Endothelial cells (ECs) play an important role in tumor progression. Currently, the main target of anti-angiogenic therapy is the vascular endothelial growth factor (VEGF) pathway. Some patients do benefit from anti-VEGF/VEGFR therapy; however, a large number of patients do not have response or acquire drug resistance after treatment. Moreover, anti-VEGF/VEGFR therapy may lead to nephrotoxicity and cardiovascular-related side effects due to its action on normal ECs. Therefore, it is necessary to identify targets that are specific to tumor ECs and could be applied to various cancer types. We integrated single-cell RNA sequencing data from six cancer types and constructed a multi-cancer EC atlas to decode the characteristic of tumor ECs. We found that tip-like ECs mainly exist in tumor tissues but barely exist in normal tissues. Tip-like ECs are involved in the promotion of tumor angiogenesis and inhibition on anti-tumor immune responses. Moreover, tumor cells, myeloid cells, and pericytes are the main sources of pro-angiogenic factors. High proportion of tip-like ECs is associated with poor prognosis in multiple cancer types. We also identified that prostate-specific membrane antigen (PSMA) is a specific marker for tip-like ECs in all the cancer types we studied. In summary, we demonstrate that tip-like ECs are the main differential EC subcluster between tumors and normal tissues. Tip-like ECs may promote tumor progression through promoting angiogenesis while inhibiting anti-tumor immune responses. PSMA was a specific marker for tip-like ECs, which could be used as a potential target for the diagnosis and treatment of non-prostate cancers.

Lymphocytes regulate the immune response by circulating between the vascular and lymphatic systems. High endothelial venules, HEVs, special blood vessels expressing selective adhesion molecules, such as PNAd and MAdCAM-1, mediate naïve lymphocyte migration from the vasculature into the lymph nodes and Peyer\'s patches. We have identified that DACH1 is abundantly expressed in developing HEV-type endothelial cells. DACH1 showed a restricted expression pattern in lymph node blood vessels during the late fetal and early neonatal periods, corresponding to HEV development. The proportion of MAdCAM-1+ and CD34+ endothelial cells is reduced in the lymph nodes of neonatal conventional and vascular-specific Dach1-deficient mice. Dach1-deficient lymph nodes in adult mice demonstrated a lower proportion of PNAd+ cells and lower recruitment of intravenously administered lymphocytes from GFP transgenic mice. These findings suggest that DACH1 promotes the expression of HEV-selective adhesion molecules and mediates lymphocyte trafficking across HEVs into lymph nodes.

A growing awareness for vascular contribution to pathogenesis of brain diseases increases the need for techniques that allow high-resolution imaging and quantification of changes in function and structure of cerebral microvessels. Cerebral vessels are very sensitive structures, making them vulnerable for injury. In addition, they are uniquely characterized with the blood-brain barrier, and an extra caution is required during procedures that involve engagement of cerebral vessels (i.e., craniotomy). Using state of the art facilities, including 3D intravital microscope, we describe here in details:•The steps and equipment required for drilling a craniotomy and removing of the dura, while keeping brain parenchyma and vessels intact. This enables long duration of live and direct monitoring of pial vessels and imaging of BBB permeability.•We present the craniotomy procedure that relevant and compatible with imaging pial vessels and monitoring the blood-brain barrier in small rodents.

This study aimed to investigate the long-term biocompatibility, safety, and degradation of the ultrathin nitrided iron bioresorbable scaffold (BRS) in vivo, encompassing the whole process of bioresorption in porcine coronary arteries. Fifty-two nitrided iron scaffolds (strut thickness of 70 μm) and 28 Vision Co-Cr stents were randomly implanted into coronary arteries of healthy mini-swine. The efficacy and safety of the nitrided iron scaffold were comparable with those of the Vision stentwithin 52 weeks after implantation. In addition, the long-term biocompatibility, safety, and bioresorption of the nitrided iron scaffold were evaluated by coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, energy dispersive spectrometry and histopathological evaluations at 4, 12, 26, 52 weeks and even at 7 years after implantation. In particular, a large number of struts were almost completely absorbed in situ at 7 years follow-up, which were first illustrated in this study. The lymphatic drainage pathway might serve as the potential clearance way of iron and its corrosion products.

Recently, Nrf2/HO-1 has received extensive attention as the main regulatory pathway of intracellular defense against oxidative stress and is considered an ideal target for alleviating endothelial cell (EC) injury.
This paper aimed to summarized the natural monomers/extracts that potentially exert protective effects against oxidative stress in ECs.
A literature search was carried out regarding our topic with the keywords of \"atherosclerosis\" or \"Nrf2/HO-1\" or \"vascular endothelial cells\" or \"oxidative stress\" or \"Herbal medicine\" or \"natural products\" or \"natural extracts\" or \"natural compounds\" or \"traditional Chinese medicines\" based on classic books of herbal medicine and scientific databases including Pubmed, SciFinder, Scopus, the Web of Science, GoogleScholar, BaiduScholar, and others. Then, we analyzed the possible molecular mechanisms for different types of natural compounds in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. In addition, perspectives for possible future studies are discussed.
These agents with protective effects against oxidative stress in ECs mainly include phenylpropanoids, flavonoids, terpenoids, and alkaloids. Most of these agents alleviate cell apoptosis in ECs due to oxidative stress, and the mechanisms are related to Nrf2/HO-1 signaling activation. However, despite continued progress in research on various aspects of natural agents exerting protective effects against EC injury by activating Nrf2/HO-1 signaling, the development of new drugs for the treatment of atherosclerosis (AS) and other CVDs based on these agents will require more detailed preclinical and clinical studies.
Our present paper provides updated information of natural agents with protective activities on ECs against oxidative stress by activating Nrf2/HO-1. We hope this review will provide some directions for the further development of novel candidate drugs from natural agents for the treatment of AS and other CVDs.

The programmed cell death 10 (PDCD10) gene was originally identified as an apoptosis-related gene, although it is now usually known as CCM3, as the third causative gene of cerebral cavernous malformation (CCM). CCM is a neurovascular disease that is characterized by vascular malformations and is associated with headaches, seizures, focal neurological deficits, and cerebral hemorrhage. The PDCD10/CCM3 protein has multiple subcellular localizations and interacts with several multi-protein complexes and signaling pathways. Thus PDCD10/CCM3 governs many cellular functions, which include cell-to-cell junctions and cytoskeleton organization, cell proliferation and apoptosis, and exocytosis and angiogenesis. Given its central role in the maintenance of homeostasis of the cell, dysregulation of PDCD10/CCM3 can result in a wide range of altered cell functions. This can lead to severe diseases, including CCM, cognitive disability, and several types of cancers. Here, we review the multifaceted roles of PDCD10/CCM3 in physiology and pathology, with a focus on its functions beyond CCM.

The initiation and development of major inflammatory diseases, i.e., cancer, vascular inflammation, and some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these diseases, whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo, poor penetration across biological barriers, and rapid clearance by the reticuloendothelial system. Drug delivery strategies are potent to promote their delivery. Herein, we reviewed the potential targets for immunotherapy against the major inflammatory diseases, discussed the biologics and drug delivery systems involved in the immunotherapy, particularly highlighted the approved therapy tactics, and finally offer perspectives in this field.

Skeletal muscle injuries have bothered doctors and caused great burdens to the public medical insurance system for a long time. Once injured, skeletal muscles usually go through the processes of inflammation, repairing and remodeling. If repairing and remodeling stages are out of balance, scars will be formed to replace injured skeletal muscles. At present, clinicians usually use conventional methods to restore the injured skeletal muscles, such as flap transplantation. However, flap transplantation sometimes needs to sacrifice healthy autologous tissues and will bring extra harm to patients. In recent years, stem cells-based tissue engineering provides us new treatment ideas for skeletal muscle injuries. Stem cells are cells with multiple differentiation potential and have ability to differentiate into adult cells under special condition. Skeletal muscle tissues also have stem cells, called satellite cells, but they are in small amount and new muscle fibers that derived from them may not be enough to replace injured fibers. Bone marrow mesenchymal stem cells (BM-MSCs) could promote musculoskeletal tissue regeneration and activate the myogenic differentiation of satellite cells. Biomaterial is another important factor to promote tissue regeneration and greatly enhance physiological activities of stem cells in vivo. The combined use of stem cells and biomaterials will gradually become a mainstream to restore injured skeletal muscles in the future. This review article mainly focuses on the review of research about the application of BM-MSCs and several major biomaterials in skeletal muscle regeneration over the past decades.

UNASSIGNED: In atherosclerotic lesions, extensive inflammation of the vessel wall contributes to plaque instability. Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes in atherosclerosis.
UNASSIGNED: Here, we aim to identify the functional role and regulatory mechanisms of lncRNA hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2) in atherosclerotic inflammation.
UNASSIGNED: An atherosclerotic mouse model was induced in ApoE-/- mice by high fat diet (HFD). Endothelial cells (ECs), human aortic smooth muscle cells (SMCs) or human coronary artery endothelial cells (HCAECs) were exposed to ox-LDL to develop the in vitro model. The effects of lncRNA HIF1A-AS2 on inflammation were evaluated by determining levels of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) and levels of adhesion molecules vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and macrophage cationic peptide 1 (MCP-1).
UNASSIGNED: It was established that lncRNA HIF1A-AS2 and ATF2 were highly expressed in atherosclerotic ApoE-/- mice. Downregulating lncRNA HIF1A-AS2 in ox-LDL-exposed ECs, SMCs and HCAECs inhibited inflammation by reducing levels of pro-inflammatory factors and adhesion molecules. LncRNA HIF1A-AS2 bound to the transcription factor USF1 to elevate ATF2 expression. USF1 overexpression counteracted the suppressive effect of lncRNA HIF1A-AS2 silencing on ox-LDL-induced inflammation. Knockdown of lncRNA HIF1A-AS2 or ATF2 could also attenuate inflammation in atherosclerotic mice. Collectively, the present study demonstrates that downregulation of lncRNA HIF1A-AS2 represses the binding of USF1 to the ATF2 promoter region and then inhibits ATF2 expression, thereby suppressing atherosclerotic inflammation.
UNASSIGNED: This study suggests lncRNA HIF1A-AS2 as an promising therapeutic target for atherosclerosis.

von Willebrand factor (VWF) is exclusively expressed in endothelial cells (ECs) and megakaryocytes, which plays a crucial role in the initiation of arterial thrombosis. Recent studies have shown that VWF is also expressed in osteosarcoma (OS) cells and participates in adhesion of cancer cells to platelets, thus promoting metastasis of OS cells. However, it is unclear how OS cell-derived VWF-platelet interaction contributes to the metastasis of OS. We hypothesized that the interaction is mediated by the binding between VWF A1 and GPIbα of platelets, a molecular mechanism similar to that of thrombosis. The increased expression of VWF in SAOS2 cells may contribute to the enhancement of platelet adhesion through the VWF-GPIb pathway, which could promote the migration and invasion capacities of SAOS2 cells in vitro. Antibodies that block the pathway could significantly inhibit the platelet-induced metastasis of OS cells. Our results suggest a theoretical basis for the development of new anti-OS metastasis drugs, and further enrich the mechanism of OS metastasis.