NCAPH serves as a prognostic factor and promotes the tumor progression in glioma through PI3K/AKT signaling pathway.

Non-SMC (Structural Maintenance of Chromosomes) condensin I complex subunit H (NCAPH) has been shown to facilitate progression and predict adverse prognostic outcome in many cancer types. However, the function of NCAPH in gliomas is still unclear. Series of experiments were taken to uncover the function of NCAPH in glioma. The expression of NCAPH and potential mechanism regulating progression of glioma was verified by bioinformatics analysis. Lentiviral transfection was used for establishment of loss-of-function and gain-of-function cell lines. CCK-8 assay and Colony-formation assay were used to evaluate proliferation. Transwell assay and Cell wound healing assay were used to assess migration and invasion. Cell cycle and apoptosis were measured by flow cytometry. Protein and RNA were quantified by WB and RT-PCR, respectively. The nude mice model of glioma was used to evaluate the effect of NCAPH in vivo. The expression of NCAPH increased significantly in glioma tissues and correlated with WHO grade, IDH wild-type and non-1p/19q codeletion. Glioma patients with high expression of NCAPH had an undesirable prognosis. Functionally, upregulated NCAPH promotes the malignant hallmarks of glioma cells in vivo and in vitro. NCAPH correlated with DNA damage repair ability of glioma cells and facilitated the proliferation, invasion, and migration of glioma cells by promoting the PI3K/AKT signaling pathway. This study identifies the important pro-tumor role of NCAPH in glioma and suggests that NCAPH is a potential therapeutic target.

Intracerebral hemorrhage with massive milk-like serous fluid: a rare case report.

Computed tomography (CT) scans of acute cerebral hemorrhage are often characterized by high-density imaging with occasional mixed density and low-density imaging features. Possible reasons for this are a lack of blood coagulation, extravasation of cerebrospinal fluid, and brain tissue edema. It is rarely due to the accumulation of lipid components associated with hyperlipidemia. In the present case, preoperative lipid tests and the intraoperative finding of a large amount of milky white fluid surrounding the hematoma confirmed that the low-density imaging surrounding the hematoma visible on the CT scan represented a rare case of lipid accumulation.

MicroRNA-7 attenuates secondary brain injury following experimental intracerebral hemorrhage via inhibition of NLRP3.

BACKGROUND AND PURPOSE: The pathophysiological mechanisms underlying brain injury resulting from intracerebral hemorrhage (ICH) remain incompletely elucidated, and efficacious therapeutic interventions to enhance the prognosis of ICH patients are currently lacking. Previous research indicates that MicroRNA-7 (miR-7) can suppress the expression of Nod-like receptor protein 3 (NLRP3), thereby modulating neuroinflammation in Parkinson's disease pathogenesis. However, the potential regulatory effects miR-7 on NLRP3 inflammasome after ICH are yet to be established. This study aims to ascertain whether miR-7 mitigates secondary brain injury following experimental ICH by inhibiting NLRP3 and to investigate the underlying mechanisms. METHODS: An ICH model was established by stereotaxically injecting 100 µL of autologous blood into the right basal ganglia of Sprague-Dawley (SD) rats. Subsequently, these rats were allocated into three groups: sham, ICH + Vehicle, and ICH + miR-7, each comprising 18 animals. Twelve hours post-modeling, rats received intraventricular injections of 10 µL physiological saline, 10 µL phosphate, and 10 µL phosphate-buffered saline solution containing 0.5 nmol of miR-7 mimics, respectively. Neurological function was assessed on day three post-modeling, followed by euthanasia for brain tissue collection. Brain water content was determined using the dry-wet weight method. The expression of inflammatory cytokines in cerebral tissues surrounding the hematoma was analyzed through immunohistochemistry and Western blot assays. These cytokines were re-evaluated using Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Moreover, bioinformatics tools were employed to predict miR-7's binding to NLRP3. A wild-type luciferase reporter gene vector and a corresponding mutant vector were constructed, followed by transfection of miR-7 mimics into HEK293T cells to assess luciferase activity. RESULTS: Our study demonstrates that the administration of miR-7 mimics markedly reduced neurological function scores and attenuated brain edema in rats following ICH. A significant upregulation of NLRP3 expression in microglia/macrophage adjacent to the hematoma was observed, substantially reduced after the treatment with miR-7 mimics. Furthermore, this intervention ameliorated neurodegenerative changes and effectively decreased the protein and mRNA levels of pro-inflammatory cytokines, namely TNF-α, IL-1ß, IL-6, and Caspase1, in the cerebral tissues proximate to the hematomas. In addition, miR-7 mimics distinctly inhibited the luciferase activity associated with the wild-type reporter gene, an effect not mirrored in its mutant variant. CONCLUSIONS: The miR-7 suppressed NLRP3 expression in microglia/macrophage to reduce the production of inflammatory cytokines, leading to conducting certain neuroprotection post-ICH in rats.

TCAF2 drives glioma cellular migratory/invasion properties through STAT3 signaling.

Glioma is an intracranial tumor characterized by high mortality and recurrence rates. In the present study, the association of TRPM8 channel-associated factor 2 (TCAF2) in glioma was investigated using bioinformatics, showing significant relationships with age, WHO grade, IDH, and 1p/19q status, as well as being an independent predictor of prognosis. Immunohistochemistry of a glioma sample microarray showed markedly increased TCAF2 expression in glioblastoma relative to lower-grade glioma, with elevated expression predominating in the tumor center. Raised TCAF2 levels promote glioma cell migratory/invasion properties through the epithelial-to-mesenchymal transition-like (EMT-like) process, shown by Transwell and scratch assays and western blotting. It was further found that the effects of TCAF2 were mediated by the activation of STAT3. These results suggest that TCAF2 promotes glioma cell migration and invasion, rendering it a potential drug target in glioma therapy.

Severe inflammation in C57/BL6 mice leads to prolonged cognitive impairment by initiating the IL-1ß/TRPM2 pathway.

BACKGROUND: Sepsis could lead to chronic cognitive impairment by unclear molecular mechanisms. Transient receptor potential melastatin-2 (TRPM2) is essential against immunity-related activities and inflammation. Our study attempted to decipher the relationship between cognitive impairment caused by severe inflammation and TRPM2 expression levels. METHODS: Severe inflammation was induced by intraperitoneally injecting C57/BL6 mice with a high dosage (5 mg kg-1) of Lipopolysaccharide (LPS). Fear conditioning and a Morris water maze test were performed to examine the cognitive abilities of the mice. Moreover, the signaling and expression of pro-inflammatory cytokines and TRPM2 were measured using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometry and immunofluorescence staining helped to determine the astrocyte apoptosis rate. RESULTS: Severe inflammation can lead to long-term cognitive impairment in C57/BL6 mice. The interleukin-1 beta (IL-1ß) levels intra-hippocampus were significantly elevated until P14 post-LPS introduction. At both P7 and P14, there is an up-regulation of TRPM2 expression within hippocampus. Administration of recombinant IL-1ß to astrocytes results in a significant up-regulation of TRPM2 expression. IL-1ß or TRPM2 level knockdown helped counter the cognitive impairment caused by significant inflammation. CONCLUSIONS: A continuous increase in IL-1ß levels within the hippocampus can lead to cognitive impairment by enhancing TRPM2 levels caused by severe inflammation.

PDPN contributes to constructing immunosuppressive microenvironment in IDH wildtype glioma.

The tumor immunosuppressive microenvironment (IME) significantly affects tumor occurrence, progression, and prognosis, but the underlying molecular mechanisms remain to make known. We investigated the prognostic significance of PDPN and its role in IME in glioma. Weighted gene co-expression network analysis (WGCNA) found PDPN closely related to IDH wildtype status and higher immune score. Correlation analysis suggested PDPN was highly positively relevant to immune checkpoints expression and immune checkpoints block responding status. Correlation analysis together with verification in vitro suggested PDPN highly positively relevant tumor-associated neutrophils (TANs) and tumor-associated macrophages (TAMs). Least absolute shrinkage and selection operator (LASSO) regression employed to develop the prediction model with TANs and TAMs markers showed that high risk scores predicted worse prognosis. We highlight that PDPN overexpression is an independent prognostic indicator, and promotes macrophage M2 polarization and neutrophil degranulation, ultimately devotes to the formation of an immunosuppressive tumor microenvironment. Our findings contribute to re-recognizing the role of PDPN in IDH wildtype gliomas and implicate promising target therapy combined with immunotherapy for this highly malignant tumor.

VIP alleviates sepsis-induced cognitive dysfunction as the TLR-4/NF-κB signaling pathway is inhibited in the hippocampus of rats.

Cognitive dysfunction caused by sepsis-associated encephalopathy (SAE) is still poorly understood. It is reported that vasoactive intestinal peptide (VIP) exerts its anti-inflammatory effects in multiple diseases, while its biological function in SAE remains unclear. We aimed to figure out whether VIP has influence on sepsis-induced neuroinflammation and cognitive dysfunction. To induce sepsis, rats were subjected to cecal ligation and puncture (CLP) operation. Morris water maze test and fear conditioning test were conducted to reveal cognitive dysfunctions. TUNEL assay was performed to evaluate apoptosis. We found out that the expression of VIP was downregulated in the hippocampus of septic rats. VIP was verified to attenuate sepsis-induced memory impairment following CLP. Additionally, we examined apoptosis and inflammation in rats' hippocampus. It is worth noting that VIP inhibited the apoptosis in the hippocampus and reduced the productions of proinflammatory cytokines TNF-α, IL-6 and IL-1ß. Furthermore, our data confirmed that VIP was involved in regulating the TLR-4/NF-κB signaling. In conclusion, VIP inhibited neuroinflammation and cognitive impairment in hippocampus of septic rats through the TLR-4/NF-κB signaling pathway.

A Novel Prognostic Signature Based on Glioma Essential Ferroptosis-Related Genes Predicts Clinical Outcomes and Indicates Treatment in Glioma.

Background: Ferroptosis is a form of programmed cell death (PCD) that has been implicated in cancer progression, although the specific mechanism is not known. Here, we used the latest DepMap release CRISPR data to identify the essential ferroptosis-related genes (FRGs) in glioma and their role in patient outcomes. Methods: RNA-seq and clinical information on glioma cases were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). FRGs were obtained from the FerrDb database. CRISPR-screened essential genes (CSEGs) in glioma cell lines were downloaded from the DepMap portal. A series of bioinformatic and machine learning approaches were combined to establish FRG signatures to predict overall survival (OS) in glioma patients. In addition, pathways analysis was used to identify the functional roles of FRGs. Somatic mutation, immune cell infiltration, and immune checkpoint gene expression were analyzed within the risk subgroups. Finally, compounds for reversing high-risk gene signatures were predicted using the GDSC and L1000 datasets. Results: Seven FRGs (ISCU, NFS1, MTOR, EIF2S1, HSPA5, AURKA, RPL8) were included in the model and the model was found to have good prognostic value (p < 0.001) in both training and validation groups. The risk score was found to be an independent prognostic factor and the model had good efficacy. Subgroup analysis using clinical parameters demonstrated the general applicability of the model. The nomogram indicated that the model could effectively predict 12-, 36-, and 60-months OS and progression-free interval (PFI). The results showed the presence of more aggressive phenotypes (lower numbers of IDH mutations, higher numbers of EGFR and PTEN mutations, greater infiltration of immune suppressive cells, and higher expression of immune checkpoint inhibitors) in the high-risk group. The signaling pathways enriched closely related to the cell cycle and DNA damage repair. Drug predictions showed that patients with higher risk scores may benefit from treatment with RTK pathway inhibitors, including compounds that inhibit RTKs directly or indirectly by targeting downstream PI3K or MAPK pathways. Conclusion: In summary, the proposed cancer essential FRG signature predicts survival and treatment response in glioma.

Use of lung ultrasound for diagnosis and monitoring of coronavirus disease 2019 pneumonia: A case report.

Knowledge of lung ultrasound characteristics of coronavirus disease 2019 pneumonia might be useful for early diagnosis and clinical monitoring of patients, and lung ultrasound can help to control the spread of infection in healthcare settings. In this case report, a 36-year-old man with severe acute respiratory syndrome coronavirus 2 infection was diagnosed by reverse transcription-polymerase chain reaction testing of a nasopharyngeal swab. The lung ultrasound findings for this patient were the interstitial-alveolar damage showing bilateral, diffuse pleural line abnormalities, subpleural consolidations, white lung areas and thick, irregular vertical artifacts. When the patient recovered from the severe acute respiratory syndrome coronavirus 2 infection, lung ultrasound images showed a normal pleural line with A-lines regularly reverberating. Performing lung ultrasound at the bedside minimizes the need to move the patient, thus reducing the risk of spreading infection among healthcare staff. Lung ultrasound is useful for early diagnosis and evaluation of the severity of coronavirus disease 2019 pneumonia and for monitoring its progress over the course of the disease.

A cannabinoid receptor 2 agonist reduces blood-brain barrier damage via induction of MKP-1 after intracerebral hemorrhage in rats.

BACKGROUND AND PURPOSE: The blood-brain barrier (BBB) disruption and the following development of brain edema, is the most life-threatening secondary injury after intracerebral hemorrhage (ICH). This study is to investigate a potential role and mechanism of JWH133, a selected cannabinoid receptor type2 (CB2R) agonist, on protecting blood-brain barrier integrity after ICH. METHODS: 192 adult male Sprague-Dawley (SD) rats were randomly divided into Sham; ICH + Vehicle; ICH + JWH 1.0 mg/kg, ICH + JWH 1.5 mg/kg and ICH + JWH 2.0 mg/kg; ICH + SR + JWH respectively. Animals were euthanized at 24 h following western blots and immunofluorescence staining, we also examined the effect of JWH133 on the brain water contents, neurobehavioral deficits and blood brain barrier (BBB) permeability, meanwhile reassessed the inflammatory cytokines concentrations around the hematoma by enzyme-linked immunosorbent assay (ELISA) in each group. RESULTS: JWH133 (1.5 mg/kg) administration ameliorated brain edema, neurological deficits and blood-brain barrier damage, as well as microglia activation. The expression of pro-inflammatory mediators interleukin 1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metallopeptidase-2/9 (MMP2/9) were attenuated, but not monocyte chemoattractant protein-1 (MCP-1). Additionally, decreases in zonula occludens-1 (ZO-1) and claudin-5 expression were partially recovered by JWH133. Furthermore, JWH133 upregulated the expression level of MKP-1, which leads to the inhibition of MAPKs signaling pathway activation, especially for ERK and P38. However, these effects were reversed by pretreatment with a selective CB2R antagonist, SR144528. CONCLUSIONS: CB2R agonist alleviated neuroinflammation and protected blood-brain barrier permeability in a rat ICH model. Further molecular mechanisms revealed which is probably mediated by enhancing the expression of MKP-1, then inhibited MAPKs signal transduction.