Search

Background: Wen Dan decoction (WDD) has been a famous classic formula for resolving phlegm since ancient times in China. Currently, there are many types of WDD commercial preparations produced through modern technology. However, it is not known whether the holistic quality of WDD commercial preparations is consistent with the traditional decocting method to exert its proper effects. Therefore, the WDD material reference was studied and prepared, which can represent the traditional Chinese formulation WDD. Methods: A method based on UPLC-QTOF-MS was developed to evaluate the quality of WDD material reference and commercial prescriptions. At the same time, the multivariate statistical method was used to compare the differences between the material reference and the commercial prescription by principal component analysis (PCA) and heatmap. Finally, the UPLC-QTOF-MS method was established to quantitatively study 11 representative components, including naringin, hesperidin, neohesperidin, liquiritin, glycyrrhizic acid, adenosine, liquiritigenin, tangeretin, eriocitrin, naringenin and synephrine. Results: A total of 107 compounds were identified in the WDD material reference by comparing the retention time and fragment ion characteristics, including 54 flavonoids, 14 triterpenes, 10 organic acids, 7 alkaloids, 7 coumarins and 15 other components. The samples were almost evenly split into two groups, indicating a difference in quality between the WDD material reference and its commercial preparations in multivariate statistical analysis. Eleven major components of linearity, precision, repeatability, stability and recovery rate met the requirements, which were clearly different in commercial preparations and WDD material references. In terms of the content of 11 components in the commercial preparation, only CP8 is close to the material reference, which is in agreement with the statistical analysis of the heatmap. The concentrations of naringin and neohesperidin from the WDD material reference were higher than those from the commercial preparations. Conclusions: The quality evaluation method established in this study can be used to identify different sources of WDD but also proves that the WDD material reference contains higher naringin. Furthermore, this study confirmed that the preparation technology of WDD commercial prescriptions should be optimized on the basis of WDD material references, producing the closest possible clinical basis for the substance. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated that Sorting nexin 7 (SNX7) functions as an anti-apoptotic protein in liver tissue and plays a crucial role in the survival of hepatocytes during early embryonic development. However, its diagnostic and prognostic value as well as the predictive value of chemotherapy and immunotherapy have not been reported in hepatocellular carcinoma (HCC). Methods: SNX7 mRNA expression and its diagnostic efficacy were examined in GEO datasets, and the findings were further confirmed in TCGA, ICGC cohorts, and cell lines. The protein level of SNX7 was determined using CPTAC and HPA databases, and the results were validated through immunohistochemistry (IHC). Survival analyses were performed in TCGA and ICGC cohorts, and the results were subsequently validated via Kaplan–Meier Plotter. The response to chemotherapy and immunotherapy was predicted via GDSC dataset and TIDE algorithm, respectively. R packages were employed to explore the relationship between SNX7 expression and immune infiltration, m6A modification, as well as the functional enrichment of differentially expressed genes (DEGs). Results: The expression of SNX7 at both mRNA and protein levels was significantly upregulated in HCC tissues. SNX7 exhibited superior diagnostic efficacy compared to AFP alone for HCC detection, and combining it with AFP improved the diagnostic accuracy for HCC. High SNX7 was associated with unfavorable outcomes, including poor overall survival, disease-specific survival, progression-free survival, and advanced pathological stage, in patients with HCC, and SNX7 was identified as an independent risk factor for HCC. Moreover, elevated SNX7 expression was positively correlated with increased sensitivity to various chemotherapy drugs, including sorafenib, while it was associated with resistance to immunotherapy in HCC patients. Correlation analysis revealed a relationship between SNX7 and multiple m6A-related genes and various immune cells. Finally, enrichment analysis demonstrated strong associations of SNX7 with critical biological processes, such as cell cycle regulation, cellular senescence, cell adhesion, DNA replication, and mismatch repair pathway in HCC. Conclusions: Our study highlights the association of SNX7 with the immune microenvironment and its potential influence on HCC progression. SNX7 emerges as a promising novel biomarker for the diagnosis, prognosis, and prediction of response to chemotherapy and immunotherapy in patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in women of reproductive age that still lacks effective treatment. Inflammation is one of the important features of PCOS. Asparagus (ASP) has anti-inflammatory, antioxidant, and anti-aging pharmacological effects, and its anti-tumor effects have been demonstrated in a variety of tumors. However, the role and mechanism of ASP in PCOS remain unclear. Methods: The active components of ASP and the key therapeutic targets for PCOS were obtained by network pharmacology. Molecular docking was used to simulate the binding of PRKCA to the active components of ASP. The effects of ASP on inflammatory and oxidative stress pathways in PCOS, and the regulation of PRKCA were examined by KGN, a human derived granulosa cell line. PCOS mouse model validated the results of in vivo experiments. Results: Network pharmacology identified 9 major active ingredients of ASP with 73 therapeutic targets for PCOS. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment yielded 101 PCOS-related signaling pathways. The hub gene PRKCA was obtained after taking the gene intersection of the top 4 pathways. Molecular docking showed the binding of PRKCA to the 7 active components in ASP. In vitro and in vivo experiments showed that ASP alleviated the course of PCOS through antioxidant, anti-inflammatory effects. ASP can partially restore the low expression of PRKCA in the PCOS models. Conclusion: The therapeutic effect of ASP on PCOS is mainly achieved by targeting PRKCA through the 7 active components of ASP. Mechanistically, ASP alleviated the course of PCOS through antioxidant, anti-inflammatory effects, and PRKCA was its potential target. [ABSTRACT FROM AUTHOR]

Introduction: This study compared the effects of hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, and succinylated gelatin on oxidative stress and the inflammatory response in a rodent hemorrhagic shock model.Methods: Sodium pentobarbital-anesthetized adult male Wistar rats (200 g to 220 g) were subjected to a severe volume-controlled hemorrhage using arterial blood withdrawal (30 mL/kg to 33 mL/kg) and resuscitated with a colloid solution at the same volume as blood withdrawal (hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, or succinylated gelatin). Arterial blood gas parameters were monitored. Malondialdehyde (MDA) content and myeloperoxidase (MPO) activity in the liver, lungs, intestine, and brain were measured two hours after resuscitation. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 in the intestine were also measured.Results: Infusions of hydroxyethyl starch 130/0.4, but not hydroxyethyl starch 200/0.5 or succinylated gelatin, significantly reduced MDA levels and MPO activity in the liver, intestine, lungs and brain, and it also inhibited the production of TNF-α in the intestine two hours after resuscitation. However, no significant difference between hydroxyethyl starch 200/0.5 and succinylated gelatin was observed.Conclusions: Hydroxyethyl starch 130/0.4, but not hydroxyethyl starch 200/0.5 or succinylated gelatin, treatment after hemorrhagic shock ameliorated oxidative stress and the inflammatory response in this rat model. No significant differences were observed after hydroxyethyl starch 200/0.5 or succinylated gelatin administration at doses of approximately 33 mL/kg. [ABSTRACT FROM AUTHOR]

Background: SETD2, the single mediator of trimethylation of histone 3 at position lysine 36, has been reported associated with initiation progression and chemotherapy resistance in acute myeloid leukemia (AML). Whether polymorphisms of SETD2 affect prognosis and chemotherapy response of AML remains elusive.Methods: Three tag single-nucleotide polymorphisms (tagSNPs) of SETD2 were genotyped in 579 AML patients by using Sequenom Massarray system. Association of the SNPs with complete remission (CR) rate after Ara-C based induction therapy, overall survival (OS) and relapse-free survival (RFS) were analyzed.Result: Survival analysis indicated that SETD2 rs76208147 TT genotype was significantly associated with poor prognosis of AML (TT vs. CC + CT hazard ratio: HR = 1.838, 95% confidence interval (CI) 1.005-3.360, p = 0.048). After adjusting for the known prognostic factors including risk stratification, age, allo-SCT, WBC count and LDH count, rs76208147 TT genotype was still associated with OS in the multivariate analysis (TT vs. CC + CT HR = 1.923, 95% CI 1.007-3.675, p = 0.048). In addition, after adjusting by other clinical features, patients with rs4082155  allele G carries showed higher rate of complete remission which indicated by CR rate (AG + GG vs. AA odd ratio (OR) = 0.544, 95% CI 0.338-0.876, p = 0.012).Conclusions: SETD2 genetic polymorphism is associated with AML prognosis and chemotherapy outcome, suggesting the possibility for development in AML diagnostics and therapeutics towards SETD2. [ABSTRACT FROM AUTHOR]