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.

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.

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.

Sarcopenic obesity: research advances in pathogenesis and diagnostic criteria.

Sarcopenic obesity (SO) refers to an obesity disease accompanied by low skeletal muscle quality, strength and/or function, which is more common in the elderly and seriously affects their quality of life and can lead to falls, unstable walking, balance disorders and fractures in the elderly. The increase in aging populations and the various health problems and medical costs associated with SO have aroused widespread concern in society. However, the pathogenesis of SO has not been fully clarified and the diagnostic criteria are not uniform, meaning that there are inconsistent data on the prevalence of SO and the potential correlation between SO and health outcomes. Therefore, we review the research progress on delineating the pathogenesis and diagnostic criteria of SO, to assist in the early diagnosis and evaluation of SO and subsequent interventions.

Airway epithelial ITGB4 deficiency in early life mediates pulmonary spontaneous inflammation and enhanced allergic immune response.

Lung immune responses to respiratory pathogens and allergens are initiated in early life which will further influence the later onset of asthma. The airway epithelia form the first mechanical physical barrier to allergic stimuli and environmental pollutants, which is also the key regulator in the initiation and development of lung immune response. However, the epithelial regulation mechanisms of early-life lung immune responses are far from clear. Our previous study found that integrin ß4 (ITGB4) is decreased in the airway epithelium of asthma patients with specific variant site. ITGB4 deficiency in adult mice aggravated the lung Th2 immune responses and enhanced airway hyper-responsiveness (AHR) with a house dust mite (HDM)-induced asthma model. However, the contribution of ITGB4 to the postnatal lung immune response is still obscure. Here, we further demonstrated that ITGB4 deficiency following birth mediates spontaneous lung inflammation with ILC2 activation and increased infiltration of eosinophils and lymphocytes. Moreover, ITGB4 deficiency regulated thymic stromal lymphopoietin (TSLP) production in airway epithelial cells through EGFR pathways. Neutralization of TSLP inhibited the spontaneous inflammation significantly in ITGB4-deficient mice. Furthermore, we also found that ITGB4 deficiency led to exaggerated lung allergic inflammation response to HDM stress. In all, these findings indicate that ITGB4 deficiency in early life causes spontaneous lung inflammation and induces exaggerated lung inflammation response to HDM aeroallergen.

Respiratory syncytial virus infection-induced mucus secretion by down-regulation of miR-34b/c-5p expression in airway epithelial cells.

Severe RSV infection is the main cause of hospitalization to children under the age of five. The regulation of miRNAs on the severity of RSV infection is unclear. The aim of the study was to identify the critical differential expression miRNAs (DE miRNAs) that can regulate the pathological response in RSV-infected airway epithelial cells. In this study, miRNA and mRNA chips of RSV-infected airway epithelia from Gene Expression Omnibus (GEO) were screened and analysed, separately. DE miRNAs-targeted genes were performed for further pathway and process enrichment analysis. DE miRNA-targeted gene functional network was constructed on the basis of miRNA-mRNA interaction. The screened critical miRNA was also investigated by bioinformatics analysis. Then, RSV-infected human bronchial epithelial cells (HBECs) were constructed to verify the expression of the DE miRNAs. Finally, specific synthetic DE miRNAs mimics were used to confirm the effect of DE miRNAs on the RSV-infected HBECs. 45 DE miRNAs were identified from GEO62306 dataset. Our results showed that hsa-mir-34b-5p and hsa-mir-34c-5p decreased significantly in HBECs after RSV infection. Consistent with the biometric analysis, hsa-mir-34b/c-5p is involved in the regulation of mucin expression gene MUC5AC. In RSV-infected HBECs, the inducement of MUC5AC production by decreased hsa-mir-34b/c-5p was partly mediated through activation of c-Jun. These findings provide new insights into the mechanism of mucus obstruction after RSV infection and represent valuable targets for RSV infection and airway obstruction treatment.

Airway epithelial integrin ß4 suppresses allergic inflammation by decreasing CCL17 production.

Airway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin ß4 (ITGB4) is a structural adhesion molecule that is down-regulated in the airway epithelium of asthma patients. Although a few studies hint toward the role of ITGB4 in asthmatic inflammation pathogenesis, their specific resultant effects remain unexplored. In the present study, we determined the role of ITGB4 of AECs in the regulation of Th2 response and identified the underpinning molecular mechanisms. We found that ITGB4 deficiency led to exaggerated lung inflammation and AHR with higher production of CCL17 in house dust mite (HDM)-treated mice. ITGB4 regulated CCL17 production in AECs through EGFR, ERK and NF-κB pathways. EFGR-antagonist treatment or the neutralization of CCL17 both inhibited exaggerated pathological marks in HDM-challenged ITGB4-deficient mice. Together, these results demonstrated the involvement of ITGB4 deficiency in the development of Th2 responses of allergic asthma by down-regulation of EGFR and CCL17 pathway in AECs.

Long non-coding RNA GAS5, by up-regulating PRC2 and targeting the promoter methylation of miR-424, suppresses multiple malignant phenotypes of glioma.

PURPOSE: Malignant gliomas remain significant challenges in clinic and pose dismal prognosis on patients. In this study, we focused on growth arrest-specific 5 (GAS5), a tumor suppressive long non-coding RNA in glioma, explored its crosstalk with miR-424, and examined their biological functions in glioma. METHODS: Expressions of GAS5 and miR-424 were measured using qRT-PCR. The regulation of GAS5 on miR-424 expression was examined in GAS5-overexpressing glioma cells by combining methylation-specific PCR, western blotting, and RNA immunoprecipitation. Functional significance of GAS5 and miR-424 on in vitro cell proliferation, apoptosis, migration, invasion, and in vivo tumor growth was examined using colony formation, flow cytometry, wound healing, transwell assay, and the xenograft model, respectively. The potential targeting of AKT3 by miR-424 was investigated using luciferase reporter assay. RESULTS: GAS5 and miR-424 were significantly down-regulated in glioma cells. GAS5 directly interacted with enhancer of zeste homolog 2 (EZH2), stimulated the formation of polycomb repressive complex 2 (PRC2), reduced the levels of DNA methyltransferases (Dnmts), alleviated promoter methylation of miR-424, and promoted miR-424 expression. Functionally, GAS5, by up-regulating miR-424, inhibited cell proliferation, migration, and invasion, while increased apoptosis of glioma cells in vitro, and suppressed xenograft growth in vivo. miR-424 directly inhibited AKT3 and altered the expressions of AKT3 targets, cyclinD1, c-Myc, Bax, and Bcl-2, which might contribute to its tumor suppressive activities. CONCLUSIONS: GAS5, by inhibiting methylation and boosting expression of miR-424, inhibits AKT3 signaling and suppresses multiple malignant phenotypes. Therefore, stimulating GAS5/miR-424 signaling may benefit the treatment of glioma.

[Advances in research on the pathogenesis of hydrocephalus].

Hydrocephalus is a common neurological disease with complex etiology. It is characterized by the accumulation and continuous growth of cerebrospinal fluid in the ventricular system and subarachnoid space. Hydrocephalus can be caused by congenital genetic factors, brain trauma and cerebral hemorrhage. Through the efforts of many researchers, the pathogenesis of hydrocephalus is being completed, but it has not been fully explained. The imbalance of cerebrospinal fluid production and absorption into the sinus, and disorder of the cerebrospinal fluid circulation pathway or the osmotic pressure maintenance in the ventricle can lead to increased cerebrospinal fluid and ventricular dilatation.

[Intracranial Rosai-Dorfman disease in a child: A case report and literature review].

Intracranial Rosai-Dorfman disease (RDD) is a rare clinical histiocytosis proliferative disease. A 12-year-old boy with dizziness and headache for 1 month was admitted into Pediatric Neurosurgery of Xiangya Hospital, Central South University. The patient underwent total tumor resection and postoperative application of hormones and chemotherapy. During follow-up of 8 months, patient's condition was stable and no tumor recurrence was observed. For patient with a trend of tumor progression, stereotactic biopsy can help to confirm the diagnosis and determine the surgical strategy such as disposal of bone flaps. The treatment is mainly based on surgical intervention, supplemented by radiotherapy, chemotherapy and hormone therapy. Without affecting the nerve function, the surgeon should try to completely resect the tumor.

[Clinical characters, treatment and prognosis in 26 children with optic pathway gliomas].

OBJECTIVE: To explore the clinical characters, treatment and prognosis for pediatric optic pathway gliomas (OPGs).
 Methods: A total of 26 patients with OPGs, who were diagnosed and treated at Neurosurgery of Xiangya Hospital of Central South University between June 2010 and November 2017, were retrospectively reviewed, and their average age was 5.5 years old. The influential factors for patients' progression-free survival (PFS) and overall survival (OS) were analyzed.
 Results: All patients were classified into Type II and Type III based on Dodge classification and received surgery treatment. Vision was improved after surgery in 20 patients. Twenty-four patients (92.3%) were continually followed up, and 14 patients (58.3%) received post-radiation treatment. Twenty-one patients were still alive and 15 patients' symptoms were not progressed. The PFS and OS in patients received radiation therapy were better than those without radiation therapy (PFS: P<0.01; OS: P<0.05). The postoperative visual prognosis might be related to the choice of surgical approach.
 Conclusion: Treatment of children with OPGs should include surgery and postoperative radiotherapy. The eyesight protection in surgery is as important as tumor resection.

[Experience of shunting surgery in treatment for meningeal carcinomatosis].

OBJECTIVE: To evaluate the value of shunting surgery in the treatment for patients with meningeal carcinomatosis.
 Methods: The therapeutic process of shunting surgery was analyzed in 5 meningeal carcinomatosis patients.
 Results: The intracranial pressure could effectively be controlled, and the associated symptoms could be relieved. No complications associated with shunting surgery were found during the hospitalization and follow-up. One patient, who did not receive the surgery, died in 2 months later.
 Conclusion: Shunting surgery can effectively relieve the intracranial pressure caused by meningeal carcinomatosis, decrease the mortality and morbidity caused by intractable intracranial hypertension in these patients, and improve their live quality.

[Treatment of cryptococcal meningitis by use of shunting and review in literature].

OBJECTIVE: To evaluate the time and effect of shunt operation on cryptococcal meningitis.
 METHODS: A total 7 patients received shunt operation for the therapy of cryptococcal meningitis patients and the data was retrospectively analyzed.
 RESULTS: Intracranial hypertension-caused symptoms were resolved immediately. There was no complication, no infection dissemination and no recrudescence of cryptococcal meningitis. 
 CONCLUSION: Shunt operation is effective for intracranial hypertension caused by cryptococcal meningitis. It does not affect the antifungal treatment.

MiRNA-125a-5p inhibits glioblastoma cell proliferation and promotes cell differentiation by targeting TAZ.

Glioblastoma (GBM) is the most lethal brain tumor due to the resistance to conventional therapies, such as radiotherapy and chemotherapy. TAZ, an important mediator of the Hippo pathway, was found to be up-regulated in diverse cancers, including in GBM, and plays important roles in tumor initiation and progression. However, little is known about the regulation of TAZ expression in tumors. In this study, we found that miR-125a-5p is an important regulator of TAZ in glioma cells by directly targeting the TAZ 3' UTR. MiR-125a-5p levels are inversely correlated with that of TAZ in normal astrocytes and a panel of glioma cell lines. MiR-125a-5p represses the expression of TAZ target genes, including CTGF and survivin, and inhibits cell proliferation and induces the differentiation of GBM cells; whereas over-expression of TAZ rescues the effects of miR-125a-5p. This study revealed a mechanism for TAZ deregulation in glioma cells, and also demonstrated a tumor suppressor role of miR-125a-5p in glioblastoma cells.

[Experience of treatment for accumulation of extra-axil cerebrospinal fluid after skull surgery].

OBJECTIVE: To explore the treatment and pathophysiology of extra-axil cerebrospinal fluid accumulation aft er skull surgery. METHODS: The treatment of 46 cases of pineal regional tumor was retrospectively studied. RESULTS: The CT showed that all patients had postoperative extra-axil cerebrospinal fluid accumulation in 6 hours after operation. 5 cases displayed symptomatic accumulation of extra-axil cerebrospinal fluid. 1 died 30 days aft er discharge, 4 performed S-P shunt and 3 of them switched to V-P shunt after S-P shunt failed. CONCLUSION: Much more attention should be paid to postoperative accumulation of extra-axil cerebrospinal fluid. Both V-P and S-P are the effective strategies of therapy.

Simvastatin alleviates glymphatic system damage via the VEGF-C/VEGFR3/PI3K-Akt pathway after experimental intracerebral hemorrhage.

Current clinical practice primarily relies on surgical intervention to remove hematomas in patients with intracerebral hemorrhage (ICH), given the lack of effective drug therapies. Previous research indicates that simvastatin (SIM) may enhance hematoma absorption and resolution in the acute phase of ICH, though the precise mechanisms remain unclear. Recent findings have highlighted the glymphatic system (GS) as a crucial component in intracranial cerebrospinal fluid circulation, playing a significant role in hematoma clearance post-ICH. This study investigates the link between SIM efficacy in hematoma resolution and the GS. Our experimental results show that SIM alleviates GS damage in ICH-induced rats, resulting in improved outcomes such as reduced brain edema, neuronal apoptosis, and degeneration. Further analysis reveals that SIM's effects are mediated through the VEGF-C/VEGFR3/PI3K-Akt pathway. This study advances our understanding of SIM's mechanism in promoting intracranial hematoma clearance and underscores the potential of targeting the GS for ICH treatment.

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.

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.

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.