The application of nanoparticles-based ferroptosis, pyroptosis and autophagy in cancer immunotherapy.

Immune checkpoint blockers (ICBs) have been applied for cancer therapy and achieved great success in the field of cancer immunotherapy. Nevertheless, the broad application of ICBs is limited by the low response rate. To address this issue, increasing studies have found that the induction of immunogenic cell death (ICD) in tumor cells is becoming an emerging therapeutic strategy in cancer treatment, not only straightly killing tumor cells but also enhancing dying cells immunogenicity and activating antitumor immunity. ICD is a generic term representing different cell death modes containing ferroptosis, pyroptosis, autophagy and apoptosis. Traditional chemotherapeutic agents usually inhibit tumor growth based on the apoptotic ICD, but most tumor cells are resistant to the apoptosis. Thus, the induction of non-apoptotic ICD is considered to be a more efficient approach for cancer therapy. In addition, due to the ineffective localization of ICD inducers, various types of nanomaterials have been being developed to achieve targeted delivery of therapeutic agents and improved immunotherapeutic efficiency. In this review, we briefly outline molecular mechanisms of ferroptosis, pyroptosis and autophagy, as well as their reciprocal interactions with antitumor immunity, and then summarize the current progress of ICD-induced nanoparticles based on different strategies and illustrate their applications in the cancer therapy.

PODNL1 promotes cell migration and regulates the epithelial/mesenchymal transition process in bladder cancer.

PODNL1, a member of the small leucine-rich proteoglycans family, has been identified to be closely associated with the prognosis of ovarian cancer and glioma. In this study, we explored the role of PODNL1 in the progression of bladder cancer (BLCA). TCGA data analysis showed that the expression level of PODNL1 in BLCA tissues was significantly higher than that in adjacent tissues. The high expression of PODNL1 was related to T stage, N stage, pathological stage, pathological grade and histological type of BLCA. The results of qPCR further confirmed that the expression of PODNL1 in BLCA cell lines was significantly higher than that in normal bladder epithelial cells (SV-HUC-1). In addition, PODNL1 knockdown decreased the proliferation and migration abilities of BLCA cells, while PODNL1 overexpression promoted the proliferation and migration abilities of BLCA cells. WGCNA and functional enrichment analysis showed that PODNL1 expression was closely related to the epithelial mesenchymal transformation (EMT) pathway of BLCA. Furthermore, GSCA database analysis also showed that high expression of PODNL1 activated the EMT pathway of BLCA. The results of qPCR indicated that PODNL1 gene expression level was negatively correlated with e-cadherin expression, and positively correlated with N-cadherin expression. Thus, these results suggest that PODNL1 regulates EMT process. Additionally, high expression of PODNL1 was closely associated with poor prognosis in BLCA patients. In conclusion, PODNL1 is a potential therapeutic target and prognostic biomarker of BLCA.

Comparison of two techniques for the management of 2-3 cm lower pole renal calculi in obese patients.

OBJECTIVE: To 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 METHODS: 120 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. RESULTS: Baseline 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. CONCLUSION: In 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.

Comparison of contrast-enhanced ultrasound versus conventional ultrasound-guided percutaneous nephrolithotomy in patients with nondilated collecting system: a randomized controlled trial.

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 Application of Nanoparticles Targeting Cancer-Associated Fibroblasts.

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.

Cell membrane coated nanoparticles as a biomimetic drug delivery platform for enhancing cancer immunotherapy.

Cancer immunotherapy, a burgeoning modality for cancer treatment, operates by activating the autoimmune system to impede the growth of malignant cells. Although numerous immunotherapy strategies have been employed in clinical cancer therapy, the resistance of cancer cells to immunotherapeutic medications and other apprehensions impede the attainment of sustained advantages for most patients. Recent advancements in nanotechnology for drug delivery hold promise in augmenting the efficacy of immunotherapy. However, the efficacy is currently constrained by the inadequate specificity of delivery, low rate of response, and the intricate immunosuppressive tumor microenvironment. In this context, the investigation of cell membrane coated nanoparticles (CMNPs) has revealed their ability to perform targeted delivery, immune evasion, controlled release, and immunomodulation. By combining the advantageous features of natural cell membranes and nanoparticles, CMNPs have demonstrated their unique potential in the realm of cancer immunotherapy. This review aims to emphasize recent research progress and elucidate the underlying mechanisms of CMNPs as an innovative drug delivery platform for enhancing cancer immunotherapy. Additionally, it provides a comprehensive overview of the current immunotherapeutic strategies involving different cell membrane types of CMNPs, with the intention of further exploration and optimization.

Recent Advances in Nanomaterials for the Treatment of Acute Kidney Injury.

Acute kidney injury (AKI) is a serious clinical syndrome with high morbidity, elevated mortality, and poor prognosis, commonly considered a "sword of Damocles" for hospitalized patients, especially those in intensive care units. Oxidative stress, inflammation, and apoptosis, caused by the excessive production of reactive oxygen species (ROS), play a key role in AKI progression. Hence, the investigation of effective and safe antioxidants and inflammatory regulators to scavenge overexpressed ROS and regulate excessive inflammation has become a promising therapeutic option. However, the unique physiological structure and complex pathological alterations in the kidneys render traditional therapies ineffective, impeding the residence and efficacy of most antioxidant and anti-inflammatory small molecule drugs within the renal milieu. Recently, nanotherapeutic interventions have emerged as a promising and prospective strategy for AKI, overcoming traditional treatment dilemmas through alterations in size, shape, charge, and surface modifications. This Review succinctly summarizes the latest advancements in nanotherapeutic approaches for AKI, encompassing nanozymes, ROS scavenger nanomaterials, MSC-EVs, and nanomaterials loaded with antioxidants and inflammatory regulator. Following this, strategies aimed at enhancing biocompatibility and kidney targeting are introduced. Furthermore, a brief discussion on the current challenges and future prospects in this research field is presented, providing a comprehensive overview of the evolving landscape of nanotherapeutic interventions for AKI.

CircRPPH1 accelerates the proliferation and migration of bladder cancer via enhancing the STAT3 signaling pathway.

Bladder cancer (BCa) is a common malignant disease with high recurrence and variable prognosis. Circular RNAs (circRNAs) are implicated in the development of multiple diseases. However, the biological activities of circRNAs in BCa remain largely elusive. In the present study, it was found that circRPPH1 was upregulated in BCa cell lines compared with normal urothelial cells. CircRPPH1 downregulation could inhibit the proliferation, migration and invasion of BCa cells in vitro and in vivo. Mechanistically, it was demonstrated that circRPPH1 can act as a sponge of miR­296­5P to upregulate STAT3, and interact with FUS to promote phosphorylated (p)­STAT3 nuclear transport. Overall, circRPPH1 could promote BCa progression through sponging miR­296­5p to upregulate the expression of STAT3 and interacting with FUS to promote p­STAT3 nuclear transport. CircRPPH1 was first identified to play a tumorigenic role in BCa, which could be an underlying therapeutic target.

Antioxidant nanozymes in kidney injury: mechanism and application.

Excessive production of reactive oxygen species (ROS) in the kidneys is involved in the pathogenesis of kidney diseases, such as acute kidney injury (AKI) and diabetic kidney disease (DKD), and is the main reason for the progression of kidney injury. ROS can easily lead to lipid peroxidation and damage the tubular epithelial cell membrane, proteins and DNA, and other molecules, which can trigger cellular oxidative stress. Effective scavenging of ROS can delay or halt the progression of kidney injury by reducing inflammation and oxidative stress. With the development of nanotechnology and an improved understanding of nanomaterials, more researchers are applying nanomaterials with antioxidant activity to treat kidney injury. This article reviews the detailed mechanism between ROS and kidney injury, as well as the applications of nanozymes with antioxidant effects based on different materials for various kidney injuries. To better guide the applications of antioxidant nanozymes in kidney injury and other inflammatory diseases, at the end of this review we also summarize the aspects of nanozymes that need to be improved. An in-depth understanding of the role played by ROS in the occurrence and progression of kidney injury and the mechanism by which antioxidant nanozymes reduce oxidative stress is conducive to improving the therapeutic effect in kidney injury and inflammation-related diseases.

The role of circular RNA in tumor microenvironment and immunotherapy.

Cancer immunotherapy has favorable efficacy in various types of tumors, and has become an important weapon in the treatment of tumors in recent years. Long noncoding RNAs and microRNAs have been identified to play important roles in regulating cancer immunotherapy. Circular RNAs (circRNAs) are involved in the pathological process of many diseases, especially cancer. Many functions of circRNAs have been extensively studied. However, the functions of circRNAs in the tumor microenvironment and cancer immunotherapy do not appear to be fully elucidated. Therefore, we review the roles of circRNAs in tumor microenvironment and cancer immunotherapy.

Predictive value of CD3+ cells and interleukin 2 receptor in systemic inflammatory response syndrome after percutaneous nephrolithotomy.

Objective: 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. Methods: 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. Results: There were 50 patients (32.5%) who developed SIRS after PCNL. In multivariate analysis, positive urine culture (odds ratio [OR], 3.556; p = 0.048), long operation time (OR, 1.011; p = 0.027), high IL-2R (OR, 1.002; p = 0.018), low percentage of CD3+ cells (OR 0.931; p = 0.006), and high white blood cell (WBC) count (OR, 1.282; p = 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. Conclusions: 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.

Biological Roles and Clinical Significance of Exosome-Derived Noncoding RNAs in Bladder Cancer.

Bladder cancer (BCa) is a common heterogeneous urinary system tumor with high malignancy and limited advancement in treatment. Limited understanding of BCa has not contributed to any significant progress in diagnosis or treatment, exploring the mechanisms underlying BCa has become an urgent research focus. Exosomes, a type of extracellular vesicle (EV), have drawn substantial interest for their important roles in mediating intracellular communication. Exosomes shuttle numerous bioactive molecules, and noncoding RNAs (ncRNAs) are among the most numerous. ncRNAs including microRNA, long noncoding RNA, and circular RNA are sorted and packaged into exosomes selectively and transferred into recipient cells to regulate their function. Exosomal ncRNAs are associated with hallmarks of BCa, such as proliferation, apoptosis, epithelial-mesenchymal transition (EMT), cell cycle arrest, lymphangiogenesis, and chemotherapy resistance. Exosomal ncRNAs can also be detected in urine and serum, making them encouraging biomarkers for BCa diagnosis and prognosis. More importantly, exosomes exhibit excellent biocompatibility and potential for diversified applications. The delivery of bioactive substances and drugs into specific cells has become a promising approach for precision therapy for BCa patients. In addition, cancer vaccines have also received increasing attention. In this review, we summarize the current research on the regulatory roles of exosomal ncRNAs in BCa tumorigenesis and progression, as well as their potential clinical value in accelerating the diagnosis and therapy of BCa.

Circular RNAs in prostate cancer: Biogenesis,biological functions, and clinical significance.

Circular RNAs (circRNAs) are covalently closed RNA molecules that play important regulatory roles in various tumors. Prostate cancer (PCa) is one of the most common malignant tumors in the world, with high morbidity and mortality. In recent years, more and more circRNAs have been found to be abnormally expressed and involved in the occurrence and development of PCa, including cell proliferation, apoptosis, invasion, migration, metastasis, chemotherapy resistance, and radiotherapy resistance. Most of the circRNAs regulate biological behaviors of cancer through a competitive endogenous RNA (ceRNA) regulatory mechanism, and some can exert their functions by binding to proteins. circRNAs are also associated with many clinicopathological features of PCa, including tumor grade, lymph node metastasis, and distant metastasis. In addition, circRNAs are potential diagnostic and prognostic biomarkers for PCa. Considering their critical regulatory roles in the progression of PCa, circRNAs would be the potential therapeutic targets. In this paper, the current research status of circRNAs in PCa is briefly reviewed.