Glutathione and neodiosmin feedback sustain plant immunity.

Plants have evolved a two-layer immune system comprising pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) that is activated in response to pathogen invasion. Microbial patterns and pathogen effectors can be recognized by surface-localized pattern-recognition receptors (PRRs) and intracellularly localized nucleotide-binding leucine-rich repeat receptors (NLRs) to trigger PTI and ETI responses, respectively. At present, the metabolites activated by PTI and ETI and their roles and signalling pathways in plant immunity are not well understood. In this study, metabolomic analysis showed that ETI and PTI induced various flavonoids and amino acids and their derivatives in plants. Interestingly, both glutathione and neodiosmin content were specifically up-regulated by ETI and PTI, respectively, which significantly enhanced plant immunity. Further studies showed that glutathione and neodiosmin failed to induce a plant immune response in which PRRs/co-receptors were mutated. In addition, glutathione-reduced mutant gsh1 analysis showed that GSH1 is also required for PTI and ETI. Finally, we propose a model in which glutathione and neodiosmin are considered signature metabolites induced in the process of ETI and PTI activation in plants and further continuous enhancement of plant immunity in which PRRs/co-receptors are needed. This model is beneficial for an in-depth understanding of the closed-loop mode of the positive feedback regulation of PTI and ETI signals at the metabolic level.

Microbial volatile organic compounds 2-heptanol and acetoin control Fusarium crown and root rot of tomato.

Some microbial volatile organic compounds (mVOCs) can act as antagonistic weapons against plant pathogens, but little information is available on the contribution of individual mVOC to biocontrol and how they interact with plant pathogens. In this study, the Bacillus subtilis strain N-18 isolated from the rhizosphere of healthy plants grown in areas where Fusarium crown and root rot (FCRR) of tomato occurs could reduce the 30% of the incidence of FCRR. Moreover, the volatile organic compounds (VOCs) produced by N-18 had inhibitory effects on Fusarium oxysporum f. sp. radicis-lycopersici (FORL). The identification of VOCs of N-18 was analyzed by the solid-phase microextraction coupled to gas chromatography-mass spectrometry. Meanwhile, we conducted sensitivity tests with these potential active ingredients and found that the volatile substances acetoin and 2-heptanol can reduce the 41.33% and 35% of the incidence of FCRR in tomato plants. In addition, the potential target protein of acetoin, found in the cheminformatics and bioinformatics database, was F. oxysporum of hypothetical protein AU210_012600 (FUSOX). Molecular docking results further predicted that acetoin interacts with FUSOX protein. These results reveal the VOCs of N-18 and their active ingredients in response to FORL and provide a basis for further research on regulating and controlling FCRR.

Effect of Coated Diammonium Phosphate Combined with Paecilomyces variotii Extracts on Soil Available Nutrients, Photosynthesis-Related Enzyme Activities, Endogenous Hormones, and Maize Yield.

Coated diammonium phosphate (CDAP) is intended to release nutrients steadily in response to the demand of crop growth. A novel biostimulant extracted from Paecilomyces variotii has been shown to regulate gene expression in nutrient transport, enhance nitrogen (N) and phosphorus (P) uptake, and improve nutrient use efficiency. The application of CDAP combined with the Paecilomyces variotii extracts (ZNC) in maize is an efficient approach for reducing waste of resources, improving nutrient supply, and maintaining production stability. The effects of CDAP combined with ZNC on photosynthesis, enzyme activities, endogenous hormone content, maize yield, and P use efficiency (PUE) were investigated in this study. In a pot experiment, CDAP and diammonium phosphate (DAP) were tested together with P levels (1.80, 1.44 g pot-1, P2O5) and two ZNC application rates (0, 4.4 µg pot-1), which included the control treatment that had no P fertilizer added. Results showed that the key influencing elements of maize growth and yield were the soil available-P content, endogenous hormone content, and plant photosynthesis in this study. The combination of DAP and ZNC increased the soil available-P content and the auxin content in leaves at the key stage and hence increased the yield and PUE of maize, compared with DAP. The net photosynthetic rate of CDAP combined with ZNC was higher by 23.1% than that of CDAP alone, as well as by 32.0% than that of DAP combined with ZNC. Moreover, the combination of CDAP and ZNC increased the yield and PUE by 8.2% and 15.6 percentage points compared with DAP combined with ZNC while increasing the yield and PUE compared with CDAP. In conclusion, combining CDAP with ZNC as an environmentally friendly fertilizer could improve photosynthesis-related enzyme activity and enhance the net photosynthetic rate, resulting in an increase in maize yield and PUE significantly.

Circ_RPL23A acts as a miR-1233 sponge to suppress the progression of clear cell renal cell carcinoma by promoting ACAT2.

Clear cell renal cell carcinoma (ccRCC) is a prevalent urological carcinoma with high metastatic risk. Circular RNAs (circRNAs) have been identified as effective diagnostic and therapeutic biomarkers for ccRCC. This research aims to disclose the effect and regulatory mechanism of circRNA ribosomal protein L23a (circ_RPL23A) in ccRCC. We performed quantitative real-time polymerase chain reaction (qRT-PCR) to examine circ_RPL23A, microRNA-1233 (miR-1233) and acetyl-coenzyme A acetyltransferase 2 (ACAT2). Cell cycle progression, apoptosis, cell viability, invasion and migration, which were respectively conducted by using flow cytometry, 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT), transwell assays. The levels of ACAT2 protein and cell cycle proteins, proliferation-associated protein, and epithelial-mesenchymal transition (EMT) associated proteins were measured by western blot. Target relationship was analyzed via dual-luciferase reporter assay and RNA pull down assay. The animal model was used to study how circ_RPL23A affects in vivo. Circ_RPL23A was lower expressed in ccRCC tissues and cells. The elevated circ_RPL23A suppressed cell cycle progression, proliferation, migration and invasion but promoted apoptosis in ccRCC cells. MiR-1233 was a target of circ_RPL23A and direct targeted to ACAT2. Besides, circ_RPL23A exerted its anti-tumor effect by sponging miR-1233, and then relieved the inhibition effect of miR-1233 on ACAT2. Overexpression of circ_RPL23A also curbed ccRCC tumor growth in vivo. Circ_RPL23A inhibited ccRCC progression by upregulating ACAT2 expression by competitively binding miR-1233, which might provide an in-depth cognition for ccRCC pathogenesis and circ_RPL23A might be a promising biomarker in ccRCC diagnosis and treatment.

Suppressive effect of platycodin D on bladder cancer through microRNA-129-5p-mediated PABPC1/PI3K/AKT axis inactivation.

Platycodin D (PD) is a major constituent of Platycodon grandiflorum and has multiple functions in disease control. This study focused on the function of PD in bladder cancer cell behaviors and the molecules involved. First, we administered PD to the bladder cancer cell lines T24 and 5637 and the human uroepithelial cell line SV-HUC-1. Cell viability and growth were evaluated using MTT, EdU, and colony formation assays, and cell apoptosis was determined using Hoechst 33342 staining and flow cytometry. The microRNAs (miRNAs) showing differential expression in cells before and after PD treatment were screened. Moreover, we altered the expression of miR-129-5p and PABPC1 to identify their functions in bladder cancer progression. We found that PD specifically inhibited the proliferation and promoted the apoptosis of bladder cancer cells; miR-129-5p was found to be partially responsible for the cancer-inhibiting properties of PD. PABPC1, a direct target of miR-129-5p, was abundantly expressed in T24 and 5637 cell lines and promoted cell proliferation and suppressed cell apoptosis. In addition, PABPC1 promoted the phosphorylation of PI3K and AKT in bladder cancer cells. Altogether, PD had a concentration-dependent suppressive effect on bladder cancer cell growth and was involved in the upregulation of miR-129-5p and the subsequent inhibition of PABPC1 and inactivation of PI3K/AKT signaling.

Role of microRNA-381 in bladder cancer growth and metastasis with the involvement of BMI1 and the Rho/ROCK axis.

BACKGROUND: Emerging evidence has noted the important participation of microRNAs (miRNAs) in several human diseases including cancer. This research was launched to probe the function of miR-381 in bladder cancer (BCa) progression. METHODS: Twenty-eight patients with primary BCa were included in this study. Cancer tissues and the adjacent normal tissues were obtained. Aberrantly expressed miRNAs in BCa tissues were analyzed using miRNA microarrays. miR-381 expression in the bladder and paired tumor tissues, and in BCa and normal cell lines was determined. The target relationship between miR-381 and BMI1 was predicted online and validated through a luciferase assay. Gain-of-functions of miR-381 and BMI1 were performed to identify their functions on BCa cell behaviors as well as tumor growth in vivo. The involvement of the Rho/ROCK signaling was identified. RESULTS: miR-381 was poor regulated in BCa tissues and cells (all p < 0.05). A higher miR-381 level indicated a better prognosis of patients with BCa. Artificial up-regulation of miR-381 inhibited proliferation, invasion, migration, resistance to apoptosis, and tumor formation ability of BCa T24 and RT4 cells (all p < 0.05). miR-381 was found to directly bind to BMI1 and was negatively correlated with BMI1 expression. Overexpression of BMI1 partially blocked the tumor suppressing roles of miR-381 in cell malignancy and tumor growth (all p < 0.05). In addition, miR-381 led to decreased RhoA phosphorylation and ROCK2 activation, which were also reversed by BMI1 (all p < 0.05). Artificial inhibition of the Rho/ROCK signaling blocked the functions of BMI1 in cell growth and metastasis (all p < 0.05). CONCLUSION: The study evidenced that miR-381 may act as a beneficiary biomarker in BCa patients. Up-regulation of miR-381 suppresses BCa development both in vivo and in vitro through BMI1 down-regulation and the Rho/ROCK inactivation.

Suppressive effect of platycodin D on bladder cancer through microRNA-129-5p-mediated PABPC1/PI3K/AKT axis inactivation

Platycodin D (PD) is a major constituent of Platycodon grandiflorum and has multiple functions in disease control. This study focused on the function of PD in bladder cancer cell behaviors and the molecules involved. First, we administered PD to the bladder cancer cell lines T24 and 5637 and the human uroepithelial cell line SV-HUC-1. Cell viability and growth were evaluated using MTT, EdU, and colony formation assays, and cell apoptosis was determined using Hoechst 33342 staining and flow cytometry. The microRNAs (miRNAs) showing differential expression in cells before and after PD treatment were screened. Moreover, we altered the expression of miR-129-5p and PABPC1 to identify their functions in bladder cancer progression. We found that PD specifically inhibited the proliferation and promoted the apoptosis of bladder cancer cells; miR-129-5p was found to be partially responsible for the cancer-inhibiting properties of PD. PABPC1, a direct target of miR-129-5p, was abundantly expressed in T24 and 5637 cell lines and promoted cell proliferation and suppressed cell apoptosis. In addition, PABPC1 promoted the phosphorylation of PI3K and AKT in bladder cancer cells. Altogether, PD had a concentration-dependent suppressive effect on bladder cancer cell growth and was involved in the upregulation of miR-129-5p and the subsequent inhibition of PABPC1 and inactivation of PI3K/AKT signaling.

Effects of wogonoside on the inflammatory response and oxidative stress in mice with nonalcoholic fatty liver disease.

CONTEXT: Wogonoside has many pharmacological activities, but whether it has a protective effect against non-alcoholic fatty liver disease (NAFLD) has not been reported. OBJECTIVE: This study investigates the protective effect of wogonoside against NAFLD in mice and its potential mechanism. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into control group, NAFLD group and low-, medium- and high-dose wogonoside groups (5, 10 and 20 mg/kg, respectively) (n= 12). Mice in the control group were fed with the standard diet, and those in NAFLD group and low-, medium- and high-dose wogonoside groups were fed with a high-fat diet. The different doses of wogonoside were administered by gavage once a day for 12 weeks. RESULTS: Compared with those in NAFLD group, the liver mass, liver index and the LDL, TG, TC, IL-2, IL-6, TNF-α, MDA and NF-κB p65 levels were decreased, and the SOD and GSH-Px activities, and HDL, IκBα, Nrf2 and HO-1 contents were increased in wogonoside groups. Compared with those in the NAFLD group, wogonoside (5, 10 and 20 mg/kg) reduced AST (132.21 ± 14.62, 115.70 ± 11.32 and 77.94 ± 8.86 vs. 202.35 ± 19.58 U/L) and ALT (104.37 ± 11.92, 97.53 ± 10.12 and 56.74 ± 6.33 vs. 154.66 ± 14.23 U/L) activities in the serum. DISCUSSION AND CONCLUSIONS: Wogonoside has a protective effect against NAFLD in mice, which may be related to its anti-inflammation and inhibition of oxidative stress, suggesting that wogonoside may be a potential therapeutic agent for the treatment of NAFLD.

Humanistic care and psychological counseling on psychological disorders in medical students after COVID-19 outbreak: A protocol of systematic review.

BACKGROUND: The objective of this study is to investigate the effects of humanistic care and psychological counseling (HCPC) on psychological disorders (PD) in medical students after coronavirus disease 2019 (COVID-19) outbreak. METHODS: We will search randomized controlled trials or case-controlled studies of HCPC on PD in medical students after COVID-19 outbreak in the following electronic databases: PUBMED/MEDLINE, EMBASE, Cochrane Library, CINAHL, AMED, WANGFANG, and CNKI. The time is restricted from the construction of each database to the present. All process of study selection, data collection, and study quality evaluation will be carried out by two independent authors. Any different opinions will be solved by a third author through discussion. We will employ RevMan 5.3 software to conduct statistical analysis. RESULTS: This study will provide a better understanding of HCPC on PD in medical students after COVID-19 outbreak. CONCLUSIONS: This study may offer strong evidence for clinical practice to treat PD in medical students after COVID-19 outbreak. STUDY REGISTRATION: CRD42020193199.

Platycodin D (PD) regulates LncRNA-XIST/miR-335 axis to slow down bladder cancer progression in vitro and in vivo.

Recently, increasing evidences indicated that Platycodin D (PD) served as an effective anti-tumor drug for cancer treatment in clinic. However, the molecular mechanisms are still unclear. In the present study, we proved that PD regulated LncRNA-XIST/miR-335 axis to hamper the development of bladder cancer in vitro and in vivo. Mechanistically, PD inhibited malignant phenotypes, including cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in bladder cancer cells in a time- and dose-dependent manner. In addition, the following experiments validated that PD inhibited LncRNA-XIST expressions, while increased miR-335 expression levels in bladder cancer cells. Next, by conducting the dual-luciferase reporter gene system assay and RNA pull-down assay, we validated that LncRNA-XIST inhibited miR-335 expressions through acting as RNA sponges, and the promoting effects of PD stimulation on miR-335 levels were abrogated by upregulating LncRNA-XIST. Interestingly, both silencing LncRNA-XIST and miR-335 overexpression enhanced the inhibiting effects of PD on the malignant phenotypes in bladder cancer cells. Consistently, the xenograft tumor-bearing mice models were established, and the data indicated that PD slowed down tumor growth and inhibited tumorigenesis in vivo, which were also aggravated by downregulating LncRNA-XIST. In general, analysis of data proved that targeting LncRNA-XIST/miR-335 axis was novel to enhance the anti-tumor effects of PD in bladder cancer in vitro and in vivo, and this study provided alternative therapeutic strategies for bladder cancer treatment in clinic.

A protocol of systematic review and meta-analysis of neuromuscular electrical stimulation for interstitial cystitis.

BACKGROUND: This study will examine the effectiveness and safety of neuromuscular electrical stimulation (NMES) for the treatment of patients with interstitial cystitis (IC). METHODS: We will retrieve the following electronic databases from their commencements to the March 1, 2020 to discover all related potential studies: MEDLINE, EMBASE, Cochrane Library, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and WANFANG Database. Randomized controlled trials related to the NMES for the treatment of patients with IC will be included, regardless publication status and language. Literature selection, data collection, and study quality assessment will be independently performed by 2 authors. The extracted data will be expressed as risk ratio and 95% confidence intervals for dichotomous data, and mean difference or standard mean difference and 95% confidence intervals for continuous data. RevMan V.5.3 software will be employed for statistical analysis. RESULTS: This study will summarize current high quality randomized controlled trials to appraise the effectiveness and safety of NMES for the treatment of patients with IC. CONCLUSION: The findings of this study will provide helpful evidence to determine whether NMES is an effective treatment for patients with IC or not. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020170495.

Can docetaxel combined prednisone effectively treat hormone refractory prostate cancer?: A protocol of systematic review and meta-analysis.

BACKGROUND: Previous studies have reported that docetaxel combined prednisone (DP) has been used for the treatment of patients with hormone refractory prostate cancer (HRPC). However, its results are still inconsistent. Therefore, this study will synthesize the latest evidence of the efficacy and safety of DP for the treatment of patients with HRPC. METHODS: Cochrane Library, PUBMED, EMBASE, Web of Science, CINAHL, CBM, and CNKI will be searched to identify randomized controlled trials published from their inception to the March 1, 2020, irrespective language and publication time restrictions. We will calculate the pooled effects of dichotomous outcomes as risk ratio and 95% confidence intervals, and that of continuous outcomes as standardized mean difference or mean difference and 95% confidence intervals. Study quality will be assessed using Cochrane risk of bias, and quality of evidence for main outcome will be evaluated using Grading of Recommendations Assessment Development and Evaluation. Statistical analysis will be performed using RevMan 5.3 software. RESULTS: This study will appraise the efficacy and safety of DP for the treatment of patients with HRPC. The primary outcome includes overall survival, and the secondary outcomes comprise of progression-free survival, prostate-specific antigen response rate, duration of prostate-specific antigen response, objective tumor response rate, disease-free survival, quality of life, and adverse events. CONCLUSION: The results of this study may provide helpful evidence of DP for the treatment of patients with HRPC.Systematic review registration: INPLASY202040112.

Efficacy of pirarubicin for nonmuscle invasive bladder cancer: A protocol of systematic review and meta-analysis.

BACKGROUND: This study will aim to appraise the efficacy and safety of pirarubicin for the treatment of patients with nonmuscle invasive bladder cancer (NMIBC). METHODS: We will perform a comprehensive literature search in MEDLINE, EMBASE, Cochrane Library, Scopus, PsycINFO, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from their beginning to the February 29, 2020. All randomized controlled trials of pirarubicin for NMIBC will be included regardless limitations related to the language and publication time. Two researchers will independently select studies from searched records, extract data from included randomized controlled trials, and assess study quality using Cochrane risk of bias tool. Any differences between them will be solved with the help of another researcher. RevMan 5.3 software will be utilized for statistical analysis. RESULTS: This study will provide a synthesis of current evidence to investigate the efficacy and safety of pirarubicin for NMIBC using overall survival, progression-free survival, recurrence-free survival, quality of, rates of recurrence, and adverse events. CONCLUSION: This study will explore whether or not pirarubicin can be used as an effective and safety treatment for patients with NMIBC. REGISTRATION NUMBER: INPLASY202040113.

Identifying the mRNAs associated with Bladder cancer recurrence.

OBJECTIVE: To identify the mRNAs associated with bladder cancer (BC) recurrence. METHODS: The transcription profile of GSE31684 including 39 recurrent BC tumor samples and 54 non-recurrent BC tumor samples as well as transcription profile of GSE13507 including 36 recurrent BC tumor samples and 67 non-recurrent BC tumor samples were downlaoded from the Gene Expression Omnibus. Then, the differentially expressed genes (DEGs) were identified using linear models for microarray data (limma) and the intersections of DEGs from the two datasets were further screened. The weighed gene co-expression network analysis (WGCNA) was used to screen the modules related to BC recurrence. Protein-protein interaction (PPI) network analysis was used to analyze the genes interaction. Their functions were predicted by Gene Ontology and KEGG pathway enrichment. Moreover, The Comparative Toxicogenomics Database 2017 update (CTD) was used to search the BC related pathway. The univariate cox regression analysis was used to identify DEGs associated to the recurrence. Kaplan-Meier plots were used to illustrate recurrence free survival time (RFS). RESULTS: A total of 692 intersections DEGs were screened. WGCNA showed that 7 modules (2279 genes) were stable in both the datasets. A total of 169 intersection DEGs were mapped to the 7 modules. There existed 149 interaction relationships among 81 proteins (18 down-regulated and 63 up-regulated DEGs) in the PPI network. Two KEGG pathways including Focal adhesion and ECM-receptor interaction were enriched which were also found in the CTD. The univariate cox regression analysis showed that 3 DEGs (COL4A1, COL1A2 and COL5A1) were significant related to the prognosis. Multivariate cox regression analysis revealed that pathologic_N (N0-N1 vs N2-N3, p= 0.033) were independent prognostic factors for overall survival in patients with BC. CONCLUSION: COL4A1, COL1A2 and COL5A1 could be associated with BC recurrence.

[Effects of plasma Hcy on the contents of CO and HO-2 in the corpus cavernosum of ED rats with hyperhomocysteinemia].

OBJECTIVE: To study the changes in the activities of carbon monoxide (CO) and heme oxygenase 2 (HO-2) in ED rats with hyperhomocysteinemia (HHcy). METHODS: This study included 40 male Wistar rats weighing 280 - 310 g, 10 as normal controls (group A). HHcy models were made in the other 30 by giving 3% methionine for 4 weeks, and then divided into groups B, C and D. The rats in group B continued to be fed with 3% methionine, those in group C were treated with betaine hydrochloride, and those in group D were given zinc porphyrin IX at 45 micromol per kg per d. Penile erections of the rats were recorded, and 4 weeks later, all were killed for determination of the levels of homocysteine (Hcy) in the blood plasma and the activities of CO and HO-2 in the corpus cavernosum of the penis. RESULTS: The level of plasma Hcy, penile erection frequency and the content of CO in the corpus cavernosum were (12.55 +/- 0.82) micromol/L, (1.88 +/- 0.05) times and (10.55 +/- 1.73) micromol/L in group A, the Hcy level significantly higher while the penile erection frequency and CO content remarkably lower than in group B ([25.01 +/- 0.94] micromol/L, [0.70 +/- 0.05] times and [9.51 +/- 1.52] micromol/L, P < 0.05 or P < 0.01), with a negative correlation between the level of Hcy and that of CO and HO-2 (P < 0.01). Compared with group B, the three parameters were all significantly increased in C ([14.37 +/- 0.47] micromol/L, [1.18 +/- 0.08] times and [10.36 +/- 1.56] micromol/L, all P < 0.05 or P < 0.01). CONCLUSION: Decreased expressions of CO and HO-2 in the corpus cavernosum of the penis may result in ED in HHcy rats. Betaine can reduce the Hcy level in the blood plasma and CO content in the corpus cavernosum, which might be one of the mechanisms of its action on ED with HHcy.

[Effects of high- and low temperature stress on the leaf PSII functions and physiological characteristics of tree peony (Paeonia suffruticosa cv. 'Roufurong')].

Taking the detached leaves of tree peony (Paeonia suffruticosa cv. 'Roufurong') as test materials, this paper studied the effects of high temperature (40 degrees C) and low temperature (15 degrees C) stresses on the PS II functions and physiological characteristics of peony leaves under strong light intensity (1400 micromol x m(-2) x s(-1)), with 25 degrees C as the control. With the increasing time of high- and low temperature stress, the maximal photochemical efficiency (Fv/Fm), actual quantum yield of photosystem II (Phi(PS II)) , and efficiency of excitation capture of open PS II center (Fv'/Fm') all decreased continuously. After recovered in the dark for 4 hours, the Fv/Fm in treatments 15 degrees C and 25 degrees C quickly recovered, but that in treatment 40 degrees C only recovered to 75.5% of non-treatment, even if the leaves were treated in the dark for 15 hours. At 40 degrees C, the balance of excited energy between PS I and PS II under strong light intensity was perturbed seriously. Treatment 40 degrees C inhibited the superoxide dismutase (SOD) activity, enhanced the production of O2-, H2O2, and MDA, and reduced the contents of chlorophyll and soluble protein. This study revealed that strong light combined with high temperature impaired the photosynthetic apparatus of the tree peony irreversibly, whereas strong light plus low temperature had weaker impact.