INFLAMMATION
·
2019
·Vol. 42
·期 5
·1705-1718
·
IF 2.939
Chen Jing,Zhan Changsheng,Zhang Li,Zhang Ligang,Liu Yi,Zhang Yong,Du Hexi,Liang Chaozhao,Chen Xianguo
Treg cells are crucial for maintaining immune homeostasis in CP/CPPS, but the molecular mechanisms underlying the modulation of the function of Treg in CP/CPPS remain unclear. The main purpose of this study is to investigate the relationship between immunosuppressive function of Treg and the methylation level of Foxp3 promoter in experimental autoimmune prostatitis (EAP) mouse model. EAP model was induced by subcutaneous injecting prostate-steroid-binding protein (PSBP) and complete Freund’s adjuvant with NOD mice. Histological analysis revealed that EAP model was successfully induced. The expression of IFN-γ was increased, and TGF-β was decreased in the serum of EAP, respectively. The percentage of Tregs in splenic lymphocyte was increased in EAP. The suppressive ability of Tregs on Teffs was impaired in EAP. The methylation level of Foxp3 promoter was increased, and the expression of Foxp3 was decreased in EAP. By injection AZA which was DNA-methylation inhibitor into EAP mice, prostate inflammation was alleviated, expressions of TGF-β and Foxp3 were increased, and the suppressive function of Tregs was improved in vitro and in vivo . Thus, we concluded that aberrant increased methylation of Foxp3 promoter in Treg cells leads to the impaired suppressive function of Treg cells, exacerbating autoimmune inflammatory injury in EAP.
研究领域:
免疫学
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分子生物学
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自身免疫疾病
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表观遗传学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Yuan Yin,Dong Fei-Xue,Liu Xu,Xiao Hong-Bin,Zhou Zhong-Guang
Magnoflorine (Mag) has multiple pharmacological activities for the prevention and treatment of prostatitis. However, its molecular mechanisms andpharmacological targets are not clear. In this study, the ultra-performance liquid tandem mass spectrometry-based metabolomics method was used to clarify the intervention of Mag against prostatitis and the biological mechanism. A total of 25 biomarkers associated with the prostatitis model were identified by metabolomics, and a number of metabolic pathways closely related to the model were obtained by MetPA analysis. After given Mag treatment, the results of each indicator were shown that Mag alkaloid could inhibit the development of prostatitis effectively. We found that Mag had regulative effects on potential biomarkers of prostatitis model, which can regulate them to the control group. Our results indicated that alkaloids have an effective intervention therapy for prostatitis, and five types of metabolic pathways closely related to prostatitis model were obtained, including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, tyrosine metabolism, arginine and proline metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism. This study has provided the basic experimental data for the development of Mag in the prevention and treatment of prostatitis.
研究领域:
药理学
·
代谢组学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Li Yang,Fengxiang Zhang,Weiwei He,Boyuan Zhao,Ting Zhang,Shang Wang,Lifen Zhou,Junwei He
Ethnopharmacological relevance Hosta plantaginea (Lam.) Aschers flowers (HPF) are well-known for their high flavonoid content, which contribute to their widely as traditional Chinese medicine for alleviating inflammation. Despite their recognized potential, information regarding the total flavonoid (TF) of HPF and its therapeutic application in treating chronic prostatitis (CP) remains unknown. Aim of the study We aimed to investigate the extraction optimization, constituent analysis, and alleviating effect of TF on CP as well as its potential mechanism. Materials and methods The optimized extraction of TF from HPF was explored using response surface methodology with a Box-Behnken design model. The major flavonoids in TF were identified based on UHPLC-MS approach. Efficacy of TF (25 and 100 mg/kg, p.o.) on CP was evaluated in prostate antigen emulsion-induced autoimmune CP rat model by measuring prostatic index, the levels of leukocytes and lecithin bodies, as well as histopathological examination. The protein expression contents were detected by western blotting . Additionally, the antioxidant (DPPH and ABTS) and anti-inflammatory (cyclooxygenase 2, COX-2 inhibitory) effects of TF were also evaluated in vitro . Results The optimized conditions for TF extraction were determined as 60% ethanol concentration, 30 mL/g liquid-to-solid ratio, 30 min extraction time, and 90 °C extraction temperature, and the extraction ratio is 65.98 ± 2.14%. A total of 15 major flavonoids in TF were characterized by comparison with reference standards. TF ameliorated the efficacy of CP in rats in a dose-independent manner, including reduced prostatic index and leukocytes levels, elevated lecithin body levels, ameliorated histopathological damage to prostate, and suppressed phosphorylated protein expressions of nuclear factor kappa-B (NF-κB) p65, inhibitor of NF-κB alpha (IκBα), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt). Simultaneously, the IC 50 of TF to DPPH, ABTS radicals, and COX-2 were 2.02, 1.79, and 0.0838 mg/mL, respectively. Conclusions We first demonstrated that TF from HPF represents a promising candidate to alleviate CP through suppression of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt signaling pathways.
研究领域:
药理学
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植物化学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
·
2025
·Vol. 93
·期 5
·e70084
·
IF 2.4
Heng Wang,Zhaofei Liu,Xiangjun Xu,Haitao Zhang,Lei He,Ming Li
Background Chronic prostatitis (CP), a frequent male urological disease, is featured with chronic pelvic pain and various discomfort. Calycosin has anti-inflammatory effect and its exact mechanism in CP remains unknown. Objective Our research was designed to explain the underlying mechanism of calycosin in CP and illustrate our findings in the rats and LPS-ATP-induced RWPE-1 cells. Methods The pathology of prostate tissues was analyzed by HE staining and histological inflammation score. The concentration of inflammatory factors were detected via ELISA assay. Besides, the representative biomarkers of oxidative stress were measured through detection kits. The ROS production, NLRP3 and GSDMD expression were evaluated by immunofluorescence or immumohistochemical staining. Furthermore, the expression of NF-kBp65 pathway-associated proteins and pyroptosis-associated proteins were detected by western blotting. RWPE-1 cells growth and pyroptosis were assessed by CCK-8 and flow cytometry, respectively. mRNA levels of pyroptosis markers were detected by qRT-PCR analysis. Results The CP model in vivo and in vitro was successfully established by carrageenan and LPS-ATP, respectively. Calycosin substantially ameliorated the pathological damage of prostate tissue. Moreover, calycosin treatment promoted RWPE-1 cells viability and reduced pyroptosis. Calycosin remarkably reduced the inflammatory factors secretion and oxidative stress markers. Calycosin stimulation effectively suppressed the pyroptosis, which was linked with inactivation of the NF-kBp65 signaling pathway. These beneficial effects of calycosin were similar to the NLRP3 inhibitor (MCC950). Conclusion To sum up, our observations indicated that calycosin protects against CP via suppressing inflammation, oxidative stress, and pyroptosis through NF-kBp65 pathway, thereby serving as a promising therapy for CP treatment.
研究领域:
医学
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药理学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANDROLOGIA
·
2022
·Vol. 54
·期 8
·e14455
·
IF 2.532
Cheng Zhang,Jia Chen,Hui Wang,Jing Chen,Mei-Juan Zheng,Xian-Guo Chen,Li Zhang,Chao-Zhao Liang,Chang-Sheng Zhan
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a poorly understood disease. Accumulating evidence suggests that autoimmune dysfunction is involved in the development of CP/CPPS. Interleukin-17 (IL-17) is associated with the occurrence and development of several chronic autoimmune inflammatory diseases. However, the molecular mechanisms underlying the role of IL-17 in CP/CPPS are not clear. We confirmed that IL-17 was increased in the prostate tissues of experimental autoimmune prostatitis (EAP) mice. Corresponding to the increase of IL-17, neutrophil infiltration and the levels of CXCL1 and CXCL2 (CXC chemokine ligands 1 and 2) were also increased in the prostate of EAP. Treatment of EAP mice with an IL-17-neutralizing monoclonal antibody (mAb) decreased the number of infiltrated neutrophils and CXCL1 and CXCL2 levels. Depletion of neutrophils using anti-Ly6G antibodies ameliorated the inflammatory changes and hyperalgesia caused by EAP. Fucoidan, a could potent inhibitor of neutrophil migration, also ameliorate the manifestations of EAP. Our findings suggested that IL-17 promoted the production of CXCL1 and CXCL2, which triggered neutrophil chemotaxis to prostate tissues. Fucoidan might be a potential drug for the treatment of EAP via the effective inhibition of neutrophil infiltration.
研究领域:
免疫学
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泌尿学
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炎症
·
自身免疫性疾病
✓ 已验证
DOI
PubMed
高影响因子
OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
·
2015
·Vol. 19
·期 3
·186-195
·
IF 2.362
Hui Sun,Huiyu Wang,Aihua Zhang,Guangli Yan,Yue Zhang,Na An,Xijun Wang
Metabolomics has been increasingly applied to discovering biomarkers and identifying perturbed pathways. Berberine has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties, but its mechanisms for treating nonbacterial prostatitis (NBP) remain unclear completely. We developed the untargeted metabolomics approach based on UPLC-Q-TOF-HDMS to profile the metabolite changes in urine samples in order to discover novel potential biomarkers to clarify mechanisms of berberine in treating a rat model of capsaicin-induced nonbacterial prostatitis (NBP). The changes in metabolic profiling were restored to their base-line values after berberine treatment according to the principal component analysis (PCA) score plots. Fourteen different potential biomarkers and five acutely perturbed metabolic pathways contributing to the treatment of NBP were discovered and identified. Specifically, the berberine-treated rats are located closer to the normal group, indicating that the NBP-induced disturbances to the metabolic profile were partially reversed by berberine treatment. After treatment with berberine, the relative contents of 12 potential biomarkers were effectively regulated, which suggested that the therapeutic effects of berberine on NBP may involve regulating disturbances to the metabolism. Our results show that the protective effect of berberine occurs in part through a reversal of the NBP-caused disturbances.
研究领域:
药理学
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代谢组学
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泌尿医学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 47
·34848-34854
·
IF 3.9
Mutu Lin,Qiaohong Wang,Yun Dai,Jinyuan Chen,Yiming Lin
A highly sensitive and efficient home-use method is impressive and promising in the self-monitoring of chronic prostatitis (CP). Herein, we developed a glucose oxidase-zeolitic imidazolate framework-8-antibody composite (GOx@ZIF-8@Ab2) to achieve highly sensitive point-of-care testing (POCT) of urinary prostatic exosomal protein (PSEP) by combining it with a personal glucometer (PGM). The developed GOx@ZIF-8@Ab2 was prepared through a simple but effective biomineralization reaction and a strong binding affinity between Zn2+ and Fc region of the antibody. This bifunctional material GOx@ZIF-8@Ab2 could not only specifically recognize the PSEP via immunoreaction but also wrap a large number of GOx molecules. Following the sandwich immunoreaction, the prepared GOx@ZIF-8@Ab2 facilitated hydrolysis of glucose in a one-to-many fashion, amplifying the detection signal and greatly improving the sensitivity of PGM detection. In comparison to those of the conventional enzyme-linked immunosorbent assay (ELISA), the detection time of the developed technique was shortened to 45 minutes and its limit of detection (0.23 pg mL−1) was reduced by 4–5 orders of magnitude. This technique was successfully utilized for detecting PSEP in human urine samples with a recovery rate of 96–116%. Owing to its rapid, ultrasensitive, specific and portable features, the as-designed platform based on GOx@ZIF-8@Ab2 and the PGM device holds great promise as a home-use POCT platform for self-monitoring of CP and other chronic diseases.
研究领域:
医学诊断
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生物材料科学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Junsheng Liu,Juntong Yu,Xichun Peng
Chronic nonbacterial prostatitis (CNP) is a common male disease with high incidence and low cure rate. This study aims to investigate the anti-CNP potential of Poria cocos polysaccharides (PPs) in a λ-carrageenan-induced CNP rat model. Results showed that PPs exerted anti-CNP functions by reducing the prostate weight and prostate index as well as the level of C-reactive protein (CRP) and pro-inflammatory cytokines (TNF-α and IL-1β). Further analysis on sex hormones revealed that PPs could favor CNP alleviation by regulating the production of testosterone (T), dihydrotestosterone (DTH), and estradiol (E2). PPs could also alleviate CNP by regulating the level of inducible nitric oxide synthase (iNOS), malonaldehyde (MDA), and superoxide diamutase (SOD) in inflamed prostate, thereby enhancing the anti-oxidative stress activity. As most non-digestive polysaccharides are fermented by gut microbiota rather than being digested directly by the host, we further analyzed PP-induced changes in gut microbiota. Microbiomic analysis revealed that PPs significantly change the profile of gut microbiota. Moreover, the relative abundance of five genera was recovered by PPs with a dose–effect relationship, thereby being suggested to play critical roles in the alleviation of CNP. Epigenomic (methylomic) analysis showed that PPs remodeled the DNA methylome of intestinal epithelia, by which PPs might modify hormone production. In the present study, we reported the anti-CNP activity of PPs as well as the involved mechanisms.
研究领域:
药理学
·
泌尿学
·
微生物学
·
表观遗传学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2015
·Vol. 6
·期 11
·3540-3549
·
IF 2.791
Aihua Zhang,Huiyu Wang,Hui Sun,Yue Zhang,Na An,Guangli Yan,Xiangcai Meng,Xijun Wang
Limonin has been found to possess significant anti-inflammatory properties in animal tests and with, human cells, however, its precise metabolism mechanism has not been well explored. The aim of this study was to investigate the anti-inflammatory effects of limonin in a nonbacterial prostatitis (NBP) animal model. Global metabolite profiling was performed by ultra-high-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC/ESI-TOFMS) and in conjunction with multivariate data analysis and pathway analysis which were integrated to explore differentiating metabolites and clarify the mechanism of limonin against capsaicin-induced NBP. Limonin has a potential protective function revealed by the metabolic profiling of limonin-treated rats located closer to the normal group. Twenty potential biomarker candidates and several key metabolic pathways contributing to the treatment of NBP were discovered and identified. Among the pathways, the related glycine, serine and threonine metabolism, glycerophospholipid metabolism were acutely perturbed. The changes in metabolites were restored to their base-line levels after limonin treatment, which might be through regulating the perturbed pathways to the normal state. The results indicate that changed biomarkers and pathways may provide evidence and insight into limonin action mechanisms and enable us to increase research productivity toward metabolomics in therapeutical assessment and drug discovery.
研究领域:
药理学
·
代谢组学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Dalin Sun,Dong Xing,Dandan Wang,Yuanyuan Liu,Bin Cai,Weimin Deng,Qinglin Hu,Wenjun Ma,Baofang Jin
Background: Chronic non-bacterial prostatitis (CNP), one of the most common chronic diseases in urology, leads to pain in the prostate and dysuria, critically affecting the physical or mental health of patients. However, there are no standard treatment approaches for the treatment of CNP in the clinic. Although the clinical application of Bushen Daozhuo granule (BSDZG) offers hope to CNP patients in China, the mechanisms of BSDZG in treating CNP are still not entirely clear. Hence, we aimed to investigate the novel therapeutic mechanisms of BSDZG on CNP. Methods: In this study, we first assayed the prostate index of rats and then determined the anti-inflammatory and anti-apoptotic effects of BSDZG on CNP in vivo and in vitro by employing ELISA kits and TUNEL staining. Next, we investigated whether the anti-inflammatory and anti-apoptotic mechanisms of BSDZG on prostate protein-induced rats and lipopolysaccharide (LPS) induced RWPE-1 cells were related to the AKT, p38 MAPK, and NF-κB pathways with the help of Western blot. Finally, the influence of BSDZG on the interaction between the p38 MAPK and NF-κB pathway in LPS-induced RWPE-1 cells was explored by adopting dehydrocorydaline (DHC, p38 MAPK activator) with the help of ELISA kits and Western blot. Results: In vivo , BSDZG effectively reduced the prostate index. In vivo and in vitro , BSDZG dramatically declined the level of two pro-inflammatory cytokines, TNF-α and IL-1β, as well as the apoptosis rate. Moreover, in vivo and in vitro , BSDZG memorably upregulated the expression level of p-AKT, and substantially downregulated the expression level of p-p38 MAPK and NF-κB2. The activation of p38 MAPK significantly reversed the moderation effects of BSDZG on the level of TNF-α and IL-1β, as well as the expression level of p-p38 MAPK and NF-κB2 in vitro . Conclusion: To sum up, the in vivo and in vitro therapeutic mechanisms of BSDZG on CNP were reflected as the anti-inflammation and anti-apoptosis that was formed by inhibiting the level of pro-inflammatory cytokines, TNF-α and IL-1β, to regulate the AKT, p38 MAPK, and NF-κB pathways, and the anti-inflammatory effect of BSDZG was realized by suppressing the p38 MAPK pathway to inhibit the downstream NF-κB pathway.
研究领域:
泌尿外科
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药理学
·
分子生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Qi Xue,Cong Wang,Yao Lin,Ting-Fu Jiang,Zhihua Lv
We optimized the combination of deep eutectic solvent (DES)-based ultrasonic-assisted dispersive liquid-liquid microextraction method and 19 F qNMR for quantitation of 5 kinds of fluoroquinolone antibiotics illegally added to drugs for prostatitis treatments (Ciprofloxacin, Levofloxacin, Sparfloxacin, Gatifloxacin, Enrofloxacin). In this study, methyltrioctylammonium bromide and n-capric acid were mixed at a 2:1 M ratio to prepare hydrophobic DES. The newly prepared DES was used as the extract. Fluoroquinolone antibiotics were extracted from saturated ammonium sulfate solution and detected by 19 F qNMR. In this study, the effects of extraction conditions such as DES volume, salt dosage, ultrasonic time, centrifugal time, and vortex time on extraction efficiency were systematically investigated. Under the optimal conditions, good linearity (correlation coefficient r: 0.9993–0.9998) was obtained with a detection limit of 0.1 μg mL −1 . The extraction reproducibility (RSD) of intra-day and inter-day were below 5.01 and 5.98%, respectively. This study showed feasibility of detection of fluoroquinolone antibiotics illegally added in traditional medicines for prostatitis treatments by DES-based ultrasonic-assisted dispersion-liquid microextraction combined with 19 F qNMR method.
研究领域:
分析化学
·
药学
·
医学检测
✓ 已验证
产品关联
DOI
高影响因子
Journal of Inflammation Research
·
2022
·
IF 4.631
Meng Zhang,Yi Liu,Jing Chen,Lei Chen,Li Zhang,Xianguo Chen,Zongyao Hao,Chaozhao Liang
Background Chronic nonbacterial prostatitis (CNP) has a high incidence, low cure rate, and unclear pathogenesis. Here, we aimed to systematically identify effective diagnostic and therapeutic targets for CNP.Methods Prostate tissues were obtained from established mouse models and negative controls and were used for mRNA array sequencing and immunohistochemistry (IHC) staining. Predominant pathways were identified based on pathway enrichment analysis and pharmaceutical experiments. We also investigated the functional role of CXCL12 on CP, a critical factor belonging to the predominant chemotaxis pathway, and employed IHC staining to explore the influence of the CXCL12/CXCR4 axis on the activation of the NF-κB, AKT, and STAT3 signaling pathways. Serum samples derived from both CNP cases and healthy controls were used to determine the secretion level of CXCL12.Results By employing mRNA array sequencing and immunohistochemistry, we found that CXCR4, CXCL12, CD44, and OFLM4 were highly expressed in the infiltrated inflammatory T cells of the prostate tissues generated from CNP mice, while they were rarely expressed on the epithelial cells. Based on the pathway enrichment results, we applied pathway inhibitors to suppress the activity of these classic pathways. We found that targeting the CXCL12/CXCR4 axis with its specific antagonist AMD3100 remarkably alleviated inflammatory infiltration of the prostate in CNP models. Similar results were obtained when we replaced AMD3100 with adenovirus-associated virus (AAV)-shCxcl12. To clarify the potential mechanisms of how the CXCL12/CXCR4 axis influences the pathogenesis of CNP, we tested the classical downstream pathways. The results suggested that p-Akt, p-STAT3, and p-NF-κB were more highly expressed on the inflammatory cells of the prostate derived from the CNP model and were partly suppressed after applying AMD3100 or delivering AAV-shCxcl12, indicating that the CXCL12/CXCR4 axis potentially functioned through AKT/NF-κB and STAT3 signaling to influence the pathogenesis of CNP.Conclusion Our study provides potential diagnostic biomarkers and therapeutic targets for CNP.
研究领域:
免疫学
·
分子生物学
·
药理学
·
泌尿学
✓ 已验证
DOI
PubMed
高影响因子
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