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1.
J Cell Mol Med ; 28(10): e18445, 2024 May.
Article in English | MEDLINE | ID: mdl-38801403

ABSTRACT

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS), a prevalent urological ailment, exerts a profound influence upon the well-being of the males. Autoimmunity driven by Th17 cells has been postulated as a potential factor in CP/CPPS pathogenesis. Nonetheless, elucidating the precise mechanisms governing Th17 cell recruitment to the prostate, triggering inflammation, remained an urgent inquiry. This study illuminated that CCL20 played a pivotal role in attracting Th17 cells to the prostate, thereby contributing to prostatitis development. Furthermore, it identified prostate stromal cells and immune cells as likely sources of CCL20. Additionally, this research unveiled that IL-17A, released by Th17 cells, could stimulate macrophages to produce CCL20 through the NF-κB/MAPK/PI3K pathway. The interplay between IL-17A and CCL20 establishes a positive feedback loop, which might serve as a critical mechanism underpinning the development of chronic prostatitis, thus adding complexity to its treatment challenges.


Subject(s)
Autoimmune Diseases , Chemokine CCL20 , Chemotaxis , Interleukin-17 , Prostatitis , Th17 Cells , Male , Prostatitis/immunology , Prostatitis/pathology , Prostatitis/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Chemokine CCL20/metabolism , Chemokine CCL20/genetics , Animals , Interleukin-17/metabolism , Interleukin-17/immunology , Mice , Autoimmune Diseases/immunology , Autoimmune Diseases/metabolism , Autoimmune Diseases/pathology , Macrophages/metabolism , Macrophages/immunology , Disease Models, Animal , NF-kappa B/metabolism , Signal Transduction , Humans , Mice, Inbred C57BL , Prostate/pathology , Prostate/metabolism , Prostate/immunology , Phosphatidylinositol 3-Kinases/metabolism , Autoimmunity
2.
Asian J Androl ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38657119

ABSTRACT

Tumor metabolic reprogramming is a hallmark of cancer development, and targeting metabolic vulnerabilities has been proven to be an effective approach for castration-resistant prostate cancer (CRPC) treatment. Nevertheless, treatment failure inevitably occurs, largely due to cellular heterogeneity, which cannot be deciphered by traditional bulk sequencing techniques. By employing computational pipelines for single-cell RNA sequencing, we demonstrated that epithelial cells within the prostate are more metabolically active and plastic than stromal cells. Moreover, we identified that neuroendocrine (NE) cells tend to have high metabolic rates, which might explain the high demand for nutrients and energy exhibited by neuroendocrine prostate cancer (NEPC), one of the most lethal variants of prostate cancer (PCa). Additionally, we demonstrated through computational and experimental approaches that variation in mitochondrial activity is the greatest contributor to metabolic heterogeneity among both tumor cells and nontumor cells. These results establish a detailed metabolic landscape of PCa, highlight a potential mechanism of disease progression, and emphasize the importance of future studies on tumor heterogeneity and the tumor microenvironment from a metabolic perspective.

3.
Int Immunopharmacol ; 130: 111682, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38394885

ABSTRACT

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common inflammatory immune disease of the urogenital system. High glucose intake is considered to be a potential promoter of autoimmune diseases. However, the influence of high glucose intake on CP/CPPS is unknown. This research aimed to explore the influences of high glucose intake on experimental autoimmune prostatitis (EAP), a valid animal model of CP/CPPS, and the underlying mechanism. NOD mice received 20% glucose water or normal water treatment during EAP induction. EAP severity and Th17 cell responses were evaluated. Then, we explored the effects of an IL-17A neutralizing antibody, an inhibitor of TGF-ß, the reactive oxygen species (ROS) inhibitor NAC, and the mitochondrial ROS (mtROS) antioxidant MitoQ on glucose-fed EAP mice. The results demonstrated that high glucose intake aggravated EAP severity and promoted Th17 cell generation, which could be ameliorated by the neutralization of IL-17A. In vitro experiments showed that high dextrose concentrations promoted Th17 cell differentiation through mtROS-dependent TGF-ß activation. Treatment with TGF-ß blockade, NAC, or MitoQ suppressed Th17 cell generation both in vivo and in vitro, resulting in the amelioration of EAP manifestations caused by high glucose intake. This study revealed that high glucose intake exacerbates EAP through mtROS-dependent TGF-ß activation-mediated Th17 differentiation. Our results may provide insights into the molecular mechanisms underlying the detrimental effects of an environmental factor, such as high glucose intake, on CP/CPPS.


Subject(s)
Autoimmune Diseases , Prostatitis , Male , Humans , Mice , Animals , Prostatitis/chemically induced , Prostatitis/drug therapy , Reactive Oxygen Species , Interleukin-17 , Th17 Cells , Mice, Inbred NOD , Cell Differentiation , Transforming Growth Factor beta , Glucose , Disease Models, Animal
4.
Cancer Commun (Lond) ; 44(2): 205-225, 2024 02.
Article in English | MEDLINE | ID: mdl-38155418

ABSTRACT

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.


Subject(s)
Antineoplastic Agents , Extracellular Vesicles , Neoplasms , Humans , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Drug Resistance
5.
Andrology ; 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38095276

ABSTRACT

OBJECTIVE: To investigate the mechanism of the CXCL10/CXCR3 axis regulating Th1 cell differentiation and migration through the PI3K/AKT pathway in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Experimental autoimmune prostatitis (EAP) model, a well-described and validated animal model of CP/CPPS, was used in our study. After treatment with CXCL10, the severity of EAP and Th1 cell proportion were respectively measured by HE stains, immunohistochemistry, and flow cytometry. Then, the protein expression of the PI3K/AKT pathway in CXCL10/CXCR3-regulated Th1 cell differentiation and migration was evaluated by western blotting. Additionally, by the CXCR3 antagonist AMG487 and the PI3K inhibitor LY294002 applications, the effects of CXCL10/CXCR3 through PI3K/AKT pathway on the Th1 cell differentiation and migration were further assessed. RESULTS: The EAP model was successfully built. CXCL10 increased the proportion of Th1 cells in EAP mice, accompanied by upregulation of the PI3K/AKT pathway. Additionally, the PI3K/AKT pathway was found to be involved in CXCL10/CXCR3 axis-mediated Th1 cell differentiation and migration. CONCLUSIONS: Our investigations indicate that the CXCL10/CXCR3 axis regulates Th1 cell differentiation and migration in EAP through the PI3K/AKT pathway, which provides a new perspective on the immunological mechanisms of CP/CPPS.

6.
Am J Transl Res ; 15(8): 5508-5518, 2023.
Article in English | MEDLINE | ID: mdl-37692962

ABSTRACT

OBJECTIVES: To observe the features of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) images of renal wounds after minimally-invasive partial nephrectomy (MIPN) and evaluate their severity using these two modalities. METHODS: This prospective, observational study included 120 patients who underwent MIPN from April to December 2019 in our hospital. The postoperative US images were evaluated and classified, and contrast extravasation characteristics of CEUS were recorded. The correlation between the classification system and perioperative factors was analyzed. RESULTS: Eighty-five patients underwent US and CEUS after MIPN. Conventional US images were classified into three grades according to the surface morphology of renal wounds and overall shape of the kidney around the incision. Univariable and multivariable analyses indicated that the N component of the R.E.N.A.L. score and the resection range were preoperative and intraoperative factors, respectively, related to the US image grades (UIGs). A deep location and expanded excision contributed to an increased UIG. The extravasation rate increased with the UIG (Spearman correlation rho=0.247, P=0.022), and a higher UIG prolonged the length of extravasation. The depth of the tumor and resection range were related to the UIG. CONCLUSIONS: US and CEUS were feasible and repeatable methods that reflect the morphologic changes of renal wounds after MIPN and may be useful for evaluating their severity.

7.
Asian J Androl ; 25(2): 192-197, 2023.
Article in English | MEDLINE | ID: mdl-36629158

ABSTRACT

Reprogramming of metabolism is a hallmark of tumors, which has been explored for therapeutic purposes. Prostate cancer (PCa), particularly advanced and therapy-resistant PCa, displays unique metabolic properties. Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes. Among the many nutrients, glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa. In addition to amino acid metabolism, glutamine is also widely involved in the synthesis of other macromolecules and biomasses. Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients. This review summarizes the metabolic landscape of PCa, with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa, and suggests novel therapeutic strategies.


Subject(s)
Glutamine , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Glutamine/metabolism , Glutamine/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy
8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-998949

ABSTRACT

As one of the most severe malignant tumors, cervical cancer poses a significant threat to women. In 2020, the World Health Organization (WHO) introduced the "Global Strategy to Accelerate the Elimination of Cervical Cancer" in response to well-established tertiary prevention measures. Primary prevention measures prioritize health education and the administration of prophylactic human papillomavirus (HPV) vaccines. China currently offers five HPV vaccines supported by extensive research data specific to the Chinese population. This paper discusses the application of HPV vaccines in China and related issues that need to be paid attention to.

9.
Journal of Chinese Physician ; (12): 649-651,655, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-992353

ABSTRACT

Cervical cancer is still a serious threat to the health of women in China. The current strategy is a three-level prevention strategy, among which the diversion of screening and screening abnormalities in the secondary prevention is an important link in preventing cervical cancer. For more than 20 years, China has implemented diversified screening methods such as cytological examination, high-risk human papillomavirus (HPV) testing, and naked eye screening. With the discovery that high-risk HPV infection is closely related to the occurrence of cervical cancer, the screening method for cervical cancer has shifted from cytological examination to HPV testing as the preferred screening method. This article introduces the advantages and disadvantages of high-risk HPV testing and cytological examination as screening methods, and proposes the issues that need to be paid attention to in screening; The principle of diverting screening abnormalities was proposed, and it was proposed that in the process of diverting, individualized and refined management principles should be implemented for screening abnormality projects based on the patient′s age and fertility requirements.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-990806

ABSTRACT

Objective:To observe the features of Henle fiber layer (HFL) in eyes with central serous chorioretinopathy (CSC) using spectral domain optical coherence tomography (SD-OCT).Methods:A cross-sectional study was conducted.Thirty-five CSC patients (35 eyes) treated in the Third People's Hospital of Qingdao from January 2017 to November 2021 were enrolled.The subjects included 23 males (23 eyes) and 12 females (12 eyes), aged 24 to 60 years old, with an average age of (41.14±8.19) years, and had a CSC duration ranged from 1 day to 6 months.SD-OCT was performed on all eyes with a line scan through the central fovea horizontally.The features of HFL over subretinal fluid (SRF) area were analyzed and summarized.The study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the Third People's Hospital of Qingdao (No.2022Y0403001).Results:In 26 eyes with regular dome-shaped neurosensory retinal detachment, HFL appeared to be delimited type 1 in 25 eyes, accounting for 96.15%, delimited type 2 in 7 eyes, accounting for 26.92%, bright in 17 eyes, accounting for 65.38% over SRF area.In 21 eyes with CSC duration≤21 days, HFL all showed delimited type 1 and some presented bright or delimited type 2 at the same time.In 5 eyes with CSC duration>21 days, HFL all showed bright and some were delimited type 1 or delimited type 2 in the meantime.In 15 eyes with symmetrical nasal and temporal retinal detachment, HFL showed symmetrical reflectivity over SRF area in horizontal OCT images in 6 eyes, and showed brighter reflectivity over nasal SRF in nasal elevated OCT images in 3 eyes and over temporal SRF in temporal elevated OCT images in 6 eyes.In 11 eyes with asymmetrical nasal and temporal retinal detachment, HFL showed brighter reflectivity over temporal SRF with larger retinal detachment range on temporal side in horizontal OCT images in 3 eyes.Of the 4 eyes with nasal elevated OCT images, the retinal detachment range was larger on temporal side and HFL showed symmetrical reflectivity over SRF area in 3 eyes, and HFL was brighter over nasal SRF area with larger retinal detachment range on nasal side in 1 eye.Of the 4 eyes with temporal elevated OCT images, the retinal detachment range was larger on nasal side and HFL showed symmetrical reflectivity over SRF area in 3 eyes, and HFL was brighter over nasal SRF area with larger retinal detachment range and higher height on nasal side in 1 eye.In 9 eyes with irregular neurosensory retinal detachment, HFL appeared to be delimited type 1 in 7 eyes, accounting for 77.78%, delimited type 2 in 5 eyes, accounting for 55.56%, bright in 6 eyes, accounting for 66.67%, dark in 4 eyes, accounting for 44.44%, and indistinct in 2 eyes, accounting for 22.22%.The detached neurosensory retina was not smooth in 7 eyes, and the phenotypes of HFL changed with the directions of detached neurosensory retina.In 2 eyes with only low neurosensory retinal detachment, HFL reflectivity on the raised side was slightly weaker than that on the lowered side.Conclusions:HFL appears to be delimited type 1 and bright mostly over SRF area in CSC in SD-OCT images.The phenotypes of HFL vary regularly with the tilt directions of OCT images, CSC duration, and the symmetry, range, height, directional characteristics of detached neurosensory retina.

11.
Asian Journal of Andrology ; (6): 192-197, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-971025

ABSTRACT

Reprogramming of metabolism is a hallmark of tumors, which has been explored for therapeutic purposes. Prostate cancer (PCa), particularly advanced and therapy-resistant PCa, displays unique metabolic properties. Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes. Among the many nutrients, glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa. In addition to amino acid metabolism, glutamine is also widely involved in the synthesis of other macromolecules and biomasses. Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients. This review summarizes the metabolic landscape of PCa, with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa, and suggests novel therapeutic strategies.


Subject(s)
Male , Humans , Glutamine/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy
12.
International Eye Science ; (12): 634-639, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-965791

ABSTRACT

AIM: To analyze the similarities and differences of the clinical features between persistent hyperplastic primary vitreous(PHPV)and congenital fibrovascular pupillary membrane(CFPM).METHODS: Retrospectively analyze the ocular biometric parameters, clinical features and morphological changes in children with PHPV(PHPV group)and CFPM(CFPM group)who received surgery at the department of ophthalmology, Xijing Hospital from March 2006 to December 2021.RESULTS: The study included 56 cases(61 eyes)of PHPV and 24 cases(25 eyes)of CFPM. There were no differences on the gender and age of onset between PHPV and CFPM, and both of them were mainly unilaterally affected, with the ratio of 91% and 96%. Children with PHPV and cataract combined with other complications and ocular developmental abnormalities. CFPM was mainly presented different degrees of blockage and morphological abnormalities of pupillary area. In unilateral cases of PHPV and CFPM, the anterior chamber depth(ACD)of affected eyes was smaller than that of the fellow eyes, and in subgroups with age of operation ≤24mo, the axial length(AL)of affected eyes was smaller than that of the fellow eyes(P<0.05). The corneal diameter(CD)of the affected eyes in PHPV group was smaller and the intraocular pressure(IOP)was higher than those of the fellow eyes(all P<0.05); while there were no significant differences on CD and IOP between affected eyes and the fellow eyes in CFPM group(P>0.05). The ACD of affected eyes in PHPV group was significantly smaller than that of CFPM group(P<0.05). The fibrovascular membrane in PHPV group was located in the posterior part of the lens and vitreous cavity; while the fibrovascular membrane in CFPM group was located between the iris and the anterior capsule of the lens, rarely involving the lens.CONCLUSION: PHPV and CFPM had the similar clinical features, suggesting that they may belong to the different variants of persistent fetal vasculature(PFV). However, PHPV had a wider range of lesions and more complex conditions.

13.
Journal of Experimental Hematology ; (6): 1192-1198, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1009974

ABSTRACT

OBJECTIVE@#To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA.@*METHODS@#The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed.@*RESULTS@#A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ2=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034).@*CONCLUSIONS@#Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.


Subject(s)
Humans , Carbapenems/therapeutic use , Pseudomonas aeruginosa , Soft Tissue Infections/drug therapy , Anti-Bacterial Agents/therapeutic use , Hematologic Diseases , Survival Analysis
14.
Mil Med Res ; 9(1): 44, 2022 08 17.
Article in English | MEDLINE | ID: mdl-35978389

ABSTRACT

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.


Subject(s)
Urinary Bladder Neoplasms , Administration, Intravesical , BCG Vaccine/therapeutic use , Cystectomy , Humans , Neoplasm Invasiveness , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/therapy
15.
Front Immunol ; 13: 915218, 2022.
Article in English | MEDLINE | ID: mdl-35860242

ABSTRACT

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a very common urological disorder and has been gradually regarded as an immune-mediated disease. Multiple studies have indicated that the gut microflora plays a pivotal part in immune homeostasis and autoimmune disorder development. However, whether the gut microflora affects the CP/CPPS, and the underlying mechanism behind them remain unclear. Here, we built an experimental autoimmune prostatitis (EAP) mouse model by subcutaneous immunity and identified that its Th17/Treg frequency was imbalanced. Using fecal 16s rRNA sequencing and untargeted/targeted metabolomics, we discovered that the diversity and relative abundance of gut microflora and their metabolites were obviously different between the control and the EAP group. Propionic acid, a kind of short-chain fatty acid (SCFA), was decreased in EAP mice compared to that in controls, and supplementation with propionic acid reduced susceptibility to EAP and corrected the imbalance of Th17/Treg cell differentiation in vivo and in vitro. Furthermore, SCFA receptor G-protein-coupled receptor 43 and intracellular histone deacetylase 6 regulated by propionic acid in Th17 and Treg cells were also evaluated. Lastly, we observed that fecal transplantation from EAP mice induced the decrease of Treg cell frequency in recipient mice. Our data showed that gut dysbiosis contributed to a Th17/Treg differentiation imbalance in EAP via the decrease of metabolite propionic acid and provided valuable immunological groundwork for further intervention in immunologic derangement of CP/CPPS by targeting propionic acid.


Subject(s)
Chronic Pain , Gastrointestinal Microbiome , Prostatitis , Animals , Cell Differentiation , Humans , Male , Mice , Pelvic Pain/metabolism , Propionates/pharmacology , RNA, Ribosomal, 16S , T-Lymphocytes, Regulatory/metabolism
16.
Andrologia ; 54(8): e14455, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35560069

ABSTRACT

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.


Subject(s)
Autoimmune Diseases , Chronic Pain , Prostatitis , Animals , Chemokine CXCL1 , Chemokine CXCL2 , Chronic Disease , Disease Models, Animal , Humans , Interleukin-17 , Male , Mice , Neutrophil Infiltration , Pelvic Pain , Prostatitis/drug therapy
17.
Mil Med Res ; 9(1): 14, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35361280

ABSTRACT

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.


Subject(s)
Prostatic Hyperplasia , Transurethral Resection of Prostate , Urethral Stricture , Aged , Humans , Male , Prostate , Prostatic Hyperplasia/surgery , Quality of Life , Transurethral Resection of Prostate/adverse effects , Transurethral Resection of Prostate/methods , Urethral Stricture/etiology , Urethral Stricture/surgery
18.
Mol Cell ; 82(3): 542-554.e6, 2022 02 03.
Article in English | MEDLINE | ID: mdl-35081364

ABSTRACT

Non-covalent complexes of glycolytic enzymes, called metabolons, were postulated in the 1970s, but the concept has been controversial. Here we show that a c-Myc-responsive long noncoding RNA (lncRNA) that we call glycoLINC (gLINC) acts as a backbone for metabolon formation between all four glycolytic payoff phase enzymes (PGK1, PGAM1, ENO1, and PKM2) along with lactate dehydrogenase A (LDHA). The gLINC metabolon enhances glycolytic flux, increases ATP production, and enables cell survival under serine deprivation. Furthermore, gLINC overexpression in cancer cells promotes xenograft growth in mice fed a diet deprived of serine, suggesting that cancer cells employ gLINC during metabolic reprogramming. We propose that gLINC makes a functional contribution to cancer cell adaptation and provide the first example of a lncRNA-facilitated metabolon.


Subject(s)
Biomarkers, Tumor/metabolism , Carrier Proteins/metabolism , DNA-Binding Proteins/metabolism , Glycolysis , Membrane Proteins/metabolism , Neoplasms/enzymology , Phosphoglycerate Kinase/metabolism , Phosphoglycerate Mutase/metabolism , Phosphopyruvate Hydratase/metabolism , RNA, Long Noncoding/metabolism , Thyroid Hormones/metabolism , Tumor Suppressor Proteins/metabolism , Adenosine Triphosphate/metabolism , Animals , Biomarkers, Tumor/genetics , Carrier Proteins/genetics , Cell Proliferation , DNA-Binding Proteins/genetics , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , HEK293 Cells , HeLa Cells , Hep G2 Cells , Humans , L-Lactate Dehydrogenase/genetics , L-Lactate Dehydrogenase/metabolism , Membrane Proteins/genetics , Mice, Nude , Multienzyme Complexes , Neoplasms/genetics , Neoplasms/pathology , Phosphoglycerate Kinase/genetics , Phosphoglycerate Mutase/genetics , Phosphopyruvate Hydratase/genetics , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , RNA, Long Noncoding/genetics , Serine/deficiency , Thyroid Hormones/genetics , Tumor Burden , Tumor Suppressor Proteins/genetics , Thyroid Hormone-Binding Proteins
19.
Zhonghua Nan Ke Xue ; 28(7): 579-584, 2022 Jul.
Article in Chinese | MEDLINE | ID: mdl-37556213

ABSTRACT

OBJECTIVE: To investigate the prevalence of and risk factors for prostate calcification (PCal) in ≥40 years old males with benign prostatic enlargement (BPE) found in health checkup. METHODS: We retrospectively analyzed the data on 671 ≥40-year-old men found with BPE in health checkup and investigated the prevalence of and risk factors for PCal in BPE males aged ≥40 years by univariate and multivariate analyses. RESULTS: Among 1 582 men aged ≥40 years undergoing health checkup, 671 were found with BPE and 274 (17.3%) with both BPE and PCal. The incidence rate of PCal was 40.8% (274/671) in the BPE patients, which was increased with age (trend χ2 = 5.289, P = 0.021), with statistically significant differences in different age groups (χ2 = 9.243, P = 0.026). Significant differences were also observed in age, height, estimated glomerular filtration rate (eGFR), urine pH level and the number of cases of uneven prostatic echoes between the BPE patients with and those without PCal (P < 0.05). Logistic regression analysis showed that age (OR = 1.027, 95% CI: 1.010-1.044), urine pH (OR = 1.446, 95% CI: 1.148-1.823) and uneven prostatic echoes (OR = 2.150, 95% CI: 1.108-4.174) were the associated factors for PCal in BPE patients aged ≥40 years. CONCLUSION: The incidence rate of PCal is high and increased with age in BPE patients aged ≥40 years, and age, urine pH and uneven prostatic echoes are associated factors for PCal in this cohort.


Subject(s)
Prostate , Prostatic Hyperplasia , Male , Humans , Adult , Retrospective Studies , Prevalence , Prostatic Hyperplasia/epidemiology , Risk Factors
20.
Zhonghua Nan Ke Xue ; 28(9): 837-842, 2022 Sep.
Article in Chinese | MEDLINE | ID: mdl-37839011

ABSTRACT

Prostate cancer (PCa) is a most common malignancy in males. It has a greater heterogeneity than other cancers, which poses a real challenge to the clinical diagnosis, classification and prognostic monitoring. At present, high-, medium- and low-risk PCa patients are classified mainly by Gleason scores and the PSA level, which, however, fail to reveal the diverse molecular heterogeneity and precisely distinguish the molecular subtypes of PCa. With the development of high-throughput sequencing, more and more studies on the molecular classification of the malignancy have paved the theoretical ground for the early diagnosis, efficacy prediction and individualized treatment of PCa. This study reviews the molecular classification, prognosis prediction and individualized treatment of PCa to date, hoping to contribute to the development of the precise treatment of PCa.


Subject(s)
Prostatic Neoplasms , Male , Humans , Prognosis , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/therapy , Neoplasm Grading , Prostatectomy , Prostate-Specific Antigen
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