CircBIRC6 facilitates the malignant progression via miR-488/GRIN2D-mediated CAV1-autophagy signal axis in gastric cancer.

Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that play significant roles in tumorigenesis and tumor progression. High-throughput sequencing of gastric cancer (GC) tissues has identified circRNA BIRC6 (circBIRC6) as a potential circRNA derived from the BIRC6 gene, exhibiting significant upregulation in GC tissues. The expression of circBIRC6 is notably elevated in GC patients. Functionally, it acts as a molecular sponge for miR-488, consequently upregulating GRIN2D expression and promoting GC proliferation, migration, and invasion. Moreover, overexpression of circBIRC6 leads to increased GRIN2D expression, which in turn enhances caveolin-1 (CAV1) expression, resulting in autophagy deficiency due to miR-488 sequestration. This cascade of events significantly influences tumorigenesis in vivo. Our findings collectively illustrate that the CircBIRC6-miR-488-GRIN2D axis fosters CAV1 expression in GC cells, thereby reducing autophagy levels. Both circBIRC6 and GRIN2D emerge as potential targets for treatment and independent prognostic factors for GC patients.

Physiological ß-amyloid clearance by the liver and its therapeutic potential for Alzheimer's disease.

Cerebral amyloid-ß (Aß) accumulation due to impaired Aß clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aß is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aß and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aß42 and 8.9% of Aß40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aß receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aß levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aß clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aß burden and cognitive deficits, while enhancing hepatic Aß clearance via LRP-1 overexpression attenuated cerebral Aß deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aß and regulates brain Aß levels, suggesting that a decline of hepatic Aß clearance during aging could be involved in AD development, and hepatic Aß clearance is a novel therapeutic approach for AD.

Serpin Family A Member 1 Is Prognostic and Involved in Immunological Regulation in Human Cancers.

Serpin family A member 1 (SERPINA1) encodes a protease inhibitor participating in many human diseases, but its value in immunoregulation and prognosis of human cancers remains unclear. In this study, through comprehensive analysis of data from The Cancer Genome Atlas (TCGA) datasets, we found that SERPINA1 was dysregulated in many cancers compared with normal tissues. SERPINA1 expression was significantly associated with prognosis, immune subtype, molecular subtype, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), and the estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) score. There was a strong connection between SERPINA1 expression and tumor-infiltrating lymphocytes, and SERPINA1 showed significant relation to gene markers of immune cells in digestive tumors. Fluorescence-based multiplex immunohistochemistry confirmed that SERPINA1 protein expression was related to clinicopathologic features and immune infiltrates in hepatic cancer. This study suggests that SERPINA can potentially serve as a novel biomarker for cancer prognosis and immunotherapy.

NDUFS4 promotes tumor progression and predicts prognosis in gastric cancer.

Gastric cancer ranked third worldwide in terms of mortality. The immediate priority is to search for new prognosticative or therapeutic targets. This research aims to examine the function of the NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) in the malignant phenotype of gastric carcinoma. We analyzed the correlation between NDUFS4 expression and gastric cancer via bioinformatics analysis and cancer tissue microarray via immunohistochemistry. Also, we detected the phenotype change in gastric cancer cells after NDUFS4 was downregulated. NDUFS4's high expression in gastric cancer tissues showed an association with terminal TNM stage and unfavorable survival. Furthermore, downregulation of NDUFS4 decreased gastric cancer cell proliferation, migration and invasion. Nude mouse models revealed that NDUFS4 promotes tumor growth. This investigation highlights the prognostic role of NDUFS4 in gastric cancer. Our results also creatively ascertained NDUFS4 as a candidate for gastric cancer therapeutic targets.

Neurotrophin receptor p75 mediates amyloid ß-induced tau pathology.

Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aß) accumulation. However, the mechanism by which Aß induces tau phosphorylation in neurons remains unclear. Neurotrophin receptor p75 (p75NTR) is a receptor for Aß and mediates Aß neurotoxicity, implying that p75NTR may mediate Aß-induced tau phosphorylation in AD. Here, we showed that Aß-induced tau hyperphosphorylation and neurodegeneration, including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt) mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3ß (GSK3ß) significantly changed Aß/p75NTR-mediated p-tau levels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aß to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aß-induced tau pathology and is a potential druggable target for AD and other tauopathies.

Genome-wide identification of lncRNAs associated with chlorantraniliprole resistance in diamondback moth Plutella xylostella (L.).

BACKGROUND: Long noncoding RNAs (lncRNAs) are now considered important regulatory factors, with a variety of biological functions in many species including insects. Some lncRNAs have the ability to show rapid responses to diverse stimuli or stress factors and are involved in responses to insecticide. However, there are no reports to date on the characterization of lncRNAs associated with chlorantraniliprole resistance in Plutella xylostella. RESULTS: Nine RNA libraries constructed from one susceptible (CHS) and two chlorantraniliprole-resistant P. xylostella strains (CHR, ZZ) were sequenced, and 1309 lncRNAs were identified, including 877 intergenic lncRNAs, 190 intronic lncRNAs, 76 anti-sense lncRNAs and 166 sense-overlapping lncRNAs. Of the identified lncRNAs, 1059 were novel. Furthermore, we found that 64 lncRNAs were differentially expressed between CHR and CHS and 83 were differentially expressed between ZZ and CHS, of which 22 were differentially expressed in both CHR and ZZ. Most of the differentially expressed lncRNAs were hypothesized to be associated with chlorantraniliprole resistance in P. xylostella. The targets of lncRNAs via cis- (<10 kb upstream and downstream) or trans- (Pearson's correlation, r > 0.9 or < -0.9, P < 0.05) regulatory effects were also identified; many of the differently expressed lncRNAs were correlated with various important protein-coding genes involved in insecticide resistance, such as the ryanodine receptor, uridine diphosphate glucuronosyltransferase (UGTs), cytochrome P450, esterase and the ATP-binding cassette transporter. CONCLUSIONS: Our results represent the first global identification of lncRNAs associated with chlorantraniliprole resistance in P. xylostella. These results will facilitate future studies of the regulatory mechanisms of lncRNAs in chlorantraniliprole and other insecticide resistance and in other biological processes in P. xylostella.

Recessive mutation identifies auxin-repressed protein ARP1, which regulates growth and disease resistance in tobacco.

To study the molecular mechanism that underpins crosstalk between plant growth and disease resistance, we performed a mutant screening on tobacco and created a recessive mutation that caused the phenotype of growth enhancement and resistance impairment (geri1). In the geri1 mutant, growth enhancement accompanies promoted expression of growth-promoting genes, whereas repressed expression of defense response genes is consistent with impaired resistance to diseases caused by viral, bacterial, and oomycete pathogens. The geri1 allele identifies a single genetic locus hypothetically containing the tagged GERI1 gene. The isolated GERI1 gene was predicted to encode auxin-repressed protein ARP1, which was determined to be 13.5 kDa in size. The ARP1/GERI1 gene was further characterized as a repressor of plant growth and an activator of disease resistance based on genetic complementation, gene silencing, and overexpression analyses. ARP1/GERI1 resembles pathogen-associated molecular patterns and is required for them to repress plant growth and activate plant immunity responses. ARP1/GERI1 represses growth by inhibiting the expression of AUXIN RESPONSE FACTOR gene ARF8, and ARP1/GERI1 recruits the NPR1 gene, which is essential for the salicylic-acid-mediated defense, to coregulate disease resistance. In conclusion, ARP1/GERI1 is an integral regulator for crosstalk between growth and disease resistance in the plant.

Downregulation of leaf flavin content induces early flowering and photoperiod gene expression in Arabidopsis.

BACKGROUND: Riboflavin is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), essential cofactors for many metabolic enzymes that catalyze a variety of biochemical reactions. Previously we showed that free flavin (riboflavin, FMN, and FAD) concentrations were decreased in leaves of transgenic Arabidopsis plants expressing a turtle riboflavin-binding protein (RfBP). Here, we report that flavin downregulation by RfBP induces the early flowering phenotype and enhances expression of floral promoting photoperiod genes. RESULTS: Early flowering was a serendipitous phenomenon and was prudently characterized as a constant phenotype of RfBP-expressing transgenic Arabidopsis plants in both long days and short days. The phenotype was eliminated when leaf free flavins were brought back to the steady-state levels either by the RfBP gene silencing and consequently nullified production of the RfBP protein, or by external riboflavin feeding treatment. RfBP-induced early flowering was correlated with enhanced expression of floral promoting photoperiod genes and the florigen gene FT in leaves but not related to genes assigned to vernalization, autonomous, and gibberellin pathways, which provide flowering regulation mechanisms alternative to the photoperiod. RfBP-induced early flowering was further correlated with increased expression of the FD gene encoding bZIP transcription factor FD essential for flowering time control and the floral meristem identity gene AP1 in the shoot apex. By contrast, the expression of FT and photoperiod genes in leaves and the expression of FD and AP1 in the shoot apex were no longer enhanced when the RfBP gene was silenced, RfBP protein production canceled, and flavin concentrations were elevated to the steady-state levels inside plant leaves. CONCLUSIONS: Token together, our results provide circumstantial evidence that downregulation of leaf flavin content by RfBP induces early flowering and coincident enhancements of genes that promote flowering through the photoperiod pathway.

Expression of turtle riboflavin-binding protein represses mitochondrial electron transport gene expression and promotes flowering in Arabidopsis.

BACKGROUND: Recently we showed that de novo expression of a turtle riboflavin-binding protein (RfBP) in transgenic Arabidopsis increased H2O2 concentrations inside leaf cells, enhanced the expression of floral regulatory gene FD and floral meristem identity gene AP1 at the shoot apex, and induced early flowering. Here we report that RfBP-induced H2O2 presumably results from electron leakage at the mitochondrial electron transport chain (METC) and this source of H2O2 contributes to the early flowering phenotype. RESULTS: While enhanced expression of FD and AP1 at the shoot apex was correlated with early flowering, the foliar expression of 13 of 19 METC genes was repressed in RfBP-expressing (RfBP+) plants. Inside RfBP+ leaf cells, cytosolic H2O2 concentrations were increased possibly through electron leakage because similar responses were also induced by a known inducer of electron leakage from METC. Early flowering no longer occurred when the repression on METC genes was eliminated by RfBP gene silencing, which restored RfBP+ to wild type in levels of FD and AP1 expression, H2O2, and flavins. Flowering was delayed by the external riboflavin application, which brought gene expression and flavins back to the steady-state levels but only caused 55% reduction of H2O2 concentrations in RfBP+ plants. RfBP-repressed METC gene expression remedied the cytosolic H2O2 diminution by genetic disruption of transcription factor NFXLl and compensated for compromises in FD and AP1 expression and flowering time. By contrast, RfBP resembled a peroxisomal catalase mutation, which augments the cytosolic H2O2, to enhance FD and AP1 expression and induce early flowering. CONCLUSIONS: RfBP-repressed METC gene expression potentially causes electron leakage as one of cellular sources for the generation of H2O2 with the promoting effect on flowering. The repressive effect on METC gene expression is not the only way by which RfBP induces H2O2 and currently unappreciated factors may also function under RfBP+ background.

Plant growth enhancement and associated physiological responses are coregulated by ethylene and gibberellin in response to harpin protein Hpa1.

The harpin protein Hpa1 produced by the bacterial blight pathogen of rice induces several growth-promoting responses in plants, activating the ethylene signaling pathway, increasing photosynthesis rates and EXPANSIN (EXP) gene expression levels, and thereby enhancing the vegetative growth. This study was attempted to analyze any mechanistic connections among the above and the role of gibberellin in these responses. Hpa1-induced growth enhancement was evaluated in Arabidopsis, tomato, and rice. And growth-promoting responses were determined mainly as an increase of chlorophyll a/b ratio, which indicates a potential elevation of photosynthesis rates, and enhancements of photosynthesis and EXP expression in the three plant species. In Arabidopsis, Hpa1-induced growth-promoting responses were partially compromised by a defect in ethylene perception or gibberellin biosynthesis. In tomato and rice, compromises of Hpa1-induced growth-promoting responses were caused by a pharmacological treatment with an ethylene perception inhibitor or a gibberellin biosynthesis inhibitor. In the three plant species, moreover, Hpa1-induced growth-promoting responses were significantly impaired, but not totally eliminated, by abolishing ethylene perception or gibberellin synthesis. However, simultaneous nullifications in both ethylene perception and gibberellin biosynthesis almost canceled the full effects of Hpa1 on plant growth, photosynthesis, and EXP2 expression. Theses results suggest that ethylene and gibberellin coregulate Hpa1-induced plant growth enhancement and associated physiological and molecular responses.

Transgenic expression of a functional fragment of harpin protein Hpa1 in wheat induces the phloem-based defence against English grain aphid.

The harpin protein Hpa1 has multiple beneficial effects in plants, promoting plant growth and development, increasing crop yield, and inducing resistance to pathogens and insect pests. For these effects, the 10-40 residue fragment (Hpa110₋42) isolated from the Hpa1 sequence is 1.3- to 7.5-fold more effective than the full-length protein. Here it is reported that the expression of Hpa110₋42 under the direction of an insect-induced promoter induces the phloem-based defence to English grain aphid, a dominant species of wheat aphids. The expression of Hpa110₋42 was found to compromise the colonization preference of aphids on the plant and further inhibit aphid reproduction in leaf colonies. In Hpa110₋42-expressing wheat lines, moreover, aphid feeding from the phloem was repressed in correlation with the phloem-based defence. This defensive mechanism was shown as enhanced expression of wheat genes encoding phloem lectin proteins (PP2-A1 and PP2-A2) and ß-1,3-glucan synthase-like enzymes (GSL2, GSL10, and GSL12). Both PP2-A and ß-1,3-glucan formed high molecular mass polymers to block phloem sieve plate pores and therefore impede aphid feeding from the phloem. However, the phloem-based defence was impaired by treating plants with ethylene signalling inhibitors, suggesting the requirement for the ethylene signalling pathway. In addition, if Hpa110₋42-expressing plants were subjected to attack by a small number of aphids, they newly acquired agriculturally beneficial characters, such as enhanced vegetative growth and increased tiller numbers and grain output values. These results suggest that the defensive and developmental roles of Hpa110₋42 can be integrated into the germplasm of this agriculturally significant crop.

WSCD2 Expression: Its Relevance to Tumor-Infiltrating Immune Cells and Glioma Prognosis.

BACKGROUND: Patients with glioma have limited treatment options and experience poor prognoses. Therefore, it is urgently needed to explore new diagnostic and therapeutic targets. OBJECTIVE: This study aimed to investigate the relevance of WSC domain-containing 2 (WSCD2) expression to glioma, clinicopathological characteristics, tumor-infiltrating immune cells (TILs), and patient prognosis. METHODS: We analyzed WSCD2 mRNA expression in glioma tissues and patient survival using the Gene Expression Profiling Interactive Analysis database. Furthermore, the relationship between the expressions of WSCD2 mRNA and TILs in gliomas was evaluated utilizing the Tumor Immune Estimation Resource database. Lastly, we employed multiplex immunohistochemistry to detect the protein expressions of WSCD2 and TILs in glioma tissues. RESULTS: WSCD2 mRNA expression in glioma tissues was lower than that in tissues of benign brain disease. High WSCD2 mRNA expression was also significantly associated with a favorable outcome. Additionally, WSCD2 mRNA expression was correlated with TIL expression in glioma; however, no such relationship was detected between the protein expressions of WSCD2 and TILs in glioma tissues. Cox regression multivariate analysis and Kaplan-Meier survival analysis showed that WSCD2 expression in glioma tissues could be an independent prognostic factor. CONCLUSION: This study highlights the correlation between WSCD2 expression and TILs and demonstrates the prognostic significance of WSCD2 in glioma. Furthermore, our results suggest that WSCD2 may be a potential immunotherapy target in glioma.

Chemokine ligand 14 correlates with immune cell infiltration in the gastric cancer microenvironment in predicting unfavorable prognosis.

Objective: Gastric cancer (GC) is the world's third-leading cause of cancer-related mortality; the prognosis for GC patients remains poor in terms of a lack of reliable biomarkers for early diagnosis and immune therapy response prediction. Here, we aim to discover the connection between chemokine ligand 14 (CCL14) expression in the gastric tumor microenvironment (TME) and its clinical significance and investigate its correlation with immune cell infiltration. Methods: We assessed CCL14 mRNA expression and its interrelation with tumor-infiltrating immune cells (TILs) using bioinformatics analysis in gastric cancer. CCL14 protein expression, TILs, and immune checkpoints were detected by multiple immunohistochemistry analyses in gastric cancer tissue microarrays. Then, we conducted statistics analysis to determine the association between CCL14-related patient survival and immune cell infiltration (p < 0.05). Results: We found that the CCL14 protein was separately expressed in the carcinoma cells and TILs in stomach cancer tissues. The CCL14 protein was related to tumor differentiation and tumor depth and positively correlated with the presentation of LAG3 and PD-L1 in gastric cancer cells. In addition, the CCL14 protein in the TILs of gastric cancer tissues was related to Lauren's type cells, T cells (CD4+ and CD8+), and CD68+ macrophages in the TME. Kaplan-Meier survival and multivariate analyses showed that the CCL14 expression in gastric cancer cells was an independent prognostic factor. Conclusion: Our study illustrated that CCL14 is a poor prognosis biomarker in gastric cancer, which may be associated with the potential for immunotherapy.

TTG2-regulated development is related to expression of putative AUXIN RESPONSE FACTOR genes in tobacco.

BACKGROUND: The phytohormone auxin mediates a stunning array of plant development through the functions of AUXIN RESPONSE FACTORs (ARFs), which belong to transcription factors and are present as a protein family comprising 10-43 members so far identified in different plant species. Plant development is also subject to regulation by TRANSPARENT TESTA GLABRA (TTG) proteins, such as NtTTG2 that we recently characterized in tobacco Nicotiana tabacum. To find the functional linkage between TTG and auxin in the regulation of plant development, we performed de novo assembly of the tobacco transcriptome to identify candidates of NtTTG2-regulated ARF genes. RESULTS: The role of NtTTG2 in tobacco growth and development was studied by analyzing the biological effects of gene silencing and overexpression. The NtTTG2 gene silencing causes repressive effects on vegetative growth, floral anthocyanin synthesis, flower colorization, and seed production. By contrast, the plant growth and development processes are promoted by NtTTG2 overexpression. The growth/developmental function of NtTTG2 associates with differential expression of putative ARF genes identified by de novo assembly of the tobacco transcriptome. The transcriptome contains a total of 54,906 unigenes, including 30,124 unigenes (54.86%) with annotated functions and at least 8,024 unigenes (14.61%) assigned to plant growth and development. The transcriptome also contains 455 unigenes (0.83%) related to auxin responses, including 40 putative ARF genes. Based on quantitative analyses, the expression of the putative genes is either promoted or inhibited by NtTTG2. CONCLUSIONS: The biological effects of the NtTTG2 gene silencing and overexpression suggest that NtTTG2 is an essential regulator of growth and development in tobacco. The effects of the altered NtTTG2 expression on expression levels of putative ARF genes identified in the transcriptome suggest that NtTTG2 functions in relation to ARF transcription factors.

KRTCAP2 as an immunological and prognostic biomarker of hepatocellular carcinoma.

Alterations in protein glycosylation affect tumor progression and immune responses in the tumor microenvironment. Keratinocyte-associated protein 2 (KRTCAP2) encodes the corresponding proteins involved in N-glycosylation. The clinical predictive significance and immune role of KRTCAP2 in hepatocellular carcinoma (HCC) largely remain elusive. Combining bioinformatics tools and multiplex immunohistochemistry analysis, we evaluated the KRTCAP2 expression in the HCC tumor microenvironment. The results showed that KRTCAP2 mRNA and protein expression were markedly increased in HCC tissues. Furthermore, high KRTCAP2 expression was an independent predictive factor of unfavorable prognosis in HCC. Moreover, high KRTCAP2 protein expression was associated with a lower proportion of CD8+ T cells and CD68+ macrophages in the stroma region. There was also a lower proportion of CD8+ T cells in the tumor region with high KRTCAP2 protein expression. Specifically, KRTCAP2 expression showed an inverse relationship with programmed cell death ligand-1 in HCC. Analysis of immunophenoscore showed that the low KRTCAP2 expression group had a stronger ability to predict response to immune checkpoint inhibitors. In conclusion, KRTCAP2 had a significant prognostic value for HCC and was correlated with the immune microenvironment. Our findings suggest that KRTCAP2 is a prognostic marker for HCC patients with potential clinical implications for predicting immunotherapeutic responsiveness.

Holistic View of ALK TKI Resistance in ALK-Positive Anaplastic Large Cell Lymphoma.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase expressed at early stages of normal development and in various cancers including ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), in which it is the main therapeutic target. ALK tyrosine kinase inhibitors (ALK TKIs) have greatly improved the prognosis of ALK+ALCL patients, but the emergence of drug resistance is inevitable and limits the applicability of these drugs. Although various mechanisms of resistance have been elucidated, the problem persists and there have been relatively few relevant clinical studies. This review describes research progress on ALK+ ALCL including the application and development of new therapies, especially in relation to drug resistance. We also propose potential treatment strategies based on current knowledge to inform the design of future clinical trials.

KLHDC8A Expression in Association with Macrophage Infiltration and Oxidative Stress Predicts Unfavorable Prognosis for Glioma.

Background: The tumor immune microenvironment (TME) is associated with cancer progression and immune escape. Although KLHDC8A has been reported in glioma in vitro, the expression and clinical significance of this gene in clinical samples are unknown. Methods: The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases were used to evaluate the mRNA expression level of KLHDC8A and its significance in the glioma TME. Tissue microarray-based multiple immunohistochemical staining was conducted to determine KLHDC8A protein levels and characterize the immune signature of tumor-infiltrating immune cells in gliomas. Results: Tumor cells and tumor-associated macrophages expressed KLHDC8A. The expression of KLHDC8A was higher in glioma tissues than in normal brain tissues and was associated with patient clinical characteristics. Gliomas exhibited a high abundance of macrophages, neutrophils, regulatory T cells, and the immune checkpoint PD-L1, as well as high KLHDC8A expression. Cox regression analysis showed that KLHDC8A+CD68+ macrophages and KLHDC8A predicted unfavorable survival in patients with glioma. Finally, protein-protein interaction network analysis showed that the KLHDC8A expression was associated with hypoxia and oxidative stress. Conclusions: KLHDC8A is a potential marker for the clinical diagnosis of glioma. The immune characteristics of macrophages play a crucial role in predicting patients with glioma, providing a new avenue for targeted glioma therapy.

TP53I13 promotes metastasis in glioma via macrophages, neutrophils, and fibroblasts and is a potential prognostic biomarker.

Background: TP53I13 is a protein coding tumor suppression gene encoded by the tumor protein p53. Overexpression of TP53I13 impedes tumor cell proliferation. Nevertheless, TP53I13 role and expression in the emergence and progression of glioma (low-grade glioma and glioblastoma) are yet to be identified. Thus, we aim to use comprehensive bioinformatics analyses to investigate TP53I13 and its prognostic value in gliomas. Methods: Multiple databases were consulted to evaluate and assess the expression of TP53I13, such as the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), GeneMANIA, and Gene Expression Profiling Interactive. TP53I13 expression was further explored using immunohistochemistry (IHC) and multiplex immunohistochemistry (mIHC). Through Gene Set Enrichment Analysis (GSEA), the biological functions of TP53I13 and metastatic processes associated with it were studied. Results: The expression of TP53I13 was higher in tumor samples compared to normal samples. In samples retrieved from the TCGA and CGGA databases, high TP53I13 expression was associated with poor survival outcomes. The analysis of multivariate Cox showed that TP53I13 might be an independent prognostic marker of glioma. It was also found that increased expression of TP53I13 was significantly correlated with PRS type, status, 1p/19q codeletion status, IDH mutation status, chemotherapy, age, and tumor grade. According to CIBERSORT (Cell-type Identification by Estimating Relative Subsets of RNA Transcript), the expression of TP53I13 correlates with macrophages, neutrophils, and dendritic cells. GSEA shows a close correlation between TP53I13 and p53 signaling pathways, DNA replication, and the pentose phosphate pathway. Conclusion: Our results reveal a close correlation between TP53I13 and gliomas. Further, TP53I13 expression could affect the survival outcomes in glioma patients. In addition, TP53I13 was an independent marker that was crucial in regulating the infiltration of immune cells into tumors. As a result of these findings, TP53I13 might represent a new biomarker of immune infiltration and prognosis in patients with gliomas.

Identifying immune cells-related phenotype to predict immunotherapy and clinical outcome in gastric cancer.

Background: The tumor microenvironment is mainly composed of tumor-infiltrating immune cells (TIICs), fibroblast, extracellular matrix, and secreted factors. TIICs are often associated with sensitivity to immunotherapy and the prognosis of multiple cancers, yet the predictive role of individual cells on tumor prognosis is limited. Methods: Based on single-sample gene set enrichment analysis, we combined three Gene Expression Omnibus (GEO) cohorts to build a TIIC model for risk stratification and prognosis prediction. The performance of the TIIC model was validated using our clinical cohort and the TCGA cohort. To assess the predictive power of the TIIC model for immunotherapy, we plotted the receiver operating characteristic curve with the IMvigor210 and GSE135222 cohorts. Results: Chemokines, tumor-infiltrating immune cells, and immunomodulators differed between the two TIIC groups. The TIIC model was vital for predicting the outcome of immunotherapy. In our clinical samples, we verified that the expression levels of PD-1 and PD-L1 were higher in the low TIIC score group than in the high TIIC score group, both in the tumor and stroma. Conclusions: Collectively, the TIIC model could provide a novel idea for immune cell targeting strategies in gastric cancer and predict the survival outcome of patients.

Effects of Chemotherapy on Neuroinflammation, Neuronal Damage, Neurogenesis, and Behavioral Performance in Bone Marrow Transplantation Recipient Mice.

As bone marrow transplant (BMT) is gradually applied to the study of central nervous system (CNS) disease, it is needed to investigate the proper dose of chemotherapy to eradicate bone marrow cells while bringing little damage to brain. In the present study, we established a BMT model with varied busulfan and cyclophosphamide (Bu-Cy) dosages. The recipient mice's chimera rate, neuronal death, neuroinflammation, and behavioral functions were all investigated. Chimerism of peripheral blood cells was shown to rise with Bu-Cy treatment doses, with 60.7% in the Bu(20 mg/kg)/Cy(100 mg/kg) group and 93.0% in the Bu(35 mg/kg)/Cy(100 mg/kg) group. Recipients with Bu(35 mg/kg)/Cy(100 mg/kg) therapy had brain injury, increased neuroinflammation, diminished neurogenesis and cognitive abnormalities, whereas animals given a lesser dosage had no such brain damages. Conclusively, considering the chimerism and the possibility to damage brain, we recommend Bu(20 mg/kg)/Cy(100 mg/kg) is the ideal dose in BMT for studying CNS diseases in the C57/BL6 mouse strain.