Lupeol improves bile acid metabolism and metabolic dysfunction-associated steatotic liver disease in mice via FXR signaling pathway and gut-liver axis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has a multifactorial and complex pathogenesis. Notably, the disorder of Bile acid (BA) metabolism and lipid metabolism-induced lipotoxicity are the main risk factors of MASLD. Lupeol, traditional regional medicine from Xinjiang, has a long history of use for its anti-inflammatory, anti-tumor, and immune-modulating properties. Recent research suggests its potential as a therapeutic option for MASLD due to its proposed binding capacity to the nuclear BA receptor, Farnesoid X receptor (FXR), hence could represent a therapeutic option for MASLD. In this study, a natural triterpenoid drug lupeol improved BA metabolism and MASLD in mice through the FXR signaling pathway and the gut-liver axis. Furthermore, lupeol effectively restored gut healthiness and improved intestinal immunity, barrier integrity, and inflammation, as indicated by the reconstructed gut flora. Compared with fenofibrate (Feno), lupeol treatment significantly reduced weight gain, fat deposition, and liver injury, decreased serum total cholesterol (TC) and triglyceride (TG) levels, and alleviated hepatic steatosis and liver inflammation. BA analysis showed that lupeol treatment accelerated BA efflux and decreased uptake of BA by increasing hepatic FXR and bile salt export pump (BSEP) expression. Gut microbiota alterations could be related to enhanced fecal BA excretion in lupeol-treated mice. Therefore, consumption of lupeol may prevent HFD-induced MASLD and BA accumulation, possibly via the FXR signaling pathway and regulating the gut microbiota.

[Study on mitigating effect and mechanism of Cichorium glandulosum n-butanol extraction site on CCl_4-induced chronic liver injury in rats].

This study aims to investigate the mitigating effect and mechanism of Cichorium glandulosum n-butanol extraction site(CGE) on the disease in carbon tetrachloride(CCl_4)-induced chronic liver injury model in rats. A chronic liver injury model was constructed by subcutaneous injection of CCl_4 olive oil solution, and after four weeks of CGE treatment, serum levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(AKP), hydroxyproline(HYP), interleukin-4(IL-4), interleukin-6(IL-6), malondialdehyde(MDA), superoxide dismutase(SOD), and tumor necrosis factor-α(TNF-α) were detected. Liver tissue was processed by hematoxylin-eosin(HE) staining and Masson staining to observe the structure of the rat liver. qPCR and Western blot were used to examine the expression of transforming growth factor-ß1(TGF-ß1)/small mothers against decapentaplegic(Smad), Toll-like receptor 4(TLR4), α-smooth muscle actin(α-SMA), and fibronectin(Fn) in rat liver tissue and hepatic stellate-T6(HSC-T6) and evaluate the inhibitory effect of CGE on HSC activation. The results showed that CGE could significantly reduce the serum levels of AST, ALT, AKP, HYP, and affect the levels of related inflammatory indexes including IL-4, IL-6, and TNF-α, and MDA in CCl_4-induced chronic liver injury in rats and had no effect on SOD activity, which could delay the process of liver injury, alleviate the hepatic collagen deposition and inflammatory infiltration, and had significant efficacy in mitigating chronic liver injury in rats. CGE could inhibit α-SMA and TLR4 protein expression in the liver tissue and reverse the increased TGF-ß1/Smad, Fn, and TLR4-related expression in HSC-T6 in vitro. The above results indicated that CGE exerted hepatoprotective effects in rats by inhibiting HSC activation and alleviated CCl_4-induced chronic liver injury in rats and could ameliorate inflammatory response and slight liver fibrosis in rat liver tissue. Its pharmacodynamic mechanism might be related to TGF-ß1/Smad and TLR4-related expression.

Screening of the effective sites of Cichorium glandulosum against hyperuricemia combined with hyperlipidemia and its network pharmacology analysis.

Cichorium glandulosum, a common traditional Chinese medicine used by Uyghur and Mongolian ethnic groups, is recognized for its potential to ameliorate metabolic disorders. However, the specific efficacy and mechanisms of Cichorium glandulosum in treating the comorbidity of hyperuricaemia and hyperlipidaemia remain unexplored. This study aims to explore the pharmacological effects and mechanisms of Cichorium glandulosum on this comorbidity through a combination of animal experiments, network pharmacology, and molecular docking techniques. A rat model of hyperuricaemia combined with hyperlipidaemia was established through a high-fat and high-purine diet, and the effective parts of the aqueous extract of Cichorium glandulosum to reduce uric acid and lipid levels were screened and the components of the parts were analysed by LC-MS/MS. The active components, core targets, and key pathways were analysed using network pharmacology and validated by molecular docking. Animal experimental results indicated that the n-butanol extract of Cichorium glandulosum showed a significant therapeutic effect on this comorbidity. Analysis of the n-butanol extract yielded 35 active ingredients and 138 intersecting targets related to diseases. Key targets identified through compound-target-pathway (C-T-P) and Protein-Protein Interaction (PPI) analyses included RELA, CASP3, PTGS2, TNF, and ESR1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed 2515 functional items and 164 pathways, respectively. Molecular docking demonstrated that isochlorogenic acid A, baicalin, chicoric acid, and lactucopicrin showed the highest binding affinity to RELA and PTGS2. The n-butanol fraction from the aqueous extract of Cichorium glandulosum was found to reduce uric acid and lipid levels effectively. In summary, Cichorium glandulosum has a therapeutic effect on hyperuricaemia combined with hyperlipidaemia through its multi-component, multi-target, and multi-pathway characteristics.

Constructing Sequential Type II Heterojunction CQDs/Bi2S3/TiNbO Photoanode with Superior Charge Transfer Capability Toward Stable Photoelectrochemical Water Splitting.

Efficient charge transfer and light-trapping units are pivotal prerequisites in the realm of Ti-based photoanode photoelectrochemical (PEC) water splitting. In this work, we successfully synthesized a ternary carbon quantum dots/Bi2S3 quantum dots/Nb-doped TiO2 nanotube arrays (CQDs/Bi2S3/TiNbO) composite photoanode for PEC water splitting. CQDs/Bi2S3/TiNbO composite photoanode exhibited a considerably elevated photocurrent density of 8.80 mA cm-2 at 1.23 V vs the reversible hydrogen electrode, which was 20.00 times better than that of TiO2 (0.44 mA cm-2). Furthermore, the CQDs/Bi2S3/TiNbO composite photoanode attested to exceptional stability, maintaining 92.54% of its initial current after 5 h of stability measurement. Nb-doping boosted the electrical conductivity, facilitating charge transfer at the solid-liquid interface. Moderate amounts of Bi2S3 quantum dots (QDs) and CQDs deposited on TiNbO provided abundant active sites for the electrolyte-photoanode interaction. Simultaneously, Bi2S3 QDs and CQDs synergistically functioned as light-trapping units to broaden the light absorption range from 396 to 530 nm, stimulating increased carrier generation within the composite photoanode. In comparison with pristine TiO, CQDs/Bi2S3/TiNbO photoanodes possessed a superior ability to promote interfacial reactions. This study may provide a strategy for developing high-performance Ti-based photoanodes with efficient charge transfer and light trapping units for highly driving solar-to-hydrogen conversion.

Optimization of total flavonoids purification process in rose by uniform design method.

This study aims to establish a method for purifying total flavonoids in roses using macroporous resin columns, intending to leverage and harness their potential. We screened six macroporous resins to evaluate their capacity for their adsorption and desorption, ultimately identifying X5 macroporous resin as the most effective. To comprehensively understand the adsorption behavior, we analyzed it using various models, such as pseudo-first-order and pseudo-second-order kinetic models, particle diffusion models, and Langmuir, Freundlich, and Temkin isotherm models. Employing both single-factor and uniform design, approaches, the focus of this work was on maximizing the total flavonoid recovery rate. A 3-factor and 10-level uniform design table was utilized for optimizing the optimal process parameters and exploring the antioxidant properties of the purified flavonoids. The optimal process conditions for purifying total flavonoids from roses can be summarized as follows: a sample concentration of 2 mg/mL, pH at 2, 55 mL sample volume, eluent ethanol concentration of 75%, eluent volume of 5 BV, and the elution rate set at 1 mL/min. Following purification, the total flavonoid content peaked at 57.82%, achieving an 84.93% recovery rate, signifying substantial antioxidant potential. Consequently, the method established for purifying TFR using X5 macroporous resin in this study proves to be a dependable and reliable method consistent approach.

Multi-omics joint analysis revealed the metabolic profile of retroperitoneal liposarcoma.

Retroperitoneal liposarcoma (RLPS) is the main subtype of retroperitoneal soft sarcoma (RSTS) and has a poor prognosis and few treatment options, except for surgery. The proteomic and metabolic profiles of RLPS have remained unclear. The aim of our study was to reveal the metabolic profile of RLPS. Here, we performed proteomic analysis (n = 10), metabolomic analysis (n = 51), and lipidomic analysis (n = 50) of retroperitoneal dedifferentiated liposarcoma (RDDLPS) and retroperitoneal well-differentiated liposarcoma (RWDLPS) tissue and paired adjacent adipose tissue obtained during surgery. Data analysis mainly revealed that glycolysis, purine metabolism, pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue, whereas the tricarboxylic acid (TCA) cycle, lipid absorption and synthesis, fatty acid degradation and biosynthesis, as well as glycine, serine, and threonine metabolism were downregulated. Of particular importance, the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway (PPP) inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib. Our study not only describes the metabolic profiles of RDDLPS and RWDLPS, but also offers potential therapeutic targets and strategies for RLPS.

Bcl-2 inhibition combined with PPARα activation synergistically targets leukemic stem cell-like cells in acute myeloid leukemia.

Persistence of leukemic stem cells (LSCs) is one of the determining factors to acute myeloid leukemia (AML) treatment failure and responsible for the poor prognosis of the disease. Hence, novel therapeutic strategies that target LSCs are crucial for treatment success. We investigated if targeting Bcl-2 and peroxisome proliferator activated receptor α (PPARα), two distinct cell survival regulating mechanisms could eliminate LSCs. This study demonstrate that the Bcl-2 inhibitor venetoclax combined with the PPARα agonist chiglitazar resulted in synergistic killing of LSC-like cell lines and CD34+ primary AML cells while sparing their normal counterparts. Furthermore, the combination regimen significantly suppressed AML progression in patient-derived xenograft (PDX) mouse models. Mechanistically, chiglitazar-mediated PPARα activation inhibited the transcriptional activity of the PIK3AP1 gene promoter and down-regulated the PI3K/Akt signaling pathway and anti-apoptotic Bcl-2 proteins, leading to cell proliferation inhibition and apoptosis induction, which was synergized with venetoclax. These findings suggest that combinatorial Bcl-2 inhibition and PPARα activation selectively eliminates AML cells in vivo and vitro, representing an effective therapy for patients with relapsed and refractory AML.

Cuproptosis-related risk score predicts prognosis and characterizes the tumor microenvironment in colon adenocarcinoma.

Introduction: Cuproptosis is a novel copper-dependent regulatory cell death (RCD), which is closely related to the occurrence and development of multiple cancers. However, the potential role of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of colon adenocarcinoma (COAD) remains unclear. Methods: Transcriptome, somatic mutation, somatic copy number alteration and the corresponding clinicopathological data of COAD were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). Difference, survival and correlation analyses were conducted to evaluate the characteristics of CRGs in COAD patients. Consensus unsupervised clustering analysis of CRGs expression profile was used to classify patients into different cuproptosis molecular and gene subtypes. TME characteristics of different molecular subtypes were investigated by using Gene set variation analysis (GSVA) and single sample gene set enrichment analysis (ssGSEA). Next, CRG Risk scoring system was constructed by applying logistic least absolute shrinkage and selection operator (LASSO) cox regression analysis and multivariate cox analysis. Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) were used to exam the expression of key Risk scoring genes. Results: Our study indicated that CRGs had relatively common genetic and transcriptional variations in COAD tissues. We identified three cuproptosis molecular subtypes and three gene subtypes based on CRGs expression profile and prognostic differentially expressed genes (DEGs) expression profile, and found that changes in multilayer CRGs were closely related to the clinical characteristics, overall survival (OS), different signaling pathways, and immune cell infiltration of TME. CRG Risk scoring system was constructed according to the expression of 7 key cuproptosis-related risk genes (GLS, NOX1, HOXC6, TNNT1, GLS, HOXC6 and PLA2G12B). RT-qPCR and IHC indicated that the expression of GLS, NOX1, HOXC6, TNNT1 and PLA2G12B were up-regulated in tumor tissues, compared with those in normal tissues, and all of GLS, HOXC6, NOX1 and PLA2G12B were closely related with patient survival. In addition, high CRG risk scores were significantly associated with high microsatellite instability (MSI-H), tumor mutation burden (TMB), cancer stem cell (CSC) indices, stromal and immune scores in TME, drug susceptibility, as well as patient survival. Finally, a highly accurate nomogram was constructed to promote the clinical application of the CRG Risk scoring system. Discussion: Our comprehensive analysis showed that CRGs were greatly associated with TME, clinicopathological characteristics, and prognosis of patient with COAD. These findings may promote our understanding of CRGs in COAD, providing new insights for physicians to predict prognosis and develop more precise and individualized therapy strategies.

Orelabrutinib and venetoclax synergistically induce cell death in double-hit lymphoma by interfering with the crosstalk between the PI3K/AKT and p38/MAPK signaling.

PURPOSE: Double-hit lymphoma (DHL) is a rare and aggressive mature B-cell malignancy with concurrent MYC and BCL2 rearrangements. When DHL becomes relapsed or refractory, it becomes resistant to the majority of therapeutic approaches and has subpar clinical results. Therefore, innovative therapeutics for this particular patient population are urgently needed. METHODS: Orelabrutinib, a new oral BTK inhibitor, combined with the Bcl-2 inhibitor venetoclax, was used to confirm the antitumor effect of DHL. Cell counting kit-8 and Annexin V-FITC/PI assays were used to examine the interaction of this combined regimen on DHL cell lines and primary lymphoma cells. RNA sequencing, EdU incorporation assay, mitochondrial membrane potential assay, and western blotting were employed to explore the molecule mechanism for the cytotoxicity of orelabrutinib with or without venetoclax against DHL cell lines. RESULTS: In this study, orelabrutinib combined with venetoclax synergistically induced DHL cell death, as evidenced by the inhibition of cell proliferation, the induct of cell cycle arrest, and the promotion of cell apoptosis via the mitochondrial pathway. Orelabrutinib treatment alters genome-wide gene expression in DHL cells. The combined regimen decreases the expression of BTK and Mcl-1, potentially interfering with the activity and crosstalk of PI3K/AKT signaling and p38/MAPK signaling. In addition, the combination of orelabrutinib and venetoclax shows cytotoxic activity in primary B-lymphoma cells. CONCLUSION: In summary, these findings reveal a novel therapy targeting BCR signaling and the Bcl-2 family for DHL patients with a poor prognosis.

Therapeutic inhibition of PPARα-HIF1α-PGK1 signaling targets leukemia stem and progenitor cells in acute myeloid leukemia.

Treatment of acute myeloid leukemia (AML) with chemotherapeutic agents fails to eliminate leukemia stem cells (LSC)，and thus patients remain at high risk for relapse. Therefore, the identification of agents that target LSC is an important consideration for the development of new therapies. Enhanced glycolysis in LSC contributes to the aggressiveness of AML, which is difficult to be targeted. In this study, we showed that targeting peroxisome-proliferator-activated receptor α (PPARα), a ligand-activated transcription factor by chiglitazar provided a promising therapeutic approach. We first identified that chiglitazar reduced cell viability and proliferation of the leukemia stem-like cells population in AML. Treatment with chiglitazar blocked the ubiquitination of PPARα and increased its expression, resulting in the inhibition of glucose metabolism and apoptosis of AML cells. Consistent with its anti-leukemia stem-like cells activity in vitro, chiglitazar treatment in vivo resulted in the significant killing of leukemia stem-like cells as demonstrated in AML patient-derived xenograft (PDX) models. Mechanistically, PPARα overexpression inhibited the expression and promoter activity of PGK1 through blocking HIF1-α interaction on the PGK1 promoter. Thus, we concluded that targeting PPARα may serve as a novel approach for enhancing stem and progenitor cells elimination in AML.

Identification of cuproptosis-related subtypes, construction of a prognosis model, and tumor microenvironment landscape in gastric cancer.

Introduction: Cuproptosis is a novel identified regulated cell death (RCD), which is correlated with the development, treatment response and prognosis of cancer. However, the potential role of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of gastric cancer (GC) remains unknown. Methods: Transcriptome profiling, somatic mutation, somatic copy number alteration and clinical data of GC samples were downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database to describe the alterations of CRGs from genetic and transcriptional fields. Differential, survival and univariate cox regression analyses of CRGs were carried out to investigate the role of CRGs in GC. Cuproptosis molecular subtypes were identified by using consensus unsupervised clustering analysis based on the expression profiles of CRGs, and further analyzed by GO and KEGG gene set variation analyses (GSVA). Genes in distinct molecular subtypes were also analyzed by GO and KEGG gene enrichment analyses (GSEA). Differentially expressed genes (DEGs) were screened out from distinct molecular subtypes and further analyzed by GO enrichment analysis and univariate cox regression analysis. Consensus clustering analysis of prognostic DEGs was performed to identify genomic subtypes. Next, patients were randomly categorized into the training and testing group at a ratio of 1:1. CRG Risk scoring system was constructed through logistic least absolute shrinkage and selection operator (LASSO) cox regression analysis, univariate and multivariate cox analyses in the training group and validated in the testing and combined groups. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to evaluate the expression of key Risk scoring genes. Sensitivity and specificity of Risk scoring system were examined by using receiver operating characteristic (ROC) curves. pRRophetic package in R was used to investigate the therapeutic effects of drugs in high- and low- risk score group. Finally, the nomogram scoring system was developed to predict patients' survival through incorporating the clinicopathological features and CRG Risk score. Results: Most CRGs were up-regulated in tumor tissues and showed a relatively high mutation frequency. Survival and univariate cox regression analysis revealed that LIAS and FDX1 were significantly associated with GC patients' survival. After consensus unsupervised clustering analysis, GC patients were classified into two cuproptosis molecular subtypes, which were significantly associated with clinical features (gender, age, grade and TNM stage), prognosis, metabolic related pathways and immune cell infiltration in TME of GC. GO enrichment analyses of 84 DEGs, obtained from distinct molecular subtypes, revealed that DEGs primarily enriched in the regulation of metabolism and intracellular/extracellular structure in GC. Univariate cox regression analysis of 84 DEGs further screened out 32 prognostic DEGs. According to the expression profiles of 32 prognostic DEGs, patients were re-classified into two gene subtypes, which were significantly associated with patients' age, grade, T and N stage, and survival of patients. Nest, the Risk score system was constructed with moderate sensitivity and specificity. A high CRG Risk score, characterized by decreased microsatellite instability-high (MSI-H), tumor mutation burden (TMB) and cancer stem cell (CSC) index, and high stromal and immune score in TME, indicated poor survival. Four of five key Risk scoring genes expression were dysregulated in tumor compared with normal samples. Moreover, CRG Risk score was greatly related with sensitivity of multiple drugs. Finally, we established a highly accurate nomogram for promoting the clinical applicability of the CRG Risk scoring system. Discussion: Our comprehensive analysis of CRGs in GC demonstrated their potential roles in TME, clinicopathological features, and prognosis. These findings may improve our understanding of CRGs in GC and provide new perceptions for doctors to predict prognosis and develop more effective and personalized therapy strategies.

CXCL12, a potential modulator of tumor immune microenvironment (TIME) of bladder cancer: From a comprehensive analysis of TCGA database.

Background: Tumor immune microenvironment (TIME) plays a significant role in the initiation and progression of bladder urothelial carcinoma (BLCA). However, there are only a few researches regarding the association between immune-related genes and tumor-infiltrating immune cells (TICs) in TIME of BLCA. Methods: We calculated the proportion of immune/stromal component and TICs of 414 BLCA samples and 19 normal samples downloaded from TCGA database with the help of ESTIMATE and CIBERSORT algorithms. Differentially expressed genes (DEGs) were obtained from the comparison between Stromal and Immune Score and further analyzed by GO and KEGG enrichment analysis, as well as PPI network and COX regression analysis. CXCL12 was overlapping among the above analyses. Single gene analysis of CXCL12 was carried out through difference analysis, paired analysis and GSEA. The association between CXCL12 and TICs was assessed by difference analysis and correlation analysis. Results: Immune and stromal component in TIME of BLCA were associated with patients' clinicopathological characteristics. 284 DEGs were primarily enriched in immune-associated activities, among which CXCL12 was the most significant gene sharing the leading nodes in PPI network and being closely related with patients' survival. Single gene analysis and immunohistochemistry revealed that CXCL12 was down-regulated in BLCA samples and significantly related with the clinicopathological characteristics of patients. Further analysis suggested that CXCL12 was involved in the immune-associated activities probably through its close cross-talk with TICs. Conclusions: CXCL12 down-regulation could be a potential biomarker to predict the unbalanced immune status of TIME of BLCA, which might provide an extra insight for the immunotherapy of BLCA.

CCL19 has potential to be a potential prognostic biomarker and a modulator of tumor immune microenvironment (TIME) of breast cancer: a comprehensive analysis based on TCGA database.

The development of cancer was determined by not only the intrinsic properties of cancer cells, but also the communication between cancer cells and tumor microenvironment (TME). We applied ESTIMATE and CIBERSORT algorithms to calculate the immune/stromal component and tumor-infiltrating immune cells (TICs) in TME of BC. The results showed that immune component in TME predicted patients' survival and associated with progression of BC. Differentially expressed genes (DEGs) were primarily enriched in immune-related activities. Finally, CCL19 was acquired which shared the leading nodes in PPI network and was associated with patients' survival. High expression of CCL19 predicted better prognosis and participated in progression of BC. Genes in CCL19 up-regulated group were enriched in immune-related activities and these functions might depend on the communications between CCL19 and multiple TICs in TIME. In conclusion, CCL19 functioned as a potential prognostic biomarker and a modulator of TIME in BC through communicating with various TICs.

[The relationship between clinical pathology and prognosis of chronic rhinosinusitis].

Objective:To explore the pathological type, clinical features and their relationship with prognosis of chronic rhinosinusitis（CRS）. Methods:A retrospective study of 135 patients with CRS who underwent surgical treatment in the Affiliated Jiangning Hospital of Nanjing Medical University from January 2017 to December 2018. Review the pathological slices retrospectively and divide the CRS into 4 types, eosinophilic type（eCRS）, lymphocyte or（and） plasma cell type, neutrophil type and mixed type, the latter three are collectively referred to as "non-eosinophil type（non-eCRS）". Follow-up was conducted between January and February 2021 to analyze the distribution, clinical features, and differences in prognosis of the different endotypes. Results:①Among the 135 CRS patients, 42 cases（31.1%） were eCRS and 93 cases（68.9%） were non-eCRS（76 cases[56.3%] of lymphocyte or plasma cell type, 4 cases[3.0%] of neutrophil type and 13 cases[9.6%] of mixed type）. The difference in composition ratio between the groups was statistically significant（n=135, P<0.001）. ②The absolute value and percentage of preoperative peripheral blood eosinophils（EOS） in eCRS patients were higher than those of non-eCRS patients, and the difference was statistically significant（n=125, P（absolute value）=0.030, P（percentage）=0.033）. The results of receiver operating characteristic curve showed that both absolute value and percentage have predictive value, and cut-off value was 0.325×109/L（absolute value） or 2.750%（percentage）. There was no statistically significant difference in preoperative peripheral blood procalcitonin among the groups（n=69, P=0.647）. ③The ratio（E/M value） of the bilateral ethmoid sinus scores and bilateral maxillary sinus scores of the preoperative paranasal sinus CT in eCRS patients was 2.03±1.23, while the non-eCRS patients was 1.47±0.96, and the difference was statistically significant（n=112, P=0.009）. ④In total, 101 cases were effectively followed up, including 34 cases of eCRS（7 cases[20.6%] of control, 18 cases[52.9%] of partial control）, 9 cases[26.5%] of non-control and 67 cases of non-eCRS（32 cases[47.8%] of control, 26 cases[38.8%] were partially controlled, 9 cases[13.4%] were not controlled）, and the efficacy of the non-eCRS group was significantly better than that of the eCRS group（χ²=7.499, P=0.024）. Conclusion:When the absolute value of EOS in the preoperative blood examination is greater than 0.325×109/L or the percentage is greater than 2.750%, eCRS can be predicted, but the accuracy is low. CT of patients with eCRS is mostly characterized by inflammation of the ethmoid sinus and usually E/M>2. The efficacy of eCRS group is worse than that of the non-eCRS group 2-4 years after surgery.

Cichorium pumilum Jacq Extract Inhibits LPS-Induced Inflammation via MAPK Signaling Pathway and Protects Rats From Hepatic Fibrosis Caused by Abnormalities in the Gut-Liver Axis.

The development of liver fibrosis is closely related to the gut microbiota, and the "gut-liver axis" is the most important connection between the two. ethyl acetate extract of Cichorium pumilum Jacq (CGEA) is an herbal extract consisting mainly of sesquiterpenoids. The anti-inflammatory and hepatoprotective effects of CGEA have been reported, but the anti-fibrotic effects of CGEA via intestinal microbes and the "gut-liver axis" cycle have rarely been reported. In this study, we observed that CGEA not only directly attenuated inflammatory factor levels in inflamed mice, but also attenuated liver inflammation as well as liver fibrosis degeneration in rats with liver fibrosis caused by colitis. We observed in vitro that CGEA significantly promoted the growth of Bifidobacterium adolescentis. Similarly, fecal 16S rDNA sequencing of liver fibrosis rats showed that CGEA intervention significantly altered the composition of the intestinal microbiota of liver fibrosis rats. CGEA increased the abundance of intestinal microbiota, specifically, CGEA increased the ratio of Firmicutes to Bacteroidetes, CGEA could significantly increase the levels of Ruminococcus. In addition, CGEA intervention significantly protected intestinal mucosal tissues and improved intestinal barrier function in rats. Lactucin is the main sesquiterpenoid in CGEA, and HPLC results showed its content in CGEA was up to 6%. Lactucin has been reported to have significant anti-inflammatory activity, and in this study, we found that Lactucin decreased p38 kinases (p38), phosphorylation of the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) protein phosphorylation in lipopolysaccharide (LPS)-activated RAW264.7 cells, thereby reducing mRNA expression and protein expression of pro-inflammatory factors inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and inhibiting the release of inflammatory factors interleukin (IL)-6 and nitric oxide (NO), exerting anti-inflammatory effects. In summary, the prevention of liver fibrosis caused by intestinal inflammation by CGEA may be achieved by regulating the intestinal microbiota and restoring the intestinal barrier thereby improving the "gut-liver axis" circulation, reducing liver inflammation, and ultimately alleviating liver fibrosis. Notably, the direct anti-inflammatory effect of CGEA may be due to its content of Lactucin, which can exert anti-inflammatory effects by inhibiting the phosphorylation of Mitogen-activated protein kinase (MAPK) and Akt signaling pathways.

Simultaneous determination of the herbicide bixlozone and its metabolites in plant and animal samples by liquid chromatography-tandem mass spectrometry.

Tracing the herbicide bixlozone and its metabolites in food is necessary to assess their risks to human health. In the study, a rapid and effective analytical method using the quick, easy, cheap, effective, rugged, and safe method for the simultaneous determination of bixlozone and its metabolites (2,4-dichlorobenzoic acid, 3-hydroxy-propanamide-bixlozone, and 5'-hydroxy-bixlozone) in plant and animal samples (tomato, cucumber, apple, wheat flour, meat, milk, and egg) was developed based on ultra high performance liquid chromatography-tandem mass spectrometry. The method was validated based on the linearity (R2  > 0.99), sensitivity (limit of quantification = 0.01 mg/kg), recovery (70.2-115.1%), and precision (intraday 1.2-17.6%, interday 0.3-16.0%). Detection was achieved within 6.0 min. The method is reliable for the determination of four target compounds in all seven matrices. The satisfactory validation criteria and successful application show that the proposed methodology is suitable for the detection of four target compounds in real matrices.

Antiproliferative abietane quinone diterpenoids from the roots of Salvia deserta.

A total of twenty abietane quinone diterpenoids including ten new ones (1-10) were isolated from the roots extract of Salvia deserta. Their chemical structures were delineated by extensive spectrometric and spectroscopic techniques including HRESIMS, NMR, UV, IR, and single-crystal X-ray diffraction analysis, calculated 13C NMR-DP4+ analysis, calculated ECD, and Mo2(OAc)4-induced ECD. The absolute configurations of salvidesertone A (1), 8α,9α-epoxy-6-deoxycoleon U (18), and 7,20-epoxyroyleanone (19) were determined by single-crystal X-ray diffraction analysis. Salvidesertone A (1) represents the first example of a 9-hydroxyabieta-7(8)-ene quinone diterpenoid. This is the first report of the crystal structures of 8α,9α-epoxy-6-deoxycoleon U (18) and 7,20-epoxyroyleanone (19). Abietane quinone diterpenoids 1, 2, and 4-20 were evaluated for their antiproliferative activities against five cancer cell lines A-549, SMMC-7721, SW480, MCF-7, and HL-60 and a normal epithelial cell line BEAS-2B in vitro. Salvidesertones E (8) and F (9) selectively inhibited the proliferation of A-549, SMMC-7721, and SW480 cancer cell lines. Importantly, salvidesertones E (8) and F (9), horminone (13), taxoquinone (14), 7α-O-methylhorminone (15), and 8α,9α-epoxy-6-deoxycoleon U (18) showed more potent antiproliferative effects against A-549 than the positive control cis-platin. A preliminary structure-activity relationship for the antiproliferative effects of abietane quinone diterpenoids 1-20 was discussed.

Gas Chromatography-Mass Spectrometry (GC-MS) Analysis of the Volatile Oil of Cichorium Glandulosum Boiss et Huet and its Effects on Carbon Tetrachloride-Induced Liver Fibrosis in Rats.

BACKGROUND This study aimed to use gas chromatography-mass spectrometry (GC-MS) to identify the chemical constituents of volatile oil extracted by steam distillation from Cichorium glandulosum Boiss et Huet (CG), a traditional Uyghur medicine, and to investigate its effects on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats. MATERIAL AND METHODS Sprague-Dawley rats (n=60) included six groups: the control group (n=10), untreated model group (n=10), the volatile oil of CG high-dose group (0.15 ml/kg) (n=10), the volatile oil of CG medium-dose group (0.10 ml/kg) (N=10), the volatile oil of CG low-dose group (0.05 ml/kg) (n=10), and the silybin-treated group (0.20 ml/kg) (n=10). Rats given the essential oil extract of CG by intragastric administration, and then subcutaneously injected with a solution of CCl4 in olive oil to create the rat model of hepatic fibrosis. Serum samples were analyzed for markers of liver function, including aspartate transaminase (AST), alanine transaminase (ALT), malondialdehyde (MDA), hydroxyproline (Hyp), γ-glutamyl transpeptidase (γ-GT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and albumin (Alb). Histology and immunohistochemistry were performed on rat liver tissue. RESULTS Thirty-eight compounds were identified from the volatile oil of CG (total, 98.058%), with terpenoids, including citronellol, being the most abundant. In the animal model of liver fibrosis, all doses of volatile oil of CG significantly reduced the serum levels of AST, ALT, MDA, Hyp, γ-GT, LDH, ALP, and Alb. CONCLUSIONS GC-MS identified the components of the volatile oil of CG, which included citronellol. Treatment with volatile oil of CG reduced liver fibrosis in a rat model.

Sesquiterpenoids with diverse carbon skeletons from the roots of Cichorium glandulosum and their anti-inflammatory activities.

A total of thirteen sesquiterpenoids with diverse skeletons including four new sesquiterpenoids, glandulosines A - D (1-4), a new natural product, glandulosine E (5), and eight known sesquiterpene lactones (6-13) were isolated from the roots of Cichorium glandulosum Boiss. et Huet (Asteraceae). Their structures were determined by extensive spectroscopic experiments including NMR, electronic circular dichroism (ECD), calculated ECD, Rh2(OCOCF3)4-induced ECD, and single-crystal X-ray diffraction analysis, as well as chemical methods. This is the first report of the crystal structure of 11ß,13-dihydrolactucin (11). Thirteen isolated sesquiterpenoids (1-13) were evaluated for their anti-inflammatory activities in vitro, and three guaiane sesquiterpene lactones, glandulosine E (5), scorzoside (9), and lactucin (10) showed moderate inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages.