Mounting evidence in stem cell biology has shown that microRNAs(miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineagespecific differentiation, and somatic cell reprogramming...Mounting evidence in stem cell biology has shown that microRNAs(miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineagespecific differentiation, and somatic cell reprogramming.These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineagespecific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells.Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.展开更多
Primary intestinal lymphangiectasia(PIL)is a rare disorder characterized by dilated intestinal lymphatics and the development of protein-losing enteropathy.Patients with PIL develop hypoalbuminemia,hypocalcemia,lympho...Primary intestinal lymphangiectasia(PIL)is a rare disorder characterized by dilated intestinal lymphatics and the development of protein-losing enteropathy.Patients with PIL develop hypoalbuminemia,hypocalcemia,lymphopenia and hypogammaglobulinemia,and present with bilateral lower limb edema,fatigue,abdominal pain and diarrhea.Endoscopy reveals diffusely elongated,circumferential and polypoid mucosae covered with whitish enlarged villi,all of which indicate intestinal lymphangiectasia.Diagnosis is conf irmed by characteristic tissue pathology,which includes dilated intestinal lymphatics with diffusely swollen mucosa and enlarged villi.The prevalence of PIL has increased since the introduction of capsule endoscopy.The etiology and prevalence of PIL remain unknown.Some studies have reported that several genes and regulatory molecules for lymphangiogenesis are related to PIL.We report the case of a patient with PIL involving the entire small bowel that was confirmed by capsule endoscopy and double-balloon enteroscopy-guided tissue pathology who carried a deletion on chromosome 4q25.The relationship between this deletion on chromosome 4 and PIL remains to be investigated.展开更多
AIM:To investigate the feasibility of a single-use endoscopy as an alternative procedure to nasogastric lavage in patients with acute gastrointestinal(GI) bleeding.METHODS:Patients who presented with hematemesis,melen...AIM:To investigate the feasibility of a single-use endoscopy as an alternative procedure to nasogastric lavage in patients with acute gastrointestinal(GI) bleeding.METHODS:Patients who presented with hematemesis,melena or hematochezia were enrolled in this study.EG scan and conventional esophagogastroduodenoscopy(EGD) were subsequently performed.Active bleeding was defined as blood in the stomach,and inactive bleeding was defined as coffee ground clots and clear fluid in the stomach.The findings were recorded and compared.RESULTS:Between January and March,2011,13 patients that presented with hematemesis(n = 4),melena(n = 6),or bleeding from a previous nasogastric feeding tube(n = 3),were enrolled in this study.In 12 patients with upper GI bleeding,the EG scan device revealed that 7 patients had active bleeding and 5 patients had inactive bleeding,whereas conventional EGD revealed that 8 patients had active bleeding and 4 patients had inactive bleeding.The sensitivity and specificity of the EG scan device was 87.5% and 100% for active bleeding,with conventional EGD serving as a reference.No complication were reported during the EG scan procedures.CONCLUSION:The EG scan is a feasible device for screening acute upper GI bleeding.It may replace nasogastric lavage for the evaluation of acute upper GI bleeding.展开更多
Plastic stent insertion is a treatment option for pancreatic duct stricture with chronic pancreatitis.However, recurrent stricture is a limitation after removing the plastic stent.Self-expandable metal stents have lon...Plastic stent insertion is a treatment option for pancreatic duct stricture with chronic pancreatitis.However, recurrent stricture is a limitation after removing the plastic stent.Self-expandable metal stents have long diameters and patency.A metal stent has become an established management option for pancreatic duct stricture caused by malignancy but its use in benign stricture is still controversial.We introduce a young patient who had chronic pancreatitis and underwent several plastic stent insertions due to recurrent pancreatic duct stricture.His symptoms improved after using a fully covered self-expandable metal covered stent and there was no recurrence found at follow-up at the outpatient department.展开更多
Exogenously delivered mesenchymal stromal cells(MSCs)are therapeutically beneficial owing to their paracrine effect;they secrete various cytokines,nucleic acids,and proteins.Multiple bioengineering techniques can help...Exogenously delivered mesenchymal stromal cells(MSCs)are therapeutically beneficial owing to their paracrine effect;they secrete various cytokines,nucleic acids,and proteins.Multiple bioengineering techniques can help MSC cultures to release secretomes by providing stem cell niche-like conditions(both structurally and functionally).Various scaffolds mimic the natural extracellular matrix(ECM)using both natural and synthetic polymers,providing favorable environments for MSC proliferation and differentiation.Depending on material properties,either topographically or elastically structured scaffolds can be fabricated.Three-dimensional scaffolds have tunable substrate rigidities and structures,aiding MSC cultivation.Decellularized ECM-derived hydrogels are similar to the natural ECM,thus improving the paracrine effects of MSCs.Here,we discuss recent research on the application of scaffolds to maximize the immunomodulatory function of MSCs.展开更多
4-1BB is an inducible receptor expressed on activated T cells,while its ligand,4-1BBL,is mainly expressed in antigen-presenting cells and macrophages[1,2].To the best of our knowledge,ligandmediated transactivation of...4-1BB is an inducible receptor expressed on activated T cells,while its ligand,4-1BBL,is mainly expressed in antigen-presenting cells and macrophages[1,2].To the best of our knowledge,ligandmediated transactivation of 4-1BB is responsible for the survival and immune effector functions of T cells.展开更多
Background: Autophagy is elevated in metastatic tumors and is often associatedwith active epithelial-to-mesenchymal transition (EMT). However, the extent towhich EMT is dependent on autophagy is largely unknown. This ...Background: Autophagy is elevated in metastatic tumors and is often associatedwith active epithelial-to-mesenchymal transition (EMT). However, the extent towhich EMT is dependent on autophagy is largely unknown. This study aimed toidentify the mechanisms by which autophagy facilitates EMT.Methods: We employed a liquid chromatography-based metabolomic approachwith kirsten rat sarcoma viral oncogene (KRAS) and liver kinase B1 (LKB1)gene co-mutated (KL) cells that represent an autophagy/EMT-coactivatedinvasive lung cancer subtype for the identification of metabolites linked to autophagy-driven EMT activation. Molecular mechanisms of autophagy-drivenEMT activation were further investigated by quantitative real-time polymerasechain reaction (qRT-PCR), Western blotting analysis, immunoprecipitation,immunofluorescence staining, and metabolite assays. The effects of chemicaland genetic perturbations on autophagic flux were assessed by two orthogonalapproaches: microtubule-associated protein 1A/1B-light chain 3 (LC3) turnoveranalysis by Western blotting and monomeric red fluorescent protein-greenfluorescent protein (mRFP-GFP)-LC3 tandem fluorescent protein quenchingassay. Transcription factor EB (TFEB) activity was measured by coordinatedlysosomal expression and regulation (CLEAR) motif-driven luciferase reporterassay. Experimental metastasis (tail vein injection) mouse models were used toevaluate the impact of calcium/calmodulin-dependent protein kinase kinase 2(CAMKK2) or ATP citrate lyase (ACLY) inhibitors on lung metastasis using IVISluciferase imaging system.Results: We found that autophagy in KL cancer cells increased acetyl-coenzymeA (acetyl-CoA), which facilitated the acetylation and stabilization of theEMT-inducing transcription factor Snail. The autophagy/acetyl-CoA/acetylSnail axis was further validated in tumor tissues and in autophagy-activatedpancreatic cancer cells. TFEB acetylation in KL cancer cells sustained prometastatic autophagy in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner. Pharmacological inhibition of this axis via CAMKK2inhibitors or ACLY inhibitors consistently reduced the metastatic capacity of KLcancer cells in vivo.Conclusions: This study demonstrates that autophagy-derived acetyl-CoA promotes Snail acetylation and thereby facilitates invasion and metastasis of KRASLKB1 co-mutated lung cancer cells and that inhibition of the autophagy/acetylCoA/acetyl-Snail axis using CAMKK2 or ACLY inhibitors could be a potentialtherapeutic strategy to suppress metastasis of KL lung cancer.展开更多
We have synthesized water-stable polyaniline nanoparticles coated with tri- armed polyethylene glycol chains using a solvent-shift method and confirmed their colloidal size and aqueous solubility. Furthermore, we have...We have synthesized water-stable polyaniline nanoparticles coated with tri- armed polyethylene glycol chains using a solvent-shift method and confirmed their colloidal size and aqueous solubility. Furthermore, we have demonstrated that the polyaniline nanoparticles can be doped with biological dopants to produce distinct color changes allowing the detection of live cancer cells.展开更多
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 i...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.展开更多
Background Ursodeoxycholic acid(UDCA),statins,and ezetimibe(EZE)have demonstrated beneficial effects against nonalcoholic fatty liver disease(NAFLD).We investigated the efficacy of the combination of UDCA and the mix ...Background Ursodeoxycholic acid(UDCA),statins,and ezetimibe(EZE)have demonstrated beneficial effects against nonalcoholic fatty liver disease(NAFLD).We investigated the efficacy of the combination of UDCA and the mix of rosuvastatin(RSV)/EZE in the treatment of NAFLD.Methods NAFLD mouse models were developed by injecting thioacetamide,fasting,and high-carbohydrate refeeding,highfat diet,and choline-deficient L-amino acid-defined high-fat diet(CDAHFD).Low-dose UDCA(L-UDCA;15 mg/kg)or highdose UDCA(H-UDCA;30 mg/kg)was administered with RSV/EZE.We also employed an in vitro model of NAFLD developed using palmitic acid-treated Hepa1c1c7 cells.Results Co-administration of RSV/EZE with UDCA significantly decreased the collagen accumulation,serum alanine aminotransferase(ALT)levels,and mRNA levels of fibrosis-related markers than those observed in the vehicle group in thioacetamide-treated mice(all P<0.01).In addition,in the group fasted and refed with a high-carbohydrate diet,UDCA/RSV/EZE treatment decreased the number of apoptotic cells and serum ALT levels compared with those observed in the vehicle group(all P<0.05).Subsequently,H-UDCA/RSV/EZE treatment decreased the number of ballooned hepatocytes and stearoyl-CoA desaturase 1(SCD-1)mRNA levels(P=0.027)in the liver of high-fat diet-fed mice compared with those observed in the vehicle group.In the CDAHFD-fed mouse model,UDCA/RSV/EZE significantly attenuated collagen accumulation and fibrosis-related markers compared to those observed in the vehicle group(all P<0.05).In addition,UDCA/RSV/EZE treatment significantly restored cell survival and decreased the protein levels of apoptosis-related markers compared to RSV/EZE treatment in palmitic acid-treated Hepa1c1c7 cells(all P<0.05).Conclusion Combination therapy involving UDCA and RSV/EZE may be a novel strategy for potent inhibition of NAFLD progression.展开更多
基金supported by a South Korea Science and Engineering Foundation grant funded by the South Korea government(MEST)(2011-0019243,2011-0019254)a grant from the South Korea Health 21 R and D Project,Ministry of Health and Welfare,South Korea(A120478)a grant from the Korea Health 21 R and D Project,Ministry of Health and Welfare,South Korea(A085136)
文摘Mounting evidence in stem cell biology has shown that microRNAs(miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineagespecific differentiation, and somatic cell reprogramming.These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineagespecific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells.Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.
文摘Primary intestinal lymphangiectasia(PIL)is a rare disorder characterized by dilated intestinal lymphatics and the development of protein-losing enteropathy.Patients with PIL develop hypoalbuminemia,hypocalcemia,lymphopenia and hypogammaglobulinemia,and present with bilateral lower limb edema,fatigue,abdominal pain and diarrhea.Endoscopy reveals diffusely elongated,circumferential and polypoid mucosae covered with whitish enlarged villi,all of which indicate intestinal lymphangiectasia.Diagnosis is conf irmed by characteristic tissue pathology,which includes dilated intestinal lymphatics with diffusely swollen mucosa and enlarged villi.The prevalence of PIL has increased since the introduction of capsule endoscopy.The etiology and prevalence of PIL remain unknown.Some studies have reported that several genes and regulatory molecules for lymphangiogenesis are related to PIL.We report the case of a patient with PIL involving the entire small bowel that was confirmed by capsule endoscopy and double-balloon enteroscopy-guided tissue pathology who carried a deletion on chromosome 4q25.The relationship between this deletion on chromosome 4 and PIL remains to be investigated.
基金Supported by Basic Science Research Program through the National Research Foundation of Korea, the Ministry of Education, Science and Technology, No. 2011-0008901Research Program of Clinical Professor Research committee of Myongji Hospital, No. 20120106
文摘AIM:To investigate the feasibility of a single-use endoscopy as an alternative procedure to nasogastric lavage in patients with acute gastrointestinal(GI) bleeding.METHODS:Patients who presented with hematemesis,melena or hematochezia were enrolled in this study.EG scan and conventional esophagogastroduodenoscopy(EGD) were subsequently performed.Active bleeding was defined as blood in the stomach,and inactive bleeding was defined as coffee ground clots and clear fluid in the stomach.The findings were recorded and compared.RESULTS:Between January and March,2011,13 patients that presented with hematemesis(n = 4),melena(n = 6),or bleeding from a previous nasogastric feeding tube(n = 3),were enrolled in this study.In 12 patients with upper GI bleeding,the EG scan device revealed that 7 patients had active bleeding and 5 patients had inactive bleeding,whereas conventional EGD revealed that 8 patients had active bleeding and 4 patients had inactive bleeding.The sensitivity and specificity of the EG scan device was 87.5% and 100% for active bleeding,with conventional EGD serving as a reference.No complication were reported during the EG scan procedures.CONCLUSION:The EG scan is a feasible device for screening acute upper GI bleeding.It may replace nasogastric lavage for the evaluation of acute upper GI bleeding.
文摘Plastic stent insertion is a treatment option for pancreatic duct stricture with chronic pancreatitis.However, recurrent stricture is a limitation after removing the plastic stent.Self-expandable metal stents have long diameters and patency.A metal stent has become an established management option for pancreatic duct stricture caused by malignancy but its use in benign stricture is still controversial.We introduce a young patient who had chronic pancreatitis and underwent several plastic stent insertions due to recurrent pancreatic duct stricture.His symptoms improved after using a fully covered self-expandable metal covered stent and there was no recurrence found at follow-up at the outpatient department.
基金This research is supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(Grant No.2020R1A2C2011617)by a Chung-Ang University Research Scholarship Grants in 2019.
文摘Exogenously delivered mesenchymal stromal cells(MSCs)are therapeutically beneficial owing to their paracrine effect;they secrete various cytokines,nucleic acids,and proteins.Multiple bioengineering techniques can help MSC cultures to release secretomes by providing stem cell niche-like conditions(both structurally and functionally).Various scaffolds mimic the natural extracellular matrix(ECM)using both natural and synthetic polymers,providing favorable environments for MSC proliferation and differentiation.Depending on material properties,either topographically or elastically structured scaffolds can be fabricated.Three-dimensional scaffolds have tunable substrate rigidities and structures,aiding MSC cultivation.Decellularized ECM-derived hydrogels are similar to the natural ECM,thus improving the paracrine effects of MSCs.Here,we discuss recent research on the application of scaffolds to maximize the immunomodulatory function of MSCs.
基金This study was supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(2022R1A2C1005463[BKC],2022R1C1C1010078[SHK],and 2022R1C1C1003152[CH]from MSIT)by the National Cancer Center of Korea(NCC)grant funded by the Ministry of Health and Welfare(NCC-2212450[CH]).
文摘4-1BB is an inducible receptor expressed on activated T cells,while its ligand,4-1BBL,is mainly expressed in antigen-presenting cells and macrophages[1,2].To the best of our knowledge,ligandmediated transactivation of 4-1BB is responsible for the survival and immune effector functions of T cells.
基金Korea Health Technology R&D Project through the Korea Health Industry Development Institute,Grant/Award Number:HI14C1324National Research Foundation of Korea,Grant/Award Numbers:2020R1A2C3007792,2019R1A2C3004155,2019H1A2A1075632+2 种基金NCI Lung Cancer SPORE,Grant/Award Number:P50CA70907Cancer Prevention and Research Institute of Texas(CPRIT),Grant/Award Number:RP160652“Team Science Award”of Yonsei University College of Medicine,Grant/Award Number:6-2021-0194。
文摘Background: Autophagy is elevated in metastatic tumors and is often associatedwith active epithelial-to-mesenchymal transition (EMT). However, the extent towhich EMT is dependent on autophagy is largely unknown. This study aimed toidentify the mechanisms by which autophagy facilitates EMT.Methods: We employed a liquid chromatography-based metabolomic approachwith kirsten rat sarcoma viral oncogene (KRAS) and liver kinase B1 (LKB1)gene co-mutated (KL) cells that represent an autophagy/EMT-coactivatedinvasive lung cancer subtype for the identification of metabolites linked to autophagy-driven EMT activation. Molecular mechanisms of autophagy-drivenEMT activation were further investigated by quantitative real-time polymerasechain reaction (qRT-PCR), Western blotting analysis, immunoprecipitation,immunofluorescence staining, and metabolite assays. The effects of chemicaland genetic perturbations on autophagic flux were assessed by two orthogonalapproaches: microtubule-associated protein 1A/1B-light chain 3 (LC3) turnoveranalysis by Western blotting and monomeric red fluorescent protein-greenfluorescent protein (mRFP-GFP)-LC3 tandem fluorescent protein quenchingassay. Transcription factor EB (TFEB) activity was measured by coordinatedlysosomal expression and regulation (CLEAR) motif-driven luciferase reporterassay. Experimental metastasis (tail vein injection) mouse models were used toevaluate the impact of calcium/calmodulin-dependent protein kinase kinase 2(CAMKK2) or ATP citrate lyase (ACLY) inhibitors on lung metastasis using IVISluciferase imaging system.Results: We found that autophagy in KL cancer cells increased acetyl-coenzymeA (acetyl-CoA), which facilitated the acetylation and stabilization of theEMT-inducing transcription factor Snail. The autophagy/acetyl-CoA/acetylSnail axis was further validated in tumor tissues and in autophagy-activatedpancreatic cancer cells. TFEB acetylation in KL cancer cells sustained prometastatic autophagy in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner. Pharmacological inhibition of this axis via CAMKK2inhibitors or ACLY inhibitors consistently reduced the metastatic capacity of KLcancer cells in vivo.Conclusions: This study demonstrates that autophagy-derived acetyl-CoA promotes Snail acetylation and thereby facilitates invasion and metastasis of KRASLKB1 co-mutated lung cancer cells and that inhibition of the autophagy/acetylCoA/acetyl-Snail axis using CAMKK2 or ACLY inhibitors could be a potentialtherapeutic strategy to suppress metastasis of KL lung cancer.
文摘We have synthesized water-stable polyaniline nanoparticles coated with tri- armed polyethylene glycol chains using a solvent-shift method and confirmed their colloidal size and aqueous solubility. Furthermore, we have demonstrated that the polyaniline nanoparticles can be doped with biological dopants to produce distinct color changes allowing the detection of live cancer cells.
文摘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.
基金supported by Daewoong Pharmaceutical company,and was supported by a Faculty Research Grant from the Yonsei University College of Medicine(6-2019-0068 to S.H.Bae)by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)+2 种基金funded by the Ministry of Health&Welfare,Republic of Korea(HI17C0913 and HI16C0257 to S.H.Bae)supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(NRF-2022R1A2C2003438 to S.H.Bae,NRF-2021R1C1C2095694 to D.H.Lee)by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(2019R1A2C4070136 to S.U.Kim).
文摘Background Ursodeoxycholic acid(UDCA),statins,and ezetimibe(EZE)have demonstrated beneficial effects against nonalcoholic fatty liver disease(NAFLD).We investigated the efficacy of the combination of UDCA and the mix of rosuvastatin(RSV)/EZE in the treatment of NAFLD.Methods NAFLD mouse models were developed by injecting thioacetamide,fasting,and high-carbohydrate refeeding,highfat diet,and choline-deficient L-amino acid-defined high-fat diet(CDAHFD).Low-dose UDCA(L-UDCA;15 mg/kg)or highdose UDCA(H-UDCA;30 mg/kg)was administered with RSV/EZE.We also employed an in vitro model of NAFLD developed using palmitic acid-treated Hepa1c1c7 cells.Results Co-administration of RSV/EZE with UDCA significantly decreased the collagen accumulation,serum alanine aminotransferase(ALT)levels,and mRNA levels of fibrosis-related markers than those observed in the vehicle group in thioacetamide-treated mice(all P<0.01).In addition,in the group fasted and refed with a high-carbohydrate diet,UDCA/RSV/EZE treatment decreased the number of apoptotic cells and serum ALT levels compared with those observed in the vehicle group(all P<0.05).Subsequently,H-UDCA/RSV/EZE treatment decreased the number of ballooned hepatocytes and stearoyl-CoA desaturase 1(SCD-1)mRNA levels(P=0.027)in the liver of high-fat diet-fed mice compared with those observed in the vehicle group.In the CDAHFD-fed mouse model,UDCA/RSV/EZE significantly attenuated collagen accumulation and fibrosis-related markers compared to those observed in the vehicle group(all P<0.05).In addition,UDCA/RSV/EZE treatment significantly restored cell survival and decreased the protein levels of apoptosis-related markers compared to RSV/EZE treatment in palmitic acid-treated Hepa1c1c7 cells(all P<0.05).Conclusion Combination therapy involving UDCA and RSV/EZE may be a novel strategy for potent inhibition of NAFLD progression.