Sulforaphane Treatment of Stress Urinary Incontinence Via the Nrf2-ARE Pathway in a Rat Model

Wan, Xiang; Liu, Chong; Chen, Yan-Bo; Gu, Meng; Cai, Zhixiang; Chen, Qi; Wang, Zhong

doi:10.1159/000485880

Cited by 19 publications

(21 citation statements)

References 41 publications

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“…Both staining analyses were conducted as previously described [ 40 ]. Tumor tissues were fixed in 10% formalin for 1 day, then embedded in paraffin and cut into 4‐μm thick sections, eventually stained with H&E and Masson's trichrome staining kits (Beyotime).…”

Section: Methodsmentioning

confidence: 99%

Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β₂‐AR/MACC1 axis

Pan

Zheng

et al. 2021

Cancer Communications

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Background Depression is a common, easily ignored, accompanied disease of gastric cancer (GC) patients and is often observed with elevated plasma catecholamine levels. Depression frequently promotes GC progression and leads to poor clinical outcomes; however, the molecular mechanisms underlying depression‐induced GC progression remain poorly understood. We aimed to study the effects of depression on GC progression and explore possible mechanisms mediating the action of depression‐associated catecholamines on GC. Methods Depression states of GC patients were graded using the Patient Health Questionnaire‐9, and plasma catecholamine levels were examined by high performance liquid chromatography coupled with tandem mass spectrometry. Migrative and invasive GC cells were examined using transwell assays, and metastatic GC niches were imaged using bioluminescence technology in a depression mouse model established with chronic unpredictable mild stress. Mouse depression‐like behaviors were assessed through sucrose preference, forced swimming, and tail suspension tests. Characteristics of the neuroendocrine phenotype were observed via RT‐PCR, Western blotting, flow cytometry, and transmission electron microscopy. Results Fifty‐one GC patients (age: 53.61 ± 1.79 years; cancer duration: 3.71 ± 0.33 months; depression duration: 2.37 ± 0.38 months; male‐to‐female ratio: 1.55:1) were enrolled in the study. Depression grade was significantly higher in GC patients showing higher plasma levels of catecholamines (epinephrine: P = 0.018; noradrenaline: P = 0.009), higher oncogene metastasis‐associated in colon cancer‐1 (MACC1) level (P = 0.018), and metastasis (P < 0.001). Further, depression‐associated catecholamine specifically bound to the beta‐2 adrenergic receptor (β2‐AR) and upregulated MACC1 expression, and thus promoting neuroendocrine phenotypic transformation through direct binding between MACC1 and synaptophysin. Eventually, the neuroendocrine phenotypic transformation accelerated GC invasion in vitro and metastasis in vivo. However, β2‐AR antagonist ICI‐118,551 or MACC1 silencing effectively blocked the catecholamine‐induced neuroendocrine phenotypic transformation and eliminated depression‐enhanced GC migration and invasion. Moreover, β2‐AR blocking or MACC1 silencing prevented GC metastasis attributed to a neuroendocrine phenotype in a depression mouse model. Conclusions Catecholamine‐induced neuroendocrine phenotypes of GC cells led to depression‐accelerated GC invasion and metastasis via the β2‐AR/MACC1 axis, while β2‐AR antagonist or MACC1 silencing could reverse it, showing promising potential therapeutic strategies for improving the outcome of GC patients with comorbid depression.

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Section: Methodsmentioning

confidence: 99%

Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β₂‐AR/MACC1 axis

Pan

Zheng

et al. 2021

Cancer Communications

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“…ECM-related protein expression and serum or urinary biomarkers were examined in 51 studies [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 41 , 42 , 45 , 47 , 56 , 59 , 65 , 67 , 70 , 73 , 74 , 75 , 76 , 77 , 78 , 81 , 82 , 85 , 93 , 94 , 96 , 97 , 98 , 99 , 108 , 109 , 111 , 112 , 113 , 114 , 119 , 121 , 122 , 126 , 127 ]. Figure 4 shows an overview of human [ 23 , 24 , 25 , …”

Section: Resultsmentioning

confidence: 99%

Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies

Post

Widomska

Grens

et al. 2022

IJMS

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Stress urinary incontinence (SUI) is a common and burdensome condition. Because of the large knowledge gap around the molecular processes involved in its pathophysiology, the aim of this review was to provide a systematic overview of genetic variants, gene and protein expression changes related to SUI in human and animal studies. On 5 January 2021, a systematic search was performed in Pubmed, Embase, Web of Science, and the Cochrane library. The screening process and quality assessment were performed in duplicate, using predefined inclusion criteria and different quality assessment tools for human and animal studies respectively. The extracted data were grouped in themes per outcome measure, according to their functions in cellular processes, and synthesized in a narrative review. Finally, 107 studies were included, of which 35 used animal models (rats and mice). Resulting from the most examined processes, the evidence suggests that SUI is associated with altered extracellular matrix metabolism, estrogen receptors, oxidative stress, apoptosis, inflammation, neurodegenerative processes, and muscle cell differentiation and contractility. Due to heterogeneity in the studies (e.g., in examined tissues), the precise contribution of the associated genes and proteins in relation to SUI pathophysiology remained unclear. Future research should focus on possible contributors to these alterations.

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“…The expression levels of CAT, SOD, GSH-Px, and GSTs are mainly regulated by Nrf2 (Wan et al, 2017). Nuclear factor-E 2 -related factor 2 (Nrf2) is the key factor of oxidative stress.…”

Section: Mechanisms Of Polysaccharidesmentioning

confidence: 99%

Antioxidant activities and mechanisms of polysaccharides

2020

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Polysaccharide, as one of the effective components of traditional Chinese medicine, has the activities of anti-oxidation, anti-virus, improving immunity and so on. Chinese herbal polysaccharides have a wide range of sources. It is found that polysaccharides in many plants and microorganisms have significant antioxidant effects, mainly through the endogenous antioxidant stress Nrf2/ARE pathway to regulate the expression of downstream antioxidant enzymes. These antioxidant enzymes can further block the free radical chain reaction, thus reducing the generation of free radicals. Secondly, by inhibiting the expression of iNOS mRNA and reducing NO production, it can significantly increase the antioxidant capacity and reduce oxidative stress injury. Polysaccharides are rich in natural resources, their multi-channel, multi-target, multi-effect, and other characteristics have made great progress in antioxidants.

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Sulforaphane Treatment of Stress Urinary Incontinence Via the Nrf2-ARE Pathway in a Rat Model

Cited by 19 publications

References 41 publications

Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β₂‐AR/MACC1 axis

Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β₂‐AR/MACC1 axis

Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies

Antioxidant activities and mechanisms of polysaccharides

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Sulforaphane Treatment of Stress Urinary Incontinence Via the Nrf2-ARE Pathway in a Rat Model

Cited by 19 publications

References 41 publications

Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β2‐AR/MACC1 axis

Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β2‐AR/MACC1 axis

Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies

Antioxidant activities and mechanisms of polysaccharides

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Product

Resources

About

Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β₂‐AR/MACC1 axis

Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β₂‐AR/MACC1 axis