RESUMEN
BACKGROUND: Gastric cancer is a highly prevalent cancer type and the underlying molecular mechanisms are not fully understood. Ubiquitin-specific peptidase (USP) 29 has been suggested to regulate cell fate in several types of cancer, but its potential role in gastric carcinogenesis remains unclear. METHODS: The expression of USP29 in normal and gastric cancer tissues was analyzed by bioinformatics analysis, immunohistochemistry and immunoblot. Gene overexpression, CRISPR-Cas9 technology, RNAi, and Usp29 knockout mice were used to investigate the roles of USP29 in cell culture, xenograft, and benzo[a]pyrene (BaP)-induced gastric carcinogenesis models. We then delineated the underlying mechanisms using mass spectrometry, co-immunoprecipitation (Co-IP), immunoblot, ubiquitination assay, chromatin immunoprecipitation (ChIP), quantitative real-time PCR (qRT-PCR), and luciferase assays. RESULTS: In this study, we found that USP29 expression was significantly upregulated in gastric cancers and associated with poor patient survival. Ectopic expression of USP29 promoted, while depletion suppressed the tumor growth in vitro and in vivo mouse model. Mechanistically, transcription factor far upstream element binding protein 1 (FUBP1) directly activates USP29 gene transcription, which then interacts with and stabilizes aurora kinase B (AURKB) by suppressing K48-linked polyubiquitination, constituting a FUBP1-USP29-AURKB regulatory axis that medicates the oncogenic role of USP29. Importantly, systemic knockout of Usp29 in mice not only significantly decreased the BaP-induced carcinogenesis but also suppressed the Aurkb level in forestomach tissues. CONCLUSIONS: These findings uncovered a novel FUBP1-USP29-AURKB regulatory axis that may play important roles in gastric carcinogenesis and tumor progression, and suggested that USP29 may become a promising drug target for cancer therapy.
RESUMEN
Hydrogel microspheres are biocompatible materials widely used in biological and medical fields. Emulsification and stirring are the commonly used methods to prepare hydrogels. However, the size distribution is considerably wide, the monodispersity and the mechanical intensity are poor, and the stable operation conditions are comparatively narrow to meet some sophisticated applications. In this paper, a T-shaped stepwise microchannel combined with a simple side microchannel structure is developed to explore the liquid-liquid dispersion mechanism, interfacial evolution behavior, satellite droplet formation mechanism and separation, and the eventual successful synthesis of dextran hydrogel microspheres. The effect of the operation parameters on droplet and microsphere size is comprehensively studied. The flow pattern and the stable operation condition range are given, and mathematical prediction models are developed under three different flow regimes for droplet size prediction. Based on the stable operating conditions, a microdroplet-based method combined with UV light curing is developed to synthesize the dextran hydrogel microsphere. The highly uniform and monodispersed dextran microspheres with good mechanical intensity are synthesized in the developed microfluidic platform. The size of the microsphere could be tuned from 50 to 300 µm with a capillary number in the range of 0.006-0.742. This work not only provides a facile method for functional polymeric microsphere preparation but also offers important design guidelines for the development of a robust microreactor.
RESUMEN
Reversible protein ubiquitination is a key process for maintaining cellular homeostasis. Deubiquitinases, which can cleave ubiquitin from substrate proteins, have been reported to be deeply involved in disease progression ranging from oncology to neurological diseases. The human genome encodes approximately 100 deubiquitinases, most of which are poorly characterized. One of the well-characterized deubiquitases is ubiquitin-specific protease 29 (USP29), which is often upregulated in pathological tissues and plays important roles in the progression of different diseases. Moreover, several studies have shown that deletion of Usp29 in mice does not cause visible growth and developmental defects, indicating that USP29 may be an ideal therapeutic target. In this review, we provide a comprehensive summary of the important roles and regulatory mechanisms of USP29 in cancer and other diseases, which may help us better understand its biological functions and improve future studies to construct suitable USP29-targeted therapy systems.
Asunto(s)
Neoplasias , Humanos , Animales , Ratones , Neoplasias/genética , Genoma Humano , Ubiquitina , Ubiquitinación , Enzimas Desubicuitinizantes , Proteasas Ubiquitina-Específicas/genéticaRESUMEN
BACKGROUND: Emerging evidence have revealed that circRNAs exert important biological effects in the development and progression of various diseases, including cancer. Our study aimed to elaborated the biological effects of hsa-circ_0003570 in hepatocellular carcinoma (HCC) development at the molecular level. RESULTS: The results of functional experiments showed that knockdown of circ_0003570 induced HCC cell growth, migration and invasion, whereas overexpression of circ_0003570 presented the opposite effects. In vivo experiments, xenograft tumors grown from circ-overexpressed cells had smaller tumor volume and weight than the control group. Further investigations suggested that circ_0003570 may function as a competing endogenous RNA via competitively binding miR-182-5p and thereby regulating the repression of downstream target gene STARD13, which were demonstrated by dual luciferase reporter assay and functional rescued experiments. CONCLUSIONS: Taken together, circ_0003570 suppresses the development of HCC by modulating miR-182-5p/STARD13 axis.
RESUMEN
BACKGROUND: Poorly differentiated colorectal cancers are more aggressive. Metabolism reprogramming is a significant hallmark in cancer, and aerobic glycolysis is common. However, how cancer cells reprogramming glucose metabolism contributes to cell differentiation was largely unknown. Previous studies have reported that tumor suppressor NDRG2 could promote colorectal cancers differentiation. AIMS: This study aims to demonstrate that NDRG2 promotes the differentiation of colorectal cancers, potentially through the inhibition of aerobic glycolysis via TXNIP induction. METHODS: Western blotting, qRT-PCR and immunohistochemical staining were used to detect the expression of related molecules. MTT assay was used to reflect cell viability and proliferation. Immunofluorescent assay was performed to identify the expression and distribution of molecules. Luciferase analysis and CHIP assays were used to investigate the mechanism. Bioinformatic analysis was performed to predict the relevance. RESULTS: In colorectal cancers, NDRG2 could inhibit cell proliferation, reduce glucose uptake and decrease expression of key glycolysis enzymes. Upregulated NDRG2 is associated with differentiated cancer. However, deletion of TXNIP, a classic glucose metabolism inhibitor, could obviously alter the function of NDRG2 in differentiation, glucose uptake, expression of key glycolysis enzymes and proliferation. Mechanistically, high glucose flux promotes the activity of TXNIP promoter. And NDRG2 promotes the occupancy of transcription factor Mondo A on TXNIP promoter, predominantly through the suppression of c-myc, which could complete with Mondo A binding to TXNIP promoter. In clinical samples, high expression of TXNIP indicates good prognosis and outcome. CONCLUSIONS: NDRG2-dependent induction of TXNIP is critical for the aerobic glycolysis during colorectal cancers differentiation.
Asunto(s)
Proteínas Portadoras , Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , Proteínas Supresoras de Tumor , Proteínas Portadoras/genética , Diferenciación Celular , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/patología , Glucosa/metabolismo , Glucólisis , Humanos , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: Due to the precise vaporization of the novel 450 nm blue diode laser in soft tissues (i.e., bladder and colon) in our previous studies, porcine stomach tissues were applied here to certify its efficacy in endoscopic mucosal resection (ESR)/endoscopic submucosal dissection (ESD) for hypothetical lesions ex vivo and in vivo. MATERIALS AND METHODS: In an ex vivo study of ESR, 20 pieces of tissues (8 cm × 6 cm) from 7 fresh stomachs after spraying saline were vaporized with a three-dimensional scanning system using the blue diode laser at a maximum of 30 W, a different treatment speed and working distance (WD). In ex vivo ESD, 18 pieces of tissues from 6 fresh stomachs were used and the same laser parameters were used to perform the procedure. The depth, width, and coagulation of the laser vaporization were measured. Furthermore, the large scales (2.0 cm × 1.5 cm) for 18 hypothetical lesions of the gastric mucosa and submucosa of the 6 fresh stomachs were also resected with a modified flexible endoscope. In vivo, six hypothetical lesions of six porcine were vaporized by the novel blue laser, and the resultant lesions at the acute and chronic stages were assessed by the naked eye and hematoxylin and eosin staining. RESULTS: In the contact mode, more tissue was vaporized, and the thickness of the coagulation was stable when the WD was 0-2 mm, whose value varied from 0.33 to 1.73 mm. In the gastroscopy model, the mean thickness of coagulation from the mucosa was 0.67 mm, and a significant carbonization zone was not observed. In vivo, the laser beam could accurately act on the hypothetical target. No bleeding and clear vision were present in the procedure. After 3 weeks, tissue healing was well recovered after laser coagulation, resection, and submucosal dissection. CONCLUSIONS: In the present study, the novel 450 nm blue diode laser exhibited ideal vaporization and thinner coagulation thickness in the porcine stomach, which indicated that it could be alternately used as a new device for stomach lesions.
Asunto(s)
Resección Endoscópica de la Mucosa , Animales , Endoscopios , Mucosa Gástrica , Láseres de Semiconductores , Estómago , PorcinosRESUMEN
OBJECTIVES: Surgical resection is recommended for treating gastrointestinal stromal tumors (GISTs) >20 mm. With the emergence of minimally invasive concept, endoscopic techniques are involved. We introduce a new endoscopic technique termed as endoscopic submucosal resection preserving serosa (ESR-PS) for GISTs ≥ 20 mm with mucosal erosion or ulcer locating at deep muscularis propria. METHODS: This retrospective cohort study collected patients at the endoscopy center of the First Affiliated Hospital of Xi'an Jiaotong University between January 2019 and 2021. The primary outcome was adverse events including pneumoperitoneum, fever and delayed bleeding. The second outcomes included en bloc resection complete en bloc resection, recurrence, operation time, hospital stay time after ESR-PS, postoperative indwelling gastric tube and postoperative eating. RESULTS: A total of 49 patients were included. One patient experienced pneumoperitoneum. All patients did not experienced fever or delayed bleeding after ESR-PS. All cases achieved en bloc resection and complete en bloc resection. The median operation time of ESR-PS was 49 min (range 43-71). The indwelling gastric tubes were given to patients for 1 d or 2 d after ESR-PS. After 1 d or 2 d, patients started oral diet, staying in hospital for a median of 4 (3-4) d after ESR-PS. During the follow-up time, recurrence was not found. CONCLUSIONS: Our study indicated that ESR-PS is a feasible, effective and safe technique for GISTs ≥ 20mm with mucosal erosion or ulcer locating at deep muscularis propria. More large, multi-center and prospective studies are needed to evaluate the effectiveness and safety of ESR-PS in the future.
Asunto(s)
Resección Endoscópica de la Mucosa , Tumores del Estroma Gastrointestinal , Neoplasias Gástricas , Mucosa Gástrica , Tumores del Estroma Gastrointestinal/cirugía , Gastroscopía , Humanos , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Laparoscopic localization of gastrointestinal tumors has long been an important objective. This study aimed to evaluate the clinical application of a magnetic tracer technique during laparoscopic-assisted surgery. METHODS: Fifty-seven patients with gastrointestinal tumors, who voluntarily underwent endoscopic marking between May 2019 and May 2020, were enrolled. A magnetic ring was clamped onto tissues adjacent to the lesion and released during preoperative endoscopy. Then, another magnet ring or laparoscopic instrument was delivered to the wall of the digestive tract contralateral to the lesion and attracted, thus achieving accurate intraoperative localization. Observational evaluation included data regarding preoperative marking, intraoperative localization, operation, and safety. RESULTS: Fifty-six of the 57 (98.2%) patients with gastric tumors (n = 35), duodenal tumors (n = 1), and colorectal tumors (n = 20), successfully underwent marking, localization, and resection. The mean margins of proximal and distal resection of colorectal tumors were 106 and 78 mm, respectively. The mean (± SD) duration of endoscopic marking and laparoscopic localization for gastric/duodenal and colorectal tumors were 5.3 ± 0.3, 1.0 ± 0.1, 5.5 ± 0.4, and 1.0 ± 0.1 min, respectively. No complications occurred in 56 of the 57 patients. CONCLUSIONS: The magnetic tracer technique demonstrated promising potential as a localization method for gastrointestinal tumors, with superior safety, effectiveness, rapidity, and convenience.
Asunto(s)
Neoplasias Colorrectales , Neoplasias Gastrointestinales , Laparoscopía , Neoplasias Gástricas , Neoplasias Colorrectales/cirugía , Neoplasias Gastrointestinales/cirugía , Humanos , Laparoscopía/métodos , Fenómenos Magnéticos , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND AND AIM: Most patients with gastric tumors and precancerous lesions are asymptomatic, which often results in delayed diagnosis and treatment. Compared with conventional gastroscopy and capsule endoscopy, magnetic-controlled capsule endoscopy is a non-invasive, effective, and cost-efficient diagnostic modality for gastric examination. We retrospectively investigated magnetic-controlled capsule endoscopy as a screening tool for gastrointestinal lesions (particularly gastric tumors and precancerous lesions) in asymptomatic individuals. METHODS: In this retrospective study, 1757 patients who voluntarily underwent magnetic-controlled capsule endoscopy between January and December 2019 at nine medical centers across Shaanxi province based on strict inclusion and exclusion criteria were enrolled. The primary outcomes were gastric tumor and precancerous lesion detection rates and procedural safety. RESULTS: The upper and lower gastrointestinal lesion detection rates were 98.35% (1728/1757) and 21.61% (78/361), respectively; 2.28% of patients were diagnosed with gastric tumors including gastric cancer (4/1757) and submucosal tumors (36/1757). Three types of precancerous lesions were found in 591 patients (33.64%), including chronic atrophic gastritis (23.16%), gastric polyp (10.98%), and gastric ulcer (2.96%). For patients aged over 40 years, the detection rate of precancerous lesions was higher (14.36% vs 42.58%, P < 0.001). No patient was diagnosed with small intestinal cancer. No adverse events occurred. CONCLUSIONS: Magnetic-controlled capsule endoscopy could be used as a promising novel screening modality for diagnosis of gastrointestinal lesions in asymptomatic individuals, specifically gastric tumors and precancerous lesions, with the advantages of safety, non-invasiveness, effectiveness, and cost-efficiency.
Asunto(s)
Enfermedades Asintomáticas , Endoscopía Capsular/métodos , Enfermedades Gastrointestinales/diagnóstico , Magnetismo/métodos , Tamizaje Masivo/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Endoscopía Capsular/economía , Niño , China/epidemiología , Análisis Costo-Beneficio , Femenino , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/prevención & control , Humanos , Masculino , Tamizaje Masivo/economía , Persona de Mediana Edad , Estudios Retrospectivos , Seguridad , Adulto JovenRESUMEN
Metastasis is frequently occurred in end-stage GC. Nevertheless, the initiation and progression of metastasis in GC remains unclear. The transient receptor potential canonical (TRPC) has been confirmed to be crucial for metastasis in many kinds of tumors, including GC. However, the molecular mechanisms regulating TRPC1 is unclear. Therefore, we investigated the role and mechanisms of TRPC1 in GC metastasis. We first evaluated the role of TRPC1 in GC by searching the public database, and tested the expression of TRPC1 in 50 paired GC tissues by qRT-PCR and IHC assays. Then, we generated BGC-823-shTRPC1 cells and MKN-45-TRPC1 cells to investigate the effects of TRPC1 on metastasis in vitro. For the mechanism study, we applied luciferase reporter assay, RNA pull-down assay, as well as RIP assay to validate the interation of ciRS-7, miR-135a-5p and TRPC1 in GC cells. This study, we showed that TRPC1 exacerbate EMT in gastric cancer via ciRS-7/miR-135a-5p/TRPC1 axis, and target TRPC1 could be beneficial for end-stage GC patients.
Asunto(s)
MicroARNs/genética , MicroARNs/metabolismo , Metástasis de la Neoplasia/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Canales Catiónicos TRPC/genética , Canales Catiónicos TRPC/metabolismo , Regiones no Traducidas 3' , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis de la Neoplasia/patología , Neoplasias Gástricas/patologíaRESUMEN
AIM: Helicobacter pylori infection has been established as a definite risk factor for gastric cancer. However, the consequence of H. pylori eradication on the progression of gastroesophageal reflux disease (GERD) remains controversial. The purpose of our study was to investigate the relationship between H. pylori eradication and the development of GERD. METHODS: A comprehensive, English literature search was performed from January 1990 to April 2019. Only randomized controlled trials (RCT) that evaluated the effect of H. pylori eradication on GERD were included. Meta-analysis of pooled OR was performed using Review Manger 5.1.7. RESULTS: Seventeen articles with 6,889 subjects (intention-to-treat) that fulfilled the inclusion criteria were finally included in the analysis. Of them, 8 RCTs have the similar study design and inclusion criterion, which included patients with H. pylori infection but without GERD at baseline. The OR for the development of erosive GERD after H. pylori eradication was 1.67 (95% CI 1.12-2.48, p = 0.01). The OR for the development of GERD-related symptoms after H. pylori eradication in eradication group compared with control group was 1.04 (95% CI 0.84-1.29, p = 0.71). In addition, 9 RCTs included patients with both baseline H. pylori infection and GERD. The OR for the healing rates and relapse rates after H. pylori eradication in the H. pylori eradication group vs. control group was 0.92 (95% CI 0.47-1.82, p = 0.82) and 1.12 (95% CI 0.60-2.09, p = 0.71), respectively. CONCLUSIONS: Our meta-analyses showed H. pylori eradication may lead to the development of new erosive GERD. However, eradication of H. pylori may affect neither the healing rates nor relapse rates of preexisting GERD.
Asunto(s)
Reflujo Gastroesofágico/complicaciones , Infecciones por Helicobacter/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios de Casos y Controles , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Humanos , Factores de RiesgoRESUMEN
Increasing studies showed that long noncoding RNAs (lncRNAs) had crucial regulatory roles in various tumors, including gastric cancer (GC). Recent studies demonstrated that lncRNA nicotinamide nucleotide transhydrogenase-antisense RNA1 (NNT-AS1) played an important role in several tumors. However, the role and expression of NNT-AS1 in GC progression remain unknown. In our study, we indicated that NNT-AS1 expression was upregulated in GC samples compared with the nontumor tissues. We also showed that NNT-AS1 expression was upregulated in the GC cell lines. Ectopic expression of NNT-AS1 promoted GC cell line HGC-27 cell proliferation, cell cycle progression, and invasion. In addition, we showed that NNT-AS1 acted as a sponge competing endogenous RNA for microRNA-363 (miR-363), which was downregulated in the GC samples and cell lines. miR-363 expression was negatively related with NNT-AS1 expression in GC samples. Upregulated expression of miR-363 suppressed GC cell growth, cycle, and invasion. Furthermore, we reported that elevated expression of NNT-AS1 promoted GC cell proliferation, cycle, and invasion partly by suppressing miR-363 expression. These results indicated that lncRNA NNT-AS1 acted as an oncogene in the development of GC partly by inhibiting miR-363 expression.
Asunto(s)
Biomarcadores de Tumor/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , NADP Transhidrogenasa AB-Específica/antagonistas & inhibidores , ARN Largo no Codificante/genética , Neoplasias Gástricas/patología , Apoptosis , Ciclo Celular , Humanos , Proteínas Mitocondriales/antagonistas & inhibidores , Proteínas Mitocondriales/genética , NADP Transhidrogenasa AB-Específica/genética , Invasividad Neoplásica , Pronóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorales CultivadasRESUMEN
BACKGROUND AND AIM: Even though endoscopic submucosal dissection is an important endoscopic resection technique for gastrointestinal neoplasms, there are chances that postoperative esophageal stricture might take place as a side effect. Steroid applications were reported to be effective for the prevention of stricture formation. Therefore, this study aims to evaluate the efficacy and safety of different steroid applications. METHODS: Eligible studies published on PubMed, the Cochrane Library, Embase, Web of Science, and Chinese Biomedical Literature Database before August 2018 were reviewed. The preventions were divided as placebo/no treatment, long-term oral steroid (LOS), median-term oral steroid, short-term oral steroid, single-dose steroid injection, multiple-dose steroid injection, topical superficial steroid, steroid injection combined with oral steroid, and preemptive endoscopic balloon dilatation. The primary outcomes were postoperative esophageal stricture rate and endoscopic balloon dilatation sessions required. Complications were also analyzed. RESULTS: A total of 19 studies were included. The network meta-results illustrated that compared with the placebo, all kinds of steroid interventions were associated with lower rates of postoperative esophageal stenosis and less number of endoscopic balloon dilatation sessions. Moreover, combined therapy was no better than single regimen therapy. No significant differences between various steroid applications in the incidence of complications were spotted during this study. Based on the results of the network and clustered ranking, LOS might be the superior prevention for postoperative stricture with satisfying efficacy. CONCLUSION: The present study showed that LOS appears to be the optimal prevention method for postoperative stricture formation.
Asunto(s)
Resección Endoscópica de la Mucosa/efectos adversos , Estenosis Esofágica/prevención & control , Complicaciones Posoperatorias/prevención & control , Esteroides/administración & dosificación , Administración Oral , Humanos , Inyecciones , Metaanálisis en RedRESUMEN
BACKGROUND: MicroRNAs are classes of endogenous noncoding RNAs that play a substantial role in tumor processes through regulating the targets at posttranscriptional level. However, little is known about the upstream transcription regulatory mechanism although it is a prerequisite for investigation of its aberrant expression and function. AIMS: This report evaluates miR-106a's direct transcriptional factor from upstream level to in depth elucidate their communication in gastric cancer development. METHODS: Gastric cancer tissues were collected to analyze the miR-106a expression using real-time PCR methods. The combination of Kruppel (or Krüppel)-like factor 4 (KLF4) to miR-106a promoter was testified through bioinformatics followed by construction of luciferase reporter plasmid and chromatin immunoprecipitation assay. Functional experiments and mouse models for evaluating cell growth and metastasis were conducted to observe the biological effect of KLF4 on miR-106a. The interplay between KLF4 and miR-106a was tested with Wnt activator and confirmed in clinical specimens. RESULTS: The up-regulated miR-106a linked to gastric cancer metastasis and epithelial-mesenchymal transition. UCSC and JASPAR predicted the promoter sequence of miR-106a and its binding site with transcriptional factor KLF4. Construction of reporter gene further verified their direct combination at upstream level. Moreover, the inhibitory effect of KLF4 on the phenotype of gastric cancer cells could be restored by miR-106a. CHIR-induced experiment and clinical specimens confirmed the negative regulation of KLF4 on miR-106a. CONCLUSIONS: Our findings provide novel direct insights into molecular mechanisms for interaction of KLF4 and miR-106a at upstream level and new ways for clinical application of KLF4-miR-106a axis in advanced gastric cancer metastasis.
Asunto(s)
Factores de Transcripción de Tipo Kruppel/genética , MicroARNs/genética , Neoplasias Gástricas , Línea Celular Tumoral , Proliferación Celular , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Factor 4 Similar a Kruppel , Metástasis de la Neoplasia/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Factores de Transcripción , Regulación hacia ArribaRESUMEN
MicroRNAs (miRNAs) are small, non-coding RNAs that modulate development, cell proliferation, and apoptosis. The deregulated expression of microRNAs is found in carcinogenesis including gastric cancer (GC). In this study, we showed that the expression levels of miR-488 were downregulated in GC tissues compared to in non-tumor tissues. In addition, the expression of miR-488 was also lower in GC cell lines in contrast with the gastric epithelial cell line (GES). In addition, the expression level of miR-488 was negatively correlated with the TNM stage in GC patients, and lower miR-488 expression was found in tumors with advanced TNM stage. The ectopic expression of miR-488 suppressed the GC cell proliferation, cell cycle, colony information, and migration. PAX6 was identified as a direct target gene of miR-488 in HGC-27. Moreover, we found that the expression level of PAX6 was upregulated in the GC tissues compared with the non-tumor tissues. The PAX6 expression level was correlated with the cancer TNM stage, and higher PAX6 expression was found in tumors with advanced TNM stage. Furthermore, there was an inverse correlation between PAX6 and miR-488 expression levels in GC tissues. Therefore, these studies demonstrated that miR-488 might act as a tumor suppressor miRNA in the development of GC.
Asunto(s)
Biomarcadores de Tumor/genética , Movimiento Celular , Proliferación Celular , Genes Supresores de Tumor , MicroARNs/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Apoptosis , Western Blotting , Mucosa Gástrica/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estómago/patología , Células Tumorales CultivadasRESUMEN
P-Glycoprotein-mediated multidrug resistance is a frequent event during chemotherapy and a key obstacle for bladder cancer therapy. Search for strategies to reverse multidrug resistance is a promising approach to improve the management of bladder cancer. In the present study, we reported a novel P-glycoprotein-mediated multidrug resistant cell model 253J/DOX, which was generated from human bladder cancer 253J cell line. Furthermore, we found that the multidrug resistant phenotype of 253J/DOX cells could be overcome by sinomenine, an alkaloid derived from the stem of Sinomenium acutum. Mechanistically, the chemosensitive effect by sinomenine was mediated by down-regulating P-glycoprotein expression, as well as triggering apoptotic pathways. The chemosensitive effect of sinomenine may make it a prime candidate agent to target bladder cancer.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Morfinanos/farmacología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Western Blotting , Línea Celular Tumoral , Colorantes , Resistencia a Múltiples Medicamentos , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Colorantes Fluorescentes , Humanos , Indicadores y Reactivos , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Rodamina 123 , Sales de Tetrazolio , TiazolesRESUMEN
Gastric cancer remains a highly prevalent malignancy worldwide with its molecular features poorly understood. To gain full insight into its genetic landscape, we performed whole-transcriptome sequencing on human tumors and adjacent non-tumors to predict the function of microRNA, long coding RNA, circular RNA, and mRNA, as well as estimate their correlation with gastric cancer characteristics through construction of ceRNA, WGCNA and PPI network. Functional enrichment analysis annotated nucleic acid binding, enzyme activity and binding related to differentially expressed miRNAs (dif-miRNAs); energy binding and enzyme binding related to dif-lncRNAs; protein binding and enzyme activity related to dif-circRNAs; protein digestion and absorption related to dif-mRNAs. The expression of key miR-135a-5p, lncRNAs-MSTRG.48856.1, ENST00000569981, MSTRG.22826.1, ENST00000564492, circRNAs-CCSER2, FNDC3B, CORO1C, FAM214A were validated by real-time PCR. The ceRNA network filtered 14 miRNAs, 30 lncRNAs, and 6 mRNA in the lncRNA-ceRNA axis and 8 miRNAs, 9 circRNAs, and 3 mRNA in the circRNA-ceRNA axis. Genes involved in ceRNA were annotated to be closely related to tumor material synthesis and metabolism. The WGCNA network filtered gene clusters related to TNM traits and extracted the hub genes CLDN10, CD177, newGene_35523, newGene_51201, CEACAM7, and newGene_46634. These genes were associated with cell proliferation, metabolism, and enzyme activity regulation. The PPI network analyzed the stable interaction relationships of the hub genes. Our research provides a valuable resource for understanding the molecular mechanisms of gastric cancer from the perspective of tumor metabolism.
Asunto(s)
MicroARNs , ARN Largo no Codificante , Neoplasias Gástricas , Humanos , MicroARNs/genética , ARN Circular/genética , Neoplasias Gástricas/genética , ARN Largo no Codificante/genética , Biología Computacional , ARN Mensajero , Redes Reguladoras de GenesRESUMEN
BACKGROUND: Endoscopic submucosal dissection (ESD) has been recommended as the first-line treatment for early gastric cancer (EGC). However, poor visualization of the operative field increases both the procedure time and the risk of complications, especially for large and difficult lesions. We introduced a novel technique, magnetic anchor-guided ESD (MAG-ESD) and compared it with conventional ESD (C-ESD) for the treatment of large EGCs in terms of efficacy, safety, and advantages. METHODS: Patients with large EGCs who underwent MAG-ESD or C-ESD at the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to March 2022 were retrospectively enrolled in this study. The patients in the MAG-ESD cohort were matched to those in the C-ESD cohort using propensity score-based matching. The operation time, submucosal dissection time, complete resection status, magnetic anchor, adverse event rate, and tumor recurrence rate were evaluated. RESULTS: Twenty-two patients who underwent MAG-ESD were ultimately matched to those who underwent C-ESD. The median operation time of MAG-ESD and C-ESD was 43 minutes (IQR, 35.2-49.5) and 50.5 minutes (IQR, 42.0-76.0), respectively, among which the submucosal dissection time was 7.6 minutes (IQR, 5.2-10.4) and 14.8 minutes (IQR, 10.8-19.6), respectively. The operation time of MAG-ESD was shorter than that of C-ESD, especially the submucosal dissection time (P < .05). There was a lower incidence of adverse events associated with MAG-ESD (P < .05) when magnetic anchors were successfully placed and retrieved. CONCLUSION: MAG-ESD is feasible, effective, safe, and simple for the treatment of large EGCs at different sites and has a high anchor success rate, which could shorten the operation time and reduce the adverse event rate.
Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Estudios de Cohortes , Resultado del Tratamiento , Recurrencia Local de Neoplasia , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Fenómenos MagnéticosRESUMEN
Three-dimensional (3D) phenotyping is important for studying plant structure and function. Light detection and ranging (LiDAR) has gained prominence in 3D plant phenotyping due to its ability to collect 3D point clouds. However, organ-level branch detection remains challenging due to small targets, sparse points, and low signal-to-noise ratios. In addition, extracting biologically relevant angle traits is difficult. In this study, we developed a stratified, clustered, and growing-based algorithm (SCAG) for soybean branch detection and branch angle calculation from LiDAR data, which is heuristic, open-source, and expandable. SCAG achieved high branch detection accuracy (F-score = 0.77) and branch angle calculation accuracy (r = 0.84) when evaluated on 152 diverse soybean varieties. Meanwhile, the SCAG outperformed 2 other classic algorithms, the support vector machine (F-score = 0.53) and density-based methods (F-score = 0.55). Moreover, after applying the SCAG to 405 soybean varieties over 2 consecutive years, we quantified various 3D traits, including canopy width, height, stem length, and average angle. After data filtering, we identified novel heritable and repeatable traits for evaluating soybean density tolerance potential, such as the ratio of average angle to height and the ratio of average angle to stem length, which showed greater potential than the well-known ratio of canopy width to height trait. Our work demonstrates remarkable advances in 3D phenotyping and plant architecture screening. The algorithm can be applied to other crops, such as maize and tomato. Our dataset, scripts, and software are public, which can further benefit the plant science community by enhancing plant architecture characterization and ideal variety selection.
RESUMEN
SERS measurements for monitoring bactericides in dairy products are highly desired for food safety problems. However, the complicated preparation process of SERS substrates greatly impedes the promotion of SERS. Here, we propose acoustofluidic one-step synthesis of Ag nanoparticles on paper substrates for SERS detection. Our method is economical, fast, simple, and eco-friendly. We adopted laser cutting to cut out appropriate paper shapes, and aldehydes were simultaneously produced at the cutting edge in the pyrolysis of cellulose by laser which were leveraged as the reducing reagent. In the synthesis, only 5 µL of Ag precursor was added to complete the reaction, and no reducing agent was used. Our recently developed acoustofluidic device was employed to intensely mix Ag+ ions and aldehydes and spread the reduced Ag nanoparticles over the substrate. The SERS substrate was fabricated in 1 step and 3 min. The standard R6G solution measurement demonstrated the excellent signal and prominent uniformity of the fabricated SERS substrates. SERS detection of the safe concentration of three bactericides, including tetracycline hydrochloride, thiabendazole, and malachite green, from food samples can be achieved using fabricated substrates. We take the least cost, time, reagents, and steps to fabricate the SERS substrate with satisfying performance. Our work has an extraodinary meaning for the green preparation and large-scale application of SERS.