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Stem cell therapy and skin substitutes address the stalled healing of chronic wounds in order to promote wound closure; however, the high cost and regulatory hurdles of these treatments limit patient access. A low‐cost method to induce bioactive healing has the potential to substantially improve patient care and prevent wound‐induced limb loss. A previous study reported that bioactive factors derived from apoptotic‐like mesenchymal stem cells (MSCs) demonstrated anti‐inflammatory and proangiogenic effects and improved ischemic muscle regeneration. In this work, these MSC‐derived bioactive factors were loaded into a hydrogel foam to harness immunomodulatory and angiogenic properties from MSC components to facilitate chronic wound healing without the high cost and translational challenges of cell therapies. After incorporation of bioactive factors, the hydrogel foam retained high absorbency, moisture retention, and target water vapor transmission rate. High loading efficiency was confirmed and release studies indicated that over 90% of loaded factors were released within 24 h. Ethylene oxide sterilization and 4‐week storage did not affect the bioactive factor release profile or physical properties of the hydrogel foam dressing. Bioactivity retention of the released factors was also confirmed for as‐sterilized, 4°C‐stored, and −20°C‐stored bioactive hydrogel foams as determined by relevant gene expression levels in treated pro‐inflammatory (M1) macrophages. These results support the use of the bioactive dressings as an off‐the‐shelf product. Overall, this work reports a new method to achieve a first‐line wound dressing with the potential to reduce persistent inflammation and promote angiogenesis in chronic wounds. [ABSTRACT FROM AUTHOR]

A pre-hydrated thermosensitive collagenated biomaterial which sets at body temperature and maintains the space of the missing alveolar bone volume, OsteoBiol GTO® (GTO), has been released as a bone substitute. This study was designed to check its angiogenic and osteogenic potentials compared to OsteoBiol Gen-Os® (Gen-Os) and Geistlich Bio-Oss® (Bio-Oss). Samples of materials were incubated in culture media to obtain the extracts. Collagen release was measured in the extracts, which were used to investigate human periodontal ligament (hPDL) cell proliferation (MTT), colonization (Scratch assays) and growth factor release (ELISA). The effects on endothelial cell proliferation (MTT) and organization (Matrigel® assays) were also studied. Finally, endothelial and mesenchymal Stem Cell (hMSC) recruitment (Boyden Chambers) were investigated, and hMSC Alkaline Phosphatase (ALP) activity was measured. A higher collagen concentration was found in GTO extract, which led to significantly higher hPDL cell proliferation/colonization. All materials increased VEGF/FGF-2 growth factor secretion, endothelial cell recruitment, proliferation, and organization, but the increase was highest with GTO. All materials increased hMSC recruitment and ALP activity. However, the increase was highest with collagenated GTO and Gen-Os, which enhanced C5a and BMP-2 secretion. Overall, GTO has higher angiogenic/osteogenic potentials than the collagenated Gen-Os and the anorganic Bio-Oss. It provides a suitable scaffold for endothelial and mesenchymal stem cell recruitment, which represent essential bone regeneration requirements. [ABSTRACT FROM AUTHOR]

Mammals' immune systems react strongly to lipopolysaccharide, an endotoxin present in the outer membrane of gram-negative bacteria. Previous data show that the lipopolysaccharide challenge has a significant impact on reproductive function. This study aimed to explore the toxic effects of lipopolysaccharide on the uterine and ovarian tissues of female Wistar albino rats. Additionally, we investigated the effects of lipopolysaccharide on the expression of angiogenic and insulin growth factor 1 protein as well as oxidative stress markers in the uterus and ovaries. The experimental rats were allocated into two groups: (1) control group (n = 8): received intraperitoneal injection of pyrogen-free 0.9% NaCl and (2) treatment group (n = 12): single intraperitoneal injection of a non-lethal dose of lipopolysaccharide. Rats were sacrificed, and uterus and ovaries were collected at 6- and 72-hour time points after lipopolysaccharide infusion. The exposure of the female rats to lipopolysaccharide induced a significant change in the antioxidant activity in both ovarian and uterine tissues especially after 72 hours of exposure. The exposure of nonpregnant rats to lipopolysaccharide leads to the degeneration of the ovarian follicles and superficial epithelium layer of the uterus. Also, the exposure of female rats to lipopolysaccharide leads to the upregulation of angiogenic proteins in both the ovaries and uterus and decreased expression of insulin growth factor 1 and insulin growth factor R1, especially after 72 hours. In conclusion, lipopolysaccharide is considered as one of the most potent bacterial virulence factors that causes endometrial inflammation and reproductive disorders. [ABSTRACT FROM AUTHOR]

Blood vessels are a key target for cancer therapy. Compared with the healthy vasculature, tumor blood vessels are extremely immature, highly permeable, and deficient in pericytes. The aberrantly vascularized tumor microenvironment is characterized by hypoxia, low pH, high interstitial pressure, and immunosuppression. The efficacy of chemotherapy, radiotherapy, and immunotherapy is affected by abnormal blood vessels. Some anti-angiogenic drugs show vascular normalization effects in addition to targeting angiogenesis. Reversing the abnormal state of blood vessels creates a normal microenvironment, essential for various cancer treatments, specifically immunotherapy. In addition, immune cells and molecules are involved in the regulation of angiogenesis. Therefore, combining vascular normalization with immunotherapy may increase the efficacy of immunotherapy and reduce the risk of adverse reactions. In this review, we discussed the structure, function, and formation of abnormal vessels. In addition, we elaborated on the role of the immunosuppressive microenvironment in the formation of abnormal vessels. Finally, we described the clinical challenges associated with the combination of immunotherapy with vascular normalization, and highlighted future research directions in this therapeutic area. [ABSTRACT FROM AUTHOR]

Mesenchymal stem/stromal cell (MSC)-based therapies have been evaluated in over 1500 human clinical trials for a diverse array of disease indication, but outcomes remain unpredictable due to knowledge gaps in the quality attributes that confer therapeutic potency onto cells and their mode of action in vivo. Based on accumulated evidence from pre-clinical models, MSCs exert therapeutic effects by repressing inflammatory and immune-mediated response via paracrine action following reprogramming by the host injury microenvironment, and by polarization of tissue resident macrophages following phagocytosis to an alternatively activated (M2) state. An important tenet of this existing paradigm is that well-established stem/progenitor functions of MSCs are independent of paracrine function and dispensable for their anti-inflammatory and immune suppressive functions. Herein, we review evidence that stem/progenitor and paracrine functions of MSCs are mechanistically linked and organized hierarchically and describe how this link may be exploited to develop metrics that predict MSC potency across a spectrum of activities and regenerative medicine applications. [ABSTRACT FROM AUTHOR]

One of the most formidable challenges in oncology and tumor biology research is to provide an accurate understanding of tumor dormancy mechanisms. Dormancy refers to the ability of tumor cells to go undetected in the body for a prolonged period, followed by "spontaneous" escape. Various models of dormancy have been postulated, including angiogenic, immune-mediated, and cellular dormancy. While the former two propose mechanisms by which tumor growth may remain static at a population level, cellular dormancy refers to molecular processes that restrict proliferation at the cell level. Senescence is a form of growth arrest, during which cells undergo distinct phenotypic, epigenetic, and metabolic changes. Senescence is also associated with the development of a robust secretome, comprised of various chemokines and cytokines that interact with the surrounding microenvironment, including other tumor cells, stromal cells, endothelial cells, and immune cells. Both tumor and non-tumor cells can undergo senescence following various stressors, many of which are present during tumorigenesis and therapy. As such, senescent cells are present within forming tumors and in residual tumors post-treatment and therefore play a major role in tumor biology. However, the contributions of senescence to dormancy are largely understudied. Here, we provide an overview of multiple processes that have been well established as being involved in tumor dormancy, and we speculate on how senescence may contribute to these mechanisms. [ABSTRACT FROM AUTHOR]

Angiogenesis is the formation of new blood vessels from pre-existing vessels. Adequate oxygen transport and waste removal are necessary for tissue homeostasis. Restrictions in blood supply can lead to ischaemia which can contribute to disease pathology. Vascular endothelial growth factor (VEGF) is essential in angiogenesis and myogenesis, making it an ideal candidate for angiogenic and myogenic stimulation in muscle. We established C2C12 mouse myoblast cell lines which stably express elevated levels of (i) human VEGF-A and (ii) dual human FGF4-VEGF-A. Both stably transfected cells secreted increased amounts of human VEGF-A compared to non-transfected cells, with the latter greater than the former. In vitro, conditioned media from engineered cells resulted in a significant increase in endothelial cell proliferation, migration, and tube formation. In vivo, this conditioned media produced a 1.5-fold increase in angiogenesis in the chick chorioallantoic membrane (CAM) assay. Delivery of the engineered myoblasts on Matrigel demonstrated continued biological activity by eliciting an almost 2-fold increase in angiogenic response when applied directly to the CAM assay. These studies qualify the use of genetically modified myoblasts in therapeutic angiogenesis for the treatment of muscle diseases associated with vascular defects. [ABSTRACT FROM AUTHOR]

Background: Malaria related mortality is associated with significant deregulation of host inflammatory factors such as interferon-inducible protein 10, a member of the CXC or α-subfamily (CXCL10), and host angiogenic factors such as angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2). However, detection of these factors in malaria patients requires the drawing of blood, which is invasive and increases the risk of accidental blood-borne infections. There has been an increased interest in the use of saliva as the body fluid of choice for the diagnosis of many infectious diseases including malaria. Here, saliva levels of CXCL10, Ang-1, and Ang-2 previously shown to be predictive of severe malaria in malaria patients in Ghana were assessed in malaria patients. Methods: This study was conducted in the Shai-Osudoku District Hospital in Dodowa, Accra, Ghana and the study population comprised 119 malaria patients and 94 non-malaria subjects. The non-malaria subjects are healthy community participants with no malaria infection. Plasma and saliva levels of CXCL10, Ang-1 and Ang-2 of the study participants were measured using an enzyme-linked immunoassay. Complete blood counts of each participant were measured with a haematology autoanalyzer. Pearson correlation was used to evaluate the correlation between plasma and saliva levels of each biomarker in malaria patients. A p-value of < 0.05 was considered significant. Box plots of median biomarker concentrations were plotted. SPSS version 14.2 software was used for statistical analysis. Results: The non-malaria subjects had a median age of 29 years compared to 23 years for malaria patients (p = 0.001). Among the malaria patients, there was a strong significant relationship between CXCL10 (R2 = 0.7, p < 0.0001) and Ang-1 (R2 = 0.7, p < 0.0001). Malaria patients had lower saliva levels of Ang-1 (p = 0.009) and higher saliva levels of CXCL10 (p = 0.004) and Ang-2 (p = 0.001) compared to non-malaria subjects. Conclusions: This study provides the first evidence of elevated levels of CXCL10 and Ang-2 in the saliva of malaria patients. Detection of CXCL10, Ang-1 and Ang-2 in saliva may have a potential application for non-invasive malaria diagnosis. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a multisystem disorder of pregnancy characterized by sudden onset of hypertension and proteinuria. The appearance and diagnosis of the disease remain elusive and the only treatment is the termination of pregnancy. The onset of the disease is preceded by a shift in the balance of the angiogenic and antiangiogenic proteins in the maternal circulation. We surmised that the assessment of the levels of these proteins during pregnancy could lead to a proper diagnosis of the disease. In this study, we determined the levels of angiogenic and antiangiogenic proteins and IL-6 in maternal circulation during normotensive and hypertensive pregnancy, including PE. Serum isolated from pregnant women during antenatal visits was used to determine the concentrations of these proteins. The levels of antiangiogenic proteins, sFlt-1 and sEng, were higher in hypertensive disorders [gestational hypertension (GH), mild PE, and PE] of pregnancy and were significantly higher for PE than for GH. The levels of sFlt-1 and sEng were higher in PE samples compared to those in GH and NT samples. These proteins may have contributed to increased blood pressure. The levels of PlGF were decreased in pregnant women having GH, mild PE, and PE. The levels of the inflammatory intermediate, IL-6, were increased in PE samples compared to those in the GH and normotensive samples. The evaluation of the altered levels of antiangiogenic and angiogenic proteins can be useful for diagnosis of PE. [ABSTRACT FROM AUTHOR]

Oral cancer is a dangerous and extensive cancer with a high death ratio. Oral cancer is the most usual cancer in the world, with more than 300,335 deaths every year. The cancerous tumor appears in the neck, oral glands, face, and mouth. To overcome this dangerous cancer, there are many ways to detect like a biopsy, in which small chunks of tissues are taken from the mouth and tested under a secure and hygienic microscope. However, microscope results of tissues to detect oral cancer are not up to the mark, a microscope cannot easily identify the cancerous cells and normal cells. Detection of cancerous cells using microscopic biopsy images helps in allaying and predicting the issues and gives better results if biologically approaches apply accurately for the prediction of cancerous cells, but during the physical examinations microscopic biopsy images for cancer detection there are major chances for human error and mistake. So, with the development of technology deep learning algorithms plays a major role in medical image diagnosing. Deep learning algorithms are efficiently developed to predict breast cancer, oral cancer, lung cancer, or any other type of medical image. In this study, the proposed model of transfer learning model using AlexNet in the convolutional neural network to extract rank features from oral squamous cell carcinoma (OSCC) biopsy images to train the model. Simulation results have shown that the proposed model achieved higher classification accuracy 97.66% and 90.06% of training and testing, respectively. [ABSTRACT FROM AUTHOR]

Tissue engineering of bones often necessitates the addition of exogenous growth factors and supplements to accelerate the differentiation of mesenchymal stem cells to osteogenic lineage, thereby increasing its cost. On the postulation that a scaffold that mimics the micro-/nano-bone architecture per se can provide the essential cues to favor osteogenesis, we developed gelatin nanofibers and loaded them with zinc-doped nano-hydroxyapatite (ZnHp). To further improve its osteogenic potential, the above nano-composite was additionally decorated with rGO platelets (ZnHp@rGO) and incorporated in gelatin nanofibers. On in vitro evaluation, the respective gelatin nanofibers appeared to aid the accelerated differentiation of mesenchymal stem cells toward the osteogenic lineage without the need for any exogenous osteogenic supplement in the milieu. The biomimetic cues provided by ZnHp and ZnHp@rGO also favored angiogenesis, with enhanced CD-31 and iNOS expression. The ability of these nanofibers to induce vascularization was confirmed using an in ovo and in vivo rat model. Apart from its osteoinductive and angiogenic properties, the nanofibers exhibited favorable anti-biofilm activity by preventing the growth of Staphylococcus aureus. Although these results suggest the potential of the scaffold for inducing bone repair in vivo, it also confirms that bones can be engineered at a relatively low cost by designing scaffolds having topographical and biochemical cues that mimic the bone microarchitecture. [ABSTRACT FROM AUTHOR]

Objective:To compare the effect of comorbidities on the phenotype and outcomes of preeclampsia. Methods: A matched retrospective cohort study of women delivering at a tertiary maternity center following a diagnosis of preeclampsia. We collected data on signs and symptoms, biochemical markers, and maternal and perinatal outcomes. Results:We studied 474 women; 158 women with and 316 without comorbidities. Compared to women without comorbidities, women with comorbidities delivered earlier. They suffered fewer maternal but more neonatal complications. Conclusion: Women with comorbidities receive earlier intervention than women without comorbidities, which may lead to fewer maternal complications but worse neonatal outcomes. [ABSTRACT FROM AUTHOR]

Due to the limitations of bone autografts, we aimed to develop new composite biomaterials with pro-angiogenic and osteogenic properties to be used as scaffolds in bone tissue engineering applications. We used a porous, cross-linked and slowly biodegradable fibrin/alginate scaffold originally developed in our laboratory for wound healing, throughout which deposits of calcium phosphate (CaP) were evenly incorporated using an established biomimetic method. Material characterisation revealed the porous nature and confirmed the deposition of CaP precursor phases throughout the scaffolds. MC3T3-E1 cells adhered to the scaffolds, proliferated, migrated and differentiated down the osteogenic pathway during the culture period. Chick chorioallantoic membrane (CAM) assay results showed that the scaffolds were pro-angiogenic and biocompatible. The work presented here gave useful insights into the potential of these pro-angiogenic and osteogenic scaffolds for bone tissue engineering and merits further research in a pre-clinical model prior to its clinical translation. [ABSTRACT FROM AUTHOR]

Due to the limitations of bone autografts, we aimed to develop new composite biomaterials with pro-angiogenic and osteogenic properties to be used as scaffolds in bone tissue engineering applications. We used a porous, cross-linked and slowly biodegradable fibrin/alginate scaffold originally developed in our laboratory for wound healing, throughout which deposits of calcium phosphate (CaP) were evenly incorporated using an established biomimetic method. Material characterisation revealed the porous nature and confirmed the deposition of CaP precursor phases throughout the scaffolds. MC3T3-E1 cells adhered to the scaffolds, proliferated, migrated and differentiated down the osteogenic pathway during the culture period. Chick chorioallantoic membrane (CAM) assay results showed that the scaffolds were pro-angiogenic and biocompatible. The work presented here gave useful insights into the potential of these pro-angiogenic and osteogenic scaffolds for bone tissue engineering and merits further research in a pre-clinical model prior to its clinical translation. [ABSTRACT FROM AUTHOR]

The aim of the present study was to analyze the characteristics of angiogenic factors in patients with hypopharyngeal cancer, and to study the effects of these factors on induction chemotherapy, patient prognosis and survival. Data from 60 eligible patients with hypopharyngeal cancer that were treated between January 2012 and December 2016 were collected retrospectively. The differential expression of angiogenic factors in tumor and peritumoral tissues was analyzed retrospectively to assess the association between five differentially expressed genes, including interleukin (IL)-1β, transforming growth factor (TGF)-β, matrix metalloproteinase-9 (MMP-9), angiopoietin-2 and interferon-inducible T-cell α chemoattractant, and clinicopathological characteristics in different types of chemotherapy-associated blood vessels within samples of poorly differentiated hypopharyngeal cancer. The χ² test or t-test was used to compare the frequency data, the Kaplan-Meier method was used for survival analysis and the log-rank test was used to compare the Kaplan-Meier curves. P<0.05 was considered to indicate a statistically significant difference. The results of the present study demonstrated that there was a significant difference in the expression levels of vascular-associated factors between hypopharyngeal carcinoma and peritumoral tissues. Additionally, the results revealed a significant difference in the overall survival and prognosis of patients with a decreased vascular classification compared with patients with an unchanged vascular classification, which was assessed using narrowband imaging (NBI) following induction chemotherapy (P<0.05). The results of single factor analysis indicated that IL-1β, TGF-β and MMP-9 were associated with decreased blood vessel classification (P<0.05). In conclusion, IL-1β, TGF-β and MMP-9 may be used as predictors of the effect of induction chemotherapy on poorly differentiated hypopharyngeal cancer. Therefore, when patients with advanced hypopharyngeal cancer undergo chemotherapy, NBI vascular examination and screening for associated vascular factors should be performed before and after chemotherapy. Alterations in vascular classification, assessed using NBI, and abnormal expression of vascular factors may also be used as reference factors for prognosis. [ABSTRACT FROM AUTHOR]

Immunotherapy by immune checkpoint inhibitors (ICIs) has showed outstanding efficacy in the treatment of advanced non-small cell lung cancer (NSCLC). The combination of immunotherapy with anti-angiogenic therapy exhibited enhanced efficacy in multiline treatment. However, the potential biomarkers for predicting and monitoring the therapeutic response of the combined therapy remain undefined. In this study, we performed a pilot study by prospectively recruiting 22 advanced NSCLC patients who failed to previous lines of chemotherapy, chemoradiotherapy, TKI therapy, surgery, or any combination of the therapies, and investigated the prognostic factors for patients who received anti-PD-1 (Camrelizumab) and anti-angiogenic (Apatinib) combined therapy. The objective response rate (ORR) assessed by an independent radiology review was 22.7%, and the median progression-free survival (PFS) was 5.25 months. We found that high concentration of circulating-free DNA (cfDNA) (HR = 27.75, P = 0.003), MIKI67 mutation (HR = 114.11, P = 0.009) and gene variations related to hyper-progressive disease (HPD) (HR = 36.85, P = 0.004) were independent risk factors and exhibited significant correlation with PFS. Circulating tumor DNA (ctDNA) mutational status was also a predicting indicator for PFS. In contrast, the blood tumor mutational burden (bTMB) could not stratify the clinical benefit in this combined therapy (HR = 0.81, P = 0.137). Furthermore, we found that the variant allele fraction (VAF) of mutations in ctDNA was sensitive indicators of therapeutic response and therefore can be used to monitor the tumor relief or progression. In conclusion, cfDNA concentration, MIKI67 mutations and HPD-related mutations were independent risk factors and PFS predictors for multiline combined anti-angiogenic/ICI combined therapy. ctDNA may be a novel monitoring biomarker for therapeutic response and predicting biomarker for prognosis in future combined therapy involving PD-1 blockade. [ABSTRACT FROM AUTHOR]

Purpose: Although biomarkers for patients with metastatic colorectal cancer exist, the benefit patients with RAS mutated tumors derive from established regimens is unclear. Methods: Efficacy of therapeutic strategies available for RAS mutated patients (addition of chemotherapeutic agents and/or anti angiogenic agents) were investigated in fourteen randomized controlled phase III trials at trial level by meta-analysing individual study hazard ratios and 95% confidence intervals (95% CI) for overall survival (OS) and progression free survival (PFS). Results: 6810 of 10,748 patients (63.3%) were available (48.5% RAS wildtype, 51.5% RAS mutated). Across all treatment lines, additional treatment efficacy (chemotherapy and/or anti angiogenic agents) was significantly smaller in RAS mutated compared to wildtype tumors for OS and PFS. In detail, patients with RAS mutated metastatic colorectal cancer derived significant benefit in PFS but not in OS by the addition of either chemotherapy or anti angiogenic agents to the respective comparator. In patients with RAS wildtype metastatic colorectal cancer, PFS and OS were improved by the addition of chemotherapy or anti angiogenic agent. Conclusion: The therapeutic benefit of additional substances is less distinct in patients with RAS mutated as compared to RAS wildtype metastatic colorectal cancer, especially with regard to OS. [ABSTRACT FROM AUTHOR]

Pathological angiogenesis and apoptosis evasion are common hallmarks of cancer. The present work was an endeavor to evaluate the influence of bee venom (BV) or its major constituent melittin (MEL) as antiapoptotic and angiogenic regulator modifier on the tumor growth and the cell sensitivity to ionizing radiation targeting the improvement of cancer therapeutic protocols. BV (0.56 mg/kg/day) and MEL (500 µg/kg body weight/day) were injected intraperitoneally to mice bearing 1 cm3 solid tumor of Ehrlich ascites carcinoma (EAC) for 21 consecutive days. Mice were whole-body exposed to 1 Gray (Gy) of γ-radiation (2 fractionated doses). Treatment with BV or MEL markedly suppresses the proliferation of tumor in EAC mice. The concentrations of m-RNA for angiogenic factors (TNF-α, VEGF) as well as MMPs 2 and 9 activities and NO concentration were significantly decreased, combined with improvements in apoptotic regulators (caspase-3 activity) and normal cells redox tone (catalase and free radicals content) compared with EAC mice. Moreover, the histopathological investigation confirms the improvement exerted by BV or MEL in the EAC mice group or EAC + R group. Exposure to γ-radiation sustained the modulatory effect of BV on tumor when compared with EAC + BV mice. Convincingly, the role of BV or MEL as a natural antiangiogenic in the biological sequelae after radiation exposure is verified. Hence, BV and its major constituent MEL might represent a potential therapeutic strategy for increasing the radiation response of solid tumors. [ABSTRACT FROM AUTHOR]

The aims of this study were to study the effects of miR-2 on cerebral ischemia–reperfusion rats and to explore its further mechanism. Rats were assigned into sham, model, miR-22 control and miR-22 groups. Observation of neurological behaviors at 24 h after operation found that neurological functions were severely damaged in the model and miR-22 control groups and these damages were improved by miR-22. RT-PCR indicated that miR-22 mRNA level in the brain tissue was significantly decreased in the model and miR-22 control groups, but increased in the miR-22 group. TTC staining showed increased percentage of cerebral infarction volume in the model and miR-22 control groups and this increase was reduced by miR-22. Immunohistochemistry showed increased densities of CD34+ and VEGF+ microvessels in the cortex in the model and miR-22 control groups, which were further increased in the miR-22 group. ELISA showed increased serum VEGF and Ang-1 levels in the model and miR-22 control groups, which were also further increased in the miR-22 group. Western blot analysis showed increased phosphorylation level of PI3K and Akt in brain tissue in the model and miR-22 control groups, which were further increased in the miR-22 group. Administration of LY294002, a specific PI3K pathway inhibitor, significantly reversed all the effects of miR-22 on rats in the model group. miR-22 exerts its neuroprotective and angiogenic functions via the PI3K/Akt signaling pathway, at least partly, in rats under cerebral ischemia–reperfusion. [ABSTRACT FROM AUTHOR]

Introduction: Endothelial cells cover the surface of the capillary wall and literature review has cemented its angiogenic roles in wound healing and tissue regeneration. However, the angiogenic in vitro models available are inadequate to understand the endothelial differentiation process. Methods: A construct was made using human amniotic membrane (HAM) as a matrix to assist the dental stem cells to differentiate into endothelial-like cells. This study aimed to assess the biological interaction between stem cells from human exfoliated deciduous teeth (SHED) and the stromal side (SS) of the glycerol-preserved HAM in angiogenic-induced environment media using VEGF. The changes were evaluated through cell morphology, migration, as well as gene expression level. Results: There were morphological changes observed in SHED in angiogenic-induced media. SHED appeared to be differentiated from fibroblast-like cells to a new structure, mimicking endothelial-like structure through microscopy analysis. Besides, the cross-section of the construct revealed that the cells seeded on the matrix were able to maintain its monolayer structure at day 1, 7 and 14 but infiltrated into the HAM at day 21, suggesting cell migration. The cells were also able to maintain its stemness (Nestin, Nanog and CD29) and at the same time express the angiogenic markers (IL-8, VEGF and MMP-2). Conclusion: HAM promotes SHED proliferation, migration and has the potential as a differentiating matrix for endothelial-like cells. [ABSTRACT FROM AUTHOR]

Objective  To evaluate to what extent indicators of placenta insufficiency are associated with low concentrations of insulin-like growth factor 1 (IGF-1) and IGF-1–binding protein-1 (IGFBP-1) in neonatal blood, and to what extent the concentrations of these growth factors are associated with concentrations of proteins with inflammatory, neurotrophic, or angiogenic properties. Study Design  Using multiplex immunoassays, we measured the concentrations of IGF-1 and IGFBP-1, as well as 25 other proteins in blood spots collected weekly from ≥ 880 infants born before the 28th week of gestation, and sought correlates of concentrations in the top and bottom quartiles for gestational age and day the specimen was collected. Results  Medically indicated delivery and severe fetal growth restriction (sFGR) were associated with low concentrations of IGF-1 on the first postnatal day and with high concentrations of IGFBP-1 on almost all days. Elevated concentrations of IGF-1 and IGFBP-1 were accompanied by elevated concentrations of many other proteins with inflammatory, neurotrophic, or angiogenic properties. Conclusion  Disorders associated with impaired placenta implantation and sFGR appear to account for a relative paucity of IGF-1 on the first postnatal day. Elevated concentrations of IGF-1 and especially IGFBP-1 were associated with same-day elevated concentrations of inflammatory, neurotrophic, and angiogenic proteins. [ABSTRACT FROM AUTHOR]

Preeclampsia is a pregnancy disorder causing substantial maternal and fetal morbidity and mortality. In the UK, its diagnosis currently depends upon new onset hypertension and proteinuria. There is a clinical need for enhanced screening to prevent unnecessary resource use and improve outcomes. Here, the current practice in preeclampsia diagnosis will be summarized, with assessment of the evidence that angiogenic factors could improve its management. Although the combination of new onset hypertension and proteinuria define and hence diagnose the disorder, separately they are poorly predictive. Preeclampsia is ultimately a placental disease caused by syncytiotrophoblast dysfunction. The angiogenic factors placental growth factor, soluble fms-like tyrosine kinase 1 and soluble endoglin, all originating at least in part from the syncytiotrophoblast, are biomarkers with predictive potential for preeclampsia and related adverse outcomes. Recent work with the soluble fms-like tyrosine kinase 1/placental growth factor ratio has identified key measurement cutoffs, with one having a high negative predictive value for preeclampsia. The soluble fms-like tyrosine kinase 1/placental growth factor ratio seems particularly promising as a screening measure, able to predict accurately the short-term absence of preeclampsia and suggest the likelihood of adverse events within 4 weeks. The ratio could be used to allocate specific management plans to patients according to risk. An understanding of angiogenic factors may also lead to new therapeutic options for a condition currently only curable by delivery, although it must be remembered that the factors are markers of underlying syncytiotrophoblast stress, which would not be resolved by targeting them. [ABSTRACT FROM AUTHOR]

A number of benign and malignant neoplasms may arise from the vascular elements within the liver parenchyma. Lesions discussed in this article include angiosarcoma, epithelioid hemangioendothelioma, solitary fibrous tumor (hemangiopericytoma), infantile, and cavernous hemangiomas. Despite a common theme of vascular origin, the pathologic and imaging appearance of these entities can be heterogeneous. Angiosarcomas are bizarrely enhancing, highly aggressive tumors, which often present with metastatic disease. When solitary, epithelioid hemangioendothelioma lesions can exhibit a concentric ring or target appearance on contrast-enhanced CT and at MR and when numerous may be indistinguishable from angiosarcoma except for a more slowly advancing course. Primary solitary fibrous tumors of the liver are exceedingly rare solid masses and most often initially diagnosed on imaging as other entities such as cholangiocarcinoma. Infantile hemangiomas consist of benign proliferation of the vascular endothelium and in the absence of flow-related complications, are usually clinically silent, and may be detected incidentally as T1 hypointense, T2 hyperintense, centripetally enhancing lesions. Cavernous hemangiomas are extremely common hepatic lesions and when classic rarely offer a challenge in diagnosis, though atypical variants may mimic more serious diseases. The purpose of this review is to provide an overview of important vascular tumors of the liver in order to aid the radiologist in providing a broad differential diagnosis for focal liver lesions, and when classic, suggest specific uncommonly seen diagnoses in order to more accurately guide clinical management. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis occurs in physiologic (wound healing) and pathological conditions and plays an important role in tumor growth, progression and metastasis. Therefore, the inhibition of angiogenesis can be an important approach to treat cancer diseases. In recent years, the use of nanoparticles has been developed to control cancer cells and prevent tumor growth. Various studies have shown the role of nanoparticles in reducing angiogenesis and inhibition of cancer cells. So, in this study, the anti-angiogenic effect of silver nanoparticle synthesis by Rubina tinctorum L (Ru-AgNPs) on Chicken Chorioallantoic Membrane (CAM) was investigated. Materials and Methods: In an experimental study, 60 eggs were randomly divided into 6 groups including control, laboratory control and 4 treatment groups (10 eggs/group). On the second day of incubation, a window was created on the eggs. On the 8th day, the chorioallantoic membrane of samples was treated with different concentrations of nanoparticles and on the 12th day, the image was taken from all samples. Finally, the number and length of vessels on the chorioallantoic membrane and following that weight and length of the embryo from crown to squattiest were measured. Quantitative data were analyzed using LSD-test. Results: The results showed that the Ru-AgNPs significantly reduced the length and number of blood vessels in the treated groups compared to the control group. Also, the comparison of length and weight of embryos in treated samples with control group showed that the Ru-AgNPs had an inhibitory effect on the length of the embryos, but the weight did not differ significantly in the treatment with the control group. Conclusion: Considering the inhibitory effect of the Ru-AgNPs on the angiogenesis of the chorioallantoic membrane, with further studies, this compound can be used to control and inhibit pathological angiogenesis in many diseases such as cancers. [ABSTRACT FROM AUTHOR]

Problem Women with antiphospholipid antibodies ( aPL) are at risk for pregnancy complications despite treatment with low molecular weight heparin ( LMWH) or aspirin ( ASA). aPL recognizing beta2 glycoprotein I can target the uterine endothelium, however, little is known about its response to aPL. This study characterized the effect of aPL on human endometrial endothelial cells ( HEECs), and the influence of LMWH and ASA. Method of study HEECs were exposed to aPL or control IgG, with or without low-dose LMWH and ASA, alone or in combination. Chemokine and angiogenic factor secretion were measured by ELISA. A tube formation assay was used to measure angiogenesis. Results aPL increased HEEC secretion of pro-angiogenic VEGF and Pl GF; increased anti-angiogenic sFlt-1; inhibited basal secretion of the chemokines MCP-1, G- CSF, and GRO-α; and impaired angiogenesis. LMWH and ASA, alone and in combination, exacerbated the aPL-induced changes in the HEEC angiogenic factor and chemokine profile. There was no reversal of the aPL inhibition of HEEC angiogenesis by either single or combination therapy. Conclusion By aPL inhibiting HEEC chemokine secretion and promoting sFlt-1 release, the uterine endothelium may contribute to impaired placentation and vascular transformation. LMWH and ASA may further contribute to endothelium dysfunction in women with obstetric APS. [ABSTRACT FROM AUTHOR]

The main objectives of this study are to evaluate 28 selected pro-angiogenic and anti-angiogenic microRNA (miRNA) expressions in plasma of acute ischemic stroke (AIS) patients and controls and to assess the correlations of these miRNAs with risk and severity of AIS. In the exploring stage, 10 AIS patients and 10 controls with vascular risk factors were enrolled. And in the validating stage, 106 AIS patients and 110 controls with the same eligibility were recruited. Blood samples were collected from participants within 24 h post the onset of symptoms, and plasma levels of miRNAs were evaluated by the qPCR method. In the exploring stage, 11 differentially expressed miRNAs (DEM) were identified and included into the validating stage. In the validating stage, the expression of miR-126, miR-130a, and miR-378 in plasma declined in the AIS patients; however, miR-222, miR-218, and miR-185 plasma levels were elevated. Univariate and multivariate logistic regression analysis disclosed that miR-126, miR-130a, miR-222, miR-218, and miR-185 were independent predicting factors for AIS. When these five DEMs were combined together, they presented a good diagnostic value with an area under curve (AUC) value of 0.767 (95% CI 0.705-0.829), sensitivity of 87.7%, and specificity of 54.5% at best cutoff point. Additionally, miR-126, miR-378, miR-101, miR-222, miR-218, and miR-206 were associated with National Institutes of Health Stroke Scale (NIHSS) score. Circulating miR-126, miR-130a, miR-222, miR-218, and miR-185 could be served as promising and independent biomarkers for risk of AIS, and miR-126, miR-378, miR-222, miR-101, miR-218, and miR-206 could be used for disease severity management of AIS. [ABSTRACT FROM AUTHOR]

Bioglass® 45S5 (BG) has an outstanding ability to bond with bones and soft tissues, but its application as a load-bearing scaffold material is restricted due to its inherent brittleness. BG-based composites combine the amazing biological and bioactive characteristics of BG with structural and functional features of other materials. This article reviews the composites of Bioglass® in combination with metals, ceramics and polymers for a wide range of potential applications from bone scaffolds to nerve regeneration. Bioglass® also possesses angiogenic and antibacterial properties in addition to its very high bioactivity; hence, composite materials developed for these applications are also discussed. BG-based composites with polymer matrices have been developed for a wide variety of soft tissue engineering. This review focuses on the research that suggests the suitability of BG-based composites as a scaffold material for hard and soft tissues engineering. Composite production techniques have a direct influence on the bioactivity and mechanical behavior of scaffolds. A detailed discussion of the bioactivity, in vitro and in vivo biocompatibility and biodegradation is presented as a function of materials and its processing techniques. Finally, an outlook for future research is also proposed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3197-3223, 2017. [ABSTRACT FROM AUTHOR]

Background: Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) <3rd centile between 20+0 and 26+6 weeks of gestation.Methods: This is a 6 year European multicentre prospective cohort study, recruiting women with a singleton pregnancy where the EFW is <3rd centile for gestational age and <600 g at 20+0 to 26+6 weeks of gestation. Detailed data are collected on: maternal history; antenatal, peripartum, and postnatal maternal complications; health economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death.Discussion: The findings of the EVERREST Prospective Study will support the development of a novel therapy for severe early onset FGR by describing in detail the natural history of the disease and by identifying women whose pregnancies have the poorest outcomes, in whom a therapy might be most advantageous. The findings will also enable better counselling of couples with affected pregnancies, and provide a valuable resource for future research into the causes of FGR.Trial Registration: NCT02097667 registered 31st October 2013. [ABSTRACT FROM AUTHOR]

Background: Interleukin 12 (IL-12) is a cytokine that has been reported to exhibit potent tumoricidal effects in animal tumor models. A combined approach using Paclitaxel and platinum-based doublet chemotherapy is the most commonly used backbone regimen for treating lung cancer. Despite numerous studies regarding the anti-tumor effects of IL-12 and the widespread use of conventional chemotherapy, few direct comparisons of IL-12 and conventional chemotherapy in the treatment of lung cancer have been performed.Methods: We compared IL-12 to paclitaxel and cisplatin doublet chemotherapy in terms of efficacy against lung cancer in mouse models. The antitumor effect was measured by survival assays, histological analyses and imaging analyses. The cytokine levels were assessed using enzyme linked immunosorbent assay (ELISA) and flow cytometry (FACS). The spleen sizes were measured. CD31, CD105 and Vascular endothelial growth factor receptor 3 (VEGFR3) were analyzed using immunofluorescence. Matrix metalloprotein-9 (MMP-9) and cadherin 1 (CDH1) transcript levels were measured by quantitative PCR. Tumor cells apoptosis were examined by Tunel assay.Results: The results showed that IL-12 treatment inhibited lung tumor growth, resulting in the long-term survival of lung cancer-bearing mice. Further examination revealed that IL-12 rapidly activated NK cells to secrete IFN-γ, resulting in the inhibition of tumor angiogenesis. In contrast, paclitaxel and cisplatin doublet chemotherapy did not show the expected efficacy in orthotopic lung cancer models; the IFN-γ levels were not increased after this treatment, and the number of peripheral lymphocytes was reduced.Conclusion: Together, these animal model data indicate that IL-12 shows a better curative effect than PTX + CDDP doublet chemotherapy. [ABSTRACT FROM AUTHOR]

Adnectins are a family of binding proteins derived from the 10th type III domain of human fibronectin (10Fn3), which is part of the immunoglobulin superfamily and normally binds integrin. The 10Fn3 has the potential for broad therapeutic applications given its structural stability, ability to be manipulated, and its abundance in the human body. The most commonly studied adnectin is CT-322, which is an inhibitor of vascular endothelial growth factor receptor-2. A bispecific adnectin, El-Tandem, has also been developed and binds to epidermal growth factor receptor and insulin-like growth factor-1 receptor simultaneously. Pre-clinical studies have shown promising results in relation to reducing tumor growth, decreasing microvessel density, and promoting normalization of tumor architecture. The phase I trial with CT-322 demonstrates relatively low toxicities. However, the phase II study done with CT-322 in recurrent glioblastoma does not reveal as promising results. [ABSTRACT FROM AUTHOR]

Three-dimensional printing is a versatile technique to generate large quantities of a wide variety of shapes and sizes of polymer. The aim of this study is to develop functionalized 3D printed poly(lactic acid) (PLA) scaffolds and use a mussel-inspired surface coating and Xu Duan (XD) immobilization to regulate cell adhesion, proliferation and differentiation of human bone-marrow mesenchymal stem cells (hBMSCs). We prepared PLA scaffolds and coated with polydopamine (PDA). The chemical composition and surface properties of PLA/PDA/XD were characterized by XPS. PLA/PDA/XD controlled hBMSCs' responses in several ways. Firstly, adhesion and proliferation of hBMSCs cultured on PLA/PDA/XD were significantly enhanced relative to those on PLA. In addition, the focal adhesion kinase (FAK) expression of cells was increased and promoted cell attachment depended on the XD content. In osteogenesis assay, the osteogenesis markers of hBMSCs cultured on PLA/PDA/XD were significantly higher than seen in those cultured on a pure PLA/PDA scaffolds. Moreover, hBMSCs cultured on PLA/PDA/XD showed up-regulation of the ang-1 and vWF proteins associated with angiogenic differentiation. Our results demonstrate that the bio-inspired coating synthetic PLA polymer can be used as a simple technique to render the surfaces of synthetic scaffolds active, thus enabling them to direct the specific responses of hBMSCs. [ABSTRACT FROM AUTHOR]

Problem Women with antiphospholipid syndrome ( APS) are at increased risk of recurrent pregnancy loss ( RPL) and preeclampsia. Antiphospholipid antibodies (a PL) directly alter trophoblast function. Treatment with low molecular weight heparin ( LMWH) reduces the risk of RPL but not preeclampsia. Moreover, LMWH stimulates trophoblast sFlt-1 release, an anti-angiogenic factor associated with preeclampsia. Since vitamin D deficiency is associated with APS and preeclampsia, this study sought to determine the effect of vitamin D on trophoblast function in the setting of a PL and LMWH. Method of study A human first trimester trophoblast cell line ( HTR8) and primary trophoblast cultures were treated with or without a PL in the presence and absence of vitamin D, LMWH or both. Trophoblast secretion of inflammatory cytokines and angiogenic factors were measured by ELISA. Results Vitamin D alone or in combination with LMWH attenuated the aPL-induced trophoblast inflammatory response in the HTR8 cells and primary cultures. While vitamin D did not have any impact on a PL-mediated modulation of angiogenic factors in the primary trophoblast, it significantly inhibited LMWH-induced s Flt-1 release. Conclusion LMWH in combination with vitamin D may be more beneficial than single-agent therapy by preventing a PL-induced trophoblast inflammation and reversing LMWH-induced s Flt-1 secretion. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is a common malignancy with a poor prognosis. Sorafenib is the only systemic therapy known to improve the overall survival of patients with advanced disease. The clinical benefit of sorafenib is modest and the mechanistic basis for its activity is unknown. Four phase 3 clinical trials have failed to improve on sorafenib in the frontline setting and no agent has been shown to impact outcomes after sorafenib failure. Several factors have contributed to this recent stall in drug development but new approaches hold promise and currently are being investigated. This review will focus on the current pipeline of experimental therapeutics for patients with advanced hepatocellular carcinoma and shed a light on scientific limitations that hamper the advancement of new therapies for this disease, and ways around it. Cancer 2014;120:3122-3130. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective was to describe the effect of bioactive glass putty with and without topical simvastatin on new bone formation in critical-sized defects of rat calvaria. A calvarial bone defect was created in 20 male Wistar rats and filled with bioactive glass alone (n = 10) or combined with simvastatin (n = 10). After 4 weeks, the defects were histomorphometrically evaluated for volume fraction (Vv) of woven bone, vessel density, bioglass quantity, and inflammation. Compared to the bioglass-only group, rats treated with simvastatin had greater Vv of blood vessels (3.3% ± 0.7 vs 1.6% ± 0.1, P = .0002) and new bone (2.3% ± 0.2 vs 1.8% ± 2.5, P = .003). The Vv of the bioglass remnants in the bioglass-only group was higher than in the group treated with simvastatin (2.4% ± 0.08 vs 1.7% ± 0.3, P < .0004). Chronic inflammation was noted in 1 rat from each group. Topical simvastatin seems to improve the pro-angiogenic and pro-osteogenic properties of bioglass putty in rat calvaria critical-size defects without significant inflammation. I [ABSTRACT FROM AUTHOR]

Hypertensive disorders of pregnancy represent the second commonest cause of direct maternal death and complicate an estimated 5-10 % of pregnancies. Classification systems aim to separate hypertension similar to that seen outside pregnancy (chronic and gestational hypertension) from the potentially fatal pregnancy-specific conditions. Preeclampsia, HELLP syndrome, and eclampsia represent increasing severities of this disease spectrum. The American College of Obstetricians and Gynecologists' 2013 guidelines no longer require proteinuria as a diagnostic criterion, because of its variable appearance in the disease spectrum. The cause involves inadequate cytotrophoblastic invasion of the myometrium, resulting in placental hypoperfusion and diffuse maternal endothelial dysfunction. Changes in angiogenic and antiangiogentic peptide profiles precede the onset of clinical preeclampsia. Women with preeclampsia should be closely monitored and receive magnesium sulfate intravenously if severe features, HELLP syndrome, or eclampsia occur. Definitive therapy is delivery of the fetus. Hypertension in pregnancy increases future maternal risk of hypertension and cardiovascular disorders. [ABSTRACT FROM AUTHOR]

Background Red blood cell transfusion has been associated with adverse outcomes including infection, delayed recovery and increased mortality in some patient populations. Circulating cells that yield endothelial-like vascular progenitor cell ( VPC) clusters are correlated with vascular repair and recovery after ischaemic injury. The impact of red cell transfusion on VPC clusters and vascular repair remains uncertain. Study design We prospectively enrolled patients admitted to intensive care requiring red cell transfusion and subjects at low likelihood of requiring red cell transfusion. Levels of VPC clusters and plasma levels of angiogenic cytokines were compared. A total of 17 patients were recruited and had blood samples collected at time of enrolment and at 24-48 h, 48-72 h and 1 week following transfusion. Results We could not discern differences in the number of VPC clusters between transfused patients ( n = 6) and non-transfused subjects ( n = 11) at baseline or throughout the study period. VPC cluster levels demonstrated wide variance and were highest at 24-h post-enrolment in the entire cohort. Furthermore, levels of all 16 cytokines analysed were not significantly different between transfused and non-transfused patients and we did not observe a correlation between cytokine concentrations and levels of circulating VPC-cluster forming cells in the overall study population. Conclusions Our data suggest that assessment of vascular repair responses after red blood cell transfusion in critically ill patients is challenging. Although our study did not allow us to discern an influence of red cell transfusion on VPC cluster levels or angiogenic cytokines, new methods evaluating vascular repair mechanisms may be required. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) mediates endothelial angiogenesis via inducing the expression of integrin αvβ3. During angiogenesis, endothelial cells adhere to and migrate into the extracellular matrix through integrins. Collagen IV binds to integrin αvβ3, leading to integrin activation, which affects a number of signaling processes in endothelial cells. In the present study, we evaluated the role of collagen IV in NO-induced angiogenesis. We found that NO donor 2,2′-(hydroxynitrosohydrazino)bis-ethanamine (NOC-18) causes increases in collagen IV mRNA and protein in lung endothelial cells and collagen IV release into the medium. Addition of collagen IV into the coating of endothelial culture increases endothelial monolayer wound repair, proliferation, and tube formation. Inhibition of collagen IV synthesis using gene silencing attenuates NOC-18-induced increases in monolayer wound repair, cell proliferation, and tube formation as well as in the phosphorylation of focal adhesion kinase (FAK). Integrin blocking antibody LM609 prevents NOC-18-induced increase in endothelial monolayer wound repair. Inhibition of protein kinase G (PKG) using the specific PKG inhibitor KT5823 or PKG small interfering RNA prevents NOC-18-induced increases in collagen IV protein and mRNA and endothelial angiogenesis. Together, these results indicate that NO promotes collagen IV synthesis via a PKG signaling pathway and that the increase in collagen IV synthesis contributes to NO-induced angiogenesis of lung endothelial cells through integrin-FAK signaling. Manipulation of collagen IV could be a novel approach for the prevention and treatment of diseases such as alveolar capillary dysplasia, severe pulmonary arterial hypertension, and tumor invasion. [ABSTRACT FROM AUTHOR]

Calcium silicate-based bioactive glass has received significant attention for use in various biomedical applications due to its excellent bioactivity and biocompatibility. However, the bioactivity of calcium silicate nanoparticle-incorporated bioactive dental sealer is not much explored. Herein, three commercially available bioactive root canal sealers (Endoseal MTA (EDS), Well-Root ST (WST), and Nishika Canal Sealer BG (NBG)) were compared with a resin-based control sealer (AH Plus (AHP)) in terms of physical, chemical, and biological properties. EDS and NBG showed 200 to 400 nm and 100 to 200 nm nanoparticle incorporation in the SEM image, respectively, and WST and NBG showed mineral deposition in Hank's balanced salt solution after 28 days. The flowability and film thickness of all products met the ISO 3107 standard. Water contact angle, linear dimensional changes, and calcium and silicate ion release were significantly different among groups. All bioactive root canal sealers released calcium ions, while NBG released ~10 times more silicon ions than the other bioactive root canal sealers. Under the cytocompatible extraction range, NBG showed prominent cytocompatibility, osteogenecity, and angiogenecity compared to other sealers in vitro. These results indicate that calcium silicate nanoparticle incorporation in dental sealers could be a potential strategy for dental periapical tissue regeneration. [ABSTRACT FROM AUTHOR]

Background/Aims Alcoholic liver disease (ALD) encompasses a spectrum of hepatic injury, ranging from simple steatosis to cirrhosis. Limited literature suggests that pro-inflammatory conditions and hepatic angiogenesis influence the pathophysiology of ALD. This study aimed to explore the usefulness of plasma inflammatory and angiogenic biomarkers for noninvasive evaluation of susceptibility to ALD and progression to severity. Methods Blood samples were collected from clinically proven ALD cases (n=150: chronic liver disease [CLD], 110; cirrhosis, 40), alcoholic without liver disease (AWLD; n=93) and healthy controls (HC; n=274). Key inflammatory markers tumor necrosis factor (TNF)-α and NF-kBp65 and their target iNOS along with eNOS and COX-2 was studied at mRNA level by real-time PCR. Serum TNF-α, NF-kBp65, VEGF and PDGF-BB concentrations were analyzed using enzyme-linked immunosorbent assay. Results Serum TNF-α was increased in alcoholic-CLD (21.85±2.907 pg/mL) and cirrhosis (22.65±4.646 pg/mL) cases compared to HC (20.462±4.719 pg/mL) and AWLD (19.725±5.738 pg/mL; p=not significant). NFkBp65 was significantly increased in CLD compared to HC (p=0.034) and AWLD (p=0.048); and positively significantly correlated with higher fibroscan based liver stiffness measurement (LSM) score, SGOT levels and serum TNF-α expression. Vascular endothelial growth factor (VEGF) levels were significantly higher in CLD cases compared to HC (p=0.043) and AWLD (p=0.049) subjects showing the association with disease severity. iNOS mRNA expression fold change was higher in CLD (6.132±4.132 folds) and cirrhosis (1.272±0.937 folds) cases compared to HC, whereas it was comparable in AWLD (1.08±0.319 folds) subjects. COX-2 mRNA expression was also increased in CLD (2.431±1.395 folds) compared to AWLD subjects. The higher iNOS mRNA expression in ALD cases correlated significantly with increased TNF-α and NF-kBp65 expression. VEGF expression in turn correlated significantly with TNF-α levels in ALD cases, and LSM score. Conclusions The present data underlines the specificity and importance of the state of oxidative stress mediated by chronic alcohol and resulting in inflammatory and angiogenic conditions relating to the pathogenesis of ALD, especially CLD conditions; and therefore the above panel of markers holds prognostic significance as well as therapeutic potentials. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that myeloid cells are critical in cancer development and therapy resistance processes. Pharmacological targeting of tumor-associated myeloid cells is an emerging approach among upcoming immune therapies. Surprisingly, myeloid cells are heterogeneous, including a subset of the myeloid cell displaying angiogenic properties in solid tumors. There is an urgent need to delineate angiogenic myeloid cell populations in order to facilitate specific targeting of protumor myeloid cells among heterogeneous pool. This review article is intended to compile all the relevant information in the literature for improved understanding of angiogenic myeloid cells and their role in tumor refractoriness to cancer therapy. [ABSTRACT FROM AUTHOR]