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Development of a 3D subcutaneous construct containing insulin-producing beta cells using bioprinting

Bio-Design and Manufacturing 2022年第2期5卷 265-276页

作者： Chi B.Ahn Ji-Hyun Lee Joo H.Kim Tae H.Kim hee-sook jun Kuk H.Son Jin W.Lee Department of Molecular Medicine College of MedicineGachon University155Gaetbeol-roYeonsu-kuIncheonRepublic of Korea Department of Health Sciences and Technology GAIHSTGachon University155Gaetbeol-roYeonsu-kuIncheonRepublic of Korea College of Pharmacy Gachon University191Hambangmoe-roYeonsu-kuIncheonRepublic of Korea Department Thoracic and Cardiovascular Surgery Gachon University Gil Medical CenterCollege of MedicineGachon University21Namdong-daero 774 beon-gilNamdong-guIncheonRepublic of Korea

Type 1 diabetes is caused by insulin deficiency due to the loss of beta cells in the islets of *** severe cases,islet transplantation into the portal vein is ***,due to the loss of transplanted islets and the failure of islet function,the 5-year insulin independence rate of these patients is<50%.In this study,we developed a long-term,insulin-secreting,3 Dbioprinted construct implanted subcutaneously with the aim of preventing islet *** bioprinted construct was fabricated by the multi-layer bioprinting of beta-cell(mouse insulinoma-6:MIN-6)-encapsulated alginate bioink and poly(caprolactone)biodegradable polymer.A glucose response assay revealed that the bioprinted constructs proliferated and released insulin normally during the 4-week in vitro *** MIN-6 generated clusters with a diameter of 100-200μm,similar to the original pancreatic islets in the *** an in vivo study using type 1 diabetes mice,animals implanted with bioprinted constructs showed three times higher insulin secretion and controlled glucose levels at 8 weeks after *** the implanted,bioprinted constructs had a positive effect on insulin secretion in the experimental animals,the survival rate of the implanted group(75%)was three times higher than that of the non-implanted group(25%).The results suggest that the proposed,3 D-bioprinted,subcutaneous construct can be a better alternative to portal vein islet transplantation.

关键词： 3D bioprinting Subcutaneous construct Type 1 diabetes Insulin Beta cells

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Glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice

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World Journal of Gastroenterology 2012年第44期18卷 6420-6426页

作者： Jaeseok Han Eung-Hwi Kim Woohyuk Choi hee-sook jun Department of Microbiology and Infectious Diseases University of Calgary3330 Hospital Drive N.W.CalgaryAlberta T2N 4N1Canada Del E.Webb Neuroscience Aging and Stem Cell Research CenterSanford Burnham Medical Research InstituteLa JollaCA 92037United States Lee Gil Ya Cancer and Diabetes Institute Gachon University7-45 SondodongYeonsu-kuIncheon 406-840South Korea College of Pharmacy Gachon University7-45 Sondo-dongYeonsu-kuIncheon 406-840South Korea

AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese ***:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level *** intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter(rAd-SP-rINSfur) into diabetic Lepr db/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control(rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 *** and insulin tolerance tests were *** staining was performed to investigate islet morphology and insulin ***:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained *** tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve(AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk(AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice(AUC:9150.17 ± 1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected ***:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.

关键词：胰岛素基因 2型糖尿病血糖水平启动子葡萄糖敏感性小鼠控制

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New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

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Oncology Research 2024年第6期32卷 1021-1030页

作者： HYUNHO KIM UIJU CHO sook hee HONG HYUNG SOON PARK IN-HO KIM HO junG AN BYOUNG YONG SHIM JIN HYOUNG KANG Division of Medical Oncology Department of Internal MedicineSt.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Department of Pathology St.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Division of Medical Oncology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulKorea

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)*** cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival ***,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing ***:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with *** APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot *** blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B *** viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with ***:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with *** with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B *** treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B *** to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B ***:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR *** result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

关键词： Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC) Ataxia telangiectasia and Rad3-related(ATR) Bladder cancer DNA damage response DNA replication stress

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M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3169-3183页

作者： Ha Eun Shin jun-Hyeok Han Seungyong Shin Ga-Hyun Bae Boram Son Tae-Hyung Kim hee Ho Park Chun Gwon Park Wooram Park Department of Integrative Biotechnology Sungkyunkwan University(SKKU)SuwonGyeonggi 16419Republic of Korea Deparment of Inteligent Precision Healthcare Convergence SKKUSuwonGyeonggi 16419Republic of Korea Department of MetaBioHealth SKKU Institute for ConvergenceSKKUSuwonGyeonggi 16419Republic of Korea Department of Bioengineering Hanyang UniversitySeoul 04763Republic of Korea Department of Integrative Engineering Chung-Ang UniversitySeoul 06974Republic of Korea Department of Biomedical Engineering SKKUSuwonGyeonggi 16419Republic of Korea Korea Institute of Science and Technology(KIST) Seoul 02792Republic of Korea

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene *** nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonstrated efficacy in human use during the COVID-19 *** study introduces a novel biomaterial-based platform,M1-polarized macrophage-derived cellular nanovesicle-coated LNPs(M1-C-LNPs),specifically engineered for a combined gene-immunotherapy approach against solid *** dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles(M1-NVs),effectively facilitating apoptosis in cancer cells without impacting T and NK cells,which activate the intratumoral immune response to promote granule-mediating killing for solid tumor *** retention within tumor was observed upon intratumoral administration of M1-C-LNPs,owing to the presence of adhesion molecules on M1-NVs,thereby contributing to superior tumor growth *** findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy,with significant implications for advancing biomaterial use in cancer therapeutics.

关键词： Genetic-immunotherapy M1 macrophage-derived cellular nanovesicles Lipid nanoparticles(LNPs) Gene therapy siRNA Cancer immunotherapy Solid tumor Tumor microenvironment(TME)

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Mechanisms involved in Korean mistletoe lectin-induced apoptosis of cancer cells

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World Journal of Gastroenterology 2007年第20期13卷 2811-2818页

作者： Lee-Yong Khil Wi Kim Suyun Lyu Won Bong Park Ji-Won Yoon hee-sook jun Department of Microbiology and Infectious Diseases Faculty of MedicineUniversity of CalgaryCalgaryAlbertaT2N 4N1Canada Immune Modulation Group Boots Science BuildingSchool of PharmacyUniversity of NottinghamUniversity ParkNottinghamNG7 2RDUnited Kingdom College of Natural Science Seoul Women’s UniversitySeoul 139-774Korea Department of Pathology Chicago Medical SchoolNorth ChicagoIL60064United States Sadly Department of Pathology Chicago Medical SchoolNorth ChicagoIL60064United States SadlyDr. Ji-Won Yoon passed away on April 62006

AIM: To investigate the anti-cancer mechanisms of Korean mistletoe lectin (Viscum album coloratum agglutinin,VCA) using a human colon cancer cell line (COLO). METHODS: Cytotoxic effects of VCA on COLO cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro and tumor-killing effects in vivo. To study the mechanisms involved,the expression of various pro-caspases,anti-apoptotic proteins,and death receptors was determined by western blot. To determine which death receptor is involved in VCA-induced apoptosis of COLO cells,cytotoxicity was examined by MTT assay after treatment with agonists or antagonists of death receptors. RESULTS: VCA killed COLO cells in a time-and dose-dependent manner and induced complete regression of tumors in nude mice transplanted with COLO cells. Treatment of COLO cells with VCA activated caspase-2,-3,-8,and -9 and decreased expression of anti-apoptotic molecules including receptor interacting protein,nuclear factor-κB,X-linked inhibitor of apoptosis protein,and Akt/protein kinase B. We then examined the involvement of death receptors in VCA-induced apoptosis. Only tumor necrosis factor receptor 1,among the death receptors examined,was involved in apoptosis of COLO cells,evidenced by inhibition of VCA-induced apoptosis and decreased activation of caspases,particularly caspase-8,by tumor necrosis factor receptor 1 antagonizing ***: VCA-induced apoptotic COLO cell death is due to the activation of caspases and inhibition of anti-apoptotic proteins,in part through the tumor necrosis factor receptor 1 signaling pathway.

关键词：外源凝集素韩国细胞凋亡肿瘤细胞

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Tetradentate Pt(II) complex as a singlet exciton sensitizing host for highly efficient green fluorescent organic light-emitting diodes

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Science China Materials 2024年

作者： Unhyeok Jo Seung Chan Kim Chan hee Ryu Kang Mun Lee Jae-Min Kim jun Yeob Lee School of Chemical Engineering Sungkyunkwan University 2066 Seobu-ro Jangan-gu Suwon-si Department of Chemistry Institute for Molecular Science and Fusion Technology Kangwon National University Chuncheon Department of Advanced Materials Engineering Chung-Ang University 4726 Seodong-daero Daedeok-myeon Anseong-si SKKU Advanced Institute of Nano Technology Sungkyunkwan University 2066 Seobu-ro Jangan-gu SKKU Institute of Energy Science and Technology Sungkyunkwan University 2066 Seobu-ro Jangan-gu

Efficient green fluorescent organic light-emitting diodes were designed with a phosphorescent metal complex as a singlet exciton sensitizing host (SESH) for achieving high efficiency and low efficiency roll-off through exciton and polaron management. Tetradentate Pt(II) complex (Pt-Trz)possessing a tetradentate ligand with a bulky blocking group not only suppresses the severe formation of excimer or dimer itself but also transfers radiative excitons to fluorescent dopant effectively. The SESH assisted fluorescence (SESHF) device with Pt-Trz as the host exhibits the maximum external quantum efficiency of 13.3%and a lower efficiency roll-off compared with exciplex host device which is a general approach for harvesting triplet excitons. Numerical exciton dynamics modeling unravels that the SESHF device effectively utilizes triplet excitons in the host by intersystem crossing and resonance energy transfer from the triplet state of the host to the singlet state of the terminal emitter. Bimolecular quenching rates of the SESHF device are reduced by 11 times for triplet-triplet annihilation and 1.8 times for tripletpolaron annihilation compared with the exciplex device, which demonstrates that Pt-Trz could be a platform to be used as an efficient host for fluorophores.

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Tetradentate Pt(Ⅱ)complex as a singlet exciton sensitizing host for highly efficient green fluorescent organic light-emitting diodes

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Science China Materials 2024年第8期67卷 2618-2627页

作者： Unhyeok Jo Seung Chan Kim Chan hee Ryu Kang Mun Lee Jae-Min Kim jun Yeob Lee School of Chemical Engineering Sungkyunkwan University2066Seobu-roJangan-guSuwon-siGyeonggi-do 16419Republic of Korea Department of Chemistry Institute for Molecular Science and Fusion TechnologyKangwon National UniversityChuncheonGangwon 24341Republic of Korea Department of Advanced Materials Engineering Chung-Ang University4726Seodong-daeroDaedeok-myeonAnseong-siGyeonggi-do 17546Republic of Korea SKKU Advanced Institute of Nano Technology Sungkyunkwan University2066Seobu-roJangan-guSuwonGyeonggi 16419Republic of Korea SKKU Institute of Energy Science and Technology Sungkyunkwan University2066Seobu-roJangan-guSuwonGyeonggi 16419Republic of Korea

Efficient green fluorescent organic light-emitting diodes were designed with a phosphorescent metal complex as a singlet exciton sensitizing host(SESH)for achieving high efficiency and low efficiency roll-off through exciton and polaron *** Pt(Ⅱ)complex(Pt-Trz)possessing a tetradentate ligand with a bulky blocking group not only suppresses the severe formation of excimer or dimer itself but also transfers radiative excitons to fluorescent dopant *** SESH assisted fluorescence(SESHF)device with Pt-Trz as the host exhibits the maximum external quantum efficiency of 13.3%and a lower efficiency roll-off compared with exciplex host device which is a general approach for harvesting triplet *** exciton dynamics modeling unravels that the SESHF device effectively utilizes triplet excitons in the host by intersystem crossing and resonance energy transfer from the triplet state of the host to the singlet state of the terminal *** quenching rates of the SESHF device are reduced by 11 times for triplet-triplet annihilation and 1.8 times for tripletpolaron annihilation compared with the exciplex device,which demonstrates that Pt-Trz could be a platform to be used as an efficient host for fluorophores.

关键词： singlet annihilation polaron

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Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 51-60页

作者： Ga hee Kim Yeong Chan Lee Tae jun Kim Sung Noh Hong Dong Kyung Chang Young-Ho Kim Dong-Hoon Yang Chang Mo Moon Kyunga Kim Hyun Gun Kim Eun-Ran Kim Division of Gastroenterology Department of Internal MedicineAsan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505South Korea Department of Digital Health Samsung Advanced Institute for Health Science and TechnologySungkyunkwan University School of MedicineSeoul 06351South Korea Division of Gastroenterology Department of Internal MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Division of Gastroenterology Department of Internal MedicineEwha Womans UniversitySeoul 07985South Korea Biomedical Statistics Center Samsung Medical CenterSeoul 06351South Korea Division of Gastroenterology Department of Internal MedicineSoonchunhyang University College of MedicineSeoul 04401South Korea

BACKGROUND The incidence of colorectal cancer(CRC)and preinvasive CRC(e.g.,early colon cancer and advanced adenoma)is gradually increasing in several *** To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in *** This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC,and assess the numbers of diagnostic colonoscopies and colonoscopic ***-related complications by age group were also *** The incidence of CRC showed a rapid increase,then decreased after 2012 in the 50-75 year-age *** the study period,the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of *** 2009,the increase has been rapid,showing a pattern similar to the increase in *** rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after *** rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of *** The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies *** the risk of colonoscopy-related hospitalization and death is high in the elderly,if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75,colonoscopy-related complications can be reduced for those aged 76 years or over.

关键词： Colorectal cancer Preinvasive colorectal cancer Colorectal polypectomy Colonoscopy

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High Na-ion conductivity andmechanical integrity of anion-exchanged polymeric hydrogel electrolytes for flexible sodium ion hybrid energy storage

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SusMat 2024年第1期4卷 140-153页

作者： jungWoo Hong Harpalsinh H.Rana Jeong hee Park jun Su Kim Sang Joon Lee Gun Jang Tae Hoon Kang Kang Ho Shin Sang Ha Baek Wooseok Yang Kwang Ho Kim Ju-Hyuk Lee Ho Seok Park School of Chemical Engineering Sungkyunkwan UniversitySuwonRepublic of Korea Clean Energy Research Center Korea Institute of Science and Technology(KIST)SeoulRepublic of Korea KIST-SKKU Carbon-Neutral Research Center Sungkyunkwan University(SKKU)SuwonRepublic of Korea SKKU Institute of Energy Science and Technology(SIEST) Sungkyunkwan UniversitySuwonRepublic of Korea COSMOS LAB/92 Jomaru-ro 385beon-gilBucheon-siRepublic of Korea SKKU Advanced Institute of Nano Technology(SAINT) Sungkyunkwan UniversitySuwonRepublic of Korea Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences and Technology(SAIHST)Sungkyunkwan UniversitySuwonRepublic of Korea

The polymeric gel electrolytes are attractive owing to their higher ionic conductivities than those of dry polymer electrolytes and lowered water activity for enlarged potential ***,the ionic conductivity and mechanical strength of the Na-ion conducting polymeric gel electrolytes are limited by below 20 mS cm−1 and 2.2 ***,we demonstrate Na-ion conducting and flexible polymeric hydrogel electrolytes of the chemically coupled poly(diallyldimethylammonium chloride)-dextrin-N,N′-methylene-bisacrylamide film immersed in NaClO_(4) solution(ex-DDA-Dex+NaClO_(4))for flexible sodium-ion hybrid capacitors(f-NIHC).In particular,the anion exchange reaction and synergistic interaction of ex-DDA-Dex with the optimum ClO_(4)−enable to greatly improve the ionic conductivity up to 27.63 mS cm−1 at 25◦C and electrochemical stability window up to 2.6 V,whereas the double networking structure leads to achieve both the mechanical strength(7.48 MPa)and softness of hydrogel ***,the f-NIHCs with the ex-DDA-Dex+NaClO_(4) achieved high specific and high-rate capacities of 192.04 F g^(−1)at 500 mA g^(−1)and 116.06 F g^(−1)at 10000 mA g^(−1),respectively,delivering a large energy density of 120.03Wh kg^(−1)at 906Wkg^(−1)and long cyclability of 70%over 500 cycles as well as demonstrating functional operation under mechanical stresses.

关键词： anion exchange chemistry flexible energy storage hybrid energy storage hydrogel electrolytes renewable electrolytes sodium storage

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Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites

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Cancer Communications 2024年第1期44卷 47-75页

作者： Ji Eon Kim So-Young Park Chulhwan Kwak Yoonji Lee Dae-Geun Song Jae Woo jung Haesong Lee Eun-Ae Shin Yangie Pinanga Kyung-hee Pyo Eun Hae Lee Wonsik Kim Soyeon Kim Chang-Duck jun Jeanho Yun Sun Choi Hyun-Woo Rhee Kwang-Hyeon Liu jung Weon Lee Department of Pharmacy College of PharmacySeoul National UniversitySeoulRepublic of Korea Research Institute of Pharmaceutical Sciences College of PharmacySeoul National UniversitySeoulRepublic of Korea BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit College of Pharmacy and Research Institute of Pharmaceutical SciencesKyungpook National UniversityDaeguRepublic of Korea Department of Chemistry Seoul National UniversitySeoulRepublic of Korea College of Pharmacy Chung-Ang UniversitySeoulRepublic of Korea Natural Product Informatics Research Center Korea Institute of Science and Technology(KIST)Gangneung-siGangwon-doRepublic of Korea School of Life Sciences Gwangju Institute of Science and Technology(GIST)GwangjuRepublic of Korea Department of Biochemistry College of MedicineDong-A UniversityBusanRepublic of Korea Global AI Drug Discovery Center College of Pharmacy and Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoulRepublic of Korea Interdisciplinary Program in Genetic Engineering Seoul National UniversitySeoulRepublic of Korea

Background:Transmembrane 4 L six family member 5(TM4SF5)translocates subcellularly and functions metabolically,although it is unclear how intracellu-lar TM4SF5 translocation is linked to metabolic *** is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of ***:Here,we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites(MLCSs),using in vitro cells and in vivo animal systems,via approaches by immunofluorescence,proximity labelling based proteomics analysis,organelle reconstitution ***:Upon extracellular glucose repletion following depletion,TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8(FKBP8)and lysosomal *** labeling showed molecular clustering of phospho-dynamic-related protein I(DRP1)and certain mitophagy receptors at TM4SF5-enriched MLCSs,leading to mitochondrial fis-sion and ***4SF5 bound NPC intracellular cholesterol transporter 1(NPC1)and free cholesterol,and mediated export of lysosomal cholesterol to mitochondria,leading to impaired oxidative phosphorylation but intact tri-carboxylic acid(TCA)cycle andβ-*** mouse models,hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria,both with positive relations to liver ***:Our findings suggested that TM4SF5-enriched MLCSs regu-late glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming,presumably while hepatocellular carcinogenesis,recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial repro-gramming to support biomolecule synthesis in addition to glycolytic energetics.

关键词： cholesterol fluorescent imaging glucose catabolism hepatocellular carcinogenesis mem-brane contact sites mitochondria function mitophagy oxidative phosphorylation protein-protein interaction tetraspanin

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