Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

Lu, Feng-Bin,Chen, Da-Zhi,Chen, Lu,Hu, En-De,Wu, Jin-Lu,Li, Hui,Gong, Yue-Wen,Lin, Zhuo,Wang, Xiao-Dong,Li, Ji,Jin, Xiao-Ya,Xu, Lan-Man,Chen, Yong-Ping Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.12

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

Yong-Ping Chen,Feng-Bin Lu,Da-Zhi Chen,Lu Chen,En-De Hu,Jin-Lu Wu,Hui Li,Yue-Wen Gong,Zhuo Lin,Xiao-Dong Wang,Ji Li,Xiao-Ya Jin,Lan-Man Xu 한국분자세포생물학회 2019 Molecules and cells Vol.42 No.12

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Molecular Cloning, Characterization and Expression of a Novel Trehalose-6-phosphate Synthase Homologue from Ginkgo biloba

Wu, Weisheng,Pang, Yongzhen,Shen, Guo-An,Lu, Jie,Lin, Juan,Wang, Jin,Sun, Xiaofen,Tang, Kexuan Korean Society for Biochemistry and Molecular Biol 2006 Journal of biochemistry and molecular biology Vol.39 No.2

In many organisms, trehalose acts as protective metabolite against harsh environmental stresses, such as freezing, drought, nutrient starvation, heat and salt. Herein a cDNA (designated as GbTPS, GenBank Accession Number AY884150) encoding a trehalose-6-phosphate synthase homologue was isolated and characterized from the living fossil plant, Ginkgo biloba, which is highly tolerant to drought and cold. GbTPS encoded an 868-amino-acid polypeptide with a predicted isoelectric point of 5.83 and molecular mass of 97.9 kD. Amino acid sequence alignment revealed that GbTPS shared high identity with class II trehalose-6-phosphate synthase homologues (67% identical to AtTPS7), but had only 17% and 23% of identity with OstA from Escherichia coli and ScTPS1 from S. cerevisiae, respectively. DNA gel blot analysis indicated that GbTPS belonged to a small multi-gene family. The expression analysis by RT-PCR showed that GbTPS expressed in a tissue-specific manner in G biloba and might involve in leaf development. GbTPS was also found to be induced by a variety of stresses including cold, salt, drought and mannitol.

Theoretical study on the hydrolysis mechanism of N,N-dimethyl-N′-(2-oxo-1, 2-dihydro-pyrimidinyl)formamidine: Water-assisted mechanism and cluster-continuum model

Wu, Yong,Jin, Lu,Xue, Ying,Xie, Dai Qian,Kim, Chan Kyung,Guo, Yong,Yan, Guo Sen Wiley Subscription Services, Inc., A Wiley Company 2008 Journal of computational chemistry Vol.29 No.8

<P>The hydrolysis reaction of N,N-dimethyl-N′-(2-oxo-1, 2-dihydro-pyrimidinyl)formamidine (DMPFA), a model compound of the antivirus drug amidine-3TC (3TC = 2′, 3′-dideoxy-3′-thiacytidine), is investigated by the hybrid density functional theory B3LYP/6-31+G (d,p) method. The hydrolysis reaction of the title compound is predicted to undergo via two pathways, each of which is a stepwise process. Path A is the addition of H<SUB>2</SUB>O to the C&n.dbond;N double bond in the amidine group to form a tetrahedral structure in its first step, and then the transfer of the H atom of hydroxyl leads to the corresponding products via four possible channels. Path B simultaneously involves the nucleophilic attack of H<SUB>2</SUB>O to the C atom of the C&n.dbond;N bond and the proton transfer to the N atom of amino group leading to the cleavage of the C&n.bond;N single bond in the amidine group. The results indicate that path A is more favorable than path B in the gas phase. Moreover, to simulate the title reaction in aqueous solution, water-assisted mechanism and the cluster-continuum model, based on the SCRF/CPCM model, are taken into account in our work. The results indicate that it is rational for two water molecules served as a bridge to assist in the first step of path A and that cytosine rather than the cytosine-substituted formamide should be released from the tetrahedral intermediate via s six-membered cycle transition state (channel 2). Our calculations exhibit that the process toward the tetrahedral intermediate is the rate-determining step both in the gas phase and in aqueous solution. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008</P> <B>Graphic Abstract</B> <P> <img src='wiley_img/01928651-2008-29-8-JCC20883-gra001.gif' alt='wiley_img/01928651-2008-29-8-JCC20883-gra001'> </P>

Phase II Study of Pemetrexed as Second or Third Line Combined Chemotherapy in Patients with Colorectal Cancer

Wu, Xue-Yan,Huang, Xin-En,You, Shan-Xi,Lu, Yan-Yan,Cao, Jie,Liu, Jin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

Purpose: To investigate the safety and efficacy of pemetrexed combined with chemotherapy as second or third line in patients with stage IV colorectal cancer (CRC). Patients and Methods: This trial was conducted to evaluate the effectiveness and safety of pemetrexed given to patients with recurrent or metastatic colorectal carcinoma who previously received 5-FU-based chemotherapy. All patients were required to have a histological diagnosis of colorectal adenocarcinoma with measurable metastatic disease and prior chemotherapy. Patients received pemetrexed at a dose of 500 $mg/m^2$ by 10 minute infusion on day 1, repeated every 21 days. Doses were modified depending on nadir counts. Combined chemotherapy included Oxaliplatin, Irinotecan and cis-platinum. Results: Thirty patients were enrolled and twenty-nine were evaluable for response. One patient did not have repeat radiological testing to determine response because he went off study after only one cycle of treatment for economic reasons. For 29 evaluable patients, 1 partial response, 6 stable disease and 22 progressive disease were recorded. Response rate was 3.45% (1/29). All responses occurred in patients receiving a starting dose of pemetrexed 500 $mg/m^2$. Median time to progression for all eligible patients was 2.5 months. The most common toxicities experienced were mild to moderate fever, hepatic damage, myelosuppression, nausea, vomiting, constipation, abdominal pain, diarrhea, and skin rash. Conclusion: Pemetrexed at 500 $mg/m^2$ given every three weeks combined with chemotherapy is associated with moderate response and good tolerability in patients with stage IV CRC.

Potential Predictors of Sensitivity to Pemetrexed as First-line Chemotherapy for Patients with Advanced Non-Squamous NSCLCs

Lu, Yan-Yan,Huang, Xin-En,Xu, Lin,Liu, De-Gan,Cao, Jie,Wu, Xue-Yan,Liu, Jin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

Background: Pemetrexed (PEM) is effective in first-line treatment for patients with non-squamous non-small cell lung cancer (NSCLC). However there are currently no definitive determinants to certify which patients could benefit from PEM. To improve the efficacy of PEM combined with platinum as first-line therapy for advanced non-squamous NSCLC, we conducted this retrospective study to detect potential determinants of this regimen. Methods: We recruited 109 patients with advanced non-squamous NSCLC who received PEM with a platinum as first-line therapy from June 2006 to February 2013 in Jiangsu Cancer Hospital. Multiple variables (age, sex, smoking, degree of cell differentiation, hemoglobin, platinum drugs combined, positions of metastasis) were selected. Logistic regression analysis was used to analyse relationships between these variables and tumor response. Result: In univariate analysis, we found that age and platinum significantly influenced the results of PEM therapy (P<0.05). In multivariable analysis, no factors were independently significant. Conclusion: Our analysis did not suggest that the age, sex, metastasis of liver or other organs, hemoglobin, smoking history and pathological differentiation are associated with the response of PEM. We should conduct further analyses with larger sample size to reconfirm this issue.

Clinical Observations on Associations Between the UGT1A1 Genotype and Severe Toxicity of Irinotecan

Lu, Yan-Yan,Huang, Xin-En,Wu, Xue-Yan,Cao, Jie,Liu, Jin,Wang, Lin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean, $12.75{\mu}mol/L$) with compared to TA6/6 (mean, $9.92{\mu}mol/L$) with p<0.05. Conclusions: Our study support the conclusion that patients with a $UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the $UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.

Phase II Study on Javanica Oil Emulsion Injection (Yadanzi^®) Combined with Chemotherapy in Treating Patients with Advanced Lung Adenocarcinoma

Lu, Yan-Yan,Huang, Xin-En,Cao, Jie,Xu, Xia,Wu, Xue-Yan,Liu, Jin,Xiang, Jin,Xu, Lin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

Purpose: To investigate the efficacy and safety of Javanica oil emulsion injection (Yadanzi$^{(R)}$) combined with pemetrexed and platinum (PP) for treating patients with advanced lung cancer. Patients and Methods: From June 2011 to June 2013, we recruited 58 patients with advanced lung cancer, and divided them into two groups. Twenty eight patients received Yadanzi$^{(R)}$ (from ZheJiang Jiuxu Pharmaceutical Co., Ltd.) together with PP chemotherapy (combined group), while the others were given only PP chemotherapy (control group). After two cycles of treatment, efficacy and safety of treatment were evaluated. Results: The overall respnse rate [(CR+PR+SD)/(CR+PR+SD+PD)] of the combined group was higher than that of control group (89.7% vs. 86.2%, p>0.05). Regarding rate of life improvement, it was 82.8% in combined group, and 51.7% in the control group (p<0.05). In terms of side effects, leukopenia in combined group was less frequent than that in control group (p<0.05). More patients in the control group were found to suffer liver toxicity. Conclusions: Javanica oil emulsion injection combined with chemotherapy could be considered as a safe and effective regimen in treating patients with advanced lung adenocarcinoma. It can improve the quality of life and reduce the possibility of leukopenia. Further clinical trials with a large sample size should be conducted to confirm whether addition of Yadanzi$^{(R)}$ to chemotherapy could increase the response rate, reduce toxicity, enhance tolerability and improve quality of life for patients with advanced lung cancer.

Aprotic and Aqueous Li–O₂ Batteries

Lu, Jun,Li, Li,Park, Jin-Bum,Sun, Yang-Kook,Wu, Feng,Amine, Khalil American Chemical Society 2014 Chemical reviews Vol.114 No.11

<P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/chreay/2014/chreay.2014.114.issue-11/cr400573b/production/images/medium/cr-2013-00573b_0033.gif'></P>

HYERS-ULAM STABILITY OF DERIVATIONS IN FUZZY BANACH SPACE: REVISITED

Gang Lu,Yuanfeng Jin,Gang Wu,Sungsik Yun 한국수학교육학회 2018 純粹 및 應用數學 Vol.25 No.2

Lu et al. [27] dened derivations on fuzzy Banach spaces and fuzzy Lie Banach spaces and proved the Hyers-Ulam stability of derivations on fuzzy Banach spaces and fuzzy Lie Banach spaces. It is easy to show that the denitions of derivations on fuzzy Banach spaces and fuzzy Lie Banach spaces are wrong and so the results of [27] are wrong. Moreover, there are a lot of seroius problems in the statements and the proofs of the results in Sections 2 and 3. In this paper, we correct the denitions of biderivations on fuzzy Banach algebras and fuzzy Lie Banach algebras and the statements of the results in [27], and prove the corrected theorems.