Differential effects of rat ADSCs encapsulation in fibrin matrix and combination delivery of BDNF and Gold nanoparticles on peripheral nerve regeneration.

BACKGROUND: Fibrin as an extracellular matrix feature like biocompatibility, creates a favorable environment for proliferation and migration of cells and it can act as a reservoir for storage and release of growth factors in tissue engineering. METHODS: In this study, the inner surface of electrospun poly (lactic-co-glycolic acid) (PLGA) nanofibrous conduit was biofunctionalized with laminin containing brain derived neurotrophic factor (BDNF) and gold nanoparticles in chitosan nanoparticle. The rats were randomly divided into five groups, including autograft group as the positive control, PLGA conduit coated by laminin and filled with DMEM/F12, PLGA conduit coated by laminin and filled with rat-adipose derived stem cells (r-ADSCs), PLGA conduit coated by laminin containing gold-chitosan nanoparticles (AuNPs-CNPs), BDNF-chitosan nanoparticles (BDNF-CNPs) and filled with r-ADSCs or filled with r-ADSCs suspended in fibrin matrix, and they were implanted into a 10 mm rat sciatic nerve gap. Eventually, axonal regeneration and functional recovery were assessed after 12 weeks. RESULTS: After 3 months post-surgery period, the results showed that in the PLGA conduit filled with r-ADSCs without fibrin matrix group, positive effects were obtained as compared to other implanted groups by increasing the sciatic functional index significantly (p < 0.05). In addition, the diameter nerve fibers had a significant difference mean in the PLGA conduit coated by laminin and conduit filled with r-ADSCs in fibrin matrix groups relative to the autograft group (p < 0.001). However, G-ratio and amplitude (AMP) results showed that fibrin matrix might have beneficial effects on nerve regeneration but, immunohistochemistry and real-time RT-PCR outcomes indicated that the implanted conduit which filled with r-ADSCs, with or without BDNF-CNPs and AuNPs-CNPs had significantly higher expression of S100 and MBP markers than other conduit implanted groups (p < 0.05). CONCLUSIONS: It seems, in this study differential effects of fibrin matrix, could be interfered it with other factors thereby and further studies are required to determine the distinctive effects of fibrin matrix combination with other exogenous factors in peripheral nerve regeneration.

Improvement of Rat Sperm Chromatin Integrity and Spermatogenesis with Omega 3 following Bleomycin, Etoposide and Cisplatin Treatment.

The objective of this study is to examine the effects of omega 3 treatment on rat sperm chromatin condensation, DNA damage and spermatogenesis after bleomycin, etoposide and cisplatin (BEP) treatment. In this experimental study, 40 male rats were divided into four groups: Control, BEP, Omega 3 and BEP + Omega 3. Sperm chromatin condensation and DNA damage were assessed using aniline blue and acridine orange staining, respectively. Results show that the mean percentage of sperms with excessive histone and DNA damage was significantly increased in the BEP group after 9 weeks as compared to control group (p˂0.001). While, in the BEP + Omega 3 group, the mean percentage of sperm with excessive histone and DNA damage was decreased significantly compared with BEP group (p˂0.001). The testicular histomorphometric analysis indicated that omega 3 has a significant effect on the mean number of spermatogonia, primary spermatocytes, leydig cells and testicular histology properties following BEP treatment. The mean count of aforementioned cells significantly increased after omega 3 treatment compared with the BEP group (p˂0.001). Our data indicated omega 3 may be had beneficial effect for improving chromatin condensation, DNA damage during spermatogenesis and testicular histomorphic properties following BEP treatment.

Therapeutic effects of Cyperus rotundus rhizome extract on memory impairment, neurogenesis and mitochondria in beta-amyloid rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disturbance leading to memory deficit, cognitive decline, and behavioral disturbance. Deposition of Amyloid beta plaques, neurofibrillary tangle and mitochondrial impairment are common neuropathological signs in AD. In this study, the effect of standardized Cyperus rotundus(C. rotundus) extract in three different doses of 250, 500, and 750 mg/kg on memory, neurogenesis and mitochondrial mass in the beta amyloid rat model was assessed. For this purpose, 42 male Wistar rats were randomly divided into six groups (n = 7) to evaluate baseline training performance in Morris water maze test. Amyloid beta (Aß) was injected in animal hippocampal CA1 bilaterally in four groups. After 21 days, a decrease was observed in spending time in target quadrant in the first probe trial in Aß injected groups. Following that, 250, 500, and 750 mg/kg of C. rotundus extracts were administered to three out of four groups for a period of one month. BrdU (Bromodeoxyuridine) was intraperitoneally injected in all groups on the last 7 days of treatment. Then, 28 days after the last BrdU injection, the second probe trial was run, and rats were sacrificed. The neurogenesis and mitochondrial distribution were detected in hippocampus, by immunohistochemical staining. At last, it was observed that C. rotundus, almost recovered memory impairment, in addition to increasing in mitochondrial mass in CA1 and neurogenesis in dentate gyruse in the beta-amyloid rat model of Alzheimer's disease.

Biodelivery of nerve growth factor and gold nanoparticles encapsulated in chitosan nanoparticles for schwann-like cells differentiation of human adipose-derived stem cells.

The constant release of neurotrophic factors through a nanomaterial-based delivery system can be an important strategy in medical and pharmaceutical fields for nerve tissue engineering. The present study was aimed at encapsulating NGF and AuNPs in chitosan nanoparticles (NGF-CNPs and AuNPs-CSNPs) and its evaluation on the differentiation potential of human adipose-derived stem cells (h-ADSCs) to Schwann-like cells. The NGF-CNPs were prepared by ionotropic gelation method with tripolyphosphate (TPP) as a crosslinker. After synthesis and characterization of nanoparticles, NGF encapsulation efficiency and release profile were observed by Bradford assay. Next, the effects of NGF-CSNPs and AuNPs-CSNPs on h-ADSCs survival were assessed through MTT assay. Also, the efficacy of Schwann-like cells differentiation was assessed by immunocytochemistry and real-time RT-PCR for S100ß and MBP markers. NGF encapsulation efficiency was found about 85% and controlled and sustained release of NGF was observed during 7 days in vitro (74.63 ±â€¯2.07%). The findings revealed that these nanoparticles are cytocompatible. The immunocytochemical analysis indicated that NGF-CSNPs and AuNPs-CSNPs could significantly increase the differentiated rate and myelinogenic potential of Schwann-like cells (p < 0.05). Besides, the expression level of GFAP, S100ß, and MBP demonstrated significant upregulation in NGF-CSNPs and AuNPs-CSNPs groups compared to the control group (p < 0.05). Hence, it can be proposed that NGF-CNPs and AuNPs-CSNPs are capable of controlled release with improving the ability of h-ADSCs differentiation to Schwann-like cells. Also, the results show the potential future application of this differentiation in nerve tissue regeneration.

The Protective Effects of Omega3 on Ubiquitination and Protamination of Rat Sperm after Bleomycin, Etoposide, and Cisplatin Treatment.

The purpose of this study is evaluation the protective effect of omega3 on rat sperm protamination and ubiquitination after treatment with Bleomycin, Etoposide and Cisplatin (BEP) drugs. In present study, 40 male rats were divided into four groups: Control, BEP, Omega3 and BEP + Omega3. Sperm protamination and ubiquitination were assessed using chromomycin A3 and immunofluorescence staining respectively. The mean percentage of ubiquitinated sperm in BEP group was significantly increased relative to control group (P < .001). But, the mean percentage of sperm protamination significantly decreased in BEP group relative to control group (P < .001). Rats in BEP + Omega3 group showed a significantly decreased in the mean percentage of sperm ubiquitination as compared to BEP group (P < .05) while, sperm protamination increased significantly relative to BEP group (P < .001). Administration of Omega3 after chemotherapy showed an improvement in sperm ubiquitination and protamination. Our data indicated that omega3 after chemotherapy may be beneficial for chromatin remodeling during spermatogenesis following BEP treatment.

Electrospun tecophilic/gelatin nanofibers with potential for small diameter blood vessel tissue engineering.

Tissue engineering techniques particularly using electrospun scaffolds have been intensively used in recent years for the development of small diameter vascular grafts. However, the development of a completely successful scaffold that fulfills multiple requirements to guarantee complete vascular regeneration remains challenging. In this study, a hydrophilic and compliant polyurethane namely Tecophilic (TP) blended with gelatin (gel) at a weight ratio of 70:30 (TP(70)/gel(30)) was electrospun to fabricate a tubular composite scaffold with biomechanical properties closely simulating those of native blood vessels. Hydrophilic properties of the composite scaffold induced non-thrombogenicity while the incorporation of gelatin molecules within the scaffold greatly improved the capacity of the scaffold to serve as an adhesive substrate for vascular smooth muscle cells (SMCs), in comparison to pure TP. Preservation of the contractile phenotype of SMCs seeded on electrospun TP(70)/gel(30) was yet another promising feature of this scaffold. The nanostructured TP(70)/gel(30) demonstrated potential feasibility toward functioning as a vascular graft.

Effect of T3 hormone on neural differentiation of human adipose derived stem cells.

Human adult stem cells, which are capable of self-renewal and differentiation into other cell types, can be isolated from various tissues. There are no ethical and rejection problems as in the case of embryonic stem cells, so they are a promising source for cell therapy. The human body contains a great amount of adipose tissue that contains high numbers of mesenchymal stem cells. Human adipose-derived stem cells (hADSCs) could be easily induced to form neuron-like cells, and because of its availability and abundance, we can use it for clinical cell therapy. On the other hand, T3 hormone as a known neurotropic factor has important impressions on the nervous system. The aim of this study was to explore the effects of T3 treatment on neural differentiation of hADSCs. ADSCs were harvested from human adipose tissue, after neurosphere formation, and during final differentiation, treatment with T3 was performed. Immunocytochemistry, real-time RT-PCR, Western blotting techniques were used for detection of nestin, MAP2, and GFAP markers in order to confirm the effects of T3 on neural differentiation of hADSCs. Our results showed an increase in the number of glial cells but reduction in neuronal cells number fallowing T3 treatment.

Neuroprotective effects of rosemary extract on white matter of prefrontal cortex in old rats.

Objectives: During aging, cerebral structures undergo changes due to oxidative stress. The consumption of some plants seems to improve neurological health. For example, rosemary extract (RE) which is widely used as a flavoring food has anti-inflammatory and anti-oxidant activities. Therefore, we aimed to study the effect of RE on the changes related to the aging process in the prefrontal cortex (PFC). Materials and Methods: Twenty-four male Wistar rats including young and old were purchased. Each group was divided into two subgroups: vehicle and rosemary (old vehicle (OV), old rosemary (OR), young vehicle (YV), and young rosemary (YR) groups). Then, we examined the number of intact neurons, myelin base protein (MBP), white matter (WM), levels of malondialdehyde (MDA), and glutathione peroxidase (GPx) in the PFC. Results: The results showed that in the old vehicle rats compared to the young group without treatment, except for the MDA level (which increased), other variables significantly decreased (P≤0.05). Additionally, RE consumption demonstrated a significant elevation of WMA, MBP intensity, number of intact neurons, and GPx activity level, while MDA levels significantly reduced in the treated old rats compared to the old vehicle group (P≤0.05). However, there was no significant difference between the OR and YV groups (P≥0.05). Conclusion: Overall, it seems that RE can protect and improve aging damages in the PFC due to its anti-oxidant properties. So, the use of RE can be a suitable strategy to prevent aging complications in the brain.

Co-culture with neurotrophic factor secreting cells induced from adipose-derived stem cells: promotes neurogenic differentiation.

Adipose-derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) can be equally proper in the treatment of neurodegenerative diseases. However, ADSCs have practical benefits. In this study, we attempted to induce the secretion of neurotrophic factors (NTF) in human ADSCs. We then evaluated the effects of co-culture with NTF secreting cells in neural differentiation of human ADSCs. Isolated human ADSCs were induced to neurotrophic factors secreting cells. To evaluate the in vitro effects of NTF-secreting ADSCs on neurogenic differentiation of ADSCs, we used neurogenic induction medium (control group), the combination of neurogenic medium and conditioned medium, or co-cultured NTF-secreting ADSCs which were encapsulated in alginate beads (co-culture) for 7 days. ELISA showed increased (by about 5 times) release of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in NTF-secreting ADSCs compared to human ADSCs. Real time RT-PCR analysis revealed that NTF-secreting ADSCs highly expressed NGF and BDNF. In addition, co-culture with NTF-secreting ADSCs could also promote neuronal differentiation relative to gliogenesis. Overall, NTF-secreting ADSCs secrete a range of growth factors whose levels in culture could promote neuronal differentiation and could support the survival and regeneration in a variety of neurodegenerative diseases.

Comparing brain-derived neurotrophic factor and ciliary neurotrophic factor secretion of induced neurotrophic factor secreting cells from human adipose and bone marrow-derived stem cells.

Adipose derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) may be equally beneficial in treating neurodegenerative diseases. However, ADSCs have practical advantages. In this study, we aimed to induce neurotrophic factors secreting cells in human ADSCs. Then, we compared the level of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion in neurotrophic factors secreting cells from human adipose and bone marrow-derived stem cells. Isolated human ADSCs and BMSCs were induced to neurotrophic factor (NTF)-secreting cells. The levels of expression and secretion of BDNF and CTNF of induced cells were assessed using immunocytochemical, Real-Time polymerase chain reaction, and enzyme linked immunosorbent assay (ELISA). The level of BDNF significantly increased in both the induced mesenchymal stem cells (MSCs) relative to ADSCs and the BMSCs (P < 0.01). Moreover, ELISA analysis showed that the release of BDNF in the induced BMSCs was almost twofold more than the induced ADSCs. Overall, NTF-secreting factor cells derived BMSCs and ADSCs could secret a range of different growth factors. Therefore, the variation in neurotrophic factors of different induced MSC populations suggest the possible beneficial effect of each specific kind of neurotrophic factor secreting cells for the treatment of a particular neurodegenerative disease.

Effect of leukemia inhibitory factor on the myelinogenic ability of Schwann-like cells induced from human adipose-derived stem cells.

The Schwann cells (SCs) may be obtain from nerve biopsies for autologous transplantation. However, it is difficult to obtain sufficient amount of SCs for clinical applications. Human adipose-derived stem cells (ADSCs) can be induced to differentiate into Schwann-like cells (S-like cells) and used for autologous transplantation. However, effect of leukemia inhibitory factor (LIF) on the myelinogenic ability of SC-like cells induced from human ADSC is not investigated yet. The aim of this study was to evaluate of the effect of exogenous LIF on myelinogenic potential of differentiated cells in vitro. ADSCs were harvested from human fat tissue and characterized using flow cytometry. Human ADSCs were treated for sphere formation and LIF was added to terminal differentiation medium. GFAP/S100ß and MBP markers were used to confirm differentiation of human ADSCs, and myelinogenic ability of SC-like cells, respectively, using both immunostaining and real-time RT-PCR analysis. The analysis for GFAP(+)/S100ß(+) revealed that LIF can increase both differentiated cells rates and the percentage of myelinating SC-like cells (p < 0.05). Our data showed that SC-like cells induced from human ADSCs were able to generate myelin when exposed to LIF and these cells could be a potential source for the treatment of peripheral and central axonal injuries.

Upregulation of Neurotrophic Factors and Myelin Basic Protein in Schwann-like Cells by T3 Hormone Following Transdifferentiation of Human Adipose-derived Stem Cells.

Peripheral nerve regeneration is a complicated phenomenon. Thyroid hormones are known as critical regulators in the nervous system development. The Schwann cells have the regenerative potency in the peripheral nervous system. In this study, the human adipose-derived stem cells were assessed in vitro, for transdifferentiation potency into Shwann-like cells (SLCs) as a candidate source for clinical cell therapy, under the treatment of triiodothyronine (T3) hormone, and compared with the untreated cells. The cell viability rate, myelination and neurotrophic factors expression of SLCs were evaluated two weeks post- induction by MTT assay, immunocytochemistry and real-time RT-PCR techniques, respectively. The obtained results revealed a significant decrease in SLCs viability, compared to the adipose-derived stem cells (P < 0.001). Immunocytochemistry technique was applied to detect SLCs markers, such as S100ß, GFAP and myelin basic proteins (MBP) in the presence and absence of T3 treatment. The results indicated that administering T3 can significantly increase the differentiation and myelination potency of SLCs (P < 0.01). The findings of real-time RT-PCR technique indicated that the expression of Schwann cells markers, MBP, brain-derived neurotrophic factor and glial cell-derived neurotrophic factor were upregulated significantly with T3 hormone administration in comparison with the untreated cells (P < 0.05). The SLCs were able to express the neurotrophic factors and myelination related genes in the presence of T3 hormone. Furthermore, T3 administration improved myelination potency of adipose-derived stem cells, in vitro. Further in vivo experiments are necessary to confirm the advantages of using a combination of autologous SLCs and T3 hormone for peripheral nerve injury recovery.

Impact of Intraventricular Human Adipose-Derived Stem Cells Transplantation with Pregnenolone Treatment on Remyelination of Corpus Callosum in A Rat Model of Multiple Sclerosis.

OBJECTIVE: Multiple sclerosis (MS) is known as a nerve tissue disorder, which causes demyelination of central nervous system (CNS) fibers. Cell-based treatment is a novel strategy for the treatment of demyelinating diseases such as MS. Adipose-derived stem cells (ADSCs) have neuroprotective and neuroregenerative effects and pregnenolone as a neurosteroid has remarkable roles in neurogenesis. We intend to examine the impact of intraventricular transplantation of human ADSCs and systemic injection of pregnenolone on the remyelination of a rat model cuprizone-induced demyelination. MATERIALS AND METHODS: This experimental study was performed on 36 male Wistar rats that received a regular diet and a cuprizone diet for 3 weeks for M.S. induction. Through lipoaspirate surgery, human-ADSCs (hADSCs) were obtained from a patient. Six groups of rats (n=6): healthy, MS, sham, pregnenolone injection, ADSCs transplantation, and pregnenolone injection/ADSCs transplantation were included in this study. For assessment of remyelination, transmission electron microscopy (TEM), immunohistochemistry staining, real-time reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA) were performed. RESULTS: TEM outcomes revealed an increase in the thickness of the fibers myelin in the treatment groups (P<0.05). We also observed a significant upregulation of MBP, PDGFR-α, and MOG after treatment with hADSCs and pregnenolone compared to other study groups (P<0.001). These results were confirmed by immunostaining analysis. Moreover, there was no significant difference between the ADSCs/pregnenolone group and the control group regarding the level of MBP, A2B5, and MOG proteins in ELISA. CONCLUSION: Our data implied that the remyelination and cell recovery were more improved by intraventricular ADSCs transplantation and pregnenolone injection after inducing a rat model of MS.

Regeneration of Rat Sciatic Nerve Using PLGA Conduit Containing Rat ADSCs with Controlled Release of BDNF and Gold Nanoparticles.

Implantation of a nerve guidance conduit (NGC) carrying neuroprotective factors is promising for repairing peripheral nerve injury. Here, we developed a novel strategy for repairing peripheral nerve injury by gold nanoparticles (AuNPs) and brain-derived neurotrophic factor (BDNF)-encapsulated chitosan in laminin-coated nanofiber of Poly(l-lactide-co-glycolide) (PLGA) conduit and transplantation of rat adipose-derived stem cells (r-ADSCs) suspended in alginate. Then, the beneficial effect of AuNPs, BDNF, and r-ADSCs on nerve regeneration was evaluated in rat sciatic nerve transection model. In vivo experiments showed that the combination of AuNPs- and BDNF-encapsulated chitosan nanoparticles in laminin-coated nanofiber of PLGA conduit with r-ADSCs could synergistically facilitate nerve regeneration. Furthermore, the in vivo histology, immunohistochemistry, and behavioral results demonstrated that the AuNPs- and BDNF-encapsulated chitosan nanoparticles in NGC could significantly reinforce the repair performance of r-ADSCs, which may also contribute to the therapeutic outcome of the AuNPs, BDNF, and r-ADSCs strategies. In this study, we found that the combination of AuNPs and BDNF releases in NGC with r-ADSCs may represent a new potential strategy for peripheral nerve regeneration.

Evaluation of the leptin receptor in human spermatozoa.

BACKGROUND: Leptin, a 167 amino acid peptide hormone, profoundly effects reproduction exerting its biological effects via interaction with the leptin receptor (ObR) which is widely expressed on peripheral tissues. In this study, we have attempted to assess leptin receptor expression in the spermatozoa of fertile males and those diagnosed with male factor infertility; both at the mRNA or protein levels. METHODS: Semen samples were collected from fertile males and individuals with male factor infertility. In order to evaluate leptin receptor expression several techniques were utilized, including: reverse transcriptase-polymerase chain reaction (RT-PCR), immunostaining, flow cytometry, and western blotting. Mononuclear cells isolated from volunteers' peripheral blood were used as positive controls for leptin receptor expression. RESULTS: leptin receptor was noted on mononuclear cells but we were unable to detect this receptor on spermatozoa at the protein level. Leptin receptor expression was detected on peripheral blood mononuclear cells (PBMCs) as positive controls; however it was not detectable on the spermatozoa of both groups by immunofluorescence microscopy or flow cytometry. Furthermore, positive expression of the ObR long isoform as assessed by RT-PCR was observed in the sperm of only four cases, whereas expression of beta-Actin, a house keeping gene, and HspA2, a testis specific gene, was present in all cases. CONCLUSION: The long isoform of leptin receptor may not be present on human sperm. Species difference may be accounted for diverse reproductive physiology which depends on metabolic requirement. Leptin receptor expression at the mRNA level in some individuals may be related to contamination by other cells in semen.

Improvement of Remyelination in Demyelinated Corpus Callosum Using Human Adipose-Derived Stem Cells (hADSCs) and Pregnenolone in the Cuprizone Rat Model of Multiple Sclerosis.

Adipose-derived stem cells (ASCs) have neuroprotective effects, and their repair ability has been approved in neurodegenerative studies. Pregnenolone as a neurosteroid plays significant roles in neurogenesis. We aimed to consider the effect of ADSCs and pregnenolone injection on the multiple sclerosis (MS) model created by cuprizone. Male Wistar rats (n = 36) were fed with an ordinary diet or a diet with cuprizone (0.6%) for 3 weeks. H-ADSCs were taken from patients with lipoaspirate surgery. The rats were divided into six groups (n = 6): healthy, MS, sham, pregnenolone injection, ADSCs injection, pregnenolone and ADSCs injection. Behavioral test, histological examination and TEM were conducted. The specific markers for myelin and cell differentiation were assessed using immunohistochemistry staining. Additionally, the measure of MBP and MOG gene expression and the amount of related proteins were determined using real-time RT-PCR and ELISA techniques, respectively. Histologic results showed that induced demyelination in corpus callosum fibers. TEM revealed an increased thickness of myelin in fibers in the treated groups (P < 0.05). Injection of hADSC and pregnenolone significantly increased the expression levels of MBP and MOG (P < 0.001). The mean percentage of MOG and MBP markers were significantly increased in the treated groups compared to MS and sham groups (P < 0.05). Moreover, the OD level of MBP and MOG proteins showed that their values in the ADSCs/pregnenolone group were close to those of the control group without a significant difference. Our data indicated the remyelination potency and cell differentiation can improve with ADSCs and pregnenolone treatments in the multiple sclerosis model which created by cuprizone in rats.

Protective effects of zinc on rat sperm chromatin integrity involvement: DNA methylation, DNA fragmentation, ubiquitination and protamination after bleomycin etoposide and cis-platin treatment.

Testicular cancer is one of the most common malignancy in young men, chemotherapy induced damage in cancerous cells as well as healthy tissue, and we decided to investigate recovery effect of zinc (Zn) on chemotherapy-induced complications in rat chromatin integrity and testicular histomorphometry. The male rats (n = 40) were treated with BEP at appropriate dose levels of BEP (0.75, 7.5, and 1.5 mg/kg) for 9 weeks, with or without Zn; testicular histology, sperm DNA methylation, ubiquitination, DNA fragmentation and protamination were further assessed through immunofluorescence. BEP treatment significantly increased ubiquitination, and DNA fragmentation, considerably reducing global DNA methylation and protamination (P < 0.001), resulting in degenerative changes in testicular structure. Zn restored normal DNA methylation, protamination and structure of male gonads, maintained spermatogonial stem cells, and significantly reduced the mean percentage of ubiquitination and sperm DNA fragmentation as compared with BEP group (P < 0.001). We found that supplementation of Zn following chemotherapy can improve chromatin integrity, testicular organization and spermatogenesis.

Effects of Cyperus rotundus Extract on Spatial Memory Impairment and Neuronal Differentiation in Rat Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in the older population and characterized by progressive memory and cognitive impairment. Cyperus rotundus, a traditional medicinal herb, has analgesic, sedative, and anti-inflammatory effects and also used to increase memory in Islamic traditional medicine. This study was designed to consider the effects of C. rotundus extract on memory impairment and neurogenesis in the Beta-Amyloid rats' model. MATERIALS AND METHODS: Forty-two male Wistar rats were randomly divided into six groups (n = 7) for the evaluation of baseline training performance in the Morris water maze test. Then, amyloid-beta (Aß1-42) was injected in animal hippocampal CA1 bilaterally in four groups. The first probe trial was performed 21 days after Aß injection. Then, 250, 500, and 750 mg/kg of C. rotundus extract were administered to three Aß-injected groups for 1 month; after that, the second probe trial was performed, and rats were sacrificed after 28 days of the second probe trial. The neurogenesis was detected in the hippocampus, by immunohistochemical staining. RESULTS: This study showed that spatial memory increased in the behavioral test in AD treated group with C. rotundus extract, compared with the AD group (P = 0.02). Immunohistochemical staining revealed that neuronal differentiation has been occurred in the hippocampus in the AD-treated group with C. rotundus extract compared with the AD group (P = 0.01). CONCLUSIONS: This study showed that C. rotundus extract, repaired spatial memory impairment in the Aß rats, through increased neurogenesis in the hippocampus, which could be related to the flavonoid components in the extract.

The advances in nerve tissue engineering: From fabrication of nerve conduit to in vivo nerve regeneration assays.

Peripheral nerve damage is a common clinical complication of traumatic injury occurring after accident, tumorous outgrowth, or surgical side effects. Although the new methods and biomaterials have been improved recently, regeneration of peripheral nerve gaps is still a challenge. These injuries affect the quality of life of the patients negatively. In the recent years, many efforts have been made to develop innovative nerve tissue engineering approaches aiming to improve peripheral nerve treatment following nerve injuries. Herein, we will not only outline what we know about the peripheral nerve regeneration but also offer our insight regarding the types of nerve conduits, their fabrication process, and factors associated with conduits as well as types of animal and nerve models for evaluating conduit function. Finally, nerve regeneration in a rat sciatic nerve injury model by nerve conduits has been considered, and the main aspects that may affect the preclinical outcome have been discussed.

Effect of Zinc on Spermatogenesis and Sperm Chromatin Condensation in Bleomycin, Etoposide, Cisplatin Treated Rats.

OBJECTIVE: The incidence rate of testicular cancer among young males is high. Co-administration of bleomycin, etoposide and cisplatin (BEP) has increased survival rate of patients with testicular cancer. Although BEP is one of the most effective treatment for testicular cancer, but it severely affects the reproductive system that ultimately leads to infertility. In addition to its antioxidant activity, zinc has an important role in progression of spermiogenesis. This study aimed to evaluate the effect of zinc on sperm parameters, chromatin condensation and testicular structure after BEP treatment. MATERIALS AND METHODS: In this experimental study, 40 male rats were divided into 4 groups (control, BEP, BEP+ zinc and zinc) and examined for 2 spermatogenesis periods (i.e. 18 weeks). The rats in BEP and BEP+ zinc group were treated with BEP at appropriate doses (0.75, 7.5, and 1.5 mg/kg) for three cycles of three weeks. Zinc at a dose of 10 mg/kg/day was administered to BEP+ zinc and zinc groups. After 18 weeks, we assessed sperm parameters, and excessive histone in sperm chromatin using aniline blue staining, as well as testicular structure and germ line cells using periodic acid-Schiff staining. RESULTS: After BEP treatment, significant decreases were observed in normal sperm morphology, motility, and concentration, as well as alterations in rat sperm chromatin condensation and testicular tissue (P<0.001). Furthermore, after zinc consumption for 9 weeks, we observed significant improvements of sperm parameters and chromatin condensation as well as a significant retrieval of spermatogonia, leydig cells and tubular architecture (P<0.05). CONCLUSION: Zinc administration after chemotherapy with BEP in testicular cancer might be potentially useful in declining the off target consequence associated with oxidative stress.