Publications by authors named "Junling Zhang"

140 Publications

Landscape of IDH1/2 mutations in Chinese patients with solid tumors: A pan-cancer analysis.

Mol Genet Genomic Med 2021 Jun 18:e1697. Epub 2021 Jun 18.

Department of Medical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Isocitrate dehydrogenase (IDH) is an enzyme family involved in cell aerobic metabolism of tricarboxylic acid cycle. However, the landscape of IDH mutations in pan-cancer has not been fully characterized.

Methods: Tissue or blood samples were subjected to next-generation sequencing (NGS) for detection the IDH mutation.

Results: A total of 28.868 patients from more than 20 solid tumor species were analyzed. A total of 374 cases (1.30%) with IDH mutations were identified. Among all the IDH mutations cases, 80 (21.4%) were biliary tract cancer (BTC), 80 (21.4%) were lung cancer, 57 (15.2%) were liver cancer, and 42 (11.2%) were colorectal cancer. The most common IDH variant were IDH1 and IDH2 which were discovered in 0.81% cases and 0.47% cases, respectively. However, there were significant differences in IDH1 and IDH2 mutation frequency among different tumor species (p = 0.0003). Of the patients with IDH1 mutations, about 53.0% of these mutations occur in codons 132. Codons 172 (25.4%) was high-frequency mutation subtypes in IDH2 mutation. TP53, PBRM1, and BAP1 were the most significantly mutated genes in BTC which were different from others cancer. Moreover, TMB were significantly higher in lung cancer, colorectal cancer, and gastric cancer than BTC (p = 0.0164, p < 0.0001, p = 0.0067, respectively) and BTC patients with IDH mutation had lower TMB compared with wild-type IDH.

Conclusion: Somatic IDH mutation was found in multiple solid tumors and IDH would be a driver gene in BTC.
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http://dx.doi.org/10.1002/mgg3.1697DOI Listing
June 2021

Effects of the association between APOE rs405509 polymorphisms and gene-environment interactions on hand grip strength among middle-aged and elderly people in a rural population in southern China.

J Orthop Surg Res 2021 Jun 11;16(1):372. Epub 2021 Jun 11.

School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, China.

Background: Hand grip strength is a complex phenotype. The current study aimed to identify the effects of the association between APOE rs405509 polymorphisms and gene-environment interactions on hand grip strength among middle-aged and elderly people in a rural population in Gongcheng, southern China.

Methods: APOE rs405509 polymorphisms in 1724 participants (695 men and 1029 women, aged 45-97 years old) were genotyped using the Sequenom MassARRAY platform. Statistical analysis was conducted using SPSS 21.0 and Plink 1.90.

Results: The APOE rs405509 G allele was associated with lower hand grip strength in all participants (β = -1.04, P value <0.001), and the correlation seemed to be even stronger among women. A significant gene-environment interaction was observed between APOE rs405509 and smoking, especially in men. The hand grip strength of male smokers carrying the GG genotype was significantly higher than that of nonsmokers (P value = 0.004).

Conclusions: APOE rs405509 polymorphisms might be genetic factors that affect hand grip strength in a rural population in Gongcheng, southern China. The APOE rs405509-smoking interaction has an impact on hand grip strength.
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http://dx.doi.org/10.1186/s13018-021-02522-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194121PMC
June 2021

Rectosigmoid-Junction Squamous Cell Carcinoma With pMMR/MSS Achieved a Partial Response Following PD-1 Blockade Combined With Chemotherapy: A Case Report.

Front Oncol 2021 25;11:596342. Epub 2021 May 25.

Department of Internal Medicine-Oncology, Qingdao Tumor Hospital, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao, China.

Colorectal squamous cell carcinoma (SCC) is extremely rare and associated with a poor prognosis. And the pMMR/MSS colorectal cancer is related to a limited response to programmed death ligand-1 (PD-1) blockade monotherapy. However, the clinical activity of PD-1 blockade monotherapy or combination therapy in colorectal SCC is unknown. One patient with rectosigmoid-junction SCC was treated with PD-1 blockade combined with chemotherapy. After 3 months of PD-1 blockade and chemotherapy, the computed tomography imaging showed that this patient achieved a partial response. The next generation sequencing and immunohistochemistry analysis showed that the patient had tumors with proficient mismatch repair (pMMR) and microsatellite stability (MSS), strong PD-L1 expression, and tumor mutational burden-high (TMB-High), respectively. This case suggests that PD-1 blockade combined with chemotherapy might be an effective therapy for colorectal SCC with pMMR/MSS status. Moreover, the PD-L1 expression and TMB might be the potential predictors of PD-1 blockade response for colorectal SCC patients.
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http://dx.doi.org/10.3389/fonc.2021.596342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185331PMC
May 2021

[Clinical effects of intermittent oro-esophageal tube feeding combined with Xuanqiaoliyan decotion in stroke patients with dysphagia].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 May;33(5):552-556

Department of Neurology, Yidu Central Hospital Affiliated Hospital of Weifang Medical University, Qingzhou 262500, Shandong, China. Corresponding author: Sun Xibo, Email:

Objective: To investigate the clinical effects of intermittent oro-esophageal tube feeding (IOE) combined with Xuanqiaoliyan decotion in stroke patients with dysphagia.

Methods: A prospective study was conducted. Stroke patients with dysphagia admitted to Yidu Central Hospital Affiliated Hospital of Weifang Medical University from January 2018 to December 2019 were enrolled. According to the simple random sampling method, the patients were divided into control group and observation group, with 50 cases in each group. The control group was given routine swallowing function training, including low-frequency pulse electrical stimulation, swallowing function training and acupuncture treatment. The observation group was given IOE and Xuanqiaoliyan decoction (prescription composition: Rhizoma acori tatarinowii 15 g, Radix polygalae 10 g, Rhizoma gastrodiae 15 g, Arisaema cum bile 6 g, Rhizoma typhonii 6 g, Scorpio 6 g, Bombyx batryticatus 6 g, Perilla frutescens 10 g, Rhizoma pinelliae 10 g, Pericarpium citri reticulatae 10 g, Rhizoma zingiberis recens 3 tablets, decoction 200 mL, twice in the morning and evening by oral or nasal feeding) on the basis of the control group. Both groups were treated for 14 days. The standard swallowing function assessment (SSA) and water swallow test were used to evaluate the swallowing function before and after treatment. The time required for the improvement of swallowing function, total hospitalization time and the therapeutic effects were observed and the safety assessment was conducted.

Results: There were no significant differences in the gender, age, course of disease, and location and frequency of stroke between the two groups. After treatment, both the SSA scores in the two groups were decreased, and the grading of water swallow test was improved. The SSA scores in the observation group were significantly lower than that in the control group (19.8±1.8 vs. 23.2±3.2, P < 0.05), the recovery degree of water swallow test was higher than that in the control group [complete recovery (cases): 18 vs. 13, basic recovery (cases): 23 vs. 18, effective (cases): 9 vs. 19, χ = -2.107, P = 0.008]. The total effective rate of swallowing function in the observation group was higher than that in the control group (94.0% vs. 80.0%, Z = 4.684, P = 0.012), the time for improvement (days: 12.8±2.6 vs. 16.9±4.3, t = 11.628, P = 0.008)and total hospitalization time (days: 20.8±4.2 vs. 33.5±5.6, t = 10.924, P = 0.015) were shorter than those in the control group. In the observation group, there was 1 case of throat discomfort during the operation of IOE, and the symptoms disappeared after the operation; there was 1 case of mild elevation of alanine aminotransferase (ALT) and blood urea nitrogen (BUN) respectively, which returned to normal after the treatment. No adverse symptoms and damage to the liver and kidney were observed in the control group.

Conclusions: IOE combined with Xuanqiaoliyan decotion could significantly improve the swallowing function of stroke patients with dysphagia, shorten the hospitalization time, and improve the curative effects and lifequality.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200628-00487DOI Listing
May 2021

Clinical characteristics and prognostic value of the mutation in Chinese colorectal cancer patients.

Int J Biol Markers 2021 May 27:17246008211017152. Epub 2021 May 27.

Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Background: The mutations are high-frequency somatic mutations found in colorectal cancer patients from Western and Asian countries however, with the exception of exon 2 of , other prevalence and prognostic values have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of whole exon mutations of in Chinese colorectal cancer patients and to investigate their impact on prognosis.

Methods: A total of 7189 tumor tissue samples (iCohort) were subjected to next-generation sequencing for detection of mutations. All pathologic or likely pathologic mutations of were considered. In addition, clinical features and prognostic dates were collected from 145 patients at The Third Affiliated Hospital of Soochow University, China (sCohort) and used droplet digital™ polymerase chain reaction to detect mutations.

Results: In the iCohort, 2706 patients (37.6%) were confirmed harboring mutations. The most frequent of these mutations were (32.19%), (17.96%), and (17.59%). In the sCohort, 51 colorectal cancer patients (35.17%) had mutations, among which (64.71%), (29.41%), and (3.92%) were high-frequency. The mutations were associated with shorter median overall survival than wild-type tumors (69 vs. 55 months; HR 1.80; 95% Cl 1.22, 2.64; =0.0003). In the Cox multivariate analysis, age (HR 1.562; 95% Cl 1.10, 2.22; =0.013), tumor differentiation (HR 0.417; 95% Cl 0.19, 0.90; =0.026), and mutation (HR 1.897; 95% Cl 0.19, 0.90; =0.001) remained independent predictors of shorter overall survival. Among the common mutations, was significantly associated with shorter overall survival (HR 2.17; 95% Cl 1.31, 3.58; < 0.0001) compared with wild-type patients.

Conclusions: Our findings indicate that KRAS genes are frequently mutated, and over 30% harbored the mutation subtype. We found that the mutation is associated with inferior survival and is a biomarker of poor prognosis in Chinese patients. Our data emphasize the importance of molecular features in colorectal cancer patients, which could potentially be improved by -specific related inhibitors.
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http://dx.doi.org/10.1177/17246008211017152DOI Listing
May 2021

Weighted Gene Co-expression Network Analysis Identifies CALD1 as a Biomarker Related to M2 Macrophages Infiltration in Stage III and IV Mismatch Repair-Proficient Colorectal Carcinoma.

Front Mol Biosci 2021 29;8:649363. Epub 2021 Apr 29.

Department of General Surgery, Peking University First Hospital, Beijing, China.

Immunotherapy has achieved efficacy for advanced colorectal cancer (CRC) patients with a mismatch-repair-deficient (dMMR) subtype. However, little immunotherapy efficacy was observed in patients with the mismatch repair-proficient (pMMR) subtype, and hence, identifying new immune therapeutic targets is imperative for those patients. In this study, transcriptome data of stage III/IV CRC patients were retrieved from the Gene Expression Omnibus database. The CIBERSORT algorithm was used to quantify immune cellular compositions, and the results revealed that M2 macrophage fractions were higher in pMMR patients as compared with those with the dMMR subtype; moreover, pMMR patients with higher M2 macrophage fractions experienced shorter overall survival (OS). Subsequently, weighted gene co-expression network analysis and protein-protein interaction network analysis identified six hub genes related to M2 macrophage infiltrations in pMMR CRC patients: , , , , , and . Univariate and multivariate Cox regression analyses then determined as the independent prognostic biomarker for OS. was upregulated specifically the in CMS4 CRC subtype, and single-sample Gene Set Enrichment Analysis (ssGSEA) revealed that was significantly correlated with angiogenesis and TGF-β signaling gene sets enrichment scores in stage III/IV pMMR CRC samples. The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm and correlation analysis revealed that was significantly associated with multiple immune and stromal components in a tumor microenvironment. In addition, GSEA demonstrated that high expression of was significantly correlated with antigen processing and presentation, chemokine signaling, leukocyte transendothelial migration, vascular smooth muscle contraction, cytokine-cytokine receptor interaction, cell adhesion molecules, focal adhesion, MAPK, and TGF-beta signaling pathways. Furthermore, the proliferation, invasion, and migration abilities of cancer cells were suppressed after reducing expression in CRC cell lines. Taken together, multiple bioinformatics analyses and cell-level assays demonstrated that could serve as a prognostic biomarker and a prospective therapeutic target for stage III/IV pMMR CRCs.
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http://dx.doi.org/10.3389/fmolb.2021.649363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116739PMC
April 2021

Corrigendum: Expression of Human Epidermal Growth Factor Receptor-2 Status and Programmed Cell Death Protein-1 Ligand Is Associated With Prognosis in Gastric Cancer.

Front Oncol 2021 20;11:672599. Epub 2021 Apr 20.

Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

[This corrects the article DOI: 10.3389/fonc.2020.580045.].
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http://dx.doi.org/10.3389/fonc.2021.672599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095244PMC
April 2021

MiR-205-5p suppresses angiogenesis in gastric cancer by downregulating the expression of VEGFA and FGF1.

Exp Cell Res 2021 Jul 4;404(2):112579. Epub 2021 May 4.

Department of General Surgery, Peking University First Hospital, Beijing, 100034, China. Electronic address:

Anti-angiogenic therapy represents one of the most promising treatment modalities for human cancers. However, the response to antiangiogenic therapy in gastric cancer (GC) remains dismal. To help identify new strategies for antiangiogenic therapy in GC, we evaluated miR-205-5p expression in GC tissues from TCGA database and our hospital, and its functions in angiogenesis were explored in vitro and in vivo. We investigated miR-205-5p expression and microvessel densities (MVDs) in GC tissues and liver metastases from patients. The function and mechanisms of miR-205-5p were examined in human cell lines and in xenograft mouse models. Associations between miR-205-5p expression and clinical characteristics were analyzed using either Pearson's χ test or Fisher's exact test. Differences in overall survival (OS) distributions were evaluated using the log-rank test. Differences in measurement data were compared using Student's t-test and one-way ANOVA. We found that miR-205-5p expression was downregulated in GC tissues and was negatively correlated with CD31 expression in both TCGA and our clinical samples. GC cell lines expressed low levels of miR-205-5p, and miR-205-5p upregulation significantly impaired the proliferation and angiogenesis of GC cells. Moreover, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1) expression and activation of extracellular-related kinase (ERK) signaling were suppressed by miR-205-5p. MiR-205-5p inhibition promoted malignant phenotypes by enhancing VEGFA and FGF1 expression, as well as the activation of ERK signaling. Angiogenesis and ERK signaling were decreased in response to VEGFA and FGF1 downregulation induced by miR-205-5p overexpression. The dual-luciferase reporter assay showed that VEGFA and FGF1 were direct targets of miR-205-5p. Xenograft mouse models revealed that miR-205-5p suppressed tumor growth by inhibiting neovascularization. Altogether, these results demonstrate that miR-205-5p suppresses angiogenesis in GC by attenuating the expression of VEGFA and FGF1, indicating that upregulation of miR-205-5p may represent as an antiangiogenic therapy for GC.
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http://dx.doi.org/10.1016/j.yexcr.2021.112579DOI Listing
July 2021

Spatiotemporal Pattern of Acid Phosphatase Activity in Soils Cultivated With Maize Sensing to Phosphorus-Rich Patches.

Front Plant Sci 2021 13;12:650436. Epub 2021 Apr 13.

College of Resources and Environmental Sciences, China Agricultural University, Beijing, China.

Aims: Acid phosphatase (APase) secretion by roots allows plants to mobilize organic phosphorus (P) in low P soils. However, the spatiotemporal dynamics of soil APase activity in response to P-rich patches remain unclear.

Methods: Here, we grew maize in rhizoboxes with two contrasting soil types and different localized P supplies. soil zymography was applied to examine the spatial-temporal variation of APase activity.

Results: We found P-rich patches can induce the secretion of APase from roots, indicating that even mineral P fertilizers were localized apply, mobilization of soil organic P by roots can also be enhanced; APase hotspot areas and APase activities in the rhizosphere and bulk soil of the same rhizobox showed opposite diurnal rhythms across the whole soil profile. The APase hotspot area was 10-140% larger at noon than at midnight in the rhizosphere, which is consistent with the diurnal rhythm of photosynthesis. In contrast, in bulk soil, the area was 18-200% larger at midnight than at noon, which led to spatiotemporal niche differentiation with regard to the utilization of soil organic P; this alleviated competition between plants and soil microorganisms.

Conclusion: Our findings showed that APase secretion of roots was plastic in P-rich patches and showed an opposite diurnal rhythm with soil microorganisms in bulk soil.
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http://dx.doi.org/10.3389/fpls.2021.650436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076754PMC
April 2021

SPARC enhances 5-FU chemosensitivity in gastric cancer by modulating epithelial-mesenchymal transition and apoptosis.

Biochem Biophys Res Commun 2021 Jun 25;558:134-140. Epub 2021 Apr 25.

Division of General Surgery, Peking University First Hospital, Peking University, Beijing, PR China. Electronic address:

Previous studies have shown that secreted protein acidic and rich in cysteine (SPARC) proteins can inhibit the development of cancer cells in various ways, such as by inhibiting angiogenesis and inhibiting cell proliferation. In fact, SPARC proteins may have an effect on the chemoresistance of gastric cancer cells to 5-Fluorouracil (5-FU), which needs further research in the future. Therefore, the purpose of this study was to explore the relationship between SPARC proteins and the chemosensitivity of gastric cancer cells to 5-FU. In vitro, after SPARC protein levels were regulated by plasmid, siRNA and human recombinant SPARC protein transfection in MGC-803, SGC-7901 and BGC-823 cells, we detected epithelial-mesenchymal transition (EMT), apoptosis markers and cell viability after 5-FU treatment. In vivo, we implanted BGC-823 cells with stable SPARC overexpression into nude mice. Tumour size was measured to assess the effect of SPARC protein on tumour formation and 5-FU chemosensitivity. In SGC-7901 and BGC-823 cells, both endogenous and exogenous upregulation of SPARC protein levels decreased cell viability, destroyed cytoskeletal F-actin, inhibited cell migration, and downregulated a series of transcription factors to inhibit cell EMT; it also upregulated cell apoptosis-related proteins to promote cell apoptosis. However, we obtained opposite results in SPARC knockdown MGC-803 cells. In vivo, compared with the control group, the group engrafted with BGC-823 cells stably overexpressing SPARC had a significant smaller tumour size. After 5-FU treatment, the new tumour gradually decreased in size. Our results show that the SPARC protein could enhance 5-FU chemosensitivity in gastric cancer cell lines by inhibiting EMT and promoting cell apoptosis.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.009DOI Listing
June 2021

Nomogram for Predicting the Probability of Permanent Stoma after Laparoscopic Intersphincteric Resection.

J Gastrointest Surg 2021 Apr 26. Epub 2021 Apr 26.

Department of General Surgery, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.

Purpose: The purpose of this study was to determine the risk factors for the development of a permanent stoma in laparoscopic intersphincteric resection (LS-ISR) for ultralow rectal adenocarcinoma and to develop and validate a prediction model to predict the probability of permanent stoma after surgery.

Methods: A primary cohort consisting of 301 consecutive patients who underwent LS-ISR was enrolled in this study. Multivariable logistic regression analysis was used to identify risk factors and develop the nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. An independent validation cohort contained 91 consecutive patients from January 2012 to January 2019.

Results: The permanent stoma rate was 11.3% (34/301) in the primary cohort and 18.7% (17/91) in the validation cohort. Multivariable analysis revealed that nCRT (OR, 3.195; 95% CI, 1.169-8.733; P=0.024), ASA score of 3 (OR, 5.062; 95% CI, 1.877-13.646; P=0.001), distant metastasis (OR, 14.645; 95% CI, 3.186-67.315; P=0.001), and anastomotic leakage (OR, 11.308; 95% CI, 3.650-35.035; P<0.001) were independent risk factors for permanent stoma, and a nomogram was established. The AUCs of the nomogram were 0.842 and 0.858 in the primary and validation cohorts, respectively. The calibration curves showed good calibration in both cohorts. Decision curve analysis demonstrated that the nomogram was clinically useful.

Conclusion: We developed and validated a nomogram for ultralow rectal adenocarcinoma patients who underwent LS-ISR, and the nomogram could help surgeons identify which patients are at a higher risk of a permanent stoma after surgery.
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http://dx.doi.org/10.1007/s11605-021-04982-7DOI Listing
April 2021

Integrated slice-specific dynamic shimming diffusion weighted imaging (DWI) for rectal Cancer detection and characterization.

Cancer Imaging 2021 Apr 7;21(1):32. Epub 2021 Apr 7.

Department of Radiology, Peking University First Hospital, 8 XiShiKu Avenue, XiCheng District, Beijing, 100034, China.

Purpose: To compare integrated slice-specific dynamic shimming (iShim) diffusion weighted imaging (DWI) and single-shot echo-planar imaging (SS-EPI) DWI in image quality and pathological characterization of rectal cancer.

Materials And Methods: A total of 193 consecutive rectal tumor patients were enrolled for retrospective analysis. Among them, 101 patients underwent iShim-DWI (b = 0, 800, and 1600 s/mm) and 92 patients underwent SS-EPI-DWI (b = 0, and 1000 s/mm). Qualitative analyses of both DWI techniques was performed by two independent readers; including adequate fat suppression, the presence of artifacts and image quality. Quantitative analysis was performed by calculating standard deviation (SD) of the gluteus maximus, signal intensity (SI) of lesion and residual normal rectal wall, apparent diffusion coefficient (ADC) values (generated by b values of 0, 800 and 1600 s/mm for iShim-DWI, and by b values of 0 and 1000 s/mm for SS-EPI-DWI) and image quality parameters, such as signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of primary rectal tumor. For the primary rectal cancer, two pathological groups were divided according to pathological results: Group 1 (well-differentiated) and Group 2 (poorly differentiated). Statistical analyses were performed with p < 0.05 as significant difference.

Results: Compared with SS-EPI-DWI, significantly higher scores of image quality were obtained in iShim-DWI cases (P < 0.001). The SD was significantly reduced on b = 1600 s/mm images and ADC maps of iShim-DWI. Both SNR and CNR of b = 800 s/mm and b = 1600 s/mm images in iShim-DWI were higher than those of b = 1000 s/mm images in SS-EPI-DWI. In primary rectal cancer of iShim-DWI cohort, SI was significantly higher than SI in both b = 800 and 1600 s/mm images. ADC values were significantly lower in Group 2 (0.732 ± 0.08) × 10 mm/s) than those in Group 1 ((0.912 ± 0.21) × 10 mm/s). ROC analyses showed significance of ADC values and SI between the two groups.

Conclusion: iShim-DWI with b values of 0, 800 and 1600 s/mm is a promising technique of high image quality in rectal tumor imaging, and has potential ability to differentiate rectal cancer from normal wall and predicting pathological characterization.
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http://dx.doi.org/10.1186/s40644-021-00403-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028796PMC
April 2021

The curcumin analog EF24 is highly active against chemotherapy-resistant melanoma cells.

Curr Cancer Drug Targets 2021 Mar 2. Epub 2021 Mar 2.

Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL 32610. United States.

Background: Malignant melanoma (MM) is an aggressive type of skin cancer with a poor prognosis, because MM cells are characterized by unresponsiveness to chemotherapy.

Objective: In this study, we evaluated the effectiveness of several curcumin analogs on four MM cell lines (SK-MEL-28, MeWo, A-375, and CHL-1), and explored their underlying mechanisms of action.

Methods: Cell viability was measured by a Tetrazolium-based MTS assay. Cell apoptosis, reactive oxygen species (ROS), and cell cycle were assayed by flow cytometry. Protein levels were assayed by western blotting.

Results: MM cells are quite resistant to the conventional chemotherapeutics cisplatin and dacarbazine, and the targeted therapy drug vemurafinib. Among the curcumin analogs, EF24 is the most potent compound against the resistant MM cells. EF24 dose- and time-dependently reduced the viability of MM cells by inducing apoptosis. Although EF24 did not increase the production of reactive oxygen species (ROS), it upregulated the endoplasmic reticulum (ER) stress marker BiP, but downregulated the unfolded protein response (UPR) signaling. Moreover, treatment of MM cells with EF24 downregulated the expression of the anti-apoptotic protein Bcl-2, as well as the inhibitor of apoptosis proteins (IAPs) XIAP, cIAP1, and Birc7, which are known to protect MM cells from apoptosis. The downregulation of Bcl-2 and IAP expression by EF24 was associated with the inhibition of the NF-κB pathway.

Conclusion: These findings demonstrate that EF24 is a potent anti-MM agent. The anti-MM effect is likely mediated by the suppression of UPR and the NF-κB pathway.
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http://dx.doi.org/10.2174/1568009621666210303092921DOI Listing
March 2021

Polycysteine as a new type of radio-protector ameliorated tissue injury through inhibiting ferroptosis in mice.

Cell Death Dis 2021 02 18;12(2):195. Epub 2021 Feb 18.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, 300000, Tianjin, China.

Amifostine has been the only small molecule radio-protector approved by FDA for decades; however, the serious adverse effects limit its clinical use. To address the toxicity issues and maintain the good potency, a series of modified small polycysteine peptides had been prepared. Among them, compound 5 exhibited the highest radio-protective efficacy, the same as amifostine, but much better safety profile. To confirm the correlation between the radiation-protective efficacy and the DNA binding capability, each of the enantiomers of the polycysteine peptides had been prepared. As a result, the L-configuration compounds had obviously higher efficacy than the corresponding D-configuration enantiomers; among them, compound 5 showed the highest DNA binding capability and radiation-protective efficacy. To our knowledge, this is the first study that has proved their correlations using direct comparison. Further exploration of the mechanism revealed that the ionizing radiation (IR) triggered ferroptosis inhibition by compound 5 could be one of the pathways for the protection effect, which was different from amifostine. In summary, the preliminary result showed that compound 5, a polycysteine as a new type of radio-protector, had been developed with good efficacy and safety profile. Further study of the compound for potential use is ongoing.
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http://dx.doi.org/10.1038/s41419-021-03479-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977147PMC
February 2021

Expression of Human Epidermal Growth Factor Receptor-2 Status and Programmed Cell Death Protein-1 Ligand Is Associated With Prognosis in Gastric Cancer.

Front Oncol 2020 1;10:580045. Epub 2021 Feb 1.

Department of Oncology, Henan Cancer Hospital, Zhengzhou, China.

Background: PD-L1 and HER-2 are routine biomarkers for gastric cancer (GC). However, little research has been done to investigate the correlation among PD-L1, HER-2, immune microenvironment, and clinical features in GC.

Methods: Between January 2013 and May 2020, a total of 120 GC patients treated with chemotherapy were admitted to Henan Tumor Hospital. We retrospectively identified PD-L1, HER-2 level before chemotherapy and abstracted clinicopathologic features and treatment outcomes. Univariate and multivariate survival analyses were performed to assess the relationship between PD-L1/HER-2 levels and progression-free survival (PFS). The mRNA and tumor microenvironment of 343 patients with GC from The Cancer Genome Atlas (TCGA) were used to explore the underlying mechanism.

Results: We retrospectively analyzed 120 patients with gastric cancer, including 17 patients with HER-2 positive and 103 patients with HER-2 negative GC. The results showed that the expression of PD-L1 was closely correlated with HER-2 (P = 0.015). Patients with PD-L1/HER-2 positive obtained lower PFS compared to PD-L1/HER-2 negative (mPFS: 6.4 . 11.1 months, P = 0.014, mPFS: 5.3 . 11.1 months, P = 0.002, respectively), and the PD-L1 negative and HER-2 negative had the best PFS than other groups (P = 0.0008). In a multivariate model, PD-L1 status, HER-2 status, tumor location, and tumor differentiation remained independent prognostic indicators for PFS (P < 0.05). The results of database further analysis showed that the proportion of PD-L1+/CD8A+ in HER-2 negative patients was higher than that in HER-2 positive patients (37.6 20.3%), while PD-L1-/CD8A- was significantly higher in HER-2 positive patients than HER-2 negative patients (57.8 . 28.8%). In addition, it showed that not only CD4+T cells, macrophages, and CD8+T cells, but also the associated inflammatory pathways such as IFN-/STAT1 were associated with HER-2.

Conclusion: HER-2 status could predict the efficacy of immune checkpoint inhibitors, and HER-2 status combined with PD-L1 level could predict the prognosis of GC patients.
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http://dx.doi.org/10.3389/fonc.2020.580045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882725PMC
February 2021

High microbial diversity stabilizes the responses of soil organic carbon decomposition to warming in the subsoil on the Tibetan Plateau.

Glob Chang Biol 2021 May 27;27(10):2061-2075. Epub 2021 Feb 27.

Centre for Resources, Environment and Food Security, College of Resources and Environmental Sciences, China Agricultural University, Key Laboratory of Plant-Soil Interactions, Ministry of Education, Beijing, China.

Soil microbes are directly involved in soil organic carbon (SOC) decomposition, yet the importance of microbial biodiversity in regulating the temperature sensitivity of SOC decomposition remains elusive, particularly in alpine regions where climate change is predicted to strongly affect SOC dynamics and ecosystem stability. Here we collected topsoil and subsoil samples along an elevational gradient on the southeastern Tibetan Plateau to explore the temperature sensitivity (Q ) of SOC decomposition in relation to changes in microbial communities. Specifically, we tested whether the decomposition of SOC would be more sensitive to warming when microbial diversity is low. The estimated Q value ranged from 1.28 to 1.68, and 1.80 to 2.10 in the topsoil and subsoil, respectively. The highest Q value was observed at the lowest altitude of forests in the topsoil, and at the highest altitude of alpine meadow in the subsoil. Variations in Q were closely related to changes in microbial properties. In the topsoil the ratio of gram-positive to gram-negative bacteria (G+:G-) was the predominant factor associated with the altitudinal variations in Q . In the subsoil, SOC decomposition showed more resilience to warming when the diversity of soil bacteria (both whole community and major groups) and fungi was higher. Our results partly support the positive biodiversity-ecosystem stability hypothesis. Structural equation modeling further indicates that variations in Q in the subsoil were directly related to changes in microbial diversity and community composition, which were affected by soil pH. Collectively our results provide compelling evidence that microbial biodiversity plays an important role in stabilizing SOC decomposition in the subsoil of alpine montane ecosystems. Conservation of belowground biodiversity is therefore of great importance in maintaining the stability of ecosystem processes under climate change in high-elevation regions of the Tibetan Plateau.
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http://dx.doi.org/10.1111/gcb.15553DOI Listing
May 2021

An investigation on gastric cancer staging using CT structured report.

Eur J Radiol 2021 Mar 13;136:109550. Epub 2021 Jan 13.

Department of Radiology, Peking University First Hospital, Beijing, China. Electronic address:

Objective: To evaluate the clinical performance of structured report (SR) for CT in patients with pre-operative staging of gastric cancer, compared to non-SR.

Methods: Retrospectively, 51 consecutive cases with primary gastric cancer staging were enrolled. Every SR or non-SR was performed by two GI radiologists (1 junior and 1 senior). Interobserver agreement was conducted between the junior and senior groups for both SR and non-SR. 10 key features required for lesion description and staging were assessed between SR and non-SR. Diagnostic content between SR and non-SR was also compared. Accuracy of SR and non-SR on T staging was measured. Subjective evaluation of SR vs. non-SR was also conducted in form of survey by 20 radiologists and 3 GI surgeons.

Results: Interobserver agreement showed excellent in SR (Kappa = 1, P < 0.001), but poor in non-SR (Kappa = 0.036, P = 0.455). For the 10 key features required for lesion assessment, non-SR showed 6.84 ± 0.83 while SR reported all of them (P < 0.001). Statistically significant improvement was observed in the SR for parts of key features, especially for assessment of adjacent organs and vessels (P < 0.001). Accuracy comparison of T staging showed higher in SR for cohort of T4a (P = 0.028<0.05). The scores of subjective evaluation were higher (P < 0.05) in SR than in non-SR by both radiologists and surgeons. Meanwhile, the inter-observer agreement among surgeons was good in SR with significance (w=0.53, P = 0.005 for efficiency; w=0.638, P < 0.001 for integrity) but poor in non-SR.

Conclusions: SR of gastric multiphasic CT ensured reliable detection of all relevant key features for staging along with reproducible documentation, which was not always the case for non-SR. In addition, SR has the potential in improving diagnostical accuracy of T staging and was welcomed by clinicians.
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http://dx.doi.org/10.1016/j.ejrad.2021.109550DOI Listing
March 2021

Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial.

J Immunother Cancer 2020 11;8(2)

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Background: Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response.

Methods: In this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m) and oxaliplatin (85 mg/m). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment.

Results: 54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28).

Conclusion: Camrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX.

Trial Registration Number: NCT03486678.
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http://dx.doi.org/10.1136/jitc-2020-001240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656907PMC
November 2020

Efficacy and safety of a topical moisturizer containing linoleic acid and ceramide for mild-to-moderate psoriasis vulgaris: A multicenter randomized controlled trial.

Dermatol Ther 2020 11 14;33(6):e14263. Epub 2020 Sep 14.

Department of Biostatistics, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Psoriasis is a chronic, recurrent skin disease requiring long-term management. Agents that repair the skin's barrier function are invaluable additives in topical treatments of psoriasis. This multicenter, randomized, controlled trial evaluated the efficacy and safety of a linoleic acid-ceramide-containing moisturizer (LA-Cer) for mild-to-moderate psoriasis vulgaris. We randomized 178 patients from both northern and southern regions of China into two groups: 81 patients in the control group received mometasone furoate (MF, 0.1%) cream, while MF in combination with LA-Cer was administered to 86 patients in the treatment group for 4 weeks. The LA-Cer-MF group maintained the use of moisturizer after topical glucocorticoid administration. The primary endpoint, Psoriasis Area and Severity Index 50 (PASI 50) response, revealed the superiority of LA-Cer-MF with lower relapse rates at week 8. The use of the LA-Cer-containing moisturizer as maintenance therapy resulted in a continuous improvement in the clinical state in terms of body surface area, PASI, investigators' assessment of skin dryness and desquamation, and Physician Global Assessment of Psoriasis score, and in the patients' quality of life. Thus, the LA-Cer-containing moisturizer is a promising agent to prevent and treat psoriasis as it enhances the therapeutic effect induced by topical glucocorticoids and delays relapse.
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http://dx.doi.org/10.1111/dth.14263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816244PMC
November 2020

Characterization and Localization of 2 in Both the Testis and Ovary of the Japanese Flounder ().

Animals (Basel) 2020 Aug 26;10(9). Epub 2020 Aug 26.

Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education; Shanghai Collaborative Innovation Center for Aquatic Animal Genetics and Breeding; Shanghai Ocean University, Shanghai 201306, China.

Although its function in mammalian gonads has been gradually recognized, the expression and function of calretinin (CALB2)-a Ca-binding protein-in the testis and ovary of fish are still unclear. Here, we identified the cDNA sequences of 2 in (); analyzed its gene structure and phylogenetic and syntenic relationship by bioinformatics; and investigated its tissue distribution and localization in the gonads by real-time PCR, western blotting, and immunohistochemistry. The 2 gene has 11 exons and 10 introns, and the full-length cDNA is 1457 bp, including an open reading frame (ORF) of 816 bp encoding 271 amino acids. The CALB2 of has a higher homology with (99%) compared with other species. The conserved synteny of 2 neighboring gene loci was also detected in fish. Real-time PCR showed that the expression of 2 mRNA is abundant not only in the brain, but also in the gonads, and exhibits a higher expression in the testis than in the ovary. Western blotting indicated that the CALB2 protein has a higher expression in the testis compared with the ovary. Immunohistochemistry demonstrated that the CALB2 protein appears in Leydig cells and the ovarian germ epithelium. These results reveal that 2 plays an important role in the gonads of .
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http://dx.doi.org/10.3390/ani10091503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552167PMC
August 2020

The Blurred Boundaries Between Budget Transparency and State Secrecy: a Survey of Three Departments Across 36 Chinese Municipalities.

East Asia (Piscataway) 2020 Aug 19:1-16. Epub 2020 Aug 19.

School of Public Finance and Taxation Affairs, Southwestern University of Finance and Economics, Chengdu, China.

The tension between ensuring open government information and maintaining national security is a widespread problem around the world. This study focuses on the disclosure of budgetary information and its tension with vaguely defined state secrecy requirements in the Chinese context. Through a survey of three government departments that potentially involve state secrets across 36 Chinese municipalities, we find that there exists no consensus on whether to make budgetary information public, even for the same department across different jurisdictions. In addition, departments that chose disclosure vary considerably in the scope and depth of their transparency. Without having the boundaries clarified by law, disclosure by request, as a supplemental behavior to proactive disclosure, can rarely be successful. Our findings suggest that future legislation ought to clarify the legitimate scope of restrictions on budget transparency on the grounds of state secrecy.
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http://dx.doi.org/10.1007/s12140-020-09345-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434559PMC
August 2020

Sitagliptin Mitigates Total Body Irradiation-Induced Hematopoietic Injury in Mice.

Oxid Med Cell Longev 2020 25;2020:8308616. Epub 2020 Jul 25.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.

Sitagliptin, an inhibitor of the dipeptidyl peptidase IV (DPP4), has been implicated in the regulation of type 2 diabetes. However, the role and mechanism of sitagliptin administration in total body irradiation (TBI)- induced hematopoietic cells injury are unclear. In this study, we demonstrated that sitagliptin had therapeutic effects on hematopoietic damage, which protected mice from 7.5 Gy TBI-induced death, increased the numbers and colony formation ability of hematopoietic cells. These therapeutic effects might be attributed to the inhibition of NOX4-mediated oxidative stress in hematopoietic cells, and the alleviation of inflammation was also helpful. Therefore, sitagliptin has potential as an effective radiotherapeutic agent for ameliorating TBI-induced hematopoietic injury.
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http://dx.doi.org/10.1155/2020/8308616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397422PMC
May 2021

Paxillin knockdown suppresses metastasis and epithelial‑mesenchymal transition in colorectal cancer via the ERK signalling pathway.

Oncol Rep 2020 Sep 14;44(3):1105-1115. Epub 2020 Jul 14.

Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.

Paxillin (PXN) is a cytoplasmic protein that plays an important role in regulating focal adhesion, cytoskeletal rearrangements and cell motility. The present study aimed to investigate the role of PXN in the metastasis of human colorectal cancer (CRC) and its possible mechanisms. Immunohistochemical staining of tissues from 102 surgical CRC patients revealed that high PXN expression was positively correlated with tumour‑node‑metastasis (TNM) stage, lymph node metastasis, distant metastasis, and recurrence at distant sites after radical surgery. In 24 cases of stage IV CRC, PXN expression in liver metastasis was higher than that in the matched primary tumour. The knockdown of PXN inhibited the proliferation, migration and invasion potential of SW480 cells in vitro and in vivo. Transmission electron microscopy revealed the effect of PXN on ultrastructural characteristics, observed mainly in microvilli and desmosomes. The downregulation of PXN decreased the activation of extracellular regulated protein kinase (ERK) and suppressed the epithelial‑mesenchymal transition (EMT) process. Following the downregulation of PXN, the addition of an ERK activator or inhibitor restored or further suppressed EMT, respectively, accompanied by corresponding changes in cell migration and invasion. Collectively, the present results confirmed the important role of PXN in CRC metastasis and revealed that PXN regulated EMT progression via the ERK signalling pathway. PXN may represent a future therapeutic strategy to prevent the EMT‑associated progression and invasion of CRC.
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http://dx.doi.org/10.3892/or.2020.7687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388420PMC
September 2020

Unambiguous Phosphosite Localization through the Combination of Trypsin and LysargiNase Mirror Spectra in a Large-Scale Phosphoproteome Study.

J Proteome Res 2020 06 26;19(6):2185-2194. Epub 2020 May 26.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Lifeomics, Beijing 102206, China.

Understanding of the kinase-guided signaling pathways requires the identification and analysis of phosphosites. Mass spectrometry (MS)-based phosphoproteomics is a rapid and highly sensitive approach for high-throughput identification of phosphosites. However, phosphosite determination from MS data with a single protease is more likely to be ambiguous, regardless of the strategy used for phosphopeptide detection. Here, we explored the application of LysargiNase, which was recently reported to mirror trypsin in specificity to cleave arginine and lysine residues exclusively at the N-terminal side. We found that the combination of trypsin and LysargiNase mirror spectra resulted in higher ion coverage in MS spectra. The median ion coverage values of b ions in tryptic spectra, LysargiNase spectra, and combined spectra are 8.3, 20.5, and 25.0%, respectively. As for the median ion coverage of y ions, these values are 27.8, 10.0, and 32.3%. Higher ion coverage was helpful to pinpoint the precise phosphosites. Compared to trypsin alone, the combined use of trypsin and LysargiNase mirror spectra enabled 67.1% of mirror spectra with unreliable scores (confidence score <0.75) to become reliable (confidence score ≥ 0.75). Meanwhile, all of the mirror peptide-spectrum matches (PSMs) with multiple potential phosphosites from trypsin and LysargiNase digests could be assigned one precise phosphosite after applying the combination strategy. Besides, the combination strategy could identify more novel phosphosites than the union strategy did. We synthesized three phosphopeptides corresponding to the three novel phosphosites and validated the reliability of the identification. Taken together, our data demonstrated the distinctive potential of the combination strategy presented here for unambiguous phosphosite localization (Project accession PXD011178).
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http://dx.doi.org/10.1021/acs.jproteome.9b00562DOI Listing
June 2020

Effects of Hypoxia and Radiation-Induced Exosomes on Migration of Lung Cancer Cells and Angiogenesis of Umbilical Vein Endothelial Cells.

Radiat Res 2020 07;194(1):71-80

Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.

Numerous studies have shown that exosomes play important roles in tumor biology development. However, the function of exosomal protein in cancer progression under different oxygen condition after irradiation is poorly understood. In this study, non-small cell lung cancer (NSCLC) A549 cells were γ-ray irradiated under normoxic or hypoxic conditions, then the exosomes released from the irradiated cells were collected and co-cultured with nonirradiated A549 cells or human umbilical vein endothelial cells (HUVECs). It was found that the exosomes significantly promoted the proliferation, migration and invasion of A549 cells as well as the proliferation and angiogenesis of HUVECs. Moreover, the exosomes released from hypoxic cells and/or irradiated cells had more powerful driving force in tumor progression compared to that generated from normoxia cells. Meanwhile, the proteins contained in the exosomes derived from A549 cells under different conditions were detected using tandem mass tag (TMT), and their expression profiles were analyzed. It was found that the exosome-derived protein of angiopoietin-like 4 (ANGPTL4) contributed to the migration of A549 cells as well as the angiogenesis of HUVECs, suggesting its potential as an effective diagnostic biomarker of metastasis and even a therapeutic target of lung cancer.
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http://dx.doi.org/10.1667/RR15555.1DOI Listing
July 2020

PM2.5 induces apoptosis, oxidative stress injury and melanin metabolic disorder in human melanocytes.

Exp Ther Med 2020 May 9;19(5):3227-3238. Epub 2020 Mar 9.

Department of Dermatology, Tianjin First Center Hospital, Tianjin 300192, P.R. China.

Recent growing evidence suggested that particulate matter 2.5 (PM2.5) has strong toxic effects on skin systems. However, the possible effects and the mechanisms of PM2.5 on vitiligo remain poorly understood. Therefore, the present study aimed to further investigate the effects and possible mechanisms of PM2.5 on vitiligo. Human keratinocytes (HaCaT cells) and human melanocytes (PIG1 cells and PIG3V cells) were exposed to PM2.5 (0-200 µg/ml) for 24 h. The cell viability of the three cell lines was measured by a Cell Counting Kit-8 assay. The secretions of stem cell factor (SCF) and basic fibroblast growth factor (bFGF) in HaCaT cells were evaluated by ELISA. The melanin contents, cellular tyrosinase activity, apoptosis, cell migration, malondialdehyde (MDA) contents, superoxide dismutase (SOD) levels, glutathione peroxidase (GSH-Px) levels and related protein expressions in PIG1 cells and PIG3V cells were evaluated by a NaOH assay, DOPA assay, Annexin V-FITC/Propidium Iodide staining, MDA assay, SOD assay, GSH-Px assay and western blotting, respectively. It was demonstrated that PM2.5 exposure inhibited cell viability of all three cell lines (HaCaT, PIG1 and PIG3V cells). PM2.5 exposure attenuated the secretions of SCF and bFGF in HaCaT cells. Moreover, PM2.5 exposure attenuated the activation of tyrosinase and melanogenesis, inhibited cell migration, and induced apoptosis and oxidative stress injury in PIG1 cells and PIG3V cells. In addition, PM2.5 exposure caused upregulated cytosolic cytochrome C and activated caspase-3 in PIG1 cells and PIG3V cells. Furthermore, PM2.5 exposure activated the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 signaling pathway. The present results suggested that PM2.5 exposure could inhibit the secretions of SCF and bFGF in keratinocytes, and cause oxidative stress injury and melanin metabolic disorder in melanocytes. Therefore, PM2.5 could be a new risk factor for vitiligo.
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http://dx.doi.org/10.3892/etm.2020.8590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138919PMC
May 2020

A Novel Intergenic LSM14A-RET Fusion Variant in a Patient With Lung Adenocarcinoma.

J Thorac Oncol 2020 04;15(4):e52-e53

Department of Medical Oncology, The Jiangyin Clinical College of Xuzhou Medical University, Jiangyin, P.R. China. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2019.11.025DOI Listing
April 2020

Organic fertilizer application and Mg fertilizer promote banana yield and quality in an Udic Ferralsol.

PLoS One 2020 18;15(3):e0230593. Epub 2020 Mar 18.

Key Laboratory of Plant-Soil Interactions, Ministry of Education, College of Resources and Environmental Sciences, China Agricultural University, Beijing, China.

Low soil fertility, high rates of fertilizer application and low yields and quality are major problems in intensive banana production in acid soils of south China. A field experiment was carried out for two years to determine the optimum management practices for maximizing soil health and banana yield and quality. The experiment consisted of an unamended control (CK) and lime (Lime), calcium magnesium phosphate fertilizer (CMP), organic fertilizer (OF), and organic fertilizer combined with calcium magnesium phosphate fertilizer (OFC) treatments. Soil nutrient concentrations and banana shoot biomass, nutrient uptake, yield and fruit quality were determined. Application of lime and CMP was found to increase soil pH and nutrient availability and increase banana yield. Yet, the banana biomass and yields in the Lime and CMP treatments were significantly lower than those in the OF and OFC treatments in which soil organic matter (SOM) content increased. Total soluble solids and soluble sugar contents increased in the CMP and organic fertilizer treatments. A consistent increase in Mg concentrations in banana leaves over the two years in the CMP and organic fertilizer treatments indicates that Mg is essential for banana production and quality. Short-term adding Mg from banana corms increased total soluble solids and soluble sugar content. The application of organic fertilizer combined with CMP or Mg solution is therefore recommended to increase soil health and promote the yield and quality of banana in intensively managed plantations in subtropical regions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230593PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080258PMC
June 2020

The novel long noncoding RNA CRART16 confers cetuximab resistance in colorectal cancer cells by enhancing ERBB3 expression via miR-371a-5p.

Cancer Cell Int 2020 4;20:68. Epub 2020 Mar 4.

1Department of General Surgery, Peking University First Hospital, Beijing, 100034 People's Republic of China.

Background: Long noncoding RNAs (lncRNAs) have been shown to participate in multiple biological processes and confer drug resistance. However, it remains unclear whether lncRNAs are involved in conferring cetuximab resistance in colorectal cancer (CRC) cells.

Methods: Cell Counting Kit-8 (CCK-8) assays were performed to assess the sensitivity of CRC cell lines to cetuximab treatment. We incubated Caco-2 cells, which are partially responsive to cetuximab, with increasing concentrations of cetuximab for approximately 6 months to generate Caco-2 cetuximab-resistant (Caco-2 CR) cells. Microarray analysis comparing Caco-2 CR with Caco-2 cells was used to identify lncRNAs that were potentially related to cetuximab resistance. Caco-2 cells were stably transduced with cetuximab resistance-associated RNA transcript 16 (CRART16) or an empty vector using lentiviral infection; the cells were designated Caco-2-CRART16 and Caco-2-NC, respectively, and were analyzed with RNA sequencing (RNA-seq). Quantitative real-time PCR (qRT-PCR) was performed to investigate RNA expression. Flow cytometry and TUNEL assays were used to assess apoptosis levels induced by cetuximab. The cell cycle, stemness biomarkers and membrane proteins of CRC cells were assessed via flow cytometry. RNA fluorescence in situ hybridization (FISH) was used to examine CRART16 localization and expression. Bioinformatics analysis was performed to predict the potential mechanism of CRART16, which was further validated by a dual-luciferase reporter assay. Differences in measurement data were compared using Student's t test, one-way ANOVA followed by Dunnett's test and two-way ANOVA.

Results: The novel lncRNA CRART16 was upregulated in Caco-2 CR cells. CRART16 overexpression reversed the effects of cetuximab on cell viability and reduced cetuximab-induced apoptosis. Meanwhile, CRART16 overexpression led to increases in the proportion of CD44/CD133 cells. In addition, CRART16 acts as a competing endogenous RNA (ceRNA) for miR-371a-5p to regulate V-Erb-B2 Erythroblastic Leukemia Viral Oncogene Homolog 3 (ERBB3) expression. MiR-371a-5p mimics counteracted the cetuximab resistance induced by CRART16 overexpression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that after CRART16 was overexpressed, the resulting differentially expressed mRNAs were mainly enriched in the MAPK signaling pathway.

Conclusions: CRART16 overexpression may contribute to cetuximab resistance through the miR-371a-5p/ERBB3/MAPK pathway. Additionally, CRART16 contributes to the acquisition of stemness properties.
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http://dx.doi.org/10.1186/s12935-020-1155-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057486PMC
March 2020

Air pollution, environmental perceptions, and citizen satisfaction: A mediation analysis.

Environ Res 2020 05 21;184:109287. Epub 2020 Feb 21.

School of Public Administration, Chongqing University, China. Electronic address:

Air pollution is more than an environmental or health issue. Our findings suggest that Chinese citizens exposed to more industrial sulfur dioxide (SO) and dust emissions are less likely to be satisfied with environmental administration. Chinese citizens living with poorer air quality also tend to be dissatisfied with law enforcement. Last, perceptions of air pollution are affected by measured industrial emissions and shape citizen satisfaction. In sum, this paper provides evidence that air pollution corrodes citizen satisfaction via environmental perceptions. This improves understanding of the political costs of environmental degradation and the underlying mechanism.
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http://dx.doi.org/10.1016/j.envres.2020.109287DOI Listing
May 2020