Gene Expression Profile Identifies LncRNA AL355974.3 As a Potential Glioma Biomarker.

OBJECTIVE: Glioma is a central nervous system tumor arising from glial cells. Despite significant advances in diagnosis and treatment, most patients with high-grade gliomas have a poor prognosis. Many studies have shown that long noncoding RNAs (lncRNAs) may play important roles in the development, progression and treatment of many tumors, including gliomas. Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma. Therefore, we hope that by studying differentially expressed lncRNAs (DElncRNAs) in glioma, we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients. METHODS: First, the expression of lncRNAs in 5 normal brain (NB) tissues and 10 glioma tissues was examined by RNA sequencing (RNA-seq). Next, we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas (TCGA) database to assess the prognostic value of these variables. Finally, functional analysis of the DElncRNAs was performed by means of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma (LGG) and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma (GBM). Among them, AL355974.3 was the most upregulated lncRNA. LINC00632 was the most downregulated lncRNA. Second, LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database. Finally, bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways, such as cell metabolic and developmental processes. CONCLUSION: Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.

Gut microbiota in infants with food protein enterocolitis.

BACKGROUND: We explored the effects of two formulas, extensively hydrolyzed formula (EHF) and amino acid-based formula (AAF), on the gut microbiota and short-chain fatty acids (SCFAs) in infants with food protein-induced enterocolitis syndrome (FPIES). METHODS: Fecal samples of thirty infants with bloody diarrhea receiving EHF or AAF feeding were collected at enrollment, diagnosis of FPIES, and four weeks after diagnosis. The gut microbiota and SCFAs were analyzed using 16 S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. RESULTS: Microbial diversity of FPIES infants was significantly different from that of the controls. FPIES infants had a significantly lower abundance of Bifidobacterium and a higher level of hexanoic acid compared with controls. In EHF-fed FPIES infants, microbial richness was significantly decreased over time; while the microbial diversity and richness in AAF-fed FPIES infants exhibited no differences at the three time points. By four weeks after diagnosis, EHF-fed FPIES infants contained a decreased abundance of Acinetobacter, whereas AAF-fed FPIES infants contained an increased abundance of Escherichia-Shigella. EHF-fed infants experienced significantly decreased levels of butyric acid and hexanoic acid at four weeks after diagnosis. CONCLUSIONS: Infants with FPIES had intestinal dysbiosis and different formulas differentially affected gut microbiota and SCFAs in FPIES infants. IMPACT: We firstly report the impacts of two different nutritional milk formulas on the gut microbial composition and SCFAs levels in infants with FPIES. We show that infants with FPIES have obvious intestinal dysbiosis and different formulas differentially affect gut microbiota and SCFAs in FPIES infants. Understanding the effects of different types of formulas on gut microbial colonization and composition, as well as the related metabolites in infants with FPIES could help provide valuable insights for making choices about feeding practices.

Prognostic impact of sodium fluorescein-guided microsurgery on cognitive function, neuropeptide dynamics, and short-term outcomes in brain glioma patients.

This study conducted a retrospective analysis on 107 brain glioma patients treated from January 2018 to February 2020 to assess the impact of sodium fluorescein-guided microsurgery on postoperative cognitive function and short-term outcomes. Patients were divided into two groups: a control group (n=50 patients) undergoing routine surgery and a research group (n=57 patients) receiving sodium fluorescein-guided microsurgery. The study compared postoperative total resection rates, changes in cognitive scores, and neuropeptide levels in cerebrospinal fluid between the groups. The findings revealed that the research group experienced shorter surgical time and hospitalization duration, reduced blood loss, and higher total resection rates compared to the control group. Furthermore, the research group demonstrated improvements in cognitive scores and an increase in neuropeptide levels after surgery. There was no significant difference in the comparison of the incidence of postoperative complications between the two groups. The WHO classification and preoperative performance scores were independent prognostic factors for the evaluation of 3-year survival, highlighting the clinical significance of sodium fluorescein-guided microsurgery in improving quality of life and cognitive functions of patients without compromising their long-term survival outcomes.

HIF-1A regulates cognitive deficits of post-stroke depressive rats.

Post-stroke depression (PSD) is a serious neuropsychiatric complication post stroke and leads to cognitive deficits. This study was conducted to explore the molecular mechanism of hypoxia-inducible factor-1α (HIF-1A) in cognitive dysfunction in rats with PSD. The rat model of PSD was established by middle cerebral artery occlusion, followed by 3 weeks of treatment with chronic unpredictable mild stress. The levels of miR-582-5p, HIF-1A, and neighbor of Brca1 gene (NBR1) in brain tissues were determined using RT-qPCR. The behaviors and cognitive capacity of rats were evaluated by various behavioral tests. PSD rats were injected with HIF-1A/miR-582-5p lowexpression vectors or NBR1 overexpression vectors via stereotactic method. The binding of HIF-1A to NBR1 or miR-582-5p was analyzed by chromatin immunoprecipitation and dual-luciferase assay. HIF-1A and NBR1 were highly expressed while miR-582-5p was poorly expressed in the brain of PSD rats. HIF-1A inhibition alleviated cognitive dysfunction of PSD rats. miR-582-5p was the upstream miRNA of HIF-1A, and HIF-1A specifically interacted with the NBR1 promoter to enhance NBR1 expression. miR-582-5p downregulation and NBR1 upregulation reversed the alleviative role of HIF-1A inhibition in cognitive dysfunction of PSD rats. In summary, HIF-1A inhibition may be a therapeutic target for cognitive dysfunction post PSD.

Alterations of the gut microbiota and short chain fatty acids in necrotizing enterocolitis and food protein-induced allergic protocolitis infants: A prospective cohort study.

Background: Even though presenting with similar clinical manifestations, necrotizing enterocolitis (NEC) and food protein-induced allergic protocolitis (FPIAP) have completely different treatments and prognosis. Our study aimed to quantify and evaluate differences in gut microbiota and short chain fatty acids (SCFAs) between infants with NEC and FPIAP to better identify these two diseases in clinical settings. Methods: A total of 43 infants with NEC or FPIAP in Children's Hospital of Chongqing Medical University, China between December 2020 and December 2021 were enrolled. Stool samples were prospectively collected and froze. Infants defined as NEC were those who presented with clinical courses consistent with NEC and whose radiographs fulfilled criteria for Bell's stage 2 or 3 NEC, while those who were healthy in appearance and had blood in the stool (visible or may be microscopic), had normal bowel sounds in physical examination, were resolved after eliminating the causative food, and/or had recurrence of symptoms after oral food challenge (OFC) were defined as FPIAP. Primers specific for bacterial 16S rRNA genes were used to amplify and pyrosequence fecal DNA from stool samples. Gas chromatography-mass spectrometry (GC-MS) technology was used to determine the concentrations of SCFAs. Results: Among the 43 infants, 22 were diagnosed with NEC and 21 were diagnosed with FPIAP. The microbial community structure in NEC infant stools differed significantly from those in FPIAP infant stools. NEC infants had significantly higher proportion of Actinobacteria and reduced proportion of Bacteroidetes compared with FPIAP infants, and the proportions of Halomonas, Acinetobacter, Bifidobacterium, and Stenotrophomonas in NEC infants were significantly higher than that of FPIAP infants. In addition, infants with NEC had significantly lower levels of acetic acid, propionic acid, butyric acid, isovaleric acid, and total SCFAs, and higher level of hexanoic acid as compared to the infants of the FPIAP group. Conclusions: The differences of gut microbiota composition and concentrations of SCFAs might represent suitable biomarker targets for early identification of NEC and FPIAP.

High Expression of Fibronectin 1 Predicts a Poor Prognosis in Glioblastoma.

OBJECTIVE: Glioblastoma multiforme (GBM), the most malignant intracranial neoplasm, is associated with a high mortality and recurrence rate due to the aggressive nature and heterogeneity of the tumor. Some of the molecular markers involved in the tumorigenesis of GBM are essential in prognosis, diagnosis, and treatment. Due to the limitations of therapeutic effects, this study aims to explore novel biomarkers with prognostic value and to provide new insights into therapeutic targets. METHODS: The expression profile of mRNAs in GBM was detected by RNA-sequencing, and differentially expressed genes were identified by integrating the data from RNA-seq results and the GEPIA2 database. Of the total 40 hub genes, FN1, P4HB, and PPIB showed prognostic significance based on both GEPIA2 and CGGA databases. The validation of FN1, P4HB, and PPIB expression by qPCR and correlation analysis with clinicopathological features were performed in 41 GBM tissues from our institution. RESULTS: Kaplan-Meier analysis revealed that FN1 and P4HB expressions levels were related to the overall survival (OS) of GBM patients (P<0.05). Multivariate analysis showed that FN1 overexpression (HR=9.199, P=0.002) was an independent and unfavorable prognostic factor for GBM patients. The median survival time was 8.5 months and 21 months for high and low expressions of FN1, respectively. CONCLUSION: It was suggested that FN1 could be an ideal target for prognosis and a potential therapeutic target in GBM.

Identification of Dysregulated microRNAs in Glioma Using RNA-sequencing.

Glioma is the most common malignant brain tumor in central nervous system. Despite advances in the treatment of glioma such as surgery and chemoradiotherapy, most patients are easy to relapse, resulting in adverse clinical outcomes. Hence, effective molecular-targeting treatment may be one of attractive strategies for glioma therapy. The dysregulated microRNAs (miRNAs), one of the candidates of therapeutic targets, are believed to play an important role in the progression of glioma. In this study, we aimed to examine the expression profile of miRNAs in glioma and provide a reference for glioma therapy. Firstly, expression profile of miRNAs in 5 normal brain tissues, 5 low-grade glioma (LGG) tissues and 5 glioblastoma (GBM) tissues was detected by RNA sequencing (RNA-seq). Next, the target genes of differentially expressed miRNAs (DEmiRNAs) were predicted and then GO enrichment and KEGG pathway analysis performed by bioinformatics. Finally, 10 miRNAs which were significantly up- or down-regulated both in GBM and LGG were validated by real-time quantitative PCR (qRT-PCR). RNA-seq results indicated a number of DEmiRNAs in glioma. There were 64 up-regulated miRNAs and 17 down-regulated miRNAs in LGG, and 181 up-regulated miRNAs and 124 down-regulated miRNAs in GBM, respectively. Bioinformatics analysis showed that the target genes of these DEmiRNAs were enriched in various biological processes and signaling pathways such as cell metabolic and developmental process. Selected DEmiRNAs were further confirmed by qRT-PCR. miRNA-10b-5p, miRNA-92b-3p and miRNA-455-5p were significantly up-regulated in both GBM and LGG; while miRNA-542-3p was significantly up-regulated in LGG; miRNA-184 and miRNA-206 were significantly down-regulated in both GBM and LGG; miRNA-766-5p and miRNA-1-3p were significantly down-regulated in GBM. The subject of our study demonstrated several dysregulated miRNAs may serve as a potential therapeutic target for glioma.

Landfill leachate treatment by coagulation/flocculation combined with microelectrolysis-Fenton processes.

Landfill leachate was pretreated by chemical flocculation with polyaluminum chloride (PAC) as a flocculant, and subsequently purified by the microelectrolysis-Fenton (MEF) process. Response surface methodology was employed to optimize the MEF process, and the optimal conditions were initial pH 3.20, H2O2 concentration 3.57 g/L, and Fe-C dosage 104.52 g/L. The PAC coagulation combined with MEF processes obtained a superior decontamination performance, and the predicted chemical oxygen demand (COD) and humic acids (HA) removal were respectively 90.27% and 93.79%. The strong fluorescence peak at 425 nm and the trapping experiment showed that ⋅OH was generated during MEF, which had a strong oxidation ability to degrade organic recalcitrant pollutants. The ultraviolet-visible spectra and three-dimensional excitation-emission matrices spectra (3D-EEMs) indicated that PAC coagulation could preferentially remove protein-like substances, while the MEF process was effective in destructing organic recalcitrant pollutants, especially humic-like and fulvic-like substances.

Characterization and mechanism of lead and zinc biosorption by growing Verticillium insectorum J3.

Verticillium insectorum J3 was isolated from a local lead-zinc deposit tailing, and its biosorption characteristics and reaction to the toxicities of different Pb(II) and Zn(II) concentrations were investigated. SEM, FTIR, a pH test and a desorption experiment were carried out to identify a possible mechanism. The biosorption of J3 presented an inhibition trend at low concentrations (25-75 mg L-1) and promotion at high concentrations (100-300 mg L-1). J3 absorbed Pb(II) prior to Zn(II) and produced alkaline substances, while mycelial and pellet morphology modifications were important for the removal of Pb(II) and Zn(II) under different stressful conditions (SEM results). Both intracellular accumulation and extracellular absorption may contribute to the removal of Pb(II) at lower concentrations (25-50 mg L-1), although mainly extracellular biosorption occurred at higher concentrations (75-300 mg L-1). However, Zn(II) bioaccumulation occurred at all concentrations assayed. Verticillium insectorum J3 may have evolved active defenses to alleviate the toxicity of heavy metals and proved to be a highly efficient biosorbent, especially for Pb(II) at high concentrations. This study is a useful reference for the development of biotreatment technologies to mitigate heavy metal waste.

Graphene oxide in the marine environment: Toxicity to Artemia salina with and without the presence of Phe and Cd2.

Given the increasing potential of graphene oxide entering marine environments, it is imperative to assess the risks of GO on marine ecosystem, including its direct toxicity to marine organisms and indirect toxicity brought by co-existing aquatic pollutants, as a result of the remarkable adsorption capacity of GO. In the present study, the acute toxicity of GO, Phe, Cd2+, GO-Phe, and GO-Cd2+ to Artemia salina were systemically assessed and compared for the first time. Although the lethal effects of GO alone to A. salina only appeared at high GO dose (500 mg/L), its sublethal toxicity (growth inhibition) at concentrations as low as 1 mg/L was observed by microscopy, which was likely closely related to the GO-induced oxidative stress in A. salina. Compared with the toxicity of Phe alone, GO-Phe exhibited a synergistic effect to A. salina at a high GO concentration. For GO-Cd2+, the toxicity was positively correlated with both GO dose and Cd2+ dose. The increased toxicity of GO-Phe or GO-Cd2+ at high doses might be attributed to the promoted bioaccumulation of toxicants by GO, as the adhesion of GO complexes to intestinal tract of A. salina was observed during the toxicity tests, which probably resulted in further toxicological effects.

Involvement of X-chromosome Reactivation in Augmenting Cancer Testis Antigens Expression: A Hypothesis.

Cancer testis antigens (CTAs) are attractive targets for tumor immunotherapy because of their tumor-specific expression. Since more than half of confirmed CTAs are located on the X-chromosome, we asked whether there is a link between CTA expression and X-chromosomes. Recent reports have shown that reactivation of the inactive X-chromosome, known as X-chromosome reactivation (XCR), a unique phenomenon that exists in many high-risk tumors in women, can transform the expression of many X-linked genes from monoallelic to biallelic. In this review, we discuss the link between CTA and XCR with the hopes of providing some novel insights into tumor biology.

Nonmissile Penetrating Head Injuries: Surgical Management and Review of the Literature.

BACKGROUND: Nonmissile penetrating head injuries (NPHIs) in the civilian population are rare but potentially fatal. Although numerous cases have been reported in the literature, the surgical management of such injuries is still ambiguous, especially with development of surgical techniques. Here, we report 5 cases of NPHIs managed with different surgical techniques and review the literature on surgical treatment of these injuries to outline the appropriate management for these patients from a neurosurgical perspective. METHODS: We retrospectively reviewed 5 cases of NPHIs managed surgically in our department. The clinical data were collected, including cause, type of objects, way of penetration, initial clinical evaluation, imaging, surgical intervention, postoperative care, complication, follow-up, and outcome. In addition, a systematic review of the literature was performed in the PubMed database to search for articles on surgical treatment of these injuries. RESULTS: These 5 cases were caused by twisted steel bar, electric welding rod, and sewing needle, respectively. Preoperative imaging, including computed tomography, magnetic resonance imaging, and digital subtraction angiography, was selectively performed to assist the operative plan. Foreign objects were removed surgically in all cases. Postoperative prophylactic administration of antibiotics and anticonvulsants was used to prevent infectious and epileptic complications. Most of the patients achieved a better outcome except for one. CONCLUSIONS: NPHIs can be fatal but they can be managed with satisfactory results by proper preoperative imaging evaluation, rapid appropriate surgical management, and accurate postoperative care. Personalized surgical intervention should be undertaken depending on the mechanism and extent of the NPHI.

Effect of Calcium Ions on Dewaterability of Enzymatic-Enhanced Anaerobic Digestion Sludge.

Waste-activated sludge (WAS) solubilized remarkably after enzymatic-enhanced anaerobic digestion, but its dewaterability was deteriorated. In this study, a novel method was performed to improve the dewaterability of enzymatic-enhanced anaerobic digestion sludge by adding CaCl2 (0.01~1.00 g/g total sludge). The capillary suction time (CST), moisture content, and filtrate turbidity were employed to characterize the dewaterability of WAS, and the possible mechanisms involved were clarified. The results showed the dewaterability did not worsen when CaCl2 was added before sludge digestion, and the CST, moisture content, and filtrate turbidity were notably reduced with the increase of CaCl2 dosage. It also shown that calcium ions played an important role in the bioflocculation of digested sludge by neutralizing negative charges on the surface of sludge. In addition, soluble protein initially lowered a little and then observably improved with the addition of CaCl2, while soluble carbohydrate was reduced sharply first and then bounced back afterwards. The interactions between calcium ions and the biopolymer further enhanced the dewatering of sludge through bridging of colloidal particles together.

[Microsurgical resection of anterior clinoid meningiomas-- 46 cases report].

OBJECTIVE: To investigate the microsurgical tchniques and effects for the resection of anterior clinoid meningioma (ACM). METHODS: Between January 2003 and March 2013, a total of 46 ACM patients were operated on via the pterion approach or lateral subfrontal approach. There were 16 male patients and 30 female patients, their mean age was 48.5 (16-69) years. Symptoms lasted from 1 month to 9 years(average 24.7 months). Preoperative CT and MRI examination showed that the tumors were located in the anterior clinoid process (25 cases on the right side, 21 cases on the left side). The average maximal tumor diameter was 4.4 cm (1.9-7.4 cm). The patients were peroidly followed-up on outpatient on 3 months to 6 months, then every year postoperativelly. The clinical data, radiological findings, surgical records and outcome of patients were retrospectively analyzed, and the prognostic factors were ananlyzed by using of the unpaired data χ(2) test with continuity correction. RESULTS: Of fourty-six patients operated on, apparently complete removal was achieved in 36 patients (78.3%), 10 patients (21.7%) had minimal residual tumors, 5 of which had gamma knife radiosurgery. Preexisting visual deficit improved in 21 of 41 patients (51.2%), unchanged in 16(35.6%), and worsened in 9(20.0%). At 3-6 months after discharge, 37(80.4%) patients had a good recovery, 7(15.6%) patients were moderately disabled, 1(2.2%) presented with severe disability, and 1 (2.2%) patient died of surgery-related causes. The tumor wrapping blood vessels (χ(2) = 4.676, P = 0.031) and violating cavernous sinus(χ(2) = 4.973, P = 0.026) were causes of unfavorable prognosis. During the mean follow-up of 35.1 months (range, 4-107 months) for 40 patients, the average Karnofsky score was 83.2. Tumor recurred in 4 cases: 2 of which required reoperation, and 2 had gamma knife radiosurgery. CONCLUSIONS: Tumor wrapped vessels and invasion of the cavernous sinus are important unfavorable prognostic factors for ACM resection. By using appropriate surgical strategies and techniques, ACM can be removed safely via the pterion approach or lateral subfrontal approach with relatively low morbidity and mortality.

Induction of T-cell responses against cutaneous T-cell lymphomas ex vivo by autologous dendritic cells transfected with amplified tumor mRNA.

Sézary syndrome (SzS), the leukemic variant of cutaneous T-cell lymphomas, is incurable. Dendritic cells (DCs) transfected with tumor mRNA can stimulate antitumor immunity in certain cancer patients. In this study, we determined whether mRNAs from Sézary cells could be used for loading DCs and stimulating antitumor immunity. Autologous DCs were generated from monocytes of the peripheral blood from 10 patients with SzS. Total RNA was extracted from Sézary cells and amplified by T7 in vitro transcription. The induction of antitumor IFN-gamma and granzyme B (GrB)-producing cytotoxic T lymphocytes (CTL) by RNA-transfected DCs was determined by ELISPOT assays. We found that IFN-gamma was required for IL-12p70 production by monocyte-derived DCs from SzS. The oncogenic transcription factor Twist and the tyrosine kinase receptor EphA4 were expressed in total RNA from Sézary cells and the paired amplified mRNAs. RNA-transfected DCs induced antitumor IFN-gamma-producing CTLs in 7 of 10 subjects and GrB-producing CTLs in 6 of 9 subjects. Both CD3+CD8+ T cells and CD4+CD25+ T cells were expanded without induction of regulatory T cells. These data support the concept of using tumor mRNA for a vaccine strategy that requires small amounts of tumor cells without need for specific antigens in patients with SzS.