N-methyl Formamide Electrolyte Additive Enabling Highly Reversible Zn Anodes.

Parasitic side reactions and dendrites formation hinder the application of aqueous zinc ion batteries due to inferior cycling life and low reversibility. Against this background, N-methyl formamide (NMF), a multi-function electrolyte additive is applied to enhance the electrochemical performance. Studied via advanced synchrotron radiation spectroscopy and DFT calculations, the NMF additive simultaneously modifies the Zn2+ solvation structure and ensures uniform zinc deposition, thus suppressing both parasitic side reactions and dendrite formation. More importantly, an ultralong cycling life of 3115 h in the Zn||Zn symmetric cell at a current density of 0.5 mA cm-2 is achieved with the NMF additive. Practically, the Zn||PANI full cell utilizing NMF electrolyte shows better rate and cycling performance compared to the pristine ZnSO4 aqueous electrolyte. This work provides useful insights for the development of high-performance aqueous metal batteries.

Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies.

Severe immunosuppression is a hallmark of colorectal cancer (CRC). Myeloid-derived suppressor cells (MDSCs), one of the most abundant components of the tumor stroma, play an important role in the invasion, metastasis, and immune escape of CRC. MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells, including T and natural killer cells, as well as by inducing the proliferation of immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages, which, in turn, promote the growth of cancer cells. Thus, MDSCs are key contributors to the emergence of an immunosuppressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity. In this narrative review, we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment, the current therapeutic approaches and technologies targeting MDSCs, and the therapeutic potential of modulating MDSCs in CRC treatment. This study provides ideas and methods to enhance survival rates in patients with CRC.

Wogonin Inhibits Colorectal Cancer Proliferation and Epithelial Mesenchymal Transformation by Suppressing Phosphorylation in the AKT Pathway.

Colorectal cancer is the third leading cause of cancer-related death worldwide. Hence, there is a need to identify new therapeutic agents to improve the current repertoire of therapeutic drugs. Wogonin, a flavonoid from the herbal medicine Scutellaria baicalensis, has unique antitumor activity. Our study aimed to further explore the inhibitory effects of wogonin on colorectal cancer and its specific mechanism. The results showed that wogonin significantly inhibited the proliferation of colorectal cancer cells as well as their ability to invade and metastasize. We detected phosphorylation of tumor-associated signaling pathways using a phosphorylated protein microarray and found that wogonin intervention significantly inhibited the phosphorylation level of the AKT protein in colorectal cancer cells. Through in vitro and in vivo experiments, it was confirmed that wogonin exerted its antitumor effects against colorectal cancer by inhibiting phosphorylation in the AKT pathway. Our discovery of wogonin as an inhibitor of AKT phosphorylation provides new opportunities for the pharmacological treatment of colorectal cancer.

Therapeutic potential of traditional Chinese medicine in the prevention and treatment of digestive inflammatory cancer transformation: Portulaca oleracea L. as a promising drug.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been used for centuries to treat various types of inflammation and tumors of the digestive system. Portulaca oleracea L. (POL), has been used in TCM for thousands of years. The chemical composition of POL is variable and includes flavonoids, alkaloids, terpenoids and organic acids and other classes of natural compounds. Many of these compounds exhibit powerful anti-inflammatory and anti-cancer-transforming effects in the digestive system. AIM OF STUDY: In this review, we focus on the potential therapeutic role of POL in NASH, gastritis and colitis and their associated cancers, with a focus on the pharmacological properties and potential mechanisms of action of the main natural active compounds in POL. METHODS: The information and data on Portulaca oleracea L. and its main active ingredients were collated from various resources like ethnobotanical textbooks and literature databases such as CNKI, VIP (Chinese literature), PubMed, Science Direct, Elsevier and Google Scholar (English literatures), Wiley, Springer, Tailor and Francis, Scopus, Inflibnet. RESULTS: Kaempferol, luteolin, myricetin, quercetin, genistein, EPA, DHA, and melatonin were found to improve NASH and NASH-HCC, while kaempferol, apigenin, luteolin, and quercetin played a therapeutic role in gastritis and gastric cancer. Apigenin, luteolin, myricetin, quercetin, genistein, lupeol, vitamin C and melatonin were found to have therapeutic effects in the treatment of colitis and its associated cancers. The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. CONCLUSION: The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. However, clinical data describing the mode of action of the naturally active compounds of POL are still lacking. In addition, pharmacokinetic data for POL compounds, such as changes in drug dose and absorption rates, cannot be extrapolated from animal models and need to be measured in patients in clinical trials. On the one hand, a systematic meta-analysis of the existing publications on TCM containing POL still needs to be carried out. On the other hand, studies on the hepatic and renal toxicity of POL are also needed. Additionally, well-designed preclinical and clinical studies to validate the therapeutic effects of TCM need to be performed, thus hopefully providing a basis for the validation of the clinical benefits of POL.

Application of two-dimensional polymerase chain reaction to detect four types of microorganisms in feces for assisted diagnosis of IBD.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) continues to increase annually, accounting for about 6.8 million cases in 2017 worldwide. However, there is currently no gold standard for the diagnosis of IBD. METHODS: A method for the detection of four microorganisms in feces by two-dimensional polymerase chain reaction (2D-PCR) has been developed. Plasmids were used to validate the sensitivity and specificity of the method. Clinical samples were tested using a 2D-PCR method. Optimal diagnostic thresholds for IBD were determined based on ROC results. RESULTS: Of the 112 samples, 78 were from IBD patients and 34 from patients with other gastrointestinal (GI) diseases. Thomasclavelia ramosum and univ907-1062 positivity are necessary, and two or more positives of the three bacteria (Thomasclavelia spiroforme, Thomasclavelia saccharogumia or Clostridium cluster XVIII) are the optimal diagnostic thresholds for IBD. The area under the curve was 0.826 with a 95% confidence interval of 0.735-0.981 and a p-value of 0.000, corresponding to a sensitivity of 0.769 and a specificity of 0.853. CONCLUSIONS: Based on the detection results of microorganisms, IBD and GI can be effectively distinguished. The detection of four microorganisms in feces can assist clinicians in the differential diagnosis of IBD. Our experiment aims to provide a better program for early clinical diagnosis and regular dynamic monitoring of IBD.

Can proline dehydrogenase-a key enzyme involved in proline metabolism-be a novel target for cancer therapy?

Emerging evidence suggests that proline metabolism is important for regulating the survival and death of different types of cancer cells. Proline dehydrogenase (PRODH), an enzyme catalyzing proline catabolism, and the degradation products of proline by PRODH, such as ATP and ROS, are known to play critical roles in cancer progression. Notably, the role of PRODH in cancer is still complicated and unclear, and primarily depends on the cancer type and tumor microenvironment. For instance, PRODH induces apoptosis and senescence through ROS signaling in different types of cancers, while as a protumor factor, PRODH promotes malignant phenotypes of certain tumors under stresses such as hypoxia. In order to assess whether PRODH can serve as a novel target for cancer therapy, we will provide an overview of the biological functions of PRODH and its double-edged role in cancer in this article.

Exploring the mechanism of Jianpi Huatan recipe in protecting hepatocellular carcinoma based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Huatan Recipe (JPHTR) is an effective prescription for delaying progression of hepatocellular carcinoma (HCC) provided by Longhua Hospital affiliated to Shanghai University of traditional Chinese Medicine, and it is consisted of nine traditional Chinese drugs, but the protective mechanism of JPHTR against HCC progression is unclear. AIM OF THE STUDY: To study the mechanism of JPHTR preventing the progression of HCC based on the network pharmacology. MATERIALS AND METHODS: The chemical component and potential gene targets of JPHTR and the important gene targets of HCC were obtained by retrieving traditional Chinese medicine network pharmacology analysis system (TCMNPAS) database. The data obtained from the database are used to construct the drugs-chemical component-targets network and protein-protein interaction network by using Cytoscape software and STRING database. The potential targets of JPHTR and HCC targets were imported into TCMNPAS-related modules in order to obtain the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Finally, we used HCC rat model to verify the vital signaling pathways predicted by network pharmacology. RESULTS: A total of 197 potential compounds and 721 potential targets of JPHTR and 611 important gene targets of HCC were obtained. Through the experiment in vivo, it was found that JPHTR can reduce the serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, reduce the lipid droplets and inflammatory injury of liver tissue, and reduce the mRNA expression of Interleukin-6 (Il-6), Janus tyrosine Kinase2 (Jak2) and Forkhead box O3 (Foxo3) in FOXO pathway in the liver, thus delaying the development of HCC. CONCLUSION: Through network pharmacology and rat experiments, it is preliminarily confirmed that JPHTR may delay the progression of HCC by regulating the expression of Il-6/Jak2/Foxo3 in FOXO signal pathway, which is expected to be a new therapeutic target for the protection of HCC.

Acacetin exerts antitumor effects on gastric cancer by targeting EGFR.

Background: Gastric cancer (GC) is a common malignant tumor with a poor prognosis. Combination treatments may prolong the survival of patients with GC. Acacetin, which is a flavonoid, exerts potent inhibitory effects on several types of cancer cells; however, the mechanisms of action remain poorly understood. Methods: Network pharmacology and RNA sequencing were used to predict the targets of acacetin, which were then verified by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and molecular docking. The biological functions of acacetin in MKN45 and MGC803 cells were investigated using TUNEL assays, crystal staining and colony formation assays. The pathways affected by acacetin were verified through reverse experiments. The in vivo antitumor efficacy of acacetin was assessed in a subcutaneous xenotransplanted tumor model. Results: In this study, we identified EGFR from more than a dozen predicted targets as a protein that directly binds to acacetin. Moreover, acacetin affected the level of phosphorylated EGFR. In vitro, acacetin promoted the apoptosis of GC cells. Importantly, EGFR agonists reversed the inhibitory effects of acacetin on the STAT3 and ERK pathways. In vivo, acacetin decreased the protein levels of pEGFR in tumors, resulting in increased GC xenograft tumor regression without obvious toxicity. Conclusion: Our findings highlight EGFR as one of the direct targets of acacetin in GC cells. Acacetin inhibited the phosphatase activity of EGFR in vitro and in vivo, which played a role in the antitumor effects of acacetin. These studies provide new evidence for the use of acacetin as a potential reagent for the treatment of GC.

Sijunzi decoction granules in the prevention and treatment of recurrence of colorectal adenoma: Study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

Background: The recurrence of colorectal adenomas (CRAs) after endoscopy predisposes patients to a risk of colorectal cancer. Guided by the traditional Chinese medicine (TCM), patients with colorectal diseases usually manifest with spleen deficiency syndrome (SDS) and are treated with Sijunzi decoction (SJZD). Therefore, this trial aims to explore the efficacy and safety of SJZD in the prevention and treatment of CRAs recurrence. Methods: SJZD on prevention and treatment of CRAs recurrence after resection: a multicenter, randomized, double-blind, placebo-controlled trial was designed. Patients who undergo polypectomy of CRAs will be recruited and randomized into a SJZD group and a placebo group in a 1:1 ratio. The intervention phase will be 12 months. The follow-up period will last 24 months. The primary outcome is the CRA recurrence rate after intervention. The secondary outcomes include the CRA recurrence rate at the second year post-polypectomy, the pathological type of adenoma and the alterations in SDS scores after intervention. Discussion: Previous clinical practice has observed the sound effect of SJZD in the context of gastrointestinal diseases. A number of experiments have also validated the active components in SJZD. This trial aims to provide tangible evidence for the usage of SJZD, hoping to reduce the recurrence of CRAs.

A strategy for the treatment of gastrointestinal cancer: Targeting tumor senescent cells.

Gastrointestinal (GI) cancer includes a variety of cancers with high incidence that seriously threaten the lives of people worldwide. Although treatment strategies continue to improve, patient benefits are still very limited, and the ongoing search for new treatment strategies remains a priority. Cell senescence is closely related to the occurrence and development of tumors. For GI cancer, cell senescence may not only promote cancer but also bring new opportunities for treatment. Combined with relevant studies, we review the dual role of cell senescence in GI cancer, including the mechanism of inducing cell senescence, biomarkers of senescent cells, and potential of targeted senescence therapy for GI cancer.

The circRNA expression profile of colorectal inflammatory cancer transformation revealed potential predictive biomarkers.

Colorectal cancer (CRC) is one of the most common malignant tumors in the world, and most colorectal cancer is transformed from colorectal adenoma (CRA). Identifying biomarkers for the early prediction of colorectal cancer would be an important finding. Circular RNA (circRNA) plays a key role in the occurrence and development of tumors, and its biological characteristics make it a potential biomarker for the early diagnosis of diseases. Therefore, we explored the relationship between circRNA and the malignant transformation from colorectal adenoma to colorectal cancer. We constructed inflammation-based tumorigenesis mouse models and performed high-throughput RNA sequencing to determine the expression profile of circRNAs in tissues at different stages of disease. Subsequent STEM analysis showed that with the development of the disease, 30 circRNAs were significantly downregulated, and 10 circRNAs were significantly upregulated. After qRT-PCR and Fish analysis verification, it was clear that mmu_circ_0008035 and mmu_circ_0000420 were significantly and continuously overexpressed in the development of colorectal cancer in our mouse model. Next, through homology analysis of circRNA in human and mouse and validation of clinical normal tissues, adenoma tissues and CRC tissues, we found biomarkers of has_circ0101338 ahashsa_circ0022426 that could predict the malignant transformation of human colorectal inflammation into CRC and have certain diagnostic value. In conclusion, our results may shed light on the mechanism of progression from precancerous adenoma to cancer and provide biomarkers that may be used in the early diagnosis of CRC.

New insights into natural products that target the gut microbiota: Effects on the prevention and treatment of colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant carcinomas. CRC is characterized by asymptomatic onset, and most patients are already in the middle and advanced stages of disease when they are diagnosed. Inflammatory bowel disease (IBD) and the inflammatory-cancer transformation of advanced colorectal adenoma are the main causes of CRC. There is an urgent need for effective prevention and intervention strategies for CRC. In recent years, rapid research progress has increased our understanding of gut microbiota. Meanwhile, with the deepening of research on the pathogenesis of colorectal cancer, gut microbiota has been confirmed to play a direct role in the occurrence and treatment of colorectal cancer. Strategies to regulate the gut microbiota have potential value for application in the prevention and treatment of CRC. Regulation of gut microbiota is one of the important ways for natural products to exert pharmacological effects, especially in the treatment of metabolic diseases and tumours. This review summarizes the role of gut microbiota in colorectal tumorigenesis and the mechanism by which natural products reduce tumorigenesis and improve therapeutic response. We point out that the regulation of gut microbiota by natural products may serve as a potential means of treatment and prevention of CRC.

The Pathogenesis of HCC Driven by NASH and the Preventive and Therapeutic Effects of Natural Products.

Nonalcoholic steatohepatitis (NASH) is a clinical syndrome with pathological changes that are similar to those of alcoholic hepatitis without a history of excessive alcohol consumption. It is a specific form of nonalcoholic fatty liver disease (NAFLD) that is characterized by hepatocyte inflammation based on hepatocellular steatosis. Further exacerbation of NASH can lead to cirrhosis, which may then progress to hepatocellular carcinoma (HCC). There is a lack of specific and effective treatments for NASH and NASH-driven HCC, and the mechanisms of the progression of NASH to HCC are unclear. Therefore, there is a need to understand the pathogenesis and progression of these diseases to identify new therapeutic approaches. Currently, an increasing number of studies are focusing on the utility of natural products in NASH, which is likely to be a promising prospect for NASH. This paper reviews the possible mechanisms of the pathogenesis and progression of NASH and NASH-derived HCC, as well as the potential therapeutic role of natural products in NASH and NASH-derived HCC.

The role and therapeutic implication of endoplasmic reticulum stress in inflammatory cancer transformation.

Endoplasmic reticulum (ER) stress occurs when proteins are affected by various factors, fail to fold properly into higher structures and accumulate in the lumen of the ER, which activates the unfolded protein response (UPR) to restore normal cellular function or induce apoptosis as a self-protective mechanism. However, a growing number of studies have shown that the three branches of ER stress and the UPR can mediate inflammation and cancer development by interacting with inflammatory transformation-related signaling pathways. Targeting the UPR, especially the use of small molecules that target the active sites of the enzymes IRE1α and PERK and BIP/GRP78 inhibitors are potential strategies for treating tumors and have shown promising results in some tumor models. Therefore, in this review, we summarize the progress of ER stress/UPR research and the signaling pathways associated with inflammatory cancer transformation, provide an in-depth description of the mechanisms of these pathways, and outline strategies in the field of UPR biology in tumor therapy to provide new ideas for the mechanisms of inflammatory cancer transformation and tumor-related treatment.

Research progress in the role and mechanism of LPCAT3 in metabolic related diseases and cancer.

Lysophosphatidylcholine acyltransferases (LPCATs) are among the lysophopholipid acyltransferases (LPLATs) that specifically regulate the abundance of different phosphatidylcholine (PC) species in a variety of cell and tissue types, thereby playing an important role in lipid metabolism and homeostasis. Lysophosphatidylcholine acyltransferase 3 (LPCAT3, MBOAT5) is a member of the LPCAT family that primarily regulates the levels of arachidonic PC species. LPCAT3 is regulated by the liver X receptor, which plays an important role in lipoprotein production in the liver and small intestine. Increasing lines of research have demonstrated that LPCAT3 plays important roles in the occurrence and development of many diseases, such as atherosclerosis, intestinal tumors, and nonalcoholic steatohepatitis (NASH). The development of many diseases has been linked to the proinflammatory effects of LPCAT3. This review focuses on the current knowledge of LPCAT3, including its function and mechanism in different diseases. We aim to provide a comprehensive and in-depth understanding of LPCAT3 and to provide new ideas for the treatment of some diseases.

Secondary Bile Acids and Tumorigenesis in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common and deadly cancers in the world and is a typical inflammatory tumor. In recent years, the incidence of CRC has been increasing year by year. There is evidence that the intake of high-fat diet and overweight are associated with the incidence of CRC, among which bile acids play a key role in the pathogenesis of the disease. Studies on the relationship between bile acid metabolism and the occurrence of CRC have gradually become a hot topic, improving the understanding of metabolic factors in the etiology of colorectal cancer. Meanwhile, intestinal flora also plays an important role in the occurrence and development of CRC In this review, the classification of bile acids and their role in promoting the occurrence of CRC are discussed, and we highlights how a high-fat diet affects bile acid metabolism and destroys the integrity of the intestinal barrier and the effects of gut bacteria.

Can Natural Products be Used to Overcome the Limitations of Colorectal Cancer Immunotherapy?

Colorectal cancer (CRC) is a common cancer of the digestive system that endangers human health. Immunotherapy is widely used in the treatment of patients with cancer. Some patients with dMMR/MSI-H CRC benefit from treatments that use immune checkpoint inhibitors, but most CRC patients are not sensitive to immunotherapy. Furthermore, internal resistance and immune escape lead to a reduced immunotherapy response. Therefore, the development of an effective combination therapy to improve the response rate to immunotherapy is a goal of cancer research. Natural products are potential candidates for comprehensive cancer treatments due to their wide range of immunomodulatory effects through multifactorial underlying mechanisms. In this review, we summarize the challenges in the treatment of CRC and assess the immunomodulatory effects of natural products and their active components. Our work suggests that natural products represent potential options for combined CRC immunotherapy.

RNA-Seq profiling of circular RNAs in human colorectal cancer 5-fluorouracil resistance and potential biomarkers.

BACKGROUND: Colorectal cancer (CRC) is a commonly diagnosed cancer of the digestive system worldwide. Although chemotherapeutic agents and targeted therapeutic drugs are currently available for CRC treatment, drug resistance is a problem that cannot be ignored and needs to be solved. AIM: To explore the relationship between circular RNA (circRNA) and CRC drug resistance. circRNA plays a key role in the occurrence and development of cancers, but its function in the process of drug resistance has not been widely revealed. METHODS: To explore the role of circRNA in 5-fluorouracil (5-Fu) resistance, we performed the circRNA expression profile in two CRC cell lines and their homologous 5-Fu resistant cells by high-throughput sequencing. RESULTS: We validated the differentially expressed circRNAs in other two paired CRC cells, confirmed that circ_0002813 and circ_0000236 could have a potential competitive endogenous RNA mechanism and be involved in the formation of 5-Fu resistance. And we combined the sequencing results of mRNA to construct the regulatory network of circRNA-miRNA-mRNA. CONCLUSION: Our study revealed that circ_0002813 and circ_0000236 may as the biomarkers to predict the occurrence of 5-Fu resistance in CRC.

Liquiritigenin alleviates doxorubicin-induced chronic heart failure via promoting ARHGAP18 and suppressing RhoA/ROCK1 pathway.

Chronic heart failure (CHF) is one of the most common chronic diseases with increasing incidence and mortality. Liquiritigenin (LQG) is shown to protect mice from cardiotoxicity. However, its underlying mechanism remains unclear. Our study aimed to reveal the role of ARHGAP18 in LQG-mediated cardioprotective effects in CHF. In the current study, CHF cell model and rat model were established by the application of doxorubicin (DOX). The reactive oxygen species (ROS) level and cell apoptosis were determined by flow cytometry. The cardiac function of rats was evaluated by measuring left ventricular systolic pressure, left ventricular end diastolic pressure, and serum level of lactate dehydrogenase and brain natriuretic peptide. The expression of active RhoA was elevated and that of ARHGAP18 was decreased in DOX-induced CHF cell model. ARHGAP18 could reduce DOX-induced RhoA activation, ROS elevation, and cell apoptosis. Meanwhile, the knockdown of ARHGAP18 could promote the activation of RhoA, the level of ROS, and the rate of cell apoptosis, which could be reversed by the application of RhoA inhibitor. LQG promoted the expression of ARHGAP18 and exerted similar effects of ARHGAP18 in CHF cell model. The application of LQG could also reverse the effects mediated by ARHGAP18 knockdown. Moreover, LQG significantly improved cardiac function and ameliorated DOX-induced cardiotoxicity of CHF rats. In conclusion, LQG could alleviate DOX-induced CHF via promoting ARHGAP18 and suppressing RhoA/ROCK1 pathway. LQG was a potential agent for CHF treatment.