Anti-Leishmanial Effects of a Novel Biocompatible Non-Invasive Nanofibers Containing Royal Jelly and Propolis against Iranian Strain of Leishmania major (MRHO/IR/75/ER): an In-Vitro Study

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

In Vitro Cytotoxicity Of Folate-Silica-Gold Nanorods On Mouse Acute Lymphoblastic Leukemia And Spermatogonial Cells

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

Toxicity of silver nanoparticles on Endometrial Receptivity in Female Mice

Nanoparticles (NPs) have many toxic effects on fertility and can prevent successful implantation by affecting the maternal uterine tissue. Herein, by deploying thirty female NMRI mice, the effect of silver nanoparticles on the endometrium and implantation has been investigated. Using spherical silver nanoparticles of a diameter of 18-30 nm at doses of 2 and 4 mg/kg, mice in both 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, ICP, and examination of pinopods. The results revealed that the levels of IL6 and IL1β and the accumulation of nanoparticles in endometrial tissue in the group receiving nanoparticles at a dose of 4 mg/kg had a major increase relative to the other two groups (pThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Left ventricular thrombus formation in a COVID‐19 patient with a complex course of pericarditis and myocardial infarction

Key Clinical Message Our case demonstrated that thrombotic complications such as coronary thrombosis and left ventricular clot could occur even in coronavirus disease 2019 (COVID‐19) patients with nonspecific symptoms which indicates the mysterious face of COVID‐19. This complex process highlights the necessity of screening patients for COVID‐19 disease even with nonspecific cardiac symptoms

Mobilization of stem cell with granulocyte-colony stimulating factor promotes recovery after traumatic brain injury in rat

  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<0.01). This benefit was visible 7 days after TBI and persisted until 42 days (end of trial). Histological analysis showed that Brdu cell positive was more in the lesion boundary zone at treatment animal group than all injected animals.   Discussion: We believe that G-CSF therapeutic protocol reported here represents an attractive strategy for the development of a clinically significant noninvasive traumatic brain injury therapy

Promotion of Remyelination by Adipose Mesenchymal Stem Cell Transplantation in A Cuprizone Model of Multiple Sclerosis

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

17β-Estradiol Enhances the Efficacy of Adipose-Derived Mesenchymal Stem Cells on Remyelination in Mouse Model of Multiple Sclerosis

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 M

Triple combination of heat, drug and radiation using alginate hydrogel co-loaded with gold nanoparticles and cisplatin for locally synergistic cancer therapy

Although multimodal cancer therapy has shown superior antitumor efficacy in comparison to individual therapy due to the potential generation of synergistic interactions among the treatments, its clinical usage is highly hampered by systemic dose-limiting toxicities. Herein, we developed a multi-responsive nanocomplex constructed from alginate hydrogel co-loaded with cisplatin and gold nanoparticles (AuNPs) (abbreviated as ACA) to combine chemotherapy, radiotherapy (RT) and photothermal therapy. The nanocomplex markedly improved the efficiency of drug delivery where ACA resulted in noticeably higher tumor growth inhibition than free cisplatin. The tumor treated with ACA showed an increased heating rate upon 532 nm laser irradiation, indicating the photothermal conversion ability of the nanocomplex. While RT alone resulted in slight tumor growth inhibition, thermo-chemo therapy, chemoradiation therapy and thermo-radio therapy using ACA dramatically slowed down the rate of tumor growth. Upon 532 nm laser and 6 MV X-ray, the nanocomplex could enable a trimodal thermo-chemo-radio therapy that yielded complete tumor regression with no evidence of relapse during the 90-days follow up period. The results of this study demonstrated that the incorporation of AuNPs and cisplatin into alginate hydrogel network can effectively combine chemotherapy, RT and photothermal therapy to achieve a locally synergistic cancer therapy. (C) 2020 Elsevier B.V. All rights reserved

Intravenous Injection of Human Umbilical Cord Matrix Stem Cell (Wharton Jelly Stem Cell) Provides Functional Recovery in a Rat Model of Traumatic Brain Injury

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