HIF-1α induced FGF18 alleviates renal ischemia/reperfusion injury via YAP.

Acute kidney injury (AKI) is a devastating clinical condition characterized by an abrupt loss of renal function. The pathophysiology of AKI involves diverse processes and elements, of which survival and regeneration have been established to be significant hallmarks. And early studies have confirmed the fundamental role of FGFs in the regulation of AKI pathology, although the association between FGF18 and AKI still remains elusive. Our study demonstrates a substantial up-regulation of FGF18 in the renal tubules of mice subjected to ischemia. Notably, targeted overexpression of FGF18 effectively mitigates the impairment of kidney function induced by AKI. Mechanistically, FGF18 facilitates cell proliferation and anti-apoptosis in RTECs by enhancing the expression of YAP and facilitating its translocation to the nucleus. Aside from that, we also discovered that the substantial expression of FGF18 under ischemic conditions is HIF-1α dependent. This study aims to uncover the inherent mechanism behind the beneficial effects of FGF18 in attenuating AKI. By doing so, it aims to offer novel insights into the development of therapeutic strategies for AKI.

Clinical utility of multi-row spiral CT in diagnosing hepatic nodular lesions, gastric cancer, and Crohn's disease: a comprehensive meta-analysis.

A retrieval of relevant literature on hepatic nodular lesions, gastric cancer (GC), and Crohn's disease (CD) was conducted from Chinese and English databases. Meta-analysis was performed using Review Manager 5.4 software and the MIDAS package in Stata 18.0. Results from 11 studies comprising 1847 patients were synthesized. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio with 95% confidence intervals were: 0.91 (0.84-0.95), 0.73 (0.65-0.79), 3.30 (2.60-4.30), 0.13 (0.07-0.23), and 26.00 (12.00-53.00), respectively. Significant statistical heterogeneity was found in sensitivity and specificity (P<0.05), with specificity heterogeneity originating from n, type, and mode (P<0.05). Sensitivity and specificity for n, type, object, and mode were non-heterogeneous (P>0.05). The combined AUC from SROC curve analysis of the 11 studies was 0.85. Deeks' funnel plot asymmetry test yielded a p-value of 0.01, indicating potential bias across studies in the diagnostic odds ratio funnel plot. Fagan's nomogram demonstrated that using CT for diagnostic modeling increased the post-test probability of correctly diagnosing hepatic nodular lesions, GC, and CD from 50.00% to 77.00%. Overall, multi-detector CT shows good diagnostic value for hepatic nodular lesions, GC, and CD, supporting its clinical flexibility based on patient-specific considerations.

Valproic acid regulates the miR-155/Jarid2 axis by affecting miR-155 promoter methylation in glioma.

The most frequent primary brain tumor in adults is glioma, yet no effective curative treatments are currently available. Our previous study demonstrated the enhancing effects of JARID2 on glioma sensitivity to TMZ treatment. In this study, miR-155 is predicted to target JARID2. miR-155 is overexpressed in clinical glioma specimens and cell lines. miR-155 overexpression in glioma cells enhances cell viability and represses cell apoptosis. Through targeting, miR-155 inhibits JARID2 expression. miR-155 inhibition inhibits glioma cell viability and enhances cell apoptosis, whereas JARID2 knockdown enhances cell viability and inhibits cell apoptosis; JARID2 knockdown partially reverses miR-155 inhibition effects on glioma phenotypes. miR-155 inhibition reduces but knockdown of JARID2 promotes the tumor formation ability of glioma cells in vivo. Valproic acid (VPA) upregulates JARID2 expression, inhibits glioma cell viability and enhances cell apoptosis. VPA downregulates the expression level of miR-155 by increasing the methylation level of the miR-155 promoter, suggesting that the miR-155/JARID2 axis is implicated in VPA inhibition of glioma cell viability and enhancement of glioma cell apoptosis. This study demonstrates a new mechanism of VPA treatment of gliomas by affecting the miR-155/JARID2 axis, which could be regarded as a new strategy for the prevention and treatment of glioma.

Integrative bioinformatics analysis to identify the effects of circadian rhythm on Crohn's disease.

Background: Crohn's disease (CD) is a multifactorial inflammatory bowel disease characterized by complex aberrant autoimmune disorders. Currently, the involvement of the circadian rhythm in the pathogenesis of CD is unknown. Methods: Bulk and single-cell RNA-seq data and associated clinical data from patients with CD were downloaded from the Gene Expression Omnibus (GEO). Single-sample gene set enrichment analysis was performed to calculate the enrichment score (ES) of circadian rhythm-related genes. Differential expression analysis was used to identify differentially expressed genes. Functional enrichment analysis was used to explore potential disease mechanisms. CIBERSORT was used to estimate immune cell abundance. Single-cell RNA-seq data were analyzed using the R package "Seurat." Results: The ES of circadian rhythm-related genes was lower in the CD tissue than in the normal tissue. Ubiquitin-specific protease 2 (USP2), a circadian rhythm-related gene, was identified as a potential modulator of CD pathogenesis. USP2 expression was reduced in CD and was associated with disease severity. Moreover, the analysis of bulk RNA-seq and single-cell RNA-seq data showed that monocyte and neutrophil abundance was elevated in CD and was negatively correlated with USP2 expression. It should be noted that USP2 expression in acinar cells was negatively correlated with monocyte and neutrophil abundance. Functional enrichment analysis revealed several canonical pathways to be enriched in CD, including the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, cytokine-cytokine receptor interaction, toll-like receptor signaling pathway, and nod-like receptor signaling pathway. Conclusion: Aberrant expression of circadian rhythm-related genes is correlated with CD pathogenesis. USP2 might be related to crosstalk among the different cell types in CD. These findings provide insights into future chronotherapy for CD.

LINC01232 Promotes Metastasis and EMT by Regulating miR-506-5p/PAK1 Axis in Gastric Cancer.

Background: Long non-coding RNA LINC01232 plays an important role in the progression of metastasis in several cancers. However, the function of LINC01232 in gastric cancer is limited. Authors aimed to investigate the role and mechanism of LINC01232 in the metastasis of gastric cancer. Methods: The expression levels and correlation of LINC01232, miR-506-5p, and PAK1 were analyzed by GEPIA or ENCORI, and the abundance of LINC01232 and miR-506-5p was measured in tissues and cells via qRT-PCR, the location of LINC01232 in gastric cells was analyzed by nuclear and cytoplasmic fractionation, while the protein levels of PAK1, E-cadherin and vimentin were additionally quantified by Western blotting. Interactions between LINC01232, miR-506-5p, and PAK1 were detected through luciferase reporter assays, qRT-PCR and Western blotting. Cellular viability was evaluated through CCK8 assays, migration ability was measured by transwell assays, invasion ability was tested by wound healing experiment. Results: LINC01232 was overexpressed in gastric cancer tissues and cells, and mainly located in nucleus. The inhibition of LINC01232 could suppress migration, invasion and EMT of gastric cancer cells. MiR-506-5p was downregulated in gastric cancer tissues and cells. LINC01232 sponged miR-506-5p to accelerate migration and EMT. PAK1 was certified to be a target of miR-506-5p, inhibition of PAK1 could interrupt LINC01232 overexpression-induced migration of gastric cancer cells. Conclusion: The LINC01232/miR-506-5p/PAK1 axis promotes metastasis of gastric cancer cells.

A Red-Emitting COF Ionic Exchanged With Green-Emitting Tb(III) Complex Anion: Synthesis, Characterization, Ratiometric Emission Sensing, and Removal of Picric Acid.

Picric acid (PA) is an important chemical product which has been widely used in dye manufacturing, antiseptics, and pharmaceuticals. Owing to PA's extreme electron-deficient structure, its natural degradation is hard, leading to accumulation in the environment and finally threatening the ecosystem and human health. In this case, PA detection and removal becomes more and more important, concerning environmental protection and human health. In this study, an ionic covalent organic framework (I-COF) was synthesized and modified with a luminescent Tb(III) emitter (Tb(DPA)3 3-, DPA = pyridine-2,6-dicarboxylic acid), via ionic exchange. The resulting composite material (Tb-COF) was fully characterized by geometric analysis, IR, XRD, porosity analysis, SEM/TEM, and elemental analysis. It was found that Tb(DPA)3 3- was loaded into the hexagonal cage in an I-COF host with an ionic exchange ratio of 41%. The as-synthesized Tb-COF showed weak Tb(III) emission and strong red COF emission, after adding PA, Tb(III) emission was increased whereas COF emission weakened greatly, showing sensing behavior. Linear working curves were observed with good selectivity. The sensing mechanism was revealed as follows. PA molecules replaced the [Tb(PDA)3]3- component trapped in Tb-COF, releasing free luminescent [Tb(PDA)3]3-. After incorporating PA in the hexagonal cage, the COF emission was quenched. This sensing mechanism ensured a good selectivity over competing species, including cations, anions, and nitrocompounds. The adsorption and removal performance of I-COF for PA were investigated as well.

A Series of Photosensitizes for Fe3+ in Aqueous Solution and Cells With Colorimetric and Fluorescent Channels: Synthesis and Performance.

Ferrum (Fe) is a widely existing metal element and nearly the most important trace element in living species, including human beings. The design of chemosensors for Fe ions faces issues related to the d-d transition of Fe(II) and Fe(III) ions, which makes them efficient electron trappers and energy quenchers. Most fluorescent dyes cannot afford such d-d quenching, showing emission turn off effect towards both Fe(II) and Fe(III) ions with poor selectivity. As a consequence, the development for Fe with emission turn on effect and good selectivity shall be continued and updated. In this work, three rhodamine-derived chemosensors modified by different lengths of alkyl chains having electron-donating N and O atoms were synthesized and explored for the selective optical sensing of Fe(III). These chemosensors showed colorimetric and fluorescent emission turn on sensing for Fe(III), showing two sensing channels. These chemosensors showed good selectivity, which was assigned to the sieving effect of alkyl chains with electron-donating N and O atoms. The N atom was found to be more effective in associating with Fe(III), compared to the O atom. Their fluorescent cell imaging experiment was carried out to confirm the possibility of being used for cell imaging.

The function and mechanism of the JARID2/CCND1 axis in modulating glioma cell growth and sensitivity to temozolomide (TMZ).

A maximal surgical resection followed by radiotherapy and chemotherapy with temozolomide (TMZ) as the representative agent is the standard therapy for gliomas. However, tumor cell resistance to radiotherapy and chemotherapy leads to poor prognosis and high mortality in patients with glioma. In the present study, we demonstrated that JARID2 was downregulated and CCND1 was upregulated within glioma tissues of different grades and glioma cells. In tissue samples, JARID2 was negatively correlated with CCND1. JARID2 overexpression significantly inhibited glioma cell viability, promoted glioma cell apoptosis upon TMZ treatment, and increased p21, cleaved-PARP, and cleaved-caspase3 in TMZ-treated glioma cells. JASPAR tool predicted the possible binding sites between JARID2 and CCND1 promoter regions; through direct binding to CCND1 promoter region, JARID2 negatively regulated CCND1 expression. Under TMZ treatment, JARID2 overexpression inhibited CCND1 expression, promoted glioma cell apoptosis, and increased p21, cleaved-PARP, and cleaved-caspase3 in glioma cells treated with TMZ; meanwhile, CCND1 overexpression exerted opposite effects on glioma cells treated with TMZ and partially reversed the effects of JARID2 overexpression. In conclusion, JARID2 targets and inhibits CCND1. The JARID2/CCND1 axis modulates glioma cell growth and glioma cell sensitivity to TMZ.