Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates a wide variety of cellular functions, including cell growth, cellular differentiation, apoptosis, and wound healing. TGF-beta1, the prototype member of the TGF-beta superfamily, is well established as a central mediator of renal fibrosis. In chronic kidney disease, dysregulation of expression and activation of TGF-beta1 results in the relentless synthesis and accumulation of extracellular matrix proteins that lead to the development of glomerulosclerosis and tubulointerstitial fibrosis, and ultimately to end-stage renal disease. Therefore, specific targeting of the TGF-beta signaling pathway is seemingly an attractive molecular therapeutic strategy in chronic kidney disease. Accumulating evidence demonstrates that the multifunctionality of TGF-beta1 is connected with the complexity of its cell signaling networks. TGF-beta1 signals through the interaction of type I and type II receptors to activate distinct intracellular pathways. Although the Smad signaling pathway is known as a canonical pathway induced by TGF-beta1, and has been the focus of many previous reviews, importantly TGF-beta1 also induces various Smad-independent signaling pathways. In this review, we describe evidence that supports current insights into the mechanism and function of TGF-beta-activated kinase 1 (TAK1), which has emerged as a critical signaling molecule in TGF-beta-induced Smad-independent signaling pathways. We also discuss the functional role of TAK1 in mediating the profibrotic effects of TGF-beta1.
Apoptosis ; Extracellular Matrix Proteins ; Fibrosis ; Kidney ; Kidney Diseases ; Kidney Failure, Chronic ; MAP Kinase Kinase Kinases ; Negotiating ; Phosphotransferases ; Renal Insufficiency, Chronic ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Wound Healing

Mitochondria are energy-producing organelles that not only satisfy the high metabolic demands of the kidney but sense and respond to kidney injury-induced oxidative stress and inflammation. Kidneys are rich in mitochondria. Mitochondrial dysfunction plays a critical role in the progression of acute kidney injury and chronic kidney disease. Mitochondrial responses to specific stimuli are highly regulated and synergistically modulated by tightly interconnected processes, including mitochondrial dynamics (fission, fusion) and mitophagy. The counterbalance between these processes is essential in maintaining a healthy network of mitochondria. Recent literature suggests that alterations in mitochondrial dynamics are implicated in kidney injury and the progression of kidney diseases. A decrease in mitochondrial fusion promotes fission-induced mitochondrial fragmentation, but a reduction in mitochondrial fission produces excessive mitochondrial elongation. The removal of dysfunctional mitochondria by mitophagy is crucial for their quality control. Defective mitochondrial function disrupts cellular redox potential and can cause cell death. Mitochondrial DNA derived from damaged cells also act as damage-associated molecular patterns to recruit immune cells and the inflammatory response can further exaggerate kidney injury. This review provides a comprehensive overview of the role of mitochondrial dysfunction in acute kidney injury and chronic kidney disease. We discuss the processes that control mitochondrial stress responses to kidney injury and review recent advances in understanding the role of mitochondrial dysfunction in inflammation and tissue damage through the use of different experimental models of kidney disease. We also describe potential mitochondria-targeted therapeutic approaches.

Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.
Aged ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Hepatocellular/drug therapy/physiopathology/*radiography ; Female ; Humans ; Liver Neoplasms/drug therapy/physiopathology/*radiography ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Niacinamide/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/*therapeutic use ; Tomography, X-Ray Computed

PURPOSE: This study was designed to investigate the reliability and validity of the World Health Organization Quality of Life Assessment Instrument (WHOQOL) in patients with breast cancer according to depressive symptoms. METHODS: One-hundred seventeen patients with breast cancer who had undergone a radical operation were recruited. The 100 item-WHOQOL instrument and Hamilton Rating Scale for Depression were used to measure all the subjects. The five domain scores, except for the WHOQOL spiritual domain, were compared between patients with and without depressive symptoms, and then the reliability and validity of the five domains were calculated. RESULTS: Depressed patients with breast cancer had lower scores in all five domains of the WHOQOL than those who were not depressed in all five domains of WHOQOL [df=(1, 115), F=46.6, p<0.001]. Reliability and validity in the physical domain of depressed patients with breast cancer decreased markedly. CONCLUSION: WHOQOL is a valid and useful instrument for evaluating the quality of life in patients with breast cancer, but is limited in scoring of depressed patients with breast cancer, particularly in the physical domain. Therefore, quality of life must be interpreted with carefully hand in depressed patients with breast cancer.
Breast ; Breast Neoplasms ; Depression ; Hand ; Humans ; Quality of Life ; Reproducibility of Results ; World Health ; World Health Organization