Jaridon 6, a new diterpene from Rabdosia rubescens (Hemsl.) Hara, can display anti-gastric cancer resistance by inhibiting SIRT1 and inducing autophagy.

Tumor resistance is the main cause of treatment failure and is associated with many tumor factors. Jaridon 6, a new diterpene extracted from Rabdosia rubescens (Hemsl.) Hara, which has been previously extracted by our research team, has been tested having more obvious advantages in resistant tumor cells. However, its mechanism is unclear. In this study, we studied the effect and the specific mechanism of Jaridon 6 in resistant gastric cancer cells. Cytotoxicity test, colony test, western blotting, and nude test verified the anti-drug resistance ability of Jaridon 6 in the MGC803/PTX and MGC803/5-Fu cells. Jaridon 6 has shown obvious inhibitory effects in the sirtuin 1 (SIRT1) enzyme test. Transmission electron microscopy and immunofluorescence tests further proved the autophagic action of Jaridon 6. Jaridon 6 could inhibit the proliferation of the resistant gastric cancer cell in vivo and in vitro. Jaridon 6 inhibited SIRT1 enzyme and induced autophagy by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway. Thus, it may be considered for treating gastric cancer resistance by individual or combined administration, as an SIRT1 inhibitor and autophagy inducer.

[Differences of Energy Spectrum CT Findings between Small Cell Lung Cancer with Mediastinal Lymph Node Metastasis and Mediastinal Sarcoidosis].

Objective To compare the differences of energy spectrum CT between small cell lung cancer(SCLC)with mediastinal lymph node metastasis and mediastinal sarcoidosis.Methods Twenty-five SCLC patients with mediastinal lymph node metastasis(SCLC group)and 26 patients with mediastinal sarcoidosis(sarcoidosis group)confirmed by bronchoscopy and biopsy in Tangshan People's Hospital from January 2018 to June 2019 were selected as the research objects.The CT value,iodine concentration,water concentration and energy spectrum curve slope under different single energy levels were compared between SCLC group and sarcoidosis group.Results The single-energy CT values of 40-80 keV segments in the arterial phase of the SCLC group were significantly higher than those in the sarcoidosis group(all P <0.05).The single-energy CT values of 90-140 keV segments were not significantly different from those in the sarcoidosis group(all P >0.05).The single-energy CT values of 40-90 keV segments in venous phase of the SCLC group were significantly higher than those of the sarcoidosis group(all P <0.05),and the single-energy CT values of 100-140 keV segments were not significantly different from those of the sarcoidosis group(all P >0.05).The concentrations of iodine in the arterial phase and venous phase of the SCLC group were(11.56±4.06)µg/cm 3 and(13.39±0.87)µg/cm 3,respectively,which were significantly higher than those [(4.43±3.85)µg/cm 3,t=11.564,P=0.026;(7.23±2.71)µg/cm 3,t=13.653,P=0.021] in the sarcoidosis group.The concentrations of water in the arterial and venous phases of the SCLC group were(1040.67±5.62)mg/cm 3 and(1035.23±8.57)mg/cm 3,respectively,which showed no statistically significant difference compared with those [(1028.87±6.94)mg/cm 3,t=3.155,P=1.861;(1021.53±4.68)mg/cm 3,t=3.265,P=1.687] in the sarcoidosis group.The slopes of energy spectrum curve at 40-70 keV,70-100 keV and 100-140 keV in venous phase of the SCLC group were significantly higher than those of the sarcoidosis group(all P <0.05),whereas they showed no significant difference between the two groups in arterial phase(all P >0.05).Conclusion The differences between SCLC with mediastinal lymph node metastasis and mediastinal sarcoidosis can be shown on the single-energy CT values of 40-80 keV in arterial phase and 40-90 keV in venous phase,iodine concentrations in arterial phase and venous phase,and the slope of energy spectrum curve in venous phase.

[Different Energy Spectrum CT Findings between Anterior Mediastinal Lymphoma and Thymic Carcinoma].

Objective To investigate the differences in energy spectrum CT findings between anterior mediastinal lymphoma and thymic carcinoma. Methods Twenty-two cases of anterior mediastinal lymphoma and 28 cases of thymic carcinoma confirmed by biopsy in Tangshan People's Hospital were selected.The CT values and changes of iodine content and water content in lesion sites were measured by energy spectrum analysis software.The differences between anterior mediastinal lymphoma and thymic carcinoma were compared. Results The single-energy CT value of 40-80 keV in thymus carcinoma was higher than that in anterior mediastinal lymphoma(P=0.001,P=0.037,P=0.042,P=0.034,P=0.002;P=0.016,P=0.013,P=0.018,P=0.024,P=0.012).The difference in the single-energy CT value of 90-110 keV between anterior mediastinal lymphoma and thymic carcinoma showed no statistical significance(all P>0.05).The concentrations of water in the arterial and venous stages of thymic carcinoma were significantly lower than those in the anterior mediastinal lymphoma(P=0.030,P=0.037),whereas the iodine concentrations were significantly higher(P=0.026,P=0.000). Conclusion Anterior mediastinal lymphoma and thymic carcinoma have remarkably different 40-80 keV single energy CT value and iodine concentration in arterial and venous phases,which may be helpful for the differential diagnosis of these two malignancies.

Molecular mechanisms of TLR2-mediated antigen cross-presentation in dendritic cells.

Cross-presentation is a key function of dendritic cells (DCs), which present exogenous Ags on MHC class I molecules to prime CTL responses. The effects of TLR triggering on the cross-presentation of exogenous Ags by DCs remain unclear. In this study, we used synthetic dipalmitoylated peptides and TLR2 agonist-conjugated peptides as models to elucidate the mechanisms of TLR2-mediated cross-presentation. We observed that the internalization of dipalmitoylated peptides by bone marrow-derived DCs was facilitated by TLR2 via clathrin-mediated endocytosis. The administration of these dipalmitoylated peptide-pulsed bone marrow-derived DCs eliminated established tumors through TLR2 signaling. We further demonstrated that the induction of Ag-specific CTL responses and tumor regression by dipalmitoylated peptides was TAP independent. In addition, presentation of dipalmitoylated peptides by MHC class I molecules was blocked in the presence of an endosomal acidification inhibitor (chloroquine) or a lysosomal degradation inhibitor (Z-FL-COCHO). The endocytosed dipalmitoylated peptide also passed rapidly from early endosome Ag-1-positive endosomes to RAS-related GTP-binding protein 7 (Rab7)-associated late endosomes compared with their nonlipidated counterparts. Furthermore, we found that dipalmitoylated peptide-upregulated Rab7 expression correlated with Ag presentation via the TLR2/MyD88 pathway. Both JNK and ERK signaling pathways are required for upregulation of Rab7. In summary, our data suggest that TLR2-mediated cross-presentation occurs through the upregulation of Rab7 and a TAP-independent pathway that prime CTL responses.

Comparative efficacy of 13 antimicrobial dressings and different securement devices in reducing catheter-related bloodstream infections: A Bayesian network meta-analysis.

PURPOSE: The purpose of our study is to carry out a Bayesian network meta-analysis comparing the efficacy of different antimicrobial dressings for prevention of catheter-related blood infections (CRBSI) and rank these antimicrobial dressings for practical consideration. METHODS: We searched the PubMed, Cochrane library, Embase, earlier relevant meta-analysis and reference lists of included studies for randomized controlled trials (RCTs) that compared dressings for prevention of CRBSI. Two authors independently extracted data from each included RCT according to a predesigned Excel spreadsheet and assessed the methodological quality of included RCTs using the Cochrane risk of bias tool. Data was analyzed using the WinBUGS (V.1.4.3) and the Stata (V.15.0). RESULTS: Finally, 35 RCTs involving 8494 patients and evaluating 13 dressings were included. Network meta-analysis showed that transparent dressing may be the best way to prevent CRBSI. Suture and bordered polyurethane dressing might have the lowest risk of CRBSI rate per 1000 catheter-days, and sutureless securement device might lead to the lowest incidence of catheter failure. CONCLUSIONS: This network meta-analysis indicated that transparent dressings may be selected for the prevention of CRBSI in patients with central venous catheters, which is of importance in future research. Although evidence is scant, more attention should be paid to head-to-head comparisons of the most commonly used dressings in this field.

The effect of text message reminders on medication adherence among patients with coronary heart disease: A systematic review and meta-analysis.

BACKGROUND: To determine the effectiveness of text message reminders (TMR) on medication adherence (MA) and to investigate the effects of TMR on clinical outcomes. METHODS: The PubMed, Cochrane library, EMbase, and China Biology Medicine databases were searched for randomized-controlled trials with TMR as the intervention for patients with coronary heart disease. Two reviewers independently extracted data and assessed the risk of bias. Meta-analysis was conducted using Stata 15.0 software. RESULTS: In total, 1678 patients in 6 trials were included. Compared with the control group, the MA was 2.85 times greater among the intervention group (RR [relative risk] 2.85; 95% confidence interval [CI] 1.07-7.58). TMR reduced systolic blood pressure (BP) (weighted mean difference) = -6.51; 95% CI -9.79 to -3.23), cholesterol (standard mean difference = -0.26; 95% CI -0.4 to -0.12) and increased the number of patients with BP <140/90 mm Hg (RR 1.39; 95% CI 1.26-1.54). CONCLUSION: TMR significantly promoted MA and reduced systolic BP, cholesterol level, and body mass index, but had no effect on mortality, diastolic BP, or lipoproteins. However, substantial heterogeneity existed in our analyses.

Comparative efficacy of various antimicrobial lock solutions for preventing catheter-related bloodstream infections: A network meta-analysis of 9099 patients from 52 randomized controlled trials.

OBJECTIVES: It remains uncertain which catheter lock solution (CLS) to prevent catheter-related bloodstream infections (CRBSI) works best and is safest for patients. This study was performed to compare the efficacy of different CLSs for the prevention of CRBSI and ranked these CLSs for practical consideration. METHODS: The PubMed, Web of Science, Embase, and MEDLINE databases, earlier relevant meta-analyses, and the reference lists of included studies were searched. The primary outcome was CRBSI; secondary outcomes were catheter-related thrombosis and exit-site infections. A network meta-analysis was performed to estimate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 52 randomized controlled trials involving 9099 patients and evaluating 13 CLSs (single and combinations) were included. With regard to the quality of the evidence, the risk of bias was typically low or unclear (45 out of 52 trials, 86.5%). In the network meta-analysis, saline (OR 8.44, 95% CI 2.19-32.46), gentamicin+citrate (OR 2.92, 95% CI 1.32-6.42), ethanol (OR 5.33, 95% CI 1.22-23.32), and cloxacillin+heparin (OR 2.07, 95% CI 1.19-5.49) were associated with a greater effect on CRBSI than heparin. CONCLUSIONS: This network meta-analysis showed that minocycline-ethylenediaminetetraacetic acid (EDTA) seemed to be the most effective for the prevention of CRBSI and exit-site infection, and cefotaxime+heparin seemed to be the most effective for catheter-related thrombosis.

Geridonin, a novel derivative of oridonin, inhibits proliferation of MGC 803 cells both in vitro and in vivo through elevating the intracellular ROS.

OBJECTIVES: To study the antitumour activity of a novel derivative of oridonin named geridonin in vitro and in vivo. METHODS: MTT and colony formation assay were used to test the cytotoxicity of geridonin; apoptosis, cell cycle arrest and the levels of reactive oxygen species were measured by flow cytometry; JC-1 staining assay was used to examine the mitochondrial membrane potential; the MGC 803 xenograft model was established to evaluate the antitumour effect of geridonin in vivo; H&E staining was performed for the histological analysis. KEY FINDINGS: In vitro, geridonin remarkably inhibited proliferation of gastrointestinal cancer cells including oesophageal, gastric, liver and colon cancers. On oesophageal, gastric cancer cells, geridonin displayed strong cytotoxicity than that of oridonin. In gastric cancer MGC 803 cells, geridonin triggered apoptosis through the mitochondrial pathway depending on caspase. In addition, geridonin sharply reduced the formation of cell colony, increased the intracellular levels of ROS and induced cell cycle arrest at G2/M phase. In vivo, geridonin delayed the growth of MGC 803 xenograft in athymic mice without obvious loss of bodyweight. CONCLUSIONS: The novel derivative of oridonin, geridonin, inhibited the growth of human gastric cancer cells MGC 803 both in vitro and in vivo mainly via triggering apoptosis depending on elevating intracellular level of ROS.

A novel liposomal recombinant lipoimmunogen enhances anti-tumor immunity.

Synthetic liposomes provide a biocompatible and biodegradable approach for delivering drugs and antigens. In addition, self-adjuvanting recombinant lipoproteins (rlipoproteins) can enhance Th1 anti-tumor immune responses via the TLR2 signaling pathway. To generate a liposomal rlipoprotein for a cancer immunotherapeutic vaccine, we assessed 3 types of synthetic liposomes for use with the rlipoproteins rlipoE7m and rlipoOVA. We determined that the cationic liposome DOTAP could stabilize anionic rlipoproteins and delay rlipoprotein release. Surprisingly, rlipoproteins and DOTAP could synergistically up-regulate CD83 expression in bone marrow-derived dendritic cells (BMDCs). Compared with other liposome formulations, the rlipoprotein/DOTAP formulation elicited higher cytotoxic T-lymphocyte (CTL) responses. To explore the mechanism of BMDC activation by rlipoprotein/DOTAP, we assessed the production of reactive oxygen species (ROS) and the TNF-α secretion of BMDCs. We observed that rlipoprotein/DOTAP induced ROS to the same extent as DOTAP did. In addition, TLR2 signaling was also required for the TNF-α secretion of rlipoprotein/DOTAP-treated BMDCs. Moreover, compared with rlipoOVA-treated BMDCs, rlipoOVA/DOTAP-treated BMDCs increased the levels of IFN-γ produced by OVA-specific T cells. We also observed that rlipoE7m/DOTAP treatment but not rlipoE7m treatment delayed tumor growth. These results indicate that the rlipoprotein/DOTAP formulation can synergistically activate BMDCs via ROS and the TLR2 signaling pathway. In summary, rlipoprotein/DOTAP is a novel and stable formulation for cancer immunotherapy.