Novel Natural Carrier-Free Self-Assembled Nanoparticles for Treatment of Ulcerative Colitis by Balancing Immune Microenvironment and Intestinal Barrier.

Ulcerative colitis (UC) is a chronic inflammatory illness affecting the colon and rectum, with current treatment methods being unable to meet the clinical needs of ulcerative colitis patients. Although nanomedicines are recognized as promising anti-inflammatory medicines, their clinical application is limited by their high cost and unpredictable safety risks. This study reveals that two natural phytochemicals, berberine (BBR) and hesperetin (HST), self-assemble directly to form binary carrier-free multi-functional spherical nanoparticles (BBR-HST NPs) through noncovalent bonds involving electrostatic interactions, π-π stacking, and hydrogen bonding. Because of their synergistic anti-inflammatory activity, berberine-hesperetin nanoparticles (BBR-HST NPs) exhibit significantly better therapeutic effects on UC and inhibitory effects on inflammation than BBR and HST at the same dose by regulating the immune microenvironment and repairing the damaged intestinal barrier. Furthermore, BBR-HST NPs exhibit good biocompatibility and biosafety. Thus, this study proves the potential of novel natural anti-inflammatory nanoparticles as therapeutic agents for UC, which could promote the progress of drug development for UC and eventually benefit patients who suffering from it.

[Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond].

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Study on syndrome rules of stagnated heat in liver and stomach of non-erosive reflux disease based on microecology of tongue coating.

INTRODUCTION: At present, the pathogenesis of non-erosive reflux disease (NERD) is still unclear, and proton pump inhibitors are the main treatment drug. However, the effect is limited. Traditional Chinese medicine treatment of NERD has advantages. Stagnated heat in liver and stomach syndrome is the most important traditional Chinese medicine syndrome type of this disease. Tongue diagnosis is an important basis for the diagnosis of stagnated heat in liver and stomach syndrome. The microecology of tongue coating suggests the occurrence and development of disease. The purpose of this study aims to clarify the regular changes of tongue coating microecology in stagnated heat in liver and stomach syndrome of NERD. METHODS AND ANALYSIS: This is a cross-sectional clinical trial. This study is divided into NERD stagnated heat in liver and stomach syndrome group, qi stagnation, and phlegm obstruction syndrome control group and normal control group, with 20 cases in each group. Tongue coating samples will be collected from 3 groups, and 16SrRNA gene sequencing technology will be used to detect the genome of tongue coating flora in patients with NERD with stagnated heat in liver and stomach syndrome, control group with qi stagnation and phlegm obstruction syndrome and normal control group. The main outcome measures are the distribution, diversity, and richness of the tongue flora in patients and healthy controls. DISCUSSION: The results of this study will clarify the internal relationship between NERD stagnated heat in liver and stomach syndrome and the microecological changes in tongue coating.

Effectiveness and safety of moxibustion for vascular dementia: A systematic review and meta-analysis.

BACKGROUND: Vascular dementia (VD) is the only type of dementia that can be prevented and treated. Compared to conventional treatment methods, moxibustion therapy is more effective for VD. This study evaluated the effectiveness and safety of moxibustion in the treatment of VD through a meta-analysis, to provide a complete overview to the advantages of traditional Chinese medicine and provide guidance for clinical application. METHODS: Clinical trials on the therapeutic effects of moxibustion or moxibustion combined with acupuncture on VD were retrieved from the VIP information database, Wanfang, CNKI, PubMed, EMBase, and other resources. The included studies were conducted from January 2000 to October 2020. Among the retrieved studies, the content met the standards upon being collated and extracted, and RevMan5.3 was used for meta-analysis. RESULTS: Thirteen randomized controlled trials (RCTs) were included with 997 patients. The RevMan bias risk assessment revealed that the quality of the studies was generally low. The meta-analysis showed that compared to conventional treatments, moxibution therapy in terms of effective rate, posttreatment Hasegawa Dementia Scale, Mini-Mental State Examination (MMSE), Activity of Daily Living Scale (ADL), Somatostatin (SS), Arginine Vasopressin (AVP), and Syndrome Differentiation Scale of VD were more favorable, and the difference in efficacy was statistically significant. Furthermore, no adverse events were observed in either group. Sensitivity analysis showed strong homogeneity and stable results, whereas funnel plot analysis revealed no significant publication bias. CONCLUSIONS: Moxibustion is effective and safe in the treatment of VD, but more high-quality evidence from further studies is required to support this.

Guided meditation for vision acuity training on adolescent myopia: study protocol for an open-label, prospective, multicenter, randomized controlled trial.

BACKGROUND: Currently, the population with myopia climbs steadily, and is developing toward younger age, posing a great concern to the health of adolescents. Myopia in severe cases can cause irreversible consequences such as glaucoma, blindness, and other complications. At present, the solutions for myopia are glasses, medication, and surgery. This study aims to investigate the role of a physiotherapy category based on guided meditation for vision acuity training on adolescent myopia. METHODS: This is a prospective, randomized, multicenter clinical trial. One thousand one hundred forty primary and secondary school students aged 8-18 years old from 27 schools will be recruited and randomly divided into an experimental and a control group at a ratio of 2:1 in two phases, with a training period of 30 days in each phase and a follow-up period of 3 months. No interventions will be conducted during the follow-up period, nor will other interventions employed. Inclusion criteria will meet the diagnostic criteria for simple myopia and -6.00D ≤ spherical lenses ≤ -0.50D and cylindrical lenses ≤1.50D. The primary observation index will be to compare the statistical differences in distant visual acuity between the two groups; the secondary observation indexes will be ocular symptoms (mainly including eye fatigue, dryness, pain, double vision, neck pain, thought disorders, and lags in response), diopter, and astigmatism. DISCUSSION: The purpose of this two-phase trial is to compare the clinical effectiveness of focused vision-guided meditation with Chinese eye exercises that are also non-pharmacological, non-invasive interventions for myopia, and to maximize the benefit to the subjects. The results will indicate whether the training based on focused vision-guided meditation has the ability to improve distant visual acuity, relieve ocular symptoms, and ameliorate diopter. In addition, this trial will provide clinical efficacy of the training, which is expected to provide meaningful data for vision rehabilitation. At the same time, the vision acuity training method, which is permeated with the concept of Traditional Chinese Medicine (TCM) rehabilitation and health maintenance, will be applied to achieve the goal of preventing or alleviating myopic development and reducing myopia rate. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000038642 . Registered on 26 September 2020.