Primary intraorbital inflammatory lumpy lesion: A rare case report.

RATIONALE: Eosinophilic angiocentric fibrosis (EAF) is considered to be a kind of benign IgG4-related disease, and it is more often found in the nasal cavity. We present a pretty rare case of orbital EAF that is unlike any other reported case for this case is an IgG4 negative orbital EAF and successfully treated by the fronto orbitozygomatic approach surgery. PATIENT CONCERNS: This is a 68-year-old man from a rural area of Inner Mongolia Autonomous Region, went to our hospital for a 2-month history of vision loss with a local hospital orbital computer tomography which showed that there was a lesion in his left orbit. The inspection of the patient revealed that the patient left eye was protruding outward and the left eyelid unable to complete open or close. And his left eyeball movement had difficulty in all directions. Postoperative pathology diagnosed that this was a case of IgG4-negative EAF case. DIAGNOSES: Orbital EAF. INTERVENTIONS: Surgical radical resection and postoperative glucocorticoid therapy. OUTCOMES: After surgery, the left eye vision of this patient increased to 0.6 tested in the standard logarithmic visual acuity chart. And his left eyeball movement dysfunction and eyeball outward protruding get a partially relief. LESSONS: EAF occurring in the orbit is a very rare disease and immunohistochemical results of EAF can be IgG4 negative.

Intraspinal choristoma in the lumbar region: A case report.

RATIONALE: Intraspinal choristoma is a relatively uncommon intervertebral canal tumor. Prior to our reports, only 2 cases of intraspinal choristoma had been reported. Because this disease is not common and looks like a mass of fatty tissue on the magnetic resonance imaging (MRI), intraspinal choristoma can be easily misdiagnosed as teratomas or lipomas (like the case of this article presenting) without a pathology report. So if a lumber intraspinal lesion is discovered in a clinical examination, intraspinal choristoma should be considered as a differential diagnosis. We present a case of intraspinal choristoma that is unlike any other reported case. PATIENT CONCERNS: A 35-year-old woman with left lower extremity hypoesthesia and burning-like pain in the lumbar region for 1 month visited the local hospital for plain lumbar spine MRI. The patient was diagnosed with a lumbar space-occupying lesion. A second plain lumbar spine MRI scan and a MRI scan with enhancement were performed in our hospital to confirm the presence of a congenital lipoma in the spinal canal. A postoperative biopsy of the lumbar spinal mass indicated that the mass was an intraspinal choristoma located in the spinal canal. DIAGNOSIS: Intraspinal choristoma. INTERVENTION: The lesion was surgically removed, and follow-up plain and enhanced MRI images of the patient's lumbar spine were obtained. OUTCOMES: After surgery, the patient no longer experienced the burning pain in her lumbar region or the left lower extremity hypoesthesia when the patient was discharged. And there was no evidence of recurrence 2 years after the surgery. LESSONS: The MRI presentation of intraspinal choristoma is similar to intraspinal lipoma. Therefore, a pathological assessment is critical to provide an accurate diagnosis.

Long noncoding RNA MEG3 contributes to dysfunction of brain microvascular endothelial cells after intracerebral hemorrhage by regulating the miR-1930-5p/Mllt1 axis.

BACKGROUND: Intracerebral hemorrhage (ICH) is a subtype of stroke and causes disability and death worldwide. The roles of long noncoding RNAs (lncRNAs) in brain function and neurological diseases have been revealed. LncRNA maternally expressed gene 3 (MEG3) is involved in neurological impairment, but its role in ICH remains unknown. AIMS: The aim of this research is to explore the role of MEG3 in ICH. METHODS AND RESULTS: Here, we established an ICH mouse model via intracerebral injection of autologous blood. Primary brain microvascular endothelial cells (BMECs) were treated with oxygen-and-glucose-deprivation (OGD) plus hemin to establish the model in vitro. We observed that MEG3 expression was significantly upregulated in both ICH mouse model and OGD/hemin (OGD/H) induced BMECs. The downregulation of MEG3 suppressed cell apoptosis and the activation of NOD-like receptor family protein 3 (NLRP3) inflammasome in OGD/H-induced BMECs. In ICH mice, MEG3 downregulation inhibited cell apoptosis and improved brain dysfunction. Mechanistically, MEG3 was confirmed to act as a molecular sponge for microRNA (miR)-1930-5p, and Mllt1 was a downstream target for miR-1930-5p. MEG3 competitively bound with miR-1930-5p to upregulate Mllt1. We further verified that Mllt1 overexpression reversed the inhibitory effect of miR-1930-5p in OGD/H-induced BMECs. CONCLUSIONS: In conclusion, lncRNA MEG3 promoted the dysfunction of BMECs by modulating the miR-1930-5p/Mllt1 axis, which provides a potential target in gene therapy for brain injury following ICH.

Propofol Protects Hippocampal Neurons from Hypoxia-Reoxygenation Injury by Decreasing Calcineurin-Induced Calcium Overload and Activating YAP Signaling.

OBJECTIVES: Propofol is a popular anesthetic drug that is neuroprotective. However, the mechanisms of propofol for hippocampal neuroprotection remain elusive. This study is aimed at investigating the neuroprotective effect and mechanism of propofol in hippocampal neurons exposed to ischemia-reperfusion (I/R) injury. METHODS: Hypoxia-reoxygenated (H/R) HT-22 cells were used to mimic I/R injury of the hippocampus in vitro. An MTT assay was used to determine cell viability. Cell apoptosis was detected by a TUNEL assay and a flow cytometry cell apoptosis assay. Expression levels of proteins were measured by Western blotting. Intracellular calcium was assessed by Fura-2/AM staining. Flow cytometry was used to determine the mitochondrial membrane potential (MMP). Coimmunoprecipitation was used to evaluate the stability of the FKBP-RyR complex. Calcineurin enzymatic activity was measured with a colorimetric method. YAP nuclear translocation was tested by immunofluorescence staining. RESULTS: H/R induced HT-22 cell viability depression, and apoptosis was reversed by propofol treatment. Propofol could alleviate H/R-induced intracellular calcium accumulation and MMP loss by inhibiting calcineurin activity and FKBP12.6-RyR disassociation in a concentration-dependent manner. In addition, YAP expression was crucial for propofol to protect HT-22 cell apoptosis from H/R injury. Propofol could activate YAP through dephosphorylation. Activated YAP stimulated the transcription of the Bcl2 gene, which promotes cellular survival. Our data also demonstrated that propofol activated YAP through the RhoA-Lats1 pathway without large G proteins or MST involvement. In addition, we showed that there was no interaction between calcineurin signaling and YAP activation in HT-22 cells. CONCLUSIONS: Propofol protected hippocampal neurons from I/R injury through two independent signaling pathways, including the calcineurin/FKBP12.6-RyR/calcium overload pathway and the RhoA/Lats1/YAP/Bcl-2 pathway.

Gypenoside Attenuates ß Amyloid-Induced Inflammation in N9 Microglial Cells via SOCS1 Signaling.

Reducing ß amyloid- (Aß-) induced microglial activation is believed to be effective in treating Alzheimer's disease (AD). Microglia can be activated into classic activated state (M1 state) or alternative activated state (M2 state), and the former is harmful; in contrast, the latter is beneficial. Gypenoside (GP) is the major bioactive constituent of Gynostemma pentaphyllum, a traditional Chinese herb medicine. In this study, we hypothesized that GP attenuates Aß-induced microglial activation by ameliorating microglial M1/M2 states, and the process may be mediated by suppressor of cell signaling protein 1 (SOCS1). In this study, we found that Aß exposure increased the levels of microglial M1 markers, including iNOS expression, tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6 releases, and coadministration of GP reversed the increase of M1 markers and enhanced the levels of M2 markers, including arginase-1 (Arg-1) expression, IL-10, brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF) releases in the Aß-treated microglial cells. SOCS1-siRNA, however, significantly abolished the GP-induced effects on the levels of microglial M1 and M2 markers. These findings indicated that GP attenuates Aß-induced microglial activation by ameliorating M1/M2 states, and the process may be mediated by SOCS1.

Langerhans' cell histiocytosis of the temporal fossa: A case report.

Langerhans' cell histiocytosis (LCH) is a rare disease with a wide spectrum of clinical manifestations, varying from an isolated lesion to systemic involvement. The etiology of this disease remains to be elucidated. The present study reports a case of LCH with temporal fossa localization in an 8-year-old male patient, who had exhibited left temporal pain and headache for 1 month. Physical examination revealed slight exophthalmos and conjunctival hemorrhage in the patient's left eye, and non-contrast computed tomography imaging of the head revealed a soft tissue mass with unclear margins located in the left temporal fossa, as well as a wide bony defect. Magnetic resonance imaging revealed a heterogeneously contrast-enhanced mass near the left temporal pole, which eroded into the patient's left orbit and maxillary sinus. The lesion was totally excised and confirmed to be LCH through biopsy.

Pro-apoptotic effects of splice-switching oligonucleotides targeting Bcl-x pre-mRNA in human glioma cell lines.

Alternative splicing is a near-ubiquitous phenomenon with important roles in human diseases, including cancers. Splice-switching oligonucleotides (SSOs) have emerged as a class of antisense therapeutics that modulate alternative splicing by hybridizing to the pre-mRNA splice site. The Bcl-x gene is alternatively spliced to express anti­apoptotic Bcl-xL and pro-apoptotic Bcl-xS. Bcl-xL expression is upregulated in many cancers and is considered a general mechanism by which cancer cells evade apoptosis. By redirecting Bcl-x pre-mRNA splicing from Bcl-xL to Bcl-xS, SSO exerted pro-apoptotic and chemosensitizing effects in various cancer cell lines. In this study, we investigated the effects of SSO targeting Bcl-x pre-mRNA in human glioma cell lines. First, we performed reverse transcription-polymerase chain reaction (RT-PCR) and western blotting to determine the mRNA and protein expression levels of Bcl-xL in glioma cell lines (U87 and U251) and a normal human astrocyte cell line (HA1800). Then, the Bcl-x SSO was designed to bind to the downstream 5' alternative splice site of exon 2 in Bcl-x pre-mRNA and was modified using 2'-O-methoxyethyl-phosphorothioate. An oligonucleotide targeting aberrantly spliced human ß-globin intron was used as a negative control. The SSOs were delivered with a cationic lipid into glioma and astrocyte cell lines. The antitumor effects of the SSOs were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and flow cytometry, and the switch in production from Bcl-xL to Bcl-xS was analyzed by RT-PCR and western blotting. Bcl-xL mRNA and protein were highly expressed in both glioma cell lines. The Bcl-x SSO modified Bcl-x pre-mRNA splicing and had pro-apoptotic effects on the glioma cell lines. By contrast, the lipid alone and the control SSO did not affect Bcl-xL expression or induce apoptosis. Our study demonstrated the antitumor activity of an SSO that targets Bcl-x pre-mRNA splicing in glioma cell lines. Bcl-x SSO may be a potential strategy for treating gliomas.

Differential effects of estrogen and estrogen receptor antagonist, ICI 182 780, on the expression of calbindin-D9k in rat pituitary prolactinoma GH3 cells.

OBJECTIVE: To detect the effects of 17ß-estradiol (E2) on the expression of calbindin-D9k (CaBP-9k) in pituitary GH3 cells, and to determine the antagonistic effect of a selective estrogen receptor (ER) antagonist (ICI 182 780) on CaBP-9k expression. METHODS: A rat pituitary prolactinoma cell line (GH3 cells) was used in an in vitro model. The localization of CaBP-9k in GH3 cells was observed by immunofluorescence. GH3 cells were cultured with the addition of E2 medium for 24 hours. The levels of CaBP-9k mRNA and protein expression in different groups were analyzed by RT-PCR and Western blot analysis. The ER antagonist, ICI 182 780, was added to GH3 cells before E2 (10(-8) M) at a concentration of 10(-6) M to investigate the regulation of an ER-mediated pathway on CaBP-9k expression. RESULTS: E2 had a stimulatory effect on CaBP-9k expression of GH3 cells in a dose-dependent manner; the level of CaBP-9k expression was higher when treated with a higher concentration of E2. ICI 182 780 suppressed the stimulatory effect of E2 on CaBP-9k expression in GH3 cells. The level of CaBP-9k expression was significantly reduced by co-administration of E2 with ICI 182 780 in GH3 cells. The immunoprecipitation results confirmed that CaBP-9k interacts directly with ERα, and E2 increases the interaction between CaBP-9k and ERα. CONCLUSION: Estrogen induces CaBP-9k expression via an ERα-mediated pathway and CaBP-9k directly combines with ERα, suggesting that CaBP-9k is involved in the biological effects mediated by an ER pathway in GH3 cells.