SLC7A11 promotes EMT and metastasis in invasive pituitary neuroendocrine tumors by activating the PI3K/AKT signaling pathway.

Invasive pituitary neuroendocrine tumors (PitNETs) are the most prevalent types of intracranial and neuroendocrine tumors. Their aggressive growth and difficulty in complete resection result in a high recurrence rate. Cystine transporter solute carrier family 7 member 11 (SLC7A11) is overexpressed in various cancers, which contributes to tumor growth, progression, and metastasis by promoting cystine uptake and glutathione biosynthesis. We identified SLC7A11 as an invasive biomarker based on three Gene Expression Omnibus cohorts. This study aimed to investigate the role of SLC7A11 in invasive PitNETs. Cell proliferation was assessed using CCK-8 and colony formation assays, while cell apoptosis was estimated with flow cytometry. Wound healing assays and transwell assays were utilized to evaluate migration and invasion ability. Our findings demonstrated that SLC7A11 was markedly upregulated in invasive PitNETs, and was associated with the invasiveness of PitNETs. Knockdown of SLC7A11 could largely suppress tumor cell proliferation, migration, and invasion, while inducing apoptosis. Furthermore, SLC7A11 depletion was implicated in regulating epithelial-mesenchymal transition and inactivating the PI3K/AKT signaling pathway. These insights suggest SLC7A11 as a potential therapeutic target for invasive PitNETs.

Investigation of cuproptosis regulator-mediated modification patterns and SLC30A7 function in GBM.

BACKGROUND: Copper-dependent controlled cell death (cuproptosis) is a novel cell death modality that is distinct from known cell death mechanisms. Nonetheless, the potential role of the cuproptosis regulator in tumour microenvironment (TME) of GBM remains unknown. METHODS: Based on 13 widely recognised cuproptosis regulators, the cuproptosis regulation patterns and the biological characteristics of each pattern were comprehensively assessed in GBMs. Machine learning strategies were used to construct a CupScore to quantify the cuproptosis regulation patterns of individual tumours. A PPI network was constructed to predict core-associated genes of cuproptosis regulators. The function of the novel cuproptosis regulators SLC30A7 was examined by in vitro and in vivo experiment. RESULTS: We identified three distinct cuproptosis regulation patterns, including immune activation, metabolic activation, and immunometabolic double deletion patterns. The CupScore was shown to predict the abundance of tumour inflammation, molecular subtype, stromal activity, gene variation, signalling pathways, and patient prognosis. The low CupScore subtype was characterised by immune activation, isocitrate dehydrogenase mutations, sensitivity to chemotherapy, and clinical benefits. The high CupScore subtype was characterised by activation of the stroma and metabolism and poor survival. Novel cuproptosis regulator SLC30A7 knockdown inhibited the cuproptosi via JAK2/STAT3/ATP7A pathway in GBM. CONCLUSION: Cuproptosis regulators have been shown to play a vital role in TME complexity. Constructing CupScores were trained to evaluate the regulation patterns of cuproptosis in individual tumours. The novel cuproptosis-related genes SLC30A7 was involved in regulation the tumorigenicity of GBM cell via JAK2/STAT3/ATP7A pathway in vitro and in vivo.

Primary pituitary stalk mucosa-associated lymphoid tissue lymphoma: a case report and literature review.

Background: Primary extranodal mucosa-associated lymphoid tissue (MALT) lymphoma in the sellar region is a rare indolent B-cell lymphoma. Case presentation: A newly diagnosed patient with MALT lymphoma originating from the pituitary stalk is reported. A space-occupying lesion in the sellar region was found in a 24 year-old man who had no clinical symptoms except for those relating to a sex hormone disorder (rising estrogen and falling androgen) identified during a pre-employment physical examination. MALT lymphoma was diagnosed pathologically. Radiotherapy and chemotherapy were proposed after surgery. However, the patient selected androgen replacement therapy only rather than chemoradiotherapy. Over the next 3 months, no visual disturbance, headache, cranial nerve abnormality, or other symptoms occurred. Conclusion: Primary sellar region MALT lymphoma is an extremely rare disease. The differential diagnosis of sellar and parasellar masses should include primary sellar region MALT lymphoma. Early detection and treatment of this lymphoma can effectively improve the prognosis.

LncRNA TSIX knockdown restores spinal cord injury repair through miR-30a/SOCS3 axis.

Spinal cord injury (SCI) is a serious injury to the central nervous system. Previous studies have discovered that the development of SCI is associated with gene expression. The purpose of this study was to explore the significance of lncRNA TSIX in SCI and its underlying mechanism involved. An in vivo SCI mice model and an in vitro hypoxia-treated HT22 cells model were applied in this study. TSIX and SOCS3 expression in SCI tissues was measured by qRT-PCR, western blot and FISH assay. LV-sh-TSIX was injected into SCI mice intrathecally or subjected to HT22 cells to access the consequent alteration in inflammation response, cell apoptosis and functional recovery through ELISA, immunohistochemistry, TUNEL, flow cytometry assays and BMS scores. Then, the underlying mechanism of TSIX was analyzed by bioinformatics analysis and then confirmed by RIP, RNA pull-down and dual-luciferase reporter assay. It was identified that TSIX was up-regulated in HT22 cells under hypoxia operation and spinal cord tissues of SCI mice. TSIX knockdown improved the lesion size and BMS score and inhibited inflammation and cell apoptosis. MiR-30a was identified as a target for TSIX and SOCS3, and TSIX binds to miR-30a by competing with SOCS3, thereby counteracting miR-30a-mediated SOCS3 inhibition. In addition, LV-sh-TSIX effects were significantly overturned by miR-30a inhibition or SOCS3 over-expression. Knockdown of TSIX improved functional recovery and attenuated the inflammation response and cell apoptosis via miR-30a/SOCS3 axis. These results may provide a potential novel insight for SCI treatment.

Assessing electrocardiogram changes after ischemic stroke with artificial intelligence.

OBJECTIVE: Ischemic stroke (IS) with subsequent cerebrocardiac syndrome (CCS) has a poor prognosis. We aimed to investigate electrocardiogram (ECG) changes after IS with artificial intelligence (AI). METHODS: We collected ECGs from a healthy population and patients with IS, and then analyzed participant demographics and ECG parameters to identify abnormal features in post-IS ECGs. Next, we trained the convolutional neural network (CNN), random forest (RF) and support vector machine (SVM) models to automatically detect the changes in the ECGs; Additionally, We compared the CNN scores of good prognosis (mRS ≤ 2) and poor prognosis (mRS > 2) to assess the prognostic value of CNN model. Finally, we used gradient class activation map (Grad-CAM) to localize the key abnormalities. RESULTS: Among the 3506 ECGs of the IS patients, 2764 ECGs (78.84%) led to an abnormal diagnosis. Then we divided ECGs in the primary cohort into three groups, normal ECGs (N-Ns), abnormal ECGs after the first ischemic stroke (A-ISs), and normal ECGs after the first ischemic stroke (N-ISs). Basic demographic and ECG parameter analyses showed that heart rate, QT interval, and P-R interval were significantly different between 673 N-ISs and 3546 N-Ns (p < 0.05). The CNN has the best performance among the three models in distinguishing A-ISs and N-Ns (AUC: 0.88, 95%CI = 0.86-0.90). The prediction scores of the A-ISs and N-ISs obtained from the all three models are statistically different from the N-Ns (p < 0.001). Futhermore, the CNN scores of the two groups (mRS > 2 and mRS ≤ 2) were significantly different (p < 0.05). Finally, Grad-CAM revealed that the V4 lead may harbor the highest probability of abnormality. CONCLUSION: Our study showed that a high proportion of post-IS ECGs harbored abnormal changes. Our CNN model can systematically assess anomalies in and prognosticate post-IS ECGs.

Evaluation of the Gross Total Resection Rate of Suprasellar Pituitary Macroadenomas with and without the Removal of the Tuberculum Sellae Bone.

OBJECTIVE: Improving the gross total resection (GTR) rate of suprasellar pituitary macroadenomas (SPMAs) using the pure endoscopic endonasal transsphenoidal approach (EETA) has been a long-standing focus of neurosurgeons. This study was aimed at evaluating the influences of the removal of the tuberculum sellae bone (TSB) without opening the dura of the tuberculum sellae on the GTR rate of SPMAs via the EETA. METHODS: We retrospectively analyzed medical reports of patients with SPMAs who underwent EETA between February 2015 and November 2020. Data on clinical manifestations, endocrinologic types, imaging features (Hardy classification, morphology, and texture), clinical outcomes, and TSB removal status were collected. All patients were followed up for 6 months postoperatively. RESULTS: Seventy-eight patients were enrolled in our study. The GTR rates of the TSB removal group (45/78, 57.7%) and nonremoval group (33/78, 42.3%) were 80.0% (36/45) and 57.6% (19/33), respectively. Univariate logistic regression analysis found that the removal of TSB, rounded morphology, and low Hardy classification were correlated with higher GTR rates. Multiple logistic regression analysis indicated that even after adjusting for tumor types and imaging features, the removal of TSB had an independent effect on the GTR rate (odds ratio, 7.6; 95% confidence interval, 1.8-31.6; P = 0.005). The incidence rates of postoperative cerebrospinal fluid leakage and diabetes insipidus were not significantly different between the TSB removal group and TSB nonremoval group. CONCLUSIONS: TSB removal using EETA without opening the tuberculum sellae dura improves the GTR rate of SPMAs without increasing the incidence of postoperative complications.

TUBA1C expression promotes proliferation by regulating the cell cycle and indicates poor prognosis in glioma.

Gliomas are the major type of primary brain tumors. Accumulating research has demonstrated that tubulin is connected with the development and malignant progression of tumors. TUBA1C is a subtype of α-tubulin and is linked to prognosis in multiple cancers. In this study, the prognosis-related gene TUBA1C in glioma was identified and analyzed by bioinformatic approaches such as Kaplan-Meier (KM) survival time analysis, univariate and multivariate Cox analysis, receiver operating characteristic (ROC) analysis and functional enrichment analysis. Based on the above analyses, we found that glioma tissues had significantly higher expression of TUBA1C than normal brain tissues, and high expression of TUBA1C has worse prognosis in glioma. Gene set enrichment analysis (GSEA) revealed the signaling pathways related to the cell cycle. Furthermore, knockdown of TUBA1C also inhibited proliferation and migration and caused apoptosis and G2/M phase arrest in glioma cells. This study demonstrated that high TUBA1C expression correlated with poor outcomes in glioma patients and that knocking down TUBA1C suppressed glioma cell proliferation via cell cycle arrest. In addition, TUBA1C might be a therapeutic biomarker for gliomas.

Sepiapterin reductase: Characteristics and role in diseases.

Sepiapterin reductase, a homodimer composed of two subunits, plays an important role in the biosynthesis of tetrahydrobiopterin. Furthermore, sepiapterin reductase exhibits a wide distribution in different tissues and is associated with many diseases, including brain dysfunction, chronic pain, cardiovascular disease and cancer. With regard to drugs targeting sepiapterin reductase, many compounds have been identified and provide potential methods to treat various diseases. However, the underlying mechanism of sepiapterin reductase in many biological processes is unclear. Therefore, this article summarized the structure, distribution and function of sepiapterin reductase, as well as the relationship between sepiapterin reductase and different diseases, with the aim of finding evidence to guide further studies on the molecular mechanisms and the potential clinical value of sepiapterin reductase. In particular, the different effects induced by the depletion of sepiapterin reductase or the inhibition of the enzyme suggest that the non-enzymatic activity of sepiapterin reductase could function in certain biological processes, which also provides a possible direction for sepiapterin reductase research.

Intravenous administration of human amniotic mesenchymal stem cells improves outcomes in rats with acute traumatic spinal cord injury.

We previously reported that intraspinal transplantation of human amniotic mesenchymal stem cells (hAMSCs) promotes functional recovery in a rat model of acute traumatic spinal cord injury (SCI). However, whether intravenous transplantation of hAMSCs also has therapeutic benefit remains uncertain. In this study, we assessed whether intravenous transplantation of hAMSCs improves outcomes in rats with acute traumatic SCI. In addition, the potential mechanisms underlying the possible benefits of this therapy were investigated. Adult female Sprague-Dawley rats were subjected to SCI using a weight drop device, and then hAMSCs or PBS were administered after 2 h via the tail vein. Our results indicated that transplanted hAMSCs could migrate to injured spinal cord lesion. Compared with the control group, hAMSCs transplantation significantly decreased the numbers of ED1 macrophages/microglia and caspase-3 cells, and reduced levels of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6 and IL-1ß. In addition, hAMSCs transplantation significantly attenuated Evans blue extravasation, promoted angiogenesis and axonal regeneration. hAMSCs transplantation also significantly improved functional recovery. These results suggest that intravenous administration of hAMSCs provides neuroprotective effects in rats after acute SCI, and could be an alternative therapeutic approach for the treatment of acute SCI.

A mobile hemangioblastoma of the cauda equina: Case report and review of the literature.

Context: Cases of migratory spinal tumors have been reported since 1963. Most involve spinal schwannomas, which are benign tumors of the lining of nerve cells. We report a rare case of a mobile spinal hemangioblastoma, which is a type of benign vascular tumor. Findings: A 50-year-old man visited the hospital for painful swelling in his lower back. An MRI scan indicated that a lesion was at the L5 vertebral level. Two weeks later, however, an enhanced MRI showed that the lesion had migrated to the L4 vertebral level. During surgery, the location of the lesion remained consistent with the enhanced MRI reviewed. The histopathological diagnosis was hemangioblastoma. Conclusion: This is the first known report of a mobile spinal hemangioblastoma. Mobile spinal hemangioblastoma requires careful preoperative and intraoperative evaluation of its real-time location to avoid performing surgery at the wrong vertebral level.

Postoperative Cervical Sagittal Realignment Improves Patient-Reported Outcomes in Chronic Atlantoaxial Anterior Dislocation.

BACKGROUND: Chronic atlantoaxial anterior dislocation (AAD) not only results in myelopathy, but dislocation-related kyphosis also results in cervical malalignment, which permanently affects neck function and patient-reported outcomes (PROs). OBJECTIVE: To investigate the effect of kyphotic correction on realigning cervical spine and independent cervical alignment parameters, which may be correlated with an improvement of PROs. METHODS: The study included 21 patients with chronic AAD-related kyphosis who underwent C1-2 reduction and correction surgery. Radiographic parameters were measured to assess cervical realignment preoperatively and postoperatively. Neck disability index (NDI), short form 12 physical component summary (SF-12 PCS), and Japanese Orthopaedic Association (JOA) scores were recorded to reveal changes in PROs. The independent parameters correlated with the improvements of PROs were analyzed. RESULTS: Of the radiographic parameters, the C1-2 Cobb angle, the C2-7 Cobb angle, thoracic inlet angle, cervical tilt, and T1 slope were significantly changed from -4.0° ± 16.2°, -29.2° ± 11.2°, 73.1° ± 13.3°, 30.4° ± 8.5°, and 29.1° ± 8.8° preoperatively to -13.5° ± 8.1° (P = .005), -18.0° ± 12.0° (P < .001), 67.1° ± 11.6° (P = .042), 23.1° ± 10.3° (P = .007), and 24.0° ± 7.0° (P = .011) at last follow-up, respectively. NDI, JOA, and SF-12 PCS scores were significantly improved postoperatively. The C1-2 Cobb angle was an independent parameter correlated with the improvements in SF-12 PCS, NDI, and JOA scores. CONCLUSION: Correction and reduction surgery can realign cervical spine in chronic AAD patients. The C1-2 Cobb angle was an independent parameter correlated with the improvements of PROs.

Long noncoding RNA activated by TGF-ß in human cancers: A meta-analysis.

BACKGROUND: Because long non-coding RNA ATB (activated by TGF-ß) is dysregulated in many cancers, we performed a meta-analysis to determine its prognostic potential in malignant tumors. METHODS: We searched electronic databases, including PubMed, Medline, OVID, Cochrane Library and Web of Science from inception until November 15, 2016 and identified eight studies with 818 cancer patients for the meta-analysis. We analyzed the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the relationship between lncRNA-ATB expression and overall survival (OS), recurrence -free survival (RFS), disease-free survival (DFS). We also use RevMan5.3 software to calculate odds ratio (ORs) to assess the association between lncRNA-ATB expression and pathological parameters including lymph node metastasis (LNM), distant metastasis (DM) and tumor stage. RESULTS: Our analysis showed that increased lncRNA-ATB expression was associated with OS (HR=2.82, 95% CI:1.98-4.00, P<0.00001), DFS (HR=2.75, 95% CI:1.73-4.38, P<0.0001), RFS(HR=3.96, 95% CI:2.30-6.81, P<0.00001), LNM (OR=4.07, 95% CI 1.74-9.53, P=0.001), DM (OR=3.21, 95% CI 1.06-9.72, P=0.04) and high tumor stage (OR=2.81, 95% 1.78-4.43, P<0.0001) in patients with other types of cancers that excluded pancreatic cancer. CONCLUSIONS: Meta-analysis demonstrated that increased lncRNA-ATB expression can be a useful prognostic biomarker in human cancer.

Over-expression of LRIG1 suppresses biological function of pituitary adenoma via attenuation of PI3K/AKT and Ras/Raf/ERK pathways in vivo and in vitro.

Pituitary adenomas (PAs) are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. ErbB receptors family signaling pathway regulates the expression of PAs activation associated gene. Inhibition of epidermal growth factor receptor (EGFR) can inhibit proliferation of PAs. Leucine-rich repeats and immunoglobulin-like domains protein 1 ( LRIG1), a negative mediated gene of ErbB receptors family, plays a role in many tumors. However, there are seldom researches about the functional role of LRIG1 in PAs. The aim of this study is to explore the potential effect of LRIG1 and its regulating mechanism in PAs. First, we investigated the role of LRIG1 in cell migration, invasion of PAs with transfected LRIG1 or control. Then, we explored its impact on cell proliferation and apoptosis of PAs in vivo. To study the regulating mechanism of LRIG1, we examined the expression of molecular factor of PI3K/AKT and Ras/Raf/ERK pathway using Western blotting in vitro and RT-PCR in vitro and in vivo. It was found that LRIG1 over-expression inhibited cell migration, invasion and proliferation, and promoted apoptosis of PAs in vivo and in vitro. Furthermore, LRIG1 suppressed the expression of signaling of PI3K/AKT and Ras/Raf/ERK pathways in PAs. LRIG1, as a negative mediated gene of tumor, can inhibit biological function of PAs via inhibiting PI3K/AKT and Ras/Raf/ERK pathways, and it might be a new target for gene therapy of PAs.

Annexin A5 promotes invasion and chemoresistance to temozolomide in glioblastoma multiforme cells.

Glioblastoma multiforme (GBM) is the prevalent and most fatal brain tumor in adults. Invasion and a high rate of recurrence largely contribute to the poor prognosis of GBM. The current standard therapy for GBM includes surgery with maximum feasible resection, radiotherapy, and treatment with chemotherapeutic agent temozolomide. Annexin A5 reportedly promotes progression and chemoresistance in a variety of cancers. In the present study, we explored the effects of annexin A5 on GBM cell invasion and chemoresistance to temozolomide. Stable overexpression and knockdown of annexin A5 were performed in both U-87 MG and U-118 MG human GBM cell lines. Overexpression of annexin A5 in both cell lines significantly increased cell invasion, matrix metalloproteinase-2 (MMP-2) expression/activity, Akt phosphorylation at serine 473, and the half maximal inhibitory concentration (IC50) values of temozolomide and markedly decreased temozolomide-induced apoptosis, all of which were abolished by selective PI3K inhibitor BKM120. On the other hand, knockdown of annexin A5 markedly decreased cell invasion, MMP-2 expression/activity, Akt phosphorylation at serine 473, and the IC50 values of temozolomide and significantly increased temozolomide-induced apoptosis. In conclusion, our study provides the first evidence that annexin A5 promotes GBM cell invasion, MMP-2 expression/activity, and chemoresistance to temozolomide through a PI3K-dependent mechanism. It adds new insights not only into the biological function of annexin A5 but also into the molecular mechanisms underlying GBM progression and chemoresistance.

[Effects of nitric oxide synthase inhibitor on dentate gyrus neurogenesis after diffuse brain injury in adult rats].

OBJECTIVE: To investigate the effects of selective nitric oxide synthase (NOS) inhibitors on dentate gyrus (DG) neurogenesis after diffuse brain injury (DBI) in adult rats. METHODS: DBI models were established in adult male SD rats, followed by systemic bromodeoxyuridine (BrdU) labeling of the dividing cells and immunohistochemical assay of the proliferation rates of neural precursor cells in the DG for comparison between NOS inhibitor (7-nitroindazole and Aminoguanidine) groups and the corresponding control groups at various time points after DBI. RESULTS: Intraperitoneal administration of 7-nitroindazole significantly reduced the number of BrdU-labeled cells in the DG of adult rats 2, 4 and 6 d after DBI (P<0.05). Aminoguanidine also significantly inhibited the proliferation of neural precursor cells in the DG induced by DBI at various time points (P<0.01). CONCLUSIONS: The activation of NOS after DBI may be an important regulatory factor for DG neurogenesis in adult rats, and NO generated by nNOS is probably involved mainly in the early stage of enhanced neurogenesis after DBI, while the NO from iNOS might participated primarily in the later stages.