1.A Study on iPSC-Associated Factors in the Generation of Hepatocytes
Delger BAYARSAIKHAN ; Govigerel BAYARSAIKHAN ; Hyun A KANG ; Su Bin LEE ; So Hee HAN ; Teruo OKANO ; Kyungsook KIM ; Bonghee LEE
Tissue Engineering and Regenerative Medicine 2024;21(8):1245-1254
BACKGROUND:
Hepatocytes are an attractive cell source in hepatic tissue engineering because they are the primary cells of the liver, maintaining liver homeostasis through their intrinsic function. Due to the increasing demand for liver donors, a wide range of methods are being studied to obtain functionally active hepatocytes. iPSCs are one of the alternative cell sources, which shows great promise as a tool for generating hepatocytes.
METHODS:
This study determined whether factors associated with iPSCs contributed to variation in hepatocyte-like cells derived from iPSCs. The factors of concern for the iPSCs included the culture system, the source of iPSCs, and cell seeding density for initiating the differentiation.
RESULTS:
Our results found iPSC-dependent variances among differentiated hepatocyte-like cells. The matrix used in culturing iPSCs significantly impacts cell morphologies, characteristics, and the expression of pluripotent genes, such as OCT4 and SOX2, varied in iPSCs derived from different sources. These characteristics, in turn, play a consequential role in determining the functional activity of the iPSC-derived hepatocyte-like cells. In addition, cell seeding density was observed to be an essential factor for the efficient generation of iPSC-derived hepatocyte-like cells, with 2- 4 * 10 cells/cm of seeding density resulting in good morphology and functionality.
CONCLUSION
This study provides the baseline of effective differentiation protocols for iPSC-derived hepatocyte-like cells with the appropriate conditions, including cell culture media, iPSC source, and the seeding density of iPSCs.
2.Extraction process optimization and quality standard establishment for Jigen Standard Decoction
Guo-Chun YANG ; Ya-Fang YANG ; Su-E XU ; Jin KE ; Ling-Yun CHEN ; An-Guo HOU ; Wen-Bin JIN
Chinese Traditional Patent Medicine 2024;46(6):1773-1781
AIM To optimize the extraction process for Jigen Standard Decoction,and to establish its quality standard.METHODS With soaking time,water addition and first decoction time as influencing factors,comprehensive score for 3,6'-disinapoyl sucrose content and yield rate as an evaluation index,the extraction process was optimized by response surface method on the basis of single factor test.The content and transfer rate of 3,6'-dimustayl sucrose were determined,after which HPLC characteristic chromatograms were established,cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed.RESULTS The optimal conditions were determined to be 60 min for soaking time,(12+11)times for water addition,and(47+20)min for decoction time,the comprehensive score was 97.98.Fifteen batches of standard decoctions demonstrated the average yield rate and transfer rate of 14.182%and 20.468%,respectively,whose characteristic chromatograms existed six common peaks with the similarities of more than 0.9(except for S4,S8).Various batches of standard decoctions were clustered into two types,three principal components displayed the acumulative variance contribution rate of 91.4%,peaks 2,6 were quality markers.CONCLUSION This precise,stable and reproducible method can be used for the preparation and quality control of Jigen Standard Decoction.
3.A Study on iPSC-Associated Factors in the Generation of Hepatocytes
Delger BAYARSAIKHAN ; Govigerel BAYARSAIKHAN ; Hyun A KANG ; Su Bin LEE ; So Hee HAN ; Teruo OKANO ; Kyungsook KIM ; Bonghee LEE
Tissue Engineering and Regenerative Medicine 2024;21(8):1245-1254
BACKGROUND:
Hepatocytes are an attractive cell source in hepatic tissue engineering because they are the primary cells of the liver, maintaining liver homeostasis through their intrinsic function. Due to the increasing demand for liver donors, a wide range of methods are being studied to obtain functionally active hepatocytes. iPSCs are one of the alternative cell sources, which shows great promise as a tool for generating hepatocytes.
METHODS:
This study determined whether factors associated with iPSCs contributed to variation in hepatocyte-like cells derived from iPSCs. The factors of concern for the iPSCs included the culture system, the source of iPSCs, and cell seeding density for initiating the differentiation.
RESULTS:
Our results found iPSC-dependent variances among differentiated hepatocyte-like cells. The matrix used in culturing iPSCs significantly impacts cell morphologies, characteristics, and the expression of pluripotent genes, such as OCT4 and SOX2, varied in iPSCs derived from different sources. These characteristics, in turn, play a consequential role in determining the functional activity of the iPSC-derived hepatocyte-like cells. In addition, cell seeding density was observed to be an essential factor for the efficient generation of iPSC-derived hepatocyte-like cells, with 2- 4 * 10 cells/cm of seeding density resulting in good morphology and functionality.
CONCLUSION
This study provides the baseline of effective differentiation protocols for iPSC-derived hepatocyte-like cells with the appropriate conditions, including cell culture media, iPSC source, and the seeding density of iPSCs.
4.A Study on iPSC-Associated Factors in the Generation of Hepatocytes
Delger BAYARSAIKHAN ; Govigerel BAYARSAIKHAN ; Hyun A KANG ; Su Bin LEE ; So Hee HAN ; Teruo OKANO ; Kyungsook KIM ; Bonghee LEE
Tissue Engineering and Regenerative Medicine 2024;21(8):1245-1254
BACKGROUND:
Hepatocytes are an attractive cell source in hepatic tissue engineering because they are the primary cells of the liver, maintaining liver homeostasis through their intrinsic function. Due to the increasing demand for liver donors, a wide range of methods are being studied to obtain functionally active hepatocytes. iPSCs are one of the alternative cell sources, which shows great promise as a tool for generating hepatocytes.
METHODS:
This study determined whether factors associated with iPSCs contributed to variation in hepatocyte-like cells derived from iPSCs. The factors of concern for the iPSCs included the culture system, the source of iPSCs, and cell seeding density for initiating the differentiation.
RESULTS:
Our results found iPSC-dependent variances among differentiated hepatocyte-like cells. The matrix used in culturing iPSCs significantly impacts cell morphologies, characteristics, and the expression of pluripotent genes, such as OCT4 and SOX2, varied in iPSCs derived from different sources. These characteristics, in turn, play a consequential role in determining the functional activity of the iPSC-derived hepatocyte-like cells. In addition, cell seeding density was observed to be an essential factor for the efficient generation of iPSC-derived hepatocyte-like cells, with 2- 4 * 10 cells/cm of seeding density resulting in good morphology and functionality.
CONCLUSION
This study provides the baseline of effective differentiation protocols for iPSC-derived hepatocyte-like cells with the appropriate conditions, including cell culture media, iPSC source, and the seeding density of iPSCs.
5.A Study on iPSC-Associated Factors in the Generation of Hepatocytes
Delger BAYARSAIKHAN ; Govigerel BAYARSAIKHAN ; Hyun A KANG ; Su Bin LEE ; So Hee HAN ; Teruo OKANO ; Kyungsook KIM ; Bonghee LEE
Tissue Engineering and Regenerative Medicine 2024;21(8):1245-1254
BACKGROUND:
Hepatocytes are an attractive cell source in hepatic tissue engineering because they are the primary cells of the liver, maintaining liver homeostasis through their intrinsic function. Due to the increasing demand for liver donors, a wide range of methods are being studied to obtain functionally active hepatocytes. iPSCs are one of the alternative cell sources, which shows great promise as a tool for generating hepatocytes.
METHODS:
This study determined whether factors associated with iPSCs contributed to variation in hepatocyte-like cells derived from iPSCs. The factors of concern for the iPSCs included the culture system, the source of iPSCs, and cell seeding density for initiating the differentiation.
RESULTS:
Our results found iPSC-dependent variances among differentiated hepatocyte-like cells. The matrix used in culturing iPSCs significantly impacts cell morphologies, characteristics, and the expression of pluripotent genes, such as OCT4 and SOX2, varied in iPSCs derived from different sources. These characteristics, in turn, play a consequential role in determining the functional activity of the iPSC-derived hepatocyte-like cells. In addition, cell seeding density was observed to be an essential factor for the efficient generation of iPSC-derived hepatocyte-like cells, with 2- 4 * 10 cells/cm of seeding density resulting in good morphology and functionality.
CONCLUSION
This study provides the baseline of effective differentiation protocols for iPSC-derived hepatocyte-like cells with the appropriate conditions, including cell culture media, iPSC source, and the seeding density of iPSCs.
6.A Study on iPSC-Associated Factors in the Generation of Hepatocytes
Delger BAYARSAIKHAN ; Govigerel BAYARSAIKHAN ; Hyun A KANG ; Su Bin LEE ; So Hee HAN ; Teruo OKANO ; Kyungsook KIM ; Bonghee LEE
Tissue Engineering and Regenerative Medicine 2024;21(8):1245-1254
BACKGROUND:
Hepatocytes are an attractive cell source in hepatic tissue engineering because they are the primary cells of the liver, maintaining liver homeostasis through their intrinsic function. Due to the increasing demand for liver donors, a wide range of methods are being studied to obtain functionally active hepatocytes. iPSCs are one of the alternative cell sources, which shows great promise as a tool for generating hepatocytes.
METHODS:
This study determined whether factors associated with iPSCs contributed to variation in hepatocyte-like cells derived from iPSCs. The factors of concern for the iPSCs included the culture system, the source of iPSCs, and cell seeding density for initiating the differentiation.
RESULTS:
Our results found iPSC-dependent variances among differentiated hepatocyte-like cells. The matrix used in culturing iPSCs significantly impacts cell morphologies, characteristics, and the expression of pluripotent genes, such as OCT4 and SOX2, varied in iPSCs derived from different sources. These characteristics, in turn, play a consequential role in determining the functional activity of the iPSC-derived hepatocyte-like cells. In addition, cell seeding density was observed to be an essential factor for the efficient generation of iPSC-derived hepatocyte-like cells, with 2- 4 * 10 cells/cm of seeding density resulting in good morphology and functionality.
CONCLUSION
This study provides the baseline of effective differentiation protocols for iPSC-derived hepatocyte-like cells with the appropriate conditions, including cell culture media, iPSC source, and the seeding density of iPSCs.
7.Patient-Reported Outcomes of Postoperative NSCLC Patients with or without Staged Chinese Herb Medicine Therapy during Adjuvant Chemotherapy (NALLC 2): A Randomized, Double-Blind, Placebo-Controlled Trial.
Yi-Lu ZHANG ; Li-Jing JIAO ; Ya-Bin GONG ; Jian-Fang XU ; Jian NI ; Xiao-Yong SHEN ; Jie ZHANG ; Di ZHOU ; Cheng-Xin QIAN ; Qin WANG ; Jia-Lin YAO ; Wen-Xiao YANG ; Ling-Zi SU ; Li-Yu WANG ; Jia-Qi LI ; Yi-Qin YAO ; Yuan-Hui ZHANG ; Yi-Chao WANG ; Zhi-Wei CHEN ; Ling XU
Chinese journal of integrative medicine 2024;30(11):963-973
OBJECTIVE:
To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone.
METHODS:
A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis.
RESULTS:
Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52).
CONCLUSION
The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).
Humans
;
Carcinoma, Non-Small-Cell Lung/surgery*
;
Male
;
Middle Aged
;
Female
;
Lung Neoplasms/pathology*
;
Double-Blind Method
;
Drugs, Chinese Herbal/therapeutic use*
;
Chemotherapy, Adjuvant
;
Patient Reported Outcome Measures
;
Quality of Life
;
Aged
;
Postoperative Period
;
Prospective Studies
8.Mining Novel Anti-Nocardia Drug Targets Based on Pan-genomics and Subtractive Proteomics
Er-tong LI ; Ya-lin SU ; Wen-bin LIU ; Xiao-bao JIN
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(6):974-982
ObjectiveNocardia is an apathogen that causes opportunistic infections in humans and has a global distribution. In recent years, resistance of Nocardia to commonly used drugs have been observed, highlighting the urgent need for the identification of new drug targets and the development of novel antimicrobial agents against Nocardia. MethodsThirty-one complete genome sequences of Nocardia strains were retrieved from the GenBank database. Pan-genomic analysis was performed using BPGA, and drug target candidates were screened using subtractive proteomics. Homology modeling was employed to predict the 3D structures of target proteins, and potential drugs targeting these proteins were predicted using DrugBank. Molecular docking techniques were utilized to validate the binding activity between the drugs and target proteins. ResultsThe pan-genomic analysis of the 31 Nocardia strains revealed 1 421 core proteins. Fifteen candidate drug target proteins were identified through subtractive proteomics analysis. Among them, the physicochemical properties of the OG1493 protein (such as amino acid count, molecular weight, isoelectric point, grand average of hydropathicity, fat index,and instability index Ⅱ) were found to be most suitable for a drug target protein. Using the DrugBank database, seven compounds, namely Adenosine-5'-Rp-Alpha-Thio-Triphosphate, alpha,beta-Methyleneadenosine 5'-triphosphate, Phosphoaminophosphonic Acid-Adenylate Ester ,Radicicol,2-Hydroxyestradiol, p-Coumaric acid, and Ethylmercurithiosalicylic acid were identified as potential compounds capable of exerting anti-Nocardia effects by targeting this protein. Molecular docking results indicated a strong binding affinity between the target protein and these compounds. The experimental result showed that that Radicicol could be a potential antibacterial drug targeting this particular protein. ConclusionPan-genomic analysis and subtractive proteomics are valuable approaches for mining novel anti-Nocardia drug targets.
10. Protein phosphorylation involved in psychedelic-induced head-twitch response in rats
Shao-Wen WANG ; Ya-Nan ZHOU ; Shao-Wen WANG ; Ya-Nan ZHOU ; Yi SUN ; Rui-Bin SU
Chinese Pharmacological Bulletin 2023;39(10):1899-1904
Aim To investigate the potential protein post-translational modifications of psychedelic-induced Head-twith response and underling mechanism. Methods Psychedelics LSD, DOM, or Psilocin was administered to rats by intraperitoneal injection to induce head-twitch response, then the most effective dosage was identified to create animal models of head-twitch behavior. Western blot was performed in detecting the protein phosphorylation, acetylation, and ubiquitination in prefrontal cortex of SD rats after 10 min or 30 min injection. Results LSD (0.025 mg • kg~, i. p.), DOM (3 mg•kg

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