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Ghrelin reduces A-type potassium channels in nigral dopaminergic neurons via PKC but not PKA pathway

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Ghrelin reduces A-type potassium channels in nigral dopamine...

Mori Cortex extract ameliorates nonalcoholic fatty liver disease( NAFLD) and insulin resistance in high-fat-diet/streptozotocininduced type 2 diabetes in rats

中国神经科学学会第十二届全国学术会议

作者： Bao Xue Limin Shi Junxia Xie Department of Physiology Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders and State Key Disciplines: The department of Physiology Qingdao University

Objective The excitability of dopaminergic neurons in the substantia nigra pars compacta(SNc) that supply the striatum with dopamine determines the function of nigrostriatal system for motor coordination. Our previous studies showed that the braingut peptide ghrelin could enhance pacemaker firing of nigral dopaminergic neurons by inhibiting voltage-gated potassium Kv7/KCNQ/M-channels. However, whether the other potassium channels are also involved in the ghrelin-induced excitability of dopaminergic neurons still remain unclear. In this study, we focus on A-type potassium channels(I), which has a wide expression on dopaminergic neurons and play a key role in pacemaker control. Method Brain slices of the SNc were prepared from C57 BL/6 mice of postnatal 15-20 days. The effects of ghrelin on discharge frequency and I current of dopaminergic neurons were observed by whole cell patch clamp technique. To examine whether the effects of ghrelin on I was mediated by activation of PKA or PKC pathway, a slective PKA inhibitor H89 or PKC inhibitor GF109203 X was applied before the administration of ghrelin. Results Ghrelin(100 n M) can significantly increase the discharge frequency of dopaminergic neurons and inhibit the amplitude of I current. Application of either H89(1mM) or GF109203 X(5mM) alone had no effect on I;However, GF109203 X abolished ghrelin-induced inhibition of I. In addition, GF109203 X and the I specific blocker 4-AP could occlude the excitatory effects of ghrelin. Conclusion These results demonstrated that inhibition of I may contribute to the ghrelin-induced excitation of dopaminergic neurons. Ghrelin reduces I by activation of PKC but not PKA pathway.

关键词： Ghrelin A-type potassium channels dopaminergic neurons Protein kinase C

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Chinese Journal of Natural Medicines 2018年第6期16卷 411-417页

作者： MA Li-Li YUAN Yan-Yan ZHAO Ming ZHOU Xin-Rong Tashina Jehangir WANG Fu-Yan XI Yang BU Shi-Zhong Runliang Diabetes Laboratory Diabetes Research Center School of Medicine Ningbo University

Nonalcoholic fatty liver disease(NAFLD) and type 2 Diabetes Mellitus(T2 DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2 DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2 DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract(MCE; 10 g·kg-1·d-1) lowered the blood lipid levels and reversed insulin resistance(IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1 c(SREBP-1 c) and carbohydrate-responsive element binding protein(Ch REBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and m RNA expression levels of SREBP-1 c and Ch REBP. In conclusion, down-regulation of SREBP-1 c and Ch REBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2 DM associated with NAFLD.

关键词： Mori Cortex extract Type 2 diabetes Non-alcoholic fatty liver Sterol receptor element-binding protein-It Carbohy-drate-responsive element binding protein

Mechanisms of Qi-blood circulation and Qi deficiency syndrome in view of blood and interstitial fluid circulation

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Journal of Traditional Chinese Medicine 2013年第4期33卷 538-544页

作者： Wei Yao Hongwei Yang Guanghong Ding Department of Mechanics and Engineering Science Fudan University Shanghai Research Center of Acupuncture

OBJECTIVE: Based on comparison between fundamental theories of Traditional Chinese Medicine (TCM) and Western Medicine (WM) and modern scientific research on meridians, we find that "Qi" in TCM is closely related to tissue fluid. In this study, the essence of Qi is explored in the view of circulation of blood and interstitial fluid. METHODS: Because the concept of Qi is complicated, Qi deficiency syndrome (QDS) is chosen to probe the relationship between of Qi deficiency and Qi-blood circulation (QBC). We analyze Qi-blood theory in terms of WM, set up a hemodynamic model to describe QBC, and review clinical research on QDS in the view of blood-interstitial fluid circulation. RESULTS: QDS is caused by imbalances of substance exchanges between blood and interstitial fluid, leading to an increase in the interstitial liquid volume or a decrease in nutrients and retention ofmetabolic wastes in interstitial fluid. CONCLUSION: This study describes the essence of Qi, providing support for further research on theories of Qiand Qi-blood circulation inTCM.

关键词：循环机制组织液气血血液虚证中国传统医学动力学模型基础理论

Fast-tracking regenerative medicine for traumatic brain injury

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Neural Regeneration Research 2020年第7期15卷 1179-1190页

作者： Brooke Bonsack Matt Heyck Chase Kingsbury Blaise Cozene Nadia Sadanandan Jea-Young Lee Cesar V. Borlongan center of Excellence for Aging and Brain Repair University of South Florida College of Medicine

Traumatic brain injury remains a global health crisis that spans all demographics,yet there exist limited treatment options that may effectively curtail its lingering *** brain injury pathology entails a progression from primary injury to inflammation-mediated secondary cell *** this inflammation as a means of ameliorating the greater symptomology of traumatic brain injury has emerged as an attractive treatment *** this review,we recapitulate and evaluate the important developments relating to regulating traumatic brain injury-induced neuroinflammation,edema,and blood-brain barrier disintegration through pharmacotherapy and stem cell *** these studies of stand-alone treatments have yielded some positive results,more therapeutic outcomes have been documented from the promising area of combined drug and stem cell *** the facilitatory properties of certain pharmaceuticals with the anti-inflammatory and regenerative effects of stem cell transplants creates a synergistic effect greater than the sum of its *** burgeoning evidence in favor of combined drug and stem cell therapies warrants more elaborate preclinical studies on this topic in order to pave the way for later clinical trials.

关键词： clinical trials combined therapy inflammatory cascade neuroinflammation neuroprotection neurotrauma pharmacotherapy preclinical studies secondary cell death stem cells

Boosting of the enhanced permeability and retention effect with nanocapsules improves the therapeutic effects of cetuximab

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Cancer Biology & Medicine 2020年第2期17卷 433-443页

作者： Chao Yang Yanli Tan Hongzhao Qi Junhu Zhou Lixia Long Qi Zhan Yunfei Wang Xubo Yuan Chunsheng Kang Department of Neurosurgery Tianjin Medical University General HospitalTianjin 300052China Tianjin Neurological Institute Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous SystemMinistry of Education and Tianjin CityTianjin 300052China Department of Pathology Affiliated Hospital of Hebei UniversityBaoding 071000China Department of Pathology Hebei University Medical CollegeBaoding 071000China Tianjin Key Laboratory of Composite and Functional Materials School of Material Science and EngineeringTianjin UniversityTianjin 300072China institute for Translational Medicine Qingdao UniversityQingdao 266021China Affiliated Cancer Hospital 8l Institute of Guangzhou Medical University Guangzhou 510095China

Objective:The introduction of therapeutic antibodies(tAbs)into clinical practice has revolutionized tumor treatment strategies,but their tumor therapy efficiency is still far below expectations because of the rapid degradation and limited tumor accumulation of ***:We developed a nanocapsule-based delivery system to induce the self-augmentation of the enhanced permeability and retention(EPR)*** system constantly penetrated across the blood-tumor barrier into the tumor while avoiding the attack of tAbs by the immune *** biodistribution and therapeutic effect were tested with single dose administration of nanocapsule-tAbs in ***:The accumulation of Nano(cetuximab)within subcutaneous PC9 tumors was gradually enhanced over 6 days after single dose administration,which was contrary to the biodistribution of native ***(cetuximab)accumulated in tumor tissues via the EPR effect and released *** released cetuximab acted on vascular endothelial cells to destroy the blood-tumor barrier and induce self-augmentation of the EPR effect,which in turn contributed to further tumor accumulation of long-circulating Nano(cetuximab).Compared with single dose administration of native cetuximab,Nano(cetuximab)showed an effective tumor suppressive effect for 3 ***:The nanocapsule-based delivery system efficiently delivered tAbs to tum or tissues and released them to boost the EPR effect,which facilitated further tumor accumulation of the *** novel self-augmentation of the EPR effect facilitated by the biological characteristics of tAbs and nanotechnology contributed to the improvement of the therapeutic effect of tAbs,and stimulated new ideas for antibody-based tumor therapy.

关键词： Endothelial cells EPR effect nanocapsule single dose administration therapeutic antibody

Characteristics of homologous recombination repair pathway genes mutation in ovarian cancers

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Cancer Innovation 2022年第3期1卷 220-228页

作者： Zongbi Yi Min Chen Shaoxing Sun Chunxu Yang Zijie Mei Hui Yang Qingming Xiang Hui Qiu Department of Radiation and Medical Oncology Hubei Key Laboratory of Tumour Biological BehaviorsHubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhanChina

Background:Few studies have investigated the characteristics of non‐BRCA homologous recombination repair(HRR)pathway somatic mutations,and the impact of these mutations on efficacy of treatment in ovarian cancer patients is not ***,we conducted this study to analyze the frequency and spectrum of somatic mutations in HRR pathway genes in patients with ovarian cancer and to examine the relationships between somatic mutations in HRR pathway genes and their effects on the efficacy of platinum‐based ***:We performed targeted sequencing of 688 genes related to the occurrence,development,treatment,and prognosis of solid *** mutations were identified by paired analysis of tumor tissue and germline DNA in blood ***:A total of 38 patients with ovarian cancer were included in the study,and 35(92.1%)patients were diagnosed with high‐grade serous *** patients exhibited somatic mutations in the tumor tissue *** commonly mutated genes were TP53(73.7%),BRCA2(55.3%),NF1(52.6%),BRCA1(47.4%),and CDH1(47.4%).Overall,71.1%of the patients exhibited mutation in at least one HRR pathway *** most frequently altered HRR genes were BRCA2(55.3%),followed by BRCA1(47.4%),ATM(44.7%),BARD1(42.1%),and CHEK1(36.8%).The median progression‐free survival(PFS)in patients with HRR pathway mutation was 36.0 months compared with 13.6 months in patients with no HRR pathway mutation(hazard ratio[HR],0.25;95%confidence interval[CI],0.08–0.77;p=0.016).Patients harboring BRCA1/2 and/or CDK12 mutations displayed a longer PFS(median,36.0 months)compared with patients with no BRCA1/2 or CDK12 mutation(median,13.6 months;HR,0.21;95%CI,0.07–0.61;p=0.004).In multivariate analysis Cox proportional hazards models,after adjustment for tumor stage at diagnosis and histology of initial diagnosis,patients with HRR pathway mutation had a longer PFS than patients with HRR wild‐type genes(p=0.006).Conclusions:HRR pathway somatic mutations are common in

关键词： ovarian cancer genetic testing somatic mutation homologous recombination repair platinum-based therapy

Familial Eosinophilia with Cardiac Involvement: A Distinct Subset?

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Open Journal of Immunology 2023年第3期13卷 86-97页

作者： Puthalath Koroth Raghuprasad Sudhir Amaram Department of Internal Medicine Medical Center Hospital Odessa Texas USA

In this paper we present a five-generation kindred with familial eosinophilia, associated with valvular heart disease in one of seven members of the second generation, four of sixteen members of the third generation, four of thirty-one members of the fourth generation, and two of twenty members of the fifth generation;the clinical features of the two members of the first generation are unavailable. Of a total of 48 members, 26 had eosinophilia, with counts ranging from 1761 to 6045 cells/mm3, with apparent autosomal dominant propagation;this confirms the experience of the authors of previous studies on this condition. Genetic analysis on eight members, which we reported in an earlier paper [1], revealed a pericentric inversion of chromosome 10 in two members. The entity of Familial Eosinophilia has been generally considered benign. However, the clinical presentation of this kindred was unusual in that valvular and endocardial damage, was frequent findings, without apparent involvement of the other organs and tissues. Mitral valve damage leading to both stenosis and regurgitation and requiring mitral valve replacement was noted in the index patient. This unique presentation may suggest that in patients with mitral valve disease, if blood eosinophilia is noted, it could point to a non-rheumatic etiology, thus a possible opportunity for treatment to prevent further damage to the heart. This recommendation may be even more timely, as many effective treatments are now available to treat even high-grade hypereosinophilia.

关键词： Familial Eosinophilia Autosomal Dominant Propagation High-Grade Hypereosinophilia

Advances in Mathematical Modeling of NFκB Signal Transduction in Mammals

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Agricultural Biotechnology 2013年第4期2卷 47-49,52页

作者： Jinshan ZHAO Ke JIANG Zhenghao DAI Xiaoli REN Yumei WANG Yongping JIANG Mingtuan LIU Yonglian DAI Lele HOU Hegang LI qingdao Institute of Animal Science and Veterinary Medicine Laixi Municipal Bureau of Animal Husbandry and Veterinary Wangcheng Supervision Station for Animal Epidemic Prevention and Animal Product Quality of Laixi City Rizhuang Agricultural Service center of Laixi City

NFκB is a basic transcription factor of cell signal transduction in mammals. Mathematical modeling can be used to simulate NFκB signal transduction and investigate the molecular mechanism. The initial IKB-NFκB signal transduction model emphasized the effects of negative feedback on NFκB temporal dynamics and gene expression control, while subsequent studies are concentrated on other feedback loops, input-output behaviors of modules, crosslinking of several NFκB activation paths and NFκB oscillation. Computer technology will continue to contribute to studies of NFKB signaling pathway. Finally, several potential development trends were discussed in this paper.

关键词： NFκB Signal transduction Mathematical modeling

Environmental selection and evolutionary process jointly shape genomic and functional profiles of mangrove rhizosphere microbiomes

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mLife 2023年第3期2卷 253-266页

作者： Xiaoli Yu Qichao Tu Jihua Liu Yisheng Peng Cheng Wang Fanshu Xiao Yingli Lian Xueqin Yang Ruiwen Hu Huang Yu Lu Qian Daoming Wu Ziying He Longfei Shu Qiang He Yun Tian Faming Wang Shanquan Wang Bo Wu Zhijian Huang Jianguo He Qingyun Yan Zhili He State Key Laboratory for Biocontrol Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)School of Environmental Science and EngineeringEnvironmental Microbiomics Research CenterSun Yat‐sen UniversityGuangzhouChina Institute of Marine Science and Technology Shandong UniversityQingdaoChina College of Forestry&Landscape Architecture South China Agricultural UniversityGuangzhouChina Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) School of Marine ScienceSun Yat‐sen UniversityGuangzhouChina Department of Civil and Environmental Engineering The University of TennesseeKnoxvilleTennesseeUSA Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems School of Life SciencesXiamen UniversityXiamenChina Xiaoliang Research Station for Tropical Coastal Ecosystems and Key Laboratory of Vegetation Restoration and Management of Degraded Ecosystems South China Botanical GardenChinese Academy of SciencesGuangzhouChina School of Life Sciences Sun Yat‐sen UniversityGuangzhouChina

Mangrove reforestation with introduced species has been an important strategy to restore mangrove ecosystem ***,how such activities affect microbially driven methane(CH4),nitrogen(N),and sulfur(S)cycling of rhizosphere microbiomes remains *** understand the effect of environmental selection and the evolutionary process on microbially driven biogeochemical cycles in native and introduced mangrove rhizospheres,we analyzed key genomic and functional profiles of rhizosphere microbiomes from native and introduced mangrove species by metagenome sequencing *** with the native mangrove(Kandelia obovata,KO),the introduced mangrove(Sonneratia apetala,SA)rhizosphere microbiome had significantly(p<0.05)higher average genome size(AGS)(5.8 vs.5.5 Mb),average 16S ribosomal RNA gene copy number(3.5 vs.3.1),relative abundances of mobile genetic elements,and functional diversity in terms of the Shannon index(7.88 vs.7.84)but lower functional potentials involved in CH4 cycling(e.g.,mcrABCDG and pmoABC),N2 fixation(nifHDK),and inorganic S cycling(dsrAB,dsrC,dsrMKJOP,soxB,sqr,and fccAB).Similar results were also observed from the recovered Proteobacterial metagenome-assembled genomes with a higher AGS and distinct functions in the introduced mangrove ***,salinity and ammonium were identified as the main environmental drivers of functional profiles of mangrove rhizosphere microbiomes through deterministic *** study advances our understanding of microbially mediated biogeochemical cycling of CH_(4),N,and S in the mangrove rhizosphere and provides novel insights into the influence of environmental selection and evolutionary processes on ecosystem functions,which has important implications for future mangrove reforestation.

关键词： average genome size functional potential mangrove rhizosphere metagenome metagenome-assembled genome