Discovery of bioactive-chemical Q-markers of Acanthopanax sessiliflorus leaves: An integrated strategy of plant metabolomics, fingerprint and spectrum-efficacy relationship research.

An integrated bioactive-chemical quality markers (Q-markers) discovery strategy, which was based on the LC-MS plant metabolomics, HPLC fingerprint as well as the chemical spectrum-efficacy relationships, was designed to develop a methodology for accurate and comprehensive evaluation of the quality of Acanthopanax sessiliflorus leaves (ASL). Firstly, a high resolution and sensitivity UHPLC-Q-Orbitrap MS method was used for plant metabolomics analysis to obtain component characterization and screen potential chemical markers that differentiate between different harvesting periods. A total of 53 chemical components were identified, and 8 potential chemical markers were discovered, such as sucrose, maltol and phenylalanine. Secondly, a selective HPLC fingerprint analysis of ASL and its pancreatic lipase activity assay method was successfully investigated in vitro. In the study of chemical spectrum-efficacy relationships, neochlorogenic acid, chlorogenic acid, caffeic acid and hyperoside were screened and showed the inhibited pancreatic lipase activity with IC50 values, 0.16 ± 0.01, 0.13 ± 0.01, 0.31 ± 0.01, and 0.44 ± 0.02 mg/mL, respectively, which indicated the above four constituents were selected as the bioactive-chemical Q-markers of ASL. Finally, an accurate and reliable quantitative HPLC assay was developed and validated for simultaneous determination of four bioactive-chemical Q-markers in ASL, and their content levels in ASL varied widely in different harvesting periods. The systematic and efficient screening strategy for bioactive-chemical Q-markers in this study, based on " LC-MS plant metabolomics, HPLC fingerprint, and spectrum-efficacy relationships," could have effectively improved the quality assessment level of ASL.

Isovitexin prevents DSS-induced colitis through inhibiting inflammation and preserving intestinal barrier integrity through activating AhR.

Isovitexin (ISO) is a glycosylated flavonoid obtained from Asian rice that has been reported to have anti-inflammatory effect. However, the effects of ISO on colitis have not been reported. In the present study, we aimed to explore the protective effects of isovitexin on colitis using the dextran sodium sulfate (DSS)-induced model. In vitro, the protective mechanism was investigated in TNF-α-stimulated IEC cells. Inflammatory cytokines were measured by ELISA. The signaling pathways were measured by Western blot analysis. ISO attenuated DSS-induced colitis through reducing body weight loss and colonic histological changes. Also, the levels of TNF-α and IL-1ß induced by DSS were inhibited by ISO. The MPO activity induced by DSS was attenuated by ISO. In vitro, ISO inhibited IL-6 and IL-1ß production in TNF-α-stimulated cells. ISO increased the expression of tight junction proteins ZO-1 and occludin. Also, ISO inhibited TNF-α-induced NF-κB activation. In addition, ISO was found to increase the expression of aryl hydrocarbon receptor (AhR). And inhibition of AhR by its antagonist CH223191 could reverse these effects of ISO. ISO inhibited DSS-induced colitis in mice through suppressing inflammation and preserving intestinal barrier integrity through activating AhR. ISO may be useful as a potential therapeutic agent for colitis.

Roles of m6A modification in oral cancer (Review).

Oral cancer is one of the highly malignant tumors with poor prognosis. The pathogenic mechanisms of oral cancer have remained to be fully elucidated and this brings significant challenges to the treatment. RNA modification is a common intracellular chemical modification that has been related to various pathological processes, such as blood diseases, immune system diseases and cancer. As the most common and abundant RNA modification in eukaryotic mRNA, N6­methyladenosine (m6A) modification has a crucial role in several cancers, including oral cancer. m6A modification directly affects gene expression levels and regulates various physiological and pathological processes. It has been demonstrated that m6A modification may affect the proliferation, migration and invasion of oral cancer cells by regulating the level of m6A modification. In the present review, the effects of m6A modification on the proliferation and death of oral cancer cells, as well as the occurrence and development of oral cancer, were analyzed in order to provide a new target for treatment. Furthermore, the roles of m6A modification in chemotherapy resistance and potential immunotherapy were analyzed and new treatment ideas were provided.

Quercetin Mediated TET1 Expression Through MicroRNA-17 Induced Cell Apoptosis in Melanoma Cells.

A previous report suggested that the expression of ten-eleven translocation (TET) proteins is abnormal in certain cancers. Quercetin has been demonstrated as anti-cancer role in cancer development. In order to explore the inhibitory effect and mechanism of quercetin on uveal melanoma cells, the expression of TET proteins was analyzed in the present study. Our results suggest that the expression of TET1 was increased following treatment with quercetin in OCM-1, SK-MEL-1, and B16 cells. In addition, quercetin treatment induced apoptosis and inhibited migration and invasion. To further investigate the association of the expression of TET1 with cell growth, apoptosis, migration, and invasion, cell lines in which TET1 was knocked-down or overexpressed were constructed. The results showed that the increased expression of TET1-induced apoptosis, increased 5-hydroxymethylcytosine (5 hmC). and inhibited invasion. Our bioinformatics studies indicated that TET1 is a target gene of microRNA-17 (miR-17) Our results showed that inhibition of the expression of miR-17 resulted in increased TET1 expression in OCM-1 cells. Furthermore, our results indicated that quercetin treatment increased TET1 expression and inhibited melanoma growth in nude mice. Taken together, our results suggest that quercetin can regulate cell proliferation and apoptosis through TET1 via miR-17 in melanoma cells.

Advances of hydrogel combined with stem cells in promoting chronic wound healing.

Wounds can be divided into two categories, acute and chronic. Acute wounds heal through the normal wound healing process. However, chronic wounds take longer to heal, leading to inflammation, pain, serious complications, and an economic burden of treatment costs. In addition, diabetes and burns are common causes of chronic wounds that are difficult to treat. The rapid and thorough treatment of chronic wounds, including diabetes wounds and burns, represents a significant unmet medical need. Wound dressings play an essential role in chronic wound treatment. Various biomaterials for wound healing have been developed. Among these, hydrogels are widely used as wound care materials due to their good biocompatibility, moisturizing effect, adhesion, and ductility. Wound healing is a complex process influenced by multiple factors and regulatory mechanisms in which stem cells play an important role. With the deepening of stem cell and regenerative medicine research, chronic wound treatment using stem cells has become an important field in medical research. More importantly, the combination of stem cells and stem cell derivatives with hydrogel is an attractive research topic in hydrogel preparation that offers great potential in chronic wound treatment. This review will illustrate the development and application of advanced stem cell therapy-based hydrogels in chronic wound healing, especially in diabetic wounds and burns.

Advances in CAR T-cell therapy in bile duct, pancreatic, and gastric cancers.

Bile duct, pancreatic, and gastric cancers are deadly digestive system tumors with high malignancy and poor patient prognosis. The efficiencies of conventional surgical treatment, radiation therapy, and chemotherapy are limited. In contrast, chimeric antigen receptor (CAR) T-cell therapy represents a landmark therapeutic approach to antitumor immunity with great efficacy in treating several hematological malignancies. CAR T-cell therapy involves genetically engineering the expression of specific antibodies based on the patient's T-cell surface and amplifying these antibodies to identify and target tumor-associated antigens. CAR T-cell therapy can effectively inhibit disease progression and improve the survival of patients with bile duct, pancreatic, and gastric cancers. The effectiveness of CAR T cells in tumor therapy can be validated using xenograft models, providing a scientific testing platform. In this study, we have reviewed the progress in CAR T-cell production and its development, focusing on the current status and optimization strategies for engineered CAR T cells in the bile duct, pancreatic, and gastric cancers.

The role of RNA modification in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly mortal type of primary liver cancer. Abnormal epigenetic modifications are present in HCC, and RNA modification is dynamic and reversible and is a key post-transcriptional regulator. With the in-depth study of post-transcriptional modifications, RNA modifications are aberrantly expressed in human cancers. Moreover, the regulators of RNA modifications can be used as potential targets for cancer therapy. In RNA modifications, N6-methyladenosine (m6A), N7-methylguanosine (m7G), and 5-methylcytosine (m5C) and their regulators have important regulatory roles in HCC progression and represent potential novel biomarkers for the confirmation of diagnosis and treatment of HCC. This review focuses on RNA modifications in HCC and the roles and mechanisms of m6A, m7G, m5C, N1-methyladenosine (m1A), N3-methylcytosine (m3C), and pseudouridine (ψ) on its development and maintenance. The potential therapeutic strategies of RNA modifications are elaborated for HCC.

Corrigendum: Advances in CAR T-cell therapy in bile duct, pancreatic, and gastric cancers.

[This corrects the article DOI: 10.3389/fimmu.2022.1025608.].

Green Process without Thinning Agents for Preparing Sebacic Acid via Solid-Phase Cleavage.

A green and environmentally friendly route of no thinning agent was designed to prepare sebacic acid. Sodium ricinoleate was selected as the raw material to carry out solid-phase cleavage in a tubular furnace. The reaction parameters including catalyst, ratio of sodium ricinoleate/KOH, reaction time, reaction temperature, and absolute pressure were optimized to obtain a high yield of sebacic acid. A satisfactory yield (70.2%) of sebacic acid was received in the presence of 1% catalyst (Fe2O3) by weight (w/w), with 5:4 (w/w) ratio of sodium ricinoleate/KOH at 543 K under the absolute pressure of 0.09 MPa in 60 min. Sebacic acid was identified by gas chromatography analysis, and the purity (98.1%) of the product was further assessed by its melting point (306.3 K). Alkaline enhancement generates a better cracking effect. The yield of sebacic acid can be improved by a certain absolute pressure as a result of avoiding oxidation of sodium ricinoleate as well as reducing the residence time of hydrogen.