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Exosome-guided direct reprogramming of tumor-associated macrophages from protumorigenic to antitumorigenic to fight cancer

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Bioactive Materials 2023年第7期25卷 527-540页

作者： Hyosuk Kim Hyun-Ju Park Hyo Won Chang Ji Hyun Back Su Jin Lee Yae Eun Park Eun Hye Kim Yeonsun Hong Gijung Kwak Ick Chan Kwon Ji Eun Lee Yoon Se Lee Sang Yoon Kim Yoosoo Yang Sun Hwa Kim Medicinal Materials research Center Biomedical Research InstituteKorea Institute of Science and TechnologySeoul02792Republic of Korea department of Functional Genomics KRIBB School of BioscienceKorea University of Science and Technology(UST)Daejeon34141Republic of Korea department of Otolaryngology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul05505Republic of Korea Chemical&Biological Integrative research Center Biomedical Research InstituteKorea Institute of Science and TechnologySeoul02792Republic of Korea department of biotechnology College of Life Sciences and BiotechnologyKorea UniversitySeoul02841Republic of Korea department of Life sciences Korea UniversitySeoul02841Republic of Korea

Highly immunosuppressive tumor microenvironment containing various protumoral immune cells accelerates malignant transformation and treatment *** particular,tumor-associated macrophages(TAMs),as the predominant infiltrated immune cells in a tumor,play a pivotal role in regulating the immunosuppressive tumor *** a potential therapeutic strategy to counteract TAMs,here we explore an exosome-guided in situ direct reprogramming of tumor-supportive M2-polarized TAMs into tumor-attacking M1-type *** derived from M1-type macrophages(M1-Exo)promote a phenotypic switch from anti-inflammatory M2-like TAMs toward pro-inflammatory M1-type macrophages with high conversion *** M1 macrophages possessing protein-expression profiles similar to those of classically activated M1 macrophages display significantly increased phagocytic function and robust cross-presentation ability,potentiating antitumor immunity surrounding the ***,these M1-Exo also lead to the conversion of human patient-derived TAMs into M1-like macrophages that highly express MHC class II,offering the clinical potential of autologous and allogeneic exosome-guided direct TAM reprogramming for arming macrophages to join the fight against cancer.

关键词： Exosome Cancer therapy Tumor microenvironment Tumor-associated macrophage Direct conversion

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Visceral leishmaniasis: An immunological viewpoint on asymptomatic infections and post kala azar dermal leishmaniasis

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Asian Pacific Journal of Tropical Medicine 2018年第2期11卷 98-108页

作者： Neeraj Tiwari Dhiraj Kishore Surabhi Bajpai Rakesh K.Singh department of Biochemistry Institute of ScienceBanaras Hindu University department of Medicine Institute of Medical SciencesBanaras Hindu University department of bioscience and biotechnology Banasthali University

Elimination of visceral leishmaniasis is a priority programme in Indian *** World Health Organization has set a new target to eliminate kala-azar by the year 2020 as previous target elimination year(2015) has *** elimination programme has successfully curbed the rate of infection in endemic regions; however, there are still few challenges in its *** current drug control regime is extremely limited and comprises only two(amphotericin B and miltefosine) drugs, which are also susceptible for parasites ***, these drugs do not produce sterile cure, and cured patients may develop post kala-azar dermal leishmaniasis even after a decade of cure leaving behind a potent source of parasitic reservoirs for further disease transmission.A significant proportion of endemic population remain seropositive but aymptomatic for many years without any clinical symptom that serve as latent parasitic *** lack of tools to identify live parasites in asymptomatic infections and there association in disease transmission, parameters of sterile cure along with post kala-azar dermal leishmaniasis progression remain a major threat in its *** this review, we discuss the potential of host immune inhibitory mechanisms to identify immune correlates of protective immunity to understand the mystery of asymptomatic infections, sterile cure and post kala azar dermal leishmaniasis.

关键词： Visceral leishmaniasis Immune response Asymptomatic infection Sterile cure Post kala-azar dermal leishmaniasis

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Role of rice cytosolic hexokinase OsHXK7 in sugar signaling and metabolism

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Journal of Integrative Plant Biology 2016年第2期58卷 127-135页

作者： Hyun-Bi Kim Jung-Il Cho Nayeon Ryoo Dong-Ho Shin Youn-Il Park Yong-Sic Hwang Sang-Kyu Lee Gynheung An Jong-Seong Jeon Crop Biotech institute & Graduate School of biotechnology Kyung Hee University National Academy of Agricultural science Rural Development Administration Center for Neuroscience Korea Institute of Science and Technology department of Biology Chungnam National University department of bioscience and biotechnology Konkuk University

We characterized the function of the rice cytosolic hexokinase OsHXK7 （Qryza sativa HexokindseZ）, which is highly upregulated when seeds germinate under O2- deficient conditions. According to transient expression assays that used the promoter：luciferase fusion construct, OsHXK7 enhanced the glucose （Glc）-dependent repression of a rice n-amylase gene （RAmy3D） in the mesophyll protoplasts of maize, but its catalytically inactive mutant alleles did not. Consistently, the expression of OsHXK7, but not its catalytically inactive alleles, complemented the Arabidopsis glucose insensitive2-1 （gin2-1） mutant, thereby resulting in the wild type characteristics of Glc-dependent repression, seedling development, and plant growth. Interestingly, OsHXK7-mediated Glc-dependent repression was abolished in the O2-deficient mesophyll protoplasts of maize. This result provides compelling evidence that OsHXK7 functions in sugar signaling via a glycolysis-dependent manner under normal conditions, but its signaling role is suppressed when O2 is deficient. The germination of two null OsHXK7 mutants, oshxk7-1 and oshxk7-2, was affected by O2 deficiency, but overexpression enhanced germination in rice. This result suggests the distinct role that OsHXK7 plays in sugar metabolism and efficient germination by enforcing glycolysis-mediated fermentation in O2-deficient rice.

关键词： Germination metabolism OsHXK7 O2 deficiency rice signaling sugar

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Extracellular nucleoprotein exacerbates influenza viruspathogenesis by activating Toll-like receptor 4 and the NLRP3inflammasome

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Cellular & Molecular Immunology 2022年第6期19卷 715-725页

作者： Chang-Ung Kim Yu-Jin Jeong Pureum Lee Moo-Seung Lee Jong-Hwan Park Young-Sang Kim Doo-Jin Kim Infectious Disease research Center Korea Research Institute of Bioscience and Biotechnology(KRIBB)DaejeonSouth Korea department of Biochemistry Chungnam National UniversityDaejeonSouth Korea Environmental Diseases research Center Korea Research Institute of Bioscience and Biotechnology(KRIBB)DaejeonSouth Korea University of science and Technology(UST) DaejeonSouth Korea College of Veterinary Medicine Chonnam National UniversityGwangjuSouth Korea

Host immune responses, such as those initiated by pattern recognition receptor (PRR) activation, are important for viralclearance and pathogenesis. However, little is known about the interactions of viral proteins with surface PRRs or, moreimportantly, the association of innate immune activation with viral pathogenesis. In this study, we showed that internalinfluenza virus proteins were released from infected cells. Among these proteins, nucleoprotein (NP) played a critical role inviral pathogenesis by stimulating neighboring cells through toll-like receptor (TLR)2, TLR4, and the NLR family pyrin domaincontaining 3 (NLRP3) inflammasome. Through the activation of these PRRs, NP induced the production of interleukin (IL)-1β andIL-6, which subsequently led to the induction of trypsin. Trypsin induced by NP increased the infectivity of influenza virus,leading to increases in viral replication and pathology upon subsequent viral infection. These results reveal the role of releasedNP in influenza pathogenesis and highlight the importance of the interactions of internal viral proteins with PRRs in theextracellular compartment during viral pathogenesis.

关键词： Influenza virus Viral protein release Nucleoprotein Toll-like receptor Cyotkine-trypsin cycle

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ANNEXIN 8 negatively regulates RPW8.1-mediated cell death and disease resistance in Arabidopsis

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Journal of Integrative Plant Biology 2021年第2期63卷 378-392页

作者： Zhi-Xue Zhao Yong-Ju Xu Yang Lei Qin Li Ji-Qun Zhao Yan Li Jing Fan Shunyuan Xiao Wen-Ming Wang Rice research institute and Key Laboratory for Major Crop Diseases Sichuan Agricultural UniversityChengdu 611130China institute for bioscience and biotechnology research&department of Plant science and Landscape Architecture University of MarylandRockvilleMaryland 20850USA

Study on the regulation of broad-spectrum resistance is an active area in plant biology. RESISTANCE TO POWDERY MILDEW 8.1(RPW8.1)is one of a few broad-spectrum resistance genes triggering the hypersensitive response(HR) to restrict multiple pathogenic infections. To address the question how RPW8.1 signaling is regulated,we performed a genetic screen and tried to identify mutations enhancing RPW8.1-mediated ***, we provided evidence to connect an annexin protein with RPW8.1-mediated resistance in Arabidopsis against powdery mildew. We isolated and characterized Arabidopsis b7-6 mutant.A point mutation in b7-6 at the At5 g12380 locus resulted in an amino acid substitution in ANNEXIN8(AtANN8). Loss-of-function or RNA-silencing of AtANN8 led to enhanced expression of RPW8.1,RPW8.1-dependent necrotic lesions in leaves, and defense against powdery mildew. Conversely,over-expression of AtANN8 compromised RPW8.1-mediated disease resistance and cell death. Interestingly, the mutation in AtANN8 enhanced RPW8.1-triggered H2O2. In addition, mutation in AtANN8 led to hypersensitivity to salt stress. Together, our data indicate that AtANN8 is involved in multiple stress signaling pathways and negatively regulates RPW8.1-mediated resistance against powdery mildew and cell death, thus linking ANNEXIN’s function with plant immunity.

关键词： AtANN8 cell death disease resistance H2O2 hypersensitive response powdery mildew RPW8.1

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Biomonitoring of endosulfan toxicity in human

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BIOCELL 2022年第7期46卷 1771-1777页

作者： SANTOSH KUMAR KARN ADITYA UPADHYAY AWANISH KUMAR department of biotechnology Sardar Bhagwan Singh UniversityFormer Sardar Bhagwan Singh Post Graduate Institute of Biomedical Science&ResearchDehradun248161India department of biotechnology National Institute of TechnologyRaipur492010India

Chemicals are comprehensively used worldwide to control herbs,weeds,pests,and other competing agents with various growing *** consumption of crops grown with these chemicals(even in small quantities)can upshot into accumulation in the human *** can accidentally inhale these hazardous chemicals if they are in an area where they were *** chemicals can be ingested in a human with contaminated food and *** it causes various adverse effects(chronic toxicity,teratogenic,mutagenic,carcinogenic effect,reproductive,and organ toxicity)on human *** the pool of these chemicals used as pesticides in the environment,exposure of endosulfan to humans has a potential health risk throughout the *** poisoning of endosulfan is reported frequently in society,therefore,this article highlights the toxicological and other harmful properties of endosulfan to humans and emphasized its essential *** quick monitoring and effective hazard evaluation are possible with multiomics technologies and some other analytical *** review summarizes the introduction and mechanism of action of endosulfan along with some other toxic chemicals used in the agriculture work,the toxicity of endosulfan in human/environment,and importantly its biomonitoring(detection of chemicals and their metabolites in a biological sample)in human because biomonitoring is often considered as the most preferred *** could be easily done in human samples(blood,hair,milk,and urine)with a multi-omics approach,which is a quick,reliable,and state-of-the-art technique.

关键词： Endosulfan Agricultural use Toxicity Biomonitoring in human

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Neuroprotective effects of ischemic preconditioning on hippocampal CA1 pyramidal neurons through maintaining calbindin D28k immunoreactivity following subsequent transient cerebral ischemia

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Neural Regeneration research 2017年第6期12卷 918-924页

作者： In Hye Kim Yong Hwan Jeon Tae-Kyeong Lee Jeong Hwi Cho Jae-Chul Lee Joon Ha Park Ji Hyeon Ahn Bich-Na Shin Yang Hee Kim Seongkweon Hong Bing Chun Yan Moo-Ho Won Yun Lyul Lee department of Neurobiology School of Medicine Kangwon National University department of Radiology School of Medicine Kangwon National University department of biomedical science Research Institute of Bioscience and Biotechnology Hallym University department of Physiology College of Medicine Hallym University department of Surgery School of Medicine Kangwon National University institute of Integrative Traditional & Western Medicine Medical College Yangzhou University

Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the neuroprotective effects of ischemic preconditioning（2-minute transient cerebral ischemia） on calbindin D28k immunoreactivity in the gerbil hippocampal CA1 area following a subsequent fatal transient ischemic insult（5-minute transient cerebral ischemia）. A large number of pyramidal neurons in the hippocampal CA1 area died 4 days after 5-minute transient cerebral ischemia. Ischemic preconditioning reduced the death of pyramidal neurons in the hippocampal CA1 area. Calbindin D28k immunoreactivity was greatly attenuated at 2 days after 5-minute transient cerebral ischemia and it was hardly detected at 5 days post-ischemia. Ischemic preconditioning maintained calbindin D28 k immunoreactivity after transient cerebral ischemia. These findings suggest that ischemic preconditioning can attenuate transient cerebral ischemia-caused damage to the pyramidal neurons in the hippocampal CA1 area through maintaining calbindin D28k immunoreactivity.

关键词： hippocampal subsequent minute pyramidal maintaining attenuated hippocampus neuronal occlusion fatal

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CRISPR ribonucleoprotein-mediated genetic engineering in plants

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Plant Communications 2021年第2期2卷 38-50页

作者： Yingxiao Zhang Brian Iaffaldano Yiping Qi department of Plant science and Landscape Architecture University of MarylandCollege ParkMD 20742USA institute for bioscience and biotechnology research University of MarylandRockvilleMD 20850USA

CRISPR-derived biotechnologies have revolutionized the genetic engineering field and have been widely applied in basic plant research and crop *** used Agrobacterium-or particle bombardment-mediated transformation approaches for the delivery of plasmid-encoded CRISPR reagents can result in the integration of exogenous recombinant DNA and potential off-target *** efficiency is also highly dependent on the design of the expression cassette and its genomic insertion *** engineering using CRISPR ribonucleoproteins(RNPs)has become an attractive approach with many advantages:DNA/transgene-free editing,minimal off-target effects,and reduced toxicity due to the rapid degradation of RNPs and the ability to titrate their dosage while maintaining high editing *** RNP-mediated genetic engineering has been demonstrated in many plant species,its editing efficiency remains modest,and its application in many species is limited by difficulties in plant regeneration and *** this review,we summarize current developments and challenges in RNPmediated genetic engineering of plants and provide future research directions to broaden the use of this technology.

关键词： CRISPR RNP genetic engineering genome editing transgene free

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Fluorescent nanoswitch for monitoring specific pluripotency-related microRNAs of induced pluripotent stem cells： Development of polyethyleneimine- oligonucleotide hybridization probes

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Nano research 2017年第8期10卷 2545-2559页

作者： Seungmin Han Hye Young Son Byunghoon Kang Eunji Jang Jisun Ki Na Geum Lee Jongjin Park Moo-Kwang Shin Byeonggeol Mun Jeong-Ki Min Seungjoo Haam department of Chemical and Biomolecular Engineering College of Engineering Yonsei University Seou1120-749 Republic of Korea department of Radiology College of Medicine Yonsei University Seou1120-752 Republic of Korea Severance biomedical science institute College of Medicine Yonsei University Seou1120-752 Republic of Korea Biotherapeutics Translational research Center Korea Research Institute of Bioscience and Biotechnology Daejeon 34141 Republic of Korea department of Biomolecular science University of Science & Technology Daejeon 34113 Republic of Korea

The isolation of high-grade （i.e. high-pluripotency） human induced pluripotent stem cells （hiPSCs） is a decisive factor for enhancing the purity of hiPSC populations or differentiation efficiency. A non-invasive imaging system that can monitor microRNA （miRNA） expression provides a useful tool to identify and analyze specific cell populations. However, previous studies on the monitoring/isolation of hiPSCs by miRNA expression have limited hiPSCs＇ differentiation system owing to long-term incubation with miRNA imaging probe-nanocarriers. Therefore, we focused on monitoring high-grade hiPSCs without influencing the pluripotency of hiPSCs. We reduced nanoparticle transfection time, because hiPSCs are prone to spontaneous differentiation under external factors during incubation. The fluorescent nanoswitch （＂ON＂ with target miRNA）, which can be applied for either imaging or sorting specific cells by fluorescence signals, contains an miRNA imaging probe （miP） and a PEI-PEG nanoparticle （miP-P）. Consequently, this nanoswitch can sense various endogenous target miRNAs within 30 min in vitro, and demonstrates strong potential for not only imaging but also sorting pluripotent hiPSCs without affecting pluripotency. Moreover, miP-P-treated hiPSCs differentiate well into endothelial cells, indicating that miP-P does not alter the pluripotency of hiPSCs. We envisage that this miRNA imaging system could be valuable for identifying and sorting high-grade hiPSCs for improved practical applications.

关键词： induced pluripotent stem cells (iPSCs) pluripotency microRNA (miRNA) fluorescence imaging nanoparticle

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Impact of glucocorticoid on neurogenesis

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Neural Regeneration research 2017年第7期12卷 1028-1035页

作者： Haruki Odaka Naoki Adachi Tadahiro Numakawa department of Life science and Medical bioscience School of Advanced Science and EngineeringWaseda University department of Cell Modulation Institute of Molecular Embryology and GeneticsKumamoto University department of biomedical Chemistry School of Science and TechnologyKwansei Gakuin University department of Mental Disorder research National Institute of NeuroscienceNational Center of Neurology and Psychiatry (NCNP)

Neurogenesis is currently an area of great interest in *** is closely linked to brain diseases,including mental disorders and neurodevelopmental *** embryonic and adult neurogeneses are influenced by glucocorticoids secreted from the adrenal glands in response to a variety of ***,proliferation/differentiation of the neural stem/progenitor cells（NSPCs）is affected by glucocorticoids through intracellular signaling pathways such as phosphoinositide 3-kinase（PI3K）/Akt,hedgehog,and *** review presents recent evidence of the impact of glucocorticoids on NSPC behaviors and the underlying molecular mechanisms;this provides important information for understanding the pathological role of glucocorticoids on neurogenesis-associated brain diseases.

关键词： neural progenitor cells glucocorticoids neurogenesis in tracellular signaling pathways

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