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Understanding the link between type 2 diabetes mellitus and Parkinson's disease:role of brain insulin resistance

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Neural Regeneration Research 2025年第11期20卷 3113-3123页

作者： Theodora Ntetsika Sergiu-Bogdan Catrina Ioanna Markaki department of Clinical Neuroscience Karolinska InstituteStockholmSweden department of Neurology Karolinska University HospitalStockholmSweden department of molecular Medicine and Surgery Karolinska InstituteStockholmSweden Center for Diabetes Academic Specialist CenterStockholmSweden Center for Neurology Academic Specialist CenterStockholmSweden

Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic *** data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular *** insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological *** contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.

关键词： brain insulin resistance brain insulin signaling diabetes type 2 GLP-1 receptor agonists GLP-1 signaling insulin resistance insulin signaling neurodegeneration Parkinson's disease targeted therapy

molecular processes in iron and zinc homeostasis and their modulation for biofortification in rice

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Journal of Integrative Plant biology 2018年第12期60卷 1181-1198页

作者： Yuta Kawakami Navreet K.Bhullar Plant biotechnology Department of Biology ETH Zurich

More than a billion people suffer from iron or zinc deficiencies globally. Rice(Oryza sativa L.) iron and zinc biofortification; i.e., intrinsic iron and zinc enrichment of rice grains, is considered the most effective way to tackle these deficiencies. However, rice iron biofortification, by means of conventional breeding, proves difficult due to lack of sufficient genetic variation. Meanwhile,genetic engineering has led to a significant increase in the iron concentration along with zinc concentration in rice grains. The design of impactful genetic engineering biofortification strategies relies upon vast scientific knowledge of precise functions of different genes involved in iron and zinc uptake, translocation and storage. In this review, we present an overview of molecular processes controlling iron and zinc homeostasis in rice. Further,the genetic engineering approaches adopted so far to increase the iron and zinc concentrations in polished rice grains are discussed in detail, highlighting the limitations and/or success of individual strategies. Recent insight suggests that a few genetic engineering strategies are commonly utilized for elevating iron and zinc concentrations in different genetic backgrounds, and thus, it is of great importance to accumulate scientific evidence for diverse genetic engineering strategies to expand the pool of options for biofortifying farmer-preferred cultivars.

关键词： molecular processes in iron and zinc homeostasis and their modulation for biofortification in rice Zn

Viroids:Small Probes for Exploring the Vast Universe of RNA Trafficking in Plants

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Journal of Integrative Plant biology 2010年第1期52卷 28-39页

作者： Ying Wang Biao Ding department of Plant Cellular and molecular biology and Plant biotechnology Center The Ohio State University The Center for RNA biology The Ohio State University molecular Cellular and DeVelopmental Biology Program The Ohio State University Columbus OH 43210 USA

Cell-to-cell and long-distance trafficking of RNA is a rapidly evolving frontier of integrative plant biology that broadly impacts studies on plant growth and development, spread of infectious agents and plant defense responses. The fundamental questions being pursued at the forefronts revolve around function, mechanism and evolution. In the present review, we will first use specific examples to illustrate the biological importance of cell-to-cell and long-distance trafficking of RNA. We then focus our discussion on research findings obtained using viroids that have advanced our understanding of the underlying mechanisms involved in RNA trafficking. We further use viroid examples to illustrate the great diversity of trafficking machinery evolved by plants, as well as the promise for new insights in the years ahead. Finally, we discuss the prospect of integrating findings from different experimental systems to achieve a systems-based understanding of RNA trafficking function, mechanism and evolution.

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Macrophage migration inhibitory factor stimulated by He/icobacter py/oriincreases proliferation of gastric epithelial cells

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World Journal of Gastroenterology 2005年第13期11卷 1946-1950页

作者： Harry Hua-Xiang Xia Shiu Kum Lam Annie O.O.Chan Marie Chia Mi Lin Hsiang Fu Kung Keiji Ogura Douglas E.Berg Benjamin Chun-Yu Wong department of Medicine Institute of molecular biology department of molecular Microbiology

AIM: Helicobacter pylori (H pylori) is associated with increased gastric inflammatory and epithelial expression of macrophage migration inhibitory factor (MIF) and gastric epithelial cell proliferation. This study aimed at determining whether H pylori directly stimulates release of MIF in monocytes, whether the cag pathogenicity island (PAI) is involved for this function, and whether MIF stimulated by H pylori increases gastric epithelial cell proliferation in vitro. METHODS: A cytotoxic wild-type H pylori strain (TN2), its three isogenic mutants (TN2Δcag,TN2ΔcagA and TN2ΔcagE) were co-cultured with cells of a human monocyte cell line, THP-1, for 24 h at different organism/ cell ratios. MIF in the supernatants was measured by an ELISA. Cells of a human gastric cancer cell line, MKN45, were then co-cultured with the supernatants, with and without monoclonal anti-MIF antibody for 24 h. The cells were further incubated for 12 h after addition of 3H-thymidine, and the levels of incorporation of 3H-thymidine were measured with a liquid scintillation counter. RESULTS: The wild-type strain and the isogenic mutants, TN2ΔcagA and TN2ΔcagE, increased MIF release at organism/cell ratios of 200/1 and 400/1, but not at the ratios of 50/1 and 100/1. However, the mutant TN2Δcag did not increase the release of MIF at any of the four ratios. 3H-thymidine readings for MKN-45 cells were significantly increased with supernatants derived from the wild-type strain and the mutants TN2ΔcagA and TN2ΔcagE, but not from the mutant TN2Δcag. Moreover, in the presence of monoclonal anti-MIF antibody, the stimulatory effects of the wild-type strain on cell proliferation disappeared. CONCLUSION: H pylori stimulates MIF release in monocytes, likely through its cag PAI, but not related to cagA or cagE. H pylori-stimulated monocyte culture supernatant increases gastric cell proliferation, which is blocked by anti-MIF antibody, suggesting that MIF plays an important role in H pylori-induced gastric ep

关键词： H pylori MIF PAI

Hyperglycemia in acute ischemic stroke: physiopathological and therapeutic complexity

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Neural Regeneration Research 2022年第2期17卷 292-299页

作者： Federica Ferrari Antonio Moretti Roberto Federico Villa department of biology and biotechnology Laboratory of Pharmacology and Molecular Medicine of Central Nervous SystemUniversity of PaviaVia FerrataPaviaItaly

Diabetes mellitus and associated chronic hyperglycemia enhance the risk of acute ischemic stroke and lead to worsened clinical outcome and increased mortality. However, post-stroke hyperglycemia is also present in a number of non-diabetic patients after acute ischemic stroke, presumably as a stress response. The aim of this review is to summarize the main effects of hyperglycemia when associated to ischemic injury in acute stroke patients, highlighting the clinical and neurological outcomes in these conditions and after the administration of the currently approved pharmacological treatment, i.e. insulin. The disappointing results of the clinical trials on insulin(including the hypoglycemic events) demand a change of strategy based on more focused therapies. Starting from the comprehensive evaluation of the physiopathological alterations occurring in the ischemic brain during hyperglycemic conditions, the effects of various classes of glucose-lowering drugs are reviewed, such as glucose-like peptide-1 receptor agonists, DPP-4 inhibitors and sodium glucose cotransporter 2 inhibitors, in the perspective of overcoming the up-to-date limitations and of evaluating the effectiveness of new potential therapeutic strategies.

关键词： acute ischemic stroke diabetes mellitus DPP-4 inhibitor glucose-like peptide-1 receptor agonist hyperglycemia hypoglycemia insulin physiopathology sodium glucose cotransporter 2 inhibitor

Therapeutic Effect of Dimethyl Dimethoxy Biphenyl Dicarboxylate on Collagen-Induced Arthritis in Rats

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Chinese Journal of Integrative Medicine 2015年第11期21卷 846-854页

作者： Roba M Talaat Amira S Abo-EI-Atta Sabah M Farou Karima I EI-Dosoky molecular biology department Genetic Engineering and Biotechnology Research InstituteMenofia UniversitySadat Branch Pathology department Faculty of MedicineTanta University

Objective： To study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate （DDB） on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis （CIA）. Methods： Wistar rat model of CIA was set up using bovine collagen type H. Fifty rats were divided into five groups randomly： normal, CIA model, DDB treatment, methotrexate （MTX） treatment, and combined DDB＋MTX treatment. Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints. Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining. Plasma levels of vascular endothelial growth factor （VEGF）, platelet derived growth factor, interleukin-8 （IL-8）, IL-4, tumor necrosis factor α （TNF-α）, and cyclooxygenase-2 （COX-2） were quantified by enzyme-linked immunosorbent assay. Nitric oxide levels were detected by Griess reagent. Results： Compared with the CIA model group, a remarkable reduction in various angiogenic （VEGF and IL-8） and inflammatory mediators （TNF-α, IL-4 and COX-2） after treatment with DDB either alone or combined with MTX （P〈0.05 or P〈0.01）. Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect. The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal. Conclusion： Our data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis （RA） compared with a choice drug （MTX） and it may be offered as a second-line drug in the treatment of RA.

关键词： rheumatoid arthritis collagen-induced arthritis dimethyl dimethoxy biphenyl dicarboxylate angiogenesis inflammation

Functional analysis of a cotton glucuronosyltransferase promoter in transgenic tobaccos

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Cell Research 2007年第2期17卷 174-183页

作者： Ai-Min Wu~1 Shi-You Lv~1 Jin-Yuan Liu ~1Laboratory of molecular biology and Protein Science Laboratory of the Ministry of Education,department of Biological Sciences and biotechnology,Tsinghua Universi.ty,Beijing 100084,China department of Biological Sciences and biotechnology Laboratory of Molecular Biology and Protein Science Laboratory of the Ministry of Education Tsinghua University Beijing China

The 5’fragment(1647 bp)of the cotton glucuronosyltransferase gene(GhGlcAT1)was transcriptionally fused to theβ-glucuronidase(GUS)gene,and functionally analyzed for important regulatory regions controlling gene expression intransgenic tobacco *** activity analysis revealed that the full-length promoter drives efficient expression of theGUS gene in the root cap,seed coat,pollen grains and *** of the transgenic tobacco to various abioticstresses showed that the promoter was mainly responsive to the sugars(glucose and sucrose)as well as gibberellic *** upstream deletion analyses of the promoter showed that the region from-281 to +30 bp is sufficient to drivestrong GUS expression in the trichomes of shoot,suggesting that the 311 bp region contains all c/s-elements needed fortrichome-specific ***,deletion analysis also revealed that the essential cis-element(s)for sucroseinduction might be located between -635 and -281 *** addition,sequence analysis of the regulatory region indicatedseveral conserved motifs among which some were shared with previously reported seed-specific elements and sugar-responsive elements,while others were related with trichome *** findings indicate that a 1647-bp frag-ment of the cotton GhGlcAT1 promoter contains specific transcription regulatory elements,and provide clues about theroles of GhGlcAT1 in cotton fiber *** analyses of these elements will help to elucidate the molecularmechanisms regulating the expression of the GhGlcAT1 gene during fiber elongation.

关键词： glucuronosyltransferase cotton sugar-induced expression regulatory elements promoter activity transgenic tobacco

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World Journal of Gastroenterology 2016年第30期22卷 6800-6816页

作者： Mahmoud Fathy Dondeti Eman Anwar El-Maadawy Roba Mohamed Talaat Genetic Engineering and biotechnology Research Division National Research Centre molecular biology department Genetic Engineering and Biotechnology Research Institute University of Sadat City

Hepatocellular carcinoma(HCC) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of HCC; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of HCC development. Cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related HCC.

关键词： Hepatocellular carcinoma Hepatitis C virus Hepatitis B virus Cytokines Polymorphism

Transforming growth factor-beta 1 enhances discharge activity of cortical neurons

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Neural Regeneration Research 2025年第2期20卷 548-556页

作者： Zhihui Ren Tian Li Xueer Liu Zelin Zhang Xiaoxuan Chen Weiqiang Chen Kangsheng Li Jiangtao Sheng department of Microbiology and Immunology Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular ImmunopathologyShantou University Medical CollegeShantouGuangdong ProvinceChina department of Neurosurgery First Affiliated Hospital of Shantou University Medical CollegeShantouGuangdong ProvinceChina

Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system *** neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types ***-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related ***,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain *** this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from *** found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 *** VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical *** findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological ***,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

关键词： central nervous system cortical neurons ERK firing properties JNK Nav1.3 p38 transforming growth factor-beta 1 traumatic brain injury voltage-gated sodium currents