PD-L1-related IncRNAs are associated with malignant characteristics and immune microenvironment in glioma.

BACKGROUND: The expression of long non-coding RNA (lncRNA) can function as diagnostic and therapeutic biomarker for tumors. This research explores the role of PD-L1-related lncRNAs in affecting malignant characteristics and the immune microenvironment of glioma. METHODS: Downloading gene expression profiles and clinicopathological information of glioma from TCGA and CGGA databases, 6 PD-L1-related lncRNAs were identified through correlation analysis, Cox and LASSO regression analysis, establishing the risk score model based on them. Bioinformatics analysis and cell experiments in vitro were adopted to verify the effects of LINC01271 on glioma. RESULTS: Risk scores based on 6 PD-L1-related lncRNAs (AL355974.3, LINC01271, AC011899.3, MIR4500HG, LINC02594, AL357055.3) can reflect malignant characteristics and immunotherapy response of glioma. Patients with high LINC01271 expression had a worse prognosis, a higher abundance of M1 subtype macrophages in the immune microenvironment, and a higher degree of tumor malignancy. Experiments in vitro confirmed its positive regulatory effect on the proliferation and migration of glioma cells. CONCLUSIONS: The risk score model based on 6 PD-L1-related lncRNAs can reflect the malignant characteristics and prognosis of glioma. LINC01271 can independently be used as a new target for prognosis evaluation and therapy.

A portable electrochemical microsensor for in-site measurement of dissolved oxygen and hydrogen sulfide in natural water.

Dissolved oxygen (O2) and hydrogen sulfide (H2S) are two important indicators of water quality, their levels are of intimate dependence and varying over time. It is of great significance to monitoring of dissolved O2 and H2S simultaneously in natural water, yet has not been reported because of lack of effective approaches. In this work, a portable electrochemical microsensor was developed for simultaneously quantifying dissolved O2 and H2S. Here, Pd@Ni nanoparticles (NPs) were self-assembled onto the microelectrode by MXene titanium carbide (Ti3C2Tx), which were of responsibility towards O2 and H2S detection within single electrochemical reduction process. On this regard, Pd NPs facilitated catalyzing the electrochemical reduction of O2, while Ni NPs were employed as recognition element for H2S detection. With the electrochemical reduction sweep, the initial application of a positive voltage rendered the Ni to be oxidized to be Ni ions, contributing to their following capture of surrounding S2- to form nickel sulfide. Nickel sulfide with highly electrochemical activity were capable of generating detecting reduction current. In consequence, the as-designed microsensor can simultaneously determine O2 concentrations ranging from 36 to 318 µM and H2S levels ranging from 0.1 to 2.5 µM with high selectivity. Finally, the portable microsensor was successfully applied to simultaneous detection dissolved O2 and H2S in natural water in-site, the results of which were comparable to the classical methods.

Machine learning-based identification of SOX10 as an immune regulator of macrophage in gliomas.

Gliomas, originating from the glial cells, are the most lethal type of primary tumors in the central nervous system. Standard treatments like surgery have not significantly improved the prognosis of glioblastoma patients. Recently, immune therapy has become a novel and effective option. As a conserved group of transcriptional regulators, the Sry-type HMG box (SOX) family has been proved to have a correlation with numerous diseases. Based on the large-scale machine learning, we found that the SOX family, with significant immune characteristics and genomic profiles, can be divided into two distinct clusters in gliomas, among which SOX10 was identified as an excellent immune regulator of macrophage in gliomas. The high expression of SOX10 is related to a shorter OS in LGG, HGG, and pan-cancer groups but benefited from the immunotherapy. It turned out in single-cell sequencing that SOX10 is high in neurons, M1 macrophages, and neural stem cells. Also, macrophages are found to be elevated in the SOX10 high-expression group. SOX10 has a positive correlation with macrophage cytokine production and negative regulation of macrophages' chemotaxis and migration. In conclusion, our study demonstrates the outstanding cluster ability of the SOX family, indicating that SOX10 is an immune regulator of macrophage in gliomas, which can be an effective target for glioma immunotherapy.

Identification of CD73 as a Novel Biomarker Encompassing the Tumor Microenvironment, Prognosis, and Therapeutic Responses in Various Cancers.

CD73 is essential in promoting tumor growth by prohibiting anti-tumor immunity in many cancer types. While the mechanism remains largely unknown, our paper comprehensively confirmed the onco-immunological characteristics of CD73 in the tumor microenvironment (TME) of pan-cancer. This paper explored the expression pattern, mutational profile, prognostic value, tumor immune infiltration, and response to immunotherapy of CD73 in a continuous cohort of cancers through various computational tools. The co-expression of CD73 on cancer cells, immune cells, and stromal cells in the TME was also detected. Especially, we examined the correlation between CD73 and CD8+ (a marker of T cell), CD68+ (a marker of macrophage), and CD163+ (a marker of M2 macrophage) cells using multiplex immunofluorescence staining of tissue microarrays. CD73 expression is significantly associated with a patient's prognosis and could be a promising predictor of these cancers. High CD73 levels are strongly linked to immune infiltrations, neoantigens, and immune checkpoint expression in the TME. In particular, enrichment signaling pathway analysis demonstrated that CD73 was obviously related to activation pathways of immune cells, including T cells, macrophages, and cancer-associated fibroblasts (CAFs). Meanwhile, single-cell sequencing algorithms found that CD73 is predominantly co-expressed on cancer cells, CAFs, M2 macrophages, and T cells in several cancers. In addition, we explored the cellular communication among 14 cell types in glioblastoma (GBM) based on CD73 expression. Based on the expression of CD73 as well as macrophage and T cell markers, we predicted the methylation and enrichment pathways of these markers in pan-cancer. Furthermore, a lot of therapeutic molecules sensitive to these markers were predicted. Finally, potential anticancer inhibitors, immunotherapies, and gene therapy responses targeting CD73 were identified from a series of immunotherapy cohorts. CD73 is closely linked to clinical prognosis and immune infiltration in many cancers. Targeting CD73-dependent signaling pathways may be a promising therapeutic strategy for future tumor immunotherapy.

Choroid plexus epithelium and its role in neurological diseases.

Choroid plexus epithelial cells can secrete cerebrospinal fluid into the ventricles, serving as the major structural basis of the selective barrier between the neurological system and blood in the brain. In fact, choroid plexus epithelial cells release the majority of cerebrospinal fluid, which is connected with particular ion channels in choroid plexus epithelial cells. Choroid plexus epithelial cells also produce and secrete a number of essential growth factors and peptides that help the injured cerebrovascular system heal. The pathophysiology of major neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, as well as minor brain damage diseases like hydrocephalus and stroke is still unknown. Few studies have previously connected choroid plexus epithelial cells to the etiology of these serious brain disorders. Therefore, in the hopes of discovering novel treatment options for linked conditions, this review extensively analyzes the association between choroid plexus epithelial cells and the etiology of neurological diseases such as Alzheimer's disease and hydrocephalus. Finally, we review CPE based immunotherapy, choroid plexus cauterization, choroid plexus transplantation, and gene therapy.

Novel therapeutic modulators of astrocytes for hydrocephalus.

Hydrocephalus is mainly characterized by excessive production or impaired absorption of cerebrospinal fluid that causes ventricular dilation and intracranial hypertension. Astrocytes are the key response cells to inflammation in the central nervous system. In hydrocephalus, astrocytes are activated and show dual characteristics depending on the period of development of the disease. They can suppress the disease in the early stage and may aggravate it in the late stage. More evidence suggests that therapeutics targeting astrocytes may be promising for hydrocephalus. In this review, based on previous studies, we summarize different forms of hydrocephalus-induced astrocyte reactivity and the corresponding function of these responses in hydrocephalus. We also discuss the therapeutic effects of astrocyte regulation on hydrocephalus in experimental studies.

The pathogenesis of idiopathic normal pressure hydrocephalus based on the understanding of AQP1 and AQP4.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder without a recognized cause. Aquaporins (AQPs) are transmembrane channels that carry water through cell membranes and are critical for cerebrospinal fluid circulation and cerebral water balance. The function of AQPs in developing and maintaining hydrocephalus should be studied in greater detail as a possible diagnostic and therapeutic tool. Recent research indicates that patients with iNPH exhibited high levels of aquaporin 1 and low levels of aquaporin 4 expression, suggesting that these AQPs are essential in iNPH pathogenesis. To determine the source of iNPH and diagnose and treat it, it is necessary to examine and appreciate their function in the genesis and maintenance of hydrocephalus. The expression, function, and regulation of AQPs in iNPH are reviewed in this article, in order to provide fresh targets and suggestions for future research.

Organic Small Molecule Contrast Agent for Targeted Photoacoustic Imaging of Patient-Derived Brain Tumors.

Traditional glioblastoma (GBM) cell lines do not maintain the heterogeneity of the original tumor, cell interactions, and therapy response, thus limiting their investigation in GBM theranostics. Herein, a kind of GBM tumor-targeting nanoparticles (NPs) TCFNP@iRGD are designed and constructed, which are generated by photoacoustic (PA) contrast agent 2-(3-cyano-4,5,5-trimethylfuran-2(5H)-ylidene) malononitrile (TCF)-OH through facile nanoprecipitation and decorated with an active targeting ligand iRGD. Their potential in GBM detection via PA imaging on glioma patient-derived cells intracranial xenograft models is evaluated for the first time. Excellent tumor-specific PA mapping performance of GBM is realized by TCFNP@iRGD, demonstrating its promising potential in the clinical diagnosis of GBM.

Ependymal Cilia: Physiology and Role in Hydrocephalus.

Cerebrospinal fluid (CSF), a colorless liquid that generally circulates from the lateral ventricles to the third and fourth ventricles, provides essential nutrients for brain homeostasis and growth factors during development. As evidenced by an increasing corpus of research, CSF serves a range of important functions. While it is considered that decreased CSF flow is associated to the development of hydrocephalus, it has recently been postulated that motile cilia, which line the apical surfaces of ependymal cells (ECs), play a role in stimulating CSF circulation by cilia beating. Ependymal cilia protrude from ECs, and their synchronous pulsing transports CSF from the lateral ventricle to the third and fourth ventricles, and then to the subarachnoid cavity for absorption. As a result, we postulated that malfunctioning ependymal cilia could disrupt normal CSF flow, raising the risk of hydrocephalus. This review aims to demonstrate the physiological functions of ependymal cilia, as well as how cilia immobility or disorientation causes problems. We also conclude conceivable ways of treatment of hydrocephalus currently for clinical application and provide theoretical support for regimen improvements by investigating the relationship between ependymal cilia and hydrocephalus development.

Targeting choroid plexus epithelium as a novel therapeutic strategy for hydrocephalus.

The choroid plexus is a tissue located in the lateral ventricles of the brain and is composed mainly of choroid plexus epithelium cells. The main function is currently thought to be the secretion of cerebrospinal fluid and the regulation of its pH, and more functions are gradually being demonstrated. Assistance in the removal of metabolic waste and participation in the apoptotic pathway are also the functions of choroid plexus. Besides, it helps to repair the brain by regulating the secretion of neuropeptides and the delivery of drugs. It is involved in the immune response to assist in the clearance of infections in the central nervous system. It is now believed that the choroid plexus is in an inflammatory state after damage to the brain. This state, along with changes in the cilia, is thought to be an abnormal physiological state of the choroid plexus, which in turn leads to abnormal conditions in cerebrospinal fluid and triggers hydrocephalus. This review describes the pathophysiological mechanism of hydrocephalus following choroid plexus epithelium cell abnormalities based on the normal physiological functions of choroid plexus epithelium cells, and analyzes the attempts and future developments of using choroid plexus epithelium cells as a therapeutic target for hydrocephalus.

Research Progress on the Inflammatory Effects of Long Non-coding RNA in Traumatic Brain Injury.

Globally, traumatic brain injury (TBI) is an acute clinical event and an important cause of death and long-term disability. However, the underlying mechanism of the pathophysiological has not been fully elucidated and the lack of effective treatment a huge burden to individuals, families, and society. Several studies have shown that long non-coding RNAs (lncRNAs) might play a crucial role in TBI; they are abundant in the central nervous system (CNS) and participate in a variety of pathophysiological processes, including oxidative stress, inflammation, apoptosis, blood-brain barrier protection, angiogenesis, and neurogenesis. Some lncRNAs modulate multiple therapeutic targets after TBI, including inflammation, thus, these lncRNAs have tremendous therapeutic potential for TBI, as they are promising biomarkers for TBI diagnosis, treatment, and prognosis prediction. This review discusses the differential expression of different lncRNAs in brain tissue during TBI, which is likely related to the physiological and pathological processes involved in TBI. These findings may provide new targets for further scientific research on the molecular mechanisms of TBI and potential therapeutic interventions.

Tumor Immune Microenvironment and Immunotherapy in Brain Metastasis From Non-Small Cell Lung Cancer.

Brain metastasis (BM), a devastating complication of advanced malignancy, has a high incidence in non-small cell lung cancer (NSCLC). As novel systemic treatment drugs and improved, more sensitive imaging investigations are performed, more patients will be diagnosed with BM. However, the main treatment methods face a high risk of complications at present. Therefore, based on immunotherapy of tumor immune microenvironment has been proposed. The development of NSCLC and its BM is closely related to the tumor microenvironment, the surrounding microenvironment where tumor cells live. In the event of BM, the metastatic tumor microenvironment in BM is composed of extracellular matrix, tissue-resident cells that change with tumor colonization and blood-derived immune cells. Immune-related cells and chemicals in the NSCLC brain metastasis microenvironment are targeted by BM immunotherapy, with immune checkpoint inhibition therapy being the most important. Blocking cancer immunosuppression by targeting immune checkpoints provides a suitable strategy for immunotherapy in patients with advanced cancers. In the past few years, several therapeutic advances in immunotherapy have changed the outlook for the treatment of BM from NSCLC. According to emerging evidence, immunotherapy plays an essential role in treating BM, with a more significant safety profile than others. This article discusses recent advances in the biology of BM from NSCLC, reviews novel mechanisms in diverse tumor metastatic stages, and emphasizes the role of the tumor immune microenvironment in metastasis. In addition, clinical advances in immunotherapy for this disease are mentioned.

Linear scleroderma in a child with central nervous system involvement: clinical and radiological features.

Linear scleroderma is the most common type of localized scleroderma in children. Lesions rarely involve areas other than the skin, and nervous system involvement is even rare. We reported a case of a 6-year-old girl who was admitted to the hospital with recurrent seizures for 4 weeks. Before that, she had left frontal plaques for more than 1 year. Radiological imaging of the brain showed multiple abnormal lesions and skin biopsy of the plaques indicated scleroderma. After drug therapy, the girl had no recurrence of epilepsy, and no obvious abnormalities were found in the reexamination of neuroimaging. We performed further radiological examination on this patient and reviewed the literatures for this rare case.

A new triarylindanone and a new isobenzofuranone derivative from Selaginella tamariscina.

A new triarylindanone, namely selagindanone A (1), and a new isobenzofuranone (2), 3,4-bis(4-hydroxyphenyl)isobenzofuran-1(3H)-one, were isolated from Selaginella tamariscina. Their structures were elucidated by comprehensive spectroscopic and mass spectrometric analyses, including 1 D-, 2 D-NMR and HR-ESI-MS. Compound 1 possesses a unique structural feature of triaryl-substituted in the skeleton of 1-indanone. In addition, compound 2 showed weak cytotoxicity against human hepatocellular carcinoma SMMC-7721 and HepG2 cell lines.

A pan-cancer and single-cell sequencing analysis of CD161, a promising onco-immunological biomarker in tumor microenvironment and immunotherapy.

Background: CD161 has been linked to the appearance and development of various cancers. Methods: The mutation map and the variation of CNVs and SNVs of CD161 were displayed according to cBioportal and GSCALite. We also evaluated the pathway enrichment and drug sensitivity of CD161 according to GSCALite. We performed a single-cell sequencing analysis of cancer cells and T cells in melanoma. The cell communication patterns related to CD161 were further explored. Multiplex immunofluorescence staining of tissue microarrays was used to detect the association between CD161 expression and macrophages and T cells. Results: A high CD161 level was related to neoantigens expression, pathway enrichment, and drug sensitivity. In addition, single-cell sequencing analysis showed that CD161 was mainly expressed in T cells, M1 and M2 Macrophages, neoplastic, microglial cells, neurons, and cancer cells in many tumor types. Further study on pseudotime trajectories and functional annotation of CD161 proved the critical role of CD161 in tumor progression and T cell immunity in melanoma. Multiplex immunofluorescence revealed that CD161 is closely correlated with the immune infiltration of T cells and macrophages in multiple cancers. In addition, high CD161 expression predicted a favorable immunotherapy response. Conclusion: CD161 is involved in the immune infiltration of T cells and macrophages and might be a promising target for tumor immunotherapy.

MicroRNA-455-5p/CPEB1 pathway mediates Aß-related learning and memory deficits in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD), a common neurodegenerative disease, is the main cause of dementia, with cognitive decline as the core symptom observed during diagnosis. Synaptic loss may be the main cause of early cognitive dysfunction in AD, but the detailed mechanism is still unclear. In this study, we investigated the role of abnormal miR-455-5p/CPEB1 pathway in AD mouse model. We found that miR-455-5p was upregulated, while its downstream target, cytoplasmic polyadenylation element-binding 1 (CPEB1), was downregulated in the hippocampus of APP/PS1 mice at the age of 9 m. Abnormal miR-455-5p/CPEB1 pathway mediated cognitive deficits in APP/PS1 mice through suppressing α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor expressions. And miR-455-5p suppression, CPEB1 overexpression or application of a peptide disrupting the miR-455-5p/CPEB1 interaction in CA1 of APP/PS1 mice rescued AD-like phenotypes in mice, including deficits in synaptic plasticity and memory. In conclusion, our results indicated that miRNA-455-5p/CPEB1 pathway mediated synaptic and memory deficits in Alzheimer's Disease through targeting on AMPARs, providing a potential therapeutic strategy for AD.

miRNA-34b/c regulates mucus secretion in RSV-infected airway epithelial cells by targeting FGFR1.

Respiratory syncytial virus (RSV) infection in airway epithelial cells is the main cause of bronchiolitis in children. Excessive mucus secretion is one of the primary symbols in RSV related lower respiratory tract infections (RSV-related LRTI). However, the pathological processes of mucus hypersecretion in RSV-infected airway epithelial cells remains unclear. The current study explores the involvement of miR-34b/miR-34c in mucus hypersecretion in RSV-infected airway epithelial cells by targeting FGFR1. First, miR-34b/miR-34c and FGFR1 mRNA were quantified by qPCR in throat swab samples and cell lines, respectively. Then, the luciferase reporters' assay was designed to verify the direct binding between FGFR1 and miR-34b/miR-34c. Finally, the involvement of AP-1 signalling was assessed by western blot. This study identified that miR-34b/miR-34c was involved in c-Jun-regulated MUC5AC production by targeting FGFR1 in RSV-infected airway epithelial cells. These results provide some useful insights into the molecular mechanisms of mucus hypersecretion which may also bring new potential strategies to improve mucus hypersecretion in RSV disease.

Novel therapeutics for hydrocephalus: Insights from animal models.

Hydrocephalus is a cerebrospinal fluid physiological disorder that causes ventricular dilation with normal or high intracranial pressure. The current regular treatment for hydrocephalus is cerebrospinal fluid shunting, which is frequently related to failure and complications. Meanwhile, considering that the current nonsurgical treatments of hydrocephalus can only relieve the symptoms but cannot eliminate this complication caused by primary brain injuries, the exploration of more effective therapies has become the focus for many researchers. In this article, the current research status and progress of nonsurgical treatment in animal models of hydrocephalus are reviewed to provide new orientations for animal research and clinical practice.

Erratum: The expression of Wnt-1 inducible signaling pathway protein-2 in astrocytoma: Correlation between pathological grade and clinical outcome.

[This corrects the article DOI: 10.3892/ol.2014.2663.].

Aging-related genes are potential prognostic biomarkers for patients with gliomas.

Aging has a significant role in the proliferation and development of cancers. This study explored the expression profiles, prognostic value, and potential roles of aging-related genes in gliomas. We designed risk score and cluster models based on aging-related genes and glioma cases using LASSO Cox regression analysis, consensus clustering analysis and univariate cox regression analyses. High risk score was related to malignant clinical features and poor prognosis based on 10 datasets, 2953 cases altogether. Genetic alterations analysis revealed that high risk scores were associated with genomic aberrations of aging-related oncogenes. GSVA analysis exhibited the potential function of the aging-related genes. More immune cell infiltration was found in high-risk group cases, and glioma patients in high-risk group may be more responsive to immunotherapy. Knock-down of CTSC, an aging-related gene, can inhibit cell cycle progression, colony formation, cell proliferation and increase cell senescence in glioma cell lines in vitro. Indeed, high expression of CTSC was associated with poor prognosis in glioma cases. In conclusion, this study revealed that aging-related genes have prognostic potential for glioma patients and further identified potential mechanisms for aging-related genes in tumorigenesis and progression in gliomas.