Ischemia-reperfusion injury (IRI) is a complex pathophysiological process that is often characterized as a blood circulation disorder caused due to various factors (such as traumatic shock, surgery, organ transplantation, burn, and thrombus). Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. Theoretically, IRI can occur in various tissues and organs, including the kidney, liver, myocardium, and brain, among others. The advances made in research regarding restoring tissue perfusion in ischemic areas have been inadequate with regard to decreasing the mortality and infarct size associated with IRI. Hence, the clinical treatment of patients with severe IRI remains a thorny issue. Peroxisome proliferator-activated receptor γ (PPARγ) is a member of a superfamily of nuclear transcription factors activated by agonists and is a promising therapeutic target for ameliorating IRI. Therefore, this review focuses on the role of PPARγ in IRI. The protective effects of PPARγ, such as attenuating oxidative stress, inhibiting inflammatory responses, and antagonizing apoptosis, are described, envisaging certain therapeutic perspectives.
ObjectiveThe choice of surgical method for clinically diagnosed T2 or higher stage kidney cancer remains controversial. Here, we systematically reviewed and collected published comparative studies on renal function, oncologic outcomes, and perioperative results of partial nephrectomy (PN) versus radical nephrectomy (RN) for larger renal tumors (T2 and above), and performed a meta-analysis.Evidence AcquisitionFollowing searches of PubMed, Web of Science, and Embase, the original studies on PN vs. RN in the treatment of T2 renal cancer were screened through strict inclusion and exclusion criteria. RevMan 5.4 was used for data analysis of the perioperative results, renal function, and oncologic outcomes of the two surgical methods for T2 renal tumor therapy. The weighted mean difference was used as the combined effect size for continuous variables, while the odds ratio (OR) or risk ratio (RR) was used as the combined effect size for binary variables. Both variables used a 95% confidence interval (CI) to estimate statistical accuracy. In cases with low heterogeneity, the fixed-effects model was used to pool the estimated value; otherwise, the random-effects model was used when significant heterogeneity was detected.ResultsFifteen retrospective studies including 5,056 patients who underwent nephrectomy (PN: 1975, RN: 3081) were included. The decline in estimated GFR (eGFR) after PN was lower than RN [(MD: −11.74 ml/min/1.73 m2; 95% CI: −13.15, −10.32; p < 0.00001)]. The postoperative complication rate of PN was higher than that of PN (OR: 2.09; 95% CI: 1.56, 2.80; p < 0.00001)], and the postoperative overall survival (OS) of PN was higher than that of RN (HR: 0.77; 95% CI: 0.65, 0.90; p = 0.002), and tumor recurrence (RR, 0.69; 95% CI: 0.53, 0.90; p = 0.007). No obvious publication bias was found in the funnel chart of the OS rates of the two groups of patients.ConclusionsPN is beneficial for patients with T2 renal tumors in terms of OS and renal function protection. However, it is also associated with a higher risk of surgical complications.
Renal cell carcinoma (RCC) is a genitourinary system tumor that seriously threatens people's lives and health. The complex pathophysiological process of RCC, which makes up approximately 16% of patients, is metastatic at the time of diagnosis and has a low 5-year relative survival rate, resulting in more than 65,000 new cases being diagnosed and almost 15,000 deaths every year in the United States. 1 There are three major histological subtypes of RCC, including clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC). Among these three histological subtypes, ccRCC accounts for 70%-80% of RCC cases. 2 Surgical resection is the primary recommended therapeutic method for localized ccRCC; however, poor prognosis was also reported; approximately 30%-40% of ccRCC patients initially diagnosed with advanced-stage disease developed metastatic recurrence, with 50%, 30%, and less than 11.2% survival rates at 1, 3, and 5 years, respectively, according to recent reports. 3,4 Herein, a comprehensive understanding of RCC is paramount to the development of improved patient management and treatment. In particular, the identification of some precise biomarkers during the process of RCC progression and pathophysiologic procedures is critical for improving the diagnosis and management of RCC.Thanks for the considerable development in transcriptome profiling, providing robust data that allow
Background: The immune microenvironment profoundly affects tumor prognosis and therapy. The present study aimed to reveal potential immune escape mechanisms and construct a novel prognostic signature via systematic bioinformatic analysis of the bladder cancer (BLCA) immune microenvironment.Patients and Methods: The transcriptomic data and clinicopathological information for patients with BLCA were obtained from The Cancer Genome Atlas (TCGA). Consensus clustering analysis based on the CIBERSORT and ESTIMATE algorithms was performed with patients with BLCA, which divided them into two clusters. Subsequently, the differentially expressed genes (DEGs) in the two were subjected to univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses to identify prognostic genes, which were used to construct a prognostic model. The predictive performance of the model was verified by receiver operating characteristic (ROC) and Kaplan–Meier (K-M) analyses. In addition, we analyzed the differentially altered immune cells, mutation burden, neoantigen load, and subclonal genome fraction between the two clusters to reveal the immune escape mechanism.Results: Based on the ESTIMATE and clustering analyses, patients with BLCA were classified into two heterogeneous clusters: ImmuneScoreH and ImmuneScoreL. Univariate Cox and LASSO regression analyses identified CD96 (HR = 0.83) and IBSP (HR = 1.09), which were used to construct a prognostic gene signature with significant predictive accuracy. Regarding potential immune escape mechanisms, ImmuneScoreH and ImmuneScoreL were characterized by inactivation of innate immune cell chemotaxis. In ImmuneScoreL, a low tumor antigen load might contribute to immune escape. ImmuneScoreH featured high expression of immune checkpoint molecules.Conclusion: CD96 and IBSP were considered prognostic factors for BLCA. Innate immune inactivation and a low tumor antigen load may be associated with immune escape mechanisms in both clusters. Our research complements the exploration of the immune microenvironment in BLCA.
Renal ischemia-reperfusion injury (RIRI) is a common pathological process that causes kidney injury. Previous studies have indicated that both peroxisome proliferator-activated receptor γ (PPARγ) and microRNA-21 (miR-21) exert protective effects against RIRI. However, their relationship is not well understood. In the present study, we investigated the role of the PPARγ/miR-21/programmed cell death 4 (PDCD4) axis in IRI, both in vivo and in vitro. In vitro cell hypoxia/reoxygenation (H/R) and in vivo RIRI models were established, and cell viability, cell apoptosis, and key molecule expression profiles were analyzed. Our results showed that both PPARγ and miR-21 had protective effects against RIRI to varying degrees, and there was an interaction between PPARγ and miR-21. PPARγ could promote the expression of miR-21 and partially protect against RIRI by reducing the level of the miR-21 target protein (PDCD4). Our findings underscore the potential utility of future clinical investigations of PPARγ activation and targeting of the underlying miR-21/PDCD4/caspase-3 pathway, which may participate in the pathogenesis of human IRI.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.