A new nucleoside and two new pyrrole alkaloid derivatives from Cordyceps militaris.

A new nucleoside, a new natural product nucleoside, and two new pyrrole alkaloids derivatives with eight known compounds were isolated from the fruiting body of Cordyceps militaris. The structures of the new compounds were elucidated through extensive analysis of spectroscopic data including 1D and 2D NMR, HRESIMS, IR and UV. All the isolated compounds were detected for their bioactivities against LPS-induced NO production in RAW 264.7 cells. Unfortunately, all the isolates have shown no obvious activity.

Self-Healing and Recyclable Hydrogels Reinforced with in Situ-Formed Organic Nanofibrils Exhibit Simultaneously Enhanced Mechanical Strength and Stretchability.

In this work, self-healing and recyclable polymer hydrogels with simultaneously enhanced mechanical strength and stretchability are fabricated through the complexation of poly(acrylic acid) (PAA) with complexes of branched poly(ethylenimine) and 1-pyrenybutyric acid (PEI-PYA) to generate PAA/PEI-PYA complexes, which are further molded, dried, and rehydrated. The in situ-formed PYA nanofibrils with aggregated structures during the complexation process enable the simultaneous enhancement of the tensile strength and stretchability of the PAA/PEI-PYA hydrogels. The PAA/PEI-PYA hydrogels have a tensile strength of 1.13 ± 0.04 MPa and stretchability of 2970 ± 154%, which are 2.2 and 2.1 times higher than those of the PAA/PEI hydrogels. Meanwhile, the damaged PAA/PEI-PYA hydrogels can be efficiently healed or recycled at room temperature to regain their original mechanical strength and integrity because the dynamic nature of hydrogen-bonding and electrostatic interactions among PAA, PEI, and PYA endows the hydrogels with excellent healing and recycling capacity. This strategy of using aggregated nanofibrils to simultaneously enhance the tensile strength and stretchability of hydrogels can be extended to PAA/PEI hydrogels reinforced with aggregated nanofibrils of 9-anthracenecarboxylic acid and N,N'-di(propanoic acid)-perylene-3,4,9,10-tetracarboxylic diimide, demonstrating its generality for fabricating hydrogels with enhanced mechanical properties.

Amorphous solid dispersion of Berberine mitigates apoptosis via iPLA2ß/Cardiolipin/Opa1 pathway in db/db mice and in Palmitate-treated MIN6 ß-cells.

Aims: Berberine (BBR) improves beta-cell function in Type 2 diabetes (T2D) because of its anti-apoptotic activity, and our laboratory developed a new preparation named Huang-Gui Solid Dispersion (HGSD) to improve the oral bioavailability of BBR. However, the mechanism by which BBR inhibits beta-cell apoptosis is unclear. We hypothesized that the Group VIA Ca2+-Independent Phospholipase A2 (iPLA2ß)/Cardiolipin(CL)/Opa1 signaling pathway could exert a protective role in T2D by regulating beta-cell apoptosis and that HGSD could inhibit ß-cell apoptosis through iPLA2ß/CL/Opa1 upregulation. Methods: We examined how iPLA2ß and BBR regulated apoptosis and insulin secretion through CL/Opa1 in vivo and in vitro. In in vitro studies, we developed Palmitate(PA)-induced apoptotic cell death model in mouse insulinoma cells (MIN6). iPLA2ß overexpression and silencing technology were used to examine how the iPLA2ß/CL/Opa1 interaction may play an important role in BBR treatment. In in vivo studies, db/db mice were used as a diabetic animal model. The pancreatic islet function and morphology, beta-cell apoptosis and mitochondrial injury were examined to explore the effects of HGSD. The expression of iPLA2ß/CL/Opa1 was measured to explore whether the signaling pathway was damaged in T2D and was involved in HGSD treatment. Results: The overexpression of iPLA2ß and BBR treatment significantly attenuated Palmitate- induced mitochondrial injury and apoptotic death compared with Palmitate-treated MIN6 cell. In addition, iPLA2ß silencing could simultaneously partly abolish the anti-apoptotic effect of BBR and decrease CL/Opa1 signaling in MIN6 cells. Moreover, HGSD treatment significantly decreased beta-cell apoptosis and resulted in the upregulation of iPLA2ß/CL/Opa1 compared to those of the db/db mice. Conclusion: The results indicated that the regulation of iPLA2ß/CL/Opa1 by HGSD may prevent beta-cell apoptosis and may improve islet beta-cell function in Type 2 diabetic mice and in palmitate-treated MIN6 cells.

Radiofrequency ablation versus partial nephrectomy for treatment of renal masses: A systematic review and meta-analysis.

Our study was to collect the data available in the literature on radiofrequency ablation (RFA) and partial nephrectomy (PN) and conduct a cumulative analysis on perioperative outcomes, renal function outcomes, and survival to evaluate the overall safety and efficacy of RFA versus PN for small renal cell cancer (SRCC). A literature search was carried out using various electronic databases. Data including age, tumor size, comorbid disease, operation duration, hospital stay, pre- and postoperative estimated glomerular filtration rate (eGFR), major and minor complications, and local tumor recurrence and metastasis were collected for meta-analysis. Sixteen studies were included for this meta-analysis. The age of patients treated with RFA was significantly older than that of patients treated with PN [weighted mean difference (WMD) = 5.07 years]. There were more patients with cardiovascular disease in RFA group as compared with PN group [odds ratio (OR) = 4.24] before treatment. RFA was associated with a shorter length of hospital stay compared with PN (WMD = -2.02 days). No significant difference was found in major and minor complications between the two groups (major: OR = 0.74; minor: OR = 0.45). Preoperative eGFR and eGFR decline in RFA patients was significantly lower than that in PN patients (WMD = -7.27 and -4.82, respectively), whereas there was no significant difference in postoperative eGFR (WMD = -1.18). The local tumor recurrence rate in RFA group was higher than that in PN group (OR = 1.81). However, the distant metastasis rate was no statistical difference between the two groups (OR = 1.63). RFA is a suitable therapeutic option for older patients and those at high risk for SRCC because of a low risk of operation and better preservation of renal function.

Robot-Assisted Radical Prostatectomy vs. Open Retropubic Radical Prostatectomy for Prostate Cancer: A Systematic Review and Meta-analysis.

Open retropubic radical prostatectomy (ORP) remains the "gold standard" for surgical treatment of clinically localized prostate cancer (PCa). Robot-assisted radical prostatectomy (RARP) is a robotic surgery used worldwide. The aim of this study is to collect the data available in the literature on RARP and ORP, and further evaluate the overall safety and efficacy of RARP vs. ORP for the treatment of clinically localized PCa. A literature search was performed using electronic databases between January 2009 and October 2013. Clinical data such as operation duration, transfusion rate, positive surgical margins (PSM), nerve sparing, 3- and 12-month urinary continence, and potency were pooled to carry out meta-analysis. Six studies were enrolled for this meta-analysis. The operation duration of RARP group was longer than that of ORP group (weighted mean difference = 64.84). There was no statistically significant difference in the transfusion rate, PSM rate, and between RARP and ORP (transfusion rate, OR = 0.30; PSM rate, OR = 0.94). No significant difference was seen in 3- and 12-month urinary continence recovery (3 months, OR = 1.32; 12 months, OR = 1.30). There was a statistically significant difference in potency between the 3- and 12-month groups (3 months, OR = 2.80; 12 months, OR = 1.70). RARP is a safe and feasible surgical technique for the treatment of clinically localized PCa owing to the advantages of fewer perioperative complications and quicker patency recovery.

Combination of chloroquine and GX15-070 (obatoclax) results in synergistic cytotoxicity against pancreatic cancer cells.

Pancreatic cancer is an aggressive disease with a poor prognosis. Therefore, new treatment is urgently required. GX15-070 is a pan-Bcl-2 inhibitor which has shown promising antitumor activity in different malignancies. We previously demonstrated that clinically achievable concentrations of GX15-070 caused growth arrest in pancreatic cancer cell lines. However, they only induced minimal levels of apoptosis. We hypothesized that GX15-070 induced autophagy in pancreatic cancer cells which blocked apoptosis. In this study, we investigated the effects of GX15-070 on autophagy and the antitumor activities of the combination of GX15-070 and chloroquine (CQ), an autophagy inhibitor, in six pancreatic cancer cell lines. We found that GX15-070 treatment indeed induced autophagy in 5 of the 6 pancreatic cancer cell lines, reflected by the conversion of LC3B-I to LC3B-II and detection of autophagosomes by transmission electron microscopy. Furthermore, we found additive to synergistic antitumor interactions in all six cell lines by MTT assays. CQ significantly enhanced GX15-070-induced apoptosis in the cell line models, possibly due to downregulation of Bcl-2, Bcl-xL and Mcl-1 in the cells by the two agents. These results provide compelling evidence for the further development of the combination of GX15-070 and CQ in pancreatic cancer.