Difenoconazole disrupts carp intestinal physical barrier and causes inflammatory response via triggering oxidative stress and apoptosis.

As a common fungicide, difenoconazole (DFZ) is widespread in the natural environment and poses many potential threats. Carp makes up a significant proportion of China's freshwater aquaculture population and are vulnerable to the DFZ. Therefore, this study investigated the effects of DFZ (0.488 mg/L and 1.953 mg/L) exposure for 4 d on the intestinal tissues of carp and explored the mechanisms. Specifically, DFZ exposure caused pathological damage to the intestinal tissues of carp, reducing the expression levels of intestinal tight junction proteins, and leading to damage to the intestinal barrier. In addition, DFZ exposure activated the NF-κB signaling pathway, increasing the levels of pro-inflammatory factors (TNF-α, IL-1ß, IL-6) and decreasing the levels of anti-inflammatory factors (IL-10, TGF-ß1). As disruption of the intestinal barrier is closely linked to oxidative stress and apoptosis, we have conducted research in both areas for this reason. The results showed that DFZ exposure elevated reactive oxygen species in carp intestines, decreased antioxidant enzyme activity, and suppressed the expression of oxidative stress-related genes. TUNEL results showed that DFZ induced the onset of apoptosis. In addition, the expression levels of apoptosis-related genes and proteins were examined. Western blotting results showed that DFZ could upregulate the protein expression levels of Bax, Cytochrome C and downregulate the protein levels of Bcl-2. qPCR results showed that DFZ could upregulate the transcript levels of Bax, Caspase-3, Caspase-8 and Caspase-9 and downregulate the transcript levels of Bcl-2 transcript levels. This suggests that DFZ can induce apoptosis of mitochondrial pathway in carp intestine. In conclusion, DFZ can induce oxidative stress and apoptosis in carp intestine, leading to the destruction of intestinal physical barrier and the occurrence of inflammation. Our data support the idea that oxidative stress and apoptosis are important triggers of pesticide-induced inflammatory bowel illness.

Disruption of the intestinal barrier by avermectin in carp involves oxidative stress and apoptosis and leads to intestinal inflammation.

Avermectin (AVM) is a widely used insecticide. Due to its sensitive toxicity to aquatic organisms, the toxicology of AVM on fish intestines remains unclear. Here, we established a 96 h AVM acute toxicity model to explore the effects of AVM on the intestinal tract of carp. The 96 h LC50 of carps exposed to AVM was 24.04 µg/L, 12.02 µg/L was selected as the high-dose group and 3.005 µg/L was selected as the low-dose group. After 96 h of exposure, intestinal tissues were collected and subsequently analyzed for histopathology, the activities of antioxidant oxidases (CAT, SOD, GSH-Px), and the expression of mRNA associated with oxidative stress, inflammation, and apoptosis. Our study showed that AVM exposure caused intestinal damage in carp, decreased the expression of the tight junction protein gene, activated oxidative stress, induced apoptosis, and induced intestinal inflammation in carp. Therefore, we demonstrated that AVM exposure compromised the integrity of the intestinal barrier in carp, activated oxidative stress, induced endogenous apoptosis, and induced intestinal inflammatory responses. These results indicate that AVM, as a drug-sensitive to aquatic organisms, has a much more complex toxic effect on the fish intestinal tract, which provides a new perspective for studying the toxicology of AVM on the fish intestinal tract.

Protective effect of quercetin on avermectin induced splenic toxicity in carp: Resistance to inflammatory response and oxidative damage.

Avermectin pollution is an important problem that cannot be ignored in aquatic system in recent years. It has brought great trouble to freshwater aquaculture, especially fishery aquaculture. Plant-derived quercetin has anti-inflammatory and antioxidant properties and is widely used as a dietary additive, but its protective effect on immune damage induced by avermectin in freshwater carp remains unclear. This study evaluated the role of dietary additive quercetin supplementation in chronic avermectin exposure of carp spleen. Sixty carp were divided into 4 groups (n = 15/ group), including control group, avermectin treatment group, quercetin treatment group, quercetin and avermectin co-treatment group. Carp were exposed to a 1/10 96 h LC50 dose of avermectin for 30 d and fed a carp diet containing 400 mg/kg quercetin twice a day (3% body weigh/ carp). The results showed that chronic avermectin exposure caused the loose parenchymal structure of carp spleen tissue and the increase of inflammatory cells, accompanied by increased transcription levels of pro-inflammatory il-1ß, il-6, tnf-α and decreased levels of anti-inflammatory factors il-10 and tgf-ß1, ROS accumulation in spleen tissue. MDA content increased and T-AOC, CAT and GSH levels decreased. Quercetin down-regulates the NF-κB pathway by inhibiting the expression of iNOS and activating p38 MAPK, blocking the transcription of inflammatory factors, and alleviating the inflammation of carp spleen caused by chronic avermectin exposure. In addition, quercetin inhibits the over-activation of Nrf2/Keap-1 signaling axis, blocks ROS accumulation, and restores the spleen REDOX homeostasis. In conclusion, quercetin, as a dietary additive for carp feed, can effectively improve the immune damage caused by avermectin pollution in aquatic environment, resist spleen inflammation and oxidative stress, and provide a theoretical basis for clinical development of freshwater carp feed.

Semisynthesis and in Vitro Anti-cancer Effect of New Magnolol Derivatives on the Cell Proliferation, Apoptosis, Migration, and Invasion of Human Hepatocellular Carcinoma SMMC-7721 Cells.

Four new magnolol derivatives were synthesized and evaluated for their in vitro anti-cancer properties. Among these, compound 3 showed the most potent cytotoxic activity against the SMMC-7721, SUN-449, and HepG2 human hepatocellular carcinoma cell lines, with IC50 values of 3.39, 4.11, and 6.88 µM, respectively. Compound 3 also induced apoptosis of SMMC-7721 cells by down-regulating Bcl-2 and Akt protein levels, up-regulating of Bax protein level, and cleaving caspase-9 and -3. In addition, transwell assays showed that compound 3 significantly suppressed the migration and invasion of SMMC-7721 cells, which was confirmed based on the down-regulation of hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-2 and -9 (MMP-2, and MMP-9) protein levels.

In Situ TEM Observation of Stagnant Liquid Layer Activation in Nanochannel.

The kinetics of mass transfer in a stagnant fluid layer next to an interface govern numerous dynamic reactions in diffusional micro/nanopores, such as catalysis, fuel cells, and chemical separation. However, the effect of the interplay between stagnant liquid and flowing fluid on the micro/nanoscopic mass transfer dynamics remains poorly understood. Here, by using liquid cell transmission electron microscopy (TEM), we directly tracked microfluid unit migration at the nanoscale. By tracking the trajectories, an unexpected mass transfer phenomenon in which fluid units in the stagnant liquid layer migrated two orders faster during gas-liquid interface updating was identified. Molecular dynamics (MD) simulations indicated that the chemical potential difference between nanoscale liquid layers led to convective flow, which greatly enhanced mass transfer on the surface. Our study opens up a pathway toward research on mass transfer in the surface liquid layers at high spatial and temporal resolutions.

Avermectin induces carp neurotoxicity by mediating blood-brain barrier dysfunction, oxidative stress, inflammation, and apoptosis through PI3K/Akt and NF-κB pathways.

Avermectin, a "low toxicity insecticide", has been widely used in recent years, but its non-target toxicity, especially to aquatic organisms, has been neglected. In this study, we evaluated the neurotoxic effects of avermectin on carp by establishing a 96 h avermectin acute toxicity test, and its possible mechanism was discussed. The 96 h LC50 of avermectin in carp was found to be 24.04 µg/L. Therefore, 3.005 µg/L and 12.02 µg/L were used as the low-dose and high-dose groups, respectively, to investigate the neurotoxic effects of avermectin on carp. The results of high-performance liquid chromatography (HPLC) analysis showed that avermectin accumulated in the carp brain. Histopathological observation and immunohistochemical analysis (IHC) of TNF-α and Bax showed that avermectin exposure led to inflammatory cell infiltration and neuronal necrosis. The mRNA levels of tight junction genes and the IHC results of ZO-1 and Occludin showed that the structure of the blood-brain barrier (BBB) was destroyed. Biochemical analysis showed that avermectin induced the accumulation of MDA in the brain and decreased the activity of antioxidant enzymes CAT and SOD, leading to oxidative stress. In addition, avermectin induces brain inflammation by activating NF-κB pathway and releasing inflammatory factors IL-1ß, IL-6, TNF-α and iNOS. TEM and TUNEL assays showed that exposure to avermectin induced apoptosis in brain. what is more, the expression of apoptosis-related genes and proteins suggested that avermectin-induced apoptosis may be associated with inhibition of the PI3K/Akt signaling pathway. This study also showed that avermectin-induced NF-κB signaling activation was partially dependent on its upstream PI3K/Akt signaling pathway. Therefore, this study concludes that avermectin can induce neurotoxicity in carp by disrupting the blood-brain barrier structure and generating oxidative stress, inflammation, and apoptosis and that NF-κB and PI3K/Akt signaling pathways are involved in this process.

Non-target toxic effects of avermectin on carp spleen involve oxidative stress, inflammation, and apoptosis.

Avermectin is one of the most widely used pesticides, but its toxicity to non-target organisms, especially aquatic organisms, has been ignored. Therefore, an acute spleen injury model of avermectin in carp was established to assess the non-target toxicity of avermectin to carp. In this study, 3.005 µg/L and 12.02 µg/L were set as the low and high dose groups of avermectin, respectively, and a four days acute exposure experiment was conducted. Pathological structure observation showed that avermectin damaged spleen tissue structure and produced inflammatory cell infiltration. Biochemical analysis showed that avermectin significantly reduced the activities of antioxidant enzymes CAT, SOD, and GSH-px, but increased the content of MDA, a marker of oxidative damage. Avermectin exposure also significantly increased the transcription levels of inflammatory cytokines such as IL-1ß, IL-6, TNF-α, and INOS, and also significantly enhanced the activity of the inflammatory mediator iNOS, but suppressed the transcription levels of anti-inflammatory factors TGF-ß1 and IL-10. In addition, TUNEL detected that the apoptosis rate increased significantly with the increase of avermectin dosage, and the transcription levels of apoptosis-related genes BAX, P53, and Caspase 3/9 also increased in a dose-dependent manner. This study is preliminary evidence that avermectin induces spleen injury in carp through oxidative stress, inflammation, and apoptosis, which has important implications for subsequent studies on the effects of avermectin on non-target organisms.

Narrow H3K4me2 is required for chicken PGC formation.

The development of primordial germ cells (PGCs) undergoes epigenetic modifications. The study of histone methylation in regulating PGCs is beneficial to understand the development and differentiation mechanism of germ stem cells. Notably, it provides a theoretical basis for directed induction and mass acquisition in vitro. However, little is known about the regulation of PGC formation by histone methylation. Here, we found the high enrichment of H3K4me2 in the blastoderm, genital ridges, and testis. Chromatin immunoprecipitation sequencing was performed and the results revealed that genomic H3K4me2 is dynamic in embryonic stem cells, PGCs, and spermatogonial stem cells. This trend was consistent with the H3K4me2 enrichment in the gene promoter region. Additionally, narrow region triggered PGC-related genes (Bmp4, Wnt5a, and Tcf7l2) and signaling pathways (Wnt and transforming growth factor-ß). After knocking down histone methylase Mll2 in vitro and vivo, the level of H3K4me2 decreased, inhibiting Cvh and Blimp1 expression, then repressing the formation of PGCs. Taken together, our study revealed the whole genome map of H3K4me2 in the formation of PGCs, contributing to improve the epigenetic study in PGC formation and providing materials for bird gene editing and rescue of endangered birds.

Exercise and Hyperlipidemia.

Hyperlipidemia is one of the common pathological conditions of human, which occurs due to lipid metabolism disorder in the human body, resulting in serum lipid concentration beyond normal levels. Due to heredity, diet, nutrition, medicine, and other factors, the incidence of hyperlipidemia has been significantly enhanced and has become one of the most common pathological condition of the human. By introducing the background and pathogenesis of hyperlipidemia and the positive effects of exercise on a variety of related diseases, this chapter discusses the relationship between exercise and serum lipid concentration and the effects of different types of exercise on hyperlipidemia.

Exercise and Muscle Atrophy.

The incidence of muscle atrophy is increasing with each passing year, which imposes a huge burden on the quality of life of patients. It is a public health issue that causes a growing concern around the world. Exercise is one of the key strategies to prevent and treat various diseases. Appropriate exercise is conducive to compensatory muscle hypertrophy, to improve muscle strength and elasticity, and to train muscle coordination, which is also beneficial to the recovery of skeletal muscle function and the regeneration of muscle cells. Sequelae of paralysis of patients with limb dyskinesia caused by muscle atrophy will be significantly alleviated after regular exercise therapy. Furthermore, exercise therapy can slow down or even reverse muscle atrophy. This article aims to introduce the characteristics of muscle atrophy and summarize the role and mechanism of exercise in the treatment of muscle atrophy in the existing studies, in order to further explore the mechanism of exercise to protect muscle atrophy and provide protection for patients with muscular atrophy.

Sophocarpine Inhibits Tumorgenesis of Colorectal Cancer via Downregulation of MEK/ERK/VEGF Pathway.

Colorectal cancer (CRC) is one of the most common malignant tumors and the third leading cause of cancer-related deaths in the world. It was reported that sophocarpine could attenuate the progression of CRC in mice. However, the mechanisms by which sophocarpine regulate the proliferation and migration in CRC remain unclear. Thus, this study aimed to investigate anti-tumor mechanisms of sophocarpine in CRC cells. CCK-8 assay, wound healing assay and transwell migration were used to detect cell proliferation and migration, respectively. In addition, Western blotting and enzyme-linked immunosorbent assay (ELISA) were used to further detect protein expressions and cytokines in vitro. The results revealed that sophocarpine significantly inhibited proliferation in HCT116 and SW620 cells, respectively. Meanwhile, sophocarpine inhibited CRC cells migration via downregulation of the levels of N-cadherin, matrix metalloproteinase (MMP)-9, phosphorylated extracellular signal-regulated kinase (p-ERK), p-mitogen-activated protein kinase kinase (MEK), vascular endothelial growth factor (VEGF)-A, VEGF-C and VEGF-D. Moreover, overexpression of MEK reversed the anti-migration effects of sophocarpine on CRC cells via upregulation of VEGF-A/C/D. Our findings indicated that sophocarpine could inhibit CRC cells migration via downregulation of MEK/ERK/VEGF pathway. Thus, sophocarpine may act as a potential agent for the treatment of CRC.

Ursolic Acid Inhibits Tumor Growth via Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells.

Ursolic acid (UA), a natural pentacyclic triterpenoid, is a promising compound for cancer prevention and therapy. However, its mechanisms of action have not been well elucidated in colorectal cancer cells. Here, using cultured human colon cancer cell lines SW620 and HCT116, this assay demonstrates that UA reduces cell viability, inhibits cell clone formation, and induces caspase-3 mediated apoptosis. Additional experiments show that UA inhibits cell migration and epithelial-mesenchymal transition (EMT), including E-cadherin, Vimentin, Integrin, Twist, and Zeb1 biomakers. These results suggest that UA inhibits cell proliferation, invasion, and metastasis in colorectal cancer cells by affecting mechanisms that regulate EMT. Taken together, the results suggested that the anti-proliferation and anti-metastasis activities of UA was through EMT inhibition in colorectal cancer.

MAPK8 regulates chicken male germ cell differentiation through JNK signaling pathway.

The study aims to analyze the key signaling pathways in regulating the process of embryonic stem cells (ESCs) differentiation into spermatogonial stem cells (SSCs). We explored the specific regulating mechanisms of C-Jun amino-terminal kinase (JNK) signaling in this process. Interference/overexpression of MAPK8 allows the JNK signaling pathway to be blocked/activated. In Retinoic acid (RA) induced in vitro differentiation assays, the expression of germ cell marker genes, cvh, c-kit, integrin α6 and integrin ß1, was observed to upregulate while activating JNK signaling significantly. Fluorescence Activated Cell Sorting (FACs) analysis showed that the proportion of cvh+ and integrin α6+ cells in the overexpression group was significantly higher than which in the RA + shRNA-MAPK8 group. In in vivo situations, shRNA-MAPK8 could stably express in chicken embryos and significantly down-regulate expression of MAPK8 and downstream genes in JNK signaling pathway. With PAS stain, we found that PGCs (primordial germ cells) was significantly decreased after inhibiting MAPK8. With real-time quantitative PCR (qRT-PCR) and Western Blot, we identified that reproductive related genes expression was significantly suppressed after inhibiting MAPK8 in vivo. We preliminarily concluded that knockdown/ overexpression of MAPK8 could affect differentiation of ESC by inhibiting/activating JNK signal.

Nanos2 promotes differentiation of chicken (Gallus gallus) embryonic stem cells to male germ cells.

Nanos2 is an evolutionarily conserved RNA-binding protein containing 2 CCHC-type zinc finger motives. Here, we report that Nanos2 is strongly expressed in the testis compared to other tissues in chicken (Gallus gallus). Overexpression and knockout plasmid vectors were constructed, and in-vitro Cas9/gRNA digestion and T7 endonuclease I (T7E1) assay indicated that Nanos2-g1 possessed the highest knockout activity. In vitro and in vivo, Nanos2 overexpression accelerated the production of embryoid bodies (EBs) and SSC-like cells and promoted cvh, c-kit, and integrin α6 expression. Immunofluorescence staining, periodic acid schiff (PAS) and flow cytometry (FCM) assay showed that primordial germ cells (PGCs) and spermatogonial stem cells (SSCs) formation were significantly promoted. On the contrary, Nanos2 knockout delayed the production of EBs and SSC-like cells and correspondingly reduced cvh, c-kit, and integrin α6 expression. Simultaneously, the quantity of PGCs and SSCs was blocked. Collectively, these results uncovered a novel function of Nanos2 involved in chicken male germ cell differentiation, where it acts as a facilitator.

Wnt signaling pathway regulates differentiation of chicken embryonic stem cells into spermatogonial stem cells via Wnt5a.

In this study, we investigated the mechanism of signaling pathway-mediated differentiation of embryonic stem cells (ESCs) into spermatogonial stem cells (SSCs) in chicken. The Wnt signaling pathway was identified based on previous RNA Sequencing results and was proven a crucial signaling pathway that participates in the differentiation of ESCs into SSCs. In retinoic acid (RA) induction experiments in vitro, we found that Wnt signaling expression was inhibited by Wnt5a-shRNA, resulting in decreased expression of corresponding marker genes in SSCs, C-kit, Cvh, integrin α6 and integrin ß1, but it was significantly promoted by RA treatment. Immunofluorescence assay showed that percentage of C-kit, Cvh, and integrin α6 and integrin ß1-positive cells in RA treatment group and Wnt5a overexpression group was significantly higher than that in Wnt5a signaling interference group. Results of fluorescence-activated cell sorting analysis (FACS) also showed that proportion of germ-like cells was reduced by 14.3% (from 18.3% to 4.0%) at day 4 and 15.4% (from 18.6% to 3.2%) at day 12 after transfection, respectively. In experiments in vivo, shRNA-Wnt5a was stably expressed in fertilized chicken embryos and significantly reduced germ cell formation by 11.3% (from 21.7% to 10.4%) and 3.7% (6.4% from 10.1%). Results of quantitative PCR (qRT-PCR) and western blot assays showed that the expression of some specific germ cell marker genes, integrin α6 and integrin ß1, was significantly suppressed following Wnt5a signaling interference in vivo. Taken together, our study suggests that Wnt signaling pathway could regulate positively the differentiation of chicken ESCs into SSCs through Wnt5a.

Regulation of fibroblast growth factor 8 (FGF8) in chicken embryonic stem cells differentiation into spermatogonial stem cells.

Fibroblast growth factors (FGFs) are essential in regulating the formation of spermatogonial stem cells (SSCs). Here, we explored the effect of FGF8 on chicken SSCs formation by knockdown or overexpression of FGF8 in chicken embryonic stem cells (ESCs) both in vitro and in vivo. Our results showed that knockdown of FGF8 could facilitate the differentiation of ESCs into SSCs, overexpression of FGF8 could promote PGCs self-renewal, inhibit SSCs formation. This study further revealed the positive correlation between the expression level of FGF8 and MAPK/ERK signal. In the absence of FGF8, the expression of downstream genes such as FGFR2, GRB2, RAS, BRAF, RAF1, and MEK2 was not maintained, while overexpressing FGF8 enhances them. Thus, our study demonstrated that FGF8 can regulate germ cell fate by modulating the dynamic equilibrium between differentiation and self-renewal, which provides a new idea for the study of germ cell regulatory network.

Hsd3b2 associated in modulating steroid hormone synthesis pathway regulates the differentiation of chicken embryonic stem cells into spermatogonial stem cells.

Steroid hormones regulate differentiation of various types of cell during embryogenesis. Testosterone is one of the androgens that bind to receptors to regulate gene expression and promote spermatogenesis. Our results showed that testosterone, as a product of steroid hormones synthesis pathway, could facilitate the differentiation of embryonic stem cells (ESCs) into spermatogonial stem cells (SSCs). The analysis of the steroid hormones synthesis pathway demonstrated that 3beta-hydroxysteroid dehydrogenase2 (Hsd3b2) plays a major role in the synthesis of testosterone. In the absence of Hsd3b2, the expression of downstream genes such as Cyp1a1, Ugt1a1, and Hsd17b7 was not maintained. This reduction is probably due to the down-regulation of the steroid hormones synthesis pathway. Furthermore, qRT-PCR, immunofluorescence, and flow cytometry analysis confirmed that the steroid hormones synthesis pathway could facilitate the differentiation of ESCs. Altogether, these results lead to a model in which Hsd3b2 regulates ESCs differentiation via modulating the activity of steroid hormones synthesis pathway.

The inhibition role of miR-22 in hepatocellular carcinoma cell migration and invasion via targeting CD147.

BACKGROUND: Recently, miR-22 is identified as a tumor-suppressing microRNA in many human cancers. CD147 is a novel cancer-associated biomarker that plays an important role in the invasion and metastasis of malignant tumor. However, the involvement of miR-22 in CD147 regulation and hepatocellular carcinoma (HCC) progression and metastasis has not been investigated. METHODS: We measured miR-22 expression level in 34 paired of HCC and matched normal tissues, HCC cell lines by real-time quantitative RT-PCR. Invasion assay, MTT proliferation assay and wound-healing assay were performed to test the invasion and proliferation of HCC cell after overexpression of miR-22. The effect of miR-22 on HCC in vivo was validated by murine xenograft model. The relationship of miR-22 and its target gene CD147 was also investigated. RESULTS: We found that the expression of miR-22 in HCC tissues and cell lines were much lower than that in normal control, respectively. The expression of miR-22 was inversely correlated with HCC metastatic ability. Moreover, overexpression of miR-22 could significantly inhibit the HCC cell proliferation, migration and invasion in vitro and decrease HCC tumor growth in vivo. Finally, we found that miR-22 interacted with CD147 and decreased its expression, via a specific target site within the CD147 3'UTR by luciferase reporter assay. The expression of CD147 was inversely correlated with miR-22 expression in HCC tissues. CONCLUSION: Our results suggested that miR-22 was downexpressed in HCC and inhibited HCC cell proliferation, migration and invasion through downregulating cancer-associated gene CD147 which may provide a new bio-target for HCC therapy.

Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.

OBJECTIVE: Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC. MATERIAL AND METHODS: In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3. RESULTS: Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation. CONCLUSIONS: TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.