Therapeutic effect of platelet-rich plasma on glucocorticoid-induced rat bone marrow mesenchymal stem cells in vitro.

BACKGROUND: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a progressive and disabling disease caused by long-term or high-dose glucocorticoid use. Decreased osteogenesis and proliferation of bone marrow mesenchymal stem cells (BMSCs) are the main pathogenesis of GIONFH. Platelet-rich plasma (PRP) has been shown to play a promising role in bone regeneration. However, the effects of PRP on glucocorticoid-induced BMSCs inhibition remains elusive. The objective of this study was to explore whether PRP could improve the in vitro biological activities of BMSCs inhibited by high-dose glucocorticoid in vitro. METHODS: In this study, a dexamethasone (Dex)-induced in vitro cell model was established. The effects of PRP on proliferation, migration, cell cycle and apoptosis of rat BMSCs induced with high-dose Dex compared to BMSCCTRL, using CCK-8 assay, transwell, flow cytometry and TUNEL assay, respectively. We further performed the alkaline phosphatase (ALP) and alizarin red (ALR) staining to explore the influence of PRP on osteogenic differentiation. Western Blot was used to detect the expression of Bcl-2, Caspase-3, RUNX2 apoptosis, and osteogenic-related proteins. RESULTS: We observed increased apoptosis rate and Caspase-3 expression, and the decreased migration and osteogenic differentiation, and down-regulation of RUNX-2 and Bcl-2 expression in Dex-induced BMSCs. PRP could reverse these inhibitory effects of Dex, and enhance the BMSCs proliferation, migration, and osteogenic ability in vitro. CONCLUSION: Our vitro study showed that PRP significantly protected BMSCs from Dex-induced apoptosis, and further promoted BMSCs proliferation, migration, and osteogenic differentiation. This study provides a scientific basis for the prevention and treatment of GIONFH with PRP. Meanwhile, it also lays the foundation for the application of PRP in other musculoskeletal diseases.

The Effectiveness of Trigeminal Nerve Stimulation on Traumatic Brain Injury.

OBJECTIVES: Trigeminal nerve stimulation (TNS) is a promising strategy in treating diseases of the nervous system. In this study, the effects of TNS on traumatic brain injury (TBI) were investigated in a mouse model. MATERIALS AND METHODS: TBI was induced using a weight-drop device, and TNS treatment was delivered in the first hour after the TBI. Twenty-four hours later, the mice's behavior, brain edema, and expression of inflammatory factors were tested. Functional magnetic resonance imaging also was used to explore the possible effects of TNS on brain activity. RESULTS: TNS alleviates TBI-induced neurological dysfunction in animal behavior tests, besides protecting the blood-brain barrier and reducing the level of brain edema. TNS also effectively reduces the level of tumor necrosis factor-α and interleukin 6 and downregulates the cleaved caspase-3 signaling pathway. A series of brain areas was found to be possibly regulated by TNS, thus affecting the neural functions of animals. CONCLUSION: This study elucidates the role of TNS as an effective treatment for TBI by inhibiting the occurrence of a secondary brain injury.

Recent Advances on Glioblastoma Multiforme and Nano-drug Carriers: A Review.

Glioblastoma Multiforme (GBM) is the most frequent glioma with a poor prognosis. The mainstay treatment for GBM is chemotherapy, but the average survival of GBM remains unsatisfactory due to therapeutic resistance. Poor permeability restricted by the Blood Brain Barrier (BBB) and the presence of Glioblastoma Stem Cells (GSCs) remain as two problems for chemotherapy. Recently, nanocarriers have attracted much attention in the research of GBM, owing to their advantages in self-assembly, biosafety, release controllability, and BBB penetrability, making them promising candidates for GBM treatment. This article aims to review the biologic signatures of BBB and GSCs, as well as the new development of nano-drug delivery systems to facilitate our understanding of targeted treatment for GBM.

Comparison of Significant Carotid Stenosis for Nasopharyngeal Carcinoma between Intensity-Modulated Radiotherapy and Conventional Two-Dimensional Radiotherapy.

Radiotherapy (RT) serves as the most efficient treatment for nasopharyngeal carcinoma (NPC) and can cause carotid stenosis. This work compared the incidence of significant carotid stenosis between intensity-modulated radiotherapy (IMRT) and two-dimensional conventional radiotherapy (2D-RT) for NPC and explored the risk factors. We retrospectively reviewed 233 cases with NPC who underwent carotid ultrasound post IMRT or 2D-RT from 2006 to 2015. The incidence of significant stenosis after RT was 19.3%. Significant stenosis was identified in 20 (14.6%) of 137 patients treated with IMRT and 25 (26.0%) of 96 patients with 2D-RT, respectively (p = 0.035). Multivariate logistic analysis indicated age (odds ratio = 1.054, 95% CI = 1.011-1.099, p = 0.014), radiation technique (IMRT) (odds ratio = 0.471, 95%CI = 0.241-0.919, p = 0.027) and time interval (odds ratio = 1.068, 95%CI = 1.033-1.105, p = 0.001) as independent predictors for significant carotid stenosis. Our study suggests that IMRT was associated with decreased incidence of significant carotid stenosis versus 2D-RT for NPC. Prevention and carotid ultrasound should be considered for older NPC survivors with longer interval from RT, especially those treated with 2D-RT.

Human Umbilical Cord Blood Serum-derived α-Secretase: Functional Testing in Alzheimer's Disease Mouse Models.

Alzheimer's disease (AD) is an age-related disorder that affects cognition. Our previous studies showed that the neuroprotective fragment of amyloid procurer protein (APP) metabolite, soluble APPα (sAPPα), interferes with ß-site APP-cleaving enzyme 1 (BACE1, ß-secretase) cleavage and reduces amyloid-ß (Aß) generation. In an attempt to identify approaches to restore sAPPα levels, we found that human cord blood serum (CBS) significantly promotes sAPPα production compared with adult blood serum (ABS) and aged blood serum (AgBS) in Chinese hamster ovary cells stably expressing wild-type human APP. Interestingly, CBS selectively mediated the α-secretase cleavage of human neuron-specific recombinant APP695 in a cell-free system independent of tumor necrosis factor-α converting enzyme (TACE; a disintegrin and metalloproteinase domain-containing protein 17 [ADAM17]) and ADAM. Subsequently, using 3-step chromatographic separation techniques (i.e., diethylaminoethanol, size-exclusion, and ion-exchange chromatography), we purified and ultimately identified a CBS-specific fraction with enhanced α-secretase catalytic activity (termed αCBSF) and found that αCBSF has more than 3,000-fold increased α-secretase catalytic activity compared with the original pooled CBS. Furthermore, intracerebroventricular injection of αCBSF markedly increased cerebral sAPPα levels together with significant decreases in cerebral Aß production and abnormal tau (Thr231) phosphorylation compared with the AgBS fraction with enhanced α-secretase activity (AgBSF) treatment in triple transgenic Alzheimer's disease (3xTg-AD) mice. Moreover, AgBSF administered intraperitoneally to transgenic mice with five familial Alzheimer's disease mutations (5XFAD) via an osmotic mini pump for 6 weeks (wk) ameliorated ß-amyloid plaques and reversed cognitive impairment measures. Together, our results propose the necessity for further study aimed at identification and characterization of α-secretase in CBS for novel and effective AD therapy.

Neurotropin inhibits neuroinflammation via suppressing NF-κB and MAPKs signaling pathways in lipopolysaccharide-stimulated BV2 cells.

Neurotropin (NTP) is a widely used drug in China and Japan mainly for the treatment of chronic pain and peripheral inflammation. Nevertheless, the effects of NTP on neuroinflammation have not been explored. In this study, we investigated the anti-inflammatory effects of NTP in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and its underlying mechanisms. BV-2 cells were pretreated with NTP for 12 h before exposure to LPS. The expression of pro-inflammatory cytokines (TNF-α and IL-6) were detected by RT-PCR and EILSA at mRNA and protein levels, respectively. Western blotting was conducted to measure the protein levels of major genes in MAPKs and NF-κB signaling pathways. Results demonstrated that NTP could attenuate the production of pro-inflammatory cytokines. Furthermore, NTP inhibited the activation of NF-κB signaling by decreasing the translocation of NF-κB p65 to the nucleus and suppressed the MAPKs signaling pathway via inhibition of the phosphorylation of p38, ERK and JNK. Taken together, these findings suggest that neurotropin exerts anti-inflammatory effects by suppressing the production of pro-inflammatory mediators via inhibition of NF-κB and MAPKs signaling pathways in LPS-stimulated BV-2 cells.

LED enhances anti-inflammatory effect of luteolin (3',4',5,7-tetrahydroxyflavone) in vitro.

Neuroinflammation is a complex pathological process usually results from abnormal microglial activation, thus, intervention in a microglial stimulation pathway could be a promising approach for the treatment of neurodegenerative diseases. Luteolin is an important bioflavonoid possesses anti-inflammatory properties, which is widely studied over these years. Light emitting diode (LED) therapy is reported to be a potential therapeutic strategy for many diseases including neurodegenerative diseases. However, little is known about the anti-inflammatory effect of LED therapy on activated microglial cells, even less is known whether there is a synergistic anti-inflammatory effect exist in LED and luteolin therapy. In this study, we aimed to confirm the anti-inflammatory effect of luteolin and LED combination therapy in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. We showed that luteolin inhibited LPS-induced cytotoxicity, tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) production through modulation of p38 and extracellular signal-regulated kinase (ERK) signaling in BV2 cells. In addition, LED therapy enhanced the anti-inflammatory effect of luteolin. These results suggest that a synergistic effect between luteolin and LED could be a new effective therapy in relieving neuroinflammation.

Bilateral ptosis as first presentation of cytophagic histiocytic panniculitis: a case report.

BACKGROUND: Cytophagic histiocytic panniculitis (CHP) is a rare form of nodular panniculitis that may progress to panniculitis-like T-cell lymphoma. We report a case of CHP that first manifested as bilateral ptosis, which is the first reported case of this presentation. CASE PRESENTATION: A 25-year-old woman without medical history was referred to the neurology department of our hospital for evaluation of bilateral ptosis. Three months previously, she suddenly complained of bilateral ptosis without apparent cause. Simultaneously, non-painful tender subcutaneous nodules and eschar-like skin lesions were observed on her extremities and trunk. A diagnosis of CHP was made based on skin biopsy from the left thigh showing lobular panniculitis, vasculitis, and adiponecrosis, with infiltration of inflammatory cells, including lymphocytes, histiocytes, and phagocytic histiocytes. Her condition continued to worsen with corticosteroid and immunosuppressive agent (thalidomide) treatment. Significant improvement was noticed after three cycles of chemotherapy of THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone). CONCLUSIONS: CHP is a rare condition whose clinical presentation may include bilateral ptosis and biopsy is required for diagnosis of CHP.

Late-onset cystic brain necrosis after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Cystic brain radionecrosis (CBRN) is a late-onset devastating complication after radiotherapy for head and neck neoplasms, especially for nasopharyngeal carcinoma (NPC). To our knowledge, it has scarcely been reported. METHODS: We retrospectively reviewed all available medical records of NPC patients with CBRN who were treated with surgical intervention. RESULTS: Sixteen patients were identified in this study and the mean latency of CBRN was 9.2 ± 0.9 years. The total irradiation dose of the nasopharynx ranged from 60 to 78 Gy. Cyst-like lesions were observed and there were slightly enhancements on the cyst wall in five patients on patients' brain MRI. All the included patients underwent surgical resection of the cystic necrotic lesion thought temporal approach. Specimens from surgery revealed reactive gliosis and immunopositive cytokines including TNF-α, IL-6 and HIF-2α. Only one patient experienced recurrence and received reoperation after surgery. All the other patients made a good recovery and no operation-related mortality was observed. CONCLUSIONS: CBRN is a delayed but irreversible neurological sequel in irradiated NPC patients. Post-radiotherapy follow-up is quite necessary for those with high risk of CBRN. Proper treatment is needed for early CBRN patients to suppress inflammation in the brain. Timely neurosurgery may benefit patients with late-stage CBRN by alleviating increased intracranial pressure and inflammatory responses.

Graphene quantum dots conjugated neuroprotective peptide improve learning and memory capability.

Alzheimer disease (AD) is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence extracellular neuritic plaques and with a large number of neurons lost. In this paper, we design a new nanomaterial, graphene quantum dots (GQDs) conjugated neuroprotective peptide glycine-proline-glutamate (GQDG) and administer it to APP/PS1 transgenic mice. The in vitro assays including ThT and CD proved that GQDs and GQDG could inhibit the aggregation of Aß1-42 fibrils. Morris water maze was performed to exanimate learning and memory capacity of APP/PS1 transgenic mice. The surface area of Aß plaque deposits reduced in the GQDG group compared to the Tg Ctrl groups. Furthermore, newly generated neuronal precursor cell and neuron were test by immunohistochemical. Besides, neurons were impregnated by DiI using gene gun to show dendritic spine. Results indicated enhancement of learning and memory capacity and increased amounts of dendritic spine were observed. Inflammation factors and amyloid-ß (Aß) were tested with suspension array and ELISA, respectively. Several pro-inflammatory cytokines (IL-1α, IL-1ß, IL-6, IL-33, IL-17α, MIP-1ß and TNF-α) had decreased in GQDG group compared with Control group. Reversely, anti-inflammatory cytokines (IL-4, IL-10) had increased in GQDG group compared with Control group. Thus, we demonstrate that the GQDG is a promising drug in treatment of neurodegenerative diseases such as AD.

PI3K/AKT/mTOR/p70S6K Pathway Is Involved in Aß25-35-Induced Autophagy.

Disruption or deregulation of the autophagy system has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Aß plays an important role in this autophagic system. In many cases, autophagy is regulated by the phosphatidylinositol 3-phosphate kinase/AKT/mammalian target of rapamycin/p70 ribosomal protein S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway. However, whether this signaling pathway is involved in Aß-induced autophagy in neuronal cells is not known. Here, we studied whether Aß25-35 induces autophagy in HT22 cells and C57 mice and investigated whether PI3K is involved in the autophagy induction. We found that Aß25-35 inhibited HT22 cell viability in a dose- and time-dependent manner. Aß25-35 induced autophagosome formation, the conversion of microtubule-associated protein light chain 3 (LC3), and the suppression of the mTOR pathway both in vitro and in vivo. Furthermore, Aß25-35 impaired the learning abilities of C57 mice. Our study suggests that Aß25-35 induces autophagy and the PI3K/AKT/mTOR/p70S6K pathway is involved in the process, which improves our understanding of the pathogenesis of AD and provides an additional model for AD research.

Effects of Nogo-A Silencing on TNF-α and IL-6 Secretion and TH Downregulation in Lipopolysaccharide-Stimulated PC12 Cells.

Parkinson's disease (PD) is a common degenerative disease that lacks efficient treatment. Myelin-associated neurite outgrowth inhibitor A (Nogo-A) is relevant with inhibition of nerve regeneration and may play vital role in pathogenesis of PD. The study aimed to establish the shRNA expression plasmids of Nogo-A gene and explore the regulatory effects of Nogo-A silencing on the expression of inflammation factor tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) as well as tyrosine hydroxylase (TH) in lipopolysaccharide- (LPS-) stimulated rat PC12 cells. The results showed that both mRNA and protein levels of Nogo-A in pGenesil-nogoA-shRNA group were downregulated. The viabilities of PC12 cells decreased with increase of LPS concentrations. LPS significantly increased the supernatant TNF-alpha and IL-6 concentrations and reduced TH protein expression in PC12 cells, while silencing Nogo-A could block these effects. These results suggested that LPS can activate PC12 cells to secrete inflammatory cytokines and lower the TH expression, which can be regulated by Nogo-A gene silencing. Nogo-A silencing might provide new ideas for PD treatment in the future.