- Advancing pharmacotherapy for diabetic foot ulcers. [Journal Article]
- EOExpert Opin Pharmacother 2019; 20(9):1153-1160
- Standard treatment for diabetic foot ulcers (DFUs) includes off-loading, debridement, moisture balance, management of infection and peripheral arterial disease (PAD) as well as adequate glycemic cont…
Standard treatment for diabetic foot ulcers (DFUs) includes off-loading, debridement, moisture balance, management of infection and peripheral arterial disease (PAD) as well as adequate glycemic control. The outcomes so far are unsatisfactory. Areas covered: Herein, the authors provide an outline of newer pharmacological agents for the management of DFUs and give their expert perspectives on future treatment strategies. Expert opinion: Evidence-based healthcare calls for high quality evidence from large RCTs before the implementation of new guidelines for the management of DFUs. Empagliflozin and liraglutide can be recommended for glucose control in patients with DFUs and PAD, while intensive lipid lowering therapy with evolocumab when primary cholesterol goals are not met could be offered to patients with DFUs. Further clinical studies are warranted to develop a structured algorithm for the treatment of DFUs that fail to heal after four weeks of current standard of care. Sucrose octasulfate dressings, becaplermin gel, and platelet-rich plasma (PRP) could also be considered as advanced treatment options for the management of hard to heal DFUs.
- [rhPDGF-BB promotes migration of bone marrow stromal stem cells in diabetic rats]. [Journal Article]
- SKShanghai Kou Qiang Yi Xue 2018; 27(6):579-584
- CONCLUSIONS: rhPDGF-BB promotes the migration of diabetic rat BMSCs and regulates its migration by regulating SDF-1/CXCR4 axis.
- A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma. [Journal Article]
- NCNat Commun 2019 03 11; 10(1):1152
- Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis r…
Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of the zinc finger family, regulates lipid homeostasis in clear cell renal cell carcinoma (ccRCC). We show that KLF6 supports the expression of lipid metabolism genes and promotes the expression of PDGFB, which activates mTOR signalling and the downstream lipid metabolism regulators SREBF1 and SREBF2. KLF6 expression is driven by a robust super enhancer that integrates signals from multiple pathways, including the ccRCC-initiating VHL-HIF2A pathway. These results suggest an underlying mechanism for high mTOR activity in ccRCC cells. More generally, the link between super enhancer-driven transcriptional networks and essential metabolic pathways may provide clues to the mechanisms that maintain the stability of cell identity-defining transcriptional programmes in cancer.
- Identification of a homozygous GFPT2 variant in a family with asthenozoospermia. [Journal Article]
- GENEGene 2019 May 30; 699:16-23
- CONCLUSIONS: Homozygosity of the GFPT2 p.Arg366Gln mutation was associated with increased levels of reactive oxygen species (ROS) in spermatozoa and decreased sperm motility.
- Growth Factor Screening in Dystrophic Muscles Reveals PDGFB/PDGFRB-Mediated Migration of Interstitial Stem Cells. [Journal Article]
- IJInt J Mol Sci 2019 Mar 05; 20(5)
- Progressive muscle degeneration followed by dilated cardiomyopathy is a hallmark of muscular dystrophy. Stem cell therapy is suggested to replace diseased myofibers by healthy myofibers, although so …
Progressive muscle degeneration followed by dilated cardiomyopathy is a hallmark of muscular dystrophy. Stem cell therapy is suggested to replace diseased myofibers by healthy myofibers, although so far, we are faced by low efficiencies of migration and engraftment of stem cells. Chemokines are signalling proteins guiding cell migration and have been shown to tightly regulate muscle tissue repair. We sought to determine which chemokines are expressed in dystrophic muscles undergoing tissue remodelling. Therefore, we analysed the expression of chemokines and chemokine receptors in skeletal and cardiac muscles from Sarcoglycan-α null, Sarcoglycan-β null and immunodeficient Sgcβ-null mice. We found that several chemokines are dysregulated in dystrophic muscles. We further show that one of these, platelet-derived growth factor-B, promotes interstitial stem cell migration. This finding provides perspective to an approachable mechanism for improving stem cell homing towards dystrophic muscles.
- Lateral Flow Aptasensor for Simultaneous Detection of Platelet-Derived Growth Factor-BB (PDGF-BB) and Thrombin. [Journal Article]
- MMolecules 2019 Feb 20; 24(4)
- Here we report a lateral flow aptasensor (LFA) for the simultaneous detection of platelet-derived growth factor-BB (PDGF-BB) and thrombin. Two pairs of aptamers, which are specific against PDGF-BB an…
Here we report a lateral flow aptasensor (LFA) for the simultaneous detection of platelet-derived growth factor-BB (PDGF-BB) and thrombin. Two pairs of aptamers, which are specific against PDGF-BB and thrombin, respectively, were used to prepare the LFA. Thiolated aptamers were immobilized on a gold nanoparticle (AuNP) surface and biotinylated aptamers were immobilized on the test zones of an LFA nitrocellulose membrane. The assay involved the capture of PDGF-BB and thrombin simultaneously in sandwich-type formats between the capture aptamers on the test zones of LFA and AuNP-labeled detection aptamers. AuNPs were thus captured on the test zones of the LFA and gave red bands to enable the visual detection of target proteins. Quantitative results were obtained by reading the test band intensities with a portable strip reader. By combining the highly specific molecular recognition properties of aptamers with the unique properties of lateral flow assay (low-cost, short assay time and a user-friendly format), the optimized aptasensor was capable of simultaneously detecting 1.0 nM of PDGF-BB and 1.5 nM of thrombin in association with a 10-min assay time. The biosensor was also successfully applied to detect PDGF-BB and thrombin in spiked human serum samples. The LFA shows great promise for the development of aptamer-based lateral flow strip biosensors for point-of-care or for the in-field detection of disease-related protein biomarkers.
- Effect of aeration and hydraulic loading rate on nitrogen removal by subsurface infiltration systems. [Journal Article]
- WEWater Environ Res 2019; 91(5):399-406
- This study investigated the effect of hydraulic loading rate (HLR) on matrix dissolved oxygen (DO), organic matter removal, nitrogen removal, N2 O emissions, and the abundances of functional genes pa…
This study investigated the effect of hydraulic loading rate (HLR) on matrix dissolved oxygen (DO), organic matter removal, nitrogen removal, N2 O emissions, and the abundances of functional genes participating in nitrogen removal in intermittent aerated mode (IAM) and nonaerated mode (NAM) subsurface infiltration systems (SISs). In contrast to NAM SISs, IAM SISs were able to create aerobic conditions in the upper matrix (above 50 cm depth) and anoxic or anaerobic conditions in the lower matrix (below 80 cm depth). Subsequently, this enhanced the abundance of functional genes related to nitrogen removal. Chemical oxygen demand (COD) and nitrogen removal performance were significantly higher under IAM SISs than with NAM SISs. Under a HLR of 0.3 m3 /(m2 d), the IAM SIS was able to achieve low N2 O emissions (12.6 mg/[m2 d]) along with removal efficiencies of 90.5%, 91.4%, and 85.7% for COD, ammonia nitrogen (NH 4 + -N), and total nitrogen (TN), respectively. PRACTITIONER POINTS: Intermittent aeration successfully realized sequential aerobic and anaerobic conditions at 50 cm depth and at 80 and 110 cm depths of a subsurface infiltration system. Intermittent aeration reduced N2 O emissions and improved hydraulic loading rate and organic matter, nitrogen removal efficiencies. Intermittent aeration enhanced the abundances of amoA, nxrA, napA, narG, nirS, nirK, qnorB, and nosZ.
- Five-CpG-based prognostic signature for predicting survival in hepatocellular carcinoma patients. [Journal Article]
- CBCancer Biol Med 2018; 15(4):425-433
- CONCLUSIONS: This study provides a novel signature for predicting HCC survival, and should be helpful for early HCC diagnosis and personalized treatment.
- Anti-proliferative and anti-migratory effects of Scutellaria strigillosa Hemsley extracts against vascular smooth muscle cells. [Journal Article]
- JEJ Ethnopharmacol 2019 May 10; 235:155-163
- CONCLUSIONS: SSHE significantly inhibited the PDGF-BB-induced VSMC proliferation, migration, and neointimal hyperplasia of carotid artery caused by ligation. Upregulation of SM22α expression, inhibition of ROS generation and ERK phosphorylation were, at least, partly responsible for the effects of SSHE on VSMCs.
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- Cyclin Dependent Kinase 1 (CDK1) Activates Cardiac Fibroblasts via Directly Phosphorylating Paxillin at Ser244. [Journal Article]
- IHInt Heart J 2019 Mar 20; 60(2):374-383
- Atrial fibrillation has caused severe burden for people worldwide. Differentiation of fibroblasts into myofibroblasts, and consequent progress in atrial structural remodeling have been considered the…
Atrial fibrillation has caused severe burden for people worldwide. Differentiation of fibroblasts into myofibroblasts, and consequent progress in atrial structural remodeling have been considered the basis for persistent atrial fibrillation, yet little is known about the molecular mechanisms underlying the process. Here, we show that cyclin-dependent kinase 1 (CDK1) is activated in atrial fibroblasts from patients with atrial fibrillation (AFPAF) and in platelet derived growth factor BB (PDGF-BB)-treated atrial fibroblasts from patients with sinus rhythm (AFPSR). We also demonstrate that inhibition of CDK1 suppresses fibroblast differentiation and focal adhesion (FA) complex formation. The FA protein paxillin is phosphorylated directly at Ser244 by CDK1. Importantly, transfection of a paxillin construct harboring a Ser to Ala mutation causes FA complex disassembly and greatly inhibits fibroblast activation. AFPSRs applied with a lentiviral vector carrying the shRNA sequence of paxillin dramatically prevents PDGF-BB induced functional activation. Taken together, all these results suggest that phosphorylation of paxillin at Ser244 by CDK1 is a key mechanism in fibroblast differentiation and could eventually assist atrial fibrosis.