Emerging strategies to disrupt the central TGF- β axis in kidney fibrosis.

Emerging strategies to disrupt the central TGF-β axis in kidney fibrosis. Transl Res. 2019 Apr 24;: Authors: Rauchman M, Griggs D Abstract Chronic kidney disease (CKD) affects more than 20 million people in the United States and the global burden of this disorder is increasing. Many affected individuals will progress to end stage kidney disease necessitating dialysis or transplantation. CKD is also a major independent contributor to the risk of cardiovascular morbidity and mortality. Tubulointerstitial fibrosis is a final common pathway for most causes of progressive CKD. Currently, there are no clinically available therapies targeting fibrosis that can slow the decline in kidney function. Although it has long been known that TGF-β signaling is a critical mediator of kidney fibrosis, translating this knowledge to the clinic has been challenging. In this review, we highlight some recent insights into the mechanisms of TGF-β signaling that target activation of this cytokine at the site of injury or selectively inhibit pro-fibrotic gene expression. Molecules directed at these targets hold the promise of attaining therapeutic efficacy while limiting toxicity seen with global inhibition of TGF-β. Kidney injury has profound epigenetic effects leading to altered expression of more than a thousand genes. We discuss how drugs targeting epigenetic modifications, some of which are in use for cancer therapy, have the potential to reprogram gene r...
Source: Translational Research : the journal of laboratory and clinical medicine - Category: Laboratory Medicine Authors: Tags: Transl Res Source Type: research

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Purpose of review Prolyl-hydroxylase inhibitors are a novel class of orally administered drugs that are under development for the treatment of anemia in patients with chronic kidney disease. This review discusses the biology of these drugs and their target – hypoxia-inducible factor and potential advantages and disadvantages of these therapies. Finally, we will discuss current trials in patients with both chronic kidney disease and end-stage renal disease. Recent findings Recent smaller studies have found that prolyl-hydroxylase are as effective as erythropoietin in treating anemia of chronic kidney disease. We ...
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: DIALYSIS AND TRANSPLANTATION: Edited by Anil Chandraker and J. Kevin Tucker Source Type: research
In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone. Permanently Boosting Levels of Natural Killer Cells in Mice to Increase Cancer Resistance https://www.fightaging.org/archives/2019/09/permanently-boosting-levels-of-natural-killer-cells-in-mice-to-increase-cancer-resistance/ Researchers here demonstrate a very interesting approach to immunotherapy: they introduce engineered stem cells in mice that will give rise to additional natural killer T cells, boosting the capability of the ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
stic Anemia Working Party of the European Society for Blood and Marrow Transplantation Abstract This follow-up study of the randomized prospective trial included 192 patients with newly diagnosed severe aplastic anemia receiving Antithymoglobulin and Cyclosporine, with and without G-CSF. We aimed to evaluate the long-term effect of G-CSF on overall survival, event-free survival, probability of secondary myelodysplastic syndrome or acute myeloid leukemia, clinical paroxysmal nocturnal hemoglobinuria, relapse, avascular osteonecrosis and chronic kidney disease. The median follow-up was 11.7 years (10.9-12.5). Overal...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Publication date: Available online 9 September 2019Source: American Journal of Kidney DiseasesAuthor(s): Lilia Cervantes, Romana Hasnain-Wynia, John F. Steiner, Michel Chonchol, Stacy FischerMembers of racial and ethnic minority groups make up nearly 50% of US patients with end-stage kidney disease and face a disproportionate burden of socioeconomic challenges (ie, low income, job insecurity, low educational attainment, housing instability, and communication challenges) compared with non-Hispanic whites. Patients with end-stage kidney disease who face social challenges often have poor patient-centered and clinical outcomes...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
We examined human lung tissue from COPD patients and normal control subjects, and found a substantial increase in p16-expressing alveolar cells in COPD patients. Using a transgenic mouse deficient for p16, we demonstrated that lungs of mice lacking p16 were structurally and functionally resistant to CS-induced emphysema due to activation of IGF1/Akt regenerative and protective signaling. Fat Tissue Surrounds Skeletal Muscle to Accelerate Atrophy in Aging and Obesity https://www.fightaging.org/archives/2019/09/fat-tissue-surrounds-skeletal-muscle-to-accelerate-atrophy-in-aging-and-obesity/ Researchers her...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined. Mean nonfasting cholesterol concentration was 72...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, we show here that sEVs are responsible for mediating paracrine senescence and speculate that they could be involved in inducing bystander senescence during therapy-induced senescence or aging. In fact, when compared to soluble factors, sEVs have different biophysical and biochemical properties as they have a longer lifespan than do soluble factors and they are more resistant to protease degradation. The idea that blocking sEV secretion could be a potential therapeutic approach to alleviate senescence "spreading" during chemotherapy-induced senescence or in aging tissues presents itself as a very at...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
President Donald Trump on Wednesday signed an executive order aimed at streamlining the overburdened kidney care and transplantation system—a move meant to “bring new hope to millions of Americans suffering from kidney disease,” Trump said. The policy is intended to improve kidney care in three major ways: by emphasizing more effective and convenient treatments; making more kidneys available for transplant; and improving preventive care and education with the goal of reducing the number of people who develop end-stage renal disease by 25% by 2030. Kidney disease tends not to attract as much attention as o...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized medicine onetime White House Source Type: news
Conclusions: We identified key factors that increase the risk of ASE in patients with CKD. Opportunities exist to reduce ASE in CKD.Am J Nephrol
Source: American Journal of Nephrology - Category: Neurology Source Type: research
CONCLUSIONS: We identified key factors that increase the risk of ASE in patients with CKD. Opportunities exist to reduce ASE in CKD. PMID: 31216553 [PubMed - as supplied by publisher]
Source: American Journal of Nephrology - Category: Urology & Nephrology Authors: Tags: Am J Nephrol Source Type: research
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