Mitochondrial­associated endoplasmic reticulum membrane interference in ovarian cancer (Review).

The mitochondria­associated endoplasmic reticulum (ER) membrane (MAM), serving as a vital link between the mitochondria and ER, holds a pivotal role in maintaining the physiological function of these two organelles. Its specific functions encompass the participation in the biosynthesis and functional regulation of the mitochondria, calcium ion transport, lipid metabolism, oxidative stress and autophagy among numerous other facets. Scientific exploration has revealed that MAMs hold potential as effective therapeutic targets influencing the mitochondria and ER within the context of cancer therapy. The present review focused on elucidating the related pathways of mitochondrial autophagy and ER stress and their practical application in ovarian cancer, aiming to identify commonalities existing between MAMs and these pathways, thereby extending to related applications of MAMs in ovarian cancer treatment. This endeavor aimed at exploring new potential for MAMs in clinically managing ovarian cancer.

Heparan sulfate targeting strategy for enhancing liposomal drug accumulation and facilitating deep distribution in tumors.

Nanoparticles (NPs), such as liposomes, effectively evade the severe toxicity of unexpected accumulation and passively shuttle drugs into tumor tissues by enhanced permeability and retention. In the case of non-small cell lung cancer and pancreatic ductal adenocarcinoma, cancer-associated fibroblasts promote the aggregation of a gel-like extracellular matrix that forms a physical barrier in the desmoplastic stroma of the tumor. These stroma are composed of protein networks and glycosaminoglycans (GAGs) that greatly compromise tumor-penetrating performance, leading to insufficient extravasation and tissue penetration of NPs. Moreover, the presence of heparan sulfate (HS) and related proteoglycans on the cell surface and tumor extracellular matrix may serve as molecular targets for NP-mediated drug delivery. Here, a GAG-binding peptide (GBP) with high affinity for HS and high cell-penetrating activity was used to develop an HS-targeting delivery system. Specifically, liposomal doxorubicin (L-DOX) was modified by post-insertion with the GBP. We show that the in vitro uptake of L-DOX in A549 lung adenocarcinoma cells increased by GBP modification. Cellular uptake of GBP-modified L-DOX (L-DOX-GBP) was diminished in the presence of extracellular HS but not in the presence of other GAGs, indicating that the interaction with HS is critical for the cell surface binding of L-DOX-GBP. The cytotoxicity of doxorubicin positively correlated with the molecular composition of GBP. Moreover, GBP modification improved the in vivo distribution and anticancer efficiency of L-DOX, with enhanced desmoplastic targeting and extensive distribution. Taken together, GBP modification may greatly improve the tissue distribution and delivery efficiency of NPs against HS-abundant desmoplastic stroma-associated neoplasm.

Dexmedetomidine alleviates hepatic injury via the inhibition of oxidative stress and activation of the Nrf2/HO-1 signaling pathway.

Dexmedetomidine (Dex), frequently used as an effective sedative, was reported to play a critical role in the protection of multiple organs. However, its underlying mechanism of a putative protective effect on ischemia/reperfusion (I/R)-induced liver injury is still unclear. A hepatocyte injury model was established by treating WRL-68 cells with oxygen and glucose deprivation/reoxygenation (OGD/R). Enzyme Linked Immunosorbent Assay (ELISA) kits were used to determine the level of inflammatory factors (IL-6, IL-1ß, and TNF-α), and oxidative stress indicators (ROS, MDA, GSH-Px, and SOD). MTT assay and flow cytometry analysis were used to determine the influence of Dex on cell viability and cell apoptosis. Expression of nuclear factor erythroid-derived 2- like 2 (Nrf2), HO-1, and apoptosis-related proteins (Bax, Bcl-2, caspase3, and caspase9) were detected by qRT-PCR and western blotting. Dex promoted cell viability and suppressed cell apoptosis in OGD/R-treated WRL-68 cells. Dex reduced TNF-α, IL-6, IL-1ß, ROS, and MDA production, whereas it increased that of SOD and GSH-Px in OGD/R-treated WRL-68 cells. Moreover, Nrf2, HO-1, and Bcl-2 expression was upregulated, whereas, in contrast, transcripts for Bax, caspase3, and caspase9 were downregulated following Dex treatment under OGD/R. Knockdown of Nrf2 reversed the Dex effects on cell proliferation, apoptosis, and expression of TNF-α, IL-6, IL-1ß, ROS, MDA, SOD, and GSH-Px. Dex protects WRL-68 cells against OGD/R-induced injury by inhibiting inflammation, oxidative stress, and cell apoptosis via the activation of Nrf2/HO-1 signaling pathway, suggesting that Dex may be a potential protector against hepatic injury.

Impact of medical staff loyalty on patient satisfaction:a study based on structural equation model / 中华医院管理杂志

Objective To learn the relationship and operating mechanism between medical staff's loyalty and patient satisfaction.Methods Medical staff and inpatients of a tertiary hospital in Nanjing were sampled at a 1:2 ratio for study,with 840 questionnaires released and 269 valid questionnaires recovered;medical staff service quality as perceived by inpatients served as the intermediate variable,with Mplus7.0 used to build a structural formula model for an empirical study of the relationship between staff loyalty and patient satisfaction.Results Staff loyalty exerts certain positive influence on patient satisfaction and staff service quality ( P direct effect value 0.143).Conclusions Structural formula model can reveal the relationship and extent of the influence of staff loyalty on patient satisfaction.This indicates that hospitals should enhance the loyalty,medical competence and communication skills of their medical staff for higher patient satisfaction.

Solanine induces the apoptosis of human prostate cancer cells via ROS/p38 signaling pathway / 西安交通大学学报(医学版)

Objective To investigate the molecular mechanism of solanine-induced apoptosis of prostate cancer cells Du145 and LNCaP.Methods The effects of solanine on the viability of Du145 and LNCaP cells were evaluated by MTT assay.The generation of intracellular reactive oxygen species (ROS) and solanine-induced apoptosis were measured by flow cytometry.The protein levels of p38 and p-p38 expressions were examined by Western blot.Results Solanine significantly inhibited the viability of Du145 and LNCaP cells in a dose-dependent manner (P＜0.01).The inhibition of solanine on cell viability was suppressed by the ROS scavenger NAC.ROS generation,apoptosis and phosphorylation of p38 were induced by treatment with solanine at 40 μmol/L for 24 h.The expression of p38 and solanine-induced apoptosis were suppressed by NAC and SB203580.Conclusion Solanine induces the apoptosis of human prostate cancer cell via the RO.S-p38 signaling pathway.

Leucaena leucocephala leachate compromised membrane integrity, respiration and antioxidative defence of water hyacinth leaf tissues.

BACKGROUND: Water hyacinth is an invasive aquatic weed in many regions of the world. In this study, the bioherbicidal potential of allelopathic plant Leucaena leucocephala against water hyacinth was investigated using a leaf disc assay. RESULTS: L. leucocephala leachate enhanced electrolyte leakage from water hyacinth leaf discs in a concentration-dependent manner. Control experiments eliminated the possibilities that increased membrane permeability in the leachate-treated leaf discs was due to pH or osmotic effects of the leachate. Thus, the loss of membrane stability in the leachate-treated leaf discs was likely due to phytotoxins detected in the leachate, namely mimosine and phenolic constituents. Decline in tissue respiration was detected in leachate-treated water hyacinth leaf discs. This suggests that the L. leucocephala leachate may contain compounds which acted as respiratory inhibitors. Enhanced reactive oxygen species production coincided with inhibition of catalase and ascorbate peroxidase activities in the leachate-treated water hyacinth leaf tissues. The injurious effects of L. leucocephala leachate on water hyacinth leaf discs probably involved direct inhibition of antioxidant enzymes in addition to direct involvement of some allelochemicals in reactive oxygen species formation. CONCLUSION: In summary, the toxic effects of L. leucocephala leachate on water hyacinth leaf discs likely lay in its ability to effectively compromise the membrane integrity, tissue respiration and antioxidant defence of the latter.

A meta-analysis of fish intake and the risk of renal cell cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the association of fish intake with the risk of renal cancer.</p><p><b>METHODS</b>PubMed, Embase, CNKI and CA databases were searched for case-control studies or cohort studies examining the relationship between fish or fish products intake and renal cancer. Heterogeneity among the selected studies was assessed using I2 score, and the publication bias was assessed using funnel plots.</p><p><b>RESULTS</b>Seventeen articles were included in the analysis with a heterogeneity across the studies (P=0.003, I(2)=52.3%). A random-effects model was used to generate the pooled risk ratio (RR) and 95% confidence interval (CI), and no statistically significant association was found between the risk of renal cancer and fish intake (RR=0.90; 95% CI, 0.78-1.02). In subgroup analysis, no evidence was found that the study design, study region or publication date influenced the results; but in the gender subgroup analysis, fish intake we found to decrease the risk of renal cancer in men but not in women.</p><p><b>CONCLUSION</b>The results of meta-analysis do not support an association between fish intake and a lowered risk of renal cancer.</p>

Construction of a recombinant lentiviral vector of p38 MAPK and establishment of a human prostatic carcinoma cell line stably expressing p38 MAPK / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a recombinant lentiviral vector for p38 MAPK and establish a human prostatic carcinoma cell line that stably expresses p38 MAPK.</p><p><b>METHODS</b>EGFP/p38 fusion gene was subcloned into the lentiviral vector pTYF- EF1α-IRES-EGFP. The recombinant lentiviral vector pTYF-EF1α-EGFP/p38 was indentified by restriction enzyme digestion, and packaged in HEK 293T cells using lipofectamintm2000 with the packaging plasmid psPAX2 and envelope plasmid pMD2.G. The viral titer was tested according to the expression level of GFP. The resulting recombinant lentiviral vector was transduced into human prostatic carcinoma DU145 cells, and stably transduced cells were selected by limiting dilution analysis. The intracellular expression level of total p38 was detected by Western blotting and the cell growth curve was drawn.</p><p><b>RESULTS</b>DNA restriction enzyme digestion demonstrated that the recombinant lentiviral vector of the fusion gene EGFP/p38 (pTYF-EF1α-EGFP/p38) was constructed successfully. The recombinant lentiviral vector was packaged in 293T with a viral titer of 4.7×10(6) TU/ml. A stable cell line, EGFP/p38-DU145, was established, which stably expressed exogenous EGFP/p38 MAPK fusion protein as detected by Western blotting and showed a lowered growth rate compared to the control cells.</p><p><b>CONCLUSION</b>We have successfully constructed a recombinant lentiviral vector of the fusion gene EGFP/p38 and established a stable cell line EGFP/p38-DU145. Overexpression of p38 has a significant inhibitory effect on the proliferation of DU145 cells in vitro.</p>