Remodeling Osteoarthritic Articular Cartilage under Hypoxic Conditions.

Osteoarthritis (OA) is one of the leading joint diseases induced by abnormalities or inflammation in the synovial membrane and articular cartilage, causing severe pain and disability. Along with the cartilage malfunction, imbalanced oxygen uptake occurs, changing chondrocytes into type I collagen- and type X collagen-producing dedifferentiated cells, contributing to OA progression. However, mounting evidence suggests treating OA by inducing a hypoxic environment in the articular cartilage, targeting the inhibition of several OA-related pathways to bring chondrocytes into a normal state. This review discusses the implications of OA-diseased articular cartilage on chondrocyte phenotypes and turnover and debates the hypoxic mechanism of action. Furthermore, this review highlights the new understanding of OA, provided by tissue engineering and a regenerative medicine experimental design, modeling the disease into diverse 2D and 3D structures and investigating hypoxia and hypoxia-inducing biomolecules and potential cell therapies. This review also reports the mechanism of hypoxic regulation and highlights the importance of activating and stabilizing the hypoxia-inducible factor and related molecules to protect chondrocytes from mitochondrial dysfunction and apoptosis occurring under the influence of OA.

Potential role of dental pulp stem cells conditioned medium for odontoblastic differentiation.

BACKGROUND: Functional bioengineered tooth regeneration using autologous or allogeneic alternative differentiated cells sources are thought to have a great potential in replacing conventional dentures. This study investigated the potential of dental pulp stem cells (DPSCs) conditioned medium for odontoblastic differentiation of Wharton's jelly mesenchymal stem cells (WJMSCs). The DPSCs derived from healthy adult permanent first molars were cultured at high confluence prior to conditioned medium collection. The WJMSCs were cultured in six different treatments, with varying ratios of culture media to DPSCs-conditioned medium. MTT assay was used to measure the rate of proliferation of WJMSCs, while immunocytochemistry staining was utilised to detect the expression of dental matrix protein 1 (DMP-1). The deposited calcium was detected and analysed via Alizarin-Red Staining (ARS). RESULTS: It was found that the proliferation of WJMSCs cultured under the mixture of complete medium and DPSCs conditioned medium showed significantly lower than the control; presumably the cells started to exit proliferative state prior differentiation. In 14 days of induction, the cells in all treatments showed osteoblastic-like morphology, calcium compound deposits were observed at day 7, 10 and 14 of differentiation suggested that DPSCs conditioned medium could lead to osteoblastic/odontoblastic differentiation. However, the DMP-1 protein can be seen only expressed minimally at day 14 of conditioned medium induction. CONCLUSIONS: In conclusion, DPSCs conditioned medium appeared as a potential odontoblastic induction approach for WJMSCs. To further investigate the stimulatory effects by DPSCs conditioned medium, specific signalling pathway need to be elucidated to enhance the differentiation efficiency.

Safety study of allogeneic mesenchymal stem cell therapy in animal model.

Intravenous (IV) infusion of mesenchymal stem cells (MSCs) from nascent tissues like Wharton's Jelly of the umbilical cord is reported to offer therapeutic effects against chronic diseases. However, toxicological data essential for the clinical application of these cells are limited. Thus, this study aimed to determine the safety of IV infusion of Wharton's Jelly derived MSCs (WJ-MSCs) in rats. Fifteen male Sprague-Dawley rats were randomised into the control or treatment group. Each group received an equal volume of saline or WJ-MSC (10 × 106 cell/kg) respectively. The animals were evaluated for physical, biochemical and haematological changes at Week 0, 2, 4, 8 and 12 during the 12-week study. Acute toxicity was performed during Week 2 and sub-chronic toxicity during Week 12. At the end of the study, the relative weight of organs was calculated and histology was performed for lung, liver, spleen and kidney. The findings from physical, serum biochemistry and complete blood count demonstrated no statistically significant differences between groups. However, pathological evaluation reported minor inflammation in the lungs for all groups, but visible healing and resolution of inflammation were observed in the treatment group only. Additionally, the histological images of the treatment group had significantly improved pulmonary structures compared to the control group. In summary, the IV administration of WJ-MSC was safe in the rats. Further studies are needed to determine the long-term safety of the WJ-MSC in both healthy and diseased animal models.

Electrospun Fiber-Coated Human Amniotic Membrane: A Potential Angioinductive Scaffold for Ischemic Tissue Repair.

Cardiac patch implantation helps maximize the paracrine function of grafted cells and serves as a reservoir of soluble proangiogenic factors required for the neovascularization of infarcted hearts. We have previously fabricated a cardiac patch, EF-HAM, composed of a human amniotic membrane (HAM) coated with aligned PLGA electrospun fibers (EF). In this study, we aimed to evaluate the biocompatibility and angiogenic effects of EF-HAM scaffolds with varying fiber thicknesses on the paracrine behavior of skeletal muscle cells (SkM). Conditioned media (CM) obtained from SkM-seeded HAM and EF-HAM scaffolds were subjected to multiplex analysis of angiogenic factors and tested on HUVECs for endothelial cell viability, migration, and tube formation analyses. All three different groups of EF-HAM scaffolds demonstrated excellent biocompatibility with SkM. CM derived from SkM-seeded EF-HAM 7 min scaffolds contained significantly elevated levels of proangiogenic factors, including angiopoietin-1, IL-8, and VEGF-C compared to plain CM, which was obtained from SkM cultured on the plain surface. CM obtained from all SkM-seeded EF-HAM scaffolds significantly increased the viability of HUVECs compared to plain CM after five days of culture. However, only EF-HAM 7 min CM induced a higher migration capacity in HUVECs and formed a longer and more elaborate capillary-like network on Matrigel compared with plain CM. Surface roughness and wettability of EF-HAM 7 min scaffolds might have influenced the proportion of skeletal myoblasts and fibroblasts growing on the scaffolds and subsequently potentiated the angiogenic paracrine function of SkM. This study demonstrated the angioinductive properties of EF-HAM composite scaffold and its potential applications in the repair and regeneration of ischemic tissues.

Cellular Interaction of Human Skin Cells towards Natural Bioink via 3D-Bioprinting Technologies for Chronic Wound: A Comprehensive Review.

Skin substitutes can provide a temporary or permanent treatment option for chronic wounds. The selection of skin substitutes depends on several factors, including the type of wound and its severity. Full-thickness skin grafts (SGs) require a well-vascularised bed and sometimes will lead to contraction and scarring formation. Besides, donor sites for full-thickness skin grafts are very limited if the wound area is big, and it has been proven to have the lowest survival rate compared to thick- and thin-split thickness. Tissue engineering technology has introduced new advanced strategies since the last decades to fabricate the composite scaffold via the 3D-bioprinting approach as a tissue replacement strategy. Considering the current global donor shortage for autologous split-thickness skin graft (ASSG), skin 3D-bioprinting has emerged as a potential alternative to replace the ASSG treatment. The three-dimensional (3D)-bioprinting technique yields scaffold fabrication with the combination of biomaterials and cells to form bioinks. Thus, the essential key factor for success in 3D-bioprinting is selecting and developing suitable bioinks to maintain the mechanisms of cellular activity. This crucial stage is vital to mimic the native extracellular matrix (ECM) for the sustainability of cell viability before tissue regeneration. This comprehensive review outlined the application of the 3D-bioprinting technique to develop skin tissue regeneration. The cell viability of human skin cells, dermal fibroblasts (DFs), and keratinocytes (KCs) during in vitro testing has been further discussed prior to in vivo application. It is essential to ensure the printed tissue/organ constantly allows cellular activities, including cell proliferation rate and migration capacity. Therefore, 3D-bioprinting plays a vital role in developing a complex skin tissue structure for tissue replacement approach in future precision medicine.

Comparison of three different skin substitutes in promoting wound healing in an ovine model.

Skin substitutes are designed dressings intended to promote wound closure. In previous in vitro and in vivo studies on small animal, an acellular skin patch made of collagen hydrogel with dermal fibroblast conditioned medium (Col-DFCM), a collagen sponge scaffold with freshly harvested skin cells (OTC), and a platelet-rich-plasma gel with freshly harvested skin cells (PRP) have been developed and tested for immediate treatment of full-thickness wound. However, to determine the safety and efficacy of these skin patches for clinical applications, further study in a large animal model is needed. The aim of this study is to evaluate the potential of Col-DFCM, OTC and PRP in treating full-thickness wound in an ovine model via histological analysis and immunohistochemistry staining were performed, with the untreated (NT) group serving as the control. Gross examination was conducted on day 7, 14 and 21 to determine the wound closure rate. The findings of percentage of wound size reduction showed that the wound healed fastest in the presence of Col-DFCM (91.34 ± 23.35%) followed by OTC (84.49 ± 23.13%), PRP (77.73 ± 20.9%) and NT group (73.94 ± 23.71%). Histological evaluation with Hematoxylin & Eosin (H & E) and Masson's trichrome staining was used to study the structure of the wound area. The results showed that OTC treated wound was more mature as indicated by the presence of a thinner epidermis followed by the Col-DFCM, PRP and NT group. Immunohistochemistry analysis also confirmed the integrity and maturity of the regenerated skin, with positive expression of cytokeratin 10 (CK10) and involucrin in the epidermal layer. In conclusion, Col-DFCM, OTC and PRP treatments promote healing of full-thickness wound and have the potential to be used clinically for rapid treatment of full-thickness wound.

Stem cells as a potential therapy in managing various disorders of metabolic syndrome: a systematic review.

Recent explorations on mesenchymal stem/stromal cells (MSC) have reported a promising future for cell-based therapies. MSCs are widely sourced from various tissues and express unique properties of regenerative potential and immunomodulation. Currently, there is a growing interest in utilizing MSC for treatment of chronic diseases to overcome the drawbacks of chemical drugs. Metabolic Syndrome (MetS) is described as a cluster of metabolic abnormalities categorized as abdominal obesity, dyslipidaemia, hypertension, hypertriglyceridemia, and hyperglycaemia. Patients diagnosed with MetS have a high predisposition for developing cardiovascular complications, diabetes, non-alcoholic fatty liver diseases, bone loss, cancer, and mortality. Hence, research on MSC as therapy for MetS and related diseases, is greatly valued and are advantaged by the low immunogenicity with high regenerative capacity. However, there are many obstacles to be addressed such as the safety, efficacy, and consistency of different MSC sources. Additionally, factors such as effective dose level and delivery method are equally important to achieve uniform therapeutic outcomes. This systematic review discusses the potential roles of MSC in managing the multiple clusters of MetS. Research articles during the past 20 years were systematically searched and filtered to update the progress in the field of MSC therapy in managing various components of MetS. The different sources of MSC, dosage, method of delivery and outcome measures for the stem cell therapies were compiled from the systematically selected research articles. It can be concluded from the review of the selected articles that MSCs can improve the various disorders of MetS such as abdominal obesity, hyperglycaemia, hypertriglyceridemia and hypertension, and represent a promising alternative to conventional therapy of the MetS cluster.

Evaluating Feasibility of Human Tissue Engineered Respiratory Epithelium Construct as a Potential Model for Tracheal Mucosal Reconstruction.

The normal function of the airway epithelium is vital for the host's well-being. Conditions that might compromise the structure and functionality of the airway epithelium include congenital tracheal anomalies, infection, trauma and post-intubation injuries. Recently, the onset of COVID-19 and its complications in managing respiratory failure further intensified the need for tracheal tissue replacement. Thus far, plenty of naturally derived, synthetic or allogeneic materials have been studied for their applicability in tracheal tissue replacement. However, a reliable tracheal replacement material is missing. Therefore, this study used a tissue engineering approach for constructing tracheal tissue. Human respiratory epithelial cells (RECs) were isolated from nasal turbinate, and the cells were incorporated into a calcium chloride-polymerized human blood plasma to form a human tissue respiratory epithelial construct (HTREC). The quality of HTREC in vitro, focusing on the cellular proliferation, differentiation and distribution of the RECs, was examined using histological, gene expression and immunocytochemical analysis. Histological analysis showed a homogenous distribution of RECs within the HTREC, with increased proliferation of the residing RECs within 4 days of investigation. Gene expression analysis revealed a significant increase (p < 0.05) in gene expression level of proliferative and respiratory epithelial-specific markers Ki67 and MUC5B, respectively, within 4 days of investigation. Immunohistochemical analysis also confirmed the expression of Ki67 and MUC5AC markers in residing RECs within the HTREC. The findings show that calcium chloride-polymerized human blood plasma is a suitable material, which supports viability, proliferation and mucin secreting phenotype of RECs, and this suggests that HTREC can be a potential candidate for respiratory epithelial tissue reconstruction.

Molecular Action of Hydroxytyrosol in Attenuation of Intimal Hyperplasia: A Scoping Review.

Objective: Hydroxytyrosol (HT), a polyphenol of olive plant is well known for its antioxidant, anti-inflammatory and anti-atherogenic properties. The aim of this systematic search is to highlight the scientific evidence evaluating molecular efficiency of HT in halting the progression of intimal hyperplasia (IH), which is a clinical condition arises from endothelial inflammation. Methods: A systematic search was performed through PubMed, Web of Science and Scopus, based on pre-set keywords which are Hydroxytyrosol OR 3,4-dihydroxyphenylethanol, AND Intimal hyperplasia OR Neointimal hyperplasia OR Endothelial OR Smooth muscles. Eighteen in vitro and three in vitro and in vivo studies were selected based on a pre-set inclusion and exclusion criteria. Results: Based on evidence gathered, HT was found to upregulate PI3K/AKT/mTOR pathways and supresses inflammatory factors and mediators such as IL-1ß, IL-6, E-selectin, P-selectin, VCAM-1, and ICAM-1 in endothelial vascularization and functioning. Two studies revealed HT disrupted vascular smooth muscle cells (SMC) cell cycle by dephosphorylating ERK1/2 and AKT pathways. Therefore, HT was proven to promote endothelization and inhibit vascular SMCs migration thus hampering IH development. However, none of these studies described the effect of HT collectively in both vascular endothelial cells (EC) and SMCs in IH ex vivo model. Conclusions: Evidence from this concise review provides an insight on HT regulation of molecular pathways in reendothelization and inhibition of VSMCs migration. Henceforth, we propose effect of HT on IH prevention could be further elucidated through in vivo and ex vivo model.

Preliminary Study of In Vitro Three-Dimensional Skin Model Using an Ovine Collagen Type I Sponge Seeded with Co-Culture Skin Cells: Submerged versus Air-Liquid Interface Conditions.

Three-dimensional (3D) in vitro skin models have been widely used for cosmeceutical and pharmaceutical applications aiming to reduce animal use in experiment. This study investigate capability of ovine tendon collagen type I (OTC-I) sponge suitable platform for a 3D in vitro skin model using co-cultured skin cells (CC) containing human epidermal keratinocytes (HEK) and human dermal fibroblasts (HDF) under submerged (SM) and air-liquid interface (ALI) conditions. Briefly, the extracted OTC-I was freeze-dried and crosslinked with genipin (OTC-I_GNP) and carbodiimide (OTC-I_EDC). The gross appearance, physico-chemical characteristics, biocompatibility and growth profile of seeded skin cells were assessed. The light brown and white appearance for the OTC-I_GNP scaffold and other groups were observed, respectively. The OTC-I_GNP scaffold demonstrated the highest swelling ratio (~1885%) and water uptake (94.96 ± 0.14%). The Fourier transformation infrared demonstrated amide A, B and I, II and III which represent collagen type I. The microstructure of all fabricated sponges presented a similar surface roughness with the presence of visible collagen fibers and a heterogenous porous structure. The OTC-I_EDC scaffold was more toxic and showed the lowest cell attachment and proliferation as compared to other groups. The micrographic evaluation revealed that CC potentially formed the epidermal- and dermal-like layers in both SM and ALI that prominently observed with OTC-I_GNP compared to others. In conclusion, these results suggest that OTC_GNP could be used as a 3D in vitro skin model under ALI microenvironment.

Molecular Action of Hydroxytyrosol in Wound Healing: An In Vitro Evidence-Based Review.

Hydroxytyrosol (HT) is an essential molecule isolated from the phenolic fraction of olive (Olea europaea). HT has been implicated for its health-stimulating effect mainly due to its antioxidative capacity. The current review summarises and discusses the available evidence, related to HT activities in wound healing enhancement. The literature search of related articles published within the year 2010 to 2020 was conducted using Medline via Ebscohost, Scopus, and Google Scholar databases. Studies were limited to in vitro research regarding the role of HT in wound closure, including anti-inflammation, antimicrobial, antioxidative, and its direct effect to the cells involved in wound healing. The literature search revealed 7136 potentially relevant records were obtained from the database search. Through the screening process, 13 relevant in vitro studies investigating the role of HT in wound repair were included. The included studies reported a proangiogenic, antioxidative, antiaging, anti-inflammatory and antimicrobial effect of HT. The current in vitro evidence-based review highlights the cellular and molecular action of HT in influencing positive outcomes toward wound healing. Based on this evidence, HT is a highly recommended bioactive compound to be used as a pharmaceutical product for wound care applications.

The Effects of Pro-Inflammatory and Anti-Inflammatory Agents for the Suppression of Intimal Hyperplasia: An Evidence-Based Review.

Anti-atherogenic therapy is crucial in halting the progression of inflammation-induced intimal hyperplasia. The aim of this concise review was to methodically assess the recent findings of the different approaches, mainly on the recruitment of chemokines and/or cytokine and its effects in combating the intimal hyperplasia caused by various risk factors. Pubmed and Scopus databases were searched, followed by article selection based on pre-set inclusion and exclusion criteria. The combination of keywords used were monocyte chemoattractant protein-1 OR MCP-1 OR TNF-alpha OR TNF-α AND hyperplasia OR intimal hyperplasia OR neointimal hyperplasia AND in vitro. These keywords combination was incorporated in the study and had successfully identified 77 articles, with 22 articles were acquired from Pubmed, whereas 55 articles were obtained from Scopus. However, after title screening, only twelve articles meet the requirements of defined inclusion criteria. We classified the data into 4 different approaches, i.e., utilisation of natural product, genetic manipulation and protein inhibition, targeted drugs in clinical setting, and chemokine and cytokines induction. Most of the articles are working on genetic manipulation targeted on specific pathway to inhibit the pro-inflammatory factors expression. We also found that the utilisation of chemokine- and cytokine-related treatments are emerging throughout the years. However, there is no study utilising the combination of approaches that might give a better outcome in combating intimal hyperplasia. Hopefully, this concise review will provide an insight regarding the usage of different novel approaches in halting the progression of intimal hyperplasia, which serves as a key factor for the development of atherosclerosis in cardiovascular disease.

Antibacterial-Integrated Collagen Wound Dressing for Diabetes-Related Foot Ulcers: An Evidence-Based Review of Clinical Studies.

Diabetic foot ulcer (DFU) is a chronic wound frequently delayed from severe infection. Wound dressing provides an essential barrier between the ulcer and the external environment. This review aimed to analyse the effectiveness of antibacterial collagen-based dressing for DFU treatment in a clinical setting. An electronic search in four databases, namely, Scopus, PubMed, Ovid MEDLINE(R), and ISI Web of Science, was performed to obtain relevant articles published within the last ten years. The published studies were included if they reported evidence of (1) collagen-based antibacterial dressing or (2) wound healing for diabetic ulcers, and (3) were written in English. Both randomised and non-randomised clinical trials were included. The search for relevant clinical studies (n) identified eight related references discussing the effectiveness of collagen-based antibacterial wound dressings for DFU comprising collagen impregnated with polyhexamethylene biguanide (n = 2), gentamicin (n = 3), combined-cellulose and silver (n = 1), gentian violet/methylene blue mixed (n = 1), and silver (n = 1). The clinical data were limited by small sample sizes and multiple aetiologies of chronic wounds. The evidence was not robust enough for a conclusive statement, although most of the studies reported positive outcomes for the use of collagen dressings loaded with antibacterial properties for DFU wound healing. This study emphasises the importance of having standardised clinical trials, larger sample sizes, and accurate reporting for reliable statistical evidence confirming DFU treatment efficiency.

Plant- vs. Bacterial-Derived Cellulose for Wound Healing: A Review.

Cellulose is a naturally existing element in the plant's cell wall and in several bacteria. The unique characteristics of bacterial cellulose (BC), such as non-toxicity, biodegradability, hydrophilicity, and biocompatibility, together with the modifiable form of nanocellulose, or the integration with nanoparticles, such as nanosilver (AgNP), all for antibacterial effects, contributes to the extensive usage of BC in wound healing applications. Due to this, BC has gained much demand and attention for therapeutical usage over time, especially in the pharmaceutical industry when compared to plant cellulose (PC). This paper reviews the progress of related research based on in vitro, in vivo, and clinical trials, including the overall information concerning BC and PC production and its mechanisms in wound healing. The physicochemical differences between BC and PC have been clearly summarized in a comparison table. Meanwhile, the latest Food and Drug Administration (FDA) approved BC products in the biomedical field are thoroughly discussed with their applications. The paper concludes on the need for further investigations of BC in the future, in an attempt to make BC an essential wound dressing that has the ability to be marketable in the global marketplace.

Synergistic Effect of Laminin and Epidermal Growth Factor on Biological and Morphological Properties of Co-Cultured Myoblasts and Fibroblasts.

BACKGROUND: One of the long-standing problems of myoblasts in vitro expansion is slow cell migration and this causes fibroblast population to exceed myoblasts. In this study, we investigated the synergistic effect of laminin and epidermal growth factor (EGF) on co-cultured myoblasts and fibroblasts for cell attachment, proliferation and migration. METHODS: Skeletal human muscle cells were cultured in four different conditions; control, EGF, laminin (Lam) and laminin EGF (Lam + EGF). Using live imaging system, their cellular properties; attachment, migration and growth were exposed to Rho kinase inhibitor, Y-27632, and EGF-receptor (EGF-R) inhibitor, gefitinib were measured. RESULTS: Myoblast migration and proliferation was enhanced significantly by synergistic stimulation of laminin and EGF (0.61 ± 0.14 µm/min, 0.008 ± 0.001 h-1) compare to that by EGF alone (0.26 ± 0.13 µm/min, 0.004 ± 0.0009 h-1). However, no changes in proliferation and migration were observed for fibroblasts among the culture conditions. Inhibition of Rho kinase resulted in the increase of the myoblast migration on the laminin-coated surface with EGF condition (0.64 ± 0.18 µm/min). Compared to the untreated conditions, myoblasts cultured on the laminin-coated surface and EGF demonstrated elongated morphology, and average cell length increase significantly. In contrast, inhibition of EGF-R resulted in the decrease of myoblast migration on the laminin coated surface with EGF supplemented condition (0.43 ± 0.05 µm/min) in comparison to the untreated control (0.53 ± 0.05 µm/min). CONCLUSION: Laminin and EGF preferentially enhance the proliferation and migration of myoblasts, and Rho kinase and EGF-R play a role in this synergistic effect. These results will be beneficial for the propagation of skeletal muscle cells for clinical applications.

Miswak and oral health: An evidence-based review.

Poor oral health has been associated with several chronic and systemic disease. Currently, the most common method of teeth cleaning is the use of a toothbrush together with dentifrices. However, natural chewing stick such as S. persica miswak is still used in many developing countries due to their low cost and availability. The present review aims to summarize the evidences on effectiveness of miswak in promoting oral health. The search was performed using Medline via Ebscohost, Scopus and Google Scholar database to obtain relevant articles published between 2010 to May 2020 using the following set of keywords 1) Miswak OR Salvadora OR persica AND 2) dental OR caries OR plaque OR oral OR orthodontics. Isolated microbial inhibition studies were excluded from the review due to its well-established wealth of literature. Miswak was administered as ten different forms, namely mouthwash, toothpaste, chewing stick, essential oil, aqueous extract, ethanol extract, probiotic spray, dental varnish, dental cement or chewing gum. All studies reported a positive effect of miswak as an anti-plaque, anti-gingivitis, anti-cariogenic, promotion of gingival wound healing, whitening properties, orthodontic chain preservation, and biocompatibility with oral cells. Miswak in its different forms demonstrated positive effect towards oral health maintenance and management.

Nigella sativa and Its Active Compound, Thymoquinone, Accelerate Wound Healing in an In Vivo Animal Model: A Comprehensive Review.

Nigella sativa (NS) has been reported to have a therapeutic effect towards skin wound healing via its anti-inflammatory, tissue growth stimulation, and antioxidative properties. This review examines all the available studies on the association of Nigella sativa (NS) and skin wound healing. The search was performed in Medline via EBSCOhost and Scopus databases to retrieve the related papers released between 1970 and March 2020. The principal inclusion criteria were original article issued in English that stated wound healing criteria of in vivo skin model with topically applied NS. The search discovered 10 related articles that fulfilled the required inclusion criteria. Studies included comprise different types of wounds, namely excisional, burn, and diabetic wounds. Seven studies unravelled positive results associated with NS on skin wound healing. Thymoquinone has anti-inflammatory, antioxidant, and antibacterial properties, which mainly contributed to wound healing process.

Development and physicochemical analysis of genipin-crosslinked gelatine sponge as a potential resorbable nasal pack.

Nasal injury following nasal surgery is an adverse consequence, and prompt treatment should be initiated. Nasal packing, either non-absorbable or absorbable, are commonly used after nasal surgery to prevent bleeding and promote wound healing. In the current study, a novel gelatine sponge crosslinked with genipin was evaluated for suitability to be used as nasal packing and compared to one of the frequently used commercial nasal packing made up of polyurethane. Gelatine at 7% and 10% (w/v) concentration were crosslinked with varying concentrations of genipin, 0.5%, 0.25%, and 0.2% (v/v). The gelatine sponges were further characterised by its water uptake ability, biodegradation, water vapour transmission rate, porosity, contact angle, chemical composition, crosslinking degree, and mechanical properties. The gelatine sponges absorbed five times more water than their dry weight and were degraded within five days. The water vapour transmission rate of the gelatine sponges was 1187.7 ± 430.2 g/(m-2 day) for 7% gelatine and 779.4 ± 375.5 g/(m-2 day) for 10% gelatine. Crosslinking of gelatine with genipin resulted in lower porosity and did not affect the wettability of gelatine sponge (contact angle: 95.3 ± 12.1° for 7% gelatine and 88.4 ± 7.2° for 10% gelatine). In terms of biodegradability, the gelatine sponges took 24-48 h to degrade completely. Genipin crosslinking improved the degradation resistance and mechanical strength of gelatine sponge. The physical and chemical properties of the gelatine sponge, i.e. biodegradability and mechanical durability, support its potential as nasal packing.

Effect of Kelulut Honey on the Cellular Dynamics of TGFß-Induced Epithelial to Mesenchymal Transition in Primary Human Keratinocytes.

Over-induction of epithelial to mesenchymal transition (EMT) by tumor growth factor beta (TGFß) in keratinocytes is a key feature in keloid scar. The present work seeks to investigate the effect of Kelulut honey (KH) on TGFß-induced EMT in human primary keratinocytes. Image analysis of the real time observation of TGFß-induced keratinocytes revealed a faster wound closure and individual migration velocity compared to the untreated control. TGFß-induced keratinocytes also have reduced circularity and display a classic EMT protein expression. Treatment of 0.0015% (v/v) KH reverses these effects. In untreated keratinocytes, KH resulted in slower initial wound closure and individual migration velocity, which sped up later on, resulting in greater wound closure at the final time point. KH treatment also led to greater directional migration compared to the control. KH treatment caused reduced circularity in keratinocytes but displayed a partial EMT protein expression. Taken together, the findings suggest the therapeutic potential of KH in preventing keloid scar by attenuating TGFß-induced EMT.

Cardioprotective Effects of Honey and Its Constituent: An Evidence-Based Review of Laboratory Studies and Clinical Trials.

Cardiovascular disease is a major public health burden worldwide. Myocardial infarction is the most common form of cardiovascular disease resulting from low blood supply to the heart. It can lead to further complications such as cardiac arrhythmia, toxic metabolite accumulation, and permanently infarcted areas. Honey is one of the most prized medicinal remedies used since ancient times. There is evidence that indicates honey can function as a cardioprotective agent in cardiovascular diseases. The present review compiles and discusses the available evidence on the effect of honey on cardiovascular diseases. Three electronic databases, namely, PubMed, Scopus, and MEDLINE via EBSCOhost, were searched between January 1959 and March 2020 to identify reports on the cardioprotective effect of honey. Based on the pre-set eligibility criteria, 25 qualified articles were selected and discussed in this review. Honey investigated in the studies included varieties according to their geological origin. Honey protects the heart via lipid metabolism improvement, antioxidative activity, blood pressure modulation, heartbeat restoration, myocardial infarct area reduction, antiaging properties, and cell apoptosis attenuation. This review establishes honey as a potential candidate to be explored further as a natural and dietary alternative to the management of cardiovascular disease.