Bone marrow mesenchymal stem cell-derived exosomal microRNAs target PI3K/Akt signaling pathway to promote the activation of fibroblasts.

BACKGROUND: Fibroblast plays a major role in tendon-bone healing. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) can activate fibroblasts and promote tendon-bone healing via the contained microRNAs (miRNAs). However, the underlying mechanism is not comprehensively understood. Herein, this study aimed to identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets, and to verify their effects as well as mechanisms on fibroblasts. AIM: To identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets and verify their effects as well as mechanisms on fibroblasts. METHODS: BMSC-derived exosomal miRNAs data (GSE71241, GSE153752, and GSE85341) were downloaded from the Gene Expression Omnibus (GEO) database. The candidate miRNAs were obtained by the intersection of three data sets. TargetScan was used to predict potential target genes for the candidate miRNAs. Functional and pathway analyses were conducted using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, by processing data with the Metascape. Highly interconnected genes in the protein-protein interaction (PPI) network were analyzed using Cytoscape software. Bromodeoxyuridine, wound healing assay, collagen contraction assay and the expression of COL I and α-smooth muscle actin positive were applied to investigate the cell proliferation, migration and collagen synthesis. Quantitative real-time reverse transcription polymerase chain reaction was applied to determine the cell fibroblastic, tenogenic, and chondrogenic potential. RESULTS: Bioinformatics analyses found two BMSC-derived exosomal miRNAs, has-miR-144-3p and has-miR-23b-3p, were overlapped in three GSE datasets. PPI network analysis and functional enrichment analyses in the GO and KEGG databases indicated that both miRNAs regulated the PI3K/Akt signaling pathway by targeting phosphatase and tensin homolog (PTEN). In vitro experiments confirmed that miR-144-3p and miR-23b-3p stimulated proliferation, migration and collagen synthesis of NIH3T3 fibroblasts. Interfering with PTEN affected the phosphorylation of Akt and thus activated fibroblasts. Inhibition of PTEN also promoted the fibroblastic, tenogenic, and chondrogenic potential of NIH3T3 fibroblasts. CONCLUSION: BMSC-derived exosomes promote fibroblast activation possibly through the PTEN and PI3K/Akt signaling pathways, which may serve as potential targets to further promote tendon-bone healing.

Identification and Verification of Potential Biomarkers in Gastric Cancer By Integrated Bioinformatic Analysis.

Background: Gastric cancer (GC) is a common cancer with high mortality. This study aimed to identify its differentially expressed genes (DEGs) using bioinformatics methods. Methods: DEGs were screened from four GEO (Gene Expression Omnibus) gene expression profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. A protein-protein interaction (PPI) network was constructed. Expression and prognosis were assessed. Meta-analysis was conducted to further validate prognosis. The receiver operating characteristic curve (ROC) was analyzed to identify diagnostic markers, and a nomogram was developed. Exploration of drugs and immune cell infiltration analysis were conducted. Results: Nine up-regulated and three down-regulated hub genes were identified, with close relations to gastric functions, extracellular activities, and structures. Overexpressed Collagen Type VIII Alpha 1 Chain (COL8A1), Collagen Type X Alpha 1 Chain (COL10A1), Collagen Triple Helix Repeat Containing 1 (CTHRC1), and Fibroblast Activation Protein (FAP) correlated with poor prognosis. The area under the curve (AUC) of ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (ADAMTS2), COL10A1, Collagen Type XI Alpha 1 Chain (COL11A1), and CTHRC1 was >0.9. A nomogram model based on CTHRC1 was developed. Infiltration of macrophages, neutrophils, and dendritic cells positively correlated with COL8A1, COL10A1, CTHRC1, and FAP. Meta-analysis confirmed poor prognosis of overexpressed CTHRC1. Conclusion: ADAMTS2, COL10A1, COL11A1, and CTHRC1 have diagnostic values in GC. COL8A1, COL10A1, CTHRC1, and FAP correlated with worse prognosis, showing prognostic and therapeutic values. The immune cell infiltration needs further investigations.

Roles of the Immune/Methylation/Autophagy Landscape on Single-Cell Genotypes and Stroke Risk in Breast Cancer Microenvironment.

This study sought to perform integrative analysis of the immune/methylation/autophagy landscape on breast cancer prognosis and single-cell genotypes. Breast Cancer Recurrence Risk Score (BCRRS) and Breast Cancer Prognostic Risk Score (BCPRS) were determined based on 6 prognostic IMAAGs obtained from the TCGA-BRCA cohort. BCRRS and BCPRS, respectively, were used to construct a risk prediction model of overall survival and progression-free survival. Predictive capacity of the model was evaluated using clinical data. Analysis showed that BCRRS is associated with a high risk of stroke. In addition, PPI and drug-ceRNA networks based on differences in BCPRS were constructed. Single cells were genotyped through integrated scRNA-seq of the TNBC samples based on clustering results of BCPRS-related genes. The findings of this study show the potential regulatory effects of IMAAGs on breast cancer tumor microenvironment. High AUCs of 0.856 and 0.842 were obtained for the OS and PFS prognostic models, respectively. scRNA-seq analysis showed high expression levels of adipocytes and adipose tissue macrophages (ATMs) in high BCPRS clusters. Moreover, analysis of ligand-receptor interactions and potential regulatory mechanisms were performed. The LINC00276&MALAT1/miR-206/FZD4-Wnt7b pathway was also identified which may be useful in future research on targets against breast cancer metastasis and recurrence. Neural network-based deep learning models using BCPRS-related genes showed that these genes can be used to map the tumor microenvironment. In summary, analysis of IMAAGs, BCPRS, and BCRRS provides information on the breast cancer microenvironment at both the macro- and microlevels and provides a basis for development of personalized treatment therapy.

A prediction modeling based on SNOT-22 score for endoscopic nasal septoplasty: a retrospective study.

BACKGROUND: To create a nomogram prediction model for the efficacy of endoscopic nasal septoplasty, and the likelihood of patient benefiting from the operation. METHODS: A retrospective analysis of 155 patients with nasal septum deviation (NSD) was performed to develop a predictive model for the efficacy of endoscopic nasal septoplasty. Quality of life (QoL) data was collected before and after surgery using Sinonasal Outcome Test-22 (SNOT-22) scores to evaluate the surgical outcome. An effective surgical outcome was defined as a SNOT-22 score change ≥ 9 points after surgery. Multivariate logistic regression analysis was then used to establish a predictive model for the NSD treatment. The predictive quality and clinical utility of the predictive model were assessed by C-index, calibration plots, and decision curve analysis. RESULTS: The identified risk factors for inclusion in the predictive model were included. The model had a good predictive power, with a AUC of 0.920 in the training group and a C index of 0.911 in the overall sample. Decision curve analysis revealed that the prediction model had a good clinical applicability. CONCLUSIONS: Our prediction model is efficient in predicting the efficacy of endoscopic surgery for NSD through evaluation of factors including: history of nasal surgery, preoperative SNOT-22 score, sinusitis, middle turbinate plasty, BMI, smoking, follow-up time, seasonal allergies, and advanced age. Therefore, it can be cost-effective for individualized preoperative assessment.

MiR-1908/EXO1 and MiR-203a/FOS, regulated by scd1, are associated with fracture risk and bone health in postmenopausal diabetic women.

BACKGROUND: Stearoyl-coenzyme A desaturase-1 (SCD1) can inhibit the development of diabetic bone disease by promoting osteogenesis. In this study, we examined whether this regulation by SCD1 is achieved by regulating the expression of related miRNAs. METHODS: SCD1 expression levels were observed in human bone-marrow mesenchymal stem cells (BM-MSCs) of patients with type 2 diabetes mellitus (T2DM), and the effect of SCD1 on osteogenesis was observed in human adipose-derived MSCs transfected with the SCD1 lentiviral system. We designed a bioinformatics prediction model to select important differentially expressed miRNAs, and established protein-protein interaction and miRNA-mRNA networks. miRNAs and mRNAs were extracted and their differential expression was detected. The SCD1-miRNA-mRNA network was validated. FINDINGS: SCD1 expression in bone marrow was downregulated in patients with T2DM and low-energy fracture, and SCD1 expression promotes BM-MSC osteogenic differentiation. The predictors in the nomogram were seven microRNAs, including hsa-miR-1908 and hsa-miR-203a. SCD1 inhibited the expression of CDKN1A and FOS, but promoted the expression of EXO1 and PLS1. miR-1908 was a regulator of EXO1 expression, and miR-203a was a regulator of FOS expression. INTERPRETATION: The regulation of BM-MSCs by SCD1 is a necessary condition for osteogenesis through the miR-203a/FOS and miR-1908/EXO1 regulatory pathways.

Predicting the risk of sarcopenia in elderly patients with patellar fracture: development and assessment of a new predictive nomogram.

PURPOSE: To develop a risk prediction model for postoperative sarcopenia in elderly patients with patellar fractures in China. PATIENTS AND METHODS: We conducted a community survey of patients aged ≥55 years who underwent surgery for patellar fractures between January 2013 and October 2018, through telephone interviews, community visits, and outpatient follow-up. We established a predictive model for assessing the risk of sarcopenia after patellar fractures. We developed the prediction model by combining multivariate logistic regression analysis with the least absolute shrinkage model and selection operator regression (lasso analysis) as well as the Support Vector Machine (SVM) algorithm. The predictive quality and clinical utility of the predictive model were determined using C-index, calibration plots, and decision curve analysis. We also conducted internal sampling methods for qualitative assessment. RESULT: We recruited 137 participants (53 male; mean age, 65.7 years). Various risk factors were assessed, and low body mass index and advanced age were identified as the most important risk factor (P < 0.05). The prediction rate of the model was good (C-index: 0.88; 95% CI [0.80552-0.95448]), with a satisfactory correction effect. The C index is 0.97 in the validation queue and 0.894 in the entire cohort. Decision curve analysis suggested good clinical practicability. CONCLUSION: Our prediction model shows promise as a cost-effective tool for predicting the risk of postoperative sarcopenia in elderly patients based on the following: advanced age, low body mass index, diabetes, less outdoor exercise, no postoperative rehabilitation, different surgical methods, diabetes, open fracture, and removal of internal fixation.

Harnessing a New Co-Host System and Low Concentration of New TADF Emitters Equipped with Trifluoromethyl- and Cyano-Substituted Benzene as Core for High-Efficiency Blue OLEDs.

A strategic approach combining a new co-host system and low concentration of new thermally activated delayed fluorescence (TADF) emitters to make efficient blue TADF organic light-emitting diode (OLED) was developed. The benchmark TADF molecule, 4CzIPN, was adopted as a probe to examine the feasibility of a co-host composing of a hole transporter SimCP and an electron transporter oCF3-T2T. As a result, a sky blue device with 1 wt % 4CzIPN doped in SimCP:oCF3-T2T co-host exhibited 100% energy transfer and achieved a high external quantum efficiency (EQE) up to 26.1%. Importantly, this device showed a limited efficiency rolloff with an EQE of 24% at 1000 cd m-2. To further shift the emission toward blue, three new TADF molecules, 4CzIPN-CF3, 3CzIPN-H-CF3, and 3CzIPN-CF3, modified either by lowering the electron-withdrawing ability of the acceptor group or by reducing the number of carbazole donors of 4CzIPN, have been synthesized and characterized. Among them, 4CzIPN-CF3 and 3CzIPN-H-CF3 display hypsochromic shift emissions compared to that of 4CzIPN. These new compounds were then explored for their potential applications as TADF emitters. Blue TADF OLEDs with 1 wt % of 4CzIPN-CF3 and 3CzIPN-H-CF3 dispersed in SimCP:oCF3-T2T co-host achieved EQEs of 23.1 and 16.5% and retained high EQEs of 20.9 and 14.7% at 1000 cd m-2, respectively.

High expression of Chitinase 3-like-1 is an unfavorable prognostic factor in urothelial carcinoma of upper urinary tract and urinary bladder.

BACKGROUND: Metabolic adaptation in cancer cells is important for cancer cell survival. Alternation in cellular metabolism getting more energy to support cell proliferation played a critical role in disease progression. We initially analyzed the public transcriptome of urothelial carcinoma in Gene Expression Omnibus database (GSE31684) with particular focus on genes associated with carbohydrate metabolism, and found that Chitinase 3-like-1 (CHI3L1) was a significantly up-regulated gene associated with advanced disease status. This study was aimed to evaluate the expression and prognostic significance of CHI3L1 in upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC). MATERIALS AND METHODS: We performed immunohistochemical study to evaluate CHI3L1 expression in 2 well-defined cohorts of urothelial carcinoma, including UTUC (n = 340) and UBUC (n = 295). CHI3L1 expression level was determined by H-score method. The associations between CHI3L1 expression and clinicopathological features, disease-specific survival (DSS) and metastasis-free survival (MFS) were analyzed. RESULTS: High expression of CHI3L1 was significantly associated with adverse clinicopathological features in UTUC or UBUC, including advanced tumor status (pT), nodal metastasis, high histological grade, vascular invasion, perineural invasion, and high mitotic activity (all P < 0.05). Kaplan-Meier survival analysis revealed that patients with high CHI3L1 expression had shorter DSS and MFS in both UTUC and UBUC (all P < 0.05). In multivariate survival analyses, high expression of CHI3L1 acted as an independent prognostic factor for worse DSS (P < 0.001 in UTUC and P = 0.036 in UBUC) and MFS (P = 0.002 in UTUC and P = 0.003 in UBUC) in both UTUC and UBUC groups. CONCLUSIONS: High expression of CHI3L1 was significantly associated with aggressive clinicopathological features and acted as an independent prognostic factor for worse outcome in urothelial carcinoma.

Hypothermia-Modulating Matrix Elasticity of Injured Brain Promoted Neural Lineage Specification of Mesenchymal Stem Cells.

Both chemical and physical microenvironments appear to be important for lineage specification of umbilical cord mesenchymal stem cells (UCMSCs). However, physical factors such as the elastic modulus in traumatic brain injury (TBI) are seldom studied. Intracranial hypertension and cerebral edema after TBI may change the brain's physical microenvironment, which inhibits neural lineage specification of transplanted UCMSCs. The purpose of this study is to investigate the potential regulatory effect of mild hypothermia on the elastic modulus of the injured brain. First, we found that more UCMSCs grown on gels mimicking the elastic modulus of the brain (0.5 kPa) differentiated into neural cells, which were verified with the formation of branched cells and the expression of neural markers. Then, UCMSCs were transplanted into TBI rats, and we observed that mild hypothermia resulted in the differentiation of more neurons and astrocytes from transplanted UCMSCs. To demonstrate that more neural specification of UCMSCs was due to the regulation of the elastic modulus, we monitored intracranial pressure and cerebral edema. The results showed that mild hypothermia significantly reduced intracranial pressure and brain water content, indicating modulation of the elastic modulus by mild hypothermia. An examination with atomic force microscopy (AFM) in a cell injury model in vitro further verified hypothermia-regulated elastic modulus. In this study, we found a novel role of mild hypothermia in modulating the elastic modulus of the injured brain, resulting in the promotion of neural lineage specification of UCMSCs, which suggested that the combination of mild hypothermia had more advantages in cell-based therapy after TBI.

[New progress in precision diagnosis of prostate cancer].

The morbidity of prostate cancer presents an obvious ascending tendency. Early diagnosis plays a crucial role in the diagnosis and treatment of prostate cancer. However, the methods widely used for its diagnosis mostly lack high specificity and sensitivity. This review introduces four methods for the detection of prostate cancer, which are PCA3 and TMPRSS2:ERG, the Kallikrein panel, MRGB, and the STHLM3 model, all based on molecular biology and superior to the traditional methods in both specificity and sensitivity. These methods are expected to contribute to the realization of precision diagnosis of prostate cancer.

Intraoperative retrograde ureteroscopy during laparoscopic ureteroureterostomy: Precise localization of the lesion.

In a case of upper ureteral stricture refractory to laser ureterotomy, laparoscopic ureteroureterostomy was performed for resection of the stricture and reanastomosis of the ureter. Precise localization of the stricture segment was achieved by retrograde ureteroscopy performed concurrently with laparoscopy, with minimal change in the patient's position.

[Effect of chemical microenvironment after traumatic brain injury on temperature-sensitive umbilical cord mesenchymal stem cells].

OBJECTIVE: To simulate the chemical microenvironment of injured brain tissue, and to explore the effect of this chemical microenvironment on temperature sensitive umbilical cord mesenchymal stem cells (tsUC). METHODS: Rat models of traumatic brain injury (TBI) were made by fluid percussion injury, and then the brain tissue extracts of the injured regions were acquired. Human umbilical cord mesenchymal stem cells (UC) were isolated and cultured, and the tsUC were obtained through the infection of temperature-sensitive Simian 40 Large T- antigen (ts-SV40LT) retrovirus. After that, both the two kinds of cells were cultured on the polyacrylamide gels which mimicking the elastic modulus of brain. Four groups were included: UC cultured under normal temperature (UC group), UC cultured added brain tissue extract under normal temperature (UC plus extract group), tsUC cultured under mild hypothermia (tsUC group), and tsUC added brain tissue extract under mild hypothermia for 3 days, then normal temperature for 4 days (tsUC plus extract group). After 24 hours, the apoptosis level was checked. Cell growth and morphological changes in each group were given dynamic observation. Seven days later, cell immunofluorescences were implemented for examining neural differentiation level. RESULTS: Compared with UC plus extract group, the apoptosis and proliferation in UC plus extract group were significantly reduced (P < 0.01) and increased (P < 0.01) respectively. Cell immunofluorescence showed that the both GFAP and Neuron positive cells were significantly enhanced in UC plus extract group than those in tsUC plus extract group. CONCLUSION: tsUC combining with mild hypothermia could significantly reverse injury induced cell apoptosis, improve cell proliferation and neural differentiation under chemical microenvironment after brain injury, which confirmed the adaptation and resistance of tsUC under mild hypothermia after TBI.

[TURP plus endocrine therapy (ET) versus α1A-blockers plus ET for bladder outlet obstruction in advanced prostate cancer].

OBJECTIVE: To compare the effect of transurethral resection of the prostate combined with endocrine therapy (TURP + ET) with that of αlA-blockers combined with ET ((αlA-b + ET) in the treatment of bladder outlet obstruction (BOO) in patients with advanced prostate cancer (PCa), and to investigate the safety of the TURP + ET for the treatment of PCa with BOO. METHODS: We retrospectively analyzed 63 cases of PCa with BOO, 28 treated by αlA-b + ET and the other 35 by TURP + ET. We obtained the residual urine volume (RV), maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and quality of life score (QoL) before and after treatment along with the overall survival rate of the patients, followed by comparison of the parameters between the two methods. RESULTS: At 3 months after treatment, RV, IPSS, and QoL in the TURP + ET group were significantly decreased from (137.8 ± 27.6) ml, (22.3 ± 3.6), and (4.2 ± 0.8) to (29 ± 13.6) ml, (7.8 ± 2.1), and (1.6 ± 0.5) respectively (P < 0.05), while Qmax increased from (5.6 ± 2.1) ml/s to (17.6 ± 2.7) ml/s (P < 0.05); the former three parameters in the αlA-b + ET group decreased from (133.6 ± 24.9) ml, (21.5 ± 3.2), and (4.7 ± 1.1) to (42 ± 18.3) ml, (12.8 ± 2.6), and (2.5 ± 0.7) respectively (P < 0.05), while the latter one increased from (6.3 ± 2.4) ml/s to (11.7 ± 2.3) ml/s (P < 0.05), all with statistically significant differences between the two groups (P < 0.05). The overall survival rate of the TURP + ET group was not significantly different from that of the αlA-b + ET group (51.4% vs 46.4% , P > 0.05). CONCLUSION: TURP + ET is preferable to αlA-b + ET for its advantage of relieving BOO symptoms in advanced PCa without affecting the overall survival rate of the patients.

PIN1 promoter polymorphism (-842 G>C) contributes to a decreased risk of cancer: Evidence from meta-analysis.

Peptidyl-prolylcis-trans isomerase NIMA-interacting 1 (encoded by the PIN1 gene) regulates the conformation of proline-directed phosphorylation sites and is important in the etiology of cancer. Since the identification of a functional polymorphism of PIN1, (-842 G>C; rs2233678), in the PIN1 promoter region, numerous studies have evaluated the association between the PIN1 promoter polymorphism (-842 G>C) and cancer risk. However, the available results are inconclusive. To derive a more precise estimation, a meta-analysis of seven previous case-control studies was performed, which included 4,524 cases exhibiting different tumor types and 4,561 control subjects. The published literature was retrieved from PubMed and EMBASE. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Overall, the results of the present study demonstrated that individuals carrying the variant C allele (G/C and C/C) were associated with a significantly decreased cancer risk (OR, 0.75; 95% CI, 0.62-0.90 for GC vs. GG; OR, 0.75; 95% CI, 0.64-0.88 for GC/CC vs. GG). In further stratified analyses, a decreased cancer risk was observed in the following subgroups: Breast and lung cancer patients, Asian individuals, and in studies with a sample size >500. The results indicated that the PIN1 promoter polymorphism (-842 G>C; rs2233678) contributes to a decreased risk of cancer via attenuating the transcriptional activity.

Isolation and characteristics of lactic acid bacteria isolated from ripe mulberries in Taiwan

The objective of this study was to isolate, characterize, and identify lactic acid bacteria (LAB) from ripe mulberries collected in Taiwan. Ripe mulberry samples were collected at five mulberry farms, located in different counties of Taiwan. Eighty-eight acid-producing cultures were isolated from these samples, and isolates were divided into classes first by phenotype, then into groups by restriction fragment length polymorphism (RFLP) analysis and sequencing of 16S ribosomal DNA (rDNA). Phenotypic and biochemical characteristics led to identification of four bacterial groups (A to D). Weissella cibaria was the most abundant type of LAB distributed in four mulberry farms, and Lactobacillus plantarum was the most abundant LAB found in the remaining farm. Ten W. cibaria and one Lactococcus lactis subsp. lactis isolate produced bacteriocins against the indicator strain Lactobacillus sakei JCM 1157T. These results suggest that various LAB are distributed in ripe mulberries and W. cibaria was the most abundant LAB found in this study.

[Clinical characteristics of acute scrotum: analysis of 316 cases].

OBJECTIVE: To investigate the differential diagnosis and treatment of acute scrotum. METHODS: We retrospectively analyzed the clinical characteristics of 316 cases of acute scrotum and reviewed the related literature. RESULTS: Among the total number, there were 117 cases of acute epididymitis (37.0%), 76 acute orchitis (24.1%), 39 acute periorchitis (12.3%), 23 acute scrotal infection (7.3%), 21 testicular trauma (6.6%), 17 idiopathic scrotal edema (5.4%), 16 testicular torsion (5.1%), and 7 scrotal gangrene (2.2%). Eighty-one of them underwent surgery and 235 received conservative treatment, of whom 1 with scrotal gangrene died of toxic shock for refusing surgical drainage. Those with testicular torsion all showed positive results in Prehn's test and responded well to surgery. CONCLUSION: Acute scrotum is detrimental to male health, for which early diagnosis and prompt treatment are essential.

Unique proteomic features induced by a potential antiglioma agent, Nordy (dl-nordihydroguaiaretic acid), in glioma cells.

Nordy is a chirally synthesized compound of a natural lipoxygenase inhibitor nordihydroguaiaretic acid. In this study, we found that Nordy inhibited the growth of human glioma cell lines in vitro and their tumorigenicity in mice. In addition, Nordy promoted differentiation of highly malignant human glioma cells. Investigation into the mechanistic basis of Nordy activities revealed that it altered the pattern of protein expression profiles in tumor cells. By using 2-DE, we found that in human glioma cell lines, at least six proteins were down-regulated after Nordy treatment, while four proteins were elevated in the same cells. Among the six down-regulated proteins, microsequencing with MALDI TOF MS confirmed the identity of five: proliferation-associated gene A (PAG-A), alternative splicing factor-3 (ASF-3), beta-galactoside binding lectin, eukaryotic translation initiation factor 5A (eIF-5A), and coffilin-1 (nonmuscle). Four up-regulated proteins were GST-pi, glyceraldehyde-3-phosphate dehydrogenase, alpha-enolase, and cyclophilin. All these proteins have been reported to participate in key cellular functions including proliferation, metabolism, differentiation, apoptosis, and gene transcription. Our results suggest that Nordy may constitute a promising drug lead for the development of novel antitumor agents targeting proteins that control tumor cell function at multiple levels.

Expression of glutathione S-transferase placental mRNA in hepatic preneoplastic lesions in rats.

AIM:To detect glutathione S-transferase placental (GST-P) mRNA expression in hepatic preneoplastic lesions in rats.METHODS: Using Solit-Farber model, the GST-P mRNA expression was observed in hepatic preneoplastic lesions induced by diethylnitrosamine (DEN) in rats and normal and regenerated hepatic tissues in the control group by in situ hybridization.RESULTS: GST-P mRNA was mainly expressed in altered hepatic foci (AHF) and some of the oval cells in hepatic preneoplastic lesions and the extent of its expression was different among various foci or/and positive cells in the same focus whereas no expression was observed in normal and regenerated hepatic tissues.CONCLUSION: Cells in AHF and oval cells may be the preneoplastic cells in the experimental hepatocellular carcinoma at the molecular level and heterogeneity exists in GST-P transcription levels.