LINC00461 promotes bladder cancer cells EMT through miR-518b/HNRNPUL1 axis.

Bladder cancer (BC) is a prevalent type of tumor in the urinary system, and it has been discovered that long non-coding RNA (lncRNA) plays a significant role in its occurrence and development. However, thus far, no reports have been published on the involvement of LINC00461 in BC. Here, we found that LINC00461 levels were upregulated in BC tissues and cell lines. Besides, knockdown of LINC00461 inhibited BC cell proliferation, migration, invasion through epithelial-mesenchymal transition (EMT), and slowed down tumor growth in vivo. Moreover, we found that LINC00461 regulated HNRNPUL1 expression through miR-518b sponge activity, and the miR-518 inhibitor could reverse the inhibitory effects of LINC00461 knockdown on BC cell proliferation, migration, and EMT. Our results suggest that LINC00461 may serve as a potential biomarker and therapeutic target for BC.

Exploration and validation of ceRNA regulatory networks in colorectal cancer based on associations whole transcriptome sequencing.

Colorectal cancer (CRC) is a wide-spread gastrointestinal cancer that is associated with augmented morbidity and mortality, and we do not yet have a deep understanding of its epidemiology and carcinogenicity. The transcriptome can reveal the complexity and heterogeneity of tumors and uncover new biomarkers or treatment options. In this study, we identified messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), round RNAs (circRNAs), and microRNAs (miRNAs) using whole-transcriptome sequencing and generated competing endogenous RNA (ceRNA) modulatory axes. We conducted whole transcriptome sequencing on 10 CRC and para-cancer (CRCP) samples and discovered 2465 differentially expressed (DE) mRNAs (DEmRNAs), 77 DE miRNAs (DEmiRNAs). 2852 DE lncRNAs (DElncRNAs) and 1477 DE circRNAs (DEcircRNAs). In addition, utilizing co-DE analysis, we generated the ceRNA axis. Subsequently, we employed the ceRNA axis to identify essential genes and corresponding associations with lncRNAs, circRNAs, and miRNAs in CRC. ceRNA regulatory network including mRNA-miRNA-lncRNA and mRNA-miRNA-circRNA. These modulatory axes potentially modulate the positive regulation of smooth muscle contraction, melanosome, plasma membrane, integral plasma membrane component and so on. Finally, the results of RNA sequencing (RNA-SEQ) were combined with the TCGA and GEO databases, and the DEGs strongly correlated with the TCGA-COAD overall survival (OS) as estimated by univariate cox and logarithmic rank analyses were cross-analyzed, and the co-upregulated DEGs were screened. Among the many DEs, KPNA2 was chosen for additional analysis. Using invitro experimentations, western blot, CCK8, EdU and other experiments were performed to verify the results. We found siRNA-based KPNA2 depletion reduces bladder cancer cells' viability, migratory, and proliferative activities, which showed that the DEmRNA profiles were comparable to the sequencing information, confirming that the sequencing data were very reliable. These evidences highlight the ceRNA regulatory mechanisms in CRC and will aid future research into the molecular mechanisms behind colorectal cancer prevention and treatment.

The Discovery of Novel α2a Adrenergic Receptor Agonists Only Coupling to Gαi/O Proteins by Virtual Screening.

Most α2-AR agonists derived from dexmedetomidine have few structural differences between them and have no selectivity for α2A/2B-AR or Gi/Gs, which can lead to side effects in drugs. To obtain novel and potent α2A-AR agonists, we performed virtual screening for human α2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity. Compound P300-2342 and its three analogs significantly decreased the locomotor activity of mice (p < 0.05). Furthermore, P300-2342 and its three analogs inhibited the binding of [3H] Rauwolscine with IC50 values of 7.72 ± 0.76 and 12.23 ± 0.11 µM, respectively, to α2A-AR and α2B-AR. In α2A-AR-HEK293 cells, P300-2342 decreased forskolin-stimulated cAMP production without increasing cAMP production, which indicated that P300-2342 activated α2A-AR with coupling to the Gαi/o pathway but without Gαs coupling. P300-2342 exhibited no agonist but slight antagonist activities in α2B-AR. Similar results were obtained for the analogs of P300-2342. The docking results showed that P300-2342 formed π-hydrogen bonds with Y394, V114 in α2A-AR, and V93 in α2B-AR. Three analogs of P300-2342 formed several π-hydrogen bonds with V114, Y196, F390 in α2A-AR, and V93 in α2B-AR. We believe that these molecules can serve as leads for the further optimization of α2A-AR agonists with potentially few side effects.

Therapeutic stapled peptides: Efficacy and molecular targets.

Peptide stapling, by employing a stable, preformed alpha-helical conformation, results in the production of peptides with improved membrane permeability and enhanced proteolytic stability, compared to the original peptides, and provides an effective solution to accelerate the rapid development of peptide drugs. Various reviews present peptide stapling chemistries, anchoring residues and one- or two-component cyclization, however, therapeutic stapled peptides have not been systematically summarized, especially focusing on various disease-related targets. This review highlights the latest advances in therapeutic peptide drug development facilitated by the application of stapling technology, including different stapling techniques, synthetic accessibility, applicability to biological targets, potential for solving biological problems, as well as the current status of development. Stapled peptides as therapeutic drug candidates have been classified and analysed mainly by receptor- and ligand-based stapled peptide design against various diseases, including cancer, infectious diseases, inflammation, and diabetes. This review is expected to provide a comprehensive reference for the rational design of stapled peptides for different diseases and targets to facilitate the development of therapeutic peptides with enhanced pharmacokinetic and biological properties.

Robust and flexible polyester fiber membrane with under-liquid dual superlyophobicity for efficient on-demand oil-water separation.

Functional materials with under-liquid dual superlyophobicity have generated a great deal of concern from researchers due to their switchable separation ability oil-water mixtures and emulsions. Conceptually, under-liquid dual superlyophobicity is a Cassie state achievable under-liquid through the synergy of an under-liquid double lyophobic surface and the construction of a highly rough surface. However, obtaining an under-liquid dual superlyophobic surface remains difficult due to its thermodynamic contradiction and complex surface composition. Herein, we successfully prepared a functional coating by modifying the mixture of cellulose nanocrystals (CNCs) and nano-TiO2 with perfluorooctanoic acid (PFOA) via a simple method, then obtained a polyester fiber membrane with under-liquid dual superlyophobicity by roll coating method. The surface wettability of the polyester (PET) membrane was altered, transforming it from the original under-water oleophobic/under-oil superhydrophilic state to the under-water superoleophobic/under-oil superhydrophobic state after coated. The resulting membrane was applied to separate oil and water on-demand. The coated PET membrane exhibited high separation efficiency (>99 %) and high separation flux, effectively separating immiscible oil-water systems as well as oil-in-water and water-in-oil emulsions. The coated PET membrane also demonstrated the ability to perform alternate separation of oil-water mixtures through wetting, washing, and rewetting cycles, with repeated processes up to 10 times without significant reduction in separation efficiency. Furthermore, compared with the previous works, our approach offers a simpler and more convenient method for constructing under-liquid dual superlyophobic surface, making it more suitable for continuous corporate production. This study may provide inspiration for the production and application in large-scale of under-liquid dual superlyophobic membranes.

lncRNA ENST00000422059 promotes cell proliferation and inhibits cell apoptosis in breast cancer by regulating the miR-145-5p/KLF5 axis.

Krüppel-like zinc-finger transcription factor 5 (KLF5) is a vital regulator of breast cancer (BC) onset and progression. The mechanism by which KLF5 regulates BC is still not clearly known. In this study, bioinformatics analysis shows that BC-affected individuals with elevated KLF5 expression levels have poor clinical outcomes. We further verify that miR-145-5p regulated KLF5 expression to promote cell apoptosis and inhibit cell proliferation in BC via dual-luciferase reporter assay, western blot analysis, qRT-PCR, CCK-8 assay and cell apoptosis assay. In addition, based on bioinformatics analysis, the binding of ENST00000422059 with miR-145-5p is confirmed by dual-luciferase reporter assay. Subsequently, FISH, western blot analysis, qRT-PCR, CCK-8 and cell apoptosis assays verified that ENST00000422059 increases KLF5 protein expression by sponging miRNA to promote cell proliferation and inhibit cell apoptosis. Finally, ENST00000422059 is found to accelerate tumor progression by regulating the miR-145-5p/KLF5 axis in vivo. In conclusion, this study suggests that ENST00000422059 upregulates KLF5 by sponging miR-145-5p to promote BC progression.

A Notch signaling-related lncRNA signature for predicting prognosis and therapeutic response in clear cell renal cell carcinoma.

Increasing evidence has confirmed the vital role of Notch signaling in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). The underlying function of long non-coding RNA (lncRNA) related to Notch signaling in ccRCC remains unclear. In present study, the prognostic value and therapeutic strategy of Notch signaling-related lncRNA are comprehensively explored in ccRCC. In total, we acquired 1422 NSRlncRNAs, of which 41 lncRNAs were identified the key NSRlncRNAs associated with the occurrence of ccRCC. The prognostic signature containing five NSRlncRNAs (AC092611.2, NNT-AS1, AGAP2-AS1, AC147651.3, and AC007406.3) was established and validated, and the ccRCC patients were clustered into the high- and low-risk groups. The overall survival of patients in the low-risk group were much more favorable than those in the high-risk group. Multivariate Cox regression analysis indicated that the risk score was an independent prognostic biomarker. Based on the risk score and clinical variables, a nomogram for predicting prognosis of ccRCC patients was constructed, and the calibration curves and DCA curves showed the superior predictive ability of nomogram. The risk score was correlated with immune cell infiltration, targeted therapy or chemotherapy sensitivity, and multiple oncogenic pathways. Additionally, consensus clustering analysis stratified the ccRCC patients into four clusters with obvious different outcomes, immune microenvironments, and expression of immune checkpoints. The constructed NSRlncRNA-based signature might serve as a potential biomarker for predicting prognosis and response to immunotherapy or targeted therapy in patients with ccRCC.

Gßγ subunit inhibitor decreases DOM-induced head twitch response via the PLCß/IP3/Ca2+/ERK and cAMP signaling pathways.

AIMS: (-)-2,5-dimethoxy-4-methylamphetamine (DOM) induces the head-twitch response (HTR) primarily by activating the serotonin 5-hydroxytryptamine 2A receptor (5-HT2A receptor) in mice. However, the mechanisms underlying 5-HT2A receptor activation and the HTR remain elusive. Gßγ subunits are a potential treatment target in numerous diseases. The present study investigated the mechanism whereby Gßγ subunits influence DOM-induced HTR. MAIN METHODS: The effects of the Gßγ inhibitor 3',4',5',6'-tetrahydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one (gallein) and antagonistic peptide ßARKct (ß-adrenergic receptor kinase C-terminal fragment) on DOM-induced HTR were studied via an HTR test. The activation of the phospholipase C ß (PLCß)/inositol triphosphate (IP3)/calcium (Ca2+) signaling pathway and extracellular signal-regulated kinase (ERK) following Gßγ subunit inhibition was detected by western blotting, Homogeneous Time-Resolved Fluorescence (HTRF) inositol phosphate (IP1) assay and Fluorometric Imaging Plate Reader (FLIPR) calcium 6 assay. The Gßγ subunit-mediated regulation of cyclic adenosine monophosphate (cAMP) was assessed via a GloSensor™ cAMP assay. KEY FINDINGS: The Gßγ subunit inhibitors gallein and ßARKct reduced DOM-induced HTR in C57BL/6J mice. Like the 5-HT2A receptor-selective antagonist (R)-[2,3-di(methoxy)phenyl]-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol (M100907), gallein inhibited PLCß phosphorylation (pPLCß), IP1 production, Ca2+ transients, ERK1/2 phosphorylation (pERK1/2) and cAMP accumulation induced by DOM in human embryonic kidney (HEK) 293T cells stably or transiently transfected with the human 5-HT2A receptor. Moreover, PLCß protein inhibitor 1-[6-[[(8R,9S,13S,14S,17S)-3-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]amino]hexyl]pyrrole-2,5-dione (U73122) (10 nmol/mouse), intracellular Ca2+ blocker 6-[6-[6-[5-acetamido-4,6-dihydroxy-2-(sulfooxymethyl)oxan-3-yl]oxy-2-carboxy-4-hydroxy-5-sulfooxyoxan-3-yl]oxy-2-(hydroxymethyl)-5-(sulfoamino)-4-sulfooxyoxan-3-yl]oxy-3,4-dihydroxy-5-sulfooxyoxane-2-carboxylic acid (heparin) (5 nmol/mouse), L-type Ca2+ channel blocker 3-O-(2-methoxyethyl) 5-O-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (nimodipine) (4 mg/kg), mitogen extracellular regulating kinase 1/2 (MEK1/2) inhibitor (Z)-3-amino-3-(4-aminophenyl)sulfanyl-2-[2-(trifluoromethyl)phenyl]prop-2-enenitrile (SL327) (30 mg/kg), and Gαs protein selective antagonist 4,4',4″,4‴-(Carbonylbis-(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakisbenzene-1,3-disulfonic acid (NF449) (10 nmol/mouse) reduced DOM-induced HTR in C57BL/6J mice. SIGNIFICANCE: The Gßγ subunits potentially mediate the HTR after 5-HT2A receptor activation via the PLCß/IP3/Ca2+/ERK1/2 and cAMP signaling pathways. Inhibitors targeting the Gßγ subunits potentially inhibit the hallucinogenic effects of 5-HT2A receptor agonists.

Quantitative Analysis of Quality of Life and Exploration of Influencing Factors in Patients Undergoing Radical Prostatectomy.

OBJECTIVE: To quantify and evaluate the quality of life of patients undergoing radical prostatectomy using the FACT-P scoring system, and to explore the predictive factors for postoperative quality of life. METHODS: Clinical data of 249 patients who underwent radical prostatectomy in our hospital from January 2021 to October 2022 were analyzed. According to the surgical method and whether the subjective quality of life of the patient decreased significantly, the patients were divided into groups, and the predictive factors for changes in subjective quality of life after surgery were analyzed. RESULTS: A total of 192 cases were finally obtained (45 cases of fascia internal approach, 147 cases of traditional radical prostatectomy), and patients who underwent fascia internal approach (FACT-P: 110.15 ± 10.55) had better postoperative quality of life than those who underwent extra-fascial radical prostatectomy (FACT-P: 102.30 ± 6.75) (P < .01). One hundred fourteen patients reported a decrease in subjective quality of life, while 78 did not. The preoperative FACT-P score was an independent predictive factor (OR=0.719, P < .01), and when the preoperative score was <116 points, the possibility of no decrease in quality of life after surgery was higher. CONCLUSION: Fascia internal approach should be performed as much as possible for suitable surgical patients, and for patients with a preoperative FACT-P score ≥116 points, the possibility of a decrease in quality of life after surgery should be fully communicated.

LncRNA ENST00000370438 promotes cell proliferation by upregulating DHCR24 in breast cancer.

Long noncoding RNAs (lncRNAs) are critically involved in the occurrence and development of breast cancer (BC). In this study, we performed RNA sequencing, and the results revealed an increase in the expression level of novel lncRNA ENST00000370438 in tissues of patients with BC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) results showed an increase in lncRNA ENST00000370438 expression level in 23 pairs of BC tissues. Next, we determined the effect of ENST00000370438 on BC cell proliferation, and the results showed that ENST00000370438 promotes cell proliferation in BC. The proteomic analysis showed a decrease in DHCR24 expression level in BC cells transfected with ENST00000370438 small interfering RNA. Western blot and qRT-PCR assay results showed that ENST00000370438 regulated DHCR24 expression. Furthermore, the rescue experiment showed that the interference with ENST00000370438 expression could restore the effect of DHCR24 overexpression on BC cell proliferation, demonstrating that ENST00000370438 could promote cell proliferation by upregulating DHCR24. Finally, we showed that lncRNA ENST000000370438 could promote tumor growth by overexpressing DHCR24 in nude mice. Our results demonstrated that lncRNA ENST00000370438 promotes BC cell proliferation by upregulating DHCR24 expression.

Solitary primary pulmonary synovial sarcoma: A case report.

BACKGROUND: Synovial sarcoma (SS) is an uncommon and highly malignant soft tissue sarcoma in the clinic, with primary pulmonary SS (PPSS) being extremely rare. Here, we describe the clinical characteristics, diagnosis, and treatment of a solitary PPSS case confirmed via surgical resection and fluorescence in situ hybridization (FISH). CASE SUMMARY: A 33-year-old man was admitted because of intermittent coughing and hemoptysis for one month, with lung shadows observed for two years. Whole-body positron emission tomography-computed tomography (PET-CT) revealed a solitary mass in the upper lobe of the right lung, with uneven radioactivity uptake and a maximum standardized uptake value of 5.6. The greyish-yellow specimen obtained following thoracoscopic resection was covered with small multi-nodulated structures and consisted of soft tissue. Hematoxylin and eosin staining revealed spindle-shaped malignant tumor cells. Immunohistochemistry indicated these tumor cells were CD99 and BCL-2-positive. Furthermore, the FISH test revealed synovial sarcoma translocation genetic reassortment, which confirmed the diagnosis of SS. CONCLUSION: PPSS is extremely rare and tends to be misdiagnosed as many primary pulmonary diseases. PET-CT, histologic analysis, and FISH tests can be used to differentiate PPSS from other diseases. Surgical resection is regularly recommended for the treatment of solitary PPSS and is helpful for improving the prognosis.

Comparison of different strategies towards the chemical synthesis of long-chain scorpion toxin AaH-II.

Long-chain scorpion toxin AaH-II isolated from Androctonus australis Hector can selectively inhibit mammalian voltage-gated sodium ion channel Nav 1.7 responsible for pain sensation. Efficient chemical synthesis of AaH-II and its derivatives is beneficial to the study of the function and mechanism of Nav 1.7 and the development of potential peptide inhibitors. Herein, we compared three different strategies, namely, direct solid-phase peptide synthesis, hydrazide-based two-segment native chemical ligation, and hydrazide-based three-segment native chemical ligation for the synthesis of AaH-II. The hydrazide-based two-segment native chemical ligation affords the target toxin with the optimal efficiency, which provides a practically robust procedure for the preparation of tool molecules derived from AaH-II to study the biological functions and modulation of Nav 1.7. Our work highlights the importance of selecting suitable segment condensation approach in the chemical synthesis of protein toxins.

Functional Preservation and Oncologic Control following Robot-Assisted versus Laparoscopic Radical Prostatectomy for Intermediate- and High-Risk Localized Prostate Cancer: A Propensity Score Matched Analysis.

AIM: To evaluate the urinary continence (UC), erectile function, and cancer control obtained following robot-assisted radical prostatectomy (RARP) and laparoscopic radical prostatectomy (LRP) for intermediate- and high-risk localized prostate cancer (PCa). MATERIALS AND METHODS: 232 patients bearing intermediate- and high-risk localized PCa were enrolled in this study. Perioperative, functional, and oncological outcomes were analyzed after applying the propensity score matched method. RESULTS: Within the matched cohort, the RARP group was corrected with a significantly shorter mean operative time than the LRP group (p < 0.001). Patients in the RARP arm were also at a lower risk of ≤ Grade II complications than those in the LRP group (p = 0.036). Meanwhile, the proportions of transfusion and ≥ Grade II complications in the RARP group were similar to those in the LRP group (p = 0.192 and p = 1.000, respectively). No significant differences regarding the rates of pT3 disease and positive surgical margin existed between the two groups. RARP versus LRP tended to a significantly higher percentage of UC recovery within the follow-up period. Significant differences were also found between the RARP and LRP arms in terms of erectile function at postoperative 6 months and the last follow-up (p = 0.013 and p = 0.009, respectively). Statistical comparability in biochemical recurrence-free survival was observed between the two groups (p = 0.228). CONCLUSIONS: For the surgical management of intermediate- and high-risk localized PCa, RARP tended to a lower risk of ≤ Grade II complications and superior functional preservation without cancer control being compromised than LRP.

Chemical Synthesis of a Full-Length G-Protein-Coupled Receptor ß2-Adrenergic Receptor with Defined Modification Patterns at the C-Terminus.

The ß2-adrenergic receptor (ß2AR) is a G-protein-coupled receptor (GPCR) that responds to the hormone adrenaline and is an important drug target in the context of respiratory diseases, including asthma. ß2AR function can be regulated by post-translational modifications such as phosphorylation and ubiquitination at the C-terminus, but access to the full-length ß2AR with well-defined and homogeneous modification patterns critical for biochemical and biophysical studies remains challenging. Here, we report a practical synthesis of differentially modified, full-length ß2AR based on a combined native chemical ligation (NCL) and sortase ligation strategy. An array of homogeneous samples of full-length ß2ARs with distinct modification patterns, including a full-length ß2AR bearing both monoubiquitination and octaphosphorylation modifications, were successfully prepared for the first time. Using these homogeneously modified full-length ß2AR receptors, we found that different phosphorylation patterns mediate different interactions with ß-arrestin1 as reflected in different agonist binding affinities. Our experiments also indicated that ubiquitination can further modulate interactions between ß2AR and ß-arrestin1. Access to full-length ß2AR with well-defined and homogeneous modification patterns at the C-terminus opens a door to further in-depth mechanistic studies into the structure and dynamics of ß2AR complexes with downstream transducer proteins, including G proteins, arrestins, and GPCR kinases.

Transvesical Versus Posterior Approach to Retzius-Sparing Robot-Assisted Radical Prostatectomy: A Retrospective Comparison With a 12-Month Follow-Up.

OBJECTIVES: To assess the perioperative, functional, and oncological outcomes of transvesical robot-assisted radical prostatectomy (T-RARP) and posterior robot-assisted radical prostatectomy (P-RARP) for localized prostate cancer. MATERIALS AND METHODS: We analyzed the data of 96 patients who underwent T-RARP or P-RARP for localized prostate cancer between January 2017 and June 2019 in a retrospective fashion. RESULTS: No significant differences in the baseline characteristics existed between the T-RARP and P-RARP arms. Both interventions were successfully performed without open conversion in either group. T-RARP was associated with a slightly more operative time (135.3 vs. 127.3 min) and estimated blood loss (105.2 vs. 94.2 mL) than P-RARP, but the differences were not significant (both p > 0.05). The likelihood of transfusion, ≤Grade II, and >Grade II postoperative complications, pT3a disease and positive surgical margins in the T-RARP group was comparable with that in the P-RARP group. No significant differences were noted between these two arms in terms of UC at the removal of catheter and nocturia (p = 0.750 and p = 0.684, respectively), and all included patients recovered UC at 3 months postoperatively. The median International Index of Erectile Function-5 score in both groups remains comparable before and after RARP. The patients in the T-RARP and P-RARP groups had a similar biochemical recurrence-free survival (p = 0.387). CONCLUSIONS: Both T-RARP and P-RARP by experienced hands are feasible for well-selected patients with prostate cancer, obtaining similar outcomes in terms of perioperative results, UC and erectile function, and oncological control within short-term follow-up.

Severe brain calcification and migraine headache caused by SLC20A2 and PDGFRB heterozygous mutations in a five-year-old Chinese girl.

BACKGROUND: Primary familial brain calcification (PFBC) is a rare inheritable neurodegenerative disease characterized by bilateral calcification in different brain regions and by a range of neuropsychiatric symptoms. Six causative genes of PFBC (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, and JAM2) have been identified. METHODS: Sanger sequencing was used to identify the causative genes associated with PFBC in this study. RESULTS: We describe the first PFBC case with both SLC20A2 and PDGFRB heterozygous mutations. Notably, this patient with the digenic mutation (who was only 5 years old) showed severe brain calcification and migraine, whereas the patient's parents, who each carried a heterozygous mutation in SLC20A2 or PDGFRB, exhibited varying degrees of brain calcification but were clinically asymptomatic. CONCLUSION: This case highlights the digenic influences on the characteristics of PFBC patients.

Bipolar plasmakinetic transurethral enucleation and resection versus bipolar plasmakinetic transurethral resection for surgically treating large (≥60 g) prostates: a propensity score-matched analysis with a 3-year follow-up.

BACKGROUND: There are extremely limited published studies comparing bipolar plasmakinetic transurethral resection of prostate (BP-TURP), bipolar plasmakinetic transurethral enucleation and resection of prostate (BP-TUERP) for enlarged prostates. Our purpose was to evaluate the safety and efficiency of BP-TUERP and BP-TURP for large (≥60 g) prostates with a 3-year follow-up. METHODS: We retrospectively identified 229 patients according to inclusion criteria between 2014 and 2016. After applying propensity score matching method, preoperative results and three-year follow-up outcomes in International Prostate Symptom Score (IPSS), urinary peek flow rate (Qmax), postvoid residual urine (PVRU) volume and quality of life (QoL) score were compared. RESULTS: Finally, within the well-balanced matched cohort, the BP-TUERP was significantly associated with longer mean operating time (OT) (P=0.039), shorter mean catheter time (CT) (P=0.001) and lower mean hemoglobin decrease (P=0.002) with more prostatic tissue removed (P=0.001) than the BP-TURP, but the median hospital stay lengths and the short- and long-term complication rates were similar between the two series. The patients in the BP-TUERP group had better long-term outcomes in IPSS, Qmax and PVRU volume than these in the BP-TURP group, but not in QoL score. CONCLUSIONS: For patients with large (≥60 g) prostates, BP-TUERP and BP-TURP are safe options, but the former is a more effective choice in long-term follow-up outcomes. BP-TUERP is related to reduced CT and hemoglobin decrease with more removal of prostatic tissue at the expense of longer OT than BP-TURP.

Corrigendum: Downregulation of HMGA1 Mediates Autophagy and Inhibits Migration and Invasion in Bladder Cancer via miRNA-221/TP53INP1/p-ERK Axis.

[This corrects the article DOI: 10.3389/fonc.2020.00589.].

TP53INP2 Modulates Epithelial-to-Mesenchymal Transition via the GSK-3ß/ß-Catenin/Snail1 Pathway in Bladder Cancer Cells.

BACKGROUND: The tumor protein p53-inducible nuclear protein 2 (TP53INP2), an autophagy protein, is essential for autophagosome formation. The deregulation of autophagy is associated with multiple human diseases, including cancer. The present study aims to explore the role of TP53INP2 in bladder cancer. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction was used to detect the mRNA level. Relative TP53INP2 protein expression was detected by immunohistochemistry and Western blot. The effect of TP53INP2 silencing on the proliferation, migration, and invasion of bladder cancer cells was investigated by CCK-8 detection kit and transwell assay. In addition, transfection and immunofluorescence were performed. RESULTS: In this study, we report that high expression of TP53INP2 is correlated with poor patient survival in bladder cancer. Results demonstrate that the depletion of TP53INP2 inhibits the migration, invasion, and epithelial-to-mesenchymal transition (EMT) of bladder cancer cells. The underlying mechanism was explored. Results show that the TP53INP2 knockdown suppresses EMT by inhibiting the active non-phosphorylated ß-catenin and decreasing the Snail1 levels. Furthermore, the glycogen synthase kinase-3 beta (GSK-3ß) inhibitor IM-12 abrogates the effect of TP53INP2 silencing. Interestingly, the induction of autophagy partially abrogates the TP53INP2 knockdown-induced decrease in active ß-catenin and inhibition of migration and invasion in bladder cancer cells. CONCLUSION: In summary, our results show that the downregulation of TP53INP2 inhibits EMT via the GSK-3ß/ß-catenin/Snail1 pathway in bladder cancer. The findings of this study uncover the novel role of TP53INP2 and offer new insights into bladder cancer clinical therapy.

Thienorphine induces antinociception without dependence through activation of κ- and δ-, and partial activation of µ- opioid receptor.

Thienorphine hydrochloride is a new anti-relapse drug for opioid abusers that is currently in phase II clinical trial. In the present study, the antinociception, dependence, and signal transduction induced by thienorphine were examined. Thienorphine showed a potent antinociception effect in acetic acid-induced writhing test and formalin test. In the hot plate test and tail-flick test, thienorphine presented the typical partial opioid agonist character with a ceiling dose-response curve in addition to a bell-shaped curve. The hot plate test revealed that thienorphine induced approximately 50% of antinociception in µ receptor knockout (µ-KO) mice compared to wild-type controls (P < 0.05). The κ, δ selective antagonist nor-binaltorphimine (nor-BNI), and naltrindole decreased approximately 50-60% of theinorphine antinociception in µ-KO mice, respectively. The ORL1 receptor-selective antagonist J113397 did not affect theinorphine antinociception in µ-KO mice. Chronic treatment with thienorphine (1.5 mg/kg) induced some tolerance that was lower compared to buprenorphine or morphine addition. In contrast to buprenorphine or morphine, thienorphine did not lead to psychological dependence by conditioned place preference (CPP). The maximum inhibition of thienorphine on protein kinase A (PKA) activity was about 36%, 100%, 100%, and 12% in CHO-µ/κ/δ/ORL1-PKAcatEGFP cells, respectively. Similar results were observed in cyclic adenosine monophosphate (cAMP) accumulation inhibited by thienorphine in cells. Thienorphine significantly increased pERK1/2 in CHO-κ/δ-PKAcatEGFP cells. These results indicated that thienorphine induced analgesia through activation of κ- and δ-, partial activation of µ- opioid receptor without a bias between G-protein- and ß-arrestin-mediated pathways. Thienorphine might be used for antinociception with minimal adverse effects.