Explore the vast range of titles available.

Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5′ caps and 3′ poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients’ survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.

Calcium oxalate (CaOx) crystal can trigger kidney injury, which contributes to the pathogenesis of nephrocalcinosis. The phenotypes of infiltrating macrophage may impact CaOx-mediated kidney inflammatory injury as well as crystal deposition. How aryl hydrocarbon receptor (AhR) regulates inflammation and macrophage polarization is well understood; however, how it modulates CaOx nephrocalcinosis remains unclear. Methods: Mice were intraperitoneally injected with glyoxylate to establish CaOx nephrocalcinosis model with or without the treatment of AhR activator 6-formylindolo(3,2-b)carbazole (FICZ). Positron emission tomography computed tomography (PET-CT) imaging, Periodic acid-Schiff (PAS) staining, and polarized light optical microscopy were used to evaluate kidney injury and crystal deposition in mice kidney. Western blotting, immunofluorescence, chromatin immunoprecipitation, microRNA-fluorescence in situ hybridization, and luciferase reporter assays were applied to analyze polarization state and regulation mechanism of macrophage. Results: AhR expression was significantly upregulated and negatively correlated with interferon-regulatory factor 1 (IRF1) and hypoxia inducible factor 1-alpha (HIF-1α) levels in a murine CaOx nephrocalcinosis model following administration of FICZ. Moreover, AhR activation suppressed IRF1 and HIF-1α levels and decreased M1 macrophage polarization in vitro. In terms of the mechanism, bioinformatics analysis and chromatin immunoprecipitation assay confirmed that AhR could bind to miR-142a promoter to transcriptionally activate miR-142a. In addition, luciferase reporter assays validated that miR-142a inhibited IRF1 and HIF-1α expression by directly targeting their 3'-untranslated regions. Conclusions: Our results indicated that AhR activation could diminish M1 macrophage polarization and promote M2 macrophage polarization to suppress CaOx nephrocalcinosis via the AhR-miR-142a-IRF1/HIF-1α pathway.

Renal tubular cell injury induced by calcium oxalate (CaOx) is a critical initial stage of kidney stone formation. Theaflavin (TF) has been known for its strong antioxidative capacity; however, the effect and molecular mechanism of TF against oxidative stress and injury caused by CaOx crystal exposure in kidneys remains unknown. To explore the potential function of TF on renal crystal deposition and its underlying mechanisms, experiments were conducted using a CaOx nephrocalcinosis mouse model established by glyoxylate intraperitoneal injection, and HK-2 cells were subjected to calcium oxalate monohydrate (COM) crystals, with or without the treatment of TF. We discovered that TF treatment remarkably protected against CaOx-induced kidney oxidative stress injury and reduced crystal deposition. Additionally, miR-128-3p expression was decreased and negatively correlated with SIRT1 level in mouse CaOx nephrocalcinosis model following TF treatment. Moreover, TF suppressed miR-128-3p expression and further abolished its inhibition on SIRT1 to attenuate oxidative stress . Mechanistically, TF interacted with miR-128-3p and suppressed its expression. In addition, miR-128-3p inhibited SIRT1 expression by directly binding its 3'-untranslated region (UTR). Furthermore, miR-128-3p activation partially reversed the acceerative effect of TF on SIRT1 expression. Taken together, TF exhibits a strong nephroprotective ability to suppress CaOx-induced kidney damage through the recovery of the antioxidant defense system regulated by miR-128-3p/SIRT1 axis. These findings provide novel insights for the prevention and treatment of renal calculus.

The recent outbreak of the coronavirus disease-2019 (COVID-19) caused serious challenges to the human society in China and across the world. COVID-19 induced pneumonia in human hosts and carried a highly inter-person contagiousness. The COVID-19 patients may carry severe symptoms, and some of them may even die of major organ failures. This study utilized the machine learning algorithms to build the COVID-19 severeness detection model. Support vector machine (SVM) demonstrated a promising detection accuracy after 32 features were detected to be significantly associated with the COVID-19 severeness. These 32 features were further screened for inter-feature redundancies. The final SVM model was trained using 28 features and achieved the overall accuracy 0.8148. This work may facilitate the risk estimation of whether the COVID-19 patients would develop the severe symptoms. The 28 COVID-19 severeness associated biomarkers may also be investigated for their underlining mechanisms how they were involved in the COVID-19 infections.

Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in the tumor microenvironment (TME), especially in solid tumors. It has been confirmed that it can not only interact with tumor cells to promote cancer progression and metastasis, but also affect the infiltration and function of immune cells to induce chemotherapy and immunotherapy resistance. So, targeting CAF has been considered an important method in cancer treatment. The rapid development of nanotechnology provides a good perspective to improve the efficiency of targeting CAF. At present, more and more researches have focused on the application of nanoparticles (NPs) in targeting CAF. These studies explored the effects of different types of NPs on CAF and the multifunctional nanomedicines that can eliminate CAF are able to enhance the EPR effect which facilitate the anti-tumor effect of themselves. There also exist amounts of studies focusing on using NPs to inhibit the activation and function of CAF to improve the therapeutic efficacy. The application of NPs targeting CAF needs to be based on an understanding of CAF biology. Therefore, in this review, we first summarized the latest progress of CAF biology, then discussed the types of CAF-targeting NPs and the main strategies in the current. The aim is to elucidate the application of NPs in targeting CAF and provide new insights for engineering nanomedicine to enhance immune response in cancer treatment.

The kidney function of patients with chronic kidney disease (CKD) is impaired irreversibly. Organ transplantation is the only treatment to restore kidney function in CKD patients. The assessment of new potential therapeutic procedures relies heavily on experimental animal models, but it is limited by its human predictive capacity. In addition, the frequently used two-dimensional in vitro human renal cell models cannot replicate all the features of the in vivo situation. In this study, we developed a three-dimensional (3D) in vitro human renal organoid model from whole kidney cells as a promising drug screening tool. At present, the renal tissue generated from human pluripotent stem cells (hPSCs) exhibits intrinsic tumorigenicity properties. Here we first developed a 3D renal organoid culture system that originated from adult differentiated cells without gene modification. Renal organoids composed of multiple cell types were created under optimal experimental conditions and evaluated for morphology, viability and erythropoietin production. As a novel screening tool for renal toxicity, 3D organoids were exposed to three widely used drugs: aspirin, penicillin G and cisplatin. The study results showed this 3D renal organoid model can be used as a drug screening tool, a new in vitro 3D human kidney model, and provide hope for potential regenerative therapies for CKD.

Objective To compare the safety, effectiveness, and feasibility of contrast-enhanced ultrasound (CEUS) versus conventional ultrasound-guided percutaneous nephrolithotomy (PCNL) in patients with nondilated collecting system. Methods Between July 2018 and July 2020, 160 kidney stone patients with nondilated collecting system planned for PCNL were randomly assigned into two groups, CEUS with retrograde ureteral contrast injection and conventional ultrasound with retrograde ureteral normal saline injection. Patient’s demographics, the success rate of puncture, success rate of a single-needle puncture, number of punctures, puncture time, perioperative outcomes, stone-free rate, and incidence of complications were compared. Results The success rate of a single-needle puncture for CEUS-guided PCNL was higher than that in the conventional ultrasound group (88.5% vs. 73.7%, p = 0.02). Patients performed with CEUS-guided PCNL required less needle passes ( p = 0.02), shorter needle puncture time ( p = 0.031), and shorter channel establishment time ( p = 0.04) than those guided with conventional ultrasound. The postoperative hemoglobin decrease in the CEUS-guided PCNL group was less than that of the control group ( p = 0.02). There was no significant difference in operating time, length of hospital stays, kidney function change, and complications between the two groups ( p > 0.05). The 1-month stone-free rate was 94.9% in the CEUS group and 90.8% in the control group ( p > 0.05). Conclusions Compared with conventional ultrasound, CEUS-guided PCNL may facilitate ultrasound-guided PCNL for patients without hydronephrosis, and benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. Trial registration Chinese Clinical Trial Registry: ChiCTR1800016981 Key Points • Compared with conventional ultrasound, CEUS-guided PCNL is a safe and efficacious procedure for kidney stone patients with nondilated collecting system . • Compared with conventional ultrasound, CEUS-guided PCNL benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop . • CEUS-guided PCNL associated with the more accurate needle puncture and acceptable complications .

The aim of the current study was to evaluate the risk factors that influence the development of postoperative systemic inflammatory response syndrome (SIRS) after percutaneous nephrolithotomy (PCNL), including cytokines and lymphocyte subsets. A total of 154 patients who underwent PCNL at our hospital between October 2019 and January 2022 were retrospectively reviewed. The development of post-PCNL SIRS was the primary endpoint of the study. Univariable analysis and multivariable logistic regression analysis were performed to identify independent risk factors of post-PCNL SIRS. A nomogram was constructed using the independent risk factors, and receiver operating characteristic (ROC) curves were drawn. There were 50 patients (32.5%) who developed SIRS after PCNL. In multivariate analysis, positive urine culture (odds ratio [OR], 3.556; = 0.048), long operation time (OR, 1.011; = 0.027), high IL-2R (OR, 1.002; = 0.018), low percentage of CD3 cells (OR 0.931; = 0.006), and high white blood cell (WBC) count (OR, 1.282 = 0.044) were independent risk factors for post-PCNL SIRS. These five significant variables were used to generate a nomogram that exhibited favorable fitting. The discrimination area under the ROC curves was 0.795. Patients with long operation times, positive urine cultures, high interleukin 2 receptor, high white blood cell counts, and low percentages of CD3 cells may be at a higher risk of developing SIRS after PCNL. In these patients, cautious and comprehensive preoperative evaluations and appropriate treatment strategies should be considered.

BackgroundBladder cancer (BLCA) is a challenging malignancy with a poor prognosis, particularly in muscle-invasive cases. Despite recent advancements in immunotherapy, response rates remain suboptimal. This study investigates the role of METTL3, an m6A RNA methylation “writer,” in regulating the immune microenvironment of BLCA.MethodsThrough bioinformatics analysis, we identified METTL3 as being associated with the formation of an immunosuppressive microenvironment in BLCA and poor response to immunotherapy. Subsequently, we silenced METTL3 expression in BLCA cells using short hairpin RNA (shRNA) or inhibited its function with STM2457. The effectiveness of these interventions in remodeling the BLCA tumor microenvironment (TME) was confirmed through animal experiments and flow cytometry. Mechanistically, RNA sequencing and methylated RNA immunoprecipitation (MeRIP) sequencing revealed the molecular pathways by which METTL3 regulates the TME. This was further validated using in vitro cell co-culture, immunoprecipitation, ELISA, and RNA degradation assays. The synergistic effect of METTL3 with anti-Programmed Cell Death Protein 1 (PD-1) treatment in BLCA was confirmed in both orthotopic and ectopic BLCA animal models.ResultsMETTL3 was found to increase CXCL5 levels and suppress CCL5 expression in an m6A-dependent manner, leading to increased recruitment of myeloid-derived suppressor cells (MDSCs) and reduced infiltration of CD8+T cells. Silencing METTL3 or inhibiting its function restored immune cell balance and significantly enhanced the efficacy of anti-PD-1 therapy. Clinically, METTL3 overexpression correlated with poor complete response rate to immune checkpoint inhibitors (ICIs) therapy, associated with an immunosuppressive microenvironment characterized by elevated MDSC levels and reduced CD8+T cell infiltration.ConclusionsThese findings highlight METTL3 as a key regulator of the immune microenvironment in BLCA and a promising therapeutic target to improve immunotherapy outcomes. Targeting METTL3 could potentially enhance the efficacy of ICIs in patients with BLCA.

ObjectiveTo compare the outcomes of mini percutaneous nephrolithotomy (mPNL) and retrograde intrarenal surgery (RIRS) for the management of 2–3 cm lower pole renal calculi (LPC) in obese patients.Patients and methods120 obese patients with 2–3 cm LPC were randomly divided into mPNL group and RIRS group. Demography, clinical characteristics, perioperative complications, and stone free rate (SFR) were recorded. Stone-free status means no stone on computed tomography 3 months after surgery, or residual fragments were less than 3 mm.ResultsBaseline characteristics were similar between the two groups. The mean stone burden was 585.39 ± 131.06 mm2 in the mPNL group and 548.64 ± 123.55 mm2 in the RIRS group (P = 0.125). The SFR of mPNL group was significantly better than that of RIRS group (86.2% vs 61.4%, P = 0.002). Besides, the overall complication rate was 22.4% in the mPNL group and 7% in the RIRS group (P = 0.02). Patients performed with mPNL required longer length of hospital stay than those with RIRS (P = 0.001). There were no significant differences in operative time and stone composition between the two groups.ConclusionIn our study, both mPNL and RIRS are safe and effective techniques for the treatment of 2–3 cm LPC in obese patients. Compared to RIRS, mPNL has better SFR at the expense of the higher incidence of complications and prolonged length of hospital stay.