Publications by authors named "Shuchun Li"

47 Publications

Comprehensive Analysis of the SBP Family in Blueberry and Their Regulatory Mechanism Controlling Chlorophyll Accumulation.

Front Plant Sci 2021 1;12:703994. Epub 2021 Jul 1.

College of Plant Science, Jilin University, Changchun, China.

SQUAMOSA Promoter Binding Protein (SBP) family genes act as central players to regulate plant growth and development with functional redundancy and specificity. Addressing the diversity of the SBP family in crops is of great significance to precisely utilize them to improve agronomic traits. Blueberry is an important economic berry crop. However, the SBP family has not been described in blueberry. In the present study, twenty genes were identified through data mining against blueberry transcriptome databases. These VcSBPs could be clustered into eight groups, and the gene structures and motif compositions are divergent among the groups and similar within each group. The VcSBPs were differentially expressed in various tissues. Intriguingly, 10 VcSBPs were highly expressed at green fruit stages and dramatically decreased at the onset of fruit ripening, implying that they are important regulators during early fruit development. Computational analysis showed that 10 s were targeted by miR156, and four of them were further verified by degradome sequencing. Moreover, their functional diversity was studied in Arabidopsis. Noticeably, three VcSBPs significantly increased chlorophyll accumulation, and qRT-PCR analysis indicated that VcSBP13a in Arabidopsis enhanced the expression of chlorophyll biosynthetic genes such as AtDVR, AtPORA, AtPORB, AtPORC, and AtCAO. Finally, the targets of VcSBPs were computationally identified in blueberry, and the Y1H assay showed that VcSBP13a could physically bind to the promoter region of the chlorophyll-associated gene . Our findings provided an overall framework for individually understanding the characteristics and functions of the SBP family in blueberry.
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http://dx.doi.org/10.3389/fpls.2021.703994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281205PMC
July 2021

An Original Ferroptosis-Related Gene Signature Effectively Predicts the Prognosis and Clinical Status for Colorectal Cancer Patients.

Front Oncol 2021 24;11:711776. Epub 2021 Jun 24.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Ferroptosis is a newly defined form of cell death, distinguished by different morphology, biochemistry, and genetics, and involved in CRC progression and treatment. This study aims to establish a predictive model to elucidate the relationship between ferroptosis and prognosis of CRC patients, to explore the potential value of ferroptosis in therapeutic options.

Methods: The ferroptosis-related genes were obtained from the GeneCards and FerrDb websites. The limma R package was used to screen the differential ferroptosis-related genes (DEGs) in CRC from The Cancer Genome Atlas (TCGA) dataset. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were to establish the 10-gene prognostic signature. The survival and receiver operating characteristic (ROC) curves were illustrated to evaluate the predictive effect of the signature. Besides, independent prognostic factors, downstream functional enrichment, drug sensitivity, somatic mutation status, and immune feature were analyzed. Moreover, all these conclusions were verified by using multiple datasets in International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO).

Results: Ten ferroptosis-related gene signature (TFAP2C, SLC39A8, NOS2, HAMP, GDF15, FDFT1, CDKN2A, ALOX12, AKR1C1, ATP6V1G2) was established to predict the prognosis of CRC patients by Lasso cox analysis, demonstrating a good performance on Receiver operating characteristic (ROC) and Kaplan-Meier (K-M) analyses. The CRC patients in the high- or low-risk group showed significantly different fractions of immune cells, such as macrophage cells and CD8+ T cells. Drug sensitivity and somatic mutation status like TP53 were also closely associated with the risk scores.

Conclusions: In this study, we identified a novel ferroptosis-related 10-gene signature, which could effectively predict the prognosis and survival time of CRC patients, and provide meaningful clinical implications for targeted therapy or immunotherapy. Targeting ferroptosis is a good therapeutic option for CRC patients. Further studies are needed to reveal the underlying mechanisms of ferroptosis in CRC.
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http://dx.doi.org/10.3389/fonc.2021.711776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264263PMC
June 2021

Assessing the accuracy of fabricated implant surgical guides by reconstructing the implant position based on cone beam computed tomography images: A dental technique.

J Prosthet Dent 2021 Jun 10. Epub 2021 Jun 10.

Lecturer, Department of Prosthodontics and Second Dental Clinical Division, Peking University School and Hospital of Stomatology, Beijing, PR China. Electronic address:

A protocol for qualitatively reviewing the accuracy of fabricated implant surgical guides is presented. Once these guides have been inserted and fixed intraorally, cone beam computed tomography (CBCT) scans are made. Implant positions can be recalculated by processing the series of sleeve images on the CBCT scans. This protocol offers an opportunity for double-checking the accuracy of a fabricated guide before surgery in certain circumstances.
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http://dx.doi.org/10.1016/j.prosdent.2021.05.005DOI Listing
June 2021

A greater lymph node yield is required during pathological examination in microsatellite instability-high gastric cancer.

BMC Cancer 2021 Mar 25;21(1):319. Epub 2021 Mar 25.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, P. R. China.

Background: The impact of microsatellite status on lymph node (LN) yield during lymphadenectomy and pathological examination has never been assessed in gastric cancer (GC). In this study, we aimed to appraise the association between microsatellite instability-high (MSI-H) and LN yield after curative gastrectomy.

Methods: We retrospectively analyzed 1757 patients with GC undergoing curative gastrectomy and divided them into two groups: MSI-H (n = 185(10.5%)) and microsatellite stability (MSS) (n = 1572(89.5%)), using a five-Bethesda-marker (NR-24, BAT-25, BAT-26, CAT-25, MONO-27) panel. The median LN count and the percentage of specimens with a minimum of 16 LNs (adequate LN ratio) were compared between the two groups. The log odds (LODDS) of positive LN count (PLNC) to negative LN count (NLNC) and the target LN examined threshold (TLNT) were calculated in both groups.

Results: Statistically significant differences were found in the median LN count between MSI-H and MSS groups for the complete cohort (30 vs. 28, p = 0.031), for patients undergoing distal gastrectomy (DG) (30 vs. 27, p = 0.002), for stage II patients undergoing DG (34 vs. 28, p = 0.005), and for LN-negative patients undergoing DG (28 vs. 24, p = 0.002). MSI-H was an independent factor for higher total LN count in patients undergoing DG (p = 0.011), but it was not statistically correlated to the adequate LN ratio. Statistically significant differences in PLNC, NLNC and LODDS were found between MSI-H GC and MSS GC (all p < 0.001). The TLNT for MSI-H and MSS groups were 31 and 25, respectively. TLNT of MSI-H GC was always higher than that of MSS GC regardless of the given value of X%.

Conclusions: MSI-H was associated with higher LN yield in patients undergoing gastrectomy for GC. Although MSI-H did not affect the adequacy of LN harvest, we speculate that a greater lymph node yield is required during pathological examination in MSI-H GC.
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http://dx.doi.org/10.1186/s12885-021-08044-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992823PMC
March 2021

Synergistic Therapy for Cervical Cancer by Codelivery of Cisplatin and JQ1 Inhibiting Plk1-Mutant Trp53 Axis.

Nano Lett 2021 03 11;21(6):2412-2421. Epub 2021 Mar 11.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

JQ1, a specific inhibitor of bromodomain-containing protein 4 (BRD4), could have great potential in the treatment of cervical cancer. However, its clinical application is limited by its short plasma half-life and limited antitumor efficacy. In this work, cisplatin (CDDP) was first utilized as the stabilizer and cooperator in the nanosystem (mPEG--P(Glu--Phe)-CDDP/JQ1, called PGP-CDDP/JQ1) to break through the efficiency limitation of JQ1. The PGP-CDDP/JQ1 had a combination index (CI) of 0.21, exerting a strong cytotoxic synergistic effect. experiments revealed that PGP-CDDP/JQ1 had a significantly higher tumor inhibition effect (tumor inhibition rate: 85% vs 14%) and plasma stability of JQ1 (area under the curve (AUC): 335.97 vs 16.88 μg × h/mL) than free JQ1. The mechanism underling the synergism of JQ1 with CDDP in PGP-CDDP/JQ1 was uncovered to be inhibiting Plk1-mutant Trp53 axis. Thus, this study provides an optional method for improving the clinical application of JQ1 in cervical cancer.
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http://dx.doi.org/10.1021/acs.nanolett.0c04402DOI Listing
March 2021

Impact of microsatellite status on negative lymph node count and prognostic relevance after curative gastrectomy.

J Surg Oncol 2021 May 2;123 Suppl 1:S15-S24. Epub 2021 Mar 2.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background And Objectives: The impact of microsatellite instability-high (MSI-H) phenotype on lymph node yield after lymphadenectomy has never been discussed in gastric cancer (GC). In this study, we aimed to assess the association of microsatellite status with negative lymph node count (NLNC) as well as its prognostic value.

Methods: We retrospectively analyzed 1491 GC patients and divided them into two groups: MSI-H (n = 141 [9.5%]) and microsatellite stability (MSS ) (n = 1350 [90.5%]). The NLNC and survival data were compared between the two groups. The log odds of positive lymph nodes (LNs) to negative LNs and the target lymph node examined threshold (TLNT) were calculated in both groups.

Results: A statistically significant difference was found in median NLNC (26 vs. 23, p < .001) between MSI-H and MSS patients. MSI status was an independent factor for NLNC (p < .001). NLNC showed positive prognostic value for cases with metastatic lymph node (LN ) in both MSI-H and MSS groups. The TLNT for MSI-H and MSS were 33 and 26, respectively.

Conclusions: MSI-H was associated with higher NLNC in GC patients and this was independent of the presence of LN . However, more LNs are needed during pathological examination to capture LN cases in MSI-H
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http://dx.doi.org/10.1002/jso.26325DOI Listing
May 2021

Artificial Intelligence in Decision-Making for Colorectal Cancer Treatment Strategy: An Observational Study of Implementing Watson for Oncology in a 250-Case Cohort.

Front Oncol 2020 4;10:594182. Epub 2021 Feb 4.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Personalized and novel evidence-based clinical treatment strategy consulting for colorectal cancer has been available through various artificial intelligence (AI) supporting systems such as Watson for Oncology (WFO) from IBM. However, the potential effects of this supporting tool in cancer care have not been thoroughly explored in real-world studies. This research aims to investigate the concordance between treatment recommendations for colorectal cancer patients made by WFO and a multidisciplinary team (MDT) at a major comprehensive gastrointestinal cancer center.

Methods: In this prospective study, both WFO and the blinded MDT's treatment recommendations were provided concurrently for enrolled colorectal cancers of stages II to IV between March 2017 and January 2018 at Shanghai Minimally Invasive Surgery Center. Concordance was achieved if the cancer team's decisions were listed in the "recommended" or "for consideration" classification in WFO. A review was carried out after 100 cases for all non-concordant patients to explain the inconsistency, and corresponding feedback was given to WFO's database. The concordance of the subsequent cases was analyzed to evaluate both the performance and learning ability of WFO.

Results: Overall, 250 patients met the inclusion criteria and were recruited in the study. Eighty-one were diagnosed with colon cancer and 189 with rectal cancer. The concordances for colon cancer, rectal cancer, or overall were all 91%. The overall rates were 83, 94, and 88% in subgroups of stages II, III, and IV. When categorized by treatment strategy, concordances were 97, 93, 89, 87, and 100% for neoadjuvant, surgery, adjuvant, first line, and second line treatment groups, respectively. After analyzing the main factors causing discordance, relative updates were made in the database accordingly, which led to the concordance curve rising in most groups compared with the initial rates.

Conclusion: Clinical recommendations made by WFO and the cancer team were highly matched for colorectal cancer. Patient age, cancer stage, and the consideration of previous therapy details had a significant influence on concordance. Addressing these perspectives will facilitate the use of the cancer decision-support systems to help oncologists achieve the promise of precision medicine.
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http://dx.doi.org/10.3389/fonc.2020.594182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899045PMC
February 2021

Microsatellite Status Affects Tumor Response and Survival in Patients Undergoing Neoadjuvant Chemotherapy for Clinical Stage III Gastric Cancer.

Front Oncol 2020 15;10:614785. Epub 2020 Dec 15.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: We assessed the association between microsatellite instability-high (MSI-H) and tumor response to neoadjuvant chemotherapy (NAC) as well as its prognostic relevance in patients with clinical stage III gastric cancer (cStage III GC).

Materials And Methods: The NAC + surgery and the control cohorts consisted of 177 and 513 cStage III GC patients, respectively. The clinical and pathological features were compared between patients with MSI-H [n=57 (8.3%)] and microsatellite stability or microsatellite instability-low (MSS/MSI-L) [n=633 (91.7%)]. Radiological and histological response to NAC were evaluated based on response evaluation criteria in solid tumors (RECIST) and tumor regression grade (TRG) systems, respectively. The log-rank test and Cox analysis were used to determine the survival associated with MSI status as well as tumor regression between the two groups in both NAC + surgery and the control cohorts.

Results: A statistically significant association was found between MSI-H and poor histological response to NAC (=0.038). Significant survival priority of responders over poor-responders could only be observed in MSS/MSI-L but not in MSI-H tumors. However, patients with MSI-H had statistically significantly better survival compared to patients with MSS/MSI-L in both the NAC + surgery (hazard ratio=0.125, 95% CI, 0.017-0.897, =0.037 ) and the control cohort (hazard ratio=0.479, 95% CI, 0.268-0.856, =0.013).

Conclusion: MSI-H was associated with poorer regression and better survival after NAC for cStage III GC. TRG evaluation had prognostic significance in MSS/MSI-L but not in MSI-H. Further studies are needed to assess the value of NAC for cStage III GC patients with MSI-H phenotype.
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http://dx.doi.org/10.3389/fonc.2020.614785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770160PMC
December 2020

Transapical Transcatheter Valve Replacement Using J-Valve for Aortic Valve Diseases.

Ann Thorac Surg 2020 Nov 27. Epub 2020 Nov 27.

Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China; Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China. Electronic address:

Background: The J-Valve system (Jie ChengMedical Technologies, Suzhou, China) is designed specifically for transapical transcatheter aortic valve replacement and has three U-shaped graspers. With the unique structure, the J-Valve is suitable for both aortic stenosis and aortic regurgitation. We used the J-Valve system for patients with aortic valve diseases and observed favorable results.

Methods: From January 2018 to August 2019, 23 patients underwent transapical transcatheter valve replacement using the J-Valve system. High-risk patients with diseased peripheral vessels (small diameter, heavily calcified, and tortuous arteries), pure aortic regurgitation, and complex prosthetic valve-in-valve cases were enrolled. Ten patients mainly had aortic stenosis, 11 patients had pure aortic regurgitation, and 2 patients had valve-in-valve aortic valve position. The Society of Thoracic Surgeons and European System for Cardiac Operative Risk Evaluation average preoperative scores were 8.9% and 8.7%, respectively.

Results: The technique success rate was 91.3% (21 of 23; 1 patient was referred for open surgery and 1 patient received intraoperative valve-in-valve), and 1 patient died of cardiogenic shock after the procedure (mortality 4.3%, 1 of 22). One patient had stroke postoperatively and recovered well; no cases needed to undergo permanent pacemaker implantation. During the follow-up period, 1 patient died of acute heart attack. No moderate or severe paravalvular leakage was found.

Conclusions: Transcatheter aortic valve replacement surgery with the J-Valve system is effective, even when it is traumatic and requires the transapical route. The applicability of the J-Valve system in pure aortic regurgitation patients is the advantage of this system.
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http://dx.doi.org/10.1016/j.athoracsur.2020.10.030DOI Listing
November 2020

GJA1 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Colorectal Cancer.

Cancer Manag Res 2020 16;12:11649-11661. Epub 2020 Nov 16.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Purpose: Previous studies found that gap junction alpha-1 protein (GJA1) was a potent tumor suppressor in colorectal cancer (CRC). We designed the present study to evaluate the clinical importance and molecular mechanisms of GJA1 in CRC.

Methods: Clinical and transcriptomic data from TCGA and GEO datasets were retrospectively collected. CRC patients were divided into two subgroups according to the expression level of GJA1 mRNA. Difference between survival time and response to neoadjuvant chemotherapy was then evaluated. Functional assays including wound-healing assay, transwell invasion assay and flow cytometry assay were performed to investigate the effects of GJA1 on invasive ability and response to chemotherapy drugs of CRC cells. Moreover, we explored the mechanisms of GJA1 by which it regulates CRC malignant phenotypes.

Results: The expression level of GJA1 was significantly higher in normal tissue than cancer tissue, indicating a tumor suppressive role of GJA1 in CRC. Patients with higher expression of GJA1 showed better prognosis than those with low GJA1 expression level. Consistently, overexpression of GJA1 suppressed the invasive ability of CRC cells while enhancing the sensitivity of CRC cells to oxaliplatin-induced apoptosis. Mechanically, we found that GJA1 suppressed the epithelial mesenchymal transition process. Moreover, GJA1 could modulating infiltrating levels of several immune cells in the tumor microenvironment.

Conclusion: These findings suggested that GJA1 was correlated with prognosis and immune infiltrating levels of CD8+ T cells, macrophages, neutrophils, and DCs in CRC. In addition, GJA1 expression contributes to regulation of tumor-associated macrophages (TAMs) and tumor infiltrating neutrophils (TINs) in CRC. These findings suggest that GJA1 is a promising biomarker for determining prognosis and immune infiltration in colorectal cancer.
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http://dx.doi.org/10.2147/CMAR.S235500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678473PMC
November 2020

Upregulation of miRNA-23a-3p rescues high glucose-induced cell apoptosis and proliferation inhibition in cardiomyocytes.

In Vitro Cell Dev Biol Anim 2020 Dec 16;56(10):866-877. Epub 2020 Nov 16.

Translational Medical Center for Development and Disease, Institute of Pediatrics, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai, 201102, China.

Maternal hyperglycemia potentially inhibits the development of the fetal heart by suppressing cardiomyocyte proliferation and promoting apoptosis. Different studies have indicated that miRNAs are key regulators of cardiomyocyte proliferation, differentiation, and apoptosis and play a protective role in a variety of cardiovascular diseases. However, the biological function of miRNA-23a in hyperglycemia-related cardiomyocyte injury is not fully understood. The present study investigated the effect of miRNA-23a-3p on cell proliferation and apoptosis in a myocardial injury model induced by high glucose. H9c2 cardiomyocytes were exposed to high glucose to establish an in vitro myocardial injury model and then transfected with miRNA-23a-3p mimics. After miRNA-23a-3p transfection, lens-free microscopy was used to dynamically monitor cell numbers and confluence and calculate the cell cycle duration. CCK-8 and EdU incorporation assays were performed to detect cell proliferation. Flow cytometry was used to measured cell apoptosis. Upregulation of miRNA-23a-3p significantly alleviated high glucose-induced cell apoptosis and cell proliferation inhibition (p < 0.01 and p < 0.0001, respectively). The cell cycle of the miRNA-23a-3p mimics group was significantly shorter than that of the negative control group (p < 0.01). The expression of cell cycle-activating and apoptosis inhibition-associated factors Ccna2, Ccne1, and Bcl-2 was downregulated by high glucose and upregulated by miRNA-23a-3p overexpression in high glucose-injured H9c2 cells. miRNA-23a-3p mimics transfection before high glucose treatment had a significantly greater benefit than transfection after high glucose treatment (p < 0.0001), and the rescue effect of miRNA-23a-3p increased as the concentration increased. This study suggests that miRNA-23a-3p exerted a dose- and time-dependent protective effect on high glucose-induced H9c2 cardiomyocyte injury.
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http://dx.doi.org/10.1007/s11626-020-00518-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723946PMC
December 2020

Traditional Chinese Medicine Regulating Lymphangiogenesis: A Literature Review.

Front Pharmacol 2020 3;11:1259. Epub 2020 Sep 3.

Cardiovascular Department, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Lymphatic vessels, as an important part of the lymphatic system, form a fine vascular system in humans and play an important role in regulating fluid homeostasis, assisting immune surveillance and transporting dietary lipids. Dysfunction of lymphatic vessels can cause many diseases, including cancer, cardiovascular diseases, lymphedema, inflammation, rheumatoid arthritis. Research on lymphangiogenesis has become increasingly important over the last few decades. Nevertheless, the explicit role of regulating lymphangiogenesis in preventing and treating diseases remains unclear owing to the lack of a deeper understanding of the cellular and molecular pathways of the specific and tissue-specific changes in lymphangiopathy. TCM, consisting of compound extracted from TCM, Injections of single TCM and formula, is an important complementary strategy for treating disease in China. Lots of valuable traditional Chinese medicines are used as substitutes or supplements in western countries. As one of the main natural resources, these TCM are widely used in new drug research and development in Asia. Moreover, as a historical and cultural heritage, TCM has been widely applied to clinical research on lymphangiogenesis leveraging new technologies recently. Available studies show that TCM has an explicit effect on the regulation of lymphatic regeneration. This review aims to clarify the function and mechanisms, especially the inhibitory effect of TCM in facilitating and inhibiting lymphatic regeneration.
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http://dx.doi.org/10.3389/fphar.2020.01259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495091PMC
September 2020

The Effectiveness of Gastrectomy With Chemoradiotherapy Among Stage IV Gastric Adenocarcinoma: A Population-Based Analysis.

Authors:
Shuchun Li Lu Zang

Front Oncol 2020 28;10:630. Epub 2020 Apr 28.

Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

The strategy for the treatment of stage IV gastric cancer remains controversial. The objective of this study was to assess whether tumor resection is beneficial to survival in gastric cancer patients with incurable stage IV disease. This is a retrospective cohort study of gastric cancer patients in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Due to the baseline bias, 1:1 propensity score matching (PSM) was used in this cohort. Patients were grouped by treatment, (1) gastrectomy with chemoradiotherapy (CRT), or (2) CRT only, and a Cox proportional hazards regression model was used to identify predictors of survival. Overall survival was compared between the two groups using the Kaplan-Meier method. After propensity score matching, 162 stage IV gastric cancer patients diagnosed from 2010 to 2015 were identified. Among these patients, half underwent gastrectomy with CRT, while the others received CRT only. The median overall survival rates were 22 months from the date of surgery for the gastrectomy with CRT group and 9.0 months for CRT only group. In the multivariable Cox regression analysis, surgery was associated with a significant improvement in overall survival [hazard ratio (HR) of death = 0.31, 95% confidence interval (CI) = 0.21-0.46, < 0.0001]. In conclusion, stage IV gastric cancer is still a fatal disease. This population-based study found that compared with CRT alone, CRT with gastrectomy may be associated with a survival benefit in patients with metastatic GC. In selected patients' survival can be prolonged when the primary tumor is removed. Prospective, randomized trials are required to determine the best strategy for metastatic GC and to describe the characteristics of the selected patients.
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http://dx.doi.org/10.3389/fonc.2020.00630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198747PMC
April 2020

N-myc downstream-regulated gene 1 inhibits the proliferation of colorectal cancer through emulative antagonizing NEDD4-mediated ubiquitylation of p21.

J Exp Clin Cancer Res 2019 Dec 12;38(1):490. Epub 2019 Dec 12.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: N-myc downstream-regulated gene 1 (NDRG1) has been shown to play a key role in tumor metastasis. Recent studies demonstrate that NDRG1 can suppress tumor growth and is related to tumor proliferation; however, the mechanisms underlying these effects remain obscure.

Methods: Immunohistochemistry (IHC) was used to detect NDRG1 and p21 protein expression in colorectal cancer tissue, and clinical significance of NDRG1 was also analyzed. CCK-8 assay, colony formation assay, flow cytometry, and xenograft model were used to assess the effect of NDRG1 on tumor proliferation in vivo and in vitro. The mechanisms underlying the effect of NDRG1 were investigated using western blotting, immunofluorescence, immunoprecipitation, and ubiquitylation assay.

Results: NDRG1 was down-regulated in CRC tissues and correlated with tumor size and patient survival. NDRG1 inhibited tumor proliferation through increasing p21 expression via suppressing p21 ubiquitylation. NDRG1 and p21 had a positive correlation both in vivo and in vitro. Mechanistically, E3 ligase NEDD4 could directly interact with and target p21 for degradation. Moreover, NDRG1 could emulatively antagonize NEDD4-mediated ubiquitylation of p21, increasing p21 expression and inhibit tumor proliferation.

Conclusion: Our study could fulfill potential mechanisms of the NDRG1 during tumorigenesis and metastasis, which may serve as a tumor suppressor and potential target for new therapies in human colorectal cancer.
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http://dx.doi.org/10.1186/s13046-019-1476-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909641PMC
December 2019

Differential Analysis of Hypertension-Associated Intestinal Microbiota.

Int J Med Sci 2019 2;16(6):872-881. Epub 2019 Jun 2.

School of Pharmacy, Minzu University of China, Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of education, Beijing 100081, P.R. China.

Hypertension is the main risk factor for cerebral stroke and death resulting from cerebral stroke. Current association studies on hypertension and intestinal microbiota focus on patients with hypertension (HTN); however, no investigations involving patients with isolated diastolic hypertension (IDH) or systolic hypertension (SH) have been conducted to date. In this study, fecal samples from 62 cases with normal blood pressure (BP) and 67 cases with high BP were used for 16S amplicon sequencing. Sixty-one cases of HTN and 61 corresponding cases with normal BP were obtained by propensity score matching (PSM), and differential analysis was conducted using the DEseq2 package. PSM was also used to match six IDH patients with six controls and to match 35 cases of SH with 35 controls. There were 54 differential genera between the HTN and normal BP groups, and there were five differential genera between the IDH and normal BP groups. There were 38 differential genera between the SH and normal BP groups, including . Bayesian network analysis showed that variations in BP influenced microbial abundance. Pearson's correlation analysis showed that bacterial abundance is correlated with BP Significant differences between the intestinal microbiota of high and normal BP groups were observed. Gut microbiota dysbiosis differed among HTN, IDH, and SH patients. In particular, diastolic blood pressure (DBP) and systolic blood pressure (SBP) were related to different intestinal microbiota.
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http://dx.doi.org/10.7150/ijms.29322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643114PMC
February 2020

Age-stratified comparative analysis of the differences of gut microbiota associated with blood glucose level.

BMC Microbiol 2019 05 27;19(1):111. Epub 2019 May 27.

School of Pharmacy, Minzu University of China, 27 South Street, Zhongguancun, Beijing, 100081, China.

Background: Gut bacteria are an important component of the microbiota ecosystem in humans and other animals, and they play important roles in human health. The aim of this study was to investigate the relationship between gut microbiota and multiple demographical-, behavioral-, or biochemical-related factors in subjects with chronic disease. Subjects with a very wide age range who participated in community-based chronic disease prevention and screening programs in China were enrolled. We analyzed the intestinal microbiota composition using 16S rRNA-based high-throughput sequencing of fecal samples, analyzed the association between gut microbiota structure and multiple demographical, behavioral, and biochemical factors, and compared the differences in microbiota composition in age-stratified groups with different blood glucose levels.

Results: Our results showed that both age and blood glucose levels had a significant impact on the gut microbiota structure. We also identified several taxa showed distinct abundance in groups with different glucose levels. Lactobacillus and Bifidobacterium at genus level and their related taxa were more abundant in the GLU high group comparing with GLU normal group and in NGR group comparing with DM group. Further analysis using the age-stratified data showed that blood glucose levels had a more significant impact on the gut microbiota in the ≥76 y age group than in the ≤75 y age group, which indicated that it is necessary to take age into account when conducting such studies. Moreover, we identified several taxa that were highly associated with blood glucose levels in the ≥76 y age group but not in the ≤75 y age group. Within the ≥76 y age group, Lachnospiraceae incertae sedis and Bacteroides were more abundant in the GLU normal group, whereas Lactobacillus and Bifidobacterium at genus level were more abundant in the GLU high group.

Conclusions: This result suggested that taxa that are capable of differentiating blood glucose levels might differ significantly in different age groups.
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http://dx.doi.org/10.1186/s12866-019-1466-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537452PMC
May 2019

KLHL5 knockdown increases cellular sensitivity to anticancer drugs.

Oncotarget 2018 Dec 21;9(100):37429-37438. Epub 2018 Dec 21.

Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.

KLHL family genes are noted for their involvement in the E3 ligase ubiquitination pathway through binding with Cullin-3 (CUL3) resulting in degradation of specific binding partners. KLHLs are thus intriguing genes for cancer as they can directly influence the degradation of therapeutically relevant cell cycle regulators such as Aurora Kinase, PLK1, or CDK1. However, most KLHL family members remain understudied within the literature. This study explores the relationship of expression of KLHL member, , with the pharmacologic effect of anti-cancer drugs. knockdown decreased the proliferation and viability of cancer cells and sensitized cancer cells to numerous anti-cancer drugs. Drugs related to cell cycle including Akt/PI3K/mTOR inhibitors were especially sensitized by knockdown. The potential of KLHL5 as a prognostic or diagnostic cancer marker was compared to other KLHLs through a pan-cancer study of The Cancer Genome Atlas (TCGA) tumor groups. While KLHL5 expression shows marginal dysregulation in cancer, other KLHLs exhibit significant dysregulation in all cancer types, and exceptionally in renal carcinomas. This study advocates for further study of KLHLs as potential alternative therapeutic targets, since while is a novel gene impacting anticancer drug effects, others may have a similar impact on drug effect while having greater potential as diagnostic or prognostic markers.
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http://dx.doi.org/10.18632/oncotarget.26462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324770PMC
December 2018

Corrigendum to "Interaction of SH3P13 and DYDC1 protein: a germ cell component that regulates acrosome biogenesis during spermiogenesis" [Eur. J. Cell Biol. 88 (2009) 509-520].

Eur J Cell Biol 2019 01 26;98(1):51-52. Epub 2018 Nov 26.

National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, 5 Dong Dan San Tiao, Beijing 100005, China.

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http://dx.doi.org/10.1016/j.ejcb.2018.11.002DOI Listing
January 2019

The identification of induction chemo-sensitivity genes of laryngeal squamous cell carcinoma and their clinical utilization.

Eur Arch Otorhinolaryngol 2018 Nov 28;275(11):2773-2781. Epub 2018 Sep 28.

Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Purpose: To identify potential molecular markers for induction chemotherapy of Laryngeal squamous cell carcinoma (LSCC).

Methods: Differently expressed genes between chemo-sensitive group (seven cases) and chemo-insensitive (five cases) group after induction chemotherapy by TPF were identified by microarrays. Bayes network and Random forest analyses were employed to identify core genes for induction chemotherapy. The diagnostic value of these core genes was also evaluated by ROC analysis.

Results: Six genes (SPP1, FOLR3, KYNU, LOC653219, ADH7 and XAGE1A) are highly expressed, while seven gene (CADM1, NDUFA4L2, CCND2, RARRES3, ERAP2, LYD6 and CNTNAP2) present significantly low expression. Among these genes, genes CADM1, FOLR3, KYNU, and CNTNAP2 are core candidates for LSCC chemo-sensitivity. And that the low expression of CADM1 may result in chemo-sensitivity, which leads to high expression of gene FOLR3 and KYNU, and low expression of gene CNTNAP2. Besides, ROC analysis shows that these four genes exhibit effective diagnostic value for induction chemo-sensitivity.

Conclusions: CADM1 may be a potential molecular marker for LSCC induction chemotherapy, while CADM1, FOLR3, KYNU, and CNTNAP2 may provide essential guidance for LSCC diagnosis and follow-up treatment strategies.
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http://dx.doi.org/10.1007/s00405-018-5134-xDOI Listing
November 2018

[Research advance in Billroth II with Braun anastomosis after distal gastrectomy].

Authors:
Shuchun Li Lu Zang

Zhonghua Wei Chang Wai Ke Za Zhi 2018 Aug;21(8):956-960

Department of Surgery, Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

Methods of digestive tract reconstruction after distal gastrectomy include Billroth I, Billroth II and Roux-en-Y. Each of them has advantages and disadvantages respectively. Alkaline reflux gastritis (ARG) is one of the complications after distal gastrectomy, which is common after Billroth II. In the past 100 years, the ways of digestive tract reconstruction have been continuously improved and developed to prevent the occurrence of alkaline reflux gastritis, and Roux-en-Y is one of them. Still, there is a high incidence of Roux stasis syndrome resulting from Roux-en-Y, with impact on quality of life. Therefore, the appropriate reconstruction is needed urgently. Braun anastomosis was proposed in 1892 to lower the incidence of afferent syndrome. Because of its effect of diverting some alkaline digestive juice, it was applied to pancreaticoduodenectomy and distal gastrectomy. Some studies have proved its effect of diverting some alkaline digestive juice, but the diverted quantity was rarely shown. Besides, compared with Roux-en-Y, Billroth II with Braun anastomosis is safer and more convenient. Meantime it is likely to have benefits in aspect of preventing anemia and malnutrition. In order to provide evidence to clinical practice, this article summarizes the history and research advance of Billroth II with Braun anastomosis by reviewing previous reports.
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August 2018

[Minimally invasive surgery in adenocarcinoma of esophagogastric junction].

Zhonghua Wei Chang Wai Ke Za Zhi 2018 Aug;21(8):875-880

Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine; Shanghai Minimally Invasive Surgery Center, Shanghai 200025, China.

Adenocarcinoma of esophagogastric junction (AEG) is the adenocarcinoma locating in the boundary of esophagus and cardia. Because of its increasing incidence, it has drawn attention widely around the world. In the 11th edition of Japanese Classification of Esophageal Cancer, the diagnosis of AEG should integrate endoscopy, upper gastrointestinal barium contrast and pathology. There are two classifications for AEG, Siewert classification and Nishi classification. In the 8th TNM staging manual, cancer crossing the esophagogastric junction (EGJ) with their epicenter within the proximal 2 cm of the stomach is incorporated into the esophagus chapter, whereas cancer crossing the EGJ with their epicenter in the proximal 2 to 5 cm of the stomach is addressed in the stomach chapter. All the tumors in stomach that do not cross the EGJ are classified as stomach cancer. The surgical approach of AEG remains controversial. Previous researches have suggested that abdominal transhiatal approach should be applied to Siewert type II and III. With respect to minimally invasive surgery, for Siewert I, the mediastinal and abdominal lymphadenectomy is conducted by thoracoscopy and laparoscopy respectively. After that a gastric tube is placed and the reconstruction is performed in the cervix. For Siewert type II, the whole procedure is accessed by laparotomy, and the lower mediastinum is accessed transhiatally. After lymphadenectomy the anastomosis can be laparoscopy-assisted or totally laparoscopic. As for Siewert type III, both circular and linear stapler can be used to perform reconstruction. With the development of surgical technology and continuous renovation of equipment, laparoscopic resection for AEG will be more and more popular.
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August 2018

Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives and Analogs Targeting the NLRP3 Inflammasome.

Molecules 2017 Jan 30;22(2). Epub 2017 Jan 30.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their antiinflammatory activities toward NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein family,pyrin domain-containing 3,also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ-09 and TBZ-21, were identified by antiproduction of IL-1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti-inflammatory activities were investigated. Several compounds were identified as anti-inflammatory agents that can reduce IL-1β expression in a dosedependent manner. A preliminary structure-activity relationship is also summarized here.
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http://dx.doi.org/10.3390/molecules22020213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155809PMC
January 2017

A meta-analysis of the effect of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of metoprolol
.

Int J Clin Pharmacol Ther 2017 Jun;55(6):483-492

Objective: To conduct a meta-analysis on the effect of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of metoprolol.

Methods: A systematic review and meta-analysis of studies on the effect of CYP2D6 polymorphism on metoprolol pharmacokinetics and pharmacodynamics was performed by using the China national knowledge infrastructure (CNKI), database for Chinese technical periodicals (VIP), Wanfang, and PubMed databases up to the end of January 2015. Review Manager 5.3 (the coherence collaboration, www.gradepro.org) and comprehensive Meta-Analysis Software v2 (CMA) Biostat, Englewood, NJ, USA) were used for meta-analysis.

Results: A total of 567 cases from 7 studies were included in the present study. Meta-analysis results showed that the area under the curve (AUC)0-∞ (RR = -6.75, 95% CI (-9.18, -4.31), p < 0.00001); Cmax (RR = -2.40, 95% CI (-3.25, -1.54), p < 0.00001); T1/2 (RR = -4.81, 95% CI (-6.86, -2.76), p < 0.00001); CL/F (RR = 1.60, 95% CI (1.03,2.17), p < 0.00001); heart rate (RR = 1.48, 95% CI (0.03, 2.92), p = 0.05), systolic blood pressure (RR = -0.69, 95% CI (-1.85,0.47), p = 0.24); and diastolic blood pressure (RR = -1.95, 95% CI (-3.14, -0.76), p = 0.001). Begg's funnel plot test showed that the pharmacokinetic parameters (AUC0-∞, Cmax, T1/2, and CL/F) and pharmacodynamic parameters (HR, DBP, and SBP) were symmetric. Egger's test showed that the pharmacokinetic parameters were asymmetrical, and its intercept was statistically significant (p < 0.05), which was indicative of publication bias. The pharmacodynamic parameter intercept was not statistically significant (p > 0.05), indicating that no publication bias existed.

Conclusion: CYP2D6 polymorphism significantly influenced the pharmacokinetic parameters of metoprolol. It also affected heart rate and diastolic blood pressure, whereas systolic pressure was not affected.
.
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http://dx.doi.org/10.5414/CP202545DOI Listing
June 2017

Tumor profiling of co-regulated receptor tyrosine kinase and chemoresistant genes reveal different targeting options for lung and gastroesophageal cancers.

Am J Transl Res 2016 15;8(12):5729-5740. Epub 2016 Dec 15.

Clinical Oncology Research Center, Jiangsu Cancer Hospital Nanjing, Jiangsu Province, People's Republic of China.

The expression of a number of genes can influence the response rates to chemotherapy while genes encoding receptor tyrosine kinases (RTKs) determine the response to most targeted cancer therapies currently used in clinics. In this study, we evaluated seven genes known to influence chemotherapeutic response (, and ) and five RTKs ( and ) in non-small cell lung cancer (NSCLC) and esophagus cancer (EC) and the data are compared to gastric cancer (GC) data reported previously. We demonstrate significant differences in the expression profiles between different cancer types as well as heterogeneity among patients within the same cancer type. In all three cancer types, five chemoresistant genes ( and ) are coordinately up-regulated in almost all EC, approximately 90% of NSCLC and one third of GC patients. Most EC and nearly half of GC patients have increased expression of the three RTKs critical to angiogenesis ( and ), while almost none of the NSCLC patients have elevated expression of angiogenic RTKs. A variable percentage of patients in the three cancer types show upregulation of the EGFR family RTKs, and/or . It is of interest to note that approximately 10% of the NSCLC and GC patients are triple-negative for the chemosensitivity genes, angiogenic and EGFR RTK genes. The results suggest significant gene expression differences between different cancer types as well as heterogeneity within each cancer type and therefore different molecules should be targeted for future drug development and clinical trials.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209524PMC
December 2016

Variation Analysis of Physiological Traits in Betula platyphylla Overexpressing TaLEA-ThbZIP Gene under Salt Stress.

PLoS One 2016 1;11(11):e0164820. Epub 2016 Nov 1.

State Key Laboratory of Tree Genetics and Breeding (Northeast Forestry University), School of Forestry, Northeast Forestry University, Harbin 150040, China.

The aim of this study was to determine whether transgenic birch (Betula platyphylla) ectopic overexpressing a late embryogenesis abundant (LEA) gene and a basic leucine zipper (bZIP) gene from the salt-tolerant genus Tamarix (salt cedar) show increased tolerance to salt (NaCl) stress. Co-transfer of TaLEA and ThbZIP in birch under the control of two independent CaMV 35S promoters significantly enhanced salt stress. PCR and northern blot analyses indicated that the two genes were ectopically overexpressed in several dual-gene transgenic birch lines. We compared the effects of salt stress among three transgenic birch lines (L-4, L-5, and L-8) and wild type (WT). In all lines, the net photosynthesis values were higher before salt stress treatment than afterwards. After the salt stress treatment, the transgenic lines L-4 and L-8 showed higher values for photosynthetic traits, chlorophyll fluorescence, peroxidase and superoxide dismutase activities, and lower malondialdehyde and Na+ contents, compared with those in WT and L-5. These different responses to salt stress suggested that the transcriptional level of the TaLEA and ThbZIP genes differed among the transgenic lines, resulting in a variety of genetic and phenotypic effects. The results of this research can provide a theoretical basis for the genetic engineering of salt-tolerant trees.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164820PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089751PMC
June 2017

Reusable fluorescent sensor for captopril based on energy transfer from photoluminescent graphene oxide self-assembly multilayers to silver nanoparticles.

Spectrochim Acta A Mol Biomol Spectrosc 2016 May 24;161:33-8. Epub 2016 Feb 24.

College of Material Science and Engineering, Huaqiao University, Xiamen 361021, China.

In this work we designed a self-assembly multilayers, in which photoluminescent graphene oxide was employed as a fluorescence probe. This multilayers film can effectively recognize captopril by resonance energy transfer from graphite oxide to silver nanoparticles. A new interfacial sensing method for captopril with high signal to noise ratio was established, by means of that multilayers was quenched by silver nanoparticles and subsequently recovered by adding captopril. The linear relation between intensity and captopril concentration was good, and the detection limit was found to be 0.1578 μM. Also, this novel detection platform demonstrated intriguing reusable properties, and the sensor could be repeated more than ten times without obviously losing its sensing performance.
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http://dx.doi.org/10.1016/j.saa.2016.02.018DOI Listing
May 2016

[Clinicopathologic characteristics of familial versus sporadic papillary thyroid carcinoma].

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2015 Jun;50(6):502-6

Email:

Objective: To investigated the clinicopathologic features of familial papillary thyroid carcinoma (PTC) compared to sporadic PTC.

Methods: Between January 2008 and August 2014, 20 patients who underwent surgery at Liaoning Cancer Hospital and Institute were diagnosed with familial PTC. We compared the clinicopathologic characteristics between familial PTC and sporadic PTC.

Results: The prevalence of familial PTC was 1.3% (20/1 587). The median age of patients at diagnosis was 37 years and there were 12 females and 8 males. Thirty percent of the familial PTC cases exhibited a parent-offspring relationship, and 70% exhibited a sibling relationship. There were significant differences between familial PTC and sporadic PTC in terms of concomitant chronic thyroiditis (P < 0.01), nodular goiter (P = 0.04), tumor multicentricity (P < 0.01), bilaterality (P < 0.01), histological subtype (P < 0.01), and central lymph node metastasis (P = 0.02). When familial PTC patients were classified based on parent-child and sibling relationship, there were significant differences in preoperative TSH level (P = 0.02) and concomitant chronic thyroiditis (P = 0.01) between the two categories.

Conclusions: There are significant differences in clinicopathologic features between familial PTC and sporadic PTC and between familial PTC with parent-child and those with sibling relationship. Familial PTC appears more aggressive than sporadic carcinoma. Optimal treatment for familial PTC is not yet established, but improved awareness and screening will permit earlier detection, more timely intervention, and improved outcomes for patients and their families.
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June 2015

Design, synthesis and antitumor activity of non-camptothecin topoisomerase I inhibitors.

Bioorg Med Chem Lett 2015 Oct 26;25(20):4693-6. Epub 2015 Jun 26.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address:

Three groups of non-camptothecin compounds with four to five fused rings have been designed and synthesized. Their in vitro anti-proliferative activity has been evaluated with five different cancer cell lines (HCT116, PC3, U87MG, HepG2, SK-OV-3). Compounds B-2 and B-3 showed the most potent cell growth inhibition with IC50 of 169 nM and 325 nM against U87MG cell line correspondingly.
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http://dx.doi.org/10.1016/j.bmcl.2015.06.042DOI Listing
October 2015

Comparisons of family environment between homeless and non-homeless individuals with schizophrenia in Xiangtan, Hunan.

Shanghai Arch Psychiatry 2015 Jun;27(3):175-82

Fifth Ren Min Hospital of Xiangtan, Hunan, Xiangtan, Hunan Province, China.

Background: Homelessness is an increasingly important problem for individuals with serious mental illness in China.

Aim: Identify the characteristics of families that are associated with homelessness among individuals with schizophrenia.

Methods: Participants were 1856 homeless individuals with schizophrenia (defined as those who had no place of residence or involved caregivers for 7 consecutive days) and 1728 non-homeless individuals with schizophrenia from Xiangtan, Hunan. The self-completion Family Environment Scale-Chinese Version (FES-CV) was administered to these participants after their acute psychotic symptoms resolved.

Results: Compared to individuals in the non-homeless group, those in the homeless group were older and more likely to be non-locals (i.e., from outside of Xiangtan), be residents of rural (versus urban) communities, have temporary (versus permanent) jobs, be married, and have a low level of education. After controlling for demographic differences using multivariate logistic regression models, homelessness was independently associated higher scores in the FES-CV intellectual-cultural orientation, organization, achievement orientation, and control subscales and with lower scores in the FES-CV cohesion, moralreligious emphasis, independence, and active-recreational orientation subscales.

Conclusion: After controlling for sociodemographic factors, certain aspects of the family environment areassociated with being homeless among patients with schizophrenia in China. Further work is needed to identify interventions that can reduce the risk of homelessness in high-risk individuals.
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http://dx.doi.org/10.11919/j.issn.1002-0829.214162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526830PMC
June 2015

Synthesis and biological evaluation of thiabendazole derivatives as anti-angiogenesis and vascular disrupting agents.

Bioorg Med Chem 2015 Jul 8;23(13):3774-80. Epub 2015 Apr 8.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address:

Thiabendazole, already approved by FDA for oral use as an anti-fungal and anti-helminthic drug since 1967, has recently been repurposed as a vascular disrupting agent. By optimization of the structure of the lead compound, we successfully identified compound TBZ-19 and the new derivative is over 100-fold more potent than the lead compound against the growth of four different cell lines (A549, HCT-116, HepG2 and HUVECs). The most potent two candidates TBZ-07 and TBZ-19, exhibiting moderate inhibitory cell proliferation activity, were also verified as anti-angiogenesis and vascular disrupting agents. Therefore, TBZ-07 and TBZ-19 would be promising candidates with vasculature targeting activity and merit further development.
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http://dx.doi.org/10.1016/j.bmc.2015.03.085DOI Listing
July 2015
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