Simvastatin attenuates silica-induced pulmonary inflammation and fibrosis in rats via the AMPK-NOX pathway.

BACKGROUND: Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms. METHODS: The rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway. RESULTS: Sim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and transforming growth factor-ß1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions. CONCLUSIONS: Sim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.

The Effect of Fermentation on the Chemical Constituents of Gastrodia Tuber Hallimasch Powder (GTHP) Estimated by UHPLC-Q-Orbitrap HRMS and HPLC.

OBJECTIVE: To compare the effect of fermentation on the chemical constituents of Gastrodia Tuder Halimasch Powder (GTHP), to establish its fingerprinting and multicomponent content determination, and to provide a basis for the processing, handling, and clinical application of this herb. METHODS: Ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to conduct a preliminary analysis of the chemical constituents in GTHP before and after fermentation. High-performance liquid chromatography (HPLC) was used to determine some major differential components of GTHP and establish fingerprints. Cluster analysis (CA), and principal component analysis (PCA) were employed for comprehensive evaluation. RESULTS: Seventy-nine compounds were identified, including flavonoids, organic acids, nucleosides, terpenoids, and others. The CA and PCA results showed that ten samples were divided into three groups. Through standard control and HPLC analysis, 10 compounds were identified from 22 peaks, namely uracil, guanosine, adenosine, 5-hydroxymethylfurfural (5-HMF), daidzin, genistin, glycitein, daidzein, genistein, and ergosterol. After fermentation, GTHP exhibited significantly higher contents of uracil, guanosine, adenosine, 5-hydroxymethylfurfural, and ergosterol and significantly lower genistein and daidzein contents. CONCLUSIONS: The UHPLC-Q-Orbitrap HRMS and HPLC methods can effectively identify a variety of chemical components before and after the fermentation of GTHP. This study provides a valuable reference for further research on the rational clinical application and quality control improvement of GTHP.

SARS-Cov-2 spike induces intestinal barrier dysfunction through the interaction between CEACAM5 and Galectin-9.

Background: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), as a typical tumor marker, has been found to exert immunomodulatory effects in many diseases. We previously reported the clinical and molecular evidences supporting that SARS-Cov-2 infected the gastrointestinal (GI) tract and found a reduction of CEACAM5 in COVID-19 patients' feces which associated with gut dysbiosis. Yet the role of CEACAM5 in GI infection is ill-defined. Methods: Mice models were established through intraperitoneally injecting with recombinant viral spike-Fc to mimic the intestinal inflammation. We collected duodenum, jejunum, ileum and colon samples after 6h, 2 days, 4 days and 7 days of spike-Fc or control-Fc injection to perform proteomic analysis. Blood was collected from healthy donors and peripheral blood mononuclear cells (PBMC) were separated by density gradient centrifugation, then CD4+ T cells were isolated with magnetic beads and co-cultured with Caco-2 cells. Results: In addition to intestinal CEACAM5, the expression of tight junction and the percent of CD4+ T lymphocytes were significantly decreased in spike-Fc group compared to control (p < 0.05), accompanied with increased level of inflammatory factors. The KEGG analysis revealed differentially expressed proteins were mainly enriched in the coronavirus disease (COVID-19), tight junction, focal adhesion, adherens junction and PI3K-Akt signaling pathway. Protein-protein interaction (PPI) network analysis identified the interaction between CEACAM5 and Galectin-9 that was also verified by molecular docking and co-IP assay. We further confirmed a reduction of CEACAM5 in SARS-CoV-2 spike stimulated enterocytes could promote the expression of Galectin-9 protein in CD4+T cells. Then it gave rise to the increasing release of inflammatory factors and increased apoptosis of CD4+T cells by inhibition of PI3K/AKT/mTOR pathway. Ultimately intestinal barrier dysfunction happened. Conclusion: Our results indicated that CEACAM5 overexpression and Galectin-9 knockdown played a protective role in intestinal barrier injury upon spike-Fc stimulation. Collectively, our findings identified firstly that SARS-CoV-2 spike induced intestinal barrier dysfunction through the interaction between CEACAM5 and Galectin-9. The result provides potential therapeutic targets in intestinal barrier dysfunction for treating severe COVID patients.

"Let them be": Family members' perspectives on the participation of advanced cancer patients in nursing research: A qualitative descriptive study.

BACKGROUND: Recruiting advanced cancer patients is crucial for nursing research in cancer care. However, nurse researchers often face various socio-cultural challenges, particularly in mainland China, where cultural taboos around death pose significant obstacles. An unexplored constraint in this context is the pivotal role Chinese family members play in patients' healthcare decision-making. This research gap underscores the need for a deeper understanding of Chinese family members' perspectives on the engagement of advanced cancer patients in nursing research. OBJECTIVE: To explore the perceptions and concerns of family members regarding the recruitment and participation of advanced cancer patients in nursing research. DESIGN: A qualitative descriptive study was conducted. SETTINGS: Three cancer hospitals in mainland China. PARTICIPANTS: A purposive sample of 18 family members, consisting of children or spouses of advanced cancer patients, was recruited as participants. METHODS: Semi-structured interviews were conducted to collect data between September 2022 and January 2023. The thematic analysis method was used to analyze the data. RESULTS: Three themes were identified: The absence of prior participation, Family members' reluctance to facilitate patient involvement, and Strategies to encourage patients' future participation. Family members were hesitant to allow their relatives with advanced cancer to engage in nursing research, primarily due to concerns about distressing patients, the use of potential sensitive language, stigma, and the risks involved in participation. To address these concerns, they emphasized the importance of gaining family approval prior to patient enrolment. They highlighted the need of family involvement on behalf of sick relatives in research, advocating for the inclusion of a wide range of patients rather than targeting specific subgroups. They also reiterated the significance of choosing the right time for participation and avoiding using sensitive terms such as 'cancer', 'dying', and 'death' when engaging with patients. Moreover, they proposed the recruitment of patients by trusted professionals, shortening the duration of research activities and simplifying research procedures. CONCLUSIONS: This study provides fresh insights into the perspectives of family members concerning the recruitment and engagement of advanced cancer patients in nursing research. It emphasizes the importance of addressing their concerns and recommendations, aiding nurse researchers in developing culturally sensitive recruitment strategies and fostering the inclusive participation of advanced cancer patients in nursing research within the context of family-centered care and cultural taboos surrounding death.

Gas Chromatographic-Ion Mobility Spectrometry Combined with Chemometrics to Study the Changes in Characteristic Odor Components of Galli gigerii Endothelium Corneum in Different Processing Methods.

Galli gigerii endothelium corneum (GGEC) is a traditional Chinese medicine commonly used in clinical practice to treat various conditions such as indigestion, vomiting, spermatorrhea, and enuresis. In this study, the volatile components of different concoctions of GGEC were examined by gas chromatography-ion mobility spectrometry (GC-IMS), and the changes of the components were compared by fingerprinting, combined with principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) to analyze the main volatile components and find out the different markers that can distinguish the different concoctions of GGEC. In the result, the GC-IMS fingerprints of GGEC and its different concoctions showed differences in their volatile components, of which 49 volatiles were clearly characterized, with some components including monomers and dimers. The characteristic volatile components of raw GGEC (SP) were n-nonanal, (E)-2-octenal, beta-ocimene, 2-ethyl-1-hexanol, etc. The characteristic volatile components of stir-fried GGEC (QC) are heptanal, 2-octanol, (E)-2-heptenal, etc. The characteristic volatile components of sand ironing GGEC (ST) are isoamyl acetate, decanal, cyclohexanone, 2-ethyl pyrazine, etc. The characteristic volatile components of stir-fried GGEC with vinegar (CZ) are thiazole, linalool, 2,3,5-trimethylpyrazine, etc. The characteristic volatile components of stir-fried GGEC with milk (FH) are 2-methylbutanoic acid, ethyl acetate, ethyl 2-hydroxypropanoate, butyl acetate, etc. By chemometric analysis, components such as n-nonanal, (E)-2-octenal, 2-pentyl-furan, butanal, 1,4-dioxane, and 2-methylpropanoic acid could be used as difference markers to distinguish different concoction products of GGEC. Furthermore, by analyzing different volatile compounds, we can examine the changes in volatile components during processing of GGEC, which can provide experimental data for the identification and establishment of quality standards.

[Difference of lipid-lowering efficacy of "Xinjianqu" before and after fermentation and its mechanism based on LKB1-AMPK pathway and 16S rDNA sequencing technology].

On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper further compared the differences in the lipid-lowering effects of Xinjianqu before and after fermentation, and studied the mechanism of Xinjianqu in the treatment of hyperlipidemia. Seventy SD rats were randomly divided into seven groups, including normal group, model group, positive drug simvastatin group(0.02 g·kg~(-1)), and low-dose and high-dose Xinjianqu groups before and after fermentation(1.6 g·kg~(-1) and 8 g·kg~(-1)), with ten rats in each group. Rats in each group were given high-fat diet continuously for six weeks to establish the model of hyperlipidemia(HLP). After successful modeling, the rats were given high-fat diet and gavaged by the corresponding drugs for six weeks, once a day, to compare the effects of Xinjianqu on the body mass, liver coefficient, and small intestine propulsion rate of rats with HLP before and after fermentation. The effects of Xinjianqu before and after fermentation on total cholesterol(TC), triacylglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), creatinine(Cr), motilin(MTL), gastrin(GAS), and the Na~+-K~+-ATPase levels were determined by enzyme-linked immunosorbent assay(ELISA). The effects of Xinjianqu on liver morphology of rats with HLP were investigated by hematoxylin-eosin(HE) staining and oil red O fat staining. The effects of Xinjianqu on the protein expression of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), liver kinase B1(LKB1), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase(HMGCR) in liver tissues were investigated by immunohistochemistry. The effects of Xinjianqu on the regulation of intestinal flora structure of rats with HLP were studied based on 16S rDNA high-throughput sequencing technology. The results showed that compared with those in the normal group, rats in the model group had significantly higher body mass and liver coefficient(P<0.01), significantly lower small intestine propulsion rate(P<0.01), significantly higher serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2(P<0.01), and significantly lower serum levels of HDL-C, MTL, GAS, Na~+-K~+-ATP levels(P<0.01). The protein expression of AMPK, p-AMPK, and LKB1 in the livers of rats in the model group was significantly decreased(P<0.01), and that of HMGCR was significantly increased(P<0.01). In addition, the observed＿otus, Shannon, and Chao1 indices were significantly decreased(P<0.05 or P<0.01) in rat fecal flora in the model group. Besides, in the model group, the relative abundance of Firmicutes was reduced, while that of Verrucomicrobia and Proteobacteria was increased, and the relative abundance of beneficial genera such as Ligilactobacillus and Lachnospiraceae＿NK4A136＿group was reduced. Compared with the model group, all Xinjianqu groups regulated the body mass, liver coefficient, and small intestine index of rats with HLP(P<0.05 or P<0.01), reduced the serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2, increased the serum levels of HDL-C, MTL, GAS, and Na~+-K~+-ATP, improved the liver morphology, and increased the protein expression gray value of AMPK, p-AMPK, and LKB1 in the liver of rats with HLP and decreased that of LKB1. Xinjianqu groups could regulate the intestinal flora structure of rats with HLP, increased observed＿otus, Shannon, Chao1 indices, and increased the relative abundance of Firmicutes, Ligilactobacillus(genus), Lachnospiraceae＿NK4A136＿group(genus). Besides, the high-dose Xinjianqu-fermented group had significant effects on body mass, liver coefficient, small intestine propulsion rate, and serum index levels of rats with HLP(P<0.01), and the effects were better than those of Xinjianqu groups before fermentation. The above results show that Xinjianqu can improve the blood lipid level, liver and kidney function, and gastrointestinal motility of rats with HLP, and the improvement effect of Xinjianqu on hyperlipidemia is significantly enhanced by fermentation. The mechanism may be related to AMPK, p-AMPK, LKB1, and HMGCR protein in the LKB1-AMPK pathway and the regulation of intestinal flora structure.

[Comparison of chemical compositions of different parts of Xanthoceras sorbifolium seeds based on UHPLC-Q-Orbitrap HRMS].

Xanthoceras sorbifolium seeds have a wide range of applications in the food and pharmaceutical industries. To compare and analyze the chemical compositions of different parts of X. sorbifolium seeds and explore the potential value and research prospects of non-medicinal parts, this study used ultra-high-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) to detect the chemical composition of various parts of the seeds. A total of 82 components were preliminary identified from X. sorbifolium seeds, including 5 amino acids, 4 polyphenols, 3 phenylpropionic acids, 7 organic acids, 15 flavonoids, 6 glycosides, and 23 saponins. Mass spectrometry molecular networking(MN) analysis was conducted on the results from different parts of the seeds, revealing significant differences in the components of the seed kernel, seed coat, and seed shell. The saponins and flavonoids in the seed kernel were superior in terms of variety and content to those in the seed coat and shell. Based on the chromatographic peaks of different parts from multiple batches of samples, multivariate statistical analysis was carried out. Four differential components were determined using HPLC, and the average content of these components in the seed kernel, seed coat, and seed shell were as follows: 0.183 6, 0.887 4, and 1.440 1 mg·g~(-1) for fraxin; 0.035 8, 0.124 1, and 0.044 5 mg·g~(-1) for catechin; 0.032 9, 0.072 0, and 0.221 5 mg·g~(-1) for fraxetin; 0.435 9, 2.114 7, and 0.259 7 mg·g~(-1) for epicatechin. The results showed that catechin and fraxetin had relatively low content in all parts, while fraxin had higher content in the seed coat and seed shell, and epicatechin had higher content in the seed kernel and seed coat. Therefore, the seed coat and seed shell possess certain development value. This study provides rapid analysis and comparison of the chemical compositions of different parts of X. sorbifolium seeds, which offers an experimental basis for the research and clinical application of medicinal substances in X. sorbifolium seeds.

Pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and JAK2/STAT3 signaling pathways.

Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic so far. Pirfenidone has consistently been shown to have anti-inflammatory and anti-fibrotic effects, but the specific mechanism by which it ameliorates fibrosis in silicosis is unclear. A rat silicosis model was established in this study, and lung tissues and serum were collected by batch execution at 14, 28, and 56 days. Also, the effects of Pirfenidone on macrophage polarization and pulmonary fibrosis were evaluated in silicosis with early intervention and late treatment by histological examination, Enzyme-linked immunosorbent assay, Hydroxyproline assay, Western blot and Quantitative reverse transcription polymerase chain reaction. The results showed that Pirfenidone significantly reduced pulmonary fibrosis in rats with silicosis, and both early intervention and late treatment effectively inhibited the expression of α-SMA, Col-I, Vimentin, Hydroxyproline, IL-1ß, IL-18, and the M2 macrophage marker CD206 and Arg-1, while only early intervention effectively inhibited E-cad, TGF-ß1, TNF-α, and the M1 macrophage marker iNOS, CD86. Furthermore, Pirfenidone dramatically reduced the mRNA expression of the JAK2/STAT3. These findings imply that Pirfenidone may reduce pulmonary fibrosis in silicosis rats by inhibiting macrophage polarization via the JAK2/STAT3 signaling pathway.

Difference analysis of different parts of chicory based on HPLC fingerprint and multi-component content determination.

Objective: To establish HPLC fingerprints of different parts of chicory stems, leaves, roots, flowers and seeds, and compare the similarities and differences of chemical components in different parts, so as to provide a scientific basis for the comprehensive utilization of chicory. Methods: To establish the HPLC fingerprint of chicory, the chromatographic column was chosen with Agilent ZORBAX Eclipse XDB-C18, the mobile phase was methanol (A) - 0.2% formic acid (B), the flow rate was 1 mL/min, the column temperature was 30 °C, and the detection wavelength was 254 nm. The Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine (2012 Edition) was used to evaluate the similarity of different parts of decoction pieces, and the determination method of multi-component content was established based on fingerprint identification chromatographic peaks, and the determination results were analyzed. Results: The HPLC fingerprinting method of chicory was established. Sixteen chromatographic peaks were identified and 10 of them were identified as: caftaric acid (1), esculin (2), chlorogenic acid (3), esculetin (4), caffeic acid (5), cichoric acid (8), hyperoside (11), rutin (12), isochlorogenic acid C (14) and luteolin (16). The similarity of different parts was 0.084-0.701. At the same time, the total content of detected chemical components was ranked as flower > leaf > stem > root > seed. Roots did not contain caftaric acid, rutin, and luteolin, flowers did not contain luteolin, and seeds did not contain caftaric acid, cichoric acid, and luteolin. The content of cichoric acid in leaves was the most, and esculin in flowers was the most. Conclusion: The results of HPLC fingerprint and multi-component content determination revealed the similarity and difference of different parts of chicory from chemical composition, indicating that there were certain differences in different parts of chicory. The established HPLC fingerprinting method can provide a reference for quality control and evaluation of different parts of the chicory.

The clinicopathological and prognostic significances of IGF-1R and Livin expression in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. However, limited effective biomarkers are associated with the tumorigenesis and prognosis of CRC. METHODS: The present study identified potential signatures from The Cancer Genome Atlas (TCGA) database and further validated the identified biomarkers in CRC tissues by immunohistochemistry (IHC). RESULTS: The expression of insulin-like growth factor 1 receptor (IGF-1R) and Livin gene was significantly upregulated in CRC samples compared to the adjacent normal samples in the TCGA dataset. IHC indicated that IGF-1R and Livin protein levels are increased in CRC and adenoma tissues compared to normal tissues. Notably, the IGF-1R protein levels differed significantly between adenoma and CRC. The elevated IGF-1R and Livin expression was associated with CRC clinicopathological features, including age, gender, histological subtype, individual cancer stages, nodal metastasis, and TP53-mutant in TCGA. Additionally, the IGF-1R promoter methylation level was closely related to CRC. Consistent with the TCGA study, IHC indicated that overexpressed IGF-1R and Livin proteins were independent risk factors for stage and metastasis. A marked correlation was established between IGF-1R and Livin expression in CRC, while the survival map showed no significant correlation with CRC. Kaplan-Meier survival curves showed that CRC patients with high IGF-1R or Livin expression had a prolonged overall disease-free survival than those with low expression in TCGA. CONCLUSION: IGF-1R and Livin are associated with CRC tumorigenesis and might be valuable for novel biomarker identification and targeted therapeutic strategy development.

Structural characterization and immunomodulatory activities of two polysaccharides from Rehmanniae Radix Praeparata.

The structures and immunomodulatory activities of two polysaccharides (SDH-WA and SDH-0.2A) from Rehmanniae Radix Praeparata (RRP) were investigated. RRP crude polysaccharide was obtained by water extraction and purified. Ion chromatography, high-performance gel permeation chromatography, Fourier-transform infrared spectroscopy, methylation analysis, gas chromatography-mass spectrometry, and nuclear magnetic resonance were used to characterize the polysaccharides. The main chain of SDH-WA was →6)-α-D-Galp-(1→6)-α-D-Galp-(1→5)-α-L-Araf-(1→3,5)-α-L-Araf-(1→, terminal sugar residue α-L-Araf-(1→ linked to residue →3,5)-α-L-Araf-(1→ on the main chain by an O-3 bond. The other two terminal sugar residues α-D-Galp-(1→ and →6)-ß-D-Galp were linked to the end of the main chain. The main chain of SDH-0.2A was →2,4)-α-L-Rhap-(1→4)-α-D-GalpA-(1→. Three branched chains α-D-Galp-(1→6)-α-D-Galp-(1→5)-α-L-Araf-(1→3,5)-α-L-Araf-(1→, →3,6)-ß-D-Galp-(1→5)-α-L-Araf-(1→, and →4)-ß-D-Galp-(1→5)-α-L-Araf-(1→ were linked to the main chain residue →2,4)-α-L-Rhap-(1→ by an O-2 bond. Three terminal sugar residues α-D-Galp-(1→, α-L-Araf-(1→, and →6)-ß-D-Galp were linked to the end of the chain. Both polysaccharides showed no cytotoxic effects on and significantly promoted the phagocytic activity of RAW264.7 cells. They dose-dependently improved lysozyme activity and stimulated the production of TNF-α and IL-6 by RAW264.7 cells, but attenuated the secretion of lysozymes, TNF-α, IL-6, IL-1ß, and nitric oxide by lipopolysaccharide-induced RAW264.7 cells. The present studies suggest that PRR polysaccharide is a valuable source with immunomodulating.

HO-1/CO Maintains Intestinal Barrier Integrity through NF-κB/MLCK Pathway in Intestinal HO-1-/- Mice.

BACKGROUND: Intestinal barrier injury is an important contributor to many diseases. We previously found that heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal barrier. This study is aimed at elucidating the molecular mechanisms of HO-1/CO in barrier loss. MATERIALS AND METHODS: We induced gut leakiness by injecting carbon tetrachloride (CCl4) to wildtype or intestinal HO-1-deficient mice. In addition, we administrated tumor necrosis factor-α (TNF-α) to cells with gain- or loss-of-HO-1 function. The effects of HO-1/CO maintaining intestinal barrier integrity were investigated in vivo and in vitro. RESULTS: Cobalt protoporphyrin and CO-releasing molecule-2 alleviated colonic mucosal injury and TNF-α levels; upregulated tight junction (TJ) expression; and inhibited epithelial IκB-α degradation and phosphorylation, NF-κB p65 phosphorylation, long MLCK expression, and MLC-2 phosphorylation after administration of CCl4. Zinc protoporphyrin completely reversed these effects. These findings were further confirmed in vitro, using Caco-2 cells with gain- or loss-of-HO-1-function after TNF-α. Pretreated with JSH-23 (NF-κB inhibitor) or ML-7 (long MLCK inhibitor), HO-1 overexpression prevented TNF-α-induced TJ disruption, while HO-1 shRNA promoted TJ damage even in the presence of JSH-23 or ML-7, thus suggesting that HO-1 dependently protected intestinal barrier via the NF-κB p65/MLCK/p-MLC-2 pathway. Intestinal HO-1-deficient mice further demonstrated the effects of HO-1 in maintaining intestinal barrier integrity and its relative mechanisms. Alleviated hepatic fibrogenesis and serum ALT levels finally confirmed the clinical significance of HO-1/CO repairing barrier loss in liver injury. CONCLUSION: HO-1/CO maintains intestinal barrier integrity through the NF-κB/MLCK pathway. Therefore, the intestinal HO-1/CO-NF-κB/MLCK system is a potential therapeutic target for diseases with a leaky gut.

Gas chromatographic-ion mobility spectrometry combined with a multivariate analysis model exploring the characteristic changes of odor components during the processing of black sesame.

Black sesame (Sesamum indicum L.) is a Chinese dietary herb that has been widely used in the medical and healthcare fields in China. According to the theory of Traditional Chinese medicine processing, reasonable processing (steaming and drying many times) can increase the tonic effect and reduce the adverse factors generated during long-term use. At present, the processing degree of black sesame is mainly judged based on subjective experience. However, due to the lack of objective and quantitative control indicators, quality fluctuations easily occur. Therefore, for better application, its processing technology needs scientific monitoring methods. Herein a gas chromatography-ion mobility spectrometry (GC-IMS) technique was applied as a monitoring method to differentiate the processed products of black sesame in different processing stages. The response data of volatile components obtained from the samples were processed by the built-in data processing software in the instrument to identify the different components for further principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). From fingerprint comparison, 70 differential signal peaks were screened, 32 of which were qualitatively identified, mainly monomers and dimers of 20 compounds. On this basis, the PCA model shows that there was a significant difference between the raw product (S1) and the processed products (H1-9); moreover, there was a certain correlation between the differential changes of samples in different processing stages (H1-9) and the processing times. The OPLS-DA model specifically shows the differential components in the processing with potential characteristics peaks of 41, 105, n-nonanal, 2 and ethanol can discriminate whether the BS has undergone the first processed. And the dynamic changes of the three characteristic peaks of 1-hexanol, acetic acid and 107 can determine the specific degree of processing of BS. The research proves that GC-IMS combined with a multivariate analysis model can provide scientific data for identifying the characteristic odor components of black sesame.

Barbaloin pretreatment attenuates myocardial ischemia-reperfusion injury via activation of AMPK.

Myocardial ischemia/reperfusion (MI/R) injury is a major cause of cardiac dysfunction during cardiovascular surgery and heart transplantation and characterized by hyperactive oxidative stress and inflammatory response. Barbaloin (BAR) is the main medicinal composition of the Chinese traditional medicine aloe vera. BAR has strong anti-oxidant, anti-inflammatory and anti-tumor properties. However, the effect of BAR on MI/R-induced myocardial injury is not explored. This study aims to investigate whether BAR provides cardio-protection against MI/R injury and the underlying mechanisms. BAR (20 mg/kg/d) or vehicle was intragastrically administered to Sprague-Dawley rats for 5 days before MI/R operation. BAR pretreatment conferred cardio-protective effects against MI/R injury by improving hemodynamic function and limiting infarction size. Moreover, BAR pretreatment effectively inhibited I/R-induced myocardial oxidative stress and inflammatory response. Furthermore, BAR pretreatment activated adenosine monophosphate-activated protein kinase (AMPK) signaling in MI/R hearts. AMPK inhibitor compound C inhibited BAR-induced AMPK activation, and blunted BAR-mediated anti-oxidative, anti-inflammatory effects and cardio-protection. Taken together our study has identified a novel function of BAR and provided a molecular basis for BAR potential applications in the treatment of MI/R injury and other ischemic disorders.

[The distribution of serum homocysteine and its associated factors in a population of 1 168 subjects in Beijing area].

OBJECTIVE: To describe serum homocysteine distribution and its associated factors in population of urban and rural areas in Beijing. METHODS: The study population was represented by a randomly selected sample with 1 168 subjects, including both males and females aged 35 - 64. The levels of serum homocycteine were compared and the correlation with other risk factors were analyzed statistically. RESULTS: (1) Geometric mean of serum homocycteine was 15.4 micromol/L in males and 12.2 micromol/L in females (P < 0.001). (2) There was a significant difference in homocysteine levels between urban population and rural population. Men from rural area had 1.5 times higher homocyteine than from urban (18.0 micromol/L vs 12.0 micromol/L, P < 0.001), while the rural women had 1.3 times higher homocysteine level than urban women did. (3) The prevalence rate of hyperhomocysteinemia was 15.3% in population aged 35 - 64 in Beijing area. (4) Gender, residential location (urban or rural), smoking and education had independent effects on level of serum homocysteine by multivariate analysis. CONCLUSION: Population in Beijing had higher serum level and prevalence rate of homocysteine than some western countries. Gender, geographic distribution, smoking and education had some influence on homocysteine level.