Search

Background and Purpose: Radiation‐induced brain injury (RBI) usually occurs six months to three years after irradiation, often shows cognitive dysfunction, epilepsy, and other neurological dysfunction. In severe cases, it can cause a wide range of cerebral edema, even herniation. It seriously threatens the survival of patients and their quality of life, and it becomes a key factor in limiting the radiation dose and lowering the therapeutic efficacy in recent years. Therefore, studying the pathogenesis of RBI and exploring new therapeutic targets are of great significance. Methods: In our study, we observed the activation and secretory function in astrocytes as well as the intracellular signal transducer and activator of transcription 3 (STAT3) signal transduction pathway activation status after exposing different doses of X‐ray irradiation by using MTT, Immunocytologic analysis, and Western blot analysis. Further, we used the same way to explore the role of vascular endothelial growth factor (VEGF) in signal transduction pathways playing in the activation of astrocytes after irradiating through the use of specificInhivascular endothelial growth factorbitors of STAT3. Results: Ast can be directly activated, reactive hyperplasia and hypertrophy, the expression of the activation marker glial fibrillary acidic protein is increased, and the expression of vascular endothelial growth factor (VEGF) in the cells is increased, which may lead to RBI. After the addition of STAT3 pathway inhibitor, most of the Ast radiation activation was suppressed, and the expression of high‐level expression of VEGF decreased after irradiation. Conclusion: Our findings demonstrated that X‐ray irradiation directly induced the activation of astrocytes in a persistent manner and X‐ray irradiation activated STAT3 signaling pathway. As the same time, we found that X‐ray irradiation induced the activation of astrocytes and secretion cytokine. The STAT3 signaling pathway may participate in the pathogenesis of radiation‐induced brain injury. [ABSTRACT FROM AUTHOR]

[Display omitted] • MICU3 expression is increased in brain of CAA mice. • MICU3 improves behavioral performances in CAA mice. • MICU3 reduces Aβ accumulation in CAA mice. • MICU3 improves neuronal survival in cortex and hippocampus of CAA mice. • MICU3 restrains oxidative stress in cortex and hippocampus of CAA mice. Cerebral amyloid angiopathy (CAA) is characterized by the cerebrovascular amyloid-β (Aβ) accumulation, and always accompanied by Alzheimer's disease (AD). Mitochondrial dysfunction-associated cellular events including cell death, inflammation and oxidative stress are implicated in the progression of CAA. Unfortunately, the molecular mechanisms revealing CAA pathogenesis are still obscure, thus requiring further studies. Mitochondrial calcium uptake 3 (MICU3), a regulator of the mitochondrial Ca2+ uniporter (MCU), mediates various biological functions, but its expression and influence on CAA are largely unknown. In the present study, we found that MICU3 expression was gradually declined in cortex and hippocampus of Tg-SwDI transgenic mice. Using stereotaxic operation with AAV9 encoding MICU3, we showed that AAV-MICU3 improved the behavioral performances and cerebral blood flow (CBF) in Tg-SwDI mice, along with markedly reduced Aβ deposition through mediating Aβ metabolism process. Importantly, we found that AAV-MICU3 remarkably improved neuronal death and mitigated glial activation and neuroinflammation in cortex and hippocampus of Tg-SwDI mice. Furthermore, excessive oxidative stress, mitochondrial impairment and dysfunction, decreased ATP and mitochondrial DNA (mtDNA) were detected in Tg-SwDI mice, while being considerably ameliorated upon MICU3 over-expression. More importantly, our in vitro experiments suggested that MICU3-attenuated neuronal death, activation of glial cells and oxidative stress were completely abrogated upon PTEN induced putative kinase 1 (PINK1) knockdown, indicating that PINK1 was required for MICU3 to perform its protective effects against CAA. Mechanistic experiment confirmed an interaction between MICU3 and PINK1. Together, these findings demonstrated that MICU3-PINK1 axis may serve as a key target for CAA treatment mainly through improving mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Cerebral amyloid angiopathy (CAA) is characterized by the cerebrovascular amyloid-β (Aβ) accumulation, and always accompanied by Alzheimer's disease (AD). The mechanisms revealing CAA pathogenesis are still unclear, and it is challenging to develop an efficient therapeutic strategy for its treatment. Vascular endothelial growth factor (VEGF) and its receptors including VEGFR-1,-2,-3 activation are involved in Aβ processing, and modulate numerous cellular events associated with central nervous system (CNS) diseases. In the present study, we attempted to explore the regulatory function of fruquintinib (also named as HMPL-013), a highly selective inhibitor of VEGFR-1,-2,-3 tyrosine kinases, on CAA progression in Tg-SwDI mice. Here, we found that HMPL-013-rich diet consumption for 12 months significantly improved the behavioral performances and cerebral blood flow (CBF) of Tg-SwDI mice compared with the vehicle group. Importantly, HMPL-013 administration considerably reduced Aβ 1-40 and Aβ 1-42 burden in cortex and hippocampus of Tg-SwDI mice through regulating Aβ metabolism process. Congo red staining confirmed Aβ deposition in vessel walls, reflecting CAA formation, which was, however, strongly ameliorated after HMPL-013 treatment. Neuron death, aberrant glial activation and pro-inflammatory response in brain tissues of Tg-SwDI mice were dramatically alleviated after HMPL-013 consumption. More studies showed that the protective effects of HMPL-013 against CAA might be partially attributed to its regulation on the expression of genes associated with blood vasculature. Intriguingly, VEGF and phosphorylated VEGFR-1,-2 protein expression levels were remarkably decreased by HMPL-013 in cortex and hippocampus of Tg-SwDI mice, which were validated in HMPL-013-treated brain vascular endothelial cells (BVECs) under hypoxia. Finally, we found that VEGF-induced human umbilical vein endothelial cells (HUVEC) proliferation and tube formation were strongly abolished upon HMPL-013 exposure. Collectively, all these findings demonstrated that oral administration of HMPL-013 had therapeutic potential against CAA by reducing Aβ deposition, inflammation and neuron death via suppressing VEGF/VEGFR-1,-2 signaling. [Display omitted] • HMPL-013 mitigates impaired behavioral performance in Tg-SwDI mice with CAA. • HMPL-013 consumption reduces Aβ accumulation in Tg-SwDI mice. • HMPL-013 ameliorates Aβ metabolism in vitro and in vivo via suppression of ROS and inflammation. • HMPL-013 improves neuron survival in Tg-SwDI mice. • HMPL-013 reduces glial cell activation in Tg-SwDI mice. [ABSTRACT FROM AUTHOR]

Abstract: Surface hardening of 17-4PH was achieved by laser transformation hardening using 5kW continuous wave CO2 laser system. The microstructure of the laser-quenched sample was investigated by optical microscopy, transmission electron microscope and 57Fe Mössbauer spectrometer. The hardness profile was determined by a Vickers hardness tester. The hardened layer with a thickness of 1.75mm was formed, and it was composed of classic lath martensite, coarse NbC and a lot of finer fcc copper-rich phases which were similar to ɛ-Cu precipitates. The maximal hardness value of hardened zone is 446HV which is 50HV higher than that of the substrate (386–397HV). The higher hardness in laser transformation layer of the 17-4PH steel could be attributed to the following aspects: the matrix with a high dislocation density; the fine microstructure; the finer fcc copper-rich phases that were similar to the ɛ-Cu precipitates as well as the transforming of retained austenite into lath martensite. [Copyright &y& Elsevier]

Hydrogen transportation by pipelines gradually becomes a critical engineering route in the worldwide adaptation of hydrogen as a form of clean energy. However, due to the hydrogen embrittlement effect, the compatibility of linepipe steels and associated welds with hydrogen is a major concern when designing hydrogen-carrying pipelines. When hydrogen enters the steels, their ductility, fracture resistance, and fatigue properties can be adversely altered. This paper reviews the status of several demonstration projects for natural gas-hydrogen blending and pure hydrogen transportation, the pipeline materials used and their operating parameters. This paper also compares the current standards of materials specifications for hydrogen pipeline systems from different parts of the world. The hydrogen compatibility and tolerance of varying grades of linepipe steels and the relevant testing methods for assessing the compatibility are then discussed, and the conservatism or the inadequacies of the test conditions of the current standards are pointed out for future improvement. [Display omitted] • Summarized projects of pure-hydrogen and natural gas-hydrogen blending pipelines. • Discussed the factors affecting hydrogen compatibility of pipeline. • Reviewed the testing methods for assessing hydrogen-steel compatibility. • Presented a new proposal for toughness test for pipeline slow loading condition. • Several challenges facing the high-pressure hydrogen pipelines are outlined. [ABSTRACT FROM AUTHOR]

Background and Purpose: Enhanced remyelination of the regenerated axons results in functional re‐innervation and improved functional motor recovery after brachial plexus root avulsion (BPRA). The neural cell adhesion molecule L1 (L1CAM, L1) regulates myelination and promotes regeneration after acute injury in the nervous system. Berberine (BBR) can exert neuroprotective roles against the lesion. Herein, we investigated whether berberine (BBR) can affect the expression of L1 and enhance the axonal remyelination in rats following BPRA. Methods: The surgical procedures were performed to build the rat brachial plexus avulsion and re‐implantation model, and then, the rats were treated with BBR. After the rehabilitation for 12 weeks, the musculocutaneous nerves were collected for quantitative real‐time PCR, Western blot analysis, and histochemical and immunofluorescence staining. Results: We observed that, BBR treatment ameliorated the abnormal musculocutaneous nerve fibers morphology, up‐regulated the L1 expression, increased the myelination‐related genes, decreased the differentiated‐associated genes, and up‐regulated the phosphorylation of ERK. Conclusion: These results suggest that BBR may enhance L1 expression and promote axonal remyelination after spinal root avulsion. [ABSTRACT FROM AUTHOR]

Background: Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps muscles, leading to the loss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proven to exert neuroprotective and anti-inflammatory effects on various disorders of the nervous system. Thus, the present study mainly focused on the influence of NAG on motor and sensory recovery after BPRA in rats and the underlying mechanisms. Methods: Male adult Sprague Dawley (SD) rats were subjected to BPRA and reimplantation surgery and subsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and the mechanical pain threshold of the affected forelimb. The morphological appearance of the spinal cord, musculocutaneous nerve, and biceps brachii was assessed by histological staining. Quantitative real-time PCR (qRT‒PCR) was used to measure the mRNA levels of remyelination and regeneration indicators in myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the spinal cord anterior horn were measured using Western blotting. Results: NAG significantly accelerated the recovery of motor function in the injured forelimbs, enhanced motoneuronal survival in the anterior horn of the spinal cord, inhibited the expression of proinflammatory cytokines and pyroptosis pathway factors, facilitated axonal remyelination in the myocutaneous nerve and alleviated atrophy of the biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA. Conclusion: NAG promotes functional motor recovery and alleviates neuropathic pain by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for the use of NAG as a novel treatment for BPRA. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease. It can lead to progressive cognitive impairment, memory loss, and behavioral alterations. So far, the exact cellular and molecular mechanisms underlying this disorder remain unclear. And there are no effective treatments to prevent, halt, or reverse AD. In recent years, Chinese traditional medicine has become a new force in the treatment of AD, and the typical representatives of natural herbal ingredients are curcumin and its derivatives. Bisdemethoxycurcumin (BDMC), which is a classical derivative of curcumin, was found to have neuroprotective effects against a cell model of Alzheimer's disease (AD) in our previous studies. This study investigated the intrinsic mechanism of BDMC against AD in animal models. Methods: In this study, BDMC was injected into the lateral ventricles of normal C57BL/6 mice, APP/PS mice, and APP/PS mice treated with EX527 (the inhibitor of SIRT1). Y maze and Morris water maze were used to test the learning and memory ability of mice. Nissl staining was used to observe the morphological changes of neurons. Immunofluorescence staining was used to detect Aβ deposition in mice. The activities of GSH and SOD were determined to observe the levels of oxidative stress in mice. And Western blot analyses were used to detect content of SIRT1 in mice. Results: In the APP/PS mice, after BDMC intervention, their cognitive function improved, oxidative stress adjusted, the number of neurons increased, Aβ deposition decreased, and the level of SIRT1 expression increased. However, when SIRT1 is inhibited, BDMC on the improvement in the learning and memory ability and the improvement on oxidative stress in APP/PS1 mice were reversed. Conclusion: Our findings demonstrated that in the AD mice, BDMC has antagonistic effect on AD. And an intermediate step in the antagonism effect is caused by SIRT1 upregulation, which leading to decreased oxidative stress. Based on these, we concluded that BDMC injection into the lateral ventricle can act against AD by upregulating SIRT1 to antioxidative stress. [ABSTRACT FROM AUTHOR]

BACKGROUND: Imbalance between subchondral bone resorption and bone fonnation occurs in osteoarthritis. Our preliminary study has found that the subchondral bone changes precede the articular cartilage changes in knee osteoarthritis rats. OBJECTIVE: To observe the changes of subchondral bone in knee osteoarthritis rats, and to explore the effect of elcatonin on the expression of p38 MAPK and absorption of subchondral bone. METHODS: Female Sprague-Dawley rats, 3 months of age, were randomly divided into three groups: sham operation group (n=6, the adipose tissue of the same size as the ovary was removed without ovariectomy, the bilateral knee joints were opened, but without cruciate ligament injury); model group (n=6, bilateral ovariectomy plus bilateral cruciate ligament injury, no treatment); elcatonin group (n=6, ovariectomy plus cruciate ligament injury, intramuscular injection of 5lU/kg elcatonin, twice weekly). The bone mineral density and p38 protein expression levels in subchondral bone were detected at 12 weeks. The serum levels of C-terminal crosslinking telopeptides of type I collagen, C-terminal crosslinking telopeptides of type II collagen, interleukin-1, interleukin-6 and bone-specific alkaline phosphatase, tartrate resistant acid phosphatase 5b were detected. RESULTS AND CONCLUSION: (1) The bone volume fraction and trabecular bone number in the elcatonin group were significantly higher than those in the model group (P < 0.05), and the trabecular separation in the elcatonin group was lower than that in the model group (P < 0.05). (2) The bone volume fraction, trabecular bone number and trabecular thickness in the model group were lower than those in the sham operation group (P < 0.01 or P < 0.05), and the trabecular separation was higher than that in the sham operation group (P < 0.01). (3) The serum levels of C-tenninal crosslinking telopeptides of type I collagen, C-tenninal crosslinking telopeptides of type II collagen, interleukin-1, interleukin-6 and tartrate resistant acid phosphatase 5b in the elcatonin group was significanUy lower than those the model group (P < 0.05). and the above levels in the model group were significantly higher than those in the sham operation group (P < 0.05). (4) The p38 expression level in subchondral bone in the elcatonin group was significantly lower than that in the model group (P < 0.01 ), and the level in the model group was significantly higher than that in the sham operation group (P < 0.01). (5) These results indicate that elcatonin may inhibit the secretion of osteoarthritis pro-inflammatory factors and subchondral bone resorption by down-regulating the expression level of p38 MAPK. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mitogen-activated protein kinase signaling pathway participates in the differentiation of osteoblasts and osteoclasts, closely related to subchondral bone reconstruction and play a key role in the occurrence and development of osteoarthritis. Bisphosphonates as bone resorption inhibitor is used to treat osteoporosis. OBJECTIVE: To observe the effect of sodium ibandronate on the knee osteoarthritis in rats, and changes of mitogen-activated protein kinase signaling pathway. METHODS: The study was approved by the Laboratory Animal Ethical Committee of the First Affiliated Hospital of South China University. Thirty female Sprague-Dawley rats were randomly divided into sham, model, and treatment groups. The rats in the latter two groups underwent ovariectomy bilaterally, and anterior cruciate ligament resection, and rats in the sham group received the fatty tissue surrounding the ovaries removed only. After 1 week of surgery, the rats in the treatment group were given intraperitoneal injection of 10 µg/kg sodium ibandronate, rats in the model group were injected with normal saline, and the sham group received no intervention. Twelve weeks late, the rats were killed to perform histological examination of cartticular cartilage and Mankin scores were detected. Micro-CT of subchondral bone and quantitative analysis of the bone microstructure were conducted. The protein and mRNA expression levels of extracellular signal regulated protein kinase and c-Jun N-terminal kinase in mitogen-activated protein kinase signaling pathway were measured. RESULTS AND CONCLUSION: (1) The cartilage structure in the model group was significantly damaged, the Mankin score was significantly higher than that in the sham group, and the Mankin score in the treatment group was significantly lower than that in the model group (P < 0.01 ). (2) The bone mineral density, trabecular bone volume ratio, trabecular number in the model group were significantly lower than those in the sham group (P < 0.01), and trabecular separation was higher than that in the sham group (P < 0.01). Compared with the model group, the treatment group had higher bone mineral density, trabecular bone volume ratio, trabecular number, and lower trabecular separation (P < 0.01 ). (3) The mRNA and protein expression levels of extracellular signal regulated protein kinase and c-Jun N-terminal kinase in the model group were significantly higher than those in the sham group (P < 0.05, P < 0.01), and the levels in the treatment group were significantly lower than those in the model group (P < 0.05). (4) To conclude, sodium ibandronate may inhibit subchondral bone loss and articular cartilage degeneration in rat models of osteoarthritis by inhibiting extracellular signal regulated protein kinase and c-Jun N-terminal kinase in mitogen-activated protein kinase signaling pathway. [ABSTRACT FROM AUTHOR]

Sleep-disordered breathing (SDB) is a frequent comorbidity in patients with wake-up stroke (WUS). It affects the occurrence of this disease through its interference of breathing changes and sleep quality. We aim to assess the performances of sleep-disordered breathing in WUS. A systematical search for the studies that investigated sleep-disordered breathing in WUS was done in PubMed, Web of Science, and Cochrane Library. Data were extracted by two independent investigators, and then analyzed using the Revman 5.0 software. A total of five studies with 591 patients were included in the meta-analysis. The pooling data of sleep parameters showed that patients with WUS had a higher AHI and ODI than those with non-WUS (NWUS) [AHI: SMD: 0.58 (0.05, 1.10), P = 0.03; ODI: SMD: 0.63 (0.06, 1.21), P = 0.03). In addition, an increased incidence of severe SAS is found in WUS (OR: 3.18; 95% CI 1.27, 7.93; P = 0.01). However, no differences were found in AI, ESS, and the number of sleep apnea syndrome (SAS) between the two groups (P > 0.05). Therefore, WUS patients intended to have a severe SDB status, affecting the respiratory effects. Early prevention and attention should be paid on potential stroke sufferers with SAS, especially those with severe SAS. [ABSTRACT FROM AUTHOR]

Background: We sought to characterize the cognitive function and neuropsychiatric symptoms in cerebral radionecrosis (CRN) patients who have received conformal radiation for nasopharyngeal carcinoma.Methods: A total of 40 patients treated with radiotherapy (RT) that developed CRN (RT + CRN), 40 patients treated with radiotherapy that did not have CRN (RT-No-CRN), and 36 newly diagnosed untreated nasopharyngeal carcinoma patients (No-RT) were recruited. The cognitive function and neuropsychiatric symptoms were evaluated with Montreal cognitive assessment (MoCA), the mini-mental state examination (MMSE), activity of daily living scale (ADL), neuropsychiatric inventory (NPI), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA).Results: The RT + CRN group had the lowest mean MMSE, MoCA and ADL scores, while highest mean NPI, HAMD and HAMA scores among the three patient groups (P < 0.05). Thirty (75%) of the RT + CRN patients were deemed cognitively impaired by the MoCA compared with 9 (22.5%) by the MMSE (χ(2) = 22.064; P < 0.001). Eighty-two percents of subject in RT + CRN group experienced neuropsychiatric symptoms within the past 4 weeks. Irritability, anxiety, depression and agitation in the RT + CRN group were of the most significantly frequent among the 3 groups.Conclusions: The CRN patients generally have manifestations in cognitive and psychological impairment, which have their typical characteristics, and should be considered in CRN treatment and rehabilitation. The MoCA classifies more CRN patients as cognitively impaired than the MMSE, justifying further studies of the MoCA as an appropriate screen for CRN. [ABSTRACT FROM AUTHOR]

This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer's disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aβ1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aβ1–42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1. [ABSTRACT FROM AUTHOR]