H2O2/pH Dual-Responsive Biomimetic Nanoenzyme Drugs Delivery System for Enhanced Tumor Photodynamic Therapy.

Phototherapy has been recognized as a photochemical process to treat tumor via induce cancer cells necrosis and death, with minimal invasiveness, higher selectivity, and few side effects. However, the therapy effects of phototherapy are often compromised by the hypoxia, high levels of hydrogen peroxide, and glutathione of tumor microenvironment (TME). Therefore, we constructed a catalase-like activity bionic metal-organic framework drugs delivery system (FA-EM@MnO2/ZIF-8/ICG) with tumor microenvironment controllable releasing. In this system, photosensitizer indocyanine green (ICG) was introduced into zeolite imidazole salt skeleton 8 (ZIF-8) by one-step methods, forming ZIF-8/ICG nano-platform, which can effectively avoid ICG-induced phototoxicity and aggregation-induced quenching during transport. MnO2 with catalase-like activity was coated on the surface of ZIF-8/ICG nano-platform, which made it have the ability of self-supplying O2 under the condition of H2O2 in TME. Exposure under near-infrared light can alleviate the anoxic TME, thus improving the phototherapy efficiency. In addition, folate-functionalized erythrocyte membrane is coated on the surface of MnO2/ZIF-8/ICG, which can endow FA-EM@MnO2/ZIF-8/ICG with the ability of targeted drug administration and immune elimination avoidance. Therefore, FA-EM@MnO2/ZIF-8/ICG nano-platform has the catalase-like activity, which can alleviate the oxidative stress state of TME and provide a beneficial environment for photodynamic therapy of tumor.

Existing form and distribution of fluorine and phosphorus in phosphate rock acid-insoluble residue.

The phosphorus-sulfur two-step production process was developed in the wet-process phosphoric acid industry to solve phosphogypsum pollution. However, phosphate rock acid-insoluble residue is produced during this process as a new type of solid waste, which had a high potential for recycling. For process reasons, this type of residue still contains a certain amount of fluorine and phosphorus, which has a massive impact on the potential uses of phosphate rock acid-insoluble residue. Therefore, X-ray photoelectron spectroscopy, Raman, electron probe spectroscopy, and scanning electron microscopy were used to examine the existing form and distribution of fluorine and phosphorus in phosphate rock acid-insoluble residue. The mass fraction of F and P2O5 were 9.407% and 11.862%, respectively. Fluorine existed mainly in the form of fluorite, fluorapatite and metal fluoride. Phosphorus existed mainly in the form of fluoroapatite, phosphate, hydrogen phosphate, and dihydrogen phosphate. The total phosphate, hydrogen phosphate and dihydrogen phosphate contents were much higher than that of fluoroapatite, whereas the fluoroapatite content was higher than that of fluorite and metal fluoride. Fluorine and phosphorus were distributed in the form of agglomerates in the phosphate rock acid-insoluble residue. Fluorine and phosphorus were partially correlated, showing a weak relationship in the high phosphorus area.

Investigation on the Q-markers of Bushen Huoxue Prescriptions for DR treatment based on chemometric methods and spectrum-effect relationship.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic retinopathy (DR) is a kind of complex complication of late diabetes mellitus with high incidence and risk of blindness. Bushen Huoxue Prescription (BHP), which consists of Rehmanniae radix (RR), Salviae miltiorrhizae radix et rhizoma (SMRR), Ginseng radix et rhizome (GRR) and Puerariae lobatae radix (PLR), has an active effect on the treatment of DR. However, the quality markers (Q-markers) of BHP are not entirely clear. PURPOSE: This study aimed to screen the Q-markers of BHP for DR treatment based on the establishment of spectrum-effect relationship and verified experiment. MATERIALS AND METHODS: In this study, 12 BHP samples (S1-S12) for fingerprint analysis and pharmacological evaluation were prepared according to a four-factor and twelve-level uniform design. High performance liquid chromatography-ultraviolet detector-evaporative light scattering detector (HPLC-UV-ELSD) was employed to analyze the fingerprint on the basis of the characteristics of BHP components. The evaluation of sample similarity was carried out by similarity analysis (SA) and hierarchical cluster analysis (HCA). The pharmacological indicators, including expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in the retina of Sprague Dawley (SD) rats induced by streptozotocin (STZ), were detected by enzyme-linked immunosorbent assay (ELISA). Besides, the spectrum-effect relationship between common peaks of fingerprints and the pharmacological results was investigated by partial least squares regression (PLSR) and canonical correlation analysis (CCA). The results of spectrum-effect relationship were verified by the expression of VEGF and HIF-1α on primary culture retinal Müller cells induced by hyperglycemia and hypoxia. RESULTS: In the HPLC-UV-ELSD fingerprint, 23 common peaks in UV and 14 common peaks in ELSD were identified. The pharmacological results indicated that the expression of VEGF and HIF-1α in the retina of SD rats was inhibited by 12 BHP samples to varying degrees compared with the model group. Based on SA and heatmap of HCA, S4 and S8 were clearly distinguished from other samples. The results of PLSR and CCA revealed that the contents of puerarin, daidzin, salvianolic acid B and ginsenoside Rb1 were inversely correlated with the expression of VEGF and HIF-1α. Hence, the four compounds may be the main active components to prevent and treat DR. The results of intervention on primary culture retinal Müller cells showed that puerarin, daidzin, salvianolic acid B, and ginsenoside Rb1 can significantly inhibit the expression of VEGF and HIF-1α. CONCLUSIONS: The spectrum-effect relationship of BHP was successfully established, and the Q-markers of BHP for the prevention and treatment of DR were preliminarily confirmed. It provides a feasible method for the research of quality control.

Simultaneous determination of six main components in Bushen Huoxue prescription by HPLC-CAD.

BACKGROUND: The Bushen Huoxue prescription is a traditional Chinese medicine formula treating diabetic retinopathy, which was developed by our research group. Catalpol, puerarin, salvianolic acid B, ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rd are six of main effective components, which could be partly representative of this prescription. The corona charged aerosol detector (corona CAD) is one kind of universal detectors equipped with the high performance liquid chromatography (HPLC). The CAD has many advantages for the analysis of complex mixtures, but too few applications in traditional Chinese medicine compounds. OBJECTIVE: The aims of this study are to establish a method for the determination of six components in Bushen Huoxue prescription, and to increase the use of the CAD in traditional Chinese medicine compounds. METHODS: HPLC-CAD analysis was performed on an Inertsil ODS-SP (4.6 mm × 250 mm, 5 µm) with a mobile phase consisting of 0.5 % formic acid solution(A)-acetonitrile(B) at a flow rate of 1 mL/min (0-7 min, 1 % B; 7-12 min, 1 %-12 % B; 12-22 min, 12 %-19 % B; 22-40 min, 19 %-28 % B; 40-43 min, 28 %-33 % B; 43-50 min, 33 % B; 50-65 min, 33 %-42 % B). The column temperature maintained at 30 ℃, the injection volume was 20 µL, the atomization temperature mode was LOW, the filtration constant (filter) was 3.6 and data collection rate was 10 Hz. The methodology was examined and the linearity of regression of different functions was compared. Sixteen batches of samples were prepared and their contents were determined. RESULTS: The six compounds showed a better linearity (R2 > 0.9990) in their concentration ranges when using the linear function. The average recoveries were 99.18 %-101.30 %. Although the RSD value of puerarin and ginsenoside Rg1 was slightly out of 3 % during the average recovery investigation, all the other methodological investigations of the six components were within 3 %. The precision, stability and repeatability of the method were good. In sixteen batches of Bushen Huoxue prescription samples, the contents of six components were 0.3138 %-0.6042 % for catalpol, 0.8095 %-1.2917 % for puerarin, 0.7416 %-1.1189 % for salvianolic acid B, 0.0231 %-0.0418 % for ginsenoside Rg1, 0.0702 %-0.1724 % for ginsenoside Rb1, 0.0384 %-0.1196 % for ginsenoside Rd. CONCLUSION: In this experiment, a method for the determination of six components in Bushen Huoxue prescription based on HPLC-CAD was established with high accuracy, good repeatability and simple operation, and it can provide references for the improvement of quality standard of the Bushen Huoxue prescription. It is reasonable and accessible for the CAD application in the determination of traditional Chinese medicine compound prescriptions.

Assessment of the Effectiveness of Vitamin Supplement in Treating Eczema: A Systematic Review and Meta-Analysis.

BACKGROUND: The morbidity of eczema has increased in the recent years, and the methods to prevent or ameliorate its effects are becoming more important. To this end, this research was conducted to determine the effectiveness of vitamin supplements in eczema therapy. METHOD: Embase, PubMed, and Cochrane Central Register of Clinical Trials were searched. Only randomized controlled trials were included, and we included all quantified eligible data where the SCORing Atopic Dermatitis (SCORAD) Index or Eczema Area and Severity Index (EASI) scores were applied to assess the severity of eczema. RESULTS: Ten studies fulfilled the inclusion criteria, and eight of them were included for quantitative analysis (total: 456 patients). Compared to the controls, the SCORAD index or EASI decreased in the vitamin supplement group (mean difference -5.96, 95% CI: -7.69 to -4.23 for vitamin D3; mean difference -5.72, 95% CI: -11.41 to -0.03 for vitamin E; and mean difference -3.19, 95% CI: -4.27 to -2.10 for vitamin B12). CONCLUSION: This study suggests that vitamin supplements could be important therapeutics to help manage eczema patients.