Growth Factor
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2021 ◽  
Siqi Long ◽  
Lina Ren ◽  
Xiaoning Liu ◽  
Jiamin Shi ◽  
Jiaxin Liu ◽  

Abstract Background With the development of tissue engineering and regenerative medicine, engineered tissue constructs have become more prevalent and are now used as substitutions of patients’ damaged organs or tissues. To date, a scaffold-free cell transplantation technique based on cell sheets have been widely used in clinic. While poor vascularization and adverse immune reactions to biomedical devices remain crucial challenges in tissue engineering. The inflammatory response represents one of mainly and important regulators of vascularization and engineered tissue function restoration. This study investigated the effect of macrophage secretion on the formation of microvascular-like structures of human umbilical vein endothelial cells (HUVECs) in the bone marrow mesenchymal stem cell (BMSC) sheets. Methods Researchers differentiated the human monocytic leukemia cell line (THP-1) cells into the resting state of macrophage (M0) by phorbol 12-myristate 13-acetate (PMA) and further activated them into pro-inflammation and pro-healing states with the use of various cytokines. Condition media derived from kinds of macrophages were used to investigate the impact of macrophage on the viability and arrangement of HUVECs on BMSC sheets. Cytokines related to angiogenesis were detected in the culture supernatant of HUVECs, BMSC sheets, and pre-vascularized sheets. Results Results indicated that macrophages may guide the arrangement of endothelial cell through the paracrine pathway. The cell sheets that were cultured in the microenvironment with pro-inflammatory macrophages had fewer cell layers compared to those generated in other media. Furthermore, after experiencing high levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α) in the first 3 days while high level of platelet-derived growth factor (PDGF)-BB but low TNF-α and VEGF concentration in the next 4 days, pre-vascularized sheets had the most significant micro-vessel network. Conclusions The fates of pre-vascularized sheets regulated by macrophages secreted factors in microenvironment and sequential released cytokines could even promote neovascularization and angiogenesis.

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Liang Wang ◽  
Shuangbo Fan ◽  
Zhenping Zhao ◽  
Qian Xu

In recent years, the incidence of craniocerebral trauma has increased, making it one of the important causes of death and disability in neurosurgery patients. The decompressive craniectomy (DC) after severe craniocerebral injury has become the preferred treatment for patients with severe craniocerebral injury, but the incidence of postoperative hydrocephalus has become a difficult problem in clinical treatment. This study observed the changes of nerve growth factor (NGF), adrenocorticotropic hormone (ACTH), and arginine vasopressin (AVP) levels in the CSF after DC in patients with craniocerebral injury and analyzed the relationship between the three indicators and communicating hydrocephalus. The results showed that the levels of NGF, ACTH, and AVP in patients with cranial injury after DC were significantly higher than those in healthy subjects, and subdural effusion, traumatic subarachnoid hemorrhage (tSAH), and the levels of NGF, ACTH, and AVP in the CSF were independent risk factors for communicating hydrocephalus. Monitoring the levels of NGF, ACTH, and AVP is of great significance for clinicians to judge the occurrence of traffic hydrocephalus, evaluate the prognosis of patients with craniocerebral injury after DC, and guide clinical treatment.

mBio ◽  
2021 ◽  
Vol 12 (5) ◽  
Jing Liu ◽  
Adam Vanarsdall ◽  
Dong-Hua Chen ◽  
Andrea Chin ◽  
David Johnson ◽  

HCMV is a herpesvirus that infects a large percentage of the adult population and causes significant levels of disease in immunocompromised individuals and birth defects in the developing fetus. The virus encodes a complex protein machinery that coordinates infection of different cell types in the body, including a trimer formed of gH, gL, and gO subunits.

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258872
Joshua Kramer ◽  
Joana Neves ◽  
Mia Koniikusic ◽  
Heinrich Jasper ◽  
Deepak A. Lamba

Retinal homeostasis relies on intricate coordination of cell death and survival in response to stress and damage. Signaling mechanisms that coordinate this process in the adult retina remain poorly understood. Here we identify Decapentaplegic (Dpp) signaling in Drosophila and its mammalian homologue Transforming Growth Factor-beta (TGFβ) superfamily, that includes TGFβ and Bone Morphogenetic Protein (BMP) signaling arms, as central mediators of retinal neuronal death and tissue survival following acute damage. Using a Drosophila model for UV-induced retinal damage, we show that Dpp released from immune cells promotes tissue loss after UV-induced retinal damage. Interestingly, we find a dynamic response of retinal cells to this signal: in an early phase, Dpp-mediated stimulation of Saxophone/Smox signaling promotes apoptosis, while at a later stage, stimulation of the Thickveins/Mad axis promotes tissue repair and survival. This dual role is conserved in the mammalian retina through the TGFβ/BMP signaling, as supplementation of BMP4 or inhibition of TGFβ using small molecules promotes retinal cell survival, while inhibition of BMP negatively affects cell survival after light-induced photoreceptor damage and NMDA induced inner retinal neuronal damage. Our data identify key evolutionarily conserved mechanisms by which retinal homeostasis is maintained.

Amna Al-Araimi ◽  
Ishraq A. Al Kindi ◽  
Asma Bani Oraba ◽  
Amira AlKharusi ◽  
Badreldin H. Ali ◽  

Norikazu Masuda ◽  
Nobuyoshi Kosaka ◽  
Hiroji Iwata ◽  
Masakazu Toi

AbstractBreast cancer is the most common type of cancer among women worldwide and in Japan. The majority of breast cancers are hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2‒), and endocrine therapy is an effective therapy for this type of breast cancer. However, recent substantial advances have been made in the management of HR+/HER2‒ advanced breast cancer (ABC) with the advent of targeted therapies, such as cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, resulting in significant improvements in survival outcomes versus endocrine therapy alone. To evaluate the optimal use of palbociclib, a CDK4/6 inhibitor, in HR+/HER2– ABC, this review summarizes clinical trial and real-world data for palbociclib. In addition, current biomarker studies in palbociclib clinical research are reviewed. In Japanese patients, palbociclib was shown to be effective with a manageable safety profile, although differences were observed in the frequency of adverse event and dosing parameters. Current evidence supporting palbociclib as a first-line treatment strategy for patients with HR+/HER2‒ ABC in Asia, and specifically japan, is also discussed.

Sabrina da Conceição Pereira ◽  
Bérengère Benoit ◽  
Francisco Carlos Amanajás Aguiar Junior ◽  
Stéphanie Chanon ◽  
Aurélie Vieille‐Marchiset ◽  

2021 ◽  
Mansoureh Hashemi ◽  
Aida abbasiazam ◽  
Saeed Oraee-Yazdani ◽  
Janice Lenzer

Abstract Glioblastoma multiforme (GBM) also categorized as a grade IV astrocytoma, is an aggressive brain tumor which invades the surrounding brain tissue. Hyperthermia is known to be effective for chemo-radiotherapy to sensitize cancer cells to radiation as a treatment option for patients with GBM. The current study was performed in order to assess and compare the properties of the astrocyte and cancer stem cells isolated from glioblastoma exposed to hyperthermia. Astrocytes and cancer stem cells were isolated from human glioblastoma tissue. Glioblastoma tissues were digested and cultured in culture medium supplemented with B27, basic fibroblast growth factor and epidermal growth factor. The morphology and specific markers were evaluated in astrocyte and cancer stem cell of human glioblastoma through immunocytochemistry and quantitative real-time RT-PCR. The multipotentiality of cancer stem cells was presented using differentiation potential into neurons, oligodendrocytes, and astrocytes. For hyperthermia, cells were exposed to temperatures at 42‑46˚C for 1h using a water bath. Cell survival rate by MTT assay and apoptosis using quantitative real-time RT-PCR and western blot were evaluated. Results demonstrated that there were two morphology types in cell culture including epithelioid morphology and fibroblastic morphology. Astrocytes were confirmed via expression of the Glial fibrillary acidic protein (GFAP) protein; whereas, cancer stem cells (CSCs) were round and floating in the culture medium. Immunocytochemical staining indicated that nestin, CD133 and SRY-box 2 (SOX2) antigens were positively expressed in primary neurospheres. Results indicated that cancer stem cells of glioblastoma are multipotent and are able to differentiate into neurons, oligodendrocytes, and astrocytes. The current study obtained evidence via apoptosis evaluation that CSCs are resistant to hyperthermia when compared to astrocytes isolated from glioblastoma. Furthermore, hyperthermia was demonstrated to decrease cell resistance, which may be effective for chemo-radiotherapy to sensitize cancer cells to radiation. Taken together, CSCs of glioblastoma could be used as a powerful tool for evaluating the tumorigenesis process in the brain and developing novel therapies for treatment of GBM.

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