ABSTRACT
BACKGROUND: Klebsiella pneumoniae (KP) accounts for high antimicrobial resistance and mortality rates of bloodstream infections (BSIs). OBJECTIVES: To investigate incidence, antimicrobial resistance and risk factors for mortality of KP BSIs in East China. METHODS: A retrospective study of patients with KP BSIs was conducted in a tertiary care hospital from 2018 to 2022. Medical records of all hospitalised patients with KP BSIs were reviewed and analysed. The incidence, antimicrobial resistance and mortality of KP BSIs were evaluated. The Kaplan-Meier method was used to plot survival curves and logistic regression was used to analyse risk factors for crude 30-day mortality. RESULTS: A total of 379 inpatients with KP BSIs were enrolled. The incidence of patients with KP BSIs was fluctuating between 4.77 and 9.40 per 100,000 patient-days. The crude 30-day mortality rate of these patients was 26.39%. Of the 379 KPisolates, 197 (51.98%) were carbapenem-resistant (CR) and 252 (66.49%) were multidrug-resistant (MDR). All isolates showed the lowest resistance to tigecycline (13.77%) and polymyxin B (14.61%). Cases with MDR/CR isolates had significantly longer length of hospital stay, higher crude 30-day mortality and medical costs than non-MDR/non-CR isolates. Age, CR phenotype, paracentesis, indwelling central venous catheter (CVC), use of carbapenems, tetracyclines, polymyxins B, and irrational empiric treatment were independently associated with crude 30-day mortality. CONCLUSION: MDR/CR KP BSIs are associated with increased mortality, healthcare costs and prolonged hospitalisation. Patients with advanced age, CR phenotype, paracentesis, CVC, exposure to some antibiotics, and irrational empirical antibiotic treatment are at higher mortality risk.
ABSTRACT
Carbonized polydopamine (cPDA) exhibits a nitrogenous graphite-like structure with n-type semiconductor property. However, the low electrical conductivity and Seebeck coefficient of cPDA cannot meet the needs of flexible thermoelectric devices. In this study, a series of metal ions were coordinated with cPDA to enhance n-type thermoelectric properties. At 300 K, all metal-coordination cPDA (metal-cPDA) samples obtain lower thermal conductivity compared to cPDA. Mn-cPDA exhibits the greatest Seebeck coefficient of -25.94 µV K-1, which is almost six times higher than cPDA. Fe-cPDA shows the best electrical conductivity of 2.45 × 105 S m-1. An optimal power factor (PF) value of 11.93 µW m-1 K-2 is achieved in Ca-cPDA with the enhanced electrical conductivity of 9.5 × 104 S m-1 and Seebeck coefficient of -11.24 µV K-1. Using Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM), we revealed the structural characterization of metal-cPDA. Our results indictate that the different metal ions (Mn2+, Zn2+, Mg2+, Al3+, Ca2+, and Fe3+) exert varying influences on the growth of graphite-like structure within metal-cPDA, which lead to the evolution of electrical conductivity. We observe that the carrier density and carrier mobility depend on both the degree of graphitization and the metal-ion coordination, which work together on electrical conductivity and Seebeck coefficient. These findings and understanding of the thermoelectric properties of PDA-based materials will help to realize high-performance n-type thermoelectric materials for flexible electronic device applications.
ABSTRACT
Background and aim: Prostate cancer is a leading malignant tumor in men, associated with a high rate of mortality. Androgen deprivation therapy is commonly used to treat prostate cancer, which contributes to the progression of castration-resistant prostate cancer (CRPC). The current therapy has a low survival rate in patients with CRPC. Our study aims to develop a novel effective approach for CRPC treatment and improve survival benefits. Experimental procedure: CRPC cell line PC-3-Luc expressing luciferase and the CRPC cell line PC-3-IL6-Luc stably overexpressing IL-6 were used to establish the xenograft tumor mouse model. The tumor was monitored weekly using Bioluminescence imaging. Infiltrated macrophages were quantified by fluorescence-activated cell sorting using flow cytometry. IL6 mRNA level was determined using quantitative real-time PCR. The protein levels of total STAT3 and phosphorylated STAT3 were determined using Western blot. Results and conclusion: Zhoushi Qi Ling decoction (ZQD) treatment significantly reduced PC3 the xenograft tumor progression and the number of infiltrated macrophages when compared with saline treatment. IL6 mRNA level was remarkedly suppressed by ZQD treatment. Notably, the protein level of phosphorylated STAT3 was significantly decreased in PC3 the xenograft tumor treated with ZQD compared to saline treatment. Our findings demonstrated that ZQD treatment significantly reduced the progression of prostate cancer, evidenced by the reduced population of infiltrated macrophages and the inhibition of the IL6/STAT3 pathway.
ABSTRACT
BACKGROUND: Prostate cancer is one of the most common cancers in men worldwide. This study aims to elucidate the roles of c-Jun N-terminal kinase (JNK) in the progression of castration-resistant prostate cancer (CRPC). METHODS: JNK overexpressing and knockdown cell lines were established on the PC-3 prostate cell line. qPCR and Western blotting were performed to determine the mRNA and protein levels of target genes in prostate tissues and cell lines. MTT and Matrigel invasion assays were conducted to evaluate the cell viability and invasive ability, respectively. The Kaplan-Meier estimator was performed to estimate the overall survival rate and second progression-free survival rate. Pearson's correlation coefficient was used to evaluate the relationship between JNK and prostate-specific antigen (PSA). RESULTS: Relative JNK expression was correlated with Gleason score and PSA value in patients with CRPC. Kaplan-Meier analysis revealed that patients with low JNK expression exhibited high overall survival and second progression-free survival rate. In vitro assays demonstrated that JNK overexpression promoted cell viability and invasion as well as the protein expressions of extracellular signal-regulated kinase (ERK) and matrix metalloproteinase 1 (MMP1) in PC-3 cell lines. CONCLUSIONS: JNK overexpression promotes the development of CRPC via the regulation of ERK and MMP1.
Subject(s)
Prostatic Neoplasms, Castration-Resistant , Humans , Male , Cell Line, Tumor , Extracellular Signal-Regulated MAP Kinases , Matrix Metalloproteinase 1 , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/metabolism , Mitogen-Activated Protein Kinase 8/metabolismABSTRACT
Current theories on lexical recognition are mostly based on studies from spoken languages or their written forms. Much less is known about the process of lexical recognition in sign languages. This study aims to examine the neural correlates of sign recognition by investigating the effects of lexical frequency, length, phonological neighborhood density, and iconicity during Chinese Sign Language comprehension. Twenty-two deaf signers viewed a set of sign videos that varied in the 4 lexical properties and decided if they referred to animals, while event-related potential responses were recorded. Data were analyzed through linear mixed-effects models with the lexical variables treated as continuous measures. The results showed that frequency modulated ERP amplitude as early as around 200 ms and in the late N400 time frame. Sign length invoked effects throughout the process, starting from 200 ms and pertaining to the last epoch. Neighborhood density effects were also observed early around 200 ms and later on the N400 and late positive complex (LPC). Iconicity produced robust effects on the N400 and LPC amplitude. Lexical frequency, length, and neighborhood density influence the neural dynamics of sign recognition in a similar way as to spoken words. Iconicity can confer a processing advantage due to closer form-meaning mappings. The results indicate that lexical recognition engages some mechanisms that are universal across the signed and spoken modality, but it can also be regulated by modality-specific properties such as the prevalent iconicity in sign languages.
Subject(s)
Electroencephalography , Semantics , Humans , Male , Female , Evoked Potentials/physiology , Linguistics , Recognition, Psychology/physiologyABSTRACT
QiLing Decoction (QLD) showed therapeutic effects against prostate cancer with an unclear underlying mechanism. This study explored the underlying mechanisms of QLD against castration-resistant prostate cancer (CRPC). Clinical specimens were collected from the patients with CRPC. Stable cells including knockdown and overexpression cell lines were established by plasmid transfection. The xenograft animal model was constructed. Cell viability was determined by using cell-counting kit 8 assay. Biochemical assays were used to determine the levels of iron (Fe2+) and lipid reactive oxygen species (ROS). qRT-PCR and Western blotting were used to determine levels of target genes, respectively. Treatment of QLD inhibited ferroptosis suppressor protein (FSP) 1 at mRNA and protein levels in patients with CRPC. Additionally, cells treated with QLD-containing serum displayed a decrease in cell viability and an increase in Fe2+ and lipid ROS with or without erastin, whereas ferroptosis inhibitor reversed QLD-induced ferroptosis. The regulatory effects of QLD on PC3 cell ferroptosis were associated with its inhibitory effects against FSP1. Consistently, QLD inhibited PC3 tumor growth by inhibiting FSP1. Moreover, treatment of QLD increased the sensitivity of PC3-AbiR cells to abiraterone by inhibiting FSP1. QLD promoted ferroptosis in CRPC cells in part by inhibiting FSP1 in vitro and in vivo.
ABSTRACT
Background: Prostate cancer is the most common malignant tumor in men, accounting for one of the top five cancer incidences worldwide. However, there is no effective pharmacological treatment for advanced prostate cancer (APC). Herein, we aim to investigate the mechanism of Zhoushi Qiling decoction (ZQD), a traditional Chinese medicine compound, in inhibiting prostate cancer cells proliferation and tumor growth. Methods: IC50 was determined in PC3 and DU145 cells. Cell viability was determined using MTT assay after interleukin (IL) 6 stimulation. Cell proliferation ability was evaluated using colony formation assay. IL-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway was analyzed using qRT-PCR and Western blot in PC3 and DU145 cells and xenograft tumor tissues. Results: It was found that ZQD significantly inhibited Il-6-induced cell viability and proliferation in PC3 and DU145 cells. Moreover, ZQD significantly reduced mRNA levels of IL-6, IL-1ß, STAT3, Bcl2, and CyclinD1, stimulated by IL-6. The protein levels of p-STAT3, Bcl2 and CyclinD1 were reduced by ZQD treatment at 40 mg/mL both in PC3 and DU145 cells. Additionally, in xenograft tumor tissues, tumor volume, weight and proliferation were significantly reduced by ZQD treatment. In addition, the mRNA and protein levels of IL-6 and pSTAT3 were significantly inhibited by ZQD treatment in vivo. Conclusion: We demonstrate that ZQD can effectively reduce cell proliferation and tumor growth by inhibiting the activation of IL-6/STAT3 signaling pathway.
ABSTRACT
Therapeutic resistance to androgen-deprivation therapy is a major challenge for prostate cancer therapy. The present study aims to explore the effects of poly (ADP-ribose) polymerase (PARP) inhibitor olaparib and STL127705 on castration-resistant prostate cancer. Cell lines including PC-3 and enzalutamide-resistant LNCaP (erLNCaP) cells were treated with enzalutamide, enzalutamide plus olaparib, enzalutamide plus STL127705, or the combination of olaparib, STL127705, and enzalutamide. Cell viabilities and cell apoptosis were determined using the sulforhodamine B (SRB) assay and Annexin V/propidium iodide staining, respectively. Flow cytometry assay was applied to determine γH2AX intensity and the percentage of homologous recombination and non-homologous end-joining. Besides, a tumor-bearing animal model was established and treated with drugs as for cell lines. STL127705 and olaparib enhanced cytotoxicity of enzalutamide on erLNCaP and PC-3 cells. Furthermore, STL127705 and olaparib promoted enzalutamide-induced cell apoptosis and enhanced γH2AX intensity. In vitro study also showed that the combination of STL127705, olaparib, and enzalutamide inhibited homologous recombination and non-homologous end-joining repair systems in PC-3 cells. In vivo study demonstrated that the combination of STL127705, olaparib, and enzalutamide exhibited a significant anti-tumor effect. STL127705 combined with olaparib have a potential therapeutic effect on castration-resistant prostate cancer through inhibiting homologous recombination and non-homologous end-joining repair.
ABSTRACT
The attentional blink (AB) refers to the impaired identification of the second target (T2) when presented within approximately 500ms after the first target (T1). Although the AB is eliminated when two targets can be integrated into a single compound word, it remains unclear whether the lexico-semantic organization of translation equivalents modulates the magnitude of the AB. In the present study, we examined consecutive targets' processing in a rapid serial visual presentation (RSVP) paradigm using Chinese-English translation equivalents and non-translation equivalents. The results demonstrated that an overall presence of the AB effect was observed when T1 and T2 were non-translation equivalents. However, the AB effect disappeared completely when the two target words were translation equivalents. Taken together, these findings suggest that Chinese-English bilinguals are translating intentionally between Mandarin and English, which facilitates lexical access to word meaning from the two languages at the initial stages of visual word processing. Furthermore, such lexico-semantic activation of translation equivalents attributes to the elimination of the AB.
Subject(s)
Attentional Blink , Humans , Attentional Blink/physiology , Semantics , Visual Perception/physiology , Language , TranslatingABSTRACT
OBJECTIVE: To study the clinical therapeutic effect as well as drug effectiveness and safety of Shizi Sanhua decoction combined with Nuoyu in the treatment of oligozoospermia in men. METHODS: 102 patients with oligozoospermia diagnosed at Longhua Hospital of Shanghai University of Traditional Chinese Medicine from February 2022 to March 2023 were selected and randomly divided into 3 groups. The treatment group was treated with Shizi Sanhua Decoction + Nuoyu; the traditional Chinese medicine group was treated with Shizi Sanhua Decoction; and the Nuoyu nutrient group was treated with Nuoyu nutrient. A review assessment and record were made after one course of treatment (3 months). RESULTS: A total of 102 patients completed the trial due to the treatment process. There were 34 cases in each of the traditional Chinese medicine group, the Nuoyu nutrient group, and the treatment group. Clinical efficacy: total effective rate of 52.94% in the traditional Chinese medicine group; 58.82% in the Nuoyu nutrient group; 82.35% in the treatment group. The clinical efficacy of the treatment group was better than that of the traditional Chinese medicine group and the Nuoyu nutrient group (P<0.05), which was statistically significant. Semen routine: the treatment group was better than the traditional Chinese medicine group and Nuoyu nutrient group in improving the total number of sperm and sperm concentration. CONCLUSION: The semen concentration and forward sperm count of patients with oligozoospermia treated with Shizi Sanhua Decoction combined with Nuoyu improved more significantly, and the clinical efficacy was remarkable. And the clinical efficacy is not affected by age and disease duration. It can be popularized and applied as a treatment for oligozoospermia.
Subject(s)
Drugs, Chinese Herbal , Oligospermia , Humans , Male , Drugs, Chinese Herbal/therapeutic use , Oligospermia/drug therapy , Oligospermia/chemically induced , Semen , China , Medicine, Chinese TraditionalABSTRACT
Abiraterone acetate has exhibited impressive results in improving progression-free survival of patients with metastatic castration-resistant prostate cancer. However, many patients may develop abiraterone resistance with a variable duration of response. Hence, identifying a remedy to overcome abiraterone resistance is critical for patients with castration-resistant prostate cancer. In this study, we aim to explore the potential of Qi Ling decoction (QLD), a traditional Chinese medicine, in attenuating abiraterone resistance in prostate cancer. Cell viability and apoptosis were respectively measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The protein levels were assessed by Western blotting assay. Autophagosome formation was quantified by counting LC3 puncta. We found that QLD was capable of promoting abiraterone-induced apoptosis and cell death of PC3-AbiR and DU145-AbiR cells in vitro. A combination of QLD and abiraterone yielded a better tumor inhibition effect than QLD alone and abiraterone alone. Further investigation revealed that QLD restored the abiraterone sensitivity of PC3-AbiR and DU145-AbiR cells through modulating autophagy. These findings suggest that QLD might serve as a potential remedy to enhance the therapeutical effect of abiraterone for patients with castration-resistant prostate cancer.
Subject(s)
Prostatic Neoplasms, Castration-Resistant , Male , Humans , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Qi , Androstenes/pharmacology , Androstenes/therapeutic use , AutophagyABSTRACT
The present study investigated the electrophysiological correlates of morpheme transposition in two-character Chinese compound words (canonical words and transposed words) and pseudowords at a very short stimulus onset asynchrony (SOA) of 83 ms, employing a dual-target rapid serial visual presentation (RSVP) task. Event-related potential (ERP) results showed that, relative to pseudowords, canonical words elicited increased positivity or decreased negativity in ERP amplitudes beginning with the 200-300 ms (P200) and continuing through the 300-450 ms (N400) into the late time window of 450-600 ms (late positive component, LPC). Critically, the morpheme transposition effects were found on the N400 component and LPC, with larger N400 and smaller LPC amplitudes in the transposed words than in the canonical words. Taken together, these results demonstrated that morpheme transposition hindered the semantic extraction and combinatorial processing of the whole word entities in very rapid succession, as reflected by the modulations of N400 and LPC.
Subject(s)
Electroencephalography , Evoked Potentials , Humans , Male , Female , Evoked Potentials/physiology , SemanticsABSTRACT
Extensive behavioral and electrophysiological evidence has demonstrated that native translations are automatically activated when bilinguals read non-native words. The present study investigated the impact of cross-language orthography and phonology on Chinese-English bilingual lexicons with a masked priming paradigm. The masked primes and targets were either translation equivalents (TE), orthographically related through translation (OR), phonologically related through translation (PR), or unrelated control (UC). Participants retained the targets in memory and decided whether the delayed catch words matched the targets. ERP data showed significant masked translation priming effects, as reflected by decreased ERP amplitudes in the TE condition in the 300-600 ms time window from frontal to parietal electrode clusters. Importantly, compared with the UC condition, the PR rather than OR condition elicited less negative ERP waveforms in the 300-500 ms time window with a frontal distribution. Taken together, these temporal and spatial dynamics suggested an automatic cross-language co-activation at the phonological and semantic levels for different-script bilinguals.
Subject(s)
Language , Multilingualism , China , Humans , Linguistics , ReadingABSTRACT
QiLing decoction (QLD) is a traditional Chinese medicine compound. This study aims to explore the therapeutic effect of QLD in castration-resistant prostate cancer (CRPC) and its potential bio-targets. A total of 51 active components and QLD 149 targets were identified using bioinformatics analysis. Additionally, five optimal hub target genes were screened including tumor protein P53 (TP53), interleukin-6 (IL-6), vascular endothelial growth factor-A (VEGF-A), caspase-3 (CASP-3), and estrogen receptor-1 (ESR-1). The interrelated network between active components of QLD and their potential targets was constructed. The molecular function, biological processes, and signaling pathways of QLD-against CRPC were identified. Moreover, QLD was found to efficiently exert a repressive effect on CRPC tumor growth mainly by suppressing the activation of HIF-α/VEGFA and TNF-α/IL6 signaling pathways, and increasing the P53 expression level. These results successfully indicated the potential anti-CRPC mechanism of the active components of QLD.
Subject(s)
Prostatic Neoplasms, Castration-Resistant , Tumor Suppressor Protein p53 , Male , Humans , Tumor Suppressor Protein p53/genetics , Vascular Endothelial Growth Factor A/genetics , Network Pharmacology , Prostatic Neoplasms, Castration-Resistant/drug therapy , Signal TransductionABSTRACT
BACKGROUND: Among reproductive cancers, ovarian cancer leads to the highest female mortality rate. Fisetin, a natural flavonoid, exerts pharmacological effects, inhibiting cancer growth with various origins. Although multiple mechanisms are involved in regulating cell death, it is still unclear whether and how fisetin exhibits anticancer effects on ovarian cancer. The present study aimed to evaluate cell apoptotic and necroptotic processes occurring in ovarian carcinoma (OC) cell lines induced by fisetin. METHODS: Cell growth was evaluated by MTT assay in OC cell lines treated with or without fisetin. Annexin V/propidium iodide staining followed by flow cytometry was used to characterize fisetin-induced cell death. The apoptotic process was suppressed by z-VAD intervention, and cell necroptosis was assessed by introducing ZBP1-knockdown OC cell lines coupled with fisetin intervention. The expression of necroptosis-related mediators and the migration capability of the respective cells were evaluated by Western blotting and in vitro cell invasion assay. RESULT: Fisetin successfully reduced cell growth in both OC cell lines in a dose-dependent manner. Both apoptosis and necroptosis were induced by fisetin. Suppression of the cell apoptotic process failed to enhance the proliferation of fisetin-treated cells. The induced cell death and robust expression of the necroptotic markers RIP3 and MLKL were alleviated by knocking down the expression of the ZBP1 protein in both OC cell lines. CONCLUSION: The present study provided in vitro evidence supporting the involvement of both apoptosis and necroptosis in fisetin-induced OC cell death, while ZBP1 regulates the necroptotic process via the RIP3/MLKL pathway.
Subject(s)
Carcinoma , Ovarian Neoplasms , Apoptosis , Carcinoma, Ovarian Epithelial , Cell Death , Cell Line , Female , Flavonols , Humans , Necroptosis , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/geneticsABSTRACT
Tumor-associated macrophages (TAMs) are critical immune cells infiltrated into tumor. In present study, we evaluated the effects of Qi Ling (QL), a traditional Chinese medicine on paclitaxel resistance in prostate cancer cells and explored the underlying mechanisms. We administrated QL to rats and collected the serum from QL-treated rats (QL-serum). We established the co-culture system of TAMs/paclitaxel resistant prostate cancer cells. We treated the TAMs with QL-serum and measured the viability of paclitaxel resistant prostate cancer cells after exposing to paclitaxel. We monitored the expression of M1 and M2 markers, the expression and activation of IL-6/STAT3 signaling pathways in TAMs after QL treatment. We treated TAMs with QL-serum together with interleukin (IL)-6, measured the expression of M1 and M2 markers, and the viability of paclitaxel resistant prostate cancer cells. In co-culture system, QL-serum-treated TAMs decreased the paclitaxel resistance in the human prostate cancer cells. QL-serum treatment significantly up-regulated the expression of M1 markers inducible nitric oxide synthase and tumor necrosis factor α while decreased the expression of M2 markers IL-10 and chemokine (C-C motif) ligand 22. QL-serum suppressed the activation of IL-6/ signal transducer and activator of transcription 3 signaling pathway. All these effects of QL-serum were abolished in the presence of IL-6. Qi Ling re-programmed TAMs and decreases paclitaxel resistance in prostate cancer cells.
Subject(s)
Paclitaxel , Prostatic Neoplasms , Qi , Animals , Humans , Interleukin-6/metabolism , Male , Paclitaxel/pharmacology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Rats , Tumor-Associated MacrophagesABSTRACT
Background: miR-143 is known to be downregulated in various cancer cells and tumors and generally plays a tumor-suppressor role. miR-143. However, the role of miR-143 in the mediation of the sensitivity of prostate cancer cells to abiraterone acetate remains unrevealed. Methods: The expression levels of miRNAs were determined by miRNA microarray and quantitative real-time PCR (qRT-PCR). The protein levels were assessed by Western blot assay. Cell viability and apoptosis were respectively measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Results: We identified that miR-143 was significantly downregulated in PC3-AbiR cells compared to PC3 cells. Overexpression of miR-143 promoted PC-AbiR sensitivity to abiraterone acetate in vitro and in vivo. We also revealed that miR-143 upregulation inhibited p-JNK (c-Jun N-terminal kinases) and increased p-Bcl2 (B-cell lymphoma 2), contributing to abiraterone acetate-induced apoptosis in PC3-AbiR cells. Finally, we showed that the combination of miR-143 and abiraterone acetate exerted the most profound tumor inhibition effect and prolonged the mice survival rate in PC3-AbiR tumor-bearing mice. Conclusion: Upregulation of miR-143 may serve as a new strategy to enhance the therapeutical effect of abiraterone acetate on prostate cancer patients who are resistant to abiraterone acetate.
ABSTRACT
To identify novel biomarker(s) in prostate cancer and demonstrate the mechanistic involvements in this disease, RNA-seq was employed to reveal the differentially expressed genes in the blood samples from prostate cancer patients. Relative expression of miR-302b-3p was evaluated using real-time PCR. The potential regulation of RELA by miR-302b-3p was assessed by luciferase reporter assay. Protein levels of NF-κB, Vimentin, N-cadherin and E-cadherin, were quantified using western blotting. Transwell chamber was employed to measure cell migratory and invasive capacity, while cell attachment/detachment assay was performed to evaluated epithelial-mesenchymal transition (EMT)-related behavior. Xenograft tumor model was adopted to determine the anti-tumor activity of miR-302b-3p in vivo. We demonstrated miR-302b-3p was down-regulated in prostate cancer both in vivo and in vitro. We predicted and identified RELA as directly targeted by miR-302b-3p. Ectopic miR-302b-3p expression in PC-3 cells significantly suppressed cell migration, invasion, attachment, detachment capacity, which was accompanied with a decrease in the expression of N-cadherin and Vimentin, and an increase of E-cadherin expression. MiR-302b-3p-proficiency greatly delayed xenograft tumor growth and associated with favorable overall survival. Co-introduction of RELA completely abolished anti-tumor effects of miR-302b-3p, which indicated a potential genetic interaction between RELA/NF-κB and miR-302b-3p. We characterized the aberrant down-regulation of miR-302b-3p in prostate cancer and unraveled a possible involvement of miR-302b-3p/RELA signaling axis in this scenario.
ABSTRACT
Docetaxel resistance developed in half of castration-resistant prostate cancer (CRPC) patients hinders its long-term clinical application. The current study was designed to investigate the effects of Chinese medicine Zhoushi Qi Ling decoction on the docetaxel resistance of prostate cancer as well as elucidate the underlying molecular mechanism. In our study, Qi Ling significantly decreased viability and colony formation as well as increased apoptosis of docetaxel-resistant (DR) CRPC cells. Qi Ling-treated DR cells exhibited decreased glucose consumption, lactate release and pyruvate production. Moreover, lncRNA SNHG10 was upregulated in DR tissues of CRPC patients and was negatively correlated with the progression-free survival. Bioinformatics analysis indicated miR-1271-5p as the associated miRNA possibly binding with SNHG10. miR-1271-5p up-regulation dramatically decreased the luciferase activity of SNHG10 in DR cells. SNHG10 knockdown sharply increased the expression of miR1271-5p in DR cells. Targetscan predicted TRIM66 as one of the downstream targets of miR-1271-5p. miR-1271-5p up-regulation drastically reduced luciferase activity as well as TRIM66 expression in DR cells. Also, the knockdown of SNHG10 remarkably suppressed the expression of TRIM66 in DR cells. Additionally, Qi Ling treatment reduced SNHG10 and TRIM66, while increased miR1271-5p, in DR cells. In summary, Qi Ling inhibited docetaxel resistance and glycolysis of CRPC possibly via SNHG10/miR-1271-5p/TRIM66 pathway.
Subject(s)
Docetaxel/pharmacology , Drugs, Chinese Herbal/pharmacology , Prostatic Neoplasms, Castration-Resistant/metabolism , RNA, Long Noncoding/genetics , Warburg Effect, Oncologic/drug effects , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Drug Resistance, Neoplasm/drug effects , Humans , Intracellular Signaling Peptides and Proteins/genetics , Male , MicroRNAs/geneticsABSTRACT
OBJECTIVE: To investigate the feasibility and effectiveness of Xialiqi capsules in rats with nonbacterial prostatitis. METHODS: A total of 90 healthy male SD rats, weighing 200-220 g, were randomly divided into a blank control group (BCG, n=30), a model group (MG, n=30), and an intervention group (IG, n=30). After establishing the model of chronic nonbacterial prostatitis, IG was treated with 50 mg/kg Xialiqi capsules via gavage. The three groups received the same dose of saline via gavage for 7 consecutive days. The differences in leukocytes, phospholipid vesicle density, number of colonies, prostate mass, apparent diffusion coefficient (ADC), degree of inflammatory cell infiltration in the prostate fluid, serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, CD3+, CD8+ levels after intervention were compared in the three groups. RESULTS: Compared with the BCG, the number of leukocytes and colonies in the prostate fluid of the MG was elevated, and the density of lipid vesicles was decreased, and the number of leukocytes and colonies in the prostate fluid of the MG significantly decreased and the density of lipid vesicles rebounded after the intervention of Xialiqi capsules (P>0.05). Compared with the BCG, the prostate mass, ADC and the degree of inflammatory cell infiltration were elevated in the MG. There was a significant reversion of the above indices after the intervention of Xialiqi capsules (P<0.05). The serum levels of TNF-α, IL-6 and IL-8 in the MG were significantly higher than those in the IG, and the levels in the IG were higher than that in the BCG (P<0.05). The serum levels of CD3+ and CD8+ in the MG were significantly lower than those in the IG, and the levels in the IG were lower than that in the BCG (P<0.05). CONCLUSION: Xialiqi capsules have a good intervention effect on nonbacterial prostatitis, which can significantly alleviate the immune status and reduce the level of cytokines in the serum and tissues of rats.