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Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

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Neural Regeneration Research 2025年第7期20卷 2053-2067页

作者： Milica Zeljkovic Jovanovic Jelena Stanojevic Ivana Stevanovic Milica Ninkovic Tihomir V.Ilic Nadezda Nedeljkovic Milorad Dragic Laboratory for Neurobiology Department of General Physiology and BiophysicsFaculty of BiologyUniversity of BelgradeBelgradeSerbia Medical Faculty of Military Medical Academy University of DefenceBelgradeSerbia

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's *** therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in *** transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's ***,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain *** purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated *** with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod ***,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate *** intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate *** with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor *** treatment with prolonged intermittent theta burst stimulation,complete motor recovery was *** improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst *** results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)***

关键词： A_(1)R A_(2A)R adenosine receptors adenosine ecto-5′-nucleotidase intermittent theta burst stimulation non-invasive brain stimulation Parkinson's disease purinergic signalling

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Creeping fat and gut microbiota in Crohn’s disease

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World Journal of Gastroenterology 2025年第1期31卷 16-23页

作者： Ana EV Quaglio Daniéla O Magro Marcello Imbrizi Ellen CS De Oliveira Luiz C Di Stasi Ligia Y Sassaki Verum Ingredients Botucatu Technology ParkBotucatu 18605-525São PauloBrazil department of Surgery Faculty of Medical SciencesState University of CampinasCampinas 13083-970São PauloBrazil department of Gastroenterology Faculty of Medical SciencesUniversity of CampinasCampinas 13083-970São PauloBrazil department of Internal Medicine Medical SchoolSão Paulo State UniversityBotucatu 18618-686São PauloBrazil department of biophysics and Pharmacology Institute of BiosciencesSão Paulo State UniversityBotucatu 18618-689São PauloBrazil

In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract,influenced by genetic predisposition,gut microbiota dysbiosis,and environmental *** microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of ***,visceral adipose tissue,particularly creeping fat,a mesenteric adipose tissue characterized by hypertrophy and fibrosis,has been implicated in CD pathogenesis,inflammation,and *** bacteria from the gut microbiota may translocate into mesenteric adipose tissue,contributing to the formation of creeping fat and influencing CD *** creeping fat may be a protective barrier against bacterial invasion,its expansion can damage adjacent tissues,leading to *** gut microbiota through interventions such as fecal microbiota transplantation,probiotics,and prebiotics has shown potential in managing ***,more research is needed to clarify the mechanisms linking gut dysbiosis,creeping fat,and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.

关键词： Creeping fat Mesenteric adipose tissue Gut microbiota Crohn’s disease Inflammatory bowel disease

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Influence of selenium induced oxidative stress on spermatogenesis and lactate dehydrogenase-X in mice testis

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Asian Journal of Andrology 2004年第3期6卷 227-232页

作者： Parminder Kaur M.P.Bansal department of biophysics Panjab UniversityChandigarh-160014IndiaDepartment of BiophysicsPanjab UniversityChandigarh-160014India

Aim: To evaluate the effect of oxidative stress on the spermatogenesis and lactate dehydrogenase-X (LDH-X) activity in mouse testis. Methods: For creating different levels of oxidative stress in mice, three selenium (Se) level diets were fed in separate groups for 8 weeks. Group 1 animals were fed yeast-based Se-deficient (0.02 ppm) diet. Group 2 and Group 3 animals were fed with the same diet supplemented with 0.2 ppm and 1 ppm Se as sodium selenite, respectively. After 8 weeks, biochemical and histopathological observations of the testis were carried out. LDH-X levels in the testis were analyzed by western immunoblot and ELISA. Results: A significant decrease in testis Se level was observed in Group 1 animals, whereas it was enhanced in Group 3 as compared to Group 2. The glutathione peroxidase (GSH-Px) activity was significantly reduced in both the liver and testis in Group 1, but not in Group 2 and 3. A significant increase in the testis glutathione-S-transferase (GST) activity was observed in Group 1, whereas no significant change was seen in Groups 2 and 3. Histological analysis of testis revealed a normal structure in Group 2. A significant decrease in the germ cell population in Group 1 was observed as compared to Group 2 with the spermatids and mature sperm affected the most. Decrease in the lumen size was also observed. In the Se-excess group (Group 3), displacement of germ cell population was observed. Further, a decrease in the LDH-X level in testis was observed in Group 1. Conclusion: Excessive oxidative stress in the Se deficient group, as indicated by changes in the GSH-Px/GST activity, affects the spermatogenic process with a reduction in mature sperm and in turn the LDH-X level.

关键词： testis lactate dehydrogenase X selenium oxidative stress

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Oxidative stress in portal hypertension-induced rats with particular emphasis on nitric oxide and trace metals

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World Journal of Gastroenterology 2005年第23期11卷 3570-3573页

作者： Titiz Izzet Krand Osman Unal Ethem Yavuz Nihat Kusaslan Ramazan Dogan Mustafa Uzun Hafize Kiziler Ali Riza Aydemir Birsen Genc Habibe Aydin Seval Simsek Gonul department of Surgery department of Biochemistry department of biophysics department of Physiology

AIM: To investigate the oxidative-stress-related changes in rats with portal hypertension with particular emphasis on nitric oxide (NO) and trace metals. METHODS: Cirrhosis was induced by partial portal vein ligation (PVL) in Wistar rats. The lipid peroxidation marker (malondialdehyde, MDA), antioxidant defense enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and agents known to have antioxidant features including nitric oxide (NO), zinc (Zn), copper (Cu) were determined both in serum and in liver tissue at 4 wk after surgery in PVL and sham-operated rats. Portal pressure of all experimental animals was measured. MDA was detected by thiobarbituric acid reactivity *** activity was determined by inhibition of nitroblue tetrazolium reduction with xanthine/xanthine oxidase used asa superoxide generator. CAT activity was determined by the breakdown of hydrogen peroxide. GSH concentrations were measured by using metaphosphoric acid for protein precipitation and 5'-5'-dithio-bis-2-nitrobenzoic acid for color development. NO was detected by the Griess method after reduction of nitrate to nitrite with nitrate reductase, and the concentrations of Zn and Cu were measured by a Shimadzu 680 AA atomic absorption spectrometer. Histopathological confirmation was done under light microscope. Statistical analyses were done by Student's t-test, and significance of the difference was tested by the unpaired Mann-Whitney test. P＜0.05 was considered statistically ***: Histopathological studies confirmed PVL induced cirrhotic changes. There was a statistically significant difference in portal pressure between PVL and control groups (P＜0.001). The results showed significant increases in the levels of MDA and NO in both tissue and serum (P＜0.05 and P＜0.001, respectively in tissue; P＜0.001 for each in serum), and Zn only in tissue (P＜0.001)in rats with PVL compared with sham-operated rats. Besides, PVL rats exhibited reduced plasma and tis

关键词： Portal hypertension Nitric oxide Lipid peroxidation Antioxidants Trace metals

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Stability and orientation of cecropin P1 on maleimide self-assembled monolayer(SAM) surfaces and suggested functional mutations

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Chinese Chemical Letters 2015年第4期26卷 485-490页

作者： Shuai Wei Charles L.Brooks Ⅲ department of Chemistry University of Michigan department of biophysics University of Michigan

One of the main challenges of biosensor design is to understand the protein or peptide stability on the chip in high resolution structural detail. Since conventional experimental methods are limited by the resolution for their applications on surface tethered peptides/proteins, a recently developed coarse grained simulation method is employed to explore the peptide/surface interaction in residue-level resolution. This work shows how the coarse grained model successfully describes peptide-surface interactions by evaluating thermal stability of the peptide cecropin PI in bulk solution and on surfaces by physical adsorption and chemical tethering. The simulation also reproduces observations of peptide orientations on the self-assembled monolayer surface from earlier experimental work. Additionally, using knowledge obtained from the simulations, specific mutations are suggested and the desired structure and pose on the surface is obtained. In summary, this work sheds a light on the reasonable biosensor design that is ~uided by simulations.

关键词： Coarse grained simulationKB Go-like modelPeptide-surface interactionThermal stabilityOrientationMutation

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Energy dependence on modes of electric activities of neuron driven by different external mixed signals under electromagnetic induction

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Science China(Technological Sciences) 2019年第3期62卷 427-440页

作者： LU LuLu JIA Ya XU Ying GE MengYan YANG LiJian ZHAN Xuan Institute of biophysics and department of Physics Central China Normal University

Energy supply and release play an important role in individual neuron and neural network. In this paper, the electrical activities and Hamilton energy of neuron are investigated when external mixed signals(i.e., the periodic stimulus current and the periodic electromagnetic field) are imposed on the neuron under the electromagnetic induction. As a result, the Hamilton energy is much dependent on the mode transition, the multiple electric activity modes and the numerical analysis of Hamilton energy are more complicated under various parameters. When the periodic high-low frequency electromagnetic radiation is imposed in neuron, it is found that the electrical activities are more complex, and the changing of energy is obvious. In addition, the response of electrical activity and Hamilton energy is much dependent on the changing of amplitude A, B when the external high-low frequency signal is imposed on the neuron, meanwhile, the energy of bursting state is lower than the one of spiking state. It can be used for investigation about the energy coding in the neuron even the neuron networks.

关键词： Hamilton energy electromagnetic induction electric activity multiple growing modes

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A network of conformational transitions in an unfolding process of HP-35 revealed by high-temperature MD simulation and a Markov state model

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Chinese Physics B 2018年第1期27卷 175-181页

作者：邵丹丹高恺夫 Institute of biophysics and department of Physics Central China Normal University

An understanding of protein folding/unfolding processes has important implications for all biological processes, in- eluding protein degradation, protein translocation, aging, and diseases. All-atom molecular dynamics （MD） simulations are uniquely suitable for it because of their atomic level resolution and accuracy. However, limited by computational ca- pabilities, nowadays even for small and fast-folding proteins, all-atom MD simulations of protein folding still presents a great challenge. An alternative way is to study unfolding process using MD simulations at high temperature. High temper- ature provides more energy to overcome energetic barriers to unfolding, and information obtained from studying unfolding can shed light on the mechanism of folding. In the present study, a 1000-ns MD simulation at high temperature （500 K） was performed to investigate the unfolding process of a small protein, chicken villin headpiece （HP-35）. To infer the folding mechanism, a Markov state model was also built from our simulation, which maps out six macrostates during the folding/unfolding process as well as critical transitions between them, revealing the folding mechanism unambiguously.

关键词： molecular dynamics simulation Markov state model folding/unfolding HP-35

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Depth perception differences between hemispheres,genders,and eye dominance A study on evoked potential

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Neural Regeneration Research 2009年第11期4卷 947-950页

作者： Ahmet Akay Gürbüz elebi Ege University Medical School Department of Biophysics

BACKGROUND： Certain neural functions, such as peripheral reflexes, differ between genders, while higher brain functions, such as language, are asymmetrically distributed between the two hemispheres. The question remains as to whether depth perception differs between hemispheric laterality and genders, and whether it is affected by eye dominance. OBJECTIVE： To determine whether depth perception is influenced by factors such as gender, eye dominance, and hemispheric lateralization by recording evoked potential associated with depth perception. DESIGN, TIME AND SETTING： A contrast observation based on neuroelectrophysiology was performed at the department of biophysics of Ege University Medical School between June 2006 and April 2007. PARTICIPANTS： A total of 34 subjects, 19 females and 15 males, were included in the study with a mean age of （31.0 ± 6.9） years. All subjects were free of neurological or psychological disorders, or problems such as strabismus or vision correction. METHODS： Random-dot stereograms were used to elicit brain activity. A specially designed signal acquisition system employing two computers was used to record evoked potentials from both hemispheres via two pairs of scalp electrodes placed over the occipitotemporal areas of both hemispheres at symmetrical locations. MAIN OUTCOME MEASURES： Negative potential with a mean latency of （211.21 ±25.55） ms and a mean amplitude of （6.05 ± 1.53） pV was recorded from both occipitotemporal areas in 30 out of 34 participants. This was termed ＂Nd＂ and represented the evoked potential associated with depth perception. RESULTS： There were no significant differences in Nd amplitude or latency between the two hemispheres, the two eyes, or genders （P 〉 0.05）. CONCLUSION： The evoked potential associated with depth perception was not influenced by gender, hemisphere, or eye dominance.

关键词： random-dot stereogram depth perception, stereovision eye dominance hemisphere lateralization: sex difference

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Tightening up the structure, lighting up the pathway:application of molecular constraints and light to manipulate protein folding, self-assembly and function

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Science China Chemistry 2014年第12期57卷 1615-1624页

作者： MARKIEWICZ Beatrice N. CULIK Robert M. GAI Feng department of Chemistry University of Pennsylvania department of Biochemistry and biophysics University of Pennsylvania

Chemical cross-linking provides an effective avenue to reduce the conformational entropy of polypeptide chains and hence has become a popular method to induce or force structural formation in peptides and ***,other types of molecular constraints,especially photoresponsive linkers and functional groups,have also found increased use in a wide variety of ***,we provide a concise review of using various forms of molecular strategies to constrain proteins,thereby stabilizing their native states,gaining insight into their folding mechanisms,and/or providing a handle to trigger a conformational process of interest with *** applications discussed here cover a wide range of topics,ranging from delineating the details of the protein folding energy landscape to controlling protein assembly and function.

关键词： protein folding aggregation self-assembly cross-linker phototrigger light-activation

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A mathematical model of a P53 oscillation network triggered by DNA damage

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Chinese Physics B 2010年第4期19卷 112-116页

作者：夏俊峰贾亚 department of Physics and Institute of biophysics Central China Normal University

Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damage signal in individual cells. The effects of the DNA damage signal and the delay time of P53-induced MDM2 expression on the behaviours of the P53 oscillation network are studied. In the oscillatory state of the P53--MDM2 oscillator, it is found that the pulse number of P53--P oscillation increases with the increase of the initial DNA damage signal, whereas the amplitude and the period of P53--P oscillation are fixed for different initial DNA damage signals, and the period numbers of P53--P oscillations decrease with the increase of time delay of MDM2 expression induced by P53. These theoretical predictions are consistent with previous experimental results. The combined negative feedback of P53--MDM2 with the time delay of P53-induced MDM2 expression causes oscillation behaviour in the P53 network.

关键词： P53 oscillation network DNA damage signal time delay kinetic model

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