A Model to Predict Prognosis of Renal Cell Clear Cell Carcinoma Based on 3 Angiogenesis-related Long Non-coding RNAs.

Background: Tumor angiogenesis is closely related to the progression of clear cell renal cell carcinoma (ccRCC). Long non-coding RNAs (lncRNAs) regulating angiogenesis could be potential biomarkers for predicting ccRCC prognosis. With this study, we aimed to construct a prognostic model based on lncRNAs and explore its underlying mechanisms. Methods: RNA data and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Angiogenesis-related genes (ARGs) were extracted from the Molecular Signatures database. Pearson correlation and LASSO and COX regression analyses were performed to identify survival-related AR-lncRNAs (sAR-lncRNAs) and construct a prognostic model. The predictive power of the prognostic model was verified according to Kaplan‒Meier curve, receiver operating characteristic (ROC) curve and nomogram analyses. The correlation between the prognostic model and clinicopathological characteristics was assessed via univariate and multivariate analyses. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was subsequently performed to elucidate the mechanisms of the sAR-lncRNAs. In vitro qPCR, immunohistochemistry, migration and invasion assays were conducted to confirm the angiogenic function of sAR-lncRNAs. Results: Three sAR-lncRNAs were used to construct a prognostic model. The model was moderately accurate in predicting 1- , 3- and 5-year ccRCC prognosis, and the risk score according to this model was closely related to clinicopathological characteristics such as T grade and T stage. A nomogram was constructed to precisely estimate the overall survival of ccRCC patients. KEGG enrichment analysis indicated that the MAPK and Notch pathways were highly enriched in high-risk patients. Additionally, we found that the expression of the lncRNAs AC005324.4 and AC104964.4 in the prognostic model was lower in ccRCC cell lines and cancer tissues than in the HK-2 cell line and paracancerous tissues, while the expression of the lncRNA AC087482.1 showed the opposite trend. In a coculture model, knockdown of lncRNA AC005324.4 and lncRNA AC104964.4 significantly promoted the migration and invasion of human umbilical vein endothelial cells (HUVECs), but siR-AC087482.1 transfection alleviated these effects. Conclusions: We constructed a prognostic model based on 3 sAR-lncRNAs and validated its value in clinicopathological characteristics and prognostic prediction of ccRCC patients, providing a new perspective for ccRCC treatment decision making.

AAT resistance-related AC007405.2 and AL354989.1 as novel diagnostic and prognostic markers in prostate cancer.

OBJECTIVE: Prostate cancer (PCa) is the second disease threatening men's health, and anti-androgen therapy (AAT) is a primary approach for treating this condition. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in the development of PCa and the process of AAT resistance. The objective of this study is to utilize bioinformatics methods to excavate lncRNAs association with AAT resistance and investigate their biological functions. METHODS: AAT resistance-related risk score model (ARR-RSM) was established by multivariate Cox analysis. Paired clinical tissue samples of 36 PCa patients and 42 blood samples from patients with PSA over 4 ng/ml were collected to verify the ARR-RSM. In vitro, RT-qPCR, CCK-8 and clone formation assays were displayed to verify the expression and function of AL354989.1 and AC007405.2. RESULTS: Pearson correlation analysis identified 996 lncRNAs were associated with AAT resistance (ARR-LncRs). ARR-RSM was established using multivariate Cox regression analysis, and PCa patients were divided into high-risk and low-risk groups. High-risk patients showed increased expression of AL354989.1 and AC007405.2 had poorer prognoses. The high-risk score correlated with advanced T-stage and N-stage. The AUC of ARR-RSM outperformed tPSA in diagnosing PCa. Silencing of AC007405.2 and AL354989.1 inhibited PCa cells proliferation and AAT resistance. CONCLUSIONS: In this study, we have discovered the clinical significance of AC007405.2 and AL354989.1 in predicting the prognosis and diagnosing PCa patients. Furthermore, we have confirmed their correlation with various clinical features. These findings provide potential targets for PCa treatment and a novel diagnostic and predictive indicator for precise PCa diagnosis.

MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis.

Bicalutamide (BIC) resistance impedes the treatment of prostate cancer (PCa) and seems to involve ferroptosis; however, the underlying mechanism remains unclear. Our study aimed to explore how miR-15b-3p modulates ferroptosis in response to BIC resistance and determine whether the miRNA is suitable for early screening of PCa. Here, we found that PCa tissues had significantly higher miR-15b-3p expression than adjacent normal tissues. Analysis of blood samples in patients who underwent prostate-specific antigen (PSA) screening revealed that miR-15b-3p was a more accurate diagnostic than PSA (miR-15b-3p area under the curve [AUC] = 0.941, PSA AUC = 0.815). In vitro experiments then demonstrated that miR-15b-3p expression was markedly higher in LNCaP, PC-3, and DU145 cells than in RWPE-1 cells. Treatment with BIC decreased miR-15b-3p expression and progressive ferroptosis. Mechanistically, we identified KLF2 as the downstream target of miR-15b-3p. Overexpressing KLF2 facilitated ferroptosis via augmenting MDA and iron concentrations, in turn inhibiting the SLC7A11/GPX4 axis and decreasing GSH concentration. Through modulating ferroptosis, miR-15b-3p mimic and inhibitor weakened and enhanced BIC sensitivity, respectively. Furthermore, BIC treatment limited xenograft tumor volume in vivo, whereas agomir-15b-3p promoted tumor growth, indicating that miR-15b-3p attenuated the tumor-suppressive effects of BIC. Taken together, our results suggested that miR-15b-3p is crucial to BIC resistance, specifically via targeting KLF2 and thereby suppressing ferroptosis. High miR-15b-3p expression in early PCa screening should reflect a higher probability of cancer. In conclusion, miR-15b-3p has strong potential as a screening and diagnostic biomarker with reliable prospects for clinical application. Furthermore, because patients with high miR-15b-3p and low KLF2 expression have a greater risk of BIC resistance and malignant progression, targeting the miRNA and its downstream protein may be a new treatment strategy.

Extracellular vesicles secreted from mesenchymal stem cells ameliorate renal ischemia reperfusion injury by delivering miR-100-5p targeting FKBP5/AKT axis.

The incidence of acute kidney injury (AKI) due to ischemia-reperfusion (IR) injury is increasing. There is no effective treatment for AKI, and because of this clinical challenge, AKI often progresses to chronic kidney disease, which is closely associated with poor patient outcomes and high mortality rates. Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUCMSC-sEVs) play increasingly vital roles in protecting tissue function from the effects of various harmful stimuli owing to their specific biological features. In this study, we found that miR-100-5p was enriched in hUCMSC-sEVs, and miR-100-5p targeted FKBP5 and inhibited HK-2 cell apoptosis by activating the AKT pathway. HK-2 cells that were exposed to IR injury were cocultured with hUCMSC-sEVs, leading to an increase in miR-100-5p levels, a decrease in FKBP5 levels, and an increase in AKT phosphorylation at Ser 473 (AKT-473 phosphorylation). Notably, these effects were significantly reversed by transfecting hUCMSCs with an miR-100-5p inhibitor. Moreover, miR-100-5p targeted FKBP5, as confirmed by a dual luciferase reporter assay. In vivo, intravenous infusion of hUCMSC-sEVs into mice suffering from IR injury resulted in significant apoptosis inhibition, functional maintenance and renal histological protection, which in turn decreased FKBP5 expression levels. Overall, this study revealed an effect of hUCMSC-sEVs on inhibiting apoptosis; hUCMSC-sEVs reduced renal IR injury by delivering miR-100-5p to HK-2 cells, targeting FKBP5 and thereby promoting AKT-473 phosphorylation to activate the AKT pathway. This study provides novel insights into the role of hUCMSC-sEVs in the treatment of AKI.

Luminol-conjugated cyclodextrin biological nanoparticles for the treatment of severe burn-induced intestinal barrier disruption.

Background: The breakdown of intestinal barrier integrity occurs after severe burn injury and is responsible for the subsequent reactions of inflammation and oxidative stress. A new protective strategy for the intestinal barrier is urgently needed due to the limitations of the traditional methods. Recently, the application of nanoparticles has become one of the promising therapies for many inflammation-related diseases or oxidative damage. Herein, we developed a new anti-inflammatory and antioxidant nanoparticle named luminol-conjugated cyclodextrin (LCD) and aimed to evaluate its protective effects in severe burn-induced intestinal injury. Methods: First, LCD nanoparticles, engineered with covalent conjugation between luminol and ß-cyclodextrin (ß-CD), were synthesized and examined. Then a mouse burn model was successfully established before the mouse body weight, intestinal histopathological manifestation, permeability, tight junction (TJ) expression and pro-inflammatory cytokines were determined in different groups. The proliferation, apoptosis, migration and reactive oxygen species (ROS) of intestinal epithelial cells (IECs) were assessed. Intraepithelial lymphocytes (IELs) were isolated and cultured for analysis by flow cytometry. Results: LCD nanoparticle treatment significantly relieved the symptoms of burn-induced intestinal injury in the mouse model, including body weight loss and intestinal permeability abnormalities. Moreover, LCD nanoparticles remarkably recovered the mechanical barrier of the intestine after severe burn, renewed TJ structures, promoted IEC proliferation and migration, and inhibited IEC apoptosis. Mechanistically, LCD nanoparticles dramatically alleviated pro-inflammation factors (tumor necrosis factor-α, IL-17A) and ROS accumulation, which could be highly involved in intestinal barrier disruption. Furthermore, an increase in IL-17A and the proportion of IL-17A+Vγ4+ γδ T subtype cells was also observed in vitro in LPS-treated Vγ4+ γδ T cells, but the use of LCD nanoparticles suppressed this increase. Conclusions: Taken together, these findings demonstrate that LCD nanoparticles have the protective ability to ameliorate intestinal barrier disruption and provide a therapeutic intervention for burn-induced intestinal injury.

Identifying endoplasmic reticulum stress-related genes as new diagnostic and prognostic biomarkers in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers worldwide, and its incidence is increasing every year. Endoplasmic reticulum stress (ERS) caused by protein misfolding has broad and profound effects on the progression and metastasis of various cancers. Accumulating evidence suggests that ERS is closely related to the occurrence and progression of ccRCC. This study aimed to identify ERS-related genes for evaluating the prognosis of ccRCC. Methods: Transcriptomic expression profiles were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), and clinical data were downloaded from the TCGA. First, the differentially expressed genes (DEGs) were analyzed using the limma package, and the DEGs related to ERS (ERS-DEGs) were identified from the GeneCards database. Second, a function and pathway enrichment analysis and a Gene Set Enrichment Analysis (GSEA) were performed. Third, a protein-protein interaction (PPI) network was constructed to identify the hub genes, and a gene-micro RNA (miRNA) network and gene-transcription factor (TF) network were established using the hub genes. Finally, a least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to establish a diagnostic model, and a Cox analysis was used to analyze the correlations between the expression of the characteristic genes and the clinical characteristics. Results: We identified 11 signature genes and established a diagnostic model. Further, the Cox analysis results revealed a correlation between the expression levels of the signature genes and the clinical characteristics. Ultimately, five signature genes (i.e., TNFSF13B, APOL1, COL5A3, and CDH5) were found to be associated with a poor prognosis. Conclusions: This study suggests that TNFSF13B, APOL1, COL5A3, and CDH5 may have potential as prognostic biomarkers in ccRCC and may provide new evidence to support targeted therapy in ccRCC.

Immune characteristics of dedifferentiated retroperitoneal liposarcomas and the reliability of regional samples in evaluating their tumor immune microenvironments.

BACKGROUND: Tumor immunotherapy is a new treatment breakthrough for retroperitoneal liposarcoma (RPLS), which is highly invasive and has few effective treatment options other than tumor resection. However, the heterogeneity of the tumor immune microenvironment (TIME) leads to missed clinical diagnosis and inappropriate treatment. Therefore, it is crucial to evaluate whether the TIME of a certain part of the tumor reliably represents the whole tumor, particularly for very large tumors, such as RPLS. METHODS: We conducted a prospective study to evaluate the TIME in different regions of dedifferentiated RPLS (DDRPLS) by detecting the expressions of markers such as CD4+, CD8+, Foxp3+, CD20+, CD68+, LAMP3+, PD-1+ tumor-infiltrating lymphocytes (TILs), and PD-L1 in tumors and corresponding paratumor tissues via immunohistochemistry and RNA sequencing. RESULTS: In DDRPLS, very few TILs were observed. Differentially expressed genes were significantly enriched in cell part and cell functions, as well as the metabolic pathway and PI3K-Akt signaling pathway. In addition, for most tumors (70-80%), the TIME was similar in different tumor regions. CONCLUSIONS: For most tumors (70-80%), the TIME in any region of the tumor reliably represents the whole tumor. DDRPLS may regulate cell functions by modulating the metabolic and PI3K-Akt signaling pathways to promote its malignant behavior.

Copy number variation of the restorer Rf4 underlies human selection of three-line hybrid rice breeding.

Cytoplasmic male sterility (CMS) lines are important for breeding hybrid crops, and utilization of CMS lines requires strong fertility restorer (Rf) genes. Rf4, a major Rf for Wild-Abortive CMS (CMS-WA), has been cloned in rice. However, the Rf4 evolution and formation of CMS-WA/Rf system remain elusive. Here, we show that the Rf4 locus emerges earlier than the CMS-WA gene WA352 in wild rice, and 69 haplotypes of the Rf4 locus are generated in the Oryza genus through the copy number and sequence variations. Eight of these haplotypes of the Rf4 locus are enriched in modern rice cultivars during natural and human selections, whereas non-functional rf4i is preferentially selected for breeding current CMS-WA lines. We further verify that varieties carrying two-copy Rf4 haplotype have stronger fertility restoration ability and are widely used in three-line hybrid rice breeding. Our findings increase our understanding of CMS/Rf systems and will likely benefit crop breeding.

Nitrogen addition stimulates N2O emissions via changes in denitrification community composition in a subtropical nitrogen-rich forest.

Microbially driven nitrification and denitrification play important roles in regulating soil N availability and N2O emissions. However, how the composition of nitrifying and denitrifying prokaryotic communities respond to long-term N additions and regulate soil N2O emissions in subtropical forests remains unclear. Seven years of field experiment which included three N treatments (+0, +50, +150 kg N ha-1 yr-1; CK, LN, HN) was conducted in a subtropical forest. Soil available nutrients, N2O emissions, net N mineralization, denitrification potential and enzyme activities, and the composition and diversity of nitrifying and denitrifying communities were measured. Soil N2O emissions from the LN and HN treatments increased by 42.37% and 243.32%, respectively, as compared to the CK. Nitrogen addition significantly inhibited nitrification (N mineralization) and significantly increased denitrification potentials and enzymes. Nitrification and denitrification abundances (except nirK) were significantly lower in the HN, than CK treatment and were not significantly correlated with N2O emissions. Nitrogen addition significantly increased nirK abundance while maintaining the positive effects of denitrification and N2O emissions to N deposition, challenging the conventional wisdom that long-term N addition reduces N2O emissions by inhibiting microbial growth. Structural equation modeling showed that the composition, diversity, and abundance of nirS- and nirK-type denitrifying prokaryotic communities had direct effects on N2O emissions. Mechanistic investigations have revealed that denitrifier keystone taxa transitioned from N2O-reducing (complete denitrification) to N2O-producing (incomplete denitrification) with increasing N addition, increasing structural complexity and diversity of the denitrifier co-occurrence network. These results significantly advance current understanding of the relationship between denitrifying community composition and N2O emissions, and highlight the importance of incorporating denitrifying community dynamics and soil environmental factors together in models to accurately predict key ecosystem processes under global change.

[Risk modeling based on HER-2 related genes for bladder cancer survival prognosis assessment].

OBJECTIVE: To investigate the correlation between the human epidermal growth factor receptor-2-related genes (HRGs) and survival prognosis of bladder cancer and to construct a predictive model for survival prognosis of bladder cancer patients based on HRGs. METHODS: HRGs in bladder cancer were found by downloading bladder tumor tissue mRNA sequencing data and clinical data from the cancer genome atlas (TCGA), downloading HER-2 related genes from the molecular signatures database (MsigDB), and crossing the two databases. Further identifying HRGs associated with bladder cancer survival (P < 0.05) by using single and multi-factor Cox regression analysis and constructing HRGs risk score model (HRSM), the bladder cancer patients were categorized into high-risk and low-risk groups accor-ding to the median risk score. Survival analysis of the patients in high- and low-risk groups was conducted using R language and correlation of HRGs with clinical characteristics. A multi-factor Cox regression analysis was used to verify the independent factors affecting the prognosis of the patients with bladder cancer. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of HRSM was calculated, and a nomogram was constructed for survival prediction of the bladder cancer patients. Analysis of HRSM and patient immune cell infiltration correlation was made using the TIMER database. RESULTS: A total of 13 HRGs associated with patient survival were identified in this study. Five genes (BTC, CDC37, EGF, PTPRR and EREG) were selected for HRSM by multi-factor Cox regression analysis. The 5-year survival rate of the bladder cancer patients in the high-risk group was significantly lower than that of the patients in the low-risk group. High expression of PTPRR was found to be significantly and negatively correlated with tumor grade and stage by clinical correlation analysis, while EREG was found to be the opposite; Increased expression of EGF was associated with high grade, however, the high expression ofCDC37showed the opposite result. And no significant correlation was found between BTC expression and clinical features. Correlation analysis of HRSM with immune cells revealed a positive correlation between risk score and infiltration of dendritic cells, CD8+T cells, CD4+T cells, neutrophils and macrophages. CONCLUSION: HRGs have an important role in the prognosis of bladder cancer patients and may serve as new predictive biomarkers and potential targets for treatment.

Small extracellular vesicles delivering lncRNA WAC-AS1 aggravate renal allograft ischemia‒reperfusion injury by inducing ferroptosis propagation.

Ferroptosis is a predominant contributor to renal ischemia reperfusion injury (IRI) after kidney transplant, evoking delayed graft function and poorer long-term outcomes. The wide propagation of ferroptosis among cell populations in a wave-like manner, developing the "wave of ferroptosis" causes a larger area of tubular necrosis and accordingly aggravates renal allograft IRI. In this study, we decipher a whole new metabolic mechanism underlying ferroptosis and propose a novel spreading pathway of the "wave of ferroptosis" in the renal tissue microenvironment, in which renal IRI cell-secreted small extracellular vesicles (IRI-sEVs) delivering lncRNA WAC-AS1 reprogram glucose metabolism in adjacent renal tubular epithelial cell populations by inducing GFPT1 expression and increasing hexosamine biosynthesis pathway (HBP) flux, and consequently enhances O-GlcNAcylation. Additionally, BACH2 O-GlcNAcylation at threonine 389 in renal tubular epithelial cells prominently inhibits its degradation by ubiquitination and promotes importin α5-mediated nuclear translocation. We present the first evidence that intranuclear BACH2 suppresses SLC7A11 and GPX4 transcription by binding to their proximal promoters and decreases cellular anti-peroxidation capability, accordingly facilitating ferroptosis. Inhibition of sEV biogenesis and secretion by GW4869 and knockout of lncRNA WAC-AS1 in IRI-sEVs both unequivocally diminished the "wave of ferroptosis" propagation and protected against renal allograft IRI. The functional and mechanistic regulation of IRI-sEVs was further corroborated in an allograft kidney transplant model and an in situ renal IRI model. In summary, these findings suggest that inhibiting sEV-mediated lncRNA WAC-AS1 secretion and targeting HBP metabolism-induced BACH2 O-GlcNAcylation in renal tubular epithelial cells may serve as new strategies for protecting against graft IRI after kidney transplant.

The conscious processing of emotion in depression disorder: a meta-analysis of neuroimaging studies.

Background: Depression is generally accompanied by a disturbed conscious processing of emotion, which manifests as a negative bias to facial/voice emotion information and a decreased accuracy in emotion recognition tasks. Several studies have proved that abnormal brain activation was responsible for the deficit function of conscious emotion recognition in depression. However, the altered brain activation related to the conscious processing of emotion in depression was incongruent among studies. Therefore, we conducted an activation likelihood estimation (ALE) analysis to better understand the underlying neurophysiological mechanism of conscious processing of emotion in depression. Method: Electronic databases were searched using the search terms "depression," "emotion recognition," and "neuroimaging" from inceptions to April 10th, 2023. We retrieved trials which explored the neuro-responses of depressive patients to explicit emotion recognition tasks. Two investigators independently performed literature selection, data extraction, and risk of bias assessment. The spatial consistency of brain activation in conscious facial expressions recognition was calculated using ALE. The robustness of the results was examined by Jackknife sensitivity analysis. Results: We retrieved 11,365 articles in total, 28 of which were included. In the overall analysis, we found increased activity in the middle temporal gyrus, superior temporal gyrus, parahippocampal gyrus, and cuneus, and decreased activity in the superior temporal gyrus, inferior parietal lobule, insula, and superior frontal gyrus. In response to positive stimuli, depressive patients showed hyperactivity in the medial frontal gyrus, middle temporal gyrus, and insula (uncorrected p < 0.001). When receiving negative stimuli, a higher activation was found in the precentral gyrus, middle frontal gyrus, precuneus, and superior temporal gyrus (uncorrected p < 0.001). Conclusion: Among depressive patients, a broad spectrum of brain areas was involved in a deficit of conscious emotion processing. The activation of brain regions was different in response to positive or negative stimuli. Due to potential clinical heterogeneity, the findings should be treated with caution. Systematic review registration: https://inplasy.com/inplasy-2022-11-0057/, identifier: 2022110057.

Evaluation of risk factors, treatment options, and prognostic-related factors in patients with benign ureteral strictures: An 8-year single-center experience.

OBJECTIVES: To investigate the etiology, therapeutic effect, and prognosis-related factors of benign ureteral strictures. METHODS: We analyzed the date of 142 patients with benign ureteral strictures from 2013 to 2021. Ninety-five patients received endourological treatment and 47 patients underwent reconstruction. Preoperative, intraoperative, and postoperative information were compared and analyzed. Symptomatic improvement and radiographic blockage alleviation defined therapeutic success. RESULTS: Stone-related factors caused 85.2% of cases. The overall success rate of endourological treatment was 51.6% versus 95.7% of reconstruction (p < 0.01). However, endourological treatment was better in terms of postoperative hospital stay time, operation time, and intraoperative blood loss (p < 0.001). In endourological group, patients with stricture length ≤2 cm, mild-to-moderate hydronephrosis, proximal or distal stricture had a higher success rate. Multivariate regression analysis showed that the surgical method was the only independent risk factor affecting success and recurrence. Reconstruction success rate was higher than endourological treatment (p = 0.001, OR 0.057, 95% CI (0.011-0.291)), and recurrence rate was also lower (p = 0.001, HR 0.074, 95% CI (0.016-0.338)). No obvious recurrence was seen in reconstruction, and the median recurrence time in endourological treatment was 51 months. CONCLUSIONS: Stone-related factors are an important cause of benign ureteral strictures. Reconstruction is the gold standard treatment due to its high success rate and low recurrence rate. Endourological therapy is also preferred as the initial treatment in proximal or distal ureter with length ≤2 cm and mild-to-moderate hydronephrosis. Further close follow-up is required after treatment.

A novel hypoxia-related lncRNA risk score model for prognosis evaluation of clear cell renal cell carcinoma.

BACKGROUND: Renal cell carcinoma is the most common aggressive tumor of the genitourinary system. The main pathological subtype is clear cell renal cell carcinoma (ccRCC), and its treatment options are very limited. Therefore, identifying specific biomarkers of ccRCC is of great significance for diagnosis and prognosis. METHODS: First, we obtained transcriptome data and clinical data of 611 patients with renal clear cell carcinoma to analyze the relationship between hypoxia-related lncRNAs and overall survival (OS). We screened hypoxia-related lncRNAs through Pearson correlation and Cox regression analysis. Univariate and multivariate regression analysis were applied to assess survival-related risk factors. According to the median risk score, patients were divided into two groups. Next, a nomogram map was built, and GSEA was used for gene function annotation. RT-qPCR, Western Blot, and Flow Cytometry were used to determine the role of SNHG19 in RCC cells. RESULTS: By analyzing the co-expression of hypoxia genes and lncRNAs, 310 hypoxia-related genes were obtained. Four sHRlncRs (AC011445.2, PTOV1-AS2, AP004609.3, and SNHG19) with the highest prognostic values were included in the group to construct the HRRS model. The high-risk group had a shorter OS than the low-risk group. HRRS was considered to be an independent prognostic factor and associated with OS. The two groups showed different pathways in GSEA. Experiments showed that SNHG19 plays essential roles in the autophagy and apoptosis of RCC cells. CONCLUSION: We constructed and validated a hypoxia-related lncRNA model for ccRCC patients. This study also provides new biomarkers for the poor prognosis of ccRCC patients.

Establishing a prognostic model based on five starvation-related long non-coding RNAs for clear cell renal cell carcinoma.

BACKGROUND: Starvation-induced tumor microenvironment significantly alters genetic profiles including long non-coding RNAs (lncRNAs), further regulating the malignant biological characteristics (invasion and migration) of clear cell renal cell carcinoma (ccRCC). METHODS: Transcriptome RNA-sequencing data of 539 ccRCC tumors and 72 normal tissues were acquired from the TCGA and paired clinical samples of 50 ccRCC patients. In vitro experiments, such as qPCR, migration and invasion assays were applied to reveal the clinical relevance of LINC-PINT, AC108449.2 and AC007637.1. RESULTS: 170 lncRNAs were verified as starvation-related lncRNAs (SR-LncRs), of which 25 lncRNAs were associated with overall survival in ccRCC patients. Furthermore, a starvation-related risk score model (SRSM) was built based on the expression levels of LINC-PINT, AC108449.2, AC009120.2, AC008702.2 and AC007637.1. ccRCC patients with high level of LINC-PINT expression were divided into high-risk group and led to higher mortality, but AC108449.2 and AC007637.1 were contrary. Analogously, LINC-PINT was highly expressed in ccRCC cell lines and tumor tissues, especially in patients with advanced stage, T-stage and M-stage, while AC108449.2 and AC007637.1 showed the opposite results. In addition, the increased levels of AC108449.2 and AC007637.1 were significantly correlated with grade. Silencing LINC-PINT reduced the invasion and migration characteristics of ccRCC cells. SiR-AC108449.2 and siR-AC007637.1 enhanced the ability of invasion and migration in ccRCC cells. CONCLUSIONS: In this study, we find the clinical significance of LINC-PINT, AC108449.2 and AC007637.1 in predicting the prognosis of ccRCC patients and verify their correlation with various clinical parameters. These findings provide an advisable risk score model for ccRCC clinical decision-making.

The effect of antibiotic prophylaxis on the incidence of surgical site infection after laparoscopic appendectomy for chronic appendicitis.

Background: The guidelinesthat specify whether antibiotic prophylaxis should be administered before laparoscopic clean-contaminated wound to prevent postoperative surgical site infection (SSI) need to be improved. Studies have shown that elective laparoscopic cholecystectomy with clean-contaminated wound does not require antibiotic prophylaxis. However, there are no studies on the effect of antibiotic prophylaxis on SSI after laparoscopic appendectomy for chronic appendicitis (LCA), which is a clean-contaminated wound. Methods: We conducted a single-center, double-blind, randomized controlled clinical trial. A total of 106 effective patients were randomly divided into the antibiotic group and saline group. Cefuroxime or clindamycin was administered intravenously in the antibiotic group (n = 52). Saline (0.9%) was administered intravenously in the saline group (n = 54). Interventions were administered as a single dose 30 min before surgery. Results: Among the 106 effective patients (median age, 37 years old [IQR, 25-45]; females, 77 [72.6%]), there were 6 cases (5.70%) of SSI: 3 cases (5.56%) in the saline group and 3 cases (5.70%) in the antibiotic group (OR = 1.00, [95% CI (0.20-5.4)], P = 0.96). There were no significant differences in the clinical outcomes of anal exhaust time, postoperative complications, and the symptom of primary abdominal pain between the two groups. Conclusion: For patients with chronic appendicitis undergoing laparoscopic appendectomy, preoperative intravenous antibiotic prophylaxis did not reduce the risk of SSI within 30 days of the surgery compared to the saline group. Trial registration: Registration number of China Clinical Trials Registration Center: ChiCTR2100048336.

Human Umbilical Cord Mesenchymal Stem Cells Protect against Renal Ischemia-Reperfusion Injury by Secreting Extracellular Vesicles Loaded with miR-148b-3p That Target Pyruvate Dehydrogenase Kinase 4 to Inhibit Endoplasmic Reticulum Stress at the Reperfusion Stages.

Renal ischemia-reperfusion (I/R) injury is a leading cause of acute kidney injury (AKI), with high mortality. Recent studies have reported that human umbilical cord mesenchymal stem cells (HucMSCs) play an important role in repairing organ and tissue injuries because of their unique characteristics. However, the potential of HucMSC extracellular vesicles (HucMSC-EVs) to promote the repair of renal tubular cells remains to be explored. This study found that HucMSC-EVs derived from HucMSCs played a protective role and were associated with kidney I/R injury. We found that miR-148b-3p in HucMSC-EVs had a protective effect against kidney I/R injury. HK-2 cells overexpressing miR-148b-3p were protected against I/R injury by inhibiting apoptosis. Next, the target mRNA of miR-148b-3p was predicted online, and the target mRNA, pyruvate dehydrogenase kinase 4 (PDK4), was identified and verified using dual luciferase. We discovered that I/R injury significantly increased endoplasmic reticulum (ER) stress, whereas siR-PDK4 inhibited these effects and protected against I/R injury. Interestingly, after administrating HucMSC-EVs to HK-2 cells, PDK4 expression and ER stress induced by I/R injury were significantly inhibited. HK-2 ingested miR-148b-3p from HucMSC-EVs, and its ER induced by I/R injury was significantly deregulated. This study suggests that HucMSC-EVs protect kidneys from I/R injury during the early I/R stage. These results suggest a new mechanism for HucMSC-EVs in treating AKI and provide a new treatment strategy for I/R injury.

miR-383-5p serves as a tumor suppressor in bladder cancer by suppressing PI3K/AKT signaling pathway.

BACKGROUND: MicroRNAs have been proven to be key molecules in human malignancy. However, to our knowledge, there is no study reporting miR-383-5p expression level and the role it plays in bladder cancer (BC). METHODS: We identified miR-383-5p to be one of the tumor-suppressing genes through using data from The Cancer Genome Atlas (TCGA) and GEO database. We evaluate the expression and activity of miR-383-5p in both BC tissue and cell lines. The impacts of miR-383-5p on proliferative, migratory ability and apoptotic rate in BC cell were evaluated by utilizing CCK-8 kits, flow cytometry, and Transwell assays. qRT-PCR, western blot, and luciferase reporter assays have been adopted to investigate the underlying mechanisms. In vivo tumorigenicity testing was conducted to determine the impact of miR-383-5p on BC cellular proliferative capacity. RESULTS: Reduced miR-383-5p expression has been determined in BC tissue than in normal bladder tissue. Furthermore, BC cell proliferative, migratory ability was inhibited while apoptosis enhanced in vitro and in vivo by miR-383-5p up-regulation. In vitro and in vivo, silencing miR-383-5p considerably improved the growth and invasive capacity of cell, while decreased the apoptotic rates of BC cells. CONCLUSION: miR-383-5p plays its role as a tumor-suppressing gene by suppressing the PI3K/AKT signaling, hence preventing the development of BC.

Survival prediction among pathologic T4 bladder cancer patients following cytoreductive cystectomy: A retrospective single-center study.

Objectives: This retrospective study aimed to describe our institutional experience with cytoreductive cystectomy (Cx) in patients with pathological T4 (pT4) bladder cancer (BCa) and to investigate the clinicopathologic factors that can predict patient survival outcomes. Methods: We reviewed the baseline demographics, clinicopathologic features, perioperative complications, and follow-up data of 44 patients who underwent Cx for pT4 BCa at our institution between 2013 and 2021. The Kaplan-Meier curve and the log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analyses were performed using the Cox regression model. Results: The median age of the patients was 68 years [95% confidence interval (CI) 49-81]. Overall, 21 patients (47.7%) were estimated to have a high age-adjusted Charlson comorbidity index (ACCI) score (>4), and nine patients (20.5%) had pT4b substage BCa. None of the patients died of complications within 30-90 days after surgery. Severe complications occurred in 16% (n = 7) of patients within 30-90 days. During a median follow-up of 51 months, disease progression was detected in 25 patients (56.8%), and 29 patients (65.9%) died of any cause. The median PFS and OS were 15.0 and 21.0 months, respectively. The Kaplan-Meier analysis indicated that patients with high ACCI scores or pT4b BCa had worse PFS (P = 0.003 and P = 0.002, respectively) and OS (P = 0.016 and P = 0.034, respectively) than those with low ACCI scores or pT4a BCa. On multivariate analysis, pT4b substage [hazard ratio (HR), 4.166; 95% CI, 1.549-11.206; P = 0.005] and ACCI score >4 (HR, 2.329; 95% CI, 1.105-4.908; P = 0.026) remained independent risk factors for PFS and OS, respectively. Conclusion: Our study revealed that the pT4b substage is associated with a poor prognosis and that the ACCI score is a relevant and practical method to evaluate survival outcomes in patients with pT4 BCa after Cx.