Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel oral agents for treating anemia in chronic kidney disease (CKD), with potential effects on lipid modulation. We aimed to systematically evaluate the effects of HIF-PHIs on lipid profiles and cardiovascular outcomes in CKD patients. PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase (Ovid) were searched for randomized controlled trials comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in dialysis-dependent (DD) or nondialysis-dependent (NDD) CKD patients. Primary outcomes included changes in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). Secondary outcomes included cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and all-cause mortality. A total of 20 trials involving 12,155 patients were analyzed in this review. Roxadustat significantly reduced LDL-C (mean difference [MD], -16.07 mg/dL; 95
Transforming growth factor-β (TGF-β) signaling plays a central role in lung tissue homeostasis, coordinating epithelial repair, immune resolution, and stromal remodeling following injury. However, persistent or dysregulated TGF-β activation is a hallmark of both idiopathic pulmonary fibrosis (IPF) and lung cancer, two devastating pulmonary diseases that are traditionally studied as distinct entities. Emerging evidence suggests that this dichotomous view may obscure shared pathogenic mechanisms driven by aberrant TGF-β signaling dynamics. In this review, we synthesize experimental, translational, and clinical findings to propose a unifying framework in which IPF and lung cancer represent endpoints along a shared TGF-β–driven pathological continuum. We highlight how the duration and intensity of TGF-β signaling determine divergent cellular outcomes across epithelial cells, fibroblasts, and immune compartments—ranging from physiological wound repair to irreversible fibrotic remodeling and the establishment of a pro-tumorigenic niche. Particular emphasis is placed on the temporal transition from acute injury responses to chronic signaling states that promote epithelial plasticity, fibroblast fixation, immune suppression, and genomic instability. By integrating fibrosis and tumorigenesis into a single pathophysiological model, this review reframes TGF-β signaling as a time-dependent disease modifier rather than a disease-specific factor. This perspective provides a conceptual basis for therapeutic strategies targeting TGF-β signaling windows to intercept disease progression before irreversible fibrosis or malignant transformation occurs.
Purpose:To determine the most effective technique for bladder cuff excision in treating upper urinary tract urothelial carcinoma.Materials and methods:We conducted a retrospective analysis of 1172 urinary tract urothelial carcinoma patients across 19 hospitals in Taiwan between July 1988 and August 2022, focusing on surgeries performed from January 11, 2001, to November 22, 2021. Patients were divided into 3 groups: open incision, transurethral, and laparoscopic (LPS)/robotic/laparoendoscopic single-site surgery (LESS). The open incision group comprised 1056 patients, while the remaining patients were divided among the other techniques.Results:Univariate analysis revealed that LPS/robotic/LESS resulted in better overall survival compared with open incision (hazard ratio [HR] = 0.612; 95% confidence interval [CI], 0.448-0.836; P = 0.002). In terms of bladder recurrence-free survival, the transurethral group showed a lower bladder recurrence rate than the open incision group (HR = 0.697; 95% CI, 0.505-0.961; P = 0.028). However, multivariate analysis indicated that the transurethral method had worse outcomes than the open incision for cancer-specific survival (HR = 2.347; 95% CI, 1.115-4.942; P = 0.025) and disease-free survival (HR = 1.831; 95% CI, 1.079-3.108; P = 0.025). Surprisingly, the transurethral group showed better bladder recurrence-free survival (HR = 0.606; 95% CI, 0.414-0.888; P = 0.01).Conclusion:Based on these findings, LPS/robotic/LESS appeared to be the preferred choice for bladder cuff excision.
Natural flavonoids (flavones) and synthetic aminoflavones are known for their anti-cancer properties; however, their immunomodulation ability has been largely unexplored. This study determined that synthetic flavones and aminoflavones modulate the cytotoxicity of natural killer (NK) cells against lung cancer cells. Notably, flavones 2, 3, and 6 and aminoflavone 8 were shown to increase the cytotoxicity of NK-92MI cells against A549 lung cancer cells without adversely affecting MRC5 normal cells. Aminoflavone 8 enhanced NK-92MI cell cytotoxicity, as evidenced by the elevated expression of cytotoxic effectors, such as IFN-γ, perforin, and granzyme B. Aminoflavone 8 also inhibited STAT3 phosphorylation in A549 lung cancer and NK-92MI cells under co-culture conditions. Moreover, aminoflavone 8 exhibited anti-tumour effects in a lung cancer xenograft mouse model. Combined therapy with aminoflavone 8 and NK-92MI cells had synergistic anti-tumour effects without liver or kidney toxicity. Our analysis revealed that the amino group in the C6 position of aminoflavone 8 was crucial to the enhanced cytotoxicity of NK cells. These findings suggest that aminoflavone 8 can potentiate NK cell cytotoxicity against lung cancer cells, highlighting its potential as a novel therapeutic agent for the treatment of lung cancer.
