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To study the mechanism of the effect of monochromatic light on physiological function in chicken, a total of 192 newly hatched chicks were randomly divided into intact, sham-operated and pinealectomy groups then exposed to white light (WL), red light (RL), green light (GL) and blue light (BL) using a light-emitting diode (LED) system for two weeks. At P14, the hypothalami were immediately collected for immunohistochemical staining of melatonin receptor subtypes (Mel1a and Mel1b) and detection of Mel1a and Mel1b expressions using RT-PCR and western blot. Immunohistochemical staining of the hypothalamus showed that the Mel1a-ir cells were distributed in the preoptic area (POA), nucleus preopticus periventricularis (POP) and suprachiasmatic nuclei (SCN), and the Mel1b-ir cells were presented in the POA and SCN. Analysis of RT-PCR and western blot showed that the mRNA and protein levels of Mel1a and Mel1b in the hypothalamus of chick exposed to GL were increased by 10.7-29.3%, 9.18-35.9% and 8.97-27.3% compared to those in the chicks exposed to WL (P=0.029-0.002), RL (P=0.027-0.001) and BL (P=0.038-0.007) in the intact group, respectively. After pinealectomy, however, these parameters decreased and there were no significant differences among the WL, RL, GL and BL groups. These findings suggested that melatonin plays a critical role in GL illumination-enhanced Mel1a and Mel1b expressions in the hypothalamus of chicks., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Insect defensins are effector components of the innate defense system. During infection, these peptides may play a role in the control of pathogens by providing protective antimicrobial barriers between epithelial cells and the hemocoel. The cDNAs encoding four defensins of the migratory locust, Locusta migratoria, designated LmDEF 1, 3-5, were identified for the first time by transcriptome-targeted analysis. Three of the members of this CSαβ defensin family, LmDEF 1, 3, and 5, were detected in locust tissues. The pro regions of their sequences have little-shared identities with other insect defensins, though the predicted mature peptides align well with other insect defensins. Phylogenetic analysis indicates a completely novel position of both LmDEF 1 and 3, compared to defensins from hymenopterans. The expression patterns of the genes encoding LmDEFs in the fat body and salivary glands were studied in response to immune-challenge by the microsporidian pathogen Nosema locustae and the fungus Metarhizium anisopliae after feeding or topical application, respectively. Focusing on Nosema-induced immunity, qRT-PCR was employed to quantify the transcript levels of LmDEFs. A higher transcript abundance of LmDEF5 was distributed more or less uniformly throughout the fat body along time. A very low baseline transcription of both LmDEFs 1 and 3 in naïve insects was indicated, and that transcription increases with time or is latent in the fat body or salivary glands of infected nymphs. In the salivary glands, expression of LmDEF3 was 20-40-times higher than in the fat body post-microbial infection. A very low expression of LmDEF3 could be detected in the fat body, but eventually increased with time up to a maximum at day 15. Delayed induction of transcription of these peptides in the fat body and salivary glands 5-15 days post-activation and the differential expression patterns suggest that the fat body/salivary glands of this species are active in the immune response against pathogens. The ability of N. locustae to induce salivary glands as well as fat body expression of defensins raises the possibility that these AMPs might play a key role in the development and/or tolerance of parasitic infections., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper, including specific financial interests and relationships and affiliations.

Background: Hepatocellular carcinoma (HCC) is a common gastrointestinal malignancy with a high incidence and poor prognosis. The subunits of the integrator complex (INTS1-14) play a crucial role in regulating genes dependent on RNA Polymerase II, which may be associated with cancer. However, the role of INTSs in HCC remains unclear. This study aims to comprehensively analyze the clinical value and potential role of INTS family genes in HCC through systematic bioinformatics analysis. Methods: We employed various public databases, including UALCAN, HPA, Kaplan–Meier Plotter, GEPIA2, TNMplot, STRING, TIMER, and TISIDB, to investigate the expression levels, clinicopathological correlations, diagnostic and prognostic value, genetic alterations, co-expression network, molecular targets, and immune infiltration of INTSs in HCC. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to investigate the biological functions of genes associated with INTSs. Furthermore, Western blot, real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR), and immunohistochemistry techniques were employed to assess the expression of relevant proteins and genes. The proliferation of HCC cells was evaluated using the CCK8 assay. Results: We found that in HCC, there was a significant upregulation of INTSs at the transcriptional level, particularly INTS1, INTS4, INTS7, and INTS8. Additionally, the protein levels of INTS1 and INTS8 were notably elevated. The overexpression of these INTSs was strongly correlated with tumor stages in HCC patients. INTS1, INTS4, INTS7, and INTS8 exhibited significant diagnostic and prognostic value in HCC. Moreover, their expression was associated with immune infiltrations and activated status, including B cells, CD8 + T cells, CD4 + T cells, NK cells, macrophages, and dendritic cells. Functional predictions indicated that INTS1, INTS4, INTS7, and INTS8 were involved in various cancer-related signaling pathways, such as TRAIL, IFN-gamma, mTOR, CDC42, Apoptosis, and the p53 pathway. Furthermore, we observed a significant upregulation of INTS1, INTS4, INTS7, and INTS8 expression in HCC cell lines compared to normal liver cell lines. The level of INTS1 protein was higher in cancerous tissues compared to adjacent non-cancerous tissues (n = 16), and the suppression of INTS1 resulted in a significant decrease in the proliferation of Huh7 cells. Conclusion: These findings indicate the potential of INTS family genes as diagnostic biomarkers and therapeutic targets in HCC. Further research is needed to understand the underlying mechanisms and explore clinical applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Brainstem gliomas, particularly those with the H3K27M mutation, represent highly aggressive tumors with limited therapeutic avenues. The exploration of tumor cell antigens in this context becomes pivotal to identifying potential treatment targets. Through multiplex immunofluorescence analysis, we unveiled a robust correlation between the widespread expression of the IL13Ra2 membrane antigen in brainstem glioma and the presence of the H3.3K27M antigen. This compelling association underscores the promise of IL13Ra2 as a prime therapeutic target for treating brainstem glioma. The objective of this study was to investigate IL13Ra2 expression in brainstem glioma (BSG) and its correlation with key markers, functions, and prognostic implications, evaluating its therapeutic potential. A total of 80 tumor samples from BSG patients were analyzed. Multiplex immunofluorescence was used to examine six markers—IL13Ra2, H3.3K27M, CD133, Ki67, HLA-1, and CD4—establishing relationships between IL13Ra2 and these markers. Survival analysis, employing Kaplan–Meier and Cox proportional hazard regression models, encompassed 66 patients with complete follow-up. RNA-Seq data from a previously published study involving 98 patients were analyzed using the DESeq2 library to determine differential gene expression between groups. Gene Ontology (GO) enrichment and single-sample gene set enrichment analysis (ssGSEA) via the clusterProfiler library were used to delineate the gene functions of differentially expressed genes (DEGs). Nearly all the BSG patients displayed varying IL13Ra2 expression, with 45.0% (36/80) exhibiting over a 20% increase. Elevated IL13Ra2 levels were notably observed in pontine gliomas, diffuse intrinsic pontine gliomas (DIPGs), H3F3A-mutant gliomas, and WHO IV gliomas. IL13Ra2 expression was strongly correlated with H3.3K27M mutant protein, Ki67, and CD133. Patients with IL13Ra2 expression >20% showed shorter overall survival compared to those with ≤20% IL13Ra2 expression. The Cox proportional hazard regression model identified H3F3A mutations, rather than IL13Ra2 expression, as an independent prognostic factor. Analysis of RNA-Seq data from our prior cohort confirmed IL13Ra2's correlation with H3.3, CD133, and Ki67 levels. Widespread IL13Ra2 expression in BSG, particularly elevated in the H3F3A mutant group, was strongly correlated with H3F3A mutations, increased proliferation, and heightened tumor stemness. IL13Ra2 represents a promising therapeutic target for BSGs, potentially benefiting patients with H3K27M mutations, DIPGs, WHO Grade IV, and pontine location-specific BSGs, particularly those with H3K27M mutations. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is a highly aggressive primary brain tumor with a poor prognosis. This study investigates the therapeutic potential of human Vγ9Vδ2 T cells in GBM treatment. The sensitivity of different glioma specimens to Vγ9Vδ2 T cell-mediated cytotoxicity is assessed using a patient-derived tumor cell clusters (PTCs) model. Methods: The study evaluates the anti-tumor effect of Vγ9Vδ2 T cells in 26 glioma cases through the PTCs model. Protein expression of BTN2A1 and BTN3A1, along with gene expression related to lipid metabolism and glioma inflammatory response pathways, is analyzed in matched tumor tissue samples. Additionally, the study explores two strategies to re-sensitize tumors in the weak anti-tumor effect (WAT) group: utilizing a BTN3A1 agonistic antibody or employing bisphosphonates to inhibit farnesyl diphosphate synthase (FPPS). Furthermore, the study investigates the efficacy of genetically engineered Vγ9Vδ2 T cells expressing Car-B7H3 in targeting diverse GBM specimens. Results: The results demonstrate that Vγ9Vδ2 T cells display a stronger anti-tumor effect (SAT) in six glioma cases, while showing a weaker effect (WAT) in twenty cases. The SAT group exhibits elevated protein expression of BTN2A1 and BTN3A1, accompanied by differential gene expression related to lipid metabolism and glioma inflammatory response pathways. Importantly, the study reveals that the WAT group GBM can enhance Vγ9Vδ2 T cell-mediated killing sensitivity by incorporating either a BTN3A1 agonistic antibody or bisphosphonates. Both approaches support TCR-BTN mediated tumor recognition, which is distinct from the conventional MHC-peptide recognition by αβ T cells. Furthermore, the study explores an alternative strategy by genetically engineering Vγ9Vδ2 T cells with Car-B7H3, and both non-engineered and Car-B7H3 Vγ9Vδ2 T cells demonstrate promising efficacy in vivo, underscoring the versatile potential of Vγ9Vδ2 T cells for GBM treatment. Conclusions: Vγ9Vδ2 T cells demonstrate a robust anti-tumor effect in some glioma cases, while weaker in others. Elevated BTN2A1 and BTN3A1 expression correlates with improved response. WAT group tumors can be sensitized using a BTN3A1 agonistic antibody or bisphosphonates. Genetically engineered Vγ9Vδ2 T cells, i.e., Car-B7H3, show promising efficacy. These results together highlight the versatility of Vγ9Vδ2 T cells for GBM treatment. [ABSTRACT FROM AUTHOR]

Background. As a common disease around the world, esophageal cancer (EC) primarily includes two subclasses: esophageal adenocarcinoma and esophageal squamous cell carcinoma. Mortality has been rising over the years; hence, exploring the mechanism of EC development has become critical. Among the alpha protein kinases, alpha protein kinase 2 (ALPK2) presumably has a connection with EC, but it has never been revealed before. Methods. In this study, IHC analysis was used for ALPK2 expression quantification in ES tissues. TE-1 and Eca-109, which are both human EC cell lines, were used for in vitro analysis of cell proliferation, migration, apoptosis, and colony formation. Results. ALPK2 was found to have an abundant expression within EC tissues (P < 0.001), as well as in the two selected human EC cell lines (P < 0.05). The data showed that ALPK2 depletion suppressed EC cell proliferation, migration, and colony formation, meanwhile stimulating apoptosis (P < 0.001). The in vivo experiments also displayed inhibitory effects caused by ALPK2 depletion on EC tumorigenesis (P < 0.001). It was further validated that ALPK2 depletion made the phosphorylation of Akt and mTOR, as well as CDK6 and PIK3CA levels downregulated (P < 0.001). Mechanistically, we identified integrin alpha 11 (ITGA11) as a downstream gene of ALPK2 regulating EC. More importantly, we found that ITGA11 elevation promoted cell proliferation and migration and rescued the suppression effects caused by ALPK2 depletion (P < 0.001). Conclusions. ALPK2 promotes esophageal cancer via integrin its downstream gene alpha 11; ALPK2 can potentially act as a target for the treatment of EC. [ABSTRACT FROM AUTHOR]

Dysregulation of collagen type XII α1 chain (COL12A1) has been found in several cancer types and could be involved in tumor progression. However, its clinical significance in gastric cancer (GC) remains under exploration. Online databases (Gene Expression Omnibus and UALCAN), reverse transcription-quantitative PCR and immunohistochemistry were utilized in the present study to evaluate the expression of COL12A1 in GC tissues and cell lines. It was found that COL12A1 expression was notably upregulated in GC. Clinicopathological analysis showed that elevated COL12A1 expression was positively correlated with tumor invasiveness, metastasis and advanced clinical stage. The prognostic analysis suggested that high COL12A1 expression contributed to poor overall survival. Multivariate Cox analysis indicated that COL12A1 overexpression was a powerful independent prognostic indicator in patients with GC (hazard ratio, 1.896; 95% CI, 1.267–2.837; P=0.002). The results highlighted the importance of COL12A1 in GC and suggested its potential role as a candidate for clinical outcome prediction and targeted therapy in patients with GC. [ABSTRACT FROM AUTHOR]

Tumor recurrence occurs in more than 70% of ovarian cancer patients, and the majority eventually becomes refractory to treatments. Ovarian Cancer Stem Cells (OCSCs) are believed to be responsible for the tumor relapse and drug resistance. Therefore, eliminating ovarian CSCs is important to improve the prognosis of ovarian cancer patients. However, there is a lack of effective drugs to eliminate OCSCs because the core signaling pathways regulating OCSCs remain unclear. Also it is often hard for biologists to identify a few testable targets and infer driver signaling pathways regulating CSCs from a large number of differentially expression genes in an unbiased manner. In this study, we propose a straightforward and integrative analysis to identify potential core signaling pathways of OCSCs by integrating transcriptome data of OCSCs isolated based on two distinctive markers, ALDH and side population, with regulatory network (Transcription Factor (TF) and Target Interactome) and signaling pathways. We first identify the common activated TFs in two OCSC populations integrating the gene expression and TF-target Interactome; and then uncover up-stream signaling cascades regulating the activated TFs. In specific, 22 activated TFs are identified. Through literature search validation, 15 of them have been reported in association with cancer stem cells. Additionally, 10 TFs are found in the KEGG signaling pathways, and their up-stream signaling cascades are extracted, which also provide potential treatment targets. Moreover, 40 FDA approved drugs are identified to target on the up-stream signaling cascades, and 15 of them have been reported in literatures in cancer stem cell treatment. In conclusion, the proposed approach can uncover the activated up-stream signaling, activated TFs and up-regulated target genes that constitute the potential core signaling pathways of ovarian CSC. Also drugs and drug combinations targeting on the core signaling pathways might be able to eliminate OCSCs. The proposed approach can also be applied for identifying potential activated signaling pathways of other types of cancers. [ABSTRACT FROM AUTHOR]

MicroRNA (miR) signatures may aid the diagnosis and prediction of cancer; therefore, miRs associated with the prognosis of esophageal squamous cell carcinoma (ESCC) were screened. miR‑sequencing (seq) and mRNA‑seq data from early‑stage ESCC samples were downloaded from The Cancer Genome Atlas (TCGA) database, and samples from subjects with a >6‑month survival time were assessed with Cox regression analysis for prognosis‑associated miRs. A further two miR expression datasets of ESCC samples, GSE43732 and GSE13937, were downloaded from the Gene Expression Omnibus database. Common miRs between prognosis‑associated miRs, and miRs in the GSE43732 and GSE13937, datasets were used for risk score calculations for each sample, and median risk scores were applied for the stratification of low‑ and high‑risk samples. A prognostic scoring system of signature miRs was subsequently constructed and used for survival analysis for low‑ and high‑risk samples. Differentially‑expressed genes (DEGs) corresponding to all miRs were screened and functional annotation was performed. A total of 34 prognostic miRs were screened and a scoring system was created using 10 signature miRs (hsa‑miR‑140, ‑33b, ‑34b, ‑144, ‑486, ‑214, ‑129‑2, ‑374a and ‑412). Using this system, low‑risk samples were identified to be associated with longer survival compared with high‑risk samples in the TCGA and GSE43732 datasets. Age, alcohol and tobacco use, and radiotherapy were prognostic factors for samples with different risk scores and the same clinical features. There were 168 DEGs, and the top 20 risk scores positively‑correlated and the top 20 risk scores negatively‑correlated DEGs were significantly enriched for six and 10 functional terms, respectively. ‘Tight junction’ and ‘melanogenesis’ were two significantly enriched pathways of DEGs. miR‑214, miR‑129‑2, miR‑37a and miR‑486 may predict ESCC patient survival, although further studies to validate this hypothesis are required. [ABSTRACT FROM AUTHOR]

To study the mechanism by which monochromatic lights affect the growth of broilers, a total of 192 newly hatched broilers, including the intact, sham-operated and pinealectomy groups, were exposed to white light (WL), red light (RL), green light (GL) and blue light (BL) using a light-emitting diode (LED) system for 2 weeks. The results showed that the GHRH-ir neurons were distributed in the infundibular nucleus (IN) of the chick hypothalamus. The mRNA and protein levels of GHRH in the hypothalamus and the plasma GH concentrations in the chicks exposed to GL were increased by 6.83–31.36%, 8.71–34.52% and 6.76–9.19% compared to those in the chicks exposed to WL ( P = 0.022–0.001), RL ( P = 0.002–0.000) and BL ( P = 0.290–0.017) in the intact group, respectively. The plasma melatonin concentrations showed a positive correlation with the expression of GHRH ( r = 0.960) and the plasma GH concentrations ( r = 0.993) after the various monochromatic light treatments. After pinealectomy, however, these parameters decreased and there were no significant differences between GL and the other monochromatic light treatments. These findings suggest that melatonin plays a critical role in GL illumination-enhanced GHRH expression in the hypothalamus and plasma GH concentrations in young broilers. [ABSTRACT FROM AUTHOR]

The present study aimed to understand the expression characteristics of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2) in individuals of Uygur, Han and Kazak ethnicity with esophageal carcinoma in Xinjiang (China) and their interrelation analysis, and to investigate the expression differences in these genes between esophageal carcinoma and pericarcinoma tissue samples, and between the three ethnic groups. The expression levels of EGFR and VEGFR-2 from 119 pairs of esophageal carcinoma tissue and corresponding pericarcinoma tissue from Uygur, Han and Kazak patients with esophageal carcinoma were detected by immunohistochemistry following surgical resection, and an additional five carcinoma in situ specimens were also tested. The relative expression was analyzed among the ethnic groups and clinicopathological parameters. The positive rate of EGFR in esophageal carcinoma tissue from patients of Uygur, Han and Kazak heritage was 70.73, 68.42 and 67.5%, respectively. For VEGFR-2 the positive rate was 73.17, 68.42 and 67.5%, respectively. No significant difference was detected in their expression between the three ethnic groups (P>0.05); however, EGFR and VEGFR-2 overexpression were correlated with lymph node metastasis (P<0.05). VEGF expression was also correlated with the expression of VEGFR-2 in esophageal carcinoma tissues. EGFR was positive in carcinoma in situ samples, while VEGFR-2 was negative. The overexpression of EGFR is therefore an early event and may have a significant role in the progression of esophageal carcinoma pathogenesis. EGFR overexpression may correlate with the expression of VEGFR-2 in esophageal cancer. These results may aid the early diagnosis of esophageal cancer, and the development of individual target treatment in the future. [ABSTRACT FROM AUTHOR]

ZFPM2, encoding a zinc finger protein and abundantly expressed in the brain, uterus and smooth muscles, plays important roles in cardiac and gonadal development. Abnormal expression of ZFPM2 in ovarian tumors and neuroblastoma has been reported but hitherto its genetic association with cancer and effects on gliomas have not been studied. In the present study, the hexamer insertion-deletion polymorphism rs71305152, located within a large haplotype block spanning intron 1 to intron 3 of ZFPM2, was genotyped in Chinese cohorts of glioma (n = 350), non-glioma cancer (n = 354) and healthy control (n = 463) by direct sequencing and length polymorphism in gel electrophoresis, and ZFPM2 expression in glioma tissues (n = 69) of different grades was quantified by real-time RT-PCR. Moreover, potential natural selection pressure acting on the gene was investigated. Disease-association analysis showed that the overall genotype of rs71305152 was significantly associated with gliomas (P = 0.016), and the heterozygous genotype compared to the combined homozygous genotypes was less frequent in gliomas than in controls (P = 0.005) or non-glioma cancers (P = 0.020). ZFPM2 mRNA expression was negatively correlated with the grades of gliomas (P = 0.002), with higher expression levels in the low-grade gliomas. In the astrocytoma subtype, higher ZFPM2 expression was also correlated with the rs71305152 heterozygous genotype (P = 0.028). In addition, summary statistics tests gave highly positive values, demonstrating that the gene is under the influence of balancing selection. These findings suggest that ZFPM2 is a glioma susceptibility gene, its genotype and expression showing associations with incidence and severity, respectively. Moreover, the balancing selection acting on ZFPM2 may be related to the important roles it has to play in multiple organ development or associated disease etiology. [ABSTRACT FROM AUTHOR]

Retinal ischemic disease is a major type of retinal diseases causing vision loss. Identifying the molecular mechanisms mediating the retinal ischemia-reperfusion (RIR) is the key to targeted intervention. In this study, we performed RNA-seq analysis of the retinal tissues of a retinal ischemia-reperfusion model of Sprague-Dawley (SD) rats, followed by differential gene expression analysis, gene ontology (GO) enrichment analysis, and protein-protein interaction (PPI) analysis. After studying we found that: The major biological processes affected after RIR was the regulation of vascular development. PPI analysis unveiled a regulatory module in which Platelet Derived Growth Factor Receptor Beta (PDGFRB) was upregulated. In the RIR cell model of human retinal microvascular endothelial cells (HRCEC) induced by oxygen-glucose deprivation/reperfusion (OGD/R), silencing PDGFRB at least partially rescued the detrimental effect on cell proliferation and in vitro angiogenic ability. In the rat model of RIR, the administration of PDGFR inhibitor alleviated the damages in the retinal microvascular system. Besides, we further demonstrated the protective effect of procyanidin against RIR induced damages in both the cell and animal model by dampening the overexpression of PDGFRB. Together, our data indicate that the upregulation of PDGFRB contributes to RIR-induced damages in retinal microvascular system, which provides a targetable strategy for therapeutic intervention. • PDGFRB is upregulated in a regulatory module after RIR induction. • PDGFRB overexpression contributes to RIR-induced injury in retinal microvasculature. • Procyanidin protects against RIR-induced damages by dampening PDGFRB expression. [ABSTRACT FROM AUTHOR]

Aims Esophageal cancer ( EC) is one of the most prevalent and deadly cancers worldwide. Along with nutrition, smoking and alcohol consumption, human papillomavirus ( HPV) infection is one of the major risk factors, which is modulated by host immune response. This study is aimed at elucidating how HPV modifies host immune system in the EC pathogenesis. Methods The HPV and HLA- DQB1 levels in primary esophageal squamous cell (ESC) cancer cells from Han, Khazak and Uygur patients were analyzed by quantitative real-time PCR and immunoblotting. The ability of HPV16 E6/E7 to transform normal primary ESCs was investigated by infecting ESC with pMSCVpuro-carried E6 or E7. The shRNA against HPV16 E6 or E7 was delivered by adenovirus into esophageal squamous cell carcinoma ( ESCC) cells with high HPV content. The DNA methylation level of HLA- DQB1 was measured by methylation-specific PCR. Results The HLA- DQB1 expression level was correlated with the levels of HPV and inversely related to DNA methylation level of HLA- DQB1. Overexpressing HPV16 E6 or E7 alone was enough to transform normal primary ESCs. However, single knockdown of either E6 or E7 in ESC cancer cells did not reduce HLA- DQB1 expression. Conclusions Oncogenic HPV E6 and E7 genes promoted ESCC pathogenesis by upregulating susceptible HLA- DQB1 via DNA demethylation. [ABSTRACT FROM AUTHOR]

• Low LINC00645 expression was associated with a high malignancy degree of RCC patients. • LINC00645 inhibited RCC cell proliferation, migration and invasion. • LINC00645 regulated ROCK1 expression by competitively binding to HNRNPA2B1 thus abolishing its protection of ROCK1 mRNA stability. • RCC with lower LINC00645 expression is more sensitive to ROCK1 inhibitors. The lncRNA plays an important role in tumorigenesis and the progression of renal cell carcinoma (RCC). LINC00645 is one of the most different expressed lncRNA between RCC and normal renal tissue. However, the regulatory mechanism of LINC00645 in RCC remains unknown. Our results indicated that LINC00645 inhibited RCC proliferation, migration, and invasion. Mechanistically, HNRNPA2B1 directly bound to ROCK1 mRNA and strengthened its stability. LINC00645 competitively bound to the RRM1 domain, which is responsible for interacting with ROCK1 mRNA, reducing ROCK1 mRNA level by affecting posttranscriptional destabilization. The expression of LINC00645 was significantly reduced in RCC cells, significantly upregulating ROCK1 by abolishing the interaction with HNRNPA2B1, finally promoting RCC proliferation, migration, and invasion. Moreover, RCC cells with lower LINC00645 expression were more sensitive to the ROCK1 inhibitor Y-27632. Our study indicates that decreased expression of LINC00645 promotes the RCC progression via HNRNPA2B1/ROCK1 axis, providing a promising treatment strategy for RCC patients with decreased LINC00645 expression. [ABSTRACT FROM AUTHOR]

Inflammatory reaction of pulp tissue plays a role in the pathogen elimination and tissue repair. The evaluation of severity of pulpitis can serve an instructive function in therapeutic scheme. However, there are many limitations in the traditional evaluation methods for the severity of pulpitis. Based on the Gene Expression Omnibus (GEO) database, our study discovered 843 differentially expressed genes (DEGs) related to pulpitis. Afterwards, we constructed a protein-protein interaction (PPI) network of DEGs and used MCODE plugin to determine the key functional subset. Meanwhile, genes in the key functional subset were subjected to GO and KEGG enrichment analyses. The result showed that genes were mainly enriched in inflammatory reaction-related functions. Next, we screened out intersections of PPI network nodes and pulpitis-related genes. Then, 20 genes were obtained as seed genes. In the PPI network, 50 genes that had the highest correlation with seed genes were screened out using random walk with restart (RWR). Furthermore, 4 pulpitis-related hub genes were obtained from the intersection of the top 50 genes and genes in the key functional subset. Finally, GeneMANIA was utilized to predict genes coexpressed with hub genes, and expression levels of the 4 hub genes in normal and pulpitis groups were analyzed based on GEO data. The result demonstrated that the 4 hub genes were mainly coexpressed with chemokine-related genes and were remarkably upregulated in the pulpitis group. In short, we eventually determined 4 potential biomarkers of pulpitis. [ABSTRACT FROM AUTHOR]

Periodontitis is a growing clinical problem worldwide. Despite various approaches that have been devoted to repairing periodontal defects, the clinical outcomes are still limited due to the decline in tissue regenerative potential after periodontitis. Fortunately, chemically modified mRNA (modRNA)-based therapeutics have emerged as a promising strategy to combat incurable diseases. However, the use of modRNA for treating periodontitis is rare and challenging. Herein, a novel therapeutic mRNA platform that allows for sustained delivery and targeted osteogenesis and cementogenesis was developed for periodontal regeneration by combining a self-assembling PLA-PEG-PLA hydrogel and newly synthesized modRNA encoding amelogenin (AMELX) via in vitro transcription. The thermosensitive PLA-PEG-PLA hydrogel significantly prevented modRNA degradation and prolonged the release of encapsulated modRNA by forming an in situ hydrogel depot at 37 °C, resulting in sustained and strong expression of AMELX in human periodontal ligament stem cells (PDLSCs). Moreover, the AMELX modRNA exhibited a great capacity for promoting osteogenesis and cementogenesis of PDLSCs, as evidenced by elevated alkaline phosphatase (ALP) activity, calcium nodule formation, and osteogenesis- and cementogenesis-related gene expression (e.g., ALP , BMP2 , CAP , BSP , COL1A1). As a result, after a single local injection, the PLA-PEG-PLA hydrogel enabled AMELX modRNA to persist and release at the defect site, thus successfully regenerating bone and periodontal ligament tissues in periodontal defects of rats. These findings provide a new approach for treating periodontal defects using self-assembling hydrogels to enable safe and effective delivery of AMELX modRNA, thereby offering various possibilities for functional tissue reconstruction with mRNA therapeutics. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs which implicated in the progression of cancers. However, the role of circRNA_102231 in lung cancer remains unclear. Gene Expression Omnibus (GEO) datasets were used to investigate aberrantly expressed circRNAs in lung cancer. CircRNA_102231 expression in lung adenocarcinoma (LAC) tissues was dertermined by qRT-PCR. Furthermore, we explored the functions of circRNA_102231 on lung cancer cells progression. In the present study, circRNA_102231 was found to be one of the most significantly upregulated circRNAs in the GEO datasets analysis (GSE101586). QRT-PCR showed that circRNA_102231 expression was significantly upregulated in LAC tissues and associated with the advanced TNM stage, lymph node metastasis, and poor overall survival of lung cancer patients. The area under the receiver operating characteristic curve (ROC) was 0.897. in addition, function assays showed that circRNA_102231 inhibition significantly suppressed lung cancer cells proliferation and invasion ability in vitro. In conclusion, our study demonstrated that circRNA_102231 could act as a potential biomarker and therapeutic target for lung cancer patients. [ABSTRACT FROM AUTHOR]

The economics of bio-solvent production are largely dependent on the cost of the fermentation substrate. Dioscorea zingiberensis C.H. Wright (DZW), the main raw material used to produce saponin, contains 13–18% starch which can be directly saccharified to a saccharification liquid of DZW starch (SLDS) that contains abundant nutrients. In this study, the water-soluble micromolecule compounds in SLDS were quantified through 1 H NMR. Using SLDS as the substrate to conduct ABE fermentation by Clostridium beijerinckii , the fermentation cycle was shortened 24 h, the maximum biomass and consumption rate of the glucose significantly increased, and the productivity of total solvents were increased by 0.244 ± 0.010 g/L/h compared to standard P 2 medium. Expression analysis of genes encoding key enzymes involved in acetone and butanol production and glucose consumption showed that they were induced by SLDS. Taken together, SLDS is a useful and renewable glycosylated solution for ABE fermentation. [ABSTRACT FROM AUTHOR]

The T gene plays a key role in chordoma pathology. To investigate the role of T gene isoforms in chordoma, 22 skull base chordomas, three chordoma cell lines and 9 infant notochords, which were used as normal controls, were collected. We first conducted droplet digital PCR to quantify the absolute expression levels of the long and short isoforms of the T gene (T-long and T-short, respectively) and revealed that T-long was dominantly expressed in all chordomas and chordoma cell lines, but not in the notochords. The T-long/T-short ratio was significantly different between the chordomas and the notochords. Next, we validated the isoform expression pattern at protein expression level using Western blot in 9 chordomas. Furthermore, the T gene single nucleotide polymorphism site rs2305089, which is the only marker reported to be associated with chordomas, was sequenced in all of the chordoma samples. Association between rs2305089 and T-long/T-short ratio was not significant, indicating it was not involved in T gene alternative splicing. In conclusion, two T gene isoforms were investigated in skull base chordomas and chordoma cell lines, and the longer isoform was dominantly expressed. The distinct expression patterns of these T gene isoforms may contribute to the pathogenesis of skull base chordomas. However, further studies on the function of these isoforms are needed. [ABSTRACT FROM AUTHOR]

Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan–Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management. [ABSTRACT FROM AUTHOR]

Objectives To understand the development of sporadic cerebral cavernous malformations (SCCM) comprehensively, we analyzed gene expression profiles in SCCMs by gene microarray. Methods The total number of the specimens collected in our study was 14, 7 of which were SCCMs, and the others were controls that were obtained from normal brain vessels. The total RNA was extracted and hybridized with oligonucleotide array containing 21522 genes. The analysis of Gene Ontology (GO) items and molecular pathways was performed based on the GO and Kyoto Encyclopedia of Genes and Genomes databases. The gene coexpression networks were constructed to identify the core genes regulating the progression of SCCMs. Results A total of 785 probes, showing differentially expressed genes (DEGs) between the 2 groups, were found by the gene chips. According to the analysis based on GO and Kyoto Encyclopedia of Genes and Genomes, 286 GO terms and 53 pathways were identified to be significantly relevant with the DEGs. All differential gene interactions were analyzed and the core genes were selected in the coexpression networks. Conclusions The gene expression profiles obtained from SCCMs were significantly distinct from those of control brain vascular specimens. These DEGs are related to multiple molecular signal pathways, such as the mitogen-activated protein kinase pathway, cytokine-cytokine receptor interaction, focal adhesion, and inflammatory response. According to the analysis of the core genes selected in the gene coexpression networks, we postulated that CSF1R , XCL1 , KCNMB1 , RHOG , and TJP1 might exert enormous functions in the pathogenesis of SCCMs. However, further studies are required to aid in the clinical diagnosis and prevention of SCCMs. [ABSTRACT FROM AUTHOR]