Metabolic reprogramming involves in transition of activated/resting CD4+ memory T cells and prognosis of gastric cancer.

Background: Little is known on how metabolic reprogramming potentially prompts transition of activated and resting CD4+ memory T cells infiltration in tumor microenvironment of gastric cancer (GC). The study aimed to evaluate their interactions and develop a risk model for predicting prognosis in GC. Methods: Expression profiles were obtained from TCGA and GEO databases. An immunotherapeutic IMvigor210 cohort was also enrolled. CIBERSORT algorithm was used to evaluate the infiltration of immune cells. The ssGSEA method was performed to assess levels of 114 metabolism pathways. Prognosis and correlation analysis were conducted to identify metabolism pathways and genes correlated with activated CD4+ memory T cells ratio (AR) and prognosis. An AR-related metabolism gene (ARMG) risk model was constructed and validated in different cohorts. Flow cytometry was applied to validate the effect of all-trans retinoic acid (ATRA) on CD4+ memory T cells. Results: Since significantly inverse prognostic value and negative correlation of resting and activated CD4+ memory T cells, high AR level was associated with favorable overall survival (OS) in GC. Meanwhile, 15 metabolism pathways including retinoic acid metabolism pathway were significantly correlated with AR and prognosis. The ARMG risk model could classify GC patients with different outcomes, treatment responses, genomic and immune landscape. The prognostic value of the model was also confirmed in the additional validation, immunotherapy and pan-cancer cohorts. Functional analyses revealed that the ARMG model was positively correlated with pro-tumorigenic pathways. In vitro experiments showed that ATRA could inhibit levels of activated CD4+ memory T cells and AR. Conclusion: Our study showed that metabolic reprogramming including retinoic acid metabolism could contribute to transition of activated and resting CD4+ memory T cells, and affect prognosis of GC patients. The ARMG risk model could serve as a new tool for GC patients by accurately predicting prognosis and response to treatment.

Urbanization, Human Inequality, and Material Consumption.

Global material consumption needs to be reduced to be within its planetary boundary. Urbanization and human inequality are two profound economic-social phenomena, which have potential impacts on material consumption. This paper aims to empirically explore how urbanization and human inequality affect material consumption. For this aim, four hypotheses are proposed and the coefficient of human inequality and material footprint per capita are employed to measure comprehensive human inequality and consumption-based material consumption, respectively. Based on an unbalanced panel data set of around 170 countries from 2010 to 2017, the regression estimations demonstrate that: (1) urbanization reduces material consumption; (2) human inequality increases material consumption; (3) the interaction effect between urbanization and human inequality reduces material consumption; (4) urbanization reduces human inequality, which explains why the interaction effect works; (5) urbanization makes more sense for reducing material consumption if the extents of human inequality are larger and the positive impacts of human inequality on material consumption are weakened if the extents of urbanization are larger. It is concluded that promoting urbanization and reducing human inequality are compatible with both ecological sustainability and social fairness. This paper contributes to understanding and achieving the absolute decoupling between economic-social development and material consumption.

The fecal arsenic excretion, tissue arsenic accumulation, and metabolomics analysis in sub-chronic arsenic-exposed mice after in situ arsenic-induced fecal microbiota transplantation.

Arsenic can be specifically enriched by rice, and the health hazards caused by high arsenic rice are gradually attracting attention. This study aimed to explore the potential of microbial detoxification via gut microbiome in the treatment of sub-chronic arsenic poisoning. We first exposed mice to high-dose arsenic feed (30 mg/kg, rice arsenic composition) for 60 days to promote arsenic-induced microbes in situ in the gastrointestinal tract, then transplanted their fecal microbiota (FMT) into another batch of healthy recipient mice, and dynamically monitored the microbial colonization by 16S rRNA sequencing and ITS sequencing. The results showed that in situ arsenic-induced fecal microbiome can stably colonized and interact with indigenous microbes in the recipient mice in two weeks, and established a more stable network of gut microbiome. Then, the recipient mice continued to receive high-dose arsenic exposure for 52 days. After above sub-chronic arsenic exposure, compared with the non-FMT group, fecal arsenic excretion, liver and plasma arsenic accumulation were significantly lower (P < 0.05), and that in kidney, hair, and thighbone present no significant differences. Metabolomics of feces- plasma-brain axis were also disturbed, some up-regulated metabolites in feces, plasma, and cerebral cortex may play positive roles for the host. Therefore, microbial detoxification has potential in the treatment of sub-chronic arsenic poisoning. However, gut flora is an extremely complex community with different microorganisms have different arsenic metabolizing abilities, and various microbial metabolites. Coupled with the matrix effects, these factors will have various effects on the efflux and accumulation of arsenic. The definite effects (detoxification or non-detoxification) could be not assured based on the current study, and more systematic and rigorous studies are needed in the future.

Functionalized chitosan as a novel support for stabilizing palladium in Suzuki reactions.

Chitosan is a versatile polysaccharide in different domains due to facile modification and good biodegradability. In this paper, taking advantage of such functional properties, we have developed a stabilizer agent [OCMCS-SB] produced from chitosan, and palladium was successfully immobilized on this designed stabilizer [OCMCS-SB-Pd(II)]. The obtained complex was illuminated by 13C CP-MAS NMR, FT-IR, TGA, XRD, XPS, SEM, TEM and ICP-OES analyses. Due to the interactions of primary hydroxyl groups on chitosan, Schiff base and carboxy groups, the Pd complex showed excellent reactivity (up to 99 %) and stability towards Suzuki reactions in eco-friendly medium. Subsequently, the reusability experiments for OCMCS-SB-Pd(II) formed from chitosan were examined in five consecutive cycles, which showed no appreciable decrease in activity. Furthermore, a reasonably trifunctional complex structure was proposed. The present bio-based system offers a promising approach in utilizing such biopolymers in organic transformations.

Salen-based hypercrosslinked polymer-supported Pd as an efficient and recyclable catalyst for C-H halogenation.

In this work, we report the first use of a salen-based hypercrosslinked polymer-supported Pd catalyst to carry out C-H halogenation. This catalyst can effectively catalyze C-H bromination and chlorination even better than its homogeneous counterpart Pd(OAc)2. It also showed excellent reusability without loss of catalytic activity for ten cycles. A broad substrate scope was explored and moderate to excellent yields were obtained.

Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS.

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. TGF-ß1/Smad3 signalling plays a major pathological role in DN; however, the contribution of Smad4 has not been examined. Smad4 depletion in the kidney using anti-Smad4 locked nucleic acid halted progressive podocyte damage and glomerulosclerosis in mouse type 2 DN, suggesting a pathogenic role of Smad4 in podocytes. Smad4 is upregulated in human and mouse podocytes during DN. Conditional Smad4 deletion in podocytes protects mice from type 2 DN, independent of obesity. Mechanistically, hyperglycaemia induces Smad4 localization to mitochondria in podocytes, resulting in reduced glycolysis and oxidative phosphorylation and increased production of reactive oxygen species. This operates, in part, via direct binding of Smad4 to the glycolytic enzyme PKM2 and reducing the active tetrameric form of PKM2. In addition, Smad4 interacts with ATPIF1, causing a reduction in ATPIF1 degradation. In conclusion, we have discovered a mitochondrial mechanism by which Smad4 causes diabetic podocyte injury.

Protective effect of curcumin against irinotecan­induced intestinal mucosal injury via attenuation of NF­κB activation, oxidative stress and endoplasmic reticulum stress.

Irinotecan (CPT­11) is a DNA topoisomerase I inhibitor which is widely used in clinical chemotherapy, particularly for colorectal cancer treatment. However, late­onset diarrhea is one of the severe side­effects of this drug and this restricts its clinical application. The present study aimed to investigate the protective effects of curcumin treatment on CPT­11­induced intestinal mucosal injury both in vitro and in vivo and to elucidate the related mechanisms involved in these effects. For this purpose, mice were intraperitoneally injected with CPT­11 (75 mg/kg) for 4 days to establish a model of late­onset diarrhea. Curcumin (100 mg/kg) was intragastrically administered 8 days before the injection of CPT­11. Injury to small intestinal tissues was examined by H&E staining. The protein expression of prolyl 4­hydroxylase subunit beta (P4HB) and peroxiredoxin 4 (PRDX4) was detected by immunohistochemistry, as well as western blot analysis. IEC­6 cell viability was detected by MTT assay. Flow cytometry was performed to examine the cell apoptotic rate, mitochondrial membrane potential and reactive oxygen species (ROS) generation. Immunofluorescence was used to observe the localization of nuclear factor (NF)­κB. The levels of cleaved caspase­3, glucose­regulated protein, 78 kDa (GRP78), P4HB, PRDX4 and CHOP were detected by western blot analysis. The results revealed that in vivo, curcumin effectively attenuated the symptoms of diarrhea and abnormal intestinal mucosa structure induced by CPT­11 in nude mice. Treatment with curcumin also increased the expression of P4HB and PRDX4 in the tissue of the small intestine. In vitro, curcumin, exhibited little cytotoxicity when used at concentrations <2.5 µg/ml for 24 h in IEC­6 cells. At this concentration, curcumin also improved cell morphology, inhibited apoptosis, maintained mitochondrial membrane potential and reduced the elevated levels of ROS induced by CPT­11 (20 µg/ml). Furthermore, curcumin abolished NF­κB signal transduction and protected the cells from CPT­11­induced apoptosis by upregulating the expression of molecular chaperones, such as GRP78, P4HB and PRDX4, and suppressing the levels of the apoptosis­related proteins, CHOP and cleaved caspase­3. On the whole, our data indicate that curcumin exerted protective effects against CPT­11­induced intestinal mucosa injury. The protective effects of curcumin are mediated by inhibiting the activation of NF­κB, and suppressing oxidative stress and endoplasmic reticulum stress.

FIBP knockdown attenuates growth and enhances chemotherapy in colorectal cancer via regulating GSK3ß-related pathways.

Colorectal cancer stem cells (CSCs), characterized by self-renewal ability and high expression of proliferative genes, contribute to the chemoresistance of colorectal cancer (CRC). We aimed to identify the molecular mechanisms underlying CRC chemoresistance through comprehensive bioinformatics screenings and experimental confirmation of gene functions. We found that high expression of FGF1 intracellular binding protein (FIBP) was correlated with chemoresistance and poor prognosis in CRC patients. Therefore, the chemoresistant CRC cell line HCT116-CSC with high expression of the stem cell markers CD44 and CD133 was established for further phenotypic tests. FIBP knockdown inhibited proliferation, enhanced chemotherapy effects, and attenuated the stemness markers of CRC cells in vivo and in vitro. Through RNA-seq and gene set enrichment analysis, we identified cyclin D1 as a key downstream target in FIBP-regulated cell cycle progression and proliferation. Moreover, FIBP bound to GSK3ß, inhibited its phosphorylation at Tyr216, and activated ß-catenin/TCF/cyclin D1 signaling in HCT116-CSCs. Additional GSK3ß knockdown reversed the FIBP silencing-induced inhibition of proliferation and decreased stemness marker expression in HCT116-CSCs. Furthermore, DNA methylation profiling suggested that FIBP regulated the stemness of CRC cells via methylation activity that was dependent on GSK3ß but independent of ß-catenin signaling. Our data illuminate the potential of FIBP as a novel therapeutic target for treating chemoresistant CRC through inhibition of GSK3ß-related signaling.

Remote C-H Activation of Various N-Heterocycles Using a Single Template.

A single and simple ortho-sulfonyl benzonitrile template was developed to achieve remote C-H olefination of six different classes of N-heterocycles. We demonstrate that, by varying precatalysts and conditions, the same template can be applied to the remote C-H activation of six structurally distinct heterocyclic scaffolds, and the site-selectivity can be predicted based on distance and geometry. Furthermore, this new development shows that template-directed remote C-H activation is possible through macrocyclopalladation processes with smaller ring sizes.

Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer.

Inherent and acquired chemoresistance reduce the effectiveness of irinotecan in the treatment of metastatic colorectal cancer (CRC). However, the molecular mechanisms underlying this resistance process are still unclear. Twist1 is one of the master transcription factors of epithelial-mesenchymal transition (EMT). Our previous study indicated that Twist1 is overexpressed in colon cancer tissues, and demonstrated that Twist1 plays a crucial role in the chemoresistance of CRC. In the present study, we further investigated how Twist1 contribute to acquired resistance to irinotecan in colon cancer. The irinotecan-resistant cells were established by gradual adaptation of increasing irinotecan concentrations in LoVo cells, named LoVo/CPT-11R cells. Results showed that cell viabilities to different anticancer drugs were markedly increased in LoVo/CPT-11R cells compared to LoVo cells. Moreover, LoVo/CPT-11R cells displayed EMT, CSC-like cellular morphology and relative biomarkers were also significantly increased. In addition, overexpressed Twist1 LoVo cells were established by lentivirus transfection assay, named LoVo/Twist1 cells. Results showed that the LoVo/Twist1 cells perform a distinctly decreased sensitivity to irinotecan, downregulated expression of E-cadherin, upregulated expression of cluster of differentiation 44 (CD44), and a significant enhancement of invasion and migration potential by regulation of MMP2 compared with control cells. In contrast, the inhibition of Twist1 transfected with siRNA could enhance the irinotecan sensitivity in LoVo/CPT-11R cells and downregulate the expression of vimentin and CD44. Our data provide evidence that EMT and CSC-like phenotype induced by Twist1 contribute to acquire resistance to irinotecan and enhanced migration and invasion in colon cancer.

Low Expression of Circulating MicroRNA-34c is Associated with Poor Prognosis in Triple-Negative Breast Cancer.

PURPOSE: The microRNA-34 (miR-34) family is important in tumor regulation. This study aimed to investigate the association of circulating miR-34 family proteins with clinicopathological features and their prognostic value in triple-negative breast cancer (TNBC) patients. MATERIALS AND METHODS: In this cohort study, 173 TNBC patients admitted to First People's Hospital of Shunde from May 1, 2009 to April 30, 2013 were enrolled. Meanwhile, 75 age-matched healthy women volunteers were identified as healthy controls (HCs). We examined the expression of miR-34 family (miR-34a/b/c) proteins in plasma collected from TNBC patients before any treatment was performed and from age-matched HCs using qPCR methods. RESULTS: The expressions of miR-34a/34b/34c were significantly lower in TNBC patients than in HC (p<0.001, p=0.027, p<0.001, respectively). miR-34a was correlated with tumor grade (p=0.038), lymph node positive (p=0.027), distant metastasis (p=0.004), and surgery (p=0.023); miR-34b was correlated with lymph node positivity (p=0.027); and miR-34c was correlated with tumor grade (p=0.017) and distant metastasis (p<0.001). Kaplan-Meier curve analysis displayed low expression of miR-34a as associated with worse overall survival (OS) (p=0.011), as well as miR-34c low expression (p=0.002). In addition, univariate and multivariate Cox proportional hazards regression was performed, and low expression of miR-34c (p=0.011) was found to be an independent risk factor for OS, as well as tumor grade (p=0.013), lymph node positive (p=0.050), and distant metastasis (p=0.021). CONCLUSION: In conclusion, this study demonstrated reduced miR-34a/c expression is highly associated with tumor progression and indicated worse prognosis. Also, miR-34c was an independent risk factor for OS in TNBC patients.

Curcumin enhances the effects of irinotecan on colorectal cancer cells through the generation of reactive oxygen species and activation of the endoplasmic reticulum stress pathway.

Although initially effective against metastatic colorectal cancer (CRC), irinotecan-based chemotherapy leads to resistance and adverse toxicity. Curcumin is well known for its anti-cancer effects in many cancers, including CRC. Here, we describe reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress as important mechanisms by which curcumin enhances irinotecan's effects on CRC cells. CRC cell lines were treated with curcumin and/or irinotecan for 24 h, and then evaluated using cell proliferation assays, cell apoptosis assays, cell cycle analysis, intracellular Ca2+ measurements, ROS measurements and immunoblotting for key ER stress-related proteins. We found that cell viability was inhibited and apoptosis was increased, accompanied by ROS generation and ER stress activation in CRC cells treated with curcumin alone or in combination with irinotecan. Blocking ROS production attenuated the expression of two markers of ER stress: binding of immunoglobulin protein (BIP) and CCAAT/enhancer-binding protein homologous protein (CHOP). Blocking CHOP expression using RNA interference also inhibited ROS generation. These results demonstrated that curcumin could enhance the effects of irinotecan on CRC cells by inhibiting cell viability and inducing cell cycle arrest and apoptosis, and that these effects may be mediated, in part, by ROS generation and activation of the ER stress pathway.

Effects of Astragalus Polysaccharides on Dysfunction of Mitochondrial Dynamics Induced by Oxidative Stress.

This paper studied the chronic fatigue induced by excessive exercise and the restoration effects of Astragalus polysaccharides (APS) on mitochondria. In vivo, we found that excessive exercise could cause oxidative stress statue which led to morphological and functional changes of mitochondria. The changes, including imbalance between mitochondria fusion-fission processes, activation of mitophagy, and decrease of PGC-1α expression, could be restored by APS. We further confirmed in vitro, and what is more, we found that APS may ameliorate mitochondrial dysfunction through Sirt1 pathway. Based on the results, we may figure out part of the molecular mechanism of mitochondrial amelioration by APS.

Three surgical planes identified in laparoscopic complete mesocolic excision for right-sided colon cancer.

BACKGROUND: Complete mesocolic excision provides a correct anatomical plane for colon cancer surgery. However, manifestation of the surgical plane during laparoscopic complete mesocolic excision versus in computed tomography images remains to be examined. METHODS: Patients who underwent laparoscopic complete mesocolic excision for right-sided colon cancer underwent an abdominal computed tomography scan. The spatial relationship of the intraoperative surgical planes were examined, and then computed tomography reconstruction methods were applied. The resulting images were analyzed. RESULTS: In 44 right-sided colon cancer patients, the surgical plane for laparoscopic complete mesocolic excision was found to be composed of three surgical planes that were identified by computed tomography imaging with cross-sectional multiplanar reconstruction, maximum intensity projection, and volume reconstruction. For the operations performed, the mean bleeding volume was 73±32.3 ml and the mean number of harvested lymph nodes was 22±9.7. The follow-up period ranged from 6-40 months (mean 21.2), and only two patients had distant metastases. CONCLUSIONS: The laparoscopic complete mesocolic excision surgical plane for right-sided colon cancer is composed of three surgical planes. When these surgical planes were identified, laparoscopic complete mesocolic excision was a safe and effective procedure for the resection of colon cancer.

Ileal versus sigmoid neobladder as bladder substitute after radical cystectomy for bladder cancer: A meta-analysis.

PURPOSE: To evaluate and compare the functional outcomes of ileal and sigmoid neobladders in patients underwent radical cystectomy. METHODS: Relevant studies were identified by searching PubMed, Embase, and Cochrane Library. The studies comparing the functional outcomes of sigmoid neobladder (SN) and ileal neobladder (IN) in patients underwent radical cystectomy were included. RESULTS: A total of 12 cohort studies were included in this meta-analysis. From our analysis, more early complications were observed in SN group than in IN group (RR = 1.37, 95% CI: 1.03-1.81). Both daytime and nighttime continence rates were significantly better in IN group than in SN group (RR = 0.87, 95%CI: 0.81-0.94) (RR = 0.73, 95%CI: 0.60-0.90). More patients could spontaneous voiding in SN group than in IN group (RR = 1.12, 95%CI: 1.00-1.26). According to the urodynamic study, ileal neobladder exhibited bigger capacity (WMD = -84.93, 95%CI: -160.36 to -9.50), lower pressure at capacity (WMD = 11.18, 95%CI: 4.29-18.06), better compliance (WMD = -25.55, 95%CI: -32.45 to -18.64), and greater post-void residual volume(WMD = -23.48, 95%CI: -36.75 to -10.21); There was no significant difference in the max voiding flow rate or void volume between the two groups (WMD = -1.00, 95%CI: -3.73-1.73) (WMD = -27.00, 95%CI: 70.05-16.06). No significant difference was found in the serum creatinine between the two groups (WMD = -0.05, 95%CI: -0.12-0.03). CONCLUSIONS: Ileal neobladder seems able to provide more favorable patient's satisfaction, while sigmoid neobladder may provide a better chance of spontaneous voiding. This meta-analysis may provide some useful evidences for urological surgeons to choose the ideal bladder substitute for patients underwent radical cystectomy.

Perioperative Allogenenic Blood Transfusion is Associated With Worse Clinical Outcome for Patients Undergoing Gastric Carcinoma Surgery: A Meta-Analysis.

Whether perioperative allogenic blood transfusion (ABT) has adverse effect on patients with gastric carcinoma (GC) surgery or not, that is controversial. Our study evaluated the association between ABT and some clinical outcomes of GC surgery patients. Data of relevant studies were based on PubMed, EMBASE, and the Cochrane Library search. The relative risk (RR) of 5-year survival rates, tumor recurrence, and postoperative complications were performed; subgroup analyses included district, transfusion rates, age, participants, sex, and tumor stage. The study was approved by the ethics committee of the First People's Hospital of Shunde. In total, 9189 participants from 16 studies were included in the meta-analysis. The 5-year survival rate was decreased for the GC patients with ABT (RR = 0.74, 95% confidence interval [CI] = 0.69-0.79), the risk of tumor recurrence was significantly higher for ABT patients (RR = 1.82, 95% CI = 1.32-2.51), and postoperative complications increased in ABT patients (RR = 1.36, 95% CI = 1.02-1.81), respectively; in subgroup analyses, 5-year survival rates were not associated with the transfusion rates (χ2 = 0.37, P = 0.54). Transfusion for patients undergoing GC surgery, even low transfusion rates, would reduce the 5-year survival rates, and elevated the risk of tumor recurrence and postoperative complication.

Twist1 is a potential prognostic marker for colorectal cancer and associated with chemoresistance.

Twist1 is a highly conserved basic helix-loophelix transcription factor, and has been shown to play an important role in carcinogenesis of many tumors including colorectal cancer (CRC). Here we aimed to investigate the role of Twist1 in the clinical significance and chemoresistance in CRC. In this study, we examined the correlation between Twist1 expression and clinicopathological characteristics using immunohistochemistry in patients with CRC. The molecular mechanisms of Twist1 expression and its effects on chemosensitivity to 5-Fluorouracil and oxaliplatin were also explored by MTT assay, colony forming assay, flow cytometry assay. The results indicate that Twist1 is overexpressed in cancer tissue, and its positive expression are related to histological grade (P=0.004), T-stage (P=0.033), N-stage (P=0.000), M-stage (P=0.040), TNM stage (P=0.002) and recurrence (P=0.023). Moreover, positive Twist1 expression is correlated with poor overall survival in CRC patients (P<0.0001), and is a significant independent prognostic indicator. In addition, we show that knockdown of Twist1 inhibits proliferation, and increased the percentage of apoptotic cells of CRC cell lines. Our findings suggest that Twist1 promotes proliferation and chemoresistance of CRC cells. Twist1 may be a potential prognostic marker and a molecular target for therapies.

Ligand-promoted ortho-C-H amination with Pd catalysts.

2,4,6-Trimethoxypyridine is identified as an efficient ligand for promoting a Pd-catalyzed ortho-C-H amination of both benzamides and triflyl-protected benzylamines. This finding provides guidance for the development of ligands that can improve or enable Pd(II)-catalyzed Csp2-H activation reactions directed by weakly coordinating functional groups.

Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells.

Colorectal cancer (CRC) is one of the most common malignancies worldwide with substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This study aimed to evaluate the molecular interactome and anticancer effect of ALS and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly arrested cells in G2/M phase in both cell lines, accompanied by remarkable alterations in the expression level of key cell cycle regulators. ALS induced apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), but activation of 5' AMP-activated protein kinase (AMPK) signaling pathways. There was a differential modulating effect of ALS on p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 cells. Collectively, it suggests that induction of cell cycle arrest, promotion of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the cancer cell killing effect of ALS on CRC cells.