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World Journal of Gastroenterology 2008年第41期14卷 6347-6354页

作者： Daisuke Kohno Shigetomo Suyama Toshihiko Yada division of Integrative physiology Department of Physiology Jichi Medical University School of Medicine Yakushiji 3311-1 Shimotsuke

AIM： To explore the mechanism for interactions of leptin with ghrelin and orexin in the arcuate nucleus （ARC） activating neuropeptide Y （NPY） neurons during physiological regulation of feeding, METHODS： Single neurons from ARC of adult rats with matured feeding function were isolated. [Ca2＋]i was measured to monitore their activities. The time course of leptin effects on ghrelin-induced versus orexin-induced [Ca2＋]i increases in NPY neurons was studied. RESULTS： Administration of ghrelin or orexin-A at 101~ mol/L increased cytosolic Ca2~ concentration （[Ca2＋]~） in NPY neurons isolated from the ARC of adult rats. Upon administration of leptin at 10^-14-10^-12 mol/L, ghrelin-induced [Ca2＋]i increases were initially （〈 10 min） inhibited but later restored, exhibiting a transient pattern of inhibition. In contrast, orexin-induced [Ca2＋]i increases were inhibited by leptin in a long- lasting manner. Furthermore, a prior administration of leptin inhibited orexin action but not ghrelin action to increase ICa 2＋li, CONCLUSION： Leptin counteracted ghrelin effects transiently and orexin effects long-lastingly in NPY neurons. The transient property with which leptin counteracts ghrelin action in NPY neurons may allow the fasting-associated increase in ghrelin levels to activate NPY neurons in the presence of physiological leptin and to stimulate feeding.

关键词： Leptin Ghrelin Orexin Arcuate nucleus Neuropeptide Y Ca2+ Feeding Phosphatidylinositol 3-kinase Phosphodiesterase 3 Signal transducer and activator of transcription 3

Co-administration of rlpaB domain of Shigella with rGroEL of s. Typhi enhances the immune responses and protective efficacy against Shigella infection

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Cellular & Molecular Immunology 2015年第6期12卷 757-767页

作者： Sekar Tamil Selvi Chitradevi Gurpreet Kaur Sivaramakrishna Uppalapati Anandprakash Yadav Dependrapratap Singh1 Anju Bansal division of Experimental Biology Defence Institute of Physiology and Allied Sciences Delhi India division of Microbiology Defence Food Research Laboratory Mysore India division of Immunomodulation Defence Institute of Physiology and Allied Sciences Delhi India

Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen （IpaB） protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant （r） domain region of IpaB （rlpaB） of S. flexneri, rlpaB was administered either alone or was co-administered with the rGroEL （heat shock protein 60） protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region （37 kDa） of S. flexneriwas amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia colicells and purified. Immunization with the rlpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody （IgG, IgA） and T-cell responses were induced when the rlpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG 1 and IgG2a antibody titers and increased interferon-gamma （IFN-γ） secretion in the co-administered group. Immunization of mice with the rlpaB domain alone protected 60%-70% of the mice from lethal infection by S. flexneri, S. boydiiand S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%-85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rlpaB domain alone. This study emphasizes that the co-administration of the rlpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL （Hsp 60） protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants.

关键词： GroEL heat shock protein IpaB Shigella S. Typhi

Role of copper in central nervous system physiology and pathology

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Neural Regeneration Research 2025年第4期20卷 1058-1068页

作者： Martina Locatelli Cinthia Farina Institute of Experimental Neurology Division of NeuroscienceIstituto di Ricovero e Cura a Carattere Scientifico(IRCCS)San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous *** copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple *** review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper ***,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

关键词： astrocytes central nervous system copper cuprizone multiple sclerosis myelin neurodegenerative disorders

Conditional gene expression in invertebrate animal models

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Journal of Genetics and Genomics 2021年第1期48卷 14-31页

作者： Brecht Driesschaert Lucas Mergan Liesbet Temmerman Animal physiology and neurobiology Department of BiologyUniversity of Leuven(KU Leuven)Naamsestraat 59-Box 2465B-3000 LeuvenBelgium

A mechanistic understanding of biology requires appreciating spatiotemporal aspects of gene expression and its functional *** expression allows for (ir)reversible switching of genes on or off,with the potential of spatial and/or temporal *** provides a valuable complement to the more often used constitutive gene (in)activation through mutagenesis,providing tools to answer a wider array of research questions across biological *** and/or temporal control are granted primarily by(combinations of) specific promoters,temperature regimens,compound addition,or *** use of such genetic tool kits is particularly widespread in invertebrate animal models because they can be applied to study biological processes in short time frames and on large scales,using organisms amenable to easy genetic *** years witnessed an exciting expansion and optimization of such tools,of which we provide a comprehensive overview and discussion regarding their use in *** mechanism,applicability,benefits,and drawbacks of each of the systems,as well as further developments to be expected in the foreseeable future,are highlighted.

关键词： Conditional gene expression Spatiotemporal control Invertebrate Model organism Drosophila melanogaster Caenorhabditis elegans

Progesterone treatment before experimental hypoxia-ischemia enhances the expression of glucose transporter proteins GLUT1 and GLUT3 in neonatal rats

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Neuroscience Bulletin 2013年第3期29卷 287-294页

作者： Xinjuan Li Hua Han Ruanling Hou Linyu Wei Guohong Wang Chaokun Li Dongliang Li Department of physiology and neurobiology Xinxiang Medical University Department of Ultrasonic Diagnosis Central Hospital of Xinxiang City Henan Key Lab of Biological Psychiatry

Progesterone is an efficient candidate for treating stroke and traumatic brain damage. The current study was designed to investigate the effects of pro gesterone on glucose transporter proteins （GLUT1 and GLUT3） during hypoxicischemic injury in a neo natal rat model. We demonstrated strong staining for GLUT1 in the walls of blood vessels and GLUT3 im munoreactivity in hippocampal neurons after hypoxia ischemia. Hypoxiaischemia elevated GLUT1 and GLUT3 at both the mRNA and protein levels in the hippocampus, and pretreatment with progesterone （8 mg/kg） further enhanced their accumulation until 24 h after hypoxicischemic injury. These results showed that progesterone treatment induced the accumula tion of both GLUT1 and GLUT3 transporters, and an energycompensation mechanism may be involved in the neuroprotective effect of progesterone during hy poxicischemic injury after cerebral ischemic attacks.

关键词： hypoxic-ischemic injury progesterone GLUT1 GLUT3 stroke

Okadaic acid: a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer's disease

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Neural Regeneration Research 2015年第3期10卷 365-367页

作者： Pradip Kumar Kamat Chandishwar Nath division of physiology and Biophysics University of LouisvilleSchool of Medicine division of Pharmacology Central Drug Research Institute(CDRI)

Okadaic acid： Okadaic acid （OKA）, a polyether （C38 fatty acid） toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A （PP2A）. It is mainly extracted from a black sponge Hallichondria okadaii and has been suggested to play a potent probe for studying the various molecular, cellular, biochemical and mechanism of neurotoxicity. It is known as a selective and potent in- hibitor of serine/threonine phosphatases 1 and 2A induces hyperphosphorylation of tau in vitro and in vivo. It has been reported that Alzheimer＇s disease （AD） is a complex multi- factorial neurodegenerative disorder and hyperphosphor- ylated tau protein is a major pathological hallmark of AD. The reduced activity of phosphatases like, PP2A has been implicated in the brain of AD patients. OKA also induced inhibition of protein phosphatases cause neurofibrillary tangles （NFTs） like pathological changes and tau hyperphos- phorylation seen in AD pathology. Our and others reports inferred that OKA induces neurodegeneration along with tau hyperphosphorylation, GSK3β activation, oxidative stress, neuroinflammation and neurotoxicity which are char- acteristic of AD pathology （Figure 1）.

关键词： a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer’s disease Okadaic acid AD

Autophagy occurs within an hour of adenosine triphosphate treatment after nerve cell damage:the neuroprotective effects of adenosine triphosphate against apoptosis

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Neural Regeneration Research 2014年第17期9卷 1599-1605页

作者： Na Lu Baoying Wang Xiaohui Deng Honggang Zhao Yong Wang Dongliang Li Department of physiology and neurobiology Xinxiang Medical University Department of Human Anatomy Xinxiang Medical University Department of Laboratory Animal Center Xinxiang Medical University

After hypoxia, ischemia, or inflammatory injuries to the central nervous system, the damaged cells release a large amount of adenosine triphosphate, which may cause secondary neuronal death. Autophagy is a form of cell death that also has neuroprotective effects. Cell Counting Kit assay, monodansylcadaverine staining, flow cytometry, western blotting, and real-time PCR were used to determine the effects of exogenous adenosine triphosphate treatment at different concentrations （2, 4, 6, 8, 10 mmol/L） over time （1, 2, 3, and 6 hours） on the apoptosis and autophagy of SH-SY5Y cells. High concentrations of extracellular adenosine triphosphate induced autophagy and apoptosis of SH-SYSY cells. The enhanced autophagy first appeared, and peaked at 1 hour after treatment with adenosine triphosphate. Cell apoptosis peaked at 3 hours, and persisted through 6 hours. With prolonged exposure to the adenosine triphosphate treatment, the fraction of apoptotic cells increased. These data suggest that the SH-SY5Y neural cells initiated autophagy against apoptosis within an hour of adenosine triphosphate treatment to protect themselves against injury.

关键词： nerve regeneration neurons adenosine triphosphate SH-SY5Y cells autophagy apoptosis cell culture monodansylcadaverine flow cytometry cell viability Bcl-2 Bax Beclin 1 neuronal damage NSFC grant neural regeneration

Wnt/β-catenin pathway might underlie the MET in transdifferentiation from MSC to MSC-derived neuron

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中国应用生理学杂志 2015年第6期31卷 572-576页

作者： Ying JING Jia-cheng ZHANG Su-ting LI Ji-hua ZHAO Jin WANG Xue-fei HAN Ying XING Stem Cell Center Zhengzhou University Department of physiology and neurobiology Basic Medical College of Zhengzhou University

Objective: To observe MET-associated alteration during the trans-differentiation from MSCs to neuron-like cells, and to explore the possible molecular mechanism. Methods: Bone marrow MSCs were isolated from rat femur and purified in continuous cell culture. After induced differentiation to neuron-like cells by the combination of butylated hydroxyanisole(BHA)and dimethyl sulfoxide(DMSO), cells were tested by comparative polymerase chain reaction(PCR) for the relative expression of MET biomarkers and transcription factors, and for cell cycle by flow cytometry. Meanwhile, target genes of Wnt/β-catenin pathway were also analyzed by comparative PCR to determine the possible involvement. Results: In MSC-induced neuron-like cells, MET-associated transcription factors such as Snail, Slug, ZEB1, ZEB2, and Twist were significantly attenuated in expression level. The Mesenchymal marker Vimentin expression level was increased. Membrane protein E-cad was slightly down-regulated, while N-cad level was marginally elevated. Percentage of proliferating cells(S phase in cell cycle) markedly shrank from 40.42% for MSCs to 6.76% for MSC-derived neuron. Additionally, Wnt/β-catenin target genes β-catenin and c-myc were decreasingly expressed. Conclusion: Chemically induced trans-differentiation from MSC to neuron caused similar MET-featured alteration in gene expression and proliferation to known MET, which might be underlied by deactivation of Wnt/ β-catenin pathway.

关键词： β-catenin 神经元样细胞信号通路分化过程 Wnt 骨髓间充质干细胞丁基羟基茴香醚 PCR分析

Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress

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World Journal of Gastroenterology 2011年第28期17卷 3310-3321页

作者： Laishram Pradeepkumar Singh Amartya Mishra Debjit Saha Snehasikta Swarnakar Department of physiology Drug Development Diagnostics and Biotechnology DivisionIndian Institute of Chemical Biology

AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric ***: Gastric ulcers were generated in rats by administration of 70% ethanol,and activity of doxycycline was tested by administration 30 min prior to ***,the effect of doxycycline was tested in an indomethacin-induced gastric ulcer *** activities and expression of MMPs were examined by zymography and Western blot ***: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen,either indomethacin or ethanol,was reversed significantly by ***-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control ***,ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities,respectively,in rat gastric *** proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric *** contrast,the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer *** the other hand,doxycycline inhibited significantly proMMP-9,-2 and -3 activities in *** addition,doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in *** results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ***: This is the first demonstration of dual action of doxycycline,that is,regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.

关键词： Doxycycline Extracellular matrix Matrix metalloproteinases Reactive oxygen species Tissue inhibitor of metalloproteinase

Ad libitum water consumption prevents exercise-associated hyponatremia and protects against dehydration in soldiers performing a 40-km route-march

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Military Medical Research 2019年第3期6卷 201-207页

作者： Heinrich WNolte Kim Nolte Tamara Hew-Butler Movement physiology Research Laboratory School of PhysiologyFaculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa division Biokinetics and Sport Science Department of PhysiologyUniversity of PretoriaPretoriaSouth Africa division of Kinesiology Wayne State UniversityDetroitMIUSA.

Background: It remains unclear if ad libitum water drinking, as a hydration strategy, prevents exercise-associated hyponatremia(EAH) during prolonged exercise. The aim of this study was to determine the incidence of EAH within the broader context of fluid regulation among soldiers performing a 40-km route-march ingesting water ad ***: Twenty-eight healthy male soldiers participated in this observational trial. Pre-and post-exercise body mass, blood and urine samples were collected. Blood samples were assessed for serum sodium([Na+]), glucose, creatinine, urea nitrogen(BUN), plasma osmolality, creatine kinase(CK), and plasma arginine vasopressin(AVP) concentrations. Plasma volume(PV) was calculated using hematocrit and hemoglobin. Urine samples were analyzed for osmolality and (Na+)Water intake was assessed by weighing bottles before, during and after the march. The mean relative humidity was 55.7%(21.9–94.3%) and the mean dry bulb temperature was 27.1°C(19.5°C-37.0°C) during the ***: Twenty-five soldiers(72±10 kg)(Mean±SD) completed the march in 09:11±00:43(hr:min). Participants consumed 736±259 ml/h of water and lost 2.8±0.9 kg(4.0%±1.4%, P<0.05) of body mass. Significant(pre-march vs. post-march;P<0.05) decreases in serum [Na+](141 mmol/L vs. 136 mmol/L), plasma osmolality(303 m Osmol/kg H2O vs. 298 m Osmol/kg H2O), and serum creatinine(111 μmol/L vs. 101 μmol/L) and urine [Na+](168 mmol/L vs. 142 mmol/L), as well as significant increases in plasma AVP(2 pg/ml vs. 11 pg/ml), plasma CK(1423 U/L vs. 3894 U/L) and urine osmolality(1035 m Osmol/kg H2O vs. 1097 m Osmol/kg H2O) were found. The soldier(72 kg) with the lowest postexercise sodium level completed the march in 08:38. He drank 800 ml/h, lost 2% body mass, and demonstrated(prepost) increases in plasma osmolality(294–314 m Osmol/kg H2O), BUN(20–30 mg/dl), AVP(2–16 pg/ml) and PV(41%). His urine osmolality decreased from 1114 m Osmol/kg H2O to 1110 m Osmol/kg H2O. No participants finished

关键词： Serum sodium concentration Exercise-associated hyponatremia Arginine vasopressin Fluid balance Electrolyte balance Military