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Abstract Malignant neoplasms are one of the main causes of death, especially in children, on a global scale, despite strenuous efforts made at advancing both diagnostic and therapeutic modalities. In this regard, a new nanocarrier Vincristine (VCR)-loaded Pluronic f127 polymer-coated magnetic nanoparticles conjugated with folic acid and transferrin (PMNP-VCR-FA-TF) were synthesized and characterized by various methods. The cytotoxicity of these nanoparticles was evaluated in vitro and ex vivo conditions. The in vitro anti-tumor effect of the nanoparticles was evaluated by colony formation assay (CFA) and reactive oxygen species (ROS) in Y79 cell line. The results showed that nanoparticles with two ligands conferred greater toxicity toward Y79 cancer cells than ARPE19 normal cells. Under an alternating magnetic field (AMF), these nanoparticles demonstrated a high specific absorption rate. The CFA and ROS results indicated that the AMF in combination with PMNP-VCR-FA-TF conferred the highest cytotoxicity toward Y79 cells compared with other groups (P

Background and Purpose: Regarding the wide-spectrum antimicrobial effects of curcumin and silver, this study aimed to evaluate the antifungal activity of green-synthesized curcumin-coated silver nanoparticles (Cur-Ag NPs) against a set of Candida and Aspergillus species.Materials and Methods: Cur-Ag NPs were synthesized by mixing 200 µL of curcumin solution (40 mM) and 15 mL of deionized water. The mixture was stirred for 3-5 min, followed by the addition of 2.5 mL of silver nitrate solution (2.5 mM). The resulting solution was incubated for 3 days. Antifungal susceptibility of 30 fungal isolates of Aspergillus and Candida to fluconazole and itraconazole, as well as the activity of Cur-Ag NPs against the isolates, were determined, both alone and in combination, using broth microdilution according to the Clinical and Laboratory Standards Institute guidelines.Results: Cur-Ag NPs demonstrated promising antifungal activity, particularly against Candida species. The geometric mean value of the minimum inhibitory concentration of Cur-Ag NPs was significantly lower than that of fluconazole for all the studied fungi. Similarly, it was lower than those of itraconazole in C. albicans and A. fumigatus. The minimum fungicidal concentrations of Cur-Ag NPs were markedly better than those of fluconazole but still inferior to those of itraconazole.Conclusion: Cur-Ag NPs demonstrated indisputable antifungal activity and great potential that can be harnessed to combat fungal infections, particularly those caused by azole-resistant strains of Aspergillus and Candida.

Background: Current medications especially the pentavalent antimonial compounds have been used as the first line treatment of cutaneous leishmaniasis (CL), but they have limitations due to serious side effects such as drug resistance, cardio and nephrotoxicity, and high costs. Hence, the demand to find more usable drugs is evident. Synthesis and devel­opment of natural, effective, biocompatible, and harmless compounds against Leishmania major is the principal priority of this study. Methods: By electrospinning method, a new type of nanofiber were synthesized from royal jelly and propolis with dif­ferent ratios. Nanofibers were characterized by Scanning Electron Microscope (SEM), Transmission Electron Micros­copy (TEM), Thermogravimetric Analysis (TGA), Contact angle, and Fourier-transform infrared spectroscopy (FTIR). The Half-maximal inhibitory concentration (IC50), Half-maximal effective concentration (EC50) and the 50% cytotoxic concentration (CC50) for different concentrations of nanofibers were determined using quantitative calorimetric meth­ods. Inductively coupled plasma-optical emission spectrometry (ICP-OES) and flow cytometry were performed as complementary tests. Results: The results showed that the proposed formulas provide a new achievement that, despite the significant killing activity on L. major, has negligible cytotoxicity on the host cells. Royal jelly nanofibers have significantly shown the best 72 hours results (IC50= 35 μg/ml and EC50=16.4 μg/ml) and the least cytotoxicity. Conclusion: This study presents a great challenge to introduce a new low-cost treatment method for CL, accelerate wound healing, and reduce scarring with minimal side effects and biocompatible materials. Royal jelly and propolis nanofibers significantly inhibit the growth of L. major in-vitro.

Abstract Gadolinium-based contrast agents (GdCAs) have been the most frequently used T 1-weighted magnetic resonance imaging (MRI) contrast agents for decades. However, they have serious disadvantages such as low longitudinal relaxivity value (r 1) and high dose associated-nephrotoxicity that restrict their wide applications. These emphasize the need for an ideal stable and biocompatible T 1-weighted CA with high contrast enhancement performance. Here, we propose a wet-chemical synthesis technique to form a nanocomposite consisting of ultrasmall iron oxide nanoparticles (US-IO) and Gd2O3 hybrid nanoparticles stabilized with dextran (FG-HNPs) for T 1-weighted MR imaging. Relaxometry study showed that FG-HNPs have a high r 1 value (42.28 mM−1S−1) and low relaxivity ratio (r 2/r 1: 1.416) at 3.0T. In vivo MRI contrast enhancement factor (ΔSNR) for FG-HNPs (257.025 ± 17.4%) was found to be 1.99-fold higher than US-IO (129.102 ± 15%) and 3.35-fold higher than Dotarem (76.71 ± 14.2%) as routinely used T 1-weighted CA. The cytotoxicity assay and histological examination confirmed the biocompatibility of FG-HNPs. The biodistribution study, transmission electron microscopy (TEM) and Prussian blue (PB) staining of tumor tissue proved the effective tumor localization of FG-HNPs. Therefore, FG-HNPs can be suggested as a promising CA for T 1-weighted MRI of tumors by virtue of their remarkable relaxivities and high biocompatibility.

Objective:One of the challenges in gene therapy is the transfer of the gene to the target cell. MicroRNAs (miRNAs)regulate gene expression after transcription by binding directly to the messenger and play a vital role in cell behaviorsand the pathogenesis of some diseases. This study was aimed at developing poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for gene delivery to endometriotic cyst stromal cells (ECSCs).Materials and Methods:In this experimental study, endometriosis cells were isolated from women with severeendometriosis (DIE) and digested by the enzymatic method (40 μg/ml DNAase I and 300 μg/ml collagenase type 3).PLGA-based NPs were synthesized and characterized. The size of sole PLGA NPs and PLGA/miRNA were 60 ± 4 nmand 70 ± 5.1 nm respectively. Poly lactic-co-glycolic-based NPs were used as vector carriers for miRNA 503 transfectionin endometriosis cells. The cells were divided into the five groups of control and four doses (25, 50, 75, and 100 μm) ofmiRNA 503/PLGA at 12, 24, 48, and 72 hours. Viability and apoptosis were evaluated by the MTT assay and AnnexinKits. Data were analyzed by one-way analysis of variance.Results:The results show that the size of PLGA/miRNA complex with dynamic light scattering (DLS) was 70 ± 5.1nm and zeta potential values of the PLGA/PEI/miRNA complexes were 27.9 mV. Based on the MTT assay results,the optimal dose of miRNA 503/PLGA was 75 μm, at which the viability of ECSCs was 52.6% ± 1.2 (P≤0.001), andthe optimal time was 48 hours. The apoptotic rates of ECSCs treated with PLGA/miRNA503 (34.75 ± 4.9%) weresignificantly higher than those of ECSCs treated with PLGA alone (3.35 ± 2.58%, P≤0.01).Conclusion:Cell death increased with increasing the concentration of miRNA; thus, it can be suggested as a treatmentfor endometriosis.

Abstract Background The purpose of the present study was to evaluate the efficacy of chemo-magnetic hyperthermia (MH), a combination of alternating magnetic field (AMF) and superparamagnetic nanoparticles (SPIONs) coated with Polyethylene glycol-Poly(butyl acrylate)-Polyethylene glycol (PEG-PBA-PEG) carrying 5-Fluorouracil (5-Fu), at inducing apoptosis in the human cancer cell lines HT29 and HCT116. This process can be mediated by alterations in the expression of apoptotic effector proteins, including Bax, Bcl-2, cleaved caspase 3&9, and cleaved PARP, which are involved in the intrinsic pathway of apoptosis. For this purpose, the cells were cultured as monolayers. Then both cell lines were treated with 5-Fu/magnetic nanoparticles and magnetic hyperthermia. Finally, the effect of treatment on cancer cells was determined by Western blot analysis and flow cytometry. Results Our results showed that combined chemo-magnetic thermotherapy significantly increased the apoptosis in colon cancer cells compared to chemotherapy or hyperthermia alone (P

Objective: In cancer treatments, smart gene delivery via nanoparticles (NPs) can be targeted for cancer cells, while concurrently minimizing damage to healthy cells. This study assessed the efficiency of poly lactic-co-glycolic acid (PLGA)-miR 143/206 transfection on apoptosis in mouse leukemia cancer cells (El4) and spermatogonial stem cells (SSCs). Materials and Methods: In this experimental study, neonatal mouse spermatogonia cells and EL4 cancer cell lines were used. MicroRNA-PLGA NPs were prepared, characterized, and targeted with folate. Several doses were evaluated to obtain a suitable miR dose that can induce appropriate apoptosis in EL4 cells, while not harming SSCs. Cells were treated separately at 3 doses of each miR (for miR 143, doses of 25, 50 and 75 nmol and for miR 206, doses of 50, 100 and 150 nmol). The experiments were performed at 24, 48 and 72 hours. Viability and apoptosis were investigated by MTT and Annexin Kits. Results: Based on MTT assay results, the optimal dose of miR 143 was 75 nmol (59.87 ± 2.85 % SSC and 35.3 ± 0.78 % EL4) (P≤0.05), and for miR 206, the optimal dose was 150 nmol (54.82 ± 6.7 % SSC and 33.92 ± 3.01% EL4) (P≤0.05). The optimal time was 48 hours. At these doses, the survival rate of the EL4 cells was below the half maximal inhibitory concentration (IC50) and SSC survival was above 50%. Annexin V staining also confirmed the selected doses (for miR 143 total apoptosis was 6.62% ± 1.8 SSC and 37.4% ± 4.2 EL4 (P≤0.05), and miR 206 was (10.98% ± 1.5 SSC and 36.4% ± 3.7 EL4, P≤0.05). Conclusion: Using intelligent transfection by NPs, we were able to induce apoptosis on EL4 cells and maintain acceptable SSC survival rates.

Objective(s): Cisplatin-induced peripheral neuropathy is a debilitating side effect in patients receiving this drug. Recent studies suggest hyperbaric oxygen (HBO) therapy as a new treatment approach for models of neural injury. The aim of the current study was to determine the protective effects of HBO preconditioning against peripheral neuropathy induced by Cisplatin (CDDP).Materials and Methods: The present study was conducted on 4 groups of rats: Sham group; HBO group (60 min/d); Control group (CDDP 2 mg/kg/d); Precondition group (HBO+CDDP). Mechanical threshold testing was weekly carried out using von Frey filament. Sciatic nerve and associated ganglia were removed five weeks after the first CDDP injection for biochemical evaluation of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity, immunohistochemistry of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), TNF-α, caspase-3 and iNOS, and transmission electron microscopic (TEM) assessments.Results: MDA levels and MPO activities were significantly decreased in preconditioned rats. Attenuated TUNEL reaction along with attenuated caspase-3, TNF-α, and iNOS expression could be significantly detected in preconditioned rats. Also, HBO preconditioning improved the nociceptive threshold. Conclusion: The results suggest that HBO preconditioning can attenuate peripheral neuropathy caused by cisplatin in rats.

Glioblastoma Multiform (GBM) known as the most common CNS malignant tumour. Therapy for GBM includes maximum tumour resection and chemotherapy. Recent advances have emphasized the use of nanoparticles, such as zinc oxide nanoparticles (ZnO-NPs). Conjugated ZnO NPs with folic acid (FA) easily pass through cell membrane. In the present study, ZnO NPs-FA applied to GBM U87MG cell line. ZnO NPs-FA synthesized according to the sol-gel method. The GBM U87MG and astrocytes 1321N1 cell lines cultured and divided into control, sham and ZnO NPs-FA groups. MTT assay used for the cell viability, and ROS assay and flow cytometry exploited. The size of nanoparticles was ≤20 nm using TEM and FTIR. After 12 hours, the viability for U87MG cells showed a significant decrease at 1.25 and 2.5 mg/ml concentrations. However, no such results obtained for astrocytes. According to the results, the ROS assay caused a significant increase in GBM cells at the mentioned concentration. It was concluded that dose-dependent conjugated NPs could play a therapeutic role in cancer therapy.

Abstract Background Numerous studies have shown the effects of rapid eye movement sleep deprivation (REM‐SD) on behavior and brain structures. The impact of REM‐SD on learning and memory, thus neurogenesis, has been reported in previous studies. Royal jelly (RJ) is known as the wealthiest biological nutrient with various physiological properties. This study aimed to study the possible effect of RJ on neurogenesis of the rat hippocampus neonates following exposure of mother to REM‐SD during pregnancy. Methods Thirty neonate rats from 15 pregnant Wistar rats were used. To induce REM‐SD, the flowerpot method was used. The pregnant rats were divided into five groups (n = 3): group 1, no treatment; group 2, REM‐SD; groups 3, 4, and 5, REM‐SD +RJ. The former group received 72 h REM‐SD during pregnancy (days 7, 14, 21), and the latter group received REM‐SD + RJ (three trial groups). At week 4, the rat neonates of all groups were sacrificed (n = 6 each group). Their brains were fixed, removed, and prepared for Nissl and Hoechst 33342 staining. By using real time polymerase chain reaction methode the brain‐derived neurotrophic factor BDNF gene expression was studied (RT‐PCR), brain‐derived neurotrophic factor (BDNF) gene expression was studied. The results were analyzed statistically, and the Pv

Background and Objectives: An important leading cause of the emergence of vancomycin-resistant enterococci, especially Enterococcus faecium, is the inefficiency of antibiotics in the elimination of drug-resistant pathogens. Consequently, the need for alternative treatments is more necessary than ever. Materials and Methods: A highly effective bacteriophage against vancomycin-resistant E. faecium called vB-EfmS-S2 was isolated from hospital sewage. The biological properties of phage S2 and its effect on biofilm structures were determined. Results: Phage S2 was specifically capable of lysing a wide range of clinical E. faecium isolates. According to Electron microscopy observations, the phage S2 belonged to the Siphoviridea family. Suitable pH spectra for phage survival was 5-11, at which the phage showed 100% activity. The optimal temperature for phage growth was 30-45°C, with the highest growth at 37°C. Based on one-step growth curve results, the latent period of phage S2 was 14 min with a burst size of 200 PFU/ml. The phage S2 was also able to tolerate bile at concentrations of 1 and 2% and required Mg2+ for an effective infection cycle. Biofilms were significantly inhibited and disrupted in the presence of the phage. Conclusion: According to the results, phage S2 could potentially be an alternative for the elimination and control of vancomycin-resistant E. faecium biofilm.

Abstract Background Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 influenza virus. Methods The nanoparticles were characterized using the inductively coupled plasma mass spectrometry, x-ray diffraction analysis, and electron microscopy. MTT assay was applied to assess the cytotoxicity of the nanoparticles, and anti-influenza activity was determined by TCID50 and quantitative Real-Time PCR assays. To study the inhibitory impact of nanoparticles on the expression of viral antigens, an indirect immunofluorescence assay was also performed. Results Post-exposure of influenza virus with PEGylated ZnO-NPs and bare ZnO-NPs at the highest non-toxic concentrations could be led to 2.8 and 1.2 log10 TCID50 reduction in virus titer when compared to the virus control, respectively (P

Objective The purpose of this study was to evaluate in vitro cytotoxicity of gold nanorods (GNRs) on the viability of spermatogonial cells (SSCs) and mouse acute lymphoblastic leukemia cells (EL4s). Materials And Methods In this experimental study, SSCs were isolated from the neonate mice, following enzymatic digestion and differential plating. GNRs were synthesized, then modified by silica and finally conjugated with folic acid to form F-Si-GNRs. Different doses of F-Si-GNRs (25, 50, 75, 100, 125 and 140 µM) were used on SSCs and EL4s. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation assay was performed to examine the GNRs toxicity. Flow cytometry was used to confirm the identity of the EL4s and SSCs. Also, the identity and functionality of SSCs were determined by the expression of specific spermatogonial genes and transplantation into recipient testes. Apoptosis was determined by flow cytometry using an annexin V/propidium iodide (PI) kit. Results Flow cytometry showed that SSCs and EL4s were positive for Plzf and H-2kb, respectively. The viability percentage of SSCs and EL4s that were treated with 25, 50, 75, 100, 125 and 140 µM of F-Si-GNRs was 65.33 ± 3.51%, 60 ± 3.6%, 51.33 ± 3.51%, 49 ± 3%, 30.66 ± 2.08% and 16.33 ± 2.51% for SSCs and 57.66 ± 0.57%, 54.66 ± 1.5%, 39.66 ± 1.52%, 12.33 ± 2.51%, 10 ± 1% and 5.66 ± 1.15% for EL4s respectively. The results of the MTT assay indicated that 100 µM is the optimal dose to reach the highest and lowest level of cell death in EL4s and in SSCs, respectively. Conclusion Cell death increased with increasing concentrations of F-Si-GNRs. Following utilization of F-Si-GNRs, there was a significant difference in the extent of apoptosis between cancer cells and SSCs.

Extensive research on the nutritional and medical application of selenium nanoparticles (SeNPs) was performed in past decades. Besides nutritional values, new characteristics such as antibacterial and anticancer properties depict a bright future for high Selenium (Se) consumption in the coming years. Se is essential for the proper functioning of most of the major body organ systems meanwhile it could be highly toxic and even cancerous. The current knowledge of Se interaction with major organ systems functionality such as the central nervous system isn’t well studied and many physiological aspects aren’t clear to the science community. Meanwhile, various results were published on increasing organ system functionality through administrated SeNPs. So with the rapid entrance of SeNPs in the medical and nutritional industry, it may cause unintended complications. The intent of this review is to investigate current knowledge of SeNPs interaction with major body organ systems functionality. Investigated pharmacokinetic parameters of SeNPs was also reviewed.

Introduction: Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, which has much benefited from animal models to find the basics of its pathophysiology. In our previous work (Haghani, Shabani, Javan, Motamedi, & Janahmadi, 2012), a non-transgenic rat model of AD was used in electrophysiological studies. However, we did not investigate the histological aspects in the mentioned study. Methods: An AD model was developed through bilateral injection of amyloid-&beta peptides (A&beta) into the frontal cortices. Behavioral and histological methods were used to assess alterations in the memory and (ultra)structures. Furthermore, melatonin has been administered to assess its efficacy on this AD model. Results: Passive avoidance showed a progressive decline in the memory following A&beta injection. Furthermore, Nissl staining showed that A&beta neurotoxicity caused shrinkage of the CA1 pyramidal neurons. Neurodegeneration was clearly evident from Fluoro-jade labeled neurons in A&beta treated rats. Moreover, higher NF-&kappaB immunoreactive CA1 pyramidal neurons were remarkably observed in A&beta treated rats. Ultrastructural analysis using electron microscopy also showed the evidence of subcellular abnormalities. Melatonin treatment in this model of AD prevented A&beta- induced increased NF-&kappaB from immunoreaction and neurodegeneration. Discussion: This study suggests that injection of A&beta into the frontal cortices results in the memory decline and histochemical disturbances in CA1 pyramidal neurons. Furthermore, melatonin can prevent several histological changes induced by A&beta.

Objective: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). Stem cell transplantation is a new therapeutic approach for demyelinating diseases such as MS which may promote remyelination. In this study, we evaluate the remyelinating potential of adipose mesenchymal stem cells (ADSCs) and their effect on neural cell composition in the corpus callosum in an experimental model of MS.Materials and Methods: This experimental study used adult male C57BL/6 mice. Cultured ADSCs were confirmed to be CD73+,CD90+, CD31-,CD45-, and labeled by PKH26. Animals were fed with 0.2% w/w cuprizone added to ground breeder chow ad libitum for six weeks. At day 0 after cuprizone removal, mice were randomly divided into two groups: the ADSCs-transplanted group and the control vehicle group (received medium alone). Some mice of the same age were fed with their normal diet to serve as healthy control group. Homing of ADSCs in demyelinated lesions was examined by fluorescent microscope. At ten days after transplantation, the mice were euthanized and their cells analyzed by luxol fast blue staining (LFB), transmission electron microscopy and flow cytometry. Results were analyzed by one-way analysis of variance (ANOVA).Results: According to fluorescent cell labeling, transplanted ADSCs appeared to survive and exhibited homing specificity. LFB staining and transmission electron microscope evaluation revealed enhanced remyelination in the transplanted group compared to the control vehicle group. Flow cytometry analysis showedan increase in Olig2 and O4 cells and a decrease in GFAP and Iba-1 cells in the transplanted group.Conclusion: Our results indicate that ADSCs may provide a feasible, practical way for remyelination in diseases such as MS.

revious studies have demonstrated the potential of monotherapy with either mesenchymal stem cells (MSCs) or estrogen in autoimmune and cuprizone models of multiple sclerosis (MS). The aim of this study was to examine the effects of co-administration of 17β-estradiol (E2) and adipose-derived mesenchymal stem cells (ADSCs) on remyelination of corpus callosum axons in a cuprizone model of MS. Forty eight male C57BL/6 mice were fed cuprizone (0.2%) for 6 weeks. At day 0 after cuprizone removal, animals were randomly divided into four groups. The E2 monotherapy, ADSCs monotherapy, E2/ADSCs combined therapy and vehicle control. Some mice of the same age were fed with their normal diet to serve as healthy control group. E2 pellets, designed to release 5.0 mg E2 over 10 days, were implanted subcutaneously. 106 PKH26 labeled ADSCs were transplanted into lateral tail. The extent of demyelination, remyelination, and cell type's composition of host brain were examined at 10 days post-transplantation in the body of the corpus callosum. Transplanted cells migrated to the corpus callosum injury. Histological examination revealed efficacy of intravenous ADSCs transplantation in remyelination of mouse cuprizone model of MS can be significantly enhanced by E2 administration. Flow cytometry showed that the mean percentages of expression of Iba-1, Olig2 and O4 were significantly increased in E2/ADSCs combined therapy in comparison with ADSCs monotherapy. In conclusion, the findings of this study revealed that E2 administration enhanced efficacy of intravenous ADSCs transplantation in remyelination of corpus callosum axons in mouse cuprizone model of MS

Objective: Transplantation of bone marrow stromal cells (BMSCs) or Schwann cells (SCs) can facilitate axonal regeneration in peripheral nerve injuries. The aim of this study was to compare the effects of transplantation of BMSCs and SCs on functional recovery after injury to the sciatic nerve in the rat.Materials and Methods:In this experimental research, adult male Wistar rats (n=24, 250-300 g) were used, BMSCs and SCs were cultured, and SCs were confirmed with anti S100 antibody. Rats were randomly divided into 3 groups (n=8 in each group): 1; control group: silicon tube filled with fibrin gel without the cells, 2; BMSCs group: silicon tube filled with fibrin gel seeded with BMSCs and 3; SCs group: silicon tube filled with fibrin gel seeded with SCs. The left sciatic nerve was exposed, a 10 mm segment removed, and a silicone tube interposed into this nerve gap. BMSCs and SCs were separately transplanted into the gap in the two experimental groups and were labeled with anti BrdU and DiI respectively. After 12 weeks electrophysiological and functional assessments were performed and analyzed by one-way analysis of variance (ANOVA).Results: Electrophysiological and functional assessments showed a significant differencebetween the experimental groups compared with the control group. Electrophysiologicalmeasures were significantly better in the SCs transplantation group compared with the BMSCs treatment group (p

Abstract Introduction: This study was designed to investigate the effects of granulocyte colony-stimulating factor (G-CSF) administration in rats for 6 weeks after traumatic brain injury (TBI). Methods: Adult male Wistar rats (n = 30) were injured with controlled cortical impact device and divided into four groups. The treatment groups (n = 10 each) were injected subcutaneously with recombinant human G-CSF. Vehicle group (n=10) received phosphate buffered saline (PBS) and only Brdu intraperitoneally. Bromodeoxyuridine (BrdU) was used for mitotic labeling. Experimental rats were injected intraperitoneally with BrdU. Rats were killed at 6th week after traumatic brain injury. Neurological functional evaluation of animals was performed before and after injury using neurological severity scores (NSS). Animals were sacrificed 42 days after TBI and brain sections were stained using Brdu immunohistochemistry. Results: Statistically significant improvement in functional outcome was observed in treatment groups when compared with control (p

Objective: Previous studies have shown that transplantation of bone marrow stromalcells (BMSCs) into the contused spinal cord improves functional recovery and that administrationof Schwann cells (SCs) after spinal cord injury (SCI) facilitates axonal regeneration.Although the efficacy of these treatments have been proven, when used individually,their resulting number of regenerated axons is small and locomotor recovery is modest;therefore, we decided to research whether co-transplantation of these cells can improvethe outcome.Materials and Methods: Adult male Wistar rats (n=56), each weighting 250-300 gramswere used. BMSCs and SCs were cultured and prelabeled with BrdU and 1,1' dioctadecyl3,3,3',3' tetramethylindocarbocyanin perchlorate respectively. Contusion model of SCIwas performed at the T8-9 level using NYU device (New York University device). The ratswere divided into seven groups, each consisting of 8 animals. These groups included: acontrol group, three experimental groups and three sham groups. In the control group,only a laminectomy was performed. The three experiment groups were the BMSC, SCand co-transplant groups, and 7 days after injury, they received intraspinal BMSCs, SCsand the combination of BMSCs & SCs respectively. The sham groups received serum inthe same manner. Locomotion in the groups was assessed using the basso, beatie andbresnahan (BBB) test at 1, 7, 14, 21, 28, 35, 42, 49 and 56 days after SCI.Results: More significant improvement was observed in the BBB scores of the co-transplantgroup (p

Objective: This study was designed to examine the effects of human umbilical cord matrixstem cell (hUCMSC) administration in rats for 6 weeks after traumatic brain injury (TBI).Materials and Methods: Adult male Wistar rats (n = 30) were injured with controlled corticalimpact device and divided into three groups. The treatment group (n = 10) was injectedwith 2 × 106 hUCMSC intravenously, the vehicle group (n=10) received phosphate bufferedsaline (PBS) whereas the control group (n = 10) receive nothing. All injections wereperformed one day after injury into the tail veins of the rats. All cells were labelled withBrdu before injection. Evaluation of the neurological function of the rats was performedbefore and after injury using Neurological Severity Scores (NSS). The rats were sacrificed6 weeks after TBI and brain sections were stained using Brdu immunohistochemistry.Results: Statistically significant improvement in functional outcome was observed in thetreatment group compared with the control group (p < 0.01). This benefit was visible 1 weekafter TBI and persisted for six weeks (end of trial). Histological analysis showed that hUCMSCwere present in the lesion boundary zone at 6 weeks in all cell injected animals.Conclusion: Rats injected with hUCMSC after TBI survive for at least six weeks and showfunctional improvemnt.

Previous studies have demonstrated the potential of monotherapy with either mesenchymal stem cells (MSCs) or estrogen in autoimmune and cuprizone models of multiple sclerosis (MS). The aim of this study was to examine the effects of co-administration of 17β-estradiol (E2) and adipose-derived mesenchymal stem cells (ADSCs) on remyelination of corpus callosum axons in a cuprizone model of MS. Forty eight male C57BL/6 mice were fed cuprizone (0.2%) for 6 weeks. At day 0 after cuprizone removal, animals were randomly divided into four groups. The E2 monotherapy, ADSCs monotherapy, E2/ADSCs combined therapy and vehicle control. Some mice of the same age were fed with their normal diet to serve as healthy control group. E2 pellets, designed to release 5.0 mg E2 over 10 days, were implanted subcutaneously. 106 PKH26 labeled ADSCs were transplanted into lateral tail. The extent of demyelination, remyelination, and cell type's composition of host brain were examined at 10 days post-transplantation in the body of the corpus callosum. Transplanted cells migrated to the corpus callosum injury. Histological examination revealed efficacy of intravenous ADSCs transplantation in remyelination of mouse cuprizone model of MS can be significantly enhanced by E2 administration. Flow cytometry showed that the mean percentages of expression of Iba-1, Olig2 and O4 were significantly increased in E2/ADSCs combined therapy in comparison with ADSCs monotherapy. In conclusion, the findings of this study revealed that E2 administration enhanced efficacy of intravenous ADSCs transplantation in remyelination of corpus callosum axons in mouse cuprizone model of MS.

Nanoparticles (NPs) have many toxic effects on fertility and can prevent successful implantation by affecting the maternal uterine tissue. Herein, by deploying 30 female NMRI mice, the effect of silver NPs on the endometrium and implantation has been investigated. Using spherical silver NPs of a diameter of 18-30 nm at doses of 2 and 4 mg/kg, mice in two groups were treated. Then, female mice mated with male mice. Endometrial tissue was extracted 4.5 days later. On the fourth day of pregnancy, the mice were anesthetized and blood samples were taken from the heart; furthermore, endometrial tissue was isolated and used for molecular tests, inductively coupled plasma, and examination of pinopods. The results revealed that the levels of interleukin 6 (IL-6) and IL-1[beta] and the accumulation of NPs in endometrial tissue in the group receiving NPs at a dose of 4 mg/kg had a major increase relative to the other two groups (p < 0.05); the group receiving a dose of 4 mg/kg exhibited a decrease in pinopods and microvillus compared with the other two groups. According to the results, NPs can reach the endometrium, suggesting that caution should be exercised due to serious exposure to NPs throughout pregnancy. Key words: endometrium, implantation, pregnancy, silver nanoparticles. Les nanoparticules (NP) ont de nombreux effets toxiques sur la fertilite et peuvent empecher de realiser l'implantation avec succes en affectant le tissu uterin maternel. Ici, nous avons utilise 30 souris femelles de souche NMRI en vue d'etudier l'effet des NPs d'argent sur l'endometre et l'implantation. Nous avons administre des NPs d'argent spheriques de 18 a 30 nm de diametre a des doses de 2 et de 4 mg/kg chez les souris des deux groupes de traitement. Puis, nous avons accouple les souris femelles avec les souris males. Nous avons preleve le tissu endometrial 4,5 jours plus tard. Au quatrieme jour de gestation, les souris ont ete anesthesiees et nous avons preleve des echantillons de sang a partir du coeur; en outre, nous avons isole du tissu endometrial, que nous avons utilise pour des epreuves moleculaires, de plasma a couplage inductif (ICP) et dont nous avons examine les pinopodes. Les resultats ont revele que les taux d'IL-6 et d'IL-1[beta] de meme que l'accumulation de NPs dans le tissu endometrial etaient beaucoup plus eleves dans le groupe recevant des NPs a 4 mg/kg que dans les deux autres groupes (p < 0,05); les pinopodes et les microvilli etaient moins nombreux chez les souris 4 mg/kg que dans les deux autres groupes. D'apres les resultats, les NP peuvent se rendre a l'endometre, ce qui laisse entendre qu'il faudrait agir avec prudence en raison de la possibilite d'une exposition grave aux NPs tout au long de la grossesse. [Traduit par la Redaction] Mots-cles : endometre, implantation, grossesse, nanoparticules d'argent., Introduction The effect of nanotechnology products on public health has been examined in both in vitro and in vivo during the last decade; exposure of pregnant women to nanoparticles (NPs) [...]

Doxorubicin (DOX), a chemotherapy drug, has demonstrated limited efficacy against glioblastoma, an aggressive brain tumor with resistance attributed to the blood–brain barrier (BBB). This study aims to overcome this challenge by proposing the targeted delivery of magnetic Janus nanoparticles (MJNPs) functionalized with folic acid ligands, fluorescent dye, and doxorubicin (DOX/MJNPs-FLA). The properties of these nanoparticles were comprehensively evaluated using bio-physiochemical techniques such as Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta potential analysis, high-resolution transmission electron microscopy (HR-TEM), vibrating sample magnetometry (VSM), fluorescence microscopy, MTT assay, hemolysis assay, and liver enzyme level evaluation. Dual-controlled DOX release was investigated under different pH and temperature conditions. Additionally, the impact of DOX/MJNPs-FLA on apoptosis induction in tumor cells, body weight, and survival time of cancerous animals was assessed. The targeted delivery system was assessed using C6 and OLN-93 cell lines as representatives of cancerous and healthy cell lines, respectively, alongside Wistar rat tumor-bearing models. Results from Prussian blue staining and confocal microscopy tests demonstrated the effective targeted internalization of MJNPs-FLA by glioblastoma cells. Additionally, we investigated the biodistribution of the nanoparticles utilizing fluorescence imaging techniques. This enabled us to track the distribution pattern of MJNPs-FLA in vivo, shedding light on their movement and accumulation within the biological system. Furthermore, the combination of chemotherapy and magnetic hyperthermia exhibited enhanced efficacy in inducing apoptosis, as evidenced by the increase of the pro-apoptotic Bax gene and a decrease in the anti-apoptotic Bcl-2 gene. Remarkably, this combination treatment did not cause any hepatotoxicity. This study highlights the potential of DOX/MJNPs-FLA as carriers for therapeutic and diagnostic agents in the context of theranostic applications for the treatment of brain malignancies. Additionally, it demonstrates the promising performance of DOX/MJNPs-FLA in combination treatment through passive and active targeting. [ABSTRACT FROM AUTHOR]