Screening of the Active Compounds against Neural Oxidative Damage from Ginseng Phloem Using UPLC-Q-Exactive-MS/MS Coupled with the Content-Effect Weighted Method.

The neuroprotective properties of ginsenosides have been found to reverse the neurological damage caused by oxidation in many neurodegenerative diseases. However, the distribution of ginsenosides in different tissues of the main root, which was regarded as the primary medicinal portion in clinical practice was different, the specific parts and specific components against neural oxidative damage were not clear. The present study aims to screen and determine the potential compounds in different parts of the main root in ginseng. Comparison of the protective effects in the main root, phloem and xylem of ginseng on hydrogen peroxide-induced cell death of SH-SY5Y neurons was investigated. UPLC-Q-Exactive-MS/MS was used to quickly and comprehensively characterize the chemical compositions of the active parts. Network pharmacology combined with a molecular docking approach was employed to virtually screen for disease-related targets and potential active compounds. By comparing the changes before and after Content-Effect weighting, the compounds with stronger anti-nerve oxidative damage activity were screened out more accurately. Finally, the activity of the selected monomer components was verified. The results suggested that the phloem of ginseng was the most effective part. There were 19 effective compounds and 14 core targets, and enriched signaling pathway and biological functions were predicted. After Content-Effect weighting, compounds Ginsenosides F1, Ginsenosides Rf, Ginsenosides Rg1 and Ginsenosides Rd were screened out as potential active compounds against neural oxidative damage. The activity verification study indicated that all four predicted ginsenosides were effective in protecting SH-SY5Y cells from oxidative injury. The four compounds can be further investigated as potential lead compounds for neurodegenerative diseases. This also provides a combined virtual and practical method for the simple and rapid screening of active ingredients in natural products.

In situ encapsulation of SQDs by zinc ion-induced ZIF-8 growth strategy for fluorescent and colorimetric dual-signal detection of alkaline phosphatase.

Controllable encapsulation of sulfur quantum dots (SQDs) into metal-organic frameworks (ZIF-8) by a surface-bound zinc ion-induced growth strategy, and SQDs@ZIF-8 was successfully prepared for alkaline phosphatase (ALP) detection. The new synthesis procedure involves first binding Zn2+ to the surface of SQDs to form SQDs/Zn, and then via zinc ion-induced in situ ZIF-8 growth to obtain SQDs@ZIF-8, which greatly improved the luminous efficiency of SQDs. The specific process of detecting ALP using pH-triggered fluorescence quenching of SQDs@ZIF-8: firstly ALP hydrolyzes 2-phosphate-l-ascorbic acid trisodium salt (AAP) to ascorbic acid (AA), and then the leakage of SQDs in the SQDs@ZIF-8 leads to a decrease in fluorescence intensity based on the destruction of ZIF-8 skeleton by H+ released by AA. A linear relationship was obtained between the fluorescence intensity and the ALP concentration in the range of 0.15-50 U/L, and the detection limit was 0.044 U/L. Moreover, it was found that free SQDs can be complexed with Fe2+ to produce wine red complexes, and the obtained UV absorbance and ALP concentration have a linear relationship in the range of 10-200 U/L. The detection range of ALP is significantly broadened based on the combination of the above two detection methods. Furthermore, SQDs@ZIF-8 exhibited excellent stability in water and was successfully applied to the fluorescence and colorimetric detection of ALP in human serum.

A quantitative comparison of five optical coherence tomography angiography systems in clinical performance.

AIM: To compare the clinical performance of 4 spectral-domain (SD) optical coherence tomography angiography (OCTA) systems: AngioVue™, AngioPlex™, Spectralis® OCTA, AngioScan, and 1 swept-source (SS) OCTA SS OCT Angio™. METHODS: Twenty-seven undilated right eyes of 27 participants underwent OCTA examination using five different systems respectively for both 3×3 and 6×6 mm2 scan pattern (Spectralis OCTA for 3×3 mm2 scan only). Image quality, including vessel valid visibility and the number of motion artifacts, and acquisition time were evaluated. Repeated measures analysis of variance (ANOVA) with Bonferroni's post-test and Friedman test with Dunn's post-test were used to compare measurements. RESULTS: The age of the subjects was 28.19±5.55y (range, 23-49y). The spherical equivalent refraction was -2.55±1.84 D (range, 0.00 to -5.25 D). Significant difference was observed in the evaluation of vessel valid visibility (AngioVue the highest: 0.111±0.031 for 3×3 mm2 scan and 0.128±0.020 for 6×6 mm2 scan), number of motion artifacts (AngioVue the fewest: 0.778±1.086 for 3×3 mm2 scan and 0.333±0.620 for 6×6 mm2 scan) and acquisition time (AngioPlex the shortest: 8.537±1.921s for 3×3 mm2 scan and 8.298±1.741s for 6×6 mm2 scan; all P<0.001). CONCLUSION: There is poor agreement of measurements among systems. AngioVue provides images with the highest vessel valid visibility and the fewest motion artifacts. AngioPlex achieves the shortest acquisition.

MiR-21 Suppresses Anoikis through Targeting PDCD4 and PTEN in Human Esophageal Adenocarcinoma.

Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix. It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis. MiR-21, the most prominent oncomiR, plays an important role in tumor progression. In this study, we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate. Because of the established anti-apoptosis effect of miR-21, it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis. qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased. Also, transfection of miR-21 mimics provided OE33 cells resisting to anoikis. By luciferase assays, we verified that PDCD4 and PTEN were the functional targets of miR-21. In mouse model, via tail vein injection experiment, we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern. Taken together, our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells. Targeting miR-21 may provide a novel strategy to prevent metastasis.

Efficiency and safety of laser photocoagulation with or without intravitreal ranibizumab for treatment of diabetic macular edema: a systematic review and Meta-analysis.

AIM: To compare the therapeutic effect and safety of laser photocoagulation along with intravitreal ranibizumab (IVR) versus laser therapy in treatment of diabetic macular edema (DME). METHODS: Pertinent publications were identified through comprehensive searches of PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov to identify randomized clinical trials (RCTs) comparing IVR+laser to laser monotherapy in patients with DME. Therapeutic effect estimates were determined by weighted mean differences (WMD) of change from baseline in best corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6, 12, or 24mo after initial treatment, and the risk ratios (RR) for the proportions of patients with at least 10 letters of improvement or reduction at 12mo. Data regarding major ocular and nonocular adverse events (AEs) were collected and analyzed. The Review Manager 5.3.5 was used. RESULTS: Six RCTs involving 2069 patients with DME were selected for this Meta-analysis. The results showed that IVR+laser significantly improved BCVA compared with laser at 6mo (WMD: 6.57; 95% CI: 4.37-8.77; P<0.00001), 12mo (WMD: 5.46; 95% CI: 4.35-6.58; P<0.00001), and 24mo (WMD: 3.42; 95% CI: 0.84-5.99; P=0.009) in patients with DME. IVR+laser was superior to laser in reducing CRT at 12mo from baseline with statistical significance (WMD: -63.46; 95% CI: -101.19 to -25.73; P=0.001). The pooled RR results showed that the proportions of patients with at least 10 letters of improvement or reduction were in favor of IVR+laser arms compared with laser (RR: 2.13; 95% CI: 1.77-2.57; P<0.00001 and RR: 0.37; 95% CI: 0.22-0.62; P=0.0002, respectively). As for AEs, the pooled results showed that a significantly higher proportion of patients suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye) in IVR+laser group compared to laser group (RR: 3.29; 95% CI: 1.53-7.09; P=0.002 and RR: 3.02; 95% CI: 1.24-7.32; P=0.01, respectively). The incidence of other ocular and nonocular AEs considered in this Meta-analysis had no statistical difference between IVR+laser and laser alone. CONCLUSION: The results of our analysis show that IVR+laser has better availability in functional (improving BCVA) and anatomic (reducing CRT) outcomes than laser monotherapy for the treatment of DME. However, the patients who received the treatment of IVR+laser may get a higher risk of suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye).

Correlation between different Chinese medicine syndromes and changes in microcirculation in septic shock patients.

OBJECTIVE: To investigate the correlation between different Chinese medicine (CM) syndromes and variations in microcirculation in septic shock patients. METHODS: seventy Septic shock patients were divided into four groups: heat damaging qi-yin group (HDQY, 23 cases); yin exhaustion and yang collapse group (YEYC, 26 cases); excessive heat in Fu organ group (EHFO, 10 cases); and heat damaging nutrient-blood group (HDNB, 11 cases). Sublingual microcirculation parameters were observed by sidestream dark-field (SDF) imaging and scored by Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA), and parameters of microcirculation perfusion variations and prognoses were analyzed. RESULTS: Compared with those with qi-yin heat damage, perfused vessel density (PVD) in other groups decreased dramatically (P<0.05), and APACHE II scores increased significantly (P<0.05). In addition, the recovery time was prolonged substantially (P<0.05), and the mixed venous oxygen saturation (SVO2) decreased (P<0.05). Blood lactic acid increased significantly (P<0.05), and the mixed SVO decreased (P<0.05), in the YEYC group. Compared with the thermal injury camp blood group, sublingual microcirculation parameter variations showed no obvious difference in the YEYC and EHFO groups (P>0.05). There were significant positive correlations between CM syndromes and APACHE II scoring in different groups (r=0.512, P<0.05). There were negative correlations between PVD and APACHE II scoring (r=-0.378, P=0.043), the proportion of perfused vessels (PPV) and APACHE II scoring (r=-0.472, P=0.008), as well as between the microvascular flow index (MFI) and APACHE II scoring (r=-0.424, P=0.023) in different patients. CONCLUSION: Sublingual microcirculation may serve as a clinical diagnostic parameter of the patient condition, as well as being a prognostic indicator.

[The clinical significance of determining the severity and prognosis by monitoring the changes in sublingual microcirculation in patients with severe sepsis].

OBJECTIVE: To investigate the clinical significance of dynamic monitoring of changes in the sublingual microcirculation in patients with severe sepsis to determine the degree of severity of the clinical condition and prognosis. METHODS: A prospective study was conducted. Sixty--five patients in the intensive care unit (ICU) in Beijing Friendship Hospital were enrolled from June 2010 to December 2010, among whom there were 30 cases of sepsis, 35 cases of severe sepsis. The severe sepsis patients received the early goal--directed resuscitation; and at 0 (before treatment), 6, 12, 24, 48, 72 hours after resuscitation, the technology of sidestream dark--field was used to measure the sublingual total vessel density (TVD), perfusing vessel density (PVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) of sublingual microcirculation in patients and acute physiology and chronic health evaluation II (APACHEII) score, ICU days and 28--day mortality were recorded. Thirty healthy individuals were enrolled as the control group. RESULTS: The sublingual PPV and MFI were significantly lower in sepsis patients than those of the control group [PPV: (73.60 ± 16.77)% vs. (85.17 ± 7.60)%; MFI: 3.23 ± 0.77 vs. 3.78 ± 0.35, both P < 0.05]; PVD, PPV, MFI in severe sepsis patients were not only significantly lower than those of the sepsis group {PVD[mm/mm²]: 7.53 ± 4.38 vs.12.15 ± 2.88; PPV: (49.13 ± 33.74)% vs. (73.60 ± 16.77)%; MFI: 2.21 ± 1.41 vs. 3.23 ± 0.77, all P < 0.05}. After the early goal--directed fluid resuscitation, the sublingual microcirculation was improved significantly compared with that before treatment (0 hour), and they were remarkably apparent at 12 hours {TVD[mm/mm²]: 5.76 ± 2.25 vs. 6.72 ± 4.37; PVD [mm/mm²]: 7.57 ± 1.77 vs. 5.48 ± 4.39; PPV:(69.47 ± 19.24)% vs. (34.55 ± 30.82)%; MFI: 3.17 ± 0.49 vs. 1.55 ± 1.14, all P < 0.05}. Compared with the sepsis group, APACHEII score of the severe sepsis group was elevated (24.77 ± 7.45 vs. 19.30 ± 10.36, but P>0.05), the length of stay in ICU (days) was longer (20.60 ± 19.87 vs. 10.33 ± 9.53, P < 0.05), and the 28--day mortality was higher (45.71% vs. 36.36%, but P>0.05). In the severe sepsis group, compared with the survival group (19 cases), the sublingual microcirculation in the non-survival group (16 cases) PVD, PPV, MFI were significantly decreased{PVD[mm/mm²]:6.70 ± 5.15 vs. 8.53 ± 3.13; PPV: (44.23 ± 37.71)% vs. (54.96 ± 28.41)%; MFI: 1.89 ± 1.65 vs. 2.58 ± 0.98, P < 0.05 or P < 0.01}, but APACHEII score and length of stay in ICU (days) were not significantly different (23.19 ± 6.46 vs. 20.31 ± 6.03; 16.13 ± 10.90 vs. 19.19 ± 9.90, both P > 0.05). Correlation analysis showed that: PPV showed a significant negative correlation with the prognosis of the patients (r = -0.374, P < 0.05). CONCLUSION: Sequential monitoring of the sublingual microcirculation in patients with severe sepsis can be used to determine the disease severity, and to forecast the outcome of the patient.