Genetic induction of hypoxia signaling by deletion of the von Hippel-Lindau (Vhl) protein in mesenchymal PDGFR-β+ cells leads to abundant HIF-2 dependent erythropoietin (EPO) expression in the cortex and outer medulla of the kidney. This rather unique feature of kidney PDGFR-β+ cells promote questions about their special characteristics and general functional response to hypoxia. To address these issues, we characterized kidney PDGFR-β+ EPO expressing cells based on additional cell markers and their gene expression profile in response to hypoxia signaling induced by targeted deletion of Vhl or exposure to low oxygen and carbon monoxide respectively, and after unilateral ureteral obstruction. CD73+, Gli1+, tenascin C+ and interstitial SMMHC+ cells were identified as zonally distributed subpopulations of PDGFR-β+ cells. EPO expression could be induced by Vhl deletion in all PDGFR-β+ subpopulations. Under hypoxemic conditions, recruited EPO+ cells were mostly part of the CD73+ subpopulation. Besides EPO production, expression of adrenomedullin and regulator of G-protein signaling 4 was upregulated in PDGFR-β+ subpopulations in response to the different hypoxic stimuli. Thus, different kidney interstitial PDGFR-β+ subpopulations exist, capable of producing EPO in response to different stimuli. Activation of hypoxia signaling in these cells also induces factors likely contributing to improved kidney interstitial tissue oxygenation.With the emergence of drug-resistant bacteria, conventional antibiotics are becoming increasingly ineffective for the treatment of bacterial infections. Nanomaterial-modified antibiotics, denoted as "nanoantibiotics", can usually circumvent most of the shortcomings of conventional antibiotics, thus improving antibacterial activities. Here, we developed triclosan-based supramolecular hydrogel nanoantibiotics by conjugating small molecule antibiotic triclosan (TCS) to self-assembling peptides. The resultant nanoantibiotics presented many beneficial characteristics (i) a stable three-dimensional nanofiber structure; (ii) increased TCS solubility by 850-fold; (iii) acid-responsive TCS release; (iv) favorable biocompatibility. In consequence, the nanoantibiotics showed potent in vitro broad-spectrum antibacterial activities against both Gram-positive and Gram-negative bacteria based on the cooperative effect of antibiotic TCS and the nanostructure-induced bacterial membrane disruption. Furthermore, the TCS-based supramolecular hydrogel nanoantibiotics exhibited enhanced antibacterial activities with low side effects, according to the in vivo antibacterial evaluation at the macro and micro level.  https://www.selleckchem.com/products/vb124.html  Therefore, the simple and effective hydrogel nanoantibiotics developed here hold great potential for the treatment of intractable bacterial infections.Therapeutic proteins are attractive candidates for the treatment of human diseases. However, their short half-life often limits their clinical application. To overcome this problem, injectable hydrogels have been developed as depots for controlled release of therapeutic proteins, but these systems have not yet achieved the desired extended, sustained drug release profile. Our strategy herein was to implement selective and strong interactions between the hydrogels and therapeutic proteins. Specifically, we investigated whether strong and specific interactions between human serum albumin (HSA) and albumin-binding peptide (ABP) can be used to achieve extended release of urate oxidase (Uox), a therapeutic protein for hyperuricemia treatment, from pH- and temperature-sensitive injectable hydrogels consisting of poly(ethylene glycol)-poly(β-amino ester urethane) (PEG-PAEU) copolymer. Thus, HSA was conjugated to Uox (Uox-HSA) and ABP was introduced in PEG-PAEU (PEG-PAEU-ABP). Polymers, conjugates, and hydrogels werelity range of these systems.Here, we report that Fe ions delivered into human mesenchymal stem cells (hMSCs) by bioreducible metal nanoparticles (NPs) enhance their angiogenic and cell-homing efficacy by controlling ion-triggered intracellular reactive oxygen species (ROS) and improve cell migration, while reducing cytotoxicity. Endosome-triggered iron-ion-releasing nanoparticles (ETIN) were designed to be low-pH responsive to take advantage of the low-pH conditions (4-5) of endosomes for in situ iron-ion release. Due to the different redox potentials of Fe and Au, only Fe could be ionized and released from our novel ETIN, while Au remained intact after ETIN endocytosis. Treatment with an optimal amount of ETIN led to a mild increase in intracellular ROS levels in hMSCs, which enhanced the expression of HIF-1α, a key trigger for angiogenic growth factor secretion from hMSCs. Treatmetn of hMSCs with ETIN significantly enhanced the expression of angiogenesis- and lesion-targeting-related genes and proteins. Transplantation of ETIN-treated hMSCs significantly enhanced angiogenesis and tissue regeneration in a wound-closing mouse model compared with those in untreated mice and mice that underwent conventional hMSC transplantation.Liver fibrosis is a common complication of diabetes mellitus, with a major global public health concern. Linagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4), is classically used to treat type 2 diabetes mellitus and improves insulin resistance. Additional potential influences of linagliptin on liver fibrosis are still unclear. The present study was undertaken to investigate the therapeutic credit of linagliptin in hepatic fibrosis induced by a high-fat diet (HFD) and streptozotocin (STZ) in rats. Moreover, the mechanisms underline its anti-fibrotic effect were explored. To induce liver fibrosis with T2DM; male Sprague-Dawley albino rats were fed on a high-fat high-sucrose diet for 28 days then exposed to a single dose of STZ (30 mg/kg, IP). After two days of STZ injection, a diabetes confirmation test was done and all diabetic rats were constantly fed on HFD for thirty days with or without treatment with linagliptin (6 mg/kg). Hepatotoxicity markers, lipid profile screening, insulin signaling, inflammatory cytokines (TNF-α, IL-6, NF-κB p65), fibrosis markers (Collagen, α-SMA, TGF-β1) and histopathological studies including hematoxylin and eosin (H&E) as well Masson's trichrome stains were performed. In our preliminary study, linagliptin at a dose of 6 mg/kg was chosen as the optimum anti-diabetic dose in rats challenged with STZ. Linagliptin significantly improved insulin sensitivity and lipid profile and reduced inflammatory mediators, and collagen depositions in rats with liver fibrosis and T2DM. In conclusion, above and beyond its anti-diabetic effect, this study introduced linagliptin as a promising option for preventing the pathological progression of liver fibrosis associated with T2DM.