Bronchial embolisation for infected pulmonary artery pseudoaneurysms causing haemoptysis.

AIM: To report the authors' experience of bronchial artery embolisation (BAE) in a series of patients to control haemoptysis associated with infected pulmonary artery pseudoaneurysms (PAPs). MATERIALS AND METHODS: All patients who underwent BAE based on computed tomography angiography (CTA) findings indicative of haemoptysis between February 2019 and September 2022 at Xiangyang Central Hospital were identified. Charts of patients with haemoptysis and infectious PAPs were reviewed retrospectively. Data were collected data on age, sex, underlying pathology, source pulmonary artery of the PAP, association with cavitary lesions or consolidation, systemic angiography findings, technical and clinical success, and follow-up. RESULTS: Seventeen PAPs were treated in 16 patients, with a mean age of 60.3 years (range: 37-82 years). The most common underlying cause was tuberculosis (15/16, 93.8%). Imaging by CTA did not identify the source pulmonary artery for 15 (88.2%) PAPs; all were associated with cavitary lesions or consolidation. All PAPs were visualised on systemic angiography. The technical and clinical success rates were both 87.5%. Two patients who experienced a recurrence of haemoptysis during follow-up underwent repeat CTA, which confirmed the elimination of the previous PAP. CONCLUSION: BAE may be a valuable technique to control haemoptysis associated with infectious PAPs that are visualised on systemic angiography. A possible contributing factor is PAPs arising from very small pulmonary arteries.

Clinical effectiveness of fluorouracil and cisplatin intraperitoneal perfusion combined with intravenous chemotherapy for peritoneal metastasis in gastric cancer.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies worldwide, often accompanied by peritoneal metastasis. This work aimed to investigate the clinical efficacy of intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy for the treatment of peritoneal metastasis in GC. PATIENTS AND METHODS: A total of 286 patients with primary GC admitted to the hospital from March 2017 to December 2020 were recruited in the study. A 1:1 matched case-control study was conducted, with the normal control (NC) group and experimental (E) group being composed of patients who underwent the corresponding treatment for primary GC with surgery within 2 months and the same pathological tumor-node-metastasis (pTNM) stage. The NC group consisted of 143 patients receiving only intravenous chemotherapy, while the E group consisted of 143 patients receiving intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy. Baseline characteristics, clinical efficacy, complications, peritoneal recurrence and metastasis, disease-free survival (DFS), and overall survival (OS) of the patients, as well as their quality of life (QoL) after chemotherapy, were compared between groups. RESULTS: After six cycles of chemotherapy, DFS was observed in both groups (70% vs. 59%; 48% vs. 29.7%; p<0.05), so did OS (85.7% vs. 85.4%; 73.1% vs. 69.3%; p>0.05). The total effective rate of treatment in the E group (46.15%) was drastically superior to that in the NC group (27.97%), and the total recurrence and metastasis rate of the E group (23.08%) was markedly inferior to that of the NC group (83.9%) (p<0.05). The total incidence of adverse reactions in the E group (11.89%) was considerably inferior to that in the NC group (35.66%) (p<0.05). In addition, the E group had markedly superior scores for physical function (PF), emotional function (EF), role function (RF), social function (SF), and cognitive function (CF) than the NC group (p<0.05). CONCLUSIONS: Intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy for the treatment of peritoneal metastasis in GC had certain benefits for patients and is worth applying in clinical practice.

Efficacy of Traditional Chinese Herbs combined with bioelectrical stimulation on patients with kidney deficiency and blood stasis type thin endometrium: a retrospective observational study.

OBJECTIVE: This study aimed to investigate the efficacy of Traditional Chinese Herbs (TCH) combined with bioelectrical stimulation (BES) on patients with kidney deficiency and blood stasis type thin endometrium. PATIENTS AND METHODS: A retrospective observational study was conducted on 83 patients diagnosed with thin endometrium, treated in our hospital from August 2019 to August 2021. The clinical data of the patients were reviewed, and 60 eligible patients were categorized into two groups based on the treatment they received: the TCH-BES group (n=30, patients received Femoston, TCH and BES treatment) and the control group (n=30, patients received Femoston only). The endometrial thickness (EMT), uterine artery resistance index (RI) and pulsatility index (PI), serum reproductive hormone levels, traditional Chinese medicine (TCM) syndrome scores, and clinical pregnancy outcomes between the two groups were compared. Continuous data were described as mean ± standard deviation (X- ± S). Student's t-test was used for comparison between the two groups and paired-sample t-test was used for comparison within the same group before and after the treatment. RESULTS: A total of 60 patients with thin endometrium, aged 20-35 years (average, 31.67±3.19 years), were included in this study. After the treatment, the EMT, E2 and progesterone (P) levels of the TCH-BES group were higher than that of the control group (p<0.001, p<0.05 and p<0.001, respectively), the PI, RI level and TCM syndrome scores of the TCH-BES group were lower than those of the control group (p<0.001). The clinical efficacy and pregnancy rate in the TCH-BES group were significantly higher than those in the control group (p<0.05). CONCLUSIONS: TCH combined with EBS has a satisfactory efficacy on patients with kidney deficiency and blood stasis type thin endometrium, and improves EMT, E2 and P levels, reduces PI, RI and TCM syndrome, and eventually leads to a favorable clinical pregnancy outcome.

Modular characteristics and mechanism of action of herbs for vascular calcification treatment in Chinese medicine: a data mining and network pharmacology-based identification.

OBJECTIVE: The aim of this study was to investigate the modular characteristics and mechanism of action of Chinese herbs for vascular calcification (VC) treatment. MATERIALS AND METHODS: Network pharmacology coupled with literature data mining was utilized to assess the Chinese herbal clinical performance as well as its similarity, characteristics, ingredient, target, and Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and network construction. RESULTS: The top 15 medications from the literature, according to the usage, and 190 active chemicals, 183 common targets between medication and VC-related targets were weeded out. Analysis of the relationships between the active ingredients, pharmacological targets, and signaling pathways helped to clearly define the therapeutic effect of Traditional Chinese Medicine (TCM). Importantly, we discovered seven most hub proteins (AKT1, CTNNB1, TNF, EGFR, TP53, JUN and IL-6) and two of the herbs' most fundamental ingredients (Formononetin and Luteolin) in TCM-mediated VC suppression. Mechanistically, the metabolic pathways [AGE-RAGE pathway, interleukin-17 (IL-17) pathway, and p53 pathway] as well as smooth muscle adaptation (functional remodeling) and oxidoreductase activity (redox homeostasis modulating) are also crucially implicated. CONCLUSIONS: Our work, accomplished by network pharmacology and data mining, increases our understanding of TCM in VC therapy and may offer insightful information for future drug discovery investigations.

Circular circ_0000885 promotes hepatocellular carcinoma proliferation by epigenetically upregulating Caprin1.

OBJECTIVE: Recently, the vital role of circular RNAs is discovered in many diseases, including tumor progression. Hepatocellular carcinoma (HCC) is one of the most ordinary malignant tumors. The purpose of our study is to detect the potential function of circ_0000885 in HCC to offer new biomarkers and targets. PATIENTS AND METHODS: The expression level of circ_0000885 in HCC tissues and cell lines was monitored by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Pearson's Chi-square test was used to determine the association of circ_0000885 expression with several clinicopathological factors. Then knockdown of circ_0000885 was constructed to uncover its function in HCC. The cell growth ability was measured through the cell counting kit-8 (CCK-8) assay, colony formation assay, and cell cycle assay. The Western blot assay was performed to analyze the protein level of Caprin1. RESULTS: Circ_0000885 was highly expressed in HCC tissues than that in adjacent samples. The miR-532-5p expression was associated with lymphatic metastasis and TNM stage. The expression of circ_0000885 was also higher in HCC cell lines. The cell growth ability of HCC cells was inhibited after circ_0000885 was silenced. Furthermore, Caprin1 was inhibited via knockdown of circ_0000885. CONCLUSIONS: Circ_0000885 could enhance cell proliferation and regulate cell cycle of HCC by promoting Caprin1.

Complement activation in patients with diabetic nephropathy.

AIM: Emerging evidence has indicated a role of the complement system in the pathogenesis of diabetic nephropathy (DN), although the pathways of complement activation and their clinicopathological relevance in DN are as yet unclear. The present study aimed to investigate levels of various complement components in plasma and urine of DN patients, and their correlation with clinicopathological parameters. METHODS: A total of 68 biopsy-proven DN patients with plasma samples were recruited, including 50 patients who also had urine samples available. Seven complement components (C1q, MBL, Bb, C4d, C3a, C5a, soluble C5b-9) were measured by enzyme-linked immunosorbent assay (Elisa), and any associations between their levels and clinicopathological parameters were then investigated. RESULTS: In DN patients, plasma levels of C1q, MBL, Bb, C4d, C3a, C5a and sC5b-9 were significantly higher than in diabetes patients without renal involvement, as were also urinary levels except for C1q, which showed no significant differences between the two groups. Also, urinary levels of C3a and C5a were significantly correlated with serum creatinine, urinary protein and estimated glomerular filtration rate, whereas urinary sC5b-9 was significantly correlated with the latter two (and not serum creatinine). In addition, urinary levels of MBL, Bb and C4d were significantly correlated with urinary protein, while C3a, C4d and Bb significantly correlated with the classification of glomerular lesions in DN. CONCLUSION: In DN patients, the complement system is activated and, of the three possible complement pathways, activation of the lectin and alternative pathways is associated with renal damage.

Complement deposition on renal histopathology of patients with diabetic nephropathy.

AIMS: As the potential role of the complement system in diabetic nephropathy (DN) is increasingly reported, this study aimed to investigate C1q and C3c deposition as seen on renal histopathology, as well as its association with clinical and pathological parameters, in DN patients. METHODS: Renal biopsy specimens from 161 DN patients were investigated using direct immunofluorescence, light, and electron microscopy. For direct immunofluorescence, staining for C1q and C3c on fresh-frozen renal tissue was performed immediately after biopsy. Complement deposition was defined as the presence of C1q or C3c of at least 1 + on a 0-4 + Scale. The association between complement deposition and clinicopathological data was also analyzed. RESULTS: On direct immunofluorescence microscopy, C1q and C3c were detected in specimens from 44/161 (27.3%) and 89/161 (55.3%) patients, respectively. Regarding clinical data, patients with C1q deposition had a significantly higher level of urinary protein (7.25 ± 4.20 g/24 h vs. 4.97 ± 3.76 g/24 h; P < 0.01) and significantly lower estimated glomerular filtration rate (eGFR; 34.16 ± 25.21 mL/min/1.73 m2 vs. 51.17 ± 31.56 mL/min/1.73 m2, respectively; P < 0.01), whereas patients with vs. without C3c deposition had a significantly lower eGFR (40.09 ± 27.97 mL/min/1.73 m2 vs. 54.48 ± 32.49 mL/min/1.73 m2, respectively; P < 0.01). On renal histopathology, patients with C1q deposition had significantly higher Scores for interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation and vascular lesions (P < 0.01, P < 0.05 and P < 0.05, respectively), whereas patients with C3c deposition had significantly higher IFTA Scores and proportions of global sclerosis (P < 0.01 and P < 0.01, respectively). CONCLUSION: Complement deposition of C1q and C3c on renal histopathology is associated with more severe kidney damage in patients with DN.

MiR-940 inhibits the progression of NSCLC by targeting FAM83F.

OBJECTIVE: We investigate whether miR-940 could target family sequence similarity 83 member F (FAM83F) and further inhibit the progression of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: The expression levels of miR-940 and FAM83F in tumor tissues and paracancerous tissues of 72 NSCLC patients were detected through quantitative real time-polymerase chain reaction (qRT-PCR). The relationship between their expression levels, tumor size, and prognosis of NSCLC was analyzed. Transfection plasmids were constructed to knockdown or overexpress miR-940 in H1299 cells (inhibitor group) and SK-MES-1 cells (mimic group). The viability of H1299 cells and SK-MES-1 cells was evaluated using cell counting kit-8 (CCK-8) assay after transfection. The combination of miR-940 and Ago2 was confirmed by RNA immunoprecipitation (RIP) experiment. The binding condition of miR-940 in FAM83F-WT and FAM83F-MUT groups was verified by luciferase reporter gene assay. RESULTS: MiR-940 expression was noticeably decreased, while FAM83F expression was distinctly upregulated in NSCLC tissues than that of paracancerous tissues. The overall survival rate of NSCLC patients with highly-expressed miR-940 was significantly higher than those with lowly-expressed miR-940. Besides, miR-940 level was negatively correlated with tumor stage and size of NSCLC patients. Knockdown of miR-940 evidently enhanced the activity of H1299 cells, while overexpression of miR-940 decreased the viability of SK-MES-1 cells. In addition, miR-940 was confirmed to combine with FAM83F. Luciferase activity of cells co-transfected with FAM83F-WT and miR-940 mimic was significantly decreased. CONCLUSIONS: MiR-940 inhibited the proliferation of cancer cells by targeting FAM83F and further restrained the progression of NSCLC.

Gemcitabine and cisplatin for treatment of lung cancer in vitro and vivo.

OBJECTIVE: To evaluate the antitumor activity of gemcitabine (GEM), cisplatin (DDP) as well as the combination of these two agents in lung cancer cells and mice. MATERIALS AND METHODS: The cell viability was evaluated by the CCK-8 assay. Cell apoptosis was measured by flow cytometry assay and Hoechst staining. The protein expression of VEGF, VEGFR2, Ang II, AT1R, and ACE2 was examined by Western blotting. The effect of GEM and DDP on tumor growth and survival time was also measured in lung cancer mice in vivo. RESULTS: The results revealed that alone or combined administration of GEM and DDP could inhibit the growth, induce apoptosis and apoptotic body formation of A549 cells compared with control cells, with the most significance detected in a combination of GEM and DDP administration. It is indicated that combined administration of GEM and DDP could delay the progress of tumor formation in nude mice. The cell apoptosis- and angiogenesis-related proteins expressions were decreased both in A549 cells and lung cancer mice. CONCLUSIONS: GEM plus DDP can be an option for patients with lung cancer treatment. However, further prospective evaluation and randomized trials are to provide more accurate information through clinical trials.

Long non-coding RNA HULC promotes proliferation and osteogenic differentiation of bone mesenchymal stem cells via down-regulation of miR-195.

OBJECTIVE: LncRNAs HULC has been reported to be important regulators in the development of various human diseases. However, the role of HULC in bone mesenchymal stem cells (BMSCs) remains unclear. The present study aimed to explore the regulatory effect of HULC on proliferation and osteogenic differentiation of BMSCs and the underlying mechanism. MATERIALS AND METHODS: The expression of HULC and miR-195 in BMSCs were altered by transfection and measured by qRT-PCR. Cell viability was measured by the CCK-8 assay. Osteogenic differentiation of BMSCs was determined by evaluation of osteogenic markers (Ocn, ALP, Runx2, and Col-1) expression levels using Western blot and qRT-PCR. Furthermore, Western blot was performed to assess the expression of proliferation-related factors, Wnt/ß-catenin and p38MAPK pathway-related factors. RESULTS: HULC overexpression significantly increased cell viability, down-regulated p21 expression but up-regulated CyclinD1 expression, and promoted the levels of osteogenic markers. However, the complete opposite effect was observed in HULC knockdown. Notably, miR-195 expression was negatively regulated by HULC and miR-195 exerted a reversed effect of HULC on BMSCs. Moreover, miR-195 mediated the regulatory effect of HULC on BMSCs proliferation and osteogenic differentiation, as miR-195 mimic abolished the effect of HULC overexpression on BMSCs. We also found that HULC overexpression enhanced the activation of Wnt/ß-catenin and p38MAPK pathway through down-regulating miR-195. CONCLUSIONS: We revealed that HULC promoted proliferation and osteogenic differentiation of BMSCs. The potential mechanism might be involved in its negative regulation on miR-195 and enhanced activation of Wnt/ß-catenin and p38MAPK pathway.

The dynamic metabolomic changes throughout mouse epididymal lumen fluid potentially contribute to sperm maturation.

Epididymal lumen fluids are directly responsible for sperm maturation. However, very little is known about the molecular details of small molecule metabolites in the epididymal lumen fluids until now. Here we identified and compared the metabolic profiles of mouse caput and cauda epididymal lumen fluids using GC-MS technique. Among 236 metabolites identified in caput and cauda epididymis, 36 were significantly enriched in caput epididymis while 18 were significantly enriched in cauda epididymis. Pathway analysis identified ascorbate and aldarate metabolism and beta-alanine metabolism as most relevant pathways in caput and cauda epididymis, respectively. Ascorbate, dehydroascorbic acid and beta-alanine associated with these two pathways were firstly reported in mouse epididymal lumen fluids and might play important roles in sperm maturation.

Determination of phloroglucinol by HPLC-MS/MS and its application to a bioequivalence study in healthy volunteers.

OBJECTIVE: The aim of this study was to compare the pharmacokinetic characteristics of phloroglucinol between an orally disintegrating tablet and an orally lyophilized tablet of phloroglucinol in healthy volunteers under fasting condition. PATIENTS AND METHODS: A rapid and simple method based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the determination of phloroglucinol in human plasma. The plasma sample was prepared by liquid-liquid extraction, and paracetamol was chosen as the internal standard. Phloroglucinol and IS were separated on a C18 column with a mobile phase consisted of methanol/water (80:20 v/v) with 0.02% formic acid. HPLC-MS/MS analyses were performed on a triple- quadruple tandem mass spectrometer by monitoring protonated parent→daughter ion pairs at m/z 125.0→56.9 for phloroglucinol, and m/z 150.2→107.0 for paracetamol (IS). The method was the high sensitivity with a lower limit of quantification (LLOQ) of 1.976 ng/mL. RESULTS: Drug and IS were detected by HPLC/MS/MS with negative electrospray ionization (ESI). Accuracy and precision for the assay were determined by calculating the intra- and inter-batch variation of quality control (QC) samples at three concentration levels. The relative standard deviation (RSD) was less than 15.0%. The detection and quantitation of drug and IS within 4.5 min make this method suitable for high-throughput analyses. In this study, the Cmax of phloroglucinol were calculated to 515.6 ± 134.4 ng/mL and 536.0 ± 144.8 ng/mL for the test drug and the reference drug, respectively. The AUC0-t values were 459.5 ± 81.03 ng·mL-1·h and 491.8 ± 95.17 ng·mL-1·h for the test drug and the reference drug; 24 subjects completed the study, respectively. The geometric mean ratio (GMR) and the 90% confidence intervals (CIs) of Cmax and AUC0-t of phloroglucinol were 97.1 (90.2-103.9) and 93.8 (88.7-99.2), respectively. CONCLUSIONS: The method was employed for the first time during pharmacokinetic studies of phloroglucinol in human plasma following a single dose of phloroglucinol 160 mg tablets. There was no significant difference in pharmacokinetic profiles between the two treatments.

Propranolol inhibits the proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms

The aim of this study was to investigate the mechanism of propranolol on the regression of hemangiomas. Propranolol-treated hemangioma tissues were collected and the expression of hypoxia inducible factor-1α (HIF-1α) was examined. We also established HIF-1α overexpression and knockdown hemangioma cells, and determined the effects of HIF-1α on the hemangioma cells proliferation, apoptosis, migration and tube formation. Significantly increased HIF-1α level was found in the hemangioma tissues compared to that in normal vascular tissues, whereas propranolol treatment decreased the HIF-1α level in hemangioma tissues in a time- and dose-dependent manner. Moreover, propranolol treatment significantly decreased cell proliferation, migration and tube formation as well as promoted cell apoptosis in HIF-1α overexpression and knockdown hemangioma cells. Propranolol suppressed the cells proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms. HIF-1α could serve as a novel target in the treatment of hemangiomas.

Circulating miR-199a-3p in plasma and its potential diagnostic and prognostic value in glioma.

OBJECTIVE: The present study aimed to examine the possibility of using plasma miR-199a-3p as a biomarker for glioma. PATIENTS AND METHODS: Plasma miR-199a-3p expression glioma patients and normal healthy controls were quantified by Quantitative reverse transcription PCR. Then, the associations of serum miR-199a-3p level with clinicopathological factors or survival of glioma patients were further evaluated. Receiver operating characteristics (ROC) and area under the ROC curve (AUC) were used to validate the diagnostic value of miR-199a-3p. Univariate and multivariate Cox regression analyses were finally performed to analyze the independent factors for overall survival. RESULTS: The qRT-PCR results showed that the miR-199a-3p expression was significantly downregulated in glioma tissues compared with the adjacent non-tumor tissues (p<0.01). Furthermore, plasma miR-199a-3p level was significantly lower in glioma patients when compared with healthy controls (p<0.01). ROC curve analysis showed that plasma miR-199a-3p was a useful marker for discriminating cases from healthy controls, with an area under the ROC curve (AUC) of 0.8466 (95% confidence interval (CI) 0.772 to 0.9211, p<0.001). Moreover, miR-199a-3p expression was associated with various clinicopathological parameters, including WHO grade (p=0.001) and KPS score (p=0.008). We found that glioma patients with low miR-199a-3p expression level had distinctly shorter overall survival than patients with high miR-199a-3p expression level (p=0.0067). Univariate and multivariate analysis suggested that miR-199a-3p expression was an independent predictor of poor prognosis. CONCLUSIONS: These findings indicated that the circulating miR-199a-3p could be used as a promising novel biomarker for the diagnosis and prognosis of glioma.

Expression of lncRNA HULC in cervical cancer and its correlation with tumor progression and patient survival.

OBJECTIVE: To investigate Long non-coding RNA HULC (HULC) expression in cervical cancer and to evaluate its clinical significance. PATIENTS AND METHODS: HULC expression in 244 pairs of human cervical cancer and adjacent normal tissues was detected by real-time quantitative RT-PCR assay. The correlation between HULC and clinicopathological factors was also evaluated. The clinical and prognostic significance of HULC expression was analyzed statistically by Kaplan-Meier estimate and Cox regression model. RESULTS: HULC expression was high in cervical cancer (p < 0.01). Also, the high HULC expression was significantly associated with the FIGO stage, lymph node metastasis and depth of cervical invasion (p < 0.05). Kaplan-Meier analysis showed that cervical cancer pa¬tients with high expression of HULC possessed poorer outcome than those with low expression of HULC (p < 0.001). Based on the univariate and multivariate analysis, the elevated expression of the HULC protein was a significant predictor of poor prognosis for cervical cancer patients (p = 0.001). CONCLUSIONS: Our data firstly showed that the expression of HULC was upregulated in cervical cancer, and associated with overall survival, indicating that HULC may serve as a predictive biomarker for the prognosis of cervical cancer.

The impact of small doses of LPS on NASH in high sucrose and high fat diet induced rats.

OBJECTIVE: We investigated the impact of small doses of lipolysaccharide (LPS) on the development of NASH in the context of a high sucrose and high fat diet in rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into groups fed a synthetic diet (n=8), a regular diet (n=8), a synthetic diet + LPS (n=8) or saline (n=8) and a regular diet + LPS (n=8) or saline (n=8). The LPS (or saline) was administered from the 6th week on (0.5 mg/kg) by subcutaneous injection every two days under the same conditions with free access to water and food. At the end of the 9th week the animals were euthanized and the liver tissue dissected for analysis. Hematoxylin and eosin (HE) and Von Gieson's (VG) staining was performed on parafin embedded sections to observe the pathological changes of the liver, the degree of fibrosis, and infiltrative lymphocytes were counted in the liver tissue. RESULTS: We quantitatively measured the levels of LPS in the plasma of rats, ALT activity, and TNF-alpha. We found that the synthetic diet + LPS group showed severe steatosis, and was associated with bridging necrosis and mild fibrosis when compared to the group fed a Synthetic diet + saline. In addition, the amount of infiltrative lymphocytes and the level of plasma ALT and TNF-alpha in the synthetic diet + LPS group were significantly increased. The difference observed were statistically significant (p < 0.05). CONCLUSIONS: Small doses of LPS promote the development of NASH induced by a high sucrose and high fat.

Cancer-associated fibroblasts induce epithelial-mesenchymal transition of breast cancer cells through paracrine TGF-ß signalling.

BACKGROUND: Cancer-associated fibroblasts (CAFs) activated by tumour cells are the predominant type of stromal cells in breast cancer tissue. The reciprocal effect of CAFs on breast cancer cells and the underlying molecular mechanisms are not fully characterised. METHODS: Stromal fibroblasts were isolated from invasive breast cancer tissues and the conditioned medium of cultured CAFs (CAF-CM) was collected to culture the breast cancer cell lines MCF-7, T47D and MDA-MB-231. Neutralising antibody and small-molecule inhibitor were used to block the transforming growth factor-ß (TGF-ß) signalling derived from CAF-CM, which effect on breast cancer cells. RESULTS: The stromal fibroblasts isolated from breast cancer tissues showed CAF characteristics with high expression levels of α-smooth muscle actin and SDF1/CXCL12. The CAF-CM transformed breast cancer cell lines into more aggressive phenotypes, including enhanced cell-extracellular matrix adhesion, migration and invasion, and promoted epithelial-mesenchymal transition (EMT). Cancer-associated fibroblasts secreted more TGF-ß1 than TGF-ß2 and TGF-ß3, and activated the TGF-ß/Smad signalling pathway in breast cancer cells. The EMT phenotype of breast cancer cells induced by CAF-CM was reversed by blocking TGF-ß1 signalling. CONCLUSION: Cancer-associated fibroblasts promoted aggressive phenotypes of breast cancer cells through EMT induced by paracrine TGF-ß1. This might be a common mechanism for acquiring metastatic potential in breast cancer cells with different biological characteristics.

Inhibition of microRNA-21 increases radiosensitivity of esophageal cancer cells through phosphatase and tensin homolog deleted on chromosome 10 activation.

The radioresistance of esophageal squamous cell carcinoma is a great obstacle to treatment. Although it has been demonstrated that microRNA-21 (miR-21) can act as an 'oncogene' in esophageal squamous cell carcinoma, its role in radioresistance remains unexplored. The aims of this study were to investigate the role of miR-21 in esophageal squamous carcinoma cells' radioresistance and to identify the possible mechanism. The relatively radioresistant esophageal squamous cancer TE-1 cells (TE-R60) was established by fractionated irradiation. By lentiviral transduction with miRZip-21, the miR-21 expression in TE-1 cells was stably downregulated, which was renamed as 'anti-miR-21 TE-1 cells.' The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was knocked down in anti-miR-21 TE-1 cells through short interfering RNA. The expression level of miR-21 and PTEN messenger RNA were measured by quantitative real-time reverse transcription polymerase chain reaction or reverse transcription polymerase chain reaction. The expression level of PTEN, phospho-Akt, and Akt protein were detected by Western blot. Clongenic assay was used to analyze the cells' radiosensitivity. miR-21 was overexpressed, and PTEN was suppressed in established radioresistant TE-R60 cells compared with the parent cells (1.3-fold and 70.83%). The inhibition of miR-21 significantly increased the cells' radiosensitivity (P < 0.05) and the PTEN protein expression (2.3-fold) in TE-1 cells. In addition, phospho-Akt protein, downstream target of PTEN, reduced significantly in anti-miR-21 TE-1 cells. Knockdown of PTEN in anti-miR-21 TE-1 cells could abrogate the miR-21 inhibition-induced radiosensitization (P < 0.05). Inhibition of miR-21 increased radiosensitivity of esophageal cancer TE-1 cells, and this effect was possibly through the activation of PTEN. Inhibition of miR-21 may form a novel therapeutic strategy to increase the radiosensitivity of esophageal cancer.

How accentuation influences semantic short-term memory representations during on-line speech processing: an event-related potential study.

In the present study, the ERP (event-related brain potentials) technique was used to investigate how accentuation influences the semantic short-term memory representations during on-line speech processing, and how this accentuation effect interacts with the distance of accentuation in the speech signal. Chinese spoken sentences were used as stimuli. The sentences included two critical words: Noun1 and Noun2, with the ERP time-locked to Noun2. During sentence comprehension, when the listener hears Noun2, he needs to retrieve Noun1 from the working memory and integrate it with Noun2. We manipulated the (de-)accentuation of Noun1 and the semantic relationship between Noun1 and Noun2 by changing Noun1 in the sentence context. Moreover, we manipulated the distance of accentuation (distance between Noun1 and Noun2) by changing the syntactic structure of the sentences. The results revealed a significant main effect of semantic relatedness, indicating that the low semantic relatedness condition elicited a larger N400 than the high semantic relatedness condition. Importantly, there was a significant two-way interaction between semantic relatedness and accentuation and a significant three-way interaction between semantic relatedness, accentuation, and distance. Further analysis demonstrated that, the semantic relatedness effect was modulated by accentuation in the long-distance sentences, but not in the short-distance sentences. That is, in the long-distance sentences, the semantic relatedness effect reached significance only when the to-be-integrated expression in the preceding sentence context was accented; however, in the short-distance sentences, the semantic relatedness effects reached significance regardless of the presence or absence of accentuation. The results indicated that, during on-line speech processing, accentuation can enhance the corresponding information's semantic short-term memory representation, and that the effect of accentuation on semantic short-term memory is somewhat flexible and shows up only when the words in the speech signal were far apart.

Neuroprotective effects of hydroxysafflor yellow A against excitotoxic neuronal death partially through down-regulation of NR2B-containing NMDA receptors.

Hydroxysafflor yellow A (HSYA) is a component of the flower Carthamus tinctorius L. that elicits neuroprotective effects in vivo and in vitro. The purpose of this study was to investigate pharmacological properties of HSYA on neurotoxicity of glutamate in primary cultured rat cortical neurons along with its possible mechanism of action. After challenge with N-methyl-d-aspartate (NMDA, 100 microM) for 30 min, loss of cell viability and excessive apoptotic cell death were observed in cultured cortical neurons. However, the excitotoxic neuronal death was attenuated markedly by HSYA treatment. Western blot analysis revealed that HSYA decreased expression of Bax and rescued the balance of pro-and anti-apoptotic proteins. In addition, HSYA significantly reversed up-regulation of NR2B-containing NMDA receptors by exposure to NMDA, while it did not affect the expression of NR2A-containing NMDA receptors. These finding suggest that HSYA protects cortical neurons, at least partially, from inhibiting the expression NR2B-containing NMDA receptors and by regulating Bcl-2 family.