Proliferation Of Human Endothelial Cells Research Articles

MiR-25-3p regulates pulmonary arteriovenous malformation after Glenn procedure in patients with univentricular heart via the PHLPP2-HIF-1α axis

The detailed mechanism of pulmonary arteriovenous malformations after Glenn surgery (G-PAVMs) in cyanotic congenital heart disease (CHD) remains unclear. Microarray in situ hybridization was performed to assess the miRNA (miRNA) profiles of serum from pediatric patients (0–6 years of age) with G-PAVMs and after the Fontan procedure without G-PAVMs. In addition, we investigated the tube formation, migration, and proliferation of human lung microvascular endothelial cells (HMVEC-L) transfected with miR-25-3p mimic, miR-25-3p inhibitor, or PHLPP2 small interfering RNA, and examined HIF-1α/VEGF-A signaling after hypoxic stimulation. Serum miRNAs that showed ≥ 2-fold higher levels in patients with G-PAVMs than in other patients were selected. MiR-25-3p was significantly upregulated in the pulmonary artery sera of the post-Glenn group than in the post-Fontan group. We identified PHLPP2 as a direct target of miR-25-3p. PHLPP2 expression was significantly decreased in HMVEC-L transfected with miR-25-3p mimic compared to the control cells. HIF-1α and VEGF-A expression levels were increased in HMVEC-L transfected with miR-25-3p mimic compared to the control cells in a PHLPP2/Akt/mTOR signaling-dependent manner after hypoxic stimulation. MiR-25-3p promoted HMVEC-L angiogenesis, proliferation, and migration under hypoxic conditions. MiR-25-3p in the pulmonary arteries may contribute to G-PAVM development.

Interleukin 29 is a novel antiangiogenic factor in angiogenesis.

Angiogenesis is tightly controlled by growth factors and cytokines in pathophysiological settings. Despite the importance of Interleukin 29 (IL-29), a newly identified cytokine of type III interferon family, its role in angiogenesis remains unknown. We aimed to elucidate IL-29's impact on angiogenesis under both and physiological and pathological conditions. We employed various assays to evaluate IL-29's effect on proliferation, apoptosis, migration and tube formation of human umbilical vein endothelial cells (HUVEC) in vitro. IL-29's angiogenic effect was assessed using mouse aortic rings ex vivo, and oxygen-induced retinopathy (OIR) mouse model in vivo. Signaling pathways possibly involved in IL-29-induced angiogenesis were investigated by Western blot. Finally, IL-29's impact on tube formation was blocked by inhibiting IL-29/interleukin 10 receptor 2 (IL-10R2) binding. IL-29 treatment inhibited endothelial cell migration, tube formation and vessel sprouting, without affecting proliferation or apoptosis. Notably, IL-29 (100ng/ml) attenuated vessel growth in pathological angiogenesis in OIR mice, accompanied by decreased expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α (HIF-1α). Mechanistically, IL-29 activated Stat3 signaling pathway, and blocking IL-29/IL-10R2 binding remarkably reversed IL-29's anti-angiogenic effect on tube formation. Our findings demonstrated that IL-29, at a relative low concentration, modulates angiogenesis in both physiological and pathological contexts. Targeting IL-29 or its receptor IL-10R2 offers a promising strategy for angiogenesis regulation in various conditions.

Angiogenesis-promoting effect of SKP-SC-EVs-derived miRNA-30a-5p in peripheral nerve regeneration by targeting LIF and ANGPT2.

Ischemia and hypoxia caused by vascular injury intensify nerve damage. Skin precursor-derived Schwann cells have demonstrated an accelerated invivo prevascularization of tissue-engineered nerves. Furthermore, extracellular vesicles from skin precursor-derived Schwann cells (SKP-SC-EVs) show the potential in aiding peripheral nerve regeneration. Nonetheless, the capacity of SKP-SC-EVs to facilitate nerve repair via angiogenesis remains uncertain. This study observed that SKP-SC-EVs significantly enhanced angiogenesis, evidenced by increased transparency of the tissue-engineered nerve graft and ultrasonic blood flow imaging. Invitro experiments confirmed that SKP-SC-EVs promote the proliferation, migration, and tube formation of human umbilical vein endothelial cells, a standard model for assessing angiogenic potential. Additionally, a comprehensive miRNA expression profile of SKP-SC-EVs was performed, leading to the identification of potential candidates through functional experiments. Among these, miR-30a-5p emerged as a significant candidate, demonstrating remarkable proangiogenic effects both invivo and invitro, akin to the effects of SKP-SC-EVs. Furthermore, luciferase reporter assay and functional experiments revealed that miR-30a-5p in SKP-SC-EVs promotes angiogenesis by targeting ANGPT2 and LIF without sufficient VEGFa. Thus, the enrichment of miR-30a-5p in SKP-SC-EVs indicates its pivotal role as a regulator of angiogenesis, presenting a promising avenue for cell-free treatment of peripheral nerve injury.

Tumor Vascular Normalization by B7-H3 Blockade Augments T Lymphocyte-Mediated Antitumor Immunity.

Triple-negative breast cancer (TNBC), defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), presents unique clinical challenges and generally predicts a less favorable prognosis. Despite recent advancements in TNBC treatment, a subset of patients remains resistant to immunotherapy. B7-H3, a member of the B7 family of immune checkpoints, is correlated with poor outcomes in various cancers and is distinctively expressed in tumor vasculature, marking it as a potential biomarker for tumor-associated endothelial cells. We found high expression of B7-H3 in the endothelial cells of the postoperative tissue of TNBC patients. Elevated gene expression of CD276 (encoding B7-H3) and PECAM1 (encoding CD31) in TNBC is associated with poor prognosis. Anti-B7-H3 blockade reduces tumor burden and promotes lymphocyte infiltration in a TNBC mouse model. Additionally, anti-B7-H3 blockade promotes tumor vessel normalization and enhances programmed cell death ligand 1 (PD-L1) expression. Synergistic effects were observed when B7-H3 blockade was combined with programmed cell death protein 1 (PD-1) inhibition in the TNBC mouse model. Furthermore, anti-B7-H3 inhibits human umbilical vein endothelial cell (HUVEC) proliferation by suppression of the nuclear factor kappa-B (NF-κB) signaling pathway. Downregulation of B7-H3 expression in HUVECs promotes lymphocyte trans-endothelial migration. These findings suggest that B7-H3 represents a promising therapeutic target for TNBC, and the combination of anti-B7-H3 and anti-PD-1 therapies may have synergetic effects in treating TNBC.

Rosae Multiflorae Fructus Extracts Regulate the Differentiation and Vascular Endothelial Cell-mediated Proliferation of Keratinocytes.

Keratinocytes are the primary component of the epidermis, so maintaining the precise balance between proliferation and differentiation is essential for conserving epidermal structure and function. Rosae multiflorae fructus extract (RMFE) has wide application in the cosmetic industry, but the molecular mechanisms underlying beneficial effects on keratinocytes are still not fully understood. In this study, we found that RMFE promoted epidermal differentiation and enhanced the barrier function of normal human epidermal keratinocytes (NHEKs) and three-dimensional epidermis model in culture. In addition, RMFE promoted human umbilical vein endothelial cell (HUVEC) proliferation and angiogenesis, whereas the conditioned medium from RMFE-treated HUVECs further promoted NHEK proliferation and increased wound healing ability. Analysis of constituent bioactivities identified a quercetin derivative as a potential mediator of NHEK and HUVEC responses to RMFE. Taken together, these results suggest that RMFE enhances epidermal functions through both direct effects on keratinocytes and indirect effects mediated by endothelial cells.

α-Ketoglutaric Acid Reprograms Macrophages by Altering Energy Metabolism to Promote the Regeneration of Small-Diameter Vascular Grafts.

Small-diameter vascular grafts still cannot clinically replace autologous blood vessels due to high restenosis rates caused by long-term inflammatory infiltration. Foreign body reactions to vascular grafts induce macrophages to adopt the pro-inflammatory M1 phenotype, releasing inflammatory factors such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). This induces a phenotypic switch in smooth muscle cells, eventually leading to intimal hyperplasia. Herein, we constructed small-diameter artificial vascular grafts capable of modulating immune responses through the controlled release of α-ketoglutaric acid (α-KG). Our findings verify that the delivery of α-KG reprograms the macrophage phenotype from a pro-inflammatory M1 to an anti-inflammatory and pro-repair M2 phenotype by regulating the energy metabolism of the tricarboxylic acid cycle (TAC). More interestingly, the delivery of α-KG positively influences the behavior of vascular cells by enhancing the proliferation of human umbilical vein endothelial cells (HUVECs) and inhibiting the expansion of mouse aortic vascular smooth muscle cells (MOVAS), thereby reducing vascular restenosis. In vivo evaluation in rabbit carotid artery replacement confirms the optimal performance of α-KG-doped vascular grafts in terms of endothelial coverage and long-term patency. Collectively, our work presents a promising approach for creating artificial vascular grafts with inflammatory regulation to ensure rapid endothelialization and sustained patency.

Effect of miR-1285-3p as a diagnostic biomarker for chronic heart failure on vascular endothelial cells

BackgroundMicroRNAs (miRNAs) are closely related to cardiovascular diseases, including chronic heart failure (CHF). Endothelial dysfunction can lead to heart failure. The purpose of this study was to evaluate the clinical significance of miR-1285-3p in CHF patients, with the aim of identifying a novel and effective biomarker for CHF. At the same time, we investigated the effect of miR-1285-3p on vascular endothelial cells.MethodsTotal RNA was extracted from plasma samples of 106 CHF patients and 106 healthy individuals. Quantitative Real-time PCR (qRT-PCR) was used to detect the expression of miR-1285-3p. The diagnostic accuracy of miR-1285-3p was tested by receiver operating characteristic (ROC) curve. Evaluated the related risk factors of CHF using logistic analysis. The proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) were detected by transfecting miR-1285-3p mimic or miR-1285-3p inhibitor in vitro using CCK8 and flow cytometry. Effect of miR-1285-3p on the angiogenesis of HUVECs were detected by in vitro angiogenesis assay.ResultsmiR-1285-3p is upregulated in CHF patients, demonstrating the ability to distinguish CHF patients from healthy individuals, with high sensitivity (83.0%) and specificity (93.4%). In vitro experiments revealed that transfection of miR-1285-3p mimic inhibited endothelial cell proliferation, accelerated apoptosis, and inhibited endothelial cell angiogenesis, which was reversed by transfection with miR-1285-3p inhibitor.ConclusionmiR-1285-3p is upregulated in CHF and may serve as a new effective biomarker for CHF diagnosis, which can inhibit HUVECs angiogenesis.

Upregulation of OGT-mediated EZH2 O-GlcNAcylation Promotes Human Umbilical Vein Endothelial Cell Proliferation, Invasion, Migration, and Tube Formation in Gestational Diabetes Mellitus

Upregulation of OGT-mediated EZH2 O-GlcNAcylation Promotes Human Umbilical Vein Endothelial Cell Proliferation, Invasion, Migration, and Tube Formation in Gestational Diabetes Mellitus

Empagliflozin promotes skin flap survival by activating AMPK signaling pathway.

Flaps are widely used in surgical wound repair, yet distal necrosis poses a significant postoperative challenge, stemming from potential factors such as inadequate blood perfusion, inflammation, ischemia/reperfusion (I/R) injury, mitochondrial impairment, and subsequent ferroptosis. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor, has pharmacological activities that promote angiogenesis, mitophagy, and inhibit inflammation, I/R injury, and ferroptosis. However, it is unclear whether EMPA can enhance flap survival. Here, we established a modified McFarlane flap model and applied EMPA to demonstrate its mechanism of action. 24 rats were evenly divided into four groups: the control, low-dose EMPA (10 mg/kg), high-dose EMPA (30 mg/kg), and inhibitor groups. Molecular biology experiments demonstrated that EMPA promoted the expression of angiogenesis-related factors vascular endothelial growth factor (VEGF) and CD34. Additionally, it also increased superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) levels, thus suppressing oxidative stress. EMPA further alleviated inflammation by downregulating the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In vitro experiments showed that EMPA promoted the proliferation of human umbilical vein endothelial cells (HUVECs) and reduce their reactive oxygen species (ROS) production. Further investigation demonstrated that EMPA improves flap prognosis by inducing the expression of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, further promoting mitophagy and inhibiting ferroptosis. These effects collectively contributed to the survival of the skin flap. Overall, our research elucidates the protective effects of EMPA on flap survival and its specific mechanisms, offering new insights into solving post-transplant flap necrosis.

Melanoma cell line-derived exosomal miR-424-5p: a key promoter of angiogenesis through LATS2 interaction.

Melanoma is a highly aggressive and metastatic form of cancer, and the role of exosomal microRNAs (miRNAs) in its progression remains largely unexplored. This study aimed to investigate the effects of melanoma cell-derived exosomal miR-424-5p on angiogenesis and its underlying mechanisms. Exosomes were isolated from melanoma cell lines A375 and A2058, and their effects on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were examined. The interaction between miR-424-5p and its target gene, large tumor suppressor kinase 2 (LATS2), was analyzed using luciferase reporter assays and functional experiments. In vivo, tumor growth and angiogenesis were studied in a xenograft model using nude mice. Melanoma cell-derived exosomes could be internalized by HUVECs, which promoted proliferation, migration, and angiogenesis. miR-424-5p was highly expressed in melanoma cells and their exosomes, and its inhibition in exosomes suppressed HUVEC proliferation, migration, and angiogenesis. LATS2 was identified as a direct target of miR-424-5p, and its silencing reversed the inhibitory effects of miR-424-5p inhibition on HUVEC functions. In vivo, exosomes derived from miR-424-5p-inhibited melanoma cells suppressed tumor growth and angiogenesis in xenograft models. Melanoma cell-derived exosomal miR-424-5p promotes angiogenesis by targeting LATS2, contributing to melanoma progression. Targeting the exosomal miR-424-5p/LATS2 axis could be a potential therapeutic strategy for melanoma.

Extraction of coronary thrombus-derived exosomes from patients with acute myocardial infarction and its effect on the function of adventitial cells.

Type I acute myocardial infarction (T1MI) has a very high morbidity and mortality rate. The role of thrombus-derived exosomes (TEs) in T1MI is unclear. The objective of this study was to identify the optimal thrombolytic drug and concentration for extracting TEs. To this end, a series of time and concentration combinations were tested. Subsequently, the effect of TEs on thrombus-adjacent cells was investigated. Finally, we conducted lncRNA microarray analysis on the extracted TEs (GSE213115). TEs has been demonstrated to promote necrosis, autophagy, and ferroptosis of human cardiomyocytes, while inhibiting the proliferation and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, TEs can stimulate the proliferation and migration of smooth muscle cells, and induce a transformation from a contractile to a secretory phenotype. Bioinformatics analysis revealed that five lncRNAs, AC068418.2, AC010186.3, AL031430.1, AC121333.1, and AL136526.1, exhibited significant differential expression in TE and regulated cell autophagy and ferroptosis by directly binding to TP53, TP63, and RELA, respectively. We demonstrate that TEs as a potential target and research direction for the treatment of heart failure after T1MI. TEs may regulate ferroptosis and autophagy in thrombus-adjacent cells through the enrichment of certain lncRNAs.

3D Printed GelMA/CHIMA Cross-Linked Network Hydrogel for Angiogenesis.

Vascularization is a key issue facing the construction of functional three-dimensional (3D) tissues, which is critical for the long-term survival and stability of tissue construct transplantation. In this study, a photocurable hydrogel material carboxymethyl chitosan (CHIMA) was successfully prepared and integrated with methacryloyl gelatin (GelMA) to construct the bioink GelMA/CHIMA, which was subsequently used 3D printing technology to prepared a bioactive scaffold with angiogenesis-inducing functionality. The results showed that the cross-linked GelMA/CHIMA bioink had a porous structure that supported cell growth and metabolism. The incorporation of CHIMA could significantly improve the hydrophilicity, swelling rate, pressure resistance and mechanical strength of the bioink. GelMA/CHIMA bioink supported the survival and continued proliferation of human umbilical vein endothelial cells (HUVECs) in the scaffold. In particular, the bioink composed of 8 wt% GelMA and 2 wt% CHIMA could stimulate the expression of angiogenesis genes. 3D printed bioactive scaffolds supported the survival of HUVECs and had abundant protein deposition including CD31 and VEGF. Therefore, this study constructed a bioactive scaffold with angiogenesis induction function, which provides a feasible strategy for the construction of vascularized complex tissues.

Phytochemicals From Salvia substolonifera With Anti-Angiogenic Properties and Substolide H Decreased Oxygen-Induced Retinal Neovascularization.

Retinal neovascularization is a pathological feature of ischemic retinopathy. Current therapeutic approaches are limited, and additional treatment options are needed. This study aims to discover lead compounds from Salvia substolonifera that inhibit angiogenesis. As a result, an undescribed norditerpene lactone, substolide H (3), and eight known compounds (1, 2, and 4-9) have been isolated. The structure was elucidated using synthetic spectroscopy and electron circular dichroism. Compounds 2, 3, 5, 7, and 9 inhibited human umbilical vein endothelial cells (HUVEC) proliferation with IC50 values of 26.47, 6.10, 43.27, 36.81, and 35.11µM, respectively. Compounds 2, 3, and 7 inhibited HUVEC migration with IC50 values of 12.48, 8.37, and 7.63µM, respectively. Further studies have shown that the substolide H (3) suppresses tube formation in human umbilical vein endothelial cells and that intravitreous administration suppresses retinal neovascularization in oxygen-induced retinopathy mice. Turning to its mechanism of action, we have shown that the anti-angiogenic effect of the substolide H may be through the downregulation of vascular endothelial growth factor expression and the phosphorylation of VEGFR2, ERK1/2, and protein kinase B. Our study represents the first report of these anti-angiogenic compounds from this plant, and substolide H may be a potential candidate for the treatment of retinal neovascularization.

Exosomes derived from minor salivary gland mesenchymal stem cells: a promising novel exosome exhibiting pro-angiogenic and wound healing effects similar to those of adipose-derived stem cell exosomes

BackgroundsMinor salivary gland mesenchymal stem cells (MSGMSCs) can be easily extracted and have a broad range of sources. Applying exosomes to wounds is a highly promising method for promoting wound healing. Exosomes derived from different stem cell types have been proven to enhance wound healing, with adipose-derived stem cell (ADSC)-derived exosomes being the most extensively researched. Considering that MSGMSCs have advantages such as easier extraction compared to ADSCs, MSGMSCs should also be a very promising type of stem cell in exosome therapy. However, whether MSGMSC-derived exosomes (MSGMSC-exos) can promote wound healing and how they compare to ADSC-derived exosomes (ADSC-exos) in the wound healing process remain unclear.MaterialsThe effects of MSGMSC-exos and ADSC-exos on angiogenesis in wound healing were investigated in vitro using CCK-8, scratch assays, and tube formation assays. Subsequently, the promotion of wound healing by MSGMSC-exos and ADSC-exos was evaluated in vivo using a full-thickness wound defect model in mice. Immunohistochemistry was used to verify the effects of MSGMSC-exos and ADSC-exos on promoting collagen deposition, angiogenesis, and cell proliferation in the wound. Immunofluorescence staining was performed to investigate the role of MSGMSC-exos and ADSC-exos in modulating the inflammatory response in the wound. Furthermore, proteomic sequencing was conducted to investigate the functional similarities and differences between the proteomes of MSGMSC-exos and ADSC-exos, with key protein contents verified by ELISA.ResultsMSGMSC-exos exhibited similar effects as ADSC-exos in promoting the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, with a comparable dose-dependent effect. In vivo experiments confirmed that MSGMSC-exos have similar wound healing-promoting functions as ADSC-exos. MSGMSC-exos promoted the neovascularization and maturation of blood vessels in vivo at a level comparable to ADSC-exos. Despite MSGMSC-exos showing less collagen deposition than ADSC-exos, they exhibited stronger anti-scar formation and anti-inflammatory effects. Proteomic analysis revealed that the proteins promoting wound healing in both MSGMSC-exos and ADSC-exos were relatively conserved, with ITGB1 identified as a critical protein for angiogenesis. Further differential analysis revealed that the functions specifically enriched in MSGMSC-exos and ADSC-exos reflected the functions of their source tissue.ConclusionsOur study confirms that MSGMSC-exos exhibit highly similar wound healing and angiogenesis-promoting functions compared to ADSC-exos, and the proteins involved in promoting wound healing in both are relatively conserved. Moreover, MSGMSC-exos show stronger anti-scar formation and anti-inflammatory effects than ADSC-exos. This suggests that MSGMSCs are a promising stem cell source with broad applications in wound healing treatment.

Adipsin improves diabetic hindlimb ischemia through SERPINE1 dependent angiogenesis

BackgroundAdipsin (complement factor D, CFD), as the first described adipokine, is well-known for its regulatory effects in diabetic cardiovascular complications. However, its role in diabetic hind-limb ischemia was not clarified. This study aimed to evaluate the possible therapeutic effect of Adipsin in hind-limb ischemia in type 2 diabetic mice and to elucidate the molecular mechanisms involved.MethodsA high-fat diet and streptozotocin (HFD/STZ)-induced diabetic mouse model, and a transgenic mouse model with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg) were employed. Hindlimb ischemia was established by femoral artery ligation, and blood flow recovery was monitored using Laser Doppler perfusion imaging. Molecular mechanisms underlying Adipsin-potentiated angiogenesis were examined using RNA sequencing and co-immunoprecipitation/mass spectrometry (Co-IP/MS) analyses.ResultsAdipsin expression was upregulated in non-diabetic mice following HLI, while suppressed in diabetic mice, indicating its potential role in ischemic recovery which is impaired in diabetes. Adipsin-Tg mice exhibited significantly improved blood flow recovery, increased capillary density, and enhanced muscle regeneration in comparison with non-transgenic (NTg) diabetic mice. Adipsin facilitated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) under hyperglycemic and hypoxic conditions. Additionally, it enhanced phosphorylation of AKT, ERK, and eNOS pathways both in vivo and in vitro. RNA sequencing and co-immunoprecipitation/mass spectrometry (Co-IP/MS) analyses identified that Adipsin promoted angiogenesis by interacting with SERBP1, which disrupted the binding of SERBP1 to SERPINE1 mRNA, resulting in reduced SERPINE1 expression and the subsequent activation of the VEGFR2 signaling cascade.ConclusionsAdipsin promotes angiogenesis and facilitates blood perfusion recovery in diabetic mice with HLI by downregulating SERPINE1 through interaction with SERBP1. These findings elucidate a novel therapeutic potential for Adipsin in the management of PAD in diabetic patients, highlighting its role in enhancing angiogenesis and tissue repair.

Assessment of Ketamine's Influence on In Vitro Angiogenesis.

Angiogenesis is associated with angiogenic therapy and wound healing processes. It is important for anesthesiologists to understand the effects of perioperative and long-term use of anesthetics on angiogenesis. This study aimed to determine the effects of ketamine on in vitro angiogenesis: the proliferation of human umbilical vein endothelial cells (HUVEC) and normal human diploid fibroblasts (NHDF), HUVEC migration, and in vitro capillary tube formation in cocultured HUVEC and NHDF. The effects of ketamine at concentrations of 1, 10, and 50 µM on the proliferation of HUVEC and NHDF for 48 hours were determined by using a water-soluble tetrazolium salt reagent. Quantitation of migration for 22 hours was achieved by measuring the fluorescence of migrating HUVEC exposed to ketamine using an angiogenesis system. The effects of ketamine on capillary tube formation with or without vascular endothelial growth factor (VEGF) were investigated in cocultured HUVEC and NHDF incubated for 3 and 10 days. Ketamine did not show any enhancing or suppressive effects on the in vitro proliferation of HUVEC and NHDF, HUVEC migration, or capillary tube formation in cocultured HUVEC and NHDF for either 3 or 10 days in the presence or absence of VEGF. Ketamine had no effects on in vitro angiogenesis using cultured HUVEC and NHDF. Ketamine can potentially be used as an anesthetic agent with no influence on angiogenesis.

MiR-185-5p is Involved in Regulating the Abnormal Proliferation of Retinal Microvascular Endothelial Cells via Targeting CXCR4.

This study aimed to explore the expression profile of miR-185-5p in proliferative DR (PDR), and further evaluate its diagnostic value and possible mechanism of miR-185-5p in PDR. The level of miR-185-5p was detected by qRT-PCR. The ROC curve was established to estimate the diagnostic ability of miR-185-5p. Transwell experiment and cell counting kit-8 (CCK-8) assays were conducted to assess the effect of miR-185-5p on the migration and proliferation of human retinal endothelial cells (HRECs) induced by high glucose. Enzyme linked immunosorbent assay (ELISA) was used to detect the concentrations of inflammatory factors. The luciferase reporter gene experiment was used to prove the interaction between miR-185-5p and CXCR4. Compared to the control group, the expression of miR-185-5p was significantly up-regulated in both the type 2 diabetes mellitus (T2DM) group and the PDR groups, with higher levels in the PDR group than in the T2DM group. The ROC curve reveals that serum miR-185-5p can distinguish PDR patients from T2DM patients. MiR-185-5p levels in HRECs increased significantly after high glucose induction. High glucose induction also promoted the migration, proliferation and inflammation response of HRECs. However, when the intracellular miR-185-5p level was down-regulated by miR-185-5p inhibitor transfection, these effects were inhibited. The luciferase reporter gene assay showed that miR-185-5p directly targets CXCR4. The expression of miR-185-5p is out of balance in PDR and it may be involved in regulating the migration and proliferation of HRECs by regulating CXCR4.

A cotton-derived carbon coating by thermolysis method for enhanced mechanical and bio-compatibility of NiTi alloy

A cotton-derived carbon coating by thermolysis method for enhanced mechanical and bio-compatibility of NiTi alloy

Histone Deacetylase 7-Derived 7-Amino Acid Peptide Increases Skin Wound Healing via Regulating Epidermal Fibroblast Proliferation and Migration.

Due to the complexity of wound healing, how to achieve successful healing is a significant clinical challenge. In this study, we found that the histone deacetylase-7-derived 7-amino acid peptide (7A, MHSPGAD), especially its phosphorylated version 7Ap (MH[pSer]PGAD), increased dermal fibroblast cell HDFα proliferation and migration via elevated delta-catenin (CTNND1) serine phosphorylation-mediated beta-catenin (CTNNB) nuclear translocation and subsequent upregulation of c-Myc and cyclin D1 expression. 7Ap physically interacted with platelet-derived growth factor receptor (PDGFR) and increased PDGFR interaction with cyclin-dependent kinase 6 (CDK6). The PDGFR siRNA or CDK6 siRNA knockdown ablated 7AP-induced CTNND1 phosphorylation and subsequent c-Myc/cyclin D1 expression, indicating a novel 7Ap-PDGFR-CDK6-CTNND1/CTNNB signal pathway in regulating fibroblast proliferation and migration. Furthermore, 7Ap increased human umbilic vein endothelial cell proliferation and tube formation, suggesting an angiogenic effect. In a full-thickness excision wound rat model, the local administration of 50 ng/mL of 7Ap in hydrogel exerted a similar effect as 1 μg/mL vascular endothelial growth factor on accelerating wound healing, featured by enhanced fibroblast proliferation and migration, collagen deposition, and increased new vessel formation during the early phase of wound healing. Taken together, this study not only elicited a novel signal pathway in fibroblast proliferation but also paved an avenue to develop 7Ap as a treatment option for skin wound healing.

Repair effects of thermosensitive hydrogels combined with iPSC-derived corneal endothelial cells on rabbit corneal endothelial dysfunction

Considering the limitations of human corneal endothelial cell proliferation as well as the severe shortage of corneal donations, it is imperative to develop improved methods of corneal endothelial cell transplantation. The purpose of this study was to construct a modified corneal endothelial cell transplantation approach using thermosensitive hydrogels combined with induced pluripotent stem cells (iPSCs)-derived human corneal endothelial cells (hCECs). In this study, thermosensitive hydrogels hydroxypropyl chitin/carboxymethyl chitosan (HPCH/CMCS) were fabricated, and their hydrogels properties and biocompatibility were investigated. Our results demonstrated that HPCH/CMCS hydrogels exhibited superior transparency, appropriate mechanical properties and favorable biocompatibility. A two-step induction method of small molecule compounds was employed, by which iPSCs were differentiated into hCECs via neural crest cells (NCCs). Additionally, a rabbit corneal endothelial dysfunction model was established in vivo, aiming to evaluate the safety and effectiveness of the combined method. Slit lamp microscope results indicated that significant transparency improvement could be noted in HPCH/CMCS/hCECs group (P = 0.006), whereas the corneal transparency was not homogeneous in different areas. Moreover, histological examinations and immunofluorescence analysis revealed that HPCH/CMCS/hCECs group showed a higher density of corneal endothelial cells and positive expressions of related markers. This study may provide ideas and experimental basis for the combined application of hydrogels and iPSC-derived corneal endothelial cells for corneal endothelial dysfunction. STATEMENT OF SIGNIFICANCE: Corneal transplantation is the most effective treatment for corneal endothelial dysfunction, which is challenged by issues such as corneal donor shortages and immune rejection. In this study, we proposed a combined transplantation method of cells and hydrogels for corneal endothelial dysfunction. We modified the protocols to obtain corneal endothelial cells from iPSCs by a two-step induction method. Besides, thermosensitive hydrogels with satisfactory biocompatibility and degradability were fabricated as fixation and support carriers of iPSC-derived corneal endothelial cells for in vivo transplantation. Experimental results demonstrated that this method could locally repair corneal endothelial dysfunction in rabbits, with the repaired corneas expressing relevant markers. This study presented a preliminary attempt to combine hydrogels and cells for corneal endothelial dysfunction.