First report on rhinoceros from the late Neogene Qin Basin of Shanxi, China.

Dihoplus is a rhinoceros distributed across East Asia and Europe from the Late Miocene to Pliocene. This study describes a new skull from the Qin Basin in Shanxi Province, China, referred to as Dihoplus ringstroemi, which has long been debated in taxonomic identity. This skull confirms that D. ringstroemi is an independent species and reveals the presence of the upper incisor and variations in the degree of constriction of the two lingual cusps of upper cheek teeth. In addition, the new skull indicates that the Qin Basin has a late Neogene sediment and fauna comparable to that of the Yushe Basin.

Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage.

BACKGROUND: Alzheimer's disease (AD) and glioblastoma are the most common and devastating diseases in the neurology and neurosurgery departments, respectively. Our previous research reports that the AD-related protein Presenilin1 represses cell proliferation by inhibiting the Wnt/ß-catenin pathway in glioblastoma. However, the function of Presenilin1 and the underlying mechanism need to be further investigated. METHODS: The correlations of two genes were conducted on the R2 microarray platform and CGGA. Wound healing, Transwell assays and glioblastoma transplantation were performed to detect invasion ability. Phalloidin staining was employed to show cell morphology. Proximity ligation assays and protein docking assays were employed to detect two protein locations. We also employed western blotting to detect protein expression. RESULTS: We found that Presenilin1 clearly repressed the migration, invasion and mesenchymal transition of glioblastoma cells. Intriguingly, we observed that the expression of Presenilin1 was positively correlated with Sortilin, which is identified as a pro-invasion molecule in glioma. Furthermore, Presenilin1 interacted with Sortilin at the transmembrane domain and repressed Sortilin expression by cleaving it in glioblastoma cells. First, we found that Sortilin introduced the function of Presenilin1 in phosphorylating ß-catenin and repressing invasion in glioblastoma cells. Last, Presenilin1 stimulation sharply suppressed the invasion and mesenchymal transition of glioblastoma in mouse subcutaneous and intracranial transplantation models. CONCLUSIONS: Our study reveals that Sortilin mediates the regulation of ß-catenin by Presenilin1 and transduces the anti-invasive function of Presenilin1, which may provide novel therapeutic targets for glioblastoma treatment. Video Abstract.

Effects and Mechanisms of Saikosaponin D Improving the Sensitivity of Human Gastric Cancer Cells to Cisplatin.

Gastric cancer (GC) is the second leading cause of cancer deaths around the world. Chemoresistance is an important reason for poor prognosis of GC. Saikosaponin D (SSD) is a natural constituent from Radix Bupleuri and exhibits various activities including antitumors. This study investigated the effects and the mechanisms of SSD on cisplatin (cis-diamminedichloroplatinum, DDP) sensitivity of GC cells. Findings suggested that SSD could promote the inhibitory effect of DDP on proliferation and invasion and increase DDP-induced apoptosis in SGC-7901 and DDP-resistant cell line SGC-7901/DDP. We further identified that SSD increased levels of LC3 B and cleaved caspase 3 and decreased levels of p62, IKK ß, p-IκB α, and NF-κB p65, suggesting that SSD might inhibit the IKK ß/NF-κB pathway and induce both cell autophagy and apoptosis in SGC-7901 and SGC-7901/DDP. A further study indicated that SSD enhanced the effect of DDP-induced cleaved caspase 3 level rise and NF-κB pathway suppression, especially in SGC-7901/DDP cells. Conclusively, SSD enhanced DDP sensitivity of GC cells; the potential molecular mechanisms were that SSD-induced apoptosis and autophagy and inhibited the IKK ß/NF-κB pathway in GC cells. These findings suggested that SSD might contribute to overcoming DDP resistance in GC treatment.

Importin ß1 mediates nuclear import of the factors associated with nonsense-mediated RNA decay.

In eukaryotic cells, nonsense-mediated RNA decay (NMD) is an essential physiological mechanism coupled to translation, regulating the stability of abnormal RNA containing premature termination codon (PTC) and a significant fraction of normal transcriptomes. So far, the molecular regulation mechanism of NMD pathway is far from fully elucidated. Previously, we observed the interaction between importin ß1 (Impß1) and UPF1, a core factor of NMD. Here, we demonstrated that Impß1 knockdown stabilized NMD reporters, and Impß1 and UPF1 interacted and co-regulated an extensive number of target transcripts. Furthermore, Impß1 affected the interaction between UPF1 and SMG5 or MAGOH, and the nuclear distributions of UPF1, SMG1, SMG5 and MAGOH. Besides, Ran knockdown extremely promoted the dissociation of UPF1 from SMG5 or MAGOH. Our findings provide molecular insight into the potential function of Impß1in nonsense-mediated RNA decay.

Multifocal glioblastoma-two case reports and literature review.

BACKGROUND: Multifocal glioblastoma is a rare type of glioblastoma with worse prognosis. In this article, we aimed to report two cases of classical multifocal glioblastoma. CASE PRESENTATION: In case 1, a 47-year-old male presented with dizziness, and once had a sudden loss of consciousness accompanied by convulsion of limbs. Contrast-enhanced MRI showed multiple lesions with heterogeneously ring-enhanced characters in the left hemisphere, diagnosed as multifocal glioblastoma. He underwent a craniotomy of all lesions, concurrent radiotherapy and chemotherapy as well as additional chemotherapy of temozolomide. After 2 cycles, repeat MRI showed that the new lesions already occurred and progressed. Eventually, he abandoned the chemotherapy after the 2 cycles and died 1 year later. In case 2, a 71-year-old male presented with a history of headache, left limb weakness, and numbness. Discontinuous convulsion of limbs once occurred. Contrast-enhanced MRI showed multiple lesions located in the right hemisphere, diagnosed as multifocal glioblastoma. He underwent a right frontoparietal craniotomy of the main lesion. Hemorrhage of the residual tumor and pulmonary artery embolism occurred synchronously. Eventually, his family decided not to pursue any further treatment and opted for hospice care and he passed away within 11 days of surgery. CONCLUSIONS: We reported two cases of typical multifocal glioblastoma. Valid diagnosis is crucial; then, resection of multiple lesions and canonical radio-chemotherapy probably bring survival benefits.

Baicalein enhanced cisplatin sensitivity of gastric cancer cells by inducing cell apoptosis and autophagy via Akt/mTOR and Nrf2/Keap 1 pathway.

Baicalein is a natural flavonoid with various pharmacological activities including antitumor. The synergistic anti-cancer effect of the combination of baicalein and Cisplatin (DDP) on gastric cancer (GC) has not been reported. MTT assay and colony formation assay were used to determine the inhibitory effect of the combination of baicalein and DDP on cell survival. Invasive assay was performed to test the effects of baicalein and DDP on cell invasive capability. A flow cytometric analysis was conducted to determine the apoptosis-induced effects of baicalein on GC cells, especially SGC-7901/DDP (resistant to DDP). Confocal laser microscope and real-time PCR were used to test autophagy-induced effects of baicalein on SGC-7901 and SGC-7901/DDP cells. Western blotting was performed to investigate the molecular mechanisms of baicalein inducing apoptosis and autophagy. Our study showed that baicalein could inhibit cell proliferation of MGC-803, HGC-27, SGC-7901 and SGC-7901/DDP, and the inhibitory effect was extremely enhanced when combining with DDP. Additionally, combination of baicalein and DDP suppressed the invasive capability and induced apoptosis and autophagy in both SGC-7901 and SGC-7901/DDP, and the effect was stronger than that of DDP or baicalein alone. The further molecular mechanism analysis indicated that baicalein modulated the activities of Akt/mTOR and Nrf2/Keap 1 signaling. Our study demonstrated that baicalein enhanced DDP sensitivity of SGC-7901/DDP gastric cancer cells by inducing apoptosis and autophagy via Akt/mTOR and Nrf2/Keap 1 pathway.

miR-215 functions as an oncogene in high-grade glioma by regulating retinoblastoma 1.

OBJECTIVES: To investigate the roles of miR-215 in high-grade glioma and to clarify the regulation of retinoblastoma 1 (RB1) by miR-215. RESULTS: miR-215 is frequently up-regulated in high-grade glioma tissues. Increased miR-215 expression is significantly associated with World Health Organization grade (P < 0.01) tumor size (P < 0.05) and poor prognosis (P < 0.01). Over-expression of miR-215 promoted cell proliferation and knockdown of miR-215 inhibited cell proliferation in vitro. RB1 was identified as a direct and functional target of miR-215. RB1 is generally down-regulated in glioma tissues and its expression inversely correlated with miR-215, which is up-regulated in high-grade glioma tissues, and its expression was negatively correlated with miR-215. CONCLUSIONS: The new miR-215/RB1 axis provides new insights into the molecular mechanism and treatment for glioma.

The 37-kDa laminin receptor precursor regulates the malignancy of human glioma cells.

Glioma is one of the most common brain tumors and one of the most aggressive cancers. Although extensive progress has been made regarding to the diagnosis and treatment, the mortality in glioma patients is still high. Therefore, finding new therapeutic targets to the glioma is critical to the advancement in cancer treatment. Recently, the 37-kDa laminin receptor precursor (37LRP) was reported to play important roles in occurrence of some types of cancer, indicating that this molecule may function as a key regulator in the tumor migration and metastasis. However, there is still no report to elucidate the correlation between 37LRP expression and glioma genesis and development. In this study, we found the higher expression of 37LRP in the glioma cells compared with the normal brain cells. We also indicated that the downregulation of 37LRP could affect the glioma biomarker expression and also weaken the proliferative, migratory, and metastatic capacity of glioma cells in vitro. Furthermore, 37LRP silencing inhibited the glioma tumor growth in vivo. Collectively, these data demonstrated that 37LRP regulates the metastasis of glioma cells in vitro and tumor growth in vivo, suggesting that 37LRP may function as a potential molecular target in the glioma treatment.

Traumatic Brain Injury Patients With a Glasgow Coma Scale Score of ≤8, Cerebral Edema, and/or a Basal Skull Fracture are More Susceptible to Developing Hyponatremia.

BACKGROUND: Traumatic brain injury (TBI) is a common injury treated at the neurosurgery department. The incidence rate is approximately 3% in the general population and the mortality rate is 25%. The incidence of hyponatremia following TBI is 33%. Hyponatremia is one of the main causes of disability and/or death in TBI patients. This study investigated the epidemiology of hyponatremia following TBI. METHODS: Patients who were admitted to our hospital with moderate or severe TBI were analyzed retrospectively. The relationship between the occurrence of hyponatremia and age, sex, type of injury, Glasgow coma scale (GCS) score, whether the patient underwent surgery, and the presence of cerebral edema and basal skull fracture was analyzed statistically using a χ2 test and multivariate logistic regression analysis. RESULTS: Out of the 136 patients recruited for the study (81 males and 55 females; mean±SD age of 48±13 y), 56 suffered from hyponatremia (ie, serum sodium level <135 mmol/L). Univariate analysis indicated that hyponatremia following TBI was not related to age (P>0.05), sex (P=0.347), or surgical history (P=0.492) but that it was related to the type of injury (P=0.031), a GCS score ≤8 (P<0.001), the presence of cerebral edema (P<0.001), and/or a basal skull fracture (P<0.001). Multivariate logistic regression analysis confirmed a strong association between the occurrence of hyponatremia and a GCS score ≤8 (P<0.016), the presence of cerebral edema (P<0.001), and a basal skull fracture (P<0.001). CONCLUSIONS: TBI patients with a GCS score ≤8, cerebral edema, and/or a basal skull fracture are particularly prone to developing hyponatremia. These patients require additional treatment that should entail the normalization of serum sodium levels to prevent deterioration of their condition.

Paeoniflorin Atttenuates Amyloidogenesis and the Inflammatory Responses in a Transgenic Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is associated with the inflammatory response in response to amyloid ß-peptide (Aß). Previous studies have suggested that paeoniflorin (PF) shows anti-inflammatory and neuroprotective effects in inflammation-related diseases. However, the impacts of PF on AD have not been investigated. In the present study, we showed that a 4-week treatment with PF could significantly inhibit Aß burden, Aß-induced over activation of astrocytes and microglia, downregulation of proinflammatory cytokines, and upregulation of anti-inflammatory cytokines in the brain. In addition, we demonstrated that chronic treatment with PF inhibited the activation of glycogen synthase kinase 3ß (GSK-3ß) and reversed neuroinflammtory-induced activation of nuclear factor-kappa B (NF-κB) signaling pathways. Moreover, PF exerted inhibitory effects on NALP3 inflammasome, caspase-1, and IL-1ß. Collectively, in the present study, we demonstrated that PF exhibits neuroprotective effects in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice via inhibiting neuroinflammation mediated by the GSK-3ß and NF-κB signaling pathways and nucleotide-binding domain-like receptor protein 3 inflammasome. Thus, these results suggest that PF might be useful to intervene in development or progression of neurodegeneration in AD through its anti-inflammatory and anti-amyloidogenic effects.

Three new pigment protein tyrosine phosphatases inhibitors from the insect parasite fungus Cordyceps gracilioides: terreusinone A, pinophilin C and cryptosporioptide A.

Three new pigment compounds--terreusinone A (1), pinophilin C (2) and cryptosporioptide A (3)-were isolated from a solid culture of Cordyceps gracilioides. The structures of these compounds were determined by extensive spectroscopic analysis including HRESIMS, 1D- and 2D-NMR. The structure of terreusinone A (1) was further confirmed by single-crystal X-ray crystallographic diffraction analysis. In an in vitro activity assay, 1, 2 and 3 exhibited high inhibitory activity against PTP1B, SHP2, CDC25B, LAR and SHP1. Terreusinone A (1) inhibited PTP1B, SHP2, CDC25B, LAR and SHP1 enzyme with IC50 values 12.5, >50, 4.1, 10.6, 5.6 µg/mL, respectively; pinophilin C (2) with IC50 values 6.8, 8.0, 4.5, 4.7, 3.4 µg/mL, respectively; and cryptosporioptide A (3) with IC50 values 7.3, 5.7, 7.6, >50, 4.9 µg/mL, respectively.

A novel oxybis cresol verticilatin with highly varying degrees of biological activities from the insect pathogenic fungus Paecilomyces verticillatus.

A novel oxybis cresol compound named verticilatin (1), together with two known compounds, 5-methylresorcinol (2) and 2,4-dihydroxy-3,6-dimethylbenzaldehyde (3), was isolated from cultures of the insect pathogenic fungi Paecilomyces verticillatus. The structures of compounds were determined by extensive spectroscopic analysis of HR-ESI-MS and 1D and 2D NMR including HSQC, HMBC, COSY, and ROESY. Fortunately, compound 1 exhibited significant inhibitory activities against CDC25B, cathepsin B, MEG2, and SHP2 enzyme, with IC50 values of 11.5, 3.5, 7.8, and 15 µg/ml, respectively.

Twenty-nine cases of resection of suprasellar meningioma through small bone window: an interhemispheric approach.

AIM OF THE STUDY: The present study aims to discuss the value and the effect of resection of suprasellar meningioma through the interhemispheric approach. MATERIAL AND METHODS: Twenty-nine cases of patients with suprasellar meningioma diagnosed through enhanced magnetic resonance imaging (MRI) scans and postoperative histopathological examination underwent resection of tumours (the largest diameter ranged from 3 cm to 6 cm) by the microsurgical technique of a small bone window (about 4 cm × 5 cm) through the interhemispheric approach. RESULTS: Among all cases, 25 (86%) (Simpson I, II) were of total resection of tumours and 4 were of subtotal resection of tumours. 19 (65%) were of improvement of vision and visual field, 2 (7%) were of postoperative diabetes insipidus, and 1 (3%) was of electrolyte imbalance. No operative death occurred. CONCLUSIONS: The small bone window interhemispheric approach can be used to expose tumours, lightly stretch brain tissues, reduce the incidence of complications, and improve the total resection rate of tumours of patients with sellae meningiomas growing forward, upward, and into the sella.

Effect of erythrocytes on brain water content and haem oxygenase-1 expression in rats with traumatic intracerebral haemorrhage.

BACKGROUND: Studies have demonstrated that brain oedema formation following spontaneous intracerebral haemorrhage is associated with substances derived from blood clots or blood components. However, these studies did not completely reveal the role of blood components in brain oedema formation following traumatic intracerebral haemorrhage (TICH). Here, we explore the role of erythrocytes in brain oedema development by studying the effect of erythrocytes on brain water content (BWC) and expression of haem oxygenase-1 (HO-1) in rats with TICH. METHODS: A total of 120 Sprague-Dawley rats were randomly divided into four experimental treatment groups: traumatic brain injury (TBI), TBI plus whole blood (WB), TBI plus lysed red blood cells (RBCs; LRBC) and TBI plus packed RBCs (PRBC). Following TBI, which was established by applying a free-falling device, WB, LRBC or PRBC were infused with stereotactic guidance into the injured cortex to produce a model of TICH. All rats were killed at 1, 3 or 5 days after TBI or TICH. BWC was measured, and immunohistochemistry for HO-1 was performed. RESULTS: In the WB, PRBC and TBI groups, BWC at 3 days post-TBI or post-TICH was the greatest. However, BWC in the LRBC group at 1 day was markedly higher than that at 3 and 5 days. Comparisons among the four groups showed that BWC in the LRBC group was the highest at 1 day, and the highest at 3 days in the WB and PRBC groups; there was no significant difference at 5 days. Positive expression of HO-1 in the WB, PRBC and LRBC groups coincided with changes in BWC. CONCLUSIONS: Our results indicate that erythrocytes play an important role in delayed brain oedema formation (3 days post-injury) following TICH, but have no significant influence on brain oedema at early stages (1 day post-injury), and that the mechanisms of delayed brain oedema involve RBC breakdown products.

[Thrombin preconditioning reduces brain injury caused by intracerebral infusion of high dose thrombin].

OBJECTIVE: To explore the effect of the cerebral thrombin preconditioning on the thrombin-induced brain edema, to detect the expression of tumor necrosis factor-alpha (TNF-alpha), and to analyse the relationship between TNF-alpha and the thrombin-induced brain edema. METHODS: Forty SD rats were randomly divided into a ST group and a TT group. The rats received 50 L saline (ST group) or 1 U thrombin infusion (TT group), and received the second infusion (10 U thrombin) 24 h later. The rats were sacrificed at 24 and 72 h after the second infusion in order to examine the changes of brain water and sodium contents as well as the expression of TNF-alpha in the brain. RESULTS: The brain water and sodium contents in the ST group were significantly higher than those on the TT group, and those on the 1st day were higher than those on the 3 th day. The positive expression of TNF-alpha and in the change of water content were identical in the TT group and the ST group. CONCLUSION: Thrombin preconditioning can alleviate the thrombin-induced brain edema. The increase of TNF-alpha expression after thrombin treatment may be related to the thrombin-induced brain edema.