sixth most prevalent form of cancer and the second major cause of cancer-associated mortalities worldwide. Cancer nanotechnology has the ability to fundamentally alter cancer treatment, diagnosis, and detection.
OBJECTIVE: In this study, we explained the development of graphene oxide/polyethylene glycol/folic acid/brucine nanocomposites (GO/PEG/Bru-FA NCs) and evaluated their antimicrobial and anticancer effect on the liver cancer HepG2 cells.
METHODOLOGY: The GO/PEG/Bru-FA NCs were prepared using the co-precipitation technique and characterized using various techniques. The cytotoxicity of the GO/PEG/Bru-FA NCs was tested against both liver cancer HepG2 and non-malignant Vero cells using an MTT assay. The antimicrobial activity of the GO/PEG/Bru-FA NCs was tested against several pathogens using the well diffusion technique. The effects of GO/PEG/Bru-FA NCs on endogenous ROS accumulation, apoptosis, and MMP levels were examined using corresponding fluorescent staining assays, respectively. The apoptotic protein expressions, such as Bax, Bcl-2, and caspases, were studied using the corresponding kits.
RESULTS: The findings of various characterization assays revealed the development of GO/PEG/Bru-FA NCs with face-centered spherical morphology and an agglomerated appearance with an average size of 197.40 nm. The GO/PEG/Bru-FA NCs treatment remarkably inhibited the growth of the tested pathogens. The findings of the MTT assay evidenced that the GO/PEG/Bru-FA NCs effectively reduced the HepG2 cell growth while not showing toxicity to the Vero cells. The findings of the fluorescent assay proved that the GO/PEG/Bru-FA NCs increased ROS generation, reduced MMP levels, and promoted apoptosis in the HepG2 cells. The levels of Bax, caspase-9, and -3 were increased, and Bcl-2 was reduced in the GO/PEG/Bru-FA NCs-treated HepG2 cells.
CONCLUSION: The results of this work demonstrate that GO/PEG/Bru-FA NCs suppress viability and induce apoptosis in HepG2 cells, indicating their potential as an anticancer candidate.
Carbohydrate polymers-based surface modified nano delivery systems for enhanced target delivery to colon cancer - A review

Ibrahim IAA, Alzahrani AR, Alanazi IM, Shahzad N, Shahid I, Falemban AH, et al.

Int J Biol Macromol, 2023 Dec 31;253(Pt 2):126581.
PMID: 37652322 DOI: 10.1016/j.ijbiomac.2023.126581

Carbohydrate polymers-based surface-modified nano-delivery systems have gained significant attention in recent years for enhancing targeted delivery to colon cancer. These systems leverage carbohydrate polymers' unique properties, such as biocompatibility, biodegradability, and controlled release. These properties make them suitable candidates for drug delivery applications. Nano-delivery systems loaded with bioactive compounds are well-studied for targeted colorectal cancer delivery. However, those drugs' target reach is still limited in various nano-delivery systems. To overcome this limitation, surface modification of nanoparticles with carbohydrate polymers like chitosan, pectin, alginate, and guar gum showed enhanced target-reaching capacity along with enhanced anticancer efficacy. Recently, a chitosan-decorated PLGA nanoparticle was constructed with tannic acid and vitamin E and showed long-term release of specific targets along with higher anticancer efficacy. Similarly, Chitosan-conjugated glucuronic acid-coated silica nanoparticles loaded with capecitabine were studied against colon cancer and found to be the pH-responsive controlled release of capecitabine with higher anticancer efficacy. Surface-modified carbohydrate polymers have promising potential for improving colon cancer target delivery. By leveraging the unique properties of these polymers, such as surface modification, pH responsiveness, mucoadhesion, controlled drug release, and combination therapy, researchers are working toward developing more effective and targeted treatment strategies for colon cancer.
Chitosan biopolymer functionalized with graphene oxide and titanium dioxide with Escin metallic nanocomposites for anticancer potential against colon cancer

Ibrahim IAA, Alzahrani AR, Alanazi IM, Shahzad N, Shahid I, Falemban AH, et al.

Int J Biol Macromol, 2023 Dec 31;253(Pt 7):127334.
PMID: 37820908 DOI: 10.1016/j.ijbiomac.2023.127334

Our study produced GO-TiO2-chitosan-escin nanocomposites (GTCEnc), characterized them using physical and biological methods, and evaluated their potential as cancer treatment candidates. Standard protocols were used to produce GTCEnc. Nanocomposites are created using XRD, FTIR, UV-Vis, and PL spectroscopy analysis. The morphology and ultrastructure of nanocomposites were investigated using SEM and TEM. Nanocomposites containing TiO2, GO, chitosan, and escin nanostructures were characterized using diffraction, microscopy, and spectroscopy; the antimicrobial activity of GTCEnc was investigated. Various methods were used to test the anticancer activity of GTCEnc against COLO 205 cell lines, including MTT, EtBr/AO, DAPI, JC-1, Annexin-V/FITC, cell cycle analysis, and activation of pro-apoptotic markers, such as caspase-3, -8, and -9. The nanocomposites were cytotoxic to COLO 205 cells, with an IC50 of 22.68 μg/mL, but not to 293T cells. In cells treated with nanomaterials, cytotoxicity, nuclear damage, apoptosis induction, and free radical production were significantly increased. Our finding suggests that GTCEnc has potent anticancer and antibacterial activity in vitro because of its unique nanocomposite properties and antibacterial and anticancer activity in vitro. Additional research is required to understand the clinical efficacy of these nanocomposites.
Fulltext Chlorambucil-Iron Oxide Nanoparticles as a Drug Delivery System for Leukemia Cancer Cells

Hussein-Al-Ali SH, Hussein MZ, Bullo S, Arulselvan P

Int J Nanomedicine, 2021;16:6205-6216.
PMID: 34526768 DOI: 10.2147/IJN.S312752

Introduction: Traditional cancer therapies may have incomplete eradication of cancer or destroy the normal cells. Nanotechnology solves the demerit by a guide in surgical resection of tumors, targeted chemotherapies, selective to cancerous cells, etc. This new technology can reduce the risk to the patient and automatically increased the probability of survival. Toward this goal, novel iron oxide nanoparticles (IONPs) coupled with leukemia anti-cancer drug were prepared and assessed.
Methods: The IONPs were prepared by the co-precipitation method using Fe+3/Fe+2ratio of 2:1. These IONPs were used as a carrier for chlorambucil (Chloramb), where the IONPs serve as the cores and chitosan (CS) as a polymeric shell to form Chloramb-CS-IONPs. The products were characterized using transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) analysis, Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM) analyses, and thermal gravimetric analysis (TGA).
Results: The as-prepared IONPs were found to be magnetite (Fe3O4) and were coated by the CS polymer/Chloramb drug for the formation of the Chloramb-CS-IONPs. The average size for CS-IONPs and Chloramb-CS-IONPs nanocomposite was found to be 15 nm, with a drug loading of 19% for the letter. The release of the drug from the nanocomposite was found to be of a controlled-release manner with around 89.9% of the drug was released within about 5000 min and governed by the pseudo-second order. The in vitro cytotoxicity studies of CS-IONPs and Chloramb-CS-IONPs nanocomposite were tested on the normal fibroblast cell lines (3T3) and leukemia cancer cell lines (WEHI). Chloramb in Chloramb-CS-IONPs nanocomposite was found to be more efficient compared to its free form.
Conclusion: This work shows that Chloramb-CS-IONPs nanocomposite is a promising candidate for magnetically targeted drug delivery for leukemia anti-cancer agents.
Fulltext A Novel Para-Amino Salicylic Acid Magnesium Layered Hydroxide Nanocomposite Anti-Tuberculosis Drug Delivery System with Enhanced in vitro Therapeutic and Anti-Inflammatory Properties

Saifullah B, Arulselvan P, El Zowalaty ME, Tan WS, Fakurazi S, Webster TJ, et al.

Int J Nanomedicine, 2021;16:7035-7050.
PMID: 34703226 DOI: 10.2147/IJN.S297040

Introduction: Mycobacterium tuberculosis infections are associated with severe local inflammatory reactions, which may be life-threatening and lead to tuberculosis pathogenesis and associated complications. Inorganic nanolayers have been vastly exploited for biomedical applications (especially in drug delivery) because of their biocompatible and biodegradable nature with the ability to release a drug in a sustained manner. Herein, we report a new nanodelivery system of inorganic nanolayers based on magnesium layered hydroxides (MgLH) and a successfully intercalated anti-tuberculosis drug para-aminosalicylic acid (PAS).
Methods: The designed anti-tuberculosis nanodelivery composite, MgLH-PAS, was prepared by a novel co-precipitation method using MgNO3 as well MgO as starting materials.
Results: The designed nano-formulation, PAS-MgLH, showed good antimycobacterial and antimicrobial activities with significant synergistic anti-inflammatory effects on the suppression of lipopolysaccharide (LPS) stimulated inflammatory mediators in RAW 264.7 macrophages. The designed nano-formulation was also found to be biocompatible with human normal lung cells (MRC-5) and 3T3 fibroblast cells. Furthermore, the in vitro release of PAS from PAS-MgLH was found to be sustained in human body simulated phosphate buffer saline (PBS) solutions of pH 7.4 and pH 4.8.
Discussion: The results of the present study are highly encouraging for further in vivo studies. This new nanodelivery system, MgLH, can be exploited in the delivery of other drugs and in numerous other biomedical applications as well.
Fulltext Healing Effect of Vicenin-2 (VCN-2) on Human Dermal Fibroblast (HDF) and Development VCN-2 Hydrocolloid Film Based on Alginate as Potential Wound Dressing

Tan WS, Arulselvan P, Ng SF, Taib CNM, Sarian MN, Fakurazi S

Biomed Res Int, 2020;2020:4730858.
PMID: 32382552 DOI: 10.1155/2020/4730858

Chronic wounds represent serious globally health care and economic issues especially for patients with hyperglycemic condition. Wound dressings have a predominant function in wound treatment; however, the dressings for the long-lasting and non-healing wounds are still a significant challenge in the wound care management market. Astonishingly, advanced wound dressing which is embedded with a synthetic drug compound in a natural polymer compound that acts as drug release carrier has brought about promising treatment effect toward injured wound. In the current study, results have shown that Vicenin-2 (VCN-2) compound in low concentration significantly enhanced cell proliferation and migration of HDF. It also regulated the production of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α from HDF in wound repair. Treatment of VCN-2 also has facilitated the expression of TGF-1β and VEGF wound healing maker in a dose-dependent manner. A hydrocolloid film based on sodium alginate (SA) incorporated with VCN-2 synthetic compound which targets to promote wound healing particularly in diabetic condition was successfully developed and optimized for its physico-chemical properties. It was discovered that all the fabricated film formulations prepared were smooth, translucent, and good with flexibility. The thickness and weight of the formulations were also found to be uniform. The hydrophilic polymer comprised of VCN-2 were shown to possess desirable wound dressing properties and superior mechanical characteristics. The drug release profiles have revealed hydrocolloid film, which is able to control and sustain the VCN-2 released to wound area. In short, hydrocolloid films consisting of VCN-2 formulations are suitably used as a potential wound dressing to promote restoration of wound injury.
Fulltext Corrigendum to "In Vitro Wound Healing Potential of Stem Extract of Alternanthera sessilis"

Muniandy K, Gothai S, Tan WS, Kumar SS, Esa NM, Chandramohan G, et al.

Evid Based Complement Alternat Med, 2020;2020:2705479.
PMID: 32617103 DOI: 10.1155/2020/2705479

[This corrects the article DOI: 10.1155/2018/3142073.].
Mini Review: Wound healing potential of edible plants

Muniandy K, Gothai S, Arulselvan P, Kumar SS, Norhaizan ME, Umamaheswari A, et al.

Pak J Pharm Sci, 2019 Mar;32(2):703-707.
PMID: 31081786

Wound healing is a natural intricate cascade process involving cellular, biochemical and molecular mechanism to restore the injured or wounded tissue. Malaysia's multi-ethnic social fabric is reflected in its different traditional folk cuisines with different nutritional important ingredients. Despite these differences, there are some commonly used pantry ingredients among Malaysians and these ingredients may possess some healing power for acute and chronic wounds. These essential nutritional ingredients are included Amla (Ribes uva-crispa), Cinnamon (Cinnamomun venum), Curry Leaves (Murraya koenigii), Coriander (Coriandrum sativum), Fenugreek (Trigonella foenum-graecum), Garlic (Allium indica), Onion (Allium cepa) and Tamarind (Tamarindus indica). This article provides a review of the remedies with confirmed wound healing activities from previous experiments conducted by various researchers. Most of the researchers have focused only on the preliminary studies through appropriate model; hence detailed investigations which including pharmacological and pre-clinical studies are needed to discover its molecular mechanisms. In this review article, we have discussed about the wound healing potential of few commonly used edible plants and their known mechanism.
Fulltext Improvement of diabetic wound healing by topical application of Vicenin-2 hydrocolloid film on Sprague Dawley rats

Tan WS, Arulselvan P, Ng SF, Mat Taib CN, Sarian MN, Fakurazi S

BMC Complement Altern Med, 2019 Jan 17;19(1):20.
PMID: 30654793 DOI: 10.1186/s12906-018-2427-y

BACKGROUND: Impaired wound healing is a debilitating complication of diabetes that leads to significant morbidity, particularly foot ulcers. The risk of developing diabetic foot ulcers for diabetic patients is 15% over their lifetime and approximately 85% of limb amputations is caused by non-healing ulcers. Unhealed, gangrenous wounds destroy the structural integrity of the skin, which acts as a protective barrier that prevents the invasion of external noxious agents into the body. Vicenin-2 (VCN-2) has been reported to contain prospective anti-oxidant and anti-inflammatory properties that enhance cell proliferation and migration. Sodium Alginate (SA) is a natural polysaccharide that possesses gel forming properties and has biodegradable and biocompatible characteristics. Therefore, the objective of this study is to evaluate the effect of SA wound dressings containing VCN-2 on diabetic wounds.
METHODS: Wounds were inflicted in type-1 diabetic-streptozotocin (STZ) induced male Sprague Dawley rats. Subsequently, relevant groups were topically treated with the indicated concentrations (12.5, 25 and 50 μM) of VCN-2 hydrocolloid film over the study duration (14 days). The control group was treated with vehicle dressing (blank or allantoin). Wounded tissues and blood serum were collected on 0, 7 and 14 days prior to sacrifice. Appropriate wound assessments such as histological tests, nitric oxide assays, enzyme-linked immunosorbent assays (ELISA) and immunoblotting assays were conducted to confirm wound healing efficacy in the in vivo model. One-way Analysis of Variance (ANOVA) was used for statistical analysis.
RESULTS: Results showed that hydrocolloid film was recapitulated with VCN-2 enhanced diabetic wound healing in a dose-dependent manner. VCN-2 reduced pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), mediators (iNOS and COX-2), and nitric oxide (NO) via the NF-κB pathway. Data suggests that the VCN-2 film facilitated healing in hyperglycemic conditions by releasing growth factors such as (VEGF and TGF-β) to enhance cell proliferation, migration, and wound contraction via the VEGF and TGF-β mechanism pathways.
CONCLUSIONS: This study's findings suggest that VCN-2 may possess wound healing potential since topical treatment with VCN-2 hydrocolloid films effectively enhanced wound healing in hyperglycemic conditions.
Fulltext Modulatory and regenerative potential of transplanted bone marrow-derived mesenchymal stem cells on rifampicin-induced kidney toxicity

Danjuma L, Mok PL, Higuchi A, Hamat RA, Teh SW, Koh AE, et al.

Regen Ther, 2018 Dec;9:100-110.
PMID: 30525080 DOI: 10.1016/j.reth.2018.09.001

INTRODUCTION: Anti-tuberculosis agent rifampicin is extensively used for its effectiveness. Possible complications of tuberculosis and prolonged rifampicin treatment include kidney damage; these conditions can lead to reduced efficiency of the affected kidney and consequently to other diseases. Bone marrow-derived mesenchymal stem cells (BMMSCs) can be used in conjunction with rifampicin to avert kidney damage; because of its regenerative and differentiating potentials into kidney cells. This research was designed to assess the modulatory and regenerative potentials of MSCs in averting kidney damage due to rifampicin-induced kidney toxicity in Wistar rats and their progenies. BMMSCs used in this research were characterized according to the guidelines of International Society for Cellular Therapy.
METHODS: The rats (male and female) were divided into three experimental groups, as follows: Group 1: control rats (4 males & 4 females); Group 2: rats treated with rifampicin only (4 males & 4 females); and Group 3: rats treated with rifampicin plus MSCs (4 males & 4 females). Therapeutic doses of rifampicin (9 mg/kg/day for 3-months) and MSCs infusions (twice/month for 3-months) were administered orally and intravenously respectively. At the end of the three months, the animals were bred together to determine if the effects would carry over to the next generation. Following breeding, the rats were sacrificed to harvest serum for biochemical analysis and the kidneys were also harvested for histological analysis and quantification of the glomeruli size, for the adult rats and their progenies.
RESULTS: The results showed some level of alterations in the biochemical indicators and histopathological damage in the rats that received rifampicin treatment alone, while the control and stem cells treated group showed apparently normal to nearly normal levels of both bio-indicators and normal histological architecture.
CONCLUSIONS: Intravenous administration of MSCs yielded sensible development, as seen from biochemical indicators, histology and the quantitative cell analysis, hence implying the modulatory and regenerative properties of MSCs.
Pharmacological insights into antioxidants against colorectal cancer: A detailed review of the possible mechanisms

Gothai S, Muniandy K, Gnanaraj C, Ibrahim IAA, Shahzad N, Al-Ghamdi SS, et al.

Biomed Pharmacother, 2018 Nov;107:1514-1522.
PMID: 30257369 DOI: 10.1016/j.biopha.2018.08.112

Colorectal cancer (CRC) is ranked as the fourth most lethal and commonly diagnosed cancer in the world according to the National Cancer Institute's latest report. Treatment methods for CRC are constantly being studied for advancement, which leads for more clinically effective cancer curing strategy. Patients with prolonged chronic inflammation caused by ulcerative colitis or similar inflammatory bowel disease are known to have high risks of developing CRC. But at a molecular level, oxidative stress due to reactive oxygen species (ROS) is an important trigger for cancer. Hence, in recent years, exogenous antioxidants have been immensely experimented in pre-clinical and clinical trials, considering it as a potential cure for CRC. Significantly, potential antioxidant compounds especially derivatives of medicinal plants have received great attention in the current research trend for CRC treatment. Though antioxidant compounds seem to have beneficial properties for the treatment of CRC, there are also limitations for pure compounds to be tested clinically. Therefore, this review aims to delineate the pharmacological awareness among researchers on using antioxidant compounds to treat CRC and the measures taken to prove the effectiveness of such compounds as impending drug candidates for CRC treatment in modern medication.
Fulltext Molecular study of wound healing after using biosynthesized BNC/Fe3O4 nanocomposites assisted with a bioinformatics approach

Moniri M, Boroumand Moghaddam A, Azizi S, Abdul Rahim R, Zuhainis Saad W, Navaderi M, et al.

Int J Nanomedicine, 2018;13:2955-2971.
PMID: 29861630 DOI: 10.2147/IJN.S159637

Background: Molecular investigation of wound healing has allowed better understanding about interaction of genes and pathways involved in healing progression.
Objectives: The aim of this study was to prepare magnetic/bacterial nanocellulose (Fe3O4/BNC) nanocomposite films as ecofriendly wound dressing in order to evaluate their physical, cytotoxicity and antimicrobial properties. The molecular study was carried out to evaluate expression of genes involved in healing of wounds after treatment with BNC/Fe3O4 films.
Study design materials and methods: Magnetic nanoparticles were biosynthesized by using Aloe vera extract in new isolated bacterial nanocellulose (BNC) RM1. The nanocomposites were characterized using X-ray diffraction, Fourier transform infrared, and field emission scanning electron microscopy. Moreover, swelling property and metal ions release profile of the nanocomposites were investigated. The ability of nanocomposites to promote wound healing of human dermal fibroblast cells in vitro was examined. Bioinformatics databases were used to identify genes with important healing effect. Key genes which interfered with healing were studied by quantitative real time PCR.
Results: Spherical magnetic nanoparticles (15-30 nm) were formed and immobilized within the structure of BNC. The BNC/Fe3O4 was nontoxic (IC50>500 μg/mL) with excellent wound healing efficiency after 48 hours. The nanocomposites showed good antibacterial activity ranging from 6±0.2 to 13.40±0.10 mm against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa. The effective genes for the wound healing process were TGF-B1, MMP2, MMP9, Wnt4, CTNNB1, hsa-miR-29b, and hsa-miR-29c with time dependent manner. BNC/Fe3O4 has an effect on microRNA by reducing its expression and therefore causing an increase in the gene expression of other genes, which consequently resulted in wound healing.
Conclusion: This eco-friendly nanocomposite with excellent healing properties can be used as an effective wound dressing for treatment of cutaneous wounds.
Fulltext Nanolayered composite with enhanced ultraviolet ray absorption properties from simultaneous intercalation of sunscreen molecules

Megat Nabil Mohsin S, Hussein MZ, Sarijo SH, Fakurazi S, Arulselvan P, Taufiq-Yap YH

Int J Nanomedicine, 2018;13:6359-6374.
PMID: 30349255 DOI: 10.2147/IJN.S171390

Introduction: The potential of layered double hydroxide (LDH) as a host of multiple ultraviolet-ray absorbers was investigated by simultaneous intercalation of benzophenone 4 (B4) and Eusolex® 232 (EUS) in Zn/Al LDH.
Methods: The nanocomposites were prepared via coprecipitation method at various molar ratios of B4 and EUS.
Results: At equal molar ratios, the obtained nanocomposite showed an intercalation selectivity that is preferential to EUS. However, the selectivity ratio of intercalated anions was shown to be capable of being altered by adjusting the molar ratio of intended guests during synthesis. Dual-guest nanocomposite synthesized with B4:EUS molar ratio 3:1 (ZEB [3:1]) showed an intercalation selectivity ratio of B4:EUS =53:47. Properties of ZEB (3:1) were monitored using powder X-ray diffractometer to show a basal spacing of 21.8 Å. Direct-injection mass spectra, Fourier transform infrared spectra, and ultraviolet-visible spectra confirmed the dual intercalation of both anions into the interlayer regions of dual-guest nanocomposite. The cytotoxicity study of dual-guest nanocomposite ZEB (3:1) on human dermal fibroblast cells showed no significant toxicity until 25 μg/mL.
Conclusion: Overall, the findings demonstrate successful customization of ultraviolet-ray absorbers composition in LDH host.
Fulltext Suppression of Proinflammatory Cytokines and Mediators in LPS-Induced RAW 264.7 Macrophages by Stem Extract of Alternanthera sessilis via the Inhibition of the NF-κB Pathway

Muniandy K, Gothai S, Badran KMH, Suresh Kumar S, Esa NM, Arulselvan P

J Immunol Res, 2018;2018:3430684.
PMID: 30155492 DOI: 10.1155/2018/3430684

Alternanthera sessilis, an edible succulent herb, has been widely used as herbal drug in many regions around the globe. Inflammation is a natural process of the innate immune system, accompanied with the increase in the level of proinflammatory mediators, for example, nitric oxide (NO) and prostaglandin (PGE2); cytokines such as interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNFα); and enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via the activation and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit p65 due to the phosphorylation of inhibitory protein, IκBα. Inflammation over a short period of time is essential for its therapeutic effect. However, prolonged inflammation can be detrimental as it is related to many chronic diseases such as delayed wound healing, cardiovascular disease, arthritis, and autoimmune disorders. Therefore, ways to curb chronic inflammation have been extensively investigated. In line with that, in this present study, we attempted to study the suppression activity of the proinflammatory cytokines and mediators as a characteristic of anti-inflammatory action, by using stem extract of A. sessilis in the lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage cell line. The results showed that the extract has significantly inhibited the production of the proinflammatory mediators including NO and PGE2; cytokines comprising IL-6, IL-1β, and TNFα; and enzymes covering the iNOS and COX-2 by preventing the IκBα from being degraded, to inhibit the nuclear translocation of NF-κB subunit p65 in order to hinder the inflammatory pathway activation. These results indicated that the stem extract of A. sessilis could be an effective candidate for ameliorating inflammatory-associated complications.
Fulltext In Vitro Wound Healing Potential of Stem Extract of Alternanthera sessilis

Muniandy K, Gothai S, Tan WS, Kumar SS, Mohd Esa N, Chandramohan G, et al.

Evid Based Complement Alternat Med, 2018;2018:3142073.
PMID: 29670658 DOI: 10.1155/2018/3142073

Impaired wound healing is one of the serious problems among the diabetic patients. Currently, available treatments are limited due to side effects and cost effectiveness. In line with that, we attempted to use a natural source to study its potential towards the wound healing process. Therefore, Alternanthera sessilis (A. sessilis), an edible and medicinal plant, was chosen as the target sample for the study. During this investigation, the wound closure properties using stem extract of A. sessilis were analyzed. Accordingly, we analyzed the extract on free radical scavenging capacity and the cell migration of two most prominent cell types on the skin, human dermal fibroblast (NHDF), keratinocytes (HaCaT), and diabetic human dermal fibroblast (HDF-D) to mimic the wound healing in diabetic patients. The bioactive compounds were identified using gas chromatography-mass spectrometry (GC-MS). We discovered that the analysis exhibited a remarkable antioxidant, proliferative, and migratory rate in NHDF, HaCaT, and HDF-D in dose-dependent manner, which supports wound healing process, due to the presence of wound healing associated phytocompounds such as Hexadecanoic acid. This study suggested that the stem extract of A. sessilis might be a potential therapeutic agent for skin wound healing, supporting its traditional medicinal uses.
Genomic plasticity between human and mycobacterial DNA: A review

Danjuma L, Ling MP, Hamat RA, Higuchi A, Alarfaj AA, Marlina, et al.

Tuberculosis (Edinb), 2017 12;107:38-47.
PMID: 29050770 DOI: 10.1016/j.tube.2017.03.006

Mycobacterium tuberculosis has a remarkable ability of long-term persistence despite vigorous host immunity and prolonged therapy. The bacteria persist in secure niches such as the mesenchymal stem cells in the bone marrow and reactivate the disease, leading to therapeutic failure. Many bacterial cells can remain latent within a diseased tissue so that their genetic material can be incorporated into the genetic material of the host tissue. This incorporated genetic material reproduces in a manner similar to that of cellular DNA. After the cell division, the incorporated gene is reproduced normally and distributed proportionately between the two progeny. This inherent adoption of long-term persistence and incorporating the bacterial genetic material into that of the host tissue remains and is considered imperative for microbial advancement and chemotherapeutic resistance; moreover, new evidence indicates that the bacteria might pass on genetic material to the host DNA sequence. Several studies focused on the survival mechanism of M. tuberculosis in the host immune system with the aim of helping the efforts to discover new drugs and vaccines against tuberculosis. This review explored the mechanisms through which this bacterium affects the expression of human genes. The first part of the review summarizes the current knowledge about the interactions between microbes and host microenvironment, with special reference to the M. tuberculosis neglected persistence in immune cells and stem cells. Then, we focused on how bacteria can affect human genes and their expression. Furthermore, we analyzed the literature base on the process of cell death during tuberculosis infection, giving particular emphasis to gene methylation as an inherited process in the neutralization of possibly injurious gene components in the genome. The final section discusses recent advances related to the M. tuberculosis interaction with host epigenetic circuitry.
3D modelling of the pathogenic Leptospira protein LipL32: A bioinformatics approach

Kumaran SK, Bakar MFA, Mohd-Padil H, Mat-Sharani S, Sakinah S, Poorani K, et al.

Acta Trop, 2017 Dec;176:433-439.
PMID: 28941729 DOI: 10.1016/j.actatropica.2017.09.011

Leptospirosis is a widespread zoonotic disease caused by pathogenic Leptospira species (Leptospiraceae). LipL32 is an abundant lipoprotein from the outer membrane proteins (OMPs) group, highly conserved among pathogenic and intermediate Leptospira species. Several studies used LipL32 as a specific gene to identify the presence of leptospires. This research was aimed to study the characteristics of LipL32 protein gene code, to fill the knowledge gap concerning the most appropriate gene that can be used as antigen to detect the Leptospira. Here, we investigated the features of LipL32 in fourteen Leptospira pathogenic strains based on comparative analyses of their primary, secondary structures and 3D modeling using a bioinformatics approach. Furthermore, the physicochemical properties of LipL32 in different strains were studied, shedding light on the identity of signal peptides, as well as on the secondary and tertiary structure of the LipL32 protein, supported by 3D modelling assays. The results showed that the LipL32 gene was present in all the fourteen pathogenic Leptospira strains used in this study, with limited diversity in terms of sequence conservation, hydrophobic group, hydrophilic group and number of turns (random coil). Overall, these results add basic knowledge to the characteristics of LipL32 protein, contributing to the identification of potential antigen candidates in future research, in order to ensure prompt and reliable detection of pathogenic Leptospira species.

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