Ultrasonography for Serial Monitoring and Management of Cerebrospinal Fluid Dynamic Disorders After Decompressive Craniectomy.

OBJECTIVE: Decompressive craniectomy (DC) is widely used to treat intracranial hypertension following severe head injury. However, impairments of cerebrospinal fluid (CSF) hydrodynamics such as hydrocephalus and subdural effusion are common complications that occur after DC. Therefore, monitoring of intracranial pressure is a staple of neurocritical care post-DC. The aim of this study was to assess the usefulness of transcranial duplex sonography (TDS) for serial monitoring and management of CSF disorders after DC. METHODS: A total of 100 patients who underwent DC between June 2016 and May 2019 were recruited for the study. Transcranial duplex sonography examinations were performed between 1-day and 1-year post-DC. Transcranial duplex sonography was mainly used for monitoring changes in ventricle size and morphology, and also to monitor intraventricular hemorrhage, hydrocephalus, intracranial hygromas, and ventricle changes during CSF release procedures. RESULTS: A total of 456 TDS examinations were performed on patients after DC. Of these, 402 were performed in the neuro-intensive care unit. Two patients had intraventricular hemorrhage and underwent TDS-guided external ventricular drainage. Twenty-nine patients were diagnosed with hydrocephalus. The results of TDS were consistent with those of cranial computed tomography. Three cases of ventriculoperitoneal shunt and 1 case of lumbar peritoneal shunt underwent valve pressure reset according to TDS, to obtain satisfactory ventricle size. Transcranial duplex sonography was used to monitor ventricle changes and control drainage volume during CSF release procedures, including 2 external ventricular drainage, 6 external lumbar drainage, and 10 lumbar punctures. Eighteen patients were detected with single or multiple intracranial effusions, including 16 subdural hygromas, 5 longitudinal fissure hygromas, and 6 brain cysts. CONCLUSIONS: Transcranial duplex sonography can efficiently help monitor changes in ventricle size and morphology and intracranial effusions. Due to its noninvasive nature, suitability for bedside application, real-time, and inexpensiveness, TDS can significantly replace cranial computed tomography and become part of the patient's daily inspection work after DC.

The Long Noncoding RNA LINC00963 Inhibits Corneal Fibrosis Scar Formation by Targeting miR-143-3p.

Corneal fibrosis is a complication of severe corneal injury, one of the major causes of vision loss. The formation of myofibroblasts has emerged as a key stimulative factor of corneal fibrosis. In the current study, we focused on the role of LINC00963 in regulating corneal fibrosis. Transforming growth factor ß1 (TGF-ß1) was used to induce human corneal stromal cells differentiating into corneal myofibroblasts, and the significant increase of α-smooth muscle actin (α-SMA) was verified by quantitative real-time PCR (qRT-PCR), western blot, and immunofluorescence, respectively. LINC00963 was identified to be one-half decreased compared with nonstimulated human corneal stromal cells, indicating that it might play a role in corneal fibrosis. Interestingly, overexpression of LINC00963 resulted in decreased formation of myofibroblasts indicating that it might exhibit an inhibiting effect. Moreover, bioinformatics tool was applied to predict the downstream target of LINC00963. We investigated that LINC00963 suppressed α-SMA induced by TGF-ß1 in corneal fibroblasts, at least in part, by downregulating the expression of miR-143-3p. In addition, either LINC00963 promotion or miR-143-3p inhibition could significantly decrease myofibroblast contractility and collagen I and III secretion, which are the key to contribute to corneal fibrosis. Taken together, our study identified LINC00963 as a promising therapeutic target.

piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity.

Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has recently been recognized, studies on the role and functional mechanism of piRNAs in lung adenocarcinoma (LUAD) development and progression are limited. In this study, we identified 10 differently expressed piRNAs in LUAD tissues compared to normal tissues, among which, piR-hsa-211106 expression levels were downregulated in LUAD tissues and cell lines. Furthermore, the effects of piR-hsa-211106 on the malignant phenotypes and chemosensitivity of LUAD cells were detected by gain- and loss-of-function analyses in vitro and in vivo, which showed that piR-hsa-211106 inhibited LUAD cell proliferation, tumor growth, and migration, but promoted apoptosis. Moreover, our finding indicated that piR-hsa-211106 is a potential therapeutic target that synergistically imparts anticancer effects with a chemotherapeutic agent for LUAD-cisplatin. Further mechanistic investigation indicated that piR-hsa-211106 could bind to pyruvate carboxylase (PC) by RNA pull down and RNA immunoprecipitation assays and inhibited PC mRNA and protein expression. Our study demonstrates that piR-hsa-211106 inhibits LUAD progression by hindering the expression and function of PC and enhances chemotherapy sensitivity, suggesting that piR-hsa-211106 is a novel diagnostic and therapeutic target for LUAD.

Exosomal circRNAs as novel cancer biomarkers: Challenges and opportunities.

Identifying high specificity and sensitivity biomarkers has always been the focus of research in the field of non-invasive cancer diagnosis. Exosomes are extracellular vesicles with a lipid bilayer membrane that can be released by all types of cells, which contain a variety of proteins, lipids, and a variety of non-coding RNAs. Increasing research has shown that the lipid bilayer can effectively protect the nucleic acid in exosomes. In cancers, tumor cell-derived exosomal circRNAs can act on target cells or organs through the transport of exosomes, and then participate in the regulation of tumor development and metastasis. Since exosomes exist in various body fluids and circRNAs in exosomes exhibit high stability, exosomal circRNAs have the potential as biomarkers for early and minimally invasive cancer diagnosis and prognosis judgment. In this review, we summarized circRNAs and their biological roles in cancers, with the emerging value biomarkers in cancer diagnosis, disease judgment, and prognosis observation. In addition, we briefly compared the advantages of exosomal circRNAs as biomarkers and the current obstacles in the exosome isolation technology, shed light to the future development of this technology.

Joint replenishment of zinc and folic acid enhances the anti-depressive effect of paroxetine via increasing serum calcium and copper and decreasing serum arsenic.

Insufficient zinc and folic acid levels are associated with depression and poor response to antidepressants. This study aimed to investigate the influences of combined zinc and folic acid replenishment on the anti-depressive effect of paroxetine. Male rats were randomly divided into five groups: control (C), model (M), paroxetine (MP), zinc + folic acid (MZnF), and zinc + folic acid + paroxetine (MZnFP) groups. Rats were exposed to mild unpredictable stress for 3 weeks as a depression model. The combinations of drug and supplements were applied via daily gavage for 4 weeks. The open field test was conducted to observe behavioral changes. A chemiluminescence method was used to detect folacin, and inductively coupled plasma mass spectrometry was used to detect serum elements. Supplementation of zinc and folic acid significantly improved behavior responses to paroxetine, including movement speed, total distance, and central zone frequency. In addition, higher calcium and copper levels and a lower arsenic level were found in the serum of the MZnFP group. Thus, supplementation of zinc and folacin can enhance the anti-depressive effect of paroxetine, and the mechanism is potentially related to the improved levels of calcium and copper and a reduced level of arsenic.

Author Correction: TGF-ß1-induced miR-503 controls cell growth and apoptosis by targeting PDCD4 in glioblastoma cells.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Aplysin Protects Against Alcohol-Induced Liver Injury Via Alleviating Oxidative Damage and Modulating Endogenous Apoptosis-Related Genes Expression in Rats.

We investigated the protective effects and possible mechanisms of Aplysin against alcohol-induced liver injury. Rats were given daily either alcohol only (alcohol model group; 8 to 12 mL/kg body weight), one of three doses of Aplysin (50, 100, or 150 mg/kg Aplysin) plus alcohol, or volume-matched saline. After 6 weeks, the effects of Aplysin were assessed in terms of changes in histology, biochemical indices, and DNA oxidative damage. Potential mechanisms were analyzed through measurements of lipid peroxidation, antioxidant defense systems, expression of cytochrome P450 2E1, and expression of apoptosis-related genes. We found that Aplysin significantly protected the liver against alcohol-induced oxidative injury, evidenced by improved hepatic histological structure, inhibited alcohol-induced elevation of serum biochemical indices, attenuated extents of hepatocellular DNA damage. At a mechanistic level, Aplysin alleviated alcohol-induced oxidative stress as illustrated by the revivification of erythrocyte membrane fluidity, the attenuation of glutathione depletion, the restoration of antioxidase activities, and reduced malondialdehyde overproduction. Furthermore, the mRNA levels of Bax, cytochrome c, and cytochrome P450 2E1 were significantly down-regulated, whereas those of Bcl-2 and caspase-9 and caspase-3 were markedly up-regulated. These findings suggest that Aplysin provides significant protection against alcohol-induced liver injury, possibly through alleviating oxidative damage and modulating endogenous apoptosis-related genes expression. PRACTICAL APPLICATION: Many natural components derived from alga have been used in the food, cosmetics, and biomedicine industries. Aplysin, a marine bromosesquiterpene, was extracted from the red alga Laurencia tristicha, which could effectively protect against alcohol-induced liver injury, might be a potential natural sources for preventing alcoholic liver damage.

Improvement of symptoms in a rat model of depression through combined zinc and folic acid administration via up-regulation of the Trk B and NMDA.

The aim of this study was to observe the influence of combined zinc and folic acid administration on depression and to explore its mechanism of action. Male Sprague Dawley rats were randomly divided into five groups: control, model, paroxetine (P), zinc + folic acid (ZnY), and zinc + folic acid + paroxetine (ZnYP) groups. Rat models of depression were established by chronic mild unpredictable stress for three weeks. These rats were then treated with different interventions for four weeks and the sucrose preference test was then performed to observe changes in rats' behavior. An HPLC-electrochemical method was used to detect the levels of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the frontal cortex. qRT-PCR was employed to detect the mRNA levels of tyrosine kinase receptor B (Trk B) and N-methyl-D-aspartate acid (NMDA) in the frontal cortex; Western blotting was used to detect the protein levels of brain derived neurotrophic factor (BDNF) in the frontal cortex. The results showed that compared with the model group, sucrose consumption, 5-HT, NE and DA levels were significantly increased in the ZnY group (P < 0.05). Also the mRNA levels of Trk B and NMDA were significantly increased in the ZnY group compared with the model group (P < 0.001). No significant up-regulation of BDNF was observed in the ZnY group. We conclude that combined administration of zinc and folic acid can improve the symptoms of depression-model rats, and its mechanism is related to increased levels of 5-HT, DA and NE in the brain, and to the up-regulation of Trk B and NMDA.

TGF-â1-induced miR-503 controls cell growth and apoptosis by targeting PDCD4 in glioblastoma cells.

Aberrant expression of microRNAs hae been shown to be closely associated with glioblastoma cell proliferation, apoptosis and drug resistance. However, mechanisms underlying the role of mcroRNAs in glioblastoma cell growth and apoptosis are not fully understood. In this study, we report that miR-503 is overexpressed in glioblastoma tissue compared with normal human brain tissue. Mechanistically, miR-503 can be induced by TGF-â1 at the transcriptional level by binding the smad2/3 binding elements in the promoter. Ectopic overexpression of miR-503 promotes cell growth and inhibits apoptosis by targeting PDCD4. In contrast, inhibition of miR-503 reduces cell growth. Furthermore, miR-503 inhibitor augments the growth inhibitory effect of temozolomide in glioblastoma cells. These results establish miR-503 as a promising molecular target for glioblastoma therapy.

Aplysin induces apoptosis in glioma cells through HSP90/AKT pathway.

Glioma is one of the most common malignancies in the world. However, an effective regiment is lacking. Increasing evidence indicated that PI3K/AKT signaling is critical for the survival of glioma. In this study, we aimed to study the effect of aplysin on the survival and proliferation of GL26 glioma cells and the involved mechanisms. The data showed that aplysin suppressed the viability of glioma cells in both dose- and time-dependent manners. It also induced G0/G1 arrest and apoptosis in glioma cells. Western blot assays revealed that aplysin treatment changed p-AKT expression by impairing the formation of Heat shock protein 90/AKT complex. Aplysin significantly increased the survival time of mice-bearing glioma and reduced the weights of the established gliomas. Collectively, aplysin can inhibit the proliferation of GL26 glioma cells and induce apoptosis in vitro, perhaps through suppressing PI3K/AKT pathway. It can also inhibit glioma growth in vivo and prolong the survival of mice. Thus, aplysin may be a novel therapeutic drug for glioma.

Aplysin enhances temozolomide sensitivity in glioma cells by increasing miR-181 level.

PURPOSE: Aplysin, a natural brominate compound from marine organisms, has been demonstrated to exhibit anti-tumor activity, mainly by inducing apoptosis and cell cycle arrest. However, its effect on glioma is still unknown. In this study, we evaluated the effects of aplysin on the malignant properties of glioma cells and its enhancing effect on temozolomide (TMZ) action against drug-resistant glioma cell lines. METHODS: We employed several human glioma cell lines and primary glioma cells to address this issue with multidisciplinary approaches. RESULTS: The combined application of aplysin and TMZ significantly sensitizes glioma cells to TMZ action, compared with TMZ alone. miRNA profile analysis revealed that the abundance of miR-181, an important glioma tumor suppressors believed to enhance TMZ effect, was greatly elevated in aplysin-treated glioma cell lines. The aplysin-induced TMZ sensitivity is dependent on MEK1 in glioma cells. Overexpression of MEK1 was able to abolish the effect of aplysin on glioma cells. CONCLUSIONS: We found that aplysin can enhance the effect of TMZ on glioma cells by increasing miR-181 expression.