Preparation of Ribes nigrum L. polysaccharides-stabilized selenium nanoparticles for enhancement of the anti-glycation and α-glucosidase inhibitory activities.

Seven kinds of selenium nanoparticles (RP-SeNPs) were prepared by using the polysaccharides extracted from Ribes nigrum L. (RP) as the stabilizer and dispersant. Among them, RP-SeNPs-1 (94.2 nm), RP-SeNPs-2 (101.2 nm) and RP-SeNPs-3 (107.6 nm) with relatively smaller mean particle size exhibited stronger α-glucosidase inhibitory activity than other RP-SeNPs (115.3-164.2 nm) and SeNPs (288.9 nm). Ultraviolet-visible spectrophotometry, Fourier transform-infrared, X-ray diffraction, energy dispersive X-ray and X-ray photoelectron spectroscopy analyses confirmed that SeNPs were ligated with RP to form nanocomposites and displayed amorphous form. Electron microscopy images revealed that RP-SeNPs-1 - RP-SeNPs-3 were regular shape spherical nanocomposites with much better dispersion than SeNPs. Compared with SeNPs, RP-SeNPs displayed relatively high thermal, storage, pH and salt ion stability. Moreover, RP-SeNPs-1-RP-SeNPs-3 showed significantly better anti-glycation and α-glucosidase inhibitory activity than SeNPs, especially RP-SeNPs-1 with the smallest particle size. Inhibitory kinetics analysis indicated that SeNPs and RP-SeNPs inhibited α-glucosidase with competitive type and reversible mechanism. In addition, the conformation of the α-glucosidase was changed after binding with the SeNPs and RP-SeNPs-1. Fluorescence quenching and isothermal titration calorimetry assays revealed that these two nanoparticles could interact with α-glucosidase to form non-fluorescent complexes through hydrogen bonding, and the formation was spontaneously driven by enthalpy.

[Anti-infectious pneumonia target discovery and molecular mechanism study of Jingfang Granules].

This study aimed to identify the direct pharmacological targets of Jingfang Granules in treating infectious pneumonia via "target fishing" strategy. Moreover, the molecular mechanism of Jingfang Granules in treating infectious pneumonia was also investigated based on target-related pharmacological signaling pathways. First, the Jingfang Granules extract-bound magnetic nanoparticles were prepared, which were incubated with lipopolysaccharide(LPS)-induced mouse pneumonia tissue lysates. The captured proteins were analyzed by high-resolution mass spectrometry(HRMS), and the target groups with specific binding to the Jingfang Granules extract were screened out. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis was used to identify the target protein-associated signaling pathways. On this basis, the LPS-induced mouse model of infectious pneumonia was established. The possible biological functions of target proteins were verified by hematoxylin-eosin(HE) staining and immunohistochemical assay. A total of 186 Jingfang Granules-specific binding proteins were identified from lung tissues. KEGG pathway enrichment analysis showed that the target protein-associated signaling pathways mainly included Salmonella infection, vascular and pulmonary epithelial adherens junction, ribosomal viral replication, viral endocytosis, and fatty acid degradation. The target functions of Jingfang Granules were related to pulmonary inflammation and immunity, pulmonary energy metabolism, pulmonary microcirculation, and viral infection. Based on the in vivo inflammation model, Jingfang Granules significantly improved the alveolar structure of the LPS-induced mouse model of infectious pneumonia and down-regulated the expressions of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6). Meanwhile, Jingfang Gra-nules significantly up-regulated the expressions of key proteins of mitochondrial function COX Ⅳ and ATP, microcirculation-related proteins CD31 and Occludin, and proteins associated with viral infection DDX21 and DDX3. These results suggest that Jingfang Gra-nules can inhibit lung inflammation, improve lung energy metabolism and pulmonary microcirculation, resist virus infection, thus playing a protective role in the lung. This study systematically explains the molecular mechanism of Jingfang Granules in the treatment of respiratory inflammation from the perspective of target-signaling pathway-pharmacological efficacy, thereby providing key information for clinical rational use of Jingfang Granules and expanding potential pharmacological application.

Probiotics protect against hepatic steatosis in tris (2-chloroethyl) phosphate-induced metabolic disorder of mice via FXR signaling.

Tris (2-chloroethyl) phosphate (TCEP), the most widely useful and most frequently detective organophosphate flame retardants in environment, has been shown potential relationship with adolescent weight. Probiotics is an effective therapy for metabolic diseases such as obesity and NAFLD with gut microbiota dysregulation. This study aims to explore the protective effects of probiotics against lipid metabolic disorder induced by chronic TCEP exposure and demonstrate the mechanism of this event. The data showed that dietary complex probiotics supplement attenuated TCEP-induced obesity, hyperlipidemia, liver dysfunction, and hepatic steatosis. In addition, dietary complex probiotics suppressed TCEP-promoted ileal FXR signaling, and upregulated hepatic FXR/SHP pathway inhibited by TCEP. Moreover, dietary complex probiotics stimulated PPARα-mediated lipid oxidation and suppressed SREBP1c/PPARγ-mediated lipid synthesis via regulation of FXR signaling. Therefore, this study indicates that dietary complex probiotics could protect against hepatic steatosis via FXR-mediated signaling pathway in TCEP-induced metabolism disorder in mice, resulting in attenuation of systemic lipid accumulation.

Carbon Quantum Dots-Based Nanozyme from Coffee Induces Cancer Cell Ferroptosis to Activate Antitumor Immunity.

Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared to natural enzymes. Thus, discovery of CQDs-based nanozymes with low toxicity from natural resources, especially daily food, implies a promising direction for exploring treatment strategies for human diseases. Here, we report a CQDs-based biocompatible nanozyme prepared from chlorogenic acid (ChA), a major bioactive natural product from coffee. We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation of GPX4-catalyzed lipid repair systems. In vivo, ChA CQDs dramatically suppressed the tumor growth in HepG2-tumor-bearing mice with negligible side toxicity. Particularly, in hepatoma H22-bearing mice, ChA CQDs recruited massive tumor-infiltrating immune cells including T cells, NK cells, and macrophages, thereby converting "cold" to "hot" tumors for activating systemic antitumor immune responses. Taken together, our study suggests that natural product-derived CQDs from coffee can serve as biologically safe nanozymes for anticancer therapeutics and may aid the development of nanotechnology-based immunotherapeutic.

Global identification of the cellular targets for a multi-molecule system by a photochemically-induced coupling reaction.

Current target identification strategies mainly focus on single compounds. However, no practical experimental methodologies have been developed for multi-molecule systems. Herein, we established a cellular target identification technology for a multi-molecule system by preparing 4,4'-dihydroxybenzophenone (DHBP)-bound Fe3O4 nanoparticles (NPs) with photochemically induced crosslinking capacity. DHBP-bound NPs reacted with the chemicals from the medicinal plant extract as a multi-molecule system under ultraviolet radiation by forming carbon-carbon bonds, thus generating extract-crosslinked NPs for capturing target proteins from cell lysates. The technology, which is named the Zhao-Yao (ZY) strategy, may promote the comprehensive interpretation of the pharmacological mechanism of multi-molecule systems via the global identification of cellular targets.

Characterization of selenized polysaccharides from Ribes nigrum L. and its inhibitory effects on α-amylase and α-glucosidase.

The polysaccharide from Ribes nigrum L. (RCP) was modified by nitric acid-sodium selenite method. After purification by Sepharose-6B, high purity native (PRCP) and three selenized polysaccharides (PRSPs) with different selenium contents were obtained. Compared with PRCP, PRSPs possessed the lower molecular weight, better water-solubility, physical stability and rheological properties. FT-IR and NMR spectra confirmed PRSPs had the characteristic absorption peaks of polysaccharides and the glycosidic bond types were not changed after selenylation modification, whereas the selenyl groups existing in PRSPs were mainly introduced at the C-6 position of sugar residue →4)-ß-d-Manp-(1→. Moreover, PRSPs displayed obviously smoother and smaller flaky structure than PRCP, and their inhibitory effects on α-amylase and α-glucosidase also were greater than PRCP. PRSPs exhibited a reversible inhibition on two enzymes in competitive manner and quenched their fluorescence through the static quenching mechanism. The polysaccharide-enzyme complex was spontaneously formed mainly driven by the hydrophobic interaction and hydrogen bonding.

Effect and safety of acupotomy in treatment of knee osteoarthritis: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the clinical efficacy and safety of acupotomy in treatment of knee osteoarthritis (OA). METHODS: Extensive literature searches were carried out in PubMed, EMBASE, Cochrane Library (Issue 5, 2017), Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, China Science and Technology Journal Database and Wanfang Database. All databases were retrieved from their inception until May 31, 2017. Randomized controlled trials incorporating acupotomy versus intra-articular sodium hyaluronate for knee osteoarthritis were included. According to Cochrane Reviews' Handbook (5.2), two reviewers screened each article and extracted data independently and were blinded to the findings of each reviewer. Meta-analysis was performed by the Cochrane Collaboration's RevMan 5.3 software. RESULTS: We identified 12 studies involving 1150 patients aged between 40 and 78 years old. The pooled analysis indicated that acupotomy showed a significant improvement for short-term effect [cure rate: odds ratio (OR) = 2.04, 95% confidence interval (CI) (1.46, 2.85), P < 0.01; total effective rate: OR = 2.25, 95% CI (1.55, 3.28), P < 0.01; pain score: standard mean difference (SMD) = －1.02; 95% CI (－1.72, －0.31); P = 0.005; Western Ontario and McMaster Universities Questionnaire (WOMAC) score: SMD = －0.74; 95% CI (－1.11, －0.37); P < 0.01]; and also for long-term effect [total effective rate: OR = 2.99, 95%CI (1.88, 4.76), Z = 4.64, P < 0.01; pain score: SMD = －1.68; 95% CI (－2.14, －1.22); P < 0.001; WOMAC score: SMD = －0.91; 95% CI (－1.40, －0.41); P < 0.001]. In addition, there was no obvious difference between acupotomy group and control group in adverse events [OR = 2.13, 95%CI (0.14, 32.28), P = 0.58]. CONCLUSION: Acupotomy is a safe and effective treatment for KOA. However, due to the methodological deficiency of the included studies, well-designed randomized controlled trials are required to further confirm the findings.

Preparation, characteristics, and antioxidant activities of carboxymethylated polysaccharides from blackcurrant fruits.

In the present study, the native polysaccharide (RNP) extracted from blackcurrant fruits was carboxymethylated. Physicochemical characteristics and antioxidant activities in vitro of RNP and three carboxymethylated polysaccharides (CRNPs) were determined. GC analysis proved that RNP and CRNPs were composed of the same six monosaccharides (galacturonic acid, rhamnose, arabinose, mannose, glucose and galactose), but the molar ratios of monosaccharides were different. HPLC demonstrated that the molecular weights of CRNPs were improved. The assays of the antioxidant properties indicated that CRNPs possessed stronger scavenging activities on radicals (hydroxyl and superoxide radicals) and better anti-lipid peroxidation activities, as well as better protection effects on erythrocyte hemolyses in vitro compared with RNP. The activities of CRNPs were significantly enhanced with the increase of the degree of substitution (DS). These results proved that the carboxymethylation could effectively increase the antioxidant activities of the polysaccharide.

Acupotomy Therapy for Chronic Nonspecific Neck Pain: A Systematic Review and Meta-Analysis.

OBJECTIVE: This review is to assess the efficacy and safety of acupotomy therapy in chronic nonspecific neck pain. METHODS: We searched six computerised databases. Randomized controlled trials incorporating acupotomy therapy alone or combined with other conventional treatments for chronic nonspecific neck pain were included. Two reviewers screened each literature and extracted data independently according to Cochrane Reviews' Handbook (5.1). The Cochrane Collaboration's RevMan 5.3 software was applied for meta-analysis. RESULTS: A total of ten trials involving 433 patients were enrolled. The pooled analysis indicated that acupotomy therapy showed a significant improving short-term and long-term effect on effective rate and cure rate. Meta-analysis demonstrated that acupotomy therapy group was superior to control group in restoring cervical lordosis and debasing VAS score. The result of continuous data did not support statistical significance of acupotomy therapy in adjusting clinical symptom score. For adverse events, acupotomy group did not reveal obvious superiority compared to control group. CONCLUSIONS: Acupotomy therapy may be beneficial to chronic nonspecific neck pain patients. To strengthen supportive evidence, future, more rigorously designed clinical trials, adequate adverse events, and follow-up project are recommended.

Traditional Uses, Chemical Constituents and Biological Activities of Plants from the Genus Sanguisorba L.

Plants from the genus Sanguisorba have been treated as medicinal ingredients for over 2000 years. This paper reviews advances in the botanical, phytochemical and pharmacological studies of the genus. To date, more than 120 chemical constituents have been isolated and identified from these plants, especially from S. officinalis and S. minor. Among these compounds, triterpenoids, phenols and flavonoids are the primary biologically active constituents. Triterpenoids can be used as quality control markers to determine the quality of medicinal materials and their preparations. In vivo and in vitro studies have shown that plants from the genus Sanguisorba exhibit a wide range of pharmacological properties, including hemostatic, antibacterial, antitumor, neuroprotective and hypoglycemic activities. In Chinese medical practice, many drugs (e.g., tablets and powders) that contain S. officinalis roots have been used to treat leukopenia, hemorrhaging and burns. However, there is still a multitude of Sanguisorba species that have garnered little or no attention. Indeed, there are few reports concerning the clinical use and toxic effects of these plants. Further attention should be focused on the study of these species in order to gather information on their respective toxicology data, any relevant quality-control measures, and the clinical value of the crude extracts, active compounds, and bioactive metabolites from Genus Sanguisorba.