Luteolin targets the AGE-RAGE signaling to mitigate inflammation and ferroptosis in chronic atrophic gastritis.

Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and precancerous lesion in stomach cancer. Abnormal activation cellular ferroptosis further damages gastric tissue, which is susceptible to inflammation. Luteolin has powerful anti-inflammatory and regulatory potential for cellular ferroptosis. We aimed to clarify the involvement of luteolin in inflammation and ferroptosis during CAG. Luteolin targets were searched to identify intersecting genes in the chronic atrophic gastritis disease database. The AGE-RAGE pathway is a potential target of luteolin for the treatment of chronic atrophic gastritis and a binding site between luteolin and RAGE was predicted through a computer simulation of molecular docking. We established a CAG rat model using N-methyl-N-nitro-N-nitroguanidine. The therapeutic effect of luteolin on CAG was detected using western blotting, qPCR, hematoxylin and eosin staining, lipid oxidation (MDA), and Fe2+ assays. Luteolin inhibited the AGE-RAGE signaling pathway and reduced the inflammatory response in gastric tissues. Additionally, luteolin downregulated the concentration of (MDA) and Fe2+, and CAG downregulated the expression levels of ACSL4 and NOX1 and upregulated the expression levels of FIH1 and GPX4 ferroptosis-related proteins, thus inhibiting the ferroptosis of gastric tissue cells, which had a therapeutic effect on CAG.

HPLC Coupled with Chemical Fingerprinting for Multi-Pattern Recognition for Identifying the Authenticity of Clematidis Armandii Caulis.

A method for identifying Chinese medicinal materials and their related adulterants was constructed by taking Clematidis Armandii Caulis (Chuanmutong, a universally used traditional Chinese medicine) as an example. Ten batches of genuine Chuanmutong varieties and five batches of related adulterants were analyzed and compared based on the high-performance liquid chromatography (HPLC) fingerprints combined with chemometrics, including cluster analysis (CA), principal component analysis (PCA), and orthogonal partial least-squares discrimination analysis (OPLS-DA). In addition, the content of ß-sitosterol was determined. The control chemical fingerprint of Chuanmutong was established, and 12 common peaks were identified. The similarity between the fingerprint of 10 batches of genuine Chuanmutong varieties and the control fingerprint was 0.910-0.989, while the similarity of five batches of adulterants was only 0.133-0.720. Based on the common peaks in the chromatogram, 15 batches of samples were classified into three content levels by PCA, and were aggregated into four categories by CA, achieving a clear distinction between authentic Chuanmutong and adulterants of Chuanmutong. Further, seven differential components that can effectively identify authentic Chuanmutong and adulterants of Chuanmutong were found through OPLS-DA. The ß-sitosterol content of 10 batches of genuine Chuanmutong varieties was 97.53-161.56 µg/g, while the ß-sitosterol content of the five batches of adulterants varied greatly, among which the ß-sitosterol content of Clematis peterae Hand.-Mazz. and Clematis gouriana Roxb. Var. finetii Rehd. et Wils. was significantly lower than that of authentic varieties of Chuanmutong. The HPLC index component content and chemical fingerprint multi-pattern recognition method established in this study provide a new strategy for effectively identifying authentic Chinese medicinal materials and related adulterants.

Application of network pharmacology in the study of mechanism of Chinese medicine in the treatment of ulcerative colitis: A review.

Network pharmacology is a research method based on a multidisciplinary holistic analysis of biological systems, which coincides with the idea of the holistic view of traditional Chinese medicine. In this review, we summarized the use of network pharmacology technology through studying Chinese medicine single medicine or Chinese medicine compound research ideas and methods for the treatment of ulcerative colitis, based on the application of the current network pharmacology in Chinese medicine research, including the important role in the mechanism of the prediction and verification, to search for new ideas for disease diagnosis and treatment, this study summarizes the application of network pharmacology in the treatment of ulcerative colitis in traditional Chinese medicine, including monotherapy and compound therapy, and considers that relevant research studies have fully demonstrated the function characteristics of the multi-component, multi-target, and multi-pathway of traditional Chinese medicine, and can also explain the connotation of "selecting appropriate treatment methods according to the differences and similarities of pathogenesis" of traditional Chinese medicine. Finally, we raised important questions about the prospects and limitations of network pharmacology, such as differences caused by different data collection methods, a considerable lag, and so on.

[Effect of modified Danggui Shaoyao Powder on SOCS3/TLR4 signaling pathway in rats with chronic atrophic gastritis].

This study aims to investigate the effect of modified Danggui Shaoyao Powder on the suppressor of cytokine signaling 3(SOCS3)/Toll-like receptor 4(TLR4) signaling pathway in gastric tissue of rats with chronic atrophic gastritis(CAG).Sixty SPF-grade SD rats were randomly assigned into the normal group, model group, Moluo Pills group, and high-, medium-, and low-dose groups of modified Danggui Shaoyao Powder.The rats in other groups except the normal group were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) to establish the CAG model.After 12 weeks of modeling, the rats in each group were administrated with corresponding drugs by gavage for 8 weeks.After the last administration, the histopathological changes of rat gastric mucosa were observed via hematoxylin-eosin(HE) staining.The serum levels of IL-6, TNF-α, and CRP were determined by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of SOCS3 and TLR4 were determined by real-time PCR.The protein levels of SOCS3, TLR4, JAK2, p-JAK2, STAT3, and p-STAT3 in rat gastric tissue were measured by Western blot.Immunohistochemical method was employed to determine the protein levels of NF-κB, MyD88, NLRP3, Bcl-2, Bax, and Bad in rat gastric tissue.The results showed that modified Danggui Shaoyao Powder alleviated gastric mucosal atrophy of rats, significantly lowered the levels of IL-6, TNF-α, and CRP in rat serum, up-regulated the mRNA level of SOCS3, and down-regulated the mRNA level of TLR4 in rat gastric tissue.Furthermore, modified Danggui Shaoyao Powder up-regulated the protein level of SOCS3, down-regulated the protein levels of TLR4, p-JAK2, p-STAT3, NF-κB, MyD88, NLRP3, Bax, and Bad, and promoted the expression of Bcl-2 protein.Therefore, modified Danggui Shaoyao Powder may mitigate the gastric mucosal atrophy of rats by regulating the SOCS3/TLR4 signaling pathway.

Application of network pharmacology in the study of the mechanism of action of traditional chinese medicine in the treatment of COVID-19.

Network pharmacology was rapidly developed based on multidisciplinary holistic analysis of biological systems, which has become a popular tool in traditional Chinese medicine (TCM) research in recent years. Its characteristics of integrity and systematization provide a new approach for the study on complex TCM systems, which has many similarities with the holistic concept of TCM. It has been widely used to explain the mechanism of TCM treatment of diseases, drug repositioning, and interpretation of compatibility of TCM prescriptions, to promote the modernization of TCM. The use of TCM have provided crucial support on prevention and treatment of diseases such as the famous "three medicines and three prescriptions". Furthermore, TCM has become an important part of the treatment of COVID-19 and is one of the main contents of the "Chinese plan" to fight the epidemic. The current review demonstrated the role of TCM in treating diseases with multiple components, multiple targets, and multiple pathways, interprets the connotation of TCM treatment method selection based on pathogenesis and also discusses the application of network pharmacology in the study of COVID-19 treatment in TCM including single drug and prescription. However, there are still some shortcomings such as the lack of experimental verification and regular upgrading of the TCM pharmacology network. Therefore, we must pay attention to the characteristics of TCM and develop a network pharmacology method suitable for TCM system research when applying network pharmacology to TCM research.

Chinese Medicine in the Treatment of Ulcerative Colitis: The Mechanisms of Signaling Pathway Regulations.

Ulcerative colitis (UC) is a common clinical inflammatory bowel disease characterized by repeated attacks, difficult treatment, and great harm to the physical and mental health of the patients. The occurrence and development of UC were closely related to the physiological and pathological processes, such as intestinal inflammatory reaction, oxidizing reaction, and immune response. Treatment of ulcerative colitis using Western medicine is often associated with a number of limitations and adverse events. There is a long history of using traditional Chinese medicine in dealing with this medical condition. Commonly used traditional Chinese medicines for the treatment of UC include Caulis Sargentodoxae, Flos Lonicerae, Fructus Cnidii, etc. Additionally, classic prescriptions such as Gegen Qinlian Formulae and Zuojin Pills can also be used to treat UC. To enrich the traditional Chinese medicine theory, the cognitive theory and perspective of network pharmacology and bioinformatics research of cell signal transduction mechanism of UC are emerging rapidly. Modern pharmacological studies focus on underlying mechanisms for the management of UC with Chinese medicine monomers, single Chinese medicines, and traditional Chinese medicine formulations, alleviating the symptoms of UC, controlling the development of intestinal inflammation, and restoring intestinal function through the regulation of key molecular signaling pathways, including PI3K/Akt, NF-[Formula: see text]B, JAK/STAT, MAPK and Notch. By summarizing current research progressions, this review provides key references for the in-depth exploration of the mechanisms focused on signaling pathways for the clinical management of UC using traditional Chinese medicine.

Preparation of an Environmentally Friendly Nano-Insecticide through Encapsulation in Polymeric Liposomes and Its Insecticidal Activities against the Fall Armyworm, Spodoptera frugiperda.

The insecticide emamectin benzoate (EB) was formulated with nanoparticles composed of DSPE-PEG2000-NH2 by the co-solvent method to determine its adverse impacts on the environment and to reinforce its dispersion, adhesion, and biocompatibility. A good encapsulation efficiency (70.5 ± 1.5%) of EB loaded in DSPE-PEG2000-NH2 polymeric liposomes was confirmed. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and contact angle meter measurements revealed that the DSPE-EB nanoparticles had a regular distribution, spherical shape, and good leaf wettability. The contact angle on corn leaves was 47.26°, and the maximum retention was higher than that of the reference product. DSPE-EB nanoparticles had strong adhesion on maize foliage and a good, sustained release property. The efficacy trial showed that the DSPE-EB nanoparticles had a strong control effect on S. frugiperda larvae, with the LC50 of 0.046 mg/L against the third-instar S. furgiperda larve after 48 h treatment. All these results indicate that DSPE-EB nanoparticles can serve as an insecticide carrier with lower environmental impact, sustained release property, and effective control of pests.

Determining the relationship between cytokeratin expression and prognostic factors in human gastric cancer.

Determining the prognosis of gastric cancer is the most crucial step in the treatment process. Cytokeratins are intermediate filaments found in the intracellular structure of epithelial tissues. Recent researches have focused on determining the relationship between the expression of cytokeratins and the degree and prognosis of tumors. This study aimed to investigate the relationship between the incidence of cytokeratin-20 and cytokeratin-7 in patients with gastric carcinoma with factors influencing the prognosis. In this regard, the study was conducted cross-sectional. The expression of cytokeratin-20 and cytokeratin-7 was evaluated on 50 gastric adenocarcinoma specimens with different degrees of differentiation by the immunohistochemical method. We determined the relationship between the incidence of cytokeratin-20 and cytokeratin-7 with factors affecting the prognosis of patients, including the degree of differentiation of gastric cancer tissue, lymph node involvement, and the depth of tumor invasion. Data were statistically analyzed by Chi-square and Spearman tests. The results showed a statistically inverse relationship between the incidence of cytokeratin-20 and cytokeratin-7 with the degree of tissue differentiation and lymph node involvement in gastric cancer. Although there was a statistically significant relationship between the incidence of tissue invasion in gastric cancer and the incidence of cytokeratin-7, there was no association between the incidence of cytokeratin-20 and tissue invasion. In general, decreased cytokeratin-20 and cytokeratin-7 are associated with decreased tissue differentiation and increased lymph node involvement.

Exploring the Potential Mechanism of Xiaokui Jiedu Decoction for Ulcerative Colitis Based on Network Pharmacology and Molecular Docking.

Introduction: Network pharmacology is in line with the holistic characteristics of TCM and can be used to elucidate the complex network of interactions between disease-specific genes and compounds in TCM herbal medicines. Here, we investigate the pharmacological mechanism of Xiaokui Jiedu decoction (XJD) for the treatment of ulcerative colitis (UC). Methods: The Computational Systems Biology Laboratory Platform (TCMSP) database was searched and screened for the active ingredients of all drugs in XJD. The Uniport database was used to retrieve possible gene targets for the therapeutic effects of XJD. GeneCards, PharmGKB, TTD, and OMIM databases were used to retrieve XJD-related gene targets. A herb-compound-protein network and a protein-protein interaction (PPI) network were constructed, and hub genes were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to validate the interrelationship between disease target proteins and active drug components. Results: A total of 135 XJD potential action targets, 5097 UC-related gene targets, and 103 XJD-UC intersection gene targets were screened. The hub gene targets of XJD that exert therapeutic effects on UC are RB1, MAPK1, TP53, JUN, NR3C1, MAPK3, and ESR1. GO enrichment analysis showed 741 biofunctional enrichments, and KEGG enrichment analysis showed 124 related pathway enrichments. Molecular docking showed that the active components of XJD (ß-sitosterol, kaempferol, formononetin, quercetin, and luteolin) showed good binding activities to five of the six hub gene targets. Discussion. The active ingredients of XJD (ß-sitosterol, kaempferol, formononetin, quercetin, and luteolin) may regulate the inflammatory and oxidative stress-related pathways of colon cells during the course of UC by binding to the hub gene targets. This may be a potential mechanism of XJD in the treatment of UC.

Glucocorticoid and pyrazolone treatment of acute fever is a risk factor for critical and life-threatening human enterovirus 71 infection during an outbreak in China, 2008.

BACKGROUND: Human enterovirus 71 (HEV71) causes outbreaks of life-threatening diseases throughout the world. The genesis of these severe diseases is unknown. METHODS: During an outbreak of HEV71 infection, we investigated risk factors for critical illness. We developed a modified pediatric index of mortality (mPIM) incorporating heart rate, temperature, white blood cell count, respiratory rate, chest infiltrates, skin color, reflexes, responsiveness, and mobility. We calculated the mPIM for 103 patients (22 deaths) using complete scoring criteria in the medical record. In a case-control study, we compared cases (mPIM > or =10 or death) with controls (mPIM = 0-9) by drugs received within 96 hours after onset of fever, initial temperature, age, and nutritional anthropometry. RESULTS: About 66% (68/103) of the patients with an mPIM score (28 cases and 40 controls) had data on initial exposures. About 50% of the 28 cases and 18% of the 40 controls received an injection to treat fever during the first 96 hours after onset (Odds ratio [OR] = 7.0, 95% confidence interval [CI]: 1.8-28). Injections containing exclusively glucocorticoids (OR = 4.8, 95% CI: 1.2-21) or pyrazolones (OR = 4.1, 95% CI: 0.91-19, P = 0.047) were risk factors for severe HEV71 infection. About 25% of cases and 5% of controls received both drugs parenterally while 7% of cases and 30% of controls received neither (OR = 21, 95% CI: 1.8-305). Conversely, cases and controls had identical average initial temperature, and did not differ significantly by age, sex, nutritional measurements, use of other drugs, or timeliness of medical care received. CONCLUSION: Fever treatment with glucocorticoids and/or pyrazolones is a risk factor for life-threatening HEV71 infection.