PRMT1 in human neoplasm: cancer biology and potential therapeutic target.

Protein arginine methyltransferase 1 (PRMT1), the predominant type I protein arginine methyltransferase, plays a crucial role in normal biological functions by catalyzing the methylation of arginine side chains, specifically monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), within proteins. Recent investigations have unveiled an association between dysregulated PRMT1 expression and the initiation and progression of tumors, significantly impacting patient prognosis, attributed to PRMT1's involvement in regulating various facets of tumor cell biology, including DNA damage repair, transcriptional and translational regulation, as well as signal transduction. In this review, we present an overview of recent advancements in PRMT1 research across different tumor types, with a specific focus on its contributions to tumor cell proliferation, metastasis, invasion, and drug resistance. Additionally, we expound on the dynamic functions of PRMT1 during distinct stages of cancer progression, elucidating its unique regulatory mechanisms within the same signaling pathway and distinguishing between its promotive and inhibitory effects. Importantly, we sought to provide a comprehensive summary and analysis of recent research progress on PRMT1 in tumors, contributing to a deeper understanding of its role in tumorigenesis, development, and potential treatment strategies.

A New Alkaloid from the Aerial Parts of Bupleurum chinense DC.

A new isoalloxazine alkaloid, named bupleurine A (1), along with five known compounds (2-6), were isolated from the aerial parts of Bupleurum chinense DC. The structure elucidation of the new alkaloid (1) was employed by combining NMR and HR-MS data with comparison of reference in the literature. Five known compounds (2-6) were isolated from Bupleurum genus for the first time. Additionally, their antiproliferative activities on HeLa cells were evaluated by MTT assay and IC50 of compounds 1 and 4-6 were below 10 µm after treatment for 24 h.

One case report of delayed severe intracerebral and intraventricular hemorrhage after cranioplasty.

BACKGROUND: Cranioplasty is a relatively simple neurosurgical procedure, and common complications of cranioplasty include dural tears, CSF leakage, infection, epilepsy, epidural hematoma and bone flap resorption. Intracerebral hemorrhage as a complication of cranioplasty is rare, and it is often fatal. The report describes one case of delayed severe intracerebral and intraventricular hemorrhage after an uneventful cranioplasty. CASE PRESENTATION: A previously healthy 29-year-old man was admitted to our hospital with a traumatic left frontotemporoparietal acute subdural hematoma, an emergency decompressive craniectomy with clot removal was performed. Four months after the surgery, cranioplasty was performed with a titanium mesh, the surgery was uneventful. Six hours after the operation, a CT scan demonstrated no bleeding or edema. In the following 2 days after cranioplasty, the patient did not have any neurological deficits, normal blood pressure was recorded every day, no trauma occurred, and routine laboratory test results were within normal limits. However, on the third day after cranioplasty, the patient suffered a sudden severe headache while playing games on his mobile phone, and then rapidly fell into deep coma; both pupils were fixed and dilated at 5 mm with no response to light. An immediate CT scan revealed a massive intracerebral hematoma and intraventricular hematoma on the left side, and the midline shifted to the right side. Therefore, an ipsilateral decompressive craniectomy was performed with evacuation of the hematoma; the obvious bleeding point was not identified, and no obvious vascular abnormalities were found during the operation. A CT scan on day 3 after reoperation revealed successful decompression, and CT angiography showed no vascular abnormalities. Despite all treatment measures, the patient did not regain consciousness, his neurological situation did not improve after the operation, and the patient lived in a vegetative state. CONCLUSION: Although intracerebral and intraventricular hemorrhage after cranioplasty is extremely rare, it is often fatal. Aside from hyperperfusion and cerebral autoregulation dysfunction, traction injuries to the fragile vessels due to posttraumatic angiogenesis may also be one of the key factors of complications after cranioplasty.

MicroRNA-182-5p attenuates cerebral ischemia-reperfusion injury by targeting Toll-like receptor 4.

Cerebral ischemia-reperfusion-induced microglial activation causes neuronal death through the release of inflammatory cytokines. Increasing evidence suggests that microRNAs (miRNAs) exert a neuroprotective effect by modulating the inflammatory process in cerebral ischemia-reperfusion injury. Furthermore, Toll-like receptor 4 (TLR4) is increasingly being considered to have a significant role in the regulation of inflammation. However, whether miRNAs mediate their neuroprotective effects by regulating TLR4-mediated inflammatory responses remains unknown. To explore this gap in the literature, we conducted both in vitro and in vivo experiments. In vitro: BV2 cells were activated by oxygen-glucose deprivation (OGD). TLR4 and inflammatory cytokine (TNF-a, IL-6, and IL-1ß) transcription and translation expression levels were assessed using RT-PCR, ELISA, and western blot. BV2 cells were transfected with miR-182-5p mimics, inhibitors, siTLR4, or negative control (NC) using lipofectamine 2000 reagent. To confirm whether TLR4 is a direct target of miR-182-5p, we performed a luciferase reporter assay. In BV2 cells, we observed that OGD upregulated TLR4 expression, but downregulated miR-182-5p expression. We determined that miR-182-5p inhibited TLR4 by directly binding to its 3'-UTR. Furthermore, miR-182-5p suppressed the release of TNF-a, IL-6, and IL-1ß. In vivo: A middle cerebral artery occlusion (MCAO) rat model was used to mimic cerebral ischemia-reperfusion. Iba1 and TLR4 double staining was used to demonstrate that the target of miR-182-5p in microglial cells, and the mediator of the anti-inflammatory effect, is TLR4. TTC staining was performed to evaluate the infarct volume. Compared to the animals treated with miR-182-5p NC and normal saline, rats treated with miR-182-5p mimics demonstrated significantly enhanced neurological functions. TTC staining results were consistent with neurological function test findings. In summary, our data suggested that miR-182-5p exhibits potential neuroprotective effects in the cerebral ischemia-reperfusion injury via the regulation of the TLR4-mediated inflammatory response.

[Experimental study of dendritic cells transfected with cancer stem like cells RNA against 9L brain tumors].

OBJECTIVE: To investigate the anti-tumor efficacy of dendritic cells (DC) vaccination transfected with total RNA of cancer stem like cells and to discuss the mechanism of immune response, so as to provide experimental basis for clinical application. METHODS: Dendritic cells were isolated from F344 bone marrow cells, then these dendritic cells were transfected with total RNA of 9L cancer stem cells or 9L monolayer cells. F344 rats bearing with 9L brain tumors were treated by subcutaneous injection of either PBS, unpulsed DC, DC transfected with 9L monolayer cells RNA (DC-9LTS) or DC transfected with 9L tumor spheres RNA (DC-9L)3, 10, 17. And 21 days after tumor implantation, the brains and sera were obtained from the different groups, the lymphocytes infiltration was detected by immunohistochemistry, and the concentration of interferon-γ (IFN-γ) was tested by ELISA. The survival time was observed and determined using the method of Kaplan Meier analysis. RESULTS: The rats vaccinated with DC transfected with 9L tumor spheres RNA (DC-9LTS) and the monolayer cell RNA (DC-9L) expired with median survival time of 36 and 31 days, respectively. The animals bearing intracranial 9L gliosarcoma were vaccinated with un-pulsed DC vaccine, all expired with a median survival time of 21 days. The Kaplan-Meier survival curve showed that the rats treated with DC-9LTS had longer survival than the other groups (P<0.01). There was significant difference among DC-9L group, DC group, and PBS group (P<0.01). There was no significant difference between DC group and PBS group (χ2=0.071, P=0.789).The concentration of IFN-gamma of DC-9LTS group [(157.08±7.25) ng/L] was much higher than those of the other groups (P<0.05). DC-9LTS could effectively enhance T-cell infiltration, a large number of CD8+ cells were detected in and around the tumor in DC-9LTS group, compared with DC-9L group, DC and PBS group (P<0.001). The expression of CD8+ cell was not detected in DC group and PBS group. However no expression of CD4+ cells was observed in all the groups. CONCLUSION: Immunotherapy using DC transfected with 9L CSLCs total RNA was more effective for the treatment of 9L brain gliomas, and the strategy prolonged the survival of 9L glioma-bearing rats significantly, which provides a scientific foundation for further investigation of this approach to eradicate gliomas.

PRMT6 facilitates EZH2 protein stability by inhibiting TRAF6-mediated ubiquitination degradation to promote glioblastoma cell invasion and migration.

Invasion and migration are the key hallmarks of cancer, and aggressive growth is a major factor contributing to treatment failure and poor prognosis in glioblastoma. Protein arginine methyltransferase 6 (PRMT6), as an epigenetic regulator, has been confirmed to promote the malignant proliferation of glioblastoma cells in previous studies. However, the effects of PRMT6 on glioblastoma cell invasion and migration and its underlying mechanisms remain elusive. Here, we report that PRMT6 functions as a driver element for tumor cell invasion and migration in glioblastoma. Bioinformatics analysis and glioma sample detection results demonstrated that PRMT6 is highly expressed in mesenchymal subtype or invasive gliomas, and is significantly negatively correlated with their prognosis. Inhibition of PRMT6 (using PRMT6 shRNA or inhibitor EPZ020411) reduces glioblastoma cell invasion and migration in vitro, whereas overexpression of PRMT6 produces opposite effects. Then, we identified that PRMT6 maintains the protein stability of EZH2 by inhibiting the degradation of EZH2 protein, thereby mediating the invasion and migration of glioblastoma cells. Further mechanistic investigations found that PRMT6 inhibits the transcription of TRAF6 by activating the histone methylation mark (H3R2me2a), and reducing the interaction between TRAF6 and EZH2 to enhance the protein stability of EZH2 in glioblastoma cells. Xenograft tumor assay and HE staining results showed that the expression of PRMT6 could promote the invasion of glioblastoma cells in vivo, the immunohistochemical staining results of mouse brain tissue tumor sections also confirmed the regulatory relationship between PRMT6, TRAF6, and EZH2. Our findings illustrate that PRMT6 suppresses TRAF6 transcription via H3R2me2a to enhance the protein stability of EZH2 to facilitate glioblastoma cell invasion and migration. Blocking the PRMT6-TRAF6-EZH2 axis is a promising strategy for inhibiting glioblastoma cell invasion and migration.

Dual expression of hTERT and VEGF prolongs life span and enhances angiogenic ability of aged BMSCs.

Previous studies have confirmed the therapeutic effects of bone marrow stromal cells (BMSCs) transplantation on cerebral ischemia. However, the proliferative, differentiative, and homing capacity of BMSC from the elderly are significantly reduced, especially after several passages expansion in vitro. In this study, by introducing lentivirus-mediated hTERT and VEGF genes to modify human BMSCs from aged donors, we observed extended lifespan, promoted angiogenic capacity while less enhanced tumorigenicity of the genetically engineering BMSCs. These results therefore suggest that the modification of aged BMSCs by dual expression of hTERT and VEGF may be used for autologous cell replacement for ischemic cerebrovascular disease in elderly patients.

Comparison of the neural differentiation potential of human mesenchymal stem cells from amniotic fluid and adult bone marrow.

Human mesenchymal stem cells (MSCs) are considered a promising tool for cell-based therapies of nervous system diseases. Bone marrow (BM) has been the traditional source of MSCs (BM-MSCs). However, there are some limitations for their clinical use, such as the decline in cell number and differentiation potential with age. Recently, amniotic fluid (AF)-derived MSCs (AF-MSCs) have been shown to express embryonic and adult stem cell markers, and can differentiate into cells of all three germ layers. In this study, we isolated AF-MSCs from second-trimester AF by limiting dilution and compared their proliferative capacity, multipotency, neural differentiation ability, and secretion of neurotrophins to those of BM-MSCs. AF-MSCs showed a higher proliferative capacity and more rapidly formed and expanded neurospheres compared to those of BM-MSCs. Both immunocytochemical and quantitative real-time PCR analyses demonstrated that AF-MSCs showed higher expression of neural stemness markers than those of BM-MSCs following neural stem cell (NSC) differentiation. Furthermore, the levels of brain-derived growth factor and nerve growth factor secreted by AF-MSCs in the culture medium were higher than those of BM-MSCs. In addition, AF-MSCs maintained a normal karyotype in long-term cultures after NSC differentiation and were not tumorigenic in vivo. Our findings suggest that AF-MSCs are a promising and safe alternative to BM-MSCs for therapy of nervous system diseases.

Tightening Continuous Suture Loops in Microvascular Anastomosis with a Microneedle.

AIM: To present a technique for tightening continuous suture loops in microvascular side-to-side anastomosis with a microneedle. MATERIAL AND METHODS: The technique for tightening continuous suture loops with a microneedle was presented in side-to-side microvascular anastomosis in chicken thighs arteries and rat common carotid arteries. After all the spiral continuous suture loops were loosely placed, the tip of the microneedle was used to precisely and gently tighten the second suture loop, then microforceps was used to pick this loop up and gently tighten it, while the body of the microneedle was gently applied to create a counterforce on the inner or outer surface of the vessel to help tighten the first loop under appropriate tension and place it in an appropriate position. RESULTS: With this technique the author described, there is no need to change to any other surgical instruments during anastomosis, and these continuous suture loops in continuous microvascular anastomosis could be effectively tightened with a microneedle. And the technique was successfully applied in side-to-side microvascular anastomosis in chicken thighs arteries and rat common carotid arteries. CONCLUSION: Microneedle could be safely and effectively used as a microretractor to tighten the continuous suture loops in continuous microvascular anastomosis. The judicious and discreet use of a microneedle as a multifunctional instrument for functions other than suturing could minimize the exchange of instruments and improve operative efficiency.

Three types of end-to-side microvascular anastomosis training models using rat common iliac arteries.

Background: : Instead of only practicing these perfectly matched end-to-side anastomoses in microsurgical laboratories, we must learn how to perform these so-called "imperfect" end-to-side anastomoses in the laboratory. Methods: Three types of end-to-side microvascular anastomoses using the rat common iliac artery (CIA), one with the proximal end of the CIA to the contralateral side of the CIA, another with the distal end of the CIA to the contralateral side of the CIA, and the third with the distal end of the CIA to the ipsilateral side of the common iliac vein (CIV), were presented to simulate different end-to-side anastomosis situations in a microsurgical laboratory. Diameters of CIA and CIV, distances between temporary clips, the length of arteriotomy or venotomy, and the distribution of stitches were recorded. The patency rates were evaluated immediately after the anastomosis was completed and 30 min later. After animal euthanasia, the donor vessel was cut close to the anastomotic site, and the orifice size and intimal attachment were evaluated by inspecting them through inside the vessel. Results: The diameters of the CIA and CIV were 0.8-1.2 mm and 1.2-1.5 mm, respectively. The end-to-side microvascular anastomosis arteriotomy or venotomy is approximately 2.00-2.50 mm, the distance between the aneurysm clips on the recipient CIA or CIV is approximately 4.00-7.00 mm, and the distance between the corner of the arteriotomy or venotomy and the temporary aneurysm clip was 1.00-3.00 mm. Three types of end-to-side anastomoses using the CIA were successfully performed, and 100% patency rates were achieved immediately and 30 min postoperatively. Good distribution of stitches, wide orifice, and intimal attachment were recorded in the study in all groups. Conclusions: Three types of end-to-side anastomoses using rat CIAs could be efficiently used to mimic three different anastomotic situations.

PRMT6-CDC20 facilitates glioblastoma progression via the degradation of CDKN1B.

PRMT6, a type I arginine methyltransferase, di-methylates the arginine residues of both histones and non-histones asymmetrically. Increasing evidence indicates that PRMT6 plays a tumor mediator involved in human malignancies. Here, we aim to uncover the essential role and underlying mechanisms of PRMT6 in promoting glioblastoma (GBM) proliferation. Investigation of PRMT6 expression in glioma tissues demonstrated that PRMT6 is overexpressed, and elevated expression of PRMT6 is negatively correlated with poor prognosis in glioma/GBM patients. Silencing PRMT6 inhibited GBM cell proliferation and induced cell cycle arrest at the G0/G1 phase, while overexpressing PRMT6 had opposite results. Further, we found that PRMT6 attenuates the protein stability of CDKN1B by promoting its degradation. Subsequent mechanistic investigations showed that PRMT6 maintains the transcription of CDC20 by activating histone methylation mark (H3R2me2a), and CDC20 interacts with and destabilizes CDKN1B. Rescue experimental results confirmed that PRMT6 promotes the ubiquitinated degradation of CDKN1B and cell proliferation via CDC20. We also verified that the PRMT6 inhibitor (EPZ020411) could attenuate the proliferative effect of GBM cells. Our findings illustrate that PRMT6, an epigenetic mediator, promotes CDC20 transcription via H3R2me2a to mediate the degradation of CDKN1B to facilitate GBM progression. Targeting PRMT6-CDC20-CDKN1B axis might be a promising therapeutic strategy for GBM.

LncRNA SPRY4-IT1 facilitates cell proliferation and angiogenesis of glioma via the miR-101-3p/EZH2/VEGFA signaling axis.

BACKGROUND: SPRY4-IT1 (SPRY4 intronic transcript 1) is a long non-coding RNA (lncRNA) that has been identified as a novel oncogene in various cancers, including glioma. However, its function and underlying mechanism in glioma remain largely unclear. Here, we investigated the role of SPRY4-IT1 in the development of glioma and its underlying mechanism. METHODS: Bioinformatics analysis and RT-qPCR assay were used to examine the expression of SPRY4-IT1 in glioma tissues. The CCK-8, EdU, and Xenograft tumor assays wereperformed to assess the proliferation effect of glioma cells. The tube forming assay and Chick Embryo Chorioallantoic Membrane (CAM) assay were conducted to detect the angiogenesis effect of HUVECs. RNA-sequencing, western blotting, RT-qPCR, ELISA, and IHC assays were employed to verify the regulatory mechanism of the SPRY4-IT1/ miR-101-3p/EZH2/VEGFA axis. RESULTS: Analysis of the TCGA dataset and data from our own cohort demonstrated that SPRY4-IT1 was overexpressed in patients with glioma, and high SPRY4-IT1 expression correlated with poor prognosis. In vitro and in vivo experiments showed that SPRY4-IT1 promoted the proliferation of glioma cells. RNA sequencing and Gene Ontology (GO) enrichment analysis indicated significant enrichment of angiogenesis. HUVEC tube forming assay and CAM assay confirmed that SPRY4-IT1 could induce angiogenesis of glioma cells in vitro and in vivo. Mechanistically, SPRY4-IT1 upregulated EZH2 expression by sponging miR-101-3p to induce VEGFA expression in glioma cells. Moreover, SPRY4-IT1 activated the VEGFR2/AKT/ERK1/2 pathway in HUVECs mediated by glioma cells. Rescue experiments further confirmed that SPRY4-IT1 promoted glioma cell proliferation and angiogenesis via the miR-101-3p/EZH2/VEGFA signaling axis. CONCLUSIONS: Our findings provide compelling evidence showing that SPRY4-IT1 upregulated EZH2 to induce VEGFA by sponging miR-101-3p, thereby achieving cell proliferation and angiogenesis in glioma. Therefore, targeting SPRY4-IT1/miR-101-3p/EZH2/VEGFA axis may improve the outcomes of patients with glioma.

Side-to-Side Microvascular Anastomosis Using Rat Cervical Vessels.

BACKGROUND: Side-to-side anastomosis is the most challenging anastomosis owing to the difficult intraluminal suturing technique, which requires practice in the microsurgical laboratory before application in patients in the operating room. The objective of this study was to describe 2 side-to-side microvascular anastomosis training models using rat cervical vessels. METHODS: Two side-to-side microvascular anastomosis training models, one with rat cervical vessels between bilateral common carotid arteries (CCAs) (CCA-CCA anastomosis) and one with a unilateral CCA and the anterior facial vein of the external jugular vein (EJV) (CCA-EJV anastomosis), were studied. Diameters of CCA and anterior facial vein, distances between temporary clips and length of arteriotomies, and vascular clipping time were recorded. Patency rates were evaluated immediately and 7 days after the procedure. RESULTS: Diameters of CCA and anterior facial vein were 1.00-1.20 mm and 1.40-1.80 mm, respectively. A segment of vessel slightly longer than the arteriotomy or venotomy was temporarily clipped; mean lengths between temporary clips in CCA-CCA anastomosis and CCA-EJV anastomosis of 6.48 ± 0.66 mm and 8.02 ± 0.45 mm, respectively, were used in the study. The minimum distance between the corner of the arteriotomy or venotomy and the clip was 1 mm. The mean vascular temporary clipping times in CCA-CCA anastomosis and CCA-EJV anastomosis were 40.05 ± 3.92 minutes and 42.50 ± 4.82 minutes, respectively. Patency rates of 100% were achieved in all anastomoses. CONCLUSIONS: CCA-CCA and CCA-EJV side-to-side anastomosis models using rat cervical vessels are feasible and effective side-to-side anastomosis training models.

MEOX2-mediated regulation of Cathepsin S promotes cell proliferation and motility in glioma.

Nuclear transcription factor Mesenchyme Homeobox 2 (MEOX2) is a homeobox gene that is originally discovered to suppress the growth of vascular smooth muscle and endothelial cells. However, whether or not it is connected to cancer is yet unknown. Here, we report that MEOX2 functions as a tumor-initiating element in glioma. Bioinformatic analyses of public databases and investigation of MEOX2 expression in patients with glioma demonstrated that MEOX2 was abundant at both mRNA and protein levels in glioma. MEOX2 expression was shown to be inversely linked with the prognosis of glioma patients. MEOX2 inhibition changed the morphology of glioma cells, inhibited cell proliferation and motility, whereas had no effect on cell apoptosis. Besides, silencing MEOX2 also hampered the epithelial-mesenchymal transition (EMT), focal adhesion formation, and F-actin assembly. Overexpression of MEOX2 exhibited opposite effects. Importantly, RNA-sequencing, ChIP-qPCR assay, and luciferase reporter assay revealed Cathepsin S (CTSS) as a novel transcriptional target of MEOX2 in glioma cells. Consistently, MEOX2 causes glioma tumor development in mice and greatly lowers the survival period of tumor-bearing mice. Our findings indicate that MEOX2 promotes tumorigenesis and progression of glioma partially through the regulation of CTSS. Targeting MEOX2-CTSS axis might be a promising alternative for the treatment of glioma.

A case report of frontal spontaneous epidural hematoma associated with cranial osteomyelitis and epidural abscess due to paranasal sinusitis.

BACKGROUND: Intracranial epidural hematoma (EDH) is frequently secondary to trauma, but in some rare cases, spontaneous EDH (SEDH) could develop without trauma. Cranial osteomyelitis is an uncommon osseous infection that most frequently presents as a postoperative complication but also rarely originates from paranasal sinusitis and can develop extracranially to form a subperiosteal abscess or intracranially to form an epidural, subdural, or cerebral abscess. Intracranial epidural abscess (EDA) is an uncommon infection that forms in the space between the cranial bone and dura mater. It is rare to have a case of SEDH associated with cranial osteomyelitis and EDA due to paranasal sinusitis. CASE DESCRIPTION: An 18-year-old male was admitted to the hospital with headache, nausea, and vomiting for 2 days. The patient denied a history of head trauma, operation, and any other infectious and systemic diseases, and he was not taking any medication. CT scan demonstrated a mixed density lenticular mass with some air collection in the frontal region. The axial sinus CT image demonstrated opacification of the left frontal, ethmoid, and maxillary sinuses. An emergency operation confirmed the diagnosis of frontal SEDH associated with EDA and frontal osteomyelitis. The frontal EDH, abscess, and the infected bone were completely removed during the operation without opening the dura. The patient recovered well after receiving 8 weeks of antibiotic therapy, and a cranioplasty was performed 9 months after the craniectomy. CONCLUSION: To the best of our knowledge, SEDH associated with EDA is very rare. It is important to recognize the possibility of SEDH associated with cranial osteomyelitis and EDA due to paranasal sinusitis, and the presence of an EDA should, therefore, be considered in the differential diagnosis of cases of SEDH.

Microvascular Patch Graft Angioplasty of the Common Carotid Arteries in Rats.

BACKGROUND: Microvascular patch graft angioplasty is one of the most important revascularization techniques in cerebrovascular neurosurgery. It is necessary for surgeons to develop the microvascular patch graft angioplasty technique in the laboratory before performing it in a real human body. OBJECTIVE: To provide a training model for microvascular patch graft angioplasty of the common carotid arteries (CCAs) in rats. METHODS: Using male Sprague-Dawley rats (n=20), an oval-shaped arterial patch 3 mm in length and 1.2 mm in width was prepared from a segment of left CCA, and a linear longitudinal arteriotomy 3 mm in length was made along the anterior aspect of the right CCA, then the arterial patch graft was anastomosed to the right CCA with 10-0 sutures in an interrupted fashion. Patency was assessed immediately and 30 minutes after the procedure. RESULTS: All microvascular patch graft angioplasties of the rat common carotid arteries were successful, and all the patency rates immediately after the operation and thirty minutes after the restoration of blood flow were 100%. CONCLUSION: The training model for microvascular patch angioplasty with rat CCAs can serve as a training tool for mastering the procedure, and this technique could provide an alternative strategy for the surgical repair of microvascular aneurysms and microvascular vessel injuries.

Training model for the intraluminal continuous suturing technique for microvascular anastomosis.

Microvascular anastomosis is a critical procedure in cerebral bypass surgeries. In some rare cases, the extraluminal interrupted technique is not optimal because the vessels are immobile and cannot be rotated, and anastomosis can be performed effectively through the intraluminal continuous suturing technique. The authors reported the application of the intraluminal continuous suturing technique in microanastomosis training with silicone tube, rat's common iliac arteries and abdominal aorta. A silicone tube with a diameter of 1.5 mm was used to practice microanastomosis in intraluminal continuous suturing technique. Then the technique was applied in side-to-side, end-to-side anastomoses of common iliac arteries and the end-to-end abdominal aorta anastomoses of rat. The suturing time and patency rates were compared with an alternative intraluminal continuous suturing technique and one-way-up interrupted suturing technique in silicone tube and rat vessel anastomoses. The intraluminal continuous suturing technique could be gained through practicing with silicone tube, and the technique has also been demonstrated effective in side-to-side, end-to-side anastomoses of common iliac arteries of rat and the abdominal aorta end-to-end anastomoses. In all the animal experimental groups with different suturing techniques, there was no difference between the patency rates, all the immediate patency rate was 100%. There was no significant suturing time difference between the two intraluminal continuous suturing techniques, but the two intraluminal continuous suturing techniques were faster than the interrupted technique. The intraluminal continuous suturing technique described in the study could be used as an efficient method for side-to-side, end-to-side and end-to-end anastomosis, especially under the situation the posterior wall of the anastomosis could not be rotated. Proficiency of the technique could be achieved through practicing in laboratory with silicone tube and live animals.

New flavonoids from the aerial part of Bupleurum chinense DC.

Four new flavonoids (1-4) and fourteen known compounds (5-18), were isolated from the aerial part of Bupleurum chinense DC. The structural determination of the new flavonoids was accomplished using comprehensive spectroscopic methods, including 1D and 2D NMR spectra with references to the literatures, as well as high-resolution mass spectrometric analysis. The anti-proliferative activities of the flavonoids (1-18) against HeLa cells were evaluated using the MTT assay with cisplatin as the positive control.

HucMSCs-Derived miR-206-Knockdown Exosomes Contribute to Neuroprotection in Subarachnoid Hemorrhage Induced Early Brain Injury by Targeting BDNF.

Early brain injury (EBI) is the most important potentially treatable cause of mortality and morbidity following subarachnoid hemorrhage (SAH). Apoptosis is one of the main pathologies of SAH-induced EBI. Numerous studies suggest that human umbilical cord derived mesenchymal stem cells (hucMSCs) may exert neuroprotective effect through exosomes instead of transdifferentiation. In addition, microRNA-206 (miR-206) targets BDNF and plays a critical role in brain injury diseases. However, the therapy effect of miR-206 modified exosomes on EBI after SAH and its regulatory mechanism have not been elucidated. Here, to identify whether hucMSCs-derived miR-206-knockdown exosomes have a better neuroprotective effect, we established SAH rat model and treated it with the exosomes to research the mechanism of miR-206 in EBI after SAH. We found that treatment with hucMSCs-derived miR-206-knockdown exosomes has a greater neuroprotective effect on SAH-induced EBI compared to treatment with simple exosomes. The miR-206-knockdown exosomes could significantly improve neurological deficit and brain edema and suppress neuronal apoptosis by targeting BDNF. Moreover, the BDNF/TrkB/CREB pathway was activated following treatment with miR-206 modified exosomes in vivo. In summary, these findings indicate that the hucMSCs-derived miR-206-knockdown exosomes prevent early brain injury by inhibiting apoptosis via BDNF/TrkB/CREB signaling. This may serve as a novel therapeutic target for treatment of SAH-induced EBI.

Expression of Nestin, CD133 and Sox2 in Meningiomas.

AIM: To investigate the expression of cancer stem cell markers in meningiomas. MATERIAL AND METHODS: CD133, Nestin and Sox2 expression levels in 35 paraffin-embedded meningioma tissue samples were assessed using immunohistochemistry. RESULTS: In this study, five cases were atypical (WHO Grade II), two were anaplastic (WHO Grade III), and 28 were benign (WHO Grade I). Among atypical and anaplastic meningiomas, all were positive for Nestin and CD133, and 4 were positive for Sox2. Of the 28 benign meningiomas, 23 were positive for Nestin, 11 were positive for CD133, and none were positive for Sox2. In addition, Nestin and CD133 were expressed at significantly higher levels in the non-benign group than in the benign group. CONCLUSION: Nestin, CD133 and Sox2 expression levels may be correlated with the WHO pathological grade. Specifically, more aggressive meningiomas are characterized by higher positivity rates and higher levels of Nestin, CD133 and Sox2 expression in positive cells.