Designing and synthesis of injectable hydrogel based on carboxymethyl cellulose/carboxymethyl chitosan containing QK peptide for femoral head osteonecrosis healing.

Femoral head necrosis is a debilitating disorder that typically caused by impaired blood supply to the hip joint. In this study, a novel injectable hydrogel based on Oxidized Carboxymethyl Cellulose (OCMC)-Carboxymethyl Chitosan (CMCS) polymers containing an angiogenesis stimulator peptide (QK) with a non-toxic crosslinking interaction (Schiff based reaction) was synthesized to enhance angiogenesis following femoral head necrosis in an animal model. The physicochemical features of fabricated injectable hydrogel were analyzed by FTIR, swelling and degradation rate, rheometry, and peptide release. Also, the safety and efficacy were evaluated following an in vitro hydrogel injection study and an avascular necrosis (AVN) animal model. According to the results, the hydrogel exhibited an appropriate swelling ratio and water uptake (>90 %, 24 h) as well as a suitable degradation rate over 21 days accompanied by a continuous peptide release. Also, data showed that hydrogels containing QK peptide boosted the proliferation, differentiation, angiogenesis, and osteogenic potential of both Bone Marrow mesenchymal Stem Cells (BM-MSCs) and human umbilical vein endothelial cells (HUVECs) (****p < 0.0001 and ***p < 0.001, respectively). Furthermore, molecular and histological evaluations significantly demonstrated the overexpression of Runx2, Osteocalcin, Collagen I, VEGF and CD34 genes (**p < 0.01 and ***p < 0.001, respectively), and also femoral head necrosis was effectively prohibited, and more blood vessels were detected in defect area by OCMC-CMCS hydrogel containing QK peptide (bone trabeculae >9000, ***p < 0.001). In conclusion, the findings demonstrate that OCMC-CMCS-QK injectable hydrogel could be considered as an impressive therapeutic construct for femoral head AVN healing.

Celiac Disease: A Review from Genetic to Treatment.

Celiac disease (CD) is a complex disorder influenced by genetic and environmental factors. When people with a genetic predisposition to CD consume gluten, an inflammatory response is triggered in the small intestine, and this reaction can be alleviated by the elimination of gluten from the diet. The clinical manifestations of CD vary greatly from person to person and begin at a young age or in adulthood. Influence of genetic factors on CD development is evident in carriers of the DQ2 and/or DQ8 allele. HLA genotypes are associated with gut colonization by bacteria, particularly in individuals suffering from CD. In addition, beneficial gut microbes are crucial for the production of DPP-4, which plays a key role in immune function, as well as metabolic and intestinal health. Therefore, probiotics have been recommended as a complementary food supplement in CD.

Lipocalin-2 Upregulation in Nasopharyngeal Carcinoma: A Novel Potential Diagnostic Biomarker.

Background: Lipocalin-2 (LCN2) deregulation has been reported in several types of cancer and is implicated in the proliferation, migration, angiogenesis, and progression of tumors. However, its aberrant expression has been rarely studied in nasopharyngeal carcinoma (NPC). In the present study, we investigated the expression of LCN2 in NPC patients. Methods: In this descriptive cross-sectional study, 29 NPC and 20 non-cancerous control paraffin pathology blocks were obtained from the seven-year (2011 to 2018) archive of Razi Laboratory in Rasht, Iran. LCN2 mRNA expression was evaluated through quantitative real-time PCR. In addition, immunohistochemistry was performed to evaluate LCN2 expression at the protein level. The fold change value and total immunostaining score (TIS) were applied for quantitative evaluation. The nonparametric Mann-Whitney U test and Fisher's exact test were used through GraphPad Prism 8.3.0 software. P<0.05 was considered statistically significant. Results: Our results revealed that LCN2 mRNA and protein levels in NPC tissues were significantly higher than control tissues (P=0.028 and P=0.002, respectively). At the protein level, 65.51% (19/29) of NPC patients were categorized as having high LCN2 expression (TIS>3) and 34.47% (10/29) as low expression (TIS≤3). While in the control group, 25% (5/20) of subjects represented a high expression of LCN2 (TIS>3), and 75% (15/20) showed no or weak expression (TIS≤3). No significant correlation was found between the overexpression of LCN2 at the protein level and the demographic features of the patients. Conclusion: Our findings suggest that LCN2 might be considered a potential new diagnostic marker for NPC. However, this warrants further studies.

Study of Three Potential Diagnostic Biomarkers in Nasopharyngeal Carcinoma Samples from Guilan, North of Iran

Abstract Introduction Finding biomarkers for highly lethal cancers is a priority. Objective The current study was designed to understand the clinical significance of vascular endothelial growth factor (VEGF), latent membrane protein 1 (LMP1), and tumor necrosis factor-α (TNF-α) expression as the biomarkers, and evaluate their correlation with each other, in nasopharyngeal carcinoma (NPC) in the province of Guilan, North of Iran. Methods Gene expression was evaluated in 25 formalin-fixed paraffin-embedded (FFPE) blocks from cases of confirmed NPC and 20 FFPE samples of non-NPC by quantifying messenger ribonucleic acid (mRNA) and protein levels, using real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) methods, respectively. Furthermore, the correlations among the protein levels of different genes, along with the patients' demographic characteristics were assessed. Results Our findings on mRNA and protein levels demonstrated that the expression of the LMP1 gene in the NPC group was significantly elevated compared with that of the non-NPC group. In addition, the protein levels in the NPC group indicated a positive and significant correlation between LMP1 and VEGF expression. It was noted that both protein and mRNA levels showed no significant differences in the expression of TNF-α and VEGF genes between the NPC and control groups. Furthermore, there was no significant relationship between the expression of these proteins and the demographic characteristics of NPC patients. Conclusion Overall, a significant increase in LMP1 expression was observed in NPC patients, which may serve as a diagnostic biomarker for NPC. Also, LMP1 might be involved in NPC progression by inducing VEGF gene expression.

Study of Three Potential Diagnostic Biomarkers in Nasopharyngeal Carcinoma Samples from Guilan, North of Iran.

Introduction Finding biomarkers for highly lethal cancers is a priority. Objective The current study was designed to understand the clinical significance of vascular endothelial growth factor (VEGF), latent membrane protein 1 (LMP1), and tumor necrosis factor-α (TNF-α) expression as the biomarkers, and evaluate their correlation with each other, in nasopharyngeal carcinoma (NPC) in the province of Guilan, North of Iran. Methods Gene expression was evaluated in 25 formalin-fixed paraffin-embedded (FFPE) blocks from cases of confirmed NPC and 20 FFPE samples of non-NPC by quantifying messenger ribonucleic acid (mRNA) and protein levels, using real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) methods, respectively. Furthermore, the correlations among the protein levels of different genes, along with the patients' demographic characteristics were assessed. Results Our findings on mRNA and protein levels demonstrated that the expression of the LMP1 gene in the NPC group was significantly elevated compared with that of the non-NPC group. In addition, the protein levels in the NPC group indicated a positive and significant correlation between LMP1 and VEGF expression. It was noted that both protein and mRNA levels showed no significant differences in the expression of TNF-α and VEGF genes between the NPC and control groups. Furthermore, there was no significant relationship between the expression of these proteins and the demographic characteristics of NPC patients. Conclusion Overall, a significant increase in LMP1 expression was observed in NPC patients, which may serve as a diagnostic biomarker for NPC. Also, LMP1 might be involved in NPC progression by inducing VEGF gene expression.

Multifunctional nanostructures: Intelligent design to overcome biological barriers.

Over the past three decades, nanoscience has offered a unique solution for reducing the systemic toxicity of chemotherapy drugs and for increasing drug therapeutic efficiency. However, the poor accumulation and pharmacokinetics of nanoparticles are some of the key reasons for their slow translation into the clinic. The is intimately linked to the non-biological nature of nanoparticles and the aberrant features of solid cancer, which together significantly compromise nanoparticle delivery. New findings on the unique properties of tumors and their interactions with nanoparticles and the human body suggest that, contrary to what was long-believed, tumor features may be more mirage than miracle, as the enhanced permeability and retention based efficacy is estimated to be as low as 1%. In this review, we highlight the current barriers and available solutions to pave the way for approved nanoformulations. Furthermore, we aim to discuss the main solutions to solve inefficient drug delivery with the use of nanobioengineering of nanocarriers and the tumor environment. Finally, we will discuss the suggested strategies to overcome two or more biological barriers with one nanocarrier. The variety of design formats, applications and implications of each of these methods will also be evaluated.

Bioceramics/Electrospun Polymeric Nanofibrous and Carbon Nanofibrous Scaffolds for Bone Tissue Engineering Applications.

Bone tissue engineering integrates biomaterials, cells, and bioactive agents to propose sophisticated treatment options over conventional choices. Scaffolds have central roles in this scenario, and precisely designed and fabricated structures with the highest similarity to bone tissue have shown promising outcomes. On the other hand, using nanotechnology and nanomaterials as the enabling options confers fascinating properties to the scaffolds, such as precisely tailoring the physicochemical features and better interactions with cells and surrounding tissues. Among different nanomaterials, polymeric nanofibers and carbon nanofibers have attracted significant attention due to their similarity to bone extracellular matrix (ECM) and high surface-to-volume ratio. Moreover, bone ECM is a biocomposite of collagen fibers and hydroxyapatite crystals; accordingly, researchers have tried to mimic this biocomposite using the mineralization of various polymeric and carbon nanofibers and have shown that the mineralized nanofibers are promising structures to augment the bone healing process in the tissue engineering scenario. In this paper, we reviewed the bone structure, bone defects/fracture healing process, and various structures/cells/growth factors applicable to bone tissue engineering applications. Then, we highlighted the mineralized polymeric and carbon nanofibers and their fabrication methods.

The Effect of Rainbow Trout (Oncorhynchus mykiss) Collagen Incorporated with Exo-Polysaccharides Derived from Rhodotorula mucilaginosa sp. on Burn Healing.

Burn is one of the physically debilitating injuries that can be potentially fatal; therefore, providing appropriate coverage in order to reduce possible mortality risk and accelerate wound healing is mandatory. In this study, collagen/exo-polysaccharide (Col/EPS 1-3%) scaffolds are synthesized from rainbow trout (Oncorhynchus mykiss) skins incorporated with Rhodotorula mucilaginosa sp. GUMS16, respectively, for promoting Grade 3 burn wound healing. Physicochemical characterizations and, consequently, biological properties of the Col/EPS scaffolds are tested. The results show that the presence of EPS does not affect the minimum porosity dimensions, while raising the EPS amount significantly reduces the maximum porosity dimensions. Thermogravimetric analysis (TGA), FTIR, and tensile property results confirm the successful incorporation of the EPS into Col scaffolds. Furthermore,the biological results show that the increasing EPS does not affect Col biodegradability and cell viability, and the use of Col/EPS 1% on rat models displays a faster healing rate. Finally, histopathological examination reveals that the Col/EPS 1% treatment accelerates wound healing, through greater re-epithelialization and dermal remodeling, more abundant fibroblast cells and Col accumulation. These findings suggest that Col/EPS 1% promotes dermal wound healing via antioxidant and anti-inflammatory activities, which can be a potential medical process in the treatment of burn wounds.

Fabrication, characterization and biological properties evaluation of bioactive scaffold based on mineralized carbon nanofibers.

Tissue engineering as an innovative approach aims to combine engineering, biomaterials and biomedicine to eliminate the drawbacks of conventional bone defect treatment. In the current study, we fabricated bioengineered electroactive and bioactive mineralized carbon nanofibers as the scaffold for bone tissue engineering applications. The scaffold was fabricated using the sol-gel method and thoroughly characterized by SEM imaging, EDX analysis and a 4-point probe. The results showed that the CNFs have a diameter of 200 ± 19 nm and electrical conductivity of 1.02 ± 0.12 S cm-1. The in vitro studies revealed that the synthesized CNFs were osteoactive and supported the mineral crystal deposition. The hemolysis study confirmed the hemocompatibility of the CNFs and cell viability/proliferation sassy using an MTT assay kit showed the proliferative activities of mineralized CNFs. In conclusion, this study revealed that the mineralized CNFs synthesized by the combination of sol-gel and electrospinning techniques were electroactive, osteoactive and biocompatible, which can be considered an effective bone tissue engineering scaffold.Communicated by Ramaswamy H. Sarma.

Chemical Composition, Antioxidant Activity and Cytocompatibility of Polyphenolic Compounds Extracted from Food Industry Apple Waste: Potential in Biomedical Application.

Apple pomace (AP) from the food industry is a mixture of different fractions containing bioactive polyphenolic compounds. This study provides a systematic approach toward the recovery and evaluation of the physiochemical and biological properties of polyphenolic compounds from AP. We studied subcritical water extraction (SCW) and solvent extraction with ethanol from four different AP fractions of pulp, peel, seed, core, and stem (A), peel (B), seed and core (C), and pulp and peel (D). The subcritical water method at the optimum condition resulted in total polyphenolic compounds (TPC) of 39.08 ± 1.10 mg GAE per g of AP on a dry basis compared to the ethanol extraction with TPC content of 10.78 ± 0.94 mg GAE/g db. Phloridzin, chlorogenic acid, and quercetin were the main identified polyphenolics in the AP fractions using HPLC. DPPH radical scavenging activity of fraction B and subcritical water (SW) extracts showed comparable activity to ascorbic acid while all ethanolic extracts were cytocompatible toward human fibroblast (3T3-L1) and salivary gland acinar cells (NS-SV-AC). Our results indicated that AP is a rich source of polyphenolics with the potential for biomedical applications.

Mitochondrial transplantation protects against sepsis-induced myocardial dysfunction by modulating mitochondrial biogenesis and fission/fusion and inflammatory response.

BACKGROUND: Sepsis-induced myocardial dysfunction is associated with worse clinical outcomes and high mortality, but no effective therapeutic intervention has been explored, reinforcing the urgent need to develop innovative strategies. Mitochondrial dysfunction underlies the pathogenesis of sepsis-induced myocardial dysfunction. Herein, we assessed the effect of mitochondrial transplantation on sepsis-induced myocardial dysfunction in a rat model of cecal ligation and puncture (CLP)-induced sepsis. METHODS: Male Wistar rats (n = 80, 12 weeks old, 250-300 g) were divided into groups with/without CLP-induced sepsis receiving mitochondrial transplantation in single or two repetitive injections (1 h or 1 and 7 h post-CLP, respectively). Mitochondria were isolated from donor rats and injected intravenously (400 µl of mitochondrial suspension containing 7.5 × 106 mitochondria/ml of respiration buffer) in recipient groups. Twenty-four hours post-operation, LDH and cTn-I levels, mitochondrial functional endpoints, expression of mitochondrial biogenesis (SIRT-1 and PGC-1α) and fission/fusion (Drp1/Mfn1 and Mfn2) genes, and inflammatory cytokines (TNF-α, IL-1ß, and IL-6) levels were evaluated. Survival was tested over 72 h post-operation. RESULTS: Mitotherapy significantly improved 72-hours survival (P < .05) and decreased LDH and cTn-I levels (P < .01). It also restored mitochondrial function and expression of mitochondrial biogenesis and fusion genes, and decreased the expression of mitochondrial fission gene and the levels of inflammatory cytokines (P < .05 to P < .01). Mitotherapy with repetitive injections at 1 and 7 h post-CLP provided noticeable mitoprotection in comparison with the group receiving mitotherapy at single injection. CONCLUSION: Mitotherapy improved mitochondrial function, biogenesis, and dynamic associated with SIRT-1/PGC-1α network and suppressed inflammatory response in CLP-induced sepsis model, therefore, offers a promising strategy to overcome life-threatening sepsis challenge.

Exopolysaccharide from the yeast Papiliotrema terrestris PT22AV for skin wound healing.

INTRODUCTION: Exopolysaccharides (EPSs) are high-value functional biomaterials mainly produced by bacteria and fungi, with nutraceutical, therapeutic and industrial potentials. OBJECTIVES: This study sought to characterize and assess the biological properties of the EPS produced by the yeast Papiliotrema terrestris PT22AV. METHODS: After extracting the yeast's DNA and its molecular identification, the EPS from P. terrestris PT22AV strain was extracted and its physicochemical properties (structural, morphological, monosaccharide composition and molecular weight) were characterized. The EPS's in vitro biological activities and in vivo wound healing potential were also evaluated. RESULTS: The obtained EPS was water-soluble and revealed an average molecular weight (Mw) of 202 kDa. Mannose and glucose with 97% and 3% molar percentages, respectively, constituted the EPS. In vitro antibacterial activity analysis of the extracted EPS exhibited antibacterial activity (>80%) against Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis at a concentration of 2 mg/mL. The EPS showed cytocompatibility against the human fibroblast and macrophage cell lines and the animal studies showed a dose-dependent wound healing capacity of the EPS with higher wound closure at 10 mg/mL compared to negative and positive control after 14 days. CONCLUSION: The EPS from P. terrestris PT22AV could serve as a promising source of biocompatible macromolecules with potential for skin wound healing.

Evaluation of two fungal exopolysaccharides as potential biomaterials for wound healing applications.

Microbial exopolysaccharides (EPSs) are mostly produced by bacteria and fungi and have potential use in the production of biomedical products such as nutraceuticals and in tissue engineering applications. The present study investigated the in vitro biological activities and in vivo wound healing effects of EPSs produced from a Sclerotium-forming fungus (Sclerotium glucanicum DSM 2159) and a yeast (Rhodosporidium babjevae), denoted as scleroglucan (Scl) and EPS-R, respectively. EPS yields of 0.9 ± 0.07 g/L and 1.11 ± 0.4 g/L were obtained from S. glucanicum and R. babjevae, respectively. The physicochemical properties of the EPSs were characterized using infrared spectroscopy and scanning electron microscopy. Further investigations of the biological properties showed that both EPSs were cytocompatible toward the human fibroblast cell line and demonstrated  hemocompatibility. Favorable wound healing capacities of the EPSs (10 mg/mL) were also established via in vivo tests. The present study therefore showed that the EPSs produced by S. glucanicum and R. babjevae have the potential use as biocompatible components for the promotion of dermal wound healing.

Electrochemical Biosensors for Pathogen Detection: An Updated Review.

Electrochemical biosensors are a family of biosensors that use an electrochemical transducer to perform their functions. In recent decades, many electrochemical biosensors have been created for pathogen detection. These biosensors for detecting infections have been comprehensively studied in terms of transduction elements, biorecognition components, and electrochemical methods. This review discusses the biorecognition components that may be used to identify pathogens. These include antibodies and aptamers. The integration of transducers and electrode changes in biosensor design is a major discussion topic. Pathogen detection methods can be categorized by sample preparation and secondary binding processes. Diagnostics in medicine, environmental monitoring, and biothreat detection can benefit from electrochemical biosensors to ensure food and water safety. Disposable and reusable biosensors for process monitoring, as well as multiplexed and conformal pathogen detection, are all included in this review. It is now possible to identify a wide range of diseases using biosensors that may be applied to food, bodily fluids, and even objects' surfaces. The sensitivity of optical techniques may be superior to electrochemical approaches, but optical methods are prohibitively expensive and challenging for most end users to utilize. On the other hand, electrochemical approaches are simpler to use, but their efficacy in identifying infections is still far from satisfactory.

Thermochemical Liquefaction of Pomace Using Sub/Supercritical Ethanol: an Integrated Experimental and Preliminary Economic Feasibility Study.

Fossil sourced chemicals such as aromatics, are widely employed in the chemical industry for the production of commodity items. Recognizing the un-sustainability of existing approaches in the production of these chemicals, the current study investigated the valorization of apple pomace (AP) for their production. The present study assessed AP valorization by imposing variations in processing conditions of temperature (100-260 °C), time (0.5-12 h), alcohol/water ratio v/v (0:1-1:0), and Fe3+/H2O2 molar ratio (10:1-100-1), in accordance to the Box-Behnken experimental design. The optimal yield of the oil was 24.6 wt.%, at the temperature, time, alcohol/water ratio v/v, and Fe3+/H2O2 molar ratio of 260 °C, 4.7 h, 1, and 100, respectively. Notably, the application of gas chromatography-mass spectroscopy showed that the oil product contained mainly aromatics and interestingly also alkanes, indicating that the experimental conditions imposed promoted secondary hydrogenation reactions of oxygen-containing species during AP valorization. A consideration of the comparative economics of the proposed AP valorization and the existing AP management approach, using approximate estimation techniques, highlighted the potential of a ~ 59% reduction in the unit cost of AP management. The study therefore presents a compelling basis for future investigations into AP waste management using the thermochemical liquefaction technology.

Microorganism-derived biological macromolecules for tissue engineering.

According to literature, certain microorganism productions mediate biological effects. However, their beneficial characteristics remain unclear. Nowadays, scientists concentrate on obtaining natural materials from live creatures as new sources to produce innovative smart biomaterials for increasing tissue reconstruction in tissue engineering and regenerative medicine. The present review aims to introduce microorganism-derived biological macromolecules, such as pullulan, alginate, dextran, curdlan, and hyaluronic acid, and their available sources for tissue engineering. Growing evidence indicates that these materials can be used as biological material in scaffolds to enhance regeneration in damaged tissues and contribute to cosmetic and dermatological applications. These natural-based materials are attractive in pharmaceutical, regenerative medicine, and biomedical applications. This study provides a detailed overview of natural-based biomaterials, their chemical and physical properties, and new directions for future research and therapeutic applications.

Anionic exopolysaccharide from Cryptococcus laurentii 70766 as an alternative for alginate for biomedical hydrogels.

Alginates are widely used polysaccharides for biomaterials engineering, which functional properties depend on guluronic and mannuronic acid as the building blocks. In this study, enzymatically crosslinked hydrogels based on sodium alginate (Na-Alg) and the exopolysaccharide (EPS) derived from Cryptococcus laurentii 70766 with glucuronic acid residues were synthesized and characterized as a new potential source of polysaccharide for biomaterials engineering. The EPS was extracted (1.05 ± 0.57 g/L) through ethanol precipitation. Then the EPS and Na-Alg were functionalized with tyramine hydrochloride to produce enzymatically crosslinked hydrogels in the presence of horseradish peroxidase (HRP) and H2O2. Major characteristics of the hydrogels such as gelling time, swelling ratio, rheology, cell viability, and biodegradability were studied. The swelling ratio and degradation profile of both hydrogels showed negative values, indicating an increased crosslinking degree and a lower water uptake percentage. The EPS hydrogel showed similar gelation kinetics compared to the Alg hydrogel. The EPS and its hydrogel were found cytocompatible. The results indicate the potential of EPS from C. laurentii 70766 for biomedical engineering due to its biocompatibility and degradability. Further studies are needed to confirm this EPS as an alternative for Alg in tissue engineering applications, particularly in the development of wound dressing products.

Bacterial Polyglucuronic Acid/Alginate/Carbon Nanofibers Hydrogel Nanocomposite as a Potential Scaffold for Bone Tissue Engineering.

3D nanocomposite scaffolds have attracted significant attention in bone tissue engineering applications. In the current study, we fabricated a 3D nanocomposite scaffold based on a bacterial polyglucuronic acid (PGU) and sodium alginate (Alg) composite with carbon nanofibers (CNFs) as the bone tissue engineering scaffold. The CNFs were obtained from electrospun polyacrylonitrile nanofibers through heat treatment. The fabricated CNFs were incorporated into a PGU/Alg polymeric solution, which was physically cross-linked using CaCl2 solution. The fabricated nanocomposites were characterized to evaluate the internal structure, porosity, swelling kinetics, hemocompatibility, and cytocompatibility. The characterizations indicated that the nanocomposites have a porous structure with interconnected pores architecture, proper water absorption, and retention characteristics. The in vitro studies revealed that the nanocomposites were hemocompatible with negligible hemolysis induction. The cell viability assessment showed that the nanocomposites were biocompatible and supported bone cell growth. These results indicated that the fabricated bacterial PGU/Alg/CNFs hydrogel nanocomposite exhibited appropriate properties and can be considered a new biomaterial for bone tissue engineering scaffolds.

Fungal exopolysaccharides: Properties, sources, modifications, and biomedical applications.

Fungal exopolysaccharides (EPSs) are natural biopolymers with diverse potential applications in the biomedical, packaging, cosmetic, and food industries. Fungal EPSs are easy to extract and purify polysaccharides that are biodegradable, biocompatible, with low immunogenicity, bioadhesion ability, antibacterial activity, and contain different reactive groups such as hydroxyl, carboxyl, and amine for chemical modifications. Despite fast progress in identifying and characterization fungal EPSs for biomedical applications, i.e., wound healing, drug, and gene delivery, only a few products have been commercialized based on fungal EPSs. This review critically discusses potential biomedical applications of fungi sourced EPSs in tissue engineering (TE), drug and gene delivery.

Evaluation of anti-tumor effect of the exopolysaccharide from new cold-adapted yeast, Rhodotorula mucilaginosa sp. GUMS16 on chronic myeloid leukemia K562 cell line.

Recently, the development and application of fungal exopolysaccharides (EPS) as natural biopolymers are on the rise. The present study is based on the investigation of possible antiproliferative and antioxidant activities of EPS from the Rhodotorula mucilaginosa sp. GUMS16 on BCR-ABL positive cells (K562). The cytotoxicity, colony formation assays lactate and dehydrogenase (LDH) activity were performed to assess the possible cancer cell death. To elucidate the underlying antiproliferative mechanism of the EPS, cell cycle analysis following real-time PCR (gene expression assessment) were evaluated. The results indicated that, the EPS with an IC50 dose of 1500 µg/ml, reduced the viability of K562 cells without having toxic effects on normal cells as well as decrease in size and number of colonies in EPS-treated group (p < 0.0001). The increase of LDH was 2.75 times more than the control (p < 0.0001). Gene expression revealed up- and down-regulation of apoptotic and anti-apoptotic genes in EPS group compared with the control. Moreover, the DPPH scavenging activity of the EPS in treated cells was significantly higher than the control group (p < 0.0001). Taken together, we concluded that the EPS from GUMS16 strain is able to inhibit the growth of K562 cells besides having antioxidant activities.