Astaxanthin alleviates chronic prostatitis/chronic pelvic pain syndrome by increasing colonization of Akkermansia muciniphila in the intestine.

BACKGROUND: Astaxanthin (AST) is a natural compound with anti-inflammatory/immunomodulatory properties that has been found to have probiotic properties. However, the role and mechanism of AST in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still not fully understood. PURPOSE: The aim of this study was to evaluate the effect of AST on CP/CPPS and elucidate the mediating role of the gut microbiota. MATERIALS AND METHODS: An experimental autoimmune prostatitis (EAP) mouse model was utilized to test the potential role of AST on CP/CPPS. Antibiotic cocktail (ABX) treatment and fecal microbiota transplantation (FMT) were used to elucidate the gut microbiota-mediated effects on AST. In addition, 16S rRNA gene sequencing and qRT-PCR analyses were used to analyze changes in the gut microbiota of EAP mice and CP/CPPS patients. Finally, the mechanism by which AST exerts a protective effect on CP/CPPS was explored by untargeted metabolomics and gut barrier function assays. RESULTS: Oral administration of AST reduced prostate inflammation scores, alleviated tactile sensitization of the pelvic region in EAP mice, reduced CD4+ T cell and CD68+ macrophage infiltration in the prostatic interstitium, and inhibited the up-regulation of systemic and localized pain/pro-inflammatory mediators in the prostate. After ABX, the protective effect of AST against CP/CPPS was attenuated, whereas colonization with fecal bacteria from AST-treated EAP mice alleviated CP/CPPS. 16S rRNA gene sequencing and qRT-PCR analyses showed that Akkermansia muciniphila in the feces of EAP mice and CP/CPPS patients showed a trend toward a decrease, which was associated with poor progression of CP/CPPS. In contrast, oral administration of AST increased the relative abundance of A. muciniphila, and oral supplementation with A. muciniphila also alleviated inflammation and pain in EAP mice. Finally, we demonstrated that both AST and A. muciniphila interventions increased serum levels of SCFAs acetate, up-regulated expression of colonic tight junction markers, and decreased serum lipopolysaccharide levels in EAP mice. CONCLUSION: Our results showed that AST improved CP/CPPS by up-regulating A. muciniphila, which provides new potentially effective strategies and ideas for CP/CPPS management.

Synergistic mediating effect of edible fungal polysaccharides (Auricularia and Tremellan) and Crataegus flavonoids in hyperlipidemic rats.

Both edible fungal polysaccharides (Auricularia and Tremellan) and Crataegus flavonoids promote the balance of dyslipidemia, which have a positive biological regulating effect on intestinal flora. In this study, the extraction of water-soluble polysaccharides from Auricularia and Tremellan was investigated and optimized firstly. Polysaccharides and flavonoids were then combined to study the effects on the mediating role of abnormal blood lipid concentration and intestinal flora in vivo. The rats were divided into 10 groups, the NC (normal control), HM (model), PCI (Simvastatin control), PCII (Fenofibrate control), AAP (Auricularia auricular Polysaccharide), TFP (Tremella fuciformis Polysaccharide), HF (Crataegus Flavonoid), LDC (Low-dose combination), MDC (Medium dose combination), and HDC (High-dose combination), used to explore the impact of polysaccharides and flavonoids complex on state of blood lipid, liver, and intestinal flora of dyslipidemia rats. The results showed that the combination of polysaccharides and flavonoids could significantly decrease the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and increase the level of high-density lipoprotein cholesterol (HDL-C). It also significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and improved liver morphology. What is more, the HDC favorably alters the intestinal microflora balance, promotes intestinal integrity and mobility, and inhibits the growth of harmful bacteria such as Escherichia coli/Shigella and Clostridium compared with HM group. In brief, the combination of polysaccharides and flavonoids had a synergistic effect on the remission of dyslipidemia, and promoted health by improving lipid metabolism, protecting liver tissue, and regulating the intestinal flora in hyperlipidemia rats.

Comparisons of the Safety and Effectiveness of Robot-Assisted vs Laparoscopic Partial Nephrectomy for Central Renal Angiomyolipomas: A Propensity Score-Matched Analysis Study.

Objective: To compare the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) vs laparoscopic partial nephrectomy (LPN) in the treatment of central renal angiomyolipomas (AMLs). Methods: We retrospectively analyzed the clinical data of 103 patients who were treated with either RAPN or LPN for central AMLs between January 2017 and June 2022. Propensity scores were matched according to sex, age, laterality, body mass index, symptoms, diameter of tumor, location of tumor distribution, R.E.N.A.L score, preoperative hemoglobin, preoperative serum creatinine, preoperative estimated glomerular filtration rate, chronic disease, previous abdominal surgery, preoperative selective arterial embolization, American Society of Anesthesiologists scale, and duration of follow-up, and after matching, perioperative and prognostic data of the two groups were compared. Results: A total of 57 patients underwent RAPN, and 46 patients underwent LPN. Before matching, there were more complex AMLs in the RAPN group, and R.E.N.A.L scores differed between the two groups (10 vs 9, p < 0.001). After matching, the median warm ischemic time in the RAPN group was significantly shorter than that in the LPN group (21.5 minutes vs 28 minutes, p = 0.034), as well as the median time of postoperative mobilization (1 day vs 2 days, p < 0.001). The other indicators were not significantly different between the groups. Conclusions: For central AMLs, both RAPN and LPN were safe and feasible surgical treatments, but RAPN might be associated with shorter warm ischemia time and earlier postoperative mobilization.

Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma.

BACKGROUND: The response of advanced clear cell renal cell carcinoma (ccRCC) to immunotherapy is still not durable, suggesting that the immune landscape of ccRCC still needs to be refined, especially as some molecules that have synergistic effects with immune checkpoint genes need to be explored. METHODS: The expression levels of CENPM and its relationship with clinicopathological features were explored using the ccRCC dataset from TCGA and GEO databases. Quantitative polymerase chain reaction (qPCR) analysis was performed to validate the expression of CENPM in renal cancer cell lines. Kaplan-Meier analysis, COX regression analysis and Nomogram construction were used to systematically evaluate the prognostic potential of CENPM in ccRCC. Besides, single gene correlation analysis, protein-protein interaction (PPI) network, genetic ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to predict the biological behaviour of CENPM and the possible signalling pathways involved. Finally, a comprehensive analysis of the crosstalk between CENPM and immune features in the tumor microenvironment was performed based on the ssGSEA algorithm, the tumor immune dysfunction and exclusion (TIDE) algorithm, the TIMER2.0 database and the TISIDB database. RESULTS: CENPM was significantly upregulated in ccRCC tissues and renal cancer cell lines and was closely associated with poor clinicopathological features and prognosis. Pathway enrichment analysis revealed that CENPM may be involved in the regulation of the cell cycle in ccRCC and may have some crosstalk with the immune microenvironment in tumors. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. Furthermore, the TISIDB database provides evidence that not only CENPM is positively associated with immune checkpoint genes such as CTLA4, PDCD1, LAG3, TIGIT, but also chemokines and receptors (such as CCL5, CXCL13, CXCR3, CXCR5) may be responsible for the malignant phenotype of CENPM in ccRCC. Meanwhile, predictions based on the TIDE algorithm support that patients with high CENPM expression have a worse response to immunotherapy. CONCLUSIONS: The upregulation of CENPM in ccRCC predicts a poor clinical outcome, and this malignant phenotype may be associated with its exacerbation of the immunosuppressive state in the tumor microenvironment.

[Construction and quality evaluation of strawberry seedling index model]. / 草莓种苗壮苗指数模型的构建与质量评价.

With the development of strawberry cultivated area in China, the demands for high-quality strawberry seedlings are increasing year by year. The research on the evaluation index of strawberry seedlings is needed to ensure the quality of the seedlings. This study aimed to establish an optimal index model of strawberry seedlings to improve the accuracy of seedlings evaluation. In this study, 320 seedlings of 'Benihoppe' strawberry seedlings growing for 40 days were taken as the materials. Based on the determination of 16 individual indicators including the growth of aboveground and underground parts, fresh weight, and dry weight, we firstly conducted the membership function corresponding to single indicator. Then the comprehensive evaluation index of strawberry seedlings was calculated using weighted fuzzy evaluation method. Furthermore, the key indicators out of the 16 indicators which were filtered out by means of the principal component analysis method were combined into different index models of strawberry seedlings. The correlation analysis between the comprehensive evaluation index and seedling index models was done and finally the optimal seedling index model was selected and verified. The results showed that there were significant differences in 16 indices of 320 randomly selected strawberry seedlings. The comprehensive evaluation index of strawberry seedlings was in the range of 0.165-0.817, indicating that the comprehensive evaluation index could totally reflect the quality of seedlings and could be used as the evaluation basis. The 16 individual indices of strawberry seedlings were classified into three principal components, including aboveground related indicators, underground related indicators, and the pigment indicators. The cumulative contribution rate of three principal components was 79.7%. Twenty-seven seedlings index models were combined by randomly selecting three indices with a large contribution value from each principal component. Five strawberry seedlings index mo-dels were selected from 27 models due to the highest correlation with the comprehensive evaluation index. Among them, the model "aboveground dry weight×root surface area×chlorophyll a" was identified as the optimal one to evaluate the quality of strawberry seedlings, due to the highest correlation with the comprehensive evaluation index. The correlation coefficient of between strong seedling index and comprehensive evaluation index in three strawberry variety 'Benihoppe', 'Kantoseika' and 'Sweet Charlie' were 0.879, 0.924, and 0.975, respectively. According to the comprehensive evaluation index, the quality of strawberry seedlings were classified into three grades: grade Ⅰ (comprehensive evaluation index ≥0.5, seedling index ≥4.0) with high-quality seedlings; grade Ⅱ (comprehensive evaluation index 0.3-0.5, seedling index 0.5-4.0) with qualified seedlings; grade Ⅲ (comprehensive evaluation index ≤0.3, seedling index ≤0.5) with weak seedlings. The results provided a theoretical basis and scientific method for the evaluation of the health status of strawberry seedlings or other fruits and vegetable seedlings.

Progress in Clinical Research on Gonadotropin-Releasing Hormone Receptor Antagonists for the Treatment of Prostate Cancer.

Gonadotropin-releasing hormone (GnRH) receptor agonists are still the most commonly used androgen deprivation treatment (ADT) drugs for prostate cancer in clinical practice. Currently, the GnRH receptor antagonists used for endocrine therapy for prostate cancer primarily include degarelix and relugolix (TAK-385). The former is administered by subcutaneous injection, while the latter is an oral drug. Compared to GnRH agonists, GnRH antagonists reduce serum testosterone levels more rapidly without an initial testosterone surge or subsequent microsurges. This review focuses on the mechanism of action of GnRH antagonists and agonists, the developmental history of GnRH antagonists, and emerging data from clinical studies of the two antagonists used as endocrine therapy for prostate cancer.

Development of prognostic signature based on RNA binding proteins related genes analysis in clear cell renal cell carcinoma.

RNA binding proteins (RBPs) play significant roles in the development of tumors. However, a comprehensive analysis of the biological functions of RBPs in clear cell renal cell carcinoma (ccRCC) has not been performed. Our study aimed to construct an RBP-related risk model for prognosis prediction in ccRCC patients. First, RNA sequencing data of ccRCC were downloaded from The Cancer Genome Atlas (TCGA) database. Three RBP genes (EIF4A1, CARS, and RPL22L1) were validated as prognosis-related hub genes by univariate and multivariate Cox regression analyses and were integrated into a prognostic model by least absolute shrinkage and selection operator (LASSO) Cox regression analysis. According to this model, patients with high risk scores displayed significantly worse overall survival (OS) than those with low risk scores. Moreover, the multivariate Cox analysis results indicated that risk score, tumor grade, and tumor stage were significantly correlated with patient OS. A nomogram was constructed based on the three RBP genes and showed a good ability to predict outcomes in ccRCC patients. In conclusion, this study identified a three-RBP gene risk model for predicting the prognosis of patients, which is conducive to the identification of novel diagnostic and prognostic molecular markers.

[Effects of Solanum lycopersicum rootstock on biomass, amnio acid content and reactive oxygen species metabolism of grafted seedlings under salt stress]. / ç›èƒè¿«ä¸‹ç•ªèŒ„ç §æœ¨å¯¹å«æŽ¥è‹—ç”Ÿç‰©é‡ã€æ°¨åŸºé ¸å«é‡å’Œæ´»æ€§æ°§ä»£è°¢çš„å½±å“.

To explore the mechanism of Solanum lycopersicum rootstock function in enhancing salt tolerance of grafted seedlings, we examined the growth, Na+ accumulation, amino acid contents and active oxygen metabolism (ROS) in three grafted seedlings treated with and without 175 mmol·L-1 NaCl conditions. RS grafted seedlings were formed by split grafting using salt-sensitive variety 'Zhongza 9'(S) as scion and salt-tolerant variety 'OZ-006'(R) as rootstock, while the other two experiment materials were the scion self-grafted (SS) and rootstock self-grafted (RR) seedlings. The results showed that NaCl stress significantly increased the salt damage index and Na+ content, concomitantly with substantial decrease in growth rate and chlorophyll content of seedlings. More-over, there were significant differences among the grafting combinations, with an order of SS>RS>RR. NaCl stress significantly increased total amino acid content in the leaves and roots of the grafted seedlings. The amino acid contents were significantly higher than those in the control. There were 9 kinds of amino acid in RR and RS leaves, and 8 kinds in RR and RS roots, with the most significant change in proline. Only 2 and 4 kinds of amino acids in leaves and roots of SS were significantly higher than those in control, respectively. Amino acid contents among three grafted seedlings showed RR>RS>SS under NaCl stress. The contents of amino acid in RR and RS leaves increased by 32.8% and 16.6% compared with SS, and those in RR and RS roots increased by 53.1% and 32.5%, respectively. The changes of ROS were caused by NaCl stress, which enhanced the activities of antioxidant enzymes, the production rate of O2-· and MDA content in both leaves and roots. Among different grafted seedlings, RR had the most prominent increase of antioxidant enzymes activities in leaves and roots, followed by RS, and SS showed the smallest. The active oxygen levels among the three grafted seedlings were show as SS>RS>RR. In summary, rootstock alleviated salt damage of grafted seedlings by inhibiting Na+ transport upward, enhancing amino acid content and antioxidant enzyme activities. The salt tolerance ability showed remarkable difference among three different combinations of rootstock and scion, with a order of RR>RS>SS. Our results suggested that salt tolerance of S. lycopersicum grafted seedlings was mainly affected by the ability of rootstock salt tolerance, followed by scion, and also closely related to the regulation of both amino acid and active oxygen metabolism in seedlings.

Comparison of robot-assisted retroperitoneal laparoscopic adrenalectomy versus retroperitoneal laparoscopic adrenalectomy for large pheochromocytoma: a single-centre retrospective study.

BACKGROUND: To evaluate the feasibility and safety of robot-assisted retroperitoneal laparoscopic adrenalectomy (RARLA) for large pheochromocytomas (PHEOs; size≥6 cm) compared with retroperitoneal laparoscopic adrenalectomy (RLA). METHODS: Fifty-one patients who underwent adrenalectomy for large PHEOs between March 2016 and January 2019 were enrolled and divided into two groups, including 32 RLA cases and 19 RARLA cases. We compared the perioperative efficacy and long-term follow-up results between the two groups. RESULTS: Preoperative data, including demographics, comorbidities and tumour characteristics, were similar between the groups. Intraoperatively, the RARLA group had a lower incidence of haemodynamic instability (26.3% vs. 56.2%, P = 0.038) and less intraoperative blood loss (100 ml vs. Two hundred milliliter, P = 0.042) than the RLA group. The groups showed no significant differences in operative time or transfusion rates. Postoperatively, the time to diet resumption, time to ambulation, time to drainage removal and postoperative hospital stay were shorter in the RARLA group than in the RLA group (1 d vs. 2 d, P = 0.027; 1 d vs. 2 d, P = 0.034; 3 d vs. 5 d, P = 0.002; 5 d vs. 6 d, P = 0.02, respectively). The groups exhibited no significant differences in the duration of anaesthetic use, complications, or long-term follow-up results for the blood pressure (BP) improvement rate. CONCLUSIONS: Compared with RLA, RARLA is a safe, feasible and even optimized procedure for large PHEOs.

Exploration of the Main Sites for the Transformation of Normal Prion Protein (PrPC) into Pathogenic Prion Protein (PrPsc).

INTRODUCTION: The functions and mechanisms of prion proteins (PrPC) are currently unknown, but most experts believe that deformed or pathogenic prion proteins (PrPSc) originate from PrPC, and that there may be plural main sites for the conversion of normal PrPC into PrPSc. In order to better understand the mechanism of PrPC transformation to PrPSc, the most important step is to determine the replacement or substitution site. MATERIAL AND METHODS: BALB/c mice were challenged with prion RML strain and from 90 days post-challenge (dpc) mice were sacrificed weekly until all of them had been at 160 dpc. The ultra-structure and pathological changes of the brain of experimental mice were observed and recorded by transmission electron microscopy. RESULTS: There were a large number of pathogen-like particles aggregated in the myelin sheath of the brain nerves, followed by delamination, hyperplasia, swelling, disintegration, phagocytic vacuolation, and other pathological lesions in the myelin sheath. The aggregated particles did not overflow from the myelin in unstained samples. The phenomenon of particle aggregation persisted all through the disease course, and was the earliest observed pathological change. CONCLUSION: It was deduced that the myelin sheath and lipid rafts in brain nerves, including axons and dendrites, were the main sites for the conversion of PrPC to PrPSc, and the PrPSc should be formed directly by the conversion of protein conformation without the involvement of nucleic acids.

[Effects of exogenous gamma-aminobutyric acid on polyamine metabolism of melon seedlings under hypoxia stress].

Taking melon cultivar 'Xiyu No. 1 ' as test material, a hydroponic experiment was conducted to investigate the effects of exogenous gamma-aminobutyric acid (GABA) on the seedlings polyamine metabolism under hypoxia stress. Compared with the control in normoxic treatment, the seedlings under hypoxia stress had significantly higher glutamic acid decarboxylase (GAD) activity and GABA content, and their polyamine synthesis enzymes activities all enhanced significantly, which led to a marked increase of polyamines contents. Meanwhile, the seedlings leaf- and root diamine oxidase (DAO) and polyamine oxidase (PAO) activities also had a significant increase. The increment of root arginine decarboxylase (ADC) activity was higher, which induced a higher content of free putrescine (Put) in roots, while the increment of leaf ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activities were higher, inducing a higher content of free spermidine (Spd) in leaves. The PBs-extractable DAO and PAO activies in roots were significantly lower than those in leaves, but the cell wall-bound PAO activity was in adverse. Under hypoxia stress, the addition of exogenous GABA increased the leaf- and root GABA and glutamic acid contents and decreased the GAD activity significantly. The increase of arginine, ornithine, and methionine contents promoted the activities of polyamines synthesis enzymes, which led to the significant increase of polyamines contents and the significant decrease of DAO and PAO activities.

Cloning, expression, and genus-specificity analysis of 28-kDa OmpK from Vibrio alginolyticus.

Some Vibrio species are universal marine pathogens and Vibrio infections are often encountered due to consumption of raw or uncooked seafood. The outer membrane proteins, playing a key role in interaction between bacteria and hosts, are potential candidates for development of vaccine and markers of the genus Vibrio. In this study, the ompK (outer membrane protein K) genes of Vibrio alginolyticus, V. vulnificus, V. parahaemolyticus, V. fluvialis, and V. mimicu were cloned with 798 to 822 nucleotides encoding 266 to 274 amino acids. The ompK gene from V. alginolyticus was expressed in Escherichia coli using pET-22b expression vector. The recombinant fusion OmpK protein with 6xHis tag was purified with nickel chelate affinity chromatography. The polyclonal antibody (titer, 1:102400) against V. alginolyticus OmpK was developed in guinea pigs and it positively reacted with each of 5 Vibrio species but negative to other 18 Gram-negative bacterial strains. The result suggests that Vibrio OmpK protein could be a genus-specific antigen, which can be used for developing vaccines and rapid detection of multiple Vibrio species.