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BACKGROUND: Patients with rectal cancer undergoing radical resection often have poor postoperative recovery due to preoperative fasting and water deprivation and the removal of diseased tissue, and have a high risk of complications. Therefore, it is of great significance to apply appropriate rehydration regimens to patients undergoing radical resection of rectal cancer during the perioperative period to improve the postoperative outcomes of patients. AIM: To analyze the effects of goal-directed fluid therapy (GDFT) with a preoperative glucose load regimen on postoperative recovery and complications in patients undergoing radical resection for rectal cancer. METHODS: Patients with rectal cancer who underwent radical resection (n = 184) between January 2021 and December 2023 at our hospital were randomly divided into either a control group or an observation group (n = 92 in each group). Both groups received a preoperative glucose load regimen, and routine fluid replacement and GDFT were additionally implements in the control and observation groups, respectively. The operative conditions, blood levels of lactic acid and inflammatory markers, postoperative recovery, cognitive status, hemodynamic indicators, brain oxygen metabolism, and complication rates were compared between the groups. RESULTS: The colloidal fluid dosage, total infusion, and urine volume, as well as time to first exhaust, time to food intake, and postoperative length of hospital stay, were lower in the observation group (P < 0.05). No significant differences were observed between the two groups in terms of operation time, bleeding volume, crystalloid liquid consumption, time to tracheal extubation, complication rate, heart rate, or mean arterial pressure (P > 0.05). Compared with the control group, in the observation group the lactic acid level was lower immediately after the surgery (P < 0.05); the Mini-Mental State Examination score was higher on postoperative day 3 (P < 0.05); the pulse pressure variability (PPV) was lower at 30 min after pneumoperitoneum (P < 0.05), though the differences in the PPV of the two groups was not significant at the remaining time points (P > 0.05); tumor necrosis factor-α and interleukin-6 levels were lower on postoperative day 3 (P < 0.05); and the left and right regional cerebral oxygen saturation was higher immediately after the surgery and 30 min after pneumoperitoneum (P < 0.05). CONCLUSION: GDFT combined with the preoperative glucose load regimen is a safe and effective treatment strategy for improving postoperative recovery and risk of complications in patients with rectal cancer undergoing radical resection.
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BACKGROUND: Highly reactive oxygen species (ROS) could lead to serious damage in living cells and are associated with many diseases like cancers. Metal cluster with strong fluorescence has great potential in biosensing and many thiolate ligands-protected clusters have been applied in ROS sensing. RESULTS: In this work, we synthesized levonorgestrel protected Au10 cluster with specific sensing ability for highly ROS via crystal transformation from Au8 cluster, demonstrating the significance of inner core structure on detecting performance. The detection limit of Au10 cluster for ClO- could reach as low as 0.1 µM. This fluorescent probe not only achieving detection of exogenous ClO- in living cells and zebrafish, but also successful imaging of endogenous ClO- in HeLa and HepG2 cells. SIGNIFICANCE: In comparison to previously reported cluster-based sensors for ROS, this work proposes a different reaction mechanism of metal nanoclusters for ROS detection (breakage of gold-alkynyl bond and oxidation of alkynyl group). This provides new directions for designing specific ROS probes and broadens the applications of metal clusters in disease diagnostics.
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Colorantes Fluorescentes , Oro , Ácido Hipocloroso , Levonorgestrel , Pez Cebra , Humanos , Oro/química , Células HeLa , Ácido Hipocloroso/análisis , Animales , Células Hep G2 , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Levonorgestrel/química , Imagen Óptica , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/análisis , Nanopartículas del Metal/químicaRESUMEN
Colorectal cancer (CRC) is the third most common cancer and causes high mortality worldwide. Although CRC has been studied widely, the molecular mechanism is not completely known. Eukaryotic translation elongation factor 1 delta (EEF1D) participates in the progression of various tumors, however, the effect of EEF1D on CRC remains unclear. Here, we aimed to identify the potential mechanism of EEF1D in CRC. The expression levels of EEF1D were assessed in CRC samples. Functional analysis of EEF1D in CRC was detected in vitro and in vivo. The regulatory mechanism of EEF1D was identified with RNA immunoprecipitation, RNA pull-down assay, and proteomics analysis. Our findings confirmed that EEF1D was upregulated in human CRC tissues. Functionally, EEF1D overexpression accelerated cell proliferation and metastasis, whereas EEF1D knockdown inhibited cell proliferation and metastasis both in vitro and in vivo CRC models. Furthermore, we showed that EEF1D was upregulated by SRSF9 via binding to 3'UTR of EEF1D mRNA. EEF1D knockdown reversed the malignant phenotype induced by SRSF9 overexpression. These findings demonstrated that EEF1D promotes CRC progression, and EEF1D may be a molecular target against CRC.
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Proliferación Celular , Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , Factor 1 de Elongación Peptídica , Factores de Empalme Serina-Arginina , Animales , Femenino , Humanos , Masculino , Ratones , Regiones no Traducidas 3'/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Ratones Desnudos , Metástasis de la Neoplasia , Factor 1 de Elongación Peptídica/genética , Factor 1 de Elongación Peptídica/metabolismo , Factores de Empalme Serina-Arginina/metabolismo , Factores de Empalme Serina-Arginina/genética , Regulación hacia ArribaRESUMEN
Ferroptosis, a newly discovered form of programmed cell death characterized by lipid peroxidation, crafts a new perspective on cancer treatment. Serine and arginine rich splicing factor 9 (SFRS9) is frequently described as a proto-oncogene in cervical and bladder cancer. However, the role of SFRS9 in colorectal cancer (CRC) and whether SFRS9 exerts its function associated with ferroptosis is largely unknown. Herein, we found that the expression of SFRS9 mRNA and protein in the CRC tissues was obviously higher than that in the paracancerous tissues. Function assays revealed that SFRS9 overexpression (SFRS9-OE) significantly promoted cell viability, cell cycle progression and colony formation of CRC cells. While SFRS9 knockdown by shRNAs transfection inhibited these progressions. Furthermore, cell death and lipid peroxidation induced by ferroptosis inducers erastin and sorafenib were suppressed by SFRS9-OE. Bioinformatics analysis indicated that SFRS9 can bind to peroxidase 4 (GPX4) mRNA which is a central regulator of ferroptosis. Western blot showed that GPX4 protein expression was clearly elevated upon SFRS9-OE, while it was decreased in SFRS9-inhibited CRC cells. RNA immunoprecipitation experiment was carried out in HCT116 cells to confirm the binding of SFRS9 and GPX4 mRNA specifically. SiGPX4 transfection reversed the inhibitory effects of SFRS9-OE on the erastin and sorafenib-induced ferroptosis. Consistent with our in vitro observations, SFRS9 promoted the growth of tumors while SFRS9 knockdown significantly inhibited tumor growth in nude mice. In conclusion, SFRS9 represents an obstructive factor to ferroptosis by upregulating GPX4 protein expression, and knocking down SFRS9 might be an effective treatment for CRC.
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Hepatocellular carcinoma (HCC) is the most common visceral neoplasms with its heterogeneity and high rate of recurrence. HCC is characterized to be delayed diagnosis and the development of resistant disease. However, the molecular mechanism for HCC pathogenesis and progression remains largely unknown. Here, we demonstrated that ubiquitin-specific protease14 (USP14) is highly expressed in HCC samples, and the higher expression of USP14 is positively correlated with poor prognosis. Interestingly, USP14 is involved in the maintenance of HIF1-α stability to activate HIF1-α-induced transactivation via its deubiquitinase activity. USP14 depletion or its specific inhibitor IU1 treatment decreased cell proliferation, invasion, migration, and Vascular Mimicry (VM) formation even under hypoxia conditions in HCC cell lines. Moreover, we provided the evidence to show that knockdown of USP14 or USP14 inhibitor (IU1) treatment inhibited tumor growth in tumor-bearing nude mice. Our findings suggest that USP14 maintains HIF1-α stability through its deubiquitination activity, providing a potential biomarker for the early diagnosis and therapy of HCC.
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Carcinoma Hepatocelular/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Ubiquitinación , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Modelos Biológicos , Invasividad Neoplásica , Pronóstico , Estabilidad Proteica , Activación Transcripcional/genética , Resultado del Tratamiento , Ubiquitina Tiolesterasa/genéticaRESUMEN
Flexible sensing materials have attracted tremendous attention in recent years because of their potential applications in the fields of health monitoring, artificial intelligence, and so on. However, the preparation of rate sensing materials with self-healing performance is always a huge challenge. Herein, we first report the design and synthesis of a highly stretchable, recyclable, self-healing polysiloxane elastomer with rate sensing capability. The elastomer is composed of a dynamic dual network with boron/oxygen dative bonds and hydrogen bonds, which overcomes the structural instability of conventional solid-liquid materials. It exhibits certain adhesion, satisfactory mechanical robustness, and superior elongation at break (up to 1171%). After heating treatment at 80 °C for 2-4 h, the mechanical properties of damaged materials can be almost completely restored. Because of the "solid-liquid" property of the elastomer, it has irreplaceable functions which can sense different rates by resistance change after blending with multiwalled carbon nanotubes, principally in the range of 10 mm/min-150 mm/min. Especially, this rate sensing elastomer can be personalized by 3D printing at room temperature. This rate sensing strategy coupled with the introduction of dynamic dual-network structure is expected to help design advanced wearable devices for human rhythmic movement.
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Ferroptosis, a newly iron-dependent form of cell death, is often accompanied by the damage of membrane lipid peroxide. Recently, the ferroptosis inducer erastin has been reported to exhibit potential anti-cancer activities. The aim of this study was to investigate the effects of SRSF9 on the sensitivity of colorectal cancer (CRC) to erastin and explore the underlying molecular mechanism. Short hairpin RNAs (shRNAs) or SRSF9 overexpression vector (SRSF9-OE) was transfected into erastin-induced human CRC cells to inhibit or overexpress SRSF9. Results showed that SRSF9 inhibition promoted the cell death induced by erastin, conversely, SRSF9 overexpression augmented the resistance to erastin-induced death in human CRC cells. SRSF9 decreased lipid peroxide damage which was a key event during erastin-induced ferroptosis in human CRC cells. Furthermore, we found that SRSF9 inhibition increased erastin-induced ferroptosis by downregulating GPX4 level. In an In vivo study, SRSF9 shRNA or SRSF9-OE stably transfected human CRC cells were subcutaneously injected into the right flank of nude mice. SRSF9 overexpression partly abolished the tumor growth inhibition and ferroptosis induced by erastin. Our data indicated SRSF9's regulation of GPX4 as an essential mechanism driving CRC tumorigenesis and resistance of erastin-induced ferroptosis. This molecular mechanism may provide a novel method for improving the sensitivity of CRC to erastin.
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Neoplasias Colorrectales/metabolismo , Ferroptosis , Hierro/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/antagonistas & inhibidores , Piperazinas/farmacología , Factores de Empalme Serina-Arginina/antagonistas & inhibidores , Animales , Células CACO-2 , Muerte Celular/fisiología , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Células HCT116 , Humanos , Peroxidación de Lípido , Masculino , Ratones , Ratones Desnudos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Especies Reactivas de Oxígeno/metabolismo , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, with unmet need for the pharmacological therapy. The functions of ATXN7L3 in HCC progression are not known. METHODS: RNA sequence, quantitative real-time PCR, and western blot were performed to detect gene expression. Chromatin immunoprecipitation was performed to detect possible mechanisms. Immunohistochemical stain was performed to examine the protein expression. Colony formation, cell growth curve and xenograft tumor experiments were performed to examine cell growth in vitro and in vivo. FINDINGS: ATXN7L3 functions as a coactivator for ERα-mediated transactivation in HCC cells, thereby contributing to enhanced SMAD7 transcription. ATXN7L3 is recruited to the promoter regions of SMAD7 gene, thereby regulating histone H2B ubiquitination level, to enhance the transcription of SMAD7. A series of genes regulated by ATXN7L3 were identified. Moreover, ATXN7L3 participates in suppression of tumor growth. In addition, ATXN7L3 is lower expressed in HCC samples, and the lower expression of ATXN7L3 positively correlates with poor clinical outcome in patients with HCC. INTERPRETATION: This study demonstrated that ATXN7L3 is a novel regulator of SMAD7 transcription, subsequently participating in inhibition of tumor growth in HCC, which provides an insight to support a previously unknown role of ATXN7L3 in HCC progression. FUND: This work was funded by 973 Program Grant from the Ministry of Science and Technology of China (2013CB945201), National Natural Science Foundation of China (31871286, 81872015, 31701102, 81702800, 81902889), Foundation for Special Professor of Liaoning Province, Natural Science Foundation of Liaoning Province (No.20180530072); China Postdoctoral Science Foundation (2019M651164).
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteína smad7/genética , Factores de Transcripción/metabolismo , Animales , Biomarcadores de Tumor , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Receptor alfa de Estrógeno/metabolismo , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/patología , Ratones , Modelos Biológicos , Unión Proteica , ARN Interferente Pequeño/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Androgen receptor (AR) signaling is considered to be crucial for the pathogenesis of hepatocellular carcinoma (HCC) with obvious sexual dimorphism. Pre-mRNA processing factor 6 (PRPF6) was identified as a coactivator of AR. However, the molecular mechanism underlying the modulation function of PRPF6 on AR-mediated transcriptional activity in HCC needs to be further clarified. In this study, we analyzed data from The Cancer Genome Atlas to show that PRPF6 is highly expressed in HCC. . Our data indicated that PRPF6 interacts with AR/AR splice variants (AR-Vs) and upregulates AR/AR splice variant 7-mediated transcriptional activity even without dihydrotestosterone treatment. We observed that AR is obviously induced by androgen treatment and is mainly expressed in the nucleus in HCC-derived cell lines. Moreover, overexpression of PRPF6 enhances AR expression accompanied with the increase of AR-Vs expression. We provided evidence that PRPF6 participates in upregulating AR self-transcription. PRPF6 facilitates the recruitment of AR to the androgen responsive element region of the AR gene. Finally, PRPF6 depletion inhibits cell proliferation in HCC cells and mouse xenografts. Taken together, our results suggest that PRPF6 as a splicing factor enhances AR self-transcription, thereby coactivating oncogenic AR/AR-Vs actions in HCC.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Factores de Empalme de ARN/genética , Receptores Androgénicos/genética , Factores de Transcripción/genética , Animales , Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Dihidrotestosterona/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Xenoinjertos , Humanos , Neoplasias Hepáticas/patología , Ratones , Transducción de Señal , Activación Transcripcional/genéticaRESUMEN
Although increasing evidence have confirmed that carbon monoxide release molecule-2(CORM-2) plays an active role in the treatment of inflammation and tumors, poor aqueous solubility and short CO-release duration restrict its extensive application. Our previous work synthesized styrene-maleic acid copolymer-encapsulated CORM-2 (SMA/CORM-2) to overcome above-mentioned deficiencies and demonstrated satisfactory effects in colitis. This study is to investigate the function of SMA/CORM-2 on colorectal cancer proliferation and metastasis. CCK-8 experiment is used to clarify the half maximal inhibitory concentration (IC50) of SMA/CORM-2 and to detect cell proliferation. Transwell assay coated with or without matrigel was to detect cell invasion and migration. Western blot was used to detect ß-catenin, AKT, p-AKT, VEGF, MMP-2 and MMP-9 proteins. At last, nude mice xenograft was used to further investigate the anti-tumor effect of SMA/CORM-2 in vivo. After SW480 and C26â¯cells were treated with 0.5â¯mg/ml SMA/CORM-2, CRC cells proliferation, migration and invasion were inhibited. In vivo, SMA/CORM-2 treatment remarkably suppressed tumor growth and lung metastasis in nude mice. Furthermore, the expression of ß-catenin, p-AKT, VEGF, MMP-2 and MMP-9 proteins could be down-regulated after SMA/CORM-2 treatment. SMA/CORM-2 exerted both in vitro and in vivo anti-proliferation and anti-metastatic effects, which may yield a novel therapeutic strategy for CRC.
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Antineoplásicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Portadores de Fármacos/química , Maleatos/química , Compuestos Organometálicos/farmacología , Animales , Antineoplásicos/química , Monóxido de Carbono/farmacocinética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Liberación de Fármacos , Humanos , Masculino , Ratones Endogámicos BALB C , Compuestos Organometálicos/química , Solubilidad , Estireno/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A new kind of polysiloxane-supported ionogel is successfully designed via locking ionic liquids (ILs), 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][Tf2 N]), into poly(aminopropyl-methylsiloxane) (PAPMS) grafted with [2-(methacryloyloxy)ethyl] trimethylammonium chloride (METAC) in the presence of tannic acid (TA). The novel ionogel exhibits good mechanical and recovery properties, as well as high ionic conductivity (1.19 mS cm-1 ) at 25 °C. In addition, the totally physical dual-crosslinked network based on ionic aggregates among METAC and the hydrogen bonds between PAPMS and TA provides excellent self-healing ability, which allows the damaged ionogel to almost completely heal (≈83%) in 12 h at room temperature. Interestingly, the obtained ionogel also shows satisfactory adhesive behavior to various solid materials. Moreover, this novel ionogel can maintain its high ionic conductivity and recovery property even at subzero temperatures. Therefore, this polysiloxane-supported ionogel is anticipated to be advantageous in flexible electronic devices such as sensors and supercapacitors, even at low temperatures.
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Adhesivos/química , Siloxanos/química , Conductividad Eléctrica , Geles/química , Iones/química , TemperaturaRESUMEN
It is a challenge to synthesize materials that possess the properties of high stretchability and self-healability. Herein a new poly(dimethylsiloxane) elastomer with high stretchability, room-temperature self-healability, repeatable reprocessability, and controlled degradability is reported by incorporating an aromatic disulfide bond and imine bond. The as-prepared elastomer can be stretched to over 2200% of its original length. Without external stimuli, a damaged sheet can completely heal in 4 h. In addition, the elastomer can be reprocessed multiple times without obvious performance degradation and degraded controllably by three ways. All these properties of the elastomer can be ascribed to the unique dual-dynamic-covalent sacrificial system.
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Dimetilpolisiloxanos/química , Elastómeros/química , TemperaturaRESUMEN
PURPOSE: B-cell translocation gene 3 (BTG3) has been identified as a candidate driver gene for various cancers, but its specific role in colorectal cancer (CRC) is poorly understood. We aimed to investigate the relationship between expression of BTG3 and clinicopathological features and prognosis, as well as to explore the effects and the role of a possible BTG3 molecular mechanism on aggressive colorectal cancer behavior. METHODS: BTG3 expression was assessed by immunohistochemistry (IHC) on specimens from 140 patients with CRC. The association of BTG3 expression with clinicopathological features was examined. To confirm the biological role of BTG3 in CRC, two CRC cell lines expressing BTG3 were used and BTG3 expression was knocked down by shRNA. CCK-8, cell cycle, apoptosis, migration, and invasion assays were performed. The influence of BTG3 knockdown was further investigated by genomic microarray to uncover the potential molecular mechanisms underlying BTG3-mediated CRC development and progression. RESULTS: BTG3 was downregulated in colorectal cancer tissues and positively correlated with pathological classification (p = 0.037), depth of invasion (p = 0.016), distant metastasis (p = 0.024), TNM stage (p = 0.007), and overall survival (OS) and disease-free survival (DFS). BTG3 knockdown promoted cell proliferation, migration, invasion, relieved G2 arrest, and inhibited apoptosis in HCT116 and LoVo cells. A genomic microarray analysis showed that numerous tumor-associated signaling pathways and oncogenes were altered by BTG3 knockdown. At the mRNA level, nine genes referred to the extracellular-regulated kinase/mitogen-activated protein kinase pathway were differentially expressed. Western blotting revealed that BTG3 knockdown upregulated PAK2, RPS6KA5, YWHAB, and signal transducer and activator of transcription (STAT)3 protein levels, but downregulated RAP1A, DUSP6, and STAT1 protein expression, which was consistent with the genomic microarray data. CONCLUSIONS: BTG3 expression might contribute to CRC carcinogenesis. BTG3 knockdown might strengthen the aggressive colorectal cancer behavior.