Chunhua Jiao

Nanjing Medical University

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Elliott H. Sohn

University of Iowa

Robert F. Mullins

University of Iowa

Edwin M. Stone

University of Iowa

Budd A. Tucker

University of Iowa

Hongjie Zhang

Jiangsu Province Hospital

Gina C. Schatteman

University of Iowa

Nana Tang

Nanjing Medical University

Phillip B. Hylemon

Hunter Holmes McGuire VA Medical Center

Jingjing Ma

Henan University

Ian C. Han

University of Iowa

Cooperative Institutions

Canon (Japan)

213

European Foundation for the Study of Chronic Liver Failure

213

University of Iowa

Nanjing Medical University

Inova Fairfax Hospital

Jiangsu Province Hospital

Inserm

Chinese Academy of Sciences

University of Iowa Hospitals and Clinics

Assistance Publique – Hôpitaux de Paris

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Gut microbiota drive the development of neuroinflammatory response in cirrhosis in mice

Hepatology (2016)

Dae Joong Kang Naga S. Betrapally Siddhartha Ghosh R. Balfour Sartor Phillip B. Hylemon

The mechanisms behind the development of hepatic encephalopathy (HE) are unclear, although hyperammonemia and systemic inflammation through gut dysbiosis have been proposed. The aim of this work was to define the individual contribution of hyperammonemia and systemic inflammation on neuroinflammation in cirrhosis using germ‐free (GF) and conventional mice. GF and conventional C57BL/6 mice were made cirrhotic using CCl 4 gavage. These were compared to their noncirrhotic counterparts. Intestinal microbiota, systemic and neuroinflammation (including microglial and glial activation), serum ammonia, intestinal glutaminase activity, and cecal glutamine content were compared between groups. GF cirrhotic mice developed similar cirrhotic changes to conventional mice after 4 extra weeks (16 vs. 12 weeks) of CCl 4 gavage. GF cirrhotic mice exhibited higher ammonia, compared to GF controls, but this was not associated with systemic or neuroinflammation. Ammonia was generated through increased small intestinal glutaminase activity with concomitantly reduced intestinal glutamine levels. However, conventional cirrhotic mice had intestinal dysbiosis as well as systemic inflammation, associated with increased serum ammonia, compared to conventional controls. This was associated with neuroinflammation and glial/microglial activation. Correlation network analysis in conventional mice showed significant linkages between systemic/neuroinflammation, intestinal microbiota, and ammonia. Specifically beneficial, autochthonous taxa were negatively linked with brain and systemic inflammation, ammonia, and with Staphylococcaceae, Lactobacillaceae , and Streptococcaceae. Enterobacteriaceae were positively linked with serum inflammatory cytokines. Conclusion : Gut microbiota changes drive development of neuroinflammatory and systemic inflammatory responses in cirrhotic animals. (H epatology 2016;64:1232‐1248)

Hyperammonemia

Dysbiosis

10.1002/hep.28696

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Citations (96)

Early-Life Gut Microbiota Governs Susceptibility to Colitis via Microbial-Derived Ether Lipids

Research (2023)

Yanjun Liu Chunhua Jiao Tao Zhang Xue Li Panpan Li

Localized intestine inflammation could induce short-term increases in colonic oxygenation and leads to increases in the aerobic bacteria population and reduction in the anaerobic bacteria population by changing the intestinal environment. However, the mechanisms involved and the associated functions of intestinal anaerobes in gut health still remain unclear. Here, we found that early-life depletion of gut microbiota exacerbated later colitis, while mid-life microbiota depletion showed partially reduced colitis. Notably, we observed that early-life gut microbiota depletion confers susceptibility to ferroptosis in colitis. In contrast, restitution of early-life microbiota conferred protection against colitis and inhibited ferroptosis triggered by gut microbiota dysbiosis. Similarly, colonization with anaerobic microbiota from young mice suppressed colitis. These results may attribute to high abundance of plasmalogen-positive (plasmalogen synthase [PlsA/R]-positive) anaerobes and plasmalogens (one of the common ether lipids) in young mice but reduced abundance in the development of inflammatory bowel disease. Early-life anaerobic bacteria elimination also resulted in the aggravation of colitis, while this aggravation phenotype was reverted by plasmalogen administration. Interestingly, plasmalogens inhibited ferroptosis triggered by microbiota dysbiosis. We further find that the alkenyl-ether group of plasmalogens was critical to colitis prevention and ferroptosis inhibition. These data point to one of the mechanisms by which the gut microbiota controls susceptibility to colitis and ferroptosis early in life via microbial-derived ether lipids.

Dysbiosis

Plasmalogen

10.34133/research.0037

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Citations (17)

Shenling Baizhu San ameliorates ulcerative colitis by regulating the gut microbiota and its tryptophan metabolites: A complementary medicine to mesalamine

Journal of Ethnopharmacology (2022)

Chunhua Jiao Qianwen Zhang Mengjiao Yang Jingjing Ma Xiaojing Zhao

10.1016/j.jep.2022.115145

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Citations (13)

Assessment of transduction efficiency and tropism of different adeno-associated virus (AAV) serotypes based on route of delivery in rats

Investigative Ophthalmology & Visual Science (2018)

Ian C. Han Chunhua Jiao Emily E. Kaalberg Sajag Bhattarai Erin R. Burnight

Adeno-associated virus

Transduction (biophysics)

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Murine epidermal side population possesses unique angiogenic properties

Experimental Cell Research (2007)

Christopher C. Oberley Françoise A. Gourronc Shinkai Hakimi Margaret Riordan Sarah M. Bronner

10.1016/j.yexcr.2007.11.002

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Differential Healing Activities of CD34 ⁺ and CD14 ⁺ Endothelial Cell Progenitors

Arteriosclerosis Thrombosis and Vascular Biology (2006)

Ola Awad Eduard I. Dedkov Chunhua Jiao Steven A. Bloomer Robert J. Tomanek

Peripheral blood contains primitive (stem cell-like) and monocytic-like endothelial cell progenitors. Diabetes apparently converts these primitive progenitors, from a pro-angiogenic to anti-angiogenic phenotype. Monocytic progenitors seem to be less affected by diabetes, but potential pro-angiogenic activities of freshly isolated monocytic progenitors remain unexplored. We compared the ability of primitive and monocytic endothelial cell progenitors to stimulate vascular growth and healing in diabetes and investigated potential molecular mechanisms through which the cells mediate their in vivo effects.Human CD34+ primitive progenitors and CD14+ monocytic progenitors were injected locally into the ischemic limbs of diabetic mice. CD14+ cell therapy improved healing and vessel growth, although not as rapidly or effectively as CD34+ cell treatment. Western blot analysis revealed that cell therapy modulated expression of molecules in the VEGF, MCP-1, and angiopoietin pathways.Injection of freshly isolated circulating CD14+ cells improves healing and vascular growth indicating their potential for use in acute clinical settings. Importantly, CD14+ cells could provide a therapeutic option for people with diabetes, the function of whose CD34+ cells may be compromised. At least some progenitor-induced healing probably is mediated through increased sensitivity to VEGF and increases in MCP-1, and possibly modulation of angiopoietins.

Endothelial progenitor cell

10.1161/01.atv.0000203513.29227.6f

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Citations (112)

Sa1734 Evaluation of a Novel Full Covered Biodegradable Esophageal Stents in Porcine Esophagus Models

Gastroenterology (2015)

Yadong Feng Chunhua Jiao Ruihua Shi

10.1016/s0016-5085(15)31050-7

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Endoscopic nasojejunal feeding tube placement in patients with severe hepatopancreatobiliary diseases: a retrospective study of 184 patients.

PubMed (2010)

Feng Ji Zhao Jing-li Xi Jin Chunhua Jiao Yu-Yao Hu

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Citations (1)

[Preliminary exploration on submucosal tunneling endoscopic resection for middle and lower esophagus submucosal tumors].

PubMed (2013)

Chunhua Jiao Shuping Yang Xueliang Li Jing Ding Yinghong Xu

To evaluate the efficacy and safety of submucosal tunneling endoscopic resection (STER) in the treatment of middle and lower esophagus submucosal tumors (SMT) originating from muscularis propria (MP) layer.A total number of 33 esophagus submucosal tumor (SMT) originating from MP layer underwent tumor resection by STER after endoscopic ultrasonography (EUS) and CT examination at Endoscopy Center, Department of Gastroenterology, First Affiliated Hospital, Nanjing Medical University from March 2012 to March 2013. There were 17 males and 16 females with an age range of (50 ± 10) years. Their lesion size, lesion origin, pathology, operative duration and complication rate were analyzed.Among them, the origins were of submucosal (n = 4, 12.1%), superficial muscularis propria layer (SMP) (n = 18, 54.6%), deep muscularis layer (DMP) (n = 10, 30.3%) and serosa (n = 1, 3.0%). There were single tumor (n = 30, 90.9%), double tumors (n = 2, 6.1%) and triple tumors (n = 1, 3.0%). Except for 1 case of non-resected hemangioma, 36 operative specimens were examined pathologically, including 30 leiomyomas tumors (83.3%), 5 stromal tumors (GIST) (13.9%) and 1 lipoma tumor (2.8%). Thirty-two lesions were successfully resected by STER with a complete resection rate of 97.0%. Average lesion size was (1.7 ± 1.0) cm and average operative duration (49 ± 26) min. A number of (7.8 ± 2.5) hemostatic clips were used to close the mucosal incision site. Subcutaneous emphysema occurred in 3 patients (9.1%) while puncture and pneumothorax developed in one case (3.0%). All of them recovered uneventfully through conservative treatments.As a new safe, efficacious and feasible treatment for middle and lower esophagus submucosal tumors, STER may completely resect SMT and provide accurate histopathological evaluations. And it is feasible to regain the mucosal integrity of GI tract and prevent the occurrences of leakage and secondary infections.

Submucosa

Granular Cell Tumor

Stromal tumor

Muscularis mucosae

Endoscopic mucosal resection

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Citations (5)

Development of a biodegradable retinal cell graft for the treatment of retinal degenerative blindness

The FASEB Journal (2017)

Katherine N. Gibson‐Corley Kristan S. Worthington Jessica R. Thompson Emily Kaalberg Chunhua Jiao

Background Vision loss in inherited retinal diseases such as age‐related macular degeneration or retinitis pigmentosa result from death of the photoreceptor cells of the outer retina. Subretinal transplantation of induced pluripotent stem cell‐derived retinal progenitor cells (iPSC‐RPCs) has been found somewhat effective in restoring vision in blind animals, although survival of transplanted cells is poor. Polymeric support scaffolds have been shown to greatly enhance cellular survival and integration post‐transplantation, however attempts to materialize this concept have been largely unsuccessful for two reasons: 1) mechanical mis‐matching between material and the host retina and 2) improper cell packing . The goal of this study was to determine the ideal polymer fabrication parameters that promote optimal cell packing and biocompatibility. Methods Methacrylate‐functionalized PCL scaffolds were polymerized with either Irgacure 651 or Irgacure 369 using two‐photon polymerization. Compressive modulus was measured using dynamic mechanical analysis. Four‐month‐old Yucatan mini pigs (n=10, 5 with Irgacure 651 and 5 with Irgacure 369) received 5mm diameter scaffolds containing iPSC‐RPCs via subretinal transplantation. Animals were examined clinically at 1 month post‐surgery and were subsequently sacrificed for histological analysis of the retina. Results PCL scaffolds were successfully generated using both photoinitiators. Scaffolds generated using Irgacure 651 cured rapidly and had a tendency to curl. Both Irgacure 651‐ and Irgacure 369‐generated scaffolds supported attachment and survival of human iPSC‐RPCs and both were successfully transplanted into the porcine subretinal space. At one month post‐transplantation, 50% of the retinas that received the Irgacure 651 scaffolds were attached. In the animals that received Irgacure 369 scaffolds all of the retinas reattached with no signs of ocular inflammation. In these animals retinal integrity, including maintenance of photoreceptor outer segments, was maintained. Conclusion PCL scaffolds support the maintenance of human iPSC‐RPCs and were biocompatible in the pig retina. These scaffolds may be ideal for retinal transplantation. Support or Funding Information Wynn Institute for Vision Research

Retinal regeneration

Biocompatibility

10.1096/fasebj.31.1_supplement.333.1

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