Fabrication and evaluation of the regenerative effect of a polycaprolactone/chitosan nanofibrous scaffold containing bentonite nanoparticles in a rat model of deep second-degree burn injury.

Objectives: In the present study, we evaluated the effect of a nanofibrous scaffold including polycaprolactone (PCL), chitosan (CHT), and bentonite nanoparticles (Ben-NPS) on wound healing in order to introduce a novel dressing for burn wounds. Materials and Methods: PCL, PCL/CHT, and PCL/CHT/Ben-NPS nanofibrous scaffolds were fabricated by the electrospinning technique. Their structural and physiochemical characteristics were investigated by Fourier-transform infrared spectroscopy (FTIR) analysis, scanning electron microscopy (SEM), tensile strength, water contact angle, as well as, swelling and degradation profiles test. The disc diffusion assay was carried out to investigate the antibacterial potential of the scaffolds. In addition, the cell viability and proliferation ability of human dermal fibroblasts (HDFs) on the scaffolds were assessed using MTT assay as well as SEM imaging. The wound-healing property of the nanofibrous scaffolds was evaluated by histopathological investigations during 3,7, and 14 days in a rat model of burn wounds. Results: SEM showed that all scaffolds had three-dimensional, beadles-integrated structures. Adding Ben-NPS into the PCL/CHT polymeric composite significantly enhanced the mechanical, swelling, and antibacterial properties. HDFs had the most cell viability and proliferation values on the PCL/CHT/Ben-NPS scaffold. Histopathological evaluation in the rat model revealed that dressing animal wounds with the PCL/CHT/Ben-NPS scaffold promotes wound healing. Conclusion: The PCL/CHT/Ben-NPS scaffold has promising regenerative properties for accelerating skin wound healing.

Preparation and evaluation of a polycaprolactone/chitosan/propolis fibrous nanocomposite scaffold as a tissue engineering skin substitute.

Introduction: Recently, the application of nanofibrous mats for dressing skin wounds has received great attention. In this study, we aimed to fabricate and characterize an electrospun nanofibrous mat containing polycaprolactone (PCL), chitosan (CTS), and propolis for use as a tissue-engineered skin substitute. Methods: Raw propolis was extracted, and its phenolic and flavonoid contents were measured. The physiochemical and biological properties of the fabricated mats, including PCL, PCL/CTS, and PCL/CTS/Propolis were evaluated by scanning electron microscopy (SEM), atomic force microscopy (AFM), mechanical analysis, swelling and degradation behaviors, contact angle measurement, cell attachment, DAPI staining, and MTT assay. On the other hand, the drug release pattern of propolis from the PCL/CTS/Propolis scaffold was determined. A deep second-degree burn wound model was induced in rats to investigate wound healing using macroscopical and histopathological evaluations. Results: The results revealed that the propolis extract contained high amounts of phenolic and flavonoid compounds. The fabricated scaffold had suitable physicochemical and mechanical properties. Uniform, bead-free, and well-branched fibers were observed in SEM images of mats. AFM analysis indicated that the addition of CTS and propolis to PCL elevated the surface roughness. MTT results revealed that the electrospun PCL/CTS/Propolis mat was biocompatible. The presence of fibroblast cells on the PCL/CTS/Propolis mats was confirmed by DAPI staining and SEM images. Also, propolis was sustainably released from the PCL/CTS/Propolis mat. The animal study revealed that addition of propolis significantly improved wound healing. Conclusion: The nanofibrous PCL/CTS/Propolis mat can be applied as a tissue-engineered skin substitute for healing cutaneous wounds, such as burn wounds.

Efficacy of Mesenchymal Stem Cells Therapy in Parasitic Infections: Are Anti-parasitic Drugs Combined with MSCs More Effective?

PURPOSE: Mesenchymal stem cells (MSCs) are mesodermal-origin postnatal stem cells that are able to self-renew and differentiate into several cell lineages. MSCs possess anti-inflammatory and anti-apoptotic activity, immunomodulatory action, as well as regenerative properties. Since MSCs also have antimicrobial properties, it has been suggested that they should be utilized for treating infectious diseases. In this study, the last pre-clinical advances in the efficacy of MSCs' therapy against parasitic diseases were reviewed. METHODS: Data about the effects of MSCs' therapy on experimental and pre-clinical parasitic infections were collected by searching relevant articles and reviewing them. RESULTS: In the present study, empirical findings on the impacts of MSCs' therapy against parasitic diseases were recapitulated. Studies have reported that the administration of MSCs reduces the burden of the parasite and modulates the levels of inflammatory and anti-inflammatory cytokines in parasitic diseases, including schistosomiasis, malaria, cystic echinococcosis, toxocariasis, leishmaniasis, and trypanosomiasis. Also, the administration of MSCs combined with anti-parasitic drugs enhanced anti-parasitic effects and immunomodulatory actions. CONCLUSION: Based on this review, empirical studies have revealed the beneficial effects of MSCs against some parasitic infections. This new therapeutic strategy showed both anti-parasitic and immunomodulatory effects. Also, the combination of anti-parasitic drugs with MSCs' therapy promoted anti-parasitic and immunomodulatory activities against parasitic infections.

Long-term intake of aspartame-induced cardiovascular toxicity is reflected in altered histochemical parameters, evokes oxidative stress, and trigger P53-dependent apoptosis in a mouse model.

Aspartame (ASP) is probably the best known artificial sugar substitute that is used widely in food. Many experimental studies have reported the toxicity of long-term administration of ASP in various organ tissues. However, there is little evidence available about the nature and mechanisms of the adverse effects of long-term consumption of ASP on the cardiovascular system. This study was conducted to evaluate the possible effects of ASP on heart tissue. For this study 36 mature male mice were divided into one control group and three groups which received respectively 40 mg/kg, 80 mg/kg and 160 mg/kg ASP orally, for 90 days. ASP at the doses of 80 and 160 mg/kg increased the serum content of malondialdehyde (MDA), but decreased serum nitric oxide (NO), creatine kinase (CK) and CK-MB, as well as blood superoxide dismutase (SOD) levels. Serum level of total anti-oxidant capacity (TAC) in blood was also reduced in serum at the dose of 80 mg/kg. Histochemical staining, including Periodic acid-Schiff, Masson's trichrome and Verhoeff-van Gieson staining, indicated that ASP at doses of 80 and 160 mg/kg reduced glycogen deposition and decreased the number of collagen and elastic fibres in the cardiac tissue. The cardiac expression of pro-apoptotic genes, including P53, Bax, Bcl-2 and Caspase-3, was modulated at the dose of 160 mg/kg. Moreover, transcription of Caspase-3 was up-regulated at the dose of 80 mg/kg. In conclusion, long-term consumption of ASP any higher than the acceptable daily intake (40 mg/kg) appears to act by promoting oxidative stress, has the potential to alter both histopathological and biochemical parameters, and induces P53-dependent apoptosis in cardiac tissue.

Insight into the mechanism of aspartame-induced toxicity in male reproductive system following long-term consumption in mice model.

Aspartame is one of the most common consumed artificial sweeteners utilized in many food products and beverages. It has been indicated that long-term consumption of aspartame leads to reproductive toxicity but its mechanism is not well-clear. In this study we investigated mechanism of aspartame-induced reproductive toxicity in male mice. For this purpose, 36 NMRI mature male mice received three doses of 40, 80, and 160 mg/kg body weight of aspartame, respectively per day by gavage for 90 days and also a control group was considered which received 0.5 mL of normal saline as the same route. The results revealed that long-term administration of aspartame at high doses significantly (P < .05) reduced gonadosomatic index, serum concentration of pituitary-testicular axis hormones (FSH, LH, and testosterone). It also decreased sperm parameters and total antioxidant capacity, antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), while it caused increase in nitric oxide and malondialdehyde levels in testis tissue and sperm samples. Also, it decreased attenuated testicular histomorphometric indices (tubular differentiation index, spermiogenesis index, and repopulation index), and steroidogenic foci, while increased mRNA damages and apoptosis rate, downregulated antiapoptotic (Bcl-2) and upregulated proapoptotic (P53, BAX, and caspase-3) mediators respectively in testis. These findings indicated that consumption of aspartame for a long period results in male reproductive toxicity by decrease in serum concentration of pituitary-testis axis hormones and induction of oxidative stress and apoptosis in testis.

Carob (Ceratonia siliqua L.) fruit hydro-alcoholic extract alleviates reproductive toxicity of lead in male mice: Evidence on sperm parameters, sex hormones, oxidative stress biomarkers and expression of Nrf2 and iNOS.

OBJECTIVE: Carob (Ceratonia siliqua L.) is an evergreen tree with fruits that have potent antioxidant activity. The aim of this study was to investigate alleviative effects of carob fruit hydro-alcoholic extract (CFHAE) against reproductive toxicity induced by lead (Pb) in male mice. MATERIALS AND METHODS: Forty-two NMRI adult male mice were randomly categorized into 7 groups (N=6). Group I was the control group and received no treatment. Group II was the sham group and received 0.2 ml distilled water per day. Group III (Pb group) received Pb acetate 1000 ppm/kg/day. Groups IV and V received CFHAE 500 and 1000 mg/kg/day, respectively. Groups VI and VII received both Pb 1000 ppm/kg/day and CFHAE at doses of 500 and 1000 mg/kg/day, respectively at the same time. The groups were treated by gavage. After 35 days, sperm parameters (count, motility, morphology, viability, DNA damage, and teratozoospermia index), total antioxidant capacity (TAC), reduced glutathione content (GSH), antioxidant enzymes (SOD, CAT, and GPx) activity, MDA levels, and sex hormones (FSH, LH, and testosterone) concentrations in serum, testicular expression of Nrf2 and iNOS genes and histopathological alterations were evaluated. RESULTS: Our findings revealed that co-administration of CFHAE with Pb significantly (p<0.05 to p<0.01) improved sperm parameters, elevated sex hormones, TAC, GSH content, and antioxidant enzymes activity of serum, decreased serum MDA levels, and down-regulated testicular expression of Nrf2 and iNOS genes compared with Pb group. Also, CFHAE ameliorated histopathological alterations in testis tissue caused by Pb. CONCLUSION: CFHAE can alleviate reproductive toxicity following Pb exposure in male mice.

Protective effects of hydro-alcoholic extract of Quercus brantii against lead-induced oxidative stress in the reproductive system of male mice.

OBJECTIVE: Exposure to heavy metals such as lead (Pb) results in oxidative stress induction in the male reproductive system. Herbal medicine can be utilized as antioxidant agents against oxidative stress. Quercus brantii (QB) has shown antioxidant activity in previous studies. The aim of the present study was to evaluate effects of QB hydro-alcoholic extract against Pb-induced oxidative stress in the male mice reproductive system. MATERIALS AND METHODS: Forty-two NMRI adult male mice were randomly divided into 7 groups of 6 animals each. Group I was the control group that received no treatment. Group II was the sham group and received 0.2 ml distilled water. Groups III and IV received QB hydro-alcoholic extract 500 and 1000 mg/kg bw, respectively. Group V received Pb 1000 ppm/kg bw. Group VI and VII received Pb 1000 ppm/kg bw and QB extract 500 and 1000 mg/kg bw, respectively. All groups received treatment via oral gavage. After 35 days, sperm parameters (i.e. sperm motility, count and morphology) were evaluated. Levels of sex hormones including LH, FSH, and testosterone, total antioxidant capacity (TAC), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured in animals' serum. RESULTS: Exposure to Pb negatively affected sperm parameters (i.e. sperm motility, count and morphology), decreased serum concentrations of sex hormones (i.e. LH, FSH, and testosterone), TAC and SOD activity but increased MDA levels. However, co-administration of 500 and 1000 mg/kg bw QB hydro-alcoholic extract and Pb considerably improved sperm parameters (i.e. sperm motility, count and morphology), increased sex hormones (i.e.LH, FSH, and testosterone), TAC, and SOD activity while decreased MDA levels in animals' serum. CONCLUSION: Administration of QB extracts (Low dose and high dose) is able to protect the male reproductive system of mice against Pb-induced oxidative stress.