Marine algae-derived oligosaccharide via protein crotonylation of key targeting for management of type 2 diabetes mellitus in the elderly.

Global aging is a tendency of the world, as is the increasing prevalence of diabetes, and the two are closely linked. In our early research, Enteromorpha prolifera oligosaccharide (EPO) possesses the excellent ability of anti-oxidative, anti-inflammatory, and anti-diabetic. We aim to further explore the deeper mechanism of how EPO delays aging and regulates glycometabolism. EPO effectively impacts crotonylation procession to enhance glucose metabolism and reduce cell senescence in aging diabetic rats. Crotonylation modification of XPO1 influences the expression of critical genes, including p53, CDK1, and CCNB1, which affect cell cycle regulation and aging. Additionally, EPO improves glucose metabolism by inhibiting the crotonylation modification of HSPA8-K126 and activating the AKT pathway. EPO promotes crotonylation of histones in intestinal cells, influencing the aging process by increasing the butyric acid-producing bacteria Ruminococcaceae. The observed enhancement in pyrimidine metabolism underscores EPO's potential role in regulating intestinal health, presenting a promising avenue for delaying aging. In summary, our findings affirm EPO as a naturally bioactive ingredient with significant potential for anti-aging and antidiabetic interventions.

Recent progress in promoting the bioavailability of polyphenols in plant-based foods.

Polyphenols are important constituents of plant-based foods, exhibiting a range of beneficial effects. However, many phenolic compounds have low bioavailability because of their low water solubility, chemical instability, food matrix effects, and interactions with other nutrients. This article reviews various methods of improving the bioavailability of polyphenols in plant-based foods, including fermentation, natural deep eutectic solvents, encapsulation technologies, co-crystallization and amorphous solid dispersion systems, and exosome complexes. Several innovative technologies have recently been deployed to improve the bioavailability of phenolic compounds. These technologies may be utilized to increase the healthiness of plant-based foods. Further research is required to better understand the mechanisms of action of these novel approaches and their potential to be used in food production.

Marine algae-derived characterized bioactive compounds as therapy for cancer: A review on their classification, mechanism of action, and future perspectives.

In 2022, there were around 20 million new cases and over 9.7 million cancer-related deaths worldwide. An increasing number of metabolites with anticancer activity in algae had been isolated and identified, which were promising candidates for cancer therapy. Red algae are well-known for the production of brominated metabolites, including terpenoids and phenols, which have the capacity to induce cell toxicity. Some non-toxic biological macromolecules, including polysaccharides, are distinct secondary metabolites found in many algae, particularly green algae. They possess anticancer activities by inhibiting tumor angiogenesis, stimulating the immune response, and inducing apoptosis. However, the structure-activity relationship between these components and antitumor activity, as well as certain taxa within the algae, remains relatively unstudied. This work is based on the reports published from 2003 to 2024 in PubMed and ISI Web of Science databases. A comprehensive review of the characterized algal anticancer active compounds, together with their structure and mechanism of action was performed. Also, their structure-activity relationship was preliminarily summarized to better assess their potential properties as a natural, safe bioactive product to be used as an alternative for the treatment of cancers, leading to new opportunities for drug discovery.

Synthesis of bioactive oligosaccharides and their potential health benefits.

Oligosaccharides, a low polymerization degree of carbohydrate, possess various physiological activities, such as anti-diabetes, anti-obesity, anti-aging, anti-viral, and gut microbiota regulation, having a widely used in food and medical fields. However, due to the limited natural oligosaccharides, many un-natural oligosaccharides from complex polysaccharides are being studied for amplifying the available pool of oligosaccharides. More recently, various oligosaccharides were developed by using several artificial strategies, such as chemical degradation, enzyme catalysis, and biosynthesis, then they can be applied in various sectors. Moreover, it has gradually become a trend to use biosynthesis to realize the synthesis of oligosaccharides with clear structure. Emerging research has found that un-natural oligosaccharides exert more comprehensive effects against various human diseases through multiple mechanisms. However, these oligosaccharides from various routes have not been critical reviewed and summarized. Therefore, the purpose of this review is to present the various routes of oligosaccharides preparations and healthy effects, with a focus on diabetes, obesity, aging, virus, and gut microbiota. Additionally, the application of multi-omics for these natural and un-natural oligosaccharides has also been discussed. Especially, the multi-omics are needed to apply in various disease models to find out various biomarkers to respond to the dynamic change process of oligosaccharides.

The flavors of edible mushrooms: A comprehensive review of volatile organic compounds and their analytical methods.

Due to their distinctive flavors, edible mushrooms have gained attention in flavor-related research, and the quality of their flavors determines their consumption. The odor is a vital element of food flavor that significantly impacts consumers' perceptions and purchase decisions. The volatile organic compounds (VOCs) of the odorant ingredient is the primary factors affecting scent characteristics. VOCs analysis and identification require technical assistance. The production and use of edible mushrooms can be aided by a broader examination of their volatile constituents. This review discusses the composition of VOCs in edible mushrooms and how they affect flavors. The principles, advantages, and disadvantages of various methods for extraction, isolation, and characterization of the VOCs of edible mushrooms are also highlighted. The numerous VOCs found in edible mushrooms such as primarily C-8 compounds, organic sulfur compounds, aldehydes, ketones, alcohols, and esters are summarized along with their effects on the various characteristics of scent. Combining multiple extraction, isolation, identification, and quantification technologies will facilitate rapid and accurate analysis of VOCs in edible mushrooms as proof of sensory attributes and quality.

COL1A1 as a potential new biomarker and therapeutic target for type 2 diabetes.

Type 2 diabetes (T2D) is a public health problem with a rising incidence worldwide. In this study, a potential new biomarker for T2D and mechanisms underlying the hypoglycemic effects of Enteromorpha prolifera oligosaccharide were investigated. Tandem mass tag labeling with LC-MS/MS was used to identify the differentially expressed proteins (DEPs) between the jejunum of diabetic rats and control rats. Correlations between glycometabolic parameters and DEPs were revealed by a network analysis. The expression levels of target genes in key metabolic pathways were further evaluated to identify candidate biomarkers. Among 6810 total proteins, approximately 88 % were quantified, of which 148 DEPs with a fold change of <0.83 or>1.2 and a corrected p-value of <0.05 were identified. A KEGG enrichment analysis indicated that the hypoglycaemic effects of E. prolifera oligosaccharide involved the PI3K/AKT and extracellular matrix receptor interaction signaling pathways. More importantly, Col1a1 was the most significant gene in the extracellular matrix receptor interaction pathway and was linked to hypoglycaemic activity for the first time. Thus, Col1a1 is a novel potential therapeutic target for alleviating T2D.

CSF-1R inhibition disrupts the dialog between leukaemia cells and macrophages and delays leukaemia progression.

Research in the last few years has revealed that leukaemic cells can remodel the bone marrow niche into a permissive environment favouring leukaemic stem cell expansion. Tumour-associated macrophages (TAMs) are prominent components of the tumour microenvironment and play an important role in the onset and progression of solid tumours. However, little is known about their role in the development of acute lymphoblastic leukaemia (ALL). Using a unique mouse model of T-ALL induced by injection of EL4 T-cell lymphoma cells to syngeneic C57BL/6 mice, we report herein that ALL leads to the invasion of leukaemia-associated monocyte-derived cells (LAMs) into the bone marrow and spleen of T-ALL mice. Furthermore, we found that leukaemia cells could polarize bone marrow-derived macrophages (BMDMs) into LAMs. In turn, LAMs were able to protect leukaemia cells from drug-induced apoptosis in vitro. Therapies targeted against the TAMs by inhibiting colony stimulating factor-1 receptor (CSF-1R) have emerged as a promising approach for cancer treatment. In this study, we demonstrate that CSF-1R inhibition inhibits the viability of BMDMs, blocks LAMs polarization and reduces the abundance of LAMs in T-ALL mice. In vivo, combination treatment of CSF-1R inhibitor and vincristine (VCR) dramatically increased the survival of T-ALL mice and delayed leukaemia progression compared with VCR monotherapy. Finally, these data reinforce the role of microenvironments in leukaemia and suggest that macrophages are a potential target for the development of novel therapeutic strategies in T-ALL.

New attempts for central nervous infiltration of pediatric acute lymphoblastic leukemia.

The cure rate of acute lymphoblastic leukemia (ALL), the commonest childhood cancer, has been sharply improved and reached almost 90% ever since the central nervous system (CNS)-directed therapy proposed in the 1960s. However, relapse, particularly in the central nervous system (CNS), is still a common cause of treatment failure. Up to now, the classic CNS-directed treatment for CNS leukemia (CNSL) has been aslant from cranial radiation to high-dose system chemotherapy plus intrathecal (IT) chemotherapy for the serious side effects of cranial radiation. The neurotoxic effects of chemotherapy and IT chemotherapy have been reported in recent years as well. For better prevention and treatment of CNSL, plenty of studies have tried to improve the detection sensitivity for CNSL and prevent CNSL from happening by targeting cytokines and chemokines which could be key factors for the traveling of ALL cells into the CNS. Other studies also have aimed to completely kill ALL cells (including dormant cells) in the CNS by promoting the entering of chemotherapy drugs into the CNS or targeting the components of the CNS niche which could be in favor of the survival of ALL cells in CNS. The aim of this review is to discuss the imperfection of current diagnostic methods and treatments for CNSL, as well as new attempts which could be significant for better elimination of CNSL.

Potential therapeutic natural compounds for the treatment of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a complicated neurodegenerative disease with cognitive impairment occurring in the older people, in which extracellular accumulation of ß-amyloid and intracellular aggregation of hyperphosphorylated tau are regarded as the prevailing theories. However, the exact AD mechanism has not been determined. Moreover, there is no effective treatment available in phase III trials to eradicate AD, which is imperative to explore novel treatments. PURPOSE: A number of up-to-date pre-clinical studies on cognitive impairment is beneficial to clarify the pathology of AD. This review recapitulates several advances in AD pathobiology and discusses the neuroprotective effects of natural compounds, such as phenolic compounds, natural polysaccharides and oligosaccharides, peptide, and lipids, underscoring the therapeutic potential for AD. METHODS: Electronic databases involving PubMed, Web of Science, and Google Scholar were searched up to October 2023. Articles were conducted using the keywords like Alzheimer's disease, pathogenic mechanisms, natural compounds, and neuroprotection. RESULT: This review summarized several AD pathologies and the neuroprotective effects of natural compounds such as natural polysaccharides and oligosaccharides, peptide, and lipids. CONCLUSION: We have discussed the pathogenic mechanisms of AD and the effect natural products on neurodegenerative diseases particularly in treating AD. Specifically, we investigated the molecular pathways and links between natural compounds and Alzheimer's disease such as through NF-κB, Nrf2, and mTOR pathway. Further investigation is necessary in exploring the bioactivity and effectiveness of natural compounds in clinical trials, which may provide a promising treatment for AD patients.

Recent Progress in Human Milk Oligosaccharides and Its Antiviral Efficacy.

Gastrointestinal (GI)-associated viruses, including rotavirus (RV), norovirus (NV), and enterovirus, usually invade host cells, transmit, and mutate their genetic information, resulting in influenza-like symptoms, acute gastroenteritis, encephalitis, or even death. The unique structures of human milk oligosaccharides (HMOs) enable them to shape the gut microbial diversity and endogenous immune system of human infants. Growing evidence suggests that HMOs can enhance host resistance to GI-associated viruses but without a systematic summary to review the mechanism. The present review examines the lactose- and neutral-core HMOs and their antiviral effects in the host. The potential negative impacts of enterovirus 71 (EV-A71) and other GI viruses on children are extensive and include neurological sequelae, neurodevelopmental retardation, and cognitive decline. However, the differences in the binding affinity of HMOs for GI viruses are vast. Hence, elucidating the mechanisms and positive effects of HMOs against different viruses may facilitate the development of novel HMO derived oligosaccharides.

The novel angiotensin-I-converting enzyme inhibitory peptides from Scomber japonicus muscle protein hydrolysates: QSAR-based screening, molecular docking, kinetic and stability studies.

Food-derived angiotensin-converting enzyme-inhibitory (ACE-I) peptides have attracted extensive attention. Herein, the ACE-I peptides from Scomber japonicus muscle hydrolysates were screened, and their mechanisms of action and inhibition stability were explored. The quantitative structure-activity relationship (QSAR) model based on 5z-scale metrics was developed to rapidly screen for ACE-I peptides. Two novel potential ACE-I peptides (LTPFT, PLITT) were predicted through this model coupled with in silico screening, of which PLITT had the highest activity (IC50: 48.73 ± 7.59 µM). PLITT inhibited ACE activity with a mixture of non-competitive and competitive mechanisms, and this inhibition mainly contributed to the hydrogen bonding based on molecular docking study. PLITT is stable under high temperatures, pH, glucose, and NaCl. The zinc ions (Zn2+) and copper ions (Cu2+) enhanced ACE-I activity. The study suggests that the QSAR model is effective in rapidly screening for ACE-I inhibitors, and PLITT can be supplemented in foods to lower blood pressure.

A nanoluciferase SFTSV for rapid screening antivirals and real-time visualization of virus infection in mice.

BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen that causes severe hemorrhagic fever in humans, but no FDA-approved specific antivirals or vaccines are available to treat or prevent SFTS. METHODS: The plasmids construction and transfection were performed to generate the recombinant SFTSV harboring the nanoluciferase gene (SFTSV-Nluc). Immunostaining plaque assay was performed to measure viral titers, and DNA electrophoresis and Sanger sequencing were performed to evaluate the genetic stability. Luciferase assay and quantitative RT-PCR were performed to evaluate the efficacy of antivirals in vitro. Bioluminescence imaging, titration of virus from excised organs, hematology, and histopathology and immunohistochemistry were performed to evaluate the efficacy of antivirals in vivo. FINDINGS: SFTSV-Nluc exhibited high genetic stability and replication kinetics similar to those of wild-type virus (SFTSVwt), then a rapid high-throughput screening system for identifying inhibitors to treat SFTS was developed, and a nucleoside analog, 4-FlU, was identified to effectively inhibit SFTSV in vitro. SFTSV-Nluc mimicked the replication characteristics and localization of SFTSVwt in counterpart model mice. Bioluminescence imaging of SFTSV-Nluc allowed real-time visualization and quantification of SFTSV replication in the mice. 4-FlU was demonstrated to inhibit the replication of SFTSV with more efficiency than T-705 and without obvious adverse effect in vivo. INTERPRETATION: The high-throughput screening system based on SFTSV-Nluc for use in vitro and in vivo revealed that a safe and effective antiviral nucleoside analog, 4-FlU, may be a basis for the strategic treatment of SFTSV and other bunyavirus infections, paving the way for the discovery of antivirals. FUNDING: This work was supported by grants from the National Key Research and Development Plan of China (2021YFC2300700 to L. Zhang, 2022YFC2303300 to L. Zhang), Strategic Priority Research Program of Chinese Academy of Sciences (XDB0490000 to L. Zhang), National Natural Science Foundation of China (31970165 to L. Zhang, U22A20379 to G. Xiao), the Science and Technology Commission of Shanghai Municipality (21S11903100 to Y. Xie), Hubei Natural Science Foundation for Distinguished Young Scholars (2022CFA099 to L. Zhang).

Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies.

BACKGROUND: Chimeric antigen receptor T (CAR-T) therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignancies, but the cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet to be fully understood. This study aims to explore the molecular determinants of cancer cell sensitivity to CAR-T cell-mediated killing and to provide a better understanding of the underlying mechanisms and potential modulation to improve clinical efficacy. METHODS: The human whole-genome CRISPR/Cas9-based knockout screening was conducted to identify key genes that enable cancer cells to evade CD19 CAR-T-cell-mediated killing. The in vitro cytotoxicity assays and evaluation of tumor tissue and bone marrow specimens were further conducted to confirm the role of the key genes in cancer cell susceptibility to CAR-T cells. In addition, the specific mechanisms influencing CAR-T cell-mediated cancer clearance were elucidated in mouse and cellular models. RESULTS: The CRISPR/Cas9-based knockout screening showed that the enrichment of autophagy-related genes (ATG3, BECN1, and RB1CC1) provided protection of cancer cells from CD19 CAR-T cell-mediated cytotoxicity. These findings were further validated by in vitro cytotoxicity assays in cells with genetic and pharmacological inhibition of autophagy. Notably, higher expression of the three autophagy-related proteins in tumor samples was correlated with poorer responsiveness and worse survival in patients with relapsed/refractory B-cell lymphoma after CD19 CAR-T therapy. Bulk RNA sequencing analysis of bone marrow samples from B-cell leukemia patients also suggested the clinical relevance of autophagy to the therapeutic response and relapse after CD19 CAR-T cell therapy. Pharmacological inhibition of autophagy and knockout of RB1CC1 could dramatically sensitize tumor cells to CD19 CAR-T cell-mediated killing in mouse models of both B-cell leukemia and lymphoma. Moreover, our study revealed that cancer-intrinsic autophagy mediates evasion of CAR-T cells via the TNF-α-TNFR1 axis-mediated apoptosis and STAT1/IRF1-induced chemokine signaling activation. CONCLUSIONS: These findings confirm that autophagy signaling in B-cell malignancies is essential for the effective cytotoxic function of CAR-T cells and thereby pave the way for the development of autophagy-targeting strategies to improve the clinical efficacy of CAR-T cell immunotherapy.

Structural characterization of Euglena gracilis polysaccharide and its in vitro hypoglycemic effects by alleviating insulin resistance.

Diabetes mellitus, characterized by hyperglycemia and insulin resistance, is a disorder of the endocrine metabolic system which has emerged as a common chronic disease worldwide. Euglena gracilis polysaccharides have ideal development potential in the treatment of diabetes. However, their structure and bioactivity are largely unclear. A novel purified water-soluble polysaccharide (EGP-2A-2A) from E. gracilis with a molecular weight of 130.8 kDa consisted of xylose, rhamnose, galactose, fucose, glucose, arabinose, and glucosamine hydrochloride. The SEM image for EGP-2A-2A suggested a rough surface with the presence of globule-like protrusions. Methylation and NMR spectral analyses revealed that EGP-2A-2A was mainly composed of →6)-ß-D-Galp-(1 â†’ 2)-α-D-Glcp-(1 â†’ 2)-α-L-Rhap-(1 â†’ 3)-α-L-Araf-(1 â†’ 6)-ß-D-Galp-(1 â†’ 3)-α-D-Araf-(1 â†’ 3)-α-L-Rhap-(1 â†’ 4)-ß-D-Xylp-(1 â†’ 6)-ß-D-Galp-(1 â†’ with complex branching structure. EGP-2A-2A significantly increased glucose consumption and glycogen content in IR-HeoG2 cells and modulates glucose metabolism disorders by regulating PI3K, AKT, and GLUT4 signaling pathways. EGP-2A-2A significantly suppressed TC, TG, and LDL-c levels, and enhanced that of HDL-c. EGP-2A-2A ameliorated abnormalities caused by disorders of glucose metabolism and the hypoglycemic activity of EGP-2A-2A may be mainly positively related to its high glucose content and the ß-configuration in the main chain. These results suggested that EGP-2A-2A played an important role in alleviating disorders of glucose metabolism through insulin resistance and has the potential for development as a novel functional food with nutritional and health benefits.

Screening and Metabolomic Analysis of Lactic Acid Bacteria-Antagonizing Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a conditional Gram-negative pathogen that produces extracellular virulence factors that can lead to bloodstream invasion, severely harm tissues, and disseminate bacteria, ultimately leading to various diseases. In this study, lactic acid bacteria (LAB) with strong antagonistic ability against P. aeruginosa were screened, and the regulatory mechanism of LAB against P. aeruginosa was evaluated. The results showed that the three selected LAB strains had strong inhibition ability on the growth, biofilm formation, and pyocyanin expression of P. aeruginosa and a promoting effect on the expression of autoinducer-2. Among them, Lactipantibacillus plantarum (Lp. plantarum) LPyang is capable of affecting the metabolic processes of P. aeruginosa by influencing metabolic substances, such as LysoPC, oxidized glutathione, betaine, etc. These results indicate that LPyang reduces the infectivity of P. aeruginosa through inhibition of its growth, biofilm formation, pyocyanin expression, and regulation of its metabolome. This study provides new insights into the antagonistic activity of Lp. plantarum LPyang against P. aeruginosa.

Honeybee as a food nutrition analysis model of neural development and gut microbiota.

Research on the relationships between the gut microbiota and the neurophysiology and behavior of animals has grown exponentially in just a few years. Insect behavior may be controlled by molecular mechanisms that are partially homologous to those in mammals, and swarming insects may be suitable as experiment models in these types of investigations. All core gut bacteria in honeybees can be cultivated in vitro. Certain gut microflora of bees can be genetically engineered or sterilized and colonized. The bee gut bacteria model is established more rapidly and has a higher flux than other sterile animal models. It may help elucidate the pathogenesis of intestinal diseases and identify effective molecular therapeutic targets against them. In the present review, we focused on the contributions of the honeybee model in learning cognition and microbiome research. We explored the relationship between honeybee behavior and neurodevelopment and the factors determining the mechanisms by which the gut microbiota affects the host. In particular, we concentrated on the correlation between gut microbiota and brain development. Finally, we examined strategies for the effective use of simple animal models in animal cognition and microbiome research.

Electrochemical Oxidation Enables Regioselective 1,3-Hydroxyfunctionalization of Cyclopropanes.

The direct construction of 1,3-hydroxyfunctionalized molecules is still a significant challenge, as they can currently be obtained through multiple synthetic steps. Herein, we report a general and efficient 1,3-hydroxyfunctionalization of arylcyclopropanes by electrochemical oxidation with a strategic choice of nucleophiles and H2O. 1,3-Amino alcohols, 1,3-alkynyl alcohols, 1,3-hydroxyesters, and 1,3-halo alcohols are achieved with high levels of chemo- and regio-selectivity, opening a new dimension for 1,3-difunctionalization reaction.

Metabolomic analysis and pathway profiling of paramylon production in Euglena gracilis grown on different carbon sources.

Paramylon (ß-1,3-glucan) produced by Euglena gracilis displays antioxidant, antitumor, and hypolipidaemic functions. The biological properties of paramylon production by E. gracilis can be understood by elucidating the metabolic changes within the algae. In this study, the carbon sources in AF-6 medium were replaced with glucose, sodium acetate, glycerol, or ethanol, and the paramylon yield was measured. Adding 0.1260 g/L glucose to the culture medium resulted in the highest paramylon yield of 70.48 %. The changes in metabolic pathways in E. gracilis grown on glucose were assessed via non-targeted metabolomics analysis using ultra-high-performance liquid chromatography coupled to high-resolution quadrupole-Orbitrap mass spectrometry. We found that glucose, as a carbon source, regulated some differentially expressed metabolites, including l-glutamic acid, γ-aminobutyric acid (GABA), and l-aspartic acid. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes further showed that glucose regulated the carbon and nitrogen balance through the GABA shunt, which enhanced photosynthesis, regulated the flux of carbon and nitrogen into the tricarboxylic acid cycle, promoted glucose uptake, and increased the accumulation of paramylon. This study provides new insights into E. gracilis metabolism during paramylon synthesis.

Suppression of hepatocellular carcinoma by Ulva lactuca ulvan via gut microbiota and metabolite interactions.

INTRODUCTION: Ulva lactuca polysaccharide (ULP) is green algae extract with numerous biological activities, including anticoagulant, anti-inflammatory, and antiviral effects. However, the inhibitory ability of ULP in the development of hepatocellular carcinoma warrants further studies. OBJECTIVES: To elucidate the anti-tumor mechanism of ULP action and evaluate its regulatory effect on gut microbiota and metabolism in H22 hepatocellular carcinoma tumor-bearing mice. METHODS: An H22 tumor-bearing mouse model was established by subcutaneously injecting H22 hepatoma cells. The gut microbiota composition in cecal feces was assessed and subjected to untargeted metabolomic sequencing. The antitumor activity of ULP was verified further by western blot, RT-qPCR, and reactive oxygen species (ROS) assays. RESULTS: Administration of ULP alleviated tumor growth by modulating the compositions of the gut microbial communities (Tenericutes, Agathobacter, Ruminiclostridium, Parabacteroides, Lactobacillus, and Holdemania) and metabolites (docosahexaenoic acid, uric acid, N-Oleoyl Dopamine, and L-Kynurenine). Mechanistically, ULP promoted ROS production by inhibiting the protein levels of JNK, c-JUN, PI3K, Akt, and Bcl-6, thereby delaying the growth of HepG2 cells. CONCLUSION: ULP attenuates tumor growth in H22 tumor-bearing mice by modulating gut microbial composition and metabolism. ULP inhibits tumor growth mainly by promoting ROS generation.

A 3D co-culture intestinal organoid system for exploring glucose metabolism.

Many treatments have been used for glucose metabolism diseases such as type 2 diabetes, and all of those treatments have several advantages as well as limitations. This review introduces a 3D co-culture intestinal organoid system developed from stem cells, which has the special function of simulating human tissues. Recent studies have revealed that the gut is an important site for exploring the interactions among glucose metabolism, gut microbial metabolism, and gut microbiota. Therefore, 3D intestinal organoid systems can be used to imitate the congenital errors of human gut development, drug screening, food transportation and toxicity analysis. The intestinal organoid system construction methods and their progress as compared with traditional 2D culture methods have also been summarised in the manuscript. This paper discusses the research progress in terms of intestinal organoids applicable to glucose metabolism and provides new ideas for developing anti-diabetic drugs with high efficiency and low toxicity.