Publications by authors named "Min Ren"

202 Publications

The association of triglyceride and glucose index, and triglyceride to high-density lipoprotein cholesterol ratio with prehypertension and hypertension in normoglycemic subjects: A large cross-sectional population study.

J Clin Hypertens (Greenwich) 2021 Jun 12. Epub 2021 Jun 12.

Tianjin Chest Hospital, Tianjin, China.

Insulin resistance (IR) plays an important role in the development of hypertension. Triglyceride and glucose index (TyG index), and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c) as effective IR surrogate indexes have been verified in numerous studies. Therefore, the authors conducted a large cross-sectional study to explore the association of TyG index and TG/HDL-c with prehypertension and hypertension in the same normoglycemic subjects from Tianjin, China. A total of 32 124 adults were eligible for this study. According to the level of blood pressure, the enrolled individuals were divided into three groups, which were normotension, prehypertension, and hypertension. In multiple logistic regression analysis, there was associated with prehypertension and hypertension when comparing the highest TyG index to the lowest TyG index and corresponding ORs were 1.795 (1.638, 1.968) and 2.439 (2.205, 2.698), respectively. For TG/HDL-c, the corresponding ORs were 1.514 (1.382, 1.658) and 1.934 (1.751, 2.137), respectively. Furthermore, when comparing the fourth quartile to the first quartile of TyG index and TG/HDL-c, respectively, both corresponding ORs of hypertension were higher than prehypertension. Elevated TyG index and TG/HDL-c levels were associated with prehypertension and hypertension in normoglycemic individuals. Moreover, the TyG index was more significant than TG/HDL-c in distinguishing hypertension. They have the potential to become cost-effective monitors in the hierarchical management of prehypertension and hypertension.
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http://dx.doi.org/10.1111/jch.14305DOI Listing
June 2021

Pharmacodynamic Biomarkers Predictive of Survival Benefit with Lenvatinib in Unresectable Hepatocellular Carcinoma: From the Phase 3 REFLECT Study.

Clin Cancer Res 2021 Jun 9. Epub 2021 Jun 9.

Beatson West of Scotland Cancer Centre, University of Glasgow.

Purpose: In REFLECT, lenvatinib demonstrated an effect on overall survival (OS) by confirmation of noninferiority to sorafenib in unresectable hepatocellular carcinoma. This analysis assessed correlations between serum or tissue biomarkers and efficacy outcomes from REFLECT.

Experimental Design: Serum biomarkers (VEGF, ANG2, FGF19, FGF21, and FGF23) were measured by ELISA. Gene expression in tumor tissues was measured by the nCounter PanCancer Pathways Panel. Pharmacodynamic changes in serum biomarker levels from baseline, and associations of clinical outcomes with baseline biomarker levels were evaluated.

Results: 407 patients were included in the serum analysis set (lenvatinib n=279, sorafenib n=128); 58 patients were included in the gene-expression analysis set (lenvatinib n=34, sorafenib n=24). Both treatments were associated with increases in VEGF; only lenvatinib was associated with increases in FGF19 and FGF23 at all timepoints. Lenvatinib-treated responders had greater increases in FGF19 and FGF23 versus non-responders at C4D1 (FGF19: 55.2% vs 18.3%, P=0.014; FGF23: 48.4% vs 16.4%, P=0.0022, respectively). Higher baseline VEGF, ANG2, and FGF21 correlated with shorter OS in both treatment groups. OS was longer for lenvatinib than sorafenib (median, 10.9 vs 6.8 months, respectively; HR, 0.53; 95% CI, 0.33-0.85; P=0.0075; P-interaction=0.0397) with higher baseline FGF21. In tumor tissue biomarker analysis, VEGF/FGF enriched groups showed improved OS with lenvatinib versus the intermediate VEGF/FGF group (HR 0.39; 95% CI 0.16-0.91; P=0.0253).

Conclusions: Higher baseline levels of VEGF, FGF21, and ANG2 may be prognostic for shorter OS. Higher baseline FGF21 may be predictive for longer OS with lenvatinib compared with sorafenib, but this needs confirmation.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4219DOI Listing
June 2021

Qindan Capsule Attenuates Myocardial Hypertrophy and Fibrosis in Pressure Overload-Induced Mice Involving mTOR and TGF-1/Smad Signaling Pathway Inhibition.

Evid Based Complement Alternat Med 2021 28;2021:5577875. Epub 2021 Apr 28.

Department of Traditional Chinese Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Qindan capsule (QC), a traditional Chinese medicine compound, has been used to treat hypertension in the clinic for over 30 years. It is still not known about the effects of QC on pressure overload-induced cardiac remodeling. Hence, this study aims to investigate the effects of QC on pressure overload-induced cardiac hypertrophy, fibrosis, and heart failure in mice and to determine the possible mechanisms. Transverse aortic constriction (TAC) surgery was used to induce cardiac hypertrophy and heart failure in C57BL/6 mice. Mice were treated with QC or losartan for 8 weeks after TAC surgery. Cardiac function indexes were evaluated with transthoracic echocardiography. Cardiac pathology was detected using HE and Masson's trichrome staining. Cardiomyocyte ultrastructure was detected using transmission electron microscopy. Hypertrophy-related fetal gene expression was investigated using real-time RT-PCR. The expression of 8-OHdG and the concentration of MDA and Ang-II were assessed by immunohistochemistry stain and ELISA assay, respectively. The total and phosphorylated protein levels of mTOR, p70S6K, 4EBP1, Smad2, and Smad3 and the expression of TGF-1 and collagen I were measured using western blot. The results showed that low- and high-dose QC improved pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction. QC inhibited ANP, BNP, and -MHC mRNA expression in failing hearts. QC improved myocardial ultrastructure after TAC surgery. Furthermore, QC downregulated the expression of 8-OHdG and the concentration of MDA, 15-F-IsoP, and Ang-II in heart tissues after TAC surgery. We also found that QC inhibited the phosphorylation of mTOR, p70S6K, and 4EBP1 and the expression of TGF-1, p-Smad2, p-Smad3, and collagen I in pressure overload-induced failing hearts. These data indicate that QC has direct benefic effects on pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction. The protective effects of QC involve prevention of increased oxidative stress injury and Ang-II levels and inhibition of mTOR and TGF-1/Smad pathways in failing hearts.
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http://dx.doi.org/10.1155/2021/5577875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102107PMC
April 2021

Safety and efficacy of lenvatinib by starting dose based on body weight in patients with unresectable hepatocellular carcinoma in REFLECT.

J Gastroenterol 2021 Jun 4;56(6):570-580. Epub 2021 May 4.

Toranomon Hospital, Tokyo, Japan.

Background: REFLECT was an open-label, phase 3 study comparing the efficacy and safety of lenvatinib versus sorafenib in patients with unresectable hepatocellular carcinoma (uHCC). Based on phase 2 study (Study 202) results, body weight-based dosing for lenvatinib was used in REFLECT to minimize dose disruptions and modifications needed to address dose-related adverse events. This post hoc analysis of REFLECT data assessed lenvatinib efficacy and safety by body weight group.

Methods: The study randomly administered lenvatinib (n = 476) or sorafenib (n = 475) to patients with untreated (no prior systemic therapy) uHCC. Lenvatinib starting-dose data were stratified by body weight: patients weighing < 60 kg received 8 mg/day; patients weighing ≥ 60 kg received 12 mg/day. Overall survival (OS), progression-free survival (PFS), objective response rate, and safety were assessed.

Results: Survival outcomes and safety profiles appeared similar between the two body-weight-based lenvatinib starting-dose groups. Median OS for patients in the < 60 kg body weight group (n = 153) was 13.4 months [95% confidence interval (CI) 10.5-15.7] compared to 13.7 months (95% CI 12.0-15.6) in the ≥ 60 kg body weight group (n = 325). In both lenvatinib groups, PFS was 7.4 months (< 60 kg group: 95% CI 5.4-9.2; ≥ 60 kg group: 95% CI 6.9-9.0). Treatment-emergent adverse events (TEAEs) required dose modifications in 43.0% in the < 60 kg body weight group and 57.5% in the ≥ 60 kg body weight group.

Conclusions: This exploratory analysis of data from REFLECT indicated that body weight-based lenvatinib dosing in patients with uHCC was successful in maintaining efficacy, with comparable rates of TEAEs and dose modifications in the two body weight groups.

Clinincal Trial: Trial registration ID: ClinicalTrials.gov # NCT01761266.
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http://dx.doi.org/10.1007/s00535-021-01785-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137475PMC
June 2021

Halogen-Bond Mediated 3D Confined Assembly of AB Diblock Copolymer and C Homopolymer Blends.

Small 2021 May 18;17(18):e2007570. Epub 2021 Mar 18.

Key Laboratory of Materials Chemistry for Energy Conversion and Storage, Ministry of Education (HUST), School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan, 430074, China.

Halogen-bond driven assembly, a world parallel to hydrogen-bond, has emerged as an attractive tool for constructing (macro)molecular arrangement. However, knowledge about halogen-bond mediated confined-assembly in emulsion droplets is limited so far. An I N bond mediated confined-assembly pathway to enable order-order phase transitions is reported here. Compared to hydrogen bonds, the distinct features of halogen bonds (e.g., higher directionality, hydrophobicity, favored in polar solvents), offers opportunities to achieve novel nanostructures and materials. Polystyrene-b-poly(4-vinyl pyridine) (PS-b-P4VP) AB diblock copolymer is chosen as halogen acceptor, while an iodotetrafluorophenoxy substituted C-type homopolymer, (poly(3-(2,3,5,6-tetrafluoro-4-iodophenoxy)propyl acrylate), PTFIPA) is designed as halogen donor, synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Formation of halogen bonding donor-acceptor pairs between the PTFIPA homopolymer and the P4VP segments presented in PS-b-P4VP, increase the volume of P4VP domains, in turn inducing an order-to-order morphology transition sequence: changing from spherical → cylindrical → lamellar → inverse cylindrical, by tuning the PTFIPA content and choice of surfactant. Subsequent selective swelling/deswelling of the P4VP domains give rise to further internal morphology transitions, creating tailored mesoporous microparticles, disassembled nanodiscs, and superaggregates. It is believed that these results will stimulate further examinations of halogen bonding interactions in emulsion droplets and many areas of application.
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http://dx.doi.org/10.1002/smll.202007570DOI Listing
May 2021

Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer.

Eur J Cancer 2021 Apr 19;147:51-57. Epub 2021 Feb 19.

Massachusetts General Hospital Cancer Center, Boston, MA, USA.

Background: Lung metastases may worsen overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). We investigated (post hoc) the impact of lung metastases on survival in SELECT (a phase 3 study).

Patients And Methods: 392 patients with RR-DTC were randomised 2:1 to lenvatinib 24 mg daily (n = 261) or placebo (n = 131). Placebo-treated patients could crossover to open-label lenvatinib following progression. Patients were grouped by size of baseline lung metastases. Safety/efficacy outcomes, collated by these lung-metastases subgroups, were generated.

Results: Lenvatinib-treated population distributions per baseline lung metastases subgroup were any lung metastases (target/nontarget lesions; n = 226), and by maximum size of target lung lesions ≥1.0 cm (n = 199), ≥1.5 cm (n = 150), ≥2.0 cm (n = 94) and <2.0 cm (n = 105). In patients with any lung metastases, no statistically significant difference in OS was observed between treatment arms (HR: 0.76; 95% CI: 0.57-1.01; P = 0.0549). Median OS for lung metastases of ≥1.0 cm was 44.7 months (lenvatinib) versus 33.1 months (placebo) (HR: 0.63; 95% CI: 0.47-0.85; P = 0.0025). OS was significantly prolonged with lenvatinib versus placebo among patients with lung metastases of ≥1.0 cm, ≥1.5 cm, ≥2.0 cm and <2.0 cm; median OS was shorter in the ≥2.0 cm subgroup (lenvatinib: 34.7 months) versus other subgroups (lenvatinib: 44.1-49.2 months). Multivariate analysis demonstrated lenvatinib significantly prolonged OS in patients with lung metastases of ≥1.0 cm after adjustment for baseline characteristics.

Conclusions: Lenvatinib treatment resulted in longer OS in patients with lung metastases of ≥1.0 cm versus placebo (even with the 89% crossover rate). Early initiation of lenvatinib may improve outcomes in patients with RR-DTC and lung metastases of ≥1.0 cm.

Source Study Registration: ClinicalTrials.Gov Identifier: NCT01321554.
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http://dx.doi.org/10.1016/j.ejca.2020.12.032DOI Listing
April 2021

AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development.

Cell Death Dis 2021 02 10;12(2):172. Epub 2021 Feb 10.

Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei, China.

As evidenced by the behavior of loss-of-function mutants of PTEN in the context of a gain-of-function mutation of AKT1, the PTEN-AKT1 signaling pathway plays a critical role in human cancers. In this study, we demonstrated that a deficiency in PTEN or activation of AKT1 potentiated the expression of platelet-derived growth factor receptor α (PDGFRα) based on studies on Pten-/- mouse embryonic fibroblasts, human cancer cell lines, the hepatic tissues of Pten conditional knockout mice, and human cancer tissues. Loss of PTEN enhanced PDGFRα expression via activation of the AKT1-CREB signaling cascade. CREB transactivated PDGFRα expression by direct binding of the promoter of the PDGFRα gene. Depletion of PDGFRα attenuated the tumorigenicity of Pten-null cells in nude mice. Moreover, the PI3K-AKT signaling pathway has been shown to positively correlate with PDGFRα expression in multiple cancers. Augmented PDGFRα was associated with poor survival of cancer patients. Lastly, combination treatment with the AKT inhibitor MK-2206 and the PDGFR inhibitor CP-673451 displayed synergistic anti-tumor effects. Therefore, activation of the AKT1-CREB-PDGFRα signaling pathway contributes to the tumor growth induced by PTEN deficiency and should be targeted for cancer treatment.
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http://dx.doi.org/10.1038/s41419-021-03433-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876135PMC
February 2021

Epidemiology of norovirus gastroenteritis in hospitalized children under five years old in western China, 2015-2019.

J Microbiol Immunol Infect 2021 Jan 26. Epub 2021 Jan 26.

West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address:

Objectives: Norovirus is associated with one-fifth of all gastroenteritis cases, but basic epidemiological data is lacking, especially in developing countries. As long-term surveillance on norovirus gastroenteritis is scarce in western China, this study aims to update the epidemiological knowledge of norovirus gastroenteritis and to characterize the genotypes of norovirus strains.

Methods: Stool samples were collected from hospitalized children under 5 years old with gastroenteritis in Chengdu, China. All samples were tested for norovirus as well as rotavirus, sapovirus, enteric adenovirus, and astrovirus by real-time RT-PCR. RdRp and VP1 genes were sequenced in norovirus-positive samples to investigate viral phylogenies.

Results: Of the 1181 samples collected from 2015 to 2019, 242 (20.5%) were positive for norovirus. Among norovirus-positive cases, 65 cases had co-infection with another virus; norovirus/enteric adenovirus was most frequently detected (50.8%, 33/65). The highest positive rate was observed in children aged 13-18 months (23.7%, 68/287). Norovirus infection peaked in autumn (36.6%, 91/249), followed by summer (20.3%, 70/345). Pearson correlation analysis showed significant correlation between the norovirus-positive rate and humidity (r = 0.773, P < 0.05). GII.4 Sydney 2012 [P31] (48.5%, 79/163) and GII.3 [P12] (35.6%, 58/163) were the dominant norovirus strains.

Conclusions: Norovirus has become one of the most common causes of viral gastroenteritis in children under 5 years old in western China. Continuous monitoring is imperative for predicting the emergence of new epidemic strains and for current vaccine development.
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http://dx.doi.org/10.1016/j.jmii.2021.01.002DOI Listing
January 2021

Distribution of risk factors of hypertension patients in different age groups in Tianjin.

BMC Public Health 2021 01 29;21(1):247. Epub 2021 Jan 29.

Department of Cardiology, Tianjin Chest Hospital, No. 261 of Taierzhuang South Road, Jinnan District, Tianjin, 300222, China.

Background: To analyze the risk factors for hypertension in different age groups of urban and rural residents in Tianjin.

Methods: A total of 33,997 people (35-75 years old) from 13 community health service centers and primary hospitals in Tianjin participated in this study. They were divided into the youth group (≤ 40 years old), middle-aged group (41-65 years old), and elderly group (> 65 years old). Then, a questionnaire survey was administered, followed by physical and blood biochemical examinations. The demographic characteristics and prevalence were recorded and counted. Subsequently, risk factors were analyzed using univariate and stepwise multivariate logistic regression analysis.

Results: In the youth, middle-aged, and elderly groups, the prevalence rate of hypertension was 18.65, 51.80, and 76.61%, respectively. Logistic regression analysis showed that obesity(OR: 3.263, 95% CI: 1.039-1.656), men (OR: 2.117, 95% CI: 1.691-2.651), diabetes (OR: 1.978, 95% CI: 1.398-2.799), high triglycerides(OR 1.968 95% CI: 1.590-2.434) and family history of stroke (OR: 1.936, 95% CI: 1.287-2.911) are the five factors in youth. In middle-aged group, the significantly associating factors were obesity (OR: 2.478, 95% CI: 2.330-2.636), diabetes (OR: 2.173, 95% CI: 1.398-2.799), family history of stroke (OR: 1.808, 95% CI: 1.619-2.020), maleness (OR: 1.507, 95% CI: 1.412-1.609),Hypertriglyceridemia (OR 1.490 95% CI: 1.409-1.577),family history of cardiovascular disease (OR: 1.484, 95% CI: 1.307-1.684),Hypercholesterolemia (OR 1.228 95% CI: 1.160-1.299). In the elderly group, obesity (OR: 2.104, 95% CI: 1.830-2.418), family history of strokes (OR: 1.688, 95% CI: 1.243-2.292), diabetes mellitus (OR: 1.544, 95% CI: 1.345-1.773), family history of cardiovascular disease (OR: 1.470, 95% CI: 1.061-2.036), hypertriglyceridemia (OR: 1.348, 95% CI: 1.192-1.524) increased the risk for hypertension. Waist circumference (WC) and waist-to-height ratio (WHtR) increased with age, and the value of these two measures for predicting hypertension was better than BMI in middle-aged group.

Conclusion: Obesity is the most important risk factor for hypertension in all age groups. Diabetes, family history of strokes and high triglyceride were also significant risk factors for all age groups. There was a gender difference between the young and middle-aged groups, with men more likely to hypertension. Waist circumference (WC) and waist-to-height ratio (WHtR) were better predictors of hypertension than BMI in middle-aged group.
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http://dx.doi.org/10.1186/s12889-021-10250-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846994PMC
January 2021

Concordance of the 21-gene assay between core needle biopsy and resection specimens in early breast cancer patients.

Breast Cancer Res Treat 2021 Apr 13;186(2):327-342. Epub 2021 Jan 13.

Department of Pathology, Fudan University Shanghai Cancer Center, No. 270 Dong An Road, Shanghai, 200032, China.

Background: Adjuvant therapy decisions may be partly based on the results of a multigene quantitative reverse transcription-polymerase chain reaction (RT-PCR)-based assay: the 21-gene recurrence score (RS) test of resection specimens. When necessary, core needle biopsy (CNB) may be considered as a surrogate. Here, we evaluated the concordance in gene expression according to results from RT-PCR-based RS testing between paired CNBs and resection specimens.

Methods: CNBs and resection specimens from 50 breast cancer (BC) patients were tested to calculate RSs. First, we examined the concordance of the ER, PR and HER-2 status of tissue samples indicated by immunohistochemical (IHC) and RT-PCR analyses. Then, we compared the IHC findings of ER, PR, HER-2 and Ki-67 staining across paired samples. Ultimately, the RS and single-gene results for ER, PR, HER-2 and Ki-67 were explored between paired samples.

Results: The concordance between IHC and RT-PCR was 100%, 80.0% and 100% for ER, PR and HER-2, respectively, in both resection specimens and CNBs. The concordance for IHC ER, PR, HER-2 and Ki-67 status was 100%, 94.0%, 52.0% and 82.0%, respectively, between paired samples. RS results from paired samples showed a strong correlation. The overall concordance in RS group classification between samples was 74%, 72% and 78% based on traditional cutoffs, TAILORx cutoffs and ASCO guidelines, respectively. ER, PR, HER-2 and Ki-67 were modestly- to- strongly correlated between paired samples according to the RT-PCR results.

Conclusion: A modest- to- strong correlation of ER, PR, HER-2 and Ki-67 gene expression and RS between CNBs and resection specimens was observed in the present study. The 21-gene RS test could be reliably performed on CNBs. ER, PR and HER-2 status showed remarkable concordance between the IHC and RT-PCR analyses. The concordance between paired samples was high for the IHC ER, PR and Ki-67 results and low for HER-2.
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http://dx.doi.org/10.1007/s10549-020-06075-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804587PMC
April 2021

Comparative transcriptome analysis reveals resistant and susceptible genes in tobacco cultivars in response to infection by Phytophthora nicotianae.

Sci Rep 2021 Jan 12;11(1):809. Epub 2021 Jan 12.

Key Laboratory of Tobacco Genetic Improvement and Biotechnology, Tobacco Research Institute, Chinese Academy of Agricultural Sciences, Qingdao, 266100, China.

Phytophthora nicotianae is highly pathogenic to Solanaceous crops and is a major problem in tobacco production. The tobacco cultivar Beihart1000-1 (BH) is resistant, whereas the Xiaohuangjin 1025 (XHJ) cultivar is susceptible to infection. Here, BH and XHJ were used as models to identify resistant and susceptible genes using RNA sequencing (RNA-seq). Roots were sampled at 0, 6, 12, 24, and 60 h post infection. In total, 23,753 and 25,187 differentially expressed genes (DEGs) were identified in BH and XHJ, respectively. By mapping upregulated DEGs to the KEGG database, changes of the rich factor of "plant pathogen interaction pathway" were corresponded to the infection process. Of all the DEGs in this pathway, 38 were specifically regulated in BH. These genes included 11 disease-resistance proteins, 3 pathogenesis-related proteins, 4 RLP/RLKs, 2 CNGCs, 7 calcium-dependent protein kinases, 4 calcium-binding proteins, 1 mitogen-activated protein kinase kinase, 1 protein EDS1L, 2 WRKY transcription factors, 1 mannosyltransferase, and 1 calmodulin-like protein. By combining the analysis of reported susceptible (S) gene homologs and DEGs in XHJ, 9 S gene homologs were identified, which included 1 calmodulin-binding transcription activator, 1 cyclic nucleotide-gated ion channel, 1 protein trichome birefringence-like protein, 1 plant UBX domain-containing protein, 1 ADP-ribosylation factor GTPase-activating protein, 2 callose synthases, and 2 cellulose synthase A catalytic subunits. qRT-PCR was used to validate the RNA-seq data. The comprehensive transcriptome dataset described here, including candidate resistant and susceptible genes, will provide a valuable resource for breeding tobacco plants resistant to P. nicotianae infections.
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http://dx.doi.org/10.1038/s41598-020-80280-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804271PMC
January 2021

Reconstituted high density lipoprotein (rHDL), a versatile drug delivery nanoplatform for tumor targeted therapy.

J Mater Chem B 2021 01;9(3):612-633

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.

rHDL is a synthesized drug delivery nanoplatform exhibiting excellent biocompatibility, which possesses most of the advantages of HDL. rHDL shows almost no toxicity and can be degraded to non-toxic substances in vivo. The severe limitation of the application of various antitumor agents is mainly due to their low bioavailability, high toxicity, poor stability, etc. Favorably, antitumor drug-loaded rHDL nanoparticles (NPs), which are known as an important drug delivery system (DDS), help to change the situation a lot. This DDS shows an outstanding active-targeting ability towards tumor cells and improves the therapeutic effect during antitumor treatment while overcoming the shortcomings mentioned above. In the following text, we will mainly focus on the various applications of rHDL in tumor targeted therapy by describing the properties, preparation, receptor active-targeting ability and antitumor effects of antineoplastic drug-loaded rHDL NPs.
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http://dx.doi.org/10.1039/d0tb02139cDOI Listing
January 2021

Evolution of SHORT VEGETATIVE PHASE (SVP) genes in Rosaceae: Implications of lineage-specific gene duplication events and function diversifications with respect to their roles in processes other than bud dormancy.

Plant Genome 2020 11 17;13(3):e20053. Epub 2020 Sep 17.

College of Horticulture, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China.

MADS-box genes that are homologous to Arabidopsis SHORT VEGETATIVE PHASE (SVP) have been shown to play key roles in the regulation of bud dormancy in perennial species, particularly in the deciduous fruit trees of Rosaceae. However, their evolutionary profiles in Rosaceae have not yet been analyzed systematically. Here, The SVP genes were found to be significantly expanded in Rosaceae when compared with annual species from Brassicaceae. Phylogenetic analysis showed that Rosaceae SVP genes could be classified into five clades, namely, SVP1, SVP2-R1, SVP2-R2, SVP2-R3 and SVP3. The SVP1 clade genes were retained in most of the species, whereas the SVP2-R2 and SVP2-R3 clades were found to be Maleae- and Amygdaleae-specific (Both of the lineages belong to Amygdaloideae), respectively, and SVP2-R1 was Rosoideae-specific in Rosaceae. Furthermore, 10 lineage-specific gene duplication (GD) events (GD1-10) were proposed for the expansion of SVP genes, suggesting that the expansion and divergence of Rosaceae SVP genes were mainly derived by lineage-specific manner during evolution. Moreover, tandem and segmental duplications were the major reasons for the expansion of SVP genes, and interestingly, tandem duplications, a well-known evolutionary feature of SVP genes, were found to be mainly Amygdaloideae-specific. Sequence alignment, selection pressure, and cis-acting element analysis suggested large functional innovations and diversification of SVP genes in different lineages of Rosaceae. Finally, the different growth cycle of Rosa multiflora and their novel expression patterns of RmSVP genes provided new insights into the functional diversification of SVP genes in terms of their roles in processes other than bud dormancy.
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http://dx.doi.org/10.1002/tpg2.20053DOI Listing
November 2020

Combination of Scalp Acupuncture with Exercise Therapy Effectively Counteracts Ischemic Brain Injury in Rats.

J Stroke Cerebrovasc Dis 2020 Nov 3;29(11):105286. Epub 2020 Sep 3.

Department of Rehabilitation, Pudong New Area People's Hospital affiliated to Shanghai University of Medicine & Health Sciences, Shanghai 201299, P. R. China.

Background: Stroke is one of the leading causes of death and disability worldwide. Scalp acupuncture and exercise therapy have been proven as two effective methods for the treatment of stroke. However, their combined action and mechanisms have not been fully elucidated. The present study aimed to investigate the protective effect of scalp acupuncture combined with exercise therapy on neurons in rats with ischemic brain injury.

Methods: 100 rats were randomly divided into 5 groups including sham group, model group, acupuncture group, rehabilitation group, and experimental group (scalp acupuncture combined with exercise therapy). Middle cerebral artery occlusion (MCAO) model in rats was established according to Longa modified suture method to mimic ischemic stroke. The modified Bedexer's neurological function score was used to evaluate the neurological deficits of rats and the brain infarct volume was measured using 2, 3, 5-triphenyl tetrazolium chloride monohydrate (TTC) staining. Moreover, the apoptosis in the hippocampus was detected by western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), reactive oxygen species (ROS) and superoxide dismutase (SOD) were determined by corresponding kits. Immunohistochemistry or immunofluorescence was performed to detect the expression of brain-derived neurotrophic factor (BDNF), S100β and glial fibrillary acidic protein (GFAP) in the hippocampi of rats.

Results: The neurological deficit score, the expression levels of apoptotic factors such as cleaved caspase-3 and Bax, and the TUNEL-positive cell rate of the experimental group were significantly lower than those of the acupuncture group and the rehabilitation group. However, apoptosis inhibitor Bcl-2 showed downregulated expression in the MCAO model rats but this trend was reverted by single and combinatorial treatments. In addition, the contents of TNF-α, IL-1β and ROS in the acupuncture group and the rehabilitation group were significantly lower than those in the model group, but higher than the experimental group. While the opposite results were obtained in SOD activity. Furthermore, compared with the model group, the ratios of BDNF, S100β, and GFAP-positive cells in the acupuncture, rehabilitation and experimental groups were significantly increased, and the highest ratios were recorded in the experimental group.

Conclusions: This study demonstrated that scalp acupuncture combined with exercise therapy effectively counteracts ischemic brain injury via the downregulation of pro-inflammatory mediators and ROS, the increased production of the antioxidant enzyme SOD, neurotrophic factor BDNF and astrocyte activities.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105286DOI Listing
November 2020

Clinicopathological, immunohistochemical and fluorescence in-situ hybridisation features of early subungual melanoma: an analysis of 65 cases.

Histopathology 2021 Apr 25;78(5):717-726. Epub 2020 Dec 25.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.

Aims: Very limited data are available concerning the clinicopathological and molecular features of early subungual melanoma (SM), especially with regard to the Asian population. The aim of this study was to investigate the clinical, histological, immunohistochemical and chromosomal features of early SM.

Methods And Results: Fifty-two in-situ and 13 thin (Breslow thickness ≤1.0 mm) SM cases were retrospectively reviewed. All patients presented with longitudinal melanonychia involving a single digit, and the thumb was the most affected digit (35 of 65, 53.8%). Microscopically, most cases showed small to medium nuclear enlargement (58 of 65) and mild to moderate nuclear atypia (57 of 65). Hyperchromatism and irregular contours of nuclei were persistent features in all cases. The variation of melanocyte count (the number of melanocytes per mm dermal-epithelial junction) ranged from 31 to 255. Intra-epithelial mitoses were identified in 34 cases (52.3%). Statistically, features of in-situ lesions including higher melanocyte count (>70), presence of multinucleated melanocytes, inflammatory infiltrate and cutaneous adnexal extension, were associated with early invasion. Melan-A, human melanoma B (HMB)45, mouse monoclonal melanoma antibody (PNL2) and SOX10 antibodies (>95.0%) showed superior diagnostic sensitivity to S-100 protein (83.1%). Fluorescence in-situ hybridisation (FISH) results were positive in 15 of 23 successfully analysed cases.

Conclusions: To the best of our knowledge, this is the largest single-institution study of early SM in an Asian population, and the largest cohort tested by FISH. Early SM mainly showed small to medium nuclear enlargement and mild to moderate nuclear atypia. High melanocyte count, hyperchromatism and irregular contours of nuclei and intra-epithelial mitoses are crucial diagnostic parameters. Immunohistochemistry, especially SOX10 staining, and FISH analysis are valuable in the diagnosis of SM.
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http://dx.doi.org/10.1111/his.14279DOI Listing
April 2021

Detection of Klebsiella pneumoniae cfDNA in pleural fluid and its clinical value.

Ann Palliat Med 2020 Sep 10;9(5):3379-3384. Epub 2020 Sep 10.

Department of Respiratory and Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang, China.

Background: Klebsiella pneumoniae (KP) is an important opportunistic pathogen that can easily cause pneumonia and pleural effusion when body resistance is reduced. However, the positive rate of KP detected from clinical pleural effusion by traditional methods, including bacterial culture, is meager. Therefore, new detection methods are urgently needed to improve the positive detection rate of KP and other bacteria in pleural effusion.

Methods: Simulated pleural fluid of KP infection was first set up. Then circulating cell-free DNA (cfDNA) was extracted from cultured hydrothorax and detected by fluorescence polymerase chain reaction (PCR) to verify KP cfDNA in the pleural fluid. The specificity, sensitivity, and repeatability of this method are verified by detecting the cfDNAs in pleural effusion, samples of malignant pleural effusion, tuberculous pleural effusion, and other common microbial infections. Finally, this method was compared with three traditional methods, pleural effusion, precipitation DNA, sputum culture, and pleural effusion culture to explore the clinical diagnostic value of this method.

Results: KP cfDNA was positive by fluorescence PCR from the simulated KP infected pleural effusion, which confirmed KP cfDNA in pleural effusion. KP cfDNA was positive by fluorescence PCR from the pleural effusion of KP infected patients, while with the same detection method, KP cfDNA in clinical carcinomatous hydrothorax, tuberculosis hydrothorax, and other standard microbial infection samples was negative, which confirmed the method had high specificity, high sensitivity, and reproducibility. Compared with the three traditional methods, this method has a higher positive rate. Compared with the gold standard, sputum bacterial culture, the sensitivity, specificity, positive predictive value, and negative predictive value of this method were 91.67%, 95.45%, 91.7%, and 95.5%, respectively.

Conclusions: The detection of cfDNA by fluorescence PCR is possible. Moreover, the positive rate of this method in clinical pleural effusions is high.
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http://dx.doi.org/10.21037/apm-20-1574DOI Listing
September 2020

The value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as complementary diagnostic tools in the diagnosis of rheumatoid arthritis: A multicenter retrospective study.

J Clin Lab Anal 2021 Jan 19;35(1):e23569. Epub 2020 Sep 19.

Science and Education Section, Wujin Hospital Affiliated with Jiangsu University, Changzhou City, China.

Background: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have drawn attention in recent years as novel non-specific inflammatory markers; however, only a few studies have been conducted to investigate their value in RA.

Objective: To investigate the value of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as complementary diagnostic tools in rheumatoid arthritis (RA).

Method: This study included 1009 patients with RA, 170 patients with other rheumatic diseases, and 245 healthy individuals from four medical centers. The patients' general data, including complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF), were retrospectively analyzed, and the NLR and PLR were calculated. Potential effective indicators were screened by logistic regression analysis, and a receiver operating characteristic (ROC) curve was plotted to evaluate their diagnostic value for RA.

Results: (a) The NLR and PLR were significantly higher in the RA group than in the non-RA group and the control group (P < .05). (b) Spearman's Rho showed that the NLR was positively correlated with the PLR (r = .584, P < .05), RF (r = .167, P < .01), and CRP (r = .280, P < .01) but was not significantly correlated with ESR (r = .100, P > .05). The PLR was positively correlated with RF (r = .139, P < .01), CRP (r = .297, P < .01), and ESR (r = .262, P < .05). (c) Logistic analysis showed that RF, CRP, ESR, and the NLR had diagnostic value for RA. (d) For the NLR, the area under the curve (AUC) of the ROC curve was 0.831; at the cutoff value of 2.13, the diagnostic sensitivity, specificity, accuracy, and Youden index were 76.7%, 75.9%, 76.4%, and 0.5424, respectively.

Conclusion: The NLR was less effective than CRP and RF but was superior to ESR in the diagnosis of RA. The NLR can thus be used as a complementary diagnostic indicator in the diagnosis of RA.
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http://dx.doi.org/10.1002/jcla.23569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843258PMC
January 2021

A single-center retrospective study of the clinical significance of chorionic bump at early stage of gestation.

Am J Reprod Immunol 2021 03 5;85(3):e13346. Epub 2020 Oct 5.

Department of Ultrasound, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

Problem: The chorionic bump is a distinct rare sonographic abnormality. Until now, there is contradictory evidence about if it associates with poor pregnancy outcomes. We performed this retrospective study to provide additional clinical data to investigate the clinical significance of chorionic bump at early stage of pregnancy.

Method Of Study: A single-center retrospective study was performed using the sonographic and clinical data of the pregnant women who had antenatal checkup and childbirth at Shanghai First Maternal and Child Health Care Center from December 2018 to December 2019. Sonographic examination was performed by experts at 5-10 weeks' gestation. Maternal age and gestational age matched controls from the same period were selected for analysis.

Results: We observed 83 chorionic bump cases showing a prevalence of 0.33%. We found previous intrauterine operations and/or adverse maternal history posed a risk of having chorionic bump. In our cohort, chorionic bump associates with poor pregnancy outcomes. Poor pregnancy outcomes were more frequently found in the patients whose lesions were detected early (<56 days of pregnancy), or in the patients with the lesion relative sizes more than 40% of the sizes of the gestational sac, or in the patients with multiple lesions.

Conclusion: Intrauterine operations and/or adverse maternal history associate with an increased incidence of chorionic bump, which associates with poor pregnancy outcomes. Early detection, bigger relative size, and multiple lesions are factors likely leading to poor pregnancy outcomes.
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http://dx.doi.org/10.1111/aji.13346DOI Listing
March 2021

Cell Cycle Regulation by Berberine in Human Melanoma A375 Cells.

Bull Exp Biol Med 2020 Aug 11;169(4):491-496. Epub 2020 Sep 11.

Clinical Medical Research Center, Inner Mongolia Medical University, Huhhot, Inner Mongolia, P.R. China.

We studied the effects of berberine on the proliferation, apoptosis, and migration of skin melanoma A375 cells, as well as cell cycle-related miRNAs and their target genes, CDK1, CDK2, and cyclins D1 and A. The inhibitory effect of berberine on the growth of A375 cells was evaluated by MTT assay. Cell apoptosis was detected by trypan blue staining. Cell migration was assessed by the scratch test. Cell cycle phases were determined by flow cytometry. The levels of miRNA-582-5p and miRNA-188-5, and mRNA of their target genes encoding CDK1, CDK2, and cyclins D1 and A were measured by qRT-PCR. The expression of cell cycle-related proteins (CDK1, CDK2, and cyclins D1 and A) was determined by Western blotting. Berberine inhibited the proliferation of A375 cells in a time- and dose-dependent manner and significantly and dose-dependently enhanced cell apoptosis. Scratch assay showed an inhibitory effect of berberine on migration of A375 cells. Berberine in low concentrations (20 and 40 μM) caused cell cycle arrest in the S and G2/M phases, while treatment with high concentrations of berberine (60 and 80 μM) arrested cell-cycle in the G2/M phase. The increase in berberine concentration led to an increase in miRNA-582-5p and miRNA-188-5p expression and a decrease in the expression of mRNA for the corresponding target genes encoding CDK1, CDK2, and cyclins D1 and A. Western blotting also revealed reduced expression of CDK1, CDK2, and cyclins D1 and A. Thus, berberine suppressed the growth and migration of human melanoma cells and promoted their apoptosis. Berberine can increase the expression of cell cycle-related miRNAs and cause degradation of the corresponding target genes, thereby blocking the cell cycle progression and inhibiting the melanoma A375 cells.
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http://dx.doi.org/10.1007/s10517-020-04916-4DOI Listing
August 2020

Fermentation Characteristics of subsp. Isolated From Naturally Fermented Dairy Products and Screening of Potential Starter Isolates.

Front Microbiol 2020 4;11:1794. Epub 2020 Aug 4.

Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China.

It is well known that consumers are keen to try fermented milk products with different flavors and starter cultures are important in determining the resulting fermented dairy products. Here, we present the phenome of 227 subsp. isolates from traditionally fermented dairy products and the selection of potential starter strains. Large-scale phenotyping revealed significant technological diversity in fermentation characteristics amongst the isolates including variation in fermentation time, viscosity, water holding capacity (WHC) and free amino nitrogen (FAN) production. The 16 isolates with the best fermentation characteristics were compared, in a sensory evaluation, with the commercial starter Chr. Hansen R-704 as excellent fermentation characteristics to identify potential starter isolates and find the isolate which can product good flavors. From these, and from solid phase micro extraction (SPME) - gas chromatography (GC)-mass spectrometry (MS) analysis, we identified IMAU11823 and IMAU11919 as producing 3-methyl butanal and 3-methyl-2-butanone which contribute to the malt aroma. This study expands the characterization of subsp. phenotypic dataset and technological diversity and identified isolates with potential culture starter in the fermentation industry.
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http://dx.doi.org/10.3389/fmicb.2020.01794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438938PMC
August 2020

Genetic diversity and fingerprinting of 33 standard flue-cured tobacco varieties for use in distinctness, uniformity, and stability testing.

BMC Plant Biol 2020 Aug 17;20(1):378. Epub 2020 Aug 17.

Key Laboratory of Tobacco Improvement and Biotechnology, Tobacco Research Institute of Chinese Academy of Agricultural Sciences, No.11 Keyuanjingsi Road, Qingdao, 266100, Shandong, China.

Background: At present, the distinctness, uniformity, and stability (DUS) testing of flue-cured tobacco (Nicotiana tabacum L.) depends on field morphological identification, which is problematic in that it is labor intensive, time-consuming, and susceptible to environmental impacts. In order to improve the efficiency and accuracy of tobacco DUS testing, the development of a molecular marker-based method for genetic diversity identification is urgently needed.

Results: In total, 91 simple sequence repeats (SSR) markers with clear and polymorphic amplification bands were obtained with polymorphism information content, Nei index, and Shannon information index values of 0.3603, 0.4040, and 0.7228, respectively. Clustering analysis showed that the 33 study varieties, which are standard varieties for flue-cured tobacco DUS testing, could all be distinguished from one another. Further analysis showed that a minimum of 25 markers were required to identify the genetic diversity of these varieties. Following the principle of two markers per linkage group, 48 pairs of SSR markers were selected. Correlation analysis showed that the genetic relationships revealed by the 48 SSR markers were consistent with those found using the 91 SSR markers.

Conclusions: The genetic fingerprints of the 33 standard varieties of flue-cured tobacco were constructed using 48 SSR markers, and an SSR marker-based identification technique for new tobacco varieties was developed. This study provides a reliable technological approach for determining the novelty of new tobacco varieties and offers a solid technical basis for the accreditation and protection of new tobacco varieties.
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http://dx.doi.org/10.1186/s12870-020-02596-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433079PMC
August 2020

Nevus cell aggregates massively occupying parenchyma of an external iliac lymph node: A case report and review of the literature.

J Cutan Pathol 2020 Dec 10;47(12):1175-1180. Epub 2020 Sep 10.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.

We report a case of nevus cell aggregates (NCAs) in an external iliac lymph node from a patient with a compound congenital nevus in the corresponding drainage skin. Melanocytes in parenchyma were in band, nest-like or nodular fashion, and partly continuous with those in capsule and trabeculae. The largest nodule in parenchyma measured 6.5 mm. Melanocytes mostly exhibited benign appearance identical to cutaneous nevus. A few regions abundant in cells displayed atypical features, including increased nucleo-cytoplasmic ratio, small nucleoli, and occasional mitotic figures. Immunohistochemistry showed that melanocytes stained positive for p16, but negative for HMB-45 and nestin. Ki-67 labeling was less than 1% and reticulin mainly surrounded individual melanocytes. Besides, Vysis melanoma fluorescence in situ hybridization (FISH) plus another 2 probes targeting 9p21(CDKN2A) and 8q24(MYC) showed normal results. The patient is alive without malignant tumor after 52-month follow up. Our case provides a new evidence for the existence of intraparenchymal NCAs in deep lymph node and indicates that melanocytes with some atypical features can occur in nodal nevi. Nevus cells in parenchyma connected to those in capsule and trabeculae are a significant clue to distinguish nodal nevi from metastatic melanomas. Additionally, immunohistochemistry and FISH assay are useful in differential diagnosis.
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http://dx.doi.org/10.1111/cup.13805DOI Listing
December 2020

Tunable Photonic Microspheres of Comb-Like Supramolecules.

Small 2020 Jul 22;16(29):e2001315. Epub 2020 Jun 22.

State Key Lab of Materials Processing and Die and Mould Technology and Key Lab of Materials Chemistry for Energy Conversion and Storage of Ministry of Education (HUST), School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan, 430074, China.

Photonic crystals (PCs) are ideal candidates for reflective color pigments with high color purity and brightness due to tunable optical stop band. Herein, the generation of PC microspheres through 3D confined supramolecular assembly of block copolymers (polystyrene-block-poly(2-vinylpyridine), PS-b-P2VP) and small molecules (3-n-pentadecylphenol, PDP) in emulsion droplets is demonstrated. The intrinsic structural colors of the PC microspheres are effectively regulated by tuning hydrogen-bonding interaction between P2VP blocks and PDP, where reflected color can be readily tuned across the whole visible spectrum range. Also, the effects of both PDP and homopolymer (hPS) on periodic structure and optical properties of the microspheres are investigated. Moreover, the spectral results of finite element method (FEM) simulation agree well with the variation of structural colors by tuning the periodicity in PC microspheres. The supramolecular microspheres with tunable intrinsic structural color can be potentially useful in the various practical applications including display, anti-counterfeit printing and painting.
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http://dx.doi.org/10.1002/smll.202001315DOI Listing
July 2020

First-in-human phase I study of immunomodulatory E7046, an antagonist of PGE-receptor E-type 4 (EP4), in patients with advanced cancers.

J Immunother Cancer 2020 06;8(1)

Département d'Innovation Thérapeutique et d'Essais Précoces, Gustave Roussy, Université Paris-Saclay, Villejuif, France.

Background: E7046 is a highly selective, small-molecule antagonist of the E-type prostanoid receptor 4 (EP4) for prostaglandin E2, an immunosuppressive mediator of the tumor immune microenvironment. This first-in-human phase 1 study assessed the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose (MTD) and recommended phase 2 dose of E7046.

Methods: This first-in-human study enrolled 30 patients with advanced tumors of cancer types associated with high levels of myeloid infiltrates. E7046 was administered orally once-daily in sequential escalating dose cohorts (125, 250, 500, and 750 mg) with ≥6 patients per cohort. Tumor assessments were performed every 6 weeks. Paired tumor biopsies and blood samples, before and on treatment, were collected for pharmacokinetic and pharmacodynamic characterization of the treatment.

Results: No dose-limiting toxicities were observed, and the MTD was not reached. E7046 had an elimination half-life (t) of 12 hours, and drug exposure increased dose-dependently from 125 to 500 mg. Target modulation by E7046 was supported by changes in genes downstream of EP4 with concurrent enhanced antitumoral immune responses. A best response of stable disease (per irRECIST) was reported in 23% of patients treated with E7046 (n=30) (125 mg: n=2; 250 mg: n=2; 750 mg: n=3). Over half (4/7) of the patients with stable disease had treatment duration of 18 weeks or more, and three patients (3/15; 20%) achieved metabolic responses.

Conclusions: In this first-in-human study, E7046 administered orally once daily demonstrated manageable tolerability, immunomodulatory effects, and a best response of stable disease (≥18 weeks) in several heavily pretreated patients with advanced malignancies. The 250 and 500 mg doses are proposed for further development in the combination setting.

Trial Registration Number: NCT02540291.
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http://dx.doi.org/10.1136/jitc-2019-000222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304851PMC
June 2020

RcMYB84 and RcMYB123 mediate jasmonate-induced defense responses against Botrytis cinerea in rose (Rosa chinensis).

Plant J 2020 08 8;103(5):1839-1849. Epub 2020 Jul 8.

College of Horticulture, Nanjing Agricultural University, Nanjing, 210095, China.

Jasmonates (JAs) are important for pathogen resistance in many plants, but the role of these phytohormones in fungal pathogen resistance in rose is unclear. Here, we determined that exogenous application of methyl jasmonate increased resistance to the important fungal pathogen Botrytis cinerea in Rosa chinensis 'Old blush', whereas silencing the JA biosynthetic pathway gene Allene Oxide Synthase (AOS) and JA co-receptor gene CORONATINE INSENSITIVE 1 (COI1) suppressed this response. Transcriptome profiling identified various MYB transcription factor genes that responded to both JA and B. cinerea treatment. Silencing Ri-RcMYB84/Ri-RcMYB123 increased the susceptibility of rose plants to B. cinerea and inhibited the protective effects of JA treatment, confirming the crucial roles of these genes in JA-induced responses to B. cinerea. JAZ1, a key repressor of JA signaling, directly interacts with RcMYB84 and RcMYB123 to deplete their free pools. The JAZ1-RcMYB84 complex binds to the RcMYB123 promoter via the CAACTG motifs to block its transcription. Upon JA treatment, the expression of RcMYB123 is de-repressed, and free forms of RcMYB84 and RcMYB123 are released due to JAZ1 degradation, thereby activating the defense responses of plants to B. cinerea. These findings shed light on the molecular mechanisms underlying JA-induced pathogen resistance in roses.
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http://dx.doi.org/10.1111/tpj.14871DOI Listing
August 2020

Targeting tumor-associated macrophages in head and neck squamous cell carcinoma.

Oral Oncol 2020 07 18;106:104723. Epub 2020 Apr 18.

State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China; Department of Operative Dentistry and Endodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, China; National Clinical Research Centre for Oral Diseases, Sichuan University, Chengdu 610064, China. Electronic address:

In head and neck squamous cell carcinoma (HNSCC), tumor-associated macrophages (TAMs) are associated with a poorer prognosis. TAMs, derived from inflammatory monocyte, play a critical role in regulating tumor progression. Generally, TAMs promote tumor progression and suppress immune response via both innate and adaptive immune mechanisms. However, as the double-blade sword, TAMs retain the potential pro-inflammatory ability to inhibit tumor progression. By depleting the immunosuppressive function or evoking anti-tumor ability, therapeutic strategies targeting TAMs show promising preclinical and clinical effects. Now, macrophage-centered therapeutic approaches are entering the clinical arena. In this review, we discuss the immunosuppressive role of TAMs in the tumor microenvironment and the therapeutic approaches targeting macrophages which offer promise in improving HNSCC outcome.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104723DOI Listing
July 2020

Clinicopathological diversity and outcome of longitudinal melanonychia in children and adolescents: analysis of 35 cases identified by excision specimens.

Histopathology 2020 Sep;77(3):380-390

Department of Pathology, First People's Hospital, Shanghai Jiaotong University, Shanghai, China.

Aims: Longitudinal melanonychia in paediatric patients often represents a difficult diagnostic challenge, and studies emphasising its clinical and histopathological features are limited due to its low incidence in childhood.

Methods And Results: We retrospectively analysed 35 paediatric cases identified by excision specimens on their clinicopathological features, and performed fluorescence in-situ hybridisation on 13 available cases. Fingernails (77.1%) were more likely to be affected. Total melanonychia and Hutchinson's sign were observed in 10 (28.6%) and 14 (40.0%) cases, respectively. Nail dystrophy at diagnosis was present in five cases. After complete excision of the lesions, four patients relapsed during follow-up (mean = 38 months). Seventeen cases were diagnosed as lentigines and 18 as naevi, among which 11 cases were categorised as lentigines/naevi with atypical melanocytic hyperplasia. Mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and peri-ungual skin involvement were found in 25.7% (9 of 35), 40.0% (14 of 35), 40.0% (14 of 35) and 40.0% (14 of 35) of cases, respectively. Thirteen cases tested by fluorescence in-situ hybridisation showed no copy number aberration at the probed loci. There was a statistically significant difference in the following features between patients aged less and more than 10 years (P < 0.05): cytomorphology, mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and melanocyte count.

Conclusions: Some concerning clinicopathological characteristics, which are signs indicative of melanoma in adults, are not uncommon in paediatric longitudinal melanonychia, especially in patients aged ≤ 10 years. Owing to the extremely low incidence of melanoma in paediatric longitudinal melanonychia, in most circumstances a more conservative clinical management strategy should be adopted.
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http://dx.doi.org/10.1111/his.14121DOI Listing
September 2020

Uterine artery Doppler velocimetry at mid-term gestation as a potential predictive factor for the resolution of placenta previa at the end of third trimester of pregnancy.

J Obstet Gynaecol Res 2020 Jun 12;46(6):883-889. Epub 2020 Apr 12.

Department of Ultrasound, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

Aim: The incidence of placenta previa before the third trimester is high. But many cases resolve as pregnancy progresses. Our study was to evaluate the efficacy of uterine artery Doppler velocimetry at mid-term gestation for predicting placenta previa resolution in third trimester.

Methods: A single-center retrospective study was done. A study cohort of 504 subjects with placenta-cervix os distance measured both at 22-24 weeks and after 36 weeks of gestation and uterine artery Doppler velocimetry measured at 22-24 weeks of gestation were selected. The subjects were assigned to control group (n = 351), resolving group (n = 89) and placenta previa group (n = 64) according to their diagnosis of placenta previa at mid-term and the end of the third trimester. The averages of the bilateral ratio of uterine artery systolic to end-diastolic maximum blood flow velocity (S/D ratio), pulsatility index (PI) and resistance index (RI) were used for analysis.

Results: The means of S/D ratio, PI and RI of uterine arteries in the placenta previa group were significantly lower than that in either control group or resolving group. No differences were observed between control group and resolving group. The areas under the receiver operating characteristic curve were 0.7632, 0.7579 and 0.7644 for the means of S/D ratio, PI and RI, respectively (P < 0.0001).

Conclusion: The means of S/D ratio, PI and RI of the uterine arteries at mid-term gestation are reduced in patients with persistent placenta previa, indicating unique pathogenic changes at mid-term gestation, and have the potential to be a predictive factor on placenta previa resolution.
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http://dx.doi.org/10.1111/jog.14246DOI Listing
June 2020

Systemic hypoxia potentiates anti-tumor effects of metformin in hepatocellular carcinoma in mice.

Acta Biochim Biophys Sin (Shanghai) 2020 Apr;52(4):421-429

School of Basic Medical Sciences, Nanchang University, Nanchang 330006, China.

Local hypoxia is a universal phenomenon in most solid tumors. The role of local hypoxia in the tumor microenvironment and cancer growth and metastasis has been well established. However, the effect of acute systemic hypoxia (exposing the whole body to 10% O2 environment) on cancer has not yet been investigated. In this study, we investigated the potential effects of acute systemic hypoxia itself and in combination with metformin on hepatocellular carcinoma (HCC) growth and metastasis in a mouse model of HCC. Acute systemic hypoxia significantly decreased tumor volume and weight in H22 tumor-bearing mice. Interestingly, the combined treatment of acute systemic hypoxia and metformin showed a more pronounced effect in reducing tumor volume and weight. Moreover, acute systemic hypoxia and metformin in combination had a potent inhibitory effect on tumor progression. More importantly, the expressions of hypoxia response genes including hypoxia-inducible factor-1 α, vascular endothelial growth factor, and matrix metalloproteinase 2 were significantly decreased in the tumor tissues with combination treatment. Our study demonstrated that acute systemic hypoxia repressed tumor progression of the HCC and potentiated the anti-tumor activities of metformin. This study supports that combination of systemic hypoxia and metformin treatment may represent a novel strategy for HCC.
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http://dx.doi.org/10.1093/abbs/gmaa010DOI Listing
April 2020

Large-scale identification of expression quantitative trait loci in Arabidopsis reveals novel candidate regulators of immune responses and other processes.

J Integr Plant Biol 2020 Oct 4;62(10):1469-1484. Epub 2020 May 4.

Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, Indiana, 47907, USA.

The extensive phenotypic diversity within natural populations of Arabidopsis is associated with differences in gene expression. Transcript levels can be considered as inheritable quantitative traits, and used to map expression quantitative trait loci (eQTL) in genome-wide association studies (GWASs). In order to identify putative genetic determinants for variations in gene expression, we used publicly available genomic and transcript variation data from 665 Arabidopsis accessions and applied the single nucleotide polymorphism-set (Sequence) Kernel Association Test (SKAT) method for the identification of eQTL. Moreover, we used the penalized orthogonal-components regression (POCRE) method to increase the power of statistical tests. Then, gene annotations were used as test units to identify genes that are associated with natural variations in transcript accumulation, which correspond to candidate regulators, some of which may have a broad impact on gene expression. Besides increasing the chances to identify real associations, the analysis using POCRE and SKAT significantly reduced the computational cost required to analyze large datasets. As a proof of concept, we used this approach to identify eQTL that represent novel candidate regulators of immune responses. The versatility of this approach allows its application to any process that is subjected to natural variation among Arabidopsis accessions.
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http://dx.doi.org/10.1111/jipb.12930DOI Listing
October 2020