Role of brain metabolites during acute phase of mild traumatic brain injury in prognosis of post-concussion syndrome: A 1H-MRS study.

This study has investigated the potency and accuracy of early magnetic resonance spectroscopy (MRS) to predict post-concussion syndrome (PCS) in adult patients with a single mild traumatic brain injury (mTBI) without abnormality on a routine brain scan. A total of 48 eligible mTBI patients and 24 volunteers in the control group participated in this project. Brain MRS over regions of interest (ROI) and signal stop task (SST) were done within the first 72 hours of TBI onset. After six months, PCS appearance and severity were determined. In non-PCS patients, N-acetyl aspartate (NAA) levels significantly increased in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) relative to the control group, however, this increase of NAA levels were recorded in all ROI versus PCS subjects. There were dramatic declines in creatinine (Cr) levels of all ROI and a decrease in choline levels of corpus callosum (CC) in the PCS group versus control and non-PCS ones. NAA and NAA/Cho values in ACC were the main predictors of PCS appearance. The Cho/Cr level in ACC was the first predictor of PCS severity. Predicting accuracy was higher in ACC than in other regions. This study suggested the significance of neuro-markers in ACC for optimal prediction of PCS and rendered a new insight into the biological mechanism of mTBI that underpins PCS.

Regenerative medicine improve neurodegenerative diseases.

Regenerative medicine is a subdivision of medicine that improves methods to regrow, repair or replace unhealthy cells and tissues to return to normal function. Cell therapy, gene therapy, nanomedicine as choices used to cure neurodegenerative disease. Recently, studies related to the treatment of neurodegenerative disorders have been focused on stem cell therapy and Nano-drugs beyond other than regenerative medicine. Hence, by data from experimental models and clinical trials, we review the impact of stem cell therapy, gene therapy, and nanomedicine on the treatment of Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). Indeed, improved knowledge and continued research on gene therapy and nanomedicine in treating Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis lead to advancements in effective and practical treatments for neurodegenerative diseases.

¬Transcranial direct current stimulation improves sleep quality in patients with insomnia after traumatic brain injury.

INTRODUCTION: Insomnia is a serious problem after traumatic brain injury (TBI) and partially improves via sleeping pills. We investigated the efficacy of transcranial direct current stimulation (tDCS) with a focus on the role of age and gender. MATERIALS AND METHODS: In a randomized double-blind clinical trial, 60 eligible TBI-induced insomnia patients were assigned to real and sham tDCS groups and were treated for three weeks. Sham but not real tDCS took sleeping pills for the first three weeks of the study and then used the placebo until the end of the study. The placebo was used by the real-tDCS group throughout the study. Sleep quality and insomnia severity were respectively evaluated by Pittsburg Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) at three time points. RESULTS: Real tDCS group reported lower mean ISI and PSQI scores at 3 weeks post treatment onset and maintained this decline for six weeks post treatment onset (P < 0.001). In younger participants and those identified as men, the treatment-induced attenuation of the mean PSQI score was reported higher and more lasting in real than sham tDCS groups. CONCLUSION: Gender and age-specific tDCS protocols may be warranted to optimize the therapeutic effect of tDCS.

The association of 25 (OH) D3 serum level with ischemic cerebrovascular accident risk, severity and outcome in Iranian population.

OBJECTIVES: The role of combined presence of vitamin D deficiency and other risk factors of stroke in ischemic cerebrovascular accident (CVA) development in Iranian adults has been unclear, so far. The association of vitamin D status at admission with ischemic CVA severity and outcome in this community is not yet well elucidated. This study aimed to clarify these ambiguities. METHODS: In a cross-sectional study 104 hospitalized ischemic CVA patients and 104 healthy controls participated. The serum level of 25 (OH) D3 and baseline biochemical parameters were measured in ischemic patients within the first 24 h of admission, as well as healthy controls. The severity of CVA and clinical outcome were assessed using National Institutes Health Stroke Scale and Modified Rankin Scale, respectively. Data were analyzed using the Chi-square test, independent t-test, and multiple logistic regression. RESULTS: There was a significant difference between patients and controls regarding the presence of vitamin D3 deficiency, hypertension, smoking, and baseline level of LDL and FBS. Vitamin D3 deficiency boosted the risk of ischemic in males and those having family history of CVA. A low serum level of 25 (OH) D3 was associated with more severity and poor outcome of CVA. The CVA severity, vitamin D3 deficiency, and hypertension were predictors of poor outcome. CONCLUSIONS: The study highlights the increased risk of ischemia in Iranians by cooccurrence of vitamin D3 deficiency and other risk factors of CVA. Clinical significance of vitamin D3 deficiency control may be suggested in those at risk of CVA and functional poor outcomes.

National probabilistic risk assessment of newly registered pesticides in agricultural products to propose maximum residue limit (MRL).

Following the EPA recommended method, a chronic diet risk assessment for pesticides was recently performed for adults and children in the Iranian population. The National Theoretical Maximum Daily Intake (NTMDI) for 32 pesticides was computed using the theoretical maximum residue limits (MRLs) of food consumption regulations and data from the comprehensive database of the Iranian Research Institute of Plant Protection (IRIPP). The risk was assessed by comparing TMDI with the acceptable daily intakes (ADI) evaluated by FAO. From 32 investigated pesticides, 10 pesticides had TMDI > 65% of the ADI. Some of these ADI-exceeding compounds (spirodiclofen, abamectin, trifloxystrobin, spiromesifen, fipronil, difenoconazole, tetraconazole) were found in citrus, cucumber, grapes, tomato, and potato as the foods that have played the most roles in the consumption of these pesticides. Furthermore, a probabilistic risk assessment was performed to estimate the contingency of extravagance of the ADI. In the current research, only cyazofamid in potato for children consumers exceeded the 1 of the HQ. However, carcinogenic risk (CR) due to spirodiclofen in citrus fruit and difenoconazole in tomato was higher than the 1E-6 value; therefore, consumers were at considerable carcinogenic risk in these commodities. This scrutiny is essential for improving the activities' risk assessment, regulation, and surveillance.

Determination of multi-class pesticides residues of cow and human milk samples from Iran using UHPLC-MS/MS and GC-ECD: A probabilistic health risk assessment.

Raw, pasteurized, powdered cow milk and human milk samples from Tehran, Iran were investigated for the residual of fifty pesticides with the aid of gas chromatography coupled with electron capture detector (GC-ECD) and mass detector for confirmation; and ultra-high performance liquid chromatography-tandem mass spectroscopy (UHPLC-MS/MS). No pesticide residue was determined in more than 91% of examined samples. However, the dimethoate residue was detected in 3 raw milk samples in levels higher than EU recommended MRL. While in 3 human milk samples, organochlorine pesticides residue, p,p'-DDT, and p,p'-DDD was recognized below MRLs, only in 1 human sample residue of p,p'-DDE was more than CODEX recommended MRL. HI in adults and children were 0.72 and 3.55, respectively. However, the health risk assessment based on HI demonstrated that adult consumers are not at considerable risk. The HI, higher than 1 in children, confirms the risks raised due to ingestion of organochlorine (OCP) and organophosphorus (OPP) pesticides via milk consumption. In addition, no carcinogenic risk to milk consumers was calculated. Therefore, implementation of good farming practices on farms, improving the knowledge and consciousness of pesticide users, use other safe methods for pest control such as biotechnology-based, and use a rational program for application of pesticides, continuous monitoring of pesticides in crops, and strict government regulations on pesticide residues in food are recommended.

Pesticide residues in green-house cucumber, cantaloupe, and melon samples from Iran: A risk assessment by Monte Carlo Simulation.

This research aims to analyze 56 pesticide residues in 100 green-house cucumber and 150 cantaloupe and melon samples collected from markets in Iran by Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) extraction method based on analysis with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). In addition, non-carcinogenic and carcinogenic probabilistic health risk assessments were evaluated by Hazard Quotient (HQ), Hazard Index (HI), and Carcinogenic Risk (CR) based on the Monte Carlo Simulation (MCS) method. According to Iranian regulation, 18% of cucumber and 22% of cantaloupe and melon samples were contaminated by at least one pesticide. Arrange pesticides based on HQ ranking was diazinon > thiacloprid > imidacloprid tebuconazole for cucumbers and chlorpyrifos > thiacloprid > imidacloprid > metalaxyl for cantaloupes and melons. In addition, HI for adults was 0.067 in cucumber and 0.24 in cantaloupe and melon; and for children, 0.30 in cucumber and 0.60 in cantaloupe and melon. Arrange pesticides based on CR ranking was thiacloprid > imidacloprid > metalaxyl > chlorpyrifos > tebuconazole > diazinon. However, CR was more than 1.0E-6 value due to thiacloprid, so consumers were at considerable carcinogenic risk in these commodities.

Animal Kernicterus Models: Progress and Challenges.

Kernicterus is a leading cause of neonatal death throughout the world, especially in low-middle-income countries. It is developed by an unconjugated hyperbilirubinemia in the blood and brain tissue, triggering pathological processes that spawn neurotoxicity and neurodegeneration. However, the biological mechanism (s) of bilirubin-induced neurotoxicity and Kernicterus development remain to be well elucidated. Likewise, a practical therapeutic approach for human Kernicterus has yet to be found. Undoubtedly, animal models of Kernicterus can be helpful in the identification of underlying biological processes of hyperbilirubinemia evolution to Kernicterus, as well as the evaluation of various treatments efficacy in preclinical studies. More importantly, establishing an animal model that can mimic the Kernicterus and its behavioral, neuro-histological, and hematological manifestations is a severe priority in preclinical studies. So far, several Kernicterus animal models have been established that could partially mimic one or more clinical and paraclinical signs of human Kernicterus. The present study aimed to review all methods modeling Kernicterus with a focus on their potentials and shortcomings and subsequently provide the optimal methods for an ideal Kernicterus animal model.

Determinants of long-term health-related quality of life in adult patients with mild traumatic brain injury.

PURPOSE: Mild traumatic brain injury (mTBI) usually leads to the appearance of post-concussion symptoms (PCS) which may resolve after a short time. In this study, the mental and physical aspects of quality of life (QoL) were evaluated 6 months after mTBI, and the association of demographic and injury-related factors, post-injury primary executive function and PCS types with the long-term QoL status was investigated. METHODS: 123 eligible mTBI patients of initial sampling participated in follow-up phase of this longitudinal study. The demographic, clinical, and para-clinical data of patients were recorded. Paraclinical data comprised brain lesion volume, type and location determined by CT scan. The executive function and primary PCS were examined during the discharge using the verbal fluency task and a checklist, respectively. QoL was measured via SF-36 questionnaire. The collected data were entered into SPSS 22, and analyzed using appropriate statistical tests. RESULTS: Youngers aged between 18 and 35 years and women had a lower QoL score than others. Primary somatic and cognitive PCS together were associated with poor QoL. There was no significant difference in QoL and executive function scores between the normal and abnormal brain CT groups. However, among people with abnormal CT, those having multifocal lesions including at least an intracranial hemorrhage type such as intra parenchymal hemorrhage or extra-axial bleeding together with other intracranial lesions or skull fracture demonstrated less QoL score in SF-36. A significant correlation was discovered between the scores of the executive function and QoL in mental dimensions of SF-36. CONCLUSIONS: This study emphasizes on the clinical significance of early executive function and PCS examination in mTBI population, as well as optimal management of the victims regardless of the initial brain CT findings, especially in high-risk populations.

Rolipram optimizes therapeutic effect of bevacizumab by enhancing proapoptotic, antiproliferative signals in a glioblastoma heterotopic model.

The unstable response to bevacizumab is a big dilemma in the antiangiogenic therapy of high-grade glioma that appears to be linked to an increase in the post-treatment intratumor levels of hypoxia-inducible factor 1 α (HIF1α) and active AKT. Particularly, a selective phosphodiesterase IV (PDE4) inhibitor, rolipram is capable of inhibiting HIF1α and AKT in cancer cells. Here, the effect of bevacizumab alone and in presence of rolipram on therapeutic efficacy, intratumor hypoxia levels, angiogenesis, apoptosis and proliferation mechanisms were evaluated. BALB/c mice bearing C6 glioma were received bevacizumab and rolipram either alone or combined for 30 days (n = 11/group). At the last day of treatments, apoptosis, proliferation and microvessel density, in xenografts (3/group) were detected by TUNEL staining, Ki67 and CD31 markers, respectively. Relative expression of target proteins was measured using western blotting. Bevacizumab initially hindered the tumor progression but its antitumor effect was weakened later despite the vascular regression and apoptosis induction. Unpredictably, bevacizumab-treated tumors exhibited the highest cell proliferation coupled with PDE4A, HIF1α and AKT upregulation and p53 downregulation and reversed by co-treatment with rolipram. Unlike a similar antivascular pattern to bevacizumab, rolipram consistently led to a more tumor growth suppression and proapoptotic effect versus bevacizumab. Co-treatment maximally hampered the tumor progression and elongated survival along with the major vascular regression, hypoxia, apoptosis induction, p53 and caspase activities. In conclusion, superior and persistent therapeutic efficacy of co-treatment provides a new insight into antiangiogenic therapy of malignant gliomas, suggesting to be a potential substitute in selected patients.

The Role of Kinase Signaling in Resistance to Bevacizumab Therapy for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and is characterized by vascular hyperplasia, necrosis, and high cell proliferation. Despite current standard therapies, including surgical resection and chemoradiotherapy, GBM patients survive for only about 15 months after diagnosis. Recently, the U.S. Food and Drug Administration (FDA) has approved an antiangiogenesis medication for recurrent GBM-bevacizumab-which has improved progression-free survival in GBM patients. Although bevacizumab has resulted in significant early clinical benefit, it inescapably predisposes tumor to relapse that can be represented as an infiltrative phenotype. Fundamentally, bevacizumab antagonizes the vascular endothelial growth factor A (VEGFA), which is consistently released on both endothelial cells (ECs) and GBM cells. Actually, VEGFA inhibition on the ECs leads to the suppression of vascular progression, permeability, and the vasogenic edema. However, the consequence of the VEGFA pathway blockage on the GBM cells remains controversial. Nevertheless, a piece of evidence supports the relationship between bevacizumab application and compensatory activation of kinase signaling within GBM cells, leading to a tumor cell invasion known as the main mechanism of bevacizumab-induced tumor resistance. A complete understanding of kinase responses associated with tumor invasion in bevacizumab-resistant GBMs offers new therapeutic opportunities. Thus, this study aimed at presenting a brief overview of preclinical and clinical data of the tumor invasion and resistance induced by bevacizumab administration in GBMs, with a focus on the kinase responses during treatment. The novel therapeutic strategies to overcome this resistance by targeting protein kinases have also been summarized.

A Novel Intervention Technology for Cerebral Palsy: Brain Stimulation.

A common pediatric disorder with posture and motor dysfunction in neurological diseases is known as cerebral palsy (CP). Recently, a series of effective techniques have been developed for treatment of CP. These promising methods need high-tech equipment for brain stimulation and mainly classified into invasive and no-invasive approaches. This study aimed to introduce these techniques for treatment of patients who suffer from CP. The potential and performance of currently available brain stimulation techniques have been mentioned in detail. Moreover, the clinical application, safety, efficacy and challenges of these methods have been discussed. Here we review the recent advances in the CP treatment with an emphasis on brain stimulation techniques.

Transplantation of Adipose Tissue-Derived Stem Cells into Brain Through Cerebrospinal Fluid in Rat Models: Protocol Development and Initial Outcome Data.

BACKGROUND: Cell therapy is an important strategy for the treatment of incurable diseases including those that occur in the Central Nervous System (CNS). Among different strategies, the method of delivering or transplantation of cells into the brain has shown significant effects on regeneration. In this study, a new protocol has been developed for the transplantation of adipose tissuederived stem cells into the brain through Cerebrospinal Fluid (CSF) in rat models. METHODS: For this purpose, a wide range of ages (7-30 days old) of male neonates of Wistar rats was used. Moreover, human adipose tissue was obtained from a superficial layer of abdomen through liposuction surgery. The size of the inserted part of needle to access middle cranial fossa and subarachnoid space in animals with an average weight of 10-80 g was determined. In addition, to confirm the entrance of needle into the subarachnoid space, CSF was aspirated slowly and then injection was done within two minutes. RESULTS: The findings showed the presence of transplanted human Adipose-Derived Stem Cells (hADSC) in the cerebellum and basal ganglia following three days and also after two months that confirmed the entrance of transplanted cells into the cerebrospinal fluid and migration of them into the brain tissue. All the animals survived after the transplantation process, with the lowest side effects compared to the available conventional methods. CONCLUSION: It can be concluded that the cells could be efficiently transplanted into CSF through subarachnoid space by injection via superior orbital fissure with a minimally invasive technique.

The Role of Protein Kinase B Signaling Pathway in Anti-Cancer Effect of Rolipram on Glioblastoma Multiforme: An In Vitro Study.

INTRODUCTION: The mechanism of putative cytotoxicity of 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone (rolipram), a specific phosphodiesterase-4 (PDE4) inhibitor, on glioblastoma multiforme (GBM) is almost unknown. This study aimed to investigate the role of protein kinase B (Akt) pathway in the cytotoxic effect of rolipram on human GBM U87 MG cell line and Tumor-Initiating Cells (TICs) isolated from patient's GBM specimen. METHODS: TICs were characterized by using flow cytometry and quantitative real-time PCR. The cells were treated with rolipram at inhibitory concentration of 50% (IC50) in the presence or absence of SC79 (4µg/mL), a specific AKT activator, for 48 hours. The cell viability and apoptosis were measured by MTT assay and TUNEL staining, respectively. The relative expression of Phospho-Akt (Ser473), matrix metalloproteinase 2 (MMP2), and vascular endothelial growth factor A (VEGFA) were detected using Western blotting. RESULTS: The findings showed that rolipram could suppress cell viability in both U87MG and TICs, dose-dependently. Interestingly, the rolipram-induced cytotoxicity was significantly reduced in the presence of SC79. Nevertheless, in rolipram-treated cells, the pretreatment with SC79 significantly led to increase in U87 MG cells and TICs apoptosis and decrease in viability of U87 MG cells but not TICs relative to corresponding control. In U87 MG and TICs, rolipram-induced reduction of Phospho-Akt (Ser473) and MMP2 levels were significantly suppressed by SC79. CONCLUSION: There is a cell type-specific mechanism of anti-proliferative action of rolipram on GBM cells. The reduction of intracellular level of MMP2 but not VEGFA by rolipram is conducted through the inhibition of Akt signal. Rolipram-induced apoptosis is mediated via Akt dependent/independent mechanisms.

Perifosine enhances bevacizumab-induced apoptosis and therapeutic efficacy by targeting PI3K/AKT pathway in a glioblastoma heterotopic model.

Bevacizumab (BVZ) as an antiangiogenesis therapy leads to a transient therapeutic efficacy in high-grade glioma. However, the proapoptotic potential of BVZ has not been well elucidated, yet. There is also a tumor resistance to BVZ that is linked to post-treatment metalloproteinases and AKT activities. Herein, the association between therapeutic efficacy and putative proapoptotic activity of low-dose BVZ either alone or in combination with a specific inhibitor of AKT called perifosine (PRF), in a glioma model was investigated. BALB/c mice bearing C6 glioma tumor were treated with BVZ and PRF either alone or combined for 13 days (n = 11/group). At the end of treatments, apoptosis, proliferation and vascular density, in the xenografts (3/group) were detected by TUNEL staining, Ki67 and CD31 markers, respectively. Relative levels of cleaved-caspase3, phospho-AKT (Ser473) and matrix metalloproteinase2 (MMP2) were measured using western blotting. PRF and BVZ separately slowed down tumor growth along with the cell apoptosis induction associated with a profound increase in caspase3 activity through an AKT inhibition-related pathway for PRF but not BVZ. Unlike PRF, BVZ significantly increased the intratumor MMP2 and phospho-AKT (Ser473) levels coupled with the slight antiproliferative and significant antivascular effects. Co-administration of PRF and BVZ versus monotherapies potentiated the proapoptotic effects and reversed the BVZ-induced upregulation of phospho-AKT (Ser473) and MMP2 levels in C6 xenografts, leading to the optimal antiproliferative activity and tumor growth regression and longer survival. In conclusion, BVZ plus PRF renders a paramount proapoptotic effect, leading to a major therapeutic efficacy and might be a new substitute for GBM therapy in the clinic.

Rolipram potentiates bevacizumab-induced cell death in human glioblastoma stem-like cells.

AIMS: Glioblastoma cancer stem-like cells (GCSCs) promote themselves proliferation by secreting the vascular endothelial growth factor A (VEGFA) in an autocrine manner, positively regulated by phosphodiesterase IV (PDE4). In the current study, we investigated the putative cytotoxic effect of bevacizumab, a VEGFA blocker, alone and in combination with a specific inhibitor of PDE4 called rolipram on GCSCs isolated from human surgical tumor specimen with a focus on PI3K/AKT pathway. MAIN METHODS: CD133+/CD15+ GCSCs were characterized by flow cytometry and expanded in a serum-free primary culture system. The cell survival, apoptosis, and protein expression values were measured using MTT assay, TUNEL staining and western blot, successively. Intracellular cAMP and free secreted VEGFA levels were assessed by cAMP enzyme immunoassay and ELISA, respectively. KEY FINDINGS: Bevacizumab suppressed GCSCs survival with IC50~6.5µg/ml and enhanced the levels of apoptosis, p53 and cleaved-caspase3 along with a decrease in free VEGFA levels and ERKs activation. However, there was no significant modulation of AKT phosphorylation on serine 473, the intracellular PDE4A, VEGFA and cAMP levels. More cytotoxicity in co-treated cells coupled with a more substantial decline in the free VEGFA levels and a greater increase in the quantities of p53 and cleaved-caspase3 compared to those treated with bevacizumab alone. Co-treatment reduced phospho-AKT, endogenous VEGFA and PDE4A values but elevated cAMP levels. SIGNIFICANCE: This study highlighted a booster cytotoxic effect of combined rolipram and bevacizumab treatment on the GCSCs primary culture, suggesting that this approach is warranted in treatment of GBMs overexpressing VEGFA and PDE4A.

A new rat model of neonatal bilirubin encephalopathy (kernicterus).

INTRODUCTION: Hemolytic kernicterus, an indirect bilirubin-induced brain dysfunction, is associated with hyper-bilirubinemia in mammalian neonates. In this study, a new model of kernicterus has been developed using intra-peritoneal injections of phenyl hydrazine and subcutaneous injections of sulfisoxazole. These drugs can potentially induce kernicterus in neonatal through changes in hemolysis and hypo-albumin. METHODS: For this purpose, 7-day-old male Wistar rats (n=72; mean weight 11±1g) were used. The animals have been divided into six different groups which received the drugs alone and their combination, and the drugs' solvents and their combination. Biochemical parameters, brain iron and bilirubin, behavioural performance, auditory function and apoptosis were measured using auto-analyser instruments; atomic absorption spectroscopy, Sawasaki, footprint, auditory brainstem response (ABR) and TUNEL test, respectively. RESULT: The drug-injected groups showed a significant reduction in serum haematocrit and an increase in the concentration of brain bilirubin, total and indirect bilirubin as well as TUNEL positive cells in basal ganglia. In addition, the obtained results showed that there was a significant increase in behavioural disturbance and auditory dysfunction in the group injected with the combination of two drugs. CONCLUSION: This kernicterus-induced rat model could perfectly mimic the common conditions of the hyperbilirubinemia in human neonates. This study offers an easy technique to develop more stable models for follow-up studies.

Development of novel biocompatible hybrid nanocomposites based on polyurethane-silica prepared by sol gel process.

Due to high biocompatibility, polyurethane has found many applications, particularly in development of biomedical devices. A new nanocomposite based on thermoset polyurethane and silica nanoparticles was synthesized using sol-gel method. Sol-gel process was fulfilled in two acidic and basic conditions by using tetraethylorthosilicate (TEOS) and trimethoxyisocyanatesilane as precursors. The hybrid films characterized for mechanical and surface properties using tensile strength, contact angle, ATR-FTIR and scanning electron microscopy. Biocompatibility and cytotoxicity of the hybrids were assessed using standard MTT, LDH and TUNEL assays. The results revealed that incorporation of silica nanoparticles was significantly improved tensile strength and mechanical properties of the hybrids. Based on the contact angle results, silica nanoparticles increased hydrophilicity of the hybrids. Biocompatibility by using human lung epithelial cell line (MRC-5) demonstrated that the hybrids were significantly less cytotoxic compared to pristine polymer as tested by MTT and LDH assays. TUNEL assay revealed no signs of apoptosis in all tested samples. The results of this study demonstrated that incorporation of silica nanoparticles into polyurethane lead to the enhancement of biocompatibility, indicating that these hybrids could potentially be used in biomedical field in particular as a new coating for medical implants.

Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats.

Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.