scholarly journals Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma

Author(s):  
Tian Yuan ◽  
Rui Zheng ◽  
Xiang-min Zhou ◽  
Peng Jin ◽  
Zhi-qun Huang ◽  
...  

BackgroundNasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them.MethodsWe compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP’s role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP’s role in differentiation in an in vitro air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP.ResultsThe expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlated with proliferation and neutrophil infiltration in NIP. YAP expression was also significantly increased in NIP patients with adverse outcomes.ConclusionAbnormal expression of YAP/active YAP is associated with proliferation, differentiation, neutrophil infiltration, and adverse outcome in NIP and may present a novel target for diagnosis and intervention in NIP.

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Lihua Yin ◽  
Wenxiao Cheng ◽  
Zishun Qin ◽  
Hongdou Yu ◽  
Zhanhai Yu ◽  
...  

This study is to explore the osteogenesis potential of the human periodontal ligament stem cells (hPDLSCs) induced by naringin in vitro and in vitro. The results confirmed that 1 μM naringin performs the best effect and a collection of bone-related genes (RUNX2,COL1A2, OPN, and OCN) had significantly higher expression levels compared to the control group. Furthermore, a typical trabecular structure was observed in vivo, surrounded by a large amount of osteoblasts. These results demonstrated that naringin, at a concentration of 1 μM, can efficiently promote the proliferation and differentiation of hPDLSCs both in vitro and in vivo.


2020 ◽  
Vol 12 (4) ◽  
pp. 455-460
Author(s):  
Yuan Wu ◽  
Cuizhong Liu ◽  
Ming Gao ◽  
Qiang Liang ◽  
Yu Jiang

This study aimed to observe the effect of titanium nanomaterials on osteoblastsin vitro. Osteoblasts were identified using histochemical staining, and they were examined using an MTT (3-(4,5Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay to determine the proliferation and differentiation of osteoblasts. In addition, we observed the effect of titanium nanomaterials on the function of osteoblasts. Compared with the control group, titanium nanomaterials promoted the growth, proliferation, and differentiation of osteoblasts. Our findings showed that titanium nanomaterials can significantly promote the proliferation of osteoblasts and enhance their osteogenic activity.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Qiaoqiao Kong ◽  
Jing Li ◽  
Li Zhao ◽  
Peng Shi ◽  
Xiaobei Liu ◽  
...  

Abstract Background Human cytomegalovirus (HCMV) infection in utero is very common during pregnancy, which can lead to adverse outcomes in both pregnancy and progeny, but its pathogenesis has not been fully clarified. The decrease of extravillous cytotrophoblasts (EVT) invasion is an essential pathophysiological process of some pregnancy complications. Hippo-YAP signaling pathway plays an important role in regulating cell proliferation and apoptosis. However, whether YAP is involved in HCMV uterine infection remains to be studied. Methods The primary EVT was cultured and infected by the HCMV strain AD169 virus in vitro. Immunofluorescence staining of HCMVpp65 antigen was conducted afterward to confirm the establishment of an infection model. The optimal virus infection dose was determined by the EVT proliferation status in vitro. Real-time PCR was performed to examine the mRNA level of major genes involved in the Hippo pathway in EVT after HCMV infection. The effect of HCMV on the expression of YAP protein in EVT was evaluated by Immunofluorescence staining and Western blot. An in vitro cell invasion assay was carried out to analyze the influence of HCMV on EVT invasion. The changes of EVT invasion was accessed by establishing YAP silencing and over-expression models using YAP1 specific siRNA and plasmid pcDH. Results The optimal HCMV infection dose was 282.5TCID50/ml. Compared to the control group, the infection of HCMV significantly reduced the mRNA expression of Mst1, Mst2, SAV, Lats1, Lats2, Mob1, YAP1, TAZ, TEAD1-4 genes and YAP protein expression in the Hippo-YAP pathway. HCMV infection also decreased the EVT invasion. In non-infected EVT, the number of transmembrane EVT cells was significantly reduced when YAP1 gene was silenced, while it was significantly increased when YAP1 gene was over-expressed. In the HCMV-infected EVT, the number of transmembrane EVT cells significantly increased when over-expressed and eventually recovered to the level of NC. Conclusions HCMV may decrease EVT invasion by inhibiting the expression of mRNA and protein of YAP in the Hippo-YAP signaling pathway. HCMV eventually reduces the invasion ability of EVT by inhibiting multiple genes in the Hippo-YAP signaling pathway, especially inhibiting YAP which serves as the downstream effector.


Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1507
Author(s):  
Min-Kyu Lee ◽  
Hyun Lee ◽  
Hyoun-Ee Kim ◽  
Eun-Jung Lee ◽  
Tae-Sik Jang ◽  
...  

Nano-scale surface roughening of metallic bio-implants plays an important role in the clinical success of hard tissue reconstruction and replacement. In this study, the nano-topographical features of titanium-niobium-zirconium (TNZ) alloy surfaces were controlled by using the target-ion induced plasma sputtering (TIPS) technique to improve the in vitro osteoblastic response. The TIPS technique is a novel strategy for etching the surface of metallic bio-implants using bombardment of target metal cations, which were accelerated by an extremely high negative bias voltage applied to the substrates. The nano-topography of the TNZ surfaces was successfully controlled by modulating experimental variables (such as the ion etching energy and the type of substrate or target materials) of TIPS. As a result, various nanopatterns (size: 10–210 nm) were fabricated on the surface of the TNZ alloys. Compared with the control group, experimental groups with nanopattern widths of ≥130 nm (130 and 210 nm groups) exhibited superior cell adhesion, proliferation, and differentiation. Our findings demonstrate that TIPS is a promising technology that can impart excellent biological functions to the surface of metallic bio-implants.


2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Zi-cong Wu ◽  
Qiang Xue ◽  
Zhen-ling Zhao ◽  
Peng-jun Zhou ◽  
Qun Zhou ◽  
...  

Background. Huzhentongfeng (HZTF) is an extract from four Chinese medical herbs for treating gout. This study aims to evaluate its antigout activity and preliminary explore its mechanism in vivo and in vitro. Methods. The rats were intragastrically administered with HZTF for 5 days and then injected 0.1 ml (10 mg) of MSU crystals to their joints for generating a gout model to analyze the paw volume and histopathology of joint synovial tissues of rats with different doses. We also investigated the antioxidant capacity of HZTF in vitro using indication including lipid peroxidation, DPPH·, and ABTS+ radical-scavenging capacity; besides, we used qRT-PCR to measure the effect of HZTF on interleukin (IL)-1β, caspase-1, NLRP3, and NQO1 expression in hydrogen peroxide-stimulated RAW264.7 macrophages and IL-1β, IL-6, and tumor necrosis factor (TNF)-α in MSU crystal-induced THP-1 monocytes. Confocal microscopy analysis was used to observe the dimerization of ASC adapter proteins. In addition, we also established quality standard of HZTF by using the high-performance liquid chromatography (HPLC) method. Results. HZTF could significantly suppress the paw swelling and neutrophil infiltration induced by MSU intra-articular injection in rats compared with the control group. HZTF also showed inhibition effects of inflammatory cytokines (IL-1β, IL-6, and TNF-α) secretion at 25.00 and 50.00 μg/ml in MSU-induced THP-1 cells but showed no effects of IL-1β, IL-6, and TNF-α mRNA expression in MSU-induced THP-1 cells. Furthermore, confocal microscopy analysis showed that HZTF could prevent the oligomerization of ASC. Moreover, HZTF also showed effects in cell-free and cell-base tests of antioxidant capacity. Conclusion. The results prove that HZTF possessed the potential preventive effect against gout arthritis, and the effect may be attributed to its preventing effect on neutrophil infiltration and proinflammatory cytokines secretion such as IL-1β, IL-6, and TNF-α which were caused by the activation of inflammasome.


2019 ◽  
Vol 7 (7_suppl5) ◽  
pp. 2325967119S0038
Author(s):  
Robert W. Lindeman ◽  
Brandon S. Lanier ◽  
Douglas E. Parsell ◽  
James R. Ramsey

Objectives: The success rate and the return to sport after midshaft clavicle fracture has been shown to improve with open reduction internal fixation (ORIF) treatment versus non-operative management. The period of time for return to sport, post-ORIF, has been reported in the literature with considerable range. Return to sport times for NFL athletes are reported to typically require three to seven months, while professional cyclists have resumed training in only one week. As the percentage of clavicle fractures in athletes is likely dominated by the high school and college populations, it is clinically relevant to evaluate the success of specific return to sport protocols after clavicle ORIF with respect to age. To evaluate this aspect of care, a retrospective study utilizing an adolescent/immediate post-adolescent and an adult control patient was performed. Methods: A single surgeon performed locking plate ORIF of clavicle fractures with patient population of athletes, ages 13 to 22 years old (mean 16.7 yrs.), and an adult control group (mean 50.8 yrs.). A uniform period for return to sport of two months was utilized for the athlete group, unless complications were present. The athlete group contained 90 patients, and the adult control group contained 64 patients. The athlete group had 48% of fractures resulting from football. High energy mechanisms (auto accident, ATV accident, etc.) accounted for 23.3% of the athlete group fractures, while these mechanisms accounted for 46.9% of the adult group fractures. Post-operative complications and adverse outcomes were monitored for a minimum period of one year. Results: Clavicle fractures within both patient groups were dominantly midshaft fractures with 97.7% of the athlete fractures and 88.5% of the adult fractures being located midshaft. The athlete group exhibited minimal post-operative complication/adverse outcomes with one patient reporting pain with weightlifting and two patients requiring minor scar revisions, for a total complication/adverse outcome rate of 3.3%. The adult group included ten patients with significant residual pain and one patient requiring revision for non-union, yielding a total complication/adverse outcome rate of 15.6% in this group. Applying a Chi-square analysis, a statistically significant difference in complication/adverse outcome rates exist between the patient groups (p=0.003). Additionally, all patients in the athlete group, desiring to return to their sport, did so within the two-month post-operative period. Conclusion: Locking plate ORIF of midshaft clavicle fractures allowed for a successful two month return to sport, with a low occurrence of complications, for a young athlete patient group. High energy fracture events and an adult aged patient group were associated with higher rates of adverse clinical outcome.


Author(s):  
Dwikora Novembri Utomo ◽  
I Gde Adi Widiastana

The addition of platelet rich plasma to mesenchymal stem cell culture on growth  media and  chondrogenic  media  had  any effect  on stem cell’s proliferation and differentiation into chondroblast has not been determined. This research is to find  out  the  effect  of  platelet  rich  plasma  on  mesenchymal  stem  cell’s differentiation and proliferation into chondroblast on in vitro media. Randomized control group posttest only design. Blood was taken from the rabbit’s vein to be processed into platelet rich plasma (PRP). Mesenchymal Stem Cell (MSC) was harvested from the bone marrow of the rabbit to be cultured. The MSC’s culture were divided into three groups of modification. The first group was combination of MSC added with Complete Culture Medium (CCM) and Chondrogenic Diferentation Medium (CDM) without PRP as control group. The second group had the same combination as the first group with extra 5% PRP. The third group had the same combination as the first group with extra 10% PRP. The results were evaluated in the following 21 days. The group that received extra 5% PRP had significant increase of chondroblast count compared to the group without PRP addition (p=0,033). The same result also occured on the groups that received extra 10% PRP compared to the group without PRP addition (p=0,028). There were no significant diferences between both the second and the third groupchondroblast count (p=0,203). There was a significant effect of platelet rich plasma on mesenchymal stem cell’s diferentiation and proliferation into chondroblast on invitro media.


2010 ◽  
Vol 119 (11) ◽  
pp. 796-804 ◽  
Author(s):  
Wataru Okano ◽  
Yukio Nomoto ◽  
Ikuo Wada ◽  
Ken Kobayashi ◽  
Masao Miyake ◽  
...  

Objectives: Although our group has had mostly successful results with clinical application of a tracheal prosthesis, delayed epithelial regeneration remains a problem. In our previous studies using rats, it was demonstrated that tracheal fibroblasts accelerated proliferation and differentiation of the tracheal epithelium in vitro and in vivo. The purpose of this study was to evaluate the effects of fibroblasts on epithelial regeneration in larger tracheal defects in rabbits. Methods: We developed a bioengineered scaffold, the luminal surface of which was coated with fibroblasts. This scaffold was implanted into tracheal defects in 12 rabbits (bioengineered group), and scaffolds without fibroblasts were implanted in 12 rabbits (control group). The regenerated epithelium was histologically examined by light microscopy, scanning electron microscopy, and immunohistochemical studies. Results: In the bioengineered group, a stratified squamous epithelium was observed on the surface 7 days after transplantation. However, in the control group, the scaffolds were exposed. Fourteen days after implantation, a columnar ciliated epithelium was observed in the bioengineered group. The average thickness of the regenerated epithelium in the bioengineered group was significantly greater than that in the control group. Conclusions: This study indicated that fibroblasts had a stimulatory effect that hastened regeneration of the epithelium in large tracheal defects.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mounika Gayathri Tirumala ◽  
Pratibha Anchi ◽  
Susmitha Raja ◽  
Mahesh Rachamalla ◽  
Chandraiah Godugu

Nanotoxicology is an emerging field employed in the assessment of unintentional hazardous effects produced by nanoparticles (NPs) impacting human health and the environment. The nanotoxicity affects the range between induction of cellular stress and cytotoxicity. The reasons so far reported for these toxicological effects are due to their variable sizes with high surface areas, shape, charge, and physicochemical properties, which upon interaction with the biological components may influence their functioning and result in adverse outcomes (AO). Thus, understanding the risk produced by these materials now is an important safety concern for the development of nanotechnology and nanomedicine. Since the time nanotoxicology has evolved, the methods employed have been majorly relied on in vitro cell-based evaluations, while these simple methods may not predict the complexity involved in preclinical and clinical conditions concerning pharmacokinetics, organ toxicity, and toxicities evidenced through multiple cellular levels. The safety profiles of nanoscale nanomaterials and nanoformulations in the delivery of drugs and therapeutic applications are of considerable concern. In addition, the safety assessment for new nanomedicine formulas lacks regulatory standards. Though the in vivo studies are greatly needed, the end parameters used for risk assessment are not predicting the possible toxic effects produced by various nanoformulations. On the other side, due to increased restrictions on animal usage and demand for the need for high-throughput assays, there is a need for developing and exploring novel methods to evaluate NPs safety concerns. The progress made in molecular biology and the availability of several modern techniques may offer novel and innovative methods to evaluate the toxicological behavior of different NPs by using single cells, cell population, and whole organisms. This review highlights the recent novel methods developed for the evaluation of the safety impacts of NPs and attempts to solve the problems that come with risk assessment. The relevance of investigating adverse outcome pathways (AOPs) in nanotoxicology has been stressed in particular.


2021 ◽  
Author(s):  
Hamed Karkehabadi ◽  
Erfan Ahmadyani ◽  
Rezvan Najafi ◽  
Elham Khoshbin

Abstract Background: This study assessed the effect of Biodentine coated with Emdogain (Biodentine/Emdogain) on proliferation and differentiation of stem cells from the apical papilla (SCAP). Methods and Results: In this in vitro, experimental study, SCAP were isolated from two immature impacted third molars and cultured. After ensuring the stemness of the cells by assessing their cell surface markers, they were exposed to Biodentine, Emdogain, and Biodentine/Emdogain for 24 and 72 hours. The control cells did not receive any intervention. Cell viability was evaluated by the methyl thiazolyl tetrazolium (MTT) assay. Expression of odontogenic differentiation genes was analyzed by the quantitative reverse transcription polymerase chain reaction (qRT-PCR). Alkaline phosphatase (ALP) activity was quantified by the respective kit. Data were analyzed by one-way ANOVA, t-test, and Mann-Whitney test (α=0.05). Cell viability did not change after 24 hours of exposure to biomaterials. At 72 hours, the viability of the cells exposed to Biodentine and Biodentine/Emdogain decreased compared with the control group. The expression of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), and bone sialoprotein (BSP) genes, and ALP activity significantly increased in all three experimental groups, compared with the control group at both 24 and 72 hours; this increase was significantly greater in Biodentine/Emdogain group. The number of mineralized nodules significantly increased in all groups after 72 hours with a greater rate in Biodentine/Emdogain group.Conclusions: All biomaterials increased the differentiation of SCAP, expression of odontogenic genes, and ALP activity, but Biodentine/Emdogain was significantly more effective for this purpose.


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