Ursolic acid inhibits glioblastoma through suppressing TGFß-mediated epithelial-mesenchymal transition (EMT) and angiogenesis.

Found in many fruits and plants, Ursolic acid (UA), a pentacyclic triterpene that occurs naturally, is recognized for its anti-cancer effects, especially in combating glioblastoma. However, the intricate molecular mechanisms underpinning its anti-tumor actions are still not fully understood, despite the recognition of these effects. By examining the functions of epithelial-mesenchymal transition (EMT) and angiogenesis, crucial for glioblastoma progression, and their regulation through Transforming Growth Factor Beta (TGFß) - a key marker for glioblastoma, our research aims to fill this knowledge gap. This study explores how ursolic acid can block the progression of glioblastoma by precisely targeting TGFß-triggered EMT and angiogenesis. The findings show that UA successfully blocks the spread, movement, and invasion of glioblastoma cells. Accompanying this, there is a significant reduction in the expression of TGFß and crucial EMT indicators like snail and vimentin. Furthermore, UA shows a reduction in angiogenesis that depends on the dosage, highlighted by decreased vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs). Interestingly, increased TGFß expression in U87 and U251 glioblastoma cell lines was found to weaken UA's anti-tumor properties, shedding more light on TGFß's critical function in glioblastoma's pathology. Supporting these laboratory results, UA also showed considerable inhibition of tumor growth in a glioblastoma xenograft mouse model. Overall, our research emphasizes Ursolic acid's promise as a new treatment for glioblastoma and clarifies its action mechanism, mainly by inhibiting TGFß signaling and thereby EMT and angiogenesis.

Analysis of Changes in KPS Scores and Imaging Signs in Deep Brain Gliomas by DWI Combined with Intraoperative Ultrasound Resection.

Objective: This study investigates the efficacy of DWI combined with intraoperative ultrasound for deep brain glioma treatment, analyzing changes in Karnofsky performance status (KPS) scores and imaging signs. Objectives include elucidating the approach's advantages, addressing knowledge gaps, and contributing insights into its effectiveness for enhancing deep brain glioma management. Methods: In this retrospective study, we analyzed a total of 346 patients with deep brain glioma who underwent surgical treatment at our hospital from July 2015 to January 2022. After applying inclusion and exclusion criteria, 310 patients were selected and categorized into a control group (n = 150) and an observation group (n = 160) based on different auxiliary techniques of surgical treatment. The degree of resection and Karnofsky performance status (KPS) scores were assessed at 1 day preoperatively, 1 week, and 1 month postoperatively for both groups. Additionally, we conducted a comprehensive analysis of DWI and ultrasound imaging signs among patients with different grades of deep brain glioma. The study duration covered the specified period, and statistical analyses were performed to evaluate the outcomes. Results: In our study, the observation group demonstrated significantly improved resection degrees, with a total resection rate of 82.50% compared to the control group's 65.33%. Preoperative Karnofsky performance status scores showed no significant difference between groups (P > .05), but postoperative scores at 1 week and 1 month were significantly higher in the observation group (P < .05). Intraoperative ultrasound and DWI revealed distinct imaging signs differentiating low-grade and high-grade patients. These results highlight the efficacy of DWI combined with intraoperative ultrasound resection in enhancing resection outcomes and influencing postoperative Karnofsky performance status. Conclusions: DWI combined with intraoperative ultrasonic resection in deep brain glioma has a significant effect, with specific imaging signs, which can effectively improve the total resection rate and KPS score, and is worthy of clinical promotion. DWI combined with intraoperative ultrasound has important clinical significance in the resection of deep brain gliomas. The better resection results and improved postoperative Karnofsky performance-status score that we observed suggest a possible benefit in patient outcomes, which could influence treatment strategies. The precise imaging signs identified by this method provide valuable guidance for targeted and effective tumor resection.

Platycodin D inhibits glioblastoma cell proliferation, migration, and invasion by regulating DEPDC1B-mediated epithelial-to-mesenchymal transition.

BACKGROUND: Platycodin D (PD) is a potent bioactive constituent in the medicinal herb Platycodon grandiflorum. It has shown anticancer properties, particularly against glioblastoma (GB) and other human malignancies. DEPDC1B (DEP domain-containing protein 1B) is an oncogene associated with epithelial-mesenchymal transition (EMT). It is highly expressed in GB and correlated with tumor grade and patient prognosis. In this study, we investigated whether the antiglioma effect of PD was associated with downregulation of DEPDC1B. METHODS: Gene expression and clinical data were obtained from the China Glioma Genome Atlas and The Cancer Genome Atlas databases for glioma samples. In vitro experiments were conducted using Cell Counting Kit-8 and Transwell assays to assess the impact of PD on the proliferation, migration, and invasion of GB cells. mRNA and protein expression was evaluated using real-time polymerase chain reaction and western blotting, respectively. RESULTS: PD exerted inhibitory effects on the proliferation and motility of GB cells. PD downregulated DEPDC1B protein as well as several markers associated with EMT, namely N-cadherin, vimentin, and Snail. The suppressive effects of PD were enhanced when DEPDC1B was knocked down in GB cells, while overexpression of DEPDC1B in cells reversed the inhibitory effects of PD. CONCLUSION: PD exerts an antiglioma effect by regulating DEPDC1B-mediated EMT.

Acute paraplegia after aneurysmal subarachnoid hemorrhage: Case report of a rare complication with a 2­year follow­up.

The current overall incidence of subarachnoid hemorrhage (SAH) is ~9/100,000 individuals/year and rupture of an intracranial aneurysm is the main cause of SAH, accounting for ~85% of cases. Only a small number of cases of paraplegia after intracranial aneurysmal SAH have so far been reported and its pathogenesis has remained to be fully elucidated. The present study reports the case of a patient with an aneurysm localized in the medial and inferior lateral wall of the C5 segment of the right internal carotid artery that was treated by coil interventional embolization. The muscle strength of both lower extremities of the patient was grade I and grade 0 before and after the operation, respectively. Lumbar and thoracic magnetic resonance imaging examinations revealed slight hematoma in the subarachnoid space below the L2 level. At two weeks after the operation, the muscle strength of both lower extremities was grade II, while the muscle strength was grade III and grade V at 30 and 60 days after the operation, respectively.

Raddeanin A (RA) reduced acute inflammatory injury in mouse experimental cerebral hemorrhage by suppression of TLR4.

Spontaneous intracerebral hemorrhage (ICH) is associated with high mortality and disability rates. The microglia-induced inflammatory response is a critical factor determining brain tissue damage after ICH. Raddeanin A (RA) is a natural triterpenoid compound with anti-inflammatory effects, although its effects on ICH and the underlying molecular mechanism have not been elucidated. In this study, we found that RA reduced the volume of cerebral hematoma and cerebral edema, attenuated neuronal apoptosis and improved the behavioral indices in a murine model of acute cerebral hemorrhage. Mechanistically, RA downregulated the TLR4-mediated pro-inflammatory effectors, reduced infiltration of microglia in peri-intracerebral hemorrhage and inhibited apoptosis of neurons co-cultured with activated microglia. In conclusion, RA can alleviate ICH-related tissue damage and promote the recovery of neuronal function by suppressing microglia-induced inflammation and apoptosis.

Re-Examination of the Microstructural Evolution in Undercooled Co-18.5at.%B Eutectic Alloy.

The undercooling (∆T) dependencies of the solidification pathways, microstructural evolution, and recalescence behaviors of undercooled Co-18.5at.%B eutectic alloys were systematically explored. Up to four possible solidification pathways were identified: (1) A lamellar eutectic structure consisting of the FCC-Co and Co3B phase forms, with extremely low ΔT; (2) The FCC-Co phase primarily forms, followed by the eutectic growth of the FCC-Co and Co2B phases when ΔT < 100 K; (3) As the ΔT increases further, the FCC-Co phase primarily forms, followed by the metastable Co23B6 phase with the trace of an FCC-Co and Co23B6 eutectic; (4) When the ΔT increases to 277 K, the FCC-Co phase primarily forms, followed by an FCC-Co and Co3B eutectic, which is similar in composition to the microstructure formed with low ΔT. The mechanisms of the microstructural evolution and the phase selection are interpreted on the basis of the composition segregation, the skewed coupled zone, the strain-induced transformation, and the solute trapping. Moreover, the prenucleation of the primary FCC-Co phase was also detected from an analysis of the different recalescence behaviors. The present work not only enriches our knowledge about the phase selection behavior in the undercooled Co-B system, but also provides us with guidance for controlling the microstructures and properties practically.

Small Posterior Cranial Fossa and Cerebellopontine Cistern Volumes Are Associated With Bilateral Trigeminal Neuralgia.

Objective: To investigate whether small volumes of the posterior cranial fossa and cerebellopontine cisterns are associated with bilateral trigeminal neuralgia (BTN) and to provide further knowledge regarding the etiology and treatment of this rare disease. Methods: We retrospectively analyzed clinical data and imaging examination results for 30 BTN patients between January 2009 and December 2019. Thirty age- and sex-matched healthy individuals and 30 patients with unilateral trigeminal neuralgia (UTN) were selected as two control groups. The volume of the posterior cranial fossa (VPCF) and volumes of the cerebellopontine cisterns were measured using ITK-SNAP 3.0, which considers the cerebrospinal fluid (CSF) volume based on the region of interest (ROI). Preoperative and postoperative statuses were based on visual analog scale (VAS) pain scores and Barrow Neurological Institute (BNI) scores. Results: A total of 30 patients (11 males; 19 females) were included, and the age of the BTN participants ranged from 41 to 77 (59.93 ± 9.89) years. The duration of TN ranged from 1 to 20 (5.36 ± 3.92) years, and the interval between the two sides ranged from 0 to 3 (1.10 ± 0.79) years. Three patients (10%) in the BTN group had familial trigeminal neuralgia, with no other hereditary history of neurological disorders. In BTN patients, with 25 (83.3%) cases on the left side and 26 (86.7%) on the right side, veins were identified in the operative field and regarded as the individual or offending vessel. The mean VPCF was significantly lower in the patients with BTN than in the healthy controls (4,813 ± 1,155 mm3 vs. 5,127 ± 1,129 mm3, p = 0.008). The volumes of the cerebellopontine cisterns on both sides were significantly smaller in the BTN patients than in the healthy controls (477 ± 115 mm3 vs. 515 ± 112 mm3 on the left side, p = 0.001; and 481 ± 114 mm3 vs. 515 ± 110 mm3 on the right side, p = 0.007). There was no significant difference between the BTN group and the UTN group in terms of the VPCF (4,843 ± 1,184 mm3 vs. 4,813 ± 1,155 mm3, p = 0.402), and there was also no significant difference between the two groups in terms of preoperative VAS pain scores or BNI scores. Conclusion: Overcrowding in the posterior fossa will lead to closer neurovascular relations and, a higher incidence of NVC, and ultimately may be more likely to lead to TN. Veins are the common offending vessels that cause BTN; they might be associated with abnormal vascular development leading to NVC. Microsurgical vascular decompression (MVD) is a safe and effective method for the treatment of BTN, similar to UTN.

Long-Term Retrospective Analysis of Microvascular Decompression in Patients With Recurrent Trigeminal Neuralgia.

Objective: To explore the clinical characteristics of patients with recurrent trigeminal neuralgia (TN) and the experience of microvascular decompression (MVD) in the treatment of such patients. Methods: We retrospectively analyzed clinical data, imaging examination results, surgical methods, and treatment efficacies in 127 patients with recurrent typical TN from January 2005 to December 2014. Results: The age of the recurrent group was higher than that of the non-recurrent group (p < 0.05). The duration of pain before the first MVD procedure was longer in the recurrent group than in the non-recurrent group (p < 0.05). Patients in the recurrent group were more likely to have compression of the trigeminal nerve by the vertebrobasilar artery (VBA) or multiple vessels than patients in the non-recurrent group (p < 0.05). A Kaplan-Meier curve showed a median pain-free survival of 12 months after the first MVD procedure. The severity of pain (preoperative visual analog scale [VAS] score) in patients with recurrence was lower than that in patients with first-onset TN (p < 0.05). Vessel compression, Teflon compression or granuloma and arachnoid adhesion were considered the main causes of recurrence. Postoperative Barrow Neurological Institute (BNI) scores in the redo MVD group were excellent (T = 2) for 69 patients (53.33%) and good (T = 3) for 46 patients (36.22%). The postoperative follow-up was 63-167 months (105.92 ± 25.66). During the follow-up, no recurrence was noted. All complications were cured or improved. Conclusions: Microvascular decompression (MVD) is an effective surgical method for the treatment of TN. For recurrent patients, reoperation can achieve good results.

Verbascoside suppresses the migration and invasion of human glioblastoma cells via targeting c-Met-mediated epithelial-mesenchymal transition.

Verbascoside (VB), a glycosylated phenylpropanoid compound, is derived from the plant Syringa vulgaris (Oleaceae) and has been shown to have antitumor effects in multiple human cancers, including glioblastoma (GBM); however, the underlying mechanism has not been completely elucidated. Epithelial-to-mesenchymal transition (EMT) is the pivotal event in tumor progression. c-Met, a receptor tyrosine kinase, plays an important role in GBM aggressiveness via promoting EMT. The current study aimed to explore whether VB suppresses c-Met-induced EMT and investigated the mechanism of c-Met degradation. We found that VB inhibited GBM cell growth and downregulated c-Met and the EMT markers (snail, vimentin, and zeb1) in vitro and in an orthotopic xenograft mouse model. In addition, overexpressing c-Met in glioblastoma cells abolished the effects of VB on EMT. We also used a microscale thermophoresis (MST) assay to show that VB could directly bind to the c-Met protein, and we showed that VB degraded the c-Met protein via the ubiquitination-proteasome pathway. Our study is the first to identify a new mechanism for the anticancer effects of VB, namely, the inhibition of EMT by directly targeting c-Met; the inhibition of EMT results in c-Met protein degradation through the ubiquitination-proteasome pathway. Our current research indicates that VB is a potential agent to treat GBM via the ubiquitin-mediated degradation of c-Met.

Characteristics of osseous septum of split cord malformation in patients presenting with scoliosis: a retrospective study of 48 cases.

BACKGROUND/AIMS: The coexistence of scoliosis and split cord malformation (SCM) is often encountered. The characteristics of the osseous septum of SCM are still unknown to us. Here we try to delineate the configuration and nature of the osseous septa. The correlation between scoliosis and SCM is also discussed. METHODS: 48 patients hospitalized for scoliosis were studied. SCM was subsequently identified in all of the patients. These patients underwent operations and were retrospectively evaluated. RESULTS: The figuration, component, location and nature of osseous septa are described. 47 of the 48 SCMs (98%) were type I. Only 1 case was type II. 43 patients (90%) had 1 osseous septum. The other 5 patients (10%) had 2 osseous septa at different levels. 41 septa (78%) were mainly made of cortical bone, another 6 septa (11%) were mainly made of cancellous bone, while the other 6 (11%) were bone together with soft tissues. The prominent central blood vessels were found in 19 cases (36%). 10 osseous septa (19%) were derived from neural arches. 15 osseous septa (28%) were from both vertebral bodies and neural arches. CONCLUSION: We assumed that SCM might contribute to the progress of scoliosis. It is recommended that removal of the spur be carried out before corrective surgery on the spine.