Design, Synthesis, Antifungal Evaluation, Structure-Activity Relationship (SAR) Study, and Molecular Docking of Novel Spirotryprostatin A Derivatives.

Phytopathogenic fungi cause plant diseases and economic losses in agriculture. To efficiently control plant pathogen infections, a total of 19 spirotryprostatin A derivatives and 26 spirooxindole derivatives were designed, synthesized, and tested for their antifungal activity against ten plant pathogens. Additionally, the intermediates of spirooxindole derivatives were investigated, including proposing a mechanism for diastereoselectivity and performing amplification experiments. The bioassay results demonstrated that spirotryprostatin A derivatives possess good and broad-spectrum antifungal activities. Compound 4d exhibited excellent antifungal activity in vitro, equal to or higher than the positive control ketoconazole, against Helminthosporium maydis, Trichothecium roseum, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium graminearum, Alternaria brassicae, Alternaria alternate, and Fusarium solan (MICs: 8-32 µg/mL). Compound 4k also displayed remarkable antifungal activity against eight other phytopathogenic fungi, including Fusarium oxysporium f. sp. niveum and Mycosphaerella melonis (MICs: 8-32 µg/mL). The preliminary structure-activity relationships (SARs) were further discussed. Moreover, molecular docking studies revealed that spirotryprostatin A derivatives anchored in the binding site of succinate dehydrogenase (SDH). Therefore, these compounds showed potential as natural compound-based chiral fungicides and hold promise as candidates for further enhancements in terms of structure and properties.

SPIKE1 Activates the GTPase ROP6 to Guide the Polarized Growth of Infection Threads in Lotus japonicus.

In legumes, rhizobia attach to root hair tips and secrete nodulation factor to activate rhizobial infection and nodule organogenesis. Endosymbiotic rhizobia enter nodule primordia via a specialized transcellular compartment known as the infection thread (IT). The IT elongates by polar tip growth, following the path of the migrating nucleus along and within the root hair cell. Rho-family ROP GTPases are known to regulate the polarized growth of cells, but their role in regulating polarized IT growth is poorly understood. Here, we show that LjSPK1, a DOCK family guanine nucleotide exchange factor (GEF), interacts with three type I ROP GTPases. Genetic analyses showed that these three ROP GTPases are involved in root hair development, but only LjROP6 is required for IT formation after rhizobia inoculation. Misdirected ITs formed in the root hairs of Ljspk1 and Ljrop6 mutants. We show that LjSPK1 functions as a GEF that activates LjROP6. LjROP6 enhanced the plasma membrane localization LjSPK1 in Nicotiana benthamiana leaf cells and Lotus japonicus root hairs, and LjSPK1 and LjROP6 interact at the plasma membrane. Taken together, these results shed light on how the LjROP6-LjSPK1 module mediates the polarized growth of ITs in L. japonicus.

The Triglyceride Glucose (TyG) Index as a Sensible Marker for Identifying Insulin Resistance and Predicting Diabetic Kidney Disease.

BACKGROUND Patients with insulin-resistant diabetes have the highest risk of kidney disease. The triglyceride glucose (TyG) index is considered a reliable and simple marker of insulin resistance. We studied the relationship between the TyG index, diabetic kidney disease (DKD), and related metabolic disorders in patients with type 2 diabetes. MATERIAL AND METHODS This retrospective study included a consecutive case series from January 2021 to October 2022 in the Department of Endocrinology at Hebei Yiling Hospital. In total, 673 patients with type 2 diabetes met the inclusion criteria. The TyG index was calculated by napierian logarithmic (ln) (fasting triglyceride×fasting glucose /2). Patient demographic and clinical indicators were obtained from medical records, and statistical analysis was conducted using SPSS version 23. RESULTS The TyG index was significantly related to metabolic indicators (low-density lipoprotein, high-density lipoprotein, alanine aminotransferase, plasma albumin, serum uric acid, triglyceride, and fasting glucose) and urine albumin (P<0.01) but not with serum creatinine and estimated glomerular filtration rate. In multiple regression analysis, an increase in the TyG index was revealed to be an independent risk factor for DKD (OR: 1.699, P<0.001). CONCLUSIONS The TyG index was independently related to DKD and related metabolic disorders; therefore, the TyG index can be used as an early sensitive target for clinical guidance in the treatment of DKD with insulin resistance.

Application of the Mannich reaction in the structural modification of natural products.

The Mannich reaction is commonly used to introduce N atoms into compound molecules and is thus widely applied in drug synthesis. The Mannich reaction accounts for a certain proportion of structural modifications of natural products. The introduction of Mannich bases can significantly improve the activity, hydrophilicity, and medicinal properties of compounds; therefore, the Mannich reaction is widely used for the structural modification of natural products. In this paper, the application of the Mannich reaction to the structural modification of natural products is reviewed, providing a method for the structural modification of natural products.

Quantitative proteomics reveals effects of environmental radiofrequency electromagnetic fields on embryonic neural stem cells.

The effects of environmental radiofrequency electromagnetic fields (RF-EMF) on embryonic neural stem cells have not been determined, particularly at the proteomic level. This study aims to elucidate the effects of environmental levels of RF-EMF radiation on embryonic neural stem cells. Neuroectodermal stem cells (NE-4C cells) were randomly divided into a sham group and an RF group, which were sham-exposed and continuously exposed to a 1950 MHz RF-EMF at 2 W/kg for 48 h. After exposure, cell proliferation was determined by a Cell Counting Kit-8 (CCK8) assay, the cell cycle distribution and apoptosis were measured by flow cytometry, protein abundance was detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and mRNA expression was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We did not detect differences in cell proliferation, cell cycle distribution, and apoptosis between the two groups. However, we detected differences in the abundance of 23 proteins between the two groups, and some of these differences were consistent with alterations in transcript levels determined by qRT-PCR (P < 0.05). A bioinformatics analysis indicated that the differentially regulated proteins were mainly enriched in 'localization' in the cellular process category; however, no significant pathway alterations in NE-4C cells were detected. We conclude that under the experimental conditions, low-level RF-EMF exposure was not neurotoxic but could induce minor changes in the abundance of some proteins involved in neurodevelopment or brain function.

Effects of pulsed electromagnetic fields on tumor cell viability: a meta-analysis of in vitro randomized controlled experiments.

Malignant tumor treatment remains a big challenge till now, and expanding literature indicated that pulsed electromagnetic fields (PEMF) is promising in tumor treatment with the advantage of safety and being economical, but it is still controversial on whether PEMF could affect the tumor cell viability. Therefore, we conducted the meta-analysis to evaluate effects of PEMF on tumor cell viability. The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies published up to February 2021. Studies on the direct effects of PEMF on tumor cell viability, determined using colorimetric analysis, were included. Two authors extracted the data and completed the quality assessment. A meta-analysis was performed to calculate the absorbance values and 95% confidence intervals (CIs) using random-effects models. Seven studies, including 32 randomized controlled experiments, were analyzed. Compared with the control group, tumor cell viability in the PEMF exposure group was obviously lower (SMD, -0.67; 95% CI: -1.12 to -0.22). The subgroup meta-analysis results showed that PEMF significantly reduced epithelial cancer cell viability (SMD, -0.58; 95% CI: -0.92 to -0.23) but had no influence on stromal tumor cell viability (SMD, -0.93; 95% CI: -0.21 to 0.15). Our study demonstrated that PEMF could inhibit tumor cell proliferation to some extent, but the risk of bias and high heterogeneity (I2 > 75%) weakened the strength of the conclusions drawn from the analysis.

[Analysis of chemical components in Cordyceps by online gradient extraction-HPLC].

Online gradient extraction-high performance liquid chromatography( HPLC) method was developed for simultaneous determination of high and low polar components in Cordyceps. The sample powder of Cordyceps was uniformly mixed with diatomaceous earth,packed into extraction tank,and installed into the HPLC system. Online gradient extraction was conducted with mobile phase at 70 ℃. The separation was performed on Zorbax SB-AQ( 4. 6 mm×150 mm,5 µm) column with 0. 1% formic acid solution-methanol as the mobile phase for gradient elution at 1. 0 mL·min~(-1). The column temperature was 30 ℃,and detection wavelength was set at 260 nm. The results showed that the high and low polar components in Cordyceps could be simultaneously extracted and separated by the developed method. Meanwhile,six high polar compounds( uracil,uridine,thymine,inosine,guanosine and adenosine) and one low polar compound( ergosterol) were identified by comparison with the reference peaks. The established method is rapid,stable and environment friendly,which is helpful to improve the quality evaluation level for Cordyceps.

Synthesis and Self-Assembly of Shape Amphiphiles Based on POSS-Dendron Conjugates.

Shape has been increasingly recognized as an important factor for self-assembly. In this paper, a series of shape amphiphiles have been built by linking polyhedral oligomeric silsesquioxane (POSS) and a dendron via linkers of different lengths. Three conjugates of octahedral silsesquioxanes (T8-POSS) and dendron are designed and synthesized and are referred to as isobutyl T8-POSS gallic acid derivatives (BPOSS-GAD-1, BPOSS-GAD-2, BPOSS-GAD-3). These samples have been fully characterized by ¹H-NMR, 13C-NMR, Fourier transform infrared (FT-IR) spectroscopy and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry to establish their chemical identity and purity. Driven by different interactions between POSS and dendron, ordered superstructure can be found upon self-assembly. The stabilities and structures of these samples are further studied by using differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), wide-angle X-ray diffraction (WAXD), and molecular simulations. The results show that their melting points range from 74 °C to 143 °C and the molecular packing schemes in the assemblies can form lamellar structure of BPOSS-GAD-3 as determined by the different linkers.

[Simultaneous determination of cordycepin and 2'-deoxyadenosine in Cordyceps genus by online SPE-HPLC].

An online SPE-HPLC method for simultaneous determination of cordycepin (3'-deoxyadenosine) and 2'-deoxyadenosine in Cordyceps genus (C. sinensis,C. militaris,Hirsutella sinensis and C. sobolifera) was developed. The samples were enriched on a ZORBAX SB-AQ (4.6 mm×12.5 mm,5 µm) column with isocratic elution by 9% methanol solution. The separation of analytes was performed on a ZORBAX SB-AQ (4.6 mm×150 mm,5 µm) column with gradient elution by 0.1% formic acid solution and methanol (91∶9). The flow rate was 1.0 mL•min⁻¹. Column temperature was 40 ℃ and detection wavelength was 260 nm. This method has been applied for analysis of different Cordyceps genus. The 2'-deoxyadenosine was detected in C. sinensis,Hirsutella sinensis and C. sobolifera. The cordycepin was detected in C. militaris. In summary,the cordycepin chromatographic peak from C. sinensis in some past reports may be the 2'-deoxyadenosine chromatographic peak or the mixture peak of 2'-deoxyadenosine and cordycepin in which 2'-deoxyadenosine content was higher than cordycepin. The developed method is suitable for analysis of cordycepin and 2'-deoxyadenosine in Cordyceps genus.

[Quantitative analysis of nucleosides in four Cordyceps genus by HPLC].

To compare the main nucleosides in Cordyceps genus herbs (C. sinensis, C. millitaris, Hirsutella sinensis and C. sobolifera), an HPLC method for simultaneous determination of uridine, inosine, guanosine, adenosine and cordycepine in Cordyceps genus herbs was developed. The sample was extracted with 0.5% phosphoric acid solution to prepare test solution. The separation was performed on a Zorbax SB-Aq (4.6 mm×150 mm, 5 µm) column with gradient elution by 0.04 mol•L⁻¹ potassium dihydrogen phosphate solution and acetonitrile, column temperature 30 ℃,flow rate 0.8 mL•min⁻¹,and detection wavelength 260 nm. The content of nucleosides in four Cordyceps genus herbs was evaluated by fingerprint analysis and hierarchical cluster analysis (HCA). The calibration curves of five nucleosides showed good linear regression (r>0.99) and the average recoveries were between 95.0% and 105.0%. The contents of the five nucleosides in the four Cordyceps genus herbs were different and could be obviously distinguished by HCA. The fingerprint analysis result showed that the similarity between C. sinensis and the others was less than 0.9. The method was accurate and reliable, which can be used for quality control of Cordyceps genus herbs.

Validation of the nonmotor symptoms questionnaire for Parkinson's disease: results from a Chinese pilot study.

We performed a cross-sectional study of 82 Chinese patients with Parkinson's disease (PD) enrolled during an 18-month period. We used a clinical interview to evaluate a Chinese version of the nonmotor symptoms questionnaire (NMSQuest) as an instrument for measuring the nonmotor symptoms (NMS) in Chinese patients with PD. The patients' cognitive deficit, depression/sleep, disease severity and motor status were assessed based on the mini-mental state examination (MMSE), the Hamilton depression scale (HAMD)/Parkinson's disease sleep scale (PDSS), the modified Hoehn and Yahr staging scale (H&Y) and the unified Parkinson's disease rating scale part III (UPDRS III), respectively. Thirty items distributed in nine different domains of the NMSQuest were evaluated, and the association between the NMSQuest and MMSE, H&Y, UPDRS, HAMD and PDSS was identified. Significant correlations were observed between the NMSQuest and disease duration (rs = 0.272, p = 0.013), UPDRS total score (rs = 0.444, p < 0.001), UPDRS II (rs = 0.415, p < 0.001) and UPDRS III (rs = 0.228, p = 0.039). Furthermore, the sleep disorder and mood (depression/anxiety) domain of the NMSQuest were significantly correlated with the PDSS (rs = -0.471, p < 0.001) and HAMD (rs = 0.687, p < 0.001), respectively. Our results indicate that the Chinese version of the NMSQuest, a useful screening tool, can be considered as a comprehensive, practical measure for NMS evaluation in Chinese PD patients. The NMSQuest highlights the prevalence of the wide range of NMS and indicated good responsiveness and interpretability. We strongly recommend routine use of the simplified Chinese version of NMSQuest in this country.

MAGEC2, an epithelial-mesenchymal transition inducer, is associated with breast cancer metastasis.

MAGEC2 is a member of melanoma antigen (MAGE) family of cancer-testis antigens and associated with tumor relapse and metastasis. Here, we investigated the expression of MAGEC2 in patients with breast cancer and its clinical effects with underlying mechanisms. The expression levels of MAGEC2 were compared between 420 invasive ductal carcinoma (IDC) and 120 ductal carcinoma in situ of the breast. Correlations between MAGEC2 expression and clinico-pathologic factors or survival of patients with IDC were analyzed. In addition, MAGEC2 expression levels in tumor tissues dissected from the primary focus and matched tumor-invaded axillary lymph nodes were analyzed in 8 breast cancer patients. The functional effects of MAGEC2 overexpression were assessed in vitro using scratch assay and transwell chamber assay. MAGEC2 expression was increased in metastatic breast cancer in comparison to the non-metastatic. MAGEC2 expression was significantly associated with ER negative expression (P = 0.037), high tumor grade (P = 0.014) and stage (P = 0.002), high incidence of axillary lymph node metastasis (P = 0.013), and distant metastasis (P = 0.004). Patients with tumor with MAGEC2 positive expression have a worse prognosis and a shorter metastasis free interval. Multivariate analyses showed that MAGEC2 expression was an independent risk factor for patient overall survival and metastasis-free survival. Breast cancer cells that overexpressed MAGEC2 had stronger migratory and invasive potential than control-treated cells. Epithelial markers (E-cadherin and cytokeratin) were down-regulated in MAGEC2-overexpressing cells compared to controls, whereas mesenchymal markers (vimentin and fibronectin) were upregulated. Our results indicate that MAGEC2 has a role in breast cancer metastasis through inducing epithelial-mesenchymal transition. In addition, MAGEC2 is a novel independent poor prognostic factor in patients with IDC. Thus, targeting MAGEC2 may provide a novel therapeutic strategy for breast cancer treatment.

Advances in CAR-NK cell therapy for lung cancer: is it a better choice in the future?

Lung cancer remains one of the leading causes of cancer-related mortality worldwide necessitating the development of innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents a promising advancement in the field of oncology offering a novel approach to target and eliminate tumor cells with high specificity and reduced risk of immune-related adverse effects. This paper reviews the mechanism, potential targets, and recent advances in CAR-NK cell therapy for lung cancer, including the design and engineering of CAR-NK cells, preclinical studies, and the outcomes of early-phase clinical trials. We highlight the unique advantages of using NK cells, such as their innate ability to recognize and kill cancer cells and their reduced potential for inducing graft-versus-host disease (GvHD) and cytokine release syndrome (CRS) compared to CAR T-cell therapies. Results from recent studies demonstrate significant antitumor activity in lung cancer models with improved targeting and persistence of CAR-NK cells observed in vitro and in vivo. Finally, we discuss the challenges in optimizing CAR-NK cell therapies, including the potential resistance mechanisms. The paper concludes with an outlook on the future directions of CAR-NK cell research and its implications for lung cancer treatment emphasizing the importance of continued innovation and collaboration in the field.

Atherogenic Index of Plasma as an Early Marker of Chronic Kidney Disease and Liver Injury in Type 2 Diabetes.

Background: Diabetic kidney disease (DKD) is the main cause of end-stage renal disease and has a high mortality rate. Currently, no effective treatments are available to reduce the progression of kidney damage associated with diabetes. Objectives: To explore the influence and predictive value of the atherogenic index of plasma (AIP) on early chronic kidney disease and liver injury in patients with type 2 diabetes mellitus (T2DM). Methods: Medical records of 1057 hospitalized adult patients with T2DM between January 2021 and December 2022 were collected. The predictive value of AIP, renal function, and liver injury in patients with T2DM were analyzed using Pearson's correlation, multiple logistic regression, and receiver operating characteristic (ROC) curve analyses. Results: AIP was a sensitive indicator of early liver and kidney injury in patients with T2DM. Patients in the DKD group showed increased AIP that positively correlated with serum creatinine, uric acid, and ß2-microglobulin levels. Increased AIP negatively correlated with estimated glomerular filtration rate (eGFR). AIP significantly correlated with alanine aminotransferase and aspartate aminotransferase levels and glutamyl transpeptidase-to-platelet ratio (GPR). An eGFR of 60-100 mL/min/1.73 m2 significantly increased the risk of DKD as the AIP increased. At lower GPR levels, the risk of DKD significantly increased with increasing AIP. However, no significant difference was found between the 2 groups when the GPR was >0.1407. The ROC curve analysis showed that AIP could predict early liver injury. Conclusions: AIP is directly involved in early liver and kidney injury in T2DM and may be a sensitive indicator for early detection.

Diabetes and its complications are a global public health concern. Diabetic kidney disease (DKD) is the main cause of end-stage renal disease, and metabolism-related disease factors are found throughout the progression of DKD. This study identified common sensitive indicators of early metabolism-related damage to liver and kidney function in patients with T2DM.

Defoaming and Toughening Effects of Highly Dispersed Graphene Oxide Modified by Amphoteric Polycarboxylate Superplasticizer on Oil Well Cement.

The aggregation of graphene oxide (GO) during the hydration process limits its wide application. Polymer superplasticizers have been used to improve the dispersion state of GO due to their adsorption and site-blocking effects, though the formation of a large amount of foam during the mixing process weakens the mechanical properties of cement. A highly dispersed amphoteric polycarboxylate superplasticizer-stabilized graphene oxide (APC/GO) toughening agent was prepared by electrostatic self-assembly. Results demonstrate that the APC/GO composite dispersed well in a cement pore solution due to the steric effect offered by the APC. Additionally, the well-dispersed GO acted as an antifoaming agent in the cement since GO nanosheets can be absorbed at the air-liquid interface of APC foam via electrostatic interactions and eliminate the air-entraining effect. The well-dispersed APC/GO sheets promoted cement hydration and further refined its pore structure owing to the nucleation effect. The flexural and compressive strength of the cement containing the APC/GO composite were enhanced by 21.51% and 18.58%, respectively, after a 7-day hydration process compared with a blank sample. The improved hydration degree, highly polymerized C-S-H gel, and refined pore structure provided enhanced mechanical properties.

Copper-Catalyzed Enantioselective Synthesis of Spirohydroindoles by Ethoxyformylmethylene Oxindole and Iminoester 1,3-Dipole Cycloaddition: An Examination of Associated Biological Activities.

A highly enantioselective 1,3-dipolar cycloaddition of ethoxyformylmethylene oxindole with iminoesters has been achieved using the Cu(I)-(S,Sp)-Ph Phosferrox catalytic system, generating a series of chiral spiro[pyrrolidin-3,3'-oxindole] compounds with four consecutive stereocenters, including a spirocycle quaternary center (71%-99% yield, up to >20:1 dr and 95:5 er). The compounds exhibited good inhibitory activity against Valsa mali (V.m.), Fusarium oxysporium (F.o.), and Alternaria brassicae (A.b.).

Papillary renal neoplasm with reverse polarity: an observational study of histology, immunophenotypes, and molecular variation.

Background: Papillary renal neoplasm with reverse polarity (PRNRP) is a novel entity with unique clinicopathological characteristics, and only a small number of patients with PRNRP have been described. Methods: We retrospectively analyzed the data for nine patients with PRNRP and evaluated differences in the clinical, histomorphological, immunohistochemical, and molecular features; prognosis; and differential diagnosis of PRNRP from other renal tumors with papillary structure. Results: There were six males and three females aged 36 to 74 years (mean: 62.33 years; median: 68 years). All the tumors were solitary and ranged from 1 to 3.7 cm (mean: 2.17 cm; median: 2 cm), with three and six tumors arose in the left and right renal tract, respectively. Pathologically, PRNRP is a small, well-circumscribed neoplasm with predominant papillary formations. The lining epithelium is composed of a monolayer of cuboidal to low-columnar cells with low-grade nuclei arranged against the apical pole of the tumor cells. Edema, mucinous degeneration, and hyaline degeneration are found in the fibrovascular cores. Foamy macrophages, psammoma bodies, hemosiderin deposition, and infiltrative tumor boundaries were present in some patients. Immunohistochemically, all tumors showed diffuse positive staining for GATA3. Sanger sequencing confirmed the presence of KRAS mutation in seven patients. All patients had a good prognosis after surgery and were relapse free. Positive staining for GATA3 and negative staining for vimentin were the most significant markers for differentiating PRNRP from other renal tumors with analogous structure. Conclusions: These findings suggested that PRNRP is a distinctive subtype of renal tumor with specific pathological features and indolent behaviors that should be distinguished from other renal tumors, especially papillary renal cell carcinoma. A monolayer of tumor cells with an inverted nuclear pattern, positive staining for GATA3, and KRAS mutation are essential for pathological diagnosis. Owing to its satisfactory prognosis, the surveillance and follow-up of patients with PRNRP should be additionally formulated.

Outcomes of endoscopic submucosal dissection versus esophagectomy for poorly differentiated superficial esophageal squamous cell carcinoma: A 10-year cohort study.

BACKGROUNDS: The efficacy of endoscopic submucosal dissection (ESD) to treat poorly differentiated superficial esophageal squamous cell carcinoma (SESCC) is unclear. AIMS: To exploring the efficacy and prognosis of ESD treatment poorly differentiated SESCC compared with esophagectomy. METHODS: A retrospective cohort study was conducted, the data of poorly differentiated SESCC patients who received ESD or esophagectomy from Jan 2011 to Jan 2021 were analyzed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and procedure-related variables were compared between ESD and esophagectomy group. RESULTS: 95 patients underwent ESD, while 86 underwent esophagectomy. No significant differences were found between the two groups in OS (P = 0.587), DSS (P = 0.172), and RFS (P = 0.111). Oncologic outcomes were also similar between the two groups in propensity score-matched analysis. For T1a ESCC, the rates of R0 resection, LVI or nodal metastasis and additional therapy were similar between ESD and esophagectomy groups. But for T1b ESCC, the rates of positive resection margin and additional therapy were significantly higher in ESD group than those in esophagectomy group. CONCLUSIONS: ESD is a minimally invasive procedure that has comparable oncologic outcomes with esophagectomy for treatment poorly differentiated T1a ESCC. However, ESD is not suitable for poorly differentiated T1b ESCC, additional surgery or radiochemotherapy should be required.

TCTP overexpression is associated with the development and progression of glioma.

Upregulation of translationally controlled tumor protein (TCTP) has been reported in a variety of malignant tumors. However, the impact of TCTP in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of TCTP in glioma patients. Western blot analysis was used to characterize the expression patterns of TCTP in 45 glioma and 22 normal brain tissues. Immunohistochemistry on a tissue microarray containing 127 cases of glioma was performed to analyze the association between TCTP expression and clinicopathological features. Compared with normal brain tissues, TCTP expression was significantly higher in glioma tissues (p <0.001). In addition, high TCTP expression in glioma was significantly associated with advanced pathological grade (p = 0.018). Kaplan-Meier analysis showed that patients with glioma and higher TCTP expression tend to have shorter overall survival time (p <0.001). In multivariate analysis, TCTP expression was proved to be an independent prognostic factor for patients with glioma (p <0.001). In conclusion, this study confirmed the overexpression of TCTP and its association with tumor progression in glioma. It also provided the first evidence that TCTP expression in glioma was an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of glioma.

A specific miRNA signature promotes radioresistance of human cervical cancer cells.

BACKGROUND: The mechanisms responsible for cervical cancer radioresistance are still largely unexplored. The present study aimed to identify miRNAs associated with radioresistance of cervical cancer cells. METHODS: The radioresistant cervical cancer cell variants were established by repeated selection with irradiation. The miRNA profiles of radioresistant cells and their corresponding controls were analyzed and compared using microarray. Differentially expressed miRNAs were confirmed by quantitative real-time PCR. Cervical cancer cells were transfected with miRNA-specific mimics or inhibitors. Radiosensitivity of cervical cancer cells were determined using colony-forming assay. RESULTS: Among the differentially expressed miRNAs, 20 miRNAs showed the similar pattern of alteration (14 miRNAs were overexpressed whilst 6 were suppressed) in all three radioresistant cervical cancer cell variants compared to their controls. A miRNA signature consisting of 4 miRNAs (miR-630, miR-1246, miR-1290 and miR-3138) exhibited more than 5 folds of increase in radioresistant cells. Subsequent analysis revealed that these four miRNAs could be up-regulated in cervical cancer cells by radiation treatment in both time-dependent and dose-dependent manners. Ectopic expression of each of these 4 miRNAs can dramatically increase the survival fraction of irradiated cervical cancer cells. Moreover, inhibition of miR-630, one miRNA of the specific signature, could reverse radioresistance of cervical cancer cells. CONCLUSIONS: The present study indicated that miRNA is involved in radioresistance of human cervical cancer cells and that a specific miRNA signature consisting of miR-630, miR-1246, miR-1290 and miR-3138 could promote radioresistance of cervical cancer cells.