The Three-Dimensional In Vitro Cell Culture Models in the Study of Oral Cancer Immune Microenvironment.

The onset and progression of oral cancer are accompanied by a dynamic interaction with the host immune system, and the immune cells within the tumor microenvironment play a pivotal role in the development of the tumor. By exploring the cellular immunity of oral cancer, we can gain insight into the contribution of both tumor cells and immune cells to tumorigenesis. This understanding is crucial for developing effective immunotherapeutic strategies to combat oral cancer. Studies of cancer immunology present unique challenges in terms of modeling due to the extraordinary complexity of the immune system. With its multitude of cellular components, each with distinct subtypes and various activation states, the immune system interacts with cancer cells and other components of the tumor, ultimately shaping the course of the disease. Conventional two-dimensional (2D) culture methods fall short of capturing these intricate cellular interactions. Mouse models enable us to learn about tumor biology in complicated and dynamic physiological systems but have limitations as the murine immune system differs significantly from that of humans. In light of these challenges, three-dimensional (3D) culture systems offer an alternative approach to studying cancer immunology and filling the existing gaps in available models. These 3D culture models provide a means to investigate complex cellular interactions that are difficult to replicate in 2D cultures. The direct study of the interaction between immune cells and cancer cells of human origin offers a more relevant and representative platform compared to mouse models, enabling advancements in our understanding of cancer immunology. This review explores commonly used 3D culture models and highlights their significant contributions to expanding our knowledge of cancer immunology. By harnessing the power of 3D culture systems, we can unlock new insights that pave the way for improved strategies in the battle against oral cancer.

Current and Novel Emerging Medical Therapies for Peripheral Artery Disease: A Literature Review.

Despite the improvements in endovascular techniques during the last decades, there is still an increase in the prevalence of peripheral artery disease (PAD) with limited practical treatment, which timeline impact of any intervention for critical limb ischemia (CLI) is poor. Most common treatments are not suitable for many patients due to their underlying diseases, including aging and diabetes. On the one hand, there are limitations for current therapies due to the contraindications of some individuals, and on the other hand, there are many side effects caused by common medications, for instance, anticoagulants. Therefore, novel treatment strategies like regenerative medicine, cell-based therapies, Nano-therapy, gene therapy, and targeted therapy, besides other traditional drugs combination therapy for PAD, are newly considered promising therapy. Genetic material encoding for specific proteins concludes with a potential future for developed treatments. Novel approaches for therapeutic angiogenesis directly used the angiogenetic factors originating from key biomolecules such as genes, proteins, or cell-based therapy to induce blood vessel formation in adult tissues to initiate the recovery process in the ischemic limb. As PAD is associated with high mortality and morbidity of patients causing disability, considering the limited treatment choices for these patients, developing new treatment strategies to prevent PAD progression and extending life expectancy, and preventing threatening complications is urgently needed. This review aims to introduce the current and the novel strategies for PAD treatment that lead to new challenges for relief the patient's suffered from the disorder.

Strategies and Challenges in the Treatment of Dental Enamel.

Enamel tissue, the hardest body tissue, which covers the outside of the tooth shields the living tissue, but it erodes and disintegrates in the acidic environment of the oral cavity. On the one hand, mature enamel is cell-free and, if damaged, does not regenerate. Tooth sensitivity and decay are caused by enamel loss. On the other hand, the tissue engineering approach is challenging because of the unique structure of tooth enamel. To develop an exemplary method for dental enamel rebuilding, accurate knowledge of the structure of tooth enamel, knowing how it is created and how proteins interact in its structure, is critical. Furthermore, novel techniques in tissue engineering for using stem cells to develop enamel must be established. This article aims to discuss current attempts to regenerate enamel using synthetic materials methods, recent advances in enamel tissue engineering, and the prospects of enamel biomimetics to find unique insights into future possibilities for repairing enamel tissue, perhaps the most fascinating of all tooth tissues.

Potential applications of medicinal herbs and phytochemicals in oral and dental health: Status quo and future perspectives.

OBJECTIVE: Herbal therapies are utilized to treat a broad diversity of diseases all over the globe. Although no clinical studies have been conducted to demonstrate the antibacterial, antimicrobial, and antiplaque characteristics of these plants, this does not imply that they are ineffectual as periodontal treatments or anti-cariogenic drugs. However, there is a scarcity of research confirming their efficacy and worth. SUBJECT: Herbs are utilized in dentistry as antimicrobial, antineoplastic, antiseptic, antioxidant, and analgesics agents as well as for the elimination of bad breath. In addition, the application of herbal agents in tissue engineering improved the regeneration of oral and dental tissues. This study reviews the application of medicinal herbs for the treatment of dental and oral diseases in different aspects. METHODS: This article focuses on current developments in the use of medicinal herbs and phytochemicals in oral and dental health. An extensive literature review was conducted via an Internet database, mostly PubMed. The articles included full-text publications written in English without any restrictions on a date. CONCLUSION: Plants have been suggested, as an alternate remedy for oral-dental problems, and this vocation needs long-term dependability. More research on herbal medicine potential as pharmaceutical sources and/or therapies is needed.

Preparation of rutin-loaded mesoporous silica nanoparticles and evaluation of its physicochemical, anticancer, and antibacterial properties.

BACKGROUND: The studies have shown that rutin has great potential as an anticancer and antimicrobial plant base agent; nevertheless, poor bioavailability and low aqueous solubility of rutin limit its application. One of the beneficial routes to increase the solubility and bioavailability of rutin is the development of nanoparticulate material. This study aimed to assess the anticancer and antibacterial effects of rutin-loaded mesoporous silica nanoparticles (RUT-MSNs). METHODS: RUT-MSNs were prepared and physicochemically characterized. The cytotoxicity of RUT-MSNs on the HN5 cells as head and neck cancer cells was evaluated. The expression level of apoptosis-related genes such as Bcl-2 and Bax genes were evaluated. In addition, ROS production of RUT-MSNs treated cells was assessed. In addition, minimum inhibitory concentration (MIC), biofilm, and attachment inhibitory effects of RUT-MSNs compared with free rutin were assessed against different bacterial strains. RESULTS: Transmission electron microscopy (TEM) showed mesoporous rod-shaped nanoparticles with an average particle size of less than 100 nm. RUT-MSNs displayed the cytotoxic effect with IC50 of 20.23 µM in 48 h of incubation time (p < 0.05). The elevation in the ratio of Bax/Bcl-2 was displayed within the IC50 concentration of RUT-MSNs in 48 h (p < 0.05). The antibacterial action of rutin was improved by loading rutin in MSNs to the nano-sized range in the MIC test. CONCLUSION: The anticancer and antibacterial effects of RUT-MSNs were considerably more than rutin. RUT-MSNs inhibited the growth of HN5 cells by inducing apoptosis and producing ROS. These results suggest that RUT-MSNs may be useful in the treatment of cancers and infections.

Effect of Curcumin-Loaded Mesoporous Silica Nanoparticles on the Head and Neck Cancer Cell Line, HN5.

Curcumin is an active ingredient isolated from Curcuma longa. It has several pharmacological effects, including anticancer, anti-inflammatory, and antioxidant effects. Due to its low bioavailability, chemical structure instability, and easy oxidation, the application of curcumin has been limited. In this study, to overcome these limitations, curcumin-loaded mesoporous silica nanoparticles (Cur-MSN) were prepared, and the anticancerous effect of Cur-MSNs on head and neck cancer cells, HN5, was investigated. Transmission electron microscopy (TEM) revealed rod-shaped mesoporous nanoparticles with average particle size smaller than 100 nm. Higher cytotoxicity of Cur-MSNs was seen in treated cancer cells compared with free curcumin. The expression of Bcl-2 was significantly reduced in the presence of Cur-MSNs compared to the control (untreated HN5 cells) (p < 0.05). A 3.43-fold increase in the Bax/Bcl-2 ratio was seen in Cur-MSNs treated HN5 cells at the IC50. Cur-MSNs increased intracellular reactive oxygen species (ROS) production. Based on these novel results, we suggest that Cur-MSNs offer efficacy for cancer treatment and future studies should further characterize their properties in various experimental cancer models.

Cell homing strategy as a promising approach to the vitality of pulp-dentin complexes in endodontic therapy: focus on potential biomaterials.

INTRODUCTION: Over the last two decades, an increasing body of research suggests that well-designed biomaterials can attract resident stem cells to injured areas and control their behaviors and activities to encourage tissue regeneration. Fabricated biomaterials can enhance cell recruitment, multiplication, and transformation while also acting as a delivery system for targeted cells. These capabilities might play a role in their ability to promote tooth regeneration. AREAS COVERED: This review aims to introduce the various materials used in endodontics. The potential of biomaterial-based approaches involved in cell homing for endodontics is also discussed. EXPERT OPINION: Applying the cell homing technique in restorative dentistry can affect various aspects of healthcare, industry, economy, and science. Biomaterial scaffolds can be used to encapsulate cells or for structural replacements. Also, both cell transplantation and cell homing are legitimate scientific procedures in endodontic therapy. Although the suggested biomaterials and procedures may hold promise for future dental pulp tissue regeneration, tooth structure's complexity and multicellular interconnections lead to significant problems that need to be overcome before any clinical trial.

A Biodegradable Flexible Micro/Nano-Structured Porous Hemostatic Dental Sponge.

A biodegradable micro/nano-structured porous hemostatic gelatin-based sponge as a dentistry surgery foam was prepared using a freeze-drying method. In vitro function evaluation tests were performed to ensure its hemostatic effect. Biocompatibility tests were also performed to show the compatibility of the sponge on human fetal foreskin fibroblasts (HFFF2) cells and red blood cells (RBCs). Then, 10 patients who required the extraction of two teeth were selected, and after teeth extraction, for dressing, the produced sponge was placed in one of the extracavities while a commercial sponge was placed in the cavity in the other tooth as a control. The total weight of the absorbed blood in each group was compared. The results showed a porous structure with micrometric and nanometric pores, flexibility, a two-week range for degradation, and an ability to absorb blood 35 times its weight in vitro. The prepared sponge showed lower blood clotting times (BCTs) (243.33 ± 2.35 s) and a lower blood clotting index (BCI) (10.67 ± 0.004%) compared to two commercial sponges that displayed its ability for faster coagulation and good hemostatic function. It also had no toxic effects on the HFFF2 cells and RBCs. The clinical assessment showed a better ability of blood absorption for the produced sponge (p-value = 0.0015). The sponge is recommended for use in dental surgeries because of its outstanding abilities.

Synthetic electrospun nanofibers as a supportive matrix in osteogenic differentiation of induced pluripotent stem cells.

Continuous remodeling is not able to repair large bone defects. Bone tissue engineering is aimed to repair these defects by creating bone grafts. To do this, several technologies and biomaterials have been employed to fabricate an in vivo-like supportive matrix. Electrospinning is a versatile technique to fabricate porous matrices with interconnected pores and high surface area, replicating in vivo microenvironment. Electrospun scaffolds have been used in a large number of studies to provide a matrix for bone regeneration and osteogenic differentiation of stem cells such as induced pluripotent stem cells (iPSCs). Electrospinning uses both natural and synthetic polymers, either alone or in combination, to fabricate scaffolds. Among them, synthetic polymers have had a great promise in bone regeneration and repair. They allow the fabrication of biocompatible and biodegradable scaffolds with high mechanical properties, suitable for bone engineering. Furthermore, several attempts have done to increase the osteogenic properties of these scaffolds. This paper reviewed the potential of synthetic electrospun scaffolds in osteogenic differentiation of iPSCs. In addition, the approaches to improve the osteogenic differentiation of these scaffolds are addressed.

The Role of Cytokines in Nephrotic Syndrome.

Idiopathic nephrotic syndrome (INS) is an important primary glomerular disease characterized by severe proteinuria. Evidence supports a role for T cell dysfunction in the pathogenesis of INS. Glucocorticoids are the primary therapy for INS; however, steroid-resistant NS (SRNS) patients are at a higher risk of drug-induced side effects and harbor poor prognosis. Although the exact mechanism of the resistance is unknown, the imbalances of T helper subtype 1 (Th1), Th2, and regulatory T cells (Tregs) and their cytokines may be involved in the pathogenesis of glucocorticoid responsiveness. Up to now, no confirmed biomarkers have been able to predict SRNS; however, a panel of cytokines may predict responsiveness and identify SRNS patients. Thus, the introduction of distinctive cytokines as novel biomarkers of SRNS enables both preventions of drug-related toxicity and earlier switch to more effective therapies. This review highlights the impacts of T cell population imbalances and their downstream cytokines on response to glucocorticoid responsiveness state in INS.

Curcumin nanoformulations: Beneficial nanomedicine against cancer.

Curcumin is a phytochemical achieved from the plant turmeric. It is extensively utilized for the treatment of several types of diseases such as cancers. Nevertheless, its efficiency has been limited because of rapid metabolism, low bioavailability, poor water solubility, and systemic elimination. Scientists have tried to solve these problems by exploring novel drug delivery systems such as lipid-based nanoparticles (NPs) (e.g., solid lipid NPs, nanostructured lipid carriers, and liposomes), polymeric NPs, micelles, nanogels, cyclodextrin, gold, and mesoporous silica NPs. Among these, liposomes have been the most expansively studied. This review mainly focuses on the different curcumin nanoformulations and their use in cancer therapy in vitro, in vivo, and clinical studies. Despite the development of curcumin-containing NPs for the treatment of cancer, potentially serious side effects, including interactions with other drugs, some toxicity aspects of NPs may occur that require more high-quality investigations to firmly establish the clinical efficacy.

The Antimicrobial, Antioxidative, and Anti-Inflammatory Effects of Polycaprolactone/Gelatin Scaffolds Containing Chrysin for Regenerative Endodontic Purposes.

The appropriate endodontic material should eliminate the infection and inflammation to provide a situation for regeneration and healing of pulp tissue besides biomineralization. Chrysin is one of the active ingredients of plant flavonoids, which has significant anti-inflammatory and antimicrobial properties. In the present study, this natural substance was evaluated for antioxidant, anti-inflammatory, and mineralization properties on dental pulp stem cells (DPSCs). SEM, FTIR, and TGA tests were used to determine the successful synthesize of chrysin-loaded scaffolds. The antimicrobial effects of the synthesized scaffold against Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis were assessed by the agar diffusion test and live/dead assay. The proliferation of DPSCs on these scaffolds was determined by the MTT assay, DAPI staining, and DNA extraction. Moreover, the antioxidant and anti-inflammation activity of chrysin-loaded scaffolds on inflamed DPSCs was evaluated. Alkaline phosphatase activity and Alizarin Red S Stain tests were done to evaluate the mineralization of DPSCs seeded on these scaffolds. The chrysin-loaded scaffolds reported antimicrobial effects against evaluated bacterial strains. The proliferation of DPSCs seeded on these scaffolds was increased significantly (p < 0.05). The TNFα and DCF levels in inflamed DPSCs showed a significant decrease in the presence of chrysin-loaded scaffolds (p < 0.05). The ALP activity and formation of mineralized nodules of DPSCs on these scaffolds were significantly increased compared with the control group (p < 0.05). These results indicated that chrysin as an ancient therapeutic agent can accelerate the healing and regeneration of damaged pulp tissue, and this active ingredient can be a potential natural substance for regenerative endodontic procedures.

Targeted combined therapy in 2D and 3D cultured MCF-7 cells using metformin and erlotinib-loaded mesoporous silica magnetic nanoparticles.

AIM: This research aims to develop potential therapeutic nanostructures (NSs) encapsulating metformin (MET) and erlotinib (ER) for combinational therapy in breast cancer. METHODS: The ER and MET, both were loaded on mesoporous silica magnetic nanoparticles conjugated with polyethylene glycol and methotrexate to achieve targeted NSs. The developed NSs were characterised using SEM, DLS, and FTIR. Afterward, MTT, Trypan blue, and DNA extraction assays were operated for biological evaluations in the 2D and 3D MCF-7 cells. RESULTS: Physicochemical approaches indicated the mean diameter of 69.4 nm ± 9.5 (PDI = 0.64), and neutral charge (2 mv) for the developed NSs. MET and ER-loaded NSs exhibited 62.56% ± 4.41 and 67.73% ± 3.03 drug release amount in pH = 5.4, respectively. MTT assay revealed that ER- and MET-loaded NSs had less metabolic activity (≈ 20%) in comparison with non-targeted NSs. CONCLUSION: Overall, our combined ER and MET-loaded targeted NSs result in a synergistic inhibitory impact on MCF-7 cells.

Osteogenic Differentiation of Mesenchymal Stem Cells via Curcumin-Containing Nanoscaffolds.

The diverse pleiotropic pharmacological effects of curcumin nanoformulations have turned it into an attractive natural compound in different health-related problems. A great body of evidence has shown the impact of curcumin and its nanoformulations on the differentiation of stem cells. The current review highlights cellular and molecular mechanisms connected with the osteogenic differentiation of mesenchymal stem cells (MSCs) in the scaffolds benefiting from the presence of nanocurcumin pointing toward the role of inhibitory or stimulant signal transduction pathways in detail. Moreover, the effects of different concentrations as well as the structural modifications of curcumin on the differentiation of MSCs have been addressed.

Role of cellulose family in fibril organization of collagen for forming 3D cancer spheroids: In vitro and in silico approach.

Introduction: Cell aggregation of three-dimensional (3D) culture systems (the so-called spheroids) are designed as in vitro platform to represent more accurately the in vivo environment for drug discovery by using semi-solid media. The uniform multicellular tumor spheroids can be generated based on the interaction of cells with extracellular matrix (ECM) macromolecules such as collagen and integrin. This study aimed to investigate the possible interactions between the cellulose family and collagen using both in vitro and in silico approaches. Methods: The 3D microtissue of JIMT-1 cells was generated using hanging drop method to study the effects of charge and viscosity of the medium containing cellulose family. To determine the mode of interaction between cellulose derivatives (CDs) and collagen-integrin, docking analysis and molecular simulation were further performed using open source web servers and chemical simulations (GROMACS), respectively. Results: The results confirmed that the addition of CDs into the 3D medium can promote the formation of solid spheroids, where methylcellulose (MC) yielded uniform spheroids compared to carboxymethyl cellulose (CMC). Moreover, the computational analysis showed that MC interacted with both integrin and collagen, while sodium carboxymethyl cellulose (NaCMC) only interacted with collagen residues. The stated different behaviors in the 3D culture formation and collagen interaction were found in the physicochemical properties of CDs. Conclusion: Based on in vitro and in silico findings, MC is suggested as an important ECM-mimicking entity that can support the semi-solid medium and promote the formation of the uniform spheroid in the 3D culture.

Prominent roles of microRNA-142 in cancer.

MicroRNAs (miRNAs) are single-stranded non-coding RNAs that regulate gene expression post-transcriptionally via mRNA degradation, or translational repression. They have important roles in normal development and homeostasis maintenance. Many studies have revealed that aberrant expression of miRNAs is associated with development of pathological conditions, including cancers. MiRNAs can either promote or suppress tumorigenesis based on the regulation of gene expression by targeting multiple molecules. In recent years, several miRNAs have been reported to be dysregulated in various cancers. Most recent findings have shown that miR-142 gene, located at chromosome 17q22, is involved in cellular migration, proliferation, and apoptosis in different human cancers. The present review discusses some molecular mechanisms and the expression status of miRNA-142 in the pathogenesis of various cancers.

Gelatin-hydroxyapatite nano-fibers as promising scaffolds for guided tissue regeneration (GTR): Preparation, assessment of the physicochemical properties and the effect on mesenchymal stem cells.

Background: Periodontitis can lead to progressive destruction of periodontal tissues supporting the tooth. Developing biomaterials for tissue engineering has noticeably improved the existing treatment options. The present study investigated the gelatin-hydroxyapatite nano-fibers as promising scaffolds for guided tissue regeneration (GTR). Methods: The scaffolds were prepared through electrospinning technique, and then the physicochemical properties and the cytotoxic effects on dental-derived mesenchymal stem cells were assessed. Results: The nano-scaffolds were successfully prepared with a mono-dispersed nano-scale diameter (102±0.10 nm), negative surface charge (-20±0.17 mV), and uniform network-shaped morphology. The mesenchymal stem cells derived from the human dental pulp stem cells (hDPSC) with gelatin-hydroxyapatite nano-fibers showed that the prepared scaffolds had a significant proliferative effect. Besides, the applied method can be used to prepare fiber-based structures via other polymeric materials. Conclusion: The incorporation of different materials to decrease the degradation rate of the fibers can match the speed of tissue regeneration. In this case, the prepared nano-fibers can be applied as a membrane biomaterial.

Fucosylated umbilical cord blood hematopoietic stem cell expansion on selectin-coated scaffolds.

Despite the advantages of transplantation of umbilical cord blood's (UCB's) hematopoietic stem cells (uHSCs) for hematologic malignancy treatment, there are two major challenges in using them: (a) Insufficient amount of uHSCs in a UCB unit; (b) a defect in uHSCs homing to bone marrow (BM) due to loose binding of their surface glycan ligands to BM's endothelium selectin receptors. To overcome these limitations, after poly l-lactic acid (PLLA) scaffold establishment and incubation of uHSCs with fucosyltransferase-VI and GDP-fucose, ex vivo expansion of these cells on selectin-coated scaffold was done. The characteristics of the cultured fucosylated and nonfucosylated cells on a two-dimensional culture system, PLLA, and a selectin-coated scaffold were evaluated by flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony-forming unit (CFU) assay, and CXCR4 expression at the messenger RNA and protein levels. According to the findings of this study, optimized attachment to the scaffold in scanning electron microscopy micrograph, maximum count of CFU, and the highest 570 nm absorption were observed in fucosylated cells expanded on selectin-coated scaffolds. Furthermore, real-time polymerase chain reaction showed the highest expression of the CXCR4 gene, and immunocytochemistry data confirmed that the CXCR4 protein was functional in this group compared with the other groups. Considered together, the results showed that selectin-coated scaffold could be a supportive structure for fucosylated uHSC expansion and homing by nanotopography. Fucosylated cells placed on the selectin-coated scaffold serve as a basal surface for cell-cell interaction and more homing potential of uHSCs. Accordingly, this procedure can also be considered as a promising technique for the hematological disorder treatment and tissue engineering applications.

ABC-transporter blockage mediated by xanthotoxin and bergapten is the major pathway for chemosensitization of multidrug-resistant cancer cells.

Furanocoumarins derived from herbal and citrus extracts can act as antibacterial, antioxidant, immunomodulator, apoptotic, and selective anticancer agents, prompting a biological investigation to determine and predict their clinical therapeutic significance. Here, the cell cytotoxic effects of bergapten and xanthotoxin were analyzed alone and in combination with standard chemotherapeutics on three multidrug resistant cells and their nonresistant parental counterparts. The furanocoumarins modulatory effects on MDR1, BCRP, and MRP pump expression and function were investigated. Although quantitative real time PCR demonstrated that the MDR transcript level changes in a time dependent manner, flow cytometric analyses using fluorescent-labeled antibodies have indicated that bergapten and xanthotoxin had no significant effect on the protein levels. FACS analyses indicated that these prominent anticancer agents significantly blocked MDR1, BCRP, and MRP transporter function. Maximum furanocoumarin-mediated pump activity blockage in the MDR-resistant cells was quantified as 87% of normal and consequently, chemotherapeutic accumulation increased up to 2.7-fold and cytotoxicity tension increased 104-fold. MDR1 efflux kinetics also revealed that the maximum velocity and the pump affinity to daunorubicin were uncompetitively decreased. We conclude that bergapten and xanthotoxin are cytotoxic agents capable of preventing daunorubicin, mitoxantrone, and cisplatin binding to ABC-transporters and subsequently inhibiting their efflux out of cells and they may be a potential combination therapy for malignant cancers.

The effect of pioglitazone on weight, lipid profile and liver enzymes in type 2 diabetic patients.

BACKGROUND: Pioglitazone is one of the antidiabetic agents used in the management of type 2 diabetes mellitus (DM). The effect of pioglitazone on blood glucose, lipid profile, liver enzymes and weight has been shown with conflicting results. In this study we aim to evaluate the effect of pioglitazone on the weight, lipid profile and liver enzymes in patients with DM. METHODS: In this single-arm clinical trial, 110 poorly controlled diabetic type 2 patients (63.6% female with mean age of 54.26 ± 8.96 years) who were on maximal dosage of metformin and glibenclamide were enrolled. Patients were treated with pioglitazone for 3 months and laboratory. Fasting blood sugar (FBS), haemoglobin A1C (HbA1C), cholesterol, triglyceride, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), alkaline phosphatase (ALK-P), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and weight changes were measured before and at the end of the study. RESULTS: The levels of FBS (p < 0.001), HbA1c (p < 0.001), triglyceride (p = 0.001), ALT (p = 0.005) and ALK-P (p = 0.001) were significantly decreased, but weight was significantly increased (p < 0.001) after the intervention. There were no significant difference in cholesterol, LDL and HDL values before and after study. CONCLUSION: Although pioglitazone causes a significant decrease in FBS, HbA1C and triglyceride levels, it is associated with weight gain, which would limit its utility. IRCT registration code: IRCT201209276712N2.