The Application of Nanomaterials in Angiogenesis

Induction of angiogenesis has enormous potential in the treatment of ischemic diseases and the promotion of bulk tissue regeneration. However, the poor activity of angiogenic cells and proangiogenic factors after transplantation is the main problem that imposes its wide applications. Recent studies have found that the development of nanomaterials has solved this problem to some extent. Nanomaterials can be mainly classified into inorganic nanomaterials represented by metals, metal oxides and metal hydroxides, and organic nanomaterials including DNA tetrahedrons, graphene, graphene oxide, and carbon nanotubes. These nanomaterials can induce the release of angiogenic factors either directly or indirectly, thereby initiating a series of signaling pathways to induce angiogenesis. Moreover, appropriate surface modifications of nanomaterial facilitate a variety of functions, such as enhancing its biocompatibility and biostability. In clinical applications, nanomaterials can promote the proliferation and differentiation of endothelial cells or mesenchymal stem cells, thereby promoting the migration of hemangioblast cells to form new blood vessels. This review outlines the role of nanomaterials in angiogenesis and is intended to provide new insights into the clinical treatment of systemic and ischemic diseases.

Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice

It is of great clinical significance to develop potential novel strategies to prevent cardio-cerebrovascular complications in patients with hyperlipidemia. Vascular Endothelial integrity and function play a key role in the prevention of cardio-cerebrovascular diseases. Endothelial progenitor cells (EPCs) can home to sites of ischemic injury and promote endothelial regeneration and neovascularization. Hypercholesterolemia impairs the function of EPC. The present study attempted to identify the effect of piperlongumine on EPCs’ angiogenic potential and cerebral ischemic injury in high-fat diet-fed (HFD-fed) mice. Here, we showed that treatment with low-does piperlongumine (0.25 mg/kg/day) for 8 weeks significantly improved EPCs function and reduced the cerebral ischemic injury (both infarct volumes and neurobehavioral outcomes) in HFD-fed mice. In addition, low-dose piperlongumine administration increased intracellular NO level and reduced intracellular O2- level in EPCs of HFD-fed mice. Moreover, incubation with piperlongumine (1.0 μM, 24 h) reduced thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) expression levels in EPCs from HFD-fed mice, increased the therapeutic effect of EPC from HFD-fed mice on cerebral ischemic injury reduction and angiogenesis promotion in HFD-fed mice, and the donor derived EPCs homed to the recipient ischemic brain. In conclusion, low-dose piperlongumine can enhance EPCs’ angiogenic potential and protect against cerebral ischemic injury in HFD-fed mice. It is implied that treatment with low-dose piperlongumine might be a potential option to prevent ischemic diseases (including stroke) in patients with hyperlipidemia, and priming with piperlongumine might be a feasible way to improve the efficacy of EPC-based therapy for ischemic diseases.

Mesenchymal Stromal Cells Used for Cellular Cardiomyoplasty As a Way To Treat Myocardial Infarction and Heart Failure

Heart disease is one of the leading causes of morbidity and mortality worldwide. Two of these diseases are heart failure and myocardial infarction. In America alone, there are about 6.2 million people with heart failure, and every 40 seconds, a patient with a heart attack is recorded. Myocardial infarction, known as a heart attack, occurs after the blocking or occlusion of a coronary artery, disabling the delivery of oxygenated blood to regions of the heart. Heart failure, usually occurring after ischemic diseases like myocardial infarction, is where the heart loses the ability to pump a sufficient blood supply to meet the body’s needs. The major ways of treating heart failure and myocardial infarction today are either too expensive or hard to come by, so a new sort of treatment is direly needed. Cellular cardiomyoplasty, a form of cell therapy, is being looked into as a new way to treat these two and other cardiomyopathies. Additionally, though there have been a few cells that have shown a possibility of use for cardiomyoplasty, this review focuses on mesenchymal stem cells, specifically called mesenchymal stromal cells. The purpose of this review is to look into what cellular cardiomyoplasty is, how it may be used in the future, and how mesenchymal stromal cells have shown potential to be used for it.

Obstetric A&E unit admission and hospitalization for obstetrical management during COVID-19 pandemic in a third-level hospital of southern Italy

Background The COronaVIrus Disease 2019 (COVID-19) has spread in Italy since February 2020, inducing the government to call for lockdown of any activity, apart primary needs, during the months March–May 2020. During the lockdown, a reduction of admissions and hospitalizations for ischemic diseases was noticed. Purpose of this study was to observe if there has been the same reduction trend in Accident & Emergency (A&E) unit admissions also for obstetric-gynecological conditions. Methods Medical records and electronic clinical databases were searched for all patients who were admitted to the obstetric A&E department or hospitalized at the Gynecology and Obstetrics Unit of University hospital of Naples Federico II, during the quarter March–May in the years 2019 and 2020. The mean ± standard deviation (SD) of monthly admission to the obstetric A&E department and hospitalization of the year 2020 was compared with that of the year 2019, using the unpaired T test with α error set to 0.05 and 95% confidence intervals (95% CI). Results Admissions were 1483 in the year 2020 and 1786 in 2019. Of total, 1225 (37.5%) women were hospitalized: 583 in the year 2020, 642 in 2019. Mean ± SD of patients monthly admitted to our obstetric A&E department was 494 ± 33.7 in the year 2020, and 595.3 ± 30.9 in 2019, with a mean difference of − 101.3 (95% CI − 103.5 to − 99.1; p < 0.0001). Mean ± SD of patients monthly hospitalized to our department was 194 ± 19.1 in the year 2020, 213.7 ± 4.7 in 2019, with a mean difference of − 19.7 (95% CI − 23.8 to − 15.6; p < 0.0001). Conclusion A significant decrease in the mean of monthly admissions and hospitalizations during the COVID-19 pandemic when compared to the previous year was found also for obstetric–gynecological conditions. Further studies are necessary to assess COVID-19 impact and to take the most appropriate countermeasures.

The discovery and clinical significance of the “Twin Open Skylight and Summon Effects” of the Ilizarov tibial transverse transport technique

Ilizarov’s tibial transverse transport (TTT) technique can promote vascular regeneration. It has been used in the treatment of a variety of lower limb ischemic diseases, such as thromboangiitis obliterans, diabetic foot ulcers, etc. Recently, several novel therapeutic effects have been discovered based on TTT treatment. For instance, in the treatment of thromboangiitis obliterans, an “Open Skylight Effect” was well defined in which the symptom of resting pain disappeared following tibial cortex osteotomy (Long Qu, 2001). During the treatment of bilateral diabetic foot gangrene, patients that received TTT treatment on the one side of the lower limb were observed to have a simultaneous healing of ulcers on both sides, which was termed as the “Summon Effect” (Qikai Hua, 2017). In 2019, we characterized the above discoveries as the “Twin Open Skylight and Summon Effects”. These findings will inspire more potential clinical applications of TTT technique.

Application of stem cell-derived exosomes in ischemic diseases: opportunity and limitations

Ischemic diseases characterized by an insufficient blood flow that leads to a decrease in oxygen and nutrient uptake by cells have emerged as an important contributor to both disability and death worldwide. Up-regulation of angiogenesis may be a key factor for the improvement of ischemic diseases. This article searched articles in PubMed with the following keywords: stem cells, exosomes, angiogenesis, ischemic diseases either alone or in grouping form. The most relevant selected items were stem cell-derived exosomes and ischemic diseases. A growing body of evidence indicates that stem cells produce exosomes, which is the novel emerging approach to cell-to-cell communication and offers a new standpoint on known therapeutic strategies of ischemic diseases. Exosomes transport biological molecules such as many types of proteins, RNAs, DNA fragments, signaling molecules, and lipids between cells. Different stem cells release exosomes representing beneficial effects on ischemic diseases as they promote angiogenesis both in vitro and in vivo experiments. Application of exosomes for therapeutic angiogenesis opened new opportunities in the regenerative medicine, however, some limitations regarding exosomes isolation and application remain concerned. In addition, most of the experiments were conducted in preclinical and therefore translation of these results from bench to bed requires more effort in this field. Exosomes from stem cells are a promising tool for the treatment of ischemic diseases. In addition, translation of pre-clinic results into clinic needs further studies in this field.

Simvastatin accelerated motoneurons death in SOD1G93A mice through inhibiting Rab7-mediated maturation of late autophagic vacuoles

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by motoneuron loss, for which there is currently no effective treatment. Statins, as inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, are used as drugs for treatment for a variety of disease such as ischemic diseases, neurodegenerative diseases, cancer, and inflammation. However, our previous evidence has demonstrated that simvastatin leads to cytotoxicity in NSC34-hSOD1G93A cells by aggravating the impairment of autophagic flux, but the role of simvastatin in ALS model remains elusive. In present study, we reported that after simvastatin treatment, SOD1G93A mice showed early onset of the disease phenotype and shortened life span, with aggravated autophagic flux impairment and increased aggregation of SOD1 protein in spinal cord motoneurons (MNs) of SOD1G93A mice. In addition, simvastatin repressed the ability of Rab7 localization on the membrane by inhibiting isoprenoid synthesis, leading to impaired late stage of autophagic flux rather than initiation. This study suggested that simvastatin significantly worsened impairment of late autophagic flux, resulting in massive MNs death in spinal cord and accelerated disease progression of SOD1G93A mice. Together, these findings might imply a potential risk of clinic application of statins in ALS.

Lipid peroxidation and the subsequent cell death transmitting from ferroptotic cells to neighboring cells

Ferroptosis is a regulated cell death due to the iron-dependent accumulation of lipid peroxide. Ferroptosis is known to constitute the pathology of ischemic diseases, neurodegenerative diseases, and steatohepatitis and also works as a suppressing mechanism against cancer. However, how ferroptotic cells affect surrounding cells remains elusive. We herein report the transfer phenomenon of lipid peroxidation and cell death from ferroptotic cells to nearby cells that are not exposed to ferroptotic inducers (FINs). While primary mouse embryonic fibroblasts (MEFs) and NIH3T3 cells contained senescence-associated β-galactosidase (SA-β-gal)-positive cells, they were decreased upon induction of ferroptosis with FINs. The SA-β-gal decrease was inhibited by ferroptotic inhibitors and knockdown of Atg7, pointing to the involvement of lipid peroxidation and activated autophagosome formation during ferroptosis. A transfer of cell culture medium of cells treated with FINs, type 1 or 2, caused the reduction in SA-β-gal-positive cells in recipient cells that had not been exposed to FINs. Real-time imaging of Kusabira Orange-marked reporter MEFs cocultured with ferroptotic cells showed the generation of lipid peroxide and deaths of the reporter cells. These results indicate that lipid peroxidation and its aftereffects propagate from ferroptotic cells to surrounding cells, even when the surrounding cells are not exposed to FINs. Ferroptotic cells are not merely dying cells but also work as signal transmitters inducing a chain of further ferroptosis.