Dongping Wang

China Pharmaceutical University

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Weiqiang Ju

Sun Yat-sen University

Zhiyong Guo

The First Affiliated Hospital, Sun Yat-sen University

Linwei Wu

Guangxi University of Chinese Medicine

Qiang Zhao

The First Affiliated Hospital, Sun Yat-sen University

Xiaofeng Zhu

First Affiliated Hospital of Fujian Medical University

Maogen Chen

Sun Yat-sen University

Xiaoshun He

Sun Yat-sen University

Xiaoshun He

Key Laboratory of Guangdong Province

Yi Ma

Electric Power Research Institute

Anbin Hu

Sun Yat-sen University

Cooperative Institutions

Sun Yat-sen University

257

The First Affiliated Hospital, Sun Yat-sen University

215

Key Laboratory of Guangdong Province

119

Chinese Academy of Medical Sciences & Peking Union Medical College

Chinese Academy of Sciences

Peking University

Shanghai Jiao Tong University

China International Science and Technology Cooperation

Capital Medical University

Guangzhou Medical University

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ATP-sensitive isoforms of P2X5: A reevaluation of its function across species

bioRxiv (Cold Spring Harbor Laboratory) (2025)

Xiao‐Na Yang Dongping Wang Chen‐Hui Shen Xijing Chen Hui Ying Yang

The P2X receptor family comprises ATP-gated non-selective cation channels central to physiological processes across the nervous, immune, cardiovascular, respiratory, and reproductive systems. While P2X1, P2X2, P2X3, P2X4, and P2X7 are well-established as ATP-sensitive, P2X5 isoforms and transcript variants (TVs) have traditionally been considered ATP-insensitive, limiting their functional exploration. This study identifies previously overlooked ATP-sensitive P2X5 isoforms across diverse species. Through gene profiling and next-generation sequencing (NGS), we found that the zfP2X5TV2 isoform dominates ATP-sensitive forms in zebrafish. In mice, ATP-sensitive mP2X5G317 (mP2X5.1) comprises ~90% of transcripts, while in rats, exon 3-containing rP2X5F191 accounts for over 70%. In human cell lines, ATP-sensitive isoforms retaining exons 3, 7, and 10 represent ~15-30% of P2X5 transcripts. RNA-seq from human tissues confirms frequent retention of exons 3 and 7 and polymorphic exon 10 expression. ATP-sensitive P2X5 variants were also identified in chickens, bullfrogs, dogs, cows, and naked mole-rats. These findings challenge the prevailing assumption of ATP-insensitivity, highlighting the need to reassess P2X5's roles in physiological and pathological contexts.

10.1101/2025.01.10.632374

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iRhom2 Mutation Leads to Aberrant Hair Follicle Differentiation in Mice

PLoS ONE (2014)

Leilei Yang Liu Bing Yang Li Shaoxia Wang Yuan Xu

iRhom1 and iRhom2 are inactive homologues of rhomboid intramembrane serine proteases lacking essential catalytic residues, which are necessary for the maturation of TNFα-converting enzyme (TACE). In addition, iRhoms regulate epidermal growth factor family secretion. The functional significance of iRhom2 during mammalian development is largely unclear. We have identified a spontaneous single gene deletion mutation of iRhom2 in Uncv mice. The iRhom2Uncv/Uncv mice exhibit hairless phenotype in a BALB/c genetic background. In this study, we observed dysplasia hair follicles in iRhom2Uncv/Uncv mice from postnatal day 3. Further examination found decreased hair matrix proliferation and aberrant hair shaft and inner root sheath differentiation in iRhom2Uncv/Uncv mutant hair follicles. iRhom2 is required for the maturation of TACE. Our data demonstrate that iRhom2Uncv cannot induce the maturation of TACE in vitro and the level of mature TACE is also significantly reduced in the skin of iRhom2Uncv/Uncv mice. The activation of Notch1, a substrate of TACE, is disturbed, associated with dramatically down-regulation of Lef1 in iRhom2Uncv/Uncv hair follicle matrix. This study identifies iRhom2 as a novel regulator of hair shaft and inner root sheath differentiation.

Inner root sheath

Hairless

10.1371/journal.pone.0115114

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Citations (14)

Pathogenicity of duck circovirus 1 in experimentally infected specific pathogen-free ducks

Poultry Science (2023)

Xuezhi Cui Yudong Zhu Qiong Wu Dalin He Mingtian Mao

Ducks infected with duck circovirus (DuCV) show symptoms such as feather loss, growth retardation and low body weight in the flock. The virus induces immunosuppression and increases the prevalence of infection with other pathogens. However, most studies on duck circovirus were focused on co-infection, and fewer studies had been conducted on the pathogenicity of duck circovirus alone. The aim of the present study was to investigate the pathogenesis of DuCV-1 in experimentally infected specific pathogen-free ducks. In this study, we sequenced the whole genome of a strain of duck circovirus and identified the virus genotype as DuCV-1b. This strain of duck circovirus was named SDLH(OR567883). Animal pathogenicity experiments were then conducted, wherein specific pathogen-free ducks were infected by mucosal injection and abdominal injection. Infected ducks were sampled for four consecutive weeks after infection and showed symptoms of dwarfism. We further examined the replication of DuCV-1 in the ducks. The highest virus titers in the two infection groups were found in the liver and spleen, with different results for the different routes of infection. Pathological sections of duck organs were made and it was found that organs such as the liver and spleen were damaged by DuCV-1. In conclusion, our experimental results indicate that DuCV-1 can infect ducks individually and cause widespread organ damage in infected ducks.

Circovirus

Specific-pathogen-free

Flock

10.1016/j.psj.2023.103301

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Citations (4)

[Study on the Mechanism of Multi-Drug Resistance of Agaricus Blazei Extract FA-2-b-β Mediated Wnt Signaling Pathway to Reverse Acute T Lymphoblastic Leukemia].

PubMed (2023)

Wenwen Feng Yu Bai Dongping Wang Fu-Yan Fan Yanqing Sun

To investigate the mechanism of drug reversing resistance of Agaricus blazei extract FA-2-b-β on T cell acute lymphoblastic leukemia (T-ALL) cell lines.Cell proliferation was detected by CCK-8 assay; the apoptosis, cell cycle mitochondrial membrane potential, and intracellular rhodamine accumulation were detected by flow cytometry, and apoptosis-related gene and protein expression were detected by qPCR and Western blot; the membrane surface protein MDR1 was observed by immunofluorescence microscopy.Different concentrations of FA-2-b-β significantly inhibited proliferation and induced apoptosis of CCRF-CEM and CEM/C1 (P<0.05), and CCRF-CEM cell cycle were arrested at S phase, and CEM/C1 cells were arrested at G0/G1 phase. Western blot and qPCR results show that FA-2-b-β inhibited ABCB1、ABCG2、CTNNB、MYC and BCL-2 expression, but upregulated Bax expression. In addition, FA-2-b-β reversed the resistance characteristics of CEM/C1 drug-resistance cells, which decreased mitochondrial membrane potential, and significantly increased the intracellular rhodamine accumulation, and weakening of the expression of the membrane surface protein MDR1. With the Wnt/β-catenin inhibitor (ICG001), the process was further intensified.Agaricus Blazei Extract FA-2-b-β inhibits cell proliferation, promotes apoptosis, regulates the cell cycle, reduces mitochondrial energy supply, and down-regulate MDR1 expression to reverse the resistance of CEM/C1, which all suggest it is through regulating the Wnt signaling pathway in T-ALL.秦巴硒菇提取物FA-2-b-β介导Wnt信号通路逆转急性Ｔ淋巴细胞白血病细胞多药耐药性的机制研究.探讨秦巴硒菇提取物FA-2-b-β对急性T淋巴细胞白血病细胞的逆转耐药作用机制.采用CCK-8法检测细胞增殖；流式细胞术检测细胞凋亡、线粒体膜电位、细胞周期以及胞内罗丹明蓄积情况；qPCR和Western blot检测凋亡相关基因与蛋白表达；免疫荧光观察膜表面蛋白MDR1表达.不同浓度秦巴硒菇提取物FA-2-b-β能够显著抑制CCRF-CEM及CEM/C1细胞增殖(P<0.05)，促进其凋亡，并调控CCRF-CEM细胞阻滞于S期、CEM/C1细胞阻滞于G0/G1期。Western blot及qPCR检测结果显示，FA-2-b-β可抑制ABCB1、ABCG2、CTNNB、MYC、BCL-2表达，并上调BAX表达。另外，FA-2-b-β可逆转CEM/C1耐药株的耐药特性，使得其线粒体膜电位下降，细胞内罗丹明蓄积明显增多，膜表面蛋白MDR1表达减弱。加入ICG001后，该过程进一步加强.秦巴硒菇提取物 FA-2-b-β通过抑制细胞增殖促进凋亡、调控细胞周期、减少线粒体供能及下调MDR1蛋白表达等方式逆转CEM/C1细胞的耐药性，其机制可能通过调控Wnt信号通路实现.

Rhodamine 123

Viability assay

10.19746/j.cnki.issn.1009-2137.2023.03.001

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The Determination of Blood Physiological Indexes of p21~(HBsAg/HBsAg) and p21~(HBX/HBX) Transgenic Mice of Different Ages

Laboratory animal science (2007)

Dongping Wang Deqiang Kong

Objective To determine blood physiological indexes of p21~(HBsAg/HBsAg) and p21~(HBX/HBX) transgenic mice of different ages so as to delve further into the effect of HBsAg/HBsAg and HBX/HBX transferred into p21 locus of mice on their blood physiological indexes. Methods The blood physiological indexes of p21~(HBsAg/HBsAg) and p21~(HBX/HBX) transgenic mice of different ages were determined and the results were compared with those of wild mice.Results The differences in many blood physiological indexes between male and female mice were very significant,and the differences in blood physiological indexes between p21~(HBsAg/HBsAg),p21~(HBX/HBX) transgenic mice and wild mice were very significant.Conclusion The transferring of HBsAg/HBsAg and HBX/HBX gene into p21 locus of mice could exert the effect on their blood physiological indexes.

HBx

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Addition of a liver to the normothermic perfusion circuit reduces renal pro‐inflammatory factors

Artificial Organs (2023)

Fangcong Li Yimin Zhang Hehuan Ruan Yu He Liqiang Zhan

Normothermic machine perfusion (NMP) provides a novel platform to preserve isolated organs in an artificial condition. Our study aimed to explore the interaction between the liver and kidney at an ex vivo organ level by adding a liver to the kidney NMP circuit.Porcine kidney and liver obtained from abattoir were subjected to 9 h NMP after suffering 30-min warm ischemia time and 90-min cold ischemia time. The liver-kidney NMP group (n = 5) and the single-kidney NMP group (n = 5) were designed. During the NMP, perfusion parameters, blood gas analysis, and tissue samples were compared.The perfusate of both groups remained stable, and continuous urine production was observed during NMP. In the liver-kidney NMP group, the lactate level was low, while blood urea nitrogen increased and glucose levels decreased. After the NMP, the renal tissue in the liver-kidney group exhibited fewer histological changes such as tubular epithelium vacuolization, along with reduced expression of IL-6, IL-8, IL-1β, NLRP3, and GSDMD.Our results indicated that the expression of renal pro-inflammatory factors was reduced in the liver-kidney NMP system.

Liver perfusion

10.1111/aor.14626

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Sirolimus conversion in liver transplant recipients with calcineurin inhibitor-related renal insufficiency after liver transplantation

Zhonghua gan-dan waike zazhi (2010)

Ju Weiqiang He Xiaoshun Dongping Wang Linwei Wu Qiang Tai

Objective To investigate the efficacy and safety of sirolimus in treating calcineurin inhibitor-related renal insufficiency after liver transplantation. Methods Eleven patients with calci-neurin inhibitor-related renal insufficiency after liver transplantation received sirolimus conversion.Simultaneously, the dose of tacrolimus was decreased or tacrolimus was withdrawn. Blood creatinine,sirolimus level, tacrolimus level, liver function, rejection episodes and drug side-effect were moni-tored. Results All the 11 patients survived today with 6 to 20 months of follow-up. All patients showed improvement of renal function after conversion to sirolimus. Blood creatinine level was reduced from (163.8±47.9)μmol/L to(108.1±26.6)μmol/l. (P<0.05). One patient's liver function had an acute rejection episode that was successfully treated with increase of dose of tacrolimus. The side-effects of sirolimus included hyperlipidemia (4 patients), anaemia (1) and mouth ulcers (2).Conclusion Siolimus can be effectively and safely used in liver transplant recipients suffering from ta-crolimus-related renal insufficiency. Key words: Liver transplantation; Sirolimus; Calcineurin inhibitor; Renal insufficiency

Sirolimus

Liver function

10.3760/cma.j.issn.1007-8118.2010.02.011

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The first case of ischemia-free organ transplantation in humans: A proof of concept

American Journal of Transplantation (2017)

Xiaoshun He Zhiyong Guo Qiang Zhao Weiqiang Ju Dongping Wang

Ischemia and reperfusion injury (IRI) is an inevitable event in conventional organ transplant procedure and is associated with significant mortality and morbidity post-transplantation. We hypothesize that IRI is avoidable if the blood supply for the organ is not stopped, thus resulting in optimal transplant outcomes. Here we described the first case of a novel procedure called ischemia-free organ transplantation (IFOT) for patients with end-stage liver disease. The liver graft with severe macrovesicular steatosis was donated from a 25-year-old man. The recipient was a 51-year-old man with decompensated liver cirrhosis and hepatocellular carcinoma. The graft was procured, preserved, and implanted under continuous normothermic machine perfusion. The recipient did not suffer post-reperfusion syndrome or vasoplegia after revascularization of the allograft. The liver function test and histological study revealed minimal hepatocyte, biliary epithelium and vascular endothelium injury during preservation and post-transplantation. The inflammatory cytokine levels were much lower in IFOT than those in conventional procedure. Key pathways involved in IRI were not activated after allograft revascularization. No rejection, or vascular or biliary complications occurred. The patient was discharged on day 18 post-transplantation. This marks the first case of IFOT in humans, offering opportunities to optimize transplant outcomes and maximize donor organ utilization. Ischemia and reperfusion injury (IRI) is an inevitable event in conventional organ transplant procedure and is associated with significant mortality and morbidity post-transplantation. We hypothesize that IRI is avoidable if the blood supply for the organ is not stopped, thus resulting in optimal transplant outcomes. Here we described the first case of a novel procedure called ischemia-free organ transplantation (IFOT) for patients with end-stage liver disease. The liver graft with severe macrovesicular steatosis was donated from a 25-year-old man. The recipient was a 51-year-old man with decompensated liver cirrhosis and hepatocellular carcinoma. The graft was procured, preserved, and implanted under continuous normothermic machine perfusion. The recipient did not suffer post-reperfusion syndrome or vasoplegia after revascularization of the allograft. The liver function test and histological study revealed minimal hepatocyte, biliary epithelium and vascular endothelium injury during preservation and post-transplantation. The inflammatory cytokine levels were much lower in IFOT than those in conventional procedure. Key pathways involved in IRI were not activated after allograft revascularization. No rejection, or vascular or biliary complications occurred. The patient was discharged on day 18 post-transplantation. This marks the first case of IFOT in humans, offering opportunities to optimize transplant outcomes and maximize donor organ utilization.

Proof of concept

10.1111/ajt.14583

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Citations (134)

Effects of ischemic preconditioning on the activity of HMGCR of hepatocytes following cryopreservation in rats

Zhonghua shiyan waike zazhi (2011)

Weiqiang Ju Zhipeng Wu Xiaoshun He Zhiyong Guo Dongping Wang

Objective To investigate the effects of ischemic preconditioning on the activity of 3-hydroxy-3-methylglutary coenzyme A reductase (HMGCR) of hepatocytes following cryopreservation in rats. Methods Twenty-five rats were randomly divided into five groups: control group ( C), cryopreservation group (Ⅰ), ischemic preconditioning group (IP), atorvastatin (30 γμmol/L) treatment group (A30) and atorvastatin (100 μmol/L) treatment group (A100). In control group, normal donor livers were flushed with 4 ℃ UW solution. In group I, donor livers were cryopreserved for 8 h after UWs flushing. In group IP, donor livers were subjected to ischemic preconditioning, and then flushed and cryopreserved in UWs. In group A30, donor livers were treated as in group I except that 30 μmol/L atorvastatin was added to the UWs. In group A100, donor lovers were treated as in group I with the exception that 100 μmol/L atorvastatin was added to the UWs. The activity of HMGCR was assessed. Results HMGCR activity in the donor cantly increased after ischemic preconditioning[(3746±231 ) nmol/(min-mg)]. The enhanced HMGCR activity induced by ischemic preconditioning was inhibited by atorvastatin in a concentration-dependent mantivity by up-regulating its protein expression and this effect can be abrogated by atorvastatin. Key words: Hepatocytes; Ischemic preconditioning; Cold preservation; 3-hydroxy-3-methylglutary coenzyme A reductase

Ischemic Preconditioning

10.3760/cma.j.issn.1001-9030.2011.08.039

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Left branch of portal vein thrombosis in a liver transplant recipient with donation after cardiac death donor

Medicine (2016)

Maogen Chen Weiqiang Ju Xiaohong Lin Qiang Zhao Dongping Wang

Introduction: Portal vein thrombosis (PVT) is one of the most severe complications after liver transplantation, which usually causes graft loss and recipient mortality. The founding of the embolic branch of portal system and its result are not well described in the literature. Clinical findings and diagnoses: We report here an unusual case of complete right branch thrombosis of portal vein after orthotopic liver transplantation from a donation after cardiac death donor, without obvious malaise. The interventions and outcomes: The branch thrombosis of portal vein was detected by Doppler ultrasound 11 days after transplantation, followed by angiography for further verification. After treatment with urgent indwelling catheter thrombolysis with urokinase, results improved and the patient showed stable liver function. The patient has been in remission for 22 months with normal graft function. Conclusion: In this case report, we show that frequent ultrasound inspection should be adopted to detect the unobstructed vessel in the early stage of liver transplantation, and local thrombolytic therapy can be used to prevent liver injury and keep the vessel open.

Portal vein thrombosis

Liver function

10.1097/md.0000000000005520

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Citations (1)