scholarly journals Upregulation of PDGF Mediates Robust Liver Regeneration after Nanosecond Pulsed Electric Field Ablation by Promoting the HGF/c-Met Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Junjie Qian ◽  
Jianpeng Liu ◽  
Liangjie Hong ◽  
Haohao Lu ◽  
Danjing Guo ◽  
...  
Keyword(s):  
Liver Function ◽  
Electric Field ◽  
Liver Regeneration ◽  
Molecular Mechanisms ◽  
Pulsed Electric Field ◽  
Serum Levels ◽  
Nanosecond Pulsed Electric Field ◽  
The Impact ◽  
Proliferation Of Hepatocytes

Nanosecond pulsed electric field (nsPEF) has emerged as a promising tool for hepatocellular carcinoma ablation recently. However, little is known about how nsPEF affects liver regeneration while being applied to eliminate liver lesions. Besides, the impact of nsPEF ablation on liver function should also be taken into consideration in the process. In this paper, we study the impact of nsPEF ablation on liver function by the measurement of serum levels of AST and ALT as well as liver regeneration and relevant molecular mechanisms in vivo. We found that mouse liver function exhibited a temporary injury without weight loss after ablation. In addition, local hepatic nsPEF ablation promoted significant proliferation of hepatocytes of the whole liver with an increase in HGF level. Moreover, the proliferation of hepatocytes was dramatically inhibited by the inhibitor of c-Met. Of interest, the periablational area is characterized by high level of PDGF and a large amount of activated hepatic stellate cells. Furthermore, neutralizing PDGF was able to significantly inhibit liver regeneration, the increased HGF level, and the accumulation of activated HSCs. Our findings demonstrated that nsPEF not only was a safe ablation approach but also could stimulate the regeneration of the whole liver through the activation of the HGF/c-Met pathway by upregulation of PDGF within the periablational zone.

scholarly journals miR-155 accelerates proliferation of mouse hepatocytes during liver regeneration by directly targeting SOCS1

2018 ◽  
Vol 315 (4) ◽  
pp. G443-G453 ◽  
Author(s):  
Xia Lin ◽  
Li Chen ◽  
Haiyan Li ◽  
Yu Liu ◽  
Yanhong Guan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Molecular Mechanisms ◽  
Pharmacological Intervention ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Proliferation Of Hepatocytes

Liver regeneration after two-thirds partial hepatectomy (PH) is a clinically significant repair process for restoring proper liver architecture. Although microRNA-155 (miR-155) has been found to serve as a crucial microRNA regulator that controls liver cell function and proliferation, little is known about its specific role in the regenerating liver. Using a mouse model with miR-155 overexpression or miR-155 knockout, we investigated the molecular mechanisms of miR-155 in liver regeneration. We found a marked induction of miR-155 in C57BL/6 mice after PH. Furthermore, RL-m155 mice showed enhanced liver regeneration as a result of accelerated progression of hepatocytes into the cell cycle, mainly through an increase in cyclin levels. However, proliferation of hepatocytes was delayed in miR-155-deficient livers. Expression of suppressor of cytokine signaling 1 (SOCS1) was dramatically downregulated in the process of liver regeneration, and enhancement of SOCS1 contributed to impaired proliferation of hepatocytes. Additionally, in vitro and in vivo experiments showed that adenovirus- or adeno-associated virus-mediated overexpression of SOCS1 attenuated improved liver regeneration induced by miR-155 overexpression. Our study shows that miR-155 is a pro-proliferative regulator in liver regeneration by facilitating the cell cycle and directly targeting SOCS1. NEW & NOTEWORTHY Our findings suggest a microRNA-155 (miR-155)-mediated positive regulation pattern in liver regeneration. A series of in vivo and in vitro studies showed that miR-155 upregulation enhanced partial hepatectomy-induced proliferation of hepatocytes by promoting the cell cycle without inducing DNA damage or apoptosis. Suppressor of cytokine signaling 1, a target gene of miR-155, antagonized the proliferation-promoting effect of miR-155. Therefore, pharmacological intervention targeting miR-155 may be therapeutically beneficial in various liver diseases.

In vivo experimental study of nanosecond pulsed electric field effects on solid tumors

2013 ◽  
Vol 20 (4) ◽  
pp. 1266-1272 ◽  
Author(s):  
Masataka Nagahama ◽  
Naoyuki Shimomura ◽  
Akito Nakagawa ◽  
Kenji Teranishi ◽  
Yoshihiro Uto ◽  
...  
Keyword(s):  
Experimental Study ◽  
Electric Field ◽  
Solid Tumors ◽  
Pulsed Electric Field ◽  
Electric Field Effects ◽  
Field Effects ◽  
Nanosecond Pulsed Electric Field

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

scholarly journals F4/80+ Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2231
Author(s):  
Qingjun Lu ◽  
Hao Shen ◽  
Han Yu ◽  
Jing Fu ◽  
Hui Dong ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Regenerative Process ◽  
Oncostatin M ◽  
Hepatocyte Proliferation ◽  
Initiation Phase ◽  
Distinct Role

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80+ KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80+ KCs during the regenerative process. In RNA sequencing of isolated F4/80+ KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-β2 pathway were performed. Depletion of F4/80+ KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80+ KCs in the initiation and progression phases of liver regeneration. F4/80+ KC depletion in post-PHx could significantly increase TGF-β2 serum levels, while TGF-βRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80+ KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80+ KCs release OSM to inhibit TGF-β2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.

scholarly journals Excitation of murine cardiac myocytes by nanosecond pulsed electric field

2019 ◽  
Vol 30 (3) ◽  
pp. 392-401 ◽  
Author(s):  
Jan E. Azarov ◽  
Iurii Semenov ◽  
Maura Casciola ◽  
Andrei G. Pakhomov
Keyword(s):  
Electric Field ◽  
Cardiac Myocytes ◽  
Pulsed Electric Field ◽  
Nanosecond Pulsed Electric Field

scholarly journals Safety and Efficacy of Nanosecond Pulsed Electric Field Treatment of Sebaceous Gland Hyperplasia

2020 ◽  
Vol 46 (6) ◽  
pp. 803-809 ◽  
Author(s):  
Girish S. Munavalli ◽  
Brian D. Zelickson ◽  
Mona M. Selim ◽  
Suzanne L. Kilmer ◽  
Thomas E. Rohrer ◽  
...  
Keyword(s):  
Electric Field ◽  
Sebaceous Gland ◽  
Pulsed Electric Field ◽  
Safety And Efficacy ◽  
Nanosecond Pulsed Electric Field ◽  
Pulsed Electric Field Treatment ◽  
Electric Field Treatment

Nanosecond Pulsed Electric Field Lab‐on‐Chip Integrated in Super‐Resolution Microscope for Cytoskeleton Imaging

2019 ◽  
Vol 5 (3) ◽  
pp. 1900669 ◽  
Author(s):  
Daniel Havelka ◽  
Djamel Eddine Chafai ◽  
Ondrej Krivosudský ◽  
Anastasiya Klebanovych ◽  
František Vostárek ◽  
...  
Keyword(s):  
Electric Field ◽  
Super Resolution ◽  
Pulsed Electric Field ◽  
Lab On Chip ◽  
Nanosecond Pulsed Electric Field ◽  
On Chip

scholarly journals Concepts and Capabilities of In-House Built Nanosecond Pulsed Electric Field (nsPEF) Generators for Electroporation: State of Art

2020 ◽  
Vol 10 (12) ◽  
pp. 4244
Author(s):  
Paulius Butkus ◽  
Arūnas Murauskas ◽  
Sonata Tolvaišienė ◽  
Vitalij Novickij
Keyword(s):  
Electric Field ◽  
High Frequency ◽  
Pulsed Electric Field ◽  
Cell Permeabilization ◽  
Pulse Generators ◽  
Nanosecond Pulsed Electric Field ◽  
Forming Characteristics ◽  
State Of Art ◽  
Frequency Pulse

Electroporation is a pulsed electric field triggered phenomenon of cell permeabilization, which is extensively used in biomedical and biotechnological context. There is a growing scientific demand for high-voltage and/or high-frequency pulse generators for electropermeabilization of cells (electroporators). In the scope of this article we have reviewed the basic topologies of nanosecond pulsed electric field (nsPEF) generators for electroporation and the parametric capabilities of various in-house built devices, which were introduced in the last two decades. Classification of more than 60 various nsPEF generators was performed and pulse forming characteristics (pulse shape, voltage, duration and repetition frequency) were listed and compared. Lastly, the trends in the development of the electroporation technology were discussed.

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