Polysaccharide-polyphenol interactions: a comprehensive review from food processing to digestion and metabolism.

Most studies on the beneficial effects of polyphenols on human health have focused on polyphenols extracted using aqueous organic solvents, ignoring the fact that a portion of polyphenols form complexes with polysaccharides. Polysaccharides and polyphenols are interrelated, and their interactions affect the physicochemical property, quality, and nutritional value of foods. In this review, the distribution of bound polyphenols in major food sources is summarized. The effect of food processing on the interaction between polyphenols and cell wall polysaccharides (CWP) is discussed in detail. We also focus on the digestion, absorption, and metabolic behavior of polysaccharide-polyphenol complexes. Different food processing techniques affect the interaction between CWP and polyphenols by altering their structure, solubility, and strength of interactions. The interaction influences the free concentration and extractability of polyphenols in food and modulates their bioaccessibility in the gastrointestinal tract, leading to their major release in the colon. Metabolism of polyphenols by gut microbes significantly enhances the bioavailability of polyphenols. The metabolic pathway and product formation rate of polyphenols and the fermentation characteristics of polysaccharides are affected by the interaction. Furthermore, the interaction exhibits synergistic or antagonistic effects on the stability, solubility, antioxidant and functional activities of polyphenols. In summary, understanding the interactions between polysaccharides and polyphenols and their changes in food processing is of great significance for a comprehensive understanding of the health benefits of polyphenols and the optimization of food processing technology.

Highly specific vaginal microbiome signature for gynecological cancers.

To investigate the vaginal microbiota signature of patients with gynecologic cancer and evaluate its diagnostic biomarker potential. We incorporated vaginal 16S rRNA-seq data from 529 women and utilized VSEARCH to analyze the raw data. α-Diversity was evaluated utilizing the Chao1, Shannon, and Simpson indices, and ß-diversity was evaluated through principal component analysis using Bray-Curtis distances. Linear discriminant analysis effect size (LEfSe) was utilized to determine species differences between groups. A bacterial co-abundance network was constructed utilizing Spearman correlation analysis. A random forest model of gynecologic tumor risk based on genus was constructed and validated to test its diagnostic efficacy. In gynecologic cancer patients, vaginal α-diversity was significantly greater than in controls, and vaginal ß-diversity was significantly separated from that of controls; there was no correlation between these characteristics and menopause status among the subject women. Women diagnosed with gynecological cancer exhibited a reduction in the abundance of vaginal Firmicutes and Lactobacillus, while an increase was observed in the proportions of Bacteroidetes, Proteobacteria, Prevotella, Streptococcus, and Anaerococcus. A random forest model constructed based on 56 genus achieved high accuracy (area under the curve = 84.96%) in gynecological cancer risk prediction. Furthermore, there were discrepancies observed in the community complexity of co-abundance networks between gynecologic cancer patients and the control group. Our study provides evidence that women with gynecologic cancer have a unique vaginal flora structure and microorganisms may be involved in the gynecologic carcinogenesis process. A gynecological cancer risk prediction model based on characteristic genera has good diagnostic value.

Specific vaginal and gut microbiome and the anti-tumor effect of butyrate in cervical cancer women.

OBJECTIVE: To investigate the vaginal and gut microbes changes during the carcinogenesis of cervical and the auxiliary diagnostic value. To investigate the effect of microbiome-specific metabolites butyric on cervical cancer cells. METHODS: We studied 416 vaginal 16S rRNA sequencing data and 116 gut sequencing data. Reads were processed using VSEARCH. We used Shannon index, Chao1 index, Simpson diversity index, ß diversity index, Linear discriminant analysis Effect Size (LEfSe), co-abundance network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore microbiome differences between groups. We constructed random forest models based on genus and verified its discriminant effect. Finally, we used the cell counting kit-8 (CCK-8) method to detect cell proliferation capacity and flow cytometry to detect apoptosis and induction of cell cycle progression. RESULTS: Compared to the non-cancerous population, patients with cervical cancer had unique microbial community characteristics in both vaginal and gut ecological niches. Our predictive model based on genus in two ecological regions achieved high accuracy in the diagnosis of cervical cancer (vaginal model AUC=91.58 %; gut model AUC=99.95 %). Butyric inhibited cervical cancer cell proliferation in a concentration-dependent manner and promoted apoptosis of cancer cells. CONCLUSION: Significant differences were found in vaginal and gut microbes in patients with cervical cancer compared to the non-cancerous population. The prediction models constructed at the genus level in both ecological sites have good diagnostic value. Microorganisms may be involved in cervical cancer progression in a metabolite-dependent way, and targeting butyric may provide therapeutic options for cervical cancer.

6-O-endosulfatases in tumor metastasis: heparan sulfate proteoglycans modification and potential therapeutic targets.

Metastasis is the leading cause of cancer-associated mortality. Although advances in the targeted treatment and immunotherapy have improved the management of some cancers, the prognosis of metastatic cancers remains unsatisfied. Therefore, the specific mechanisms in tumor metastasis need further investigation. 6-O-endosulfatases (SULFs), comprising sulfatase1 (SULF1) and sulfatase 2 (SULF2), play pivotal roles in the post-synthetic modifications of heparan sulfate proteoglycans (HSPGs). Consequently, these extracellular enzymes can regulate a variety of downstream pathways by modulating HSPGs function. During the past decades, researchers have detected the expression of SULF1 and SULF2 in most cancers and revealed their roles in tumor progression and metastasis. Herein we reviewed the metastasis steps which SULFs participated in, elucidated the specific roles and mechanisms of SULFs in metastasis process, and discussed the effects of SULFs in different types of cancers. Moreover, we summarized the role of targeting SULFs in combination therapy to treat metastatic cancers, which provided some novel strategies for cancer therapy.

Polyphenols synergistic drugs to ameliorate non-alcoholic fatty liver disease via signal pathway and gut microbiota: A review.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease with an increasing incidence worldwide. Single drug therapy may have toxic side effects and disrupt gut microbiota balance. Polyphenols are widely used in disease intervention due to their distinctive nutritional properties and medicinal value, which a potential gut microbiota modulator. However, there is a lack of comprehensive review to explore the efficacy and mechanism of combined therapy with drugs and polyphenols for NAFLD. AIM OF REVIEW: Based on this, this review firstly discusses the link between NAFLD and gut microbiota, and outlines the effects of polyphenols and drugs on gut microbiota. Secondly, it examined recent advances in the treatment and intervention of NAFLD with drugs and polyphenols and the therapeutic effect of the combination of the two. Finally, we highlight the underlying mechanisms of polyphenol combined drug therapy in NAFLD. This is mainly in terms of signaling pathways (NF-κB, AMPK, Nrf2, JAK/STAT, PPAR, SREBP-1c, PI3K/Akt and TLR) and gut microbiota. Furthermore, some emerging mechanisms such as microRNA potential biomarker therapies may provide therapeutic avenues for NAFLD. KEY SCIENTIFIC CONCEPTS OF REVIEW: Drawing inspiration from combination drug strategies, the use of active substances in combination with drugs for NAFLD intervention holds transformative and prospective potential, both improve NAFLD and restore gut microbiota balance while reducing the required drug dosage. This review systematically discusses the bidirectional interactions between gut microbiota and NAFLD, and summarizes the potential mechanisms of polyphenol synergistic drugs in the treatment of NAFLD by modulating signaling pathways and gut microbiota. Future researches should develop multi-omics technology to identify patients who benefit from polyphenols combination drugs and devising individualized treatment plans to enhance its therapeutic effect.

Characterization and stability assessment of polyphenols bound to Lycium barbarum polysaccharide: Insights from gastrointestinal digestion and colon fermentation.

Polysaccharides and polyphenols are biologically active components that coexist in Lycium barbarum fruit, and there may be interactions between them that affect the release of each other. In this study, polyphenols bound to L. barbarum polysaccharide (LBP) were characterized, and the stability of bound phenolics (BP) was assessed by gastrointestinal digestion and colon fermentation. The results showed that a total of 65 phytochemicals such as flavonoids, phenolic acids, and coumarins were identified by UPLC-MS/MS. Quantitative analysis revealed that the major phenolic constituents were rutin, p-coumaric acid, catechin, ferulic acid, protocatechuic acid, and gallic acid, and their contents were 58.72, 24.03, 14.24, 13.28, 10.39, and 6.7 mg GAE/100 g DW, respectively. The release of BP by gastric digestion and gastrointestinal digestion was 9.67 % and 19.39 %, respectively. Most polyphenols were greatly affected by gastric digestion, while rutin was released in small intestine. The BP were fully released (49.77 %) and metabolized by gut microorganisms, and a considerable number of intermediates and end-products were detected, such as phloroglucinol, phenylacetic acid, and phenyllactic acid. Microbiomics data emphasized the positive impact of LBP on gut bacteria of Bacteroides, Parabacteroides, and Clostridioides. These findings could deepen our understanding of the bioavailability and biological fate of BP and also provide reference data for nutrient release and utilization of L. barbarum as a whole.

M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets.

RNA modifications play a pivotal role in regulating cellular biology by exerting influence over distribution features and molecular functions at the post-transcriptional level. Among these modifications, N7-methylguanosine (m7G) stands out as one of the most prevalent. Over recent years, significant attention has been directed towards understanding the implications of m7G modification. This modification is present in diverse RNA molecules, including transfer RNAs, messenger RNAs, ribosomal RNAs, and other noncoding RNAs. Its regulation occurs through a series of specific methyltransferases and m7G-binding proteins. Notably, m7G modification has been implicated in various diseases, prominently across multiple cancer types. Earlier studies have elucidated the significance of m7G modification in the context of immune biology regulation within the tumor microenvironment. This comprehensive review culminates in a synthesis of findings related to the modulation of immune cells infiltration, encompassing T cells, B cells, and various innate immune cells, all orchestrated by m7G modification. Furthermore, the interplay between m7G modification and its regulatory proteins can profoundly affect the efficacy of diverse adjuvant therapeutics, thereby potentially serving as a pivotal biomarker and therapeutic target for combinatory interventions in diverse cancer types.

The role of microbiota in the development and treatment of gastric cancer.

The stomach was once considered a sterile organ until the discovery of Helicobacter pylori (HP). With the application of high-throughput sequencing technology and macrogenomics, researchers have identified fungi and fivemajor bacterial phyla within the stomachs of healthy individuals. These microbial communities exert regulatory influence over various physiological functions, including energy metabolism and immune responses. HP is a well-recognized risk factor for gastric cancer, significantly altering the stomach's native microecology. Currently, numerous studies are centered on the mechanisms by which HP contributes to gastric cancer development, primarily involving the CagA oncoprotein. However, aside from exogenous infections such as HP and EBV, certain endogenous dysbiosis can also lead to gastric cancer through multiple mechanisms. Additionally, gut microbiota and its metabolites significantly impact the development of gastric cancer. The role of microbial therapies, including diet, phages, probiotics and fecal microbiota transplantation, in treating gastric cancer should not be underestimated. This review aims to study the mechanisms involved in the roles of exogenous pathogen infection and endogenous microbiota dysbiosis in the development of gastric cancer. Also, we describe the application of microbiota therapy in the treatment and prognosis of gastric cancer.

Identification of microbial markers associated with lung cancer based on multi-cohort 16 s rRNA analyses: A systematic review and meta-analysis.

BACKGROUND: The relationship between commensal microbiota and lung cancer (LC) has been studied extensively. However, developing replicable microbiological markers for early LC diagnosis across multiple populations has remained challenging. Current studies are limited to a single region, single LC subtype, and small sample size. Therefore, we aimed to perform the first large-scale meta-analysis for identifying micro biomarkers for LC screening by integrating gut and respiratory samples from multiple studies and building a machine-learning classifier. METHODS: In total, 712 gut and 393 respiratory samples were assessed via 16 s rRNA amplicon sequencing. After identifying the taxa of differential biomarkers, we established random forest models to distinguish between LC populations and normal controls. We validated the robustness and specificity of the model using external cohorts. Moreover, we also used the KEGG database for the predictive analysis of colony-related functions. RESULTS: The α and ß diversity indices indicated that LC patients' gut microbiota (GM) and lung microbiota (LM) differed significantly from those of the healthy population. Linear discriminant analysis (LDA) of effect size (LEfSe) helped us identify the top-ranked biomarkers, Enterococcus, Lactobacillus, and Escherichia, in two microbial niches. The area under the curve values of the diagnostic model for the two sites were 0.81 and 0.90, respectively. KEGG enrichment analysis also revealed significant differences in microbiota-associated functions between cancer-affected and healthy individuals that were primarily associated with metabolic disturbances. CONCLUSIONS: GM and LM profiles were significantly altered in LC patients, compared to healthy individuals. We identified the taxa of biomarkers at the two loci and constructed accurate diagnostic models. This study demonstrates the effectiveness of LC-specific microbiological markers in multiple populations and contributes to the early diagnosis and screening of LC.

Vaginal and tumor microbiomes in gynecological cancer (Review).

Cervical, ovarian and endometrial cancer are the three most common types of gynecologic cancer. As a hub, the vagina connects the site of gynecological cancer with the external environment. Lactobacilli participate in the formation of a healthy vaginal microenvironment as the first line of defense against pathogen invasion; a dysbiotic vaginal microenvironment loses its original protective function and is associated with the onset, metastasis, poor efficacy and poor prognosis of gynecological cancer. The early diagnosis of cancer is the key to improve the survival time of patients with cancer. The screening of Porphyromonas, Sneathia and Atopobium vaginae, and other microbial markers, can assist the diagnosis of gynecological cancer, and screen out the high-risk population as early as possible. With the in-depth study of the microbes in tumor tissues, reasearchers have analyzed the immunological associations of microorganisms in tumor tissues. Due to the structural-functional interconnection between the organ of gynecological tumorigenesis and the vagina, the present study aims to review the relationship between vaginal and tumor microorganisms and gynecological cancer in terms of occurrence, screening, treatment and prognosis.

LINC01608 activated by YY1 facilitate hepatocellular carcinoma progression by modulating the EGFR/ERK axis.

BACKGROUND: Long non-coding RNAs (LncRNAs) have been demonstrated to associate with a variety of cancers. However, the mechanisms of LncRNAs in hepatocellular carcinoma (HCC) progression are still not fully clarified. METHODS: LINC01608 expression level in HCC and adjacent normal tissues was detected by real-time-quantitively PCR (RT-qPCR) in clinical samples and in situ hybridization (ISH) in tissue microarray. Several functional assays were performed to determine the biological effects of LINC01608 in HCC cells in vitro, while subcutaneous xenograft models and lung metastasis models in nude mice and immunohistochemistry (IHC) results showed the role of LINC01608 in HCC progression in vivo. The combination of LINC01608 with miR-875-5p and target genes was elucidated by dual-luciferase report assays, RNA immunoprecipitation (RIP) assays and fluorescence in situ hybridization (FISH) assays. Finally, bioinformatics analysis and chromatin immunoprecipitation (CHIP) were performed to investigate the mechanism of Yin Yang-1 (YY1) regulating LINC01608 transcription. RESULTS: LINC01608 was overexpressed in HCC tissues, and high LINC01608 expression predicted poor overall survival (OS) and disease-free survival (DFS) in HCC patients. LINC01608 could promote HCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, we demonstrated that LINC01608 could sponge to miR-875-5p and activate the EGFR/ERK pathway. Moreover, we identified transcriptional factor YY1 could bind to the promoter of LINC01608 and induce its transcription. CONCLUSION: LINC01608 could serve as a promising prognostic biomarker of HCC. YY1-activated LINC01608 could promote HCC progression by associating with miR-875-5p to induce the EGFR/ERK signalling pathway. This discovery might provide therapeutic strategies for HCC.

Identifying distinctive tissue and fecal microbial signatures and the tumor-promoting effects of deoxycholic acid on breast cancer.

Introduction: A growing body of evidence indicates that the dysbiosis of both mammary and intestinal microbiota is associated with the initiation and progression of breast tumors. However, the microbial characteristics of patients with breast tumors vary widely across studies, and replicable biomarkers for early-stage breast tumor diagnosis remain elusive. Methods: We demonstrate a machine learning-based method for the analysis of breast tissue and gut microbial differences among patients with benign breast disease, patients with breast cancer (BC), and healthy individuals using 16S rRNA sequence data retrieved from eight studies. QIIME 2.0 and R software (version 3.6.1) were used for consistent processing. A naive Bayes classifier was trained on the RDP v16 reference database to assign taxonomy using the Vsearch software. Results: After re-analyzing with a total of 768 breast tissue samples and 1,311 fecal samples, we confirmed that Halomonas and Shewanella were the most representative genera of BC tissue. Bacteroides are frequently and significantly enriched in the intestines of patients with breast tumor. The areas under the curve (AUCs) of random forest models were 74.27% and 68.08% for breast carcinoma tissues and stool samples, respectively. The model was validated for effectiveness via cohort-to-cohort transfer (average AUC =0.65) and leave-one-cohort-out (average AUC = 0.66). The same BC-associated biomarker Clostridium_XlVa exists in the tissues and the gut. The results of the in-vitro experiments showed that the Clostridium-specific-related metabolite deoxycholic acid (DCA) promotes the proliferation of HER2-positive BC cells and stimulates G0/G1 phase cells to enter the S phase, which may be related to the activation of peptide-O-fucosyltransferase activity functions and the neuroactive ligand-receptor interaction pathway. Discussion: The results of this study will improve our understanding of the microbial profile of breast tumors. Changes in the microbial population may be present in both the tissues and the gut of patients with BC, and specific markers could aid in the early diagnosis of BC. The findings from in-vitro experiments confirmed that Clostridium-specific metabolite DCA promotes the proliferation of BC cells. We propose the use of stool-based biomarkers in clinical application as a non-invasive and convenient diagnostic method.

Preparation of edible starch nanomaterials for the separation of polyphenols from fruit pomace extract and determination of their adsorption properties.

Apple polyphenols are abundantly present in apple pomace, and their applications are limited by the low efficiency of traditional extraction methods and the tendency to pollute the environment. Starch nanoparticles (SNPs) have received much attention due to their renewable, low cost and biocompatibility. The aim of this study was to prepare SNPs of different sizes from corn starch using ultrasonic-assisted chemical precipitation with adsorption of apple polyphenols, investigate the relationship between particle size and adsorption, while experiments were performed to assess antioxidant activity, simulate in vivo digestion and polyphenol release. The results showed that the smaller the particle size of SNPs the higher the adsorption of polyphenols, and the combination of characterization and adsorption kinetics showed that this adsorption was a physicochemical binding process. DPPH radical scavenging activity showed that polyphenols bound to SNPs were more stable than free polyphenols. In vitro simulation of digestion and release processes, SNPs loaded with polyphenols showed better anti-digestive properties, polyphenols are released in small amounts in gastric juices and continuously in intestinal juices. Our results provide a theoretical basis for the direct separation of polyphenols from fruit pomace polyphenol extracts using nanomaterials and the industrial utilization of polyphenol products.

Gut Microbes in Gynecologic Cancers: Causes or Biomarkers and Therapeutic Potential.

The human intestine is home to a variety of microorganisms. In healthy populations, the intestinal flora shares a degree of similarity and stability, and they have a role in the metabolism, immunological response, and physiological function of key organs. With the rapid advent of high-throughput sequencing in recent years, several researchers have found that dysbiosis of the human gut microflora potentially cause physical problems and gynecological malignancies among postmenopausal women. Besides, dysbiosis hinders tumor treatment. Nonetheless, the importance of maintaining homeostatic gut microbiota and the effective use of probiotics in the treatment of gynecological malignancies should not be disregarded. Moreover, intestinal flora regulation and the involvement of probiotics as well as associated biologically active substances in gynecological malignancies could be an adjuvant treatment modality related to surgery and chemoradiotherapy in the future. Herein, this article aims to review the potential relationship between gut microorganisms and postmenopausal status as well as gynecologic malignancies; then the relationship between gut microbes and early screening as well as therapeutic aspects. Also, we describe the role of probiotics in the prevention, treatment, and prognosis of gynecologic malignancies.

EIF4A3-induced circTOLLIP promotes the progression of hepatocellular carcinoma via the miR-516a-5p/PBX3/EMT pathway.

BACKGROUND: Circular RNAs (circRNAs) function as crucial regulators in multiple cancers, including hepatocellular carcinoma (HCC). However, the roles of circRNAs in HCC remains largely unknown. METHODS: circTOLLIP was identified in HCC by screening of two public circRNA microarray datasets and detected in HCC cells and tissues through quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Gain- and loss-of-function assays were performed to confirm the biological effects of circTOLLIP on HCC in vitro and in vivo. Mechanistically, bioinformatics analysis of online databases, MS2-RNA pulldown, biotin-labeled circTOLLIP/miR-516a-5p RNA pulldown, RNA immunoprecipitation (RIP), luciferase reporter assay, fluorescence in situ hybridization assay (FISH) and RNA sequencing were used to confirm the regulation of Eukaryotic initiation factor 4A3 (EIF4A3) on circTOLLIP and the interaction among circTOLLIP, miR-516a-5p and PBX homeobox 3 (PBX3). RESULTS: circTOLLIP was significantly upregulated in HCC cells and tissues. High circTOLLIP expression was correlated with poor overall survival (OS) and disease-free survival (DFS) in patients. circTOLLIP promoted the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, EIF4A3 promoted the biogenesis of circTOLLIP without affecting its stability. Moreover, circTOLLIP sponged miR-516a-5p to elevate the expression of PBX3, thereby activating the epithelial-to-mesenchymal transition (EMT) pathway and facilitating tumor progression in HCC. CONCLUSIONS: Our findings indicate that EIF4A3-induced circTOLLIP promotes the progression of HCC through the circTOLLIP/miR-516a-5p/PBX3/EMT axis.

Evaluating the changes in phytochemical composition, hypoglycemic effect, and influence on mice intestinal microbiota of fermented apple juice.

Apples are rich in phenolic antioxidants, which have various beneficial effects on human health. The purposes of our study were to evaluate the effects of Lactobacillus fermentum 21828 fermentation on the phytochemical composition and bioactivity of Aksu (Fuji) apple juice (AJ), and to evaluate the hypoglycemic effect of fermented AJ (FAJ) and its effect on intestinal flora. Fermentation altered the phytochemistry and enhanced the biological activity (hypoglycemic and antioxidant activities) of AJ. FAJ improved fasting blood glucose and insulin levels in diabetic mice, regulated blood lipid metabolism, reduced oxidative damage, restored damaged islet cells, and reshaped the intestinal flora of diabetic mice by increasing the relative abundance of Actinobacteria, Bifidobacteria, and Faecalibaculum. The results indicate that FAJ is a fermented product that is rich in bioactive components and has potential hypoglycemic and antioxidant activities.

DDR1 promotes hepatocellular carcinoma metastasis through recruiting PSD4 to ARF6.

Discoidin domain receptor 1 (DDR1) is a member of the receptor tyrosine kinase family, and its ligand is collagen. Previous studies demonstrated that DDR1 is highly expressed in many tumors. However, its role in hepatocellular carcinoma (HCC) remains obscure. In this study, we found that DDR1 was upregulated in HCC tissues, and the expression of DDR1 in TNM stage II-IV was higher than that in TNM stage I in HCC tissues, and high DDR1 expression was associated with poor prognosis. Gene expression analysis showed that DDR1 target genes were functionally involved in HCC metastasis. DDR1 positively regulated the migration and invasion of HCC cells and promoted lung metastasis. Human Phospho-Kinase Array showed that DDR1 activated ERK/MAPK signaling pathway. Mechanically, DDR1 interacted with ARF6 and activated ARF6 through recruiting PSD4. The kinase activity of DDR1 was required for ARF6 activation and its role in metastasis. High expression of PSD4 was associated with poor prognosis in HCC. In summary, our findings indicate that DDR1 promotes HCC metastasis through collagen induced DDR1 signaling mediated PSD4/ARF6 signaling, suggesting that DDR1 and ARF6 may serve as novel prognostic biomarkers and therapeutic targets for metastatic HCC.

Structures and biological functions of zinc finger proteins and their roles in hepatocellular carcinoma.

Zinc finger proteins are transcription factors with the finger domain, which plays a significant role in gene regulation. As the largest family of transcription factors in the human genome, zinc finger (ZNF) proteins are characterized by their different DNA binding motifs, such as C2H2 and Gag knuckle. Different kinds of zinc finger motifs exhibit a wide variety of biological functions. Zinc finger proteins have been reported in various diseases, especially in several cancers. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated death worldwide, especially in China. Most of HCC patients have suffered from hepatitis B virus (HBV) and hepatitis C virus (HCV) injection for a long time. Although the surgical operation of HCC has been extremely developed, the prognosis of HCC is still very poor, and the underlying mechanisms in HCC tumorigenesis are still not completely understood. Here, we summarize multiple functions and recent research of zinc finger proteins in HCC tumorigenesis and progression. We also discuss the significance of zinc finger proteins in HCC diagnosis and prognostic evaluation.

Discoidin domain receptor 1 promotes hepatocellular carcinoma progression through modulation of SLC1A5 and the mTORC1 signaling pathway.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world with a high mortality rate. Receptor tyrosine kinases play important roles in the occurrence and development of various cancers. Discoid protein domain receptor 1 (DDR1) is a special type of transmembrane receptor tyrosine kinase. Here, we show that the expression of DDR1 is significantly increased in HCC and is related to a poor clinical prognosis. METHODS: The expression of DDR1 in HCC cell lines and primary HCC specimens was evaluated using Western blotting and immunohistochemistry. A correlation between DDR1 and SLC1A5 expression was also investigated in primary HCC specimens. Cell proliferation was evaluated using in vitro CCK8 and colony formation assays. Gene knock-down and overexpression assays, CHX, NH4CL and Mg132 interference tests and immunoprecipitation, as well as nude mouse xenograft models were used to assess the mechanism by which DDR1 promotes tumorigenesis in vitro and in vivo. RESULTS: We found that DDR1 promotes the proliferation of HCC cells and accelerates the growth of HCC tumor xenografts, while DDR1 downregulation had the opposite effect. We also found that loss or gain of DDR1 expression affected HCC cell cycle progression. Mechanistically, we found that DDR1 interacts with SLC1A5, which belongs to the solute carrier (SLC) family of transporters, and regulates its stability, thereby affecting the mTORC1 signaling pathway. In addition, we found that SLC1A5 regulation by DDR1 can be restored by lysosome inhibitors. We also found that DDR1 is highly expressed in HCC tissues and that increased DDR1 expression predicts a shorter overall survival (OS) time. We additionally found that the expression of SLC1A5 was positively correlated with that of DDR1. Together, our data indicate that DDR1 acts as a tumor-promoting factor that can control HCC cell proliferation and cell cycle progression by stabilizing SLC1A5 in a lysosome-dependent way. CONCLUSIONS: Our study reveals a new mechanism by which DDR1 plays a liver cancer-promoting role. We also found that DDR1 expression serves as an independent prognostic marker, and that DDR1 and SLC1A5 expression levels are positively correlated in clinical samples. Our findings provide a new perspective for understanding HCC development and offers new targets for the treatment and management of HCC.

Effects of fermentation with Lactobacillus fermentum 21828 on the nutritional characteristics and antioxidant activity of Lentinus edodes liquid.

BACKGROUND: Few studies to date have evaluated the use of Lactobacillus and Bifidobacterium in edible fungus fermentation. To obtain a fermented Lentinus edodes liquid product with good taste and effects, a strain with good fermentation performance from nine strains tested was selected, and the physicochemical properties and antioxidant capacity of the resulting product were evaluated. RESULTS: Lactobacillus fermentum 21828 exhibited adhesion, tolerance to low pH and bile salts, and good fermentation performance. The number of viable bacteria was 1.05 × 108 CFU mL-1 , and the extraction rate of crude polysaccharide from L. edodes was 2.79% after fermentation. The effects of fermentation on the contents and composition of nutrients in L. edodes liquid were marked, with changes in total soluble protein, total soluble sugar, total acid, and total phenol levels. The 2,2-diphenyl-1-picrylhydrazyl radical-scavenging rate in the fermentation liquid was 93.01%, which was significantly higher than that in non-fermented liquid (80.33%). Furthermore, analysis of volatile and 5'-nucleotide contents showed that fermentation altered the flavor of the product, whereas sensory evaluation showed that the fermented product was preferred. CONCLUSION: Our study demonstrated that the fermented L. edodes liquid exhibited better nutritional and functional properties, as well as sensory characteristics, compared with unfermented liquid. © 2021 Society of Chemical Industry.