Dried tangerine peel polysaccharide (DTPP) alleviates hepatic steatosis by suppressing TLR4/MD-2-mediated inflammation and endoplasmic reticulum stress.

Non-alcoholic fatty liver disease (NAFLD) is a complex pathogenic metabolic syndrome characterized by increased inflammation and endoplasmic reticulum stress. In recent years, natural polysaccharides derived from traditional Chinese medicine have shown significant anti-inflammatory effects, making them an attractive therapeutic option. However, little research has been conducted on the therapeutic potential of dried tangerine peel polysaccharide (DTPP) - one of the most important medicinal resources in China. The results of the present study showed that DTPP substantially reduced macrophage infiltration in vivo and suppressed the expression of pro-inflammatory factors and endoplasmic reticulum stress-related genes. Additionally, surface plasmon resonance analysis revealed that DTPP had a specific affinity to myeloid differentiation factor 2, which consequently suppressed lipopolysaccharide-induced inflammation via interaction with the toll-like receptor 4 signaling pathway. This study provides a potential molecular mechanism underlying the anti-inflammatory effects of DTPP on NAFLD and suggests DTPP as a promising therapeutic strategy for NAFLD treatment.

[Evolution and implementation pathways from desertification prevention and control to sandy land management and use in China]. / 中国从防沙治沙到管沙用沙的演变过程与实现路径.

The construction of ecological civilization emphasizes holistic protection of "mountain-water-forest-farmland-lake-grassland-sand", which has become an important concept of desertification prevention projects in arid and semi-arid areas of China. In the past, sandy land management and use have been neglected in desertification prevention and control, in that the links have not been effectively connected and the long-term and efficient desertification prevention has not been realized. Therefore, combining Qian Xuesen's understanding of "deserticulture", we comprehensively discussed the "long-term achievements" of China's desertification control miracle from the perspective of the historical evolution of the interaction of technology and practice, and the strategic development of policy guidance. Further, we defined the concepts of desertification prevention, desertification control, and sandy land management and use. We analyzed the coupling and coordination relationship between the four links and the scientific principle based on the development of ecological industry chain. Finally, we put forward the policy and market realization pathways, with efficient sandy land management as the core, desertification prevention as the basis, desertification control as the channel, and long-term sandy land use as the foundation. We expected to provide theoretical and practical guidance for creating a new miracle of China's desertification prevention and control.

Effectiveness of musculoskeletal manipulations in patients with neck pain: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Neck pain is a common problem that severely affects physical and mental health. While musculoskeletal manipulations are recommended as the first-line treatment for adults with neck pain, the comparative effectiveness of different musculoskeletal manipulations remains unclear. This systematic review and network meta-analysis of randomised controlled trials (RCTs) will compare the effectiveness of different types of musculoskeletal manipulations, with the overarching aim of guiding clinical practice. METHODS AND ANALYSIS: Two independent reviewers will search four English electronic databases (Web of Science, Cochrane Library, EMBASE, PubMed) and three Chinese electronic databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang) for relevant RCTs published from 1 January 2013 to 30 April 2023. The Clinical Trials Registry (ClinicalTrials.gov) will be searched for completed but unpublished RCTs. English and Chinese will be used to search English databases and Chinese databases, respectively. RCTs of musculoskeletal manipulations for adults (aged ≥18 years) with neck pain will be considered eligible for inclusion. A pairwise meta-analysis and network meta-analysis will be performed, and pooled risk ratios, standardised mean differences and 95% CIs will be determined. ETHICS AND DISSEMINATION: Ethics approval is not required as this study is a literature review. The results of this review will be published in peer-reviewed journals or disseminated at conferences. PROSPERO REGISTRATION NUMBER: CRD42023420775.

GLP1R boosts survival, migration and invasion of endometrial cancer cells and protects against ferroptotic cell death.

BACKGROUND: Despite the strong evidence concerning carcinogenic roles of glucagon-like peptide 1 receptor (GLP1R), the role of this gene in endometrial cancer (EC) remains elusive. This study investigated the properties of GLP1R on EC in vitro. METHODS: The expression of GLP1R in EC was detected by RT-qPCR, immunohistochemistry, and western blotting. Cell viability, cell cycle, apoptosis, migration, invasion and ferroptosis were assessed through CCK-8, flow cytometry, wound healing, transwell, DCFH-DA and western blotting, respectively. RESULTS: We found that GLP1R was up-regulated in EC than normal specimens. It had the highest expression in AN3CA cells. Cell viability, migration and invasion were significantly reduced, while cell cycle arrest and apoptosis were induced following GLP1R knockdown. The malignant biological behaviours of AN3CA cells were investigated when treated with exendin-4 (GLP1R agonist). Moreover, GLP1R lowered intracellular ROS level and expression of SLC7A11, and FTH1, but mitigated GPX4 expression in AN3CA cells. CONCLUSION: In a word, GLP1R was up-regulated in EC and its up-regulation facilitated the proliferative and metastatic potentials, and protected cells from ferroptosis, thereby accelerating EC progression. These data emphasised the potency of GLP1R as a therapeutic agent against EC.

Endometrial cancer (EC) is the second most common form of gynaecologic malignancy, with over 189,000 new cases and about 45,000 deaths worldwide per annum. The effects of glucagon-like peptide 1 receptor (GLP1R) in cancers such as colon and pancreatic cancers have been uncovered. However, whether GLP1R affects EC progression especially ferroptosis process remains elusive. In this study, up-regulation of GLP1R promotes the proliferative and metastatic potentials of EC cells, and protects EC cells from ferroptosis. The opposite results are observed in GLP1R knocking-down. Our study found that GLP1R may exert an oncogene function in EC cells, which can affect proliferative, migrated as well as invasive capacities of EC cells. Moreover, it protected EC cells from ferroptosis. Thus, our results expanded the understanding of the function of GLP1R protein and offered insights into the targeted treatment strategies against EC.

Bibliometric Analysis of Research Trends on Tuina Manipulation for Neck Pain Treatment Over the Past 10 Years.

Tuina is an effective treatment for neck pain (NP). However, there has been no bibliometric analysis of the global application and emerging trends of tuina performed for NP. Therefore, this study aimed to provide an overview of the current state and future trends in the field. Articles about tuina for NP, published from January 1, 2013, to January 1, 2023, were searched in the Web of Science Core Collection database. CiteSpace (6.1.R6) and VOSviewer (1.6.18) software were used to analyze annual trends in literature posts, countries, institutions, authors, cited references, and knowledge graphs of keyword co-occurrence, clustering, and burst using standard bibliometric indicators. The final analysis comprised 505 valid documents. The results demonstrate that the number of articles in the field of tuina therapy for NP has gradually increased over the years, showing the most active countries, institutions, journals, and authors. There were 323 keywords in the field, 322 research authors, and 292 research institutions, with the USA having the most publications (n = 140). The most published institution is Vrije University Amsterdam, and the most published journal is the Cochrane Database of Systematic Reviews. Peter R Blanpied is the most influential and most-cited author. Interventions (dry needling, massage therapy, and muscle energy techniques), common treatment sites for NP (upper trapezius), and complications (cervicogenic headache) are the top three frontiers mentioned in the field of tuina research for NP. The bibliometric study showed the current status and trends in clinical research on treating patients with NP using tuina, which may help researchers identify topics of interest and scope for future research in this field.

Efficient extraction, excellent activity, and microencapsulation of flavonoids from Moringa oleifera leaves extracted by deep eutectic solvent.

A deep eutectic solvent (choline chloride (ChCl)-urea) was chosen to extract flavonoids from Moringa oleifera leaves (FMOL), the condition of extraction was tailor-made, under the optimal extraction conditions (material-to-liquid ratio of 1:60 g/mL, extraction time of 80 min, extraction temperature of 80 °C), the highest extraction efficiency reached 63.2 ± 0.3 mg R/g DW, and nine flavonoids were identified. Then, the biological activities including antioxidant activities, antibacterial activities, and anti-tumor activities were systematically studied. FMOL was superior to positive drugs in terms of antioxidant activity. As to DPPH investigation, the IC50 of FMOL and Vc were 64.1 ± 0.7 and 176.1 ± 2.0 µg/mL; for the ABTS, the IC50 of FMOL and Vc were 9.5 ± 0.3 and 38.2 ± 1.2 µg/mL, the FRAP value of FMOL and Vc were 15.5 ± 0.6 and 10.2 ± 0.4 mg TE/g, and ORAC value of FMOL and Vc were 4687.2 ± 102.8 and 3881.6 ± 98.6 µmol TE/g. The bacteriostatic (MICs were ≤ 1.25 mg/mL) activities of FMOL were much better than propyl p-hydroxybenzoate. Meanwhile, FMOL had comparable inhibitory activity with genistein on tumor cells, IC50 was 307.8 µg/mL, and could effectively induce apoptosis in HCT116. Microcapsules were prepared with xylose-modified soybean protein isolate and gelatin as wall materials; after that, the intestinal release of modified FMOL microcapsules was 86 times of free FMOL. Therefore, this study confirmed that FMOL extracted with ChCl/urea has rich bioactive components, and microencapsulated FMOL has potential application in food industry. Supplementary Information: The online version contains supplementary material available at 10.1007/s13399-023-03877-8.

Chinese Medicine Plaster as A New Treatment for Surgical Site Infection in Patients with Cesarean Delivery: A Randomized, Double-Blind, Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy of Chinese plaster containing rhubarb and mirabilite on surgical site infection (SSI) in patients with cesarean delivery (CD) by performing a randomized controlled trial.@*METHODS@#This randomized controlled trial included 560 patients with CD due to fetal head descent enrolled at a tertiary teaching center between December 31, 2018 and October 31, 2021. Eligible patients were randomly assigned to a Chinese medicine (CM) group (280 cases) or a placebo group (280 cases) by a random number table, and were treated with CM plaster (made by rhubarb and mirabilite) or a placebo plaster, respectively. Both courses of treatment lasted from the day 1 of CD, followed day 2 until discharge. The primary outcome was the total number of patients with superficial, deep and organ/space SSI. The secondary outcome was duration of postoperative hospital stay, antibiotic intake, and unplanned readmission or reoperation due to SSI. All reported efficacy and safety outcomes were confirmed by a central adjudication committee that was unaware of the study-group assignments.@*RESULTS@#During the recovery process after CD, the rates of localized swelling, redness and heat were significantly lower in the CM group than in the placebo group [7.55% (20/265) vs. 17.21% (47/274), P<0.01]. The durution of postoperative antibiotic intake was shorter in the CM group than in the placebo group (P<0.01). The duration of postoperative hospital stay was significantly shorter in the CM group than in the placebo group (5.49 ± 2.68 days vs. 8.96 ± 2.35 days, P<0.01). The rate of postoperative C-reactive protein elevation (≽100 mg/L) was lower in the CM group than in the placebo group [27.6% (73/265) vs. 43.8% (120/274), P<0.01]. However, there was no difference in purulent drainage rate from incision and superficial opening of incision between the two groups. No intestinal reactions and skin allergies were found in the CM group.@*CONCLUSIONS@#CM plaster containing rhubarb and mirabilite had an effect on SSI. It is safe for mothers and imposes lower economic and mental burdens on patients undergoing CD. (Registration No. ChiCTR2100054626).

Safety evaluation of Tibetan medicine Qishiwei Zhenzhu Pills based on serum pharmacochemistry and network pharmacology / 中国中药杂志

To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.

Characterization of Dissolved Organic Matter in Solar Ponds by Elemental Analysis, Infrared Spectroscopy, Nuclear Magnetic Resonance and Pyrolysis-GC-MS.

The abundance and chemical composition of dissolved organic matter (DOM) in the brine of solar ponds affect the efficiency of mineral extraction and evaporation rates of the brine, and cause undesired odor and color of the products. Here, we report an investigation into the composition and changes of DOM in solar ponds from Salt Lake brine with multiple complementary analysis techniques. The results showed that the DOM derived from Salt Lake brine was primarily composed of carbohydrates, aliphatic and aromatic compounds. The concentrations of dissolved organic carbon in solar ponds increased with exposure time by up to 15-fold (from 23.4 to 330.8 mg/L) upon evaporation/irradiation of Salt Lake brine. Further qualitative analyses suggest that the relative abundance of aliphatic compounds (including functionalized ones) increased from 49.5% to 59.2% in the solar pond process, while the opposite was observed for carboxylic acid moieties, aromatics and carbohydrates, which decreased from 15.7%, 7.1% and 26.1% to 13.4%, 5.3% and 23.0%, respectively. The pyrolysis-gas chromatography-mass spectrometry results reveal that the presence of some sulfur-containing organics implied some anaerobic biotic decay, but microbiological processes were probably subordinate to photo-induced DOM transformations. In the Salt Lake brine, exposure-driven decay decreased the abundance of polysaccharides and increased that of mono- and polyaromatic pyrolysis products. Our results here provide new insights for better understanding the changes of DOM chemical composition in the solar ponds of Salt Lake brine.

Extracts of Periplaneta americana alleviate hepatic fibrosis by affecting hepatic TGF-ß and NF-κB expression in rats with pig serum-induced liver fibrosis.

INTRODUCTION: Liver fibrosis is caused by continuous wound healing responses to various harmful stimuli, including viral infection, drugs, alcohol, and autoimmune liver disease. The purpose of this study was to examine the effects of extracts of Periplaneta americana (EPA) in rats with pig serum-induced liver fibrosis to preliminarily assess the antifibrotic effect of EPA. MATERIAL AND METHODS: Seventy rats were randomly divided into 7 groups (10 rats in each group): HC, the healthy control group; FC, the fibrotic control group; TL, low-dose EPA treatment group group; TM, medium-dose EPA group; TH, high-dose EPA treatment group; TC1, Panax notoginseng/Salvia mitiorrhiza treatment control group 1; TC2, colchicine treatment control group 2. TC1 and TC2 were used as the positive control to demonstrate the difference between EPA and the effects of other compounds. The liver fibrosis model was induced by intraperitoneal injection of 0.5 mL pig serum twice a week for 13 weeks in all groups except for the HC group. The hepatic fibrosis model was established at the 7th week, and followingly, the corresponding compounds were administered once a day in all groups for 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity was determined in rat blood serum. We also measured liver fibrosis-related serum markers, including hyaluronic acid (HA), mucin layer (LN), type III pre-collagen (PC-III) and type IV collagen (IV-C). Hematoxylin and eosin (H&E) and Masson stainings were used to assess liver morphology and determine the stage of fibrosis. Immunohistochemistry was used to detect the protein expression of NF-κB, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rat liver tissue. RESULTS: Compared with that of the HC group, the liver tissue of the FC group presented obvious liver damage and collagen deposition. The serum levels of ALT, AST, HA, LN, PC-III and IV-C and the expression of NF-κB, α-SMA, TGF-ß1 and TIMP-1 in the FC group were significantly higher than those in the HC group, the EPA treatment groups, the TC1 group and the TC2 group (P < 0.01). The levels of serum ALT, AST, HA, LN, PC-III and IV-C and the expression of α-SMA, NF-κB, TGF-ß1 and TIMP-1 in the TL, TC1 and TC2 groups were significantly higher than those TM and TH groups (P < 0.05). EPA treatment significantly improved liver function, decreased collagen deposition and reversed the pathological changes related to liver fibrosis. CONCLUSIONS: We found that EPA could reduce liver inflammation, suppress liver cell degeneration and necrosis, and reduce the formation of liver fibrous tissue. Its mechanism might be associated with inhibiting the expression of TGF-ß1, TIMP-1, NF-κB and α-SMA to block signal transduction pathways in the hepatic fibrosis process. Therefore, EPA, as a traditional Chinese medicine, might be potentially used to prevent and treat hepatic fibrosis in the future. However, further more experiments are necessary to verify its effectiveness and possible signaling pathways.

Traditional Chinese medicine intervention for autism spectrum disorders: A protocol for systematic review and network meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication, social interaction, and restrictive or repetitive behaviors. Traditional Chinese medicine (TCM) has been used in the clinical management of ASD, especially in mainland China, where studies have shown promising efficacy. However, this remains to be further explored and clarified. Therefore, the purpose of this study was to evaluate the effectiveness and safety of conventional treatment-based TCM interventions for ASD. METHOD: The study will be conducted from January 2022, and the following electronic databases will be searched: China Biological Medicine Database, Chinese Scientific Journals Database, Wan Fang database, and China National Knowledge Infrastructure, the Cochrane Library, Web of Science, PubMed, and EMBASE Database. Only randomized controlled trials of TCM interventions for ASD will be included. The Autism Diagnostic Observation Scale, Autism Diagnostic Interview-Revised, and Childhood Autism Rating Scale will be the primary outcome indicators. The methodological quality of this Bayesian-based network meta-analysis will be performed using the "Risk of Bias" tool. Stata 14.0 and WinBUGS 1.4.3 will be used to analyze the data. In addition, assessment of heterogeneity, inconsistency, subgroups, sensitivity, and publication bias will be conducted using the Cochrane Collaboration's tools. RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will help patients recover better, provide clinical evidence for practitioners, and promote the use of TCM in ASD interventions.

Correlation between Traditional Chinese Medicine Syndromes and Type 2 Myocardial Infarction in Critically Ill Patients with Pulmonary Disease.

Background: Treatment based on syndrome differentiation under the traditional Chinese medicine (TCM) framework has been shown to be helpful in patients with coronary artery disease. We hypothesized that syndrome types could predict the risk of type 2 myocardial infarction (T2MI) caused by imbalance between myocardial oxygen supply and demand in critically ill patients with pulmonary disease. Methods: This retrospective study included consecutive critically ill patients with pulmonary disease admitted to the ICU at Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences from January 1, 2017, to July 1, 2019. Diagnosis of T2MI was based on the fourth universal definition of myocardial infarction. Risk factors associated with T2MI were identified using multivariate regression analysis. Results: A total of 244 patients were included in the study: 78 who developed T2MI and the remaining 166 who did not develop T2MI during hospitalization. The incidence of phlegm syndrome and deficiency syndrome was 61.9% and 38.1%, respectively. In comparison with the patients with phlegm syndrome, the incidence of T2MI in patients with deficiency syndrome is significantly higher (40.9% vs. 26.5%, P=0.019). In multivariate logistic regression, T2MI was independently associated with the baseline troponin level (OR 12.682, 95% CI 1.397∼115.121; P=0.024), hemoglobin < 55 g/L (OR 12.76, 95% CI 2.359∼69.021; P=0.003), mechanical ventilation (OR 2.244, 95% CI 1.029∼4.892; P=0.042), and TCM deficiency syndrome (OR 2.214, 95% CI 1.032∼4.749; P=0.041). After adjusting for confounding factors in Cox regression models, the hazard ratio (95% confidence interval) of qi deficiency syndrome groups was 1.183 (95% CI 1.053∼3.123, P=0.032). Conclusions: Patients with deficiency syndrome are at high risk of T2MI, especially those combined with qi deficiency syndrome.

Pediatric Tuina in children with autism spectrum disorder: a study protocol for a randomized controlled trial.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by repetitive stereotypical behavior and communication deficits. Currently, it lacks a specific clinical treatment method. Pediatric Tuina is a recent therapy in traditional Chinese medicine (TCM) and has been used to treat children with ASD. Nonetheless, it remains uncommon given the lack of large-scale evidence-based medical studies. This study aims to compare the efficacy of Tuina and conventional treatment in children with ASD. METHODS: Eligible children will be randomly assigned to either the pediatric Tuina plus conventional treatment group or to the conventional treatment alone group based on a random table at a ratio of 1:1. The effectiveness of the Tuina intervention for ASD will be evaluated by a third-party organization. The pre- and post-intervention scores on the Childhood Autism Rating Scale comprised the primary outcome, whereas pre- and post-intervention scores on the Autism Treatment Evaluation Checklist were the secondary outcomes to assess improvement in symptoms. Baseline values of the participants will be determined at the time of registration. Outcomes will be evaluated after the 30th treatment session. The follow-up period will last for 6 months after treatment. DISCUSSION: This study will evaluate the effectiveness and safety of Tuina in the treatment of ASD. The results of this study could provide reliable evidence to improve the management of patients with ASD. TRIAL REGISTRATION: Chinese Clinical Trial Registry (CHICTR), ChiCTR2000040452 . Registered on 28 November 2020.

Study on alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury based on network pharmacology and cell experiments / 中国中药杂志

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.

Dahuang Zhechong pills inhibit liver cancer growth in a mouse model by reversing Treg/Th1 balance / 中国天然药物

The infiltration of immune cells into the hepatocellular carcinoma microenvironment is the main reason why hepatocellular carcinoma patients are prone to carcinoma recurrence and the disease are incurable. Notably, the infiltration of Treg cells is the main trigger. Dahuang Zhechong pill (DHZCP) is a traditional Chinese herbal compound successful in the treatment of hepatitis and hepatocellular carcinoma. DHZCP can heal and nourish while slowing the onset of the disease, thereby strengthening the body's immune function. It can localize tumors and ultimately achieve the goal of eliminating tumors. In this study, an orthotopic liver cancer model of mice was used to explore the mechanism of DHZCP enhancing anti-tumor immunity, which showed more Th1 cells in the peripheral blood and spleen after DHZCP treatment, while more IFN-γ was secreted to activate CD8+ T cells and Treg cell production was inhibited, thereby suppressing the growth of HCC. Finally, we also analyzed the potential components of DHZCP from the perspective of modern targets using network pharmacology methods and experimental results.

Ailanthus Altissima-derived Ailanthone enhances Gastric Cancer Cell Apoptosis by Inducing the Repression of Base Excision Repair by Downregulating p23 Expression.

Chemotherapy plays an irreplaceable role in the treatment of GC, but currently available chemotherapeutic drugs are not ideal. The application of medicinal plants is an important direction for new drug discovery. Through drug screening of GC organoids, we determined that ailanthone has an anticancer effect on GC cells in vitro and in vivo. We also found that AIL can induce DNA damage and apoptosis in GC cells. Further transcriptome sequencing of PDX tissue indicated that AIL inhibited the expression of XRCC1, which plays an important role in DNA damage repair, and the results were also confirmed by western blotting. In addition, we found that AIL inhibited the expression of P23 and that inhibition of P23 decreased the expression of XRCC1, indicating that AIL can regulate XRCC1 via P23. The results of coimmunoprecipitation showed that AIL can inhibit the binding of P23 and XRCC1 to HSP90. These findings indicate that AIL can induce DNA damage and apoptosis in GC cells. Meanwhile, AIL can decrease XRCC1 activity by downregulating P23 expression to inhibit DNA damage repair. The present study sheds light on the potential application of new drugs isolated from natural medicinal plants for GC therapy.

Phenolic profiles, bioaccessibility and antioxidant activity of plum (Prunus Salicina Lindl).

Plum (Prunus Salicina Lindl) is a rich source of phenolic compounds. However, the bound phenolics and its bioaccessibility and antioxidant activity remain unclear. Hence, the purpose of this study was to determine: 1) phenolic profiles of plum, including both free and bound phenolic fractions, 2) bioaccessibility of phenolic compounds in plum during simulated gastrointestinal digestions, 3) their antioxidant properties. A total of 17 phenolic compounds were identified by UPLC-Q-Exactive Orbitrap/MS with most epicatechin, neochlorogenic acid and procyanidin B2 in the free phenolics fraction, while catechin and epicatechin was the main compounds in the bound phenolics fraction. After the gastrointestinal digestion phase, the most bioaccessible phenolics were quercetin-pentoside (61.64%), cyanidin-3-O-glucoside (43.26%), and naringenin-7-O-ß-D-glucoside (42.04%). The antioxidant capacity of both undigested plum and its digested fractions showed a positive correlation with the total phenolics, and with specific individual phenolic compounds such as neochlorogenic acid, epicatechin and procyanidin B2 in undigested plum whereas catechin, neochlorogenic acid, and epicatechin in digested one. The results confirm that bound fraction of plum contribution to the total phenolic content must be taken into account in the assessment of the improving human health effects of plum.

[Acupoint sensitization enhances inhibitory effect of electroacupuncture on jejunum mobility in rats].

OBJECTIVE: To observe the effect difference of electroacupuncture (EA) at the sensitized and non-sensitized acupoint "Tianshu" (ST25) on the motility of jejunum in rats. METHODS: Male SD rats were randomly divided into blank control, sensitized ST25 (sensitization), and non-sensitized ST25 (non-sensitization) groups (n=16 in each group). The sensitization and non-sensitization were induced by injection of 15% mustard oil (20 µL) and Paraffin oil (20 µL) into the left ST25 area respectively. The rats' behavior reactions were assessed by recording the numbers and duration of licking the local sensitized skin region. At the end of experiments and after regular trans-cardiac perfusion and fixing with 10% neutral formaldehyde, the skin and muscular tissues of the ST25 region (1 cm×1 cm) were taken for H.E. staining to observe the local histopathologic changes. The intestinal motility was detected by recording the contraction pressure waves of jejunum through a small balloon-connected pressure transducer and an amplifier, followed by calculating the ratios of amplitude and frequency of contraction waves between pre- and post-EA stimulation. EA (2 Hz, 0.2-6.0 mA) was applied to the sensitized and non-sensitized ST25 regions for 20 s for comparing their effects on jejunum motility. RESULTS: Compared with the blank control group, mustard oil injection but not Paraffin oil injection resulted in histological edema and neutrophils infiltration in tissues of ST25 region, and also striking increase of the number and duration of licking (P<0.01), suggesting a sensitization of ST25 area after mustard oil injection. The ratios of spontaneous contraction amplitude and frequency of jejunum were remarkably decreased in mustard oil-treated rats compared to baseline and Paraffin oil group (P<0.001，P<0.01). The maximum inhibitory effect of EA on the intestinal movement amplitude was significantly higher in the sensitization group than in the blank control and non-sensitization groups (P<0.05，P<0.01), and there was a dose-effect relationship between the current intensity of EA (0.5-3.0 mA) and the inhibitory rate 50% of the contraction amplitude (not the frequency) in the sensitization group (P<0.001), but not in the blank control and non-sensitization groups (P>0.05). Additionally, 1.5 mA EA stimulation at the sensitized ST25 (not at the non-sensitized ST25) had an inhibitory effect on the contraction amplitude (P<0.05) rather than on the contraction frequency (P>0.05) in comparison with the blank control group. CONCLUSION: Sensitization of acupoint ST25 can modulate the motility of jejunum and enhances the inhibitory effect of EA on the contraction amplitude of jejunum in rats. The inhibitory effect of sensitized ST25 EA is evidently stronger than that of the non-sensitized ST25 EA.

Preliminary study on cerebrospinal fluid proteomics of Erxian Decoction against neurogenesis impairment in late-onset depression / 中国中药杂志

This study aims to elucidate the underlying mechanism of Erxian Decoction(EXD) against neurogenesis impairment in late-onset depression(LOD) rats based on cerebrospinal fluid(CSF) proteomics. A total of 66 20-21-month-old male Wistar rats were randomized into naturally aged(AGED) group, LOD group, and EXD group. All rats received chronic unpredictable mild stress(CUMS) for 6 weeks for LOD modeling except for the AGED group. During the modeling, EXD group was given EXD(ig, twice a day at 4 g·kg~(-1)) and other groups received equivalent amount of normal saline(ig). After modeling, a series of behavioral tests, such as sucrose preference test(SPT), open-field test(OFT), forced swimming test(FST), and Morris water maze test(MWMT) were performed. Immunofluorescence method was used to detect the number of Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area of each group. High-concentration corticosterone(CORT) was combined with D-galactose(D-gal) to simulate the changes of LOD-related stress and aging and the proliferation and differentiation of primary neural stem cells of hippocampus in each group were observed. Data independent acquisition(DIA)-mass spectrometry(MS) was used to analyze the differential proteins in CSF among groups and bioinformatics analysis was performed to explore the biological functions of the proteins. Behavioral tests showed that sucrose consumption in SPT, total traveling distance in OFT, and times of crossing the platform in MWMT were all reduced(P<0.01) and the immobility time in FST was prolonged(P<0.01) in the LOD group compared with those in the AGED group, suggesting that LOD rats had developed depression symptoms such as anhedonia, decreased locomotor activity ability, and cognitive dysfunction. Behavioral abnormalities were alleviated(P<0.01, P<0.05) in the EXD group as compared with those in the LOD group. Immunofluorescence results demonstrated that Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area were fewer(P<0.05) in LOD group than in the AGED group, and the positive cells in the EXD group were more(P<0.05) than those in the LOD group. In vitro experiment showed that the proliferation and differentiation of primary hippocampal neural stem cells under the CORT+D-gal treatment were reduced(P<0.01). The proliferation rate of neural stem cells decreased(P<0.05) in CORT+D-gal+LOD-CSF group but increased(P<0.01) in CORT+D-gal+EXD-CSF group compared with that in the CORT+D-gal group. A total of 2 620 proteins were identified from rat CSF, with 135 differential proteins between the LOD group and AGED group and 176 between EXD group and LOD group. GDF11, NrCAM, NTRK2, and GhR were related to neurogenesis and 39 differential proteins were regulated by both LOD and EXD. EXD demonstrated obvious anti-LOD effect, as it improved the locomotor activity ability and cognitive function of LOD rats and protected the proliferation and differentiation of hippocampal neural stem cells. EXD exerts anti-LOD effect by regulating the proteins related to neurogenesis in CSF, such as GDF11, NrCAM, NTRK2, and GhR and maintaining hippocampal neurogenesis.