Toll-like receptor 9 regulates metabolic profile and contributes to obesity-induced benign prostatic hyperplasia in mice

Calmasini, Fabiano Beraldi; McCarthy, Cameron G.; Priviero, Fernanda; Antunes, Edson; Webb, R.

doi:10.1007/s43440-019-00010-3

Cited by 9 publications

(5 citation statements)

References 42 publications

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“…Numerous studies have reported an association between insulin resistance and hyperglycemia with the prevalence and incidence of LUTS, especially in older adults. [8][9][10]13,14 Despite the significant reduction in quality of life and interference with daily activities noted in men with mild-to-moderate symptoms 7 , the primary treatment options have been limited to lifestyle advice, behavioral modifications, and watchful waiting. 32 In this context, using medicinal plants to improve LUTS, including symptoms such as nocturia, urge symptoms, and urinary flow weakening, or to enhance patients' quality of life (QoL) is of great interest.…”

Section: Resultsmentioning

confidence: 99%

A Single-Blind, Randomized, Controlled Trial Assessing the Efficacy and Safety Parameters of Traditional Thai Medicine, Aphayathikun, in Prediabetic Men with Lower Urinary Tract Symptoms

2023

TJNPR

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The prevalence of prediabetes in adults is rising dramatically. The global diabetes burden was expected to reach around 400 million patients in 2019. 1 This condition is recognized as a key factor linked to the increased risk of developing diabetes and its complications, such as retinopathy, neuropathy, nephropathy, etc. 2 Globally, the prevalence of prediabetes, based on impaired glucose tolerance (IGT), is expected to rise from 352.1 million individuals in 2017 to 587 million in 2045. 3 Among these, 5-10 percent of prediabetic patients develop diabetes each year, with up to 70 percent progressing to diabetes. 2,4 Adequate treatment is required to prevent the development of diabetes. Diabetes patients are more likely to suffer from cardiovascular disease, chronic lower respiratory disorders, and chronic renal disease. 5

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Section: Resultsmentioning

confidence: 99%

A Single-Blind, Randomized, Controlled Trial Assessing the Efficacy and Safety Parameters of Traditional Thai Medicine, Aphayathikun, in Prediabetic Men with Lower Urinary Tract Symptoms

2023

TJNPR

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“…In particular, H3K4me1 is located in many type-specific enhancer sites. Most enhancer regions labeled with H3K4me1 are active ( Calmasini, et al, 2020 ). H3K27ac is a candidate for distinguishing active from inactive enhancer elements ( Xu, et al, 2018 ) A total of 867 SEs were identified in C4-2B cells by detecting both H3K4me1-and H3K27ac-enriched regions ( Xu, et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated high-throughput analysis identifies super enhancers in metastatic castration-resistant prostate cancer

Zeng

Chen

et al. 2023

Front. Pharmacol.

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Background: Metastatic castration-resistant prostate cancer (mCRPC) is a highly aggressive stage of prostate cancer, and non-mutational epigenetic reprogramming plays a critical role in its progression. Super enhancers (SE), epigenetic elements, are involved in multiple tumor-promoting signaling pathways. However, the SE-mediated mechanism in mCRPC remains unclear.Methods: SE-associated genes and transcription factors were identified from a cell line (C4-2B) of mCRPC by the CUT&Tag assay. Differentially expressed genes (DEGs) between mCRPC and primary prostate cancer (PCa) samples in the GSE35988 dataset were identified. What’s more, a recurrence risk prediction model was constructed based on the overlapping genes (termed SE-associated DEGs). To confirm the key SE-associated DEGs, BET inhibitor JQ1 was applied to cells to block SE-mediated transcription. Finally, single-cell analysis was performed to visualize cell subpopulations expressing the key SE-associated DEGs.Results: Nine human TFs, 867 SE-associated genes and 5417 DEGs were identified. 142 overlapping SE-associated DEGs showed excellent performance in recurrence prediction. Time-dependent receiver operating characteristic (ROC) curve analysis showed strong predictive power at 1 year (0.80), 3 years (0.85), and 5 years (0.88). The efficacy of his performance has also been validated in external datasets. In addition, FKBP5 activity was significantly inhibited by JQ1.Conclusion: We present a landscape of SE and their associated genes in mCPRC, and discuss the potential clinical implications of these findings in terms of their translation to the clinic.

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“…Aging has been strongly associated with BPH in humans and animal models (Liu et al, 2019;Mazur, Helfand, McVary, 2012). The exact BPH pathophysiology remains unclear; however, some aging-associated conditions, such as increased oxidative stress, low-grade inflammatory state and autonomic dysregulation have been shown to play a key role in the development of BPH (Calmasini et al, 2020, Madersbacher, Sampson, Culig, 2019Calmasini et al, 2018). Regarding autonomic dysregulation, Thiyagarajan and collaborators (2002) have demonstrated a leftward shift in the potency to α-adrenoceptor-induced prostate smooth muscle contractility in a rat model of BPH.…”

Section: Discussionmentioning

confidence: 99%

Aging-associated prostate smooth muscle hypercontractility in rats

Lopes¹,

Fritoli²,

Silva

et al. 2022

Braz. J. Pharm. Sci.

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Benign prostatic hyperplasia (BPH) is a multifactorial disease, highly associated with aging and characterized by increased prostate smooth muscle (PSM) contractility. Animal models have been employed to explore the aging-associated PSM hypercontractility; however, studies have focused in old animals, neglecting the initial alterations in early ages. The determination of prostatic dysfunctions onset is crucial to understand the BPH pathophysiology and to propose new BPH treatments. Considering that PSM contractility in 10-month-old rats has already been explored, the aim of the present study was to characterize the PSM contractility in younger rats. Male Wistar control (3.5-month-old), 6-and 8-month-old rats were used. Concentrationresponse curves to phenylephrine and electrical-field stimulation (EFS) were conducted in prostate from all groups. For the first time, we showed that 6-and 8-month-old rats exhibit PSM hypercontractility. The increased prostate contractility to phenylephrine starts around at 6-month-old, worsening during the aging. The 8-month-old rats exhibited hypercontractility to phenylephrine and EFS compared to the control and 6-month-old groups. Reduced phenylephrine potency was observed in 8-month-old rats, indicating an increased age-dependent prostate sensibility to this agonist. Collectively, our findings support the use of 6-and 8-month-old aged rats as new models to explore prostate hypercontractility in BPH.

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Toll-like receptor 9 regulates metabolic profile and contributes to obesity-induced benign prostatic hyperplasia in mice

Cited by 9 publications

References 42 publications

A Single-Blind, Randomized, Controlled Trial Assessing the Efficacy and Safety Parameters of Traditional Thai Medicine, Aphayathikun, in Prediabetic Men with Lower Urinary Tract Symptoms

A Single-Blind, Randomized, Controlled Trial Assessing the Efficacy and Safety Parameters of Traditional Thai Medicine, Aphayathikun, in Prediabetic Men with Lower Urinary Tract Symptoms

Integrated high-throughput analysis identifies super enhancers in metastatic castration-resistant prostate cancer

Aging-associated prostate smooth muscle hypercontractility in rats

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