Influences of coexisting aged polystyrene microplastics on the ecological and health risks of cadmium in soils: A leachability and oral bioaccessibility based study.

Whether coexisting microplastics (MPs) affect the ecological and health risks of cadmium (Cd) in soils is a cutting-edge scientific issue. In this study, four typical Chinese soils were prepared as artificially Cd-contaminated soils with/without aged polystyrene (PS). TCLP and in vitro PBET model were used to determine the leachability (ecological risk) and oral bioaccessibility (human health risk) of soil Cd. The mechanisms by which MPs influence soil Cd were discussed from direct and indirect perspectives. Results showed that there was no significant difference in the leachability of soil Cd with/without aged PS. Additionally, aged PS led to a significant decrease in the bioaccessibility of soil Cd in gastric phase, but not in small intestinal phase. The increase in surface roughness and the new characteristic peaks (e.g., Si-O-Si) of aged PS directly accounted for the change in Cd bioaccessibility. The change in organic matter content indirectly accounted for the exceptional increase in Cd bioaccessibility of black soil with aged PS in small intestinal phase. Furthermore, the changes in cation exchange capacity and Cd mobility factor caused by aged PS explained the change in Cd leachability. These results contribute to a deeper understanding about environmental and public health in complicated emerging scenarios.

The Silence of PSMC6 Inhibits Cell Growth and Metastasis in Lung Adenocarcinoma.

The proteasome has been validated as an anticancer drug target, while the role of a subunit of proteasome, PSMC6, in lung adenocarcinoma (LUAD) has not been fully unveiled. In this study, we observed that both the RNA and protein of PSMC6 were highly upregulated in LUAD compared with the adjacent normal tissues. Moreover, a high PSMC6 expression was associated with poor prognosis. In accordance with this finding, PSMC6 was associated with poor tumor differentiation. Furthermore, the silence of PSMC6 by small interference RNAs (siRNAs) could significantly inhibit cell growth, migration, and invasion in lung cancer cell lines, suggesting that PSMC6 might serve as a promising therapeutic target in LUAD. To further explore the molecular mechanism of PSMC6 in LUAD, we observed that the proteasome subunits, such as PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, and PSMD14, were highly correlated with PSMC6 expression. Based on the gene set enrichment analysis, we observed that these proteasome subunits were involved in the degradation of AXIN protein. The correlation analysis revealed that the positively correlated genes with PSMC6 were highly enriched in WNT signaling-related pathways, demonstrating that the PSMC6 overexpression may activate WNT signaling via degrading the AXIN protein, thereby promoting tumor progression. In summary, we systematically evaluated the differential expression levels and prognostic values of PSMC6 and predicted its biological function in LUAD, which suggested that PSMC6 might act as a promising therapeutic target in LUAD.

Two new troponoides with anti-inflammatory activity from the stems of Juniperus formosana Hayata.

Two new troponoides (1-2) were isolated from a 95% ethanol extract of the stems of Juniperus formosana (Cupressaceae), together with six known compounds (3-8). The structures of the new compounds were comprehensively characterized by high resolution electrospray ionization-mass spectrometry (HR-ESI-MS), 1D and 2D nuclear magnetic resonance (NMR). Compounds 1-7 were evaluated for their anti-inflammatory against the expression of IL-1ß, IL-6 and TNF-α in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. The new compounds showed moderate anti-inflammatory effect, while other compounds did show no activity.

Successful treatment of a case with NUT midline carcinoma in the larynx and review of the literature.

In this report, we gave the first case of successful treatment for laryngeal NMC, which is exceedingly rare with dismal prognosis. intensity-modulated radiation therapy accompanied by traditional Chinese medicine was administrated for the young woman, instead of radical resection, and she got continuous remission for more than 2 years, with no recurrence detected.

[Strategies of preserving urinary continence in transurethral plasmakinetic enucleation of the prostate for benign prostate hyperplasia].

OBJECTIVE: To explore the strategies of preserving urinary continence in transurethral plasmakinetic enucleation of the prostate (PKEP) for benign prostate hyperplasia (BPH). METHODS: We treated 65 BPH patients by PKEP with preservation of urinary continence (UC-PKEP), which involved protection of the external urethral sphincter in the beginning of surgery, proper preservation of the anterior lobe of the prostate to protect the internal urethral sphincter in the middle, and preservation of the integrity of the bladder neck towards the end. We compared the postoperative status of urinary continence of the patients with that of the 54 BPH cases treated by complete plasmakinetic enucleation of the prostate (Com-PKEP). RESULTS: All the operations were performed successfully with the urinary catheters removed at 5 days after surgery. In comparison with Com-PKEP, UC-PKEP achieved evidently lower incidence rates of urinary incontinence at 24 hours (31.49% vs 13.85%, P <0.05), 1 week (18.52% vs 4.62%, P <0.05), 2 weeks (14.81% vs 3.08%, P <0.05), 1 month (3.70% vs 1.54%, P >0.05), and 3 months (3.70% vs 0%, P >0.05) after catheter removal. Compared with the baseline, the maximum urinary flow rate (Qmax) was significantly improved postoperatively in both the Com-PKEP (ï¼»7.43 ± 3.26ï¼½ vs ï¼»20.58 ± 3.22ï¼½ ml, P <0.05) and the UC-PKEP group (ï¼»8.04 ± 2.28ï¼½ vs ï¼»20.66 ± 3.08ï¼½ ml, P <0.05). CONCLUSIONS: Transurethral PKEP is a safe and effective method for the management of BPH, during which the strategies of avoiding blunt or sharp damage to the external urethral sphincter in the beginning, properly preserving the anterior lobe of the prostate in the middle and preserving the integrity of the bladder neck towards the end may help to achieve rapid recovery of urinary continence.

Distinct EphB4-mediated mechanisms of apoptotic and resistance to dasatinib in human chronic myeloid leukemia and K562 cell lines.

OBJECTIVE: To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines. METHOD: Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS. Stable under-expressing EphB4 cells (K562-R-EphB4-sh) were obtained from K562-R cells by RNA interference. K562-W, K562-R and K562-R-EphB4-sh cells (108) were respectively injected subcutaneously on the dorsal surface of BALB/C female nude mice to establish the xenografts models. RESULT: The mRNA/protein of EphB4 was overexpressed in the DAS-resistant A2-E2 in comparison with the A1-E1 human cell lines. Further, compared with K562-R cells, the expressions of EphB4 and p-Rac1/Cdc42 protein/mRNA were significantly downregulated in K562-R-EphB4-sh cells (P<0.01). K562-R cells showed the highest DAS resistance (IC50 10.54±0.67µg/ml), but K562-R-EphB4-sh cells became sensitive to DAS (IC50 1.02±0.1µg/ml, P<0.01). The expression of EphB4/p-RhoA/MCL-1 protein was gradually increased in the stimulating of EphrinB2-Fc, which partly made K562-R-EphB4-sh cells restore sensitivity to DAS (4.18±0.30µg/ml). Meanwhile, the K562-R-EphB4-sh xenografts group had relatively good efficacy compared to K562-R xenografts nude mice receiving the same dose of DAS. The analysis of xenografts tissue also suggested parallel results with the overexpression of EphB4/RhoA/ROCK1/PTEN/MCL-1 in K562-R xenografts, which decreased in the A2-R-EphB4-sh xenografts (P<0.01). CONCLUSIONS: The present study found that a new DAS resistance pathway of EphB4 overexpression was triggered by EphrinB2-Fc, which induced the resistance to DAS by activating RhoA/ROCK1/PTEN/MCL-1 signaling.

Downregulation of human Wnt3 in gastric cancer suppresses cell proliferation and induces apoptosis.

Aberrant activation of Wnt/ß-catenin signaling pathways is closely involved in the occurrence and progression of several types of human malignancies. However, as a fundamental component in this cascade, Wnt3 has not been well understood for the expression level and pathogenic mechanism in gastric carcinogenesis. Here, this research was undertaken to elucidate the important role of Wnt3 in gastric cancer. Wnt3 expression in gastric carcinomas and their respective normal tissues was examined by immunoblotting and immunohistochemistry. In all cases, Wnt3 expression was significantly elevated in gastric carcinomas compared with normal tissues. Knocking down Wnt3 in MGC-803 gastric cancer cells by small interfering RNAs transfection led to an obvious decrease in both transcript and protein levels. Silence of Wnt3 expression in gastric cancer cells inhibited the expression of ß-catenin and cyclin D1 genes in Wnt/ß-catenin pathway, significantly blocked cellular proliferation, delayed cell cycle, suppressed cell invasion and metastasis, accompanied by a higher apoptosis rate. Together, we conclude that upregulation of Wnt3 plays a crucial role in gastric tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells, and Wnt3 might be a potential target for the treatment of gastric cancer.

[Expression of Smad4 and transforming growth factor-beta1, transforming growth factor-beta receptor II in cholangiocarcinoma tissue and its biological significance].

OBJECTIVE: To study the expression of Smad4 and transforming growth factor-beta(1) (TGFbeta(1)), transforming growth factor-beta receptor II (TGFbetaRII) in cholangiocarcinoma tissue and its relationship with the biological behaviour and prognosis of the disease. METHODS: The expressions of Smad4, TGFbeta(1) and TGFbetaRII were detected by immunohistochemical technique in 47 specimens of cholangiocarcinoma and the normal bile duct tissue adjacent to the tumor. The expressions of Smad4, TGFbeta(1) and TGFbetaRII were compared with the clinical stages and pathological grades of the patients. RESULTS: The expression of TGFbeta(1) was positive in 36 cholangiocarcinomas (76.6%), which was higher than that in the normal tissue adjacent to the lesion. The positive expressions of Smad4 and TGFbetaRII were 14 (29.8%) and 28 (59.6%) in the carcinoma tissues, respectively (P < 0.05). The expression of TGFbeta(1) was related to the clinical stage, metastasis of lymph node and liver of the tumor (P < 0.05), but not with the histological grade (P > 0.05). There was positive correlation between TGFbetaRII expression and the clinical stage (P < 0.05), but no correlation between the TGFbetaRII expression and histological grade or metastasis of lymph node and liver (P > 0.05). The expression of Smad4 was associated with the histological grade, clinical stage and metastasis of lymph node and liver (P < 0.05). CONCLUSIONS: The expressions of Smad4, TGFbeta(1) and TGFbetaRII correlate with the histological grading, clinical staging and metastasis of the lymph node and liver in cholangiocarcinoma. Combined detection of Smad4, TGFbeta(1) and TGFbetaRII may be helpful in the determination of the malignant degree and the prognosis of this disease.

Randomized trial of pallidotomy versus medical therapy for Parkinson's disease.

Thirty-six patients with Parkinson's disease (PD) were randomized to either medical therapy (N = 18) or unilateral GPi pallidotomy (N = 18). The primary outcome variable was the change in total Unified Parkinson's Disease Rating Scale (UPDRS) score at 6 months. Secondary outcome variables included subscores and individual parkinsonian symptoms as determined from the UPDRS. At the six month follow-up, patients receiving pallidotomy had a statistically significant reduction (32% decrease) in the total UPDRS score compared to those randomized to medical therapy (5% increase). Following surgery, patients' showed improvement in all the cardinal motor signs of PD including tremor, rigidity, bradykinesia, gait and balance. Drug-induced dyskinesias were also markedly improved. Although the greatest improvement occurred on the side contralateral to the lesion, significant ipsilateral improvement was also observed for bradykinesia, rigidity and drug-induced dyskinesias. A total of twenty patients have been followed for 2 years to assess the effect of time on clinical outcome. These patients have shown sustained improvement in the total UPDRS (p < 0.0001), "off" motor (p < 0.0001) and complications of therapy subscores (p < 0.0001). Sustained improvement was also seen for tremor, rigidity, bradykinesia, percent on time and drug-induced dyskinesias.