Rutaecarpine Alleviates Early Brain Injury-Induced Inflammatory Response Following Subarachnoid Hemorrhage via SIRT6/NF-[Formula: see text]B Pathway.

Subarachnoid hemorrhage (SAH), a specific subtype of cerebrovascular accident, is characterized by the extravasation of blood into the interstice between the brain and its enveloping delicate tissues. This pathophysiological phenomenon can precipitate an early brain injury (EBI), which is characterized by inflammation and neuronal death. Rutaecarpine (Rut), a flavonoid compound discovered in various plants, has been shown to have protective effects against SAH-induced cerebral insult in rodent models. In our study, we used a rodent SAH model to evaluate the effect of Rut on EBI and investigated the effect of Rut on the inflammatory response and its regulation of SIRT6 expression in vitro. We found that Rut exerts a protective effect on EBI in SAH rats, which is partly due to its ability to inhibit the inflammatory response. Notably, Rut up-regulated Sirtuin 6 (SIRT6) expression, leading to an increase in H3K9 deacetylation and inhibition of nuclear factor-kappa B (NF-[Formula: see text]B) transcriptional activation, thereby mediating the inflammatory response. In addition, further data showed that SIRT6 was proven to mediate the regulation of Rut on the microglial inflammatory response. These findings highlight the importance of SIRT6 in the regulation of inflammation and suggest a potential mechanism for the protective effect of Rut on EBI. In summary, Rut may have the potential to prevent and treat SAH-induced brain injury by interacting with SIRT6. Our findings may provide a new therapeutic strategy for the treatment of SAH-induced EBI.

Amelioration of nitroglycerin-induced migraine in mice via Wuzhuyu decoction: Inhibition of the MZF1/PGK1 pathway and activation of NRF2 antioxidant response.

ETHNOPHARMACOLOGICAL RELEVANCE: Migraine, a chronic and intricate disorder, manifests as recurrent episodic headaches accompanied by various neurological symptoms. Wuzhuyu Decoction (WZYD) is a traditional Chinese medical formula with promising effects in treating migraines; however, its underlying mechanisms have not yet been clarified. AIM OF STUDY: The study aimed to evaluate WZYD's effectiveness in migraine treatment and investigate the potential mechanism of WZYD's effects on migraine and oxidative stress. MATERIALS AND METHODS: Behavior tests and immunofluorescence assay for the intensity of migraine markers to assess the migraine-relieving effect of WZYD after chronic migraine model induced by nitroglycerin in mice. The impacts of WZYD on oxidative stress-related markers, including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO1), and NAD (P)H quinone oxidoreductase 1 (NQO1) in brain tissue were examined. In addition, protein expression or mRNA levels of the MZF1/PGK1 were detected using Western blot or PCR, respectively. Finally, the MZF1 overexpression vector was constructed to the higher level of MZF1. The MZF1/PGK1 signaling pathway expression was evaluated by markers of oxidative stress including NRF2 and others in this series of experiments. RESULTS: Through murine model experimentation, we observed that WZYD effectively alleviates migraine symptoms, signifying its therapeutic efficacy. Mechanistically, WZYD emerges as a potent activator of the NRF2, acting as a robust defense against oxidative stress. In vitro investigations demonstrated that WZYD combats oxidative stress and curbs cell apoptosis induced by these detrimental conditions. Furthermore, by suppressing the transcriptional expression of PGK1, an influential player in the NRF2 pathway, WZYD effectively activates NRF2 signaling. Intriguingly, we have identified MZF1 as the mediator orchestrating the regulation of the PGK1/NRF2 pathway by WZYD. CONCLUSION: The study confirms the effectiveness of WZYD in alleviating migraine symptoms. Mechanistically, WZYD activated the NRF2 signaling pathway; moreover, the action of WZYD involved the down-regulation of PGK1 mediated by MZF1, which promoted the activation of the NRF2 pathway. This study advances our understanding of the intricate mechanisms driving WZYD's efficacy, paving the way for novel treatments in migraine management.

Dehydroevodiamine ameliorates neurological dysfunction after traumatic brain injury in mice via regulating the SIRT1/FOXO3a/Bim pathway.

BACKGROUND: Traumatic Brain Injury (TBI) poses a considerable public health challenge, resulting in mortality, disability, and economic strain. Dehydroevodiamine (DEDM) is a natural compound derived from a traditional Chinese herbal medicine. Prior studies have substantiated the neuroprotective attributes of this compound in the context of TBI. Nevertheless, a comprehensive comprehension of the exact mechanisms responsible for its neuroprotective effects remains elusive. It is imperative to elucidate the precise intrinsic mechanisms underlying the neuroprotective actions of DEDM. PURPOSE: The aim of this investigation was to elucidate the mechanism underlying DEDM treatment in TBI utilizing both in vivo and in vitro models. Specifically, our focus was on comprehending the impact of DEDM on the Sirtuin1 (SIRT1) / Forkhead box O3 (FOXO3a) / Bcl-2-like protein 11 (Bim) pathway, a pivotal player in TBI-induced cell death attributed to oxidative stress. STUDY DESIGN AND METHODS: We established a TBI mouse model via the weight drop method. Following continuous intraperitoneal administration, we assessed the neurological dysfunction using the Modified Neurological Severity Score (mNSS) and behavioral assay, followed by sample collection. Secondary brain damage in mice was evaluated through Nissl staining, brain water content measurement, Evans blue detection, and Western blot assays. We scrutinized the expression levels of oxidative stress-related indicators and key proteins for apoptosis. The intricate mechanism of DEDM in TBI was further explored through immunofluorescence, Co-immunoprecipitation (Co-IP) assays, real-time quantitative PCR (RT-qPCR), dual-luciferase assays and western blotting. Additionally, we further investigated the specific therapeutic mechanism of DEDM in an oxidative stress cell model. RESULTS: The results indicated that DEDM effectively ameliorated oxidative stress and apoptosis post-TBI, mitigating neurological dysfunction and brain injury in mice. DEDM facilitated the deacetylation of FOXO3a by up-regulating the expression of the deacetylase SIRT1, consequently suppressing Bim expression. This mechanism contributed to the alleviation of neurological injury and symptom improvement in TBI-afflicted mice. Remarkably, SIRT1 emerged as a central mediator in the overall treatment mechanism. CONCLUSIONS: DEDM exerted significant neuroprotective effects on TBI mice by modulating the SIRT1/FOXO3a/Bim pathway. Our innovative research provides a basis for further exploration of the clinical therapeutic potential of DEDM in the context of TBI.

Wu-zhu-yu Decoction reduces early brain injury following subarachnoid hemorrhage in vivo and in vitro by activating the Nrf2 antioxidant system via SIRT6 targeting.

ETHNOPHARMACOLOGICAL RELEVANCE: Early brain damage (EBI) following subarachnoid hemorrhage (SAH) is a long-lasting condition with a high occurrence. However, treatment options are restricted. Wu-zhu-yu Decoction (WZYD) can treat headaches and vomiting, which are similar to the early symptoms of subarachnoid hemorrhage (SAH). However, it is yet unknown if WZYD can reduce EBI following SAH and its underlying mechanisms. AIM OF THE STUDY: This study aimed to investigate whether WZYD protects against EBI following SAH by inhibiting oxidative stress through activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling via Sirtuin 6 (SIRT6)-mediated histone H3 lysine 56 (H3K56) deacetylation. MATERIALS AND METHODS: In the current investigation, the principal components of WZYD were identified using high-performance liquid chromatography-diode array detection (HPLC-DAD). The SAH model in rats using the internal carotid artery plug puncture approach and the SAH model in primary neurons using hemoglobin incubation were developed. WZYD with different doses (137 mg kg-1, 274 mg kg-1, 548 mg kg-1) and the positive drug-Nimodipine (40 mg kg-1) were intragastrically administered in SAH model rats, respectively. The PC12 cells were cultured with corresponding medicated for 24h. In our investigation, neurological scores, brain water content, Evans blue leakage, Nissl staining, TUNEL staining, oxidative stress, expression of apoptosis-related proteins, and Nrf2/HO-1 signaling were evaluated. The interaction between SIRT6 and Nrf2 was detected by co-immunoprecipitation. SIRT6 knockdown was used to confirm its role in WZYD's neuroprotection. RESULTS: The WZYD treatment dramatically reduced cerebral hemorrhage and edema, and enhanced neurological results in EBI following SAH rats. WZYD administration inhibited neuronal apoptosis via reducing the expression levels of Cleaved cysteinyl aspartate specific proteinase-3(Cleaved Caspase-3), cysteinyl aspartate specific proteinase-3(caspase-3), and Bcl-2, Associated X Protein (Bax) and increasing the expression of B-cell lymphoma-2(Bal2). It also decreased reactive oxygen species and malondialdehyde levels and increased Nrf2 and HO-1 expression in the rat brain after SAH. In vitro, WZYD attenuated hemoglobin-induced cytotoxicity, oxidative stress and apoptosis in primary neurons. Mechanistically, WZYD enhanced SIRT6 expression and H3K56 deacetylation, activated Nrf2/HO-1 signaling, and promoted the interaction between SIRT6 and Nrf2. Knockdown of SIRT6 abolished WZYD-induced neuroprotection. CONCLUSIONS: WZYD attenuates EBI after SAH by activating Nrf2/HO-1 signaling through SIRT6-mediated H3K56 deacetylation, suggesting its therapeutic potential for SAH treatment.

Rutaecarpine alleviates migraine in nitroglycerin-induced mice by regulating PTEN/PGK1 signaling pathway to activate NRF2 antioxidant system.

BACKGROUND: Due to its widespread prevalence, migraine is a common neurovascular condition that has a major impact on people's health and quality of life. Rutaecarpine (RUT) is one of the main effective components of Evodia rutaecarpa, which has a wide range of biological activities. However, the exact mechanism by which RUT improves migraine remain unknown. PURPOSE: The purpose of this study was to investigate whether RUT improves migraine by inhibiting oxidative stress via activating the Nrf2 antioxidant system through the PTEN/PGK1 signaling pathway. METHODS: In vivo, a mouse model of chronic migraine (CM) was established by repeated intraperitoneal injection of nitroglycerin (NTG). After treatment with RUT and Sumatriptan, behavioral tests were performed, followed by measurements of oxidative stress-related indicators in the trigeminal nucleus caudalis, expression of proteins associated with the Nrf2 antioxidant system, and the PTEN/PGK1 pathway. In vitro, PC12 cells were stimulated by 100 µM H2O2 for 24 h to induce oxidative stress, which was then treated with RUT. Furthermore, the role of PTEN in antioxidant stress of RUT was elucidated by knockout of the PTEN gene. RESULTS: The results showed that RUT treatment improved NTG-induced migraine in mice by inhibiting oxidative stress. Importantly, RUT inhibited oxidative stress in NTG-induced mice or H2O2-induced PC12 cells via activating the Nrf2 antioxidant system by inhibiting PGK1 activity through PTEN. These results provide evidence that RUT improves migraine by activation of the Nrf2 antioxidant system through the PTEN/PGK1 pathway and provide new insights into the potential use of RUT as an effective drug development candidate for migraine.

Effect of Simultaneous Multiplane Surgery on Cardiopulmonary Function in Patients with Moderate to Severe Obstructive Sleep Apnea-Hypopnea Syndrome and Its Curative Effect.

Objective: To investigate the changes in cardiopulmonary function in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) by one-stage multiplane surgery. Methods: 70 patients with moderate and severe OSAHS underwent nasal in our hospital from July 2017 to February 2021, palatopharyngeal, and/or tongue operations simultaneously and were followed up for 6 months. The Epworth Sleeping Scale (ESS) scores of patients before and after surgery were compared to observe the surgical efficacy, and the changes in the cardiopulmonary function of patients before and after surgery were detected. The static and dynamic indexes of cardiopulmonary function, respiratory disturbance index (AHI), and blood oxygen saturation (SaO2) were compared before and after the operation. Results: After surgery, all patients' indexes of static lung function were improved compared with that before surgery. After surgery, the percentage of maximal oxygen uptake peak to the predicted value, percentage of oxygen pulse to the predicted value, the ratio of oxygen uptake power, anaerobic threshold, and maximum ventilatory capacity per minute/maximum exercise volume were increased compared with that before surgery, and AHI and SaO2 were improved compared with that before surgery. Conclusion: This study suggests that it is feasible for patients with OSAHS who are unable to tolerate or unwilling to undergo noninvasive assisted ventilation to undergo simultaneous surgery for multiplane stenosis. It can reduce clinical symptoms and improve cardiopulmonary function.

Apatinib Induces Ferroptosis of Glioma Cells through Modulation of the VEGFR2/Nrf2 Pathway.

Background: Glioma is a common tumor that originated from the brain, and molecular targeted therapy is one of the important treatment modalities of glioma. Apatinib is a small-molecule tyrosine kinase inhibitor, which is widely used for the treatment of glioma. However, the underlying molecular mechanism has remained elusive. Recently, emerging evidence has proved the remarkable anticancer effects of ferroptosis. In this study, a new ferroptosis-related mechanism of apatinib inhibiting proliferation of glioma cells was investigated, which facilitated further study on inhibitory effects of apatinib on cancer cells. Methods: Human glioma U251 and U87 cell lines and normal astrocytes were treated with apatinib. Ferroptosis, cell cycle, apoptosis, and proliferation were determined. A nude mouse xenograft model was constructed, and tumor growth rate was detected. Tumor tissues were collected to estimate ferroptosis levels and to identify the relevant pathways after treatment with apatinib. Results: Treatment with apatinib could induce loss of cell viability of glioma cells, but not of normal astrocytes, through eliciting ferroptosis in vitro and in vivo. It was also revealed that apatinib triggered ferroptosis of glioma cells via inhibiting the activation of nuclear factor erythroid 2-related factor 2/vascular endothelial growth factor receptor 2 (Nrf2/VEFGR2) pathway. The overexpression of Nrf2 rescued the therapeutic effects of apatinib. Conclusion: Our study proved that treatment with apatinib could restrain proliferation of glioma cells through induction of ferroptosis via inhibiting the activation of VEGFR2/Nrf2/Keap1 pathway. Overexpression of Nrf2 could counteract the induction of ferroptosis by apatinib.

Rutaecarpine Attenuates Oxidative Stress-Induced Traumatic Brain Injury and Reduces Secondary Injury via the PGK1/KEAP1/NRF2 Signaling Pathway.

The oxidative stress response caused by traumatic brain injury (TBI) leads to secondary damage in the form of tissue damage and cell death. Nuclear transcription-related factor 2 (NRF2) is a key factor in the body against oxidative stress and has an important role in combating oxidative damage in TBI neurons. In the present study, we investigated whether rutaecarpine could activate the PGK1/KEAP1/NRF2 pathway to antagonize oxidative damage in TBI neurons. We performed controlled cortical impact (CCI) surgery on mice and taken H2O2 treatment on PC12 cells to construct TBI models. The results of western blot showed that the expression of PGK1, KEAP and NRF2 was regulated and accompanied by altered levels of oxidative stress, and the use of rutaecarpine in the TBI model mice significantly improved cognitive dysfunction, increased antioxidant capacity and reduced apoptosis in brain tissue. Similar antioxidant damage results were obtained using rutaecarpine in a PC12 cell model. Furthermore, through the use of the protein synthesis inhibitor CHX and the proteasome synthesis inhibitor MG-132, rutaecarpine was found to promote the expreesions of PGK1 and NRF2 by accelerating PGK1 ubiquitination to reduce PGK1 expression. Therefore, rutaecarpine may be a promising therapeutic agent for the treatment of TBI-related neuro-oxidative damage.

Knockdown of ETV4 promotes autophagy-dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1.

ETS variant transcription factor 4 (ETV4) is a common cancer-promoting transcription factor and its expression has been found to be significantly upregulated in glioblastoma multiforme (GBM), as determined via analysis of the Gene Expression Profiling Interactive Analysis (GEPIA) database. In addition, our previous study demonstrated that ETV4 expression was highly positively correlated with epithelial membrane protein 1 (EMP1). The present study aimed to determine whether ETV4 could influence the activation of the PI3K/AKT/mTOR signaling pathway to affect the autophagy and apoptosis of GBM cells by regulating the transcriptional activity of EMP1. In addition to the analysis of the GEPIA database, the expression levels of ETV4 were also investigated in several different GBM cell lines. After interfering with the expression of ETV4, western blotting was used to detect the expression levels of autophagy- and apoptosis-related proteins, and a TUNEL assay was used to detect the levels of cell apoptosis. Dual luciferase reporter and chromatin immunoprecipitation assays were used to verify the potential binding site of ETV4 on EMP1. Western blotting was also used to analyze the expression levels of PI3K/AKT/mTOR signaling pathway-related proteins. The results of the current study revealed that the expression levels of ETV4 were significantly upregulated in GBM cell lines compared with those in normal glial cells. In the GBM cell line, LN-229, ETV4 was discovered to bind to the EMP1 promoter and positively regulate the expression of EMP1. The knockdown of ETV4 expression inhibited the PI3K/AKT/mTOR signaling pathway activity to promote autophagy and apoptosis, and this effect could be partially reversed by overexpressing EMP1. In conclusion, these findings indicated that the knockdown of ETV4 in GBM cells may reduce the transcriptional activation of EMP1 and thereby inhibit PI3K/AKT/mTOR signaling pathway activity to promote autophagy and apoptosis. This provides a novel insight into potential strategies for the treatment of GBM via the induction of autophagy-dependent apoptosis.

Application of intraoperative ultrasound in neurosurgery for hypertensive intracerebral hemorrhage.

OBJECTIVE: To explore the clinical significance of intraoperative ultrasound in neurosurgery for hypertensive intracerebral hemorrhage (ICH). METHODS: Patients with hypertensive ICH who required to undergo surgical treatment were assigned into treatment group (126 cases), who were assisted by intraoperative ultrasound, and control group (122 cases), who were not assisted by intraoperative ultrasound. In the treatment group, intraoperative ultrasound was used for real-time positioning after opening the bone flap, so as to guide the surgery. After surgery, conventional treatment and follow-up were conducted, and the statistical analysis was eventually performed to compare the therapeutic efficacy of the two groups. RESULTS: The mean rate of hematoma clearance was (95.20 ± 5.18)% in the treatment group and (86.20 ± 4.85)% in the control group (P<0.05); the average time required for intraoperative hematoma clearance was 44.5±3.2 min in the treatment group and 66.3±5.1 min in the control group (P < 0.05). Finally, the treatment group was superior to the control group in terms of therapeutic efficacy and overall prognosis (P = 0.03 and 0.025, respectively). CONCLUSIONS: Intraoperative ultrasound possessed the features of precise positioning, real-time guidance, and being user-friendly, which can shorten the operation time, increase the efficacy of surgery, and improve patients' overall prognosis, highlighting high clinical significance of intraoperative ultrasound in neurosurgery.

Alu hypomethylation and MGMT hypermethylation in serum as biomarkers of glioma.

In order to improve prognosis of glioma patients, better tools are required for early diagnosis and treatment. Serum cell-free DNA methylation levels of Alu, MGMT, P16, RASSF1A from 124 glioma patients and 58 healthy controls were detected by the bisulfite sequencing. The median methylation level of Alu was 46.15% (IQR, 36.57%-54.00%) and 60.85% (IQR, 57.23%-65.68%) in glioma patients and healthy controls respectively. The median methylation level of MGMT in glioma samples was 64.65% (IQR, 54.87%-74.37%) compared to 38.30% (IQR, 34.13%-45.45%) in healthy controls, and all revealed significant differences including P16. However, the median methylation level of RASSF1A was not significantly altered in glioma patients. Furthermore, the methylation levels of Alu and MGMT in serum had a good diagnostic value, and was higher than P16. Interestingly, combination of Alu and MGMT identified additional patients, which were missed by either diagnosis alone. In the Alu group, the patients with high levels were associated with an increased survival rate compared to those who with low levels, with similar results observed in the MGMT group. In the present study, we demonstrated that the methylation level of Alu and MGMT in serum had a better diagnostic value than P16. Moreover, combined analysis of Alu and MGMT showed higher sensitivity for glioma diagnosis. Therefore, both serum Alu and MGMT methylation levels may represent a novel prognostic factor for glioma patients.

An IDH1 mutation inhibits growth of glioma cells via GSH depletion and ROS generation.

The isocitrate dehydrogenase 1 (IDH1) gene mutation occurs frequently in glioma. While some studies have demonstrated that IDH1 mutations are associated with prolonged survival, the mechanism remains unclear. In this study, we found that growth was significantly inhibited in glioma cells overexpressing the mutated IDH1 gene. Furthermore, these cells were characterized by decreased intracellular NADPH levels accompanied by glutathione (GSH) depletion and reactive oxygen species (ROS) generation. Moreover, the increased apoptosis and the decreased proliferation were found in the glioma cells overexpressing the mutant IDH1 gene. Accordingly, our study demonstrates that using H2O2-regulated mutant IDH1 glioma cells could obviously increase the inhibition of cell growth; nevertheless, GSH had the opposite result. Our study provides direct evidence that mutation of IDH1 profoundly inhibits the growth of glioma cells, and we speculate that this is the major factor behind its association with prolonged survival in glioma. Finally, our study indicates that depletion of GSH and generation of ROS are the primary cellular events associated with this mutation.

PAX3 is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells.

Paired box 3 (PAX3) is overexpressed in glioma tissues compared to normal brain tissues, however, the pathogenic role of PAX3 in human glioma cells remains to be elucidated. In this study, we selected the human glioma cell lines U251, U87, SHG-44, and the normal human astrocytes, 1800, which have differential PAX3 expression depending upon the person. SiRNA targeting PAX3 and PAX3 overexpression vectors were transfected into U87 and SHG-44 glioma cell lines, and cell proliferation, invasion, apoptosis, and differentiation were examined by CCK-8 assays, transwell chamber assays, tunnel staining, Annexin V/PI analysis, and Western blotting, respectively. In addition, we used subcutaneous tumor models to study the effect of PAX3 on the growth of glioma cells in vivo. We found that PAX3 was upregulated in the three glioma cell lines. PAX3 knockdown inhibited cell proliferation and invasion, and induced apoptosis in the U87MG glioblastoma cell line, whereas PAX3 upregulation promoted proliferation, inhibited apoptosis, and increased invasion in the SHG-44 glioma cell line. Moreover, we found that targeting PAX3 expression in glioma cell lines together with chemotherapeutic treatment could increase glioma cell susceptibility to the drug. In subcutaneous tumor models in nude mice using glioma cell lines U-87MG and SHG-44, inhibition of PAX3 expression in glioblastoma U-87MG cells suppressed tumorigenicity, and upregulation of PAX3 expression in glioma SHG-44 cells promoted tumor formation in vivo. These results indicate that PAX3 in glioma is essential for gliomagenesis; thus, targeting PAX3 or its downstream targets may lead to novel therapies for this disease.

Detection of serum Alu element hypomethylation for the diagnosis and prognosis of glioma.

Global genomic hypomethylation is a hallmark of cancer in humans. In the present study, the feasibility of measuring hypomethylation of Alu elements (Alu) in serum and its clinical utility were investigated. Tumor tissues and matched serum specimens from 65 glioma patients and serum samples from 30 healthy controls were examined for Alu hypomethylation by bisulfite sequencing. The median serum Alu methylation level was 47.30 % in patients (interquartile range (IQR), 35.40-54.25 %) and 57.90 % in the controls (IQR, 55.25-61.45 %). The median Alu methylation level in tumor samples was 40.30 % (IQR, 36.80-54.20 %), which shows the correlation of Alu hypomethylation between tumor and serum samples (r = 0.882) in the study group. The methylation level was higher in the low-grade glioma group than in the high-grade group both in tumor and serum samples. A correlation between high methylation level and longer survival time was detected in tumor and serum samples. Receiver operating characteristic curve analysis showed that the area under the curve for diagnosis was 0.861 (95 % confidence interval, 0.789-0.933), suggesting that Alu hypomethylation in serum may be of diagnostic value. Our results indicate that the detection of Alu hypomethylation in serum may be clinically useful for the diagnosis and prognosis of glioma.

SCY1-like 1 binding protein 1 (SCYL1-bp1) interacts with p53-induced RING H2 protein (Pirh2) after traumatic brain injury in rats.

Traumatic brain injury (TBI) triggers a complex series of neurochemical and signaling changes that lead to neuronal dysfunction and overreactive astrocytes. In the current study, we showed that interactions between SCYL1-bp1 and Pirh2 are involved in central nervous system (CNS) injury and repair. Western blot and immunohistochemical analysis of an acute traumatic brain injury model in adult rats revealed significantly increased levels of SCYL1-bp1 and Pirh2 in the ipsilateral brain cortex, compared to contralateral cerebral cortex. Immunofluorescence double-labeling analyses further revealed that SCYL1-bp1 is mainly co-expressed with NeuN. Terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling staining data supported the involvement of SCYL1-bp1 and Pirh2 in neuronal apoptosis after brain injury. We additionally examined the expression profiles of active caspase-3, which were altered in correlation with the levels of SCYL1-bp1 and Pirh2. Notably, both SCYL1-bp1 and Pirh2 were colocalized with active caspase-3, and all three proteins participated in neuronal apoptosis. Immunoprecipitation experiments further revealed interactions of these proteins with each other in the pathophysiology process. To our knowledge, this is the first study to report interactions between SCYL1-bp1 and Pirh2 in traumatic brain. Our data collectively indicate that SCYL1-bp1 and Pirh2 play important roles in CNS pathophysiology after TBI.

Different functions of HIPK2 and CtBP2 in traumatic brain injury.

Traumatic brain injury (TBI) initiates a complex series of neurochemical and signaling changes that lead to neuronal dysfunction and over-reactive astrocytes. In our study, homeodomain interacting protein kinase 2 (HIPK2) can interact with C-terminal binding protein 2 (CtBP2) in rat brain, which is a component of Wnt-regulated transcription. Up to now, the functions of HIPK2 and CtBP2 in CNS are still with limited acquaintance. In our study, we found that the interaction between HIPK2 and CtBP2 was involved in central nervous system (CNS) injury and repair. We performed an acute TBI model in adult rats. Western blot and immunohistochemistry analysis revealed that both HIPK2 and CtBP2 significantly increased in the peritrauma brain cortex in comparison to contralateral cerebral cortex. And immunofluorescence double-labeling revealed that HIPK2 was mainly co-expressed with NeuN but less GFAP. Meanwhile, we also examined that the expression profiles of active-caspase-3 was correlated with the expression of HIPK2 and the expression profiles of the proliferating cell nuclear antigen (PCNA) was correlated with the expression of CtBP2. HIPK2 participated in apoptosis of neurons, but CtBP2 was associated with the activation and proliferation of astrocytes. Immunoprecipitation further showed that they enhanced the interaction with each other in the pathophysiology process. In conclusion, this was the first description that HIPK2 interacted with CtBP2 in traumatic brains. Our data suggest that HIPK2 and CtBP2 might play important roles in CNS pathophysiology after TBI, and might provide a basis for the further study on their roles in regulating the prognosis after TBI.

[Anatomical characteristics of lingual artery in physiological condition and its relationship with tongue base].

OBJECTIVE: To provide the clinical anatomic data of the lingual artery with 3D CT reconstruction. METHOD: Ten healthy subjects were recruited. Spiral CT scan ranged from the sternoclavicular joint to the lower edge of the orbit and the data was subjected to three-dimensional reconstruction. The distance from the origin of the lingual artery to the bifurcation of the common carotid artery and tip of the greater horn of hyoid bone were measured respectively and the distance between the midline of the lingual artery and the midline of tongue were also measured. RESULT: The horizontal distance between starting level of lingual artery to the level of the hyoid horn tip was (1.51 +/- 0.35) cm. The horizontal distance between the level of the lingual artery to the carotid bifurcation was (0.95 +/- 0.31) cm. The comparison of the distance from lingual artery 1 cm anterior or posterior to foramen cecum to midline of tongue showed (t = 45.27, P < 0.01) a statistically significant difference. CONCLUSION: The lingual artery could be demonstrated clearly in 3D reconstruction. To ensure the operative safety, the depth of radiofrequency for OSAHS at the tongue base should be limited within 2 centimeters.