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Adipose-derived stem cells in stroke treatment： translational possibility and mechanism

Chinese Medical Journal 2014年第20期127卷 3657-3663页

作者： Zhou Fei Gao Shan'e Sun Chenxi Cao Limei Ren Haiyan Li Qiang Wang Guangming Dong Chuanming Zhu Liang Yang Danjing Wang Xianli Xu Jun Chen Xu department of Neurology Shanghai Eighth People's Hospitalaffiliated to Jiangsu University Shanghai 200233 China department of Neurology East Hospital Tongji University Schoolof Medicine Shanghai 200120 China

Stroke has become one of the secondary worldwide mortal diseases that burdens the family and the society both emotionally and economically. The announcement of China＇s Ministry of Health in 2008 showed that stroke had been the first cause of death in urban and rural residents.1.2 Traditional therapies such as thrombolysis, anti-platelets, and rehabilitation showed limited effects. Replacement therapy with stem cells promises to be a good solution due to its possible thorough therapy for the damaged brain area, reconstruction of neuronal circuitry, and probable long-term efficacy. Previous studies demonstrated that stem ceils have played crucial roles in various kinds of tissue repair and immune disorders such as cardiovascular diseases, skeletal diseases, arthritis diseases, and lupus erythematodes.37 Evidence from lab experiments and clinical trials implies that adipose-derived stem cells （ADSCs） would be a feasible and ideal cell therapy source because of their multi-differentiation potentials, easy collection, low invasion to donor patients, rapid in vitro amplification, reliable biosafety, non-immunogenicity, privileged immune modulation, and escaping from ethical issues.8-12： Data on neurological disease treatment found that ADSCs transplantation protected against acute inflammatory injury, delayed neuron degeneration, and improved neurological behaviors.12-15 Previously, the detailed mechanisms by which transplanted ADSCs induce functional recovery for stroke treatment are far from being clearly demonstrated. Some proposed reasonable mechanisms just stayed at the level of explanation and hypothesis due to the absence of solid experimental evidence.13-14 In this article, we analyzed the previous data to figure out some new paths or ideas which may do favor to future translational clinical studies.

关键词： adipose-derived stem cells stroke stem cell transplantation

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Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1322-1338页

作者： Fengfeng Li Man Jiang Minghui Ma Xuyang Chen Yidan Zhang Yixin Zhang Yuanyuan Yu Yunfeng Cui Jiahui Chen Hui Zhao Zhijie Sun Deli Dong department of Pharmacology(the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150086China Translational medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbin Medical UniversityHarbin 150086China department of Pharmacology China Pharmaceutical UniversityNanjing 211198China

Lipid metabolism disorders contribute to hyperlipidemia and hepatic *** is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic *** is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety *** found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in Hep G2 *** administration of nitazoxanide inhibited high-fat diet(HFD)-induced increases of liver weight,blood and liver lipids,and ameliorated HFD-induced renal lipid accumulation in *** significantly improved HFD-induced histopathologic changes of hamster *** the hamsters with pre-existing hyperlipidemia and hepatic steatosis,nitazoxanide also showed therapeutic *** administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet(WD)-induced hepatic steatosis in Apoe-/-*** present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

关键词： Nitazoxanide Tizoxanide Hyperlipidemia Hepatic steatosis AMPK Autophagy SQSTM1/P62 Mitochondrial uncoupling

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Safe upper limit of intermittent hepatic inflow occlusion for liver resection in cirrhotic rats

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World Journal of Gastroenterology 2001年第5期7卷 713-717页

作者： Dao-Xiong Lei~(1,2) Cheng-Hong Peng~1 Shu-You Peng~1 Xian-Chuan Jiang~1 Yu-Lian Wu~1 Hong-Wei Shen~1 1 department of Surgery,Second Affiliated Hospital,Zhejiang University School of medicine,Hangzhou 310009,Zhejiang Province,China2 department of Surgery,Zhongnan Hospital,Wuhan University School of medicine,Wuhan 430071,Hubei Province,China department of Surgery Zhongnan Hospital Wuhan University School of Medicine Wuhan 430071 Hubei Province China. Nicholaslei@***

AIM: To evaluate the effects of varying ischemic durations on cirrhotic liver and to determine the safe upper limit of repeated intermittent hepatic inflow occlusion. METHODS: Hepatic ischemia in cirrhotic rats was induced by clamping the common pedicle of left and median lobes after non-ischemic lobes resection. The cirrhotic rats were divided into six groups according to the duration and form of vascular clamping: sham occlusion (SO), intermittent occlusion for 10 (IO-10), 15(IO-15), 20(IO-20) and 30(IO-30) minutes with 5 minutes of reflow and continuous occlusion for 60 minutes (CO-60). All animals received a total duration of 60 minutes of hepatic inflow occlusion. Liver viability was investigated in relation of hepatic adenylate energy charge (EC). Triphenyltetrazollum chloride (TTC) reduction activities were assayed to qualitatively evaluate the degree of irreversible hepatocellular injury. The biochemical and morphological changes were also assessed and a 7-day mortality was observed. RESULTS: At 60 minutes after reperfusion following a total of 60 minutes of hepatic inflow occlusion, EC values in IO-10 (0.749 +/- 0.012) and IO-15 (0.699 +/- 0.002) groups were rapidly restored to that in SO group (0.748 +/- 0.016), TTC reduction activities remained in high levels (0.144 +/- 0.002 mg/mg protein, 0.139 +/- 0.003 mg/mg protein and 0.121 +/- 0.003 mg/mg protein in SO, IO-10 and IO-15 groups, respectively). But in IO-20 and IO-30 groups, EC levels were partly restored (0.457 +/- 0.023 and 0.534 +/- 0.027) accompanying with a significantly decreased TTC reduction activities (0.070 +/- 0.005 mg/mg protein and 0.061 +/- 0.003 mg/mg protein). No recovery in EC values (0.228 +/- 0.004) and a progressive decrease in TTC reduction activities (0.033 +/- 0.002 mg/mg protein) were shown in CO-60 group. Although not significantly different, the activities of the serum aspartate aminotransferase (AST) on the third postoperative day (POD(3)) and POD(7) and of the serum alanine

关键词： Alanine Transaminase Animals Aspartate Aminotransferases Blood Loss, Surgical Disease Models, Animal Ischemia Liver Circulation Liver Cirrhosis, experimental Male Rats Rats, Sprague-Dawley Reperfusion Research Support, Non-U.S. Gov't Surgical Instruments Time Factors

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Role of connective tissue growth factor in experimental radiation nephropathy in rats

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Chinese Medical Journal 2008年第19期121卷 1925-1931页

作者： LIU Dian-ge WANG Tie-min department of Nephrology Zhongda Hospital Southeast University School of Medicine Nanjing Jiangsu 210009 China department of Pediatrics Fourth Clinical Hospital HarbinMedical University Harbin Heilongjiang 150001 China

Background Connective tissue growth factor （CTGF） is a potent fibrogenic cytokine which has been associated with progressive glomerulosclerosis and tubulointerstitial fibrosis. We investigated the role of CTGF on the progression of a rat model of radiation nephropathy. Methods The model of radiation nephropathy in rats was established as follows： control group （n=12）, underwent only laparotomy; irradiated group （n=-20）, underwent a laparotomy, then the rats were subjected to a single dose 25 Gy X-ray to the kidneys. The rats were followed up one, three, six and nine months after renal exposure to radiation. Results Renal dysfunction was noted early in irradiated rats. Histological analysis showed focal glomerular sclerotic lesions at an early stage after irradiation. Radiation-induced glomerular and tubulointerstitial injuries were particularly severe the sixth month after irradiation as compared to the control group （P 〈0.01）. By immunohistochemistry, increased expression of CTGF was noted in the irradiated kidneys, which began to increase from the first month after irradiation, and remained significantly higher at the sixth and ninth month after irradiation （P 〈0.01）. Upon Western blot analysis CTGF protein expression showed an increase in the radiation treated kidneys compared with the control rats. The expression of CTGF closely correlated with the progression of radiation nephropathy. The expression of α-smooth muscle actin, vimentin, type Ⅲ collagen and type Ⅳ collagen was also high in the irradiated kidney as compared to control rat kidneys （P 〈0.05）, and was most severe at the sixth and ninth month after irradiation （P 〈0.01）. By double immunostaining, CTGF expressing cells were found to be α-SMA-positive myofibroblasts and vimentin-positive tubular epithelial cells. Glomerular expression of CTGF closely correlated with the glomerular expression of a-SMA （r=0.628, P 〈0.01）, vimentin （r=0.462, P 〈0.05） and accumulation of type IV collagen （r=0.584, P 〈0.01） i

关键词： connective tissue growth factor collagen radiation nephropathy glomerulosclerosis tubulointerstitial fibrosis

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SOME OF THE IMMUNOLOGICAL PARAMETERS OF GASTRIC CARCINOMA

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Medical Bulletin of Shanghai Jiaotong University 1990年第1期13卷 14-21页

作者：陆汉明金礼春 department of Internal medicine Xinhua Hospital SSMU Shanghai Tongji University Hospital Shanghai

In patients with gastric carcinoma the determination of the activities of some cellular and humoral factors may reflect the immunological state of the patient, the stage and extent of the disease, and help estimate the effects of treatment and prognosis. Moreover, experimental studies and preliminary clinical trials of some of these cellular elements and humoral factors in the treatment of gastric carcinoma have opened a new field of adoptive immunotherapy.

关键词： gastric carcinoma T lymphocyte subpopulations K cell NK cell LAK cell interleukin-2 secretory IgA oncoantigens

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Plastic Additives Decrease Agrin-Induced Acetylcholine Receptor Clusters and Myotube Formation in C2C12 Skeletal Muscle Cell Culture

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CellBio 2015年第1期4卷 12-22页

作者： Kelsey Neufeld Kelly Ezell Wade A. Grow department of Anatomy Arizona College of Osteopathic Medicine Midwestern University Glendale AZ USA

Common additives in plastics such as bisphenol A (BPA) or phthalates like di-(2-ethylhexyl) phthalate (DEHP) are environmental estrogens that have been shown to be endocrine disruptors in some experimental animal models. This project used the C2C12 cell culture model to examine how exposure to BPA or DEHP affects two aspects of skeletal muscle development, the fusion of myoblasts into myotubes and agrin-induced clustering of acetylcholine receptors (AChRs). During myotube formation AChRs cluster spontaneously. Treatment with motor neuron derived agrin increases the frequency of AChR clusters through an agrin signaling pathway that also clusters other postsynaptic components of the neuromuscular synapse. For this project C2C12 cells were exposed to BPA or DEHP while myoblasts fused into myotubes. After exposure to 10 μM BPA or 100 μM DEHP the frequency of agrin-induced AChR clusters decreased. In addition, myotube formation decreased as a higher percentage of nuclei remained in myoblasts. Furthermore, BPA or DEHP reduced the amount of the myogenic regulatory factor myogenin. This suggests that BPA and DEHP decrease AChR clustering by reducing myogenin. Moreover, plastic additives like BPA and DEHP may pose a risk for skeletal muscle development in humans.

关键词： AChR Agrin Bisphenol A (BPA) C2C12 Di-(2-Ethylhexyl) Phthalate (DEHP) Myogenin

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Visual acuity evaluation in children with hydrocephalus:An electrophysiological study with sweep visual evoked potential

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World Journal of Neuroscience 2012年第1期2卷 36-43页

作者： Silvana Alves Pereira Marcelo Fernandes Costa Nucleo de Neurociencias e Comportamento Universidade de Sao PauloSao PauloBrazil department Psicologia experimental Instituto de PsicologiaUniversidade de Sao PauloSao PauloBrazil

The objective was to measure the visual acuity (VA) of children with the diagnosis of hydrocephalus with or without peritoneal-ventricular shunt (PVS). A total of 55 children were included in the study (34 Female), with an age range of 0 to 291 weeks. The VA was measured by the sweep visual evoked potential technique. Of those with a PVS, in 31 the ventricular valve was inserted before 15 days after the diagnosis whereas in 14 the ventricular valve was inserted after 15 days. The sweep VEP was performed in all children, 95 exams (94%) were abnormal and only 6 were normal. There was a statistical difference in the VA between children with a PVS inserted before 15 days of the diagnosis and children with a PVS after 15 days (p = 0.038) or those without a shunt (p = 0.031). Children with no complications of the PVS had a better VA as compared to those with shunt complications (p < 0.001). In the group of children with complications, again those who had a shunt inserted be-fore 15 days had better VA results in com- parison to those in whom the shunt was inserted after 15 days (p = 0.029). No statistical difference in the VA was found between children without the PVS and with those in which the shunt was inserted after 15 days of the di-agnosis of hydrocephalus (p = 0.699). We conclude that the delayed insertion of the PVS may compromise the visual development of these children.

关键词： Hydrocephalus Ventricular Shunt Visual Acuity Sweep Visual Evoked Potential Visual Development

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Human umbilical cord-derived mesenchymal stem cells: Current trends and future perspectives

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Asian pacific Journal of Reproduction 2019年第3期8卷 93-101页

作者： Diego Rossetti Silvia Di Angelo Antonio David Lukanovi Tina Kunic Camilla Certelli Carmine Vascone Zaki Sleiman Unit of Gynecology and Obstetrics Desenzano del Garda HospitalSection of GavardoGavardoBresciaItaly department of Biomedicine and Prevention Section of Gynecology and ObstetricsUniversity of Rome Tor VergataRomeItaly department of Obstetrics and Gynecology University Medical Center LjubljanaLjubljanaSlovenia Gynecologic Oncology Unit Department of Experimental Clinical Oncology"Regina Elena"National Cancer InstituteRomeItaly Pineta Grande Hospital Castel VolturnoCasertaItaly Surgical Research Laboratory Medical SchoolSaint Joseph UniversityDamas StreetBeirutLebanon department of Obstetrics and Gynaecology Lebanese American UniversityBeirutLebanon

Among resources of mesenchymal stem cells, human umbilical cord appears to be a rising source capable of differentiating into all germ layers, reaching and repairing lesion areas, and promoting wound repair, and it has also the capacity to influence the immune response. Human umbilical cord-derived mesenchymal stem cells are considered to be an optimal resource compared with other mesenchymal stem cells sources because they require a non-invasive recovery. All these characteristics allow their use in heterogeneous applications. Human umbilical cord-derived mesenchymal stem cells can regenerate tissues, stimulate angiogenesis, modulate inflammatory pathway signals and recruit endogenous stem cell. Human umbilical cord-derived mesenchymal stem cells suppress mitogen-induced signals and modulate the activation and proliferation of several immune cells, modifying lymphocyte phenotypes activity. In culture, human umbilical cord-derived mesenchymal stem cellss show the capacity to create several tissues such as bone, cartilage, and fat. Human umbilical cord-derived mesenchymal stem cells can be isolated from the different compartments of umbilical cord and processed by using different techniques. Clinical applications of human umbilical cord-derived mesenchymal stem cells include graft-versus-host disease, autoimmune diseases such as Sj?gren's syndrome and diabetes mellitus types 1 and 2, gynecological disorders like endometriosis. Recent studies have shown possible application on rheumatoid arthritis, osteoarthritis, and neuronal degenerative diseases. This review is focused on the resources, molecular profiles, propriety, in vitro characterizations, clinical applications and possible future usage of human umbilical cord-derived mesenchymal stem cells.

关键词： Human umbilical cord stem cells Immunomodulation Cryopreservation Stem therapy

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Molecular targeting therapy using bevacizumab for peritoneal metastasis from gastric cancer

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World Journal of Critical Care medicine 2013年第4期2卷 48-55页

作者： Keishiro Aoyagi Kikuo Kouhuji Motoshi Miyagi Junya Kizaki Taro Isobe Kousuke Hashimoto Kazuo Shirouzu department of Surgery Kurume University School of Medicine Kurume Fukuoka 830-0011 Japan

AIM: To clarify the significance of vascular endothelial growth factor(VEGF) in peritoneal metastasis from gastric cancer, using the gastric cancer cell line MKN-45 compared with the high potential peritoneal dissemination gastric cancer cell line MKN-45 P. METHODS: The supernatant of culture medium of MKN-45 cells or MKN-45 P cells was collected and the concentrations were measured of various cytokines, matrix metalloproteinases, growth factor and angiogenic factors, including VEGF. We performed an initial pilot study to explore whether bevacizumab, a humanized monoclonal antibody against VEGF, had any suppressive effect on the peritoneal dissemination from gastric cancer in an experimental nude mouse modelof peritoneal metastasis. RESULTS: The concentrations of interleukin-6(IL-6), IL-8, VEGF and matrix metalloproteinase-2 protein in the culture supernatant were each significantly higher than each of those for MKN-45. In the in vivo study, the volume of ascites and the mitotic index were significantly lower in the therapy group than in the nontherapy group. The survival curve of the therapy group was significantly higher than that of the non-therapy group. These results suggested that VEGF was correlated with peritoneal metastasis from gastric cancer. CONCLUSION: Findings suggested that bevacizumab for inhibiting VEGF could suppress peritoneal dissemination from gastric cancer.

关键词： Gastric cancer Peritoneal metastasis Vascular endothelial growth factor MKN-45P Bevacizumab

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Can albumin administration relieve lung injury in trauma/hemorrhagic shock?

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World Journal of Gastroenterology 2006年第42期12卷 6884-6888页

作者： Zuo-Bing Chen Zi-Wei Wang Chen-Yan Ding Jian-Hua Yan Yuan Gao Yun Zhang Lin-Mei Ni Yong-Qing Zhou department of Emergency Surgery First Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310003 Zhejiang Province China

AIM: To study the effect of albumin administration on lung injury in trauma/hemorrhagic shock (T/HS). METHODS: Sixty experimental animals were randomly divided into three groups: rats undergoing laparotomy without shock (T/SS); rats with T/HS and resuscitation with blood plus twice the volume of shed blood as Ringer’s lactate (RL), and rats with T/HS and resuscitation with blood plus additional 3 mL of 50 g/L human albumin. Expression of polymorphonuclear neutrophil (PMN) CD11b/CD18, intercellular adhesion molecule-1 (ICAM-1) of jugular vein blood and the severity of lung injuries [determined mainly by measuring activity of lung tissue myeloperoxidase (MPO) and lung injury score (LIS)] were measured after a 3-h recovery period. RESULTS: All three groups showed a significant difference in the expressions of CD11b/CD18, ICAM-1, and severity of lung injury. The expressions of CD11b/ CD18 in T/SS group, T/HS + RL group, T/HS + albumin group were 17.76% ± 2.11%, 31.25% ± 3.48%, 20.36% ± 3.21%, respectively (F = 6.25, P < 0.05). The expressions of ICAM-1 (U/mL) in T/SS group, T/ HS + RL group, T/HS + albumin group were 258.76 ± 98.23, 356.23 ± 65.6, 301.01 ± 63.21, respectively (F = 5.86, P < 0.05). The expressions of MPO (U/g) in T/SS group, T/HS + RL group, T/HS + albumin group were 2.53 ± 0.11, 4.63 ± 1.31, 4.26 ± 1.12, respectively (F = 6.26, P < 0.05). Moreover, LIS in T/HS + RL group, T/HS + albumin group was 2.62 ± 0.23, 1.25 ± 0.24, respectively. The expressions of CD11b/CD18, ICAM-1 and MPO in T/HS + RL group were significantly increased compared to T/SS group (P = 0.025, P = 0.036, P = 0.028,respectively). However, administration of 3 mL of 50 g/L albumin significantly down-regulated the expressions of CD11b/CD18, ICAM-1 and lung injury index (MPO and LIS) when compared with the T/HS + RL rats (P = 0.035, P = 0.046, P = 0.038, P = 0.012, respectively). CONCLUSION: The infusion of albumin during resuscitation period can protect lung from injury and decrease the e

关键词： Albumin CD11b/CD18 Intercellular adhesion molecule-1 Lung injury Trauma/hemorrhagic shock

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