Several studies have demonstrated that hematopoietic cells originate from endothelium in early development; however, the phenotypic progression of progenitor cells during human embryonic hemogenesis ...is not well described. Here, we define the developmental hierarchy among intermediate populations of hematopoietic progenitor cells (HPCs) derived from human embryonic stem cells (hESCs). We genetically modified hESCs to specifically demarcate acquisition of vascular (VE-cadherin) and hematopoietic (CD41a) cell fate and used this dual-reporting transgenic hESC line to observe endothelial to hematopoietic transition by real-time confocal microscopy. Live imaging and clonal analyses revealed a temporal bias in commitment of HPCs that recapitulates discrete waves of lineage differentiation noted during mammalian hemogenesis. Specifically, HPCs isolated at later time points showed reduced capacity to form erythroid/megakaryocytic cells and exhibited a tendency toward myeloid fate that was enabled by expression of the Notch ligand Dll4 on hESC-derived vascular feeder cells. These data provide a framework for defining HPC lineage potential, elucidate a molecular contribu-tion from the vascular niche in promoting hematopoietic lineage progression, and distinguish unique subpopulations of hemogenic endothelium during hESC differentiation.
•Live imaging of endothelial to hematopoietic conversion identifies distinct subpopulations of hESC-derived hemogenic endothelium.•Expression of the Notch ligand DII4 on vascular ECs drives induction of myeloid fate from hESC-derived hematopoietic progenitors.
Abstract
The Covid-19 pandemic poses a threat of forest destruction, especially forest fires, along with the increase of intensity of humans entering and exploring the forest. It is suspected that ...many people who live in urban areas have lost their jobs due to layoffs and moved to villages, and then opened new lands because their supporting facilities were no longer relevant to the current conditions, the COVID-19 pandemic. These people who abruptly start their activities in the forest and do not understand the rules of preventing forest fires are making the forests vulnerable to fires. The purpose of this study was to determine the effect of the COVID-19 pandemic on the dangers of forest and land fires in South Sulawesi. It used a descriptive method, and data was collected through in-depth interviews with communities that are affected by the COVID-19 pandemic and live around the fire-prone forest areas. The results of the observation were processed by descriptive analysis to get the conclusion. The results showed that about 72% of the affected people are carried out activities in forest areas which 78% of them did not understand the rules of forest and land fire hazards. The results of this study will be recommended to the government, particularly to the policymakers in controlling forest and land fires, especially during the Covid-19 pandemic.
The status of a Special Allotment Forest Area (KHDTK) was obtained by the Forestry Education and Training Center of the Makassar Environmental and Forestry Education and Training Center in accordance ...with the Decree of the Minister of Forestry No. 041/Kpts/DJ/I/1980 on February 28, 1980 and the zoning by the Minister of Forestry No. SK.13 / Menhut-II / 2010 on January 14, 2010. The main function is to support the educational activities. Several forms of activities and utilization have been carried out in this area, including Research and Development, Nature Tourism, Environmental Services and non-timber forest products (NTFPs). Related to its main function as a means of supporting education, all the training activities, especially aspects of skills, are directed at KHDTK.Since established, KHDTK has numerous conflicts with the community. However, all existing conflicts have been acted on and a number of solutions have been made to resolve the existing problems. Regional stakeholders have managed the risks with a variety of activities, such as community empowerment, fostering the farmer groups, provision of assistance and facilitation as well as pre-emptive, preventive and repressive activities that are carried out routinely in the hope of aware the people, so that the KHDTK will receive recognition from the surrounding community.
Epithelial ovarian carcinoma is characterized by high frequency of recurrence (70% of patients) and carboplatin resistance acquisition. Carcinoma-associated mesenchymal stem cells (CA-MSC) have been ...shown to induce ovarian cancer chemoresistance through trogocytosis. Here we examined CA-MSC properties to protect ovarian cancer cells from carboplatin-induced apoptosis. Apoptosis was determined by Propidium Iodide and Annexin-V-FITC labelling and poly-ADP-ribose polymerase cleavage analysis. We showed a significant increase of inhibitory concentration 50 and a 30% decrease of carboplatin-induced apoptosis in ovarian cancer cells incubated in the presence of CA-MSC-conditioned medium (CM). A molecular analysis of apoptosis signalling pathway in response to carboplatin revealed that the presence of CA-MSC CM induced a 30% decrease of effector caspases-3 and -7 activation and proteolysis activity. CA-MSC secretions promoted Akt and X-linked inhibitor of apoptosis protein (XIAP; caspase inhibitor from inhibitor of apoptosis protein (IAP) family) phosphorylation. XIAP depletion by siRNA strategy permitted to restore apoptosis in ovarian cancer cells stimulated by CA-MSC CM. The factors secreted by CA-MSC are able to confer chemoresistance to carboplatin in ovarian cancer cells through the inhibition of effector caspases activation and apoptosis blockade. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway and the phosphorylation of its downstream target XIAP underlined the implication of this signalling pathway in ovarian cancer chemoresistance. This study reveals the potentialities of targeting XIAP in ovarian cancer therapy.
Large-scale, genomic studies of specific tumors such as The Cancer Genome Atlas have provided a better understanding of the alterations of pathways involved in the development of solid tumors ...including glioblastoma, breast cancer, ovarian and endometrial cancers, colon cancer and lung squamous cell carcinoma. This tremendous effort of the scientific community has confirmed the view that cancer actually represents a wide variety of diseases originating from different organs. These studies showed that TP53 and PI3KCA are the two most mutated genes in all types of cancers and that 30-70% of all solid tumors harbor potentially 'actionable' mutations that can be exploited for patient stratification or treatment optimization. Translation of this huge oncogenomic data set to clinical application in personalized medicine programs is now the main challenge for the future. The gap between our basic knowledge and clinical application is still wide. Closing the gap will require translational personalized trials, which may initiate a radical change in our routine clinical practice in oncology.
Mesenchymal stem cells (MSCs) are the most promising seed cells for cell therapy and can be isolated from various sources of human adult tissues such as bone marrow (BM-MSC) and adipose tissue. ...However, cells from these tissues must be obtained through invasive procedures. We, therefore, characterized MSCs isolated from fresh placenta (Pl-MSC) and fetal membrane (Mb-MSC) through morphological and fluorescent-activated cell sorting (FACS). MSC frequency is higher in membrane than placenta (2.14% ± 0.65 versus 15.67% ± 0.29%). Pl/Mb-MSCs in vitro expansion potential was significantly higher than BM-MSCs. We demonstrated that one of the MSC-specific marker is sufficient for MSC isolation and that culture in specific media is the optimal way for selecting very homogenous MSC population. These MSCs could be differentiated into mesodermal cells expressing cell markers and cytologic staining consistent with mature osteoblasts and adipocytes. Transcriptomic analysis and cytokine arrays demonstrated broad similarity between placenta- and membrane-derived MSCs and only discrete differences with BM-MSCs with enrichment of networks involved in bone differentiation. Pl/Mb-MSCs displayed higher osteogenic differentiation potential than BM-MSC when their response to osteoactivin was evaluated. Fetal-tissue-derived mesenchymal cells may, therefore, be considered as a major source of MSCs to reach clinical scale banking in particular for bone regeneration.
Uterine transplantation: Review in human research Favre-Inhofer, A.; Rafii, A.; Carbonnel, M. ...
Journal of gynecology obstetrics and human reproduction,
06/2018, Letnik:
47, Številka:
6
Journal Article
Recenzirano
Uterine transplantation is the solution to treat absolute uterine fertility. In this review, we present the historical, medical, technical, psychological and ethical perspectives in human uterine ...transplantation research. We reviewed the PubMed database following PRISMA guidelines and added data presented by several research teams during the first international congress on uterine transplantation.
Angiogenesis is thought to be involved in the development of acute leukemia (AL). We investigated whether bone marrow stromal cells (BMSCs) derived from stem cells might be responsible for the ...increase in microvascular density (MVD), and compared 13 bone marrow samples from AL patients with 23 samples from patients in complete remission (controls). We demonstrated that AL-derived BMSC secreted more insulin growth factor-1 (IGF-1) and SDF-1alpha than controls. In addition, in contrast to normal adherent BMSCs, adherent BMSCs derived from CD133+/CD34+ stem cells from AL patients were able to form capillary-like structures ('vasculogenic mimicry') on Matrigel. The increase in vasculogenic mimicry occurred through PI3 kinase and rho GTPase pathway as inhibitors of these signaling pathways (wortmannin and GGTI-298, respectively) were able to reduce or prevent capillary tube formation. In normal BMSC, addition of exogenous IGF-1 generated capillary-like tubes through the same pathway as observed spontaneously in AL-derived BMSC. The involvement of IGF-1 in the mimicry process was confirmed by the addition of a neutralizing antibody against IGF-1R or a IGF-1R pathway inhibitor (picropodophyllin). In conclusion, AL-derived BMSC present functional abnormalities that may explain the increase in MVD in the bone marrow of AL patients.
Recent advances in computer-modeling software allow reconstruction of facial symmetry in a virtual environment. This study evaluates the use of preoperative computer modeling and intraoperative ...navigation to guide reconstruction of the maxillofacial skeleton.
Three patients with traumatic maxillofacial deformities received preoperative, thin-cut axial CT scans. Three-dimensional reconstructions, virtual osteotomies, and bony reductions were performed using MIMICS planning software (Materialise, Ann Arbor, MI). The original and "repaired" virtual datasets were then imported into an intraoperative navigation system and used to guide the surgical repair.
Postoperative CT scans and photographs reveal excellent correction of enophthalmos to within 1 mm in patient 1, significant improvement in symmetry of the nasoethmoid complex in patient 2, and reconstruction of the zygomaticomaxillary complex location to within 1 mm in patient 3.
Computer modeling and intraoperative navigation is a relatively new tool that can assist surgeons with reconstruction of the maxillofacial skeleton.