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Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain
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作者 Xiaoyu Zhang Yuqi Liu +6 位作者 Fangxia Xu Chengcheng Zhou Kaimei Lu Bin Fang Lijuan Wang Lina Huang Zifeng Xu 《Neural Regeneration Research》 SCIE CAS 2025年第9期2682-2696,共15页
Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein ... Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain. 展开更多
关键词 dorsal root ganglion heterogeneous nuclear ribonucleoprotein F neuropathic pain protein arginine methyltransferase-6 sensory neurons
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Altered profiles of nuclear matrix proteins during the differentiation of human gastric mucous adenocarcinoma MGc80-3 cells 被引量:13
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作者 Chun-Hong Zhao Qi-Fu Li 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第30期4628-4633,共6页
AIM: To find and identify specific nuclear matrix proteins associated with proliferation and differentiation of carcinoma cells, which will be potential markers for cancer diagnosis and targets in cancer therapy. MET... AIM: To find and identify specific nuclear matrix proteins associated with proliferation and differentiation of carcinoma cells, which will be potential markers for cancer diagnosis and targets in cancer therapy. METHODS: Nuclear matrix proteins were selectively extracted from MGcS0-3 cells treated with or without hexamethylamine bisacetamide (HMBA), and subjected to 2-D gel electrophoresis. The resulted protein patterns were analyzed by Melanie software. Spots of nuclear matrix proteins differentially expressed were excised and subjected to in situ digestion with trypsin. Peptide masses were obtained by matrix-assisted laser-desorption/ ionization time of flight mass spectrometry (MALDI-TOFMS) analysis and submitted for database searching using Mascot tool. RESULTS: The MGc80-3 cells were induced into differentiation by HMBA. There were 22 protein spots which changed remarkably in the nuclear matrix, from differentiation of MGcS0-3 cells compared to control. Eleven of which were identified. Seven proteinsactin, prohibitin, porin 31HL, heterogeneous nuclear dbonucleoprotein A2/B1, vimentin, ATP synthase, and heat shock protein 60 were downregulated, whereas three proteins - heat shock protein gp96, heat shock protein 90-beta, and valosin-containing protein were upregulated, and the oxygen-regulated protein was only found in the differentiated MGc80-3 cells. CONCLUSION: The induced differentiation of carcinoma cells is accompanied by the changes of nuclear matrix proteins. Further characterization of those proteins will show the mechanism of cellular proliferation and differentiation, as well as cancer differentiation. 展开更多
关键词 nuclear matrix proteins Cell differentiation Human gastric mucous adenocarcinoma MGc80-3 Hexamethylamine bisacetamide
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Altered expression of nuclear matrix proteins in etoposide induced apoptosis in HL-60 cells 被引量:4
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作者 JinML ZhanP 《Cell Research》 SCIE CAS CSCD 2001年第2期125-134,共10页
The events of cell death and the expression of nuclear matrix protein (NMP) have been investigated in a promyelocytic leukemic cell line HL-60 induced with etoposide. By means of TUNEL assay, the nuclei displayed a ch... The events of cell death and the expression of nuclear matrix protein (NMP) have been investigated in a promyelocytic leukemic cell line HL-60 induced with etoposide. By means of TUNEL assay, the nuclei displayed a characteristic morphology change, and the amount of apoptotic cells increased early and reached maximun about 39% after treatment with etoposide for 2 h. Nucleosomal DNA fragmentation was observed after treatment for 4 h. The morphological change of HL-60 cells, thus, occurred earlier than the appearance of DNA ladder. Total nuclear matrix proteins were analyzed by 2-dimensional gel electrophoresis. Differential expression of 59 nuclear matrix proteins was found in 4 h etoposide treated cells. Western blotting was then performed on three nuclear matrix acssociated proteins, PML, HSC70 and NuMA. The expression of the suppressor PML protein and heat shock protein HSC70 were significantly upregulated after etoposide treatment, while NuMA, a nuclear mitotic apparatus protein, was down regulated. These results demonstrate that significant biochemical alterations in nuclear matrix proteins take place during the apoptotic process. 展开更多
关键词 Antineoplastic Agents Phytogenic Apoptosis DNA DNA Fragmentation Electrophoresis Gel Two-Dimensional Electrophoresis Polyacrylamide Gel ETOPOSIDE Gene Expression Regulation Neoplastic HL-60 Cells HSC70 Heat-Shock proteins HSP70 Heat-Shock proteins Humans In Situ Nick-End Labeling Neoplasm proteins nuclear Matrix nuclear proteins Transcription Factors Tumor Suppressor proteins
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Alreration of nuclear matrix-intermediate filament system and differential expression of nuclear matrix proteins during human hepatocarcinoma cell differentiation 被引量:4
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作者 Jian Tang Jing-Wen Niu +3 位作者 Dong-Hui Xu Zhi-Xing Li Qi-Fu Li Jin-An Chen 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第20期2791-2797,共7页
AIM: To investigate the association between the configurational and compositional changes of nuclear matrix and the differentiation of carcinoma cells. METHODS: Cells cultured with or without 5 × 10^-3 mmol/L o... AIM: To investigate the association between the configurational and compositional changes of nuclear matrix and the differentiation of carcinoma cells. METHODS: Cells cultured with or without 5 × 10^-3 mmol/L of hexamethylene bisacetamide (HMBA) on Nickel grids were treated by selective extraction and prepared for whole mount observation under electron microscopy. The samples were examined under transmission electron microscope. Nuclear matrix proteins were selectively extracted and subjected to subcellular proteomics study. The protein expression patterns were analyzed by PDQuest software. Spots of differentially expressed nuclear matrix proteins were excised and subjected to in situ digestion with trypsin. The peptides were analyzed by matrix-assisted laser- desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Data were submitted for database searching using Mascot tool (www.matrixscience.com). RESULTS: The nuclear matrix (NM) and intermediate filament (IF) in SMMC-7721 hepatocarcinoma cells were found relatively sparse and arranged irregularly. The nuclear lamina was non-uniform, and two kinds of filaments were not tightly connected. After induction for differentiation by HMBA, the NM-IF filaments were concentrated and distributed uniformly. The heterogeneous population of filaments, including highly branched utrathin filaments could also be seen in the regular meshwork. The connection between the two kinds of filaments and the relatively thin, condensed and sharply demarcated lamina composed of intermediate- sized filaments was relatively fastened. Meanwhile, 21 NM proteins changed remarkably during SMMC-7721 cell differentiation. Four proteins, i.e. mutant Pystl, hypothetical protein, nucleophosminl, and LBP were downregulated, whereas four other proteins, eIF6, p44 subunit, 13-tubulin, and SIN3B were upregulated with the last one, SR2/ASF found only in the differentiated SMMC-7721 cells. CONCLUSION: The induced differentiation of SMMC-7721 cells by HMBA is accompanied by the configurational changes of nuclear matrix-intermediate filament (NM-IF) system and the compositional changes of nuclear matrix protein expression. These changes may be important morphological or functional indications of the cancer cell reversion. 展开更多
关键词 nuclear matix-intermediate filament system nuclear matrix protein Hexamethylamine bisacetamide SMMC-7721 cells Cell differentiation
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Major royal-jelly proteins intake modulates immune functions and gut microbiota in mice 被引量:2
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作者 Hang Wu Shican Zhou +7 位作者 Wenjuan Ning Xiao Wu Xiaoxiao Xu Zejin Liu Wenhua Liu Kun Liu Lirong Shen Junpeng Wang 《Food Science and Human Wellness》 SCIE CSCD 2024年第1期444-453,共10页
In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the prolifer... In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability. 展开更多
关键词 Major royal-jelly proteins Immunity ESTROGEN Gut microbiota Cytokines
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Interplay between the glymphatic system and neurotoxic proteins in Parkinson’s disease and related disorders:current knowledge and future directions 被引量:2
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作者 Yumei Yue Xiaodan Zhang +2 位作者 Wen Lv Hsin-Yi Lai Ting Shen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第9期1973-1980,共8页
Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired eli... Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired elimination of these neurotoxic protein.Atypical parkinsonism,which has the same clinical presentation and neuropathology as Parkinson’s disease,expands the disease landscape within the continuum of Parkinson’s disease and related disorders.The glymphatic system is a waste clearance system in the brain,which is responsible for eliminating the neurotoxic proteins from the interstitial fluid.Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease,as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage.Therefore,impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration.Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson’s disease and related disorders;however,many unanswered questions remain.This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson’s disease and related disorders.The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins,including loss of polarization of aquaporin-4 in astrocytic endfeet,sleep and circadian rhythms,neuroinflammation,astrogliosis,and gliosis.This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson’s disease and related disorders,and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy. 展开更多
关键词 atypical parkinsonism glymphatic system magnetic resonance imaging neurotoxic proteins Parkinson’s disease
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Calmodulins and calmodulin-like proteins-mediated plant organellar calcium signaling networks under abiotic stress 被引量:1
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作者 Shuang Liu Liyan Zhao +4 位作者 Maozi Cheng Jinfeng Sun Xiaomeng Ji Aman Ullah Guosheng Xie 《The Crop Journal》 SCIE CSCD 2024年第5期1321-1332,共12页
Plant calmodulins(CaMs)and calmodulin-like proteins(CMLs)mediate Ca~(2+)signaling in response to abiotic stresses.Manipulation of this signaling in crops could increase stress tolerance.We review methods for detecting... Plant calmodulins(CaMs)and calmodulin-like proteins(CMLs)mediate Ca~(2+)signaling in response to abiotic stresses.Manipulation of this signaling in crops could increase stress tolerance.We review methods for detecting Ca~(2+)signals,regulatory roles of Ca Ms and CMLs,binding targets,and Ca~(2+)networks under abiotic stress in organelles. 展开更多
关键词 Abiotic stress CALMODULIN Calmodulin-like protein Organellar calcium signaling pathway
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Influence of norcantharidin on proliferation,proliferation-related gene proteins prolifera-ting cell nuclear antigen and Ki-67 of human gallbladder carcinoma GBC-SD cells 被引量:5
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作者 Yue-Zu Fan, Jin-Ye Fu, Ze-Ming Zhao and Cun-Qiu Chen Shanghai, China Department of Surgery, Tongji Hospital of Tongji U- mversity, Shanghai 200065, China Department of Surgery, Pudong People’ s Hospital, Shanghai 201200 , Chi- na 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2004年第4期603-607,共5页
BACKGROUND: Gallbladder carcinoma is a highly lethal and aggressive disease with early metastasis, strong invasion and poor prognosis. Most patients with this disease are at the advanced and un-resectable stage and sh... BACKGROUND: Gallbladder carcinoma is a highly lethal and aggressive disease with early metastasis, strong invasion and poor prognosis. Most patients with this disease are at the advanced and un-resectable stage and should be consi- dered for palliative treatment such as chemotherapy and ra- diotherapy. Unfortunately, reports of chemotherapy and radiotherapy for gallbladder carcinoma are disappointing. We investigated the influence of norcantharidin (NCTD) on proliferation, proliferation-related gene proteins PCNA and Ki-67 of human gallbladder carcinoma GBC-SD cells in vitro. METHODS: GBC-SD cell lines of human gallbladder carci- noma were cultured by the cell culture technique. The ex- periment was divided into NCTD group and control group. The tetrazolium-based colorimetric assay was used to evaluate cell growth. The streptavidin-biotin complex method was used to determine the expressions of prolifera- tion-related gene proteins PCNA and Ki-67 of human gall- bladder carcinoma GBC-SD cells. RESULTS: NCTD inhibited the growth and proliferation of GBC-SD cells from 10 mg/L or after 6 hours in a dose- and time-dependent manner, with the IC50 value of 56.18 μg/ ml at 48 hours. After treatment with NCTD, the expression of PCNA (0.932 ±0.031 vs. 0.318 ±0.023, P<0.001) and Ki-67 (0.964 ±0.092 vs. 0.297 ±0.018, P<0.001) proteins were decreased significantly. CONCLUSION: NCTD inhibits the proliferation of human gallbladder carcinoma GBC-SD cells in vitro and the expres- sion of their proliferation-related gene proteins PCNA and Ki-67. 展开更多
关键词 gallbladder neoplasm NORCANTHARIDIN cell culture immunohistochemistry cell proliferation proliferating cell nuclear antigen Ki-67
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Analysis of quality-related proteins in golden pompano(Trachinotus ovatus)fillets with modified atmosphere packaging under superchilling storage
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作者 Chuang Pan Xiaofan Zhang +4 位作者 Shengjun Chen Yong Xue Yanyan Wu Yueqi Wang Di Wang 《Food Science and Human Wellness》 SCIE CAS CSCD 2024年第4期2253-2265,共13页
Here,we aimed to study the changes in proteome of golden pompano fillets during post-mortem storage.Tandem mass tags(TMT)-labeled quantitative proteomic strategy was applied to investigate the relationships between pr... Here,we aimed to study the changes in proteome of golden pompano fillets during post-mortem storage.Tandem mass tags(TMT)-labeled quantitative proteomic strategy was applied to investigate the relationships between protein changes and quality characteristics of modified atmosphere packaging(MAP)fillets during superchilling(-3°C)storage.Scanning electron microscopy was used to show that the muscle histology microstructure of fillets was damaged to varying degrees,and low-field nuclear magnetic resonance was used to find that the immobilized water and free water in the muscle of fillets changed significantly.Total sulfhydryl content,TCA-soluble peptides and Ca2+-ATPase activity also showed that the fillet protein had a deterioration by oxidation and denaturation.The Fresh(FS),MAP,and air packaging(AP)groups were set.Total of 150 proteins were identified as differential abundant proteins(DAPs)in MAP/FS,while 209 DAPs were in AP/FS group.The KEGG pathway analysis indicated that most DAPs were involved in binding proteins and protein turnover.Correlation analysis found that 52 DAPs were correlated with quality traits.Among them,8 highly correlated DAPs are expected to be used as potential quality markers for protein oxidation and water-holding capacity.These results provide a further understanding of the muscle deterioration mechanism of packaging golden pompano fillets during superchilling. 展开更多
关键词 Tandem mass tags(TMT)proteomics Trachinotus ovatus Modified atmosphere packaging Superchilling storage Low-field nuclear magnetic resonance protein deterioration
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Aberrant expression of nuclear matrix proteins during HMBA-induced differentiation of gastric cancer cells 被引量:2
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作者 Jing, Guang-Jun Xu, Dong-Hui +4 位作者 Shi, Song-Lin Li, Qi-Fu Wang, San-Ying Wu, Fu-Yun Kong, Hai-Yan 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第17期2176-2182,共7页
AIM: To investigate the aberrant expression of nuclear matrix proteins in human gastric cancer cells before and after hexamethylene bisacetamide (HMBA) treatment.METHODS: Proteomics analysis of differential nuclear ma... AIM: To investigate the aberrant expression of nuclear matrix proteins in human gastric cancer cells before and after hexamethylene bisacetamide (HMBA) treatment.METHODS: Proteomics analysis of differential nuclear matrix proteins was performed by two dimensional electrophoresis polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.The expression levels of three nuclear matrix proteins were further confirmed by Western blotting and their locations in nuclear matrix filament were observed by quantum dots-based immunofluorescence.RESULTS: Proteomics analysis showed that 43 protein spots were significantly changed due to HMBA treatment.Fifteen proteins were identified in the HMBAinduced differentiation of gastric tumor cells.Eight proteins spots were down-regulated while seven were up-regulated.Among these proteins,prohibitin,nucleophosmin and hnRNP A2/B1 were significantly decreased in HMBA-treated human gastric cancer cells,and their locations in nuclear matrix were altered by HMBA.Our results proved the alteration of specific nuclear matrix proteins during the differentiation of human gastric cancer cells.And the aberrant expressions of nuclear matrix proteins were of significance in revealing the regulatory mechanism of tumor cell proliferation and differentiation.CONCLUSION: The aberrant expressions and intracellular redistributions of nuclear matrix proteins before and after HMBA treatment indicated that nuclear matrix proteins play a pivotal role in the differentiation of gastric cancer cells. 展开更多
关键词 Human gastric tumor cell Hexamethylene bisacetamide DIFFERENTIATION nuclear matrix PROLIFERATION
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Liver Nuclear Activation of Carbon Tetrachloride or Bromotrichloromethane to Trichloromethyl and Trichloromethylperoxyl Free Radicals.Their Reactions With Lipids and Proteins 被引量:4
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作者 S. L. FANELLI G. D. CASTRO M. E. GALELLI AND J. A. CASTRO (Centro de Investigaciones Toxicologicas(CEITOX)-CITEFA/CONICET, Zufriategui 4380, 1603 Villa Martelli,Buenos Aires, Argentina)(Send correspondence to Dr. Jose Alberto Castro, Zufriategui 4380, 1 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 1998年第2期101-114,共14页
The formation of·CCl3 radicals in liver nuclei was suggested by spin trapping of them with N-t-butyl-α-phenylnitrone followed by GC/MS detection of the resulting adduct. Comparison of its formation in microsomal... The formation of·CCl3 radicals in liver nuclei was suggested by spin trapping of them with N-t-butyl-α-phenylnitrone followed by GC/MS detection of the resulting adduct. Comparison of its formation in microsomal biotransformation of CCl4 was made. In aerobic nuclear activation mixtures containing NADPH and CCl4, significant decrease in the arachidonic acid content of nuclear lipids was observed (27. 8%, compared to control), the intensity of this decrease was lower than that occurring in the corresponding microsomal incubation mixtures (29.1%). Significant decreases in arachidonic acid content of nuclear and endoplasmic reticulum lipids were also observed in animals at 6 hours of poisoning with the haloalkane. During aerobic nuclear metabolism of CCl4 or CBrCl3, cholesterol oxidation products were detected: a ketocholesterol, an epoxide like structure and 7-ketocholesterol. Nuclear protein carbonyl formation was not promoted during nuclear CCl4 biotransformation. NADPH by itself may lead to protein carbonyl formation during prolonged periods of incubation. CBrCl3 in contrast, led to decreased protein carbonyl formation. No increase in nuclear protein carbonyl formation was observed in CCl4 intoxicated animals during periods of time between 1 to 6 hours after treatment. The results indicate that during nuclear biotransformation of CCl4 or CBrCl3 reactive free radicals, PUFA degradation, reactive aldehydes and cholesterol oxidation products are formed, nearby DNA and regulatory proteins. 展开更多
关键词 NADPH Liver nuclear Activation of Carbon Tetrachloride or Bromotrichloromethane to Trichloromethyl and Trichloromethylperoxyl Free Radicals.Their Reactions With Lipids and proteins Free
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Essential proteins identification method based on four-order distances and subcellular localization information
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作者 卢鹏丽 钟雨 杨培实 《Chinese Physics B》 SCIE EI CAS CSCD 2024年第1期765-772,共8页
Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have b... Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have been proposed to identify essential proteins. Unfortunately, most methods based on network topology only consider the interactions between a protein and its neighboring proteins, and not the interactions with its higher-order distance proteins. In this paper, we propose the DSEP algorithm in which we integrated network topology properties and subcellular localization information in protein–protein interaction(PPI) networks based on four-order distances, and then used random walks to identify the essential proteins. We also propose a method to calculate the finite-order distance of the network, which can greatly reduce the time complexity of our algorithm. We conducted a comprehensive comparison of the DSEP algorithm with 11 existing classical algorithms to identify essential proteins with multiple evaluation methods. The results show that DSEP is superior to these 11 methods. 展开更多
关键词 proteinprotein interaction(PPI)network essential proteins four-order distances subcellular localization information
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Systematic Analysis of Post-Translational Modifications for Increased Longevity of Biotherapeutic Proteins
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作者 Justin Kim Karanveer Sadiora 《Computational Molecular Bioscience》 2024年第3期125-145,共21页
Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and... Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p < 0.1) and human growth hormone (p < 0.0001), and both phosphorylation and methylation were somewhat optimal for erythropoietin (p < 0.1 and p < 0.0001, respectively). Acetylation consistently provided the worst benefits with the most negative indices, while methylation had the most positive indices throughout. However, PTM efficacy varied between PPTs, supporting previous studies regarding how each PTM can confer different benefits based on the unique structures of recipient proteins. 展开更多
关键词 Post-Translational Modification protein-Based Therapeutics Therapeutic Half-Life protein Aggregation protein Reception
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Phosphorylation and biosynthesis of high molecular weight proteins of tumor nuclear matrix
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作者 BAZARNOVA TM TV BULDYAEVA +2 位作者 LS FILATOVA SB AKOPOV IB ZBARSKY(NK Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov Street, 117344 Moscow,Russia) 《Cell Research》 SCIE CAS CSCD 1998年第3期195-207,共13页
Our previous studies showed a predominance of high molecular weight protein group in tumor nuclear matrices. Contrary to normal cells, proteins of this group are preferentially phosphorylated. Phosphoproteins of hepat... Our previous studies showed a predominance of high molecular weight protein group in tumor nuclear matrices. Contrary to normal cells, proteins of this group are preferentially phosphorylated. Phosphoproteins of hepatoma nuclear matrix are selectively subjected to rapid proteolysis. By alkali treatment and a monoclonal antibody against phosphotyrosyl residue the presence of two high molecular weight bands of phosphotyrosyl-containing proteins was detected in nuclear matrices of tumor but not of normal liver cells. High molecular weight protein group of tumor nuclear matrices revealed also a rapid turnover and preferential incorporation of labeled amino acids selectively inhibited by chloramphenicol. 展开更多
关键词 Animals Antigens nuclear Hela Cells Humans Male MICE Mice Inbred C57BL Mice Inbred CBA Molecular Weight Neoplasms nuclear Matrix nuclear proteins PHOSPHOproteins PHOSPHORYLATION Phosphotyrosine RATS Rats Wistar Research Support Non-U.S. Gov't
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A potential hyphal fusion protein complex with an important role in development and virulence interacts with autophagy-related proteins in Fusarium pseudograminearum
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作者 Linlin Chen Yixuan Shan +6 位作者 Zaifang Dong Yake Zhang Mengya Peng Hongxia Yuan Yan Shi Honglian Li Xiaoping Xing 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2024年第12期4093-4106,共14页
Hyphal fusion(anastomosis)is a common process serving many important functions at various developmental stages in the life cycle of ascomycetous fungi.However,the biological roles and molecular mechanisms in plant pat... Hyphal fusion(anastomosis)is a common process serving many important functions at various developmental stages in the life cycle of ascomycetous fungi.However,the biological roles and molecular mechanisms in plant pathogenic fungi were widely unknown.In this study,a hyphal fusion protein FpHam-2 was screened from a T-DNA insertion mutant library of Fusarium pseudograminearum,and FpHam-2 interacts with another 2 hyphal fusion protein homologues FpHam-3 and FpHam-4.Each of these 3 genes deletion mutant revealed in similar defective phenotypes compared with the WT and complemented strains,including reduction in growth rate,defects in hyphal fusion and conidiation,more sensitive for cell membrane,cell wall and oxidative stress responses,and decreased in virulence.The yeast two-hybrid assay was used to identify that FpHam-2 interacts with 3 autophagy-related proteins,including FpAtg3,FpAtg28 and FpAtg33.Furthermore,FpHam-2-deletion mutant showed decreased accumulation of autophagic bodies in hypha.In conclusion,FpHam-2,FpHam-3 and FpHam-4 have an essential role for hyphal fusion and regulating the growth,conidiation and virulence in F.pseudograminearum. 展开更多
关键词 Fusarium pseudograminearum hyphal fusion FpHam-2 VIRULENCE autophagy-related proteins
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The Role of Toll-Like Receptors and Nuclear Factor κB p65 Protein in the Pathogenesis of Otitis Media
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作者 Qingchen He Yongbo Zhu Bi Qiang 《Journal of Biosciences and Medicines》 2024年第10期246-257,共12页
The role of Toll-like receptor 4 (TLR4) and nuclear factor κB p65 (NF-κB p65) proteins in the pathogenesis of otitis media is explored. In recent years, the incidence of otitis media has been rising globally, becomi... The role of Toll-like receptor 4 (TLR4) and nuclear factor κB p65 (NF-κB p65) proteins in the pathogenesis of otitis media is explored. In recent years, the incidence of otitis media has been rising globally, becoming a significant threat to human health. More and more studies have found that Toll-like receptor 4 (TLR4), as a member of the Toll-like receptor family, can promote the generation of inflammatory factors and is closely related to the body’s immune response and inflammatory response. Nuclear factor-κB p65 (NF-κB p65) is a nuclear transcription factor that can interact with various cytokines, growth factors, and apoptotic factors, participating in processes such as oxidative stress, apoptosis, and inflammation in the body [1]. This article elaborates on the structure, function, and signaling pathways of TLR4 and NF-κB p65 proteins in the pathogenesis of otitis media, aiming to provide more precise targets and better therapeutic efficacy for the diagnosis and treatment of otitis media. The role of inflammation in disease. 展开更多
关键词 Otitis Media Toll-Like Receptors nuclear Factor κB p65 Signaling Pathway
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The 5'-flanking cis-acting elements of the human ε-globin gene associates with the nuclear matrix and binds to the nuclear matrix proteins
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作者 YANZHIJIANG RUOLANQIAN 《Cell Research》 SCIE CAS CSCD 1998年第3期209-218,共10页
The nucleax mains attachment regions(MARs) and the binding nuclear matrix proteins in the 5’-flalildng cisacting elements of the humanε-globin gene have been examined. Using in vitro DNA-matrix binding assay,it has ... The nucleax mains attachment regions(MARs) and the binding nuclear matrix proteins in the 5’-flalildng cisacting elements of the humanε-globin gene have been examined. Using in vitro DNA-matrix binding assay,it has been shown that the positive stage-specific regulatory element (ε-PREII, -446bp-419bp) upstream of this gene could specifically associate with the nuclear matrix from K562 cells, indicating thatε-PREII mad be an erythroidspecilic facultstive MAR. In gel mobility shift assay and Southwestern blotting assal an eothroid-specific nuclear matrix protein (ε-NMPk) in K562 cells has been revealed to bind to this positive regulatory element (E-PREII). Furthermore, we demonstrated that the silencer (-392hp -177bp) uP8tream of the humanε-globin gene could associate with the nuclear matrices from K562, HEL and Raji cells. In addition, the nucleax matrix proteins prepared from these three cell lines could also bind to this silencer, suggesting that this silencer element linght be a constitutive nuclear mains attachment region (constitutive MAR). Our results demonstrated that the nucleax madrid and nuclear mains proteins lxilght play an important role in the regulation of the human 5-globin gene expression. 展开更多
关键词 Human ε-globin gene nuclear matrix attachment regions nuclear matrix proteins K562 cells
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JAZ proteins:Key regulators of plant growth and stress response
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作者 Xiaoqian Zhao Yongqi He +2 位作者 Yuxin Liu Zhoufei Wang Jia Zhao 《The Crop Journal》 SCIE CSCD 2024年第6期1505-1516,共12页
The jasmonate ZIM-domain(JAZ)family of proteins serves as co-receptors and transcriptional repressors of jasmonic acid(JA)in plants.Their functional diversity and multiple roles make them important components of the r... The jasmonate ZIM-domain(JAZ)family of proteins serves as co-receptors and transcriptional repressors of jasmonic acid(JA)in plants.Their functional diversity and multiple roles make them important components of the regulatory network of JA and other hormonal signaling pathways.In this review,we provide an overview of the latest findings on JAZ family proteins and emphasize their roles in plant growth and development,and response to biotic and abiotic stress,along with their underlying mechanisms.Moreover,existing challenges and future applications are outlined with the aim of offering a reference for further research on JAZ proteins in the context of plant physiology. 展开更多
关键词 Jasmonate ZIM-domain proteins Transcription factors Plant growth Stress tolerance
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Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer:A systematic review and meta-analysis
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作者 Eric Toshiyuki Nakamura Amanda Park +2 位作者 Marina Alessandra Pereira Daniel Kikawa Francisco Tustumi 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第4期1578-1595,共18页
BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic signific... BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer. 展开更多
关键词 Heat-shock proteins Heat-shock response PROGNOSIS Esophageal neoplasms META-ANALYSIS
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Preliminary study of the role of inner ear proteins in vestibular neuritis
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作者 Rong Wang Weiwei Han +4 位作者 Li Li Lulu Li Xiaoxia Liu Yunqin Wu Weinv Fan 《Journal of Otology》 CAS CSCD 2024年第3期140-143,共4页
Objective:To evaluate the plasma levels of the otoconial proteins,otoconin-90 and otolin-1,in individuals diagnosed with vestibular neuritis(VN)and determine the feasibility of using these proteins as biomarkers for V... Objective:To evaluate the plasma levels of the otoconial proteins,otoconin-90 and otolin-1,in individuals diagnosed with vestibular neuritis(VN)and determine the feasibility of using these proteins as biomarkers for VN.Methods:In this preliminary study,30 patients diagnosed with VN and 70 healthy individuals were recruited and followed to confirm whether they had benign paroxysmal positional vertigo(BPPV)during the following time.The recorded data included measurements of height,weight,and history of diabetes mellitus or hypertension.Additionally,levels of plasma otoconin-90,and otolin-1 were measured and compared.Results:The plasma concentrations of otoconin-90 and otolin-1 may not be significantly different between patients with VN and healthy controls,nor among patients with BPPV secondary to VN and patients with VN without BPPV.Conclusions:Plasma otoconin-90 and otolin-1 levels may not serve as biomarkers of acute VN episodes or predict BPPV occurrence secondary to VN. 展开更多
关键词 Vestibular neuritis Inner ear protein Otoconin-90 Otolin-1
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