Renal interstitial fibrosis (RIF), the central pathological driver of chronic kidney disease (CKD) progression, remains mechanistically incompletely defined. While long non-coding RNAs (lncRNAs) are emerging as critical regulators of CKD, their roles in RIF pathogenesis are poorly understood. Here, we identify the fibrosis-associated lncRNA P4HA2-AS1 as a key modulator of RIF through integrated analyses of unilateral ureteral obstruction (UUO) mice and TGF-β-stimulated human renal tubular epithelial cells (HK-2), combined with RNA sequencing, RNA pull-down, ubiquitination profiling, and autophagic flux assays. P4HA2-AS1 was markedly upregulated in fibrotic kidneys, and its suppression attenuated fibrotic phenotypes in vivo and in vitro while restoring autophagic flux. Mechanistically, P4HA2-AS1 directly binds the E3 ubiquitin ligase TRIM32, impeding its proteasomal degradation. This stabilization enhances TRIM32-mediated K63-linked ubiquitination of ULK1, a master autophagy initiator, leading to aberrant autophagic activation and fibrotic progression. Our study uncovers a previously unrecognized P4HA2-AS1/TRIM32/ULK1 axis that couples dysregulated autophagy to RIF, proposing lncRNA-protein interaction targeting as a therapeutic strategy against renal fibrosis. LncRNA P4HA2-AS1 drives renal fibrosis by stabilizing TRIM32 to promote K63-linked ubiquitination of ULK1.

BACKGROUND:To explore the independent influencing factors of PCa bone metastasis and evaluate the role of prostate imaging. METHODS:The clinic data such as age, prostate volume, tPSA and fPSA . Univariate and multivariate analyses were performed to investigate the independent influencing point of the risk factors. Nomogram and ROC curve were generated to establish the prediction model. The calibration curve, leave-one-out cross validation and independent external validation were performed to evaluate the prediction model. RESULTS:This study enrolled 325 newly diagnosed PCa patients at two hospitals. Univariate and multivariate analyses showed only tPSA , cTx, ALP, and PI-RADS v2 score were the independent influencing factors of PCa bone metastasis. The cut-off points of PI-RADS v2 score to distinguish bone metastasis was 5. The nomogram was established with a sensitivity of 81.3% and a specificity of 74.5% to predict the probability of PCa bone metastasis. The calibration curve and ROC curve displayed a good value of the prediction model. Leave-one-outcross validation showed the prediction model could classify 79.8% cases accurately. External data validation displayed sensitivity of 78.4% and a specificity of 79.1%. CONCLUSIONS:PI-RADS v2 score could predict PCa bone metastasis, the prediction model may help discovered PCa bone metastasis.

Dysfunction of renal macrophagic phagocytosis is closely associated with calcium oxalate (CaOx) kidney stone formation; however, its underlying mechanisms remain poorly understood. In this study, we identified the mechanism by which histidine-rich glycoprotein (HRG)-mediated communication between renal tubular epithelial cells (RTEC) and macrophages mediates the phagocytosis of stone crystals in clinical samples, in vivo, and in vitro stone models, using integrated proteomic and transcriptomic analyses coupled with biochemical experiments. Mechanistically, RTEC exhibited reduced HRG secretion under stone-forming conditions. Reduced HRG weakens interactions with FcgammaRI (FcγRI) receptors on macrophages, thereby inhibiting downstream phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) signaling pathways, which downregulates Ras-related protein rab-20 (RAB20) expression to diminish macrophage phagocytosis of crystals and reduces interleukin-33 (IL-33) expression to inhibit M2 polarization of macrophages. These combined effects impair macrophage crystal phagocytosis, ultimately promoting the formation of CaOx kidney stones. Additionally, we found that enhancing HRG expression significantly suppresses oxalate crystal aggregation in kidneys and renal injury induced by glyoxylate (Gly). Through pharmacological analysis, we also identified Hesperidin, a natural compound derived from traditional Chinese medicine and validated in mice, which may exert protective effects against CaOx kidney stones by targeting HRG. In summary, this study reveals an HRG-based RTEC-macrophage communication axis that regulates crystal macrophagic phagocytosis, providing new insights into the prevention and treatment of CaOx kidney stones.

To evaluate stent-related symptoms (SRS) and the encrustation of stents in diabetic patients receiving loop-tail (LT) stents versus conventional double J (DJ) stents following uncomplicated flexible ureterorenoscopy (fURS). This study retrospectively analyzed data collected from diabetic patients who underwent fURS between July 2022 and May 2025. A total of 108 patients were eligible in this study, including 56 patients received conventional DJ stents and 52 patients received LT stents. Stent-related symptoms were assessed using the Chinese validated version of the Ureteric Stent Symptom Questionnaire (USSQ) at 3 day and 4 weeks post-stent insertion. Encrustation of stents was assessed upon stent removal. Statistical analyses were conducted to compare USSQ domains, encrustation scores, and complications between the two groups. There were no significant differences between the two groups in USSQ domains at 3 days post-stent insertion. At 4 weeks, the LT group demonstrated a significantly better outcome in the urinary symptoms domain (P = 0.037) and visual analogue scale (VAS) for pain (P = 0.042) compared with the DJ group. Patients in the LT group reported lower scores of urinary frequency (P = 0.003), incomplete emptying (P = 0.031), burning at voiding (P = 0.047), and pain interfering with life (P = 0.015) than those in the DJ group. Encrustation scores in bladder segment were significantly lower in the LT group than in the DJ group (p < 0.001). No significant differences were found between the two groups in the incidence of stent-related complications. In diabetic patients, LT stents are associated with fewer stent-related urinary symptoms and less pain. They also show lower encrustation scores compared to conventional DJ stents at 4 weeks post-insertion. LT stents may be a preferable option for LT stent placement in diabetic patients undergoing fURS.

Objective Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. Cuproptosis is a new type of programmed cell death that is mediated by protein lipid acylation and is closely linked to mitochondrial metabolism. Methods The Cancer Genome Atlas (TCGA) database provided us with RNA-Seq data together with the related clinical and prognostic information. Using univariate Cox, 135 prognostic lncRNAs associated with cuproptosis were identified for use in prognostic model construction. Multivariate Cox analysis was subsequently used to further integrate these lncRNAs. We used subject operating characteristic (ROC) curve analysis and Kaplan-Meier (K-M) survival curve analysis to assess the model's prognostic ability. In order to predict immune escape and potential therapeutic drugs in the two groups, we also looked at the differences in immunological and tumor mutational burden between the high- and low-risk groups. The quantitative polymerase chain reaction (Q-PCR) was then used to validate the risk model. Results The lncRNA profile linked to cuproptosis is used to divide patients into two risk categories, with the lower risk group having a better prognosis. The tumor mutational burden was larger, immune escape was more likely to occur, and immunotherapy results were generally worse in the high-risk group. The traditional chemotherapeutic medications sunitinib, AKT inhibitor VIII, rapamycin, and lapatinib were more effective in low-risk individuals. Six prognostic lncRNAs were ultimately confirmed in human cell lines, including HK-2, ACHN, 769-P, and CAKI-1. Conclusions A risk model based on six cuproptosis-related lncRNAs has a high predictive value for ccRCC and might be a medical target for cuproptosis.

Acute kidney injury (AKI) is a common clinical condition characterized by high morbidity and mortality rates, with a notable lack of effective therapeutic drugs. Complex pathological processes-such as oxidative stress overload, aberrant macrophage polarization, mitochondrial dysfunction, and renal tubular epithelial cell apoptosis-contribute to the current absence of effective clinical treatments for AKI. Although mesoporous cerium dioxide nanospheres have been widely applied in various diseases due to their remarkable ROS-scavenging and drug-loading capabilities, their poor targeting ability limits their use in ischemia-reperfusion injury models. To address this, we developed a multifunctional nanoplatform RGD-CeO₂@Que. based on mesoporous hollow cerium dioxide (AhCeO₂). This system achieves targeted accumulation in injured kidneys by binding to integrin αvβ3 receptors, which are overexpressed under oxidative stress. Through the Nrf2/HO-1/GPX4/SOD1 pathway, it alleviates oxidative stress and reduces apoptosis. Moreover, the platform is loaded with the bioactive molecule quercetin to promote mitophagy in renal tubular epithelial cells (HK-2). In vivo studies demonstrated that RGD-CeO₂@Que. improves renal function, ameliorates pathological damage, and reduces inflammatory infiltration in AKI mice. In summary, this integrated nanoplatform combines multiple restorative mechanisms, offering a novel and targeted therapeutic strategy for AKI induced by renal ischemia-reperfusion injury.

OBJECTIVE:SPON2 is an extracellular matrix constituent belonging to the Mindin-F-spondin protein family. Our previous study proved that SPON2 emerges as a novel biomarker in renal fibrogenesis. However, the role of SPON2 in regulation and its impact on RCC progression remains uncertain. METHODS:The TCGA and GEO databases were used to explore the expression of SPON2 in RCC. Western blot was used to detect the expression of SPON2 between RCC and normal samples. Survival analysis and gene set variation analysis were performed to discover the prognostic significance and underlying mechanism of SPON2 in RCC. The role of SPON2 was detected by CCK8, wound healing, invasion, and xenograft model assays. Autophagy-related experiments verified the bioinformatic findings. RESULTS:Bioinformatic analysis revealed significantly higher SPON2 expression in RCC, which was found to be associated with improved overall survival in patients with high SPON2 levels. Detection of clinical samples revealed an increase in SPON2 expression within the context of ccRCC tissues. In addition, data from in vitro assays revealed that SPON2 overexpression significantly enhanced the proliferative and migratory capacity of cell lines. Xeno-graft experiments demonstrated the accelerated tumor growth effect of SPON2. Mechanistic investigation showed that the PI3K/AKT/mTOR pathway was inhibited by SPON2. CONCLUSION:Our data illustrated that SPON2 functions as an oncogene in the tumorigenesis of RCC tumorigenesis, which is accompanied by an inverse relationship between SPON2 expression levels and patient prognosis. The underlying mechanism likely involves the promotion of autophagy by modulating the PI3K/AKT/mTOR pathway.

Kidney stones result from abnormal biomineralization, although the mechanism behind their formation remains unclear. Annexin A6 (AnxA6), a calcium-dependent lipid-binding protein, is associated with several mineralization-related diseases, but its role in kidney stones is unknown. This study aimed to explore the role and mechanism of AnxA6 in calcium oxalate (CaOx) kidney stones. An in vitro model in which renal tubular epithelial cells (RTECs) were treated with 1 mmol/L oxalate was established, and AnxA6 protein and mRNA expression were examined. Genetic engineering, drug intervention, and biochemical assays were used to investigate the role of AnxA6. The results revealed that AnxA6 was significantly overexpressed in the CaOx model. AnxA6 knockdown in RTECs reduced oxalate-induced oxidative stress, ROS accumulation, and mitochondrial damage, whereas AnxA6 overexpression exacerbated these effects. Blocking ryanodine receptor-mediated calcium release reversed AnxA6-induced oxidative damage. Additionally, AnxA6 increased oxalate adhesion to RTECs by binding to oxalate. In conclusion, AnxA6 contributes to CaOx kidney stone formation by promoting both oxidative stress via calcium release and crystal-cell adhesion by binding to oxalate. This study offers new insight into CaOx kidney stone formation.

Few approaches have been conducted in the treatment of renal cell carcinoma (RCC) after nephrectomy, resulting in a high mortality rate in urological tumours. Mitophagy is a mechanism of mitochondrial quality control that enables selective degradation of damaged and unnecessary mitochondria. Previous studies have found that glycerol-3-phosphate dehydrogenase 1-like (GPD1L) is associated with the progression of tumours such as lung cancer, colorectal cancer and oropharyngeal cancer, but the potential mechanism in RCC is still unclear. In this study, microarrays from tumour databases were analysed. The expression of GPD1L was confirmed by RT-qPCR and western blotting. The effect and mechanism of GPD1L were explored using cell counting kit 8, wound healing, invasion, flow cytometry and mitophagy-related experiments. The role of GPD1L was further confirmed in vivo. The results showed that GPD1L expression was downregulated and positively correlated with prognosis in RCC. Functional experiments revealed that GPD1L prevented proliferation, migration and invasion while promoting apoptosis and mitochondrial injury in vitro. The mechanistic results indicated that GPD1L interacted with PINK1, promoting PINK1/Parkin-mediated mitophagy. However, inhibition of PINK1 reversed GPD1L-mediated mitochondrial injury and mitophagy. Moreover, GPD1L prevented tumour growth and promoted mitophagy by activating the PINK1/Parkin pathway in vivo. Our study shows that GPD1L has a positive correlation with the prognosis of RCC. The potential mechanism involves interacting with PINK1 and regulating the PINK1/Parkin pathway. In conclusion, these results reveal that GPD1L can act as a biomarker and target for RCC diagnosis and therapy.

Autophagy has been increasingly recognized as a critical regulatory mechanism in the maintenance of cellular homeostasis. A previous study showed that phospholipase C-like protein 1 (PLCL1) is associated with lipid metabolism in renal cell carcinoma (RCC). However, it is unclear whether PLCL1 regulates autophagy, thereby influencing the progression of RCC. Bioinformatics analysis of five microarray datasets revealed that expression of PLCL1 is decreased in tumours and is positively correlated with prognosis in RCC patients. Three independent public datasets, clinical RCC tissues and RCC cell lines, were validated using real-time qPCR, western blotting and immunohistochemistry. Using wound healing and transwell assays, we observed that elevated PLCL1 levels decreased the migratory distance and the invasive number of 786-O and ACHN cells, but PLCL1 knockdown reversed these changes in 769P cell lines compared to those in controls. The results of flow cytometry analysis indicated that PLCL1 promotes apoptosis. Moreover, transcriptional analysis based on stable overexpression of PLCL1 in 786-O cells revealed that PLCL1 is related to autophagy, and western blotting and autophagic experimental results further verified these findings. Mechanistic investigations confirmed that PLCL1 activates the AMPK/mTOR pathway and interacts with decidual protein induced by progesterone (DEPP). Collectively, our data suggest that PLCL1 functions as a suppressor of RCC progression by activating the AMPK/mTOR pathway, interacting with DEPP, initiating autophagy and inducing apoptosis. PLCL1 may be a promising therapeutic target for the diagnosis and treatment of ccRCC patients.

Heart failure (HF) is the end stage of the progression of many cardiovascular diseases. Cardiac remodeling is the main pathophysiological process of cardiac function deterioration in HF patients. Inflammation is a key factor that stimulates cardiomyocyte hypertrophy, fibroblast proliferation, and transformation leading to myocardial remodeling, which severity is significantly related to the prognosis of patients. SAA1 (Serum amyloid A1) is a lipid-binding protein that was an important regulator involved in inflammation, whose biological functions in the heart remain rarely known. In this research, we intended to test the role of SAA1 in SAA1-deficient (SAA1(-/-)), and wild-type mice were exposed to transverse aortic banding surgery to establish the model of cardiac remodeling. Besides, we assessed the functional effects of SAA1 on cardiac hypertrophy and fibrosis. The expression of SAA1 was increased in the mice transverse aortic banding model induced by pressure overload. After 8 weeks of transverse aortic banding, SAA1(-/-) mice displayed a lower level of cardiac fibrosis than wild-type mice, but did not significantly influence the cardiomyocyte hypertrophy. In addition, there was also no significant difference in cardiac fibrosis severity between wild-type-sham and knockout-sham mice. These findings are the first to reveal SAA1 absence hinders cardiac fibrosis after 8 weeks of transverse aortic banding. Furthermore, SAA1 deficiency had no significant effect on cardiac fibrosis and hypertrophy in the sham group in this study.

目的 分析香叶木素对小鼠肾缺血再灌注(I/R)损伤是否具有保护作用及其潜在机制.方法 将45只BALB/c雄性小鼠分为假手术组、模型组和香叶木素处理组,通过检测血生化指标和肾组织HE染色损伤评分评价香叶木素对小鼠肾功能的保护作用,通过免疫组化和蛋白免疫印迹检测NF-κB家族关键分子p-P65表达水平变化的情况,通过实时荧光定量聚合酶链式反应检测NF-κB信号通路下游炎症因子的变化情况.结果 与假手术组比较,模型组小鼠血肌酐和尿素氮水平显著升高,小鼠肾组织损伤显著,p-P65以及下游炎症因子表达显著增加.通过香叶木素处理后,可改善肾功能血生化指标,减轻小鼠肾组织损伤,并发现香叶木素可以下调肾I/R损伤中p-P65和相关炎症因子的表达.结论 香叶木素可能通过抑制NF-κB信号通路的激活,从而在小鼠肾I/R损伤中起到保护作用.

Background: Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma (RCC), is insensitive to radiotherapy and chemotherapy after surgery. Deoxyribonuclease 1-like 3 (DNASE1L3), an endonuclease that cleaves both membrane-encapsulated single- and double-stranded DNA, suppresses cell cycle progression, proliferation and metabolism in hepatocellular carcinoma cells. There is currently no established link between DNASE1L3 and RCC inhibition. We are gonging to explored the mechanism underlying the relationship between DNASEL1L3 and RCC. Methods: RNA sequencing data for RCC tissue and peritumoral tissue were downloaded from The Cancer Genome Atlas database and analyzed. The expression levels of DNASE1L3 in RCC and normal samples were verified using the Gene Expression Omnibus (GEO) database, Human Protein Atlas database and western blotting. The role and potential mechanism of DNASE1L3 were investigated by analysis of immune-related databases and wound healing, invasion, cell counting kit 8 and immunofluorescence assays. Results: We revealed that DNASE1L3 expression was downregulated in RCC group compared with control group [The Cancer Genome Atlas (TCGA): 7.98 vs. 10.87, P < 0.001]. Meanwhile, DNASE1L3 expression correlated with the clinical characteristics of patients. Patients with low DNASE1L3 expression had worse survival (P < 0.001) and larger (r=-0.32, P < 0.001) and heavier tumors (r=-0.17, P < 0.001). DNASE1L3 overexpression inhibited the proliferation ( 786-O: 0.135 +/- 0.014 vs. 0.322 +/- 0.027, P < 0.001) and invasion (786- O: 1,479 +/- 134 vs. 832 +/- 67, P < 0.05) of RCC cells. The expression of DNASE1L3 was significantly correlated with the tumor immune microenvironment and drug sensitivity in ccRCC. Moreover, the level of the key phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway protein P-AKT was decreased in the group of cells transfected with DNASE1L3. Conclusions: This study strongly suggest that DNASE1L3 may be a promising potential biomarker for the diagnosis and treatment of ccRCC patients.

The basement membrane (BM) affects the invasion and growth of malignant tumors. The role and mechanism of BM-associated lncRNAs in clear cell renal cell carcinoma (ccRCC) are unknown. In this study, we identified biomarkers of ccRCC and developed a risk model to assess patient prognosis. We downloaded transcripts and clinical data from the Cancer Genome Atlas (TCGA). Differential analysis, co-expression analysis, Cox regression analysis, and lasso regression were used to identify BM-associated prognostic lncRNAs and create a risk prediction model. We evaluated and validated the accuracy of the model using multiple methods and constructed a nomogram to predict the prognosis of ccRCC. GO, KEGG, and immunity analyses were used to explore differences in biological function. We constructed a risk model containing six BM-associated lncRNAs (LINC02154, IGFL2-AS1, NFE4, AC112715.1, AC092535.5, and AC105105.3). The risk model has higher diagnostic efficiency compared to clinical characteristics and can be used to forecast patient prognoses. We used renal cancer cells and tissue microarrays to verify the expression of lncRNAs in the risk model. We found that knocking down LINC02154 and AC112715.1 could inhibit the invasion ability of renal cancer cells. The risk model based on BM-associated lncRNAs can well predict ccRCC and guide clinical treatment.

Objective:To investigate the effect and mechanism of microfibril-associated protein 4 (MFAP4) on renal clear cell carcinoma (ccRCC) using an in vitro model. Methods:Totally, 30 pairs of tissue specimens of renal cancer patients collected from Department of Urology, Renmin Hospital of Wuhan University during June 2020 to December 2020, and renal cancer cell lines were used to detect the expression of MFAP4 protein by real-time quantitative immunofluorescence PCR and Western blotting. Adenovirus vector was used to construct stably transfected tumor cell lines overexpressing MFAP4, which were detected by cell migration and invasion assays. The action mechanism of MFAP4 on ccRCC was detected by immunofluorescence and Western blotting.Results:The expression of MFAP4 was significantly increased in renal cancer tissue samples and renal tumor cell lines (5.22±2.61 vs. 32.08±7.12, t=17.68, P<0.05; 1.00±0.01 vs. 2.30±0.25, t=9.18, P<0.05). Compared with the transfection control group, overexpression of MFAP4 significantly increased the number of ccRCC invasive cells (cells: 907±63 vs. 1 997±101, t=12.87, P<0.05; 1 208±98 vs. 2 364±121, t=15.87, P<0.05), inhibited the expression of LC3B (1.00±0.01 vs. 0.65±0.08, t=46.42, P<0.05; 1.00±0.01 vs. 0.67±0.06, t=26.46, P<0.05), and promoted the expression of p62 (1.00±0.01 vs. 2.27±0.04, t=7.93, P<0.05; 1.00±0.01 vs. 2.17±0.08, t=9.15, P<0.05). Conclusion:MFAP4 may promote the progression of renal cancer by inhibiting autophagy.

Despite the great progress of deep neural networks (DNNs), they are vulnerable to backdoor attacks. To detect and provide concrete proof for the existence of backdoors, existing techniques generally adopt the reverse engineering approach. However, most of them suffer from high computational complexity and weak scalability. In this paper, we make a key observation that the weights connected to the backdoor target labels in trojaned DNNs tend to have abnormal distributions, including dissimilarity to other labels and anomalously large magnitude. Based on this observation, we propose an efficient and scalable backdoor detection framework guided by static weight analysis. Our approach first detects the outlier existing in weight distributions and identifies suspicious backdoor target/victim label pairs. Then we conduct reverse engineering to recover the triggers, including a newly designed reverse engineering approach for global transformation attacks and one existing approach for local patch attacks. Finally, we analyze the characteristics of the recovered triggers to suppress false positives. Experimental results show that our approach has state-of-the-art performance on MNIST, CIFAR-10, ImageNet, and TrojAI. In particular, it outperforms NC, ABS, and K-Arm by 31%, 8.7%, and 5% on the public detection benchmark TrojAI in terms of detection accuracy while maintaining the highest efficiency.

Objective:To verify the safety and reliability of the unilateral approach through the lateral wall of the superior pyramidal transverse process, compare and analyze the data of the unilateral approach through the pedicle in the treatment of osteoporotic vertebral compression fracture, and discuss the application value of the unilateral approach through the lateral wall of the superior pyramidal transverse process in kyphoplasty with balloon expansion.Methods:The 3D Slicer was used to verify the simple, safe and reliable approach through the lateral wall of the cone at the upper edge of the transverse process. A total of 77 patients in our hospital from November 2019 to December 2020 were collected, including 40 patients with unilateral lateral wall approach through the upper edge of the transverse process and 37 patients with unilateral pedicle approach, respectively. The indicators in the treatment process and long-term treatment effects of the two approaches were compared.Results:Both groups completed treatment without complications. Postoperative ODI and VAS in two groups were significantly decreased ( t=0.000, P<0.05), and there was no statistically significant difference in scores (preoperative VAS t=0.690, postoperative VAS t=0.231, postoperative VAS t=0.866; preoperative ODI t=0.979, postoperative ODI t=0.563, postoperative 3-month ODI t=0.375, P>0.05). There was no statistically significant difference in vertebral height recovery ( t=0.684, P>0.05). There was no significant difference in intraoperative bone cement perfusion ( t=0.912, P>0.05). The operation duration [15 (14-16) min vs. 22 (20-24) min, t=0.000, P<0.05] was shortened and the number of fluoroscopic channels [5 (4.00-6.00) vs. 10 (8.00-10.75), t=0.000, P<0.05] was reduced in the unilateral transpedicle approach group as compared with those in the unilateral transpedicle approach group. Postoperative X-ray results showed that bone cement perfusion was located in the median line of the anterior margin of the vertebral body (35 vs. 5, t=0.000, P<0.05). Conclusion:Both approaches can make patients get satisfactory therapeutic effects. In the vertebral lateral wall group, bone cement can be pushed into the anterior edge of the vertebral body and cross the mid line of the vertebral body, which is more stable in biomechanics. Moreover, the operation time is short, the times of the X-ray examinations are less, and the lateral wall approach through the superior transverse process is not easy to damage the spinal cord, and the operation is simple, safe and reliable.

Background Oxidative stress (OS) reactions are closely related to the development and progression of bladder cancer (BCa). This project aimed to identify new potential biomarkers to predict the prognosis of BCa and improve immunotherapy. Methods We downloaded transcriptomic information and clinical data on BCa from The Cancer Genome Atlas (TCGA). Screening for OS genes was statistically different between tumor and adjacent normal tissue. A coexpression analysis between lncRNAs and differentially expressed OS genes was performed to identify OS-related lncRNAs. Then, differentially expressed oxidative stress lncRNAs (DEOSlncRNAs) between tumors and normal tissues were identified. Univariate/multivariate Cox regression analysis was performed to select the lncRNAs for risk assessment. LASSO analysis was conducted to establish a prognostic model. The prognostic risk model could accurately predict BCa patient prognosis and reveal a close correlation with clinicopathological features. We analyzed the principal component analysis (PCA), immune microenvironment, and half-maximal inhibitory concentration (IC50) in the risk groups. Results We constructed a model containing eight DEOSlncRNAs (AC021321.1, AC068196.1, AC008750.1, SETBP1-DT, AL590617.2, THUMPD3-AS1, AC112721.1, and NR4A1AS). The prognostic risk model showed better results in predicting the prognosis of BCa patients and was strongly correlated with clinicopathological characteristics. We found great agreement between the calibration plots and prognostic predictions in this model. The areas under the receiver operating characteristic (ROC) curve (AUCs) at 1, 3, and 5 years were 0.792, 0.804, and 0.843, respectively. This model also showed good predictive ability regarding the tumor microenvironment and tumor mutation burden. In addition, the high-risk group was more sensitive to eight therapeutic agents, and the low-risk group was more responsive to five therapeutic agents. Sixteen immune checkpoints were significantly different between the two risk groups. Conclusion Our eight DEOSlncRNA risk models provide new insights into predicting prognosis and clinical progression in BCa patients.

Acute renal injury (AKI) secondary to ischemia reperfusion (IR) injury continues to be a significant perioperative problem and there is no effective treatment. Mindin belongs to the mindin/F-spondin family and involves in inflammation, proliferation, and cell apoptosis. Previous studies have explored the biological functions of mindin in liver and brain ischemic injury, but its role in AKI is unknown. To investigate whether mindin has a pathogenic role, mindin knockout (KO) and wild-type (WT) mice were used to establish renal IR model. After 30 min of ischemia and 24 h of reperfusion, renal histology, serum creatinine, and inflammatory response were examined to assess kidney injury. In vitro, proinflammatory factors and inflammatory signaling pathways were measured in mindin overexpression or knockdown and vector cells after hypoxia/reoxygenation (HR). Following IR, the kidney mindin level was increased in WT mice and deletion of mindin provided significant protection for mice against IR-induced renal injury as manifested by attenuated the elevation of serum creatinine and blood urea nitrogen along with less severity for histological alterations. Mindin deficiency significantly suppressed inflammatory cell infiltration, TNF-α and MCP-1 production following renal IR injury. Mechanistic studies revealed that mindin deficiency inhibits TLR4/JNK/NF-κB signaling activation. In vitro, the expression levels of TNF-α and MCP-1 were increased in mindin overexpression cells compared with vector cells following HR. Moreover, TLR4/JNK/NF-κB signaling activation was elevated in the mindin overexpression cells in response to HR stimulation while mindin knockdown inhibited the activation of TLR4/JNK/ NF-κB signaling after HR in vitro. Further study showed that mindin protein interacted directly with TLR4 protein. And more, mindin protein was confirmed to be expressed massively in renal tubule tissues of human hydronephrosis patients. These data demonstrate that mindin is a critical modulator of renal IR injury through regulating inflammatory responses. TLR4/JNK/NF-κB signaling most likely mediates the biological function of mindin in this model of renal ischemia.

HCC has remained one of the challenging cancers to treat, owing to the paucity of drugs targeting the critical survival pathways.Considering the cancer cells are deficient in DNase activity, the increase of an autonomous apoptisis endonuclease should be a reasonable choice for cancer treatment.In this study, we investigated whether DNASE1L3, an endonuclease implicated in apoptosis, could inhibit the progress of HCC.We found DNASE1L3 was down-regulated in HCC tissues, whereas its high expression was positively associated with the favorable prognosis of patients with HCC.Besides, serum DNASE1L3 levels were lower in HCC patients than in healthy individuals.Functionally, we found that DNASE1L3 inhibited the proliferation of tumor cells by inducing G0/G1 cell cycle arrest and cell apoptosis in vitro.Additionally, DNASE1L3 overexpression suppressed tumor growth in vivo.Furthermore, we found that DNASE1L3 overexpression weakened glycolysis in HCC cells and tissues via inactivating the rate-limiting enzymes involved in PTPN2-HK2 and CEBPβ-p53-PFK1 pathways.Finally, we identified the HBx to inhibit DNASE1L3 expression by up-regulating the expression of ZNF384.Collectively, our findings demonstrated that DNASE1L3 could inhibit the HCC progression through inducing cell apoptosis and weakening glycolysis.We believe DNASE1L3 could be considered as a promising prognostic biomarker and therapeutic target for HCC.