The Role of Preoperative CT Perfusion Imaging in Assessing Colorectal Cancer Angiogenesis and its Clinical Value.

Purpose: Angiogenesis, the formation of new blood vessels, plays a crucial role in tumor growth and metastasis. Understanding the vascular characteristics of colorectal cancer through preoperative computed tomography (CT) perfusion parameters can provide valuable insights into the tumor's aggressiveness and potential for spread. Additionally, exploring the correlation between these parameters and serum tumor marker levels may offer a comprehensive perspective on the disease's biological behavior. Methods: In this retrospective study, we investigated 42 colorectal cancer patients. Based on microvascular density (MVD) measured by immunohistochemistry (IHC), participants were categorized into either a high-density group (n = 24) with MVD ≥ 35/field of view or a low-density group (n = 18) with MVD < 35/field of view. Additionally, a control group comprised 25 patients with pathologically confirmed benign colorectal lesions. This study design allowed us to assess the correlation between MVD and colorectal cancer, differentiating between high and low microvascular density groups, while also comparing results to a control group for comprehensive analysis. Results: Colorectal cancer was associated with significantly higher levels of blood volume (BV; high-density group: 7.65±1.36 mL/100g; low-density group: 6.73±1.29 mL/100g), blood flow (BF; high-density group: 67.33±12.16 ml/(100g·min); low-density group: 52.84±11.43 ml/(100g·min)), permeability surface (PS; high-density group: 35.19±6.32 ml/(100g·min); low-density group: 22.27±4.85 ml/(100g·min)), serum glycoprotein antigen 19-9 (CA19-9; high-density group: 45.38±5.41 g/ml); low-density group: 23.43±3.59 g/ml), glycoprotein antigen 125 (CA125; high-density group: 27.56±3.73 g/ml); low-density group: 12.63±2.59 g/ml), and carcinoembryonic antigen (CEA; high-density group: 17.87±3.12 g/ml); low-density group: 8.51±2.87 g/ml) versus benign colorectal lesions, with more significant changes observed in the high-density group versus the low-density group (P ≤ .001). The three groups showed similar mean transit time (MTT). The AUCs under the ROC curves for BV, BF, PS, and TTP were 0.901, 0.898, 0.963, and 0.983, respectively. Pearson correlation analysis showed a positive correlation of patients' serum CA19-9 with BV, BF, and PS., Serum CA125 and CEA were positively correlated with BF and PS, and the above indicators were negatively correlated with TTP. Conclusions: In conclusion, our study highlights the potential of preoperative CT perfusion imaging as a valuable tool for evaluating angiogenesis in colorectal cancer and its correlation with serum tumor markers. The identified associations open avenues for further research to delve into specific aspects of angiogenesis and tumor markers. Future investigations could focus on elucidating the molecular mechanisms underlying the observed correlations, potentially identifying novel therapeutic targets. Additionally, exploring the dynamic changes in angiogenesis and tumor markers during different stages of colorectal cancer progression may provide a more comprehensive understanding. Moreover, assessing the prognostic value of these imaging and biomarker correlations in larger, diverse patient cohorts could enhance their clinical utility. Our findings lay the groundwork for these future research directions, emphasizing the need for continued exploration to advance our knowledge and improve clinical strategies for colorectal cancer management.

A comprehensive review on Schisandrin and its pharmacological features.

Schisandrin stands as one of the primary active compounds within the widely used traditional medicinal plant Schisandra chinensis (Turcz.) Baill. This compound exhibits sedative, hypnotic, anti-aging, antioxidant, and immunomodulatory properties, showcasing its effectiveness across various liver diseases while maintaining a favorable safety profile. However, the bioavailability of schisandrin is largely affected by hepatic and intestinal first-pass metabolism, which limits the clinical efficacy of schisandrin. In this paper, we review the various pharmacological effects and related mechanisms of schisandrin, in order to provide reference for subsequent drug research and promote its medicinal value.

Schisandrin protects against ulcerative colitis by inhibiting the SGK1/NLRP3 signaling pathway and reshaping gut microbiota in mice.

BACKGROUND: According to the Chinese Pharmacopoeia, the fruit of Schisandra chinensis (Turcz.) Baill. (SC) is an important traditional Chinese medicine that can be used to treat diarrhea. Despite the increasing research on the anti-inflammatory and anti-oxidant aspects of SC, the studies on the anti-ulcerative colitis of Schisandrin (SCH), the main constituent of SC, are relatively few. METHODS: The mice used in the study were randomly distributed into 6 groups: control, model, 5-ASA, and SCH (20, 40, 80 mg/kg/d). The mice in the model group were administered 3% (w/v) dextran sulfate sodium (DSS) through drinking water for 7 days, and the various parameters of disease activity index (DAI) such as body weight loss, stool consistency, and gross blood were measured. ELISA was used to detect inflammatory factors, and bioinformatics combined with transcriptome analysis was done to screen and verify relevant targets. 16S rDNA high-throughput sequencing was used to analyze the composition of the gut microbiota(GM), while mass spectrometry was done to analyze the changes in the content of bile acids (BAs) in the intestine. RESULTS: Mice treated with SCH experienced significant weight gain, effectively alleviating the severity of colitis, and decreasing the levels of inflammatory factors such as TNF-α, IL-1ß, IL-18, IL-6, and other related proteins (NLRP3, Caspase-1, SGK1) in UC mice. Furthermore, the analysis of GM and BAs in mice revealed that SCH increased the relative abundance of Lactobacilli spp, reduced the relative abundance of Bacteroides, and promoted the conversion of primary BAs to secondary BAs. These effects contributed to a significant improvement in the DSS-induced GM imbalance and the maintenance of intestinal homeostasis. CONCLUSION: It seems that there is a close relationship between the SCH mechanism and the regulation of SGK1/NLRP3 pathway and the restoration of GM balance. Therefore, it can be concluded that SCH could be a potential drug for the treatment of UC.

The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis.

BACKGROUND: Dehydroandrographolide (Deh) from Andrographis paniculata (Burm.f.) Wall has strong anti-inflammatory and antioxidant activities. PURPOSE: To explore the role of Deh in acute lung injury (ALI) of coronavirus disease 19 (COVID-19) and its inflammatory molecular mechanism. METHODS: Liposaccharide (LPS) was injected into a C57BL/6 mouse model of ALI, and LPS + adenosine triphosphate (ATP) was used to stimulate BMDMs in an in vitro model of ALI. RESULTS: In an in vivo and in vitro model of ALI, Deh considerably reduced inflammation and oxidative stress by inhibiting NLRP3-mediated pyroptosis and attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis through the suppression of ROS production by inhibiting the Akt/Nrf2 pathway. Deh inhibited the interaction between Akt at T308 and PDPK1 at S549 to promote Akt protein phosphorylation. Deh directly targeted PDPK1 protein and accelerated PDPK1 ubiquitination. 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP and 223-ASP may be the reason for the interaction between PDPK1 and Deh. CONCLUSION: Deh from Andrographis paniculata (Burm.f.) Wall presented NLRP3-mediated pyroptosis in a model of ALI through ROS-induced mitochondrial damage through inhibition of the Akt/Nrf2 pathway by PDPK1 ubiquitination. Therefore, it can be concluded that Deh may be a potential therapeutic drug for the treatment of ALI in COVID-19 or other respiratory diseases.

Integrating Bioinformatics and Network Pharmacology to Explore the Therapeutic Target and Molecular Mechanisms of Schisandrin on Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is currently the leading cause of sudden death in adolescent athletes. Schisandrin is a quality marker of the traditional Chinese medicine Schisandra chinensis, which has an excellent therapeutic effect on HCM, but its pharmacological mechanism remains unclear. OBJECTIVE: This study aimed to explore the potential and provide scientific evidence for schisandrin as a lead compound against hypertrophic cardiomyopathy. METHODS: The drug-like properties of schisandrin were predicted using the SwissADME website. Then, the PharmMapper database was used to predict potential drug targets and match gene names in the Uniprot database. HCM targets were collected from NCBI, OMIM, and Genecards databases and intersected with drug targets. The intersection targets were imported into the STRING database for PPI analysis, and core targets were identified. KEGG and GO enrichment analysis was performed on the core targets through the DAVID database, and all network maps were imported into Cytoscape software for visualization optimization. HCM-related datasets were downloaded from the GEO database to analyze core targets and screen differentially expressed target genes for molecular docking. RESULTS: After the PPI network analysis of the intersection targets of drugs and diseases, 12 core targets were screened out. The KEGG analysis results showed that they were mainly involved in Rap1, TNF, FoxO, PI3K-Akt, and other signaling pathways. After differential analysis, PPARG, EGFR, and MMP3 targets were also screened. The molecular docking results showed that schisandrin was well bound to the protein backbone of each target. CONCLUSION: This study used network pharmacology combined with differential expression and molecular docking to predict that schisandrin may treat HCM by acting on PPARG, EGFR, and MMP3 targets, and the regulatory process may involve signaling pathways, such as Rap1, TNF, FoxO, and PI3K-Akt, which may provide a valuable reference for subsequent studies.

Two novel compounds from green walnut husks (Juglans mandshurica Maxim.).

Phytochemical investigation on the ethanol extract of green walnut husks (Juglans mandshurica Maxim.) led to the isolation of two previously unknown compounds, including a macrolide compound (13S)-8-oxo-(9E, 11E)-8-oxo-octadeca-9,11-dien-13-olide (1) and a diarylheptanoid compound 1-(3'-methoxy-4'-hydroxyphenyl)-7-(3″,4″-dimethoxyphenyl)heptan-3-one (2), together with 19 known compounds. The structures of these 21 compounds were elucidated by extensive analyses of NMR and HR-MS data, and the basis of spectroscopic analysis.

Integrated Analysis of Basic Helix Loop Helix Transcription Factor Family and Targeted Terpenoids Reveals Candidate AarbHLH Genes Involved in Terpenoid Biosynthesis in Artemisia argyi.

Artemisia argyi is a valuable traditional medicinal plant in Asia. The essential oil from its leaves is rich in terpenoids and has been used to enhance health and well-being. In China, the market scale of industries related to A. argyi has attained tens of billions of Chinese Yuan. The basic helix-loop-helix (bHLH) family is one of the largest transcription factors families in plants that plays crucial roles in diverse biological processes and is an essential regulatory component of terpenoid biosynthesis. However, the bHLH TFs and their regulatory roles in A. argyi remain unknown. Here, 53 AarbHLH genes were identified from the transcriptome of A. argyi and were classified into 15 subfamilies based on the classification of bHLH proteins in Arabidopsis thaliana. The MEME analysis showed that the conserved motif 1 and motif 2 constituted the most conserved bHLH domain and distributed in most AarbHLH proteins. Additionally, integrated analysis of the expression profiles of AarbHLH genes and the contents of targeted terpenoids in different tissues group and JA-treated group were performed. Eleven up-regulated AarbHLHs and one down-regulated AarbHLH were screened as candidate genes that may participate in the regulation of terpenoid biosynthesis (TPS-AarbHLHs). Correlation analysis between gene expression and terpenoid contents indicated that the gene expression of these 12 TPS-AarbHLHs was significantly correlated with the content changes of 1,8-cineole or ß-caryophyllene. Protein-protein interaction networks further illustrated that these TPS-AarbHLHs might be involved in terpenoid biosynthesis in A. argyi. This finding provides a basis to further investigate the regulation mechanism of AarbHLH genes in terpenoid biosynthesis, and will be helpful to improve the quality of A. argyi.

[Prodrug structural modifications of cyclovirobuxine D and their biological activity].

AIM: To search for compounds for the treatment of cardiovascular diseases through prodrug structural modifications of cyclovirobuxine D, a single efficient composition distilled from Box plant in China, which was used to treat angina and myocardial infarction. METHODS: According to prodrug design principle, a series of cyclovirobuxine D analogues were prepared, suc as succinate, phosphate and amino acid ester, and their biological activities were tested. RESULTS: Seven new compounds were obtained and confirmed with 1H NMR, MS, and element analysis. CONCLUSION: In pharmacology experiment, for treating arrhythmia induced by aconitine, succinate and amino acid ester of cyclovirobuxine D (I and VII) showed better activities than that of cyclovirobuxine D. The normal rhythm of the heart duration of I and VII were ( 11.53 +/- 7.62) min and (12.68 +/- 9.25) min, compared with 0.9% NaCl solution and cyclovirobuxine D, (2.36 +/- 1.68) min and (10.25 +/- 6.59) min (P < 0.01), respectively. Another pharmacology experiment, for treating arrhythmia induced by chloroform, the negative ratio of I and VII were 80% and 82%, compared with 0.9% NaCl solution and cyclovirobuxine D, 43% and 52% (P < 0.05), respectively. The difference between new compounds and cyclovirobuxine D was distinct.

[Structural modification and bioactivity of cyclovirobuxine D].

AIM: To search for new compounds for the treatment of cardiovascular diseases by structural modification of cyclovirobuxine D. METHODS: According to rational drug design principle, a series of cyclovirobuxine D analogues were prepared, and their bioactivities were tested. RESULTS: Ten new compounds were syntheized and confirmed by spectra. CONCLUSION: Endurance lacking oxygen activity and antiarrhythmia effects of some analogues of cyclovirobuxine D were tested. Some compounds showed better activity than cyclovirobuxine D.