[Process in the role of vasoactive intestinal peptide in the treatment of ulcerative colitis by regulating the balance of T follicular helper cells/T follicular regulatory cells].

Ulcerative colitis (UC) is an autoimmune disease based on the persistent damage of colonic mucosal barrier. It has been found that the abnormal expression of follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells is closely related to the occurrence and development of UC. Tfh cells can secrete pro-inflammatory factors and assist B cells to produce antibodies, which can promote the development of UC, while Tfr cells can inhibit the activity of Tfh cells and secrete anti-inflammatory factors. How to regulate the balance between them has become one of the potential therapeutic targets of UC. Vasoactive intestinal peptide (VIP) has preventive and therapeutic effect on UC, and its mechanism is closely related to the regulation of Tfh/Tfr cell balance, which can provide help for the treatment of UC.

Reyanning mixture inhibits M1 macrophage polarization through the glycogen synthesis pathway to improve lipopolysaccharide-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Reyanning (RYN) mixture is a traditional Chinese medicine composed of Taraxacum, Polygonum cuspidatum, Scutellariae Barbatae and Patrinia villosa and is used for the treatment of acute respiratory system diseases with significant clinical efficacy. AIM OF THE STUDY: Acute lung injury (ALI) is a common clinical disease characterized by acute respiratory failure. This study was conducted to evaluate the therapeutic effects of RYN on ALI and to explore its mechanism of action. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the chemical components of RYN. 7.5 mg/kg LPS was administered to induce ALI in rats. RYN was administered by gavage at doses of 2 ml/kg, 4 ml/kg or 8 ml/kg every 8 h for a total of 6 doses. Observations included lung histomorphology, lung wet/dry (W/D) weight ratio, lung permeability index (LPI), HE staining, Wright-Giemsa staining. ELISA was performed to detect the levels of TNF-α, IL-6, IL-10, Arg-1,UDPG. Immunohistochemical staining detected IL-6, F4/80 expression. ROS, MDA, SOD, GSH/GSSG were detected in liver tissues. Multiple omics techniques were used to predict the potential mechanism of action of RYN, which was verified by in vivo closure experiments. Immunofluorescence staining detected the co-expression of CD86 and CD206, CD86 and P2Y14, CD86 and UGP2 in liver tissues. qRT-PCR detected the mRNA levels of UGP2, P2Y14 and STAT1, and immunoblotting detected the protein expression of UGP2, P2Y14, STAT1, p-STAT1. RESULTS: RYN was detected to contain 1366 metabolites, some of the metabolites with high levels have anti-inflammatory, antibacterial, antiviral and antioxidant properties. RYN (2, 4, and 8 ml/kg) exerted dose-dependent therapeutic effects on the ALI rats, by reducing inflammatory cell infiltration and oxidative stress damage, inhibiting CD86 expression, decreasing TNF-α and IL-6 levels, and increasing IL-10 and Arg-1 levels. Transcriptomics and proteomics showed that glucose metabolism provided the pathway for the anti-ALI properties of RYN and that RYN inhibited lung glycogen production and distribution. Immunofluorescence co-staining showed that RYN inhibited CD86 and UGP2 expressions. In vivo blocking experiments revealed that blocking glycogen synthesis reduced UDPG content, inhibited P2Y14 and CD86 expressions, decreased P2Y14 and STAT1 mRNA and protein expressions, reduced STAT1 protein phosphorylation expression, and had the same therapeutic effect as RYN. CONCLUSION: RYN inhibits M1 macrophage polarization to alleviate ALI. Blocking glycogen synthesis and inhibiting the UDPG/P2Y14/STAT1 signaling pathway may be its molecular mechanism.

Multisignals Sensing Platform for Highly Sensitive, Accurate, and Rapid Detection of p-Aminophenol Based on Adsorption and Oxidation Effects Induced by Defective NH2-Ag-nMOFs.

Labile toxic pollutants detection remains a challenge due to the problem that a single method is prone to producing false-negative/-positive signals. The construction of a multisignal sensing platform with the advantages of different strategies is an effective way to solve this problem. Herein, a novel resonant light scattering (RLS), fluorescent and rapid visual multisignals sensing strategy for p-aminophenol (p-AP) detection was designed based on the adsorption and oxidation effects of defective amino-functionalized Ag-based nano metal-organic frameworks (NH2-Ag-nMOFs). In this reaction process, NH2-Ag-nMOFs with incomplete coordination oxidize H2O2 to produce singlet oxygen (1O2) which rapidly oxidizes p-AP, leading to the reduction of Ag+ to Ag0, thereby disrupting the structure of NH2-Ag-nMOFs and resulting in fluorescence quenching of NH2-Ag-nMOFs. Synchronously, owing to Ag0 aggregation and p-AP oxidation, the color of the system changed from colorless to purplish-red and pale brown within 20 s. The assay has realized the rapid naked-eye detection of 5 µM p-AP rapidly. Additionally, thanks to the intermolecular hydrogen bonding, NH2-Ag-nMOFs-p-AP aggregates formed, which enhanced the RLS signal. With the RLS signal, the designed multisignals sensing platform can analyze p-AP at a concentration as low as 11 nM and yield a wider dynamic response range than any single signal strategy reported before, which can quickly meet the measurement requirement of different actual samples. Overall, the proposed strategy without assembling various signal indicators presented an accurate, rapid, cost-effective, and sensitive multisignals sensing platform for p-AP analysis and has great prospects in labile toxic pollutants monitoring.

Molecular Mechanism of Qingzaojiufei Decoction in the Treatment of Pulmonary Fibrosis based on Network Pharmacology and Molecular Docking.

BACKGROUND: In recent years, pulmonary fibrosis (PF) has increased in incidence and prevalence. Qingzaojiufei decoction (QD) is a herbal formula that is used for the treatment of PF. OBJECTIVE: In this research, network pharmacology and molecular docking methods were used to explore the major chemical components and potential mechanisms of QD in the treatment of PF. METHODS: The principal components and corresponding protein targets of QD were used to screen on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) and high-throughput experiment-and reference-guided database (HERB), Cytoscape 3.7.2 was used to construct the drug-component-target network. PF targets were collected by GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The protein-protein interaction (PPI) network was constructed by importing compound-disease intersection targets into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape3.7.2. We further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersecting targets. In the last, we validated the core targets and active compounds by molecular docking. RESULTS: The key compounds of quercetin, (-)-epigallocatechin-3-gallate, and kaempferol of QD were obtained. The key targets of AKT1, TNF, and IL6 of QD were obtained. The molecular docking results show that quercetin, (-)-epigallocatechin-3-gallate and kaempferol work well with AKT1, TNF and IL6. CONCLUSION: This research shows the multiple active components and molecular mechanism of QD in the treatment of PF and offers resources and suggestions for future studies.

Multi-omics analysis reveals the mechanism of action of ophiopogonin D against pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with limited therapeutic strategies. Therefore, there is an urgent need to search for safe and effective drugs to treat this condition. Ophiopogonin D (OP-D), a steroidal saponin compound extracted from ophiopogon, possesses various pharmacological properties, including anti-inflammatory, antioxidant, and antitumor effects. However, the potential pharmacological effect of OP-D on pulmonary fibrosis remains unknown. PURPOSE: The aim of this study was to investigate whether OP-D can improve pulmonary fibrosis and to explore its mechanism of action. METHODS: The effect of OP-D on pulmonary fibrosis was investigated in vitro and in vivo using a mouse model of IPF induced by bleomycin and an in vitro model of human embryonic lung fibroblasts induced by transforming growth factor-ß1 (TGF-ß1). The mechanism of action of OP-D was determined using multi-omics techniques and bioinformatics. RESULTS: OP-D attenuated epithelial-mesenchymal transition and excessive deposition of extracellular matrix in the lungs, promoted the apoptosis of lung fibroblasts, and blocked the differentiation of lung fibroblasts into myofibroblasts. The multi-omics techniques and bioinformatics analysis revealed that OP-D blocked the AKT/GSK3ß pathway, and the combination of a PI3K/AKT inhibitor and OP-D was effective in alleviating pulmonary fibrosis. CONCLUSION: This study demonstrated for the first time that OP-D can reduce lung inflammation and fibrosis. OP-D is thus a potential new drug for the prevention and treatment of pulmonary fibrosis.

Xiaojianzhong decoction attenuates aspirin-induced gastric mucosal injury via the PI3K/AKT/mTOR/ULK1 and AMPK/ULK1 pathways.

CONTEXT: Xiaojianzhong decoction (XJZD), classically prescribed in Chinese medicine, has protective and healing effects on gastric mucosal injury. However, the exact mechanism behind this effect remains unclear. OBJECTIVE: To investigate the effect of XJZD on gastric mucosal injury and explore its underlying mechanisms. MATERIALS AND METHODS: C57BL/6 mice were randomized into six groups (n = 10): the control group receiving sterile water, the model (aspirin 300 mg/kg), the XJZD high-dose (12 g/kg), XJZD medium-dose (6 g/kg), XJZD low-dose (3 g/kg) and omeprazole (20 mg/kg) groups, by gavage daily for 14 days. The area of gastric mucosal injury, mucosal injury index and degree of histopathological damage were analysed. Gastric mucosal epithelial cell apoptosis was detected. Epithelial cell autophagy was observed. The expression levels of tight junction proteins and proteins related to apoptosis, autophagy and the pentose phosphate pathway were analysed. RESULTS: The results showed that after treatment with XJZD (12, 6 and 3 g/kg), the mucosal injury area was reduced (83.4%, 22.6% and 11.3%), the expression level of ZO-1 and occludin was up-regulated, the apoptosis rate of epithelial cells was reduced (40.8%, 25.4% and 8.7%), the expression of autophagy-related proteins LC3 and Beclin1 was decreased and the expression of p62 was increased, the PI3K/AKT/mTOR/ULK1(ser757) signalling pathway was activated, and the AMPK/ULK1(ser317) signalling pathway was inhibited. In addition, XJZD can antagonize the imbalance of redox homeostasis caused by aspirin and protect the gastric mucosa. DISCUSSION AND CONCLUSIONS: XJZD protects against aspirin-induced gastric mucosal injury, implying it to be a potential therapeutic agent.

Recent advances in metal-organic frameworks: Synthesis, application and toxicity.

Metal-organic frameworks (MOFs) are a new class of crystalline porous hybrid materials with high porosity, large specific surface area and adjustable channel structure and biocompatibility, which are being investigated with increasing interest for energy storage and conversion, gas adsorption/separation, catalysis, sensing and biomedicine. However, the practical applications of MOFs make them release into the environment inevitable, posing a threat to humans and organisms. In this article, we cover advances in the currently available MOFs synthesis methods and the emerging applications of MOFs, especially in the biomedical field (therapeutic agents and bioimaging). Additionally, after evaluating the current status of main exposure routes and affecting factors in the field of MOFs-toxicity, the molecular mechanism is also clarified and identified. Knowledge gaps are identified from such a summarization and frontier development are explored for MOFs. Afterwards, we also present the limitations, challenges, and future perspectives in the study of the entire life cycle of MOFs. This review emphasizes the need for a more targeted discussion of the latest, widely used and effective versatile material class in order to exploit the full potential of high-performance and non-toxicity MOFs in the future.

Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells.

BACKGROUND: Gastric precancerous lesions (GPL) precede the development of gastric cancer (GC). They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation, bacterial infection, and injury. Abnormalities in autophagy and glycolysis affect GPL progression, and their effective regulation can aid in GPL treatment and GC prevention. Xiaojianzhong decoction (XJZ) is a classic compound for the treatment of digestive system diseases in ancient China which can inhibit the progression of GPL. However, its specific mechanism of action is still unclear. AIM: To investigate the therapeutic effects of XJZ decoction on a rat GPL model and the mechanisms underlying its effects on autophagy and glycolysis regulation in GPLs. METHODS: Wistar rats were randomly divided into six groups of five rats each and all groups except the control group were subjected to GPL model construction for 18 wk. The rats' body weight was monitored every 2 wk starting from the beginning of modeling. Gastric histopathology was examined using hematoxylin-eosin staining and Alcian blue-periodic acid-Schiff staining. Autophagy was observed using transmission electron microscopy. The expressions of autophagy, hypoxia, and glycolysis related proteins in gastric mucosa were detected using immunohistochemistry and immunofluorescence. The expressions of the following proteins in gastric tissues: B cell lymphoma/Leukemia-2 and adenovirus E1B19000 interacting protein 3 (Bnip-3), microtubule associated protein 1 light chain 3 (LC-3), moesin-like BCL2-interacting protein 1 (Beclin-1), phosphatidylinositol 3-kimase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), p53, AMP-activated protein kinase (AMPK), and Unc-51 like kinase 1 (ULK1) were detected using western blot. The relative expressions of autophagy, hypoxia, and glycolysis related mRNA in gastric tissues was detected using reverse transcription-polymerase chain reaction. RESULTS: Treatment with XJZ increased the rats' body weight and improved GPL-related histopathological manifestations. It also decreased autophagosome and autolysosome formation in gastric tissues and reduced Bnip-3, Beclin-1, and LC-3II expressions, resulting in inhibition of autophagy. Moreover, XJZ down-regulated glycolysis-related monocarboxylate transporter (MCT1), MCT4, and CD147 expressions. XJZ prevented the increase of autophagy level by decreasing gastric mucosal hypoxia, activating the PI3K/AKT/mTOR pathway, inhibiting the p53/AMPK pathway activation and ULK1 Ser-317 and Ser-555 phosphorylation. In addition, XJZ improved abnormal gastric mucosal glucose metabolism by ameliorating gastric mucosal hypoxia and inhibiting ULK1 expression. CONCLUSION: This study demonstrates that XJZ may inhibit autophagy and glycolysis in GPL gastric mucosal cells by improving gastric mucosal hypoxia and regulating PI3K/AKT/mTOR and p53/ AMPK/ULK1 signaling pathways, providing a feasible strategy for the GPL treatment.

Mechanism of Nrf2 in the treatment of ulcerative colitis via regulating macrophage polarization. / Nrf2é€šè¿‡è°ƒæŽ§å·¨å™¬ç»†èƒžæžåŒ–æ²»ç–—æºƒç–¡æ€§ç»“è‚ ç‚Žçš„æœºåˆ¶.

Ulcerative colitis (UC) is an inflammatory bowel disease induced by multiple factors, which causes abnormal activation of intestinal immune cells and excessive release of antibodies and inflammatory factors, repeatedly damaging the intestinal mucosa. Macrophages, as innate intestinal immune cells, often maintain the balance of M1/M2 macrophages polarization to normalize the regression inflammation, and the imbalance of their polarization will cause repeated damage of intestinal mucosa and persistent inflammation, which is a main cause of UC. Nuclear factor E2-related factor 2 (Nrf2), as an important regulator of antioxidant and anti-inflammatory, is often used as a target for the treatment of autoimmune diseases.Nrf2 alleviates intestinal high oxidative stress and inflammatory factors by balancing macrophage polarization, which may be of great significance for the prevention and treatment of UC. Summarizing the mechanism of macrophage polarization imbalance on the course of UC and the possible regulatory mechanism of Nrf2 may provide basis for the development of UC targeted therapeutic drugs.

Cataluminescence System Coupled with Vacuum Desorption-Sampling Methodology for Real-Time Ozone Sensing during the Self-Decomposition Process on Functional Boron Nitride.

The treatment and detection of ozone have been widely studied in recent decades with respect to toxicity and contamination, while the measurement method of ozone is relatively toneless. Fortunately, a new concept of the cataluminescence (CTL) sensor provides a scheme of real-time ozone sensing in a tiny system. Here, a novel CTL sensor system was specially developed with silica-hydroxyl functional boron nitride as the sensing material for rapid and sensitive ozone detection. Coupled with the construction of a pulse vacuum static sampling system, ozone on the surface of sensing material can be desorbed rapidly and can step into the next detection circulation in a few seconds. Based on the strong emission initiated by the transient of reactive oxygen species (ROS) including singlet oxygen, a trioxide group, and an oxygen radical, the detection limit of ozone could be optimized to be as low as 51.2 ppb. Besides, the sensor system exhibited remarkable anti-interference performance in which humidity changes and common VOCs do not disturb or weakly disturb ozone sensing, and the CTL mechanism of the multistep degradation process was further discussed on the basis of multiple pieces of experimental evidence and a DFT transient calculation. A real-time degradation-sensing module was further attached to the system to realize the functions of ozone decomposition and real-time monitoring.

Xiaojianzhong decoction attenuates gastric mucosal injury by activating the p62/Keap1/Nrf2 signaling pathway to inhibit ferroptosis.

Gastric mucosal injury is the initial stage of the occurrence and development of gastric diseases. Oxidative stress and ferroptosis caused by the imbalance of redox and iron dynamics in gastric mucosal epithelial cells are present throughout the occurrence and development of gastric mucosal injury. Therefore, the inhibition of oxidative stress and ferroptosis is a potential target for the treatment of the gastric mucosal injury. Xiaojianzhong decoction (XJZ), which consists of six Chinese herbal medicines and extracts, is used for the treatment of diseases related to gastrointestinal mucosal injury; however, its specific mechanism of action has yet to be clarified. In this study, we clarified the protective effect of XJZ on gastric mucosa and revealed its underlying mechanism. We established a gastric mucosal injury model using aspirin and administered XJZ. Furthermore, we systematically evaluated the mucosal injury and examined the expression of genes related to oxidative stress, ferroptosis, and inflammation. The study found that XJZ significantly counteracted aspirin-induced gastric mucosal injury and inhibited oxidative stress and ferroptosis in mice. Upon examining SQSTM1/p62(p62)/Kelch-like ECH-associated protein 1 (Keap1)/Nuclear Factor erythroid 2-Related Factor 2 (Nrf2), a well-known signaling pathway involved in the regulation of oxidative stress and ferroptosis, we found that its activation was significantly inhibited by aspirin treatment and that this signaling pathway was activated after XJZ intervention. Our study suggests that XJZ may inhibit aspirin induced oxidative stress and ferroptosis via the p62/Keap1/Nrf2 signaling pathway, thereby attenuating gastric mucosal injury.

[Experimental study on effects of berberine combined with 6-shogaol on intestinal inflammation and flora in mice with ulcerative colitis].

Cold-heat combination is a common method in the treatment of ulcerative colitis, which is represented by classic drug pair, Coptidis Rhizoma and Zingiberis Rhizoma.The present study explored the synergetic effects of berberine and 6-shogaol, the primary components of Coptidis Rhizoma and Zingiberis Rhizoma, respectively, on intestinal inflammation and intestinal flora in mice with ulcerative colitis to reveal the effect and mechanism of cold-heat combination in the treatment of ulcerative colitis.The ulcerative colitis model was induced by dextran sulfate sodium(DSS) in mice.The model mice were administered with berberine(100 mg·kg~(-1)), 6-shogaol(100 mg·kg~(-1)), and berberine(50 mg·kg~(-1)) combined 6-shogaol(50 mg·kg~(-1)) by gavage, once per day.After 20 days of drug administration, mouse serum, colon tissues, and feces were sampled.Hematoxylin-eosin(HE) staining was used to observe histopathological changes in colon tissues.Alcian blue/periodic acid-Schiff(AB/PAS) staining was used to observe the changes in the mucus layer of colon tissues.Enzyme-linked immunosorbent assay(ELISA) was employed to detect the serum content of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and interleukin-6(IL-6).Immunohistochemical method was adopted to detect the protein expression of macrophage surface markers F4/80, mucin-2, claudin-1, and zonula occludens-1(ZO-1) in colon tissues.High-throughput Meta-amplicon library sequencing was used to detect changes in the intestinal flora of mice.The results indicated that the 6-shogaol group, the berberine group, and the combination group showed significantly relieved intestinal injury, reduced number of F4/80-labeled positive macrophages in colon tissues, increased protein expression of mucin-2, claudin-1, and ZO-1, and decreased serum le-vels of TNF-α, IL-1ß, and IL-6.Shannon, Simpson, Chao, and Ace indexes of the intestinal flora of mice in the 6-shogaol group and the combination group significantly increased, and Chao and Ace indexes in the berberine group significantly increased.As revealed by the bioinformatics analysis of intestinal flora sequencing, the relative abundance of Verrucomicrobia at the phylum, class, and order levels decreased significantly in all treatment groups after drug administration, while that of Bacillibacteria gradually increased.In the 6-shogaol group and the combination group, Akkermansia muciniphila completely disappeared, but acid-producing bacillus still existed in large quantities.As concluded, both 6-shogaol and berberine can inhibit intestinal inflammation, reduce the infiltration and activation of macrophages, relieve intestinal damage, reduce intestinal permeability, improve the structure of flora, and promote intestinal microecological balance.The combined application of berberine and 6-shogaol has a significant synergistic effect.

CagA and VacA inhibit gastric mucosal epithelial cell autophagy and promote the progression of gastric precancerous lesions. / CagA和VacAæŠ‘åˆ¶èƒƒé»è†œä¸Šçš®ç»†èƒžçš„è‡ªå™¬å¹¶ä¿ƒè¿›èƒƒç™Œå‰ç— å˜çš„æ¶åŒ–.

Cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) are the keys to the pathogenic role of Helicobacter pylori and the high-risk factors for the progression of gastric precancerous lesions. Autophagy can stabilize the intracellular environment, resist Helicobacter pylori infection, prevent the accumulation of damaged DNA, and inhibit the proliferation of gastric precancerous variant cells. However, CagA and VacA can inhibit the activation of upstream signals of autophagy and the maturation of autophagy-lysosomes in various ways, thus inhibiting the autophagy of gastric mucosal cells in precancerous lesions of gastric cancer. This change can cause Helicobacter pylori to be unable to be effectively cleared by autophagy, so CagA and VacA can persist and promote the inflammation, oxidative stress, apoptosis of gastric mucosal tissue cells, and the glycolytic activity and proliferation of variant cells in gastric precancerous lesions and a series of malignant biological processes. In recent years, the research on drugs specifically inhibiting the activities of CagA and VacA has become a new direction for the prevention and treatment of Helicobacter pylori-related severe gastric diseases, and a variety of drugs or components that can precisely and effectively regulate the factors for the treatment of gastric precancerous lesions are emerged, which opens a new strategy for the treatment of gastric precancerous lesions in the future.

Treatment of ulcerative colitis with Wu-Mei-Wan by inhibiting intestinal inflammatory response and repairing damaged intestinal mucosa.

BACKGROUND: Wu-Mei-Wan (WMW), a traditional Chinese medicine, has been applied in the treatment of gastrointestinal diseases with long-term diarrhea and mucopurulent bloody stool as the main symptoms since ancient times. Studies have shown that WMW inhibits intestinal inflammation, repairs damaged intestinal mucosa, resists colon necrosis, and resists intestinal fibrosis. However, the specific mechanism of action is not yet clear. OBJECTIVE: Ulcerative colitis (UC), an intestinal disease with intestinal inflammation and injury as the main pathological manifestations, is one of the high-risk factors for colon cancer. Inhibiting the inflammatory response and promoting colonic epithelial repair are critical to the treatment of UC. However, there is still a lack of remedies with satisfactory curative effects. In this study, the role of WMW in dextran sulfate sodium (DSS)-induced colitis in mice and its related mechanisms are discussed from two aspects: intestinal inflammation and tissue repair. METHODS: DSS was used to induce colitis in mice and the therapeutic effect of WMW was analyzed by disease activity score, histopathological score, colon length measurement, serum cytokine detection, and flow cytometry. Macrophage activation and colonic stem cell proliferation were observed by immunohistochemistry. The expression of critical molecules in macrophage activation and colonic stem cell proliferation signaling pathways in colon tissue was detected with immunohistochemistry, immunofluorescence staining, RT-qPCR, and Western blot. RESULTS: WMW could significantly alleviate DSS-induced colitis. We showed that WMW could reduce disease activity, reduce pathological scores, limit weight loss, inhibit colon shortening, inhibit inflammatory factor secretion, attenuate inflammatory response, and promote the repair of damaged colonic epithelium. WMW inhibited the activation of colonic macrophages, and its mechanism might be inhibiting the Notch/NF-κB/NLRP3 pathway; WMW promoted the proliferation of colonic stem cells, and its mechanism was associated with the regulation of the Hippo/YAP signaling pathway. CONCLUSION: The results of this study suggested that WMW could treat UC via a mechanism that inhibited the intestinal inflammatory response and repaired damaged intestinal mucosa.

Fe-doped MOF-derived N-rich porous carbon nanoframe for H2 S cataluminescence sensing.

Metal-doped porous carbon matrix composites are considered as outstanding H2 S cataluminescence sensing materials for their good sulfur tolerance and high cataluminescence activity. In this work, an Fe-doped MOF-derived N-rich porous carbon nanoframe was successfully fabricated using the pyrolysis of Fe-doped ZIF-8 in an Ar atmosphere at a temperature of 900°C, and used for H2 S cataluminescence sensing. Along with zinc volatilization, the obtained porous carbon nanoframe not only had high specific surface area and abundant voids, but also had well dispersed Fe species doped in the skeleton. Compared with Fe2 O3 /ZnO composites derived from the same precursor but different pyrolysis terms, this as-prepared Fe-doped N-rich porous carbon presented a three times increase in the cataluminescence intensity towards H2 S, attributed to the porous carbon skeleton that is indispensable for dispersing catalytic active sites and providing more absorptive surface and voids. Comparably, this proposed sensor demonstrated high sensitivity and good selectivity, with the detection range of 1.57-19.58 µg·ml-1 and detection limit of 0.13 µg·ml-1 towards H2 S. This work may provide a new pathway for preparing catalysts for cataluminescence sensing with better metal distribution, higher specific surface area, and richer pores than ever before.

Wu-Mei-Wan Ameliorates Murine Ulcerative Colitis by Regulating Macrophage Polarization.

An increasing body of evidence shows that macrophages play an important role in the pathogenesis of ulcerative colitis (UC). Macrophage polarization and changes in related signaling pathways are reported to have a protective effect on intestinal inflammation. The well-known Chinese medicine Wumeiwan (WMW) has been used to treat diarrhea, one of the main symptoms of colitis, for more than 2,000 years. Increasing evidence shows that WMW can inhibit intestinal inflammation and repair damaged intestinal mucosa, but its effector mechanisms are unknown. Therefore, we studied the prophylactic effects of WMW in dextran sulfate sodium (DSS)-induced UC and its effects on macrophage mechanisms and polarization. The results show that colitis was significantly alleviated in mice in the WMW group, and the secretion and expression of pro-inflammatory factors TNF-α, IL-1, and IL-6 were inhibited in the serum and colonic tissues of mice with WMW-treated colitis, whereas anti-inflammatory factors IL-10, Arg-1, and TGF-ß1 were increased. Subsequent studies found that WMW could inhibit M1 polarization and promote M2 polarization in colonic macrophages in DSS-induced colitis mice. Network pharmacology was used to predict potential targets and pathways, and further studies confirmed the related targets The results showed that WMW gradually inhibits the activation of the P38MAPK and NF-κB signaling pathways and further activates the STAT6 signaling pathway. In summary, WMW interferes with the p38MAPK, NF-κB and STAT6 signaling pathways to regulate M1/M2 polarization in macrophages, thereby protecting mice against DSS-induced colitis.

[Mechanism of lung and intestine combination therapy in treatment of acute lung injury by inhibiting inflammatory response based on NF-κB/NLRP3 signaling pathway and alveolar macrophage activation].

Lung and intestine combination therapy(LICT) is effective in the treatment of acute lung injury(ALI). In this study, the combination of Mahuang Decoction and Dachengqi Decoction(hereinafter referred to as the combination), a manifestation of LICT, was employed to explore the effect of nuclear factor kappaB(NF-κB)/nucleotide binding oligomerization domain-like receptors-3(NLRP3) pathway and alveolar macrophage activation on the lung inflammation in rats with ALI, for the purpose of elucidating the mechanism of LICT in treating ALI. After the modeling of ALI with limpolysaccharide(LPS, ip), rats were respectively given(ig) the combination at 10, 7.5, and 5 g·kg~(-1)(high-dose, medium-dose, and low-dose LICT groups, separately), once every 8 h for 3 times. Haematoxylin-eosin(HE) staining was used to observe the histopathological changes of lung tissue, followed by the scoring of inflammation. Immunohistochemistry was applied to detect alveolar macrophage activation, enzyme-linked immunosorbent assay(ELISA) was applied to detect the serum content of tumor necrosis factor-α(TNF-α) and interleukin-18(IL-18), Western blot was applied to detect the protein expression of phosphorylated-nuclear factor kappaB p65(p-NF-κB p65), nuclear factor kappaB p65(NF-κB p65), phosphorylated-inhibitor kappaB alpha(p-IκBα), inhibitor kappaB alpha(IκBα), and NLRP3 in lung tissue, and quantitative reverse transcription-PCR(qRT-PCR) was applied to detect the mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. The results showed that LICT groups demonstrated lung injury relief, decrease in inflammation score, alleviation of alveolar macrophage activation, significant decline in serum content of inflammatory factors TNF-α and IL-18, and decrease of the protein expression of p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3, and mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. In summary, LICT has definite therapeutic effect on ALI. The mechanism is that it inhibits alveolar macrophage activation by suppressing NF-κB/NLRP3 signaling pathway, thereby reducing the activation and release of inflammatory factors and finally inhibiting inflammation.

Combination of pseudoephedrine and emodin ameliorates LPS-induced acute lung injury by regulating macrophage M1/M2 polarization through the VIP/cAMP/PKA pathway.

BACKGROUND: Acute lung injury (ALI) is an acute multifactorial infectious disease induced by trauma, pneumonia, shock, and sepsis. This study aimed to investigate the protective effects of pseudoephedrine and emodin combined treatment in experimental ALI, as well as the mechanisms underlying the regulation of inflammation and pulmonary edema via the VIP/cAMP/PKA pathway. METHODS: The wistar rats were randomly divided into fifteen groups (n = 5). Rats in each group were given intragastric administration 1 h before LPS injection. Those in the control and LPS groups were given intragastric administrations of physiological saline, rats in other groups were given intragastrically administered of differential dose therapeutic agents. The rats in the LPS and treatment groups were then injected intraperitoneally with LPS (7.5 mg/kg) to induce ALI. After being treated with pseudoephedrine and emodin for 12 h, all animals were sacrifice. Anal temperatures were taken on an hourly basis for 8 h after LPS injection. Pathological examination of lung specimen was performed by H&E staining. Cytokines (IL-1ß, TNF-α, IL-6, iNOS, IL-10, Arg-1, CD86, CD206, F4/80, VIP) in lung tissue were assayed by ELISA and immunofluorescence. The expression of VIP, CAMP, AQP-1, AQP-5, p-PKA, PKA, p-IκBα, IκBα, p-p65, p65, p-P38, P38, p-ERK1/2, ERK1/2, p-JNK1/2, JNK1/2 protein in lung was determined by western blotting. RESULTS: After rats being treated with pseudoephedrine + emodin, reduced of fever symptoms. The contents of inflammatory cytokines (IL-1ß, TNF-α, IL-6, iNOS) were decreased and anti-inflammatory cytokines (IL-10, Arg-1) were significantly increased in serum. Pseudoephedrine + emodin treatment effectively promoted VIP cAMP and p-PKA protein expression in lung tissues, and significantly inhibited NF-κB, MAPK phosphorylation, Pseudoephedrine + emodin treatment can inhibit M1 polarization and promoted M2 polarization via the VIP/cAMP/PKA signaling pathway. CONCLUSIONS: The combination of Pseudoephedrine and emodin was effective in ameliorating LPS-induced ALI in rats by inducing VIP/cAMP/PKA signaling. Inhibiting the NF-κB, MAPK inflammatory pathway, relief of pulmonary edema suppressing macrophage M1 polarization, and promoting macrophage M2 polarization.

To assess the effective and safety of compound glutamine entersoluble capsules in irritable bowel syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is one the common medical condition of functional GI disorder (FGD) characterized by bowel-related symptoms without other organic gastrointestinal (GI) disease. Compound Glutamine Entersoluble Capsules(CGEC),a compound preparation in which each capsule contains 120 mg L-glutamine, 50 mg ginseng, 50 mg licorice, 50 mg Atractylodes macrocephala and 50 mg Poria cocos, have been reported the efficacy of CGEC for patients with IBS in improving the clinical symptoms and quality of patients' life. However, there is no a systematic review related to CGEC for IBS to this day. In this study, we will systematically evaluate the effectiveness and safety of CGEC in the treatment of IBS-D with a meta-analysis method, so as to provide a solid evidence for clinical practice. METHODS: In this study, a literature search was performed by using the Chinese and English databases, which include PubMed, Embase, MEDLINE, Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI) database, Wanfang Data Knowledge Service Platform, the VIP information resource integration service platform (cqvip), China Biology Medicine Disc (Sino Med),and the Chinese Clinical Trial Registry (ChiCTR), to find the related literature of CGEC in the treatment of IBS published from the inception date of each predefined database upto January 2021. The evaluation of the risk of bias for eligible studies will be performed by two investigators. Data synthesis will be performed by RevMan 5.4 software. Heterogeneity between studies can be assessed by a heterogeneity X2 test. The degree of heterogeneity among multiple included studies can be measured by I2. The stability of systematic review or meta-analysis outcomes will be evaluated by Sensitivity analysis. Reporting bias will be evaluated by funnel plot. Finally, The Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess the quality of evidence obtained. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: Whether it is the effectiveness and safety of CGEC in the treatment of IBS will be judged in the result of this systematic review.

Novel Strategy for Engineering the Metal-Oxide@MOF Core@Shell Architecture and Its Applications in Cataluminescence Sensing.

Cataluminescence is an attractive oxydic luminescence on the gas-solid interface, and metal-oxide@MOF core@shell architectures show great potential for cataluminescence sensing due to their integrated synergistic effect from core and shell components. However, restricting the direct nucleation and growth of metal-organic frameworks (MOFs) on the topologically distinct surface of metal oxides is a great challenge, owing to the high interface energy from the topology mismatch. Herein, for the first time, a novel liquid-phase concentration-controlled nucleation strategy is exploited to induce the direct assembly of a ZIF-8 layer on the surface of CeO2 nanospheres without any sacrificial templates or further surface modifications. The results show that the construction of the CeO2@ZIF-8 core@shell architecture can be accomplished within 1 min under the mediation of boosted nucleation kinetics. Furthermore, the universality of this developed strategy is demonstrated by the encapsulation of other metal-oxide cores such as magnetic Fe3O4 and ZnCo2O4 core particles with a ZIF-8 shell. Notably, compared to the pure CeO2 and ZIF-8, the obtained CeO2@ZIF-8 nanocomposite exhibits enhanced analytical performance for the cataluminescence sensing of propanal, in which the shell acts as the major catalytic reaction center, while the core contributes to further improving the catalytic efficiency. The proposed facile synthesis strategy with excellent simplicity, rapidity, and universality brings new insights into the engineering of core@shell advanced functional materials with mismatched topologies for catering to the diverse application demands.