Clinical Characteristics and Prognoses of Chronic Subdural Hematoma Patients with and without Head Trauma: A Retrospective Comparative Study.

OBJECTIVE: Head trauma is considered as the main cause of chronic subdural hematoma (CSDH). However, many patients develop CSDH with no identified cause. Herein, we conduct a comparative study to investigate the differences in clinical characteristics and surgical outcomes of CSDH patients with and without a history of head trauma. METHODS: We retrospectively reviewed CSDH patients who underwent surgical treatment in our hospital between January 2013 and December 2021. Patients were categorized into a with head trauma (WHT) group and a without head trauma (WOHT) group for comparative analysis. RESULTS: A total of 219 patients were included, 119 (54.3%) cases in the WHT group and 100 (45.7%) cases in the WOHT group. More cancer patients were found in the WOHT group than in the WHT group (P = 0.045). Both at discharge and 6-month follow-up, patients in the WOHT group achieved better clinical outcomes than the WHT group cases (P = 0.025 and 0.034, respectively). Furthermore, ordered multiclass logistic regression analyses indicated that a history of head trauma (odds ratio 2.151, 95% confidence interval 1.052-4.386; P = 0.036) was a risk factor significantly related to the unfavorable outcomes at 6-month follow-ups of CSDH. However, we did not find significant differences between the 2 groups in clinical manifestations, radiological characteristics, postoperative complications, mortality, and recurrence rates. CONCLUSIONS: CSDH patients with a history of head trauma may be more susceptible to unfavorable outcomes; thus, they should be carefully evaluated and given more attention during hospitalization and after discharge.

Surgical treatment of chronic subdural hematoma by twist drill craniotomy: A 9-year, single-center experience of 219 cases.

OBJECTIVE: This study aims to assess the safety and efficiency of twist drill craniotomy (TDC) for surgical treatment of chronic subdural hematoma (CSDH) based on a single-center experience of 219 cases performed over nine years. METHODS: We performed a retrospective analysis of CSDH patients who underwent TDC treatment in our hospital between January 2013 and December 2021. Clinical and radiological characteristics, as well as surgical outcomes of the included patients, were reviewed and analyzed. Factors that may affect hematoma recurrence and outcomes were also investigated. RESULTS: A total of 219 patients (186 males and 33 females) were included. Eighteen (8.2%) patients experienced postoperative complications. The in-hospital mortality and recurrence rates in our series were 0.5% (1/219) and 4.1% (9/217), respectively. 91.7% (199/217) of patients achieved favorable outcomes six months after the operation. Duration of drainage catheter (odds ratio [OR] 0.135, 95% confidence interval [CI] 0.017-1.099; P = 0.030) was the only factor significantly related to the recurrence of CSDH. Moreover, brain infarction (OR 5.175, 95% CI 1.417-18.896; P = 0.013), Alzheimer's disease (OR 20.515, 95% CI 1.950-215.840; P = 0.012), and preoperative dysfunction of coagulation (OR 6.509, 95% CI 1.501-28.217; P = 0.012) were markedly associated with unfavorable functional outcomes. CONCLUSION: TDC with irrigation and closed-system drainage is a minimally invasive, simple, safe, and effective surgical technique that can serve as the first-choice for the treatment of CSDH with a low recurrence rate.

Clinical Characteristics and Surgical Outcomes of Super-Elderly Patients with Chronic Subdural Hematoma.

OBJECTIVE: Surgical intervention for chronic subdural hematoma (CSDH) in the extremely aged population remains a difficult challenge. This study aims to investigate the clinical characteristics and surgical outcomes after twist drill craniotomy (TDC) of CSDH in super-elderly (≥80 years) patients. METHODS: A retrospective analysis of super-elderly patients with CSDH who underwent TDC treatment in our hospital between January 2013 and December 2021 was performed. Their clinical characteristics and surgical outcomes were compared with those of relatively younger patients (60-79 years). Factors that may affect functional outcomes were also investigated. RESULTS: Fifty-nine super-elderly patients and 133 patients aged 60-79 years were included. The preoperative hematoma volume of the super-elderly patients was significantly larger than that of the 60-79 years group, whereas fewer super-elderly patients had headaches compared with the relatively younger counterparts. After surgical treatment using the TDC procedure, the incidence of complication and the hematoma recurrence rate were similar between the 2 groups. Moreover, according to the Markwalder score of the follow-up at 6 months after operation, the prognosis of the super-elderly group was not poorer than that of the patients of 60-79 years (P = 0.662). Preoperative dysfunction of coagulation (odds ratio, 28.421; 95% confidence interval, 1.185-681.677; P = 0.039) was an independent risk factor significantly related to unfavorable outcomes of super-elderly patients with CSDH. CONCLUSIONS: Advanced age per se does not seem to be a contraindication for the operative intervention of CSDH. Surgical treatment using the TDC procedure can still provide considerable benefits for super-elderly patients with CSDH.

Microrchidia family CW­type zinc finger 2 promotes the proliferation, invasion, migration and epithelial­mesenchymal transition of glioma by regulating PTEN/PI3K/AKT signaling via binding to N­myc downstream regulated gene 1 promoter.

Glioma is a common malignant tumor of the central nervous system with high incidence and mortality. The present study aimed to investigate the role of Microrchidia family CW­type zinc finger 2 (MORC2) in the development of glioma. Firstly, MORC2 expression was detected in several glioma cell lines (U251, SHG44, LN229 and T98G). Following MORC2 silencing, cell proliferation was evaluated using the Cell Counting Kit­8 assay and the expression of proliferation­related proteins was assessed via immunofluorescence staining or western blotting. Cell invasion and migration were assessed using transwell and wound healing assays, respectively. Western blotting and immunofluorescence staining were employed to determine the expression of epithelial­mesenchymal transition (EMT)­associated proteins. The protein expression of N­myc downstream regulated gene 1 (NDRG1) and PTEN/PI3K/AKT signaling was determined with western blot analysis. Then, the luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to evaluate the binding between MORC2 and NDRG1 promoter. Subsequently, cellular functional experiments were performed to assess the effects of NDRG1 on the progression of glioma after NDRG1 and MORC2 overexpression. In addition, tumor­bearing experiments were conducted using a U251 tumor­bearing nude mice model to detect tumor growth. The expression of proliferation (proliferating cell nuclear antigen, cyclin­dependent kinase 2 and cyclin E1), migration [matrix metalloproteinase (MMP)2 and MMP9], EMT (E­cadherin, N­cadherin and Vimentin) and PTEN/PI3K/AKT signaling proteins in tumor tissues was examined with immunohistochemistry assay or western blotting. Results revealed that MORC2 was notably unregulated in glioma cells compared with the normal human astrocyte. Loss­function of MORC2 inhibited the proliferation, invasion, migration and EMT of glioma cells. Importantly, MORC2 silencing upregulated NDRG1 expression and inactivated PTEN/PI3K/AKT signaling. Additionally, the luciferase reporter­ and ChIP assays confirmed that MORC2 could bind to the NDRG1 promoter. NDRG1 upregulation suppressed the progression of glioma and these effects were partially reversed by MORC2 overexpression. Results of tumor­bearing experiments suggested that gain­function of NDRG1 inhibited tumor growth and downregulated the expression of proliferation, migration and EMT­related proteins in tumorous tissue in U251 tumor­bearing mice, which was partially counteracted after MORC2 overexpression. In addition, MORC2 overexpression abrogated the inhibitory effect of NDRG1 on PTEN/PI3K/AKT signaling. In summary, MORC2 promoted the progression of glioma by inactivation of PTEN/PI3K/AKT signaling via binding to NDRG1 promoter, providing a novel and potent target for the treatment of glioma.

Multiple nerve root metastasis of breast carcinoma: a report of two cases.

Nerve root metastases are extremely rare with only a handful of cases ever reported. Metastasis to sites other than the primary site is common in malignant tumors whereas spinal ganglion metastasis is extremely rare and has been only reported in individual cases. The lumbar spine tends to be more common areas of presentation whereas breast cancer metastasis has been rarely reported. We herein reported two cases of breast carcinoma metastasis to multiple spinal nerve roots. The metastasis sites were S1 nerve root in Case 1 and left L5 and bilateral cervical nerve roots in Case 2. On magnetic resonance imaging (MRI), the nerve roots in the intervertebral foramen zones appeared thickened and contrast-enhanced MRI exhibited intense enhancement. Pathological examination showed that these primary lesions were breast cancer in both cases, and there were intracranial multiple metastases in both cases, including preoperative metastasis to multiple nerve roots (lumbar and cervical) and postoperative recurrence. The clinical course was characterized by worsening radicular symptoms-especially intractable pain. The radiologic appearance might mimic a neurogenic tumor, which is performed intervertebral foraminal area lesion, and the corresponding ganglion/nerve root became thickened and was enhanced significantly. Surgical intervention with tumor debulking followed by radiotherapy provides local tumor control and palliation from pain, but it is palliative. Therefore, for patients with radiological manifestations of radiculopathy, the possibility of metastatic tumors should be considered.

Cerebroprotection by dioscin after experimental subarachnoid haemorrhage via inhibiting NLRP3 inflammasome through SIRT1-dependent pathway.

BACKGROUND AND PURPOSE: Dioscin has multiple biological activities and is beneficial for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of dioscin against subarachnoid haemorrhage and the molecular mechanisms involved. EXPERIMENTAL APPROACH: Dioscin was administered after subarachnoid haemorrhage induced in rats. MCC950, a potent selective nod-like receptor pyrin domain-containing 3 (NLRP3) inhibitor, was used to suppress NLRP3 and EX527 (selisistat) was used to inhibit sirtuin 1 (SIRT1). KEY RESULTS: In vivo, dioscin inhibited acute inflammatory response, oxidative damage, neurological impairment and neural cell degeneration after subarachnoid haemorrhage along with dramatically suppressing NLRP3 inflammasome activation. While pretreatment with MCC950 reduced the inflammatory response and improved neurological outcomes it did not lessen ROS production. However, giving dioscin after MCC950 reduced acute brain damage and ROS production. Dioscin increased SIRT1 expression after subarachnoid haemorrhage, whereas EX527 abolished the up-regulation of SIRT1 induced by dioscin and offset the inhibitory effects of dioscin on NLRP3 inflammasome activation. EX527 pretreatment also reversed the neuroprotective effects of dioscin against subarachnoid haemorrhage. Similarly, in vitro, dioscin dose-dependently suppressed inflammatory response, oxidative damage and neuronal degeneration and improved cell viability in neurons and microglia co-culture system. These effects were associated with inhibition of the NLRP3 inflammasome and stimulation of SIRT1 signalling, which could be inhibited by EX527 pretreatment. CONCLUSION AND IMPLICATIONS: Dioscin provides protection against subarachnoid haemorrhage via the suppression of NLRP3 inflammasome activation through SIRT1-dependent pathway. Dioscin may be a new candidate to ameliorate early brain injury after subarachnoid haemorrhage.

Hydrogen Clathrate Structures in Uranium Hydrides at High Pressures.

Room-temperature superconductivity has always been an area of intensive research. Recent findings of clathrate metal hydrides structures have opened up the doors for achieving room-temperature superconductivity in these materials. Here, we report first-principles calculations for stable H-rich clathrate structures of uranium hydrides at high pressures. The clathrate uranium hydrides contain H cages with stoichiometries of H24, H29, and H32, in which H atoms are bonded covalently to other H atoms, and U atoms occupy the centers of the cages. Especially, a UH10 clathrate structure containing H32 cages is predicted to have an estimated T c higher than 77 K at high pressures.

Surgical treatment for antiplatelet intracerebral hemorrhage (SAP-ICH): protocol for a prospective cohort study of emergency surgery for severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet treatment.

BACKGROUND: Despite the capability of emergency surgery to reduce the mortality of severe spontaneous intracranial hemorrhage (SSICH) patients, the effect and safety of surgical treatment for severe spontaneous intracranial hemorrhage (SSICH) patients receiving long-term oral antiplatelet treatment (LOAPT) remains unclear. In consideration of this, the cohort study is aimed at figuring out the effect and safety of emergency surgery for SSICH patients on LOAPT. METHODS: As a multicenter and prospective cohort study, it will be conducted across 7 representative clinical centers. Starting in September 2019, the observation is scheduled to be completed by December 2022, with a total of 450 SSICH patients recruited. The information on clinical, radiological, and laboratory practices will be recorded objectively. All of the patients will be monitored until death or 6 months after the occurrence of primary hemorrhage. RESULTS: In this study, two comparative cohorts and an observational cohort will be set up. The primary outcome is the effect of emergency surgery, which is subject to assessment using the total mortality and comparison in the survival rate of SSICH patients on LOAPT between surgical treatment and conservative treatment. The second outcome is the safety of surgery, with the postoperative hemorrhagic complication which is compared between the operated SSICH patients on and not on LOAPT. Based on the observation of the characteristics and outcome of SSICH patients on LOAPT, the ischemic events after discontinuing LOAPT will be further addressed, and the coagulation function assessment system for operated SSICH patients on LOAPT will be established. CONCLUSIONS: In this study, we will investigate the effect and safety of emergency surgery for SSICH patients on LOAPT, which will provide an evidence for management in the future. ETHICS AND DISSEMINATION: The research protocol and informed consent in this study were approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2019-096-02). The results of this study are expected to be disseminated in peer-reviewed journals in 2023. TRIAL REGISTRATION: Name: Effect and safety of surgical intervention for severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet treatment. ChiCTR1900024406 . Date of registration is July 10, 2019.

Astaxanthin ameliorates oxidative stress and neuronal apoptosis via SIRT1/NRF2/Prx2/ASK1/p38 after traumatic brain injury in mice.

BACKGROUND AND PURPOSE: Oxidative stress and neuronal apoptosis play key roles in traumatic brain injury. We investigated the protective effects of astaxanthin against traumatic brain injury and its underlying mechanisms of action. EXPERIMENTAL APPROACH: A weight-drop model of traumatic brain injury in vivo and hydrogen peroxide exposure in vitro model were established. Brain oedema, behaviour tests, western blot, biochemical analysis, lesion volume, histopathological study and cell viability were performed. KEY RESULTS: Astaxanthin significantly reduced oxidative insults on Days 1, 3 and 7 after traumatic brain injury. Neuronal apoptosis was also ameliorated on Day 3. Additionally, astaxanthin improved neurological functions up to 3 weeks after traumatic brain injury. Astaxanthin treatment dramatically enhanced the expression of peroxiredoxin 2 (Prx2), nuclear factor-erythroid 2-related factor 2 (NRF2/Nrf2) and sirtuin 1 (SIRT1), while it down-regulated the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) and p38. Inhibition of Prx2 by siRNA injection reversed the beneficial effects of astaxanthin against traumatic brain injury. Additionally, Nrf2 knockout prevented the neuroprotective effects of astaxanthin in traumatic brain injury. In contrast, overexpression of Prx2 in Nrf2 knockout mice attenuated the secondary brain injury after traumatic brain injury. Moreover, inhibiting SIRT1 by EX527 dramatically inhibited the neuroprotective effects of astaxanthin and suppressed SIRT1/Nrf2/Prx2/ASK1/p38 pathway both in vivo and in vitro. CONCLUSION AND IMPLICATIONS: Astaxanthin improved the neurological functions and protected the brain from injury after traumatic brain injury, primarily by reducing oxidative stress and neuronal death via SIRT1/Nrf2/Prx2/ASK1/p38 signalling pathway and might be a new candidate to ameliorate traumatic brain injury.

Fucoxanthin Mitigates Subarachnoid Hemorrhage-Induced Oxidative Damage via Sirtuin 1-Dependent Pathway.

Oxidative stress is a key component of the pathological cascade in subarachnoid hemorrhage (SAH). Fucoxanthin (Fx) possesses a strong antioxidant property and has shown neuroprotective effects in acute brain injuries such as ischemic stroke and traumatic brain injury. Here, we investigated the beneficial effects of Fx against SAH-induced oxidative insults and the possible molecular mechanisms. Our data showed that Fx could significantly inhibit SAH-induced reactive oxygen species production and lipid peroxidation, and restore the impairment of endogenous antioxidant enzymes activities. In addition, Fx supplementation improved mitochondrial morphology, ameliorated neural apoptosis, and reduced brain edema after SAH. Moreover, Fx administration exerted an improvement in short-term and long-term neurobehavior functions after SAH. Mechanistically, Fx inhibited oxidative damage and brain injury after SAH by deacetylation of forkhead transcription factors of the O class and p53 via sirtuin 1 (Sirt1) activation. EX527, a selective Sirt1 inhibitor, significantly abated Fx-induced Sirt1 activation and abrogated the antioxidant and neuroprotective effects of Fx after SAH. In primary neurons, Fx similarly suppressed oxidative insults and improved cell viability. These effects were associated with Sirt1 activation and were reversed by EX527 treatment. Taken together, our study explored that Fx provided protection against SAH-induced oxidative insults by inducing Sirt1 signaling, indicating that Fx might serve as a potential therapeutic drug for SAH.

Berberine Ameliorates Subarachnoid Hemorrhage Injury via Induction of Sirtuin 1 and Inhibiting HMGB1/Nf-κB Pathway.

Excessive cerebral inflammation plays a key role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Berberine, an isoquinoline alkaloid isolated from Chinese herb Coptis chinensis, possesses anti-inflammatory, and neuroprotective effects. Here we evaluated the beneficial effects of berberine against SAH-induced inflammatory response and the subsequent brain injury. Our data showed that berberine treatment significantly inhibited microglia activation and proinflammatory cytokines release. Concomitant with suppressed cerebral inflammation, berberine mitigated the subsequent brain injury as demonstrated by improved neurological behavior, reduced brain edema, and decreased neural apoptosis. Moreover, berberine significantly inhibited high mobile group box 1 (HMGB1)/nuclear factor-κB (Nf-κB)-dependent pathway and enhanced sirtuin 1 (SIRT1) expression after SAH. Treatment with ex527, a selective SIRT1 inhibitor, reversed berberine-induced SIRT1 activation and inhibitory effects on HMGB1/Nf-κB activation. In addition, ex527 pretreatment abated the anti-inflammatory and neuroprotective effects of berberine on SAH. Taken together, these findings suggest that berberine provides beneficial effects against SAH-triggered cerebral inflammation by inhibiting HMGB1/Nf-κB pathway, which may be modulated by SIRT1 activation.

Impact of the Siloxane-Terminated Side Chain on Photovoltaic Performances of the Dithienylbenzodithiophene-Difluorobenzotriazole-Based Wide Band Gap Polymer Donor in Non-Fullerene Polymer Solar Cells.

To thoroughly disclose the role of the siloxane-terminated side chain with different substituent positions, three difluorobenzotriazole-dithienylbenzodithiophene (FTAZ-BDTT)-based polymers PBZ-1Si, PBZ-2Si, and PBZ-3Si with the siloxane-terminated side chain on the FTAZ unit (PBZ-1Si), on the BDTT unit (PBZ-2Si), and both on BDTT and FTAZ units (PBZ-3Si), respectively, were synthesized. The different side chain substitutions have slight influences on absorption behavior, thermal stability, and frontier molecular orbitals but have shown a great effect on the aggregation of the polymers. Grazing-incidence wide-angle X-ray scattering measurements reveal that, relative to PBZ-1Si with branched alkyl on the BDTT unit, polymers PBZ-2Si and PBZ-3Si, bearing the siloxane-terminated side chains on the BDTT unit, exhibit smaller π-π stacking distances and larger crystal coherence lengths, suggesting that adopting the siloxane-terminated side chain on the BDTT unit can promote the interchain π-π interaction and the ordering of molecular packing. With IT-M as the non-fullerene acceptor, among the three polymers, the PBZ-2Si-based active layer possesses the highest ordered crystals for both polymers and IT-M as well as the purest domain, which affords efficient exciton dissociation, the most balanced hole-electron transport, and reduced recombination, leading to the highest short-circuit current density (Jsc) and fill factor (FF) and then the highest power conversion efficiency (PCE) of 11.14%. In contrast, PBZ-1Si- and PBZ-3Si-based devices show lower PCEs of 8.98 and 9.92%, respectively. Moreover, PBZ-2Si:IT-M also exhibits good thickness tolerance, and its thick active layer of 240 nm shows the most limited decrease of efficiency after 77 days of storage, supplying good potential for mass fabrication. Our work suggests that the fine pairing of a siloxane-terminated side chain and an alkyl side chain is beneficial for the optimizing of a conjugated polymer donor toward high-performance non-fullerene polymer solar cells.

[Polarity of ameloblasts and odontoblasts and their related regulators].

The polarity of ameloblasts and odontoblasts is crucial for their differentiation and function. Polarity-related molecules play an important role in this process. This review summarizes the process of polarity formation of ameloblasts and odontoblasts and their related regulators.

[The role of bone morphogenetic protein signaling pathway in tooth root development].

The bone morphogenetic protein (BMP) family is an important factor in the regulation of cell ular life activities and in the development of almost all tissues. BMP-mediated signaling plays an important role in tooth root development, which is a part of tooth development. Epithelial and mesenchymal interactions are involved in tooth root development, but the BMP signaling pathway has a different effect on tooth root development in epithelial and mesenchymal. This review summarizes the advances of BMP signaling in tooth root development.

[Establishment of Mouse Model with Humanized Chronic Myeloid Leukemia].

OBJECTIVE: To establish a BALB/c nude mouse model with the huamanized chronic myeloid leukemia (CML) for the study of human CML. METHODS: The BALB/c nude mice aged 4 weeks pretreated by splenectomy, the cyclophosphamide intraperitoneal injection and sublethal irradiation (SLI) were transplanted intravenously with bone marrow mononuclear cells from CML patients. The SLI-pretreated nude mice were divided into 2 groups: group A, in which the nude mice were injected with 0.3 ml PBS; group B, in which the nude mice were infused intravenously with 4.5×107 mononuclear cells from CML patients. Then the changes of body weight and appetite were observed, the hemogram and cell morphology were determined, the expressions of human CD13 and CD45 were detected by flow cytometry, the pathologic analysis of bone, liver and intestine were performed by biopsy, and the BCR/ABL fusion gene was detected by RT-PCR. RESULTS: The mice in group B displayed weakness, auantic, less foodintake and instabiligy of gait as time want on. The average survival time was 46.2±4.2 d (45-57 d). On the third week, the CD13+CD45+ cells accounted for 0.56±0.05% and 2.56±0.36% respectively in group A and B. While on the sixth week, the CD13+CD45+ cells accounted for 0.44±0.07% and 4.97±0.43% in A and B groups respectively, these results showed that cell count in B group was significantly higher than that in A group(P<0.05). Pathological examination showed that the leukemic cells were found in bone marrow of group B. The BCR/ABL fusion gene could be detected in bone marrow. CONCLUSION: BALB/c nude mouse model with huamanized chronic myeloid leukemia(CML) model has been established by pretreating mice with SLI. The survival time of mice in this model has been long, and the cost to establish the model is low.

Adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of recurrent high-grade glioma.

BACKGROUND: This randomized, open-label, multicenter, phase II clinical trial was conducted to assess the anti-tumor efficacy and safety of replication-deficient adenovirus mutant thymidine kinase (ADV-TK) in combination with ganciclovir administration in patients with recurrent high-grade glioma (HGG). PATIENTS AND METHODS: 53 patients with recurrent HGG were randomly allocated to receive intra-arterial cerebral infusion of ADV-TK or conventional treatments. The primary end point was 6-month progression-free survival (PFS-6). Secondary end points included progression-free survival (PFS), overall survival (OS), safety, and clinical benefit. This trial is registered with Clinicaltrials.gov, NCT00870181. RESULTS: In ADV-TK group, PFS-6 was 54.5%, the median PFS was 29.6 weeks, the median OS was 45.4 weeks, and better survivals were achieved when compared with control group. The one-year PFS and OS were 22.7% and 44.6% in ADV-TK group respectively, and clinical benefit was 68.2%. There are 2 patients alive for more than 4 years without progression in ADV-TK group. In the subgroup of glioblastoma received ADV-TK, PFS-6 was 71.4%, median PFS was 34.9 weeks, median OS was 45.7 weeks respectively, much better than those in control group. The one-year PFS and OS were 35.7% and 50.0% in ADV-TK group respectively. ADV-TK/ganciclovir gene therapy was well tolerated, and no treatment-related severe adverse events were noted. CONCLUSION: Our study demonstrated a notable improvement of PFS-6, PFS and OS in ADV-TK treated group, and the efficacy and safety appear to be comparable to other reported treatments used for recurrent HGG. ADV-TK gene therapy is therefore a valuable therapeutic option for recurrent HGG.

[Effect of ginsenoside total saponinon on regulation of P450 of livers of rats after γ-ray irradiation].

Effect of ginsenoside total saponin (GTS) on the regulation of P450 of livers of rats after γ-ray irradiation was studied. Rats were irradiated by the 6°Coγ-ray for one-time dose of 5.5 Gy, dose rate of 117.1-119.2 cGy. The cocktail probe, qPCR and Western blot were used to detect expression of enzymatic activites, mRNA and protein of rats. Contrasted with blank group, expression of CYP1A2, 2B1, 2E1, 3A4 of irradiation group showed a up-regulated (P < 0.05). Contrasted with irradiation group, exprression of CYP1A2, 2B1, 2E1, 3A4 of GTS group showed a downward trend. GTS had negative agonistic action against expression of P450 of rats by irradiatied.

Knockdown of HMGB1 improves apoptosis and suppresses proliferation and invasion of glioma cells.

BACKGROUND: The purposes of this study were to explore the effects of high mobility group protein box 1 (HMGB1) gene on the growth, proliferation, apoptosis, invasion, and metastasis of glioma cells, with an attempt to provide potential therapeutic targets for the treatment of glioma. METHODS: The expressions of HMGB1 in glioma cells (U251, U-87MG and LN-18) and one control cell line (SVG p12) were detected by real time PCR and Western blotting, respectively. Then, the effects of HMGB1 on the biological behaviors of glioma cells were detected: the expression of HMGB1 in human glioma cell lines U251 and U-87MG were suppressed using RNAi technique, then the influences of HMGB1 on the viability, cycle, apoptosis, and invasion abilities of U251 and U-87MG cells were analyzed using in a Transwell invasion chamber. Also, the effects of HMGB1 on the expressions of cyclin D1, Bax, Bcl-2, and MMP 9 were detected. RESULTS: As shown by real-time PCR and Western blotting, the expression of HMGB1 significantly increased in glioma cells (U251, U-87MG, and LN-18) in comparison with the control cell line (SVG p12); the vitality, proliferation and invasive capabilities of U251 and U-87MG cells in the HMGB1 siRNA-transfected group were significantly lower than those in the blank control group and negative control (NC) siRNA group (P<0.05) but showed no significant difference between the blank control group and NC siRNA group. The percentage of apoptotic U251 and U-87MG cells was significantly higher in the HMGB1 siRNA-transfected group than in the blank control group and NC siRNA group (P<0.05) but was similar between the latter two groups. The HMGB1 siRNA-transfected group had significantly lower expression levels of Cyclin D1, Bcl-2, and MMP-9 protein in U251 and U-87MG cells and significantly higher expression of Bax protein than in the blank control group and NC siRNA group (P<0.05); the expression profiles of cyclin D1, Bax, Bcl-2, and MMP 9 showed no significant change in both blank control group and NC siRNA group. CONCLUSIONS: HMGB1 gene may promote the proliferation and migration of glioma cells and suppress its effects of apoptosis. Inhibition of the expression of HMGB1 gene can suppress the proliferation and migration of glioma cells and promote their apoptosis. Our observations provided a new target for intervention and treatment of glioma.

Lentiviral transgenic microRNA-based shRNA suppressed mouse cytochromosome P450 3A (CYP3A) expression in a dose-dependent and inheritable manner.

Cytochomosome P450 enzymes (CYP) are heme-containing monooxygenases responsible for oxidative metabolism of many exogenous and endogenous compounds including drugs. The species difference of CYP limits the extent to which data obtained from animals can be translated to humans in pharmacodynamics or pharmacokinetics studies. Transgenic expression of human CYP in animals lacking or with largely reduced endogenous CYP counterparts is recognized as an ideal strategy to correct CYP species difference. CYP3A is the most abundant CYP subfamily both in human and mammals. In this study, we designed a microRNA-based shRNA (miR-shRNA) simultaneously targeting four members of mouse CYP3A subfamily (CYP3A11, CYP3A16, CYP3A41 and CYP3A44), and transgenic mice expressing the designed miR-shRNA were generated by lentiviral transgenesis. Results showed that the CYP3A expression level in transgenic mice was markedly reduced compared to that in wild type or unrelated miR-shRNA transgenic mice, and was inversely correlated to the miR-shRNA expression level. The CYP3A expression levels in transgenic offspring of different generations were also remarkably lower compared to those of controls, and moreover the inhibition rate of CYP3A expression remained comparable over generations. The ratio of the targeted CYP3A transcriptional levels was comparable between knockdown and control mice of the same gender as detected by RT-PCR DGGE analysis. These data suggested that transgenic miR-shRNA suppressed CYP3A expression in a dose-dependent and inheritable manner, and transcriptional levels of the targeted CYP3As were suppressed to a similar extent. The observed knockdown efficacy was further confirmed by enzymatic activity analysis, and data showed that CYP3A activities in transgenic mice were markedly reduced compared to those in wild-type or unrelated miR-shRNA transgenic controls (1.11±0.71 vs 5.85±1.74, 5.9±2.4; P<0.01). This work laid down a foundation to further knock down the remaining murine CYP3As or CYPs of other subfamilies, and a basis to generate CYP knockdown animals of other species.

Skin-specifically transgenic expression of biologically active human cytoxic T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) in mice using lentiviral vector.

Xenogeneic skin, especially porcine skin, has already been used to cover large wounds in clinic practice of wound care. Our previous data showed that transgenic expression of human cytoxic T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) in murine skin graft remarkably prolonged its survival in xenogeneic burn wounds without extensive immunosuppression in recipients, suggesting that transgenic hCTLA4Ig expression in skin graft may be an effective and safe method to prolong its survival in xenogeneic wounds for coverage. Lentiviral transgenesis provides an extremely efficient and cost-effective method to produce transgenic animals. However, tissue-targeted transgenic expression of biologically functional protein by lentiviral transgenesis is rarely reported. In this work, a recombinant lentiviral vector (LV), named FKCW in this article, was constructed by inserting a skin-specific hCTLA4Ig expression cassette consisting of keratin 14 (K14) promoter, hCTLA4Ig coding sequence and an intronic fragment. Its efficacy for transgenesis and skin-specific expression of bio-active hCTLA4Ig protein was tested using mice as models. The LV FKCW was readily to be packaged and concentrated to high titres (1.287-6.254 × 10(9) TU/ml) by conventional lentivirus package system. Using eggs collected from only five mated females having been subjected to conventional super-ovulation treatment, 8 hCTLA4Ig transgenic founder mice were generated with the concentrated FKCW vector, and transgenic founder per injected and transferred egg was 6.3%, which was nearly 9-fold higher than that for DNA micro-injection with a similar transgene construct in our previous work. The lentiviral transgenic hCTLA4Ig exhibited strictly skin-specific expression at a level comparable to or even slightly higher than that of transgenic hCTLA4Ig delivered by micro-injection in a similar cassette. Lentiviral transgenic hCTLA4Ig protein remarkably suppressed human lymphocyte proliferation in vitro to a degree comparable to that of commercially purchased purified hCTLA4Ig protein with defined activity at similar concentrations. Besides, lentiviral hCTLA4Ig transgenic mouse skin grafted into rat burn wounds exhibited remarkably extended survival compared to wild-type skin of the same strain (13.8 ± 3.8 vs. 6.8 ± 3.0 days), indicating that lentiviral transgenic hCTLA4Ig did inhibit immune rejection against xenogeneic skin graft in vivo. These results laid down the foundation to further efficiently generate transgenic pigs skin-specifically expressing bio-active hCTLA4Ig by lentiviral transgenesis, and provided a demonstration that transgenic animals with tissue-targeted expression of biologically functional protein can be efficiently produced using LV.