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Current therapeutic modalities and chemopreventive role of natural products in liver cancer:Progress and promise

World Journal of Hepatology 2023年第1期15卷 1-18页

作者： Amit Kumar Singh Shiv Vardan Singh Ramesh Kumar Shashank Kumar Sabyasachi Senapati Abhay K Pandey Department of Botany Government Naveen Girls CollegeBalod(Hemchand Yadav University)DurgChattisgarhIndia Department of Biochemistry University of AllahabadPrayagraj 211002Uttar PradeshIndia Department of Biochemistry School of Basic and Applied SciencesCentral University of PunjabBathinda 151401PunjabIndia Department of Human Genetics and Molecular Medicine Central University of PunjabBathinda 151401PunjabIndia

Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after *** carcinoma(HCC)constitutes a significant subtype of liver cancer(approximate75%)and is considered primary liver *** for liver cancer mainly depends on the stage of its progression,where surgery including,hepatectomy and liver transplantation,and ablation and radiotherapy are the prime *** advanced liver cancer,various drugs and immunotherapy are used as first-line treatment,whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic *** and lenvatinib are first-line therapies,while regorafenib and ramucirumab are secondline *** metabolic and signaling pathways such as Notch,JAK/STAT,Hippo,TGF-β,and Wnt have played a critical role during HCC *** has also been implicated in liver ***-induced toxicity is a key obstacle in the treatment of liver cancer,necessitating the development of effective and safe medications,with natural compounds such as resveratrol,curcumin,diallyl sulfide,and others emerging as promising anticancer *** review highlights the current status of liver cancer research,signaling pathways,therapeutic targets,current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.

关键词： Liver cancer Hepatocellular carcinoma signaling pathways Therapeutic targets Natural products Chemopreventive

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Physiological and molecular mechanisms of insect appendage regeneration

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Cell Regeneration 2023年第1期12卷 351-362页

作者： Jiru Zhong Andi Jing Shaojuan Zheng Sheng Li Xiaoshuai Zhang Chonghua Ren Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology Guangzhou Key Laboratory of Insect Development Regulation and Application ResearchInstitute of Insect Science and TechnologySchool of Life SciencesSouth China Normal UniversityGuangzhou 510631China Guangmeiyuan R&D Center Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied TechnologySouth China Normal UniversityMeizhou 514779China

Regeneration,as a fascinating scientific field,refers to the ability of animals replacing lost tissue or body *** metazoan organisms have been reported with the regeneration phenomena,but showing evolutionarily variable *** the most diverse metazoan taxon,hundreds of insects show strong appendage regeneration *** regeneration process and ability are dependent on many factors,including macroscopic physiological conditions and microscopic molecular *** article reviews research progress on the physiological conditions and internal underlying mechanisms controlling appendage regeneration in insects.

关键词： Appendage regeneration Physiological condition Molecular mechanism signaling pathways Epigenetics Insects

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Dual Functions of Microglia in Ischemic Stroke

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Neuroscience Bulletin 2019年第5期35卷 921-933页

作者： Chuan Qin Luo-Qi Zhou Xiao-Tong Ma Zi-Wei Hu Sheng Yang Man Chen Dale B. Bosco Long-Jun Wu Dai-Shi Tian Department of Neurology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Department of Neurology Mayo Clinic Rochester MN 55905 USA

Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic stroke. Traditionally, it has been thought that microglial activation is deleterious in ischemic stroke, and therapies to suppress it have been intensively explored. However,increasing evidence suggests that microglial activation is also critical for neurogenesis, angiogenesis, and synaptic remodeling, thereby promoting functional recovery after cerebral ischemia. Here, we comprehensively review the dual role of microglia during the different phases of ischemic stroke, and the possible mechanisms controlling the post-ischemic activity of microglia. In addition, we discuss the dynamic interactions between microglia and other cells, such as neurons, astrocytes, oligodendrocytes,and endothelial cells within the brain parenchyma and the neurovascular unit.

关键词： Microglia Inflammation Ischemic stroke signaling pathways

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Transcriptomic study of the red palm weevil Rhynchophorus ferrugineus embryogenesis

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Insect Science 2015年第1期22卷 65-82页

作者： An Yin Linlin Pan Xiaowei Zhang Lei Wang Yuxin Yin Shangang Jia Wanfei Liu Chengqi Xin Kan Liu Xiaoguang Yu Gaoyuan Sun Khalid AI-hudaib Son qnian Hu Ibrahim S. AI-Mssallem Jun Yu joint Center for Genomics Research (JCGR) King Abdulaziz City for Science and Technology (KACST) and Chinese Academy ofSciences (CAS) Riyadh Kingdom of Saudi Arabia CAS Key Laboratory of Genome Sciences and Information Beijing Institute ofGenomics Chinese Academy of Sciences Beijing China University of Chinese Academy of Sciences Beijing China plant ProtectionDepartment Department of Biotechnology College of Agriculture and Food Sciences King Faisal University AI-Hssa HofufKingdom of Saudi Arabia

The red palm weevil （RPW）, Rhynchophorus ferrugineus （Coleoptera： Cur- culionidae）, is an invasive, concealed and destructive tissue borer, and it becomes a lethal pest of the palm family of plants and has been reported to attack 20 palm species around the globe. Here we report a systematic transcriptomic study on embryogenesis of RPW, where we analyze the transcriptomes across five developmental stages of RPW embryogenesis, involving four embryonic stages （El, E2, E3 and E4） and one larval stage （L1）. Using the RNA-seq and next-generation platforms, we generated 80 to 91 million reads for each library and assemble 22 532 genes that are expressed at different embryonic stages. Among the total transcripts from the five embryonic development stages, we found that 30.45 % are differentially expressed, 10.10 % show stage-specificity and even a larger fraction, 62.88 %, exhibit constitutive expression in all the stages. We also analyzes the expression dynamics of several conserved signaling pathways （such as Hedgehog, JAK-STAT, Notch, TGF-β, Ras/MAPK and Writ）, as well as key developmental genes, including those related to apoptosis, axis formation, Hox complex, neurogenesis and segmentation. The datasets provide an essential resource for gene annotation and RPW functional genomics, including studies by using tools and concepts from multiple disciplines, such as development, physiology, biochemistry, molecular biology and genetics.

关键词： insect embryogenesis red palm weevil Rhynchophorusferrugineus RNAseq signaling pathways transcriptome

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miRNA targeted signaling pathway in the early stage of denervated fast and slow muscle atrophy

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Neural Regeneration Research 2016年第8期11卷 1293-1303页

作者： Gang Li Qing-shan Li Wen-bin Li Jian Wei Wen-kai Chang Zhi Chen Hu-yun Qiao Ying-wei Jia Jiang-hua Tian Bing-sheng Liang Department of Orthopedics Second Affiliated Hospital of Shanxi Medical University

Denervation often results in skeletal muscle *** mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle *** the epigenetic level,mi RNAs are thought to be highly involved in the pathophysiological progress of denervated *** used mi RNA microarrays to determine mi RNA expression profiles from a typical slow muscle（soleus muscle） and a typical fast muscle（tibialis anterior muscle） at an early denervation stage in a rat *** showed that mi R-206,mi R-195,mi R-23 a,and mi R-30 e might be key factors in the transformation process from slow to fast muscle in denervated slow ***,certain mi RNA molecules（mi R-214,mi R-221,mi R-222,mi R-152,mi R-320,and Let-7e） could be key regulatory factors in the denervated atrophy process involved in fast *** of signaling pathway networks revealed the mi RNA molecules that were responsible for regulating certain signaling pathways,which were the final targets（e.g.,p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/m TOR pathway regulates atrogin-1 and Mu RF1 expression via Fox O phosphorylation）.Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.

关键词： nerve regeneration microRNA expression profile denervated skeletal muscle gene functions signaling pathways neural regeneration

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Measles virus hemagglutinin triggers intracellular signaling in CD150-expressing dendritic cells and inhibits immune response

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Cellular & Molecular Immunology 2016年第6期13卷 828-838页

作者： Olga Romanets-Korbut Larysa M. Kovalevska Tsukasa Seya Svetlana P. Sidorenko Branka Horvat CIRI International Center for Infectiology Research IblVteam Universite de Lyon Lyon France Inserm U1111 Lyon France CNRS UMR5308 Lyon France Universite Lyon 1 Lyon France Ecole Normale Superieure de Lyon Lyon France R.E. Kavetsky Institute of Experimental Pathology Oncology and Radiobiology NASU Kyiv Ukraine and 7Department of Microbiology and Immunology Graduate School of Medicine Hokkaido University Kita-ku Sapporo Japan Department ofMicrobiologyand Immunology Graduate School of Medicine Hokkaido University Kita-kuSapporo Japan

Measles virus （MV） is highly contagious pathogen, which causes a profound immunosuppression, resulting in high infant mortality. This virus infects dendritic cells （DCs） following the binding of MV hemagglutinin （MV-H） to CD150 receptor and alters DC functions by a mechanism that is not completely understood. We have analyzed the effect of MV-H interaction with CD150-expressing DCs on the DC signaling pathways and consequent phenotypic and functional changes in the absence of infectious context. We demonstrated that contact between CD150 on human DCs and MV-H expressed on membrane of transfected CHO cells was sufficient to modulate the activity of two major regulatory pathways of DC differentiation and function： to stimulate Akt and inhibit p38 MAPK phosphorylation, without concomitant ERK1/2 activation. Furthermore, interaction with MV-H decreased the expression level of DC activation markers CD80, CD83, CD86, and HLA-DR and strongly downregulated IL-12 production but did not modulate IL-IO secretion. Moreover, contact with MV-H suppressed DC-mediated T-cell alloproliferation, demonstrating profound alteration of DC maturation and functions. Finally, engagement of CD150 by MV-H in mice transgenic for human CD150 decreased inflammatory responses, showing the immunosuppressive effect of CD150-MV-H interaction in vivo. Altogether, these results uncover novel mechanism of MV-induced immunosuppression, implicating modulation of cell signaling pathways following MV-H interaction with CD150-expressing DCs and reveal anti-inflammatory effects of CD150 stimulation.

关键词： dendritic cells measles virus signaling pathways SLAM/CD150

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Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea

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Frontiers of Medicine 2016年第3期10卷 237-249页

作者： Muhammad Waqas Shasha Zhang Zuhong He Mingliang Tang Renjie Chai Key Laboratory for Developmental Genes and Human Disease Ministry of Education Institute of Life Sciences Southeast University Nanjing 210096 China Co-Innovation Center of Neuroregeneration Nantong University Nantong 226001 China

Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals possess limited regenerative capacity because of the active participation of various signaling pathways, including Wnt and Notch signaling. The Wnt and Notch pathways are highly sophisticated and conserved signaling pathways that control multiple cellular events necessary for the formation of sensory hair cells. Both signaling pathways allow resident supporting cells to regenerate hair cells in the neonatal cochlea. In this regard, Wnt and Notch signaling has gained increased research attention in hair cell regeneration. This review presents the current understanding of the Wnt and Notch signaling pathways in the auditory portion of the inner ear and discusses the possibilities of controlling these pathways with the hair cell fate determiner Atohl to regulate hair cell regeneration in the mammalian cochlea.

关键词： inner ear cochlea hair cell regeneration Wnt Notch signaling pathways

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Dynamic localization of hepatocellular transporters in health and disease

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World Journal of Gastroenterology 2008年第44期14卷 6786-6801页

作者： Marcelo G Roma Fernando A Crocenzi Aldo D Mottino Instituto de Fisiología Experimental (IFISE)-Facultad de Ciencias Bioquímicasy Farmacéuticas (CONICET-U.N.R.) S2002LRLRosarioArgentina

Vesicle-based traffi cking of hepatocellular transporters involves delivery of the newly-synthesized carriers from the rough endoplasmic reticulum to either the plasma membrane domain or to an endosomal,submembrane compartment,followed by exocytic targeting to the plasma membrane. Once delivered to the plasma membrane,the transporters usually undergo recycling between the plasma membrane and the endosomal compartment,which usually serves as a reservoir of pre-existing transporters available on demand. The balance between exocytic targeting and endocytic internalization from/to this recycling compartment is therefore a chief determinant of the overall capability of the liver epithelium to secrete bile and to detoxify endo and xenobiotics. Hence,it is a highly regulated process. Impaired regulation of this balance may lead to abnormal localization of these transporters,which results in bile secretory failure due to endocytic internalization of key transporters involved in bile formation. This occurs in several experimental models of hepatocellular cholestasis,and in most human cholestatic liver diseases. This review describes the molecular bases involved in the biology of the dynamic localization of hepatocellular transporters and its regulation,with a focus on the involvement of signaling pathways in this process. Their alterations in different experimental models of cholestasis and in human cholestatic liver disease are reviewed. In addition,the causes explaining the pathological condition (e.g. disorganization of actin or actin-transporter linkers) and the mediators involved (e.g. activation of cholestatic signaling transduction pathways) are also discussed. Finally,several experimental therapeutic approaches based upon the administration of compounds known to stimulate exocytic insertion of canalicular transporters (e.g. cAMP,tauroursodeoxycholate) are described.

关键词： Hepatocellular transporters Cholestasis cAMP Bile salts Vesicular trafficking Endocytosis signaling pathways

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Expression profiles of long noncoding RNAs in retinopathy of prematurity

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Neural Regeneration Research 2020年第10期15卷 1962-1968页

作者： Yue Wang Xue Wang Yuan Ma Yue-Xia Wang Yu Di Department of Ophthalmology Shengjing Hospital of China Medical University

Long noncoding RNA(lncRNA)regulates the proliferation and migration of human retinal endothelial cells,as well as retinal neovascularization in diabetic *** on similarities between the pathogenesis of retinopathy of prematurity(ROP)and diabetic retinopathy,lncRNA may also play a role in ***-day-old mice were administered 75±2% oxygen for 5 days and normoxic air for another 5 days to establish a ROP *** of lncRNA and mRNA in the retinal tissue of mice was detected by high-throughput sequencing technology,and biological functions of the resulted differentially expressed RNAs were evaluated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes *** results showed that compared with the control group,57 lncRNAs were differentially expressed,including 43 upregulated and 14 downregulated,in the retinal tissue of ROP *** with control mice,42 mRNAs were differentially expressed in the retinal tissue of ROP mice,including 24 upregulated and 18 downregulated *** expressed genes were involved in ocular development and related metabolic *** differentially expressed lncRNAs may regulate ROP in mice via microRNAs and multiple signaling *** results revealed that these differentially expressed lncRNAs may be therapeutic targets for ROP *** study was approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University on February 25,2016(approval No.2016PS074K).

关键词： bioinformatics gene therapy long noncoding RNA microglial neurovascular disease optic neuropathy retinal development retinal neovascularization retinopathy of prematurity signaling pathways

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Omega-3 polyunsaturated fatty acids promote liver regeneration after 90% hepatectomy in rats

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World Journal of Gastroenterology 2012年第25期18卷 3288-3295页

作者： Yu-Dong Qiu Sheng Wang Yue Yang Xiao-Peng Yan De-partment of Hepatobiliary Surgery Affiliated Drum Tower Hos-pitalMedical College of Nanjing UniversityJiangsu Province'sKey Medical Center for Hepatobiliary DiseaseNanjing 210008Jiangsu ProvinceChina

AIM:To evaluate the effectiveness of omega-3 polyunsaturated fatty acid(ω-3 PUFA) administration on liver regeneration after 90% partial hepatectomy(PH) in ***:ω-3 PUFAs were intravenously injected in the ω-3 PUFA group before PH ***,sparing only the caudate lobe,was performed in both the control and the ω-3 PUFA *** rates,liver weight/body weight ratios,liver weights,HE staining,transmission electron microscope imaging,nuclearassociated antigen Ki-67,enzyme-linked immunosorbent assay and signal transduction were evaluated to analyze liver ***:All rats in the control group died within 30 h after *** rates in the ω-3 PUFA group were 20/20 at 30 h and 4/20 1 wk after *** weight/body weight ratios and liver weights increased significantly in the ω-3 PUFA *** structure of sinusoidal endothelial cells and space of Disse was greatly restored in the ω-3 PUFA group compared to the control group after *** the ω-3 PUFA group,interleukin(IL)-4 and IL-10 levels were significantly increased whereas IL-6 and tumor necrosis factor-levels were dramatically *** addition,activation of protein kinase B(Akt) and of signal transducer and activator of transcription 3 signaling pathway were identified at an earlier time after PH in the ω-3 PUFA ***:Omega-3 polyunsaturated fatty acids may prevent acute liver failure and promote liver regeneration after 90% hepatectomy in rats.

关键词： Omega-3 polyunsaturated fatty acids Sur-vival rate Inflammatory cytokines signaling pathways

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