Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short‐chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies ...mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs‐mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy.
Short‐chain fatty acids (SCFAs) produced in the human colon are the major products of bacterial fermentation of undigested dietary fiber and starch that escape absorption in the small intestine, and serve as a major source of energy for colonocytes. SCFAs are microbial‐derived metabolites, which are readily absorbed and used as an energy source by colonocytes. Several mechanisms have been proposed to underlie the anticancerous mechanisms of SCFAs. SCFAs reduce epithelial inflammation and trigger cancer cell apoptosis via p21 activity, providing an important defensive capacity against colorectal carcinogenesis.
In the study, papain was chosen from five proteases to hydrolyze proteins of monkfish swim bladders for effectively utilizing monkfish (
) processing byproducts, and the hydrolysis conditions of ...papain were optimized as hydrolysis temperature of 65 °C, pH 7.5, enzyme dose 2.5% and time 5 h using single-factor and orthogonal experiments. Eighteen peptides were purified from the swim bladder hydrolysate of monkfish by ultrafiltration and gel permeation chromatography methods and identified as YDYD, QDYD, AGPAS, GPGPHGPSGP, GPK, HRE, GRW, ARW, GPTE, DDGGK, IGPAS, AKPAT, YPAGP, DPT, FPGPT, GPGPT, GPT and DPAGP, respectively. Among eighteen peptides, GRW and ARW showed significant DPPH· scavenging activities with EC
values of 1.053 ± 0.003 and 0.773 ± 0.003 mg/mL, respectively; YDYD, QDYD, GRW, ARW and YPAGP revealed significantly HO· scavenging activities with EC
values of 0.150 ± 0.060, 0.177 ± 0.035, 0.201 ± 0.013, 0.183 ± 0.0016 and 0.190 ± 0.010 mg/mL, respectively; YDYD, QDYD, ARW, DDGGK and YPAGP have significantly O2-· scavenging capability with EC
values of 0.126 ± 0.0005, 0.112 ± 0.0028, 0.127 ± 0.0002, 0.128 ± 0.0018 and 0.107 ± 0.0002 mg/mL, respectively; and YDYD, QDYD and YPAGP showed strong ABTS
· scavenging ability with EC
values of 3.197 ± 0.036, 2.337 ± 0.016 and 3.839 ± 0.102 mg/mL, respectively. YDYD, ARW and DDGGK displayed the remarkable ability of lipid peroxidation inhibition and Ferric-reducing antioxidant properties. Moreover, YDYD and ARW can protect Plasmid DNA and HepG2 cells against H
O
-induced oxidative stress. Furthermore, eighteen isolated peptides had high stability under temperatures ranging from 25-100 °C; YDYD, QDYD, GRW and ARW were more sensitive to alkali treatment, but DDGGK and YPAGP were more sensitive to acid treatment; and YDYD showed strong stability treated with simulated GI digestion. Therefore, the prepared antioxidant peptides, especially YDYD, QDYD, GRW, ARW, DDGGK and YPAGP from monkfish swim bladders could serve as functional components applied in health-promoting products because of their high-antioxidant functions.
Colorectal cancer (CRC) is a heterogeneous group of diseases that are the result of abnormal glucose metabolism alterations with high lactate production by pyruvate to lactate conversion, which ...remodels acidosis and offers an evolutional advantage for tumor cells, even enhancing their aggressive phenotype. This review summarizes recent findings that involve multiple genes, molecules, and downstream signaling in the dysregulated glycolytic pathway, which can allow a tumor to initiate acid byproducts and to progress, thereby resulting in acidosis commonly found in the tumor microenvironment of CRC. Moreover, the relationship between CRC cells and the tumor acidic microenvironment, especially for regulating lactate production and lactate dehydrogenase A levels, is also discussed, as well as comprehensively defining different aspects of glycolytic pathways that affect cancer cell proliferation, invasion, and migration. Furthermore, this review concentrates on glucose metabolism–mediated transduction factors in CRC, which include acid‐sensing ion channels, triosephosphate isomerase and key glycolysis‐related enzymes that regulate glycolytic metabolites, coupled with the effect on tumor cell glycolysis as well as signaling pathways. In conclusion, glucose metabolism mediated by glycolytic pathways that are integral to tumor acidosis in CRC is demonstrated. Therefore, selective metabolic inhibitors or agents against these targets in glucose metabolism through glycolytic pathways may be clinically useful to regulate the tumor’s acidic microenvironment for CRC treatment and to identify specific targets that regulate tumor acidosis through a cancer patient–personalized approach. Furthermore, strategies for modifying the metabolic processes that effectively inhibit cancer cell growth and tumor progression and activate potent anticancer effects may provide more effective antitumor prospects for CRC therapy.
Glucose metabolism mediated by glycolytic pathways that are integral to tumor acidosis in colorectal cancer is demonstrated. Therefore, selective metabolic inhibitors or agents against these targets in glucose metabolism through glycolytic pathways may be clinically useful to regulate the tumor’s acidic microenvironment for colorectal cancer treatment and to identify specific targets that regulate tumor acidosis through a cancer patient–personalized approach.
Soil ecology plays an important role in the growth and health of plants. Research suggests that long-term monocropping may lead to soil ecological disorders. In this study, we aimed to understand the ...reasons for the decrease in plant productivity stemming from long-term monoculture cropping. Greenhouse studies were conducted to determine the cause of continuous cropping (CC) obstacles in soils under 12 years of continuous strawberry (Fragaria × ananassa Duch.) production. The data suggested that CC led to three phases of changes in abiotic and biotic soil factors. In phase I (CC for 2–6 years), significant changes were observed only in soil physicochemical properties, such as the pH, total nitrogen (TN), ammonium nitrogen (NH4+-N), available phosphorus (AP), available potassium (AK) and soil organic matter (SOM), which obviously changed from the second year to the sixth year. In phase II (CC for 6–8 years), two biotic factors, key fungi such as Fusarium, Humicola and Arthrobotrys and soil nematodes, i.e., populations and communities of nematodes, started to change significantly in terms of their abundance. In phase III (CC for >8 years), the accumulation of phenolic acids, i.e., p-hydroxybenzoic acid (p-HBA), ferulic acid (FA), p-coumaric acid (p-CA) and cinnamic acid (CA), significantly inhibited crop growth, and the abundance of key bacteria, including Bacillus, Sphingomonas and Sphingopyxis, started to change significantly from the eighth CC year. The results in this study provide useful information for solving CC obstacles in strawberry production.
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•Continuous cropping led to changes in abiotic and biotic factors in the soil.•This is the first attempt to comprehensively interpret continuous cropping obstacles.•The continuous cropping soil changes could be divided into three main phases: Phase I, Phase II, and Phase III.•This research provides useful information to solve strawberry continuous cropping problems.
Transcription factors (TFs) like a nuclear factor of activated T‐cells (NFAT) and its controller calcineurin are highly expressed in primary intestinal epithelial cells (IECs) due to delamination, ...damage by tumor‐associated flora and selective activation in the intestinal tract tumor are crucial in the progression and growth of colorectal cancer (CRC). This study sought to summarize the current findings concerning the dysregulated calcineurin/NFAT (C/N) signaling involved in CRC initiation and progression. These signalings include proliferation, T‐cell functions, and glycolysis with high lactate production that remodels the acidosis, which genes in tumor cells provide an evolutionary advantage, or even increased their attack phenotype. Moreover, the relationship between C/N and gut microbiome in CRC, especially role of NFAT and toll‐like receptor signaling in regulating intestinal microbiota are also discussed. Furthermore, this review will discuss the proteins and genes relating to C/N induced acidosis in CRC, which includes ASIC2 regulated C/N1 and TFs associated with the glycolytic by‐product that affect T‐cell functions and CRC cell growth. It is revealed that calcineurin or NFAT targeting to antitumor, selective calcineurin inhibition or targets in NFAT signaling may be useful for clinical treatment of CRC. This can further aid in the identification of specific targets via cancer patient‐personalized approach. Future studies should be focused on targeting to C/N or TLR signaling by the combination of therapeutic agents to regulate T‐cell functions and gut microbiome for activating potent anticancer property with the prospect of potentiating the antitumor therapy for CRC.
The link between T‐cells perform glycolysis and ASICs–mediated acidosis signaling in colorectal cancer. Roles of calcineurin/nuclear factor of activated T‐cells and toll‐like receptor signaling altered tumor‐associated microbiota in the development of an intestinal tumor.
In this paper, we investigate the initial value problem for the sixth order Boussinesq type equation in the framework of modulation spaces. Under suitable conditions, we first prove that the problem ...has a unique local solutions and global solutions. Then scattering and stability of solutions are also discussed. The proof is mainly based on the decay properties of the solutions operator in modulation spaces and the contraction mapping principle.
In this paper, we consider the initial value problem for the compressible Navier‐Stokes‐Korteweg system in several space variables. Optimal decay estimate of mild solutions in the critical Besov ...spaces is established. The proof is based on the decay estimate of solutions operator in the low‐frequency region and the energy estimate in the high‐frequency region.
In this study, isoliquiritigenin (ISL) incorporated nanoliposomes were prepared and their effects on colorectal cancer (CRC) cell lines were investigated. Herein, we sought to explore the anti-cancer ...mechanisms of ISL loaded nanoliposomes (ISL-NLs) on AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathways mediated glycolysis. Also, the key targets such as caveolin 1 (CAV1), glucose transporters and Akt/mTOR that promote glycolysis, and are activated via the induction of α-enolase (ENO1), fructose bisphosphate aldolase A (ALDOA) and monocarboxylate transporter 4 (MCT4) expressions were also investigated. It was shown that ISL-NLs significantly suppressed the proliferation and glucose uptake of CRC cell by potentially regulating the glycolysis and lactate targets as well as pathways that formed the basis of the anti-CRC effects of ISL-NLs. The mechanism underlying this effect was further validated via the regulation of some key targets such as ENO1, ALDOA, lactate dehydrogenase A (LDHA) and MCT4 in glycolysis coupled with cellular myelocytomatosis oncogene (c-myc), hypoxia-inducible factor 1-alpha (HIF-1α) in protein kinase B/mTOR (Akt/mTOR) pathways. Moreover, the AMPK proteins were identified to be up-regulated while the lactic acid production was suppressed by ISL-NLs in the CRC cells, indicating that ISL-NLs had an inhibitory effect on AMPK mediated glycolysis and lactate production. Altogether, these results have provided insights into the mechanism underlying the key role that liposomal ISL played in the multiple inhibition of AMPK and Akt/mTOR mediated glycolysis and lactate generation, which may be regulated as the alternative metabolic pathways of CRC as well as serve as adjuvant therapy for the disease.
Alterations in cellular energy metabolism play a critical role in colorectal cancer (CRC), which has been identified as the definition of consensus molecular subtypes (CMSs), and CMS3 tumors exhibit ...energy metabolism signatures along with Kirsten rat sarcoma viral oncogene homolog (KRAS)‐activating mutations. This review summarizes the relationship between CMS3 tumors associated with mutated KRAS and energy metabolism in CRC, especially for the dysregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review concentrates on the role of metabolic genes and factors and signaling pathways, which coupled with a primary energy source connected with the CMS3 associated with mutated KRAS, induce metabolic alterations. The strategies to target energy metabolism for the metabolic alterations in mutated KRAS CRC are also introduced. In conclusion, dysregulated energy metabolism has a close relationship with mutated KRAS in CMS3 tumors. Therefore, selective inhibitors or agents against metabolic targets or KRAS signaling may be clinically useful for CMS3 tumor treatment through a personalized approach for patients with cancer.
The interactions and mutational profile of metabolic oncoregulators with energy metabolism in mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) colorectal cancer.
Selective inhibitors or agents against metabolic targets or KRAS signaling may be clinically useful for consensus molecular subtype 3 tumor treatment through a cancer‐patient‐personalized approach.
In strawberry cultivation, continuous cropping (CC) obstacles seriously threaten production. A patented soil amendment (SA) can effectively relieve the CC obstacles to strawberry cultivation, but ...knowledge of the recovery mechanisms underlying this phenomenon is limited.
In this study, transcriptomic profiling of strawberry roots in soil with and without the SA was conducted using RNA-Seq technology to reveal gene expression changes in response to SA treatment. In total, 188 differentially expressed genes (DEGs), including 144 upregulated and 44 downregulated DEGs, were identified. SA treatment resulted in genotype-dependent responses, and the response pattern, including an overall increase in the expression of nutrient transport genes and a decrease in the expression of defense response genes, may be a possible mechanism underlying recovery strategies in strawberry roots after the application of the SA to CC soil. We also found that 9 Hsp genes involved in plant defense pathways were all downregulated in the SA-treated roots.
This research indicated that strawberry plants reallocated defense resources to development when SA treatment alleviated the stress caused by a CC soil environment. The present study provides an opportunity to reveal the fundamental mechanisms of the tradeoff between growth and defense in strawberry.