Heng Zhang

Introduction: Kushenol E is a prenylated flavonoid derived from Sophora flavescens. Although preliminary studies have suggested that Kushenol E possesses anticancer activity, its effects and molecular mechanisms in Colorectal Cancer (CRC) remain largely unexplored. Therefore, this study investigated the therapeutical effects of Kushenol E and its underlying molecular mechanisms against CRC. Methods: HT-29 cells, colorectal organoids, and an AOM/DSS-induced colorectal tumor model in mice were used. Cellular biomarkers related to growth, damage, programmed cell death, mitochondrial membrane integrity, and activation of the p38, ERK, and AKT signal cascades were measured. In vivo, survival rate, body weight, disease activity index, colon length, tumor volume, H&E staining, TUNEL assays, immunohistochemistry, and ELISA were assessed. Results: Kushenol E inhibited HT-29 cell proliferation, induced apoptosis, increased the expression of mitochondrial apoptosis-related proteins Bax and Caspase-3, and reduced Bcl-2 expression. Kushenol E also reduced phospho-ERK and phospho-AKT levels while increasing phospho-p38. In CRC organoids, Kushenol E significantly reduced organoid diameter on day 3 (p < 0.01) and decreased organoid viability (p < 0.01). In AOM/DSS-treated mice, Kushenol E showed increased TUNEL positivity and Bax and caspase-3 expression, together with reduced Ki67 and PCNA expression. Moreover, ELISA analysis showed that Kushenol E reduced serum levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and lowered the tumorassociated biomarker CEA. Discussion: Kushenol E inhibited CRC cell and organoid growth and attenuated AOM/DSSinduced colorectal tumorigenesis. These effects are associated with mitochondrial apoptosis and alterations in p38/ERK/AKT signaling, and are accompanied by reduced inflammatory cytokine and CEA levels in vivo. Conclusion: Kushenol E has shown excellent antitumor activity against CRC and warrants further mechanistic, pharmacological, and safety evaluation.

This case sought to manage a duodenal fistula patient who underwent an open abdomen with vacuum-assisted temporary abdominal closure (VAC) by evaluating his tolerance to early enteral nutrition therapy (ENT). A review of the patient suggested that he developed an abdominal infection as a result of a high duodenal fistula, which necessitated an open abdomen and VAC. Prior to the initiation of ENT, the patient had a patient-generated subjective global assessment (PG-SGA) score of 8 (1st day) suggesting the need for nutritional intervention. Upon ENT intervention, the patient's PG-SGA score dropped to 2 (30th day) indicating an improvement in the nutritional status, probably due to measures such as formulation, implementation, and management of early ENT. The improved nutritional status of the patient led to the success of duodenal fistula repair and abdominal wall defect reconstruction within a short time, thus ensuring a successful surgery.

Objective. To investigate the relationship between polymorphism of FOXA1 gene rs12894364 and rs7144658 and susceptibility to gastric cancer. Methods. A case-control study was conducted to select 577 cases of primary gastric cancer and 678 cases of normal control. We extracted whole blood genomic DNA and amplified the target gene fragment by PCR. The genotyping and allele was tested through a snapshot method. Results. There was no significant difference in the frequency distribution of genotype between the case group and control group ( ). Stratified analyses showed the SNPs were not correlated with the susceptibility of GC according to different age, gender, cigarette smoking, and alcohol drinking status. Conclusion. There is no significant correlation between the polymorphisms of FOXA1 gene rs12894364 and rs7144658 and the risk of gastric cancer.

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.

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.