Anti-sulfatide antibody-related Guillain-Barré syndrome presenting with overlapping syndromes or severe pyramidal tract damage: a case report and literature review.

Introduction: Anti-sulfatide antibodies are key biomarkers for the diagnosis of Guillain-Barré syndrome (GBS). However, case reports on anti-sulfatide antibody-related GBS are rare, particularly for atypical cases. Case description case 1: A 63 years-old man presented with limb numbness and diplopia persisting for 2 weeks, with marked deterioration over the previous 4 days. His medical history included cerebral infarction, diabetes, and coronary atherosclerotic cardiomyopathy. Physical examination revealed limited movement in his left eye and diminished sensation in his extremities. Initial treatments included antiplatelet agents, cholesterol-lowering drugs, hypoglycemic agents, and medications to improve cerebral circulation. Despite this, his condition worsened, resulting in bilateral facial paralysis, delirium, ataxia, and decreased lower limb muscle strength. Treatment with intravenous high-dose immunoglobulin and dexamethasone resulted in gradual improvement. A 1 month follow-up revealed significant neurological sequelae. Case description case 2: A 53 years-old woman was admitted for adenomyosis and subsequently experienced sudden limb weakness, numbness, and pain that progressively worsened, presenting with diminished sensation and muscle strength in all limbs. High-dose intravenous immunoglobulin, vitamin B1, and mecobalamin were administered. At the 1 month follow-up, the patient still experienced limb numbness and difficulty walking. In both patients, albuminocytologic dissociation was found on cerebrospinal fluid (CSF) analysis, positive anti-sulfatide antibodies were detected in the CSF, and electromyography indicated peripheral nerve damage. Conclusion: Anti-sulfatide antibody-related GBS can present with Miller-Fisher syndrome, brainstem encephalitis, or a combination of the two, along with severe pyramidal tract damage and residual neurological sequelae, thereby expanding the clinical profile of this GBS subtype. Anti-sulfatide antibodies are a crucial diagnostic biomarker. Further exploration of the pathophysiological mechanisms is necessary for precise treatment and improved prognosis.

Identification and validation of SOCS1/2/3/4 as potential prognostic biomarkers and correlate with immune infiltration in glioblastoma.

Suppressor of cytokine signalling (SOCS) 1/2/3/4 are involved in the occurrence and progression of multiple malignancies; however, their prognostic and developmental value in patients with glioblastoma (GBM) remains unclear. The present study used TCGA, ONCOMINE, SangerBox3.0, UALCAN, TIMER2.0, GENEMANIA, TISDB, The Human Protein Atlas (HPA) and other databases to analyse the expression profile, clinical value and prognosis of SOCS1/2/3/4 in GBM, and to explore the potential development mechanism of action of SOCS1/2/3/4 in GBM. The majority of analyses showed that SOCS1/2/3/4 transcription and translation levels in GBM tissues were significantly higher than those in normal tissues. qRT-PCR, western blotting (WB) and immunohistochemical staining were used to verify that SOCS3 was expressed at higher mRNA and protein levels in GBM than in normal tissues or cells. High SOCS1/2/3/4 mRNA expression was associated with poor prognosis in patients with GBM, especially SOCS3. SOCS1/2/3/4 were highly contraindicated, which had few mutations, and were not associated with clinical prognosis. Furthermore, SOCS1/2/3/4 were associated with the infiltration of specific immune cell types. In addition, SOCS3 may affect the prognosis of patients with GBM through JAK/STAT signalling pathway. Analysis of the GBM-specific protein interaction (PPI) network showed that SOCS1/2/3/4 were involved in multiple potential carcinogenic mechanisms of GBM. In addition, colony formation, Transwell, wound healing and western blotting assays revealed that inhibition of SOCS3 decreased the proliferation, migration and invasion of GBM cells. In conclusion, the present study elucidated the expression profile and prognostic value of SOCS1/2/3/4 in GBM, which may provide potential prognostic biomarkers and therapeutic targets for GBM, especially SOCS3.

Engineered extracellular vesicles (EVs): Promising diagnostic/therapeutic tools for pediatric high-grade glioma.

Diffuse intrinsic pontine glioma (DIPG) is a highly malignant brain tumor that mainly occurs in children with extremely low overall survival. Traditional therapeutic strategies, such as surgical resection and chemotherapy, are not feasible mostly due to the special location and highly diffused features. Radiotherapy turns out to be the standard treatment method but with limited benefits of overall survival. A broad search for novel and targeted therapies is in the progress of both preclinical investigations and clinical trials. Extracellular vesicles (EVs) emerged as a promising diagnostic and therapeutic candidate due to their distinct biocompatibility, excellent cargo-loading-delivery capacity, high biological barrier penetration efficiency, and ease of modification. The utilization of EVs in various diseases as biomarker diagnoses or therapeutic agents is revolutionizing modern medical research and practice. In this review, we will briefly talk about the research development of DIPG, and present a detailed description of EVs in medical applications, with a discussion on the application of engineered peptides on EVs. The possibility of applying EVs as a diagnostic tool and drug delivery system in DIPG is also discussed.

Multi-omics analyses of CD276 in pan-cancer reveals its clinical prognostic value in glioblastoma and other major cancer types.

BACKGROUND: CD276 (also known as B7-H3) is one of the most important immune checkpoints of the CD28 and B7 superfamily, and its abnormal expression is closely associated with various types of cancer. It has been shown that CD276 is able to inhibit the function of T cells, and that this gene may potentially be a promising immunotherapy target for different types of cancer. METHODS: Since few systematic studies have been published on the role of CD276 in cancer to date, the present study has employed single-cell sequencing and bioinformatics methods to analyze the expression patterns, clinical significance, prognostic value, epigenetic alterations, DNA methylation level, tumor immune cell infiltration and immune functions of CD276 in different types of cancer. In order to analyze the potential underlying mechanism of CD276 in glioblastoma (GBM) to assess its prognostic value, the LinkedOmics database was used to explore the biological function and co-expression pattern of CD276 in GBM, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. In addition, a simple validation of the above analyses was performed using reverse transcription-quantitative (RT-q)PCR assay. RESULTS: The results revealed that CD276 was highly expressed, and was often associated with poorer survival and prognosis, in the majority of different types of cancer. In addition, CD276 expression was found to be closely associated with T cell infiltration, immune checkpoint genes and immunoregulatory interactions between lymphoid and a non-lymphoid cell. It was also shown that the CD276 expression network exerts a wide influence on the immune activation of GBM. The expression of CD276 was found to be positively correlated with neutrophil-mediated immunity, although it was negatively correlated with the level of neurotransmitters, neurotransmitter transport and the regulation of neuropeptide signaling pathways in GBM. It is noteworthy that CD276 expression was found to be significantly higher in GBM compared with normal controls according to the RT-qPCR analysis, and the co-expression network, biological function and chemotherapeutic drug sensitivity of CD276 in GBM were further explored. In conclusion, the findings of the present study have revealed that CD276 is strongly expressed and associated with poor prognosis in most types of cancer, including GBM, and its expression is strongly associated with T-cell infiltration, immune checkpoint genes, and immunomodulatory interactions between lymphocytes and non-lymphoid cells. CONCLUSIONS: Taken together, based on our systematic analysis, our findings have revealed important roles for CD276 in different types of cancers, especially GBM, and CD276 may potentially serve as a biomarker for cancer.

Systematic characterization and biological functions of non-coding RNAs in glioblastoma.

Glioblastoma multiforme (GBM) is the most malignant and aggressive type of glioma. Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins but widely exist in eukaryotic cells. The common characteristics of these RNAs are that they can all be transcribed from the genome without being translated into proteins, thus performing biological functions, particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs. Studies have found that ncRNAs are associated with the occurrence and development of GBM, and there is a complex regulatory network among ncRNAs, which can regulate cell proliferation, migration, apoptosis and differentiation, thus provide a basis for the development of highly specific diagnostic tools and therapeutic strategies in the future. The present review aimed to comprehensively describe the biogenesis, general features and functions of regulatory ncRNAs in GBM, and to interpret the potential biological functions of these ncRNAs in GBM as well as their impact on clinical diagnosis, treatment and prognosis and discusses the potential mechanisms of these RNA subtypes leading to cancer in order to contribute to the better design of personalized GBM therapies in the future.

Case Report: Mycobacterium senegalense Infection After Cholecystectomy.

Background: Mycobacterium senegalense is a non-tuberculous mycobacterium and is found everywhere in the environment. However, M. senegalense infection in human is extremely rare, especially in immunocompetent individuals. It is difficult to detect M. senegalense infection because its symptoms are non-specific, and routine diagnostic tests are less sensitive. It is also resistant to commonly used antibiotics. Here, we report the first case of M. senegalense infection after laparoscopic cholecystectomy in China. Case Presentation: A 55-year-old man was admitted because of repeated infections at multiple incision sites for more than 1 year. Although routine diagnostic test results were negative, metagenomic next-generation sequencing (mNGS) identified DNA sequences of M. senegalense in tissue samples from incision sites. The presence of M. senegalense was further confirmed by polymerase chain reaction and capillary electrophoresis. After 60 days of quadruple therapy with clarithromycin, moxifloxacin, rifampicin, and oxycycline, the patient's wound healed. Conclusion: We believe the case findings contribute to the limited amount of knowledge about M. senegalense infection and raises awareness that this infection can result in poor wound healing, even in an immunocompetent host. Owing to a lack of early, precise diagnosis, it is difficult to treat M. senegalense infections. Based on our findings, mNGS is a sensitive diagnostic test for M. senegalense infections.

Comprehensive Analysis of Sterol O-Acyltransferase 1 as a Prognostic Biomarker and Its Association With Immune Infiltration in Glioma.

Metabolic reprogramming is a hallmark of glioma, and sterol O-acyltransferase 1 (SOAT1) is an essential target for metabolic therapy. However, the prognostic value of SOAT1 and its association with immune infiltration has not been fully elucidated. Using RNA-seq and clinical data of glioma patients from The Cancer Genome Atlas (TCGA), SOAT1 was found to be correlated with poor prognosis in glioma and the advanced malignancy of clinicopathological characteristics. Next, the correlation between SOAT1 expression and tumor-infiltrating immune cells was performed using the single-sample GSEA algorithm, gene expression profiling interactive analysis (GEPIA), and tumor immune estimation resource version 2 (TIMER2.0); it was found that SOAT1 expression was positively correlated with multiple tumor-infiltrating immune cells. To further verify these results, immunofluorescence was conducted on paraffin-embedded glioma specimens, and a positive trend of the correlation between SOAT1 expression and Treg infiltration was observed in this cohort. Finally, differentially expressed gene analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore the biological processes and signaling pathways that SOAT1 may be involved in during glioma pathogenesis. A protein-protein interaction network was established, and co-expression analysis was conducted to investigate the regulatory mechanism of SOAT1 in glioma. To the best of our knowledge, this is the first comprehensive study reporting that SOAT1 may serve as a novel prognostic biomarker associated with immune infiltrates, providing a novel perspective for glioma metabolic therapy.

Study on the serum level of CoQ10B in patients with Moyamoya disease and its mechanism of affecting disease progression.

BACKGROUND: At present, the etiology and pathogenesis of Moyamoya disease (MMD) are not completely clear. Patients are usually diagnosed after cerebrovascular events. Therefore, it is of great clinical significance to explore the predictive factors of MMD. OBJECTIVE: This study aimed to investigate the serum level of CoQ10B, the amount of endothelial progenitor cells (EPCs), and mitochondrial function of EPCs in MMD patients. METHODS: Forty-one MMD patients and 20 healthy controls were recruited in this study. Patients with MMD were divided into two groups: Ischemic type (n=23) and hemorrhagic type (n=18). Blood samples were collected from the antecubital vein and analyzed by CoQ10B ELISA and flow cytometry. Measures of mitochondrial function of EPCs include oxygen consumption rate (OCR), mitochondrial membrane potential, Ca2+ concentration, adenosine triphosphatases activity and ROS level. RESULTS: The serum CoQ10B level in MMD patients was significantly lower than that in healthy controls (p<0.001). The relative number of EPCs in MMD patients was significantly higher than that in healthy controls (p<0.001). Moreover, the OCR, mitochondrial membrane potential and ATPase activity were decreased and the Ca2+ and reactive oxygen species levels were increased in MMD patients (p<0.001). CONCLUSIONS: Our results showed obviously decreased serum CoQ10B level and increased EPCs number in patients with MMD compared with healthy patients, and the mitochondria function of EPCs in MMD patients was abnormal.

SOCS3 Acts as an Onco-immunological Biomarker With Value in Assessing the Tumor Microenvironment, Pathological Staging, Histological Subtypes, Therapeutic Effect, and Prognoses of Several Types of Cancer.

The suppressor of cytokine signaling (SOCS) family contains eight members, including SOCS1-7 and CIS, and SOCS3 has been shown to inhibit cytokine signal transduction in various signaling pathways. Although several studies have currently shown the correlations between SOCS3 and several types of cancer, no pan-cancer analysis is available to date. We used various computational tools to explore the expression and pathogenic roles of SOCS3 in several types of cancer, assessing its potential role in the pathogenesis of cancer, in tumor immune infiltration, tumor progression, immune evasion, therapeutic response, and prognostic. The results showed that SOCS3 was downregulated in most The Cancer Genome Atlas (TCGA) cancer datasets but was highly expressed in brain tumors, breast cancer, esophageal cancer, colorectal cancer, and lymphoma. High SOCS3 expression in glioblastoma multiforme (GBM) and brain lower-grade glioma (LGG) were verified through immunohistochemical experiments. GEPIA and Kaplan-Meier Plotter were used, and this bioinformatics analysis showed that high SOCS3 expression was associated with a poor prognosis in the majority of cancers, including LGG and GBM. Our analysis also indicated that SOCS3 may be involved in tumor immune evasion via immune cell infiltration or T-cell exclusion across different types of cancer. In addition, SOCS3 methylation was negatively correlated with mRNA expression levels, worse prognoses, and dysfunctional T-cell phenotypes in various types of cancer. Next, different analytical methods were used to select genes related to SOCS3 gene alterations and carcinogenic characteristics, such as STAT3, SNAI1, NFKBIA, BCL10, TK1, PGS1, BIRC5, TMC8, and AFMID, and several biological functions were identified between them. We found that SOCS3 was involved in cancer development primarily through the JAK/STAT signaling pathway and cytokine receptor activity. Furthermore, SOCS3 expression levels were associated with immunotherapy or chemotherapy for numerous types of cancer. In conclusion, this study showed that SOCS3 is an immune-oncogenic molecule that may possess value as a biomarker for diagnosis, treatment, and prognosis of several types of cancer in the future.

Study on the serum level of CoQ10B in patients with Moyamoya disease and its mechanism of affecting disease progression / Estudo sobre o nível sérico de CoQ10B em pacientes com doença de Moyamoya e seu mecanismo de afetar a progressão da doença

ABSTRACT Background: At present, the etiology and pathogenesis of Moyamoya disease (MMD) are not completely clear. Patients are usually diagnosed after cerebrovascular events. Therefore, it is of great clinical significance to explore the predictive factors of MMD. Objective: This study aimed to investigate the serum level of CoQ10B, the amount of endothelial progenitor cells (EPCs), and mitochondrial function of EPCs in MMD patients. Methods: Forty-one MMD patients and 20 healthy controls were recruited in this study. Patients with MMD were divided into two groups: Ischemic type (n=23) and hemorrhagic type (n=18). Blood samples were collected from the antecubital vein and analyzed by CoQ10B ELISA and flow cytometry. Measures of mitochondrial function of EPCs include oxygen consumption rate (OCR), mitochondrial membrane potential, Ca2+ concentration, adenosine triphosphatases activity and ROS level. Results: The serum CoQ10B level in MMD patients was significantly lower than that in healthy controls (p<0.001). The relative number of EPCs in MMD patients was significantly higher than that in healthy controls (p<0.001). Moreover, the OCR, mitochondrial membrane potential and ATPase activity were decreased and the Ca2+ and reactive oxygen species levels were increased in MMD patients (p<0.001). Conclusions: Our results showed obviously decreased serum CoQ10B level and increased EPCs number in patients with MMD compared with healthy patients, and the mitochondria function of EPCs in MMD patients was abnormal.

RESUMO Antecedentes: No momento, a etiologia e a patogênese da doença de Moyamoya (DMM) não são completamente claras. Os pacientes geralmente são diagnosticados após eventos cerebrovasculares. Sendo assim, é de grande importância clínica explorar os fatores preditivos de DMM. Objetivo: Este estudo teve como objetivo investigar o nível sérico de CoQ10B, a quantidade de células progenitoras endoteliais (CPE) e a função mitocondrial de CPE em pacientes com DMM. Métodos: Quarenta e um pacientes com DMM e 20 controles saudáveis foram recrutados neste estudo. Aqueles com DMM foram divididos em dois grupos: tipo isquêmico (n=23) e tipo hemorrágico (n=18). Amostras de sangue foram coletadas da veia antecubital e analisadas por CoQ10B Ensaio de Imunoadsorção Enzimática (ELISA) e citometria de fluxo. As medidas da função mitocondrial de CPE incluem taxa de consumo de oxigênio (TCO), potencial de membrana mitocondrial, concentração de Ca2+, atividade de adenosina trifosfatases (ATPase) e nível de espécies reativas de oxigênio (ROS). Resultados: O nível sérico de CoQ10B em pacientes com DMM foi significativamente menor do que em controles saudáveis (p<0,001). O número relativo de CPE em pacientes com MMD foi significativamente maior do que em controles saudáveis (p<0,001). Além disso, a TCO, o potencial de membrana mitocondrial e a atividade ATPase diminuíram e os níveis de Ca2+e ROS aumentaram em pacientes com MMD (p<0,001). Conclusões: Nossos resultados mostraram obviamente diminuição do nível sérico de CoQ10B e aumento do número de CPE em pacientes com DMM em comparação com pacientes saudáveis, e a função mitocondrial de CPE em pacientes com DMM estava anormal.

Cholesterol metabolism and its implication in glioblastoma therapy.

Glioblastoma (GBM) is the most lethal malignant tumor in the central nervous system, with a median survival of only 14 months. Cholesterol, which is the main component of cell membrane and the precursor of many hormones, is one of the most important lipid components in human body. Since reprogramming of the cholesterol metabolic profile has been discovered in many cancers including GBM, cholesterol metabolism becomes a promising potential target for therapy. Since GBM cells rely on external cholesterol to survive and accumulate lipid droplets to meet their rapid growth needs, targeting the metabolism of cholesterol by different strategies including inhibition of cholesterol uptake and promotion of cholesterol efflux by activating LXRs and disruption of cellular cholesterol trafficking, inhibition of SREBP signaling, inhibition of cholesterol esterification, could potentially oppose the growth of glial tumors. In this review, we discussed the above findings and describe cholesterol synthesis and homeostatic feedback pathways in normal brain tissues and brain tumors, statin use in GBM and the role of lipid rafts and cholesterol precursors and oxysterols in the treatment and pathogenesis of GBM are also summarized.

LncRNA BBOX1-AS1 promotes pituitary adenoma progression via sponging miR-361-3p/E2F1 axis.

Pituitary adenoma is one of the most common intracranial tumors, more and more studies have shown that long non-coding RNA (lncRNA) plays a very important role in pituitary adenoma. However, there are few reports on the function of lncRNA BBOX1-AS1 in pituitary adenomas, and further exploration is needed. The objective of this research is to figure out what function BBOX1-AS1 plays in pituitary adenoma and how it regulates it. The expression of the E2F1, miR-361-3p and BOX1-AS1 genes was measured using a quantitative real-time PCR method. The functional involvement of BBOX1-AS1 in pituitary adenoma was examined utilizing the Transwell assay, western blot assays and the cell counting kit-8. RNA immunoprecipitation and luciferase reporter assays revealed that miR-361-3p binds to E2F1 or BBOX1-AS1. In addition, in-vivo assays were carried out. The expression of BBOX1-AS1 in pituitary adenoma tissues and cells has been increased, according to our findings. Furthermore, it is also noted that downregulation of BBOX1-AS1causes the inhibition of pituitary adenoma cells which result in invasion, apoptosis and proliferation, as well as boosting tumor development in vivo . In addition, BBOX1-AS1 knockdown inhibited tumor development in vivo . We identify BBOX1-AS1 bind to miR-361-3p and to suppress its expression in a negative way. Moreover, miR-361-3p has been shown to bind with E2F1 and inhibit its expression. E2F1 also corrected miR-361-3p-mediated cell invasion, proliferation and apoptosis in BBOX1-AS1-dysregulated pituitary adenoma cells in rescue tests. BBOX1-AS1 increases pituitary adenoma malignant activity by sponging miR-361-3p to upregulate E2F1 expression, which may lead to a new path in pituitary adenoma therapeutic attempts.

Clinical Significance and Immune Landscape of a Pyroptosis-Derived LncRNA Signature for Glioblastoma.

Introduction: Pyroptosis was recently implicated in the initiation and progression of tumors, including glioblastoma (GBM). This study aimed to explore the clinical significance of pyroptosis-related lncRNAs (PRLs) in GBM. Methods: Three independent cohorts were retrieved from the TCGA and CGGA databases. The consensus clustering and weighted gene coexpression network analysis (WGCNA) were applied to identify PRLs. The LASSO algorithm was employed to develop and validate a pyroptosis-related lncRNA signature (PRLS) in three independent cohorts. The molecular characteristics, clinical significances, tumor microenvironment, immune checkpoints profiles, and benefits of chemotherapy and immunotherapy regarding to PRLS were also explored. Results: In the WGCNA framework, a key module that highly correlated with pyroptosis was extracted for identifying PRLs. Univariate Cox analysis further revealed the associations between PRLs and overall survival. Based on the expression profiles of PRLs, the PRLS was initially developed in TCGA cohort (n = 143) and then validated in two CGGA cohorts (n = 374). Multivariate Cox analysis demonstrated that our PRLS model was an independent risk factor. More importantly, this signature displayed a stable and accurate performance in predicting prognosis at 1, 3, and 5 years, with all AUCs above 0.7. The decision curve analysis also indicated that our signature had promising clinical application. In addition, patients with high PRLS score suggested a more abundant immune infiltration, higher expression of immune checkpoint genes, and better response to immunotherapy but worse to chemotherapy. Conclusion: A novel pyroptosis-related lncRNA signature with a robust performance was constructed and validated in multiple cohorts. This signature provided new perspectives for clinical management and precise treatments of GBM.

Loss of FBXW7 Correlates with Increased IDH1 Expression in Glioma and Enhances IDH1-Mutant Cancer Cell Sensitivity to Radiation.

F-box and WD repeat domain containing 7 (FBXW7) is a substrate receptor of the ubiquitin ligase SKP1-Cullin1-F-box complex and a potent tumor suppressor that prevents unregulated cell growth and tumorigenesis. However, little is known about FBXW7-mediated control of cell metabolism and related functions in cancer therapy. Here, we report that FBXW7 expression inversely correlates with the expression levels of the key metabolic enzyme isocitrate dehydrogenase 1 (IDH1) in patients with glioma and public glioma datasets. Deletion of FBXW7 significantly increased both wild-type (WT) and mutant IDH1 expression, which was mediated by blocking degradation of sterol regulatory element binding protein 1 (SREBP1). The upregulation of neomorphic mutant IDH1 by FBXW7 deletion stimulated production of the oncometabolite 2-hydroxyglutarate at the expense of increasing pentose phosphate pathway activity and NADPH consumption, limiting the buffering ability against radiation-induced oxidative stress. In addition, FBXW7 knockout and IDH1 mutations induced nonhomologous end joining and homologous recombination defects, respectively. In vitro and in vivo, loss of FBXW7 dramatically enhanced the efficacy of radiation treatment in IDH1-mutant cancer cells. Taken together, this work identifies FBXW7 deficiency as a potential biomarker representing both DNA repair and metabolic vulnerabilities that sensitizes IDH1-mutant cancers to radiotherapy. SIGNIFICANCE: Deficiency of FBXW7 causes defects in DNA repair and disrupts NADPH homeostasis in IDH1-mutant glioma cells, conferring high sensitivity to radiotherapy.

SOCS proteins and their roles in the development of glioblastoma.

Glioblastoma multiforme (GBM) is the most common type of primary brain tumor in adults. GBM is characterized by a high degree of malignancy and aggressiveness, as well as high morbidity and mortality rates. GBM is currently treatable via surgical resection, chemotherapy and radiotherapy, but the prognosis of patients with GBM is poor. The suppressor of cytokine signaling (SOCS) protein family comprises eight members, including SOCS1-SOCS7 and cytokine-inducible SH2-containing protein. SOCS proteins regulate the biogenesis of GBM via the JAK/STAT and NF-κB signaling pathways. Driven by NF-κB, the expression of SOCS proteins can serve as a negative regulator of the JAK/STAT signaling pathway and exerts a potential inhibitory effect on GBM. In GBM, E3 ubiquitin ligase is involved in the regulation of cellular functions, such as the receptor tyrosine kinase (RTK) survival signal, in which SOCS proteins negatively regulate RTK signaling, and kinase overexpression or mutation can lead to the development of malignancies. Moreover, SOCS proteins affect the proliferation and differentiation of GBM cells by regulating the tumor microenvironment. SOCS proteins also serve specific roles in GBM of different grades and different isocitrate dehydrogenase mutation status. The aim of the present review was to describe the biogenesis and function of the SOCS protein family, the roles of SOCS proteins in the microenvironment of GBM, as well as the role of this protein family and E3 ubiquitin ligases in GBM. Furthermore, the role of SOCS proteins as diagnostic and prognostic markers in GBM and their potential role as GBM therapeutics were explored.

The role of ubiquitin-specific peptidases in glioma progression.

The balance between ubiquitination and deubiquitination is crucial for protein stability, function and location under physiological conditions. Dysregulation of E1/E2/E3 ligases or deubiquitinases (DUBs) results in malfunction of the ubiquitin system and is involved in many diseases. Increasing reports have indicated that ubiquitin-specific peptidases (USPs) play a part in the progression of many kinds of cancers and could be good targets for anticancer treatment. Glioma is the most common malignant tumor in the central nervous system. Clinical treatment for high-grade glioma is unsatisfactory thus far. Multiple USPs are dysregulated in glioma and have the potential to be therapeutic targets. In this review, we collected studies on the roles of USPs in glioma progression and summarized the mechanisms of USPs in glioma tumorigenesis, malignancy and chemoradiotherapy resistance.

Diminished schwann cell repair responses play a role in delayed diabetes-associated wound healing.

Diabetes mellitus is the most common metabolic disease associated with impaired wound healing. Recently, Schwann cells (SCs), the glia of the peripheral nervous system, have been suggested to accelerate normal skin wound healing. However, the roles of SCs in diabetic wound healing are not fully understood. In this study, Full-thickness wounds were made in the dorsal skin of C57/B6 mice and db/db (diabetic) mice. Tissue samples were collected at different time points, and immunohistochemical and immunofluorescence analyses were performed to detect markers of de-differentiated SCs, including myelin basic protein, Sox 10, p75, c-Jun, and Ki67. In addition, in vitro experiments were performed using rat SC (RSC96) and murine fibroblast (L929) cell lines to examine the effects of high glucose conditions (50 mM) on the de-differentiation of SCs and the paracrine effects of SCs on myofibroblast formation. Here, we found that, compared with that in normal mice, wound healing was delayed and SCs failed to rapidly activate a repair program after skin wound injury in diabetic mice. Furthermore, we found that SCs from diabetic mice displayed functional impairments in cell de-differentiation, cell-cycle re-entry, and cell migration. In vitro, hyperglycemia impaired RSC 96 cell de-differentiation, cell-cycle re-entry, and cell migration, as well as their paracrine effects on myofibroblast formation, including the secretion of TGF-ß and Timp1. These results suggest that delayed wound healing in diabetes is due in part to a diminished SC repair response and attenuated paracrine effects on myofibroblast formation.

Experimental study of fat derived pellets promoting wound healing in rats.

To observe the effect of fat-derived pellets (FDP) on wound healing in rats, the inguinal fat of rats was obtained, and the FDP were obtained after centrifugation. The cell activity and growth factor secretion of FDP were measured. The wounds in rats were created, and FDP was used to treat the wounds of rats. The phenotype of macrophages and the expression of angiogenic factors expression in wounds were measured. The cell viability in FDP remains in high level after centrifugation and the expression of vascular endothelial growth factor (VEGF) and Basic Fibroblast Growth Factor (bFGF) from FDP was observed in vitro. The FDP significantly promoted the wound healing of rats compared with that in control groups. Moreover, the expression of M2 macrophages and VEGF in FDP group were significantly higher than that in the control group. FDP is a kind of stem cell product, which can be obtained from adipose tissue by physical centrifugation. The cytotherapeutic effect of FDP makes it a promising product for wound healing in clinics.

Emerging roles of suppressor of cytokine signaling 3 in human cancers.

As a member of the suppressor of cytokine signaling (SOCS) family, SOCS3 is a cytokine-inducible protein that inhibits cytokine signaling in a variety of signaling pathways. Increasing evidence shows that SOCS3 regulates tumor development through multiple pathological and physiological processes. It is worth mentioning that SOCS3 negatively regulates JAK/STAT signaling by binding to JAK/cytokine receptors or phosphorylation docking sites on STAT receptors, thus preventing tumor cell proliferation and inhibiting tumor cell invasion and metastasis. The kinase inhibitory region KIR of SOCS3 is the key to JAK inhibition. In addition, SOCS3 may also regulate tumor progression through other molecules or signaling pathways, such as microRNAs (miRNAs), IL-6 and NF-κB signaling pathway. MicroRNAs inhibit SOCS3 expression by binding to the 3' untranslated region of SOCS3 mRNA, thus regulating tumor development processes, including tumor cell proliferation, invasion, metastasis, differentiation, cell cycle and apoptosis, as well as tumor metastasis and chemotherapy resistance. On the whole, SOCS3 acts as an inhibitor of the majority of tumors through various pathways. In the present review, the role of SOCS3 in multitudinous tumors was comprehensively summarized, the molecular mechanisms and modes of action of SOCS3 in tumors were discussed, and the association between SOCS3 expression and the clinical characteristics of patients with cancer were emphasized.

SLC7A11 negatively associates with mismatch repair gene expression and endows glioblastoma cells sensitive to radiation under low glucose conditions.

The cystine/glutamate antiporter xCT (SLC7A11) is frequently upregulated in many cancers, including glioblastoma (GBM). SLC7A11-mediated cystine taken up is reduced to cysteine, a precursor amino acid for glutathione synthesis and antioxidant cellular defense. However, little is known about the biological functions of SLC7A11 and its effect on therapeutic response in GBM. Here, we report that the expression of SLC7A11 is higher in GBM compared with normal brain tissue, but is negatively associated with tumor grades and positively impacts survival in the bioinformatic analysis of TCGA and CGGA database. Additionally, a negative association between SLC7A11 and mismatch repair (MMR) gene expression was identified by Pearson correlation analysis. In the GBM cells with glucose-limited culture conditions, overexpression of SLC7A11 significantly decreased MMR gene expression, including MLH1, MSH6, and EXO1. SLC7A11-overexpressed GBM cells demonstrated elevated double-strand break (DSB) levels and increased sensitivity to radiation treatment. Taken together, our work indicates that SLC7A11 might be a potential biomarker for predicting a better response to radiotherapy in GBM.