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Chikungunya fever is an acute infectious disease caused by chikungunya virus (CHIKV), which is transmitted by Aedes mosquitoes. Simple, rapid, and sensitive detection of CHIKV is critical for its prevention and spread. To address this issue, we combined one-tube, reverse transcription semi-nested, multi-enzyme isothermal rapid amplification, and lateral flow dipstick strips assay to detect CHIKV RNA. The study used a 318-bp gene fragment of CHIKV NSP4 as the target of the assay. This method of amplification takes 30 min for two-step amplification at 39°C. The dilution of amplification products was added to the LFD strip with results visible to the naked eye after 10 min. The method has a sensitivity of 1 copy/µL for the detection of CHIKV RNA, which is 100-fold higher than the conventional reverse transcription-multi-enzyme isothermal rapid amplification and 10-fold higher than the reverse transcription quantitative PCR (RT-qPCR) method. In addition, the method demonstrated good specificity and a better detection rate (85.7%, 18 of 21) than RT-qPCR (80.9%, 17 of 21) in clinically confirmed patient plasma samples. Thus, the rapid CHIKV RNA assay developed in this study will be an important tool for the rapid and accurate screening of patients for chikungunya fever. IMPORTANCE: This study presents a new one-tube, reverse transcription semi-nested, multi-enzyme isothermal rapid amplification assay combined with lateral flow dipstick strips for the detection of CHIKV. This technique significantly improves sensitivity and outperforms RT-qPCR for the detection of CHIKV, especially in samples with low viral loads. It is also significantly faster than conventional RT-qPCR and does not require special equipment or a standard PCR laboratory. The combination of the isothermal amplification technology developed in this study with point-of-care molecular testing offers the potential for rapid, on-site, low-cost molecular diagnosis of CHIKV.
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PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.
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Terapia Neoadyuvante , Neoplasias del Recto , Microambiente Tumoral , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Quimioradioterapia , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Heavy metal pollution of agricultural soils, especially from cadmium (Cd) contaminationcaused serious problems in both food security and economy. Sorghum bicolor (L.) showed a great potential in phytoremediation of Cd contamination due to its fast growth, high yield and easy harvesting. However, the growth of S. bicolor plants tends to be inhibited under Cd exposure, which limited its application for Cd remediation. Plant growth-promoting rhizobacteria may enhance the Cd resistance of S. bicolor and thus improve its Cd removal efficiency. In this study, three Cd-resistant bacteria were screened based on Cd and acid tolerance and identified as Bacillus velezensis QZG6, Enterobacter cloacae QZS3 and Bacillus cereus QZS8, by 16S rRNA sequencing. Inoculation of hydroponic plants with strains QZG6, QZS3 or QZS8 significantly promoted the biomass of sorghum plants by 31.52%, 50.20% and 26.93%, respectively, compared with those of uninoculated plants under Cd exposure. The activity of SOD, POD and MDA content in Cd-stressed S. bicolor plants were reduced of 65.74%, 31.52%, and 80.91%, respectively, when inoculated with the strains QZS3. For pot experiment, strains QZG6, QZS3 and QZS8 significantly promoted the biomass of sorghum plants by 47.30%, 19.27% and 58.47%, compared with those of uninoculated plants under Cd exposure. The activity of SOD, POD and MDA content in Cd-stressed S. bicolor plants were reduced of 67.20%, 22.40%, and 40.65%, respectively, when inoculated with the strains QZS3. All these three strains significantly increased the Cd removal efficiency of the plants by 42.16% (QZG6), 18.76% (QZS3) and 21.06% (QZS8). To investigate the bacterial characteristics associated with growth promotion of S. bicolor plants, the ability on nitrogen fixation, phosphorus solubilization, siderophores production, and phytohormones production were determined. All the strains were able to fix nitrogen. Phosphorus release was observed for strains QZG6 (inorganic or organic phosphorus) and QZS3 (inorganic phosphorus). Both QZG6 and QZS8 were able to produce siderophores, while only QZG6 was positive for ACC deaminase. All the strains produced IAA, SA and GA. These results indicated that the three strains promoted the plant growth under Cd stress, probably through Cd detoxification by siderophores, as well as through growth regulation by N/P nutrient supply and phytohormone. The present study showed a great potential of the three Cd-resistant strains combined with S. bicolor plants in the remediation of Cd-polluted soils, which may provide a new insight into combining the advantages of microbes and plants to improve the remediation of Cd-contaminated soils.
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Contaminantes del Suelo , Sorghum , Cadmio/toxicidad , Cadmio/análisis , Sorghum/genética , ARN Ribosómico 16S/genética , Reguladores del Crecimiento de las Plantas , Biodegradación Ambiental , Suelo , Bacillus cereus , Sideróforos , Fósforo , Superóxido Dismutasa , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisisRESUMEN
Gastric cancer (GC) is one of the most prevalent malignancies of the digestive tract. Ginsenoside Rh1 was reported to exert effects on GC. The current study set out to explore the mechanism underlying Ginsenoside Rh1 effects on GC. With oxaliplatin (OXA) serving as the positive control, human GC cells AGS were treated with 0, 10, 25, 50, 74, or 100 µM of ginsenoside Rh1 for 48 h. Proliferation, migration, invasion, and apoptosis were subsequently assessed by means of MTT, scratch test, Transwell, and TUNEL, respectively. AGS cells were further jointly treated with Rh1 and the TGF-ß/Smad pathway activator Kartogenin, followed by detection of TGF-ß/Smad pathway effects on AGS biological behaviours. Moreover, TGF-ß/Smad pathway activation was detected with a Western blot assay. Furthermore, xenograft tumour models were established and tumour growth was recorded. Ki-67 expression patterns and apoptosis were detected with immunohistochemistry and TUNEL, respectively. In vitro, Ginsenoside Rh1 repressed AGS cell proliferation, migration, and invasion, and further promoted apoptosis, with a concentration of 50 µM Rh1 exerting the equivalent effects as OXA. In vivo, Ginsenoside Rh1 inhibited GC proliferation and induced tumour cell apoptosis. Mechanistically, Ginsenoside Rh1 reduced TGF-ß1 and TGF-ß2 levels and Smad2 and Smad3 phosphorylation levels. Collectively, our findings highlighted that ginsenoside Rh1 inhibited GC cell growth and tumour growth in xenograft tumour models via inhibition of the TGF-ß/Smad pathway.
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Ginsenósidos , Neoplasias Gástricas , Animales , Humanos , Ratones , Movimiento Celular , Ginsenósidos/farmacología , Ratones Desnudos , Transducción de Señal , Neoplasias Gástricas/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Proteínas Smad/metabolismoRESUMEN
Protein kinase RNA-like Endoplasmic Reticulum Kinase (PERK) is an endoplasmic reticulum stress sensor that possesses pro-survival capability and contributes to cell homeostasis and survival. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) has been recognized as a stem cell marker in intestinal epithelial cells. To determine whether PERK modulates the proliferation of intestinal stem cells, we investigated the effects of PERK knock-down on intestinal Lgr5-positive stem cells in mice. Lgr5-EGFP knock-in mice were fed with lentivirus-PERK shRNA twice a day for three days. Isolated intestinal Lgr5-positive stem cells were treated with lentivirus-PERK shRNA. The number of Lgr5-positive cells, the proliferation and apoptotic indices, several biomarkers for proliferation and differentiation, and Akt expression in intestinal stem cells were detected in vivo, in vitro and in two intestinal epithelial injury models caused by radiotherapy and sepsis. PERK knock-down could significantly diminish the number and proliferation of Lgr5-positive cells, induce the low expression of several proliferation markers and the high expression of several differentiation markers in Lgr5-positive cells, enhance the apoptotic Lgr5-positive cells, and reduce the Akt expression in intestinal Lgr5-positive stem cells. Similar results were observed in radiotherapy- and sepsis-induced intestinal injuries. Moreover, PERK inhibition markedly decreased the survival of mice in response to radiation and sepsis. These results suggest a critical role for PERK in the proliferation and survival of intestinal stem cells in mice.
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Proliferación Celular/genética , Receptores Acoplados a Proteínas G/genética , Células Madre/metabolismo , eIF-2 Quinasa/genética , Animales , Apoptosis/genética , Diferenciación Celular/genética , Linaje de la Célula/genética , Retículo Endoplásmico/genética , Células Epiteliales/citología , Células Epiteliales/metabolismo , Mucosa Intestinal/citología , Mucosa Intestinal/crecimiento & desarrollo , Intestinos/citología , Intestinos/crecimiento & desarrollo , Lentivirus/genética , Ratones , Células Madre/citologíaRESUMEN
We aimed to evaluate the clinical response to platinum-based chemotherapy and treatment outcome of gastric cancer patients in the present of ERCC1, ERCC2, NBN, RAD51, and XRCC3 gene polymorphisms. A number of 415 patients of gastric cancer that received platinum-based chemotherapy were enrolled in the present study. The presence of ERCC1 rs11615 and rs2298881, ERCC2 rs1799793 and rs13181, NBN rs1805794, rs709816, and RAD51 rs1801321 and XRCC3 rs1799794 were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Conditional regression analysis identified that CC genotype of ERCC1 rs11615 and AA genotype of ERCC2 rs1799793 was associated with a better response to chemotherapy in gastric cancer patients, and the odds ratio (ORs)(95% confidence interval (CI)) were 2.70(1.33-5.70) and 3.12(1.52-6.84), respectively. By the Cox analysis, the CC genotype of ERCC1 rs11615, AA genotype of ERCC2 rs1799793, and CC genotype of NBN rs1805794 were significantly associated with a longer overall survival (OS) of gastric cancer. In conclusion, our results suggest that ERCC1 rs11615, ERCC2 rs1799793, and NBN rs1805794 polymorphisms in the DNA repair pathways may influence the response to chemotherapy and OS of gastric cancer.
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Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Proteínas Nucleares/genética , Recombinasa Rad51/genética , Neoplasias Gástricas/genética , Proteína de la Xerodermia Pigmentosa del Grupo D/genética , Adulto , Anciano , Reparación del ADN/efectos de los fármacos , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Platino (Metal)/uso terapéutico , Polimorfismo Genético , Polimorfismo de Nucleótido Simple/genética , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Análisis de SupervivenciaRESUMEN
OBJECTIVE: The aim of this study is to investigate the clinicopathologic significance and potential role of metastasis-associated in colon cancer-1 (MACC1) in the progression of cervical cancer. METHODS: MACC1 expression was examined in cervical cancer cell lines, 6 matched cervical cancer tissues, and adjacent noncancerous tissues using Western blotting and real-time reverse transcriptase polymerase chain reaction. MACC1 protein expression and localization were determined in 181 paraffin-embedded archived cervical cancer samples using immunohistochemistry. Statistical analyses were applied to evaluate the clinicopathologic significance. The effects of MACC1 on cell migration, invasion, and angiogenesis were examined using migration assay, wound healing assay, 3-dimensional morphogenesis assay, and chicken chorioallantoic membrane assay. Western blotting was performed to examine the impact of MACC1 on the Akt and nuclear factor κB signaling pathways. RESULTS: Both protein and messenger RNA levels of MACC1 was up-regulated in cervical cancer cell lines and cervical cancer tissues, as compared with normal tissues. High MACC1 expression was detected in 96 (53%) of 181 of the cervical cancer tissues. In addition, high MACC1 expression correlated significantly with aggressiveness of cervical cancer, including International Federation of Gynecology and Obstetric stage (P = 0.001), pelvic lymph node metastasis (P = 0.004), recurrence (P = 0.037), and poor survival (P = 0.001). Moreover, enforced expression of MACC1 in cervical cancer cell lines significantly enhanced cell migration, invasion, and angiogenesis. Conversely, knockdown of MACC1 caused an inhibition of cell migration, invasion, and angiogenesis. Up-regulation of MACC1 increased, but knockdown of MACC1 decreased the expression of matrix metalloproteinase-2 and matrix metalloproteinase-9. Furthermore, enforced expression of MACC1 could enhance, but knockdown of MACC1 could reduce AKT and nuclear factor κB pathway activity. CONCLUSIONS: Our findings suggest that MACC1 protein, as a valuable marker of cervical cancer prognosis, plays an important role in the progression of human cervical cancer cells.
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Adenocarcinoma/patología , Carcinoma de Células Escamosas/patología , Regulación Neoplásica de la Expresión Génica , Neovascularización Patológica , Factores de Transcripción/fisiología , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/genética , Biomarcadores de Tumor/fisiología , Western Blotting , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/genética , Movimiento Celular , Proliferación Celular , Membrana Corioalantoides/metabolismo , Femenino , Humanos , Técnicas para Inmunoenzimas , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Tasa de Supervivencia , Transactivadores , Células Tumorales Cultivadas , Neoplasias del Cuello Uterino/irrigación sanguínea , Neoplasias del Cuello Uterino/genéticaRESUMEN
The rationality of a fuzzy choice function is a hot research topic in the study of fuzzy choice functions. In this paper, two common fuzzy sets are studied and analyzed in the framework of the Banerjee choice function. The complete rationality and bounded rationality of fuzzy choice functions are defined based on the two fuzzy sets. An assumption is presented to study the fuzzy choice function, and especially the fuzzy choice function with bounded rationality is studied combined with some rationality conditions. Results show that the fuzzy choice function with bounded rationality also satisfies some important rationality conditions, but not vice versa. The research gives supplements to the investigation in the framework of the Banerjee choice function.
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Algoritmos , Inteligencia Artificial , Técnicas de Apoyo para la Decisión , Lógica Difusa , Conducta de Elección , Humanos , Reproducibilidad de los ResultadosRESUMEN
There are many studies on specific macromolecules and their contributions to tissue repair. Macromolecules have supporting and protective effects in organisms and can help regrow, reshape, and promote self-repair and regeneration of damaged tissues. Macromolecules, such as proteins, nucleic acids, and polysaccharides, can be constructed into hydrogels for the preparation of slow-release drug agents, carriers for cell culture, and platforms for gene delivery. Hydrogels and microspheres are fabricated by chemical crosslinking or mixed co-deposition often used as scaffolds, drug carriers, or cell culture matrix, provide proper mechanical support and nutrient delivery, a well-conditioned environment that to promote the regeneration and repair of damaged tissues. This review provides a comprehensive overview of recent developments in the construction of macromolecules into hydrogels and microspheres based on the proteins, nucleic acids, polysaccharides and other polymer and their application in tissue repair. We then discuss the latest research trends regarding the advantages and disadvantages of these composites in repair tissue. Further, we examine the applications of microspheres/hydrogels in different tissue repairs, such as skin tissue, cartilage, tumor tissue, synovial, nerve tissue, and cardiac repair. The review closes by highlighting the challenges and prospects of microspheres/hydrogels composites.
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Hidrogeles , Ácidos Nucleicos , Microesferas , Hidrogeles/química , Preparaciones de Acción Retardada , Polisacáridos , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
Objective: Gastric cancer (GC) remains a prevailing threat to life. Baicalein exhibits anti-cancer properties. This study estimated the mechanism of baicalein in GC cell apoptosis by mediating endoplasmic reticulum stress (ERS) through the PI3K/AKT pathway. Methods: After treatment with different concentrations of baicalein, GC cell (HGC-27 and AGS) viability was detected by MTT assay. AGS cells more sensitive to baicalein treatment were selected as study subjects. The IC50 of baicalein on AGS cells was determined. Colony formation, cell cycle, and apoptosis were detected using crystal violet staining and flow cytometry. Levels of ERS-related and BTG3/PI3K/AKT pathway-related proteins were determined by Western blot. Intracellular Ca2+ level was measured using Fluo-3 AM fluorescence working solution. GC mouse models were established by subcutaneously injecting AGS cells into the right rib and were intragastrically administrated with baicalein. Tumor volume and weight were recorded. Expression of Ki67 in tumor tissues and positive expression of apoptotic cells were detected by immunohistochemistry and TUNEL staining. Results: Baicalein inhibited cell proliferation and induced G0/G1 arrest and apoptosis by regulating the cell cycle, and triggered ERS in GC cells. Baicalein impeded the PI3K/AKT pathway by activating BTG3, thereby triggering ERS and inducing apoptosis. BTG3 inhibition reversed baicalein-induced apoptosis and ERS. Baicalein regulated GC cells in a concentration-dependent manner. Moreover, in xenograft mice, baicalein prevented tumor growth, decreased Ki67-positive cells, activated BTG3, and inhibited the PI3K/AKT pathway, thus activating ERS and increasing apoptotic cells. Conclusion: Baicalein facilitates GC cell apoptosis by triggering ERS via repression of the PI3K/AKT pathway.
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The purpose of this research is to investigate the effect of tanshinone IIA, an extract of the Chinese medicine Que Xie Hua Yu Tang, on uric acid nephropathy (UAN) and to elucidate the underlying mechanisms. UAN rat model was established. Fifty UAN rats were randomly allocated into 5 groups: adenine-treated group, allopurinol-treated group, and low/middle/high dose of tanshinone IIA-treated groups. Meanwhile, another 10 rats were used as normal controls. Serum uric acid (UA), blood urea nitrogen (BUN), serum creatinine (Scr), MCP-1, and IL-1ß levels were measured. Histological staining was performed. Comparison between the adenine group and treatment (allopurinol and tanshinone IIA) groups showed compound treatment could attenuate the inflammation status of the kidneys and decrease serum UA levels. Among different kinds of medicine, tanshinone IIA had similar effects as allopurinol and exerted anti-inflammatory and renal protective effect in a dose-dependent manner. Furthermore, we found tanshinone IIA alone could also inhibit urate-induced MCP-1 and IL-1ß overexpression both in vivo and in vitro, accompanied with inhibition of NF-κB translocation from cytosome to nucleus. Tanshinone IIA could protect rats from uric acid-induced kidney damage, probably by attenuating renal inflammatory status.
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Abietanos/farmacología , Enfermedades Renales/tratamiento farmacológico , FN-kappa B/antagonistas & inhibidores , Ácido Úrico/sangre , Animales , Nitrógeno de la Urea Sanguínea , Quimiocina CCL2/sangre , Creatinina/sangre , Medicamentos Herbarios Chinos/farmacología , Interleucina-1beta/sangre , Interleucina-1beta/genética , Enfermedades Renales/metabolismo , Masculino , FN-kappa B/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Distant metastasis is the major contributor to the high mortality rate of colorectal cancer (CRC). To overcome the poor prognosis caused by distant metastasis, the mechanisms of CRC metastasis should be further explored. Epigenetic events are the main mediators of gene regulation and further affect tumor progression. Recent studies have found that some epigenetic enzymes are often dysregulated or mutated in multiple tumor types, which prompted us to study the roles of these enzymes in CRC metastasis. In this review, we summarized the alteration of enzymes related to various modifications, including histone modification, nonhistone modification, DNA methylation, and RNA methylation, and their epigenetic mechanisms during the progression of CRC metastasis. Existing data suggest that targeting epigenetic enzymes is a promising strategy for the treatment of CRC metastasis.
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Neoplasias Colorrectales , Neoplasias Colorrectales/patología , Metilación de ADN , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , HumanosRESUMEN
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. The identification of novel diagnostic and prognostic biomarkers for CRC is a key research imperative. Immunohistochemical analysis has revealed high expression of centromere protein K (CENPK) in CRC. However, the role of CENPK in the progression of CRC is not well characterized. AIM: To evaluate the effects of knockdown of CENPK and overexpression of Cullin 4A (CUL4A) in RKO and HCT116 cells. METHODS: Human colon cancer samples were collected and tested using a human gene expression chip. We identified CENPK as a potential oncogene for CRC based on bioinformatics analysis. In vitro experiments verified the function of this gene. We investigated the expression of CENPK in RKO and HCT116 cells using quantitative polymerase chain reaction (qPCR), western blot, and flow cytometry. The effect of short hairpin RNA (shRNA) virus-infected RKO cells on tumor growth was evaluated in vivo using quantitative analysis of fluorescence imaging. To evaluate the effects of knockdown of CENPK and overexpression of CUL4A in RKO and HCT116 cells, we performed a series of in vitro experiments, using qPCR, western blot, MTT assay, and flow cytometry. RESULTS: We demonstrated overexpression of CENPK in human colon cancer samples. CENPK was an independent risk factor in patients with CRC. The downstream genes FBX32, CUL4A, and Yes-associated protein isoform 1 were examined to evaluate the regulatory action of CENPK in RKO cells. Significantly delayed xenograft tumor emergence, slower growth rate, and lower final tumor weight and volume were observed in the CENPK short hairpin RNA virus infected group compared with the CENPK negative control group. The CENPK gene interference inhibited the proliferation of RKO cells in vitro and in vivo. The lentivirus-mediated shRNA interference of CENPK inhibited the proliferation of RKO and HCT116 colon cancer cells, with overexpression of the CUL4A. CONCLUSION: We indicated a potential role of CENPK in promoting tumor proliferation, and it may be a novel diagnostic and prognostic biomarker for CRC.
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Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Lentivirus/genética , ARN Interferente Pequeño/genética , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Línea Celular Tumoral , Neoplasias del Colon/patología , Regulación Neoplásica de la Expresión Génica , Interferencia de ARN , Movimiento Celular , Proteínas de Unión al ADN/genética , Proteínas Nucleares/metabolismoRESUMEN
The association between selenium and peptide in gastric cancer is an important research topic. The present study reported the facile synthesis of anticancer bioactive peptide (ACBP)functionalized selenium (ACBPSSe) particles with enhanced anticancer activities and a detailed mechanistic evaluation of their ability to regulate oxidative stress in vitro. Structural and chemical characterizations were revealed by ultraviolet absorption, Fourier transform infrared, Xray photoelectron, nuclear magnetic resonance carbon and hydrogen, energy dispersive Xray spectroscopy and inductively coupled plasma mass spectrometry, as well as scanning electron microscopy. Sulfhydrylation modifications of ACBP were achieved with Sacetylmercaptosuccinic anhydride via chemical absorption. After the polypeptide was modified by sulfhydrylation, the ACBP chain was linked to sulfhydryl groups by amide bonds to form the ACBPchelated selenium complex. Two gastric cancer cell lines (MKN45 and MKN74 cells) demonstrated high susceptibility to ACBPSSe particles and displayed significantly decreased proliferation ability following treatment. The results suggested that the bioactive peptidechelated selenium particles effectively inhibited the proliferation of MKN45 and MKN74 cells in vitro. The genes encoding CDK inhibitor 1A (CDKN1A), cyclin B1, thioredoxin (TXN) and mitogenactivated protein kinase kinase kinase 5 are associated with regulation of oxidative stress, while CDKN1A and TXN protect cells by decreasing oxidative stress and promoting cell growth arrest. Therefore, ACBPSSe may be an ideal chemotherapeutic candidate for human cancer, especially gastric cancer.
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Antineoplásicos/farmacología , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Péptidos/farmacología , Selenio/farmacología , Neoplasias Gástricas/genética , Antineoplásicos/química , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Ciclina B1/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ontología de Genes , Redes Reguladoras de Genes , Humanos , MAP Quinasa Quinasa Quinasa 5/genética , Péptidos/química , Selenio/química , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Tiorredoxinas/genéticaRESUMEN
OBJECTIVE: We analyzed the efficacy and pharmacological mechanisms of action of Zhen Ren Yang Zang decoction (ZRYZD) on ulcerative colitis (UC) using meta-analysis and network pharmacology. METHODS: The major databases were searched for randomized controlled trials of ZRYZD for the treatment of UC. Meta-analysis of the efficacy of ZRYZD on UC was conducted using RevMan software. Active compounds and target genes were acquired using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. UC-related genes were searched using the GeneCards database. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using RGUI. A compound-target network was constructed using Cytoscape software, and a protein-protein interaction network was constructed using the STRING database. Molecular docking simulations of the macromolecular protein targets and their corresponding ligand compounds were performed using the AutoDock tool and AutoDock Vina software. RESULTS: Meta-analysis revealed that the total effective rate and recovery rate of clinical efficacy were significantly higher in the experimental group than those of the control group. The screening identified 169 active compounds and 277 active target genes for ZRYZD. The 277 active target genes were compared with the 4,798 UC-related genes. This identified 187 active target genes of ZRYZD for UC that correlated with 138 active compounds. GO functional enrichment and KEGG pathway enrichment analyses were performed, and compound-target and protein-protein interaction networks were constructed. The key compounds and key target proteins were then selected. Finally, target protein binding with the corresponding compound was analyzed using molecular docking. CONCLUSION: Our findings demonstrate the effectiveness and safety of ZRYZD for the treatment of UC and provide insight into the underlying pharmacological mechanisms of action. Furthermore, key compounds were identified, laying the foundation for future studies on ZRYZD for the treatment of UC.
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Few cases of portal vein thrombosis secondary to gastric cancer surgery have been reported. Here we report the diagnosis and management of two such cases. Case 1: Gastric carcinoma with acute hematemesis was detected by endoscopy in the gastric body of a 48-year-old woman. Histologic examination revealed signet-ring cell carcinoma with marked invasion of the vessels and nerves. Laparoscopic partial gastrectomy and Roux-en-Y gastrogastrostomy were performed. One month after surgery, imaging examination showed the formation of thrombi in the main portal vein and the right hepatic vein. Case 2: Gastric carcinoma with pyloric obstruction was clinically diagnosed in a 66-year-old woman. Laparoscopic partial gastrectomy and Billroth Roux-en-Y gastrogastrostomy were again performed. Two months after surgery, an abdominal imaging examination detected a thrombus in the right hepatic vein. Clinicians should consider portal vein thrombosis in patients with hyperthermia combined with an abnormal increase in procalcitonin.
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Neoplasias Gástricas , Trombosis , Anciano , Femenino , Gastrectomía , Humanos , Persona de Mediana Edad , Vena Porta/diagnóstico por imagen , Vena Porta/cirugía , Complicaciones Posoperatorias/etiología , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND: Individuals at a prediabetic stage have had an augmented cardiovascular disease (CVD) risk and CVD-related mortality compared to normal glucose tolerance (NGT) individuals, which may be attributed to the impaired vascular endothelial repair capacity. In this study, circulating endothelial progenitor cells' (EPCs) number and activity were evaluated, and the underlying mechanisms in premenopausal women with impaired glucose regulation were explored. METHODS: Circulating EPCs' number and activity and flow-mediated dilation (FMD) were compared in premenopausal women with NGT, isolated impaired fasting glucose (i-IFG), or isolated impaired glucose tolerance (i-IGT). Plasma nitric oxide (NO), EPCs-secreted NO, and intracellular BH4 levels were also measured. The key proteins (Tie2, Akt, eNOS, and GTPCH I) in the guanosine triphosphate cyclohydrolase/tetrahydrobiopterin (GTPCH/BH4) pathway and Tie2/Akt/eNOS signaling pathway were evaluated in these women. RESULTS: It was observed that the i-IGT premenopausal women not i-IFG premenopausal women had a significant reduction in circulating EPCs' number and activity as well as reduced FMD when compared to NGT subjects. Plasma NO levels or EPCs-secreted NO also decreased only in i-IGT women. The expression of GTCPH I as well as intracellular BH4 levels declined in i-IGT women; however, the alternations of key proteins' expression in the Tie2/Akt/eNOS signaling pathway were not observed in either i-IGT or i-IFG women. CONCLUSIONS: The endothelial repair capacity was impaired in i-IGT premenopausal women but was preserved in i-IFG counterparts. The underlying mechanism may be associated with the downregulated GTCPH I pathway and reduced NO productions.
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OBJECTIVE: Hepatocellular carcinoma is one of the most common diseases that seriously threaten human life and health. In this study, we evaluated the inhibitory effect of tanshinone IIA (Tan IIA) combined with adriamycin (ADM) on human hepatocellular carcinoma and developed a platform to assess the function if Chinese herbal ingredients combined with chemotherapy drugs have synergistic antitumor effects in vivo. METHODS: Established animal model of human hepatocarcinoma HepG2 cell in nude mice. Mice were divided into model control group, Tan IIA group, ADM group, and Tan IIA + ADM group. The changes from general condition, weight, tumor volume, and inhibition rate were observed. The data were gathered from serum AST level and histopathological changes. The content and activity of cytochrome P450 were determined by spectrophotometric analysis. CYP3A4 protein expression was analyzed by western blotting. The binding model crystal structure of Tan IIA and ADM with pregnane X receptor (PXR) was evaluated by Discovery Studio 2.1. RESULTS: A combination of Tan IIA with ADM could improve life quality by relieving ADM toxicity, decreasing tumor volume, declining serum AST level, and improving liner pathological section in tumor-bearing mice. The inhibitory rates of Tan IIA, ADM, and cotreatment were 32.77%, 60.96%, and 73.18%, respectively. The Tan IIA group significantly enhanced the content of cytochrome b5, P450, and erythromycin-N-demethylase activity. CYP3A4 protein expression was enhanced obviously by the Tan IIA + ADM group. Virtual molecular docking showed that both Tan IIA and ADM could be stably docked with the same binding site of PXR but different interactions. CONCLUSIONS: Tan IIA in combination with ADM could improve the life quality in tumor-bearing mice and enhance the antitumor effect. The Tan IIA group increased the concentration of cytochrome P450 enzymes and activity. Combined Tan IIA with ADM could upregulate the CYP3A4 protein expression and make relevant interaction with protein PXR by virtual docking.
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OBJECTIVE: The role and mechanism of tetrathiomolybdate (TM) in cancer-associated fibroblasts (CAFs) in colon cancer using three-dimensional (3D) culture were investigated, and the associations between the focal adhesion kinase (FAK) pathway and epithelial-mesenchymal transition (EMT) in CAFs were explored. METHODS: A 3D co-culture model of colon cancer LOVO cells with CAFs and normal fibroblasts (NFs) was established using Matrigel as a scaffold material. The differential expression of LOXL2 (lysyl oxidase-like 2) in the supernatant of CAFs and NFs was determined using ELISA, and expression levels of EMT-related proteins and FAK signaling pathway-related proteins were determined using western blot. RESULTS: LOXL2 levels secreted by CAFs were higher compared with that secreted by NFs. In the CAF + LOVO group, compared with the LOVO group, E-cadherin expression decreased significantly, while N-cadherin and F-PAK expression increased significantly. TM results were opposite compared with the above results. CONCLUSIONS: CAFs stimulate EMT in human colon cancer LOVO cells by secreting LOXL2 to activate the FAK signaling pathway, thereby promoting tumor metastasis. TM inhibited the occurrence of EMT in the CAF-induced colon cancer LOVO cell line, thereby reducing the invasion and metastasis of colon cancer cells.
Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias del Colon , Línea Celular Tumoral , Movimiento Celular , Transición Epitelial-Mesenquimal , Fibroblastos , Proteína-Tirosina Quinasas de Adhesión Focal , HumanosRESUMEN
Traditional Chinese Medicine (TCM) has been recognized to be conducive to enhancing the efficiency and reducing the side effects in the whole course of cancer treatment. The mechanisms of TCM/chemotherapy combination involved with interleukin-7 (IL-7) potentially enhance immune responses against tumor. In the present study, we emphasized on a herbal formulation Yi-qi-yang-yin-tian-sui-fang or TCM for short, and investigated its roles in chemotherapy in non-small cell lung cancer (NSCLC). The mice bared with tumor were treated with cisplatin (DDP) and simultaneously administrated with/without low, medium and high doses of TCMs (effective content: 0.5, 2.0 and 8.0 g/per mice) via oral gavage. The results indicated that combination of TCM further elevated the therapy efficiency of DDP in a dose-dependent manner. The growth of tumor cells was estimated by Ki-67 stain and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assay. The addition of TCM to the DDP treatment could significantly decrease the expression of Ki-67 and promote the apoptosis of tumor cells. In addition, the serum IL-7 level was down-regulated by DDP but restored by the treatment of TCM. The expression of IL-7 and its receptor IL-7R in tumor tissues was also recovered by TCM. Furthermore, the side effect from bone marrow suppression (myelosuppression) induced by DDP were assessed. TCM could abrogate DDP-induced apoptosis of bone marrow and also remarkably induced the expressions of IL-7 and hematopoietic growth factors including G-CSF, GM-CSF, SCF, and SDF-1 in bone marrow. These data indicated that this TCM combined with DDP showed superior anti-tumor effects with reduced myelosuppression via up-regulating IL-7.