Peripheral nerve defects repaired with autogenous vein grafts flled with platelet-rich plasma and active nerve microtissues and evaluated by novel multimodal ultrasound techniques

Yaqiong Zhu,Nan Peng,Jing Wang,Zhuang Jin,Lianhua Zhu,Yu Wang,Siming Chen,Yongqiang Hu,Tieyuan Zhang,Qing Song,Fang Xie,Lin Yan,Yingying Li,Jing Xiao,Xinyang Li,Bo Jiang,Jiang Peng,Yuexiang Wang,Yukun 한국생체재료학회 2022 생체재료학회지 Vol.26 No.3

Background: Developing biocompatible nerve conduits that accelerate peripheral nerve regeneration, lengthening and functional recovery remains a challenge. The combined application of nerve microtissues and platelet-rich plasma (PRP) provides abundant Schwann cells (SCs) and various natural growth factors and can compensate for the deficiency of SCs in the nerve bridge, as well as the limitations of applying a single type of growth factor. Multimodal ultrasound evaluation can provide additional information on the stiffness and microvascular flow perfusion of the tissue. This study was designed to investigate the effectiveness of a novel tissue-engineered nerve graft composed of an autogenous vein, nerve microtissues and PRP in reconstructing a 12-mm tibial nerve defect and to explore the value of multimodal ultrasound techniques in evaluating the prognosis of nerve repair. Methods: In vitro, nerve microtissue activity was first investigated, and the effects on SC proliferation, migration, factor secretion, and axonal regeneration of dorsal root ganglia (DRG) were evaluated by coculture with nerve microtissues and PRP. In vivo, seventy-five rabbits were equally and randomly divided into Hollow, PRP, Micro-T (Microtissues), Micro-T + PRP and Autograft groups. By analysing the neurological function, electrophysiological recovery, and the comparative results of multimodal ultrasound and histological evaluation, we investigated the effect of these new nerve grafts in repairing tibial nerve defects. Results: Our results showed that the combined application of nerve microtissues and PRP could significantly promote the proliferation, secretion and migration of SCs and the regeneration of axons in the early stage. The Micro-T + PRP group and Autograft groups exhibited the best nerve repair 12 weeks postoperatively. In addition, the changes in target tissue stiffness and microvascular perfusion on multimodal ultrasound (shear wave elastography; contrast-enhanced ultrasonography; Angio PlaneWave UltrasenSitive, AngioPLUS) were significantly correlated with the histological results, such as collagen area percentage and VEGF expression, respectively. Conclusion: Our novel tissue-engineered nerve graft shows excellent efficacy in repairing 12-mm defects of the tibial nerve in rabbits. Moreover, multimodal ultrasound may provide a clinical reference for prognosis by quantitatively evaluating the stiffness and microvescular flow of nerve grafts and targeted muscles

Apoptotic effect of pheophorbide a-mediated photodynamic therapy on DMBA/TPA-induced mouse papillomas.

Zhang, Xianglan,Choi, Eun Joo,Zheng, Zhenlong,Zhu, Lianhua,Cho, Sung Bin,Kim, Ki-Yoel,Kim, Jin,Cha, In-Ho Baillière Tindall ; Springer London 2015 LASERS IN MEDICAL SCIENCE Vol.30 No.1

<P>Pheophorbide a (Pa) is a chlorine-based photosensitizer, and Pa-mediated photodynamic therapy (PDT) reportedly exhibits antitumor activity against various malignancies. The aim of our study was to investigate the therapeutic effect of Pa-mediated PDT on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorobol-13-acetate (TPA)-induced mouse papillomas. Thirty mice received a topical application of DMBA/TPA on their backs to induce mouse papillomas. One week after two sessions of Pa-mediated PDT, immunohistochemical stains and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to evaluate the apoptotic effects thereof on the papillomas. Among 63 mouse papillomas treated with Pa-mediated PDT, 17.5% of the lesions were completely removed 1 week after the first treatment, while 31.7% disappeared 1 week after the second treatment. Statistical analyses revealed significant differences in therapeutic outcomes for the Pa-mediated PDT group in comparison to a solvent-PDT group and a Pa group. Additionally, a marked downregulation of proliferating cell nuclear antigen expression, as well as upregulation of cleaved caspase 3 and cleaved poly(ADP-ribose) polymerase expression, was noted in the Pa-PDT group, compared to the solvent-PDT group and Pa group. TUNEL assay revealed higher apoptotic cell counts in the Pa-PDT group, although the difference was not statistically significant. Our data demonstrated that Pa-mediated PDT is effective in treating DMBA/TPA-induced mouse papillomas.</P>

Risk of radiation-induced pneumonitis after helical and static-port tomotherapy in lung cancer patients and experimental rats

Zhang, Xianglan,Shin, You Keun,Zheng, Zhenlong,Zhu, Lianhua,Lee, Ik Jae BioMed Central 2015 Radiation oncology Vol.10 No.-

<P><B>Background</B></P><P>Radiotherapy (RT) is one of the major non-operative treatment modalities for treating lung cancer. Tomotherapy is an advanced type of intensity-modulated radiotherapy (IMRT) in which radiation may be delivered in a helical fashion. However, unexpected pneumonitis may occur in patients treated with tomotherapy, especially in combination with chemotherapy, as a result of extensive low-dose radiation of large lung volumes. The aim of our study was to investigate the risk of radiation-induced pneumonitis after helical-mode and static-mode tomotherapy in patients with lung cancer and in an animal model.</P><P><B>Method</B></P><P>A total of 63 patients with primary lung cancer who were treated with static or helical tomotherapy with or without concurrent chemoradiotherapy (CCRT) were analyzed. Additionally, rats with radiation-induced pulmonary toxicity, which was induced by the application of helical or static tomography with or without CCRT, were evaluated.</P><P><B>Results</B></P><P>Helical-mode tomotherapy resulted in a significantly higher rate of late radiation pneumonitis in lung cancer patients than static-mode tomotherapy when evaluated by the Radiation Therapy Oncology Group (RTOG) and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) scoring system. In the animal model, helical tomotherapy alone induced significantly higher expression of interleukin (IL)-1α, IL-1β, IL-6, and transforming growth factor (TGF)-β in lung specimens, especially on the untreated side, compared to static tomotherapy alone. Additionally, rats treated with helical tomotherapy and CCRT demonstrated significantly higher expression of inflammatory cytokines compared to those treated with static tomotherapy and CCRT.</P><P><B>Conclusion</B></P><P>Rat models treated with tomotherapy with or without CCRT could present similar patterns of pulmonary toxicity to those shown in lung cancer patients. The models can be used in further investigations of radiation induced pulmonary toxicity.</P>

Effects of G-Rh2 on mast cell-mediated anaphylaxis via AKT-Nrf2/NF-κB and MAPK-Nrf2/NF-κB pathways

Chang Xu,Liangchang Li,Chongyang Wang,Jingzhi Jiang,Li Li,Lianhua Zhu,Shan Jin,Zhehu Jin,Jung Joon Lee,Guanhao Li,Guanghai Yan 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.4

Background: The effect of ginsenoside Rh2 (G-Rh2) on mast cell-mediated anaphylaxis remains unclear. Herein, we investigated the effects of G-Rh2 on OVA-induced asthmatic mice and on mast cell-mediatedanaphylaxis. Methods: Asthma model was established for evaluating airway changes and ear allergy. RPMCs and RBL-2H3 were used for in vitro experiments. Calcium uptake, histamine release and degranulation weredetected. ELISA and Western blot measured cytokine and protein levels, respectively. Results: G-Rh2 inhibited OVA-induced airway remodeling, the production of TNF-a, IL-4, IL-8, IL-1b andthe degranulation of mast cells of asthmatic mice. G-Rh2 inhibited the activation of Syk and Lyn in lungtissue of OVA-induced asthmatic mice. G-Rh2 inhibited serum IgE production in OVA induced asthmaticmice. Furthermore, G-Rh2 reduced the ear allergy in IgE-sensitized mice. G-Rh2 decreased the earthickness. In vitro experiments G-Rh2 significantly reduced calcium uptake and inhibited histaminerelease and degranulation in RPMCs. In addition, G-Rh2 reduced the production of IL-1b, TNF-a, IL-8, andIL-4 in IgE-sensitized RBL-2H3 cells. Interestingly, G-Rh2 was involved in the FcεRI pathway activation ofmast cells and the transduction of the Lyn/Syk signaling pathway. G-Rh2 inhibited PI3K activity in adose-dependent manner. By blocking the antigen-induced phosphorylation of Lyn, Syk, LAT, PLCg2, PI3KERK1/2 and Raf-1 expression, G-Rh2 inhibited the NF-kB, AKT-Nrf2, and p38MAPK-Nrf2 pathways. However, G-Rh2 up-regulated Keap-1 expression. Meanwhile, G-Rh2 reduced the levels of p-AKT,p38MAPK and Nrf2 in RBL-2H3 sensitized IgE cells and inhibited NF-kB signaling pathway activation byactivating the AKT-Nrf2 and p38MAPK-Nrf2 pathways. Conclusion: G-Rh2 inhibits mast cell-induced allergic inflammation, which might be mediated by theAKT-Nrf2/NF-kB and p38MAPK-Nrf2/NF-kB signaling pathways