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1.
Aging (Albany NY) ; 16(12): 10216-10238, 2024 06 28.
Article in English | MEDLINE | ID: mdl-38943627

ABSTRACT

This study aimed to reveal the specific role of early growth response protein 1 (EGR1) and nuclear receptor 4A3 (NR4A3) in nucleus pulposus cells (NPCs) and the related molecular mechanism and to identify a new strategy for treating intervertebral disc degeneration (IVDD). Bioinformatics analysis was used to explore and predict IVDD-related differentially expressed genes, and chromatin immunoprecipitation sequencing (ChIP-seq) revealed NR4A3 as the EGR1 target gene. An in vitro NPC model induced by tributyl hydrogen peroxide (TBHP) and a rat model induced by fibrous ring acupuncture were established. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemical staining, immunofluorescence staining, and flow cytometry were used to detect the effects of EGR1 and NR4A3 knockdown and overexpression on NPC apoptosis and the expression of extracellular matrix (ECM) anabolism-related proteins. Interactions between EGR1 and NR4A3 were analyzed via ChIP-qPCR and dual luciferase assays. EGR1 and NR4A3 expression levels were significantly higher in severely degenerated discs (SDD) than in mildly degenerated discs (MDD), indicating that these genes are important risk factors in IVDD progression. ChIP-seq and RNA-seq revealed NR4A3 as a direct downstream target of EGR1, and this finding was verified by ChIP-qPCR and dual luciferase reporter experiments. Remarkably, the rescue experiments showed that EGR1 promotes TBHP-induced NPC apoptosis and impairs ECM anabolism, dependent on elevated NR4A3 expression. In summary, the EGR1-NR4A3 axis mediates the progression of NPC apoptosis and ECM impairment and is a potential therapeutic target in IVDD.


Subject(s)
Apoptosis , Early Growth Response Protein 1 , Intervertebral Disc Degeneration , Nucleus Pulposus , Oxidative Stress , Receptors, Thyroid Hormone , Up-Regulation , Early Growth Response Protein 1/metabolism , Early Growth Response Protein 1/genetics , Nucleus Pulposus/metabolism , Nucleus Pulposus/pathology , Animals , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/pathology , Rats , Male , Humans , Receptors, Thyroid Hormone/metabolism , Receptors, Thyroid Hormone/genetics , Rats, Sprague-Dawley , Receptors, Steroid/metabolism , Receptors, Steroid/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Female , Middle Aged , Adult , Nerve Tissue Proteins
2.
Inorg Chem ; 63(25): 11572-11582, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38866714

ABSTRACT

Recently synthesized two-dimensional (2D) monolayer quasi-hexagonal-phase fullerene (qHPC60) demonstrates excellent thermodynamic stability. Within this monolayer, each fullerene cluster is surrounded by six adjacent C60 cages along an equatorial plane and is connected by both C-C single bonds and [2 + 2] cycloaddition bonds that serve as bridges. In this study, we investigate the stability mechanism of the 2D qHPC60 monolayer by examining the electronic structure and chemical bonding through state-of-the-art theoretical methodologies. Density functional theory (DFT) studies reveal that 2D qHPC60 possesses a moderate direct electronic band gap of 1.46 eV, close to the experimental value (1.6 eV). It is found that the intermolecular bridge bonds play a crucial role in enhancing the charge flow and redistribution among C60 cages, leading to the formation of dual π-aromaticity within the C60 sphere and stabilizing the 2D framework structure. Furthermore, we identify a series of delocalized superatom molecular orbitals (SAMOs) within the 2D qHPC60 monolayer, exhibiting atomic orbital-like behavior and hybridization to form nearly free-electron (NFE) bands with σ/π bonding and σ*/π* antibonding properties. Our findings provide insights into the design and potential applications of NFE bands derived from SAMOs in 2D qHPC60 monolayers.

3.
Inorg Chem ; 63(14): 6173-6183, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38530927

ABSTRACT

Unfolding the solution coordination chemistry of high-valent transuranium elements with the "CHON"-type ligands is important to understand the fundamental chemistry of actinides and to design more efficient extractants for partitioning of transuranium elements in advanced nuclear fuel cycles. Here, the complexation of a hexavalent neptunyl ion (NpO22+ or Np(VI)) with oxydiacetic acid (ODA) has been systematically investigated in comparison with its amide analogues N,N-dimethyl-3-oxa-glutaramic acid (DMOGA) and N,N,N',N'-tetramethyl-3-oxa-glutaramide (TMOGA) both experimentally and computationally. The formation of both 1:1 and 1:2 complexes between Np(VI) and the three ligands was identified by spectrophotometry, and their stability constants were obtained and compared with those of hexavalent U(VI) and Pu(VI). The corresponding bonding nature is elucidated by using energy decomposition analysis (EDA), electrostatic potential (ESP), ELF contours, and natural orbitals for chemical valence (NOCV) methods, which shows that the Np-O bonds are essentially ionic in character and the unoccupied 6d orbitals of Np play a key role in enhancing the covalent interactions between Np(VI) and the three ligands.

4.
Chem Sci ; 13(29): 8518-8525, 2022 Jul 29.
Article in English | MEDLINE | ID: mdl-35974750

ABSTRACT

Versatile graphene-like two-dimensional materials with s-, p- and d-block elements have aroused significant interest because of their extensive applications while there is a lack of such materials with f-block elements. Herein we report a unique one composed of the f-block element moiety of uranyl (UO2 2+) through a global-minimum structure search. Its geometry is found to be similar to that of graphene with a honeycomb-like hexagonal unit composed of six uranyl ligands, where each uranyl is bridged by two superoxido groups and a pair of hydroxyl ligands. All the uranium and bridging oxygen atoms form an extended planar 2D structure, which shows thermodynamic, kinetic and thermal stabilities due to σ/π bonding as well as electrostatic interactions between ligands. Each superoxido ligand has one unpaired (2pπ*)1 electron and is antiferromagnetically coupled through uranyl bridges with 2pπ*-5f δ -2pπ* superexchange interactions, forming a rare type of one-dimensional Heisenberg chain with p-orbital antiferromagnetism, which might become valuable for application in antiferromagnetic spintronics.

5.
Phys Chem Chem Phys ; 23(17): 10244-10250, 2021 May 05.
Article in English | MEDLINE | ID: mdl-33885071

ABSTRACT

The multiple bonds between actinide atoms and their derivatives are computationally investigated extensively and compounds with an unsupported actinide-actinide bond, especially in low oxidation states, have attracted great attention. Herein, high level relativistic quantum chemical methods are used to probe the Ac-Ac bonding in compounds with a general formula LAcAcL (L = AsH3, PH3, NH3, H, CO, NO) at both scalar and spin-orbit coupling relativistic levels. H3AsAcAcAsH3, H3PAcAcPH3 and OCAcAcCO compounds show a type of zero valence Ac[triple bond, length as m-dash]Ac triple bond with a 1σ2g1π4u configuration, and H3AsAcAcAsH3 has been found to have the shortest Ac-Ac bond length of 3.012 Å reported so far. The Ac2 unit is very sensitive to the σ donor ligands and can form triple, double and even single bonds when suitable ligands are introduced, up to 3.652 Å with an Ac-Ac single bond in H3NAcAcNH3.

6.
Cell Death Dis ; 12(2): 168, 2021 02 10.
Article in English | MEDLINE | ID: mdl-33568625

ABSTRACT

Bladder cancer (BCa) is an aggressive malignancy because of its distant metastasis and high recurrence rate. Circular RNAs (circRNAs) exert critical regulatory functions in cancer progression. However, the expression patterns and roles of circRNAs in BCa have not been well investigated. In this study, we first screened circRNA expression profiles using a circRNA microarray of paired BCa and normal tissues, and the expression of circST6GALNAC6 was confirmed by qRT-PCR and fluorescence in situ hybridization (FISH). MTT, colony formation and Transwell assays were performed to measure cell proliferation, migration and invasion. We investigated the regulatory effect of circST6GALNAC6 on miRNA and its target genes to explore the potential regulatory mechanisms of circST6GALNAC6 by chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), MS2-tagged RNA affinity purification (MS2-TRAP), immunofluorescence (IF) and dual luciferase activity assays. A nude mouse xenograft model was used to examine the functions of circST6GALNAC6/STMN1 in tumour metastasis in vivo. We found that 881 circRNAs were significantly dysregulated in BCa tissues compared to normal tissues. circST6GALNAC6(hsa_circ_0088708) was downregulated in BCa tissues and cells. Overexpression of circST6GALNAC6 effectively inhibited the cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and suppressed BCa metastasis in vivo. Mechanistically, we showed that the SP1 transcription factor, which binds to the circST6GALNAC6 mRNA transcript, activates circST6GALNAC6 transcription. Next, we verified that circST6GALNAC6 serves as a sponge that directly binds miR-200a-3p to regulate stathmin (STMN1) expression. Furthermore, we found that STMN1 is involved in circST6GALNAC6/miR-200a-3p axis-regulated BCa EMT and metastasis. Thus, our findings indicate an important underlying mechanism in BCa metastasis by which SP1-induced circST6GALNAC6 sponges miR-200a-3p to promote STMN1/EMT signalling. This mechanism could provide pivotal potential prognostic biomarkers and therapeutic targets for BCa.


Subject(s)
Cell Movement , Epithelial-Mesenchymal Transition , MicroRNAs/metabolism , RNA, Circular/metabolism , Stathmin/metabolism , Urinary Bladder Neoplasms/metabolism , Animals , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Mice, Nude , MicroRNAs/genetics , Neoplasm Invasiveness , RNA, Circular/genetics , Signal Transduction , Sp1 Transcription Factor/genetics , Sp1 Transcription Factor/metabolism , Stathmin/genetics , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology
7.
Zhonghua Nan Ke Xue ; 26(7): 579-587, 2020 Jul.
Article in Chinese | MEDLINE | ID: mdl-33377711

ABSTRACT

OBJECTIVE: To analyz the correlation of the expression of ERp29 with the clinicopathological characteristics of PCa and investigate the effect of small interfering RNA (siRNA) silencing the ERp29 gene on the biological behavior of PCa LNCaP cells. METHODS: The expression of the ERp29 gene in the BPH and PCa tissues was detected by immunohistochemistry and that of the ERp29 protein in the PCa and adjacent normal tissues of 6 PCa patients determined by Western blot. Human LNCaP cells were transfected with siRNA using LipofectamineTM 2000, and the expressions of ERp29 mRNA and protein in the LNCaP cells detected by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. The proliferation of the LNCaP cells was measured by MTT assay, their in vitro migration and invasiveness evaluated by the Transwell method, and the expressions of E-cadherin and Vimentin determined by qRT-PCR. RESULTS: The expression of ERp29 was significantly lower in the PCa than in the adjacent normal tissue (73.9% vs 91.9%, P < 0.05), with a significant correlation between the down-regulated ERp29 expression and metastasis (M) staging (P < 0.05). After transfection with siRNA, the LNCaP cells showed dramatically increased proliferation, migration and invasiveness (P < 0.05), and the expression of E-cadherin was markedly down-regulated while that of Vimentin up-regulated as compared with those in the normal control group (P < 0.05). CONCLUSIONS: The ERp29 gene may be a novel repressor of tumor metastasis. Silencing ERp29 can promote the invasiveness of human PCa cells in vitro by down-regulating the expression of E-cadherin and increasing epithelial-mesenchymal transition.


Subject(s)
Gene Expression Regulation, Neoplastic , Gene Silencing , Heat-Shock Proteins/genetics , Prostatic Neoplasms/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Humans , Male , Neoplasm Invasiveness/genetics , Prostatic Neoplasms/genetics , RNA, Small Interfering/genetics
8.
Chem Sci ; 12(1): 227-238, 2020 Oct 29.
Article in English | MEDLINE | ID: mdl-34168742

ABSTRACT

Inverse-sandwich samarium and ytterbium biphenyl complexes were synthesized by the reduction of their trivalent halide precursors with potassium graphite in the presence of biphenyl. While the samarium complex had a similar structure as previously reported rare earth metal biphenyl complexes, with the two samarium ions bound to the same phenyl ring, the ytterbium counterpart adopted a different structure, with the two ytterbium ions bound to different phenyl rings. Upon the addition of crown ether to encapsulate the potassium ions, the inverse-sandwich samarium biphenyl structure remained intact; however, the ytterbium biphenyl structure fell apart with the concomitant formation of a divalent ytterbium crown ether complex and potassium biphenylide. Spectroscopic and computational studies were performed to gain insight into the electronic structures and bonding interactions of these samarium and ytterbium biphenyl complexes. While the ytterbium ions were found to be divalent with a 4f14 electron configuration and form a primarily ionic bonding interaction with biphenyl dianion, the samarium ions were in the trivalent state with a 4f5 electron configuration and mainly utilized the 5d orbitals to form a δ-type bonding interaction with the π* orbitals of the biphenyl tetraanion, showing covalent character.

9.
Asian J Androl ; 21(5): 433-437, 2019.
Article in English | MEDLINE | ID: mdl-31134920

ABSTRACT

Prostate cancer is the most common malignancy in the reproductive system of older males. Androgen deprivation therapy (ADT) is an important treatment for prostate cancer patients. However, almost all prostate cancer patients unavoidably progress to the castration-resistant stage after ADT treatment. Recent studies have shown that tumor-associated immune cells play major roles in the initiation, progression, and metastasis of prostate cancer. Various phenotypes of tumor-associated immune cells have tumor-promoting or antitumor functions mediated by interacting with tumor cells. Here, we review the current knowledge of tumor-associated immune cells in prostate cancer.


Subject(s)
Lymphocytes, Tumor-Infiltrating/pathology , Prostatic Neoplasms/immunology , Disease Progression , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Macrophages/immunology , Macrophages/pathology , Male , Neutrophils/immunology , Neutrophils/pathology , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Prostatic Neoplasms, Castration-Resistant/immunology , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/therapy
10.
Sci Rep ; 9(1): 6280, 2019 04 18.
Article in English | MEDLINE | ID: mdl-31000754

ABSTRACT

In recent years, several studies have reported monocyte lymphocyte ratio (MLR) to predict prognosis in various tumors. Our study was performed to evaluate the association between preoperative MLR between prognostic variables in urothelial carcinoma patients. Systematic literature search was conducted in PubMed, Embase, Web of science. The correlation between preoperative MLR and overall survival (OS), cancer specific survival (CSS), disease free survival (DFS)/relapse free survival (RFS), progression free survival(PFS) was evaluated in urothelial carcinoma patients. Meanwhile, the association between MLR and clinicopathological characteristics was assessed. Finally, 12 comparative studies comprising a total of 6209 patients were included for pooled analysis. The hazard ratios (HRs), odds ratios (ORs)and 95% confidence intervals (CIs) were further analyzed as effect measures. The pooled results demonstrated that elevated preoperative MLR indicated unfavorable OS (HR = 1.29, 95%CI = 1.18-1.39, I2 = 33.6%), DFS/RFS (HR = 1.42, 95%CI = 1.30-1.55, I2 = 0.0%) and CSS (HR = 1.41, 95%CI = 1.29-1.52, I2 = 0.0%). Moreover, the pooled results also suggested that elevated preoperative MLR was correlated with high tumor stage (OR = 1.22, 95%CI = 1.07-1.37, I2 = 0.0%) in urothelial carcinoma patients. No significant association was found between preoperative MLR and PFS in upper urinary tract urothelial carcinoma (UUTUC) patients. Collectively, elevated preoperative MLR predicted poor prognosis in urothelial carcinoma and have the potential to be a feasible and cost-effective prognostic predictor for management of urothelial carcinoma.


Subject(s)
Carcinoma, Transitional Cell/blood , Lymphocytes/metabolism , Monocytes/metabolism , Urologic Neoplasms/blood , Biomarkers, Tumor/blood , Carcinoma, Transitional Cell/epidemiology , Carcinoma, Transitional Cell/pathology , Disease-Free Survival , Female , Humans , Male , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Prognosis , Proportional Hazards Models , Urologic Neoplasms/epidemiology , Urologic Neoplasms/pathology , Urothelium/pathology
11.
Transl Cancer Res ; 8(8): 2713-2724, 2019 Dec.
Article in English | MEDLINE | ID: mdl-35117029

ABSTRACT

BACKGROUND: Bladder cancer is one of the most frequent urologic tumours in the world. MicroRNA-200c (miR-200c) has been considered a regulator of tumour angiogenesis. Akt2/mTOR was considered a regulator of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α). However, the mechanism by which miR-200c regulates bladder cancer angiogenesis remains unknown. METHODS: Western blotting and qRT-PCR were used to detect the expression of protein and mRNA, respectively. Cell proliferation, migration and invasion were detected using MTT, wound-healing and transwell assays, respectively. A dual luciferase reporter assay was used to identify the binding site between miR-200c and Akt2. A tube formation assay was also applied to detect the angiogenesis ability. RESULTS: Significantly higher expression levels of HIF-1α and VEGF and lower levels of miR-200c were observed in three types of bladder cancer cell lines. Transfection with the miR-200c mimic markedly inhibited cell viability, angiogenesis, and the expression of VEGF and HIF-1α. Overexpression of miR-200c remarkably suppressed the expression of Akt2, and the binding site between them was identified. Knockdown of Akt2 remarkably decreased the expression of VEGF and HIF-1α by regulating mTOR. miR-200c influenced the expression of VEGF and HIF-1α through the Akt2/mTOR signalling pathway and further regulated angiogenesis in bladder cancer cells. CONCLUSIONS: We proved that miR-200c could suppress HIF-1α/VEGF expression in bladder cancer cells and inhibit angiogenesis, and these regulations were achieved by targeting Akt2/mTOR. This study may provide new insight into the prevention and treatment of bladder cancer.

12.
Am J Chin Med ; 46(6): 1357-1368, 2018.
Article in English | MEDLINE | ID: mdl-30149755

ABSTRACT

Bladder cancer has a high recurrence rate and requires adjuvant intravesical management after surgery. The use of traditional agents for bladder cancer therapy is constrained by their toxicity and limited efficacy. This emphasizes the need for the development of safer, more effective compounds such as instillation agents. Curcumin is the major component of turmeric, the powdered root of Curcuma longa, which is known for its anti-inflammatory, anti-oxidant and anticancer properties. First, a microarray profiling and qPCR analysis were conducted in the T24 and SV-HUC-1 cell lines. Then, we examined the potential tumorigenicity of miR-7641 in the T24 and SV-HUC-1 cell lines with or without curcumin. Western blot analysis showed that p16 is a target of miR-7641 in T24 cells. We found that, for the first time, curcumin directly downregulates a tumor-promoting microRNA (miRNA), miR-7641, in bladder cancer, which has tumor-promoting characteristics. Curcumin induces the downregulation of miR-7641 and subsequent upregulation of p16 which is a target of miR-7641 at the post-transcriptional level, which leads to the decreased invasion and increased apoptosis of bladder cancer cells. This is the first report to show a direct effect of curcumin on inducing changes in a miRNA suppressor with direct anticancer consequences in bladder cancer. Our study shows that curcumin may be a candidate agent for the clinical management of non-muscle-invasive bladder cancer.


Subject(s)
Curcumin/pharmacology , Cyclin-Dependent Kinase Inhibitor p16/genetics , Cyclin-Dependent Kinase Inhibitor p16/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Gene Expression , Humans , Up-Regulation
13.
Oncotarget ; 9(38): 25294-25303, 2018 May 18.
Article in English | MEDLINE | ID: mdl-29861872

ABSTRACT

BACKGROUND: Tumor associated macrophages (TAMs) have multifaceted roles in the development of many tumor types. However, the prognostic value of TAMs in bladder cancer is still not conclusive. EXPERIMENTAL DESIGN: This review evaluated the prognostic value of TAMs density in bladder cancer by reviewing published literatures and integrating the results via a meta-analysis. A systematic search was conducted in PubMed, Embase and Chinese National Knowledge Infrastructure (CNKI), WanFang, and Web of Science databases for relevant studies. Overall survival (OS), relapse free survival (RFS), disease specific survival (DSS), and progression free survival (PFS) were assessed in bladder cancer patients. RESULTS: The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) indicated that TAMs identified with CD68 alone have no significant correlation with OS (HR = 1.01, 95% CI = 1.00-1.02), RFS (HR = 0.99, 95% CI = 0.91-1.06), or PFS (HR = 1.19, 95% CI = 0.70-1.68) in bladder cancer patients. Subgroup analyses involved with Bacillus Calmette Guerin (BCG) treatment or sample locations either showed that CD68+ TAMs presented no prognostic value with regard to OS in bladder cancer patients. However, TAMs detected by CD163 are significantly correlated with poor RFS in bladder cancer patients (HR = 1.54, 95% CI = 1.16-1.92). CONCLUSIONS: Our data indicated that TAMs identified only with CD68 have no significant correlation with the prognosis and clinicopathological parameters of bladder cancer patients. However, TAMs detected with CD163 could serve as a prognostic marker for bladder cancer patients. These findings invite further research on the role of TAM subsets in bladder cancer patients.

14.
Fitoterapia ; 101: 188-93, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25596094

ABSTRACT

Four new Amaryllidaceae alkaloids, (+)-1-hydroxy-ungeremine (1), (+)-6ß-acetyl-8-hydroxy-9-methoxy-crinamine (2), (+)-2-hydroxy-8-demethyl-homolycorine-α-N-oxide (3), (+)-N-methoxylcarbonyl-2-demethyl-isocorydione (4), together with two known compounds, (+)-6ß-acetyl-crinamine (5) and 8-demethyl-homolycorine-α-N-oxide (6) were isolated from the ethanol extract of the bulbs of Lycoris radiata. Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D ((1)H-(1)H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. All the isolated alkaloids were in vitro evaluated for their cytotoxic activities against eight tumor cell lines (BEN-MEN-1, CCF-STTG1, CHG-5, SHG-44, U251, BGC-823, HepG2 and SK-OV-3) and anti-inflammatory activities against Cox-1 and Cox-2. As a result, alkaloids 1 and 4 exhibited significant cytotoxic activities against all tested tumor cell lines except against BEN-MEN-1. Additionally, alkaloids 1 and 4 possessed selective inhibition of Cox-2 comparable with the standard drug NS-398 (>90%).


Subject(s)
Amaryllidaceae Alkaloids/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Cyclooxygenase Inhibitors/chemistry , Indolizines/chemistry , Lycoris/chemistry , Cell Line, Tumor , Humans , Molecular Structure , Plant Roots/chemistry
15.
BMJ Open ; 3(12): e004152, 2013 Dec 13.
Article in English | MEDLINE | ID: mdl-24334199

ABSTRACT

OBJECTIVE: This study assessed the characteristics of pathogens identified in clinical isolates from patients with urinary tract infection (UTI) and their in vitro sensitivity to commonly used antibiotics in the clinical setting in China. DESIGN AND SETTING: Multicenter study was conducted between January and December 2011 in 12 hospitals in China. PARTICIPANTS: Urine samples were collected from 356 symptomatic patients treated in the study hospitals for acute uncomplicated cystitis, recurrent UTI or complicated UTI. PRIMARY AND SECONDARY OUTCOME MEASURES: Minimal inhibitory concentrations (MICs) were measured using broth microdilution according to the Clinical and Laboratory Standards Institute 2011 guidelines. Thirteen antimicrobial agents were tested: fosfomycin tromethamine, levofloxacin, moxifloxacin, cefdinir, cefixime, cefaclor, cefprozil, cefuroxime, amoxicillin/clavulanic acid, cefotaxime, azithromycin, nitrofurantoin and oxacillin. Escherichia coli isolates were screened and extended spectrum ß-lactamases (ESBL) production was confirmed by a double-disk synergy test. RESULTS: 198 urine samples were culture-positive and 175 isolates were included in the final analysis. E coli was detected in 50% of cultures, followed by Staphylococcus epidermidis (9%), Enterococcus faecalis (9%) and Klebsiella pneumoniae (5%). The detection rate of ESBL-producing E coli was 53%. Resistance to levofloxacin was the most common among all the isolates. Nitrofurantoin and fosfomycin tromethamine had the greatest activity against E coli; overall, 92% and 91% of isolates were susceptible to these antimicrobials. E faecalis had the highest susceptibility rates to fosfomycin tromethamine (100%). CONCLUSIONS: The most frequently identified pathogens in our patients were ESBL-producing E coli and E faecalis. Fosfomycin tromethamine and nitrofurantoin showed a good antimicrobial activity against UTI pathogens. They may represent good options for the empiric treatment of patients with UTI.

16.
BMJ Open ; 3(12): e004157, 2013 Dec 04.
Article in English | MEDLINE | ID: mdl-24309172

ABSTRACT

OBJECTIVE: To evaluate the clinical and microbiological efficacy and safety of three doses of 3 g fosfomycin tromethamine administered orally to treat lower urinary tract infections. DESIGN AND PARTICIPANTS: This prospective, uncontrolled, open-label study was conducted in 12 medical centres in China, between January and December 2011. According to the diagnosis criteria of Chinese Guidelines on Urological Infections, patients (18-70 years) with acute uncomplicated cystitis, recurrent lower urinary tract infection or complicated lower urinary tract infection received three doses of 3 g fosfomycin tromethamine orally, at days 1, 3 and 5. PRIMARY AND SECONDARY OUTCOME MEASURES: Efficacy endpoints (clinical efficacy, microbiological efficacy and overall efficacy) were evaluated on day 15. Clinical symptoms, physical signs, urinalysis, liver and kidney function, patient records and evaluation of adverse events (AEs) and serious AEs up to day 15 were evaluated for analysis of safety. RESULTS: 361 patients were included in the full analysis set, 356 in the safety analysis set and 335 in the per-protocol set (PPS). In the PPS, the clinical efficacy rates at day 15 for acute uncomplicated cystitis, recurrent lower urinary tract infection and complicated lower urinary tract infection were 94.71% (179/189), 77.22% (61/79) and 62.69% (42/67), respectively. The microbiological efficacy rates (day 15) were 97.65% (83/85), 94.44% (34/36) and 83.87% (26/31), respectively. The overall efficacy rates (day 15) were 95.29% (81/85), 77.78% (28/36) and 64.52% (20/31), respectively. 20/356 (5.6%) patients reported drug-related AEs, the most common being diarrhoea. No serious drug-related AEs were reported. CONCLUSIONS: This fosfomycin tromethamine dosing regimen showed clinical and microbiological efficacy with some AEs and good tolerability in patients with acute uncomplicated cystitis, recurrent lower urinary tract infection and complicated lower urinary tract infection.

17.
Onkologie ; 36(10): 592-6, 2013.
Article in English | MEDLINE | ID: mdl-24107915

ABSTRACT

Prostate cancer is one of the most common cancers in men. Various signaling pathways and proteins are involved in prostate carcinogenesis. Ubiquitination and deubiquitination of the related proteins contribute to the development of prostate cancer in various ways. The ubiquitin-proteasome (UPS) system is a common cellular process for protein degradation in eukaryotes. In this article we review recent advances related to the involvement of the UPS pathway in prostate cancer. The UPS pathway plays an important role in the regulation of cellular proteins with respect to cell cycle control, transcription, apoptosis, cell adhesion, angiogenesis, and tumor growth. It is involved in prostate cancer in various ways by modulating prostate cancer-related genes/proteins such as androgen receptor, cyclin-dependent kinase inhibitor P27, cyclin D1, and PTEN. Some ubiquitin-like modifier proteins have also been found to be associated with prostate cancer. The UPS pathway represents a potential therapeutic target for prostate cancer, and proteasome inhibitors represent a class of chemotherapeutic agents that inhibit tumor growth. The UPS pathway is related to prostate cancer in different ways. More research on that link is needed, as targeting the UPS pathway has led to some success in prostate cancer treatment.


Subject(s)
Models, Biological , Neoplasm Proteins/metabolism , Prostate/metabolism , Prostatic Neoplasms/metabolism , Proteasome Endopeptidase Complex/metabolism , Ubiquitin/metabolism , Animals , Humans , Male
18.
Iran Red Crescent Med J ; 15(4): 279-84, 2013 Apr.
Article in English | MEDLINE | ID: mdl-24082997

ABSTRACT

ABSTRACT: Prostate cancer is one of the life threatening disorders of male. Although, over the last two decades, a high rate of overdiagnosis, and overtreatment has lowered the incidence rate of prostate cancer, the treatment or prevention strategies are not enough to control the high rate of disease related mortality. Current medical treatment approaches include surgery, radiation therapy, chemotherapy, hormonal therapy, cryosurgery and other methods. These approaches are more or less effective either as monotherapy or in multimodal approach. However, many adverse or side effects exist with these strategies. Researches are ongoing to find out the way or better strategies to eliminate the adverse effects. Dietary modifications may also contribute to decrease prostate cancer risk. Several nutraceuticals against prostate cancer have also been identified. This review article summarizes some of the current treatment, and prevention strategies with the protection of prostate cancer, which may be helpful to control and prevent this highly frequent life threatening disease.

19.
Article in English | MEDLINE | ID: mdl-23762117

ABSTRACT

Cystitis glandularis (CG) is a proliferative disorder in the urinary bladder. The outcome of current treatments in some patients is not satisfactory. Curcumin, a herbal medicine that has been used for centuries, has shown great potential in treating various diseases. Our pilot study aimed to explore the feasibility of an intravesical treatment for CG using curcumin. 14 patients diagnosed with CG that remained symptomatic after primary treatments were enrolled, underwent a 3-month curcumin intravesical treatment (50 mg/50 mL, 1 hour, once per week for first 4 weeks and once per month for next 2 months) and were followed up for 3 months. Efficacy of the treatment was evaluated using core lower urinary tract symptom score (CLSS) questionnaire. 10 patients demonstrated persistent improvement in symptoms up to the end of the 6-month study. Their CLSS decreased significantly after the 3-month treatment (6.0 ± 0.8; P < 0.01) from the baseline (10.5 ± 1.6) and maintained decreasing till the end of the study (6.2 ± 0.7; P < 0.01). 4 patients were classified as nonresponders. Our study suggests the feasibility of further randomized controlled trials on curcumin intravesical treatment in CG patients who remain symptomatic after primary treatments.

20.
Asian Pac J Trop Med ; 6(7): 574-7, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23768832

ABSTRACT

OBJECTIVE: To study the expression of ALDH1 in colon cancer and its clinical significance. METHODS: The expression of ALDH1 was examined in 98 surgical specimens of primary colonic carcinoma and 15 normal colon tissues with immunohistochemistry method. The correlations of the expression with clinicopathological parameters and prognosis of colon cancer were analyzed. RESULTS: The positive rate of expression of ALDH1 was 76.5% (75/98) in the cancer tissues and 13.3% (2/15) in normal colon tissues. There were an obvious statistical difference (P<0.05) between the two groups. The ALDH1 expression was significantly correlated with the histological grade, TNM stages and lymph node metastasis in colon cancer (P<0.05). It was also related with patients' survival time, those with positive expressions had a poor prognosis (P<0.05). CONCLUSIONS: The results suggeste that the overexpression of ALDH1 plays important roles in proliferation and progression in colon cancer, the ALDH1 may be a valuable marker to predict the biological behavior and trend of metastasis of colon cancer.


Subject(s)
Colonic Neoplasms/enzymology , Isoenzymes/metabolism , Retinal Dehydrogenase/metabolism , Adult , Aldehyde Dehydrogenase 1 Family , Colonic Neoplasms/mortality , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Survival Rate
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