Seipin is involved in oxygen-glucose deprivation/reoxygenation induced neuroinflammation by regulating the TLR3/TRAF3/NF-κB pathway.

Seipin plays a crucial role in lipid metabolism and is involved in neurological disorders. However, the function and mechanism of action of seipin in acute ischemic stroke have not yet been elucidated. Here, we aimed to investigate the effect of seipin on neuroinflammation induced by oxygen-glucose deprivation/reoxygenation (OGD/R) and further explore the molecular mechanism by functional experiments. Our results revealed a significant decrease in seipin mRNA levels, accompanied by enhanced expression of TNF-α in patients with AIS, and a significant negative correlation between seipin and TNF-α was observed. Additionally, there was a negative correlation between seipin levels and the National Institutes of Health Stroke Scale (NIHSS) score. Furthermore, seipin levels were also decreased in middle cerebral artery occlusion/reperfusion (MCAO/R) mice and OGD/R-treated BV2 cells. RNA sequencing analysis showed that seipin knockdown altered the Toll-like receptor 3 (TLR3) signaling pathway. It was further confirmed in vitro that seipin knockdown caused significantly increased secretion of inflammatory factors including TNF-α, interleukin (IL)-1ß, and interferon (IFN)-ß. Meanwhile, seipin knockdown activated the Tlr3 signal pathway while this effect could be reversed by Tlr3 inhibitor in OGD/R treated BV2 cells. Furthermore, neuroinflammation induced by OGD/R was significantly reduced by seipin overexpression. Overall, our study demonstrate that seipin deficiency aggravates neuroinflammation by activating the TLR3/TRAF3/NF-κB signaling pathway after OGD/R stimuli, and suggest that seipin may be a potential therapeutic target for AIS.

The Important Role of Preoperative D-Dimer in Constrictive Pericarditis.

Background: The impact of coagulation indicators on postoperative outcomes of patients with constrictive pericarditis undergoing pericardiectomy has been poorly investigated. This study aimed to assess the prognostic role of preoperative coagulation indicators in these patients. Methods: We retrospectively included 158 patients with constrictive pericarditis undergoing pericardiectomy. The diagnostic values of coagulation indicators for postoperative complications were evaluated by ROC curves. Patients were divided into two groups according to the cutoff value calculated by ROC curve. Postoperative outcomes were compared between the two groups. Logistic regression analysis was performed to identify risk factors of postoperative complications. Results: ROC curve showed that among different coagulation indicators, preoperative D-dimer (DD) level could effectively identify patients with postoperative complications (AUC 0.771, 95% CI 0.696-0.847, P < 0.001). Patients were divided into the low DD group and the high DD group. The comparison of postoperative outcomes suggested that high preoperative DD level was significantly associated with longer durations of vasoactive agents using (P = 0.018), intubation (P = 0.020), ICU stay (P = 0.008), chest drainage (P=0.004) and hospital stay (P = 0.002). Multivariable analysis showed that high preoperative DD level was the independent risk factor of postoperative complications (OR 6.892, 95% CI 2.604-18.235, P < 0.001). Conclusion: High preoperative DD level was significantly linked to poor postoperative outcomes and could provide an effective prediction ability for postoperative complications in patients with constrictive pericarditis.

FOXP3 promote the progression of glioblastoma via inhibiting ferroptosis mediated by linc00857/miR-1290/GPX4 axis.

The oncogenic properties of members belonging to the forkhead box (FOX) family have been extensively documented in different types of cancers. In this study, our objective was to investigate the impact of FOXP3 on glioblastoma multiforme (GBM) cells. By conducting a screen using a small hairpin RNA (shRNA) library, we discovered a significant association between FOXP3 and ferroptosis in GBM cells. Furthermore, we observed elevated levels of FOXP3 in both GBM tissues and cell lines, which correlated with a poorer prognosis. FOXP3 was found to promote the proliferation of GBM cells by inhibiting cell ferroptosis in vitro and in vivo. Mechanistically, FOXP3 not only directly upregulated the transcription of GPX4, but also attenuated the degradation of GPX4 mRNA through the linc00857/miR-1290 axis, thereby suppressing ferroptosis and promoting proliferation. Additionally, the FOXP3 inhibitor epirubicin exhibited the ability to impede proliferation and induce ferroptosis in GBM cells both in vitro and in vivo. In summary, our study provided evidences that FOXP3 facilitates the progression of glioblastoma by inhibiting ferroptosis via the linc00857/miR-1290/GPX4 axis, highlighting FOXP3 as a potential therapeutic target for GBM.

Naringenin Inhibits Acid Sphingomyelinase-Mediated Membrane Raft Clustering to Reduce NADPH Oxidase Activation and Vascular Inflammation.

Macrophage inflammation and oxidative stress promote atherosclerosis progression. Naringenin is a naturally occurring flavonoid with antiatherosclerotic properties. Here, we elucidated the effects of naringenin on monocyte/macrophage endothelial infiltration and vascular inflammation. We found naringenin inhibited oxidized low-density lipoprotein (oxLDL)-induced pro-inflammatory cytokines such as IL-1ß, IL-6, and TNF-α toward an M2 macrophage phenotype and inhibited oxLDL-induced TLR4 (Toll-like receptor 4) membrane translocation and downstream NF-κB transcriptional activity. Results from flow cytometric analysis showed that naringenin reduced monocyte/macrophage infiltration in the aorta of high-fat-diet-treated ApoE-deficient mice. The aortic cytokine levels were also inhibited in naringenin-treated mice. Further, we found that naringenin reduced lipid raft clustering and acid sphingomyelinase (ASMase) membrane gathering and inhibited the TLR4 and NADPH oxidase subunit p47phox membrane recruitment, which reduced the inflammatory response. Recombinant ASMase treatment or overexpression of ASMase abolished the naringenin function and activated macrophage and vascular inflammation. We conclude that naringenin inhibits ASMase-mediated lipid raft redox signaling to attenuate macrophage activation and vascular inflammation.

[Corrigendum] Upregulation of centromere protein M promotes tumorigenesis: A potential predictive target for cancer in humans.

Subsequently to the publication of this paper, the authors' have realized that Fig. 2A on p. 3927 was published featuring an error; specifically, there was an unintentional duplication of one of the representative images chosen for the figure (the same image was selected to represent the 'BRCA/Normal' and 'Tumor/LUSC' experiments). Additionally, the sample numbers in Fig. 2A were also incorrect. The correct sample numbers are as follows: 3 samples of breast tissue, 12 samples of breast cancer tissue, 3 samples of normal cervical tissue, 9 samples of CESC, 7 samples of LIHC, 3 samples of normal lung tissue and 6 samples of LUSC. These errors were due to negligence during the storage of HPA database images.  The revised version of Fig. 2, showing the correct data for the 'Tumor/LUSC' experiment in Fig. 2A (where the error occurred), is shown on the next page. Note that this error did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree to the corrigendum. The authors do stress the importance of a larger sample size to ascertain statistically significant differences in CENPM protein expression, predominantly localized in the cell nucleus. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 3922­3934, 2020; DOI: 10.3892/mmr.2020.11461].

Clinical Significance of Preoperative Pyrazinamide-Containing Therapy in Tuberculous Constrictive Pericarditis.

Background: Tuberculous constrictive pericarditis (TCP) is recommended to be treated with anti-tuberculosis (TB) therapy before pericardiectomy. Whether different preoperative anti-TB regimens may lead to different outcomes is unclear. Methods: We retrospectively collected patients diagnosed as TCP and received pericardiectomy from April 2016 to June 2023. The study patients were assigned into the active TCP (A-TCP) group and the inactive TCP (IA-TCP) group according to the results of Mycobacterium tuberculosis (MTB) culture and MTB RNA assay. Baseline characteristics including anti-TB regimens and surgical outcomes were compared between the two groups. Logistic regression analysis and subgroup analysis were conducted to identify the protective factors of A-TCP. Results: Of the 102 study patients, 24 was in the A-TCP group and 78 was in the IA-TCP group. The rate of preoperative anti-TB regimen containing pyrazinamide was 37.5% in the A-TCP group, as compared with 74.4% in the IA-TCP group (P = 0.001). Multivariate analysis showed that preoperative use of pyrazinamide was the protective factor of A-TCP (OR 0.194, 95% CI 0.053-0.703, P = 0.013). Subgroup analysis based on age also showed consistent findings. In the analyses of surgical outcomes, A-TCP was the independent risk factor of postoperative cardiac complications (OR 4.231, 95% CI 1.317-13.593, P = 0.015) and associated with longer hospital stay (P = 0.004) and higher hospitalization cost (P = 0.001). Conclusion: A strategy involving anti-TB regimen containing pyrazinamide before pericardiectomy was superior to that without pyrazinamide in the patients with TCP. The strategy was associated with lower risk of A-TCP and might lead to better postoperative recovery and cost-effectiveness.

Gastrodin Induces Ferroptosis of Glioma Cells via Upregulation of Homeobox D10.

Gastrodin, the primary bioactive compound found in Gastrodia elata, has been shown to exhibit neuroprotective properties in a range of neurological disorders. However, the precise mechanisms through which gastrodin influences glioma cells remain unclear, and there is a scarcity of data regarding its specific effects. To ascertain the viability of glioma cell lines LN229, U251, and T98, the CCK-8 assay, a colony formation assay, and a 3D culture model were employed, utilizing varying concentrations of gastrodin (0, 5, 10, and 20 µM). Gastrodin exhibited a notable inhibitory effect on the growth of glioma cells, as evidenced by its ability to suppress colony formation and spheroid formation. Additionally, gastrodin induced ferroptosis in glioma cells, as it can increase the levels of reactive oxygen species (ROS) and peroxidized lipids, and reduced the levels of glutathione. Using a subcutaneous tumor model, gastrodin was found to significantly inhibit the growth of the T98 glioma cell line in vivo. Using high-throughput sequencing, PPI analysis, and RT-qPCR, we successfully identified Homeobox D10 (HOXD10) as the principal target of gastrodin. Gastrodin administration significantly enhanced the expression of HOXD10 in glioma cells. Furthermore, treatment with gastrodin facilitated the transcription of ACSL4 via HOXD10. Notably, the inhibition of HOXD10 expression impeded ferroptosis in the cells, which was subsequently restored upon rescue with gastrodin treatment. Overall, our findings suggest that gastrodin acts as an anti-cancer agent by inducing ferroptosis and inhibiting cell proliferation in HOXD10/ACSL4-dependent pathways. As a prospective treatment for gliomas, gastrodin will hopefully be effective.

The effect of adjuvant chemotherapy on survival in node negative colorectal cancer with or without perineural invasion: a systematic review and meta-analysis.

Purpose: It was aimed at assessing the benefits of adjuvant chemotherapy (ACT) for patients with node-negative colorectal cancer (CRC) either with or without perineural invasion (PNI). Methods: We systematically searched PubMed, Cochrane Library, Embase, and Web of Science from database inception through October 1, 2023. Survival outcomes were analyzed using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The methodological quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Heterogeneity for the descriptive meta-analyses was quantified using the I2 statistic. Results: Ten studies included in this review. ACT improved overall survival (OS) (HR 0.52, 95% CI 0.40-0.69) and disease-free survival (DFS) (HR 0.53, 95% CI 0.35-0.82) in PNI + patients but did not affect DFS (HR 1.13, 95% CI 0.72-1.77) in PNI- patients. A disease-specific survival (DSS) benefit with chemotherapy was observed in PNI + (HR 0.76, 95% CI 0.58-0.99) and PNI- patients (HR 0.76, 95% CI 0.57-1.00). And PNI decreased DFS (HR 1.94, 95% CI 1.52-2.47) and OS (HR 1.75, 95% CI 0.96-3.17) in node-negative CRC. Conclusions: In conclusion, chemotherapy appears most beneficial for survival outcomes in node-negative patients with PNI, but may also confer some advantage in those without PNI. Systematic Review Registration: Identifier INPLASY2021120103.

RNA interference of Aspergillus flavus in response to Aspergillus flavus partitivirus 1 infection.

RNA interference (RNAi) is one of the important defense responses against viral infection, but its mechanism and impact remain unclear in mycovirus infections. In our study, reverse genetics and virus-derived small RNA sequencing were used to show the antiviral responses of RNAi components in Aspergillus flavus infected with Aspergillus flavus partitivirus 1 (AfPV1). qRT-PCR revealed that AfPV1 infection induced the expression of the RNAi components in A. flavus compared with noninfected A. flavus. Knock mutants of each RNAi component were generated, but the mutants did not exhibit any obvious phenotypic changes compared with the A. flavus parental strain. However, after AfPV1 inoculation, production of AfPV1 was significantly less than in the parental strain. Furthermore, sporulation was greater in each AfPV1-infected mutant compared with the AfPV1-infected parental A. flavus. We also investigated the sensitivity of virus-free and AfPV1-infected RNAi mutants and the parental strain to cell wall stress, osmotic stress, genotoxic stress, and oxidative stress. The mutants of DCLs and AGOs infected by AfPV1 displayed more changes than RDRP mutants in response to the first three stresses. Small RNA sequencing analysis suggested that AfPV1 infection reduced the number of unique reads of sRNA in A. flavus, although there were many vsiRNA derived from the AfPV1 genome. GO term and KEGG pathway analyses revealed that the functions of sRNA affected by AfPV1 infection were closely related to vacuole production. These results provide a better understanding of the functional role of RNAi in the impact of AfPV1 on the hypovirulence of A. flavus.

Seipin overexpression attenuates cerebral ischemia-reperfusion injury via preventing apoptosis and autophagy.

BACKGROUND: Ischemic cerebrovascular disease (ICVD) is one of three fatal diseases in humans, along with heart disease and malignant tumors. Cerebral ischemia/reperfusion injury (CI/RI) is the primary cause of ICVD. Recently, seipin was reported to be crucial for lipid droplet formation, hepatic steatosis, and axonal atrophy. However, the function and mechanism of seipin in CI/RI has not been explicitly stated. METHODS: Oxygen-glucose deprivation/reoxygenation (OGD/R) hippocampal neuron cell line (HT-22) and middle cerebral artery occlusion (MCAO) in rats were established. The levels of apoptosis- and autophagy-related proteins and seipin were confirmed by western blot. Cell proliferation was assessed with CCK-8, and ischemic infarction and pathological structure were monitored by TTC and H&E staining, and tissue apoptosis was assessed through TUNEL assay. RESULTS: The proliferative activity was decreased, and apoptosis and autophagy pathways could also be induced in the OGD/R HT-22 cells. Seipin overexpression accelerated viability and inhibited apoptosis and autophagy in the OGD/R HT-22 cells. Moreover, the data revealed that seipin overexpression could also attenuate cerebral infarction, apoptosis. Autophagy pathways could be repressed by seipin in the MCAO rats. CONCLUSION: Seipin has a protective role against CI/RI in rats, and its mechanism might be relevant to the suppression of apoptosis and autophagy, suggesting that seipin might be a latent target for CI/RI.

An immune signature to predict the prognosis of ATRX-wildtype glioma patients and guide immune checkpoint blockade therapy.

Immune and stromal cells contribute to glioma progression by infiltrating the tumor microenvironment. We used clinical characteristics, RNA sequencing data and the ESTIMATE algorithm to obtain stromal and immune scores for alpha thalassemia retardation syndrome X-linked (ATRX)-mutation-type (ATRX-mt) and ATRX-wildtype (ATRX-wt) glioma tissues from The Cancer Genome Atlas. To identify specific immune biomarkers of glioma, we compared the gene expression profiles of ATRX-wt glioma tissues with high vs. low immune/stromal scores, and discovered 162 differentially expressed genes. The protein-protein interaction network based on these results contained 80 interacting genes, of which seven (HOXA5, PTPN2, WT1, HOXD10, POSTN, ADAMDEC1 and MYBPH) were identified as key prognostic genes via LASSO and Cox regression analyses. A risk model constructed using the expression of these seven genes could predict survival for ATRX-wt glioma patients, but was ineffective for ATRX-mt patients. T cells and macrophages were more prevalent in low-risk than in high-risk glioma tissues. Immune checkpoint blockade treatment was highly beneficial for patients with low risk scores. High-risk gliomas were predicted to be more sensitive to rapamycin, dasatinib, 5-fluorouracil and gemcitabine. Thus, our model can be used for the diagnosis, prognostic prediction and treatment planning of ATRX-wt glioma patients.

Complete genome sequence of a novel chrysovirus infecting Aspergillus terreus.

A double-stranded RNA (dsRNA) mycovirus was obtained from Aspergillus terreus strain HJ3-26 and designated "Aspergillus terreus chrysovirus 1" (AtCV1). It consists of four dsRNA segments (dsRNA1-4) with lengths of 3612 bp, 3132 bp, 3153 bp, and 3144 bp, respectively. Sequence analysis showed that dsRNA1 encodes an RNA-dependent RNA polymerase (RdRp), dsRNA2 encodes a capsid protein, and both dsRNA3 and dsRNA4 encode hypothetical proteins. Phylogenetic analysis of the RdRp suggested that AtCV1 is a member of a new species of the genus Alphachrysovirus in the family Chrysoviridae. This is the first chrysovirus obtained from A. terreus.

Resveratrol Attenuates the Disruption of Lipid Metabolism Observed in Amyloid Precursor Protein/Presenilin 1 Mouse Brains and Cultured Primary Neurons Exposed to Aß.

To examine whether resveratrol (RSV), an activator of silent mating-type information regulation 2 homolog 1 (SIRT1), can reverse the disruption of lipid metabolism caused by ß-amyloid peptide (Aß), APP/PS1 mice or cultured primary rat neurons were treated with RSV, suramin (inhibitor of SIRT1), ZLN005, a stimulator of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), or PGC-1α silencing RNA. In the brains of the APP/PS1 mice, expressions of SIRT1, PGC-1α, low-density lipoprotein receptor (LDLR) and very LDLR (VLDLR) were reduced at the protein and, in some cases, mRNA levels; while the levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein E (ApoE), total cholesterol and LDL were all elevated. Interestingly, these changes were reversed by administration of RSV, while being aggravated by suramin. Furthermore, activation of PGC-1α, but inhibition of SIRT1, decreased the levels of PCSK9 and ApoE, while increased those of LDLR and VLDLR in the neurons exposed to Aß, and silencing PGC-1α, but activation of SIRT1, did not influence the levels of any of these proteins. These findings indicate that RSV can attenuate the disruption of lipid metabolism observed in the brains of APP mice and in primary neurons exposed to Aß by activating SIRT1, in which the mechanism may involve subsequently affecting PGC-1α.

Recombinant Adenovirus-Mediated HIF-lα Ameliorates Neurological Dysfunction by Improving Energy Metabolism in Ischemic Penumbra After Cerebral Ischemia-Reperfusion in Rats.

Background: Hypoxia inducible factor-1α (HIF-1α) regulates glucose metabolism during ischemia. This study investigated the effect of recombinant adenovirus HIF-1ɑ on neurological function and energy metabolism in a rat cerebral ischemia-reperfusion model. Methods: Rats were divided into four groups: sham-operated (Sham) group, cerebral ischemia-reperfusion (CIR) group, recombinant adenovirus empty vector (Ad) group, and recombinant adenovirus-mediated HIF-1α (AdHIF-1α) group. The AdHIF-1α group and the Ad group were injected with AdHIF-1α and Ad in the lateral ventricle. The mNSS was performed at post-ischemia day 0 (P0) and P1, P14 and P28. At P14, the cerebral infarct volume was compared. At P28, HE staining, Nissl stains and TUNEL staining were performed. The expression of HIF-1α, GLUT1 and PFKFB3 were evaluated by Western Blot and immunohistochemistry. High performance liquid chromatography (HPLC) was used to determine the expression of GLUT1 and PFKFB3, and the level of energy metabolites: ATP, ADP and AMP. Results: mNSS scores in the AdHIF-1α group were consistently lower than those in the CIR and Ad groups from P14 (P < 0.05) and Ad groups (P < 0.05). The cerebral infarct volume was reduced in the AdHIF-1α group compared with that in CIR group and Ad group (P < 0.05). At P28, HE showed better pathological changes in AdHIF-1α group. The number of Nissl bodies was increased in the AdHIF-1α group compared with the CIR and Ad groups (P < 0.05). The number of apoptotic cells in the AdHIF-1α group was fewer than that in the CIR and Ad groups (P < 0.05). The expression of HIF-1α, GLUT1 and PFKFB3 was significantly higher in the AdHIF-1α group compared with the CIR and Ad groups (P < 0.05). The ATP, ADP and AMP in the ischemic penumbra were also higher in the AdHIF-1α group (P < 0.05). Conclusion: HIF-lα promoted neurological function recovery and decreased cerebral infarct volume in rats after cerebral ischemia-reperfusion injury by improving energy metabolism.

Lycorine induces apoptosis of acute myeloid leukemia cells and inhibits triglyceride production via binding and targeting FABP5.

Acute myeloid leukemia (AML) is the most common hematopoietic malignancy with abnormal lipid metabolism. However, currently available information on the involvement of the alterations in lipid metabolism in AML development is limited. In this study, we demonstrate that FABP5 expression facilitates AML cell viability, protects AML cells from apoptosis, and maintains triglyceride production. Our bioinformatics analysis revealed that FABP5 expression was upregulated and correlated with unfavorable overall survival of AML patients. FABP5 expression may be used to distinguish normal and AML with high accuracy. FABP5-based risk score was an independent risk factor for AML patients. AML patients with highly expressed FABP5 predicted resistance to drugs. In vitro study showed that FABP5 expression was remarkably elevated in primary AML blasts and an AML cell line. Silencing FABP5 expression attenuated AML cell viability, reduced triglyceride production and lipid droplet accumulation, and induced apoptosis. We utilized AutoDock online tool to identify lycorine as an FABP5 inhibitor by binding FABP5 at amino acid residues Ile54, Thr56, Thr63, and Arg109. Lycorine treatment downregulated the expression levels of FABP5 and its target PPARγ, impaired AML cell viability, triggered apoptosis, and reduced triglyceride production in AML cells. These results demonstrate that FABP5 is critical for AML cell survival and highlight a novel metabolic vulnerability for AML.

Non­diagnostic electromagnetic navigation bronchoscopy biopsy: Predictive factors and final diagnoses.

The present study aimed to explore the final diagnosis of pulmonary nodules with an initial non-diagnostic result on electromagnetic navigation bronchoscopy (ENB) biopsy and the predictive factors for a non-diagnostic result. A total of 198 nodules from 194 patients that were suspected to be malignant tumors were included in the present study. The initial biopsy pathology results were divided into two groups: The diagnostic group and the non-diagnostic group. The diagnostic group was defined as a successful initial biopsy to obtain a diagnosis, including malignant and benign diagnoses. The non-diagnostic group was defined as a non-specific benign diagnosis, normal lung tissue or an unsuccessful biopsy. Among the 198 nodules, 139 (70.2%) were in the diagnostic group and 59 (29.8%) were in the non-diagnostic group. Predictive factors for a non-diagnostic biopsy included nodule size ≤1.5 cm [odds ratio (OR), 2.05; 95% confidence interval (CI), 1.03-4.09], non-solid nodules (OR, 2.71; 95% CI, 1.33-5.64) and nodules in the left lung (OR, 2.50; 95% CI, 1.27-4.92). Of the 59 non-diagnostic biopsies, 46 were finally confirmed to be malignant by surgery. Notably, non-diagnostic biopsies with non-solid nodules (OR, 7.64; 95% CI, 3.11-18.76) were more likely to be malignant. In conclusion, the predictive factors for a non-diagnostic biopsy were nodule size ≤1.5 cm and non-solid nodules. It was not rare for patients to finally be diagnosed with a malignancy in the non-diagnostic group. Therefore, care should be taken when the results of an ENB are non-diagnostic to prevent misdiagnosis.

TEDC2 correlated with prognosis and immune microenvironment in lung adenocarcinoma.

Tubulin epsilon and delta complex 2 (TEDC2) is a protein coding gene whose functions are poorly identified yet. This study aimed to identify the role of TEDC2 in prognosis and immune microenvironment of lung adenocarcinoma (LUAD). Through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, the mRNA expression of TEDC2 was upregulated in LUAD tissues compared to normal tissues. The protein level of TEDC2 was also higher in LUAD in the Human Protein Atlas. The receiver operating characteristic (ROC) curve showed that high TEDC2 level could distinguish LUAD patients from normal subjects. In addition, the impact of TEDC2 expression on prognosis was evaluated by Kaplan-Meier and Cox regression analyses, and the results suggested that high TEDC2 expression was significantly associated with poor prognosis and was the independent prognostic factor in LUAD. GO and KEGG pathway analyses indicated the co-expressed genes of TEDC2 were mainly related to mitotic cell cycle processes. Importantly, high expression of TEDC2 indicated low infiltration of immune cells, especially dendritic cells and B cells. TEDC2 was also positively correlated with immune checkpoints such as PDCD1, LAG3 and CD276. Taken together, this study preliminarily revealed the clinical significance of TEDC2 in LUAD and provided novel insights into the role of TEDC2 in immune microenvironment.

WTAP regulates autophagy in colon cancer cells by inhibiting FLNA through N6-methyladenosine.

Our study investigated the role of WTAP in colon cancer. We employed experiments including m6A dot blot hybridization, methylated RNA immunoprecipitation, dual-luciferase, and RNA immunoprecipitation to investigate the regulatory mechanism of WTAP. Western blot was performed to analyze the expression of WTAP, FLNA and autophagy-related proteins in cells. Our results confirmed the up-regulation of WTAP in colon cancer and its promoting effect on proliferation and inhibiting effect on apoptosis. FLNA was the downstream gene of WTAP and WTAP-regulated m6A modification led to post-transcriptional repression of FLNA. The rescue experiments showed that WTAP/FLNA could inhibit autophagy. WTAP-mediated m6A modification was confirmed to be crucial in colon cancer development, providing new insights into colon cancer therapy.

The influence of NQO2 on the dysfunctional autophagy and oxidative stress induced in the hippocampus of rats and in SH-SY5Y cells by fluoride.

INTRODUCTION: For investigating the mechanism of brain injury caused by chronic fluorosis, this study was designed to determine whether NRH:quinone oxidoreductase 2 (NQO2) can influence autophagic disruption and oxidative stress induced in the central nervous system exposed to a high level of fluoride. METHODS: Sprague-Dawley rats drank tap water containing different concentrations of fluoride for 3 or 6 months. SH-SY5Y cells were either transfected with NQO2 RNA interference or treated with NQO2 inhibitor or activator and at the same time exposed to fluoride. The enrichment of gene signaling pathways related to autophagy was evaluated by Gene Set Enrichment Analysis; expressions of NQO2 and autophagy-related protein 5 (ATG5), LC3-II and p62, and mammalian target of rapamycin (mTOR) were quantified by Western-blotting or fluorescent staining; and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) assayed biochemically and reactive oxygen species (ROS) detected by flow cytometry. RESULTS: In the hippocampal CA3 region of rats exposed to high fluoride, the morphological characteristics of neurons were altered; the numbers of autophagosomes in the cytoplasm and the levels of NQO2 increased; the level of p-mTOR was decreased, and the levels of ATG5, LC3-II and p62 were elevated; and genes related to autophagy enriched. In vitro, in addition to similar changes in NQO2, p-mTOR, ATG5, LC3 II, and p62, exposure of SH-SY5Y cells to fluoride enhanced MDA and ROS contents and reduced SOD activity. Inhibition of NQO2 with RNAi or an inhibitor attenuated the disturbance of the autophagic flux and enhanced oxidative stress in these cells exposed to high fluoride. CONCLUSION: Our findings indicate that NQO2 may be involved in regulating autophagy and oxidative stress and thereby exerts an impact on brain injury caused by chronic fluorosis.