Rational design of CT-coupled J-aggregation platform based on Aza-BODIPY for highly efficient phototherapy.

Supramolecular engineering is exceptionally appealing in the design of functional materials, and J-aggregates resulting from noncovalent interactions offer intriguing features. However, building J-aggregation platforms remains a significant challenge. Herein, we report 3,5-dithienyl Aza-BODIPYs with a donor-acceptor-donor (D-A-D) architecture as the first charge transfer (CT)-coupled J-aggregation BODIPY-type platform. The core acceptor moieties in one molecule interact with donor units in neighboring molecules to generate slip-stacked packing motifs, resulting in CT-coupled J-aggregation with a redshifted wavelength up to 886 nm and an absorption tail over 1100 nm. The J-aggregates show significant photoacoustic signals and high photothermal conversion efficiency of 66%. The results obtained in vivo show that the J-aggregates have the potential to be used for tumor photothermal ablation and photoacoustic imaging. This study not only demonstrates Aza-BODIPY with D-A-D as a novel CT-coupled J-aggregation platform for NIR phototherapy materials but also motivates further study on the design of J-aggregation.

Identification of Fangji Huangqi Tang as a potential herbal formula for Sjogren syndrome treatment via network pharmacology and experimental validation.

Fangji Huangqi Tang (FHT) is a well-known Chinese herbal formula that is prescribed as treatment for rheumatoid diseases. In this study, we aimed to investigate the potential therapeutic targets, efficacy, and safety of FHT in the treatment of Sjogren's syndrome (SS). The Gene Expression Omnibus (GEO) database was used to screen differentially expressed genes (DEGs) in SS. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential biological functions of the DEGs. Subsequently, an FHT-herb-active compound-target network was constructed to identify the relationship between the active compounds in FHT and the related targets. Then, enrichment analysis involving the DEGs and protein-protein interaction (PPI) network analysis were performed to analyze the biological functions of potential targets and screen hub genes. Further, molecular docking was employed to verify the binding affinity between the active compounds and the hub targets, and in vivo experiments involving NOD/LtJ mice were conducted to verify the therapeutic effects of FHT on SS-like symptoms. Finally, inhibition of PIK3CK/Akt pathway by FHT was validated by WB and rt-qPCR. A total of 1836 DEGs were identified in SS based on the GSE159574 dataset, and 114 targets of the active compounds in FHT were screened. Further, via network pharmacology analysis and molecular docking, six active compounds and five hub targets were obtained, and enrichment analysis showed that the anti-SS effect of FHT was predominantly associated with immune cells, such as T cells and neutrophils. In vivo, FHT effectively reduced lymphocyte infiltration foci, increased saliva flow rate, and inhibited increases in the levels of SS-related autoantibodies (anti-SSA and anti-SSB). Furthermore, the biosafety of FHT was verified via the serological examination of liver and kidney function. WB and rt-qPCR analysis confirmed that FHT could inhibit the expression of PIK3CG and the activation of PIK3CG/Akt pathway. Via network pharmacological analysis, molecular docking, and in vivo verification, we demonstrated the multicomponent and multitarget characteristics of FHT in SS treatment, thereby providing novel insights into the pathogenesis of SS and the therapeutic targets of FHT for SS.

Time-Series-Dependent Global Data Filtering Strategy for Mining and Profiling of Xenobiotic Metabolites in a Dynamic Complex Matrix: Application to Biotransformation of Flavonoids in the Extract of Ginkgo biloba by Gut Microbiota.

Efficient characterization of xenobiotic metabolites and their dynamics in a changing complex matrix remains difficult. Herein, we proposed a time-series-dependent global data filtering strategy for the rapid and comprehensive characterization of xenobiotic metabolites and their dynamic variation based on metabolome data. A set of data preprocessing methods was used to screen potential xenobiotic metabolites, considering the differences between the treated and control groups and the fluctuations over time. To further identify metabolites of the target, an in-house accurate mass database was constructed by potential metabolic pathways and applied. Taking the extract of Ginkgo biloba (EGB) co-incubated with gut microbiota as an example, 107 compounds were identified as flavonoid-derived metabolites (including 67 original from EGB and 40 new) from 7468 ions. Their temporal metabolic profiles and regularities were also investigated. This study provided a systematic and feasible method to elucidate and profile xenobiotic metabolism.

[Mechanism of acupuncture and moxibustion in treatment of chronic fatigue syndrome from perspective of intestinal flora].

Intestinal flora dysbiosis may play an important role in the occurrence and development of chronic fatigue syndrome (CFS), which may induce the inflammatory response and metabolic disturbance of patients with CFS. Acupuncture and moxibustion may achieve anti-fatigue effect by affecting the diversity and quantity of intestinal flora, improving intestinal barrier function, and regulating brain-gut peptides.

Protective effect of rhaponticin on ovariectomy-induced osteoporosis in rats.

Rhaponticin is a constituent isolated from numerous medicinal herbs. It has been reported earlier that rhaponticin possesses numerous biological effects like antiallergic, antidiabetic, hepatoprotective, and antithrombosis. The goal of this exploration was to scrutinize the therapeutic potential of rhaponticin on ovariectomy (OVX)-triggered osteoporosis in rats. Female Sprague Dawley rats were arbitrarily allocated to a sham-operated control group I, group II, which underwent OVX, and groups III and IV that underwent OVX were administered with rhaponticin (10 and 20 mg/kg). Rhaponticin was supplemented orally after 4 weeks of OVX and continued for about 16 weeks. Our findings exhibit that rhaponticin prevented the BMD diminution of femurs, induced by OVX, and protected the worsening of trabecular microarchitecture that are assisted through a noteworthy decline in skeletal remodeling as noticed through the diminished status of bone markers in a dose-dependent manner (10 and 20 mg/kg). OVX rats treated with rhaponticin efficiently enhanced body weight, lipid profiles, uterine index, bone turnover markers, inflammatory markers, and augmented the incidence of calcium in the OVX rats. Rhaponticin was established to restrain the functions of acid phosphatase, estradiol, and bone gla protein in OVX rats. Also, rhaponticin displayed some beneficial effects on histomorphometric and histopathological examination. It was observed that tabular area and thickness were reinstated in sham control and rhaponticin-treated OVX rats. We recognized that rhaponticin did not induce a damaging outcome on the skeletal organization of OVX rats. Moreover, we denote that rhaponticin can be an exceptional agent for the treatment and deal with associated bone diseases.

Cerebral areas affected by unilateral acupuncture on SP3 in healthy volunteers: An explorative resting-state fMRI study.

OBJECTIVE: The study aimed to explore the cerebral areas with changes in regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) values induced by effective acupuncture on the Taibai (SP3) point. METHODS: In the study, 15 healthy right-handed volunteers (seven males and eight females, 20-35 years old) were enrolled. The average ages of the subjects were 28.0 ± 4.24 years for males and 27.4 ± 3.65 years for females. A 3.0T magnetic resonance imaging (MRI) system was used to perform resting-state functional MRI scan after sham and effective acupuncture on the SP3 point. The differences in cerebral ReHo and ALFF values between posteffective acupuncture and postsham acupuncture were compared using the SPM 12 software. RESULTS: ReHo values of bilateral BA18, cuneus, and BA17, along with BA41, BA22, postcentral gyrus, and BA7 on the right side, were decreased by effective SP3 acupuncture. The ALFF values of bilateral BA 30 and left parahippocampal area were increased, whereas the values of bilateral BA18, BA19, cuneus, posterior cingulate gyrus, and BA7, along with the right superior occipital lobule, postcentral gyrus, and left precuneus, were decreased. CONCLUSIONS: The most dominant cerebral areas affected by SP3 acupuncture were bilateral visual-related cortices (lingual gyrus, cuneus, and calcarine), along with the unilateral postcentral gyrus and superior parietal lobule. These findings may be potential explanations for the available clinical reports concerning the efficacy of SP3 acupuncture. Further clinical and experimental studies on SP3 acupuncture are required.

[Phytochemistry of Cannabis sativa and its variation in different types].

Cannabis sativa, also known as marijuana or hemp, is an annual herb which belongs to Cannabinaceae family. It is often dioecious, originally produced in Central Asia and now is widely distributed in the world, wild or cultivated, with many varieties. As an ancient plant, C.sativa has been used for thousands of years, and its fiber has been used in many aspects, but it is also widely disputed because it contains tetrahydrocannabinol(THC), a psychoactive ingredient. It has been listed as one of the three major drugs by "United Nations Drug Convention", along with heroin and cocaine. Nowadays, with the deepening and comprehensive understanding of C.sativa, it has been widely studied because of its great economic value in the fields of textile, chemicals for daily use, medicine and so on. In this paper, the literature about the chemical compositios and species variation of C.sativa at home and abroad was reviewed in order to provide some reference for its researches.

Comprehensive chemical profiling of Jia-Wei-Qi-Fu-Yin and its network pharmacology-based analysis on Alzheimer's disease.

Jia-Wei-Qi-Fu-Yin (JWQFY) is a newly developed anti-Alzheimer's disease (AD) prescription modified from a classical traditional Chinese medicine formula, Qi-Fu-Yin (QFY). However, a systematic understanding of its chemical constituents and molecular mechanisms is still elusive. To address this problem, comprehensive chemical profiling followed by network pharmacology-based analysis of JWQFY was performed. Firstly, a total of 136 compounds were characterized by high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF MS), 17 of them were specifically identified in JWQFY comparing with QFY. Seventy compounds were further quantified via a validated HPLC coupled with triple quadrupole tandem mass spectrometry (QQQ MS) method. Then the protein targets of the seventy compounds were gathered from public databases for network construction. As a result, fifty-seven compounds were filtered, which interacted with 655 targets. Thirty-four of them were mapped into the KEGG pathway of AD, indicating JWQFY might exert anti-AD effects by anti-inflammation, neuronal apoptosis intervening, Aß production inhibition and phosphorylating tau protein moderating. Furthermore, in the compound-target-AD network, a list of hub compounds and hub targets was identified based on their topological features, including the degree, node betweenness and closeness. Four of the hub compounds were specifically originated from JWQFY, supporting the modification rationality of this formula. This study provided a scientific basis for understanding the bioactive compounds and the multi-target mechanism of JWQFY.

A modified data filtering strategy for targeted characterization of polymers in complex matrixes using drift tube ion mobility-mass spectrometry: Application to analysis of procyanidins in the grape seed extracts.

BACKGROUNDS: Polymers, widely existing in food or dietary materials, have been attracting researchers, facing challenges, and needing effective strategies on targeted characterization in complex matrixes. METHODS: A modified data filtering strategy (including locating with drift time and m/z ranges, multiple mass defect filtering, validating MS information, and evaluating MS/MS spectra) was developed and applied for procyanidins in the grape seed extracts (GSE) using drift tube ion mobility-mass spectrometry. The procyanidin ions' trendlines were predicted by multi-model regression. Their collision cross-sections (CCSs) were calculated using single-field methods. RESULTS AND DISCUSSION: Totally, 769 CCSs belonging to 686 procyanidins with polymer degrees at 1-15 were characterized. The exponent regression was the most reasonable model (r2 ≥ 0.9379) to reveal the trendlines. The change tendency of CCSs with their polymer degrees, charge states, and linkage types were investigated. CONCLUSION: This study provided an innovative strategy for targeted characterization of polymers in complex matrixes.

A strategy for screening bioactive components from natural products based on two-dimensional cell membrane chromatography and component-knockout approach.

Cell membrane chromatography (CMC) is a bioaffinity chromatographic method used to screen active compounds from natural products. However, since the receptor capacity of CMC column is limited, high content/affinity compounds may cause column overloading and thus lead to ignorance of other positive candidates. For avoiding this effect and comprehensively discovering bioactive components, a strategy based on two-dimensional CMC and component-knockout approach was proposed. As an illustrative case study, red yeast rice (RYR), a rice product with good myocardial protective effect in clinical studies, was selected as the model experimental sample. For discovering its potential cardioprotective compounds, a CMC model with H9c2 rat cardiac myoblasts (H9c2/CMC) with good selectivity, stability and reproducibility was established. By using two-dimensional H9c2/CMC-HPLC coupled with QTOF MS system, three components were firstly screened out. After knocking out high content/affinity compound, another four bioactive compounds were then found. By this two-round screening, column overloading caused by high concentration or infinity compounds was avoided, and trace compounds were enriched. As a result, one pigment and six monacolins from RYR were fished out. The results indicate the proposed strategy might be used to discover active compounds from complex matrix.

Formononetin Enhances the Tumoricidal Effect of Everolimus in Breast Cancer MDA-MB-468 Cells by Suppressing the mTOR Pathway.

BACKGROUND: Formononetin, an active ingredient isolated from the traditional Chinese medicinal herb Astragalus membranaceus, has anticancer and chemoresistance-reducing biological activities. We evaluated the efficacy of formononetin in improving the tumoricidal effect of everolimus by suppressing the mTOR pathway in breast cancer cells. METHODS: Cell survival was assessed using an MTT assay. Apoptosis was detected using flow cytometry. Proteins related to the mTOR pathway were detected and assessed using real-time PCR and Western blot analysis. Results. The results showed that formononetin enhances the efficacy of everolimus in suppressing breast cancer cell growth both in vitro and in vivo. The combination of formononetin and everolimus resulted in a 2-fold decrease in tumor volume and a 21.6% decrease in cell survival. The apoptosis ratio in cells treated with formononetin and everolimus increased by 27.9%. Formononetin and everolimus also inhibited the expression of p-mTOR and p-P70S6K and increased the expression of PTEN and p-4EBP-1. Notably, formononetin alone inhibited p-Akt expression but not everolimus. CONCLUSIONS: Formononetin enhances the tumoricidal effect of everolimus by inhibiting the activity of Akt.

Rapid characterization of chemical markers for discrimination of Moutan Cortex and its processed products by direct injection-based mass spectrometry profiling and metabolomic method.

BACKGROUND: Processing of herbal medicines is a characteristic pharmaceutical technique in Traditional Chinese Medicine, which can reduce toxicity and side effect, improve the flavor and efficacy, and even change the pharmacological action entirely. It is significant and crucial to perform a method to find chemical markers for differentiating herbal medicines in different processed degrees. PURPOSE: The aim of this study was to perform a rapid and reasonable method to discriminate Moutan Cortex and its processed products, and to reveal the characteristics of chemical components depend on chemical markers. METHODS: Thirty batches of Moutan Cortex and its processed products, including 11 batches of Raw Moutan Cortex (RMC), 9 batches of Moutan Cortex Tostus (MCT) and 10 batches of Moutan Cortex Carbonisatus (MCC), were directly injected in electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOF MS) for rapid analysis in positive and negative mode. Without chromatographic separation, each run was completed within 3 min. The raw MS data were automatically extracted by background deduction and molecular feature (MF) extraction algorithm. In negative mode, a total of 452 MFs were obtained and then pretreated by data filtration and differential analysis. After that, the filtered 85 MFs were treated by principal component analysis (PCA) to reduce the dimensions. Subsequently, a partial least squares discrimination analysis (PLS-DA) model was constructed for differentiation and chemical markers detection of Moutan Cortex in different processed degrees. The positive mode data were treated as same as those in negative mode. RESULTS: RMC, MCT and MCC were successfully classified. Moreover, 14 and 3 chemical markers from negative and positive mode respectively, were screened by the combination of their relative peak areas and the parameter variable importance in the projection (VIP) values in PLS-DA model. The content changes of these chemical markers were employed in order to illustrate chemical changes of Moutan Cortex after processed. CONCLUSION: These results showed that the proposed method which combined non-targeted metabolomics analysis with multivariate statistics analysis is reasonable and effective. It could not only be applied to discriminate herbal medicines and their processing products, but also to reveal the characteristics of chemical components during processing.

An UPLC-MS/MS method for simultaneous determination of multiple constituents in Guizhi Fuling capsule with ultrafast positive/negative ionization switching.

Guizhi Fuling capsule (GFC), a traditional Chinese medicine (TCM) with effects of promoting blood circulation and dissipating blood stasis, has been widely used in the clinic. Because of the complex matrix and various chemical structure types, quality control of GFC remains great challenge. In the present study, an ultra performance liquid chromatography hybrid triple-quadrupole mass spectrometry (UPLC-QQQ MS) method with ultrafast positive/negative ionization switching was developed for simultaneous determination of 18 bioactive components in GFC, including methyl gallate, ethyl gallate, oxypaeoniflorin, benzoic acid, albiflorin, paeonolide, paeoniflorin, 1, 2, 3, 4, 6-pentagalloylglucose, mudanpioside C, benzoyloxypaeoniflorin, benzoylpaeoniflorin, pachymic acid, amygdalin, cinnamaldehyde, paeonol, cinnamic acid, 4-hydroxybenzoic acid, and gallic acid. Separation was performed on an Agilent Zorbax Extend-C18 column (2.1 mm × 50 mm, 1.8 µm), using a gradient elution with acetonitrile and water containing 0.1% formic acid. Cholic acid was selected as the internal standard. This newly developed method was fully validated for linearity, precision, accuracy, and stability, and then applied to quality assessment of GFC. Finally, the batch-to-batch reproducibility of GFC samples was evaluated by the cosine ration and Euclidean distance method, which showed high quality consistency. The results demonstrated that the developed method pro vided a reasonable and powerful manner for quality control of GFC.

Multivariable optimization of the micellar system for the ionic liquid-modified MEKC separation of phenolic acids.

An ionic liquid (IL)-modified micellar electrokinetic chromatography (MEKC) method was proposed for the separation and determination of eight phenolic acids. In order to increase separation efficiency and selectivity, the micelle system consisting of aqueous mixtures of ILs, Tween 20 and borate was optimized using a D-optimal design. A 16-run experimental plan was carried out. The results indicated that the addition of ILs in background electrolyte could significantly alter the electrophoretic behavior and improve the resolution of target analytes. By evaluating the electropherograms obtained, a satisfactory separation condition for all analytes was achieved in 10min with optimized buffer composed of 0.70% (w/w) 1-butyl-3-methylimidazolium tetrafluoroborate, 8.1% (w/w) polyoxyethylene sorbitan monolaurate (Tween 20) and 10mM sodium borate at pH 9.2. Under these conditions, all calibration curves showed good linearity (r(2)>0.9969), and accuracy (recoveries ranging from 94.71 to 106.85%). Finally, the proposed method was successfully applied to determine the phenolic acids in a Chinese medicine compound, compound danshen dripping pills.

Moxibustion for the treatment of pressure ulcers: study protocol for a pilot, multicentre, randomised controlled trial.

INTRODUCTION: Pressure ulcers are common in the elderly and immobile. Currently, there are few proven effective treatments for pressure ulcers. This trial aims to evaluate the feasibility, efficacy and safety of moxibustion for pressure ulcers. METHODS/ANALYSIS: This is a multicentre, two-armed, parallel-design randomised controlled trial (RCT). 30 eligible patients with pressure ulcers will be randomised in a ratio of 1:1 to the treatment group and control group. The participants in the treatment group will undergo indirect moxibustion for 30 min before application of a dressing, one session daily, five sessions weekly for 4 weeks. The patients in the control group will only receive a dressing, applied in the same way as in the treatment group. Both groups will be followed up for 3 months. The primary outcome measures will be wound surface area (WSA) and proportion of ulcers healed within trial period (PUHTP). The secondary outcomes will be the Pressure Ulcer Scale for Healing (PUSH Tool), visual analogue scale (VAS) and adverse events. All outcomes will be evaluated at the beginning of the study, at the end of the second week, at 4 weeks after randomisation and at 1 and 3 months after treatment cessation. ETHICS/DISSEMINATION: This trial has undergone ethical scrutiny and been approved by the ethics review boards of First Affiliated Hospital of Heilongjiang University of Chinese Medicine and Second Affiliated Hospital of Heilongjiang University of Chinese Medicine (Permission number: HZYEYLP2014). The results of this study will provide clinical evidence for the feasibility, efficacy and safety of moxibustion for pressure ulcers. TRIAL REGISTRATION NUMBER: ChiCTR-TRC-13003959.