Histomorphometrical evaluation of extensor digitorum longus muscle in sciatic nerve regeneration using tissue engineering in rats.

Skeletal muscle atrophy induced by denervation is one of the common disorders in traumatic nerve injuries. The aim of this study was the evaluation of histomorphometrical changes of extensor digitorum longus muscle after denervation and its regeneration by tissue engineering. Ninety adult male Wistar rats were randomly divided into six main groups (n = 15) in three time periods (2, 4 and 8 weeks; n = 5). Control group was treated without surgery, in transection (Tr) group left sciatic nerve was transected, in scaffold (S) group only collagen gel scaffold was used, in mast cell (MC) group mast cells were used, mesenchymal stem cell (MSC) group was treated with mesenchymal stem cells and in MC+MSC group, mast cells along with mesenchymal stem cells were used. In the cellular groups, the scaffold and cells were mixed and placed in the transected nerve gap. The average diameter of muscle fibers, ratio of the muscle fibers nuclei to the fibrocytes nuclei (mn/fn), ratio of the muscle fibers nuclei number to the muscle fibers number (mn/mf), the average ratio of blood vessels to muscle fibers number (v/mf) and muscles weight in Tr group were the lowest compared to the other groups; but, in cellular and S groups, amelioration was observed according to the time period. However, in MC+MSC group, there were the highest ameliorative results. This study revealed that simultaneous use of MCs and MSCs mixed with collagen gel scaffold can be considered as a suitable approach to improve denervated skeletal muscle atrophy associated with sciatic nerve injury.

Protective effect of ethyl pyruvate on testicular histology and fertilization potential in cyclophosphamide treated mice.

In the present study, we aimed to address the use of ethyl pyruvate (EP) against the harmful effects of cyclophosphamide (CP) treatment. Thirty-nine adult male mice were divided into three groups including control group received normal saline [0.20 mL per day; intraperitoneally (IP)], CP group received CP (15.00 mg kg-1 per week, IP) and CP+EP group received EP (40.00 mg kg-1 per day, IP) along with CP and treated for 35 days. After preparation of paraffin sections and Hematoxylin and Eosin staining, the histomorphometric studies were performed on the testicular tissue. Additionally, the serum superoxide dismutase (SOD) and testosterone level, testis malondialdehyde (MDA) and in vitro fertilization rate were assessed. The results showed an increase in the tubal differentiation index, repopulation index, spermiogenesis index, thickness of testicular capsule, mean distribution of active Sertoli cells, SOD and testosterone levels of the CP+EP group in comparison with the CP group. Moreover, the MDA levels in the CP+EP group were lower than the CP group. An increase occurred in the percentage of fertilization in the CP+EP group compared to the CP group. Results of this study revealed that the EP ameliorates deleterious side effects of CP on testicular histology and in vitro fertility.

Nanomaterials for bone tissue regeneration: updates and future perspectives.

Joint replacement and bone reconstructive surgeries are on the rise globally. Current strategies for implants and bone regeneration are associated with poor integration and healing resulting in repeated surgeries. A multidisciplinary approach involving basic biological sciences, tissue engineering, regenerative medicine and clinical research is required to overcome this problem. Considering the nanostructured nature of bone, expertise and resources available through recent advancements in nanobiotechnology enable researchers to design and fabricate devices and drug delivery systems at the nanoscale to be more compatible with the bone tissue environment. The focus of this review is to present the recent progress made in the rationale and design of nanomaterials for tissue engineering and drug delivery relevant to bone regeneration.

Microparticles containing erlotinib-loaded solid lipid nanoparticles for treatment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) patients with sensitizing mutations in the exons 18-21 of the epithelial growth factor receptor (EGFR) gene show increased kinase activity of EGFR. Hence, tyrosine kinase inhibitors (TKIs) such as erlotinib (ETB) have commonly been used as the second line therapeutic option for the treatment of metastatic NSCLC. While the ETB is available as an oral dosage form, the local delivery of this TKI to the diseased cells of the lung may ameliorate its therapeutic impacts. In the current study, we report on the development of ETB-loaded solid lipid nanoparticle (SLN) based formulation of dry powder inhaler (ETB-SLN DPI). ETB-SLNs were formulated using designated amount of compritol/poloxamer 407. The engineered ETB-SLNs showed sub-100 nm spherical shape with an encapsulation efficiency of 78.21%. MTT assay and DAPI staining revealed that the ETB-SLNs enhanced the cytotoxicity of cargo drug molecules in the human alveolar adenocarcinoma epithelial A549 cells as a model for NSCLC. To attain the ETB-SLN DPI, the ETB-SLNs were efficiently spray dried into microparticles (1-5 µm) along with mannitol. The ETB-SLN DPI powder displayed suitable flowability and aerodynamic traits. The Carr's Index, Hausner ratio and Next Generation Impactor (NGI) analyses confirmed deep inhalation pattern of the formulation. Based on these findings, we propose the ETB-SLN DPI as a promising treatment modality for the NSCLC patients.

Ethyl Pyruvate Ameliorates The Damage Induced by Cyclophosphamide on Adult Mice Testes.

BACKGROUND: Cyclophosphamide (CP) is a chemotherapy drug which causes deleterious effects on testicular tissue and increases free radicals in the body. The aim of this study is to investigate the protective effects of ethyl pyruvate (EP) on testicular improvement in CP treated animals. MATERIALS AND METHODS: In this experimental study, 15 male mice (6-8 weeks) were divided into 3 groups. The control group received normal saline (0.1 ml/day), intraperitoneal (IP), CP group received CP (15 mg/kg/week, IP), and the CP+EP group received EP (40 mg/kg/day, IP) plus CP. After 35 days, we assessed serum total antioxidant capacity (TAC) along with histomorphometric and histochemical analyses of the testicles. RESULTS: The mean thickness of the germinal epithelium, diameter of seminiferous tubules, and the number of Leydig cells in the CP+EP group were higher than those of the CP group (P<0.05). The number of the mast cells in the CP+EP group significantly reduced compared with the CP group (P<0.05). Alkaline phosphatase (ALP), periodic acid-schiff (PAS) positive reactions and lipid granules in cytoplasm of the Leydig cells in the CP group increased compared with the other groups (P<0.05). TAC in the CP group significantly reduced compared with the other groups (P<0.05). CONCLUSION: This study showed the ability of EP to reduce the destructive side effects of CP in the adult mice reproductive system.

Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges.

Nanomedicine, the integration of nanotechnological tools in medicine demonstrated promising potential to revolutionize the diagnosis and treatment of various human health conditions. Nanoparticles (NPs) have shown much promise in diagnostics of cancer, especially since they can accommodate targeting molecules on their surface, which search for specific tumor cell receptors upon injection into the blood stream. This concentrates the NPs in the desired tumor location. Furthermore, such receptor-specific targeting may be exploited for detection of potential metastases in an early stage. Some NPs, such as superparamagnetic iron oxide NPs (SPIONs), are also compatible with magnetic resonance imaging (MRI), which makes their clinical translation and application rather easy and accessible for tumor imaging purposes. Furthermore, multifunctional and/or theranostic NPs can be used for simultaneous imaging of cancer and drug delivery. In this review article, we will specifically focus on the application of SPIONs in early detection and imaging of major cancer types. FROM THE CLINICAL EDITOR: Super-paramagnetic iron oxide nanoparticles (SPIONs) have been reported by many to be useful as an MRI contrast agent in the detection of tumors. To further enhance the tumor imaging, SPIONs can be coupled with tumor targeting motifs. In this article, the authors performed a comprehensive review on the current status of using targeted SPIONS in tumor detection and also the potential hurdles to overcome.

Protective effects of ethyl pyruvate on sperm quality in cyclophosphamide treated mice.

BACKGROUND: One of the affecting factors in disturbance process of spermatogenesis is chemotherapeutic-induced oxidative stress resulted from cyclophosphamide (CP) treatment which leads to diminished sperm quality via interference in spermatogenesis process. OBJECTIVE: This study was conducted to investigate the effects of ethyl pyruvate (EP) in reducing the CP-induced side effects on reproductive system. MATERIALS AND METHODS: 24 mature male mice were randomly divided into 3 equal groups and were undergone therapy for 35 days. Control group received normal saline (0.1 ml/day, IP). CP group were injected CP (15 mg/kg/week, IP) and CP+EP group received EP (40 mg/kg/day, IP) as well as CP. In the end of the treatment period, the mice were euthanized by cervical dislocation. Then, the epididymis was incubated with CO2 in a human tubal fluid medium (1 ml) for half an hour in order to float sperm. Then, the number, motility, viability (eosin-nigrosin staining), DNA breakage (acridine orange staining), nucleus maturity, and sperm morphology (aniline blue staining) were analyzed. RESULTS: The average (15.87±1.28), motility (35.77±2.75), viability (40±3.03), nucleus maturity (36±2.79) and sperm morphology (61.75±0.85) were decreased significantly in CP group in comparison with control and EP groups, whereas EP caused significant increase of these parameters. Also, the percentage of DNA damage was increased significantly in CP group (41.75±3.75) in comparison with control (2±0.71) and EP groups (22.5±4.13). CONCLUSION: The results of this study revealed ameliorating effects of EP on sperm quality of CP treated animals.

Protective effects of cornus mas extract on in vitro fertilization potential in methotrexate treated male mice.

Current study was aimed to evaluating protective effects of cornus mas fruit extract (CMFE) in mice treated with methotrexate (MTX). For this purpose, 48 young mature male mice were divided into 6 groups. Control group received only normal saline (0.1 mL per day, intraperitoneally), and the second group was administered MTX (20 mg kg(-1) per week, intraperitoneally). The third, fourth and fifth groups received MTX daily oral doses of 250, 500 and 1000 mg kg(-1) CMFE as well as MTX. The sixth group was only given CMFE with a dose of 1000 mg kg(-1) per day, orally, for 35 days. Then, the animals were anesthetically euthanized and the sperms were separated from epididymis. DNA damage level, the amount of malondialdehyde (MDA) as well as in vitro fertility was evaluated. The number of sperms with damaged DNA and MDA level in MTX-treated group showed a significant increase compared to control group (p < 0.05). In groups receiving CMFE along with MTX, DNA damage level and MDA amount suggested a decrease in comparison with MTX group (p < 0.05). Also, in vitro fertilization and embryonic development in MTX-treated group was significantly lower than the control group, and the level of embryonic arresting was higher (p < 0.05). In groups which received CMFE along with MTX, in vitro fertility and embryonic development was higher than MTX group (p < 0.05) and the arrested embryos showed a decrease. This study suggested that cornus mas is able to ameliorate the side effects of MTX.

Evaluation of antioxidant effects of crocin on sperm quality in cyclophosphamide treated adult mice.

Cyclophosphamide (CP) is one of the anti-neoplastic drugs. Despite its numerous clinical applications, it has devastating effects on the testicles and declines the sperm quality in treated patients. This study was aimed to investigate the protective effect of crocin in improving the toxicity induced by CP in reproductive system. In this study, 24 male adult mice (6 to 8 weeks) were randomly divided into three groups, control group received normal saline (0.1 mL, IP, daily), the CP group received CP (15 mg kg(-1), IP, weekly) and the CP + crocin group received CP along with crocin (200 mg kg(-1), IP, daily). After 35 days of treatment, animals were sacrificed. The samples of epididymis in human tubal fluid medium incubated for 30 min in 5% CO2 for flotation of sperm. Sperm were obtained from caudal epididymis using dissecting method. Then, the parameters of sperm quality including sperm count, motility, viability, DNA damage, nuclear maturation, and sperm morphology were evaluated. In CP group, the sperm count, motility, viability, nuclear maturation and sperm morphology were significantly decreased compared to control group (p < 0.05) and in the CP + crocin group all of these parameters significantly increased compared to CP group (p < 0.05). The percentage of sperm with DNA damage in the CP group significantly increased compared to other groups (p < 0.05). The results of this study indicated that the crocin was able to suppress free radicals and enhance the quality of sperm in CP treated animals.