It is known that lipopolysaccharides (LPS) could lead to kidney injury and may play a role in intracavitary lithotripsy surgeries such as percutaneous nephrolithotomy (PCNL). Remote ischemic preconditioning (RIPC) has been demonstrated to have protective effects against kidney injury caused by various factors; however, its role in LPS-induced kidney injury remains unclear and its mechanisms require further exploration. Previous studies have shown that extracellular vesicles (EVs) induced by hypoxia mediated the renal protective effects of RIPC. In this study, we established a kidney injury model in rats by ligating the left ureter and injecting LPS into the renal pelvis, along with simultaneous removal of the right kidney (U-L model); EVs were isolated from the plasma of rats subjected to RIPC or sham treatment and administered to U-L model rats. Separately, EVs obtained from healthy human volunteers were applied to LPS-treated human renal tubular epithelial cells (HK-2). Results indicated that RIPC-EVs(R) reduced kidney injury caused by U-L by inhibiting apoptosis, inflammation, and oxidative stress. In vitro, RIPC-EVs(H) alleviate LPS-induced HK-2 cell injury by attenuating apoptosis and inflammation. Moreover, we identified 37 significantly upregulated differential proteins in the EVs sourced from human plasma after RIPC through 4D label-free proteomics, including Tenascin-C (TNC). Mechanistic studies revealed that RIPC-EVs(H) activated β-catenin, inhibited the p53 and NF-κB signaling pathways, and alleviated kidney injury. Clinical trial data showed that RIPC reduced the expression of kidney injury biomarkers in patients undergoing PCNL for kidney stones. Overall, the present study suggested that RIPC could mitigate kidney injury induced by LPS, possibly through the protective role of Tenascin-C carried by EVs.

Neutrophils are primary effectors of the innate immune system, modulating tissue homeostasis and disease through phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETs). While neutrophil infiltration is a defining hallmark of acute kidney injury (AKI), its complex role in orchestrating the transition from acute damage to chronic fibrosis is not yet fully understood. This review provides a comprehensive synthesis of the spatiotemporal mechanisms underlying neutrophil involvement in renal pathology, incorporating recruitment cascades, phenotypic activation, and pathogenic implications of NETosis. We specifically deconstruct the spatiotemporal mechanisms and heterogeneous functional subsets by which neutrophils orchestrate the AKI-to-chronic kidney disease (CKD) transition. Furthermore, we highlight emerging therapeutic targets, such as dipeptidase 1 (DPEP1) and peptidyl arginine deiminase 4 (PAD4), and discuss the translational potential of precision immunomodulatory strategies. By elucidating the multi-dimensional roles of neutrophils, this review seeks to establish a precision, stage-specific framework for novel interventions in both acute kidney disease and CKDs.

This article presents the clinical experience of our center with the SHURUI Single-Port Serpentine-Arm Robotic System for pyeloplasty in infants with ureteropelvic junction obstruction.

T cells and their subsets play dual roles in the pathogenesis, progression, and repair of kidney injury, acting as both drivers of inflammation and fibrosis and regulators of immune homeostasis and tissue repair. Although previous research has predominantly focused on the role of T cells in classic immune-mediated kidney diseases such as lupus nephritis and glomerulonephritis, with relatively less emphasis on their involvement in broader kidney injury contexts, emerging evidence reveals a more extensive and spatiotemporally specific regulatory network of T-cell subsets in acute kidney injury (AKI), chronic kidney disease (CKD), and transplant kidney injury. Within the pathological processes of kidney injury, distinct T-cell subsets contribute to disease progression through specific mechanisms. For instance, Th17 cells exacerbate acute and chronic inflammation and fibrosis via IL-17-dependent pathways, yet may contribute to repair in later injury phases. This review primarily outlines the impact of different T-cell subsets on kidney injury and explores strategies for their therapeutic targeting.

Hedyotis diffusa Willd. (HDW), a traditional Chinese medicinal plant, exhibits a variety of pharmacological effects and has anticancer potential for a wide range of cancer types; Ferroptosis is a non-apoptosis-regulated cell death induced by iron accumulation and subsequent lipid peroxidation; and there is currently an increasing interest in the therapeutic role of ferroptosis in cancer. However, the effects of HDW on bladder cancer and its underlying molecular mechanisms remain largely unknown. In this study, a combination of in vivo and in vitro experiments, network pharmacology and data mining methods were used to investigate the effects of HDW on BLCA. The results showed that HDW exerted its anticancer activity by inducing ferroptosis in bladder cancer cells. Subsequently, we demonstrated for the first time that HDW induced ferroptosis in vitro and in vivo. To further explore the possible targets of HDW-induced ferroptosis in bladder cancer, we performed network pharmacological analyses, transcriptomic analyses, and single-cell analyses; through integrative analyses, we identified three key pivotal genes associated with iron death, CAV1, VEGFA, and JUN.Mechanistically, we showed that CAV1, VEGFA and JUN are key determinants of HDW-induced ferroptosis in BLCA. Knockdown of target genes altered the anticancer effects of HDW in 5637 and T24 cells. In conclusion, our data show for the first time that HDW exerts its anticancer effects on BLCA through CAV1, VEGFA and JUN gene-induced ferroptosis. This is expected to provide a promising compound for bladder cancer therapy.

Extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSCs) have been shown to provide significant protection against renal ischemia–reperfusion injury (IRI). Hypoxia has emerged as a promising strategy to enhance the tissue repair capabilities of MSCs. However, the specific effects of hypoxia on MSCs and MSC-EVs, as well as their therapeutic potential in renal IRI, remain unclear. In this study, we investigated the alterations occurring in MSCs and the production of MSC-EVs following hypoxia pre-treatment, and further explored the key intrinsic mechanisms underlying the therapeutic effects of hypoxic MSC-EVs in the treatment of renal IRI. Human umbilical cord MSCs were cultured under normoxic and hypoxic conditions. Proliferation and related pathways were measured, and RNA sequencing was used to detect changes in the transcriptional profile. MSC-EVs from both normoxic and hypoxic conditions were isolated and characterized. In vivo, the localization and therapeutic effects of MSC-EVs were assessed in a rat renal IRI model. Histological examinations were conducted to evaluate the structure, proliferation, and apoptosis of IRI kidney tissue respectively. Renal function was assessed by measuring serum creatinine and blood urea nitrogen levels. In vitro, the therapeutic potential of MSC-EVs were measured in renal tubular epithelial cells injured by antimycin A. Protein sequencing analysis of hypoxic MSC-EVs was performed, and the depletion of Glutathione S-Transferase Omega 1 (GSTO1) in hypoxic MSC-EVs was carried out to verify its key role in alleviating renal injury. Hypoxia alters MSCs transcriptional profile, promotes their proliferation, and increases the production of EVs. Hypoxia-pretreated MSC-EVs demonstrated a superior ability to mitigate renal IRI, enhancing proliferation and reducing apoptosis of renal tubular epithelial cells both in vivo and in vitro. Protein profiling of the EVs revealed an accumulation of numerous anti-oxidative stress proteins, with GSTO1 being particularly prominent. Knockdown of GSTO1 significantly reduced the antioxidant and therapeutic effects on renal IRI of hypoxic MSC-EVs. Hypoxia significantly promotes the generation of MSC-EVs and enhances their therapeutic effects on renal IRI. The antioxidant stress effect induced by GSTO1 is identified as one of the most critical underlying mechanisms. Our findings highlight that hypoxia-pretreated MSC-EVs represent a novel and promising therapeutic strategy for renal IRI.

Metabolic disorders, including diabetes mellitus and obesity, have become major global health burdens that significantly increase the risk of kidney disease. A central pathological feature linking these conditions is lipotoxicity-the deleterious effects of lipid overload on cellular and organ function. In the kidney, lipotoxicity contributes to disease pathogenesis through a complex interplay of molecular mechanisms-such as mitochondrial dysfunction, impaired autophagy, oxidative stress, endoplasmic reticulum stress, and sustained inflammatory responses-which are detailed with a focus on their cell-specific effects in podocytes and proximal tubular cells. These pathological processes collectively disrupt renal cellular homeostasis, promote cell death, and drive progressive fibrosis, ultimately leading to functional decline. Despite significant advances in our understanding of metabolic kidney diseases, effective pharmacological interventions specifically addressing renal lipotoxicity remain strikingly limited. Current therapeutic strategies should extend beyond mere lipid reduction to comprehensively address the underlying metabolic dysregulation and its downstream cellular consequences. This review aims to analyse the pathogenic molecular mechanisms and potential therapeutic agents for renal lipotoxicity in diabetic and obesity-associated kidney diseases. It systematically examines the cell-type-specific injury mechanisms, lipotoxicity-induced renal injury, and the available evidence from both preclinical studies and clinical trials of metabolically active agents with renoprotective effects, with a view to offering novel insights and informing future therapeutic strategies for metabolic kidney diseases.

BACKGROUND: Remote ischemic preconditioning (rIPC) has been reported to protect against kidney ischemia-reperfusion injury (IRI) through the delivery of extracellular vesicles (EVs). Among these, apoptosis-induced compensatory proliferation signaling-related vesicles (ACPSVs) can transmit proliferation signals to surrounding cells. However, the underlying mechanisms remain unclear. This study aimed to investigate the role of ACPSVs in renal IRI following rIPC and to elucidate the associated mechanisms. RESULTS: We demonstrated that rIPC plasma or ACPSVs alleviated renal damage and inflammation, with the protective effects abolished upon the removal of ACPSVs from the plasma. EVs isolated via differential centrifugation exhibited defining characteristics of ACPSVs. Co-culture experiments revealed that ACPSVs reduced apoptosis and enhanced the viability of HK-2 cells under hypoxia/reoxygenation (H/R) conditions. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted the critical role of macrophage migration inhibitory factor (MIF) protein in ACPSVs. Using CRISPR/Cas9 technology, we generated MIF-knockout HeLa cells to induce the production of MIF-deficient ACPSVs. The protective effects of ACPSVs were significantly attenuated when MIF was knocked out. Transcriptome sequencing and chromatin immunoprecipitation (ChIP) assays revealed that MIF suppresses dual-specificity phosphatase 6 (DUSP6) expression by promoting H3K9 trimethylation (H3K9me3) in the DUSP6 promoter region, thereby activating the JNK signaling pathway. In rescue experiments, treatment with the DUSP6 inhibitor BCI effectively restored the protective function of MIF-deficient ACPSVs. CONCLUSION: This study underscores the protective role of ACPSVs derived from rIPC-treated rats and serum-starved cells against renal IRI through the MIF/DUSP6/JNK signaling axis, offering a potential clinical therapeutic strategy for acute kidney injury induced by IRI.

Chronic kidney disease (CKD) represents a significant global health concern, with renal fibrosis emerging as a prevalent and ultimate manifestation of this condition. The absence of targeted therapies presents an ongoing and substantial challenge. Accumulating evidence suggests that the integrity and functionality of mitochondria within renal tubular epithelial cells (RTECs) often become compromised during CKD development, playing a pivotal role in the progression of renal fibrosis. Mitophagy, a specific form of autophagy, assumes responsibility for eliminating damaged mitochondria to uphold mitochondrial equilibrium. Dysregulated mitophagy not only correlates with disrupted mitochondrial dynamics but also contributes to the advancement of renal fibrosis in CKD. While numerous studies have examined mitochondrial metabolism, ROS (reactive oxygen species) production, inflammation, and apoptosis in kidney diseases, the precise pathogenic mechanisms underlying mitophagy in CKD remain elusive. The exact mechanisms through which modulating mitophagy mitigates renal fibrosis, as well as its influence on CKD progression and prognosis, have not undergone systematic investigation. The role of mitophagy in AKI has been relatively clear, but the role of mitophagy in CKD is still rare. This article presents a comprehensive review of the current state of research on regulating mitophagy as a potential treatment for CKD. The objective is to provide fresh perspectives, viable strategies, and practical insights into CKD therapy, thereby contributing to the enhancement of human living conditions and patient well-being.

Hydronephrosis resulting from unilateral ureteral obstruction (UUO) is a common cause of renal injury, often progressing to late-stage renal fibrosis or even potential renal failure. Renal injury and repair processes are accompanied by changes in cellular senescence phenotypes. However, the mechanism is poorly understood. The purpose of this study is to clarify the changes in senescence phenotype at different time points in renal disease caused by UUO and to further investigate whether eliminating senescent cells using the anti-senescence drug ABT263 could attenuate UUO-induced renal disease. Specifically, renal tissues were collected from established UUO rat models on days 1, 2, 7, and 14. The extent of renal tissue injury and fibrosis in rats was assessed using histological examination, serum creatinine, and blood urea nitrogen levels. The apoptotic and proliferative capacities of renal tissues and phenotypic changes in cellular senescence were evaluated. After the intervention of the anti-senescence drug ABT263, the cellular senescence as well as tissue damage changes were re-assessed. We found that before the drug intervention, the UUO rats showed significantly declined renal function, accompanied by renal tubular injury, increased inflammatory response, and oxidative stress, alongside aggravated cellular senescence. Meanwhile, after the treatment with ABT263, the rats had a significantly lower number of senescent cells, attenuated renal tubular injury and apoptosis, enhanced proliferation, reduced oxidative stress and inflammation, improved renal function, and markedly inhibited fibrosis. This suggests that the use of the anti-senescence drug ABT263 to eliminate senescent cells can effectively attenuate UUO-induced renal injury. This highlights the critical role of cellular senescence in the transformation of acute injury into chronic fibrosis.

Acute kidney injury (AKI) is a common clinical disease with a high incidence and mortality rate. It typically arises from hemodynamic alterations, sepsis, contrast agents, and toxic drugs, instigating a series of events that culminate in tissue and renal damage. This sequence of processes often leads to acute renal impairment, prompting the initiation of a repair response. Cellular senescence is an irreversible arrest of the cell cycle. Studies have shown that renal cellular senescence is closely associated with AKI through several mechanisms, including the promotion of oxidative stress and inflammatory response, telomere shortening, and the down-regulation of klotho expression. Exploring the role of cellular senescence in AKI provides innovative therapeutic ideas for both the prevention and treatment of AKI. Furthermore, it has been observed that targeted removal of senescent cells in vivo can efficiently postpone senescence, resulting in an enhanced prognosis for diseases associated with senescence. This article explores the effects of common anti-senescence drugs senolytics and senostatic and lifestyle interventions on renal diseases, and mentions the rapid development of mesenchymal stem cells (MSCs). These studies have taken senescence-related research to a new level. Overall, this article comprehensively summarizes the studies on cellular senescence in AKI, aiming is to elucidate the relationship between cellular senescence and AKI, and explore treatment strategies to improve the prognosis of AKI.

Sacral spinal cord injury (SSCI) can disrupt bladder neuromodulation and impair detrusor function. Current studies provide limited information on the histologic and genetic changes associated with SSCI-related neurogenic lower urinary tract dysfunction (NLUTD), resulting in few treatment options. This study aimed to establish a simple animal model of SSCI to better understand the disease progression. Ninety 8-week-old Sprague-Dawley (SD) rats were randomly separated into sham operation and SSCI groups. The SSCI group underwent sacral spinal cord injury, while the sham group did not. Urodynamic and histological assessments were conducted at various intervals (1, 2, 3, 4, and 6 weeks) post-injury to elucidate the disease process. Urodynamic examinations revealed significant bladder dysfunction in the SSCI group compared to the sham group, stabilizing around 3–4 weeks post-injury. Histological examination, including hematoxylin–eosin and Masson’s trichrome staining, correlated these functional changes with bladder microstructural alterations. RNA-seq was performed on bladder tissues from the sham group and SSCI group at 6 weeks to identify differentially expressed genes and pathways. Selected genes were further analyzed using polymerase chain reaction (PCR). The findings indicated a pronounced inflammatory response in the first 2 weeks post-SSCI, progressing to bladder fibrosis at 3–4 weeks. In conclusion, this study presents a reliable, reproducible, and straightforward SSCI model, providing insights into bladder functional and morphological alterations post-SSCI and laying the groundwork for future therapeutic research.

Renal fibrosis represents a critical pathological condition in the progression of renal dysfunction, characterized by aberrant accumulation of extracellular matrix (ECM) and structural alterations in renal tissue. Recent research has highlighted the potential significance of gut microbiota and demonstrated their influence on host health and disease mechanisms through the production of bioactive metabolites. This review examines the role of alterations in gut microbial composition and their metabolites in the pathophysiological processes underlying renal fibrosis. It delineates current therapeutic interventions aimed at modulating gut microbiota composition, encompassing dietary modifications, pharmacological approaches, and probiotic supplementation, while evaluating their efficacy in mitigating renal fibrosis. Through a comprehensive analysis of current research findings, this review enhances our understanding of the bidirectional interaction between gut microbiota and renal fibrosis, establishing a theoretical foundation for future research directions and potential clinical applications in this domain.

The endoplasmic reticulum (ER) is indispensable for maintaining normal life activities. Dysregulation of the ER function results in the accumulation of harmful proteins and lipids and the disruption of intracellular signaling pathways, leading to cellular dysfunction and eventual death. Protein misfolding within the ER disrupts its delicate balance, resulting in the accumulation of misfolded or unfolded proteins, a condition known as endoplasmic reticulum stress (ERS). Renal fibrosis, characterized by the aberrant proliferation of fibrotic tissue in the renal interstitium, stands as a grave consequence of numerous kidney disorders, precipitating a gradual decline in renal function. Renal fibrosis is a serious complication of many kidney conditions and is characterized by the overgrowth of fibrotic tissue in the glomerular and tubular interstitium, leading to the progressive failure of renal function. Studies have shown that, during the onset and progression of kidney disease, ERS causes various problems in the kidneys, a process that can lead to kidney fibrosis. This article elucidates the underlying intracellular signaling pathways modulated by ERS, delineating its role in triggering diverse forms of cell death. Additionally, it comprehensively explores a spectrum of potential pharmacological agents and molecular interventions aimed at mitigating ERS, thereby charting novel research avenues and therapeutic advancements in the management of renal fibrosis.

There is little known about the contribution of exosomal microRNAs (exomiRs) in the children's cardiac surgery-associated acute kidney injury (CSA-AKI). This study aimed to find diagnostic biomarkers for predicting CSA-AKI in children. A prospective observational study was conducted from April 2020 to March 2021.According to the changes of serum creatinine (SCr) value and urine volume within 48 h, the children were divided into acute kidney injury (AKI) group and non-AKI group. Serum samples were collected 4 h after cardiac surgery. Isolation of extracellular vesicles (EVs) and extraction of exomiRs from serum samples. Illumina high-throughput sequencing was used to quantify exomiRs and screen candidate microRNAs (miRNAs). Expression levels of candidate miRNAs were validated using droplet digital polymerase chain reaction (ddPCR). Normal and injuried rats' kidney tissue were collected for tissue validation. In the pre-experimental stage (4 AKI vs. 4 non-AKI), hsa-miR-184, hsa-miR-4800-3p, hsa-miR-203a-3p and hsa-miR-6766-3p were selected as candidate genes. In the verification stage (8 AKI vs. 12 non-AKI), the expression of hsa-miR-184 in AKI group was significantly lower than that in non-AKI group (P = 0.031), and the expression of hsa-miR-4800-3p and hsa-miR-6766-3p in AKI group was significantly higher than that in non-AKI group (P = 0.01 and P = 0.047). There was no significant difference in the expression of hsa-miR-203a-3p between the two groups (P > 0.05). The expression of rats' kidney tissue rno-miR-184 in AKI group was significantly lower than that in the normal group (P = 0.044). The area under the curve (AUC) of AKI predicted by hsa-miR-184 is 0.7865 and the AUC of hsa-miR-6766-3p is 0.7708. Combined with two kinds of miRNAs, the area under the curve of AKI is predicted to be 0.8646. The change of exomiRs level in circulatory system occurred in the early stage after cardiac operation, and the changes of hsa-miR-184 and hsa-miR-6766-3p content in circulatory system could predict CSA-AKI well.

The treatment of breast cancer relies heavily on chemotherapy, but chemotherapy is limited by the disadvantages of poor targeting, susceptibility to extracellular matrix (ECM) interference and a short duration of action in tumor cells. To address these limitations, we developed an amphipathic peptide containing an RGD motif, Pep1, that encapsulated paclitaxel (PTX) and losartan potassium (LP) to form the drug-loaded peptide PL/Pep1. PL/Pep1 self-assembled into spherical nanoparticles (NPs) under normal physiological conditions and transformed into aggregates containing short nanofibers at acidic pH. The RGD peptide facilitated tumor targeting and the aggregates prolonged drug retention in the tumor, which allowed more drug to reach and accumulate in the tumor tissue to promote apoptosis and remodel the tumor microenvironment. The results of in vitro and in vivo experiments confirmed the superiority of PL/Pep1 in terms of targeting, prolonged retention and facilitated penetration for antitumor therapy. In conclusion, amphipathic peptides as coloaded drug carriers are a new platform and strategy for breast cancer chemotherapy.

Rapid and accurate identification of specific sepsis pathogens is critical for patient treatment and disease control.This study aimed to establish a new application for the rapid identification of common pathogens in patients with suspected sepsis and evaluate its role in clinical application.A multiplex PCR assay was designed to simultaneously amplify specific conserved regions of 9 common pathogenic microorganisms in sepsis, including Acinetobacter baumannii, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumonia, and Candida albicans.The PCR products were analyzed by a membrane biochip.The analytical sensitivity of the assay was determined at a range of 5-100 copies/reaction for each standard strain, and the detection range was 20-200 cfu/reaction in a series dilution of simulated clinical samples at different concentrations.Out of the 179 clinical samples, the positive rate for pathogens detected by the membrane biochip assay and blood culture method was 20.11% (36/179) and 18.44% (33/179), respectively.However, by comparing the positive rate of the 9 common pathogens we detected, the membrane biochip assay tended to be more sensitive than the blood culture method (20.11%vs15.64%).The clinical sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the membrane biochip assay were 92.9%, 93.2%, 72.2% and 98.6%, respectively.Generally, this multiplex PCR combined membrane biochip assay can be used to detect major sepsis pathogens, and is useful for early initiation of effective antimicrobial treatment, and is feasible for sepsis pathogens identification in routine clinical practice.

目的 总结采用球囊扩张术治疗的原发性梗阻型巨输尿管患儿资料,探讨该治疗方法的安全性及可行性.方法 回顾性收集2018年9月至2022年1月在上海交通大学医学院附属上海儿童医学中心泌尿外科行球囊扩张术治疗的原发性梗阻型巨输尿管患儿术前及术后随访资料,包括年龄、性别、肾盂前后径、输尿管最宽径、分肾功能等数据.采取自身前后对照的方法对疗效进行分析.结果 本院共收治41例原发性梗阻型巨输尿管患儿,共42侧输尿管实施球囊扩张术.2例拔除DJ管后仍有反复腹痛,改行输尿管再植术治愈;1例球囊扩张失败,术后未予进一步治疗,随访至今已33个月,肾积水症状无缓解;1例行扩张术中输尿管破裂,经输尿管再植术治愈.其余37例(38侧输尿管)均手术成功并获随访,患儿年龄(32.9±35.7)个月,随访时间(17.2±9.5)个月,术前分肾功能(48％±10％);肾盂前后径术前为(17.8±14.7)mm,术后为(9.7±8.9)mm,差异有统计学意义(P＜0.01);输尿管最宽径术前为(13.4±2.9)mm,术后为(7.5±6.9)mm,差异有统计学意义(P＜0.01).结论 采用球囊扩张术治疗原发性梗阻型巨输尿管,短期随访上尿路积水症状明显改善.球囊扩张术操作简单,术后恢复快,具有广阔的应用前景.