The aim of this study is to observe the therapeutic effect of Inonotus Obliquus Polysaccharide(IOP)on chronic nonbacterial prostatitis(CNP)and its effect on the helper T cells(Th17)and regulatory T cells(Treg)immune i...The aim of this study is to observe the therapeutic effect of Inonotus Obliquus Polysaccharide(IOP)on chronic nonbacterial prostatitis(CNP)and its effect on the helper T cells(Th17)and regulatory T cells(Treg)immune imbalance.The CNP rat models established by injecting Xiaozhiling injection were randomly divided into the model group,cernilton(40 mg/kg,i.g.)group and low-dose(35 mg/kg,i.g.),medium-dose(70 mg/kg,i.g.)and high-dose(140 mg/kg,i.g.)groups,with the same volume of saline injected into the same site as the control group.The prostate’s wet weight and body mass served as the basis for calculating the prostate index.The serum level of prostate-specific antigen(PSA)was detected by ELISA and the histopathology of prostate tissue was detected by HE staining.The protein expression of Foxp3,ROR-γt and STAT3 in rat prostatic tissue was determined by Western blot.The levels of Th17 and Treg cells infiltrated into the spleen were measured by flow cytometry.The results showed that treatment with IOP significantly reduced the levels of prostate index and serum PSA,and attenuated the pathological injury of the prostate tissue induced by CNP.With respect to samples induced by CNP alone,IOP treatment repressed the increased mRNA levels of IL-6,IL-17,IL-21,IL-23,ROR-γt and STAT3 in prostate tissue,while increasing the mRNA levels of IL-10,TGF-βand Foxp3 in prostate tissue.Meanwhile,IOP treatment attenuated the upregulation of the protein expression levels of ROR-γt and STAT3 in prostate tissue.Additionally,the protein expression of Foxp3 in prostate tissue was increased in the IOP-treated group.Flow cytometry analysis further demonstrated that IOP treatment regulated the balance between Th17 and Treg cells in the spleen in rat with CNP.Our study is the first to elucidate that IOP has significant therapeutic effects on CNP through regulation of Th17/Treg balance.Collectively,the study provides evidence for the potential of IOP to treat CNP.展开更多
Background:Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a frequently encountered disorder characterized by voiding symptoms and pelvic or perineal pain.Proinflammatory T helper 17(Th17)cells are essenti...Background:Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a frequently encountered disorder characterized by voiding symptoms and pelvic or perineal pain.Proinflammatory T helper 17(Th17)cells are essential for triggering the development of CP/CPPS.High-salt diet(HSD)consumption has been found to cause an accumulation of sodium chloride in peripheral organs,inducing autoimmune responses via the Th17 cell axis.It is currently unknown whether HSD affects the etiology and course of CP/CPPS.Methods:Patients diagnosed with CP/CPPS were evaluated with the National Institutes of Health Chronic Prostatitis Symptom Index scoring system,and the correlation between the symptoms of CP/CPPS with HSD was analyzed.The experimental autoimmune prostatitis(EAP)mouse was established and the mice were fed either a normal-salt diet(NSD)or HSD for 6 weeks to investigate the impact of HSD on CP/CPPS.Then,16S ribosomal RNA sequencing and untargeted metabolomics were introduced to detect the differences in the gut microflora composition and metabolite profiles between NSD-fed and HSD-fed mice,followed by fecal microbiota transplantation,5-hydroxyindole acetic acid(5-HIAA)supplementation,aryl hydrocarbon receptor(AHR)inhibition,and in vitro Th17 differentiation experiments,which were performed to explore the mechanisms underlying HSD-aggravated CP/CPPS.Finally,chromatin immunoprecipitation assay and quantitative polymerase chain reaction were conducted to validate whether AHR can serve as a transcription factor by interacting with the serum and glucocorticoid-regulated kinase 1(Sgk1)promoter in CD4^(+)T cells.Results:Increased salt consumption had a positive correlation with symptom scores of CP/CPPS patients,which was validated by feeding EAP mice with HSD,and HSD worsened the prostate inflammation and tactile allodynia in EAP mice through promoting the differentiation of CD4^(+)T cells to Th17 cells.HSD exacerbated EAP by significantly reducing the relative abundance of beneficial gut microflora,such as Lactobacillaceae,and gut microbiota metabolite 5-HIAA,which is related to tryptophan metabolism.The prostate inflammation,tactile allodynia,and proportion of Th17 cells in mice that received fecal suspensions from the EAP^(+)HSD group were significantly more severe or higher than those in mice that received fecal suspensions from the EAP^(+)NSD group.However,5-HIAA supplementation ameliorated the symptoms of EAP caused by HSD through inhibiting the differentiation of CD4^(+)T cells to Th17 cells,while AHR inhibition abrogated the protective effects of 5-HIAA supplementation on EAP mice fed a HSD through promoting the differentiation of CD4^(+)T cells to Th17 cells.Mechanistically,it has been revealed that the SGK1/forkhead box protein O1(FOXO1)pathway was significantly activated during cytokine-induced Th17 cell differentiation,and AHR has been shown to inhibit SGK1 transcription by interacting with the Sgk1 promoter in CD4^(+)T cells to inhibit FOXO1 phosphorylation,consequently restoring the equilibrium of Th17 cell differentiation.Conclusions:Our findings indicated that high salt intake represented a risk factor for the development of CP/CPPS as it promoted the differentiation of CD4^(+)T cells to Th17 cells through the 5-HIAA/AHR/SGK1/FOXO1 axis,which might be a potential therapeutic target for CP/CPPS.展开更多
Objective: To study the correlation of Th17 cell function with the inflammatory response and apoptosis in the course of prostatitis. Methods: A total of 128 patients with chronic prostatitis who were treated in our ho...Objective: To study the correlation of Th17 cell function with the inflammatory response and apoptosis in the course of prostatitis. Methods: A total of 128 patients with chronic prostatitis who were treated in our hospital between January 2015 and December 2016 were collected, and 50 healthy men who received physical examination in our hospital during the same period were selected as normal control group. The differences in Th17 cell ratio and IL-17 levels in peripheral blood, inflammatory factor levels in serum, and apoptosis gene expression in prostatic fluid were compared between the two groups. Pearson test was used to assess the correlation of Th17 cell function in peripheral blood with inflammation and apoptosis in patients with chronic prostatitis. Results: Th17 cell ratio and IL-17 level in peripheral blood of observation group were higher than those of normal control group;inflammatory factors IL-1β, IL-2, IL-8, TNF-α and M-CSF levels in serum were higher than those of normal control group;apoptosis gene BAX mRNA in prostatic fluid was higher than that of control group while anti-apoptosis genes Bcl-2, livin and hPEBP4 mRNA expression were lower than those of normal control group. Pearson test showed that Th17 cell ratio and IL-17 level in peripheral blood of patients with chronic prostatitis were positively correlated with IL-1β, IL-2, IL-8, TNF-α and M-CSF levels in serum as well as BAX mRNA expression in prostatic fluid, and negatively correlated with Bcl-2, livin and hPEBP4 mRNA expression in prostatic fluid. Conclusion: There is Th17 cell hyperfunction in patients with chronic prostatitis, and it is an important cause of the systemic inflammatory response and prostate cell apoptosis aggravation.展开更多
Prostate cancer tissue is composed of both cancer cells and host cells.The milieu of host components that compose the tumor is termed the tumor microenvironment(TME).Host cells can be those derived from the tissue in ...Prostate cancer tissue is composed of both cancer cells and host cells.The milieu of host components that compose the tumor is termed the tumor microenvironment(TME).Host cells can be those derived from the tissue in which the tumor originates(e.g.,fibroblasts and endothelial cells)or those recruited,through chemotactic or other factors,to the tumor(e.g.,circulating immune cells).Some immune cells are key players in the TME and represent a large proportion of non-tumor cells found within the tumor.Immune cells can have both anti-tumor and pro-tumor activity.In addition,crosstalk between prostate cancer cells and immune cells affects immune cell functions.In this review,we focus on immune cells and cytokines that contribute to tumor progression.We discuss T-regulatory and T helper17 cells and macrophages as key modulators in prostate cancer progression.In addition,we discuss the roles of interleukin-6 and receptor activator of nuclear factor kappa-B ligand in modulating prostate cancer progression.This review highlights the concept that immune cells and cytokines offer a potentially promising target for prostate cancer therapy.展开更多
Introduction: With the advent of multiparametric MRI (mpMRI), clinicians added an important tool for helping to decide whether a man should undergo a prostate biopsy. The MRI PI-RADS system stratifies the risk of find...Introduction: With the advent of multiparametric MRI (mpMRI), clinicians added an important tool for helping to decide whether a man should undergo a prostate biopsy. The MRI PI-RADS system stratifies the risk of finding cancer on prostate biopsy. PI-RADS 3 lesions often prove to be a diagnostic challenge, and many men are advised not to proceed with a biopsy based on this finding. The goal of our paper was to evaluate the likelihood of finding cancer of clinical significance in this group. Methods: A retrospective 4-year data and quality analysis was performed of 312 evaluable men undergoing prostate MRI. Of the subset with scores of PI-RADS 3 who underwent biopsy (N = 32), 100 percent were biopsied using an MRI-guided fusion technique, greatly raising the likelihood that the MRI lesion was, in fact, the area sampled. Results: A total of 34% of the men with PI-RADS 3 lesions were found to have Grade Group ≥ 1, with 15.6 % demonstrating Grade Group ≥ 2. In the men with cancer, we analyzed and report the relationship to age, ethnicity, PSA density, and the presence or absence of cribriform findings. Conclusions: We found that many men with PI-RADS 3 findings on multiparametric MRI do, in fact, have clinically significant prostate cancer. We suggest that many factors (such as rate of rise of PSA over time, family history, and rectal examination findings) be considered in addition to the MRI PI-RADS score to advise whether or not to proceed with a biopsy of the prostate. Our findings, from a single, large, community hospital with a diverse ethnic makeup, parallel the findings of large trials done at academic centers of excellence. This demonstrates that comparable diagnostic mpMRI/biopsy quality may be found in the community setting.展开更多
基金Shanxi Province Traditional Chinese Medicine Administration Research Project(Grant No.2022ZYYC094)Science and technology innovation project of universities in Shanxi Province(Grant No.2022L342)+1 种基金Shanxi Leader Team of Medical Science&Technology Innovations(Grant No.2020TD02)Discipline Construction Project of Chinese Medicine Chemistry(Grant No.2024XKJS-25).
文摘The aim of this study is to observe the therapeutic effect of Inonotus Obliquus Polysaccharide(IOP)on chronic nonbacterial prostatitis(CNP)and its effect on the helper T cells(Th17)and regulatory T cells(Treg)immune imbalance.The CNP rat models established by injecting Xiaozhiling injection were randomly divided into the model group,cernilton(40 mg/kg,i.g.)group and low-dose(35 mg/kg,i.g.),medium-dose(70 mg/kg,i.g.)and high-dose(140 mg/kg,i.g.)groups,with the same volume of saline injected into the same site as the control group.The prostate’s wet weight and body mass served as the basis for calculating the prostate index.The serum level of prostate-specific antigen(PSA)was detected by ELISA and the histopathology of prostate tissue was detected by HE staining.The protein expression of Foxp3,ROR-γt and STAT3 in rat prostatic tissue was determined by Western blot.The levels of Th17 and Treg cells infiltrated into the spleen were measured by flow cytometry.The results showed that treatment with IOP significantly reduced the levels of prostate index and serum PSA,and attenuated the pathological injury of the prostate tissue induced by CNP.With respect to samples induced by CNP alone,IOP treatment repressed the increased mRNA levels of IL-6,IL-17,IL-21,IL-23,ROR-γt and STAT3 in prostate tissue,while increasing the mRNA levels of IL-10,TGF-βand Foxp3 in prostate tissue.Meanwhile,IOP treatment attenuated the upregulation of the protein expression levels of ROR-γt and STAT3 in prostate tissue.Additionally,the protein expression of Foxp3 in prostate tissue was increased in the IOP-treated group.Flow cytometry analysis further demonstrated that IOP treatment regulated the balance between Th17 and Treg cells in the spleen in rat with CNP.Our study is the first to elucidate that IOP has significant therapeutic effects on CNP through regulation of Th17/Treg balance.Collectively,the study provides evidence for the potential of IOP to treat CNP.
基金supported by the National Natural Science Foundation of China(82300872 and 82170787)the Anhui Provincial Natural Science Foundation(2408085Y038)+3 种基金the Supporting Projects for Innovative Leading Talents(T000529)the Distinguished Young Scholar of Anhui Colleges(2021-108-10)the Science Foundation for Outstanding Young Scholar of Anhui Colleges(2022AH020073)the Sanming Project of Medicine in Shenzhen Nanshan(SZSM20210300).
文摘Background:Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a frequently encountered disorder characterized by voiding symptoms and pelvic or perineal pain.Proinflammatory T helper 17(Th17)cells are essential for triggering the development of CP/CPPS.High-salt diet(HSD)consumption has been found to cause an accumulation of sodium chloride in peripheral organs,inducing autoimmune responses via the Th17 cell axis.It is currently unknown whether HSD affects the etiology and course of CP/CPPS.Methods:Patients diagnosed with CP/CPPS were evaluated with the National Institutes of Health Chronic Prostatitis Symptom Index scoring system,and the correlation between the symptoms of CP/CPPS with HSD was analyzed.The experimental autoimmune prostatitis(EAP)mouse was established and the mice were fed either a normal-salt diet(NSD)or HSD for 6 weeks to investigate the impact of HSD on CP/CPPS.Then,16S ribosomal RNA sequencing and untargeted metabolomics were introduced to detect the differences in the gut microflora composition and metabolite profiles between NSD-fed and HSD-fed mice,followed by fecal microbiota transplantation,5-hydroxyindole acetic acid(5-HIAA)supplementation,aryl hydrocarbon receptor(AHR)inhibition,and in vitro Th17 differentiation experiments,which were performed to explore the mechanisms underlying HSD-aggravated CP/CPPS.Finally,chromatin immunoprecipitation assay and quantitative polymerase chain reaction were conducted to validate whether AHR can serve as a transcription factor by interacting with the serum and glucocorticoid-regulated kinase 1(Sgk1)promoter in CD4^(+)T cells.Results:Increased salt consumption had a positive correlation with symptom scores of CP/CPPS patients,which was validated by feeding EAP mice with HSD,and HSD worsened the prostate inflammation and tactile allodynia in EAP mice through promoting the differentiation of CD4^(+)T cells to Th17 cells.HSD exacerbated EAP by significantly reducing the relative abundance of beneficial gut microflora,such as Lactobacillaceae,and gut microbiota metabolite 5-HIAA,which is related to tryptophan metabolism.The prostate inflammation,tactile allodynia,and proportion of Th17 cells in mice that received fecal suspensions from the EAP^(+)HSD group were significantly more severe or higher than those in mice that received fecal suspensions from the EAP^(+)NSD group.However,5-HIAA supplementation ameliorated the symptoms of EAP caused by HSD through inhibiting the differentiation of CD4^(+)T cells to Th17 cells,while AHR inhibition abrogated the protective effects of 5-HIAA supplementation on EAP mice fed a HSD through promoting the differentiation of CD4^(+)T cells to Th17 cells.Mechanistically,it has been revealed that the SGK1/forkhead box protein O1(FOXO1)pathway was significantly activated during cytokine-induced Th17 cell differentiation,and AHR has been shown to inhibit SGK1 transcription by interacting with the Sgk1 promoter in CD4^(+)T cells to inhibit FOXO1 phosphorylation,consequently restoring the equilibrium of Th17 cell differentiation.Conclusions:Our findings indicated that high salt intake represented a risk factor for the development of CP/CPPS as it promoted the differentiation of CD4^(+)T cells to Th17 cells through the 5-HIAA/AHR/SGK1/FOXO1 axis,which might be a potential therapeutic target for CP/CPPS.
文摘Objective: To study the correlation of Th17 cell function with the inflammatory response and apoptosis in the course of prostatitis. Methods: A total of 128 patients with chronic prostatitis who were treated in our hospital between January 2015 and December 2016 were collected, and 50 healthy men who received physical examination in our hospital during the same period were selected as normal control group. The differences in Th17 cell ratio and IL-17 levels in peripheral blood, inflammatory factor levels in serum, and apoptosis gene expression in prostatic fluid were compared between the two groups. Pearson test was used to assess the correlation of Th17 cell function in peripheral blood with inflammation and apoptosis in patients with chronic prostatitis. Results: Th17 cell ratio and IL-17 level in peripheral blood of observation group were higher than those of normal control group;inflammatory factors IL-1β, IL-2, IL-8, TNF-α and M-CSF levels in serum were higher than those of normal control group;apoptosis gene BAX mRNA in prostatic fluid was higher than that of control group while anti-apoptosis genes Bcl-2, livin and hPEBP4 mRNA expression were lower than those of normal control group. Pearson test showed that Th17 cell ratio and IL-17 level in peripheral blood of patients with chronic prostatitis were positively correlated with IL-1β, IL-2, IL-8, TNF-α and M-CSF levels in serum as well as BAX mRNA expression in prostatic fluid, and negatively correlated with Bcl-2, livin and hPEBP4 mRNA expression in prostatic fluid. Conclusion: There is Th17 cell hyperfunction in patients with chronic prostatitis, and it is an important cause of the systemic inflammatory response and prostate cell apoptosis aggravation.
基金supported by National Cancer Institute Grants(Nos.P01 CA093900 and R01 CA190554)National Natural Science Foundation of China(NSFC)Key Projects(Nos.81130046+1 种基金NSFC 81171993 and 81272415)Guangxi Key Project(No.2013GXNSFEA053004)
文摘Prostate cancer tissue is composed of both cancer cells and host cells.The milieu of host components that compose the tumor is termed the tumor microenvironment(TME).Host cells can be those derived from the tissue in which the tumor originates(e.g.,fibroblasts and endothelial cells)or those recruited,through chemotactic or other factors,to the tumor(e.g.,circulating immune cells).Some immune cells are key players in the TME and represent a large proportion of non-tumor cells found within the tumor.Immune cells can have both anti-tumor and pro-tumor activity.In addition,crosstalk between prostate cancer cells and immune cells affects immune cell functions.In this review,we focus on immune cells and cytokines that contribute to tumor progression.We discuss T-regulatory and T helper17 cells and macrophages as key modulators in prostate cancer progression.In addition,we discuss the roles of interleukin-6 and receptor activator of nuclear factor kappa-B ligand in modulating prostate cancer progression.This review highlights the concept that immune cells and cytokines offer a potentially promising target for prostate cancer therapy.
文摘Introduction: With the advent of multiparametric MRI (mpMRI), clinicians added an important tool for helping to decide whether a man should undergo a prostate biopsy. The MRI PI-RADS system stratifies the risk of finding cancer on prostate biopsy. PI-RADS 3 lesions often prove to be a diagnostic challenge, and many men are advised not to proceed with a biopsy based on this finding. The goal of our paper was to evaluate the likelihood of finding cancer of clinical significance in this group. Methods: A retrospective 4-year data and quality analysis was performed of 312 evaluable men undergoing prostate MRI. Of the subset with scores of PI-RADS 3 who underwent biopsy (N = 32), 100 percent were biopsied using an MRI-guided fusion technique, greatly raising the likelihood that the MRI lesion was, in fact, the area sampled. Results: A total of 34% of the men with PI-RADS 3 lesions were found to have Grade Group ≥ 1, with 15.6 % demonstrating Grade Group ≥ 2. In the men with cancer, we analyzed and report the relationship to age, ethnicity, PSA density, and the presence or absence of cribriform findings. Conclusions: We found that many men with PI-RADS 3 findings on multiparametric MRI do, in fact, have clinically significant prostate cancer. We suggest that many factors (such as rate of rise of PSA over time, family history, and rectal examination findings) be considered in addition to the MRI PI-RADS score to advise whether or not to proceed with a biopsy of the prostate. Our findings, from a single, large, community hospital with a diverse ethnic makeup, parallel the findings of large trials done at academic centers of excellence. This demonstrates that comparable diagnostic mpMRI/biopsy quality may be found in the community setting.
