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| Open AccessPalmitic acid in type 2 diabetes mellitus promotes atherosclerotic plaque vulnerability via macrophage Dll4 signaling
Patients with Type 2 Diabetes Mellitus are increasingly susceptible to atherosclerotic plaque vulnerability. Here, the authors show that elevated palmitic acid levels are linked to increased atherosclerotic plaque vulnerability.
- Xiqiang Wang
- , Ling Zhu
- & Zhongwei Liu
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Article
| Open AccessRelaxation of mitochondrial hyperfusion in the diabetic retina via N6-furfuryladenosine confers neuroprotection regardless of glycaemic status
Restoring mitochondrial function has emerged as a promising therapeutic strategy for diabetic retinopathy. Here, the authors show that mitochondrial hyperfusion blunts mitophagy during the disease process, and that rescuing this process pharmacologically confers retinal neuroprotection independent of an improved glycaemic status in type-1 diabetic mice.
- Aidan Anderson
- , Nada Alfahad
- & Jose R. Hombrebueno
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| Open AccessProgrammed microalgae-gel promotes chronic wound healing in diabetes
The treatment of infected diabetic wounds faces obstacles of bacterial infection, hypoxia, hyperexpression of reactive oxygen species, and inflammation. Here, the authors address these issues by developing a programmed treatment strategy that utilizes live Haematococcus to promote healing of diabetic wounds in a comprehensive manner.
- Yong Kang
- , Lingling Xu
- & Xiaoyuan Ji
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Article
| Open AccessDiabetic sensory neuropathy and insulin resistance are induced by loss of UCHL1 in Drosophila
The mechanisms underlying diabetic neuropathy remain elusive. Here, the authors identify that UCHL1 deubiquitinase positively regulates insulin signaling and its loss leads to axonal degeneration of sensory neurons.
- Daewon Lee
- , Eunju Yoon
- & Jongkyeong Chung
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Article
| Open AccessAutonomous artificial intelligence increases screening and follow-up for diabetic retinopathy in youth: the ACCESS randomized control trial
Diabetic retinopathy is a complication of diabetes that can be prevented through screening, yet adherence is low. Here, the authors show that autonomous AI increases diabetic eye exam completion in a diverse cohort of youth with diabetes.
- Risa M. Wolf
- , Roomasa Channa
- & Michael D. Abramoff
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Article
| Open AccessGlycerol contributes to tuberculosis susceptibility in male mice with type 2 diabetes
Patients with diabetes mellitus have an increased risk of developing tuberculosis. Here the authors show that increased blood levels of glycerol in mice with type 2 diabetes contributes to their susceptibility to infection, as glycerol is one of the main carbon sources for the bacteria.
- Nuria Martinez
- , Lorissa J. Smulan
- & Hardy Kornfeld
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| Open AccessPrevalence of diabetic retinopathy and vision-threatening diabetic retinopathy in adults with diabetes in China
Current data on the national distribution of diabetic retinopathy (DR) is lacking. Here, the authors show the national distribution, associated multi-level factors, and visual impairment of DR and vision-threatening DR in Chinese adults with diabetes.
- Xuhong Hou
- , Limin Wang
- & Weiping Jia
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Article
| Open AccessDNA methylation markers for kidney function and progression of diabetic kidney disease
Epigenetic markers are potential biomarkers for diabetes and related complications. Here, the authors identify CpG sites associated with kidney function and its subsequent decline using both single-site and multisite analyses, which are shown to have functional significance in the kidney.
- Kelly Yichen Li
- , Claudia Ha Ting Tam
- & Ronald C. W. Ma
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Article
| Open AccessEpigenetic regulation of Neuregulin 1 promotes breast cancer progression associated to hyperglycemia
Despite hyperglycemia has been associated to breast cancer, the underlying mechanisms are not completely understood. Here, the authors show that epigenetic regulation of Nrg1 gene during hyperglycemia promotes breast cancer development.
- Changhu Lee
- , Min Kim
- & Jiyoung Park
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Article
| Open AccessA natural biological adhesive from snail mucus for wound repair
Natural adhesives have received a lot of attention recently. Here, the authors develop a natural biological adhesive from snail mucus that can adhere to wet tissue and be used to accelerate healing of skin wounds.
- Tuo Deng
- , Dongxiu Gao
- & Mingyi Wu
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Article
| Open AccessDeletion of skeletal muscle Akt1/2 causes osteosarcopenia and reduces lifespan in mice
Sasako et al. show that disruption of the insulin/IGF-1 signaling by suppressing Akt activity in mouse skeletal muscle can accelerate osteosarcopenia and shortens lifespan, which is reversed by inactivation of FoxOs rather than activation of mTOR, suggesting FoxOs as therapeutic targets.
- Takayoshi Sasako
- , Toshihiro Umehara
- & Kohjiro Ueki
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Article
| Open AccessSingle cell transcriptomic landscape of diabetic foot ulcers
Diabetic foot ulcers (DFUs) remain a complication of diabetes that are difficult to heal and lead to disability. Here the authors use single-cell RNA-sequencing and spatial transcriptomics to characterize the DFU cellular landscape and identify a population of fibroblasts that is associated with successful wound closure.
- Georgios Theocharidis
- , Beena E. Thomas
- & Manoj Bhasin
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Article
| Open AccessA deep learning system for detecting diabetic retinopathy across the disease spectrum
As the leading cause of vision loss in working-age adults, diabetic retinopathy requires routinely retinal screening. Here the authors develop a deep learning system that can facilitate the screening by providing real-time image quality assessment, lesions detection, and grades across the disease spectrum.
- Ling Dai
- , Liang Wu
- & Weiping Jia
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Article
| Open AccessTargeting QKI-7 in vivo restores endothelial cell function in diabetes
Vascular endothelial cell (EC) dysfunction contributes to the occurrence of diabetic complications. Here the authors report that in diabetic conditions, upregulation of the RNA binding protein QKI-7 in ECs due to the imbalance of RNA splicing factors CUG-BP and hnRNPM contributes to EC dysfunction, and that in vivo QKI-7 silencing improves blood flow recovery in diabetic mice with limb ischemia.
- Chunbo Yang
- , Magdalini Eleftheriadou
- & Andriana Margariti
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Article
| Open AccessMD2 activation by direct AGE interaction drives inflammatory diabetic cardiomyopathy
The mechanisms underlying cardiac inflammation in diabetic cardiomyopathy are incompletely understood. Here the authors show that advanced glycation end products bind to the TLR4 co-receptor MD2 initiating pro-inflammatory pathways.
- Yi Wang
- , Wu Luo
- & Guang Liang
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| Open AccessVascular progenitors generated from tankyrase inhibitor-regulated naïve diabetic human iPSC potentiate efficient revascularization of ischemic retina
hPSCs in culture acquire a more naïve pluripotent state upon tankyrase inhibition. Here, the authors show that tankyrase inhibitor-regulated naïve hiPSCs from diabetic donors generate more vascular progenitors and more efficient engraftment into mouse retina than conventional PSCs.
- Tea Soon Park
- , Ludovic Zimmerlin
- & Elias T. Zambidis
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Article
| Open AccessNAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome
The molecular mechanisms of mitochondrial dysfunction in the premature ageing Werner syndrome were elusive. Here the authors show that NAD+ depletion-induced impaired mitophagy contributes to this phenomenon, shedding light on potential therapeutics.
- Evandro F. Fang
- , Yujun Hou
- & Vilhelm A. Bohr
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Article
| Open AccessIntradermal delivery of modified mRNA encoding VEGF-A in patients with type 2 diabetes
Chemically modified mRNA is a new approach for therapeutic protein expression that could be applied to angiogenesis. Here the authors show in a phase 1 clinical trial that a modified mRNA encoding VEGF-A is well tolerated in patients with type 2 diabetes.
- Li-Ming Gan
- , Maria Lagerström-Fermér
- & Regina Fritsche-Danielson
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Article
| Open AccessLaminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing
Laminins are important regulators of epidermal wound healing. Here, the authors show that laminins bind to multiple growth factors via their heparin-binding domains, and that incorporation of these domains into fibrin matrices increases growth factor retention, promoting wound healing in type 2 diabetic mouse models.
- Jun Ishihara
- , Ako Ishihara
- & Jeffrey A. Hubbell
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Article
| Open AccessDiabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages
Type 2 diabetes is associated with impaired wound healing, which can lead to limb loss. Here, the authors show that in Type 2 diabetic mouse models, Dnmt1 is upregulated in hematopoietic stem cells, leading to impaired differentiation towards macrophages, reduced macrophage infiltration in the wound and skewed M1/M2 polarization.
- Jinglian Yan
- , Guodong Tie
- & Louis M. Messina
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Article
| Open AccessSuccinate and its G-protein-coupled receptor stimulates osteoclastogenesis
Bone loss is common in patients with diabetes, but the underlying molecular and cellular mechanisms are unclear. Here the authors show high succinate levels in mice with type 2 diabetes and that succinate can signal through succinate receptor 1 on osteoclasts to induce bone resorption.
- Yuqi Guo
- , Chengzhi Xie
- & Xin Li
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Article
| Open AccessLight-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice
Inhibition of microRNAs using antimiRs is a potential therapeutic option for a number of diseases, but systemic inhibition may cause adverse effects. Here the authors develop light-activated antimiRs directed against miR-92a, and show localized inhibition in the skin and improved wound healing in diabetic mice.
- Tina Lucas
- , Florian Schäfer
- & Stefanie Dimmeler
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| Open AccessHyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes
Patients with diabetes often have delayed wound healing, associated with excessive inflammation. Here the authors report that REG3A inhibits TLR3-driven inflammation in skin wounds, and show that REG3A is reduced in models of diabetes, which exacerbates inflammation in diabetic wounds.
- Yelin Wu
- , Yanchun Quan
- & Yuping Lai
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Article
| Open AccessInsulin and TOR signal in parallel through FOXO and S6K to promote epithelial wound healing
The TOR and insulin/IGF signalling (IIS) network are central responses to wound healing. Here the authors develop a technique of live imaging of laser-induced epidermal wounds to flies and show that TOR and IIS are independently required for wound healing, which may have implications for diabetic wound healing and its treatment.
- Parisa Kakanj
- , Bernard Moussian
- & Maria Leptin