PAHs removal by soil washing with thiacalix[4]arene tetrasulfonate.

Remediating soil contaminated with polycyclic aromatic hydrocarbons (PAHs) presents a significant environmental challenge due to their toxic and carcinogenic properties. Traditional PAHs remediation methods-chemical, thermal, and bioremediation-along with conventional soil-washing agents like surfactants and cyclodextrins face challenges of cost, ecological harm, and inefficiency. Here we show an effective and environmentally friendly calixarene derivative for PAHs removal through soil washing. Thiacalix[4]arene tetrasulfonate (TCAS) has a unique molecular structure of a sulfonate group and a sulfur atom, which enhances its solubility and facilitates selective binding with PAHs. It forms host-guest complexes with PAHs through π-π stacking, OH-π interactions, hydrogen bonding, van der Waals forces, and electrostatic interactions. These interactions enable partial encapsulation of PAH molecules, aiding their desorption from the soil matrix. Our results show that a 0.7% solution of TCAS can extract approximately 50% of PAHs from contaminated soil while preserving soil nutrients and minimizing adverse environmental effects. This research unveils the pioneering application of TCAS in removing PAHs from contaminated soil, marking a transformative advancement in resource-efficient and sustainable soil remediation strategies.

Tumor suppressor miR-361-3p inhibits prostate cancer progression through Gli1 and AKT/mTOR signaling pathway.

BACKGROUND: The primary challenge in prostate cancer (PCa) is tumor metastasis, which seriously affects the survival time of patients. Growing evidence suggests that microRNAs play a crucial regulatory role in various malignancies and that the tumor suppressor miR-361-3p is responsible for regulating migration, proliferation, and invasion in different cancer types. However, the underlying regulatory mechanism of miR-361-3p in PCa remains unknown. METHODS: The expression of miR-361-3p in PCa cells was analyzed using quantitative real time-polymerase chain reaction. The clinical utility of miR-361-3p in PCa was evaluated using in vitro assays. The mechanism of action of miR-361-3p was investigated using western blotting, luciferase reporter assays, immunofluorescence, and rescue studies. RESULTS: The function, invasiveness, migration, and proliferation of PCa cells, as well as epithelial-mesenchymal transition (EMT), were aided by the downregulation of miR-361-3p, whereas its overexpression exerted the opposite effect. Repression of glioma-associated oncogene homolog 1 (Gli1) expression by miR-361-3p led to activation of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) signaling pathway, triggering EMT and promoting PCa metastasis. CONCLUSIONS: Downregulation of miR-361-3p along the Gli1 axis promoted tumor malignancy. Collectively, the results of this study imply that miR-361-3p has the potential to be both a biomarker and therapeutic target in PCa.

LncRNA HOXA11-AS modulates the miR-148b-3p/MLPH axis to promote prostate cancer cell proliferation.

Prostate cancer refers to the epithelial malignant tumor of the prostate. It has a high incidence and mortality rate, seriously endangering the lives of men. In recent years, lncRNAs have become a hot topic for lots of scholars for their regulation functions on assorted cancers. Several lncRNAs have been proven they can take part in the regulation of prostate cancer development. Nevertheless, how HOXA11-AS (homeobox A11 antisense RNA)functioned in prostate cancer is not explained. In our research, the expression of HOXA11-AS in prostate cancer cells was evaluated through qRT-PCR. Colony formation experiments, EdU experiments, Tanswelland TUNEL experiments, as well as caspase-3 detection, were designed to test cell proliferation, migration, invasion and apoptosis. RIP, pull down and luciferase reporter experiments examined the correlations of HOXA11-AS, miR-148b-3p and MLPH. We discovered a high level of HOXA11-AS in prostate cancer cells.HOXA11-AS silence could restrain the mentioned cell malignant behavior. Mechanically, HOXA11-AS could sponge miR-148b-3p to target MLPH. MLPH was positively associated with HOXA11-AS and overexpressed it accelerated the progression of prostate cancer. Taken together, HOXA11-AS elevated MLPH expression by sponging miR-148b-3p and accelerated prostate cancer cell proliferation.

Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1.

Background: Exosomes have been identified to mediate the transmission of RNAs among different cells in tumor microenvironment, thus affecting the progression of different diseases. However, exosomal messenger RNAs (mRNAs) have been rarely explored. RNF157 mRNA has been found to be up-regulated in PCa patients' exosomes, but the role of exosomal RNF157 mRNA in PCa development remains unclear. Methods: Online databases were utilized for predicting gene expression and binding correlation between different factors. RT-qPCR and western blot assays were respectively done to analyze RNA and protein expressions. Flow cytometry analysis was implemented to analyze M2 polarization. Results: RNF157 expression was high in PCa tissues and cells. M2 polarization of macrophages was enhanced after co-culture with PCa cells or with exosomes released by PCa cells. Upon RNF157 knockdown in PCa cells, the extracted exosomes could not lead to the facilitated M2 polarization. Mechanistically, RNF157 could bind to HDAC1 and contribute to HDAC1 ubiquitination, which led to HDAC1 degradation and resulting in promoting M2 polarization of macrophages. Animal experiments validated that exosomal RNF157 accelerated PCa tumor growth through facilitating macrophage M2 polarization. Conclusion: Exosome-mediated RNF157 mRNA from PCa cells results in M2 macrophage polarization via destabilizing HDAC1, consequently promoting PCa tumor progression.

The Epidemiological Characteristics of Noncommunicable Diseases and Malignant Tumors in Guiyang, China: Cross-sectional Study.

BACKGROUND: Studies that address the changing characteristics of diseases are of great importance for preventing and controlling the occurrence and development of diseases and for improving health. However, studies of the epidemiological characteristics of noncommunicable diseases (NCDs) and malignant tumors (MTs) of the residents in Guiyang, China, are lacking. OBJECTIVE: The aim of this study was to evaluate the prevalences of NCDs and MTs in residents of Guiyang, Guizhou Province, China, and analyze differences among ages, genders, and regions. METHODS: A multistage stratified cluster sampling method was used. Based on the inclusion and exclusion criteria, 81,517 individuals were selected for the study. Of these, 77,381 (94.9%) participants completed the study. Structured questionnaires were used to collect information on demographic characteristics, NCDs, and MTs. The chi-square test (with 95% confidence intervals) was used to analyze differences in disease prevalence among genders, ages, and geographical regions. RESULTS: The major chronic NCDs of Guiyang residents are obesity, hypertension, and diabetes. MTs in women are mostly breast cancer, cervical cancer, and endometrial cancer, whereas in men, MTs are mainly lung cancer, rectal cancer, and gastric cancer. The prevalences of hypertension and diabetes in women are higher than in men, but the prevalences of lung cancer and gastric cancer in men are higher than in women. The epidemiological characteristics of individuals in different life stages are dissimilar. In terms of regional distribution, the prevalences of the above diseases in the Baiyun and Yunyan districts of Guiyang are relatively high. CONCLUSIONS: Several NCDs (obesity, hypertension, and diabetes) and MTs (women: breast cancer, cervical cancer, and endometrial cancer; men: lung cancer, rectal cancer, and gastric cancer) should be the focus for the prevention and control of chronic diseases in the future. In particular, the Baiyun and Yunyan districts of Guiyang are the important regions to emphasize.

Transgenic construction and functional miRNA analysis identify the role of miR-7 in prostate cancer suppression.

Although miR-7 suppresses the initiation and progression in cancers, little is known about its role in prostate cancer, especially in transgenic mouse models. In present study, we found that expression of miR-7, regulated by p53, was lower in prostate cancer tissues, and miR-7 overexpression significantly mitigated prostate cancer cells growth both in vitro, in organoids and in vivo regardless of p53 status. After we generated miR-7 overexpression transgenic mice and miR-7+/TRAMP mice, we found that transgenic overexpression of miR-7 in mice is safe and miR-7+/TRAMP mice have a preferred overall survival. Moreover, in vivo treatment of miR-7 inhibited subcutaneous tumour growth in mice and prolonged the survival of mice harboring prostate cancer lung metastasis when co-injection with PD-1 antibody. In addition, miR-7 downregulated glycolysis of prostate cancer cells by inhibiting several key pathways including HIF-1α, and subsequently remodeled acidic tumour microenvironment, PanKLa level and T cell infiltration. In summary, our findings highlighted a promising target for development of miRNA-based therapeutics for prostate cancer patients regardless of p53 status.

Associations between long-term exposure to ambient air pollution and renal function in Southwest China: The China Multi-Ethnic Cohort (CMEC) study.

BACKGROUND: Limited studies have examined associations between air pollutants exposure and renal function, especially in China, with the most extensive chronic kidney disease (CKD) disease burden worldwide. OBJECTIVES: This study examines associations between long-term exposure to ambient PM2.5, NO2, CO, O3, SO2 and renal function. METHODS: We included 80,225 participants aged 30-79 years from the baseline data of the China Multi-Ethnic Cohort (CMEC) study. Three-year average concentrations of PM2.5, NO2, CO, O3, and SO2 were estimated using satellite-based spatiotemporal models. Renal function is determined by the estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. After adjusting for covariates, generalized propensity scores (GPS) weighting regression was used to estimate associations between ambient air pollutants and renal function. RESULTS: An increase of 0.1 mg/m3 CO (OR [odds ratio] =1.20 95% CI [confidence interval], 1.05-1.37) was positively associated with CKD. An increase of 1 µg/m3 in SO2 (1.07, 1.00-1.14) concentration was positively associated with CKD. An increase of 10 µg/m3 in PM2.5 (1.17, 0.99-1.38), NO2 (1.12, 0.83-1.51) and O3 (1.10, 0.81-1.50) concentration was not associated with CKD. These effects are stronger in those younger than 65, smoking and with low BMI. CONCLUSIONS: In this study, we found that long-term exposure to ambient CO and SO2 were positively associated with CKD. Gaseous pollutants should also arouse the concern of relevant departments.

MAP9 Exhibits Protumor Activities and Immune Escape toward Bladder Cancer by Mediating TGF-ß1 Pathway.

To investigate more potential targets for the treatment of human bladder cancer, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and high-content screening (HCS) analysis were performed, and microtubule-associated protein 9 (MAP9), which had the strongest proliferation inhibition from 809 downregulated genes, has been selected. MAP9 is responsible for bipolar spindle assembly and is involved in the progression of many types of tumors; however, its role in bladder cancer (BC) remains unknown. Expressive levels of MAP9 in BC tissues were determined through immunohistochemistry, and the clinical significance of MAP9 in BC was analyzed. Short hairpin ribonucleic acid- (ShRNA-) MAP9 was used to construct stable MAP9 knockdown BC cell lines. The proliferative abilities of MAP9 were measured through assays in vivo and in vitro, and the migrated and invasive abilities of MAP9 were analyzed via in vitro experiments. Quantitative reverse transcription PCR, western blotting, coimmunoprecipitation (Co-IP), and rescue assays were used to identify downstream targets of MAP9. MAP9 expression increased in the tumor tissues, and its increased level was negatively correlated with prognosis. Further, the loss of MAP9 caused decreased BC cell proliferation via inducing the growth 1/synthesis (G1/S) cell cycle arrest in vitro and slowed tumor growth in vivo. In addition, MAP9 silencing attenuated BC cell migration and invasion. Moreover, we found that the growth 1/synthesis (G1/S) cell cycle-related genes and the epithelial mesenchymal transition (EMT) marker levels decreased after silencing MAP9. Finally, we found that the transforming growth factor beta 1 (TGF-ß1) pathway is activated as a mediator for MAP9 to regulate genes related to the G1/S cell cycle and EMT. MAP9 promotes BC progression and immune escape activity through the TGF-ß1 pathway and is a potential novel target for therapies of BC.

[Effect of Astragali Radix-Curcumae Rhizoma compatibility combined with 5-fluorouracil on Th17/Treg balance and tumor-related mRNA and protein expression in orthotopic xenograft model mice of CT26.WT colorectal carcinoma].

Astragali Radix-Curcumae Rhizoma(AR-CR) is a combination commonly used in the clinical treatment of tumors. Based on the T helper 17(Th17)/regulatory T cell(Treg) balance, the present study explored the possible mechanism of AR-CR combined with 5-fluorouracil(5-FU) on the tumor growth of orthotopic xenograft model mice of colorectal carcinoma. Ninety male BALB/c mice were randomly divided into nine groups, i.e., a blank group, a model group, a 5-FU group, high-, medium-, and low-dose AR-CR(2∶1) groups, and high-, medium-, and low-dose AR-CR+5-FU groups, with 10 mice in each group. The orthotopic xenograft model of CT26.WT colorectal carcinoma was induced in mice except those in the blank group. Twenty-four hours after the ope-ration, mice in the blank group and the model group received normal saline by gavage(10 mL·kg~(-1), once per day), and those in the 5-FU group received 5-FU by intraperitoneal injection(25 mg·kg~(-1), once every other day). Mice in the AR-CR groups received AR and CR decoctions by gavage(12, 6, and 3 g·kg~(-1), once a day) and those in the combination groups received AR and CR decoctions and 5-FU(doses and administration methods were the same as above). After intervention for three weeks, all mice were sacrificed and tumor tissues were collected. The tumor mass was weighed and the average tumor weight was calculated. The changing trend of Th17/Treg(%) in the CD4~+T lymphocytes of the spleen tissues of the mice in each group was detected. The mRNA expression in the blood and protein expression in the tumor tissues of transforming growth factor-ß(TGF-ß), tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), Smad4, N-cadherin, matrix metalloproteinase-7(MMP-7) were detected. The experimental results revealed that compared with the model group, the groups with drug intervention showed reduced tumor mass(P<0.01), decreased CD4~+IL-17~+ in the spleen tissues to varying degrees(P<0.001), and increased proportion of CD4~+Foxp3~+(P<0.001 or P<0.05), indicating that Th17/Treg maintained dynamic balance, and the effect of the combination groups was predominant. Additionally, the mRNA expression in the blood and protein expression in the tumor tissues of TGF-ß, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 declined to varying degrees in a dose-dependent manner(P<0.01 or P<0.001). The AR-CR combined with 5-FU can inhibit the tumor growth of orthotopic xenograft model mice of CT26.WT colorectal carcinoma. The mechanism may be related to maintenance of Th17/Treg dynamic balance in the body and down-regulation of TGF-ß, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 expression.

[Anti-colorectal cancer mechanism of Astragali Radix-Curcumae Rhizoma-Paridis Rhizoma based on network pharmacology and experimental verification].

The present study explored the underlying mechanism of Astragali Radix-Curcumae Rhizoma-Paridis Rhizoma(AR-CR-PR) in the treatment of colorectal cancer(CRC) by network pharmacology and molecular docking and animal tests and verified the core targets based on the orthotopic transplantation model in nude mice. The active components of AR-CR-PR were retrieved from databases such as TCMSP. The targets of drugs and the disease were obtained from PubChem, SwissTargetPrediction, TTD, and DrugBank, and the intersection targets were imported into STRING for the analysis of the protein-protein interaction(PPI). Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses were performed through DAVID. AutoDock Vina was used to perform molecular docking and binding ability prediction between the active components and the core targets. The effects of AR-CR-PR on tumor growth, metastasis, and phosphorylation of core target proteins in tumor tissues based on the orthotopic transplantation model in nude mice. As revealed by network pharmacology, AR-CR-PR contained nine core components, such as quercetin, curcumin, and ß-ecdysone, and the key targets included protein kinase B(AKT1), mitogen-activated protein kinase 3(MAPK3), MAPK1, and epithelial growth factor receptor(EGFR), which was indicated that the anti-CRC effect of AR-CR-PR was presumedly achieved by regulating tumor cell proliferation, apoptosis, migration, and angiogenesis through PI3 K-AKT, MAPK and other signaling pathways. The results of molecular docking showed that the nine core components had strong binding abilities to AKT1 and MAPK3. The results in vivo showed that AR-CR-PR could reduce the volume of the orthotopic tumor, inhibit liver metastasis, and decrease the phosphorylation of AKT1 and MAPK3 in the CRC model. The mechanism of AR-CR-PR in the intervention of CRC may be related to the activation of PI3 K-AKT and MAPK signaling pathway. This study provides a scientific basis for the clinical application of AR-CR-PR in the treatment of CRC and ideas for modern research on AR-CR-PR.

Analysis of the Role of Comprehensive Treatment Model in the Treatment of Prostate Cancer.

The incidence of prostate cancer is gradually increasing. There are many methods for clinical treatment of prostate cancer, such as surgical treatment and endocrine treatment. In the case of advanced prostate cancer, we must not only extend patients' survival times but also enhance their quality of life. Endocrine medications are the most effective therapy for advanced prostate cancer. This research will investigate the therapeutic impact of a complete treatment model in prostate cancer in order to discover a trustworthy clinical treatment model. This research discovered that, as compared to endocrine treatment, radical resection of prostate cancer may diminish and reach lower serum PSA levels in a short amount of time, as well as sustain low PSA levels and delay progression to castration resistance. Moreover, the comprehensive treatment mode can effectively reduce the possibility of complications. The research results show that the comprehensive treatment model can play an important role in the treatment of prostate cancer.

[Genes and signaling pathways related to the biochemical recurrence of prostate cancer: An analysis based on the GEO database].

OBJECTIVE: To search for the potential genes associated with the recurrence of prostate cancer (PCa) after radical prostatectomy so as to improve the prognosis of the patient. METHODS: The GSE25136 microarray dataset was downloaded from the Gene Expression Omnibus (GEO), involving 39 recurrent and 40 non-recurrent PCa samples. Differentially expressed genes were identified with the Limma package and screened by hierarchical cluster analysis using the Pheatmap package. The potential functions of the differentiated genes were predicted by gene ontology functional enrichment analysis with the ClueGO module of the Cytoscape software. A protein-protein interaction (PPI) network of the genes was constructed in the Cytoscape using the String website, and the module was analyzed using CytoHubba to understand the interactions between these differential genes and identify the key genes in the protein network. The expressions of the identified genes were verified in PCa and normal prostatic tissues by immunohistochemical staining. RESULTS: Totally 167 differentially expressed genes were up-regulated and 91 down-regulated (P ≤ 0.05) in the recurrent PCa samples, with statistically significant differences from the non-recurrent ones. In the top 50 genes that were most significantly up- or down-regulated and mainly involved in the development of the limbic system and the interferon-gamma-mediated signaling pathway, CASP3 and STAT1 were found to be the key genes in the protein network and confirmed to be differentially expressed in the PCa and normal prostatic tissues by immunohistochemistry. CONCLUSIONS: Strong genetic characteristics were found in the progression of recurrent to non-recurrent PCa. The development of the limbic system and the interferon-gamma-mediated signaling pathway are closely related to the development of recurrent PCa. In addition, CASP3 and STAT1, as the key genes, may play an important role in the diagnosis and treatment of recurrent PCa.

Prospective Study of Low- and Standard-dose Chest CT for Pulmonary Nodule Detection: A Comparison of Image Quality, Size Measurements and Radiation Exposure.

OBJECTIVE: To comprehensively and accurately analyze the out-performance of low-dose chest CT (LDCT) vs. standard-dose CT (SDCT). METHODS: The image quality, size measurements and radiation exposure for LDCT and SDCT protocols were evaluated. A total of 117 patients with extra-thoracic malignancies were prospectively enrolled for non-enhanced CT scanning using LDCT and SDCT protocols. Three experienced radiologists evaluated subjective image quality independently using a 5-point score system. Nodule detection efficiency was compared between LDCT and SDCT based on nodule characteristics (size and volume). Radiation metrics and organ doses were analyzed using Radimetrics. RESULTS: The images acquired with the LDCT protocol yielded comparable quality to those acquired with the SDCT protocol. The sensitivity of LDCT for the detection of pulmonary nodules (n=650) was lower than that of SDCT (n=660). There was no significant difference in the diameter and volume of pulmonary nodules between LDCT and SDCT (for BMI <22 kg/m2, 4.37 vs. 4.46 mm, and 43.66 vs. 46.36 mm3; for BMI ≥22 kg/m2, 4.3 vs. 4.41 mm, and 41.66 vs. 44.86 mm3) (P>0.05). The individualized volume CT dose index (CTDIvol), the size specific dose estimate and effective dose were significantly reduced in the LDCT group compared with the SDCT group (all P<0.0001). This was especially true for dose-sensitive organs such as the lung (for BMI <22 kg/m2, 2.62 vs. 12.54 mSV, and for BMI ≥22 kg/m2, 1.62 vs. 9.79 mSV) and the breast (for BMI <22 kg/m2, 2.52 vs. 10.93 mSV, and for BMI ≥22 kg/m2, 1.53 vs. 9.01 mSV) (P<0.0001). CONCLUSION: These results suggest that with the increases in image noise, LDCT and SDCT exhibited a comparable image quality and sensitivity. The LDCT protocol for chest scans may reduce radiation exposure by about 80% compared to the SDCT protocol.

Health behaviors and metabolic risk factors are associated with dyslipidemia in ethnic Miao Chinese adults: the China multi-ethnic cohort study.

BACKGROUND: Cardiovascular risk factors in Chinese ethnic minority groups are rarely reported. OBJECTIVE: To quantify the cardiovascular risk factors in Miao Chinese adults and to examine the association of health behaviors and metabolic risk factors with dyslipidemia. METHODS: A cross-sectional analysis was conducted using baseline data from the China Multi-Ethnic Cohort (CMEC) study. A representative sample of 5559 Miao participants aged 30 to 79 years were surveyed and given physical and laboratory exams. The proportion of behavioral and metabolic risk factors were described in ethnic Miao adults. Logistic regression was utilized to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the association between health behaviors and metabolic risk factors with dyslipidemia. RESULTS: In Miao Chinese adults, the prevalence of dyslipidemia was 32.8%. After multivariate adjustment, subjects with poor waist-to-hip ratio (WHR), body mass index (BMI), fasting blood glucose (FBG) and blood pressure (BP) were more likely to have higher risk of triglycerides (TG) abnormality, regardless of gender and age. Furthermore, the strongly association was detected between poor WHR and low density lipoprotein cholesterol (LDL-C) abnormality (adjusted OR = 5.24, 95%CI: 2.42-11.34) in the older subgroup (≥ 60 years). Males who current smoking were an independent risk factor only for high density lipoprotein cholesterol (HDL-C) abnormality (adjusted OR = 1.44, 95%CI: 1.05-1.99). However, in the subgroup age, current smoker were at greater risk of high TG and low HDL-C. Males with regular drinking were less likely to be high LDL-C (adjusted OR = 0.51, 95%CI: 0.32-0.81). CONCLUSIONS: The present findings indicated that Miao adults with metabolic risk factors were at greater risk of dyslipidemia.

IgG4-Related Disease: A Retrospective Chinese Study of Features and Treatment Response of 98 Patients Including 4 Rare Cases.

The features and treatment of 98 Chinese patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD) referred to a single tertiary referring centre were reviewed. Patients diagnosed with IgG4-RD according to the comprehensive diagnostic criteria (CDC) were included in the retrospective study from May 2012 to March 2019. We collected data on clinical, laboratory, imaging, histological features and treatment. Totally, 98 patients with IgG4-RD were enrolled. The common clinical manifestations included abdominal pain, salivary gland swelling and lymphadenopathy. 51% of the patients had multiple organs involvement. Lymph nodes, pancreas and salivary glands were most commonly involved. Four rare sites including ulna, cerebellum, scalp, and mammary gland were found. The serum IgG4 level was increased by 85.7%. The serum IgG4 level was positively correlated with the number of involved organs, IgG and IgG4/IgG. Low C3 and C4 levels were observed in 37.5% and 12.2% patients respectively, and all patients with kidney involvement had hypocomplementemia. A total of 54 patients underwent tissue biopsies, and 55.6%, 31.5% and 11.1% cases were diagnosed as definite, probable and possible IgG4-RD, respectively. Eighty-eight patients received glucocorticoids (GCs) therapy. Five patients underwent radical surgery to remove the lesion. 73% of them presented a complete or partial remission. IgG4-RD is a systemic fibroinflammatory disease with involvement of multiple organs throughout the body including some rare sites. Most IgG4-RD patients had increased serum IgG4 levels and patients with kidney involvement showed hypocomplementemia. GCs therapy is effective. More research is needed to provide a more reliable basis for the diagnosis and treatment of patients.

miR-103a-3p Suppresses Cell Proliferation and Invasion by Targeting Tumor Protein D52 in Prostate Cancer.

Growing evidence points at an association between microRNAs and tumor development. Although dysregulation of microRNA-103a-3p (miR-103a-3p) in multiple human cancers has been reported, its expression in prostate cancer (PCa) remains unknown and there is currently no research on the relationship between miR-103a-3p and tumor protein D52 (TPD52) in PCa. Our aim in this study was to explore the effect and potential mechanism of miR-103a-3p in PCa. qRT-PCR was performed to detected the level of miR-103a-3p in PCa tissues and cells, and in normal tissues. Colony, wound-healing, invasion, proliferation, and apoptosis assays were performed in search miR-103a-3p effect in PCa. TargetScan was used to predict potential targets of miR-103a-3p. Additionally, dual-luciferase reporter, western blot, and immunofluorescence assays were performed to detected the target gene of miR-103a-3p. Finally, we explore the differences in tumor xenograft experiments between nude mice injected with stably miR-103a-3p expressing cells and those expressing a miR-negative control. Low level of miR-103a-3p was detected in PCa tissues and cells, when compared with normal tissues. Enhancement of miR-103a-3p significantly inhibited migration and invasion of PCa cells, and negatively regulated expression of the oncogenic tumor protein D52 (TPD52) through direct binding to its 3'-UTR. Interestingly, overexpression of TPD52 significantly attenuated the effect of mir-103a-3p on PCa. Our study provides the first evidence that miR-103a-3p directly targets TPD52 and inhibits the proliferation and invasion of PCa. This finding helps clarify the role of mir-103a-3p-TPD52 axis in PCa and may provide new therapeutic targets for the disease.

[Modified sandwich urethral reconstruction in laparoscopic radical prostatectomy improves early recovery of urinary continence].

OBJECTIVE: To explore the safety of modified sandwich urethral reconstruction (MSUR) in laparoscopic radical prostatectomy (LRP) and its effect on the early recovery of urinary continence. METHODS: We retrospectively analyzed the clinical data on 20 patients treated by LRP with MSUR (the MSUR group) and another 21 cases of LRP without MSUR (the conventional control group) from January 2018 to September 2019. We compared the two groups of patients in the general data, anastomosis time, operation time and urinary continence recovery. RESULTS: There were no statistically significant differences between the two groups of patients in the age, body mass index, Gleason scores, prostate volume and baseline PSA level (P > 0.05) or in operation time, intraoperative blood loss, drainage tube indwelling time, postoperative feeding time and postoperative hospital stay (P > 0.05). Anastomotic stenosis occurred in 1 case in the MSUR group postoperatively, which was cured after regular urethral dilation, and anastomotic fistula developed in 1 case in the control group, which was healed after 5 days of prolonged catheterization. The recovery rate of urinary continence at 12 weeks after catheter removal was significantly higher in the MSUR than in the control group (80.0% vs 47.6%, P < 0.05). CONCLUSIONS: Modified sandwich urethral reconstruction in LRP is a safe, effective and feasible surgical strategy, which can significantly improve postoperative urinary continence recovery of the patient.

Plasma Fibrinogen Predicts the Prognosis of Bladder Cancer Patients After Radical Cystectomy.

BACKGROUND: This study aimed to determine the potential utility of plasma fibrinogen as a prognostic factor in patients with bladder cancer (BCa) after radical cystectomy (RC). METHODS: Patients with BCa who underwent RC from 2014 to 2019 were analyzed retrospectively. The indexes of plasma coagulation and fibrinolysis system factors were collected. Kaplan-Meier survival curves were used to calculate the overall survival (OS) and disease-free survival (DFS). The prognostic value of plasma fibrinogen was analyzed by using Cox regression model, and a nomogram of BCa based on plasma fibrinogen was generated by R software. RESULTS: Among 145 patients, the optimal cut-off value of plasma fibrinogen was 3.14g/L. High level of plasma fibrinogen was related to the poor prognosis of patients with BCa, and plasma fibrinogen has a more accurate prognostic ability than other plasma coagulation and fibrinolysis system factors. Multivariate Cox regression analysis showed that plasma fibrinogen was an independent predictor of OS (>3.14 vs ≤3.14 HR, 2.58, 95% CI = 1.28-5.23; p = 0.008) and DFS (>3.14 vs ≤3.14 HR, 2.60, 95% CI = 1.20-5.65; p = 0.016), and the nomogram based on plasma fibrinogen had better accuracy and discrimination (area under the curve (AUC): OS = 0.741, DFS = 0.733). CONCLUSION: Plasma fibrinogen can be used as an independent predictor of OS and DFS for RC patients, and the nomogram based on plasma fibrinogen was a reliable model for predicting the prognosis after RC.

Tumor-associated macrophages promote prostate cancer progression via exosome-mediated miR-95 transfer.

Tumor-associated macrophages (TAMs) are vital constituents in mediating cell-to-cell communication within the tumor microenvironment. However, the molecular mechanisms underlying the interplay between TAMs and tumor cells that guide cell fate are largely undetermined. Extracellular vesicles, also known as exosomes, which are derived from TAMs, are the components exerting regulatory effects. Thus, understanding the underlying mechanism of "onco-vesicles" is of crucial importance for prostate cancer (PCa) therapy. In this study, we analyzed micro RNA sequences in exosomes released by THP-1 and M2 macrophages and found a significant increase in miR-95 levels in TAM-derived exosomes, demonstrating the direct uptake of miR-95 by recipient PCa cells. In vitro and in vivo loss-of-function assays suggested that miR-95 could function as a tumor promoter by directly binding to its downstream target gene, JunB, to promote PCa cell proliferation, invasion, and epithelial-mesenchymal transition. The clinical data analyses further revealed that higher miR-95 expression results in worse clinicopathological features. Collectively, our results demonstrated that TAM-mediated PCa progression is partially attributed to the aberrant expression of miR-95 in TAM-derived exosomes, and the miR-95/JunB axis provides the groundwork for research on TAMs to further develop more-personalized therapeutic approaches for patients with PCa.

Injured tubular epithelial cells activate fibroblasts to promote kidney fibrosis through miR-150-containing exosomes.

The kidney injury induced by ischemia-reperfusion (IR) usually comes with irreversible renal fibrosis, a process that develops into chronic kidney disease (CKD), but the underlying cellular mechanism has yet to be determined. To test our hypothesis that exosomes are tightly connected with kidney fibrosis following AKI, we studied the role of exosomes and the transfer of specific miRNA among other genetic components in injured tubular epithelial cells (TECs). We utilized an experimental IR mice model to simulate the fibrotic environment in injured tissue and detect the production of exosomes, and found that exosome deficiency could significantly alleviate the degree of kidney fibrosis following IR administration. MiRNA profiling of exosomes extracted from renal tissue samples with or without ischemia-reperfusion injury (IRI) revealed that miR-150 was markedly increased as a compelling profibrotic molecule, as evidenced by the fact that overexpression of miR-150 facilitated renal fibrosis. Exosomes isolated from hypoxia TECs also induced the increased production of miR-150. In cocultured fibroblasts with TECs-derived exosomes, we confirmed a direct uptake of exosomal miR-150 by fibroblasts. Finally, we verified that in vivo ischemia mice pretreated with exosomes enriched in miR-150 developed more profibrotic manifestations. Thus, our current study indicated that TECs have the ability to employ exosomes to initiate the activation and proliferation of fibroblasts via direct shuttling of miR-150-containing exosomes during reparative responses, and that exosome/miR-150 provides the groundwork for research to develop more personalized therapeutic approaches for controlling tissue fibrosis.