In silico screening of anti-inflammatory constituents with good drug-like properties from twigs of Cinnamomum cassia based on molecular docking and network pharmacology

Purpose: To investigate by in silico screening the anti-inflammatory constituents of Cinnamomum cassia twigs. Methods: Information on the constituents of C. cassia twigs was retrieved from the online Traditional Chinese Medicines (TCM) database and literature. Inflammation-related target proteins were identified from DrugBank, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), Genetic Association Database (GAD), and PharmGKB. The identified compounds were filtered by Lipinski’s rules with Discovery Studio software. The “Libdock” module was used to perform molecular docking; LibdockScores and default cutoff values for hydrogen bonds and van der Waals interactions were recorded. LibdockScores between the prototype ligand and target protein were set as the threshold; compounds with higher LibdockScores than threshold were regarded as active compounds. Cytoscape software was used to construct active constituent-target protein interaction networks. Results: Sixty-nine potential inflammatory constituents with good drug-like properties in C. cassia twigs were screened in silico based on molecular docking and network pharmacology analysis. JAK2, mPEGS-1, COX-2, IL-1β, and PPARγ were considered the five most important target proteins. Compounds such as methyl dihydromelilotoside, hierochin B, dihydromelilotoside, dehydrodiconiferyl alcohol, balanophonin, phenethyl (E)-3-[4-methoxyphenyl]-2-propenoate, quercetin, and luteolin each interacted with more than six of the selected target proteins. Conclusion: C. cassia twigs possess active compounds with good drug-like properties that can potentially be developed to treat inflammation with multi-components on multi-targets

Modeling and simulation of extended ant colony labor division for benefit distribution of the all-for-one tourism supply chain with front and back decoupling

This paper takes the supply chain alliance under the decoupling of the front and back of the all-for-one tourism as the research object. Considering the three behavior stimuli of self-benefit, altruism, and invariance, this article resets the attributes such as environmental stimuli and response threshold of ants based on the characteristics of the all-for-one tourism supply chain with shared services as the core under the decoupling of the front and back. Moreover, it introduces dual intervention factors to coordinate the benefit distribution process of different member companies, takes fairness as the main goal of benefit distribution, introduces relative deprivation as the measure index of fairness, and establishes a dynamic all-for-one tourism supply chain alliance benefit distribution model. The experimental results show that the extended model has good flexibility of benefit distribution and realizes the fair distribution of supply chain benefits

MindShift: Leveraging Large Language Models for Mental-States-Based Problematic Smartphone Use Intervention

Problematic smartphone use negatively affects physical and mental health. Despite the wide range of prior research, existing persuasive techniques are not flexible enough to provide dynamic persuasion content based on users' physical contexts and mental states. We first conduct a Wizard-of-Oz study (N=12) and an interview study (N=10) to summarize the mental states behind problematic smartphone use: boredom, stress, and inertia. This informs our design of four persuasion strategies: understanding, comforting, evoking, and scaffolding habits. We leverage large language models (LLMs) to enable the automatic and dynamic generation of effective persuasion content. We develop MindShift, a novel LLM-powered problematic smartphone use intervention technique. MindShift takes users' in-the-moment physical contexts, mental states, app usage behaviors, users' goals & habits as input, and generates high-quality and flexible persuasive content with appropriate persuasion strategies. We conduct a 5-week field experiment (N=25) to compare MindShift with baseline techniques. The results show that MindShift significantly improves intervention acceptance rates by 17.8-22.5% and reduces smartphone use frequency by 12.1-14.4%. Moreover, users have a significant drop in smartphone addiction scale scores and a rise in self-efficacy. Our study sheds light on the potential of leveraging LLMs for context-aware persuasion in other behavior change domains

Developing a multi-epitope vaccine candidate to combat porcine epidemic diarrhea virus and porcine deltacoronavirus co-infection by employing an immunoinformatics approach

Coinfection of porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) is common in pig farms, but there is currently no effective vaccine to prevent this co-infection. In this study, we used immunoinformatics tools to design a multi-epitope vaccine against PEDV and PDCoV co-infection. The epitopes were screened through a filtering pipeline comprised of antigenic, immunogenic, toxic, and allergenic properties. A new multi-epitope vaccine named rPPMEV, comprising cytotoxic T lymphocyte-, helper T lymphocyte-, and B cell epitopes, was constructed. To enhance immunogenicity, the TLR2 agonist Pam2Cys and the TLR4 agonist RS09 were added to rPPMEV. Molecular docking and dynamics simulation were performed to reveal the stable interactions between rPPMEV and TLR2 as well as TLR4. Additionally, the immune stimulation prediction indicated that rPPMEV could stimulate T and B lymphocytes to induce a robust immune response. Finally, to ensure the expression of the vaccine protein, the sequence of rPPMEV was optimized and further performed in silico cloning. These studies suggest that rPPMEV has the potential to be a vaccine candidate against PEDV and PDCoV co-infection as well as a new strategy for interrupting the spread of both viruses

Evaluation of genipin-crosslinked chitosan hydrogels as a potential carrier for silver sulfadiazine nanocrystals

In the present study genipin crosslinked chitosan (CHI) hydrogels, which had been constructed and reported in our previous studies (Lei Gao, et al. Colloids Surf. B Biointerfaces. 2014, 117: 398), were further evaluated for their advantage as a carrier for silver sulfadiazine (AgSD) nanocrystal systems. Firstly, AgSD nanocrystals with a mean particle size of 289 nm were prepared by wet milling method and encapsulated into genipin crosslinked CHI hydrogels. AgSD nanocrystals displayed a uniform distribution and very good physical stability in the hydrogel network. Swelling-dependent release pattern was found for AgSD nanocrystals from hydrogels and the release profile could be well fitted with Peppas equation. When AgSD nanocrystals were encapsulated in hydrogels their fibroblast cytotoxicity decreased markedly, and their antibacterial effects against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were still comparable to unencapsulated AgSD nanocrystals. In vivo evaluation in excision and burn cutaneous wound models in mice showed that AgSD nanocrystal hydrogels markedly decreased the expression of inflammatory cytokine IL-6, but increased the levels of growth factors VEGF-A and TGF-β1. Histopathologically, the wounds treated by hydrogels containing AgSD nanocrystals showed the best healing state compared with commercial AgSD cream, hydrogels containing AgSD bulk powders and blank hydrogels. The wounds treated by AgSD nanocrystal hydrogels were dominated by marked fibroblast proliferation, new blood vessels and thick regenerated epithelial layer. Sirius Red staining assay indicated that AgSD nanocrystal hydrogels resulted in more collagen deposition characterized by a large proportion of type I fibers. Our study suggested that genipin-crosslinked CHI hydrogel was a potential carrier for local antibacterial nanomedicines

Efficacy of Chuanxiong Ding Tong Herbal Formula Granule in the Treatment and Prophylactic of Migraine Patients: A Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial

Objective. To evaluate the efficacy of traditional Chinese herbal ChuanXiong Ding Tong herbal formula granule (CXDT-HFG) for migraine patients with “the Syndrome of Liver Wind and Blood Stasis.” Methods. 150 migraine patients were recruited and assigned randomly in a double-blind, placebo-controlled study to receive CXDT-HFG (n=99) plus necessary analgesics, or placebo (n=51) plus necessary analgesics for 16 weeks (12 weeks’ intervention and 4 weeks’ follow up). Outcome measures included migraine days, frequency of migraine attacks, analgesics consumption for acute treatment, and the proportion of responders as well as the visual analogue scale (VAS) scores and intensity for pain. Results. Compared with the placebo group, the CXDT-HFG group showed significant reduction in migraine days and attacks frequency at week 12 and follow-up period (P0.05). Conclusion. CXDT-HFG was more effective than placebo in decreasing days of migraine attacks, frequency, VAS scores, and relieving pain intensity for migraine patients

Central nervous system (CNS)–resident natural killer cells suppress Th17 responses and CNS autoimmune pathology

Natural killer (NK) cells of the innate immune system can profoundly impact the development of adaptive immune responses. Inflammatory and autoimmune responses in anatomical locations such as the central nervous system (CNS) differ substantially from those found in peripheral organs. We show in a mouse model of multiple sclerosis that NK cell enrichment results in disease amelioration, whereas selective blockade of NK cell homing to the CNS results in disease exacerbation. Importantly, the effects of NK cells on CNS pathology were dependent on the activity of CNS-resident, but not peripheral, NK cells. This activity of CNS-resident NK cells involved interactions with microglia and suppression of myelin-reactive Th17 cells. Our studies suggest an organ-specific activity of NK cells on the magnitude of CNS inflammation, providing potential new targets for therapeutic intervention

Evaluation of genipin-crosslinked chitosan hydrogels as a potential carrier for silver sulfadiazine nanocrystals

This paper was accepted for publication in the journal Colloids and Surfaces B: Biointerfaces and the definitive published version is available at http://dx.doi.org/10.1016/j.colsurfb.2016.06.016In the present study genipin crosslinked chitosan (CHI) hydrogels, which had been constructed and reported in our previous studies (Lei Gao, et al. Colloids Surf. B Biointerfaces. 2014, 117: 398), were further evaluated for their advantage as a carrier for silver sulfadiazine (AgSD) nanocrystal systems. Firstly, AgSD nanocrystals with a mean particle size of 289 nm were prepared by wet milling method and encapsulated into genipin crosslinked CHI hydrogels. AgSD nanocrystals displayed a uniform distribution and very good physical stability in the hydrogel network. Swelling-dependent release pattern was found for AgSD nanocrystals from hydrogels and the release profile could be well fitted with Peppas equation. When AgSD nanocrystals were encapsulated in hydrogels their fibroblast cytotoxicity decreased markedly, and their antibacterial effects against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were still comparable to unencapsulated AgSD nanocrystals. In vivo evaluation in excision and burn cutaneous wound models in mice showed that AgSD nanocrystal hydrogels markedly decreased the expression of inflammatory cytokine IL-6, but increased the levels of growth factors VEGF-A and TGF-β1. Histopathologically, the wounds treated by hydrogels containing AgSD nanocrystals showed the best healing state compared with commercial AgSD cream, hydrogels containing AgSD bulk powders and blank hydrogels. The wounds treated by AgSD nanocrystal hydrogels were dominated by marked fibroblast proliferation, new blood vessels and thick regenerated epithelial layer. Sirius Red staining assay indicated that AgSD nanocrystal hydrogels resulted in more collagen deposition characterized by a large proportion of type I fibers. Our study suggested that genipin-crosslinked CHI hydrogel was a potential carrier for local antibacterial nanomedicines