Publications by authors named "Hongyan Guo"

239 Publications

Robust prognostic model based on immune infiltration-related genes and clinical information in ovarian cancer.

J Cell Mol Med 2022 Jun 23. Epub 2022 Jun 23.

Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.

Immune infiltration of ovarian cancer (OV) is a critical factor in determining patient's prognosis. Using data from TCGA and GTEx database combined with WGCNA and ESTIMATE methods, 46 genes related to OV occurrence and immune infiltration were identified. Lasso and multivariate Cox regression were applied to define a prognostic score (IGCI score) based on 3 immune genes and 3 types of clinical information. The IGCI score has been verified by K-M curves, ROC curves and C-index on test set. In test set, IGCI score (C-index = 0.630) is significantly better than AJCC stage (C-index = 0.541, p < 0.05) and CIN25 (C-index = 0.571, p < 0.05). In addition, we identified key mutations to analyse prognosis of patients and the process related to immunity. Chi-squared tests revealed that 6 mutations are significantly (p < 0.05) related to immune infiltration: BRCA1, ZNF462, VWF, RBAK, RB1 and ADGRV1. According to mutation survival analysis, we found 5 key mutations significantly related to patient prognosis (p < 0.05): CSMD3, FLG2, HMCN1, TOP2A and TRRAP. RB1 and CSMD3 mutations had small p-value (p < 0.1) in both chi-squared tests and survival analysis. The drug sensitivity analysis of key mutation showed when RB1 mutation occurs, the efficacy of six anti-tumour drugs has changed significantly (p < 0.05).
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http://dx.doi.org/10.1111/jcmm.17360DOI Listing
June 2022

Establishment of an optimized CTC detection model consisting of EpCAM, MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics.

Chin J Cancer Res 2022 Apr;34(2):95-108

Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.

Objective: Emerging studies have demonstrated the promising clinical value of circulating tumor cells (CTCs) for diagnosis, disease assessment, treatment monitoring and prognosis in epithelial ovarian cancer. However, the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common standards.

Methods: We enrolled 160 patients with epithelial ovarian cancer as the experimental group, and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control group. We enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens (EpCAM and MUC1), and used multiple reverse transcription-polymerase chain reaction (RT-PCR) detecting three markers (EpCAM, MUC1 and WT1) for quantification. And then we used a binary logistic regression analysis and focused on EpCAM, MUC1 and WT1 to establish an optimized CTC detection model.

Results: The sensitivity and specificity of the optimized model is 79.4% and 92.2%, respectively. The specificity of the CTC detection model is significantly higher than CA125 (92.2% . 82.2%, P=0.044), and the detection rate of CTCs was higher than the positive rate of CA125 (74.5% 58.2%, P=0.069) in early-stage patients (stage I and II). The detection rate of CTCs was significantly higher in patients with ascitic volume ≥500 mL, suboptimal cytoreductive surgery and elevated serum CA125 level after 2 courses of chemotherapy (P<0.05). The detection rate of CTC and CTC was significantly higher in chemo-resistant patients (26.3% . 11.9%; 26.4% . 13.4%, P<0.05). The median progression-free survival time for CTC patients trended to be longer than CTC patients, and overall survival was shorter in CTC patients (P=0.043).

Conclusions: Our study presents an optimized detection model for CTCs, which consists of the expression levels of three markers (EpCAM, MUC1 and WT1). In comparison with CA125, our model has high specificity and demonstrates better diagnostic values, especially for early-stage ovarian cancer. Detection of CTC and CTC had predictive value for chemotherapy resistance, and the detection of CTC suggested poor prognosis.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2022.02.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086574PMC
April 2022

and its component rutin exhibit glucose-lowering activities by inhibiting hepatic glucose production AKT activation.

Acta Pharm Sin B 2022 May 18;12(5):2239-2251. Epub 2021 Nov 18.

State Key Laboratory of Membrane Biology, School of Medicine, Tsinghua University, Beijing 100084, China.

The potential medicinal value of Ma bamboo (), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that leaf extract (DLE) reduced fasting blood glucose levels, body weight, and low-density lipoprotein cholesterol with low liver toxicity in / mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways. Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase () and phosphoenolpyruvate carboxykinase 1 () expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor (IGF1R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.
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http://dx.doi.org/10.1016/j.apsb.2021.11.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136573PMC
May 2022

Oropharyngeal Probiotic ENT-K12 as an Effective Dietary Intervention for Children With Recurrent Respiratory Tract Infections During Cold Season.

Front Nutr 2022 10;9:900448. Epub 2022 May 10.

Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, Wuhan, China.

Recurrent respiratory tract infections (RRTi) cause a high burden of disease and lead to negative impact on quality of life, frequent school/work absenteeism, and doctor visits, which remain a great challenge to pediatricians because RRTi can increase the risk of various complications including antibiotic overuse and resistance, which is one of the biggest threats to global health, and there is no confirmed effective treatment. In this study, we aimed to assess the clinical efficacy and safety of oropharyngeal probiotic ENT-K12 as a dietary intervention or a complementary treatment along with standard medical treatment during acute respiratory infections among children with RRTi during cold season. The results of this study show that when comparing to practicing of standard medical treatment only, the complementary intake of oropharyngeal probiotic ENT-K12 can effectively reduce episodes of both acute and RRTi in school children, shorten the course of respiratory symptoms onset, reduce the use of antibiotics and antiviral drugs, and reduce the absence days from both children's school and parents' work. Using oropharyngeal probiotics as a complementary dietary intervention to stabilize oropharyngeal microflora, specifically inhibiting respiratory pathogens and enhancing host immunity, could possibly be a promising approach to reduce RRTi burden and combating antibiotic resistance in long term, more clinical studies will be needed to further confirm the clinical practicing guide to ensure its clinical benefit.

Methods: A total of 100 susceptible children with RRTi aged 3-10 years, living in Wuhan, China, were selected. They were randomized to the probiotic group and control group at the beginning of the trial during the cold season. Fifty children in the probiotic group took oropharyngeal probiotic ENT-K12 for 30 days, along with standard medical treatment when there was an onset of respiratory symptoms and medical treatment was needed, and fifty children in the control group did not take oropharyngeal probiotics but only had standard medical treatment when there was an onset of respiratory symptoms and medical treatment was needed. Patients were followed up for 30 days during the cold season. The primary objective of this study is to assess the complementary dietary interventional efficacy of oropharyngeal probiotic ENT-K12 on episodes of respiratory tract infections during the cold season, and the secondary objective is to assess the interventional efficacy of oropharyngeal probiotic on days of respiratory symptoms onset, using antiviral drugs, antibiotics, and antipyretics, days of children absent from school, and days of parents absent from work, as well as to confirm tolerability and safety judged by adverse event reporting.

Results: There were 47 children, 22 male and 25 female children, with an average age of 5.71 years (SD = 1.99) in the probiotic group finishing the study, and 50 children, 32 male and 18 female children, in the control group with an average age of 6.12 years (SD = 1.98) finishing the study. During the 30-day period of oropharyngeal probiotic intake, children in the probiotic group totally had 7 episodes of upper respiratory tract infections, while children in the control group totally had 17 episodes of upper respiratory tract infections, indicating that the incidence of upper respiratory tract infection in the probiotic group (14.89%) was significantly lower than that in the control group (34.00%) during the intervention period. The days of using antibiotics and antiviral drugs in the probiotic group were significantly lower than that in the control group, and the course of respiratory symptoms onset was shorter and more moderate in the probiotic group than that in the control group; in addition, compared with the control group, both the days of children absent from school and parents' absence from work in the probiotic group were significantly lower. Children treated with oropharyngeal probiotic ENT-K12 had excellent tolerability with no side effects reported, hence confirmed safety of applying oropharyngeal probiotic ENT-K12 as a prophylactic use or an effective dietary intervention along with standard medication during respiratory infections onset.

Conclusion: Intake of oropharyngeal probiotic ENT-K12 as a dietary intervention can effectively reduce episodes of upper respiratory tract infections in school children with RRTi during high peak season, reduce the days of using antibiotics and antiviral drugs, and reduce children's sick leave days, parents' absence days from work, and shorten the course of respiratory infections; the safety of oropharyngeal probiotic ENT-K12 has been confirmed with no side effects reported, excellent tolerability, and easy acceptance. Notably, this study opens up a new research idea in the field of microbe promoting human health by supplying direct proof to support its efficiency and safety.
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http://dx.doi.org/10.3389/fnut.2022.900448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132010PMC
May 2022

Efficacy and safety of photodynamic therapy mediatied by 5-aminolevulinic acid for the treatment of vaginal high-grade intraepithelial lesions.

Photodiagnosis Photodyn Ther 2022 May 14;39:102899. Epub 2022 May 14.

Department of Obstetrics and Gynecology, Peking University Third Hospital.

Background: Vaginal high-grade squamous intraepithelial lesion (HSIL) (vaginal intraepithelial neoplasia [VAIN] grade 2-3) is clinically, a precancerous lesion condition with an estimated progression rate of 10%-20%. Therefore, treatment is recommended. Because traditional treatments have limited effects, high expense and complications, here we evaluated the efficacy and safety of topical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT).

Methods: This study consisted of 56 female patients diagnosed with vaginal HSIL. A 20% 5-ALA jelly formation was topically applied to the vaginal wall, followed by 635 nm PDT at 7-14 days intervals. Cytology, human papillomavirus (HPV) genotyping, colposcopy, and pathology were assessed after treatment.

Results: Among the 56 patients in our study, 47 (83.9%) had VAIN 2 and 9 (16.1%) had VAIN 3. 35 patients underwent three courses of PDT treatment, 19 experienced six courses, and two experienced nine courses. The total pathological regression rate was 87.5%, and the HPV clearance rate during the 6-month follow-up was 41.9%. Lesions located in the vaginal stump after hysterectomy seem to be difficult to treat. 9%(4/44) and 23%(7/30) patients had recurrent disease during the 6-month and 1-year follow-up time point. The most common adverse event was increased vaginal discharge, other side effects include abdominal pain, vulvar pruritus, and vaginal bleeding. No severe adverse effect was observed during the treatment.

Conclusion: Photodynamic therapy mediatied by 5-aminolevulinic acid is an effective and safe treatment for vaginal HSIL with minimal side effects.
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http://dx.doi.org/10.1016/j.pdpdt.2022.102899DOI Listing
May 2022

Prognostic-Related Metabolic Score for Survival Prediction in Early-Stage Endometrioid Endometrial Cancer: A Multi-Center and Retrospective Study.

Front Med (Lausanne) 2022 28;9:830673. Epub 2022 Apr 28.

Key Laboratory of the Ministry of Education, Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: Patients with endometrial cancer (EC) combined with metabolic syndrome (MetS) have a worse prognosis than those without MetS. This study aimed to investigate whether partial metabolic disorder significantly influenced early-stage endometrioid EC (EEC) survival and searched for a more efficient method to evaluate metabolic status.

Methods: This is a nationwide, multicenter cohort study that included 998 patients with primary early-stage EEC from 2001 to 2018. Patients were divided into different metabolic groups based on the diagnostic criteria of the Chinese Medical Association (CDC). The progression-free survival (PFS) time was compared between various metabolic status. Meanwhile, we established an EC Prognostic-Related Metabolic Score (ECPRM Score) to explore the association of the severity of metabolic status and early-stage EEC PFS. A nomogram was established for predicting PFS, which was externally validated in a testing set that includes 296 patients.

Results: A partial metabolic disorder, as well as MetS, was an independent risk factor of poor survival of patients with early-stage EEC [hazard ratio (HR) = 7.6, 95% CI = 1.01-57.5, < 0.05]. A high ECPRM Score was associated with lower PFS (HR = 2.1, 95% CI = 1.05-4.0, < 0.001). The nomogram, in which the ECPRM Score contributed most to the prognosis, exhibited excellent discrimination of survival supported by the internal and external validations. In addition, the calibration curve supports its robust predicting ability.

Conclusion: Even though they do not meet the criteria of MetS, partial metabolic disorders were also associated with adverse outcomes in early-stage EEC. The ECPRM Score is beneficial for clinicians to evaluate the severity of metabolic abnormalities and guide patients to ameliorate the poor prognosis of metabolic disorders.
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http://dx.doi.org/10.3389/fmed.2022.830673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096267PMC
April 2022

Size-dependent biological effect of copper oxide nanoparticles exposure on cucumber (Cucumis sativus).

Environ Sci Pollut Res Int 2022 May 14. Epub 2022 May 14.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, China.

Copper oxide nanoparticles (CuO NPs) have received considerable attention for their toxic effects on crops and potential application in agriculture. In order to investigate the biological effects of CuO NPs on plants, we exposed cucumber (Cucumis sativus) to two sizes of CuO NPs (510 nm, μCuO and 43 nm, nCuO). Results indicated that with concentration increased, the available Cu content in soil increased significantly. The addition of CuO NPs increased Cu content and other nutrient element (e.g., K, P, Mn, and Zn) content in plants. However, diverse particle sizes had different effects. The nCuO treatment had larger translocation factor, higher nutrient element content in fruits, and lower oxidative damage than μCuO treatment. Moreover, nCuO of 100 mg/kg could stimulate cucumber growth, while μCuO had no obvious effects on growth. Conclusively, CuO NPs could be used as copper fertilizer to supply copper to cucumber. The nCuO had better effects on improving the bioavailability of Cu and nutritional value of fruits. These results can help develop strategies for safe disposal of CuO NPs as agricultural fertilizer.
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http://dx.doi.org/10.1007/s11356-022-20662-8DOI Listing
May 2022

Circ_FOXP1 promotes the growth and survival of high glucose-treated human trophoblast cells through the regulation of miR-508-3p/SMAD family member 2 pathway.

Endocr J 2022 May 10. Epub 2022 May 10.

Department of Gynecology and Obstetrics, Xiangyang NO.1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.

Gestational diabetes mellitus (GDM) is a health risk for pregnant women and infants. Emerging evidence suggests that the deregulation of circular RNAs (circRNAs) is associated with the progression of this disorder. The objective of this study was to investigate the role of circ_FOXP1 in GDM. Cell models of GDM were established by treating human trophoblast cells with high glucose (HG). The expression of circ_FOXP1, miR-508-3p and SMAD family member 2 (SMAD2) mRNA was detected by quantitative real-time PCR (qPCR). Cell proliferation was assessed by EdU assay and MTT assay, and cell cycle and cell apoptosis were determined by flow cytometry assay. The protein levels of proliferation- and apoptosis-related markers and SMAD2 were measured by western blot. The relationship between miR-508-3p and circ_FOXP1 or SMAD2 was validated by dual-luciferase reporter assay or pull-down assay. The expression of circ_FOXP1 was downregulated in HG-treated HTR-8/SVneo cells. Circ_FOXP1 overexpression promoted HG-inhibited HTR-8/SVneo cell proliferation and suppressed HG-induced HTR-8/SVneo cell cycle arrest and apoptosis. Circ_FOXP1 positively regulated the expression of SMAD2 by targeting miR-508-3p. MiR-508-3p was overexpressed in HG-treated HTR-8/SVneo cells, and its overexpression reversed the effects of circ_FOXP1 overexpression. MiR-508-3p inhibition also alleviated HG-induced HTR-8/SVneo cell injuries, while the knockdown of SMAD2 abolished these effects. Collectively, circ_FOXP1 promotes the growth and survival of HG-treated human trophoblast cells through the miR-508-3p/SMAD2 pathway, hinting that circ_FOXP1 was involved in GDM progression.
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http://dx.doi.org/10.1507/endocrj.EJ21-0528DOI Listing
May 2022

The prognostic miR-532-5p-correlated ceRNA-mediated lipid droplet accumulation drives nodal metastasis of cervical cancer.

J Adv Res 2022 03 22;37:169-184. Epub 2021 Sep 22.

Department of Obstetrics and Gynecology, Peking University Third Hospital, 100191 Beijing, China.

Introduction: The prognosis for cervical cancer (CC) patients with lymph node metastasis (LNM) is extremely poor. Lipid droplets (LDs) have a pivotal role in promoting tumor metastasis. The crosstalk mechanism between LDs and LNM modulated in CC remains largely unknown.

Objectives: This study aimed to construct a miRNA-dependent progonostic model for CC patients and investigate whether miR-532-5p has a biological impact on LNM by regualting LDs accumulation.

Methods: LASSO-Cox regression was applied to establish a prognostic prediction model. miR-532-5p had the lowest P-value in RNA expression (P < 0.001) and prognostic prediction (P < 0.0001) and was selected for further study. The functional role of the prognostic miR-532-5p-correlated competing endogenous RNA (ceRNA) network was investigated to clarify the crosstalk between LDs and LNM. The underlying mechanism was determined using site-directed mutagenesis, dual luciferase reporter assays, RNA immunoprecipitation assays, and rescue experiments. A xenograft LNM model was established to evaluate the effect of miR-532-5p and orlistat combination therapy on tumor growth and LNM.

Results: A novel 5-miRNAs prognostic signature was constructed to better predict the prognosis of CC patient. Further study demonstrated that miR-532-5p inhibited epithelial-mesenchymal transition and lymphangiogenesis by regulating LDs accumulation. Interestingly, we also found that LDs accumulation promoted cell metastasis in vitro. Mechanistically, we demonstrated a miR-532-5p-correlated ceRNA network in which LINC01410 was bound directly to miR-532-5p and effectively functioned as miR-532-5p sponge to disinhibit its target gene-fatty acid synthase (). Combined therapy with miR-532-5p and FASN inhibitor-orlistat further inhibited tumor growth and LNM in vivo.

Conclusion: Our findings highlight a LD accumulation-dependent mechanism of miR-532-5p-modulated LNM and support treatment with miR-532-5p/orlistat as novel strategy for treating patients with LNM in CC.
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http://dx.doi.org/10.1016/j.jare.2021.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040090PMC
March 2022

Risk Factors and Prognosis of Early Recurrence in Stage I-II Endometrial Cancer: A Large-Scale, Multi-Center, and Retrospective Study.

Front Med (Lausanne) 2022 14;9:808037. Epub 2022 Apr 14.

Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Objective: The aim of the present study was to determine overall survival (OS) and risk factors associated with early recurrence in patients with FIGO I-II stage endometrial carcinoma (EC).

Methods: Clinical features were retrospectively extracted from the database of China Endometrial Cancer Consortium from January 2000 to December 2019. A total of 2,974 patients with Federation International of Gynecology and Obstetrics (FIGO) I-II stage endometrial cancer were included. Kaplan-Meier survival analysis was used to assess OS and disease-specific survival. Cox proportional hazard model and Fine-Gray model were used to determine the factors related to OS. Binary logistic regression model was used to determine independent predictors of early relapse patients.

Results: Of these 2,974 ECs, 189 patients were confirmed to have relapse. The 5-year OS was significantly different between the recurrence and non-recurrence patients ( < 0.001). Three quarters of the relapse patients were reported in 36 months. The 5-year OS for early recurrence patients was shorter than late recurrence [relapse beyond 36 months, < 0.001]. The grade 3 [odds ratio (OR) = 1.55, 95%CI 1.17-2.05, = 0.002], lymphatic vascular infiltration (LVSI; OR = 3.36; 95%CI 1.50-7.54, = 0.003), and myometrial infiltration (OR = 2.07, 95%CI 1.17-3.65, = 0.012) were independent risk factors of early relapse. The protective factor of that is progesterone receptor (PR)-positive (OR = 0.50, 95%CI 0.27-0.92, = 0.02). Bilateral ovariectomy could reduce recurrence risk rate (OR = 0.26, 95%CI 0.14-0.51, < 0.001).

Conclusion: The OS of early relapse EC is worse. Grade 3, LVSI, and myometrial infiltration are independent risk factors for early relapse EC. In addition, the protective factor is PR-positive for those people and bilateral salpingo-oophorectomy could reduce the risk of recurrence.
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http://dx.doi.org/10.3389/fmed.2022.808037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046937PMC
April 2022

A novel method for investigating the mechanism of the anti-rheumatoid arthritis activity of Angelicae pubescentis radix by integrating UHPLC-QTOF/MS and network pharmacology.

Biomed Chromatogr 2022 Apr 28:e5389. Epub 2022 Apr 28.

Hefei Institutes of Physical Science, Chinese Academy of Sciences, Key Laboratory of Xin'an Medicine (Anhui University of Chinese Medicine), Ministry of Education, Hefei, China.

The study aimed to establish a strategy to elucidate the in vivo constituents of Angelicae Pubescentis Radix (APR, also known as Duhuo) and reveal the probable mechanisms underlying its anti-rheumatoid arthritis activity. First recorded by Shennong Bencao Jing, APR is mainly used to treat Bi syndrome. Eleven absorbed components of APR were successfully identified using the rheumatoid arthritis (RA) rat model and the UHPLC-QTOF/MS technique. Two active ingredients (osthole and columbianadin) and five corresponding targets (PTGS1, PTGS2, RXRA, CCNA2 and ACHE) were found to construct a compound-protein interaction network in RA. In addition, a non-alcoholic fatty liver disease pathway, which was related to anti-RA activity, was eventually identified by KEGG analysis. Subsequently, molecular docking was performed by establishing a mixed matrix network, including the absorbed component, corresponding target and signaling pathway with two key compounds (osthole and columbianadin) and two important targets (PTGS2 and PTGS1). The result of molecular docking is in agreement with the network pharmacology.
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http://dx.doi.org/10.1002/bmc.5389DOI Listing
April 2022

Programmed Cell Death-Dependent Host Defense in Ocular Herpes Simplex Virus Infection.

Front Microbiol 2022 8;13:869064. Epub 2022 Apr 8.

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States.

Herpes simplex virus type 1 (HSV1) remains one of the most ubiquitous human pathogens on earth. The classical presentation of HSV1 infection occurs as a recurrent lesions of the oral mucosa commonly refer to as the common cold sore. However, HSV1 also is responsible for a range of ocular diseases in immunocompetent persons that are of medical importance, causing vision loss that may result in blindness. These include a recurrent corneal disease, herpes stromal keratitis, and a retinal disease, acute retinal necrosis, for which clinically relevant animal models exist. Diverse host immune mechanisms mediate control over herpesviruses, sustaining lifelong latency in neurons. Programmed cell death (PCD) pathways including apoptosis, necroptosis, and pyroptosis serve as an innate immune mechanism that eliminates virus-infected cells and regulates infection-associated inflammation during virus invasion. These different types of cell death operate under distinct regulatory mechanisms but all server to curtail virus infection. Herpesviruses, including HSV1, have evolved numerous cell death evasion strategies that restrict the hosts ability to control PCD to subvert clearance of infection and modulate inflammation. In this review, we discuss the key studies that have contributed to our current knowledge of cell death pathways manipulated by HSV1 and relate the contributions of cell death to infection and potential ocular disease outcomes.
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http://dx.doi.org/10.3389/fmicb.2022.869064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023794PMC
April 2022

Targeting a gene regulatory element enhances rice grain yield by decoupling panicle number and size.

Nat Biotechnol 2022 Apr 21. Epub 2022 Apr 21.

State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, China.

Crop genetic improvement requires balancing complex tradeoffs caused by gene pleiotropy and linkage drags, as exemplified by IPA1 (Ideal Plant Architecture 1), a typical pleiotropic gene in rice that increases grains per panicle but reduces tillers. In this study, we identified a 54-base pair cis-regulatory region in IPA1 via a tiling-deletion-based CRISPR-Cas9 screen that, when deleted, resolves the tradeoff between grains per panicle and tiller number, leading to substantially enhanced grain yield per plant. Mechanistic studies revealed that the deleted fragment is a target site for the transcription factor An-1 to repress IPA1 expression in panicles and roots. Targeting gene regulatory regions should help dissect tradeoff effects and provide a rich source of targets for breeding complementary beneficial traits.
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http://dx.doi.org/10.1038/s41587-022-01281-7DOI Listing
April 2022

Anisotropic electrene T'-CaP with electron gas magnetic coupling as anode material for Na/K ion batteries.

Phys Chem Chem Phys 2022 May 4;24(17):10567-10574. Epub 2022 May 4.

Anhui Province Key Laboratory of Optoelectric Materials Science and Technology, Key Laboratory of Functional Molecular Solids Ministry of Education, and Department of Physics, Anhui Normal University, Wuhu, Anhui 241000, China.

There is an urgent need for high-performance rechargeable electrical storage devices as a supplement or a substitution for lithium ion batteries (LIBs) due to the shortage of lithium in nature. Herein we propose a stable 2D electrene T'-CaP as an anode material for Na/K ion batteries developed using first principles calculations. Our calculated results show that the T'-CaP monolayer is an antiferromagnetic semiconducting electrene with a spin-polarized electron gas. It exhibits suitable adsorption for both Na and K atoms, and its anisotropic migration energy barriers are 0.050/0.101 eV and 0.037/0.091 eV in the direction, respectively. The theoretical capacities for Na and K are both 482 MA h g, whereas the average working voltage platforms are 0.171-0.226 V and 0.013-0.267 V, respectively. All the results reveal that the T'-CaP monolayer has promising prospects for application as an anode material for Na/K ion batteries.
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http://dx.doi.org/10.1039/d1cp05365eDOI Listing
May 2022

Multi-omics approaches for biomarker discovery in early ovarian cancer diagnosis.

EBioMedicine 2022 May 16;79:104001. Epub 2022 Apr 16.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 10091, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 10091, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing 10091, China. Electronic address:

Ovarian cancer (OC) is a heterogeneous disease with the highest mortality rate and the poorest prognosis among gynecological malignancies. Because of the absence of specific early symptoms, most OC patients are often diagnosed at late stages. Thus, improved biomarkers of OC for use in research and clinical practice are urgently needed. The last decade has seen increasingly rapid advances in sequencing and biotechnological methodologies. Consequently, multiple omics technologies, including genomic/transcriptomic sequencings and proteomic/metabolomic mass spectra, have been widely applied to analyze tissue- and liquid-derived samples from OC patients. The integration of multi-omics data has increased our knowledge of the disease and identified valuable OC biomarkers. In this review, we summarize the recent advances and perspectives in the use of multi-omics technologies in OC research and highlight potential applications of multi-omics for identifying novel biomarkers and improving clinical assessments.
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http://dx.doi.org/10.1016/j.ebiom.2022.104001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035645PMC
May 2022

Comparison between cannabidiol and sertraline for the modulation of post-traumatic stress disorder-like behaviors and fear memory in mice.

Psychopharmacology (Berl) 2022 May 9;239(5):1605-1620. Epub 2022 Apr 9.

Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Beijing, 100850, China.

Rationale And Objectives: Post-traumatic stress disorder (PTSD) is characterized by poor adaptation to a traumatic experience and disturbances in fear memory regulation, and currently lacks effective medication. Cannabidiol is a main constituent of Cannabis sativa; it has no psychotomimetic effects and has been implicated in modulating fear learning in mammals. Using a mouse PTSD model, we investigated the effects of CBD on PTSD-like behaviors and the modulation of trauma-related fear memory, a crucial process leading to core symptoms of PTSD.

Methods: We applied the modified pre-shock model to evaluated PTSD-like behaviors from days 3 to 26. The measures included the freezing time to the conditioned context, open field test, elevated plus maze test, and social interaction test. CBD and sertraline were administered at different stages of fear memory.

Results: CBD (10 mg/kg, i.p.) administration alleviated main PTSD-like symptoms in the mouse pre-shock model by attenuating trauma-related fear memory and anxiety-like behavior, and increasing social interaction behavior. The effects of CBD were apparent irrespective of whether it was administered before, during, or after re-exposure to the aversive context. However, sertraline (15 mg/kg, p.o.) was only effective when administered before the behavioral test. CBD also reduced the consolidation, retrieval, and reconsolidation of trauma-related fear memory, whereas sertraline only reduced fear-memory retrieval.

Conclusion: CBD produced anti-PTSD-like actions in mice and disrupted trauma-related fear memory by interfering with multiple aspects of fear memory processing. These findings indicate that CBD may be a promising candidate for treating PTSD.
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http://dx.doi.org/10.1007/s00213-022-06132-6DOI Listing
May 2022

Prognostic Pathways Guide Drug Indications in Pan-Cancers.

Front Oncol 2022 14;12:849552. Epub 2022 Mar 14.

Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Pathway-level analysis is a powerful approach enabling the interpretation of post-genomic data at a higher level than that of individual molecules. Molecular-targeted therapy focusing on cascade signaling pathways has become a new paradigm in anticancer therapy, instead of a single protein. However, the approaches to narrowing down the long list of biological pathways are limited. Here, we proposed a strategy for Drug Prescription on biological pathways across pan-Cancers (CDP), by connecting drugs to candidate pathways. Applying on a list of 120 traditional Chinese medicines (TCM), we especially identified the "TCM-pathways-cancers" triplet and constructed it into a heterogeneous network across pan-cancers. Applying them into TCMs, the computational prescribing methods deepened the understanding of the efficacy of TCM at the molecular level. Further applying them into Western medicines, CDP could promote drug reposition avoiding time-consuming developments of new drugs.
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http://dx.doi.org/10.3389/fonc.2022.849552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964428PMC
March 2022

Establish of an Initial Platinum-Resistance Predictor in High-Grade Serous Ovarian Cancer Patients Regardless of Homologous Recombination Deficiency Status.

Front Oncol 2022 18;12:847085. Epub 2022 Mar 18.

Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.

Backgrounds: Ovarian cancer (OC) is still the leading aggressive and lethal disease of gynecological cancers, and platinum-based regimes are the standard treatments. However, nearly 20%-30% of patients with OC are initial platinum resistant (IPR), and there is a lack of valid tools to predict whether they will be primary platinum resistant or not prior to chemotherapy.

Methods: Transcriptome data from The Cancer Genome Atlas (TCGA) was downloaded as the training data, and transcriptome data of GSE15622, GSE102073, GSE19829, and GSE26712 were retrieved from Gene Expression Omnibus (GEO) as the validation cohorts. Differentially expressed genes (DEGs) were selected between platinum-sensitive and platinum-resistant patients from the training cohort, and multiple machine-learning algorithms [including random forest, XGboost, and least absolute shrinkage and selection operator (LASSO) regression] were utilized to determine the candidate genes from DEGs. Then, we applied logistic regression to establish the IPR signature based on the expression. Finally, comprehensive clinical, genomic, and survival feature were analyzed to understand the application value of the established IPR signature.

Results: A total of 532 DEGs were identified between platinum-resistant and platinum-sensitive samples, and 11 of them were shared by these three-machine learning algorithms and utilized to construct an IPR prediction signature. The area under receiver operating characteristic curve (AUC) was 0.841 and 0.796 in the training and validation cohorts, respectively. Notably, the prediction capacity of this signature was stable and robust regardless of the patients' homologous recombination deficiency (HRD) and mutation burden status. Meanwhile, the genomic feature was concordant between samples with high- or low-IPR signature, except a significantly higher prevalence of gain at Chr19q.12 (regions including ) in the high-IPR signature samples. The efficacy of prediction of platinum resistance of IPR signature successfully transferred to the precise survival prediction, with the AUC of 0.71, 0.72, and 0.66 to predict 1-, 3-, and 5-year survival, respectively. At last, we found a significantly different tumor-infiltrated lymphocytes feature, including lower abundance of CD4+ naive T cells in the samples with high-IPR signature. A relatively lower tumor immune dysfunction and exclusion (TIDE) value and more sensitivity to multiple therapies including Gefitinib may suggest the potency to transfer from platinum-based therapy to immunotherapy or target therapies in patients with high-IPR signature.

Conclusion: Our study established an IPR signature based on the expression of 11 genes that could stably and robustly distinguish OC patients with IPR and/or poor outcomes, which may guide therapeutic regimes tailoring.
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http://dx.doi.org/10.3389/fonc.2022.847085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971787PMC
March 2022

Willow can be recommended as a strong candidate for the phytoremediation of cadmium and pyrene co-polluted soil under flooding condition.

Environ Sci Pollut Res Int 2022 Jun 27;29(27):41081-41092. Epub 2022 Jan 27.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University (Xianlin Campus), 163 Xianlin Road, Jiangsu Province, Qixia District, Nanjing, 210023, People's Republic of China.

Soil cadmium (Cd) and pyrene (PYR) pollutions have gained worldwide attention due to their negative effects on the environment. Intermittent flooding in rain-rich areas may affect phytoremediation of Cd and PYR in soil. Therefore, a pot-culture experiment, with and without flooding, was conducted to study the effects of flooding on soil Cd and PYR phytoremediation. Concentrations of Cd, PYR, and nutrients in soils and plants, as well as plant physiological and biochemical responses, were examined. Under both flooding and non-flooding conditions, willow (Salix × aureo-pendula CL 'J1011') demonstrated a better ability to remove soil Cd and PYR. Flooding led to higher Cd accumulation in roots than that in shoots. Conversely, non-flooding resulted in higher Cd accumulation in shoots than that in roots. The maximum concentrations of Cd in shoots were 11.02 and 14.07 mg kg with and without flooding, respectively. The maximum dissipation rates of PYR in soil were 47.35% and 88.61% under flooding and non-flooding conditions, respectively. In addition, flooding significantly increased the photosynthetic pigment, photosynthetic fluorescence, and chlorophyll fluorescence parameters in leaves, compared with non-flooding treatment. Flooding also increased the concentrations of Mg, Mn, P, Fe, and K in roots and shoots. This study outlines an effective insight for the phytoremediation of Cd- and PYR-contaminated soil under flooding condition.
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http://dx.doi.org/10.1007/s11356-021-18228-1DOI Listing
June 2022

Butylphthalide Inhibits TLR4/NF-B Pathway by Upregulation of miR-21 to Have the Neuroprotective Effect.

J Healthc Eng 2022 7;2022:4687349. Epub 2022 Jan 7.

Department of Neurosurgery, The First Hospital of Qiqihar City, Qiqihar 161000, China.

Stroke is a disease with the highest incidence rate and the highest mortality rate in the world. The study aims to verify the neuroprotective effect of Butylphthalide. The mice were divided into sham group, MCAO group, and MCAO + Butylphthalide-treated group. The mice in MCAO + Butylphthalide-treated group were administered with 70 mg/kg Butylphthalide injection intraperitoneally after cerebral ischemia-reperfusion. The normal saline with the same volume was administered intraperitoneally for the mice in the MCAO group and sham group. The levels of miR-21 in brain tissue and cells were detected by qPCR. The OGD/R injury model of Neuro2A cells was used to simulate the hypoxic-ischemic environment of neurons in vitro. The proliferation rate of Neuro2A cells was detected with CCK-8. The production of ROS was detected with DCFH-DA. Compared with the mice in MCAO group, a decrease ( < 0.01) was observed in the functional neurologic impairment scoring, cerebral infarction volume, and brain loss volume in the mice treated with MCAO + Butylphthalide, but an increase ( < 0.01) was observed in the level of miR-21, which was positively correlated with functional neurologic impairment scoring ( = -0.8933, < 0.001). MTT assay showed that the cell viability of OGD/R + Butylphthalide group was significantly higher than that of other groups ( < 0.001), and the activity of ROS was significantly decreased ( < 0.001). The WB results showed that, compared with OGD/R + miR-NC and control groups, the ratio of Bcl-2/Bax in OGD/R + Butylphthalide group and OGD/R + miR-21 mimics group was significantly higher ( < 0.05), while the ratio of caspase-3/GAPDH was significantly lower ( < 0.05). In conclusion, Butylphthalide has neuroprotective effect on the mouse model of MCAO. It may upregulate the level of miR-21 to inhibit neuronal apoptosis and ROS production and improve the proliferation activity. The specific mechanism may lie in inhibiting TLR4/NF-B pathway.
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http://dx.doi.org/10.1155/2022/4687349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759846PMC
May 2022

Toxicity mechanism of cerium oxide nanoparticles on cyanobacteria Microcystis aeruginosa and their ecological risks.

Environ Sci Pollut Res Int 2022 May 15;29(23):34010-34018. Epub 2022 Jan 15.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, China.

The extensive application of cerium oxide nanoparticles (CeO NPs), a type of rare earth nanomaterial, led to pollution into aquatic environments. Cyanobacteria, a significant component of freshwater ecosystems, can interact with CeO NPs. However, little attention has been paid as to whether CeO NPs will have adverse effects on cyanobacteria. In the present study, Microcystis aeruginosa (FACHB-942) was exposed to different concentrations (0, 1, 10, and 50 mg/L) of CeO NPs. Results showed 50 mg/L CeO NPs inhibited algal growth (11.48% ± 5.76%), suppressed photosynthesis and induced the generation of reactive oxygen species (ROS) after 72 h exposure. The toxicity mechanism is the adsorption of CeO NPs on cell surface, the ROS formation and the intracellular Ce. Additionally, the intracellular microcystins (MCs) content was significantly induced (11.84% ± 1.47%) by 50 mg/L CeO NPs, while no significance was found in 1 and 10 mg/L CeO NP treatments. Results indicated high concentrations of CeO NPs could be toxic to algae through the adverse effects on algal growth and photosynthesis. Moreover, the promoted MCs production could also pose a threat to freshwater ecosystems due to the possible release into the environment.
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http://dx.doi.org/10.1007/s11356-021-18090-1DOI Listing
May 2022

Maintenance Therapy Can Improve the Oncologic Prognosis and Obstetrical Outcome of Patients With Atypical Endometrial Hyperplasia and Endometrial Cancer After Fertility-Preserving Treatment: A Multicenter Retrospective Study.

Front Oncol 2021 17;11:808881. Epub 2021 Dec 17.

Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Shanghai, China.

Objective: To evaluate the effect of maintenance therapy for patients with atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) after successful fertility-preserving management on prognosis and pregnancy outcome.

Methods: We performed a retrospectively analysis of 109 young women with atypical endometrial hyperplasia and early endometrioid endometrial cancer who had received complete response after fertility-preserving treatment at 5centers between May 2005 and March 2021. Maintenance therapy regimes included low-dose oral progesterone, levonorgestrel intrauterine device(LNG-IUD) and combination oral contraceptive (COC). The patients were divided into two groups, maintenance therapy group and non-maintenance therapy group. Clinical characteristics, treatment regimens, prognosis, and pregnancy outcome were compared between the two groups.

Results: The overall disease recurrence rate of the maintenance therapy group was significantly lower than that of the non-maintenance therapy group ( < 0.001). The recurrence rate of atypical endometrial hyperplasia and endometrial cancer in the maintenance therapy group were significantly lower than those in the non-maintenance group ( < 0.001). Maintenance therapy can reduce pregnancy rates and live birth rates. Maintenance therapy can protect the endometrium in patients treated with assisted reproductive technology (ART), greatly reducing the recurrence rate after ART (<0.001).

Conclusion: Maintenance therapy plays a very important protective role in fertility-preserving treatment for patients with atypical endometrial hyperplasia and endometrial cancer, which could significantly reduce the risk of recurrence. It is recommended that patients could receive maintenance therapy as long as possible during the period from achieving complete response to pregnancy preparation if possible. It may provide recurrence-free survival long enough for childless young women to prepare for pregnancy in the future. It can also protect the endometrium of those who are preparing to use assisted reproductive technology, possibly by reducing the risk of recurrence by excessive stimulation with assisted reproductive drugs.
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http://dx.doi.org/10.3389/fonc.2021.808881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718436PMC
December 2021

MAP4K4 mediates the SOX6-induced autophagy and reduces the chemosensitivity of cervical cancer.

Cell Death Dis 2021 12 20;13(1):13. Epub 2021 Dec 20.

Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.

There are nearly 40% of cervical cancer patients showing poor response to neoadjuvant chemotherapy that can be induced by autophagy, however, the underlying mechanism has not yet been fully clarified. We previously found that Sex-determining region of Y-related high-mobility-group box 6 (SOX6), a tumor suppressor gene or oncogene in several cancers, could induce autophagy in cervical cancer. Accordingly, this study aims to investigate the mechanism of SOX6-induced autophagy and its potential significance in the platinum-based chemotherapy of cervical cancer. Firstly, we found that SOX6 could promote autophagy in cervical cancer cells depending on its HMG domain. Mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K4) gene was identified as the direct target gene of SOX6, which was transcriptionally upregulated by binding the HMG domain of SOX6 protein to its double-binding sites within MAP4K4 gene promoter. MAP4K4 mediated the SOX6-induced autophagy through inhibiting PI3K-Akt-mTOR pathway and activating MAPK/ERK pathway. Further, the sensitivity of cervical cancer cells to cisplatin chemotherapy could be reduced by the SOX6-induced autophagy in vitro and in vivo, while such a phenomenon could be turned over by autophagy-specific inhibitor and MAP4K4 inhibitor, respectively. Moreover, cisplatin itself could promote the expression of endogenous SOX6 and subsequently the MAP4K4-mediated autophagy in cervical cancer cells, which might in turn reduce the sensitivity of these cells to cisplatin treatment. These findings uncovered the underlying mechanism and potential significance of SOX6-induced autophagy, and shed new light on the usage of MAP4K4 inhibitor or autophagy-specific inhibitor for sensitizing cervical cancer cells to the platinum-based chemotherapy.
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http://dx.doi.org/10.1038/s41419-021-04474-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688448PMC
December 2021

Implications of Isolated Para-Aortic Lymph Node Metastasis in Endometrial Cancer: A Large-Scale, Multicenter, and Retrospective Study.

Front Med (Lausanne) 2021 21;8:754890. Epub 2021 Oct 21.

Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

To systematically evaluate lymph node metastasis (LNM) patterns in patients with endometrial cancer (EC) who underwent complete surgical staging, which included systematic pelvic and para-aortic lymphadenectomy. Four thousand and one patients who underwent complete surgical staging including systematic pelvic and para-aortic lymphadenectomy for EC were enrolled from 30 centers in China from 2001 to 2019. We systematically displayed the clinical and prognostic characteristics of patients with various LNM patterns, especially the PLN-PAN+ [para-aortic lymph node (PAN) metastasis without pelvic lymph node (PLN) metastasis]. The efficacy of PAN+ (para-aortic lymph node metastasis) prediction with clinical and pathological features was evaluated. Overall, 431 of the 4,001 patients (10.8%) showed definite LNM according to pathological diagnosis. The PAN+ showed the highest frequency (6.6%) among all metastatic sites. One hundred fourteen cases (26.5%) were PLN-PAN+ (PAN metastasis without PLN metastasis), 167 cases (38.7%) showed PLN+PAN-(PLN metastasis without PAN metastasis), and 150 cases (34.8%) showed metastasis to both regions (PLN+PAN+). There was also 1.9% (51/2,660) of low-risk patients who had PLN-PAN+. There are no statistical differences in relapse-free survival (RFS) and disease-specific survival (DSS) among PLN+PAN-, PLN-PAN+, and PLN+PAN+. The sensitivity of gross PLNs, gross PANs, and lymphovascular space involvement (LVSI) to predict PAN+ was 53.8 [95% confidence interval (CI): 47.6-59.9], 74.2 95% CI: 65.6-81.4), and 45.8% (95% CI: 38.7-53.2), respectively. Over one-fourth of EC patients with LMN metastases were PLN-PAN+. PLN-PAN+ shares approximate survival outcomes (RFS and DSS) with other LNM patterns. No effective clinical methods were achieved for predicting PAN+. Thus, PLN-PAN+ is a non-negligible LNM pattern that cannot be underestimated in EC, even in low-risk patients.
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http://dx.doi.org/10.3389/fmed.2021.754890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566710PMC
October 2021

RIR1 represses plant immunity by interacting with mitochondrial complex I subunit in rice.

Mol Plant Pathol 2022 01 10;23(1):92-103. Epub 2021 Oct 10.

State Key Laboratory of Plant Genomics, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

We previously observed decreased expression of rice OsmiR159a.1 on infection with the bacterial blight-causing pathogen Xanthomonas oryzae pv. oryzae (Xoo), and identified the OsLRR_RLK (leucine-rich repeat_ receptor like kinase) gene as an authentic target of OsmiR159a.1. Here, we found that a Tos17 insertion mutant of LRR_RLK displayed increasing temporal resistance to Xoo, whereas the LRR_RLK overexpression lines were susceptible to the pathogen early on in the infection, indicating that LRR_RLK encodes a repressor of rice resistance to Xoo infection, and it was renamed as RIR1 (Rice Immunity Repressor 1). RIR1 overexpression plants were more susceptible to Xoo at late growth stage, suggesting that RIR1 mRNA levels are negatively correlated with the resistance of rice against Xoo. We discovered that OsmiR159a.1 repression in Xoo-infected plants was largely dependent on the pathogen's type III secretion system. Co-immunoprecipitation, bimolecular fluoresence complementation, and pull-down assays indicated that RIR1 interacted with the NADH-ubiquinone oxidoreductase (NUO) 51-kDa subunit of the mitochondrial complex I through its kinase domain. Notably, impairment of RIR1 or overexpression of NUO resulted in reactive oxygen species accumulation and enhanced expression of pathogen-resistance genes, including jasmonic acid pathway genes. We propose that pathogens may inhibit OsmiR159 to interfere with the RIR1-NUO interaction, and subsequently depression of rice immune signalling pathways. The resistance genes manipulated by Xoo can be a probe to explore the regulatory network during host-pathogen interactions.
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http://dx.doi.org/10.1111/mpp.13145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659553PMC
January 2022

Elevated CO levels alleviated toxicity of ZnO nanoparticles to rice and soil bacteria.

Sci Total Environ 2022 Jan 25;804:149822. Epub 2021 Aug 25.

State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210023, China. Electronic address:

Rising CO levels will change the behavior and toxicity of soil contaminants. However, it remains unclear whether elevated CO levels will change the nanoparticle dissolution or their biological effects in soil. In this study, we used a free-air CO enrichment system to examine the effects of elevated CO on phytotoxicity and bacterial toxicity of zinc oxide nanoparticles (nZnO) in a paddy soil system. The elevated CO changed the nZnO diffraction in soil, slightly increasing its dissolution but remarkably improving its bioavailability. Elevated CO did not change Zn accumulation in rice, but still alleviated the adverse effects of nZnO on rice growth, although grain protein, K and P decreased. Moreover, nZnO alone significantly decreased the number of observed soil bacterial species and altered the community organization, while elevated CO moderated such changes. Overall, these results increase our understanding of plant response and microbial variation in nanoparticle-contaminated soil under elevated-CO conditions. It is necessary to pay attention to soil pollution while facing climate change.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149822DOI Listing
January 2022

Application of conventional ultrasonography combined with contrast-enhanced ultrasonography in the axillary lymph nodes and evaluation of the efficacy of neoadjuvant chemotherapy in breast cancer patients.

Br J Radiol 2021 Sep;94(1125):20210520

Department of Breast Surgery, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Harbin, China.

Objective: Axillary lymph node status assessment has always been an important issue in clinical treatment of breast cancer. However, there has been no effective method to accurately predict the pathological complete response (pCR) of axillary lymph node after neoadjuvant chemotherapy (NAC). The objective of our study was to investigate whether conventional ultrasonography combined with contrast-enhanced ultrasonography (CEUS) can be used to evaluate axillary lymph node status of breast cancer patients after NAC.

Methods: A total of 74 patients who underwent NAC were recruited for the present study. Prior to and after NAC, examinations of conventional ultrasonography and CEUS were performed. After evaluating the images of conventional ultrasonography, four characteristics were recorded: lymph node medulla boundary, cortex of lymph node, lymph node hilus, and lymph node aspect ratio. Two additional imaging characteristics of CEUS were analyzed: CEUS way and CEUS pattern. Receiver operating characteristiccurve analysis was applied to evaluate their diagnostic performance.

Results: After 6~8 cycles of NAC, 46 (71.9%) patients had negative axillary lymph node, and 18 (28.1%) patients turned out non-pCR. According to statistical analysis, lymph node medulla, lymph node aspect ratio and CEUS way were independently associated with pCR of axillary lymph node after NAC. The area under the curve of the prediction model with three imaging characteristics was 0.882 (95% confidence interval: 0.608-0.958), and the accuracy to predict the patients' lymph node status was 78.1% ( < 0.01).

Conclusions: Conventional ultrasonography combined with CEUS technology can accurately predict axillary lymph nodes status of breast cancer patients after NAC.

Advances In Knowledge: The usefulness of CEUS technology in predicting pCR after neoadjuvant chemotherapy is highlighted.
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http://dx.doi.org/10.1259/bjr.20210520DOI Listing
September 2021

Efficacy and safety of photodynamic therapy mediated by 5-aminolevulinic acid for the treatment of cervical intraepithelial neoplasia 2: A single-center, prospective, cohort study.

Photodiagnosis Photodyn Ther 2021 Dec 1;36:102472. Epub 2021 Aug 1.

Department of Obstetrics and Gynecology, Peking University Third Hospital, 100191, 49 North Garden Rd., Haidian District, Beijing, China. Electronic address:

Background: Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (5-ALA) is a minimally-invasive treatment for cervical intraepithelial neoplasia (CIN). The present study was carried out to investigate the effect of 5-ALA-PDT on CIN2 and the factors influencing outcome of 5-ALA-PDT.

Methods: Patients diagnosed as CIN2 who met the inclusion criteria were enrolled in this study sequentially from January 2019 to April 2020. Patients were treated by PDT or cryotherapy according to their intentions. The primary endpoint was pathological regression. The secondary endpoint was HPV clearance. Affecting factors of the efficacy of PDT and adverse events were also assessed during treatment.

Results: A total of 210 patients were enrolled, including 97 patients in PDT group and 101 patients in cryotherapy group, with 12 patients excluded. There was no statistical difference in population characteristics. The pathological regression rate in PDT group was 92.0% (80/87), compared with 81.4% (79/97) in cryotherapy group (P < 0.05). The HPV clearance rate was 64.4% (56/87) in PDT group and 57.8% (56/97) in cryotherapy group (P = 0.36). The main side effects of PDT were abdominal pain (24.1%, 21/87) and increased vaginal secretions (23.0%, 20/87). On univariate analysis, the risk for lesions persisting at 6 months after PDT was increased by recurrent genital tract inflammation (P = 0.004), smoking or passive smoking (P = 0.020), and multicentric lesions (P = 0.020).

Conclusion: PDT can be a safe and efficient treatment for CIN2. Risk factors for persisting HSIL after PDT include recurrent genital tract inflammation, smoking or passive smoking, and multicentric lesions.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102472DOI Listing
December 2021

Integrative Analysis of Differently Expressed Genes Reveals a 17-Gene Prognosis Signature for Endometrial Carcinoma.

Biomed Res Int 2021 14;2021:4804694. Epub 2021 Jul 14.

Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, China.

Endometrial carcinoma (EC) is the fifth widely occurring malignant neoplasm among women all over the world. However, there is still lacking efficacy indicators for EC's prognosis. Here, we analyzed two databases including an RNA-sequencing-based TCGA dataset and a microarray-based GSE106191. After normalizing the raw data, we identified 114 common genes with upregulation and 308 common genes with downregulation in both the TCGA and GSE106191 databases. Bioinformatics analysis showed that the differently expressed genes in EC were related to the IL17 signaling pathway, PI3K-Akt signaling pathway, and cGMP-PKG signaling pathway. Furthermore, we performed the least absolute shrinkage and selection operator (LASSO) Cox regression analysis and generated a signature featuring 17 prognosis-related genes (MAL2, ANKRD22, METTL7B, IL32, ERFE, OAS1, TRPC1, SRPX, RAPGEF4, PSD3, SIMC1, TRPC6, WFS1, PGR, PAMR1, KCNK6, and FAM189A2) and found that it could predict OS in EC patients. The further analysis showed that OAS1, MAL2, ANKRD22, METTL7B, and IL32 were significantly upregulated in EC samples after comparison with normal samples. However, TRPC1, SRPX, RAPGEF4, PSD3, SIMC1, TRPC6, WFS1, PGR, PAMR1, KCNK6, and FAM189A2 were significantly downregulated in EC samples in comparison with normal samples. And correlation analysis showed that our results showed that the expressions of 17 prognosis-related hub genes were significantly correlated based on Pearson correlation. We here offer a newly genetic biomarker for the prediction of EC patients' prognosis.
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http://dx.doi.org/10.1155/2021/4804694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298166PMC
September 2021

Middle Cerebral Artery-to-Uterine Artery Pulsatility Index Ratio and Cerebroplacental Ratio Independently Predict Adverse Perinatal Outcomes in Pregnancies at Term.

Ultrasound Med Biol 2021 10 27;47(10):2903-2909. Epub 2021 Jul 27.

Department of Gynecology and Obstetrics, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, China. Electronic address:

This study aimed to investigate potential predictors, including the cerebroplacental ratio and the middle cerebral artery (MCA)-uterine artery pulsatility index (PI) ratio, for adverse perinatal outcomes in pregnancies at term. This was an observational, prospective study of recruited pregnancies at term. The data were extracted from the medical records in hospital. An adverse perinatal outcome was set as the primary observational endpoint. The receiver operating characteristic curve was plotted to investigate the predictive and cutoff values of risk factors for adverse perinatal outcomes. Univariate and multivariate logistic regression analyses evaluated independent risk factors (maternal, neonatal, prenatal ultrasound and Doppler variables) for adverse perinatal outcomes. There were 392 pregnancies at term included in the study, with 19.4% experiencing adverse perinatal outcomes. The MCA-uterine artery PI ratio was a good predictor of adverse perinatal outcomes by receiver operating characteristic curve analysis (area under the curve = 0.886, p < 0.001), and the cerebroplacental ratio (odds ratio, 0.42; 95% confidence interval, 0.20-0.93; p = 0.032) and MCA-uterine artery PI ratio (odds ratio, 0.25; 95% confidence interval, 0.16-0.42; p = 0.032) were two independent risk factors for adverse perinatal outcomes by univariate and multivariate logistic regression analyses. Notably, both MCA-uterine artery PI ratio and cerebroplacental ratio are significant predictors of adverse perinatal outcome in pregnancies at term.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.06.015DOI Listing
October 2021
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