Sulforaphane-Enriched Extracts from Broccoli Exhibit Antimicrobial Activity against Plant Pathogens, Promising a Natural Antimicrobial Agent for Crop Protection.

Sulforaphane (SFN) is one of the hydrolysates of glucosinolates (GSLs), primarily derived from Brassica vegetables like broccoli. In clinical therapy, SFN has been proven to display antimicrobial, anticancer, antioxidant, and anti-inflammatory properties. However, the antimicrobial effects and mechanism of SFN against plant pathogens need to be further elucidated, which limits its application in agriculture. In this study, the genetic factors involved in SFN biosynthesis in 33 B. oleracea varieties were explored. The finding showed that besides the genetic background of different B. oleracea varieties, myrosinase and ESP genes play important roles in affecting SFN content. Subsequently, the molecular identification cards of these 33 B. oleracea varieties were constructed to rapidly assess their SFN biosynthetic ability. Furthermore, an optimized protocol for SFN extraction using low-cost broccoli curds was established, yielding SFN-enriched extracts (SFN-ee) containing up to 628.44 µg/g DW of SFN. The antimicrobial activity assay confirmed that SFN-ee obtained here remarkably inhibit the proliferation of nine tested microorganisms including four plant pathogens by destroying their membrane integrity. Additionally, the data demonstrated that exogenous application of SFN-ee could also induce ROS accumulation in broccoli leaves. These results indicated that SFN-ee should play a dual role in defense against plant pathogens by directly killing pathogenic cells and activating the ROS signaling pathway. These findings provide new evidence for the antimicrobial effect and mechanism of SFN against plant pathogens, and suggest that SFN-ee can be used as a natural plant antimicrobial agent for crop protection and food preservation.

Trends of ischemic heart disease mortality attributable to smoking in the five countries with the highest number of smokers during 1990-2019: an age-period-cohort analysis.

Introduction: Smoking increases the risk of various cardiovascular diseases, including ischemic heart disease (IHD). This study aimed to assess the impact of age, period, and cohort on long-term trends in IHD mortality in China, India, Indonesia, the United States, and Russia, the five countries with the highest number of smokers, from 1990 to 2019. Material and methods: The data were obtained from the Global Burden of Disease (GBD) Study 2019, and the age-standardized mortality rate (ASMR) was calculated. Joinpoint regression analysis was used to assess the magnitude and direction of trends in smoking-attributable mortality from IHD. Age-period-cohort (APC) studies were used to estimate net drift (estimated annual percentage change (EAPC)s), local drift (age-specific EAPCs), and independent trends in age, period, and cohort effects. Results: The analysis revealed a significant downward trend in ASMRs attributable to IHD as a result of smoking in the United States, India, and Russia. Indonesia and China showed an upward trend. Age effects were increasing for both country and sex, with China showing the most significant increase in the older age group; period effects were decreasing in all countries except Indonesia, and cohort effects were increasing only in Indonesia and China. Conclusions: From 1990 to 2019, mortality from IHD caused by smoking showed a downward trend in these five countries. However, the pattern of increased mortality from IHD in women caused by smoking warrants further study.

Effect of Mifepristone vs Placebo for Treatment of Adenomyosis With Pain Symptoms: A Randomized Clinical Trial.

Importance: Adenomyosis is a common chronic gynecological disorder, and its treatment is an unmet need. New therapies need to be developed. Mifepristone is being tested for adenomyosis treatment. Objective: To determine whether mifepristone is effective and safe for adenomyosis treatment. Design, Setting, and Participants: This multicenter, placebo-controlled, double-blind randomized clinical trial was conducted in 10 hospitals in China. In total, 134 patients with adenomyosis pain symptoms were enrolled. Trial enrollment began in May 2018 and was completed in April 2019, and analyses were conducted from October 2019 to February 2020. Interventions: Participants were randomized 1:1 to receive mifepristone 10 mg or placebo orally once a day for 12 weeks. Main Outcomes and Measures: The primary end point was the change in adenomyosis-associated dysmenorrhea intensity, evaluated by the visual analog scale (VAS) after 12 weeks of treatment. Secondary end points included the change in menstrual blood loss, increased level of hemoglobin in patients with anemia, CA125 level, platelet count, and uterine volume after 12 weeks of treatment. Safety was assessed according to adverse events, vital signs, gynecological examinations, and laboratory evaluations. Results: In total, 134 patients with adenomyosis and dysmenorrhea were randomly assigned, and 126 patients were included in the efficacy analysis, including 61 patients (mean [SD] age, 40.2 [4.6] years) randomized to receive mifepristone and 65 patients (mean [SD] age, 41.7 [5.0] years) randomized to received the placebo. The characteristics of the included patients at baseline were similar between groups. The mean (SD) change in VAS score was -6.63 (1.92) in the mifepristone group and -0.95 (1.75) in the placebo group (P < .001). The total remission rates for dysmenorrhea in the mifepristone group were significantly better than those in the placebo group (effective remission: 56 patients [91.8%] vs 15 patients [23.1%]; complete remission: 54 patients [88.5%] vs 4 patients [6.2%]). All the secondary end points showed significant improvements after mifepristone treatment for menstrual blood loss, hemoglobin (mean [SD] change from baseline: 2.13 [1.38] g/dL vs 0.48 [0.97] g/dL; P < .001), CA125 (mean [SD] change from baseline: -62.23 [76.99] U/mL vs 26.89 [118.70] U/mL; P < .001), platelet count (mean [SD] change from baseline: -28.87 [54.30]×103/µL vs 2.06 [41.78]×103/µL; P < .001), and uterine volume (mean [SD] change from baseline: -29.32 [39.34] cm3 vs 18.39 [66.46] cm3; P < .001). Safety analysis revealed no significant difference between groups, and no serious adverse events were reported. Conclusions and Relevance: This randomized clinical trial showed that mifepristone could be a new option for treating patients with adenomyosis, based on its efficacy and acceptable tolerability. Trial Registration: ClinicalTrials.gov Identifier: NCT03520439.

Clinical efficacy of traditional Chinese medicine therapy for female stress urinary incontinence: a meta-analysis / Eficácia clínica da terapia da medicina tradicional chinesa para a incontinência urinária de esforço feminina: uma meta-análise / Eficacia clínica de la terapia de medicina tradicional china para la incontinencia urinaria de esfuerzo femenina: un metaanálisis

ABSTRACT Objectives: To investigate the efficacy of traditional Chinese medicine (TCM) in the treatment of female stress urinary incontinence (SUI). Method: PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang, and VIP databases were searched for articles published up to September 2022. Variables were analyzed using weighted mean difference (WMD), standardized mean difference (SMD), odds ratios (OR), and 95% confidence interval (CI). Results: Eight studies containing 744 patients were included in this study. The results demonstrate that TCM therapy had more advantages in improving the clinical outcome of SUI patients (OR = 2.90, 95%CI:1.92-4.37, P = 0.000), reducing the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) score (WMD = -2.41, 95%CI:-2.83- -1.98, P = 0.000), reducing 1-h urinary pad leakage urine volume (WMD = -1.86, 95%CI:-2.23- -1.49, P = 0.000) and increasing Maximum urethral closure pressure (MUCP) (SMD = 0.86, 95%CI: 0.61-1.11, P = 0.000). Conclusion: TCM therapy is effective in improving urinary incontinence symptoms, urodynamics, and quality of life in patients with SUI. This article provides a reference for the application of TCM therapy in women with urinary incontinence.

RESUMEN Objetivo: Investigar la eficacia de la medicina tradicional china (MTC) en el tratamiento de la incontinencia urinaria de esfuerzo (IUE) femenina. Método: Se llevaron a cabo búsquedas de artículos publicados hasta septiembre de 2022 en las bases de datos PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang y VIP. Las variables se analizaron mediante la diferencia de medias ponderada (DMP), la diferencia de medias estandarizada (DME), la razón de momios (RM) y el intervalo de confianza (IC) del 95%. Resultados: Este estudio incluyó ocho investigaciones con la participación de 744 pacientes. Los resultados indican que la terapia de medicina tradicional china (MTC) presentó mejoras significativas en los resultados clínicos de pacientes con incontinencia urinaria de esfuerzo (IUE) (RM = 2.90, IC del 95%: 1.92-4.37, P = 0.000), al reducir la puntuación del Cuestionario Internacional sobre la Incontinencia y su impacto en la calidad de vida (ICIQ-SF) (DMP = -2.41, IC del 95%: -2.83- -1.98, P = 0.000), así como la disminución del volumen de orina a la 1 hora de fuga de la almohadilla urinaria (DMP = -1.86, IC del 95%: -2.23- -1.49, P = 0.000) y el aumento de la presión de cierre uretral máxima (PCUM) (DME = 0.86, IC del 95%: 0.61-1.11, P = 0.000). Conclusión: La terapia de medicina tradicional china (MTC) resulta efectiva en la mejora de los síntomas de la incontinencia urinaria, la urodinámica y la calidad de vida en pacientes con incontinencia urinaria de esfuerzo (IUE). Este artículo ofrece una referencia para la aplicación de la terapia de MTC en mujeres con incontinencia urinaria.

RESUMO Objetivo: Investigar a eficácia da medicina tradicional chinesa (MTC) no tratamento da incontinência urinária de esforço (IUE) feminina. Método: Foram realizadas pesquisas de artigos publicados até setembro de 2022 nas bases de dados PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang e VIP. As variáveis foram analisadas por meio da diferença de média ponderada (DMP), da diferença média padronizada (DMP), da razão de chances (RC) e do intervalo de confiança (IC) de 95%. Resultados: Esta pesquisa envolveu oito estudos, contando com a participação de 744 pacientes. Os resultados indicam que a terapia da medicina tradicional chinesa (MTC) apresentou melhorias significativas nos resultados clínicos de pacientes com incontinência urinária de esforço (IUE) (RM = 2.90, IC de 95%: 1.92-4.37, P = 0.000), ao reduzir a pontuação do Questionário Internacional sobre a Incontinência Urinária - Versão Breve (ICIQ-SF) (Diferença de Média Ponderada = -2.41, IC de 95%: -2.83- -1.98, P = 0.000), assim como na diminuição do volume de urina na 1 hora de vazamento do absorvente urinário (Diferença de Média Ponderada = -1.86, IC de 95%: -2.23- -1.49, P = 0.000) e no aumento da pressão máxima de encerramento uretral (PMCU) (Diferença Média Padronizada = 0.86, IC de 95%: 0.61-1.11, P = 0.000). Conclusão: A terapia da medicina tradicional chinesa (MTC) é eficaz na melhoria dos sintomas da incontinência urinária, na urodinâmica e na qualidade de vida em pacientes com incontinência urinária de esforço (IUE). Este artigo fornece uma referência para a aplicação da terapia da MTC em mulheres com incontinência urinária.

Symptom control after different duration of triptorelin treatment following conservative surgery for deep infiltrating endometriosis: Post-hoc analysis of a multicentre, prospective, real-world study.

ABSTRACT: Triptorelin has been used after surgery in deep infiltrating endometriosis. This post-hoc analysis aimed to evaluate symptom control between patients receiving 1-3 triptorelin injections and those receiving 4-6 injections within 24 months of conservative surgery for deep infiltrating endometriosis, in the real-world.Included patients were divided into two groups (received up to 3 months injections in group A, 4-6 injections in group B) based on the numbers of triptorelin (Diphereline, 3.75 mg intramuscular injection once every 28 days for up to 24 weeks) administration. Evolution in score of pain intensity at 3, 6, 9, 12, 18, and 24 months after primary triptorelin administration and symptom improvement/recurrence rates between two groups were compared. Symptoms of pain intensity were assessed using a visual analogue scale (VAS) with a range from 0 to 10 cm. An improvement in symptoms was defined as a reduction of at least 3 cm or 3 units from pre-surgery levels.156 patients in group A and 228 in group B. Pain symptom score (mean ±â€Šstandard deviation) diminished to a nadir at 3-months for group A and 6-months for group B; at 6-months nadir scores were significantly lower in group B (0.9 ±â€Š1.7 vs 0.4 ±â€Š1.2 respectively, P = .002). No significant difference for pain symptom scores between both groups at 24-months (P = .269). The 6-month and 24-month cumulative improvement rates of pain (80.6% vs 89.8%, P = .014 and 82.6% vs 90.7%, P = .025) and gastro-intestinal symptoms (61.0% vs 80.8%, P = .022 and 61.0% vs 83.3%, P = .008) were significantly higher in group B, whereas there was no significant difference in rates of menstrual disorders and urinary symptoms. There is no significant difference for 12-months and 24-months cumulative recurrence rates of total symptoms between both groups (11.3% vs 13.8%, P = .568 and 16.1% vs 26.0%, P = .094).In women with deep infiltrating endometriosis, longer treatment with triptorelin following conservative surgery was associated with a decrease in symptom intensity and greater improvement of pain symptoms in the short-term and greater improvement of gastro-intestinal symptoms in the long-term.Trial registration number: ClinicalTrials.gov, NCT01942369.

Efficacy of the levonorgestrel-releasing intrauterine device is associated with different subtypes of adenomyosis: a retrospective study.

BACKGROUND: Although the levonorgestrel-releasing intrauterine device (LNG-IUD) has been widely applied in the treatment of adenomyosis, not all the patients are satisfied with its efficacy. The present retrospective study aimed to investigate the efficacy of LNG-IUD on different subtypes of adenomyosis. METHODS: The study comprised a cohort of 207 patients who received the LNG-IUD at the Women's Hospital, Zhejiang University School of Medicine, China, from June 2013 to June 2016. Different subtypes of adenomyosis were classified by magnetic resonance imaging (MRI) and patients were subcategorized into three groups (subtype I: intrinsic, n=70; subtype II: extrinsic, n=73; subtype IV: indeterminate, n=64). Multiple variables were compared among the different groups. RESULTS: Patient demographics, clinical features and the treatment effects of the LNG-IUD were compared between the three subtype groups. The numeric rating scale (NRS) and pictorial blood loss assessment chart (PBAC) score markedly decreased after insertion of the LNG-IUD compared with baseline in all patients in the three subtype groups (P<0.001 for all groups). Compared to the other two subtypes, the efficacy rate was lower and the spontaneous expulsion rate was higher in subtype IV adenomyosis patients than that in other two groups (P<0.05). The independent factor associated with the spontaneous expulsion of the system was suggested to be uterine size before IUD placement and bleeding amount after LNG-IUD treatment in the subtype I [P=0.029, hazards ratio (HR): 3.37, 95% confidence interval (CI): 1.09-6.88] and IV (P=0.045, HR: 1.02, 95% CI: 1.01-1.21) adenomyosis patients respectively. CONCLUSIONS: The LNG-IUD is proved to be an effective approach to treat subtype I and II adenomyosis. However, further study is warranted to explore a more suitable protocol to treat this subtype IV adenomyosis due to the high incidence of treatment failure and expulsion.

A new trick for an old dog: The application of mifepristone in the treatment of adenomyosis.

Adenomyosis is also called internal endometriosis and affects about 20% of reproductive-aged women. It seriously reduces life quality of patients because current drug therapies face with numerous challenges. Long-term clinical application of mifepristone exhibits wonderful therapeutic effects with mild side-effects in many disorders since 1982. Since adenomyosis is a refractory disease, we investigate whether mifepristone can be applied in the treatment of adenomyosis. In this study, we investigated the direct effects of mifepristone on human primary eutopic endometrial epithelial cells and stromal cells in adenomyosis. We found that mifepristone causes cell cycle arrest through inhibiting CDK1 and CDK2 expressions and induces cell apoptosis via the mitochondria-dependent signalling pathway in endometrial epithelial cells and stromal cells of adenomyosis. Furthermore, mifepristone inhibits the migration of endometrial epithelial cells and stromal cells through decreasing CXCR4 expression and restricts the invasion of endometrial epithelial cells via suppression of epithelial-mesenchymal transition in adenomyosis. We also found that mifepristone treatment decreases the uterine volume, CA125 concentration and increases the haemoglobin concentration in serum for adenomyosis patients. Therefore, we demonstrate that mifepristone could serve as a novel therapeutic drug in the treatment of adenomyosis, and therefore, the old dog can do a new trick.

Octahydro-Protoberberine and Protoemetine-Type Alkaloids from the Stems of Alangium salviifolium and Their Cytotoxicity.

Two octahydro-protoberberine alkaloids, alangiifoliumines A (1) and B (2), and two new protoemetine derivatives, alangiifoliumines C (3) and D (4), together with 11 known compounds, have been isolated from the stems of Alangium salviifolium. While the structures of these compounds were elucidated by spectroscopic methods, the absolute configurations of the new alkaloids were determined by conformational analysis and time-dependent density functional theory-electronic circular dichroism spectra calculations on selected stereoisomers. Compounds 1 and 2 represent the first 5,8,8a,9,12,12a,13,13a-octahydro-protoberberine derivatives, in which the aromatic ring D was reduced to cyclohexene. All the compounds isolated were evaluated for their cytotoxic activity against three human cancer cell lines: A-549, HeLa, and SKOV-3. Alkaloids 1, 3, and 6-14 exhibited inhibitory effects against all three human cancer cell lines, with half-maximal inhibitory concentration (IC50) values in the range of 3 nM to 9.4 µM.

Urinary metabonomic study of patients with acute coronary syndrome using UPLC-QTOF/MS.

This urinary metabonomic study aimed to identify the potential metabolic biomarkers in acute coronary syndrome (ACS) patients. Ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) was used to analyze the urine samples from ACS patients and healthy controls. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to characterizing the endogenous metabolites and potential biomarker, respectively. Among twenty biomarkers that functioned in nine metabolic pathways, nine biomarkers were found up-regulated significantly, including of isobutyryl­l­carnitine, 3­methylglutarylcarnitine, cinnavalininate, l­tryptophan, 3­methyldioxyindole, palmitic acid, N4­acetylaminobutanal, 3­sulfino­l­alanine and S­adenosyl­l­homocysteine. The other eleven biomarkers were showed down-regulated, including of l­lactic acid, trigonelline, nicotinuric acid, l­alanine, d­alanyl­d­alanine, creatine, N4­acetylaminobutanoate, glutathionyl spermidine, 5­methoxytryptamine, kynurenic acid and xanthurenic acid. This study also implied that fatty acid metabolism, fatty acid ß­oxidation metabolism, amino acid metabolism and TCA cycle played important roles in ACS. Therefore, urinary metabolomics may improve the diagnosis efficacy of ACS and make it more accurate and comprehensive for ACS diagnosis.

Genome-Wide Expression Profiling of Anoxia/Reoxygenation in Rat Cardiomyocytes Uncovers the Role of MitoKATP in Energy Homeostasis.

Mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) is a common end effector of many protective stimuli in myocardial ischemia-reperfusion injury (MIRI). However, the specific molecular mechanism underlying its myocardial protective effect is not well elucidated. We characterized an anoxia/reoxygenation (A/R) model using freshly isolated adult rat cardiomyocytes. MitoK(ATP) status was interfered with its specific opener diazoxide (DZ) or blocker 5-hydroxydecanote (5-HD). Digital gene expression (DGE) and bioinformatic analysis were deployed. Three energy metabolism related genes (MT-ND6, Idh2, and Acadl) were upregulated when mitoK(ATP) opened. In addition, as many as 20 differentially expressed genes (DEGs) were significantly enriched in five energy homeostasis correlated pathways (PPAR, TCA cycle, fatty acid metabolism, and peroxisome). These findings indicated that mitoK(ATP) opening in MIRI resulted in energy mobilization, which was confirmed by measuring ATP content in cardiomyocytes. These causal outcomes could be a molecular mechanism of myocardial protection of mitoKATP and suggested that the mitoK(ATP) opening plays a physiologic role in triggering cardiomyocytes' energy homeostasis during MIRI. Strategies of modulating energy expenditure during myocardial ischemia-reperfusion may be promising approaches to reduce MIRI.

Endogenous calcitonin gene-related peptide protects human alveolar epithelial cells through protein kinase Cepsilon and heat shock protein.

The intracellular mechanisms of ischemic preconditioning (PC) in preventing lung dysfunction following transplantation, shock, and trauma remain poorly understood. Previously, we have shown that alveolar epithelial cells secrete calcitonin gene-related peptide (CGRP) under inflammatory stress. Using a hypoxia/reoxygenation (H/R) and PC model, we found that CGRP was also secreted from human type II alveolar epithelial cells (A549) after PC. The locally released CGRP interacted with its receptor on the membrane of A549 cells and elicited downstream signals mediating the PC effect, because hCGRP(8-37), a specific CGRP receptor antagonist, attenuated the protective effect of PC. Pre-inhibition of CGRP protein synthesis by small interfering RNA exacerbated (but overexpression of the CGRP gene ameliorated) H/R-induced cell death, which supports the autocrine effect of CGRP on A549 cells. Exogenous bioactive CGRP mimicked the beneficial effect of PC and up-regulated the expression of heat shock protein 70 (HSP70), which might act as the end effector to maintain cell viability. These effects were sensitive to hCGRP(8-37), calphostin C (a protein kinase C (PKC) inhibitor), and 5-hydroxydecanoic acid (a mitochondrial K(+)(ATP) channel blocker) but were insensitive to protein kinase A blockers. Moreover, CGRP induced the membrane translocation of PKCepsilon. PKCV1-2 (a cell-permeable inhibitory peptide of PKCepsilon) effectively abolished CGRP-induced HSP70 expression and cell protection. Therefore, PC induces CGRP secretion from human alveolar epithelial cells, and the locally released CGRP acts back on these cells, protecting them from H/R injury. The post-receptor signaling of CGRP is through PKCepsilon-dependent expression of HSP70.