Case Report: Clinical analysis of a cluster outbreak of chlamydia psittaci pneumonia.

Objective: To explore the clinical characteristics and prognosis of clustered cases of psittacosis pneumonia. Method: We retrospectively analyzed the clinical data of a cluster outbreak of psittacosis pneumonia. The analysis included epidemiological data, clinical symptoms, laboratory results, and prognosis. The diagnosis was made using mNGS and nested PCR technology. Result: Of the four cases, two had direct contact with diseased poultry while the other two did not. All cases presented with more than 39.5 °C fever and chills. Additionally, significant increases in C-reactive protein, ferritin, creatine kinase, and lactate dehydrogenase were observed in all cases, while absolute lymphocyte count decreased. Case 2 also had increased calcitonin levels. Acute respiratory failure occurred during the treatment of case 1 and case 2, leading to tracheal intubation and ventilator-assisted ventilation. Unfortunately, case 2 passed away due to sepsis and multiple organ dysfunction, while the other cases had a positive prognosis. Conclusion: mNGS facilitated the early diagnosis of psittacosis pneumonia. It is important to note that there is still a substantial risk of human-to-human transmission in psittacosis pneumonia. Absolute lymphocyte count and calcitonin levels can predict the severity and prognosis of the disease.

Total Synthesis of Vinorine.

The asymmetric total synthesis of vinorine, a polycyclic and cage-like alkaloid, has been realized in a flexible approach. Key features of the current synthesis include an aza-Achmatowicz rearrangement/Mannich-type cyclization to install the highly functional 9-azabicyclo-[3.3.1]nonane scaffold, a high yield Fischer indole annulation to synthesize the common intermediate for sarpagine-ajamaline type alkaloids, and an Ireland-Claisen rearrangement to construct the C15-C20 bond.

Total Syntheses of Kopsaporine, Kopsinol and Kopsiloscine†A.

Kopsia alkaloids represent a complex class of natural products bearing a polycyclic ring system with two or three consecutive quaternary carbon centers. In this article, we report the first total synthesis of Kopsaporine related alkaloids. Features of our structure-unit-based strategy are an intramolecular Pummerer rearrangement induced nucleophilic cyclization/aza-Prins cyclization to construct the highly functional hexahydrocarbazole skeleton, an olefin migration vinylogous alkylation to establish the C20 all-carbon quaternary center, an iridium complex mediated radical addition to fuse the aspidofractine framework, an unprecedented IBX oxidation to introduce the α-hydroxyketone moiety, and a bioinspired retro-Aldol/Aldol reaction to convert kopsaporine to kopsiloscine A.

APOL1 Induces Pyroptosis of Fibroblasts Through NLRP3/Caspase-1/GSDMD Signaling Pathway in Ulcerative Colitis.

Background: Pyroptosis is a form of proinfammatory gasdermin-mediated programmed cell death. Abnormal infammation in the intestine is a critical risk factor for Ulcerative colitis (UC). However, at present, it is not clear whether pyroptosis of colonic fibroblasts is involved in the pathogenesis and progression of UC. Methods: In this study, key genes associated with UC were identified by bioinformatics analysis. Datasets were downloaded from the Gene Expression Omnibus (GEO) database (GSE193677). The differentially expressed genes were analyzed, and the hub genes were screened by weighted gene co-expression network analysis (WGCNA) and differentially expressed genes. We also downloaded the dataset from GEO for single-cell RNA sequencing (GSE231993). The expression of key genes was verified by immunohistochemistry, immunofluorescence and Western blot, and the specific pathways of key genes inducing pyroptosis in cell lines were explored. Results: The results of bioinformatics analysis showed that the expression of APOL1 and CXCL1 in UC tissues was significantly higher than that in normal tissues. The results of single-cell analysis showed that the two genes were co-localized to fibroblasts. These results were consistent with the results of immunohistochemistry and immunofluorescence colocalization in human intestinal mucosa specimens. Furthermore, APOL1 overexpression induced NLRP3-caspase1-GSDMD-mediated pyroptosis of fibroblasts, which was confirmed by Western blot. Conclusion: APOL1 induces pyroptosis of fibroblasts mediated by NLRP3-Caspase1-GSDMD signaling pathway and promote the release of chemokines CXCL1. Fibroblasts may play a crucial role in the pathogenesis and progression of UC.

Association of X-linked TLR-7 gene polymorphism with the risk of knee osteoarthritis: a case-control study.

Knee osteoarthritis (OA) is the most prevalent type of OA, and Toll-like receptor 7 (TLR7) may lead to the pathogenesis of OA. Recently, X-linked TLR7 polymorphism has been confirmed to be associated with arthritis. However, there is a lack of studies on TLR7 gene polymorphism associated with knee OA susceptibility. The current study aimed to determine whether TLR7 gene polymorphism is associated with the risk of knee OA. Genotyping of two polymorphic sites (rs3853839 and rs179010) in the TLR7 gene was performed in 252 OA patients, and 265 healthy controls using the SNaPshot sequencing technique. Data were analyzed statistically by Chi-square tests and logistic regression. Rs3853839-C allele showed frequencies of 28% and 27% in the healthy control and female knee OA groups, respectively. The differences were not statistically significant (P > 0.05). The rs3853839-CG genotype frequency was significantly lower in the female knee OA group as compared to the healthy control group (OR 0.60; 95%CI 0.36-0.99; P = 0.044). In the male hemizygote population, the rs3853839-CC showed significantly lower frequencies in the male knee OA group as compared to the healthy control group (OR 0.35; 95%CI 0.17-0.71; P = 0.0025). Regarding rs179010, there were no differences in the genotype distribution and allele frequencies between OA patients and healthy subjects under any models (P > 0.05). Stratified analysis showed that the frequency of the rs3853839-CG genotypes was lower in high Kellgren-Lawrence grades (KLG) (OR 0.48; 95%CI 0.21-1.08; P = 0.066), and significantly lower in OA patients with effusion synovitis (OR 0.38; 95%CI 0.17-0.88; P = 0.013). TLR7 rs3853839 polymorphism may play a role in the susceptibility of knee OA in the Chinese Han Population and may be associated with OA severity and the risk of effusion synovitis in Knee OA.

Structure units oriented approach towards collective synthesis of sarpagine-ajmaline-koumine type alkaloids.

Sarpagine-Ajmaline-Koumine type monoterpenoid indole alkaloids represent a fascinating class of natural products with polycyclic and cage-like structures, interesting biological activities, and related biosynthetic origins. Herein we report a unified approach towards the asymmetric synthesis of these three types of alkaloids, leading to a collective synthesis of 14 natural alkaloids. Among them, akuammidine, 19-Z-akuammidine, vincamedine, vincarine, quebrachidine, vincamajine, alstiphylianine J, and dihydrokoumine are accomplished for the first time. Features of our synthesis are a new Mannich-type cyclization to construct the key indole-fused azabicyclo[3.3.1]nonane common intermediate, a SmI2 mediated coupling to fuse the aza-bridged E-ring, stereoselective olefinations to install either the 19-E or 19-Z terminal alkenes presented in the natural alkaloids, and an efficient iodo-induced cyclization to establish the two vicinal all-carbon quaternary centers in the Koumine-type alkaloids.

Evaluation of Pembrolizumab Monotherapy Efficacy in Advanced Non-Small-Cell Lung Cancer by Serial Monitoring of Circulating Tumor DNA Using Next-Generation Sequencing.

INTRODUCTION: Pembrolizumab is widely used in advanced non-small-cell lung cancer (NSCLC) patients with positive programmed death-ligand 1 (PD-L1). However, efficacy evaluation along treatment by serial monitoring of circulating tumor DNA (ctDNA) using next-generation sequencing remained to be well studied. METHODS: Nine PD-L1 positive advanced NSCLC patients were prospectively enrolled and received pembrolizumab monotherapy. Pretreatment tissue and/or plasma samples were collected as baseline reference. Serial plasma samples were collected after 3 and 6 weeks of treatment as well as at disease progression. All samples underwent targeted next-generation sequencing. RESULTS: The median progression-free survival (mPFS) and median overall survival (mOS) were 4.43 and 25.53 months, respectively. In total, 3 patients achieved partial response (PR) or stable disease (SD) for more than 6 months and were thus classified into the durable clinical benefit (DCB) group, whereas the rest 6 were grouped as nondurable benefit (NDB) patients. Molecular profiling of baseline samples revealed that TP53 and APC were the 2 most frequently mutated genes in all patients, whereas POT1 and SETD2 mutations were enriched in DCB and NDB groups, respectively. Higher tumor mutational burden (TMB) was observed in DCB patients than NDB group. During serial ctDNA monitoring, 2 DCB patients showed a dramatic ctDNA reduction while 75% of NDB patients' ctDNA concentration increased at week 6. Several acquired mutations might contribute to the pembrolizumab resistance, including CDKN2A frameshift and MITF nonsense mutations. CONCLUSIONS: Genomic profiling of peripheral blood samples can be applied to dynamically monitor disease progression. The reduction in ctDNA concentration during treatment implied DCBs.

A comprehensive evolutionary and epidemiological characterization of insertion and deletion mutations in SARS-CoV-2 genomes.

SARS-CoV-2, which causes the current pandemic of respiratory illness, is evolving continuously and generating new variants. Nevertheless, most of the sequence analyses thus far focused on nucleotide substitutions despite the fact that insertions and deletions (indels) are equally important in the evolution of SARS-CoV-2. In this study, we analyzed 1,099,664 high-quality sequences of SARS-CoV-2 genomes to re-construct the evolutionary and epidemiological histories of indels. Our analysis revealed 289 circulating indel types (237 deletion and 52 insertion types, each represented by more than ten genomic sequences), among which eighteen were recurrent indel types, each represented by more than 500 genome sequences. Although indels were identified across the entire genome, most of them were identified in nsp6, S, ORF8, and N genes, among which ORF8 indel types had the highest frequencies of frameshift. Geographical and temporal analyses of these variants revealed a few alterations of dominant indel types, each accompanied by geographic expansion to different countries and continents, which resulted in the fixation of several types of indels in the field, including the current variants of concern. Evolutionary and structural analyses revealed that indels involving S N-terminal domain regions were linked to the 3/4 variants of concern, resulting in significantly altered S protein that might contribute to the selective advantage of the corresponding variant. In sum, our study highlights the important role of insertions and deletions in the evolution and spread of SARS-CoV-2.

Associations of TNF-α -238G/A, TNF-α -308G/A, and IL-6 -174G/C polymorphisms with the risk of asthma: Evidence from a meta-analysis.

BACKGROUND: Previously, many genetic epidemiological studies have investigated associations between Th1-related cytokine polymorphisms and the risk of asthma, with inconsistent results. Accordingly, we carried out a meta-analysis to more precisely estimate associations between Th1-related cytokine polymorphisms and the risk of asthma. METHODS: Systematic literature searching of Medline, Embase, Wanfang, VIP, and CNKI was conducted by the authors to identify eligible publications, and 69 genetic epidemiological studies were finally found to be eligible for quantitative analyses. RESULTS: We found that genotypic frequencies of TNF-α -238G/A (dominant comparison: odds ratio [OR] = 0.47, P = .006; overdominant comparison: OR = 1.87, P = .03; allele comparison: OR = 0.50, P = .004), TNF-α -308G/A (dominant comparison: OR = 0.76, P = .001; overdominant comparison: OR = 1.29, P = .002; allele comparison: OR = 0.81, P = .0009) and IL-6 -174G/C (dominant comparison: OR = 0.55, P = .0008) polymorphisms among patients with asthma and control subjects were significantly different. However, we did not detect such a genotypic distribution difference for the IL-1B-511C/T polymorphism. CONCLUSIONS: The present meta-analysis shows that TNF-α -238G/A, TNF-α -308G/A, and IL-6 -174G/C polymorphisms may influence the risk of asthma.

Conditionally replicative adenovirus carrying shRNA targeting EZH2 inhibits prostate cancer growth and invasion.

The present study aimed to construct conditionally replicative adenovirus (CRAds) carrying small hairpin (sh)RNA targeting enhancer of zeste homolog 2 (EZH2), in order to study its effect on inhibiting prostate cancer (PCa) cell growth and invasion. Immunohistochemical analyses of EZH2 was performed in tumor tissue samples from PCa and benign prostate hyperplasia (BPH). The human telomerase reverse transcriptase (hTERT) promoter was chosen to transcriptionally control EZH2 gene expression to obtain adenoviral replication (Ad­hTERT­EZH2shRNA) in human PCa cell lines. The inhibitory effect of Ad­hTERT­EZH2shRNA on EZH2 expression was evaluated by reverse transcription­-quantitative polymerase chain reaction and western blot analyses. Cell Counting Kit­8 assays were used to examine the effects of the Ad­hTERT­EZH2shRNA on cell proliferation. Transwell Matrigel invasion assays were used to detected cell invasion. Immunohistochemistry showed that EZH2 staining was stronger in castration­resistant prostate cancer (CRPC) samples, compared with androgen­dependent prostate cancer (ADPC) samples, and was absent in BPH. Furthermore, EZH2 expression knockdown suppressed PCa cell proliferation and invasion. In addition, it was found that Ad­hTERT­EZH2shRNA selectively replicated and significantly reduced the expression of EZH2 in PCa cells lines. The growth ability and invasion of DU145 and PC3 cells in vitro was effectively inhibited by Ad­hTERT­EZH2shRNA. Silencing the expression of EZH2 led to decreased expression of CCND1 and Ki67 and increased expression of E­cadherin, as determined by western blot analysis. Thus, it was shown that CRAds armed with EZH2 shRNA exhibited significant antitumor effects in human PCa cells. Ad­hTERT­EZH2shRNA may be developed as a treatment for hormone­refractory PCa.

Clinicopathological characteristics and survival outcomes of bladder neuroendocrine carcinomas: a population-based study.

BACKGROUND: Bladder neuroendocrine carcinomas (BNECs) are relatively a rare type of tumor. The aim of this study was to examine the clinicopathological characteristics and predictors of survival outcomes of patients with BNECs based on the analysis of the national Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Kaplan-Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of different treatments on overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 910 patients were identified between 2004 and 2014. Overall, 648 (71.2%) patients had small cell neuroendocrine carcinoma (SCNEC), 35 (3.8%) had large cell neuroendocrine carcinoma (LCNEC), 10 (1.1%) had carcinoid tumor (well-differentiated neuroendocrine tumor), 16 (1.8%) had paraganglioma/pheochromocytoma (PGL/PHEO), 619 (68.0%) had a poorly differentiated or undifferentiated histology grade, 214 (23.5%) presented with metastatic disease, 586 (64.4%) underwent transurethral ablation/destruction for bladder tumor, and 245 (26.9%) had partial/total cystectomy. Cystectomy+chemotherapy+radiotherapy (CCR) has the highest long-term survival rate among various treatments. The 1-, 3-, and 5-years CSS of CCR were 56%, 56%, and 56%, respectively. By using multivariable Cox proportional hazard model, age, histology, N stage, SEER stage, tumor size, radiotherapy, chemotherapy, and local treatment of the primary site were identified as independent predictors for OS and CSS; all P<0.05. CONCLUSION: In BNEC, SCNEC has an absolute advantage in number. SCNEC/LCNEC tend to be older men. PGL/PHEO and carcinoid tumors have younger mean ages, earlier tumor stages, and better prognosis than SCNEC/LCNEC. Surgery, radiotherapy and chemotherapy are better than conservative treatment. However, whatever cystectomy or bladder sparing, chemotherapy should be a major component of treatment.

The effect of marital status on the survival of patients with bladder urothelial carcinoma: A SEER database analysis.

To identify whether marital status is associated with survival in patients with bladder urothelial carcinoma (UC). Using Surveillance, Epidemiology, and End Results population-based data, 133,846 patients diagnosed with bladder UC between 1988 and 2009 were identified. Kaplan-Meier methods and multivariable Cox regression models were used for survival analyses and evaluation of the association between marital status and survival, after controlling for gender, age, race, primary site, tumor (topography), lymph node, metastasis stage, pathological grading, and surgery. Patients in the married group had a higher proportion of men within group comparisons, more often white, older, earlier clinical stage at diagnosis, surgical treatment, all of which were statistically significant (P < .001). Widowed patients had the worst bladder UC cause-specific survival (CSS) compared with married, never married, and so on groups classified by stage and grade. The 5-year CSS of widowed patients compared with that of married patients was, respectively, all (P < .001), 89.8% versus 95.8% at noninvasive papillary carcinoma stage, 84.1% versus 91.6% at occur in situ stage, 74.3% versus 86.1% at I stage, 41.2% versus 61.6% at II stage, 39.2 versus 52.5% at III stage, and 8.8% versus 17.0% at IV stage. Widowed patients tend to have a significantly higher risk of bladder-cancer-specific mortality. Marital status was relevant to improved CSS in patients with bladder UC.

Size-controllable synthesis of NiCoSe2 microspheres as a counter electrode for dye-sensitized solar cells.

NiCoSe2 microspheres have been successfully synthesized by a facile one-step hydrothermal method at different hydrothermal temperatures. The prepared samples are divided according to their reaction temperatures (90, 120, 150 and 180 °C) and named NiCoSe2-90, NiCoSe2-120, NiCoSe2-150 and NiCoSe2-180, respectively. The diameters of the NiCoSe2 microspheres strongly depend on the different hydrothermal temperatures. When the temperature is increased to 150 °C, the size of the resultant NiCoSe2 microspheres changes from 200 to 800 nm, and the interior of NiCoSe2-150 possesses a flocculent structure. However, NiCoSe2-180 displays a cauliflower-like aggregated structure. The prepared NiCoSe2 alloys are used as high-performance Pt-free counter electrodes (CEs) for dye-sensitized solar cells (DSSCs). Cyclic voltammogram measurement indicates that NiCoSe2-150 CE has larger current density than Pt CE. Electrochemical impedance spectroscopy shows that NiCoSe2-150 CE has a low charge-transfer resistance of 1.8 Ω cm2. Due to their unique morphologies and well-defined interior and exterior structures, DSSCs based on NiCoSe2-120 and NiCoSe2-150 CEs achieve high power conversion efficiencies of 8.48% and 8.76%, respectively, which are higher than that of the solar cell based on Pt CE (8.31%).

Inhibition of ubiquitin proteasome function prevents monocrotaline-induced pulmonary arterial remodeling.

AIMS: Previous study has indicated that inhibition of proteasome function ameliorates the development of pulmonary arterial hypertension (PAH), while its underlying mechanisms are still unclear. This study was performed to address these issues. MATERIAL AND METHODS: Male Sprague-Dawley (SD) rats were divided into five groups: control group, PAH group, vehicle treated PAH group, MG-132 treated PAH group and bortezomib treated PAH group. PAH model was established by a single intraperitoneal injection of monocrotaline (MCT). MG-132 and bortezomib were administered to inhibit proteasome function. The right ventricular systolic pressure (RVSP), the right ventricle hypertrophy index (RVHI) and the percentage of medial wall thickness (%MT) were used to evaluate the development of PAH. Hematoxylin and eosin staining was performed to measure vascular remodeling. Immunoblotting was used to determine Akt phosphorylation, expression of PTEN and NEDD4, and the level of ubiquitinated-PTEN protein. KEY FINDINGS: MCT increased RVSP, RVHI and %MT in rats, while these changes were suppressed by treatment of PAH rats with MG-132 or bortezomib. In PAH model, expression of PTEN was decreased and phosphorylation of Akt was increased, these were accompanied by an elevation of NEDD4 protein level. Treatment of PAH model with MG-132 or bortezomib increased PTEN expression and accumulation of ubiquitinated-PTEN protein and decreased Akt phosphorylation, while didn't change NEDD4 expression. SIGNIFICANCE: Inhibition of proteasome function ameliorates pulmonary arterial remodeling by suppressing UPS-mediated PTEN degradation and subsequent inhibition of PI3K/Akt pathway, indicating that UPS might be a novel target for prevention of PAH.

Diagnostic value of a plasma microRNA signature in gastric cancer: a microRNA expression analysis.

The differential expression of microRNAs (miRNAs) in plasma of gastric cancer (GC) patients may serve as a diagnostic biomarker. A total of 33 miRNAs were identified through the initial screening phase (3 GC pools vs. 1 normal control (NC) pool) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M). By qRT-PCR, these miRNAs were further assessed in training (30 GC VS. 30 NCs) and testing stages (71 GC VS. 61 NCs). We discovered a plasma miRNA signature including five up-regulated miRNAs (miR-185, miR-20a, miR-210, miR-25 and miR-92b), and this signature was evaluated to be a potential diagnostic marker of GC. The areas under the receiver operating characteristic curve of the signature were 0.86, 0.74 and 0.87 for the training, testing and the external validation stages (32 GC VS. 18 NCs), respectively. The five miRNAs were consistently dysregulated in GC tissues (n = 30). Moreover, miR-185 was decreased while miR-20a, miR-210 and miR-92b were increased in arterial plasma (n = 38). However, none of the miRNAs in the exosomes showed different expression between 10 GC patients and 10 NCs. In conclusion, we identified a five-miRNA signature in the peripheral plasma which could serve as a non-invasive biomarker in detection of GC.

Clinical efficacy of mTOR inhibitors in solid tumors: a systematic review.

The common dysregulation of the mTOR signaling pathway in tumor cells makes it a key target in oncotherapy. To better understand the effects of mTOR inhibitors, we analyzed 32 published clinical trials on solid tumors other than renal cell cancer, neuroendocrine tumors and metastatic breast cancer, for mTOR inhibitors are already approved by the US FDA to treat the three cancers. A lack of therapeutic effects was observed when mTOR inhibitors were used as a single agent. When combined with other agents, mTOR inhibitors still lacked sufficient clinical activity or just had minimal activity. More studies are required to better understand the clinically effects of mTOR inhibitors and the development of novel mTOR inhibitors is absolutely necessary.

Adipose-derived stem cell-based treatment for acute liver failure.

INTRODUCTION: Acute liver failure (ALF) is a highly lethal disease, for which effective therapeutic methods are limited. Although allogeneic liver transplantation is a viable treatment method for ALF, there is a serious shortage of liver donors. Recent studies suggest that stem cell transplantation is a more promising alternative. Hence, we investigate whether human adipose-derived stem cells (ASCs) have the therapeutic potential for ALF in this study based on the studies of rat models. METHODS: Sprague Dawley rats were used to establish ALF models by D-galactosamine injection. These rats were randomly divided into a human ASC-treated group and a phosphate-buffered saline (PBS) control group. The human ASCs or PBS was transplanted through the spleen of rats. The indices of hepatic function and hepatic histology were dynamically detected, and the survival rates of rats were also counted. Double-fluorescence immunohistochemistry was employed to detect the ASC fate after transplantation. Moreover, both concentrated ASC conditional media and ASC lysates were transplanted through the femoral vain of rats to investigate the therapeutic potential for ALF. RESULTS: The ASC transplantation group showed improved viability in comparison with the sham control. Histological and biochemical analysis suggested that liver morphology and function were improved in terms of cell proliferation and apoptosis. Although a plethora of ASCs persist in the spleen, the improvement in liver function was obvious. However, ASCs did not differentiate into hepatocytes after engrafting to livers within 3 days. In addition, both concentrated serum-free ASC conditional media and ASC lysates, characterized by high levels of hepatocyte growth factor and vascular endothelial growth factor, demonstrated obvious improvement in terms of high survival rates of ALF rats. CONCLUSION: Our data suggest that ASC transplantation has the potential for ALF treatment partly by the mechanism of secreting growth factors contributing to liver regeneration.

Efficacy of therapy with bortezomib in solid tumors: a review based on 32 clinical trials.

The ubiquitin-proteasome system is a major pathway for protein degradation, so that proteasome is now considered as an important target for drug discovery. Bortezomib, the first US FDA-approved proteasome inhibitor now used as a front-line treatment for multiple myeloma. To better understand the effects of bortezomib in cancer treatment, we carried out a review based on 32 published clinical trials to determine whether bortezomib will benefit patients with solid tumors. Information of complete response, partial response, stable disease and objective response rate was collected to assess clinical outcomes. A lack of therapeutic effects was observed when bortezomib was used as a single agent. Meanwhile, when bortezomib treatment was combined with other agents, bortezomib offered no statistically significant response versus these agents alone. High-quality studies are required to better understand the clinically effects of bortezomib and the development of a new generation of proteasome inhibitors is absolutely necessary.

Delivery of EZH2-shRNA with mPEG-PEI nanoparticles for the treatment of prostate cancer in vitro.

Small interfering RNA (siRNA) is a promising therapeutic approach for castration-resistant prostate cancer (PCa). For the clinical application of siRNA, it is vital to find a safe and efficient gene transfer vector. Nanotechnology can provide a crucial advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of new therapeutic delivery vehicles. In this study, we describe a novel nanoparticle (mPEG-PEI) as an efficient non-viral carrier and found that this copolymer displayed enhanced efficiency in the shRNA-mediated knockdown of target genes. The enhancer of zeste homolog 2 (EZH2) is often elevated in castration-resistant PCa and has been implicated in the progression of human PCa. Targeting EZH2 may have therapeutic efficacy for the treatment of metastatic, hormone-refractory PCa. mPEG-PEI binds plasmid DNA yielding nanoparticles and these complexes exhibit low cytotoxicity and high gene transfection efficiency. Taken together, mPEG-PEI may be a promising non-viral gene carrier for the delivery of EZH2 short hairpin (sh)RNA to PC3 cells for advanced PCa therapy.

miR-96 promotes cell proliferation and clonogenicity by down-regulating of FOXO1 in prostate cancer cells.

The present study aimed to investigate the biological functions of miR-96 in the processes of proliferation and clonogenicity in the prostate cancer cells. miR-96 was identified to be markedly up-regulated in prostate cancer cell and cancer tissues compared with normal prostate cell and normal prostate tissues by microarray method and RT-PCR analysis. Down-regulation of miR-96 expression reduced the proliferation and colony formation ability of PC3 prostate cancer cells, while over-expression of miR-96 induced proliferation and colony formation ability of LNCaP prostate cancer cells. Forkhead box protein O1 (FOXO1) is key tumor suppressors and has been shown to play key roles in the regulation of diverse cellular processes, including cell proliferation, differentiation, cell cycle progression and apoptosis. The expression level of FOXO1 was strikingly up-regulated in PC3 cells after transfected with miR-96 inhibitor, and FOXO1 expression was down-regulated in LNCaP cells after transfected with miR-96 mimics. miR-96 may play a vital role in promoting cell proliferation in human prostate cancer cells. Inhibition of miR-96 caused expression increase of tumor suppressor gene FOXO1, thus manipulating miR-96 expression may be a promising approach in treatment of prostate cancer.