Sertoli Cell-Conditioned Medium Induces Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells to Male Germ-Like Cells in Busulfan-Induced Azoospermic Mouse Model.

Non-obstructive azoospermia is a severe form of male infertility, with limited effective treatments. Bone marrow mesenchymal stem cells (BMSCs) can differentiate to different cell lines; therefore, transplantation of these cells is used for treatment of several diseases. Since these cells require induction factors to differentiate into germ cells, we co-transplanted bone marrow stem cells (BMSCs) with Sertoli cell-conditioned medium (SCCM) into the testis of azoospermic mice. This study was carried out in two sections, in vitro and in vivo. For in vitro study, differentiating factors (c-kit and ID4) were examined after 15 days of co-culture of bone marrow cells with Sertoli cell-conditioned medium, while for in vivo study, the azoospermia model was first created by intraperitoneal administration of a single-dose busulfan (40 mg/kg) followed by single-dose CdCl2 (2 mg/kg) after 4 weeks. Mice were divided into 4 groups including control (azoospermia), BMSC, SCCM, and BMSC + SCCM. Eight weeks after transplantation, samples were assessed for proliferation and differentiation via the expression level of MVH, ID4, SCP3, Tp1, Tp2, and Prm1 differentiation markers. The results showed that BMSC co-cultured with SCCM in vitro differentiated BMSC to germ-like cells. Similarly, in vivo studies revealed a higher level of BMSC differentiation into germ-like cells with significant higher expression of differentiation markers in transplanted groups compared to the control. This study confirmed the role of SCCM as an inductive factor for BMSC differentiation to germ cells both in vivo and in vitro conditions.

Dapsone improves the vincristine-induced neuropathic nociception by modulating neuroinflammation and oxidative stress.

BACKGROUND: Peripheral neuropathy is a dose-limiting adverse effect of vincristine (VCR) in cancer chemotherapies. Dapsone is commonly used for the prevention of opportunistic infections following cancer therapies. Therefore, a high rate of VCR and dapsone co-administration has occurred in leukemias. Recently neuroprotective effects of dapsone have been reported in various diseases. OBJECTIVES: Regarding the physiopathology of VCR-induced peripheral neuropathy (VIPN) and dapsone neuroprotection, this study evaluated the effect of dapsone on VIPN. METHODS: VIPN was induced by VCR injection (0.5 mg/kg IP, every other day, 1 week) in male Wistar rats. In the treatment group, dapsone(12.5 mg/kg IP, 1 week) was injected 30 min before VCR. Hot plate, Von Frey, motor neuron conduction velocity (MNCV), and histopathological tests were applied. The levels of TNF-α and NF-kB in the sciatic nerve and caspase-3 activity in dorsal root ganglion were measured by the ELISA method. The levels of malondialdehyde (MDA) and Glutathione (GSH) in the sciatic nerve were measured by spectrophotometry and colorimetric assays. RESULTS: VIPN was observed as araised thermal and mechanical threshold, reduced MNCV, and sciatic nerve demyelination. However, dapsone reduced the mechanical and thermal threshold and improved the MNCV. Also, dapsone reduced TNF-α, NF-kB, MDA, and Caspase-3 activity, and increased the GSH level in the sciatic nerve. Moreover, dapsone prevented VCR-induced demyelination in the sciatic nerve. CONCLUSION: This research demonstrated that dapsone could be used as a protective drug against VIPN. It improves the impaired thermal and mechanical sensations by reducing inflammatory, oxidant, and apoptosis factors and preventing demyelination in the sciatic nerve.

Topical Mentha piperita Effects on Cutaneous Wound Healing: A Study on TGF-ß Expression and Clinical Outcomes.

BACKGROUND: Wound healing is a critical clinical concept. We aimed to evaluate the effects of topical Mentha piperita essence on cutaneous wound healing. METHODS: This randomized controlled trial was conducted in Tehran University of Medical Sciences, Tehran, Iran in 2019. Square-shaped 1.5×1.5 cm wounds were made on the neck of 60 male Wistar rats in a sterile condition. Samples were randomly divided into a control group and three experimental groups. Group A treated with M. piperita essence and Vaseline. The second group received the M. piperita essence, and the third group received Vaseline. Histological specimens were obtained in 4th, 7th, and 14th days and were explored for fibroblasts, epithelial cells, inflammatory cells, and vessels. RT-PCR was performed for molecular and gene expression evaluation of TGF-ß. RESULTS: The M. piperita essence increases TGF-ß gene expression as an important factor in wound healing. After 14 d, group A, who received M. piperita and Vaseline, had 99.73% of wound healing with the mean wound size of 0.006 cm2 while wound healing in the control group was only 52%. Samples treated with M. piperita have 74.58% wound healing following by group treated with Vaseline, which was 67.02% (P<0.05), respectively. CONCLUSION: The application of the M. piperita essence for wound healing accelerates the process and improves outcomes.

Cryoprotective Effect of Pentoxifylline on Spermatogonial Stem Cell During Transplantation into Azoospermic Torsion Mouse Model.

Preserving the spermatogonial stem cells (SSCs) in long periods of time during the treatment of male infertility using stem cell banking systems and transplantation is an important issue. Therefore, this study was conducted to develop an optimal cryopreservation protocol for SSCs using 10 mM pentoxifylline (PTX) as an antioxidant in basal freezing medium. Testicular torsion-a mouse model for long-term infertility-was used to transplant fresh SSCs (n = 6), fresh SSCs treated with PTX (n = 6), cryopreserved SSCs with basal freezing medium (n = 6), and cryopreserved SSCs treated with PTX (n = 6). Eight weeks after germ cell transplantation, samples were assessed for proliferation, through evaluation of Ddx4 and Id4 markers, and differentiation via evaluation of C-Kit and Sycp3, Tnp1, Tnp2, and Prm1 markers. According to morphological and flow cytometry results, SSCs are able to form colonies and express Gfra1, Id4, α6-integrin, and ß1-integrin markers. We found positive influence from PTX on proliferative and differentiative markers in SSCs transplanted to azoospermic mice. In the recipient testis, donor SSCs formed spermatogenic colonies and sperm. Respecting these data, adding pentoxifylline is a practical way to precisely cryopreserve germ cells enriched for SSCs in cryopreservation, and this procedure could become an efficient method to restore fertility in a clinical setup. However, more studies are needed to ensure its safety in the long term.

Pentoxifylline improves the survival of spermatogenic cells via oxidative stress suppression and upregulation of PI3K/AKT pathway in mouse model of testicular torsion-detorsion.

Testicular torsion-detorsion results in enhanced formation of free radicals which contribute to the pathophysiology of testicular tissue damage. Recent reports have identified protective role of pentoxifylline (PTX) against free radicals. Thus, we determined the protective effect of pentoxifylline against testicular damage in mouse model of testicular torsion-detorsion. Twenty (6 weeks old) male mice were divided into 4 groups of 5 animals each namely: Control (sham operated group), T1 (Torsion-detosion + single dose 100 mg/kg PTX, T2 (torsion-detorsion + 20 mg/kg PTX for 2 weeks and T/D (torsion-detorsion only). Animals in T1, T2 and T/D groups underwent 2 h of testicular torsion with the left testes rotated 720° (clockwisely) followed by 30 min of detorsion. After detorsion, drug administration was done intraperitoneally. The left testes of all the animals were excised on the 35th day after torsion-detortion for histopathological and biochemical assay. Histomorphological analysis of the seminiferous tubules showed that there were significant increase (P < 0.01 or 0.05) in the mean seminiferous tubule diameter, Johnson score and germ cells of animals in Control and T1 compared to T2 and T/D with no significant difference (P > 0.05) in testes weight, sertoli, leydig and myoid cells in all groups. IHC results showed significant increase (P < 0.01 or 0.05) in id4 and scp3 protein markers in Control, T1 and T2 compared to T/D. Oxidative stress analysis revealed that Pentoxifylline significantly increased (P < 0.01 or 0.05) the level of SOD, catalase, mRNA expression of akt and pi3k genes but significantly suppress (P < 0.01 or 0.05) MDA and Caspase-3 level in Control, T1 and T2 compared to T/D. Pentoxifylline could be used as an adjunct therapy to surgery in the treatment of torsion-detorsion related testicular injury, However, Further studies are needed to evaluate the effects of pentoxifylline on testicular torsion.

Glatiramer acetate treatment inhibits inflammatory responses and improves survival in a mice model of cecal ligation and puncture-induced sepsis.

OBJECTIVES: Sepsis is a clinical crisis which has been considered as one of the important causes of mortality across the world. We hypothesized that modulation of hyper-inflammatory phase of sepsis pathophysiology can lead to protective effects on survival outcome. Glatiramer acetate (GA) is a neuroprotective drug commonly used in multiple sclerosis (MS). GA is characterized by immunom activity via regulation of innate and adaptive immunity. This study was designed to evaluate the acute treatment with GA on initial inflammatory response-induced mortality in septic mice. METHODS: Cecal ligation and puncture (CLP) model was operated on male mice as a model of Polymicrobial sepsis. GA was administrated intraperitoneally after the sepsis induction at doses of 0.5, 1, and 2 mg/kg in three treatment groups. To investigate the effect of GA on short-term survival, septic mice were observed during 72 h after CLP. Serum levels of TNF-α, IL-1ß, and IL-6 as pro-inflammatory cytokines and also IL-10 as a critical anti-inflammatory cytokine were analysed. To consider sepsis-induced acute kidney injury, renal functional biomarkers and histopathological changes was assessed. RESULTS: GA treatment significantly improved survival rate at doses of 1, and 2 mg/kg. Survival improvement was accompanied by remarkable reduction in the pro-inflammatory cytokines and enhanced production of IL-10. GA showed to have protective effects on renal function as well. CONCLUSIONS: Immunomodulatory and anti-inflammatory properties of GA resulted in increase in survival rate and decrease in inflammatory markers in mice model of cecal ligation and puncture-induced sepsis.

Promotion of Burn Wound Healing by Local Application of Adipose-Derived Mesenchymal Stem Cells: An Experimental Study.

Background:The burn wound is one of the health problems in the world that affects physical and mental health. Today, adipose-derived mesenchymal stem cells (ADSCs) have received medical attention for their accessibility and the ability to reproduce and repair. The present study was designed to investigate the effect of ADSCs on burn wound healing. Methods : The present experimental study was performed on 36 male Wistar rats divided into 1 control group and 3 experimental groups. The second-degree burns with a radius of 10 mm were induced after anesthesia. ADSCs and Dulbecco's Modified Eagle Medium (DMEM) were injected into the dermis around the burn area in the ADSCs and DMEM groups, respectively. Silver sulfadiazine (SSD) ointment was applied topically once daily as the SSD group. The control group did not receive any treatment. The rats were evaluated for 21 days. Wound healing rate, histopathological parameters, and the number of fibroblasts were evaluated by the immunofluorescence technique and vascular endothelial growth factor and transforming growth factor ß (TGF-ß) gene expression by reverse transcription-polymerase chain reaction. The results were entered into SPSS software (SPSS Inc) and analyzed with 1-way analysis of variance and repeated measures analysis. Results: The number of fibroblasts, the number of vessels, TGF-ß, and VEGF gene expression in the burn area were significantly higher in the ADSCs group than in the SSD, DMEM, and control groups. The results also showed that the amount of inflammation was significantly lower in the ADSCs group compared with the control group (p<0.001). Moreover, the percentage of wound recovery was significantly higher in the ADSCs group compared with other groups (p<0.001). Conclusion: ADSCs accelerate and improve burn wound healing by affecting fibroblasts, keratinocytes, and inflammatory cells as well as increasing the expression of the TGF-ß and VEGF genes, and thus increase in angiogenesis.

Comparison of the Effect of Adipocyte-derived Stem Cells and Curcumin Nanoliposomes with Phenytoin on Open Cutaneous Wound Healing in Rats.

BACKGROUND: Reducing the healing time of wounds can decrease the patient's immobility time and their medical costs, leading a faster return of the patients to daily work. OBJECTIVE: The aim of the present study is to compare the effect of adipose-derived stem cells and curcumin- containing liposomal nanoparticles with phenytoin on wound healing. METHODS: After anesthesia of the rats, open skin ulcers were made by a bistoury blade. Subsequently, stem cells were removed from the adipose tissue of the upper border of the epididymis. The originality of stem cells was then confirmed by the flow cytometry. The fusion method was used to prepare the liposome; and also, nanoliposomal particles were confirmed by using the DLS microscope. The percentage of recovery and the cell count was measured with IMAGEJ. The expression of genes was assessed by PCR. The number of fibroblasts was counted by immunohistochemistry techniques. The amount of collagen was determined by Tri-chromosome staining, and the number of capillaries was enumerated by H & E staining. RESULTS: The expression of the TGF-β1 gene, vascular number, wound healing rate and the number of fibroblasts increased significantly in adipose tissue-derived stem cells and curcumin nanoliposome groups (p<0.05); the wound surface was also decreased significantly (p<0.05). CONCLUSION: Based on the results of our research, adipose tissue-derived stem cells and curcumin nanoliposomes can heal wounds efficiently.

Phosphatidylserine nanoliposomes inhibit glucocorticoid-induced osteoporosis: A potential combination therapy with alendronate.

The present study aimed to investigate the effects of phosphatidylserine liposomes (PSLs) and phosphatidylserine liposomes containing alendronate (AL-PSLs) on the improvement of methylprednisolone (MP) induced osteoporosis in a rat model. AL-PSLs formulation was prepared, characterized, and evaluated in different pH media to simulate gastrointestinal condition. Osteoporosis was induced by 3 weeks oral administration of MP (10 mg/kg) and then treatment by PSLs, AL-PSLs, and alendronate (AL). Bone metabolic and biomechanical markers were measured in treated rat groups. Also, Tartrate-resistant acid phosphatase (TRAP) staining and histomorphometry were evaluated on bone tissues of treated rats. AL-PSLs were obtained in a size range of 155 nm and negatively surface charge with an entrapment efficiency of 42%. The AL leakage from AL-PSLs did not exhibit a significant difference in acidic or basic media in comparison with the neutral condition. The concentrations of calcium, osteocalcin, bone alkaline phosphatase, and osteoprotegerin (OPG) of serum were significantly increased in PSLs and AL-PSLs treated groups compared to the MP group. Also, PSLs and AL-PSLs significantly improved the thickness and volume of the cortical and trabecular bone mass in treated groups. In addition, TRAP staining indicated a significant decrease of osteoclast number in osteoporotic rats treated with AL-PSLs and PSLs. In this study, AL-PSLs and even PSLs alone made a potential bone mechanical strength in glucocorticoid-induced bone loss more than AL in rats. In conclusion, our findings suggest that PSLs consumption with or without an anti-osteoporotic drug might be an applicable choice in control of osteoporosis.

Efficacy of a Natural Topical Skin Ointment for Managing Split-Thickness Skin Graft Donor Sites: A Pilot Double-blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the safety and efficacy of a new topical skin ointment with natural ingredients (aloe vera, honey, and peppermint) for dressing skin graft donor sites. DESIGN: A double-blind, placebo-controlled, randomized clinical trial. PATIENTS AND INTERVENTION: Researchers enrolled patients who were referred for split-thickness skin graft after burns or surgical wounds on the scalp or face area. For each patient, a thin layer of skin (depth, 0.04 mm; approximate size, less than 15 × 7 cm) was harvested from the thigh by a plastic surgeon with an electric or manual dermatome. The donor sites were divided and randomized to receive either natural ointment or petroleum jelly as a topical agent to dressing. Topical agents were applied on donor site wounds on days 0, 4, 7, and 14. MAIN OUTCOME MEASURES: Wound size, pain, erythema, pruritus, patient discomfort, complications, and physician satisfaction were evaluated at each visit. MAIN RESULTS: Among 28 patients, there was no significant difference between the two treatment agents regarding the rate of wound healing (P = .415), pain (P = .081), pruritus (P = .527), and patient discomfort (P = .616). The ointment was superior to petroleum jelly in reducing wound erythema (P = .001) and was associated with significantly better treatment satisfaction (P < .001). CONCLUSIONS: The natural topical ointment investigated in this study may be an acceptable alternative to petroleum jelly in caring for split-thickness donor skin graft donor site wounds to effectively promote wound healing, prevent infection and scarring, reduce pain, and comfort the patient.

Metformin loaded phosphatidylserine nanoliposomes improve memory deficit and reduce neuroinflammation in streptozotocin-induced Alzheimer's disease model.

Alzheimer's disease (AD) is closely associated with neuroinflammation development in the brain. Co-delivery of metformin (MET) with phosphatidylserine liposomes neuroprotectant may be beneficial in ameliorating AD-related symptoms like memory impairment and inflammation. Therefore, we aimed to prepare metformin containing phosphatidylserine nanoliposomes formulation (MET-PSL) and to evaluate its effect on rats subjected to AD. Alzheimer's disease model was induced by bilateral intracerebroventricular injection of streptozotocin (3 mg/kg) into rat brains using the stereotactic technique. MET-PSL, MET, and PSL alone were administered intraperitoneally to AD-induced animals and factors including learning and memory storage in addition to cytokine and tissue inflammatory changes were evaluated after a 22-day experiment period. The learning and memory parameters significantly (P < 0.05) improved in AD-rats treated with MET-PSL. Moreover, MET-PSL administration significantly (P < 0.05) decreased cytokine levels of IL1-ß, TNF-α, and TGF-ß in hippocampal tissues of rats with AD. Histological results indicated a considerable reduction in inflammatory and necrotic neural cells along with significantly (P < 0.05) increased neurogenesis in MET-PSL treated rats. Furthermore, our results showed that MET-PSL formulation could potentially act better than the free form of MET and PSL alone in the recovery process of rats with AD. In general, our data suggest that combination therapy of metformin loaded phosphatidylserine liposomes may enhance the therapeutic performance in AD patients of a clinical study.

Protective effects of ascorbic acid and calcitriol combination on airway remodelling in ovalbumin-induced chronic asthma.

Context: Airway remodelling is one of the most refractory problems in asthma. According to the critical roles of oxidative stress and inflammation in airway remodelling, it is supposed that ascorbic acid and calcitriol have beneficial effects. However, a combination of antioxidants may be more effective for asthma therapy.Objective: This study investigated the protective effects of ascorbic acid in combination with calcitriol on airway remodelling in ovalbumin (OVA)-induced chronic asthma.Materials and methods: BALB/c mice were assigned into seven groups: (1) Control; (2) Asthma; (3) Ineffective C (orally 39 mg/kg ascorbic acid); (4) Ineffective D (intraperitoneally 1.5 µg/kg calcitriol); (5) Effective C (orally 130 mg/kg ascorbic acid); (6) Effective D (intraperitoneally 5 µg/kg calcitriol); (7) Combination (orally 39 mg/kg ascorbic acid + intraperitoneally 1.5 µg/kg calcitriol). All animals were sensitized and challenged with OVA except in the control group (normal saline). In all treatment groups, mice were administrated vitamins 30 min before each challenge (three times per week for 8 consecutive weeks).Results: In comparison with the asthma group, co-administration of ineffective doses of ascorbic acid and calcitriol led to the decreased levels of IL-13 (50.5 ± 1.85 vs. 42.13 ± 0.37 pg/mL, p = 0.02) and IgE (58.74 ± 0.43 vs. 45.78 ± 2.05 ng/mL, p = 0.003) as well as the reduction of goblet hyperplasia and subepithelial fibrosis (5 vs. 1 score, p = 0.001 and 5 vs. 2 score, p = 0.001, respectively).Discussion and conclusions: Combination of ascorbic acid with calcitriol in ineffective doses improves airway remodelling due to additive effects possibly through reduction of oxidative stress and inflammation. This study provides a scientific basis for further research and clinical applications of ascorbic acid and calcitriol and can be generalized to the broader pharmacological studies.

Histologic Evaluation of the Bone Regeneration Capacities of Bio-Oss and MinerOss X in Rabbit Calvarial Defects.

Several methods are used for periodontal regeneration and alveolar ridge reconstruction. This study aimed to compare the bone regeneration capacities of MinerOss X, Bio-Oss, and autograft in rabbit calvaria. In this animal study, four defects measuring 8 mm in diameter were created in the calvaria of 10 rabbits using a trephine bur. Three defects were randomly filled with MinerOss X, Bio-Oss, and autogenous bone. The fourth defect remained empty as a control. The rabbits were sacrificed after 4 or 8 weeks. Calvarial samples were taken and histopathologically evaluated. The mean number of osteoblasts and the amount of newly formed bone in all groups were higher at 8 compared to 4 weeks. At 4 and 8 weeks, the amount of newly formed bone and number of osteoblasts and osteocytes in MinerOss X group were significantly greater than the corresponding values in other groups, and MinerOss X was superior to Bio-Oss and autograft in all the assessed variables at both 4 and 8 weeks (P < .001). Within the limitations of this study, the results showed that the number of osteoblasts and osteocytes and the amount of newly formed bone in the MinerOss X group were higher than those in Bio-Oss and autograft groups. However, further clinical studies are warranted.

Combination of ascorbic acid and calcitriol attenuates chronic asthma disease by reductions in oxidative stress and inflammation.

Airway inflammation and oxidative stress are the two major characteristics of asthma pathogenesis. Therefore, this study evaluated the protective effects of ascorbic acid in combination with calcitriol on the oxidative damages and inflammation in asthma model. All animals, except in the control group, were sensitized and challenged with ovalbumin. One day after the last challenge, samples of bronchoalveolar lavage fluid was collected for the assessment of total white blood cell counts and differential count of white blood cell and plasma was used for the measurement of pro-oxidant/antioxidant balance level. Lung tissue samples were also stored for examining peribronchial inflammatory cell infiltration, phosphorylated nuclear factor-kappa B expression and measurement of malondialdehyde level. Induction of asthma caused significant increases in total white blood cell counts, percentage of neutrophils and eosinophils and a decrease in the percentage of lymphocytes. Moreover, asthma resulted in significant increases of peribronchial inflammatory cell infiltration, phosphorylated nuclear factor-kappa B expression and malondialdehyde level. However, no significant changes were observed in pro-oxidant/antioxidant balance level with the induction of asthma. Co-administration of low doses of ascorbic acid and calcitriol returned all to the levels measured before sensitization and challenge. Combination of low doses of ascorbic acid with calcitriol improves mouse asthma model by a possible additive effects through the decrease of oxidative stress and inflammation.

In vitro antioxidant activity and in vivo wound-healing effect of lecithin liposomes: a comparative study.

Aim: This study was conducted to determine the potentials of egg lecithin (egg-l) and soy lecithin (soy-l) liposomes in antioxidative and wound healing properties. Materials & methods: The suspensions of egg-l and soy-l were prepared using the fusion technique. The free radical scavenging activity of both lecithin liposomes was evaluated by DPPH and ABTS methods. Tissue staining was used to assess wound-healing parameter. Results: Liposomal lecithins showed an increasing trend of 1-10 mg/ml in radical-scavenging activities (p < 0.0001). Wound-healing assessments showed a significant effect (p < 0.0001) in treatment with topical lecithin liposomes. The results of wound healing also showed better outcomes of egg-l in comparison with phenytoin 1% cream. Conclusion: Antioxidant lecithin liposomes may enhance the treatment of wound injuries.

Physico-mechanical and antimicrobial properties of an orthodontic adhesive containing cationic curcumin doped zinc oxide nanoparticles subjected to photodynamic therapy.

BACKGROUND: Potential complications on the crown level during fixed orthodontic procedures are white spot, enamel demineralization and tooth decay. This study evaluated the antimicrobial properties of an orthodontic adhesive incorporating cationic curcumin doped zinc oxide nanoparticles (cCur/ZnONPs), which can have the highest concentration of cCur/ZnONPs and shear bond strength (SBS) value simultaneously, against cariogenic bacteria including Streptococcus mutans, Streptococcus sobrinus, and Lactobacillus acidophilus. MATERIALS AND METHODS: Following synthesis and confirmation of cCur/ZnONPs, SBS and adhesive remnant index (ARI) of the test adhesives containing cCur/ZnONPs (1.2, 2.5, 5, 7.5, and 10% wt.) were measured using universal testing machine and stereomicroscope, respectively. After continuously rinsed (up to 180 day), the residual antimicrobial ability of modified adhesives which can have the highest concentration of cCur/ZnONPs and SBS value simultaneously were determined by disc agar diffusion (DAD), biofilm formation inhibition, and metabolic activity assays following photo-activation using light-emitting diode (LED) for 5 min against multispecies cariogenic biofilm-producing bacteria. RESULTS: Adhesive with 7.5% wt. cCur/ZnONPs showed the highest concentration of cCur/ZnONPs and SBS value (14.89 ± 3.26 MPa, P < 0.05) simultaneously. No significant differences in ARI scores were found between the modified adhesive and control (Transbond XT without the cCur/ZnONPs). 7.5% wt. cCur/ZnONPs following photo-activation was not colonized by the test microorganisms and suppressed 100% metabolic activity of the test microorganisms up to 90 day compared to the control group (cCur/ZnONPs free LED irradiation; P < 0.05). In DAD assay, the reduction of photodynamic disinfection of the 7.5% wt. cCur/ZnONPs against test bacteria was positively associated to the time, in such a way that it was decreased significantly after 60 day. From days 120 onwards, microbial biofilm formation and metabolic activity was progressively increased on 7.5% wt. cCur/ZnONPs adhesive discs compared to the control group (cCur/ZnONPs free LED irradiation). CONCLUSIONS: Our findings highlight the photo-activated 7.5% wt. cCur/ZnONPs can serve as an orthodontic adhesive additive to control the cariogenic multispecies biofilm, and also to reduce their metabolic activity.

Silver sulfadiazine nanoethogel for burn healing: characterization and investigation of its in vivo effects.

AIM: Nanoethosomal formulation containing silver sulfadiazine (SSD) was used to reduce bacterial burden and healing time in burn injuries. MATERIALS & METHODS: Ethosomal formulations were characterized for their size, ζ-potential, morphology, drug encapsulation efficiency and in vitro release kinetics of SSD. RESULTS: The optimized nanoethosomal suspension with a size of 206.7 ± 1.18, and ζ-potential value of -67.3 ± 0.45 mV exhibited a high SSD encapsulation efficiency (92.03 ± 0.79%). Results of antimicrobial tests indicated SSD-loaded ethosome formulation led to a significant reduction of colony number. Histopathological results demonstrated a wound contraction rate of 96.83% for the group treated with SSD ethosomal gel while untreated group showed 59.41%. CONCLUSION: The SSD ethogels promotes the therapeutic effect of SSD for burn treatment.

Evaluation of the Effects of Local Application of Thyme Honey in Open Cutaneous Wound Healing.

BACKGROUND: Clinicians have been searching for ways to obtain "super normal" wound healing. Honey is a traditional remedy for the treatment of infected wounds. We aimed to evaluate the wound contraction and antibacterial properties of locally produced Thyme honey on managing full-thickness wounds in vivo. METHODS: This experimental study was conducted in 2015, in Department of Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran on 54 adult male Wistar rats weighing 200-250 gr, and ages of 3-4 months. A square 1.5*1.5 wound was made on the back of the neck. The rats were divided into control and two experimental groups. Additionally, the control and experimental groups were separated into three subgroups corresponding to 4, 7, and 14 d of study. The control group did not receive any treatment. For histological studies, samples were taken from the wound and adjacent skin. This tissue was examined using histological staining (H&E). Wound surface and wound healing were evaluated. Data were analyzed by using one-way ANOVA with post hoc Tukey test and (P<0.05) was significant. RESULTS: The macroscopic and microscopic evaluations showed that the percentage of wound healing on different days in the control and experimental groups were significant (P< 0.05). CONCLUSION: Using honey twice a day on open wounds will accelerate the healing process.

Transforming growth factor-ß (TGF-ß) activation in cutaneous wounds after topical application of aloe vera gel.

Aloe vera is a medicinal plant used to treat various skin diseases. The effects of using aloe vera gel on the healing process were investigated by microscopic methods, cell counting, and TGF-ß gene expression in the wound bed. Sixty Wistar rats weighing 200-250 g were placed under anesthesia in sterile conditions. A square 1.5 cm × 1.5 cm wound was made on the back of the neck. The rats were divided into control and 2 experimental groups. Additionally, the control and experimental groups were separated into 3 subgroups corresponding to 4, 7, and 14 days of study. In the first experimental group, aloe vera was used twice on the wound. The second experimental group received aloe vera overtreatment once on the wound. The positive control group received daily application of 1% phenytoein cream following surgical wound creation. The control group did not receive any treatment. This tissue was examined using histological staining (H&E) and Masson's Trichrome. Wound surface and wound healing were evaluated separately. TGF-ß gene expression was analyzed by RT-PCR. Results showed that fibroblasts in both experimental groups were significantly increased, thereby acceleration wound healing. Application of aloe vera gel will increase TGF-ß gene expression, ultimately accelerating the wound healing process.

Synergistic Effect of Honey and Propolis on Cutaneous Wound Healing in Rats.

Accelerating wound healing is now considered as a principle clinical treatment and increasing the quality and speed of healing which has always been emphasized by the scientists. Propolis and honey are natural bee products with wide range of biological and medicinal properties. This study was aimed to determine the synergistic effect of honey and propolis in wound healing of rat skin. A total of 75 Wistar rats weighing 200-250 gr were placed under general anesthesia and sterile conditions. Then a square shape wound with 1.5*1.5 mm dimension was made on the back of the neck. Animals were randomly divided into control, honey, propolis, combined honey propolis and phenytoin 1% groups, respectively. Rats were randomly divided into the following groups: 4th, 7th and, 14th days of treatment in each period of study. Wound area in the experimental group was covered once daily with a fixed amount of thyme honey, propolis, propolis and honey and phenytoin cream (1%), the control group did not receive any treatment. For histological studies, during the fourth, seventh and fourteenth day's rats were sacrificed and samples were taken from the wound and adjacent skin. After histological staining fibroblast, neutrophils, macrophages and vascular sections were counted in the wound bed. The macroscopic and microscopic evaluations showed that the percentage of wound healing on different days in the experimental and control groups were significant (P<0.05). The macroscopic and microscopic evaluation showed that the percentage of wound healing on different days in combined propolis and honey experimental group was significantly different from the control group (Multivariate ANOVA test) (P<0.05). Combined application of propolis and honey on the open wound healing in rats has a synergistic effect.