Single-cell RNA transcriptomic reveal the mechanism of MSC derived small extracellular vesicles against DKD fibrosis.

Diabetic kidney disease (DKD), a chronic kidney disease, is characterized by progressive fibrosis caused due to persistent hyperglycemia. The development of fibrosis in DKD determines the patient prognosis, but no particularly effective treatment. Here, small extracellular vesicles derived from mesenchymal stem cells (MSC-sEV) have been used to treat DKD fibrosis. Single-cell RNA sequencing was used to analyze 27,424 cells of the kidney, we have found that a novel fibrosis-associated TGF-ß1+Arg1+ macrophage subpopulation, which expanded and polarized in DKD and was noted to be profibrogenic. Additionally, Actin+Col4a5+ mesangial cells in DKD differentiated into myofibroblasts. Multilineage ligand-receptor and cell-communication analysis showed that fibrosis-associated macrophages activated the TGF-ß1/Smad2/3/YAP signal axis, which promotes mesangial fibrosis-like change and accelerates renal fibrosis niche. Subsequently, the transcriptome sequencing and LC-MS/MS analysis indicated that MSC-sEV intervention could restore the levels of the kinase ubiquitin system in DKD and attenuate renal interstitial fibrosis via delivering CK1δ/ß-TRCP to mediate YAP ubiquitination degradation in mesangial cells. Our findings demonstrate the unique cellular and molecular mechanisms of MSC-sEV in treating the DKD fibrosis niche at a single-cell level and provide a novel therapeutic strategy for renal fibrosis.

Local adrenomedullin gene delivery inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo.

Adrenomedullin (ADM) has beneficial effects on Leydig cells under pathological conditions, including lipopolysaccharide (LPS)-induced orchitis. Our previous studies demonstrated that ADM exerts a restorative effect on steroidogenesis in LPS-treated primary rat Leydig cells by attenuating oxidative stress, inflammation and apoptosis. In this study, we aim to investigate whether ADM inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo. Rats were administered with LPS and injected with Ad-ADM, an adeno-associated virus vector that expressed ADM. Then, rat testes were collected for 3ß-hydroxysteroid dehydrogenase (3ß-HSD) immunofluorescence staining. Steroidogenic enzymes or steroidogenic regulatory factors or protein, including steroidogenic factor-1 (SF-1), liver receptor homologue-1 (LRH1), Nur77, steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc), 3ß-HSD, cytochrome P450 17α-hydroxylase/17, 20 lyase (CYP17) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD), were detected via gene expression profiling and western blot analysis. Plasma testosterone concentrations were measured. Results showed that ADM may inhibit Leydig cell dysfunction by rescuing steroidogenic enzymes and steroidogenic regulatory factors in vivo. The reduction in the number of Leydig cells after LPS exposure was reversed by ADM. ADM rescued the gene or protein levels of SF-1, LRH1, Nur77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD and plasma testosterone concentrations. To summarize ADM could rescue some important steroidogenic enzymes, steroidogenic regulatory factors and testosterone production in Leydig cells in vivo.

A novel prognostic cancer-related lncRNA signature in papillary renal cell carcinoma.

BACKGROUND: Papillary renal cell carcinoma (pRCC) ranks second in renal cell carcinoma and the prognosis of pRCC remains poor. Here, we aimed to screen and identify a novel prognostic cancer-related lncRNA signature in pRCC. METHODS: The RNA-seq profile and clinical feature of pRCC cases were downloaded from TCGA database. Significant cancer-related lncRNAs were obtained from the Immlnc database. Differentially expressed cancer-related lncRNAs (DECRLs) in pRCC were screened for further analysis. Cox regression report was implemented to identify prognostic cancer-related lncRNAs and establish a prognostic risk model, and ROC curve analysis was used to evaluate its precision. The correlation between RP11-63A11.1 and clinical characteristics was further analyzed. Finally, the expression level and role of RP11-63A11.1 were studied in vitro. RESULTS: A total of 367 DECRLs were finally screened and 26 prognostic cancer-related lncRNAs were identified. Among them, ten lncRNAs (RP11-573D15.8, LINC01317, RNF144A-AS1, TFAP2A-AS1, LINC00702, GAS6-AS1, RP11-400K9.4, LUCAT1, RP11-63A11.1, and RP11-156L14.1) were independently associated with prognosis of pRCC. These ten lncRNAs were incorporated into a prognostic risk model. In accordance with the median value of the riskscore, pRCC cases were separated into high and low risk groups. Survival analysis indicated that there was a significant difference on overall survival (OS) rate between the two groups. The area under curve (AUC) in different years indicated that the model was of high efficiency in prognosis prediction. RP11-63A11.1 was mainly expressed in renal tissues and it correlated with the tumor stage, T, M, N classifications, OS, PFS, and DSS of pRCC patients. Consistent with the expression in pRCC tissue samples, RP11-63A11.1 was also down-regulated in pRCC cells. More importantly, up-regulation of RP11-63A11.1 attenuated cell survival and induced apoptosis. CONCLUSIONS: Ten cancer-related lncRNAs were incorporated into a powerful model for prognosis evaluation. RP11-63A11.1 functioned as a cancer suppressor in pRCC and it might be a potential therapeutic target for treating pRCC.

Small ribonucleoprotein particle protein SmD3 governs the homeostasis of germline stem cells and the crosstalk between the spliceosome and ribosome signals in Drosophila.

The ribonucleoprotein (RNP) spliceosome machinery triggers the precursor RNA splicing process in eukaryotes. Major spliceosome defects are implicated in male infertility; however, the underlying mechanistic links between the spliceosome and the ribosome in Drosophila testes remains largely unresolved. Small ribonucleoprotein particle protein SmD3 (SmD3) is a novel germline stem cell (GSC) regulatory gene identified in our previous screen of Drosophila testes. In the present study, using genetic manipulation in a Drosophila model, we demonstrated that SmD3 is required for the GSC niche and controls the self-renewal and differentiation of GSCs in the testis. Using in vitro assays in Schneider 2 cells, we showed that SmD3 also regulates the homeostasis of proliferation and apoptosis in Drosophila. Furthermore, using liquid chromatography-tandem mass spectrometry methods, SmD3 was identified as binding with ribosomal protein (Rp)L18, which is a key regulator of the large subunit in the ribosome. Moreover, SmD3 was observed to regulate spliceosome and ribosome subunit expression levels and controlled spliceosome and ribosome function via RpL18. Significantly, our findings revealed the genetic causes and molecular mechanisms underlying the stem cell niche and the crosstalk between the spliceosome and the ribosome.-Yu, J., Luan, X., Yan, Y., Qiao, C., Liu, Y., Zhao, D., Xie, B., Zheng, Q., Wang, M., Chen, W., Shen, C., He, Z., Hu, X., Huang, X., Li, H., Chen, B., Zheng, B., Chen, X., Fang, J. Small ribonucleoprotein particle protein SmD3 governs the homeostasis of germline stem cells and the crosstalk between the spliceosome and ribosome signals in Drosophila.

Long non-coding RNA FAM66C is associated with clinical progression and promotes cell proliferation by inhibiting proteasome pathway in prostate cancer.

Prostate cancer is the most prevalent malignancy in men, and the identification of novel oncogenes is clinically valuable for early screening, prevention and treatment. Recently, the studies have revealed that long non-coding RNAs (lncRNAs) play important roles in the development and progression of cancers including prostate cancer. The present study aims to identify a novel lncRNA that correlated with the survival time of prostate cancer patients and try to explore its biological functions in prostate cancer cells. After analysing the prostate carcinoma dataset of the Cancer Genome Atlas (TCGA), the lncRNA FAM66C was screened with its expression highly correlated with patient survival time, tumour stage and Gleason pattern. Real-time PCR showed that FAM66C highly expressed in prostate cancer cells, and knockdown FAM66C by siRNAs resulted in significant inhibition of cell growth. Furthermore, the results indicated that FAM66C promoted cell growth due to increasing cell proliferation but not decreasing cell apoptosis. In addition, FAM66C activated the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signalling to promote cell proliferation. The result of Western Blotting and lysosomal acidity detection showed that knockdown FAM66C increased the protein ubiquitination and the lysosomal acidity. Moreover, inhibition of proteasome pathway could increase the activation of EGFR-ERK signalling and cell proliferation. Taken together, these results suggested that lncRNA FAM66C activate EGFR-ERK signalling to promote cell proliferation by inhibiting proteasome pathway in prostate cancer. SIGNIFICANCE OF THE STUDY: We demonstrated that lncRNA FAM66C was associated with clinical progression. In addition, highly expressed lncRNA FAM66C in prostate cancer cell lines promoted cell proliferation. Moreover, lncRNA FAM66C activate the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signalling to promote cell proliferation by inhibiting proteasome pathway in prostate cancer. This study might provide lncRNA FAM66C as a potential therapeutic target gene of prostate cancer.

New insights into long noncoding RNAs and pseudogenes in prognosis of renal cell carcinoma.

BACKGROUND: Increasing evidence suggests a critical role for long noncoding RNAs (LncRNAs) and pseudogenes in cancer. Renal cell carcinoma (RCC), the most common primary renal neoplasm, is highly aggressive and difficult to treat because of its resistance to chemotherapy and radiotherapy. Despite many identified LncRNAs and pseudogenes, few have been clearly elucidated. METHODS: This study provides new insights into LncRNAs and pseudogenes in the prognosis of RCC. We searched an online database to interrogate alterations and clinical data on cBioPortal. We analysed LncRNA and pseudogene signatures to predict the prognosis of RCC based on a Cox model. We also found potential serum biomarkers of RCC and validated them in 32 RCC patients, as well as healthy controls. RESULTS: Alterations were found in 2553 LncRNAs and 8901 pseudogenes and occurred in up to 23% of all cases. Among these, 27 LncRNAs and 45 pseudogenes were closely related to prognosis. We also identified signatures of LncRNAs and pseudogenes that can predict overall survival and recurrence of RCC. We then validated the relative levels of these LncRNAs and pseudogenes in the serum of 32 patients. Six of these, including LINC00520, PIK3CD-AS1, LINC01559, CEACAM22P, MSL3P1 and TREML3P, could be non-invasive biomarkers of RCC. Finally, we selected PIK3CD-AS1 to determine its role in RCC and found that upregulation of PIK3CD-AS1 was closely associated with higher tumour stage and metastasis. CONCLUSIONS: These signatures of LncRNAs and pseudogenes can predict overall survival and recurrence of RCC. LINC00520, PIK3CD-AS1, LINC01559, CEACAM22P, MSL3P1 and TREML3P could be non-invasive biomarkers of RCC. These data suggest the important roles of LncRNAs and pseudogenes in RCC, and therefore provides us new insights into the prognosis of RCC.

Identification of CDK2 as a novel target in treatment of prostate cancer.

AIM: This study aims the potential gene involved in the metastasis of prostate cancer (Pca). METHODS: PubMed GEO datasets (GSE6605 and GSE6606) were downloaded. We used multiple bioinformatics methods to screen differentially expressed genes in Pca. Gene network was built by STRING and visualized by Cytoscape. All of the hub genes were analyzed by cBioPortal. Inhibition of CDK2 including siRNA, inhibitor and cas9-induced CDK2 knockout was followed by an invasion assay. Downstream genes of CDK2 were analyzed by western blot. RESULTS: Sequencing data were analyzed to screen the genes with expression alterations. The top genes were validated in our samples. 11 hub genes were screened out. Among these genes, STAT3 and CDK2 were significantly associated with recurrence. Further study suggested that inhibition of CDK2 reduced invasion of Pca cell lines. The invasion ability was rescued after reintroduction of CDK2. CONCLUSION: These data indicated that CDK2 was a crucial factor in metastasis of Pca and might be a novel therapy target. [Formula: see text].

[Types for 1 849 patients with urinary calculi and patients' clinical characteristics].

OBJECTIVE: To analyze types of urinary calculi and patients' clinical characteristics, and to explore the strategies for prevention and treatment of urinary calculi.
 Methods: A total of 1 849 patients with urinary calculi were treated in the Department of Urology, the Third Xiangya Hospital of Central South University. The components were analyzed by infrared spectroscopy. The relationship between stone composition and clinical parameters was analyzed according to the clinical characteristics of the patients.
 Results: The proportion of calcium oxalate stone or uric acid stone in male (84.1% or 7.7%) was higher than that in female (78.4% or 4.2%). The older patients were more likely to be diagnosed as uric acid stone. The proportions of uric acid stone in patients <18 years old, 18-<41 years old, 41-<66 years old, and ≥66 years old were 0.0%, 1.6%, 6.6%, and 12.4%, respectively. There was no significant difference in the proportion of stones in patients with different BMI. There were no significant difference in the stone composition between the patients with or without urinary tract infection, hypertension or diabetes. The proportion of uric acid stones in patients with acidic urine was higher than the other types. The proportion of uric acid stones in patients with elevated creatinine (12.1%) was higher than that in the patients with normal creatinine (4.5%).
 Conclusion: Elderly patients, or patients with high uric acid and renal insufficiency are more prone to uric acid stones. Regulation of urinary pH may be an important strategy for preventing and treating urinary calculi in Hunan Province.

[MiRNA-381 inhibits the invasion of renal carcinoma and the underlying mechanisms].

OBJECTIVE: To determine the inhibitory effect of miRNA-381 on renal carcinoma invasion and to explore the underlying mechanisms.
 METHODS: After up-regulation of miRNA-381, the inhibitory effect of miR-381 on cell invasion was investigated. We screened the target genes of miRNA-381 in a database (starBase) through combination of five programs including targetscan, picTar, RNA22, PITA and miRanda. Then, the predicted targeting genes were verified by the dual luciferase reporter assay. We also examined the expression of miRNA-381 and its target genes in renal cancer cells and tissues.
 RESULTS: Transfection and up-regulation of miRNA-381 resulted in a significant decrease in trans-membrane cell numbers and the ability of renal cell invasion. Bioinformatics analysis showed that CREB binding protein (CBP), ß-catenin and lymphoid enhancer binding factor-1 (LEF-1) were the potential targets of miRNA-381. In the luciferase reporter gene system, co-transfection of miRNA-381 with the 3'UTR of wild-type target gene led to a significant decrease in luciferase activity. The expression of miRNA-381 was decreased in various renal cancer cells, and it was particularly lower in highly metastatic cell lines (786-OHM). On the contrary, the expression levels of miRNA-381 target genes (CBP, ß-catenin and LEF-1) were significantly increased in cells and tissues.
 CONCLUSION: MiRNA-381 can inhibit cell invasion in renal cancer by block the function of CBP, ß-catenin and LEF-1.

Regulation of regulated cell death by extracellular vesicles in acute kidney injury and chronic kidney disease.

The imbalance between proliferation and death of kidney resident cells is a crucial factor in the development of acute or chronic renal dysfunction. Acute kidney injury (AKI) is often associated with the rapid loss of tubular epithelial cells (TECs). Sustained injury leads to the loss of glomerular endothelial cells (GECs) and podocytes, which is a key mechanism in the pathogenesis of glomerular diseases. This irreversible damage resulting from progressive cell loss eventually leads to deterioration of renal function characterized by glomerular compensatory hypertrophy, tubular degeneration, and renal fibrosis. Regulated cell death (RCD), which involves a cascade of gene expression events with tight structures, plays a certain role in regulating kidney health by determining the fate of kidney resident cells. Under pathological conditions, cells in the nephron have been demonstrated to constitutively release extracellular vesicles (EVs) which act as messengers that specifically interact with recipient cells to regulate their cell death process. For therapeutic intervention, exogenous EVs have exhibited great potential for the prevention and treatment of kidney disease by modulating RCD, with enhanced effects through engineering modification. Based on the functional role of EVs, this review comprehensively explores the regulation of RCD by EVs in AKI and chronic kidney disease (CKD), with emphasis on pathogenesis and therapeutic intervention.

Iron decoration in binary graphene oxide and copper iron sulfide nanocomposites boosting catalytic antibacterial activity in acidic microenvironment against antimicrobial resistance.

The strong antimicrobial resistance (AMR) of multidrug-resistant (MDR) bacteria and biofilm, especially the biofilm with extracellular polymeric substance (EPS) protection and persister cells, not only renders antibiotics ineffective but also causes chronic infections and makes the infectious tissue difficult to repair. Considering the acidic properties of bacterial infection microenvironment and biofilm, herein, a binary graphene oxide and copper iron sulfide nanocomposite (GO/CuFeSx NC) is synthesized by a surfactant free strategy and utilized as an alternative smart nanozyme to fight against the MDR bacteria and biofilm. For the GO/CuFeSx NC, the iron decoration facilitates the well distribution of bimetallic CuFeSx NPs on the GO surfaces compared to monometallic CuS NPs, providing synergistically enhanced peroxidase (POD)-like activity in acidic medium (pH 4 âˆ¼ 5) and intrinsic strong near infrared (NIR) light responsive photothermal activity, while the ultrathin and sharp structure of 2D GO nanosheet allows the GO/CuFeSx NC to strongly interact with the bacteria and biofilm, facilitating the catalytic and photothermal attacks on the bacterial surfaces. In addition, the GO in GO/CuFeSx NC exhibits a "Pseudo-Photo-Fenton" effect to promote the ROS generation. Therefore, the GO/CuFeSx NC can effectively kill bacteria and biofilm both in vitro and in vivo, finally eliminating the infections and accelerating the tissue repair when treating the biofilm-infected wound. This work paves a new way to the design of novel nanozyme for smart antibacterial therapy against antimicrobial resistance.

Melatonin serves as a novel treatment in bladder fibrosis through TGF-ß1/Smad and EMT.

BACKGROUND: Melatonin (MEL) is an indole amine molecule primarily produced in the pineal gland. Melatonin has been shown in numerous studies to have antifibrotic effects on the kidney, liver, and other organs. However, it is still unclear how melatonin works in bladder fibrosis. We explored how melatonin affects animals with bladder fibrosis and the underlying mechanisms. MATERIALS AND METHODS: MEL was used to treat human bladder smooth muscle cells (HBdSMCs) after they were stimulated with transforming growth factor-ß1 (TGF-ß1) in vitro. Proteomic analysis and bioinformatic analysis of the altered expression of these proteins were subsequently performed on HBdSMCs from the different processing methods. To construct an in vivo bladder fibrosis model, we injected protamine sulfate (PS) and lipopolysaccharide (LPS) twice a week into the rat bladder for six weeks. After two weeks of PS/LPS treatment, the mice in the treatment group were treated with MEL (20 mg/kg/d) for 4 weeks. Finally, we detected the expression of fibrosis markers from different perspectives. The TGF-ß1/Smad pathway and epithelial-mesenchymal transition (EMT) in cell and bladder tissues were also identified. Further proteomic analysis was also performed. RESULTS: In vitro, we found that TGF-ß1 treatment enhanced the expression of the fibrosis markers collagen III and α-SMA in HBdSMCs. E-cadherin expression decreased while the TGF-ß1/Smad pathway was activated. Vimentin and N-cadherin expression was also elevated at the same time. Similar findings were observed in the LPS group. After MEL treatment, the expression of collagen III and α-SMA decreased, the expression of E-cadherin increased, and the expression of vimentin and N-cadherin also decreased. According to our quantitative proteomics analysis, CCN1 and SQLE may be important proteins involved in the development of bladder fibrosis. MEL decreased the expression of these genes, leading to the relief of bladder fibrosis. Bioinformatics analysis revealed that the extracellular space structure related to metabolic pathways, actin filament binding, and stress fibers can serve as a pivotal focus in the management of fibrosis. CONCLUSION: Melatonin attenuates bladder fibrosis by blocking the TGF-ß1/Smad pathway and EMT. CCN1 appears to be a possible therapeutic target for bladder fibrosis.

[Constructing a p53-fused dual luciferase reporter and verifying its function].

OBJECTIVE: To construct a p53-fused dual luciferase reporter and to test whether this reporter can mimic wild-type p53 activities in a high-throughput screen. METHODS: A restriction endonuclease site was added to each terminus and the stop codon of the wild-type full-length p53 open reading frame (ORF) was removed by PCR. A restriction endonuclease site was added to each terminus and the start codon of the firefly luciferase ORF was removed by PCR. The two modified ORFs were inserted upstream of the IRES-induced renilla luciferase ORF in a CMV-derived vector. The p53 fusion protein was expressed in cells to test its MDM2-mediated degradation, subcellular localization, and induction of p53-responsive promoter. RESULTS: The p53-fused dual luciferase reporter was successfully constructed. After transfection into the host cells, the reporter expressing the p53 fusion protein that was degraded by oncoprotein MDM2, was mainly located inside the nucleus, and induced the p53-responsive promoter, respectively. CONCLUSION: The p53-fused dual luciferase reporter (p53FL/IRES/RL) can identify modulators of P53 protein level in a high-throughput screen of genetic or chemical libraries.

Current applications of nanomaterials in urinary system tumors.

The development of nanotechnology and nanomaterials has provided insights into the treatment of urinary system tumors. Nanoparticles can be used as sensitizers or carriers to transport drugs. Some nanoparticles have intrinsic therapeutic effects on tumor cells. Poor patient prognosis and highly drug-resistant malignant urinary tumors are worrisome to clinicians. The application of nanomaterials and the associated technology against urinary system tumors offers the possibility of improving treatment. At present, many achievements have been made in the application of nanomaterials against urinary system tumors. This review summarizes the latest research on nanomaterials in the diagnosis and treatment of urinary system tumors and provides novel ideas for future research on nanotechnologies in this field.

Anti-apoptotic effect of adrenomedullin gene delivery on Leydig cells by suppressing TGF-ß1 via the Hippo signaling pathway.

This study aims to establish whether adrenomedullin (ADM) is capable to restore the steroidogenic functions of Leydig cells by suppressing transforming growth factor-ß1 (TGF-ß1) through Hippo signaling. Primary Leydig cells were treated with lipopolysaccharide (LPS), an adeno-associated virus vector that expressed ADM (Ad-ADM) or sh-RNA of TGF-ß1 (Ad-sh-TGF-ß1). The cell viability and medium concentrations of testosterone were detected. Gene expression and protein levels were determined for steroidogenic enzymes, TGF-ß1, RhoA, YAP, TAZ and TEAD1. The role of Ad-ADM in the regulation of TGF-ß1 promoter was confirmed by ChIP and Co-IP. Similar to Ad-sh-TGF-ß1, Ad-ADM mitigated the decline in the number of Leydig cells and plasma concentrations of testosterone by restoring the gene and protein levels of SF-1, LRH1, NUR77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD. Similar to Ad-sh-TGF-ß1, Ad-ADM not only inhibited the LPS-induced cytotoxicity and cell apoptosis but also restored the gene and protein levels of SF-1, LRH1, NUR77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD, along with the medium concentrations of testosterone in LPS-induced Leydig cells. Like Ad-sh-TGF-ß1, Ad-ADM improved LPS-induced TGF-ß1 expression. In addition, Ad-ADM suppressed RhoA activation, enhanced the phosphorylation of YAP and TAZ, reduced the expression of TEAD1 which interacted with HDAC5 and then bound to TGF-ß1 gene promoter in LPS-exposed Leydig cells. It is thus suspected that ADM can exert anti-apoptotic effect to restore the steroidogenic functions of Leydig cells by suppressing TGF-ß1 through Hippo signaling.

Anacardic acid (6-pentadecylsalicylic acid) induces apoptosis of prostate cancer cells through inhibition of androgen receptor and activation of p53 signaling.

Anacardic acid (AA) is a mixture of 2-hydroxy-6-alkylbenzoic acid homologs. It is widely regarded as a non-specific histone acetyltransferase inhibitor of p300. The effects and the mechanisms of AA in LNCaP cells (prostate cancer cells) remain unknown. To investigate the effect of AA on LNCaP cells, we had carried out several experiments and found that AA inhibits LNCaP cell proliferation, induces G1/S cell cycle arrest and apoptosis of LNCaP cell. The mechanisms via which AA acts on LNCaP cells may be due to the following aspects. First, AA can regulate p300 transcription and protein level except for its mechanisms regulating function of p300 through post-translational modification in LNCaP cells. Second, AA can activate p53 through increasing the phosphorylation of p53 on Ser15 in LNCaP cells. AA can selectively activate p21 (target genes of p53). Third, AA can down-regulates androgen receptor (AR) through supressing p300. Our study suggests that AA has multiple anti-tumor activities in LNCaP cells and warrants further investigation.

Mussel-Inspired Clickable Antibacterial Peptide Coating on Ureteral Stents for Encrustation Prevention.

Long-term indwelling catheters or stents often cause complications like infection, encrustation, hematuria, pain, and so on. The source of these problems is bacteria, which can form biofilms on the stents to reduce antibiotic sensitivity and produce urease to form encrustation by increasing the urine pH. Urinary tract infection (UTI) can aggravate the body damage and even seriously endanger lives, and the encrustation will block the stents, which can cause hydronephrosis and renal function damage. Therefore, the prevention of UTI and encrustation represents a great challenge in clinical ureteral stent uses. In this work, a clickable mussel-inspired peptide and antimicrobial peptide (AMP) were used to functionalize the commercial stents' surfaces to inhibit long-term infection and encrustation caused by bacteria. Copper (Cu) ions were used to coordinate the mussel-inspired peptide to improve the stability. The AMP with an azido group was clicked to the mussel-inspired Cu-coordinated peptide coating through click chemistry. The bio-inspired antibacterial coating was constructed with excellent stability, bactericidal properties, and improved biological compatibility. In in vitro and in vivo experiments, it was further found that the coating showed bactericidal and encrustation reduction abilities. This study thus developed an effective, safe, and stable AMP coating on urinary stents/catheters capable of long-term antibacterial and encrustation inhibition.

Bio-inspired antibacterial coatings on urinary stents for encrustation prevention.

Urinary tract infection (UTI) represents one of the most common nosocomial infections, which is mainly related to indwelling catheters or stents. In addition to the formation of biofilms to reduce antibiotic sensitivity, the urease-producing bacteria can also increase urine pH, causing Ca2+ and Mg2+ deposition and finally catheter obstruction. The prevention of UTIs and its complication (i.e., encrustation) thus is a great challenge in design of catheters and ureteral stents. In this work, a metal-catechol-assisted mussel chemistry (i.e., dopamine self-polymerization) was employed for surface functionalization of commercially available catheters with antimicrobial peptides (AMP), for the purpose of long-term anti-infection and encrustation prevention. To improve the stability of the polydopamine coating on polymeric stents, we used Cu2+-coordinated dopamine self-polymerization. Then, a cysteine-terminated AMP was introduced on the polydopamine coating through Michael addition. We found that the Cu2+-coordinated polydopamine coating showed improved stability and antibacterial effect. The cytotoxicity test confirmed that the bioinspired antibacterial coating showed good biocompatibility and no obvious toxicity. The results confirmed that the stents with AMP could in situ inhibit bacterial growth and biofilm formation, and finally reduce the deposition of struvite and hydroxyapatite crystals both in vitro and in vivo. We anticipate that this bioinspired strategy would develop a safe, stable and effective antibacterial coating on urinary tract medical devices for long-term bacterial inhibition and encrustation prevention.

Current material engineering strategies to prevent catheter encrustation in urinary tracts.

Catheters and ureteric stents have played a vital role in relieving urinary obstruction in many urological conditions. With the increasing use of urinary catheters/stents, catheter/stent-related complications such as infection and encrustation are also increasing because of their design defects. Long-term use of antibiotics and frequent replacement of catheters not only increase the economic burden on patients but also bring the pain of catheter replacement. This is unfavorable for patients with long indwelling catheters or stents but inconvenient to replace. In recent years, some promising technologies and mechanisms have been used to prevent infection and encrustation, mainly drug loading coatings, functional coatings, biodegradable polymers and metallic materials for urinary devices. Obvious effects in anti-encrustation and anti-infection experiments of the above strategies in vivo or in vitro have been conducted, which is very helpful for further clinical trials. This review mainly introduces catheter/stent technology and mechanisms in the past ten years to address the potential impact of anti-encrustation coating of catheter/stent materials for the prevention of encrustation and to analyze the progress made in this field.

Long non-coding RNA HCP5 in cancer.

Cancer remains a major threat to human health worldwide. Long non-coding RNA (lncRNA) comprises a group of single-stranded RNA with lengths longer than 200 bp. LncRNAs are aberrantly expressed and play a variety of roles involving multiple cellular processes in cancer. Histocompatibility leukocyte antigen complex P5 (HCP5), initially reported in 1993, is an important lncRNA located between the MICA and MICB genes in MHC I region. HCP5 is involved many autoimmune diseases as well as malignancies. Abnormal HCP5 expression occurs in many types of cancer and its dysregulation appears closely associated with tumor progression. HCP5 is also involved in anti-tumor drug resistance as well. As such, HCP5 represents a promising biomarker and therapeutic target in cancer. In this review, we summarize recent researches and provide an overview of the role and mechanism of HCP5 in human cancer.