scholarly journals Silicon nitride with titania, calcia and silica additives for orthopaedic applications

2020 ◽  
Vol 14 (1) ◽  
pp. 63-70
Author(s):  
Cecilia Guedes-Silva ◽  
Andrea Rodas ◽  
Flávio Carvalho ◽  
Olga Higa ◽  
Thiago Ferreira
Keyword(s):  
Fracture Toughness ◽  
Cell Proliferation ◽  
Silicon Nitride ◽  
Relative Density ◽  
Biological Behaviour ◽  
Promote Cell Proliferation ◽  
Positive Effects ◽  
Good Ability

Titanium, silicon and calcium ions have demonstrated positive effects in bone healing. Therefore, this paper investigates the densification, mechanical properties and in vitro biological behaviour of TiO2, together with SiO2 and CaO, on silicon nitride ceramics to be used in clinical applications. The results revealed that the sintered samples reached high values of relative density and fracture toughness, non-cytotoxicity as well as good ability to promote cell proliferation and form a layer of carbonated hydroxyapatite on their surfaces, after immersion in simulated body fluid. The sample with the highest amount of TiO2 reached the highest value of relative density and the best results of cell proliferation and fracture toughness, indicating the great potential to be explored by in vivo experiments for later application as intervertebral devices.

scholarly journals HPV-18 E6 Oncoprotein and Its Spliced Isoform E6*I Regulate the Wnt/β-Catenin Cell Signaling Pathway through the TCF-4 Transcriptional Factor

2018 ◽  
Vol 19 (10) ◽  
pp. 3153 ◽  
Author(s):  
J. Muñoz-Bello ◽  
Leslie Olmedo-Nieva ◽  
Leonardo Castro-Muñoz ◽  
Joaquín Manzo-Merino ◽  
Adriana Contreras-Paredes ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Promote Cell Proliferation ◽  
E6 And E7 ◽  
Hpv 18

The Wnt/β-catenin signaling pathway regulates cell proliferation and differentiation and its aberrant activation in cervical cancer has been described. Persistent infection with high risk human papillomavirus (HR-HPV) is the most important factor for the development of this neoplasia, since E6 and E7 viral oncoproteins alter cellular processes, promoting cervical cancer development. A role of HPV-16 E6 in Wnt/β-catenin signaling has been proposed, although the participation of HPV-18 E6 has not been previously studied. The aim of this work was to investigate the participation of HPV-18 E6 and E6*I, in the regulation of the Wnt/β-catenin signaling pathway. Here, we show that E6 proteins up-regulate TCF-4 transcriptional activity and promote overexpression of Wnt target genes. In addition, it was demonstrated that E6 and E6*I bind to the TCF-4 (T cell factor 4) and β-catenin, impacting TCF-4 stabilization. We found that both E6 and E6*I proteins interact with the promoter of Sp5, in vitro and in vivo. Moreover, although differences in TCF-4 transcriptional activation were found among E6 intratype variants, no changes were observed in the levels of regulated genes. Furthermore, our data support that E6 proteins cooperate with β-catenin to promote cell proliferation.

scholarly journals Actions and Potential Therapeutic Applications of Growth Hormone–Releasing Hormone Agonists

Endocrinology ◽  
2019 ◽  
Vol 160 (7) ◽  
pp. 1600-1612 ◽  
Author(s):  
Andrew V Schally ◽  
Xianyang Zhang ◽  
Renzhi Cai ◽  
Joshua M Hare ◽  
Riccarda Granata ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cardiac Tissue ◽  
Human Cancer ◽  
Large Body ◽  
Neuroprotective Effects ◽  
Promote Cell Proliferation ◽  
Therapeutic Applications ◽  
Human Cancer Cells

Abstract In this article, we briefly review the identification of GHRH, provide an abridged overview of GHRH antagonists, and focus on studies with GHRH agonists. Potent GHRH agonists of JI and MR class were synthesized and evaluated biologically. Besides the induction of the release of pituitary GH, GHRH analogs promote cell proliferation and exert stimulatory effects on various tissues, which express GHRH receptors (GHRH-Rs). A large body of work shows that GHRH agonists, such as MR-409, improve pancreatic β-cell proliferation and metabolic functions and facilitate engraftment of islets after transplantation in rodents. Accordingly, GHRH agonists offer a new therapeutic approach to treating diabetes. Various studies demonstrate that GHRH agonists promote repair of cardiac tissue, producing improvement of ejection fraction and reduction of infarct size in rats, reduction of infarct scar in swine, and attenuation of cardiac hypertrophy in mice, suggesting clinical applications. The presence of GHRH-Rs in ocular tissues and neuroprotective effects of GHRH analogs in experimental diabetic retinopathy indicates their possible therapeutic applications for eye diseases. Other effects of GHRH agonists, include acceleration of wound healing, activation of immune cells, and action on the central nervous system. As GHRH might function as a growth factor, we examined effects of GHRH agonists on tumors. In vitro, GHRH agonists stimulate growth of human cancer cells and upregulate GHRH-Rs. However, in vivo, GHRH agonists inhibit growth of human cancers xenografted into nude mice and downregulate pituitary and tumoral GHRH-Rs. Therapeutic applications of GHRH analogs are discussed. The development of GHRH analogs should lead to their clinical use.

scholarly journals KLF5 Is Crucial for Androgen-AR Signaling to Transactivate Genes and Promote Cell Proliferation in Prostate Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 748 ◽  
Author(s):  
Juan Li ◽  
Baotong Zhang ◽  
Mingcheng Liu ◽  
Xing Fu ◽  
Xinpei Ci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Transcriptional Activity ◽  
Prostate Cancer Cells ◽  
Normal Prostate ◽  
Promote Cell Proliferation ◽  
Therapeutic Opportunity

Androgen/androgen receptor (AR) signaling drives both the normal prostate development and prostatic carcinogenesis, and patients with advanced prostate cancer often develop resistance to androgen deprivation therapy. The transcription factor Krüppel-like factor 5 (KLF5) also regulates both normal and cancerous development of the prostate. In this study, we tested whether and how KLF5 plays a role in the function of AR signaling in prostate cancer cells. We found that KLF5 is upregulated by androgen depending on AR in LNCaP and C4-2B cells. Silencing KLF5, in turn, reduced AR transcriptional activity and inhibited androgen-induced cell proliferation and tumor growth in vitro and in vivo. Mechanistically, KLF5 occupied the promoter of AR, and silencing KLF5 repressed AR transcription. In addition, KLF5 and AR physically interacted with each other to regulate the expression of multiple genes (e.g., MYC, CCND1 and PSA) to promote cell proliferation. These findings indicate that, while transcriptionally upregulated by AR signaling, KLF5 also regulates the expression and transcriptional activity of AR in androgen-sensitive prostate cancer cells. The KLF5-AR interaction could provide a therapeutic opportunity for the treatment of prostate cancer.

scholarly journals Nanofiber-mediated sequential photothermal antibacteria and macrophage polarization for healing MRSA-infected diabetic wounds

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhou Xu ◽  
Bin Deng ◽  
Xuewen Wang ◽  
Jie Yu ◽  
Zhuobin Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Macrophage Polarization ◽  
In Vivo Studies ◽  
Promote Cell Proliferation ◽  
Diabetic Wound Healing ◽  
Mrsa Infection ◽  
Diabetic Wounds

Abstract Background Diabetic wound healing remains a challenge because of its susceptibility to drug-resistant bacterial infection and its persistent proinflammatory state. Switching from proinflammatory M1 macrophages (Mφs) to proregenerative M2 dominant Mφs in a timely manner accelerates wound healing by coordinating inflammatory, proliferative, and angiogenic processes. Methods We propose a sequential photothermal antibacterial and subsequent M2 Mφ polarization strategy based on nanofibers (NFs) consisting of polydopamine (PDA) coating on curcumin (Cur) nanocrystals to treat Methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds. Results The PDA/Cur NFs showed excellent photothermal conversion and antibacterial effects due to the PDA shell under laser irradiation, consequently resulting in the release of the inner Cur with the ability to promote cell proliferation and reinforce the M2 Mφ phenotype in vitro. In vivo studies on MRSA-infected diabetic wounds showed that PDA/Cur NFs not only inhibited MRSA infection but also accelerated the wound regeneration process. Furthermore, the NFs displayed the ability to promote the M2 Mφ phenotype with enhanced collagen deposition, angiogenesis, and cell proliferation. Conclusion Overall, the NFs displayed great potential as promising therapeutics for healing infected diabetic wounds through a sequential photothermal antibacterial and M2 Mφ polarization strategy. Graphical abstract

scholarly journals CircRNA CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling

2021 ◽  
Author(s):  
Ji-Ping Hou ◽  
Xue-Bo Men ◽  
Lian-Ying Yang ◽  
En-Kun Han ◽  
Chun-Qi Han ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Cell Lines ◽  
Potential Interaction ◽  
Migration And Invasion ◽  
Promote Cell Proliferation ◽  
Pathologic Features ◽  
Vegfr2 Signaling

Abstract Objective This study was aimed at investigating the involvement of CircCCT3 in PC and study its interactions and functioning during the PC progression in vitro and in vivo by the use of molecular biology and bioinformatic methods.Methods The expressions of CircCCT3 and miR-613 in pancreatic carcinoma tissues and cell lines were evaluated by quantitative realtime PCR .The relationship between clinical pathologic features as well as survival rate and CircCCT3 expression was analyzed with Chi-square test and Kaplan–Meier method. CCK-8, wound healing , transwell assays and FITC-AnnexinV/PI assay were used to assess cell proliferation, migration, invasion and apoptosis after CircCCT3 overexpression or downregulation. Dual-Luciferase reporterassay, RNA immunoprecipitation (RIP) ,RNA pull down and fluorescence in situ hybridization(FISH) assays were performed to validate the potential interaction of CircCCT3, miR-613 and VEGFA.Nude mouse xenograft tumor assay was used to detect CircCCT3 effects on pancreatic tumorigenesis in vivo.Western blotting analysis was performed to examine the VEGFA and VEGFR2 protein expressions following.Results CircCCT3 expression was significantly increased in PC tissues and cell lines. CircCCT3 expression was negatively correlated with miR-613 expression. Moreover, it was found that CircCCT3 promote cell proliferation, migration, invasion and inhibited cell apoptosis in PC cells. CircCCT3 acted as a sponge for miR-613 to facilitate VEGFA and VEGFR2 expression. si-CirCCT3also inhibited tumor growth of PC in nude mice.si-CircCCT3 reduced VEGFA and VEGFR2 expression, whereas overexpression of CircCCT3 increased VEGFA and VEGFR2 expression.Conclusions Increased CircCCT3 suggests a poor prognosis in PC patients and promotes the migration and invasion through targeting VEGFA/VEGFR2 signaling. CircCCT3 may serve as a potential and promising therapeutic target for PC treatment.

scholarly journals Tumorigenic Poxviruses Up-Regulate Intracellular Superoxide To Inhibit Apoptosis and Promote Cell Proliferation

2005 ◽  
Vol 79 (9) ◽  
pp. 5799-5811 ◽  
Author(s):  
Melissa L. T. Teoh ◽  
Patricia V. Turner ◽  
David H. Evans
Keyword(s):  
Cell Proliferation ◽  
Clinical Manifestations ◽  
Myxoma Virus ◽  
Jurkat Cells ◽  
Copper Chaperone ◽  
Dependent Manner ◽  
Wild Type ◽  
Promote Cell Proliferation

ABSTRACT Tumorigenic leporipoxviruses encode catalytically inactive homologs of cellular Cu-Zn superoxide dismutase (SOD1). The function of the orthologous myxoma virus M131R and Shope fibroma virus S131R gene products is uncertain, but they inhibit SOD1 activity by a process linked to binding its copper chaperone. Using a superoxide-sensitive dye (hydroethidine), we observed that virus infection increased intracellular superoxide levels in an M/S131R-dependent manner. To see whether this effect promotes infection, we deleted the Shope fibroma virus S131R gene and compared the clinical manifestations of wild-type and mutant virus infections in rabbits. S131RΔ virus produced significantly smaller fibroxanthosarcoma-like growths in vivo and, at a point where these growths were already receding, wild-type infections still showed extensive leukocyte infiltration, necrosis, and fibromatous cell proliferation. Coincidentally, whereas Jurkat cells are protected from mitochondria- and Fas-mediated apoptosis by wild-type myxoma virus in vitro, M131RΔ virus could not block Fas-initiated apoptosis as judged by DNA laddering, terminal deoxynucleotidyltransferase-mediated dUTP-fluorescein nick end labeling, and caspase 3 cleavage assays. These data suggest that tumorigenic poxviruses can modulate intracellular redox status to their advantage to stimulate infected cell growth and inhibit programmed cell death.

scholarly journals Linc00963 Promote Cell Proliferation and Tumor Growth in Castration-Resistant Prostate Cancer by Modulating miR-655/TRIM24 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Minghua Bai ◽  
Chenchen He ◽  
Shengjia Shi ◽  
Mincong Wang ◽  
Jinlu Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Castration Resistant Prostate Cancer ◽  
Loss Of Function ◽  
Promote Cell Proliferation ◽  
Castration Resistant ◽  
Promote Tumor Growth

Previous studies have shown that both long intergenic non-coding RNA 00963 (Linc00963) and tripartite motif containing 24 (TRIM24) are activators of the PI3K/AKT pathway, and both are involved in the carcinogenesis and progression of prostate cancer. However, the regulatory mechanisms between Linc00963 and TRIM24 are still unclear. In this study, we aimed to elucidate the underlying relationship between Linc00963 and TRIM24 in castration-resistant prostate cancer (CRPC). We found that TRIM24, an established oncogene in CRPC, was positively correlated with Linc00963 in prostate cancer tissues. In addition, TRIM24 was positively regulated by Lin00963 in CRPC cells. Mechanistically, TRIM24 was the direct target of microRNA-655 (miR-655) in CRPC cells, and Linc00963 could competitively bind miR-655 and upregulate TRIM24 expression. Using gain- and loss-of- function assays and rescue assays, we identified that miR-655 inhibits TRIM24 expression and cell proliferation and colony forming ability in CRPC, and that Linc00963 promotes TRIM24 expression, cell proliferation, and colony forming ability of CRPC cells by directly suppressing miR-655 expression. We further identified that Linc00963 could promote tumor growth of CRPC cells by inhibiting miR-655 and upregulating TRIM24 axis in vivo. Taken together, our study reveals a new mechanism for the Linc00963/miR-655/TRIM24 competing endogenous RNA (ceRNA) network in accelerating cell proliferation in CRPC in vitro and in vivo, and suggests that Linc00963 could be considered a novel therapeutic target for CRPC.

scholarly journals p53 deficiency induces MTHFD2 transcription to promote cell proliferation and restrain DNA damage

2021 ◽  
Vol 118 (28) ◽  
pp. e2019822118
Author(s):  
Gen Li ◽  
Jun Wu ◽  
Le Li ◽  
Peng Jiang
Keyword(s):  
Cell Proliferation ◽  
Dna Damage ◽  
Cancer Cells ◽  
De Novo ◽  
Chemotherapeutic Agents ◽  
Metabolic Reprogramming ◽  
Promote Cell Proliferation ◽  
Metabolic Remodeling

Cancer cells acquire metabolic reprogramming to satisfy their high biogenetic demands, but little is known about how metabolic remodeling enables cancer cells to survive stress associated with genomic instability. Here, we show that the mitochondrial methylenetetrahydrofolate dehydrogenase (MTHFD2) is transcriptionally suppressed by p53, and its up-regulation by p53 inactivation leads to increased folate metabolism, de novo purine synthesis, and tumor growth in vivo and in vitro. Moreover, MTHFD2 unexpectedly promotes nonhomologous end joining in response to DNA damage by forming a complex with PARP3 to enhance its ribosylation, and the introduction of a PARP3-binding but enzymatically inactive MTHFD2 mutant (e.g., D155A) sufficiently prevents DNA damage. Notably, MTHFD2 depletion strongly restrains p53-deficient cell proliferation and sensitizes cells to chemotherapeutic agents, indicating a potential role for MTHFD2 depletion in the treatment of p53-deficient tumors.

scholarly journals E6-induced selective translation of WNT4 and JIP2 promotes the progression of cervical cancer via a noncanonical WNT signaling pathway

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Lin Zhao ◽  
Longlong Wang ◽  
Chenglan Zhang ◽  
Ze Liu ◽  
Yongjun Piao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Ectopic Expression ◽  
Wnt Signaling Pathway ◽  
Mrna Translation ◽  
Translation Efficiency ◽  
Independent Manner ◽  
Promote Cell Proliferation

Abstract mRNA translation reprogramming occurs frequently in many pathologies, including cancer and viral infection. It remains largely unknown whether viral-induced alterations in mRNA translation contribute to carcinogenesis. Most cervical cancer is caused by high-risk human papillomavirus infection, resulting in the malignant transformation of normal epithelial cells mainly via viral E6 and E7 oncoproteins. Here, we utilized polysome profiling and deep RNA sequencing to systematically evaluate E6-regulated mRNA translation in HPV18-infected cervical cancer cells. We found that silencing E6 can cause over a two-fold change in the translation efficiency of ~653 mRNAs, most likely in an eIF4E- and eIF2α-independent manner. In addition, we identified that E6 can selectively upregulate the translation of WNT4, JIP1, and JIP2, resulting in the activation of the noncanonical WNT/PCP/JNK pathway to promote cell proliferation in vitro and tumor growth in vivo. Ectopic expression of WNT4/JIP2 can effectively rescue the decreased cell proliferation caused by E6 silencing, strongly suggesting that the WNT4/JIP2 pathway mediates the role of E6 in promoting cell proliferation. Thus, our results revealed a novel oncogenic mechanism of E6 via regulating the translation of mRNAs.

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