Cancer-associated fibroblast-associated gene IGFBP2 promotes glioma progression through induction of M2 macrophage polarization.

We elucidated the molecular mechanism of cancer-associated fibroblast (CAF)-associated gene insulin-like growth factor binding protein-2 (IGFBP2)-induced M2 macrophage polarization in the tumor microenvironment involved in glioma progression. The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) provided bulk RNA-sequencing datasets, ESTIMATE scores for glioma stromal cells, and overall survival-clinicopathological correlation analyses. TIMER provided CAF abundance in the TCGA glioma-related dataset, differential gene analysis was performed for high- and low-CAF groups, and weighted gene coexpression network analysis identified CAF-related genes. Univariate and multifactorial cyclooxygenase (COX) regression analyses created the CAF risk models single sample gene set enrichment analysis, CIBERSORT, and GSE84465. Mice were implanted with gliomas, and Western blot and RT-quantitative PCR showed IGFBP2 in tumor tissues. Adeno-associated virus (AAV) decreased IGFBP2, flow cytometry measured M1 and M2 macrophage ratios, and immunohistochemistry detected markers. TCGA and CGGA transcriptome data showed malignant gliomas had higher stromal cell scores and worse prognoses. Low- and high-CAF TCGA gliomas were detected, and differential expression, WGCNA, and multifactorial COX identified 132 CAF-related genes and seven high-risk genes (CPQ, EFEMP2, IGFBP2, RAB42, TNFRSF12A, and VASN). Neither CAF risk score, grade, nor 1p/19q affected glioma prognosis. CAF only enriched EFEMP2 and IGFBP2. Gene Expression Profiling Interactive Analysis compared EFEMP2 and IGFBP2 expression in normal brain tissue and gliomas. Low-grade glioma and malignant glioblastoma highly expressed IGFBP2 and EFEMP2. GSEA raised IGFBP2. CIBERSORT linked M2 macrophage infiltration to TCGA glioma immune cell subpopulation IGFBP2 expression. IGFBP2 knockdown stopped mouse glioma and M2 macrophage polarization. CAF plays a procarcinogenic role in glioma, and the CAF-related gene IGFBP2 could promote glioma progression by inducing M2 macrophage polarization.NEW & NOTEWORTHY The cancer-associated fibroblast (CAF)-related gene insulin-like growth factor binding protein-2 (IGFBP2) is highly expressed in gliomas and is associated with poor prognosis. CAF-related gene IGFBP2 promotes glioma progression by inducing polarization of M2 macrophages. This study provides a new basis for an in-depth investigation of the functional mechanisms of the glioma tumor microenvironment and the search for key genes involved in immune regulation in CAF.

Comparison of sex differences on outcomes after aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis.

OBJECTIVE: Sex differences in outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. Therefore, the aim of this study was to investigate the sex differences in the prognosis of patients with aSAH. METHODS: This study retrospectively analyzed the clinical data of aSAH patients admitted to the Department of Neurosurgery of General Hospital of Northern Theater Command, from April 2020 to January 2022. The modified Rankin Scale (mRS) was used to evaluate outcomes at 3-month post-discharge. Baseline characteristics, in-hospital complications and outcomes were compared after 1:1 propensity score matching (PSM). RESULTS: A total of 665 patients were included and the majority (63.8%) were female. Female patients were significantly older than male patients (59.3 ± 10.9 years vs. 55.1 ± 10.9 years, P < 0.001). After PSM, 141 male and 141 female patients were compared. Comparing postoperative complications and mRS scores, the incidence of delayed cerebral ischemia (DCI) and hydrocephalus and mRS ≥ 2 at 3-month were significantly higher in female patients than in male patients. After adjustment, the analysis of risk factors for unfavorable prognosis at 3-month showed that age, sex, smoking, high Hunt Hess grade, high mFisher score, DCI, and hydrocephalus were independent risk factors. CONCLUSION: Female patients with aSAH have a worse prognosis than male patients, and this difference may be because females are more vulnerable to DCI and hydrocephalus.

MicroRNA-124 conducts neuroprotective effect via inhibiting AK4/ATF3 after subarachnoid hemorrhage.

Spontaneous subarachnoid hemorrhage (SAH) accounts for approximately 5% of all cases of stroke. SAH is correlated with elevated rates of mortality and disability. Despite significant advancements in comprehending the pathogenesis and surgical management, efficacious clinical interventions remain restricted, and the prognosis is yet to be enhanced. MicroRNAs play a crucial role in various pathological processes in organisms. Revealing these regulatory processes is conducive to the development of new treatment methods. MicroRNA-124 is highly expressed in the nervous system and has significant research value for SAH. This study aims to explore the role of miR-124 in the early post-SAH period on neural function and verify whether it is involved in the pathological and physiological processes of SAH. In this study, we used methods such as comparing the expression levels of miR-124 in cerebrospinal fluid, establishing a rat SAH model, and a mouse embryonic primary neuron hemoglobin stimulation model to verify the downstream proteins of miR-124 in SAH. Through transfection techniques, we adjusted the expression of this small RNA in Vitro and in Vivo models using miR-124 inhibitor and mimic in the primary neuron hemoglobin stimulation model and rat SAH model, and observed the phenotype. Finally, by consulting the literature and verifying in Vivo and in Vitro methods, AK4 and downstream molecule ATF3 were identified as downstream targets of miR-124.

Association between serum apolipoprotein E and cognitive function in Chinese patients with temporal lobe epilepsy.

OBJECTIVE: To investigate the effect of serum apolipoprotein E (APOE) levels on cognitive function in patients with temporal lobe epilepsy (TLE). METHODS: Clinical data were collected from 190 subjects including 110 TLE patients and 80 healthy people. Cognitive function was assessed using the Addenbrooke's Cognitive Examination Revised (ACE-R) scale. Serum levels of APOE were measured using ELISA kits. Genotyping of APOE in peripheral blood was detected by microarray hybridization. RESULTS: Patients with TLE had significantly lower ACE-R total score, memory and verbal fluency scores compared to the healthy group. Serum levels of APOE were significantly higher in TLE patients than in the healthy subjects. Serum APOE levels were significantly negatively correlated with ACE-R total score, memory and verbal fluency scores. The cognitive function score of TLE with APOE ε4 allele was lower than that of TLE without APOE ε4 allele. SIGNIFICANCE: Our study showed that serum APOE levels were higher in TLE patients than in the healthy population. And serum APOE levels were associated with cognitive dysfunction in TLE patients. APOE ε4 allele carriers have poor cognitive function in TLE patients.

The Necessity or Not of Additional Endovascular Therapy to Medical Therapy for Symptomatic Intracranial Artery Stenosis: Insights from 30-Day and 1-Year Results.

BACKGROUND: The optimal treatment between endovascular therapy and medical treatment for symptomatic intracranial artery stenosis is still unclear. This study aimed to compare the safety and efficacy of 2 treatments based on the results from currently published randomized controlled trials (RCTs). METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science were used for searching the RCTs evaluating the addition of endovascular therapy to medical therapy for treating symptomatic intracranial artery stenosis from the inception of these databases to September 30, 2022. P < 0.05 was considered statistically significant. All analyses were performed using STATA version 12.0. RESULTS: A total of 4 RCTs were involved in the current study, including 989 participants. In the 30-day results, the data showed that compared with the medical therapy alone group, the additional endovascular therapy group was associated with a higher risk of death or stroke (relative risk (RR): 2.857; 95% confidence interval (CI): 1.756-4.648; P < 0.001), ipsilateral stroke (RR: 3.525; 95% CI: 1.969-6.310; P < 0.001), death (risk differences (RD): 0.01; 95% CI: 0.004-0.03; P = 0.015), hemorrhagic stroke (RD: 0.03; 95% CI: 0.01-0.06; P < 0.001), and ischemic stroke (RR: 2.221; 95% CI: 1.279-3.858; P = 0.005). In the 1-year results, the additional endovascular therapy group was related to a greater incidence of ipsilateral stroke (RR, 2.247; 95% CI, 1.492-3.383; P < 0.001) and ischemic stroke (RR: 2.092; 95% CI: 1.270-3.445; P = 0.004). CONCLUSIONS: Given that the medical treatment alone was related to a lower risk of stroke and death in the short-term and long-term compared with endovascular therapy combined with medical therapy. Based on this evidence, these findings do not support the addition of endovascular therapy to medical therapy for treating patients with symptomatic intracranial stenosis.

Construction and verification of risk predicting models to evaluate the possibility of hydrocephalus following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Hydrocephalus following a ruptured aneurysm portends a poor prognosis. The authors aimed to establish a nomogram to predict the risk of hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A total of 421 patients with aSAH who were diagnosed by digital subtraction angiography in The General Hospital of Northern Theater Command center from January 2020 to June 2021 were screened to establish the training cohort. An additional 135 patients who enrolled between July 2021 and May 2022 were used for the validation cohort. Variate difference analysis and stepwise logistic regression (model A) and univariate and multivariate logistic regressions (model B) were respectively used to construct two models. Then, the net reclassification improvement (NRI), integrated discrimination improvement (IDI), and receiver operating characteristic (ROC) curve were used to compare the predictive abilities of the two models. Finally, two nomograms were constructed and externally validated. RESULTS: After screening, 556 patients were included. The area under the ROC curve of models A and B in the training cohort were respectively 0.884 (95 % confidence interval [CI]: 0.847-0.921) and 0.834 (95 % CI: 0.787-0.881). The prediction ability of the model A was superior to model B (NRI > 0, IDI > 0, p < 0.05). The C-index of models A and B was 0.8835 and 0.8392, respectively. Regarding clinical usefulness, the two models offered a net benefit with a threshold probability of between 0.12 and 1 in the decision curve analysis, suggesting that the two models can accurately predict hydrocephalus events. CONCLUSIONS: Both models have good prediction accuracy. Compared with model B, model A has better discrimination and calibration. Further, the easy-to-use nomogram can help neurosurgeons to make rapid clinical decisions and apply early treatment measures in high-risk groups, which ultimately benefits patients.

Long non-coding RNA MIR17HG impedes FOSL2-mediated transcription activation of HIC1 to maintain a pro-inflammatory phenotype of microglia during intracerebral haemorrhage.

Activation and polarization of microglia play decisive roles in the progression of intracerebral haemorrhage (ICH), and lactate exposure correlates with microglia polarization. This study explores molecules influencing lactate production and microglia phenotype alteration following ICH. A murine model of ICH was induced by intracerebral injection of collagenase. The mice experienced autonomous neurological function recovery, haematoma resolution and rapid lactate production, along with a gradual increase in angiogenesis activity, neuronal recovery and an M1-to-M2 phenotype change of microglia. Galloflavin, a lactate dehydrogenase antagonist, suppressed this phenotype change and the functional recovery in mice. FOS like 2 (FOSL2) was significantly upregulated in the brain tissues from day 7 post-ICH. Overexpression of FOSL2 induced an M1-to-M2 phenotype shift in microglia and accelerated lactate production in vivo and in haemoglobin-treated microglia in vitro. Long non-coding RNA MIR17HG impeded FOSL2-mediated transcription activation of hypermethylated in cancer 1 (HIC1). MIR17HG overexpression induced pro-inflammatory activation of microglia in mice, which was blocked by further HIC1 overexpression. Overall, this study demonstrates that MIR17HG maintains a pro-inflammatory phenotype of microglia during ICH progression by negating FOSL2-mediated transcription activation of HIC1. Specific inhibition of MIR17HG or upregulation of FOSL2 or HIC1 may favour inflammation inhibition and haematoma resolution in ICH.

Replacement of long-segment ureteral defect with tapered demucosalized ileum: medium-term outcomes of 4 patients.

PURPOSE: Repair of long-segment ureteral defect (LSUD) is challenging. Currently available procedures carry some potential complications. We modified the ileal graft by tapering the wall and stripping the mucosa to combat associated pitfalls and first reported the medium-term outcomes of 4 patients. MATERIAL AND METHODS: From September 2019 to October 2020, tapered demucosalized ileum (TDI) was used for LSUD reconstruction in 4 patients on the right (2 males and 2 females). Two patients were with panureteral avulsion and 2 with high-risk urothelial carcinoma in the distal ureter. TDI was made by tapering 1/2-2/3 of the antimesenteric ileal wall and stripping the mucosa with a blunt/blunt operating scissor. Follow-up modalities included serum creatinine, electrolytes, ultrasonography, CT urogram, renal scintigraphy, and ureteroscopy. RESULTS: Mean operation time was 443 min (range 360-550) and blood loss was negligible. The mean follow-up period was 29 months (range 23-36). Vesicoureteral reflux and related pyelonephritis occurred in 1 patient, necessitating a repair operation (Clavien-Dindo grade IIIb). No strictures, obstructions, metabolic disorders, or electrolyte imbalances were observed in the remaining patients. In carcinoma patients, ureteroscopy in month 18 post-operation revealed ileal mucosal regrowth in the form of dwarf isolated islands. All renal units maintained adequate drainage and function during the follow-up. CONCLUSIONS: Ileal wall tapering and mucosa stripping confined to the muscularis mucosae level will not result in shrinkage, fibrosis, or stricture formation of the ileal ureter. The present work provides evidence for further application of TDI in the replacement of LSUD in patients.

Significance of methylation-related genes in diagnosis and subtype classification of renal interstitial fibrosis.

BACKGROUND: RNA methylation modifications, such as N1-methyladenosine/N6-methyladenosine /N5-methylcytosine (m1A/m6A/m5C), are the most common RNA modifications and are crucial for a number of biological processes. Nonetheless, the role of RNA methylation modifications of m1A/m6A/m5C in the pathogenesis of renal interstitial fibrosis (RIF) remains incompletely understood. METHODS: Firstly, we downloaded 2 expression datasets from the GEO database, namely GSE22459 and GSE76882. In a differential analysis of these datasets between patients with and without RIF, we selected 33 methylation-related genes (MRGs). We then applied a PPI network, LASSO analysis, SVM-RFE algorithm, and RF algorithm to identify key MRGs. RESULTS: We eventually obtained five candidate MRGs (WTAP, ALKBH5, YTHDF2, RBMX, and ELAVL1) to forecast the risk of RIF. We created a nomogram model derived from five key MRGs, which revealed that the nomogram model may be advantageous to patients. Based on the selected five significant MRGs, patients with RIF were classified into two MRG patterns using consensus clustering, and the correlation between the five MRGs, the two MRG patterns, and the genetic pattern with immune cell infiltration was shown. Moreover, we conducted GO and KEGG analyses on 768 DEGs between MRG clusters A and B to look into their different involvement in RIF. To measure the MRG patterns, a PCA algorithm was developed to determine MRG scores for each sample. The MRG scores of the patients in cluster B were higher than those in cluster A. CONCLUSIONS: Ultimately, we concluded that cluster A in the two MRG patterns identified on these five key m1A/m6A/m5C regulators may be associated with RIF.

Endovascular Treatment Failure of Renal Arteriovenous Malformation due to an Extrarenal Feeding Artery: A Case Report.

Renal arteriovenous malformation (RAVM) is a rare pathology. It may present with heamturia, hypertension, and congestive heart failure. Digital subtraction angiography (DSA) is the standard diagnostic choice, and endovascular embolization is a preferred procedure of management in most cases. The feeding branches of RAVM are reported to originate from renal arteries. In this report, a 43-year-old female with recurrent massive hematuria and left flank pain was described. Renal angiography revealed double renal arteries supplying the left kidney and multiple renal arteriovenous fistula formation around the renal pelvis. Embolization with coils and gelfoam was performed after which her hematuria subsided. One month later, the patient was readmitted to our hospital due to the relapse of massive hematuria following heavy physical activities. DSA found another feeding artery of the RAVM originating from the aorta around the 4th lumbar vertebra. After embolization of this arterial feeder, hematuria settled. There was no recurrence during a 10-month follow-up. To our knowledge, this is the first case of RAVM with an extrarenal feeding artery, and omission of this scenario can lead to treatment failure.

Randomized, prospective, multicenter trial assessing the numen coil embolization system in the endovascular treatment of small intracranial aneurysms: outcomes from the CATCH Trial.

BACKGROUND AND PURPOSE: The CATCH (Coil Application Trial in China) trial was designed to assess the safety and efficacy of the Numen Coil Embolization System in the treatment of intracranial aneurysms in comparison with the Axium coil (ev3/Medtronic). Although the endovascular treatment of small (< 5 mm) intracranial aneurysms has been reported with favorable long-term clinical and angiographic outcomes, randomized trials are still lacking. Data for aneurysms smaller than 5 mm were extracted from the CATCH trial. MATERIALS AND METHODS: A randomized, prospective, multicenter trial was conducted at ten centers throughout China. Enrolled subjects with small intracranial aneurysms were randomly assigned to receive treatment with the Numen Coil or the Axium coil. The primary outcome was successful aneurysm occlusion at the 6-month follow-up. In contrast, the secondary outcomes included complete aneurysm occlusion, recurrence rate, clinical deterioration, and safety data at the 6-month and 12-month follow-ups. RESULTS: A total of 124 patients were enrolled in the study. Overall, 58 patients were assigned to the Numen group, and 66 were assigned to the Axium group. At the 6-month follow-up, the successful aneurysm occlusion rate was 93.1% (54/58) in the MicroPort NeuroTech group and 97.0% (64/66) in the Axium group, with a common odds ratio of 0.208 (95% confidence interval, 0.023-1.914; P = 0.184). Complications were comparable between the groups. CONCLUSIONS: Compared with the Aixum coil, the Numen coil is safe and effective in treating small intracranial aneurysms. TRIAL REGISTRATION: (13/12/2016, NCT02990156).

Hem-o-Lok clip migration into renal pelvis and stone formation as a long-term complication following laparoscopic pyelolithotomy: a case report and literature review.

BACKGROUND: Hem-o-Lok clips (HOLCs) are widely used in minimal access urological operations due to the advantage of vascular control and suture stabilization. In rare cases, however, they can develop problems themselves. Migration of HOLCs into the collecting system is a fairly rare complication after laparoscopic pyelolithotomy. To date, only two cases were reported in the literature. CASE PRESENTATION: This article describes a case of 51-year-old man with a complaint of left flank pain. He had a medical history of ipsilateral retroperitoneal laparoscopic pyelolithotomy at another hospital 8 years ago. Non-contrast CT scan demonstrated a renal stone in the left ureteropelvic junction complicated by mild hydronephrosis. A straight foreign body was found near the renal pelvis, with part of it wedging into renal pelvic wall. A percutaneous nephrolithotomy (PNL) was performed for this patient. After some fragmentation, a HOLC was found in the kernel of the stone. With an alligator plier, the clip was totally removed out of the collecting system. The postoperative period and follow-up were uneventful. CONCLUSIONS: HOLC migration into renal pelvis is a rare complication following laparoscopic pyelolithotomy. It could act as nidus for stone formation under extended exposure to urine. Using HOLCs to stabilize the anastomotic suture near renal pelvis should be avoided to prevent this complication. Instead, knotting is a better choice under such condition. The secondary calculi and dislodged HOLCs can be removed through PNL by an alligator plier after laser lithotripsy.

Current status and outlook of potential applications of biodegradable materials in cerebral vascular stents.

The treatment of intracranial aneurysms (IAs) has undergone a very significant transformation in recent decades, and endovascular interventions have gradually become one of the most common treatments. As permanent metal stents can cause some degree of long-term damage to patients, biodegradable stent materials are emerging as attractive potential alternatives. By reviewing the current research status and the advantages and disadvantages of existing biodegradable biomaterials, this review expects to provide a valuable reference for subsequent research on biodegradable biomaterials.

Hyperdense middle cerebral artery sign predicts favorable outcome after decompressive craniectomy in patients with malignant middle cerebral artery infarction.

BACKGROUND: Malignant middle cerebral artery infarction (MMI) is a life-threatening cerebral vascular event. Early decompressive craniectomy (DC) has proven to be an effective treatment strategy. However, the ideal candidate for DC continues to be debated. PURPOSE: To investigate whether a hyperdense middle cerebral artery sign (HMCAS) provides prognostic value after DC in patients with MMI. MATERIAL AND METHODS: We reviewed clinical information and radiological parameters on computed tomography of 42 patients with MMI who underwent DC. Functional outcome was assessed according to the modified Rankin scale (mRS) at three months as follows: favorable outcome (mRS ≤ 4) versus unfavorable outcome (mRS > 4). Logistic regression analysis was used to identify predictors of functional outcome after DC in patients with MMI. RESULTS: Age (odds ratio [OR] = 0.87; 95% confidence interval [CI] = 0.78-0.97; P = 0.014) and HMCAS (OR = 7.40; 95% CI = 1.35-40.48; P = 0.021) were associated with functional outcome. The area under the receiver operating characteristic curve for predicting favorable outcome using the combination of age and HMCAS was 0.882, and the sensitivity and specificity were 0.947 and 0.696, respectively. CONCLUSION: Patients with MMI with HMCAS, as well as younger patients, often showed a favorable outcome after DC in this study.

Oleanolic acid reduces oxidative stress and neuronal apoptosis after experimental subarachnoid hemorrhage by regulating Nrf2/HO-1 pathway.

Oxidative stress is an early major pathological feature after subarachnoid hemorrhage (SAH) and involves in the development of acute brain injury, neuronal apoptosis and cerebral vasospasm following SAH. Antioxidant stress is an effective way to improve the prognosis of SAH. Oleanolic acid is a widely used triterpenoid from plants, which has strong antioxidant activities, hepatoprotective, anti-inflammatory and anti-cancer activities. However, whether oleanolic acid exerts its anti-oxidant effect after SAH and the underlying mechanisms involved in it is unclear. In current study, the SAH model was established on Sprague Dawley rats using a standard intravascular puncture model. We found OA treatment significantly reduced malondialdehyde levels, and increased the levels of superoxide dismutase, catalase and GSH-Px after SAH, and reduced many EBI-related indicators, including brain edema, BBB disruption, SAH grades, and neurological score. In addition, the activation of Nrf2/HO-1 pathway after SAH was also detected. And by using Nrf2 siRNA intracerebroventricular injections, apoptosis related factors downstream of Nrf2/HO-1 pathway were detected. By TUNEL staining, OA treatment obviously reduced neuronal apoptosis. Therefore, we suggest that OA could alleviate oxidative stress and reduce neuronal apoptosis through activating Nrf 2/HO-1 pathway.

[Progress in the studies of circular RNA in prostate cancer].

Prostate cancer (PCa) has become one of the most common malignancies in men, and its incidence is increasing year by year in China. When PCa develops into castration-resistant PCa (CRPC), it deteriorates rapidly. So, it is important to find more sensitive molecular markers and effective therapeutic targets for the diagnosis and treatment of the malignancy. Circular RNA (circRNA) is a covalently closed loop non-coding RNA formed by reverse splicing, playing an important regulatory role in a variety of tumors. In recent years, many studies show that circRNA is involved in the regulation of PCa as miRNA sponge, binding with the RNA binding protein and other molecular sponges, and may be a potential molecular marker and therapeutic target for PCa. This review summarizes the advances in recent studies of circRNA in the development and progression of PCa, CRPC, and radiation-resistant PCa.

EPDR1 is related to stages and metastasize in bladder cancer and can be used as a prognostic biomarker.

BACKGROUND: Bladder cancer (BLCA) is a malignant urothelial carcinoma and has a high mortality rate. EPDR1 (ependymin related 1) is a type II transmembrane protein and related to calcium-dependent cell adhesion. METHODS: We explored the potential oncogenic roles of EPDR1 in BLCA basing on the multiple public datasets. RESULTS: We found that EPDR1 expression had a significant difference in BLCA and adjacent normal bladder tissues, and the level of EPDR1was up-regulated with advanced tumor stage and metastasis in BLCA. Meanwhile, the high expression group of EPDR1 had a shorter OS compared to the low or medium expression-group. Furthermore, EPDR1 expression was associated with tumor-infiltrating immune cells (TIICs), including NK cells, CD8 + T cells, CD4 + T cells, Macrophages cells, and so on. Moreover, EPDR1 also involved in several signaling pathways as well as PI3K/AKT pathway, Cytokine receptor interaction, and apoptosis. CONCLUSION: EPDR1 can be used as a novel prognostic biomarker as well as an effective target for diagnosis and treatment in BLCA.

Cyclophilin a signaling induces pericyte-associated blood-brain barrier disruption after subarachnoid hemorrhage.

OBJECTIVE: The potential roles and mechanisms of pericytes in maintaining blood-brain barrier (BBB) integrity, which would be helpful for the development of therapeutic strategies for subarachnoid hemorrhage (SAH), remain unclear. We sought to provide evidence on the potential role of pericytes in BBB disruption and possible involvement and mechanism of CypA signaling in both cultured pericytes and SAH models. METHODS: Three hundred fifty-three adult male C57B6J mice weighing 22 to 30 g, 29 CypA-/- mice, 30 CypA+/+ (flox/flox) mice, and 30 male neonatal C57B6J mice were used to investigate the time course of CypA expression in pericytes after SAH, the intrinsic function and mechanism of CypA in pericytes, and whether the known receptor CD147 mediates these effects. RESULTS: Our data demonstrated both intracellular CypA and CypA secretion increased after SAH and could activate CD147 receptor and downstream NF-κB pathway to induce MMP9 expression and proteolytic functions for degradation of endothelium tight junction proteins and basal membranes. CypA served as autocrine or paracrine ligand for its receptor, CD147. Although CypA could be endocytosed by pericytes, specific endocytosis inhibitor chlorpromazine did not have any effect on MMP9 activation. However, specific knockdown of CD147 could reverse the harmful effects of CypA expression in pericytes on the BBB integrity after SAH. CONCLUSIONS: This study demonstrated for the first time that CypA mediated the harmful effects of pericytes on BBB disruption after SAH, which potentially mediated by CD147/NF-κB/MMP9 signal, and junction protein degradation in the brain. By targeting CypA and pericytes, this study may provide new insights on the management of SAH patients.

Long Noncoding RNA NEAT1 Suppresses Proliferation and Promotes Apoptosis of Glioma Cells Via Downregulating MiR-92b.

BACKGROUND: The mechanisms underlying the proliferation and apoptosis of glioma cells remain unelucidated. A recent study has revealed that microRNA-92b (miR-92b) inhibits apoptosis of glioma cells via downregulating DKK3. Notably, long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) is predicted to have a possible interaction with miR-92b. OBJECTIVE: This study aimed to identify whether NEAT1 affects glioma cell proliferation and apoptosis via regulating miR-92b. METHODS: The expression of NEAT1 was compared between glioma tissues and adjacent tissues as well as between glioma cells and normal astrocytes using quantitative real-time polymerase chain reaction. Glioma cell proliferation was determined by using the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and glioma cell apoptosis was determined by using the flow cytometry. RESULTS: The expression of NEAT1 was low in glioma tissues and cells compared to the normal ones. Overexpression of NEAT1 inhibited proliferation and promoted apoptosis of glioma cell lines (U-87 MG and U251). The interaction between NEAT1 and miR-92b was confirmed using RNA immunoprecipitation, RNA pull-down assay, and luciferase reporter assay. Importantly, the tumor suppressor function of overexpressing NEAT1 was achieved by downregulating miR-92b and subsequently upregulating DKK3. CONCLUSION: Our findings indicated that NEAT1 acts as a tumor suppressor in glioma cells, which provides a novel target in overcoming glioma growth.

Soluble galectin 9 potently enhanced regulatory T-cell formation, a pathway impaired in patients with intracranial aneurysm.

Patients with intracranial aneurysm (IA) present a dysregulated immune system with lower frequency of regulatory T (Treg) cells. Here, we examined whether galectin 9 (Gal-9), the natural ligand of Tim-3, could promote Treg cells in IA patients. We first discovered that the intracellular and extracellular Gal-9 was primarily expressed by CD4+ CD25- T conventional (Tconv) cells, and also by monocytes at lower levels, but rarely by CD4+ CD25+ Treg cells. In IA patients, the Gal-9 expression was significantly lower than in healthy controls. CD4+ CD25- Tconv cells could be induced into Foxp3-expressing induced Treg (iTreg) cells using a TGF-ß-containing milieu. We found that soluble Gal-9 significantly enhanced this process by potently upregulating the expression of Foxp3, IL-10 and TGF-ß in a concentration-dependent manner. In addition, in the absence of additional Gal-9, the level of Foxp3 upregulation was directly correlated with the level of intrinsic Gal-9 expression. Notably, the strength of external Gal-9-mediated effects was significantly lower in IA patients than in healthy controls. Using a Tim-3 blocking antibody, we found that the promotion of iTreg development by soluble Gal-9 was dependent on the Tim-3 signalling pathway. Overall, our investigations demonstrated that Gal-9 presented a critical role in the development of iTreg cells. However, this mechanism was impaired in IA patients due to lower expression of both Gal-9 and Tim-3.