a-modified-model-preparation-for-middle-cerebral-artery-occlusion

A Modified Model Preparation for Middle Cerebral Artery Occlusion Reperfusion

The middle cerebral artery occlusion reperfusion (MCAO/R) model is crucial for understanding the pathological mechanisms of stroke and for drug ...

cerebral-ischemic-coma-model-induced-by-modified-four-vessel-occlusion

Cerebral Ischemic Coma Model Induced by Modified Four-Vessel Occlusion

Coma caused by cerebral ischemia is the most serious complication of cerebral ischemia. Four-vessel occlusion can establish a cerebral ischemic coma model ...

Foshan University

P-glycoprotein (P-gp) is encoded by the multidrug resistance (MDR1) gene and is well studied as a multi-drug resistance transporter. Peritoneal adhesion formation following abdominal surgery remains an important clinical problem. Here, we found that P-gp was highly expressed in human adhesion fibroblasts and promoted peritoneal adhesion formation in a rodent model. Knockdown of P-gp expression by intraperitoneal injection of MDR1-targeted siRNA significantly reduced both the peritoneal adhesion development rate and adhesion grades. Additionally, we found that operative injury up-regulated P-gp expression in peritoneal fibroblasts through the TGF-β1/Smad signaling pathway and histone H3 acetylation. The overexpression of P-gp accelerated migration and proliferation of fibroblasts via volume-activated Cl(-) current and cell volume regulation by enhancing phosphorylation of the chloride channel-3. Therefore, P-gp plays a critical role in postoperative peritoneal adhesion formation and may be a valuable therapeutic target for preventing the formation of peritoneal adhesions.

P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3.

Human amnion extracellular matrix derived bioactive hydrogel for cell delivery and tissue engineering.

Fibroblasts migrating to peritoneum injuries play an important role in the development of postoperative peritoneal adhesions due to the excessive synthesis and deposition of extracellular matrix (ECM). This effect is mainly induced by the transforming growth factor-β (TGF-β). Studies indicate that elevated TGF-β1 levels and TGF-β1/Smad signaling are both implicated in the formation of peritoneal adhesions. To confirm the effect of TGF-β1/Smad signaling interference in regulating excessive ECM synthesis, a total of four different R-Smad-targeting small interference RNA (siRNA) duplexes (Smad2-500, Smad2-956, Smad3-378, Smad3-1385) were tested in this study using a TGF-β1-stimulated adhesion tissue fibroblasts (ATFs) cell model. The  assessments show that all proposed siRNAs are capable of significantly downregulating the mRNA and protein levels of Smad2 and Smad3 in ATFs. They also inhibit the phosphorylation of both Smads, which confirms their effect in blocking the TGF-β1/Smad signaling pathway. Moreover, the siRNA duplexes can appreciably lower the elevated levels of fibronectin and collagen 3 alpha 1 (COL3A1) in TGF-β1-stimulated ATFs, and the Smad3-378 siRNA can actually restore both molecules (fibronectin and COL3A1) to normal levels. Therefore, the Smad3-378 siRNA is suitable for both adhesion prevention and wound healing. Overall, our results indicate that postoperative adhesion prophylaxis may be achieved by temporarily blocking TGF-β1/Smad signaling transduction.

The effect of Smad2- and Smad3-targeting RNA interference on extracellular matrix synthesis in rat fibroblasts of peritoneal adhesion tissues.

Two known coumarins, scopoletin (SP) and umbelliferone (UB), were isolated from Cortex Mori (CM). Their structures were elucidated by various spectroscopic analyses. Then, their effects on rat glomerular mesangial cells (RGMCs, HBZY-1) proliferation, hypertrophy, extracellular matrix (ECM) proliferation, expression of fibronectin, transforming growth factor-beta (TGF-β), and connective tissue growth factor (CTGF) induced by high glucose were studied in vitro model of diabetic glomerulosclerosis. The results show that, CM, SP, and UB can inhibit the RGMCs proliferation to attenuate the ECM proliferation and cell hypertrophy, reduced the accumulation of ECM protein fibronectin, and lowered the expression of the key fibrosis factor TGF-β and CTGF to inhibit the kidney fibrosis and thereby improved diabetic glomerulosclerosis. The two coumarins show great potentialities on treating diabetic glomerulosclerosis, but the animal experiment and mechanism is strongly needed for further proof.

Scopoletin and umbelliferone from Cortex Mori as protective agents in high glucose-induced mesangial cell as  model of diabetic glomerulosclerosis.

Numerous viral pneumonia cases have been reported in Wuhan, Hubei in December 2019. The pathogen has been identified as a novel coronavirus, which was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The biological characteristics and pathogenesis mechanism of SARS-CoV-2 are unclear and under progress. At present, no specific preventive and therapeutic drugs are available. Animal models can reproduce the viral replication cycle and the significant functions of respiratory coronavirus infection and are urgently needed to evaluate the efficacy of drugs and vaccines, the transmission route of respiratory coronavirus, clinical features, and so on. We reviewed the current animal models of respiratory coronavirus (SARS-CoV, MERS-CoV, and SARS-CoV-2) infection and made a comparative analysis of the route of inoculation, virus replication, clinical signs, histopathology, application, advantages, and disadvantages. Animal models of respiratory coronavirus include susceptible animal models, genetically modified models, and various animal models of infected virus adaptation strains, such as nonhuman primates, mice, hamsters, ferrets, New Zealand rabbits, cats, and other animal models, all of which have distinct advantages and limitations. This review will provide relevant information and important insights for disease management and control.

Review of selected animal models for respiratory coronavirus infection and its application in drug research.

To systematically evaluate the therapeutic effect of BaitouWeng Decoction in patients with ulcerative colitis (UC), evaluate its safety and effectiveness, and provide a reference for clinical medication.

ArticleTotal : 2	Year
Publication title Cited by 1	2024
Publication title Cited by 1	2024

Article	Year
P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3. Theranostics\| PubMed ID: 26877779	2016
Human amnion extracellular matrix derived bioactive hydrogel for cell delivery and tissue engineering. Materials science & engineering. C, Materials for biological applications\| PubMed ID: 29407148	2018
The effect of Smad2- and Smad3-targeting RNA interference on extracellular matrix synthesis in rat fibroblasts of peritoneal adhesion tissues. American journal of translational research\| PubMed ID: 33312378	2020
Scopoletin and umbelliferone from Cortex Mori as protective agents in high glucose-induced mesangial cell as model of diabetic glomerulosclerosis. The Chinese journal of physiology\| PubMed ID: 34169921	2021
Review of selected animal models for respiratory coronavirus infection and its application in drug research. Journal of medical virology\| PubMed ID: 35285034	2022
Efficacy and safety of BaitouWeng decoction for ulcerative colitis: A meta-analysis of randomized and controlled trials. Medicine\| PubMed ID: 38968514	2024

Xuxin Zeng

Biography

JoVE Journal Publications

Other Publications