RESUMEN
The animal species is one of the key factors affecting the quality of Bufonis Venenum. The quality of Bufonis Venenum derived from Bufo bufo gargarizans is significantly higher than that from B. melanostictus. Since Bufonis Venenum is from secretions, the conventional identification methods are difficult to identify the animal species due to the lack of the appearance and morphology of the animals. The rapid development of molecular identification technology has provided new methods for the identification of Bufonis Venenum. However, because of the low content and serve degradation of residual DNA in secretions, the research on the molecular identification of Chinese medicinal materials from secretions remains to be carried out. To understand the animal species of Bufonis Venenum, this study collected 83 samples of Bufonis Venenum, including 7 commercially available samples, 5 reference medicinal materials, and 71 animal samples from which Bufonis Venenum was prepared according to the method in the 2020 edition of the Chinese Pharmacopoeia. Different DNA extraction methods were used and compared, and the mitochondrial 16S rRNA gene fragments were amplified, on the basis of which the phylogenetic trees were built. Finally, molecular identification of the animal species of the samples was performed. The results showed that the DNA extracted from Bufonis Venenum by the reagent kit had good quality, and 16S rRNA sequences were successfully amplified from 80 out of the 83 samples. In addition, 71 16S rRNA sequences of the animal species of Bufonis Venenum were downloaded from GenBank. The phylogenetic trees constructed based on the neighbor-joining(NJ) method and the Bayesian inference(BI) method showed that the samples derived from B. bufo gargarizans and B. melanostictus were clustered into separate monophyletic clades, with the support of 100%(NJ) and 1.00(BI), respectively. The animal species of both commercially available samples and reference medicinal materials were B. bufo gargarizans. In conclusion, DNA can be extracted from Bufonis Venenum derived from secretions, and the 16S rRNA gene sequences can be amplified, which can be used for molecular identification of the animal species of Bufonis Venenum. The findings provide a reference for the quality control of Bufonis Venenum and the identification of animal species of medicinal materials derived from secretions.
Asunto(s)
Bufanólidos , Animales , ARN Ribosómico 16S/genética , Teorema de Bayes , Filogenia , Bufonidae/genética , ADNRESUMEN
Blood vessels play an important role in bone defect repair and growth, and a critical challenge of bone defect repair is the promotion of blood vessel formation. Most of the current methods promote vascularization by adding specific growth factors, which are costly and easy to inactivate. In this study, we developed a covalently cross-linked aminated bioactive glass nanoparticle-chondroitin sulfate methacrylate (ABGN-CSMA) organic-inorganic composite hydrogel with angiogenic properties. The amino groups of the ABGNs form covalent bonds with the carboxyl groups on CSMA. Surface amination modification of BGNs not only improved the dispersion of BGNs in CSMA but also significantly improved the mechanical properties of the composite hydrogel. The largest storage modulus (1200 Pa), the largest loss modulus (560 Pa) and the strongest resistance to deformation of the hydrogel are seen at 10% concentration of ABGNs. Simultaneously, the local pH stability and sustained ion release of the composite hydrogel are conducive to cell adhesion, proliferation, and angiogenesis. This work provides evidence for the development of covalently cross-linked organic-inorganic composite hydrogels with angiogenic properties.
Asunto(s)
Sulfatos de Condroitina , Materiales Biocompatibles Revestidos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Hidrogeles , Nanopartículas/química , Neovascularización Fisiológica/efectos de los fármacos , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Vidrio , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Metacrilatos/química , Metacrilatos/farmacología , Propiedades de SuperficieRESUMEN
High levels of perfluoroalkyl substances (PFASs) were observed in rural areas near a fluorochemical industrial park (FCIP) in the Yangtze River Delta region. The concentrations of total PFAS (∑PFASs) in soil, surface water, groundwater, and rainwater were in the range of 0.6-64.6 ng/g dry weight, 15.6-480.9, 4.8-614.6, and 13.4-542.2 ng/L, respectively. PFASs in rainwater and groundwater were higher than in surface water. The influence of the FCIP on rural soils extended to a distance of approximately 4 km based on the changes in PFAS compositions. The impact on surface water is mainly through direct river flow connected with contaminated sources, which may extend farther than 7 km in the case of unrestricted flow but much shorter distance for unconnected rivers. The penetration of PFASs in groundwater aquifers can extend as far as ca. 6 km, while direct water flow is the main transport route for PFASs. The influence radius of the FCIP can be as far as 60 km due to atmospheric precipitation.
Asunto(s)
Industria Química , Fluorocarburos/análisis , Contaminantes del Suelo/análisis , Contaminantes Químicos del Agua/análisis , China , Ambiente , Monitoreo del Ambiente , Agua Subterránea/químicaRESUMEN
Gallbladder carcinoma (GBC) is an aggressive neoplasm, and the treatment options for advanced GBC are limited. Recently, long non-coding RNAs (lncRNAs) have emerged as new gene regulators and prognostic markers in several cancers. In this study, we found that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression was up-regulated in GBC tissues (P < 0.05). Luciferase reporter assays and RNA pull down assays showed that MALAT1 is a target of miR-363-3p. Real-time quantitative PCR and Western blot analysis indicated that MALAT1 regulated Myeloid cell leukaemia-1 (MCL-1) expression as a competing endogenous RNA (ceRNA) for miR-363-3p in GBC cells. Furthermore, MALAT1 silencing decreased GBC cell proliferation and the S phase cell population and induced apoptosis in vitro. In vivo, tumour volumes were significantly decreased in the MALAT1 silencing group compared with those in the control group. These data demonstrated that the MALAT1/miR-363-3p/MCL-1 regulatory pathway controls the progression of GBC. Inhibition of MALAT1 expression may be to a novel therapeutic strategy for gallbladder cancer.
Asunto(s)
Neoplasias de la Vesícula Biliar/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , ARN Largo no Codificante/metabolismo , Animales , Apoptosis/genética , Secuencia de Bases , Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación hacia Abajo/genética , Neoplasias de la Vesícula Biliar/patología , Técnicas de Silenciamiento del Gen , Masculino , Ratones Desnudos , MicroARNs/genética , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , ARN Largo no Codificante/genética , Carga Tumoral/genéticaRESUMEN
BACKGROUND: Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC). METHODS: The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation. RESULTS: The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared to matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group. CONCLUSIONS: These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC.
Asunto(s)
Carcinogénesis/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proliferación Celular , Transición Epitelial-Mesenquimal , Proteínas Nucleares/metabolismo , Proteínas Represoras/metabolismo , Animales , Carcinogénesis/patología , Carcinoma Hepatocelular/genética , Regulación hacia Abajo , Masculino , Ratones , Ratones Desnudos , Invasividad Neoplásica , Proteínas Nucleares/genética , Proteínas Represoras/genética , Células Tumorales CultivadasRESUMEN
LncRNA-ROR has been reported to be involved in many kinds of human cancers. However, whether LncRNA-ROR is involved in gallbladder cancer progression remains largely unknown. The objective of this study is to investigate the role of LncRNA-ROR in gallbladder cancer. We found that LncRNA-ROR expression level was upregulated in gallbladder cancer tissues (P < 0.05) and was significantly associated with tumor sizes (P < 0.05) and lymph node metastasis (P < 0.05). High expression of LncRNA-ROR was significantly associated with poor prognosis in gallbladder cancer patients (P < 0.05). Moreover, knockdown of LncRNA-ROR inhibited cell proliferation, migration, and invasion. The epithelial-mesenchymal transition (EMT) phenotype induced by TGF-ß1 was reversed after LncRNA-ROR knocking down in SGC-996 and Noz cells. LncRNA-ROR plays an important role in the development of gallbladder cancer and mediates the EMT in gallbladder cancer. LncRNA-ROR might act as a marker of prognosis and therapeutic target for gallbladder cancer.
Asunto(s)
Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias de la Vesícula Biliar/genética , ARN Largo no Codificante/genética , Biomarcadores de Tumor/genética , Western Blotting , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Femenino , Neoplasias de la Vesícula Biliar/metabolismo , Neoplasias de la Vesícula Biliar/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Pronóstico , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Crecimiento Transformador beta1/farmacología , Vimentina/genética , Vimentina/metabolismoRESUMEN
Gallbladder cancer (GBC) is a highly malignant cancer with poor prognosis. Although long noncoding RNA (lncRNA) H19 has been reported to play vital role in many human cancers, whether it is involved in GBC proliferation is still unknown. This study was designed to explore the effect of H19 in GBC cell proliferation. The expression of H19 and AKT2 were significantly elevated in GBC tissues, and the level of miR-194-5p is markedly decreased. Moreover, the RNA levels of H19 and AKT2 were positively correlated, and H19 elevation was significantly associated with tumor size. Cell proliferation decreased significantly after knockdown of H19 in GBC-SD and NOZ cells and after knockdown of AKT2 in NOZ cells. Results from cell cycle studies indicated that the S phase were significantly decreased after knockdown of H19 in NOZ cells but significantly elevated after overexpression of H19 in GBC-SD cells. Furthermore, knockdown of H19 upregulated miR-194-5p levels, yet significantly decreased miR-194-5p targeting AKT2 gene expression in NOZ cells. Inhibitor against miR-194-5p reversed these effects. In addition, overexpression of H19 in GBC-SD cells downregulated miR-194-5p and markedly increased AKT2 expression, and miR-194-5p mimic reversed these effects. Eventually, GBC cells were arrested in G0/G1-phase after H19 knockdown, inhibition of miR-194-5p markedly promoted cells into S-phase and co-transfection of siH19, and miR-194-5p inhibitor exerted mutually counter-regulated effects on cell cycle. These results suggested that H19/miR-194-5p/AKT2 axis regulatory network might modulate cell proliferation in GBC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Proliferación Celular , Neoplasias de la Vesícula Biliar/patología , MicroARNs/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/genética , Apoptosis , Biomarcadores de Tumor/genética , Western Blotting , Estudios de Casos y Controles , Ciclo Celular , Movimiento Celular , Femenino , Estudios de Seguimiento , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/metabolismo , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Proteínas Proto-Oncogénicas c-akt/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a common cancer with increasing morbidity and mortality due to changes of social environment. AIM: To evaluate the significance of serum carbohydrate antigen 19-9 (CA19-9) and tumor size changes pre- and post-neoadjuvant therapy (NAT). METHODS: This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital. This study specifically assessed CA19-9 levels and tumor size before and after NAT. RESULTS: A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study. The average age was 65.4 ± 10.6 years and 72 (46.2%) patients were female. Before survival analysis, we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio (CR). The patients were divided into three groups: CR < 0.5, CR > 0.5 and < 1 and CR > 1. With regard to tumor size measured by both computed tomography and magnetic resonance imaging, we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio (TR). The patients were then divided into three groups: TR < 0.5, TR > 0.5 and < 1 and TR > 1. Based on these groups divided according to CR and TR, we performed both overall survival (OS) and disease-free survival (DFS) analyses. Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR (P < 0.05). CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response. Moreover, CR (hazard ratio: 1.721, 95%CI: 1.373-3.762; P = 0.006), and TR (hazard ratio: 1.435, 95%CI: 1.275-4.363; P = 0.014) were identified as independent factors associated with OS. CONCLUSION: This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.
RESUMEN
BACKGROUND: Due to the complexity and numerous comorbidities associated with Crohn's disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. AIM: To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. METHODS: A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. RESULTS: Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. CONCLUSION: Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.
RESUMEN
X-ray repair cross-complementing group 1 (XRCC1), a DNA repair enzyme, plays a crucial role in the base excision repair by generating a single nucleotide repair patch. It has been demonstrated that the XRCC1 Arg399Gln gene polymorphism was associated with variations in XRCC1 enzyme activity. The aim of this study was to quantitatively summarize the association between the XRCC1 Arg399Gln polymorphism and susceptibility to colorectal cancer (CRC). A comprehensive search of the PubMed, Embase, and China National Knowledge Infrastructure databases was conducted for studies on the association between the XRCC1 Arg399Gln polymorphism and CRC risk. Summary odds ratio (OR) with its corresponding 95 % confidence interval (95 %CI) was estimated, in a fixed-effects model or a random-effects model when appropriate, to assess the association. Totally, 26 case-control studies with 6,979 cases and 11,470 controls were included into this meta-analysis. The pooled results of total studies showed that the XRCC1 Arg399Gln polymorphism was significantly associated with increased risk of CRC in all genetic contrast models (OR(A vs. G) = 1.13, 95 %CI 1.03-1.23, P (OR) = 0.008; OR(Gln/Gln vs. Arg/Arg) = 1.24, 95 %CI 1.04-1.46, P (OR) = 0.015; OR(Gln/Gln vs. Arg/Gln + Arg/Arg) = 1.19, 95 %CI 1.03-1.38, P (OR) = 0.021; OR(Gln/Gln + Arg/Gln vs. Arg/Arg) = 1.14, 95 %CI 1.02-1.28, P (OR) = 0.022), except for the additive contrast model (OR(Arg/Gln vs. Arg/Arg) = 1.11, 95 %CI 0.99-1.25, P (OR) = 0.064). The statistically significant association between the XRCC1 Arg399Gln polymorphism and CRC risk was observed among studies with high quality and in Asians, but not in Caucasians. Sensitivity analyses by sequential omission of any individual studies further identified the significant association. Publication bias was inexistent in this meta-analysis. The meta-analysis suggests that the XRCC1 Arg399Gln polymorphism is associated with increased risk of CRC.
Asunto(s)
Neoplasias Colorrectales/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad/etnología , Pueblo Asiatico , Estudios de Casos y Controles , Neoplasias Colorrectales/etnología , Reparación del ADN , Humanos , Polimorfismo de Nucleótido Simple , Población Blanca , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
OBJECTIVE: To explore the value of video-electroencephalography plus surface electromyography (VEEG+SEMG) in providing theoretic rationales for clinical diagnosis of different motor seizure types and differentiating the application value of paroxysmal diseases. METHODS: A total of 116 suspected and repetitive motion epileptics underwent VEEG+SEMG from 2009 to 2012. According to their clinical features, different muscles were selected to record electromyography (EMG) under different activations and stimulations (bodily movement and posture activation, touching, sound stimulus, tapping tendons and arms straight test, etc) and monitor their seizure states. RESULTS: Among 68 patients, 567 attacks were recorded, including 443 epileptic seizures in 41 patients (229 epileptic mycological seizures in 22 patients, 95 tonic seizures in 8, 118 epileptic spasms in 10 and 1 atonic seizure in 1). The average durations of different epileptic motor seizures were (0.16 ± 0.04), (2.9 ± 2.4), (1.4 ± 0.8) and 2 s respectively. Their features of ictal EEG and SEMG varied.Non-epileptic seizures were recorded, including 43 non-epileptic myoclonus (NEMS) in 2 patients 81 PKD in 25. The primary differential diagnoses of epileptic motor seizures were NEMS and paroxysmal kinesigenic dyskinesia (PKD). CONCLUSION: VEEG+SEMG is a reliable tool for diagnosing different types of epileptic seizures and differentiating among paroxysmal diseases.
Asunto(s)
Electroencefalografía , Electromiografía , Epilepsia/clasificación , Epilepsia/diagnóstico , Adolescente , Adulto , Niño , Preescolar , Epilepsia/fisiopatología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To observe the clinical efficacy of bamboo-based medicinal moxibustion for chronic fatigue syndrome (CFS), and to preliminarily explore its action mechanism. METHODS: Sixty-four patients with CFS were randomly divided into a moxibustion group (32 cases, 1 case dropped off, 1 case excluded) and an acupuncture group (32 cases, 2 cases dropped off). The patients in the moxibustion group were treated with bamboo-based medicinal moxibustion, while the patients in the acupuncture group were treated with routine acupuncture. Both groups were treated once a day, 6 days as a course of treatment with 1 day interval, for a total of 2 courses of treatment. Before treatment, 1 and 2 courses into treatment and in the follow-up of 14 days after treatment, the fatigue scale-14 (FS-14) and somatic and psychological health report (SPHERE) scores were observed in the two groups. Before and after treatment, the contents of CD+3, CD+4, CD+8 of peripheral blood T lymphocyte subsets were measured and CD+4/CD+8 ratio was calculated; the clinical efficacy of the two groups was compared. RESULTS: Compared before treatment, the FS-14 and SPHERE scores in the two groups were decreased 1 and 2 courses into treatment and in the follow-up (P<0.01), and the FS-14 and SPHERE scores in the moxibustion group were lower than those in the acupuncture group (P<0.01, P<0.05). Compared before treatment, the contents of CD+3, CD+4 and CD+4/CD+8 ratio in the moxibustion group were increased after treatment (P<0.01). There was no significant difference of CD+3, CD+4, CD+8 and CD+4/CD+8 ratio between before and after treatment in the acupuncture group (P>0.05). After treatment, the contents of CD+3 and CD+4 in the moxibustion group were higher than those in the acupuncture group (P<0.05). The total effective rate was 93.3% (28/30) in the moxibustion group, which was higher than 73.3% (22/30) in the acupuncture group (P<0.05). CONCLUSION: Bamboo-based medicinal moxibustion could improve the physical and mental fatigue symptoms and psychological status in patients with CFS. Its effect may be related to regulating the contents of CD+3, CD+4 of peripheral blood T lymphocyte subsets and CD+4/CD+8 ratio.
Asunto(s)
Terapia por Acupuntura , Síndrome de Fatiga Crónica , Moxibustión , Humanos , Síndrome de Fatiga Crónica/terapia , Examen FísicoRESUMEN
BACKGROUND: Members of the transient receptor potential (TRP) protein family shape oncogenic development, but the specific relevance of TRP-related genes in hepatocellular carcinoma (HCC) has yet to be defined. AIM: To investigate the role of TRP genes in HCC, their association with HCC development and treatment was examined. METHODS: HCC patient gene expression and clinical data were downloaded from The Cancer Genome Atlas database, and univariate and least absolute shrinkage and selection operator Cox regression models were employed to explore the TRP-related risk spectrum. Based on these analyses, clinically relevant TRP family genes were selected, and the association between the key TRP canonical type 1 (TRPC1) gene and HCC patient prognosis was evaluated. RESULTS: In total, 28 TRP family genes were screened for clinical relevance, with multivariate analyses ultimately revealing three of these genes (TRPC1, TRP cation channel subfamily M member 2, and TRP cation channel subfamily M member 6) to be significantly associated with HCC patient prognosis (P < 0.05). These genes were utilized to establish a TRP-related risk model. Patients were separated into low- and high-risk groups based on the expression of these genes, and high-risk patients exhibited a significantly poorer prognosis (P = 0.001). Functional analyses highlighted pronounced differences in the immune status of patients in these two groups and associated enriched immune pathways. TRPC1 was identified as a candidate gene in this family worthy of further study, with HCC patients expressing higher TRPC1 levels exhibiting poorer survival outcomes. Consistently, quantitative, immunohistochemistry, and western blot analyses revealed increased TRPC1 expression in HCC. CONCLUSION: These three TRP genes help determine HCC patient prognosis, providing insight into tumor immune status and immunological composition. These findings will help design combination therapies including immunotherapeutic and anti-TRP agents.
RESUMEN
Pancreatic cancer is highly lethal, of which 90% is pancreatic ductal adenocarcinoma (PDAC), with a 5-year survival rate of less than 12%, lacking effective treatment options and late diagnosis. Furthermore, the tumors show an intense resistance to cytotoxic chemotherapies. As autophagy is elevated in PDAC, targeting the autophagic pathway is regarded as a promising strategy for cancer treatment. Immunofluorescence and transmission electron microscopy were utilized to assess the autophagic flux. Label-free quantitative phosphoproteomics was used to figure out critically altered tyrosine phosphorylation of the proteins. Tumor-bearing mice were used to validate that SH2 TrM-(Arg)9 restrained the growth of tumor cells. SH2 TrM-(Arg)9 inhibited collagen-induced autophagy via blocking the DDR1/PYK2/ERK signaling cascades. SH2 TrM-(Arg)9 improved the sensitivity of PANC-1/GEM cells to gemcitabine (GEM). Inhibition of autophagy by SH2 TrM-(Arg)9 may synergized with chemotherapy and robusted tumor suppression in pancreatic cancer xenografts. SH2 TrM-(Arg)9 could enter into PDAC cells and blockade autophagy through inhibiting DDR1/PYK2/ERK signaling and may be a new treatment strategy for targeted therapy of PDAC.
Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Animales , Ratones , Quinasa 2 de Adhesión Focal/metabolismo , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Transducción de Señal , Autofagia , Línea Celular Tumoral , Receptor con Dominio Discoidina 1/metabolismoRESUMEN
Several studies showed that the up-regulation of glial glutamate transporter-1 (GLT-1) participates in the acquisition of brain ischemic tolerance induced by cerebral ischemic preconditioning or ceftriaxone pretreatment in rats. To explore whether GLT-1 plays a role in the acquisition of brain ischemic tolerance induced by intermittent hypobaric hypoxia (IH) preconditioning (mimicking 5,000 m high-altitude, 6 h per day, once daily for 28 days), immunohistochemistry and western blot were used to observe the changes in the expression of GLT-1 protein in hippocampal CA1 subfield during the induction of brain ischemic tolerance by IH preconditioning, and the effect of dihydrokainate (DHK), an inhibitor of GLT-1, on the acquisition of brain ischemic tolerance in rats. The basal expression of GLT-1 protein in hippocampal CA1 subfield was significantly up-regulated by IH preconditioning, and at the same time astrocytes were activated by IH preconditioning, which appeared normal soma and aplenty slender processes. The GLT-1 expression was decreased at 7 days after 8-min global brain ischemia. When the rats were pretreated with the IH preconditioning before the global brain ischemia, the down-regulation of GLT-1 protein was prevented clearly. Neuropathological evaluation by thionin staining showed that 200 nmol DHK blocked the protective role of IH preconditioning against delayed neuronal death induced normally by 8-min global brain ischemia. Taken together, the up-regulation of GLT-1 protein participates in the acquisition of brain ischemic tolerance induced by IH preconditioning in rats.
Asunto(s)
Isquemia Encefálica/fisiopatología , Transportador 2 de Aminoácidos Excitadores/metabolismo , Hipoxia/fisiopatología , Precondicionamiento Isquémico , Regulación hacia Arriba , Animales , Western Blotting , Isquemia Encefálica/metabolismo , Inmunohistoquímica , Masculino , Ratas , Ratas WistarRESUMEN
BACKGROUND: Solitary fibrous tumor (SFT) is a rare spindle-cell benign neoplasm and located in orbit. The present research represents case reports of ten patients with orbital SFT. METHOD: Prognosis was assessed by clinic service and telephone interview. Clinical data were retrieved from the medical records. Immunohistochemistry for CD34, CD99, EMA, HMB-45, Bcl-2, GFAP, S-100, MBP, CK, and MIB-1 was performed. Distributions of time to progression and recurrence between different operative methods were estimated using the Kaplan-Meier method and compared using the log-rank test. FINDINGS: The ten patients included six men and four women (range: 19-75 years). The most common initial symptom was painless proptosis (n = 6). After the ten initial surgeries, with four requiring gross total resection (GRT) and six requiring subtotal resection (STR), an additional nine were required to remove recurrent tumors. Eighteen samples were obtained for pathological examination (the third sample for case 4 was not achieved). Cellular areas with partial hemangiopericytoma pattern were noted in four samples (4/18); scarce mitosis was noted in six samples (6/18). All SFTs (18/18) were positive for CD34, CD99 and vimentin, while all SFTs (18/18) were negative for EMA, CK, MBP, HBM-45 and GFAP. Bcl-2 was positive in 13/18 cases, while S-100 was negative in 14/18 cases. The MIB-1 labeling index varied from 1% to 3%. Follow-up was available for nine patients with a median of 88 months. All four patients who underwent GTR on initial operation did not recur; while the five patients who underwent STR recurred. The log-rank test showed that the incomplete surgical resection was significantly associated with recurrence (p = 0.015). CONCLUSIONS: Orbital SFT is a rare mesenchymal tumor and painless proptosis is the most common initial symptom. Immunohistochemistry should be used to differentiate SFT from other tumors. Orbital SFT usually has a non-aggressive histological characteristic, and has a good prognosis if GTR is performed. Postoperative regular and long-term follow-up remains mandatory to monitor recurrence.
Asunto(s)
Biomarcadores de Tumor/análisis , Recurrencia Local de Neoplasia/patología , Neoplasias Orbitales/patología , Tumores Fibrosos Solitarios/patología , Antígeno 12E7 , Adulto , Anciano , Antígenos CD/análisis , Antígenos CD34/análisis , Moléculas de Adhesión Celular/análisis , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Proteína Ácida Fibrilar de la Glía/análisis , Histiocitoma Fibroso Benigno/patología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Antígeno Ki-67/análisis , Masculino , Antígenos Específicos del Melanoma/análisis , Persona de Mediana Edad , Índice Mitótico , Mucina-1/análisis , Proteína Básica de Mielina/análisis , Recurrencia Local de Neoplasia/química , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Neoplasias Orbitales/química , Neoplasias Orbitales/mortalidad , Neoplasias Orbitales/cirugía , Pronóstico , Reoperación , Reticulina/análisis , Proteínas S100/análisis , Tumores Fibrosos Solitarios/química , Tumores Fibrosos Solitarios/mortalidad , Tumores Fibrosos Solitarios/cirugía , Análisis de Supervivencia , Vimentina/análisis , Adulto Joven , Antígeno gp100 del MelanomaRESUMEN
Saturated free fatty acids (FFAs) strongly correlate with metabolic syndromes and are well-known risk factors for cardiovascular diseases (CVDs). The mechanism of palmitic acid (PA)-induced vascular lipotoxicity under endoplasmic reticulum (ER) stress is unknown. In the present paper, we investigate the roles of spliced form of X-box-binding protein 1 (XBP1s) target gene oxidative stress-induced growth inhibitor 1 (OSGIN1) in PA-induced vascular dysfunction. PA inhibited the tube formation assay of primary human umbilical vein endothelial cells (HUVECs). Simultaneously, PA treatment induced the XBP1s expression in HUVECs. Attenuate the induction of XBP1s by silencing the XBP1s retarded cell migration and diminished endothelial nitric oxide synthase (eNOS) expression. OSGIN1 is a target gene of XBP1s under PA treatment. The silencing of OSGIN1 inhibits cell migration by decreasing phospho-eNOS expression. PA activated autophagy in endothelial cells, inhibiting autophagy by 3-methyladenine (3-MA) decreased endothelial cell migration. Silencing XBP1s and OSGIN1 would reduce the induction of LC3 II; therefore, OSGIN1 could maintain autophagy to preserve endothelial cell migration. In conclusion, PA treatment induced ER stress and activated the inositol-requiring enzyme 1 alpha-spliced XBP1 (IRE1α-XBP1s) pathway. OSGIN1, a target gene of XBP1s, could protect endothelial cells from vascular lipotoxicity by regulating autophagy.
RESUMEN
BACKGROUND: Lumbar disc herniation (LDH) is a common and frequently occurring disease in clinics. Low back pain and sciatica are the presenting symptoms of LDH. To some extent, it can be considered that measures with the capability to improve low back pain or sciatica have the potential to treat LDH. Ma's bamboo-based medicinal moxibustion therapy can effectively reduce the degree of low back pain and has been widely used. Studies of small sample size have seen significant improvement on pain relief. The aim of this trial is to evaluate the clinical efficacy and safety of Ma's bamboo-based medicinal moxibustion therapy in the treatment of LDH low back pain. METHODS/DESIGN: The trial is a multicenter, randomized, parallel-group, non-inferiority study. Three hundred and twelve patients will be randomly assigned to a Ma's bamboo-based medicinal moxibustion group (n=156) and an acupuncture group (n=156). Patients in each group will receive treatment every day, 6 times a week, 12 times in total. Follow-up will be conducted 14 days after treatment. The primary outcome will be the visual analog scale(VAS) at baseline, after 6 times of treatment, end of treatment, and follow-up. The secondary outcomes will include Oswestry disability indexes (ODI), modified Japanese Orthopaedic Association low back pain (M-JOA) score, serum ß-endorphin (ß-EP), and serum substance P (SP). ß-EP and SP, as well as safety evaluation indexes (routine blood, liver, and kidney function and electrocardiogram), will be measure at baseline and after the end of treatment. The number, nature, and severity of adverse events will be recorded. DISCUSSION: The results of the trial will compare the efficacy of low back pain in LDH between Ma's bamboo-based medicinal moxibustion group and the acupuncture group and will be expected to make a systematic and objective evaluation of the clinical efficacy and safety of Ma's bamboo-based medicinal moxibustion therapy. TRIAL REGISTRATION: ChiCTR2000038725 . Registered on 29 September 2020.
Asunto(s)
Terapia por Acupuntura , Desplazamiento del Disco Intervertebral , Dolor de la Región Lumbar , Moxibustión , Ciática , Terapia por Acupuntura/métodos , Humanos , Desplazamiento del Disco Intervertebral/complicaciones , Desplazamiento del Disco Intervertebral/diagnóstico , Desplazamiento del Disco Intervertebral/terapia , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/terapia , Moxibustión/efectos adversos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Ciática/diagnóstico , Sustancia P , betaendorfinaRESUMEN
BACKGROUND: Upper endoscopy is the gold standard for predicting esophageal varices in China. Guidelines and consensus suggest that patients with liver cirrhosis should undergo periodic upper endoscopy, most patients undergo their first upper endoscopy when esophageal variceal bleeds. Therefore, it is important to develop a non-invasive model to early diagnose esophageal varices. AIM: To develop a non-invasive predictive model for esophageal varices based on liver and spleen volume in viral cirrhosis patients. METHODS: We conducted a cross-sectional study based on viral cirrhosis crowd in the Second Affiliated Hospital of Xi'an Jiaotong University. By collecting the basic information and clinical data of the participants, we derived the independent risk factors and established the prediction model of esophageal varices. The established model was compared with other models. Area under the receiver operating characteristic curve, calibration plot and decision curve analysis were used to test the discriminating ability, calibration ability and clinical practicability in both the internal and external validation. RESULTS: The portal vein diameter, the liver and spleen volume, and volume change rate were the independent risk factors of esophageal varices. We successfully used the factors to establish the predictive model [area under the curve (AUC) 0.87, 95%CI: 0.80-0.95], which showed better predictive value than other models. The model showed good discriminating ability, calibration ability and the clinical practicability in both modelling group and external validation group. CONCLUSION: The developed non-invasive predictive model can be used as an effective tool for predicting esophageal varices in viral cirrhosis patients.
RESUMEN
Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with an increasing incidence worldwide. Comprehensive therapy for CD focuses on symptom control and healing the intestinal mucosa to improve the quality of life and prevent complications. Surgical intervention plays a vital role in comprehensive therapy. However, deciding the optimal timing for surgical intervention has long been a focus of controversy. This review provides insights into the timing of surgery for CD and guides clinicians in daily treatment.