Updated Progress on Mass Spectrometry Imaging and its Application in Cancer Treatment and Drug Discovery.

BACKGROUND: Mass spectrometry imaging (MSI) is an imaging method based on mass spectrometry technology that can simultaneously visualize the spatial distribution of various biological molecules. The use of MSI in cancer detection and drug discovery has been extensively investigated in recent years. OBJECTIVE: This review aims to summarize the latest advances of MSI and its specific applications in cancer detection and drug discovery, providing a basic understanding of the development and application of MSI in the past five years and offering references for the further application of MSI in cancer detection and drug discovery. METHODS: In the database, "mass spectrometry imaging", "cancer treatment", and "drug discovery" were used as keywords for literature retrieval, and the time range was limited to "2018- 2023". After organizing and analyzing the literature and patents, a review was conducted. RESULTS: Based on the literature, it was found that the updated progress of MSI in the past five years mostly focused on concrete methods, operation procedures, facilities, and composite applications. The patents of MSI were mainly correlated with the mass spectrometry imaging system and its application in cancer treatment. MSI is conducive to investigating the therapeutic schedule of cancer and searching for new drugs. CONCLUSION: MSI is a convenient, fast and powerful technology that has made great progress in sample preparation, instrumentation, quantitation, and multimodal imaging. MSI has emerged as a powerful technique in various biomedical applications, which has strong potential in cancer detection, treatment, formation mechanism research, discovery of biomarkers, and drug discovery process.

Gut microbiome-mediated glucose and lipid metabolism mechanism of star apple leaf polyphenol-enriched fraction on metabolic syndrome in diabetic mice.

BACKGROUND: Diabetes is a kind of metabolic syndrome (MetS) that seriously threatens human health globally. The leaf of star apple (Chrysophyllum cainito L.) is an incompletely explored folk medicine on diabetes. And, the effects and mechanisms on diabetes complicated glycolipid metabolism disorders are unknown till now. PURPOSE: This study aimed to investigate the constituents of star apple leaf polyphenol enriched-fraction (SAP), and elucidate their treatment effects and mechanism on diabetes and accompanied other MetS. METHODS: The components of SAP were tentatively identified by HPLC-Q-TOF-MS/MS. The antioxidant activity was determined by the scavenging of free radicals and hypoglycemic activities by inhibition of α-glucosidase in vitro. HepG2 cells were used for evaluating the alleviation effects of SAP on lipid accumulation. Streptozotocin and high-fat diet induced diabetic mice were grouped to evaluate the effects of different dosages of SAP. 16S rRNA was conducted to analysis gut microbiome-mediated glucose and lipid metabolism mechanism. RESULTS: It showed that myricitrin was one of the main active constituents of SAP. SAP not only showed low IC50 on -glucosidase (24.427± 0.626 µg/mL), OH·(3.680± 0.054 µg/mL) and ABTS· (9.155±0.234 µg/mL), but significantly induced the lipid accumulation in HepG2 cells (p < 0.05). SAP at 200 mg/kg·day significantly decreased the blood glucose, insulin and oral glucose tolerance test value (p < 0.05). The insulin resistance indexes and oxidative stress were alleviated after administration. SAP not only attenuated hepatic lipid deposition, but also reversed the hepatic glycogen storage. 16S rRNA sequencing results revealed that the interaction between SAP and gut microbiota led to the positive regulation of beneficial bacteria including Akkermansia, Unspecified S24_7, Alistipes and Unspecified_Ruminococcaceae, which might be one of the mechanisms of SAP on MetS. CONCLUSION: For the first time, this study explored the regulation effect of star apple leaf polyphenols on the hepatic glycolipid metabolism and studied the underlying mechanism from the view of gut microbiota. These findings indicated that SAP possesses great potential to serve as a complementary medicine for diabetes and associated MetS. It provided scientific evidence for folk complementary medicine on the treatment of diabetes-complicated multiple metabolic disorders.

Structural Characterization, Cytotoxicity, and the Antifungal Mechanism of a Novel Peptide Extracted from Garlic (Allium sativa L.).

Garlic (Allium sativa L.) is a traditional plant with antimicrobial activity. This study aimed to discover new antifungal peptides from garlic, identify their structure, and explore the antimicrobial mechanism. Peptides were separated by chromatography and identified by MALDI-TOF analysis. Structure and conformation were characterized by CD spectrum and NMR analysis. Mechanism studies were conducted by SEM, membrane depolarization, and transcriptomic analysis. The cytotoxicity to mammalian cells as well as drug resistance development ability were also evaluated. A novel antifungal peptide named NpRS with nine amino acids (RSLNLLMFR) was obtained. It was a kind of cationic peptide with a α-helix as the dominant conformation. NOESY correlation revealed a cyclization in the molecule. The peptide significantly inhibited the growth of Candida albicans. The mechanism study indicated that membrane destruction and the interference of ribosome-related pathways might be the main mechanisms of antifungal effects. In addition, the resistance gene CDR1 for azole was down-regulated and the drug resistance was hardly developed in 21 days by the serial passage study. The present study identified a novel antifungal garlic peptide with low toxicity and provided new mechanism information for the peptide at the gene expression level to counter drug resistance.

Studies on the key constituents and the related mechanisms of Clerodendranthus spicatus in the treatment of diabetes based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Clerodendranthus spicatus is a traditional Chinese medicine and has been used to treat diabetes and some kidney diseases for a long history. AIM OF THE STUDY: The research aimed to study the active constituents, the potential targets and the related mechanisms of C. spicatus in the treatment of diabetes through network pharmacology method and verify the antidiabetic activity by molecular biology experiments. MATERIALS AND METHODS: A comprehensive network pharmacology strategy was used to predict the key active constituents, the key targets and the related mechanisms and pathways of C. spicatus in the treatment of diabetes. The strategy mainly included screening and predicting potential active constituents and targets by network construction, GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Based on the predicted results, C. spicatus was extracted by ultrasonic method with 50% ethanol and enriched by using macroporous resin. The compounds with potential antidiabetic effects were separated through silica-gel column chromatography and HPLC (high performance liquid chromatography), and then identified by MS (mass spectrum) and NMR (nuclear magnetic resonance). The C. spicatus extract and isolated compounds were tested by in-vitro and cell experiments to verify their antidiabetic activities, including antioxidant activities, inhibition activities on α-glucosidase and α-amylase, the influence on glucose uptake in cell experiments and the Western blot of PI3K and Akt expression levels. RESULTS: A total of 18 active constituents and 16 key targets of C. spicatus in the treatment of diabetes were screened out through network pharmacology method. Phenolic acids might be the main target compounds for the next research. After extraction, enrichment and separation, the phenolic acids-enriched fraction of C. spicatus and four phenolic acid compounds (helisterculin C, salvianolic acid B, orthosiphoic acid E and ethyl caffeate) were obtained. Among them, salvianolic acid B was isolated from C. spicatus for the first time and orthosiphoic acid E was isolated from natural products for the first time. In experiment verification, the crude extract of C. spicatus, the phenolic acids-enriched fraction and the four compounds all showed antidiabetic potentials. The phenolic acids in C. spicatus had antioxidant activities, inhibitory activities on α-amylase and α-glucosidase and promoted glucose uptake in L6 cells through PI3K/Akt signaling pathway. CONCLUSIONS: This study showed that C. spicatus had antidiabetic activities with the mechanism of the mode of multi-compounds acting on multi-targets and multi-pathways. The main active phenolic acid compounds were also identified. It provided theoretical basis for further development and utilization of C. spicatus.

Preventive and synbiotic effects of the soluble dietary fiber obtained from Lentinula edodes byproducts and Lactobacillus plantarum LP90 against dextran sulfate sodium-induced colitis in mice.

BACKGROUND: Soluble dietary fiber (SDF) obtained from Lentinula edodes byproducts has beneficial effects on human intestinal health. This study aimed to examine the combined preventive and ameliorative effects of a kind of synbiotic (SDF with a molecular weight of 1.58 × 102 kDa and Lactobacillus plantarum LP90 (LP) at 1 × 109 CFU kg-1 ) on dextran sulfate sodium-induced colitis mice. RESULTS: The results demonstrated that synbiotic treatment could alleviate weight loss, decrease the disease activity index level and cause histological amelioration. Synbiotic treatment also promoted the production of goblet cells, increased the expression of tight junction proteins, and adjusted the production of myeloperoxidase, malondialdehyde and superoxide dismutase to repair intestinal epithelial injury. Clinical symptoms were alleviated by maintaining Th17/Treg balance, increasing interleukin 10 and immunoglobulin A levels, reducing interleukin 17a and tumor necrosis factor α production, and promoting mRNA to highly express of Foxp3 and vitamin D receptors. Moreover, synbiotic treatment could upregulate butyric acid production (4.71 ± 0.46 mol g-1 feces, P < 0.05) and diversity of intestinal microbial to maintain intestinal homeostasis. CONCLUSION: This study suggested that the combination of LP and SDF as a synbiotic has the potential for use as a nutritional supplement to alleviate colitis. © 2022 Society of Chemical Industry.

Application of Nano Drug Delivery System (NDDS) in Cancer Therapy: A Perspective.

BACKGROUND: Cancer is the biggest killer that threatens human health. Poor bioavailability and strong drug resistance of cancer drugs are common defects. In recent years, drug delivery therapy based on nanotechnology has become a focused research area, and nano drug delivery system has been widely studied in cancer treatment. OBJECTIVES: Based on the articles and patents published on the application of nano drug delivery systems in cancer treatment in the past five years, this paper summarizes the types of nano drug delivery systems and their advantages and limitations in cancer treatment in order to provide a reference for future anticancer research on nano drug delivery systems. METHODS: This perspective summarizes the types of nano drug delivery systems and their advantages and limitations in cancer treatment in recent five years, and proposes the development direction of nano drug delivery systems in the future. RESULTS: Based on the review of articles and patents, we found that the nano drug delivery system is mainly divided into encapsulated nano drug delivery system and covalently bound nanoprodrug delivery system. Its advantages in cancer treatment are mainly reflected in enhancing drug stability, improving bioavailability, reducing toxicity and better application in cancer diagnosis. However, nano drug delivery system is a new field of science, some of these drug delivery systems might have high toxicity and low bioavailability; the off-target phenomenon often occurs, and most studies are just focused on the early stage, its mechanism of action, clinical efficacy and patient tolerance, and the toxicity of treatment remains to be further investigated. CONCLUSION: This perspective systematically summarizes the types of nano drug delivery systems and their advantages and limitations in cancer treatment based on the published articles and patents obtained in the last five years. Future research on nano drug delivery system should consider the potential risks, and stable and efficient nano drug delivery systems should be designed to treat cancer by changing or functionalizing the nanomaterial.

Insight into the Progress on Natural Dyes: Sources, Structural Features, Health Effects, Challenges, and Potential.

(1) Background: Dyes play an important role in food, medicine, textile, and other industries, which make human life more colorful. With the increasing demand for food safety, the development of natural dyes becomes more and more attractive. (2) Methods: The literature was searched using the electronic databases PubMed, Web of Science, and SciFinder and this scoping review was carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). (3) Results: 248 articles were included in this review. This review summarizes the research progress on natural dyes in the last ten years. According to structural features, natural dyes mainly include carotenoids, polyphenols, porphyrins, and alkaloids, and some of the newest dyes are summarized. Some pharmacological activities of carotenoids, anthocyanin, curcumin, and betalains in the last 10 years are summarized, and the biological effects of dyes regarding illumination conditions. The disadvantages of natural dyes, including sources, cost, stability, and poor bioavailability, limit their application. Here, some feasible strategies (potential resources, biotechnology, new extraction and separation strategies, strategies for improving stability) are described, which will contribute to the development and utilization of natural dyes. (4) Conclusion: Natural dyes show health benefits and potential in food additives. However, it is necessary for natural dyes to pass toxicity tests and quality tests and receive many regulatory approvals before their final entry into the market as food colorants or as drugs.

Recent Progress in Natural Anticancer Agents Discovery from Tea (Camellia sinensis): A Review.

BACKGROUND: Tea, as the bud from the plant Camellia sinensis, is the most consumed popular beverage just next to water; especially green tea has gained much attention because of its health effects. The anticancer effects of tea components including tea polyphenols, in particular epigallocatechin gallate and tea polysaccharides, are widely investigated in recent years. OBJECTIVES: Based on the articles and patents published in the last 10 years, this review focuses on the structural activities and molecular mechanisms of the anticancer effects of tea components (mainly tea polyphenols and tea polysaccharides) to provide references for future anticancer studies of tea. METHODS: In the database, a literature search was conducted with "tea polyphenols", "tea polysaccharides", "theanine" and "anticancer" as the keywords, and the limited time range was "2010-2021". After sorting out and analyzing the retrieval results, the structure, activity and molecular mechanism, as well as the research progress on the structural modification, drug delivery system and toxicology of natural agents in tea in recent years, were summarized. RESULTS: We found that the natural anticancer agents in tea mainly include tea polyphenols, tea polysaccharides, theanine, caffeine and other components by summarizing the literature. The anticancer mechanisms can be divided into the induction of cell apoptosis, inhibition of cell proliferation, metastasis and invasion, and inhibition of angiogenesis. In the past 10 years, there was little literature on the structural modification, drug delivery system and toxicological evaluation of natural anticancer agents in tea, and there were reports of novel research on nano preparations. The studies showed that nano preparation technology could effectively improve the bioavailability and targeting treatment of anticancer tea components. In addition, in the past decade, patents on tea and natural anticancer agents in tea were relatively rich, among which pharmaceutic preparation patents were the majority, and tea polyphenols were the main ones. CONCLUSION: This paper concluded that there are many kinds of natural anticancer agents in tea, and the anticancer mechanism is complex. Further research on the structural modification, drug delivery system and toxicological evaluation of relevant anticancer active components can be carried out. In general, tea components as new anticancer substances have a certain potential for development. In addition, future research can be focused on the comprehensive study of the structure-activity relationship, the in-depth study of the molecular mechanism, the in-depth understanding of the anticancer effects in vivo, and the verification of large-scale production.