Qualitative and quantitative evaluations of Chuanxiong dispensing granules by using chemical fingerprint in combination with chemometrics methods.

To better elucidate the chemical constituents and evaluate the quality consistency of Chuanxiong dispensing granules (CDG), qualitative and quantitative analyses were performed in this study. Firstly, a high-performance liquid chromatography-diode array detector (HPLC-DAD) based fingerprint was constructed by 12 batches of CDGs from different manufacturers, in which 16 common peaks were assigned. Then, two of them were directionally isolated for structural elucidation. According to the nuclear magnetic resonance (NMR) and mass spectrometry (MS) spectra, 5,6-dihydrophthalic acid was identified as novel compound, and 8-O-4/8-O-4-dehydrotriferulic acid was firstly discovered in plant belonging to the genus Ligusticum. Secondly, a total of 46 components were detected in CDG using high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (HPLC-Q-TOF-MS), and 14 of them were unambiguously identified by comparing with reference standards. Additionally, a HPLC-DAD method was firstly established to quantify 10 characteristic peaks specified in the China National Standard of CDG, and the results revealed that ferulic acid (1.71 mg/g), chlorogenic acid (1.14 mg/g), 5,6-dihydrophthalic acid (1.13 mg/g), and senkyunolide I (1.13 mg/g) are the major components in CDGs. Chemometrics analyses suggested that phenolic acids are more important than phthalides in discrimination of CDGs from different manufacturers.

Association of dietary inflammatory index with helicobacter pylori infection and mortality among US population.

BACKGROUND: Limited research has been conducted on the potential relationship between the dietary inflammation index (DII) and mortality, particularly in individuals with Helicobacter pylori (H. pylori) infection. This study aimed to investigate the association between the DII and H. pylori infection, as well as their respective impacts on all-cause mortality in a cohort of individuals with or without H. pylori infection. METHODS: Data from the 1999-2018 National Health and Nutrition Examination Survey (NHANES) were utilized for this study, with a final of 4370 participants included. Both univariable and multivariable-adjusted logistic regression analyses were employed to explore the relationship between H. pylori infection and pertinent covariates. Cox regression analysis, as well as restricted regression cubic spline analysis, were utilized to assess the association between DII and all-cause mortality among individuals with or without H. pylori infection. RESULTS: The findings demonstrated a positive correlation between DII scores and H. pylori infection, even after adjusting for potential confounding factors. Moreover, higher DII scores were significantly associated with an elevated risk of mortality exclusively in individuals with H. pylori infection, while no such association was observed in the uninfected population. Additional analysis using restricted cubic spline modeling revealed a positive linear relationship between DII scores as a continuous variable and the adjusted risk of all-cause mortality specifically in H. pylori-infected patients. CONCLUSION: The results of this study indicated that DII was positively correlated with an increased risk of H. pylori infection and was associated with a heightened risk of all-cause mortality solely in individuals with H. pylori infection. Consequently, DII might serve as a useful tool for risk stratification in the H. pylori-infected population among U.S. adults. Further research is warranted to elucidate the underlying mechanisms and potential clinical implications of these findings.

Association of triglyceride-glucose index with atherosclerotic cardiovascular disease and mortality among familial hypercholesterolemia patients.

BACKGROUND: Familial hypercholesterolemia (FH) is an inherited metabolic disorder with a high level of low-density lipoprotein cholesterol and the worse prognosis. The triglyceride-glucose (TyG) index, an emerging tool to reflect insulin resistance (IR), is positively associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) in healthy individuals, but the value of TyG index has never been evaluated in FH patients. This study aimed to determine the association between the TyG index and glucose metabolic indicators, insulin resistance (IR) status, the risk of ASCVD and mortality among FH patients. METHODS: Data from National Health and Nutrition Examination Survey (NHANES) 1999-2018 were utilized. 941 FH individuals with TyG index information were included and categorized into three groups: < 8.5, 8.5-9.0, and > 9.0. Spearman correlation analysis was used to test the association of TyG index and various established glucose metabolism-related indicators. Logistic and Cox regression analysis were used to assess the association of TyG index with ASCVD and mortality. The possible nonlinear relationships between TyG index and the all-cause or cardiovascular death were further evaluated on a continuous scale with restricted cubic spline (RCS) curves. RESULTS: TyG index was positively associated with fasting glucose, HbA1c, fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) index (all p < 0.001). The risk of ASCVD increased by 74% with every 1 unit increase of TyG index (95%CI: 1.15-2.63, p = 0.01). During the median 114-month follow-up, 151 all-cause death and 57 cardiovascular death were recorded. Strong U/J-shaped relations were observed according to the RCS results (p = 0.0083 and 0.0046 for all-cause and cardiovascular death). A higher TyG index was independently associated with both all-cause death and cardiovascular death. Results remained similar among FH patients with IR (HOMA-IR ≥ 2.69). Moreover, addition of TyG index showed helpful discrimination of both survival from all-cause death and cardiovascular death (p < 0.05). CONCLUSION: TyG index was applicable to reflect glucose metabolism status in FH adults, and a high TyG index was an independent risk factor of both ASCVD and mortality.

Serum glycolipids mediate the relationship of urinary bisphenols with NAFLD: analysis of a population-based, cross-sectional study.

BACKGROUND: Bisphenol A (BPA) and its substitutes bisphenol S (BPS) and bisphenol F (BPF) are endocrine-disrupting chemicals widely used in consumer products, which have been proposed to induce various human diseases. In western countries, one of the most common liver diseases is non-alcoholic fatty liver disease (NAFLD). However, studies on the associations of the three bisphenols with NAFLD in human beings are scarce. METHODS: We included 960 participants aged ≥ 20 years from the NHANES 2013-16 who had available data on levels of urinary BPA, BPS and BPF. The hepatic steatosis index (HSI) > 36 was used to predict NAFLD. Logistic regression analysis and mediation effect analysis were used to evaluate the associations among bisphenols, glycolipid-related markers and NAFLD. RESULTS: A total of 540 individuals (56.3%) were diagnosed with NAFLD, who had higher concentrations of BPA and BPS but not BPF than those without NAFLD. An increasing trend in NAFLD risks and HSI levels was observed among BPA and BPS tertiles (p for trend < 0.05). After adjustment for confounders, elevated levels of BPA or BPS but not BPF were significantly associated with NAFLD. The odds ratio for NAFLD was 1.581 (95% confidence intervals [CI]: 1.1-2.274, p = 0.013) comparing the highest with the lowest tertile of BPA and 1.799 (95%CI: 1.2462.597, p = 0.002) for BPS. Mediation effect analysis indicated that serum high-density lipoprotein cholesterol and glucose had a mediating effect on the relationships between bisphenols and NAFLD. CONCLUSIONS: The present study showed that high exposure levels of BPA and BPS increased NAFLD incidence, which might be mediated through regulating glycolipids metabolism. Further studies on the role of bisphenols in NAFLD are warranted.

Michael acceptor molecules in natural products and their mechanism of action.

Purpose: Michael receptor molecules derived from plants are biologically active due to electrophilic groups in their structure. They can target nucleophilic residues on disease-related proteins, with significant therapeutic effects and low toxicity for many diseases. They provide a good option for relevant disease treatment. The aim of this study is to summarize the existing MAMs and their applications, and lay a foundation for the application of Michael receptor molecules in life science in the future. Methods: This review summarizes the published studies on Michael receptor molecules isolated from plants in literature databases such as CNKI, Wanfang Data, PubMed, Web of Science, ScienceDirect, and Wiley. Latin names of plants were verified through https://www.iplant.cn/. All relevant compound structures were verified through PubChem and literature, and illustrated with ChemDraw 20.0. Result: A total of 50 Michael receptor molecules derived from various plants were discussed. It was found that these compounds have similar pharmacological potential, most of them play a role through the Keap1-Nrf2-ARE pathway and the NF-κB pathway, and have biological activities such as antioxidant and anti-inflammatory. They can be used to treat inflammatory diseases and tumors. Conclusion: The Michael receptor molecule has electrophilicity due to its unsaturated aldehyde ketone structure, which can combine with nucleophilic residues on the protein to form complexes and activate or inhibit the protein pathway to play a physiological role. Michael receptor molecules can regulate the Keap1-Nrf2-ARE pathway and the NF-κB pathway. Michael receptor molecules can be used to treat diseases such as inflammation, cancer, oxidative stress, etc.

Seabuckthorn Berries Extract Attenuates Pulmonary Vascular Hyperpermeability in Lipopolysaccharide-Induced Acute Lung Injury in Mice.

OBJECTIVE: To investigate the effect of seabuckthorn berries extract (SBE) on pulmonary vascular hyperpermeability in the mice model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: Sixty Kunming mice were allocated into 6 groups by a random number table, including control, LPS, dexamethasone (Dex, 1 mg/kg), and 120, 240 and 480 mg/kg SBE groups, 10 mice in each group. Except the control group, mice were pre-treated with Dex and SBE, respectively, for 7 days before LPS was intraperitoneally injected to induce ALI. Pulmonary vascular hyperpermeability was evaluated by histopathologic observation and transvascular leakage determination. Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels in serum were measured using enzyme-linked immunosorbent assay. The expression of nuclear factor-kappa B (NF-κB) p65 in lung cells was determined by immunofluorescence analysis. The contents of cytoplasmic inhibitor of nuclear factor-κB kinase (IKK) and nuclear p65, as well as downstream proteins of E-selectin (CD62E) and intercellular adhesion molecule-1 (ICAM-1), were determined using Western blot analysis. RESULTS: Histopathological observation confirmed SBE treatment alleviated morphological lesion induced by LPS. Compared with the LPS group, 480 mg/kg SBE significantly decreased the water content of lung, Evans blue accumulation in lung tissue, and protein concentration and neutrophils count in bronchoalveolar lavage fluid (P<0.01); moreover, 480 mg/kg SBE significantly suppressed release of TNF-α and IL-6, and down-regulated expressions of IKK, nuclear p65, ICAM-1 and CD62E (P<0.01). CONCLUSION: SBE maintained alveolar-capillary barrier integrity under endotoxin challenge in mice by suppressing the key factors in the pathogenesis of ALI.

Clinical Impact of Thrombus Aspiration and Interaction With D-Dimer Levels in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Objectives: To evaluate the effect of thrombus aspiration (TA) strategy on the outcomes and its interaction with D-dimer levels in patients with ST-segment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (PCI) in "real-world" settings. Materials and Methods: This study included 1,295 patients with STEMI who had undergone primary PCI with or without TA between January 2013 and June 2017. Patients were first divided into a TA+PCI group and a PCI-only group, and the baseline characteristics and long-term mortality between the two groups were analyzed. Furthermore, we studied the effect of TA on the clinical outcomes of patients grouped according to quartiles of respective D-dimer levels. The primary outcome was all-cause mortality, and the secondary outcomes were new-onset heart failure (HF), rehospitalization, re-PCI, and stroke. Results: In the original cohort, there were no significant differences in all-cause mortality between the TA+PCI and PCI-only groups (hazard ratio, 0.789; 95% confidence interval, 0.556-1.120; p = 0.185). After a mean follow-up of 2.5 years, the all-cause mortality rates of patients in the TA + PCI and PCI-only groups were 8.5 and 16.2%, respectively. Additionally, differences between the two groups in terms of the risk of HF, re-PCI, rehospitalization, and stroke were non-significant. However, after dividing into quartiles, as the D-dimer levels increased, the all-cause mortality rate in the PCI group gradually increased (4.3 vs. 6.0 vs. 7.0 vs. 14.7%, p < 0.001), while the death rate in the TA+PCI group did not significantly differ (4.6 vs. 5.0 vs. 4.0 vs. 3.75%, p = 0.85). Besides, in the quartile 3 (Q3) and quartile 4 (Q4) groups, the PCI-only group was associated with a higher risk of all-cause mortality than that of the TA+PCI group (Q3: 4.0 vs. 7.0%, p = 0.029; Q4: 3.75 vs. 14.7%, p < 0.001). Moreover, the multivariate logistic regression analysis demonstrated that TA is inversely associated with the primary outcome in the Q4 group [odds ratio (OR), 0.395; 95% CI, 0.164-0.949; p = 0.038]. Conclusions: The findings of our real-world study express that routine manual TA during PCI in STEMI did not improve clinical outcomes overall. However, patients with STEMI with a higher concentration of D-dimer might benefit from the use of TA during primary PCI. Large-scale studies are recommended to confirm the efficacy of TA.

Gene expression profile and long noncoding RNA analysis in Candida albicans insoluble ß-glucan-stimulated CD14+ monocytes and THP-1 cells.

Emerging evidence suggests that long noncoding RNAs (lncRNAs) play important roles in disease development. However, the roles of lncRNAs in the pathogenesis of Candida albicans (C. albicans) remain unclear. Our study aimed to investigate and characterize the mRNA and lncRNA transcriptomes of CD14+ monocytes and THP-1 cells stimulated with insoluble ß-glucan by RNA-seq. We identified a total of 10788 differentially expressed (DE) mRNAs and 2021 DE lncRNAs in CD14+ monocytes, while 3349 DE mRNAs and 291 DE lncRNAs were observed in THP-1 cells. A total of 808 DE mRNAs and 51 DE lncRNAs overlapped between the two groups. We examined five collectively DE mRNAs and lncRNAs in both cells using quantitative real-time PCR, validating the reliability of the RNA-seq results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the 808 DE mRNAs were mostly enriched in the inflammatory response and NF-kappa B signaling pathway, respectively. Next, lncRNA-mRNA coexpression analysis was performed for the 51 DE lncRNAs and the 808 DE mRNAs in the two groups. We chose the common network pairs of the two groups to construct the coexpression network and revealed 97 network pairs comprising 8 dysregulated lncRNAs and 60 dysregulated mRNAs. We found that lncRNA lnc-CCL3L3-1:1 might be involved in the NF-kappa B signaling pathway in C. albicans infection. In conclusion, the aberrantly expressed lncRNAs might play a role in the pathogenesis of C. albicans infection and could be used as therapeutic targets in the future.

Active Ingredients and Anti-Arthritic Mechanisms of Ba-Wei-Long-Zuan Granule Revealed by 1 H-NMR-Based Metabolomics Combined with Network Pharmacology Analysis.

Ba-Wei-Long-Zuan granule (BWLZ) is a traditional herbal preparation. It has been widely used for the treatment of rheumatoid arthritis (RA). However, its active ingredients and mechanisms of action are still unclear. The present study aims to reveal the active compounds and anti-arthritic mechanisms of BWLZ against collagen-induced arthritis (CIA) by using 1 H-NMR-based metabolomics, molecular docking and network pharmacology methods. After 30 days of administration, BWLZ could effectively improve the metabolic disorders in CIA rats. The anti-arthritic effect of BWLZ was related to its restoration of 16 disturbed serum metabolites. Molecular docking and network analysis showed that 20 compounds present in BWLZ could act on multiple targets. Among them, coclaurine and hesperidin showed the highest hit rates for target proteins related to both metabolic regulation and RA, indicating that these two compounds might be potential active ingredients of BWLZ. Moreover, pathway enrichment analysis suggested that the anti-arthritic mechanisms of BWLZ might be attributed to its network regulation of several biological processes, such as steroid hormone biosynthesis, mTOR signaling pathway, alanine, aspartate and glutamate metabolism, and synthesis and degradation of ketone bodies. These results provide further evidence for the anti-arthritic properties of BWLZ and are beneficial for its quality control and clinical application. The potential targets and biological processes found in this study may provide valuable information for further studying the molecular mechanisms of BWLZ against RA. In addition, our work provides new insights for revealing the active ingredients and regulatory mechanisms of complex herbal preparations.

[Advances in the roles and mechanisms of nonsense-mediated mRNA decay in embryonic development].

Nonsense-mediated mRNA decay (NMD) is originally identified as a widespread mRNA surveillance machinery in degrading 'aberrant' mRNA species with premature termination codons (PTCs) rapidly, which protects the cells from the accumulation of truncated proteins. Recent studies show that NMD can also regulate the degradation of normal gene transcripts, which execute important cellular and physiological functions. Therefore, NMD is considered as a highly conserved post-transcriptional regulatory mechanism in eukaryotes. NMD modulates 3% to 20% of the transcriptome from yeast to human directly or indirectly, which is essential for various physiological processes, such as cell homeostasis, stress response, proliferation, and differentiation. NMD can regulate the level of transcripts that involves in development, and single knockout of most NMD factors has an embryonic lethal effect. NMD plays an important role in the self-renewal, differentiation of embryonic stem cells and is critical during embryonic development. In this review, we summarized the latest advances in the roles and mechanisms of NMD in embryonic development, in order to provide new ideas for the research on embryonic development and the treatment of embryonic development related diseases.

[Stud on quality standard for Aconiti Tatsienensis Radix].

OBJECTIVE: To establish the quality standard for Aconiti Tatsiehensis Radix. METHODS: TLC was used to detect yunaconi- tine and talasamine in Aconiti Tatsiensis Radix. HPLC was adopted to determine the content of yunaconitine. Moisture,ash,acid insolu- ble ash and ethanol soluble extractive were determined according the procedures recorded in the Appendix of Chinese Pharmacopoeia (2010 edition). The microscopic identification was also carried out. RESULTS: Aconiti Tatsienensis Radix had obvious microscopic char- acteristics,and its TLC identification had a good resolution with clear spots. An average content of moisture was 11. 48%, ash was 4. 83% ,acid insoluble was 1. 81%, ethanol soluble extractive was 20. 46% and yunaconitine was 0. 23%. CONCLUSION: The established standard is acceptable for quality evaluation of Aconiti Tatsienensis Radix.