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PURPOSE: The intratumoral microorganisms participates in the progression and immunotherapy of colorectal cancer (CRC). However, due to technical limitations, the impact of microorganisms on CRC has not been fully understood. Therefore, we conducted a systematic analysis of relationship between bacterial lipopolysaccharide (LPS)-associated genes and immune cells to explore new biomarkers for predicting the prognosis of CRC. METHODS: The single-cell RNA sequencing data and the Comparative Toxicogenomics Database were used to screen T cells-associated LPS-related genes (TALRGs). Then, we established and validated the TALRGs risk signature in The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) cohort and GSE39582 cohort. Besides, we compared the differences in tumor-infiltrating immune cell types, immunotherapeutic response, somatic mutation profiles, and tumor mutation burden (TMB) between high-risk group and low-risk group. In addition, the immunotherapeutic cohort (Imvigor210) treated with an anti-PD-L1 agent was performed to explore the potential value of the TALRGs signature on immunotherapy. RESULTS: Five prognostic TALRGs were identified and selected to build the prognostic model. The high-risk group had poor prognosis in both TCGA-COAD cohort (P < 0.0001) and GSE39582 cohort (P = 0.00019). The areas under the curves (AUCs) of TALRGs signature were calculated (TCGA-COAD cohort: 0.624 at 1 years, 0.639 at 3 years, 0.648 at 5 years; anti-PD-L1 cohort was 0.59). The high-risk group had advanced pathological stages and higher TMN stages in both TCGA-COAD cohort and GSE39582 cohort. The high-risk group had the higher infiltration of immunosuppressive cells, the expressions of immune checkpoint molecules, the IC50 values of chemotherapy drugs, and TP53 mutation rate (P < 0.05). In addition, patients with high TMB had worse prognosis (P < 0.05). Furthermore, the Imvigor210 also showed patients with high-risk scores had poor prognosis (platinum-treated cohort: P = 0.0032; non-platinum-treated cohort: P = 0.00017). CONCLUSIONS: Microorganisms are closely related to the tumor microenvironment to influence the progression and immune response of CRC via stimulating T cells through LPS-related genes. The TALRGs signature contributed to predict the prognosis and immunotherapy of CRC, and became new therapeutic targets and biomarkers of CRC.
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Background: Currently, there are few studies on immune-related prognostic analysis of hepatocellular carcinoma (HCC). Our aim was to establish an immune-correlated prognostic model for HCC. Methods: Immune-associated cells were obtained from the scRNA-seq dataset (GSE149614) of HCC. Differentially expressed genes between normal and tumor cells from immune-associated cells and the immune-related genes from the ImmPort database were used to identify immune-related differentially expressed genes (IRDEGs). Subsequently, the risk model was established in the TCGA-LIHC cohort (n = 438) from the Cancer Genome Atlas (TCGA) database by using Kaplan-Meier (K-M) survival curve, univariate/multivariate Cox regression analysis. Subsequently, we further analyzed tumor immune microenvironment characteristics, somatic mutation, immune checkpoint and its ligand expression levels between high- and low-risk groups, as well as drug sensitivity prediction. ICGC cohort was set as the validation cohort. TCGA-LIHC cohort and three independent the Gene Expression Omnibus (GEO) datasets (GSE54236, GSE14520, and GSE64041) was used to verify IRDEGs expression, as well as PCR assays using clinical samples. Results: The IRDEGs was composed of 4 genes, namely B2M, SPP1, PPIA, and HRG. The 438 HCC patients were divided into high- and low-risk group. The high-risk group was associated with poor prognosis, including higher T stage, advanced pathological stages, less immune cell infiltration, higher TP53 mutation rate, the high expression of CTLA4 and HAVCR2. Besides, high-risk populations benefit from most chemotherapy drugs. Similarly, the performance of the risk model was validated in the ICGC. All four datasets (TCGA-LIHC cohort, GSE54236, GSE14520, and GSE64041) and clinical q-PCR results demonstrated that, compared with normal samples, the expressions of B2M and HRG were lower in tumor samples, and the expression of SPP1 was higher. Conclusion: In summary, the immune-related prognostic signature had a good predictive performance on prognosis and immunotherapy for HCC patients.
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Colon cancer is one of the most common cancers, with 30-50 % of patients returning or metastasizing within 5 years of treatment. Increasingly, researchers have highlighted the influence of microbes on cancer malignant activity, while no studies have explored the relationship between colon cancer and the microbes in tumors. Here, we used tissue and blood samples from 67 colon cancer patients to identify pathogenic microorganisms associated with the diagnosis and prediction of colon cancer and evaluate the predictive performance of each pathogenic marker and its combination based on the next-generation sequencing data by using random forest algorithms. The results showed that we constructed a database of 13,187 pathogenic microorganisms associated with human disease and identified 2 pathogenic microorganisms (Synthetic.construct_32630 and Dicrocoelium.dendriticum_57078) associated with colon cancer diagnosis, and the constructed diagnostic prediction model performed well for tumor tissue samples and blood samples. In summary, for the first time, we provide new molecular markers for the diagnosis of colon cancer based on the expression of pathogenic microorganisms in order to provide a reference for improving the effective screening rate of colon cancer in clinical practice and ameliorating the personalized treatment of colon cancer patients.
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OBJECTIVES: Nearly half of patients with slow transit constipation (STC) are not completely satisfied with their traditional remedies. We aimed to evaluate the therapeutic value and possible involved mechanism of transcutaneous electrical acustimulation (TEA) at ST36 in patients with STC. MATERIALS AND METHODS: Seventy patients with STC were randomly divided into TEA (n = 35) and sham-TEA (n = 35) to undergo a two-week treatment with TEA at ST36 or sham point. After the two-week treatment, 18 patients from each group randomly underwent a few physiological tests, including the electrocardiogram (ECG), anorectal manometry, colon transit test, and blood drawing. After a two-week washout period, TEA was performed in both groups for two weeks. RESULTS: Spontaneous bowel movements per week were increased, and scores of constipation symptoms were decreased, after a two-week blind TEA but not sham-TEA, which were sustained after a two-week washout period. Improvement in quality of life and psychologic states also was observed with blind TEA treatment. Mechanistically, the two-week blind TEA accelerated colon transit assessed by barium strip excretion rate (the effect was sustained after a two-week washout period), enhanced vagal nerve activity evaluated by the spectral analysis of heart rate variability derived from the ECG, and decreased circulating vasoactive intestinal peptide. CONCLUSIONS: Noninvasive TEA relieves constipation and improves quality of life and psychologic states in patients with STC, and the effects are sustained for ≥two weeks. The therapeutic effects of TEA may be attributed to the acceleration of colon transit and decrease of vasoactive intestinal peptide mediated through the vagal mechanism.
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Qualidade de Vida , Estimulação Elétrica Nervosa Transcutânea , Humanos , Peptídeo Intestinal Vasoativo , Trânsito Gastrointestinal/fisiologia , Constipação Intestinal/terapia , ColoRESUMO
BACKGROUND: In this study, we compared the prognosis, tumor immune microenvironment (TIM), and drug treatment response between left-sided (LCC) and right-sided (RCC) colon cancer to predict outcomes in patients with LCC and RCC. METHODS: Based on identified differentially expressed genes and using single-cell RNA sequencing data, we constructed and validated a prognostic model for LCC and RCC patients in the TCGA-COAD cohort and GSE103479 cohort. Moreover, we compared the differences of TIM characteristics and drug treatment response between LCC and RCC patients. RESULTS: We constructed and validated a five-gene prognostic model for LCC patients and a four-gene prognostic model for RCC patients, and both showed excellent performance. The RCC patients with higher risk scores were significantly associated with greater metastasis (P = 2.6×10-5), N stage (P = 0.012), advanced pathological stage (P = 1.4×10-4), and more stable microsatellite status (P = 0.007) but not T stage (P = 0.200). For LCC patients, the risk scores were not significantly associated with tumor stage and microsatellite status (P > 0.05). Additionally, immune infiltration by CD8 and regulatory T cells and M0, M1, and M2 macrophages differed significantly between LCC and RCC patients (P < 0.05). APC and TP53 mutations were significantly more common in LCC patients (P < 0.05). In contrast, KRAS, SYNE1, and MUC16 mutations were significantly more common in RCC patients (P < 0.05). In addition, tumor mutation burden values were significantly higher in RCC patients than in LCC patients (P = 5.9×10-8). Moreover, the expression of immune checkpoint targets was significantly higher in RCC patients than in LCC patients (P < 0.05), indicating that RCC patients maybe more sensitive to immunotherapy. However, LCC and RCC patients did not differ significantly in their sensitivity to eight selected chemicals or target drugs (P > 0.05). The average half-maximal inhibitory concentrations for camptothecin, teniposide, vinorelbine, and mitoxantrone were significantly lower in low-risk than in high-risk RCC patients (P < 0.05), indicating that the lower risk score of RCC patients, the more sensitive they were to these four drugs. CONCLUSIONS: We investigated the differences in prognosis, TIM, and drug treatment response between LCC and RCC patients, which may contribute to accurate colon cancer prognosis and treatment of colon cancer.
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Carcinoma de Células Renais , Neoplasias do Colo , Neoplasias Renais , Humanos , RNA-Seq , Análise da Expressão Gênica de Célula Única , Prognóstico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Microambiente Tumoral/genéticaRESUMO
Background: Ca2+ channels are abnormally expressed in various tumor cells and are involved in the progression of human glioma. Here, we explored the role of a calcium channel, voltage-dependent, T-type, alpha 1H subunit (CACNA1H), which encodes T-type Ca2+ channel Cav3.2 in glioma cells. Methods: Cell viability and apoptosis were detected using cell-counting kit-8 and flow cytometry, respectively. The expression of target protein was determined using western blot analysis. Results: Cell viability of U251 cells was inhibited significantly after the knockdown of CACNA1H. The apoptosis of U251 cells was enhanced significantly after the knockdown of CACNA1H. Importantly, knockdown of CACNA1H decreased the levels of p-PERK, GRP78, CHOP, and ATF6, indicating that CACNA1H knockdown activated endoplasmic reticulum stress (ERS) in U251 cells. In addition, T-type Ca2+ channel inhibitor NNC55-0396 also induced apoptosis through the activation of ERS in U251 cells. ERS inhibitor UR906 could block CACNA1H inhibitor ABT-639-induced apoptosis. Conclusion: Suppression of CACNA1H activated the ERS and thus induced apoptosis in glioma cells. T-type Ca2+ channel inhibitors ABT-639 and NNC55-0396 also induced apoptosis through ERS in glioma cells. Our data highlighted the effect of CACNA1H as an oncogenic gene in human glioma.
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BACKGROUND: The current study probed prognosis-related potential for m6A-related lncRNAs signatures within colon tumor immune microenvironment (TIM). METHODS: After downloading transcriptomic datasets for colon cancer (CC) patients from The Cancer Genome Atlas (TCGA), they were divided, in a 1:1 ratio, within training or test datasets. m6A-related lncRNAs were then scrutinized across such dataset using Pearson correlation assessment before generating a m6A-related lncRNAs prognosis-related model using the training dataset. The latter was then validated with the test and the whole dataset. In addition, we compared the differences of TIM and the estimated IC50 of drug response between the high- and low-risk groups. RESULTS: Overall survival (OS) resulted as linked with 11 m6A-related lncRNAs, while within the developed prognosis-related model, areas-under-curves were as follows: within training dataset, values at 3-, 4-, and 5-years were 0.777, 0.819, and 0.805, accordingly, and for test one, they were 0.697, 0.682, and 0.706, respectively. Finally, the values for the whole dataset were 0.675 (3-year), 0.682 (4-years), and 0.679 (5-years), accordingly. Moreover, CC cases categorized within low-risk cohort demonstrated enhanced OS (p < .0001), lower metastasis (p = 2e-06) and lower T stage (p = .0067), more instability for microsatellite status (p = .012), and downregulation for PD-L1, PD-1, CTLA-4, LAG3, and HAVCR2 (p < .05). In addition, risk scorings were significantly linked to the degree of infiltrative intensity for CD8 and CD4 (memory resting) T-cells, T-regulatory (Tregs), and Mast cells triggering (p < .05). Patients with low infiltrative propensity for CD4 T-cells also had better OS (p = .016). Moreover, six representative drugs were found to be sensitive for treating CC patients. CONCLUSION: A robust m6A-related prognostic model with great performances was developed before exploring the TIM characteristics and its potential therapeutic drugs, which might improve the prognosis and therapeutic efficacy.
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Neoplasias do Colo , RNA Longo não Codificante , Humanos , Prognóstico , RNA Longo não Codificante/genética , Neoplasias do Colo/genética , Regulação para Baixo , Perfilação da Expressão Gênica , Microambiente TumoralRESUMO
Talaromyces marneffei and Pneumocystis jirovecii are the common opportunistic pathogens in immunodeficient patients. There have been no reports of T. marneffei and P. jirovecii coinfection in immunodeficient children. Signal transducer and activator of transcription 1 (STAT1) is a key transcription factor in immune responses. STAT1 mutations are predominately associated with chronic mucocutaneous candidiasis and invasive mycosis. We report a 1-year-2-month-old boy diagnosed with severe laryngitis and pneumonia caused by T. marneffei and P. jirovecii coinfection, which was confirmed by smear, culture, polymerase chain reaction and metagenome next-generation sequencing of bronchoalveolar lavage fluid. He has a known STAT1 mutation at amino acid 274 in the coiled-coil domain of STAT1 according to whole exome sequencing. Based on the pathogen results, itraconazole and trimethoprim-sulfamethoxazole were administered. This patient's condition improved, and he was discharged after two weeks of targeted therapy. In the one-year follow-up, the boy remained symptom-free without recurrence.
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Coinfecção , Pneumocystis carinii , Talaromyces , Masculino , Humanos , Criança , Lactente , Pneumocystis carinii/genética , Talaromyces/genética , Mutação , Fator de Transcrição STAT1/genéticaRESUMO
Glioma is a medical term that describes a tumor originating in the brain. Several risk factors could develop glioma such as occupational exposure, gene mutation and ionizing radiation. Therefore, we aim to determine the expression and biological function of interleukin 37 (IL-37) in gliomas with different pathological grades. We used 95 participants with different pathological grades of glioma as our data subjects. We used CCK-8 assay and transwell assay to explore the proliferation of U251 over-expressing IL-37 and migration and invasion of U251. We found that IL-37 expression in tumor tissues was significantly higher than in normal tissue. The reduced IL-37 expression in gliomas was significantly associated with a higher WHO grade and lower Karnofsky Performance Status score. IL-37 expression in glioma tissues showed a decline with the increase of the WHO glioma grade. Patients with low IL-37 expression showed a shorter median survival. Transwell assay indicated that migration and invasion of U251 over-expressing IL-37 was significantly lower than that of the control at 24 h. Our findings showed that low IL-37 expression was negatively correlated with pathological grade and was positively correlated with survival time.
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INTRODUCTION: Dysregulation of spinal cord development can lead to serious neuronal damage and dysfunction, causing significant health problems in newborns. MiRNA-138 appears to be crucial for proliferation, differentiation, and apoptosis of cells. However, the regulation of miRNA-138 and downstream molecules in embryonic spinal cord development remain elusive. The aim of this experiment is to determine whether overexpression of miRNA-138 or RNA interference (RNAi) can regulate the development of spinal cord in fetal rats. METHODS: Two plasmid vectors including pLenti-III-mico-GFP (miRNA-138 open reading frame [ORF]) and pLenti-III-miR-Off (miRNA-138 short hairpin) were constructed and injected into the tail vein of rats on the 14th day of pregnancy. Hematoxylin-eosin (HE) staining was used to observe the cell morphology. QRT-PCR, Western blot, and immunostaining confirmed the regulatory relationship between miRNA-138 and downstream molecules sonic hedgehog (Shh). RESULTS: Overexpression of miRNA-138 increased neuron regeneration significantly and decreased neuronal apoptosis when compared with the control. Silencing of miRNA-138 increased neuronal apoptosis and spinal cord atrophy significantly. Furthermore, miRNA-138 ORF treatment effectively increased the expression level of miRNA-138 and also upregulated the level of Shh. Comparatively, knockdown of miRNA-138 downregulated Shh levels in myelodysplastic regions. CONCLUSION: These findings indicated that miRNA-138 overexpression could protect the spinal cord development of fetal rats, and the underlying mechanisms were associated with Shh expression. The present study provides a novel strategy to promote the molecular mechanism of embryonic spinal cord development.
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MicroRNAs , Ratos , Animais , Humanos , MicroRNAs/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/farmacologia , Medula Espinal , NeurôniosRESUMO
The present study focused on identifying the immune-related signatures and exploring their performance in predicting the prognosis, immunotherapeutic responsiveness, and diagnosis of patients with colon cancer. Firstly, the immunotherapeutic response-related differential expressed genes (DEGs) were identified by comparing responders and non-responders from an anti-PD-L1 cohort using the edgeR R package. Then, the immunotherapeutic response related DEGs was intersected with immune-related genes (IRGs) to obtain the immunotherapeutic response and immune-related genes (IRIGs). Then, an immunotherapeutic response and immune-related risk score (IRIRScore) model consisting of 6 IRIGs was constructed using the univariable Cox regression analysis and multivariate Cox regression analysis based on the COAD cohort from the cancer genome atlas (TCGA) database, which was further validated in two independent gene expression omnibus database (GEO) datasets (GSE39582 and GSE17536) and anti-PD-L1 cohort. A nomogram with good accuracy was established based on the immune-related signatures and clinical factors (C-index = 0.75). In the training dataset and GSE39582, higher IRIRScore was significantly associated with higher TMN and advanced pathological stages. Based on the anti-PD-L1 cohort, patients who were sensitive to immunotherapy had significantly lower risk score than non-responders. Furthermore, we explored the immunotherapy-related signatures based on the training dataset. Kaplan-Meier curve revealed a high level of T cells regulatory (Tregs) was significantly related to poor overall survival (OS), while a high level of T cells CD4 memory resting was significantly related to better OS. Besides, the TMB value of patients in the high-risk group was significantly higher than those in a low-risk group. Moreover, patients in the high-risk group had significantly higher expression levels of immune checkpoint inhibitors. In addition, the immune-related signatures were applied to establish prediction models using the random forest algorithm. Among them, TDGF1 and NRG1 revealed excellent diagnostic predictive performance (AUC >0.8). In conclusion, the current findings provide new insights into immune-related immunotherapeutic responsiveness, prognosis, and diagnosis of colon cancer.
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Neoplasias do Colo , Biomarcadores Tumorais/genética , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , Neoplasias do Colo/terapia , Humanos , Imunoterapia , Nomogramas , Prognóstico , Fatores de RiscoRESUMO
In the learning milieu, academic stress is deemed as the most general mental condition that learners encounter throughout their educational process, and it has been viewed as one of the most central issues not only in general education but also specifically in language learning. Likewise, burnout has been the main point in this situation. The comprehensive sources of stress and the reasons for burnout are pinpointed in the literature so realizing their association with other aspects such as coping strategies, namely tolerance of uncertainty, are at the center of attention as it may help reduce burnout and decrease the level of stress. To this end, the goal of the present study is to prove the influence of the tolerance of ambiguity in explaining the role of stress and burnout. Briefly, some implications are set forth for the educational stakeholders.
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Background: Colon cancer is a common malignant tumor with poor prognosis. The aim of this study is to explore the immune-related prognostic signatures and the tumor immune microenvironment of colon cancer. Methods: The mRNA expression data of TCGA-COAD from the UCSC Xena platform and the list of immune-related genes (IRGs) from the ImmPort database were used to identify immune-related differentially expressed genes (DEGs). Then, we constructed an immune-related risk score prognostic model and validated its predictive performance in the test dataset, the whole dataset, and two independent GEO datasets. In addition, we explored the differences in tumor-infiltrating immune cell types, tumor mutation burden (TMB), microsatellite status, and expression levels of immune checkpoints and their ligands between the high-risk and low-risk score groups. Moreover, the potential value of the identified immune-related signature with respect to immunotherapy was investigated based on an immunotherapeutic cohort (Imvigor210) treated with an anti-PD-L1 agent. Results: Seven immune-related DEGs were identified as prognostic signatures. The areas under the curves (AUCs) of the constructed risk score model for overall survival (OS) were calculated (training dataset: 0.780 at 3 years, 0.801 at 4 years, and 0.766 at 5 years; test dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years; and the whole dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years). In the high-risk score group of the whole dataset, patients had worse OS, higher TMN stages, advanced pathological stages, and a higher TP53 mutation rate (p < 0.05). In addition, a high level of resting NK cells or M0 macrophages, and high TMB were significantly related to poor OS (p < 0.05). Also, we observed that high-risk score patients had a high expression level of PD-L1, PD-1, and CTLA-4 (p < 0.05). The patients with high-risk scores demonstrated worse prognosis than those with low-risk scores in multiple datasets (GSE39582: p = 0.0023; GSE17536: p = 0.0008; immunotherapeutic cohort without platinum treatment: p = 0.0014; immunotherapeutic cohort with platinum treatment: p = 0.0027). Conclusion: We developed a robust immune-related prognostic signature that performed great in multiple cohorts and explored the characteristics of the tumor immune microenvironment of colon cancer patients, which may give suggestions for the prognosis and immunotherapy in the future.
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BACKGROUND: Lack of interstitial cells of Cajal (ICC) and neuropathy were the most possible pathological mechanisms of diabetic gastroparesis. Gastric electrical stimulation (GES) is a promising way to treat gastroparesis. This study aimed to explore the impact of GES on ICC together with enteric neurons in diabetic rats and the possible mechanisms involved. MATERIALS AND METHODS: A total of 60 rats were randomized into six groups, including the normal control group, diabetic group (DM), diabetic with sham GES group (DM + SGES), and three groups of diabetic rats with GES (DM + GES1, DM + GES2, and DM + GES3). The proliferation of ICC and expressions of 5-hydroxytryptamine (serotonin) receptor 2B (5-HT2B), neuronal nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5, and glia cell line-derived neurotrophic factor (GDNF) in the antrum of the stomach were evaluated by immunofluorescence staining or Western blot. The levels of 5-HT in blood and tissue were determined by enzyme-linked immunosorbent assay. RESULTS: The proliferation of ICC was significantly reduced in the DM group, together with the DM + SGES group, but increased in the three DM + GES groups. The expression of 5-HT2B was decreased in the DM group and enhanced in the DM + GES groups. Similarly, the levels of 5-HT in the blood and distal stomach tissue were increased in the DM + GES groups. Both nNOS labeled neurons and CHAT-positive neurons were reduced in the myenteric plexus of the DM group, whereas these neurons were dramatically increased the in DM + GES groups. The expression of GDNF protein in the diabetic rats was down-regulated, whereas GES increased the expression of GDNF. CONCLUSIONS: GES improves the proliferation of ICC possibly related with the 5-HT/5-HT2B signal pathway and alters the enteric nervous system partly though the GDNF expression.
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Diabetes Mellitus Experimental , Sistema Nervoso Entérico , Gastroparesia , Células Intersticiais de Cajal , Ratos , Animais , Células Intersticiais de Cajal/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Diabetes Mellitus Experimental/terapia , Serotonina , Sistema Nervoso Entérico/metabolismo , Proliferação de Células , Estimulação ElétricaRESUMO
Background: Perivascular epithelioid cell tumor of the gastrointestinal tract (GI PEComa) is a rare mesenchymal neoplasm. GI PEComa is mostly observed in the colon and has a marked middle-aged female predominance. PEComa has no typical clinical or imaging manifestations or endoscopic characteristics. Therefore, the diagnosis of this disease mostly relies on pathological findings. HMB-45 is a sensitive immune marker of PEComa. Case presentation: We reported a case of a middle-aged female with sigmoid colon PEComa. To exclude carcinogenesis, the large basal polyp in the sigmoid colon was removed by endoscopic mucosal resection (EMR). Immunohistochemistry analysis results showed that this lesion expressed HMB-45, which is a characteristic melanin marker of PEComa. Finally, the lesion was diagnosed as sigmoid colon PEComa. At the time of submission of this report, surgical resection was the primary treatment for PEComa. Though the characteristics of tumor biology and clinical behavior in PEComa are not clear, the boundary is clear, and the tumor can be completely removed. However, close follow-up is required after the surgery because of the lesion's undetermined benign and malignant nature. Conclusion: The present case study emphasizes the importance of pathological diagnosis. Therefore, upon finding gastrointestinal polyps with a mucosal ulcer under endoscopy, the GI PEComa diagnosis should be considered. It is necessary to detect the characteristic melanin markers of PEComa. Due to the rarity of these cases, challenges are faced in diagnosing and treating PEComa.
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The present study aimed to construct a novel methylation-related prognostic model based on microsatellite status that may enhance the prognosis of colorectal cancer (CRC) from methylation and microsatellite status perspective. DNA methylation and mRNA expression data with clinical information were downloaded from The Cancer Genome Atlas (TCGA) data set. The samples were divided into microsatellite stability and microsatellite instability group, and CIBERSORT was used to assess the immune cell infiltration characteristics. After identifying the differentially methylated genes and differentially expression genes using R packages, the methylation-driven genes were further identified. Prognostic genes that were used to establish the methylation-related risk score model were generated by the univariate and multivariate Cox regression model. Finally, we established and evaluated the methylation-related prognostic model for CRC patients. A total of 69 MDGs were obtained and three of these genes (MIOX, TH, DKFZP434K028) were selected to construct the prognostic model. Patients in the low-risk score group had a conspicuously better overall survival than those in the high-risk score group (p < .0001). The area under the receiver operating characteristic curve for this model was 0.689 at 3 years, 0.674 at 4 years, and 0.658 at 5 years. The Wilcoxon test showed that higher risk score was associated with higher T stage (p = .01), N stages (p = .0028), metastasis (p = .013), and advanced pathological stage (p = .0013). However, the more instability of microsatellite status, the lower risk score of CRC patients (p = .0048). Our constructed methylation-related prognostic model based on microsatellite status presents potential significance in assessing recurrence risk stratification, tumor staging, and immunotherapy for CRC patients.
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Neoplasias Colorretais/metabolismo , Metilação de DNA , DNA de Neoplasias/metabolismo , Repetições de Microssatélites , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , DNA de Neoplasias/genética , Humanos , Proteínas de Neoplasias/genética , PrognósticoRESUMO
BACKGROUND: Gastric electrical pacing (GEP) could restore interstitial cells of Cajal in diabetic rats. M2 macrophages contribute to the repair of interstitial cells of Cajal injury though secreting heme oxygenase-1 (HO-1). The aim of the study is to investigate the effects and mechanisms of gastric electrical pacing on M2 macrophages in diabetic models. METHODS: Sixty male Sprague-Dawley rats were randomized into control, diabetic (DM), diabetic with the sham GEP (DM+SGEP), diabetic with GEP1 (5.5 cpm, 100 ms, 4 mA) (DM+GEP1), diabetic with GEP2 (5.5 cpm, 300 ms, 4 mA) (DM+GEP2), and diabetic with GEP3 (5.5 cpm, 550 ms, 4 mA) (DM+GEP3) groups. The apoptosis of interstitial cells of Cajal and the expression of macrophages were detected by immunofluorescence technique. The expression levels of the Nrf2/HO-1 and NF-κB pathway were evaluated using western blot analysis or immunohistochemical method. Malonaldehyde, superoxide dismutase, and reactive oxygen species were tested to reflect the level of oxidative stress. RESULTS: Apoptosis of interstitial cells of Cajal was increased in the DM group but significantly decreased in the DM+GEP groups. The total number of macrophages was almost the same in each group. In the DM group, M1 macrophages were increased and M2 macrophages were decreased. However, M2 macrophages were dramatically increased and M1 macrophages were reduced in the DM+GEP groups. Gastric electrical pacing improved the Nrf2/HO-1 pathway and downregulated the phosphorylation of NF-κB. In the DM group, the levels of malonaldehyde and reactive oxygen species were elevated and superoxide dismutase was lowered, while gastric electrical pacing reduced the levels of malonaldehyde and reactive oxygen species and improved superoxide dismutase. CONCLUSION: Gastric electrical pacing reduces apoptosis of interstitial cells of Cajal though promoting M2 macrophages polarization to play an antioxidative stress effect in diabetic rats, which associates with the activated Nrf2/HO-1 pathway and the phosphorylation of NF-κB pathway.
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Apoptose , Polaridade Celular , Diabetes Mellitus Experimental/fisiopatologia , Fenômenos Eletrofisiológicos , Células Intersticiais de Cajal/patologia , Macrófagos/patologia , Estresse Oxidativo , Estômago/fisiopatologia , Animais , Diabetes Mellitus Experimental/patologia , Eletroacupuntura , Heme Oxigenase-1/metabolismo , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Fator de Células-Tronco/metabolismo , Estômago/patologia , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: Long non-coding RNA testis-specific transcript, Y-linked 15 (TTTY15) is oncogenic in prostate cancer, however its expression and function in colorectal cancer remain largely unknown. METHODS: Paired colorectal cancer samples/normal tissues were collected, and the expression levels of TTTY15, miR-29a-3p and disheveled segment polarity protein 3 (DVL3) were examined by quantitative real-time polymerase chain reaction (qRT-PCR); TTTY15 shRNA and overexpression plasmids were transfected into HT29 and HCT-116 cell lines using lipofectamine reagent, respectively; the proliferation and colony formation were detected by CCK-8 assay and plate colony formation assay; qRT-PCR and Western blot were used to analyze the changes of miR-29a-3p and DVL3; dual-luciferase reporter gene assay was used to determine the regulatory relationships between miR-29a-3p and TTTY15, miR-29a-3p and DVL3. RESULTS: TTTY15 was significantly up-regulated in cancerous tissues of colorectal cancer samples, positively correlated with the expression of DVL3, while negatively correlated with the expression of miR-29a-3p. After TTTY15 shRNAs were transfected into colorectal cancer cells, the proliferation and metastasis of cancer cells were significantly inhibited, while TTTY15 overexpression had opposite biological effects. TTTY15 shRNA could reduce the expression of DVL3 on both mRNA and protein levels, and the luciferase activity of TTTY15 sequence was also inhibited by miR-29a-3p. DVL3 was also validated as a target gene of miR-29a-3p, and it could be repressed by miR-29a-3p mimics or TTTY15 shRNA. CONCLUSION: TTTY15 is abnormally upregulated in colorectal cancer tissues, and it can modulate the proliferation and metastasis of colorectal cancer cells. It functions as the ceRNA to regulate the expression of DVL3 by sponging miR-29a-3p.
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Neoplasias Colorretais/genética , Proteínas Desgrenhadas/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Movimento Celular , Proliferação de Células , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , TransfecçãoRESUMO
BACKGROUND: Previous studies have shown inconsistent results about the usefulness of bilateral inferior petrosal sinus sampling (BIPSS) in differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome. This meta-analysis evaluated the diagnostic value of BIPSS via the published literature. METHODS: This study searched PubMed, Embase, Web of Science, Cochrane library, and Wanfang database for published data on the use of BIPSS in Cushing syndrome differential diagnosis as of October 2019. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curves were calculated based on the relevant data. RESULTS: This meta-analysis included a total of 23 studies with 1642 patients. The calculated sensitivity, specificity, PLR, and NLR were 0.94 (95% confidence interval, CI: 0.91-0.96), 0.89 (95% CI: 0.79-0.95), 8.8 (95% CI: 4.3-17.9), and 0.07 (95% CI: 0.04-0.11), respectively. The pooled DOR and area under the ROC curve were 129 (95% CI: 48-345) and 0.97 (95% CI: 0.95-0.98), respectively. CONCLUSION: This meta-analysis indicated that BIPSS had high diagnostic value for detecting ACTH in patients with ACTH-dependent Cushing syndrome, and BIPSS should be used as an effective method to identify ACTH-secretion sources.
Assuntos
Síndrome de ACTH Ectópico/diagnóstico , Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/diagnóstico , Amostragem do Seio Petroso/métodos , Síndrome de ACTH Ectópico/sangue , Síndrome de Cushing/sangue , Bases de Dados Factuais , Diagnóstico Diferencial , HumanosRESUMO
INTRODUCTION: Neonatal hypoxia-ischemic brain damage (HIBD) can lead to serious neuron damage and dysfunction, causing a significant worldwide health problem. bFGF as a protective reagent promotes neuron repair under hypoxia/ischemia (HI). However, how bFGF and downstream molecules were regulated in HI remains elusive. METHODS: We established an in vitro HI model by culturing primary cortical neurons and treated with oxygen-glucose deprivation (OGD). We suppressed the expression of bFGF by using siRNA (small interfering RNA) interference to detect the neuronal morphological changes by immunofluorescence staining. To determine the potential mechanisms regulated by bFGF, the change of downstream molecular including IL-1ß was examined in bFGF knockdown condition. IL-1ß knockout (KO) rats were generated using CRISPR/Cas9-mediated technologies. We used an accepted rat model of HI, to assess the effect of IL-1ß deletion on disease outcomes and carried out analysis on the behavior, histological, cellular, and molecular level. RESULTS: We identified that OGD can induce endogenous expression of bFGF. Both OGD and knockdown of bFGF resulted in reduction of neuron numbers, enlarged cell body and shortened axon length. We found molecules closely related to bFGF, such as interleukin-1ß (IL-1ß). IL-1ß was up-regulated after bFGF interference under OGD conditions, suggesting complex signaling between bFGF and OGD-mediated pathways. We found HI resulted in up-regulation of IL-1ß mRNA in cortex and hippocampus. IL-1ß KO rats markedly attenuated the impairment of long-term learning and memory induced by HI. Meanwhile, IL-1ß-/- (KO, homozygous) group showed better neurite growth and less apoptosis in OGD model. Furthermore, serine/threonine protein kinase (AKT1) mRNA and protein expression was significantly up-regulated in IL-1ß KO rats. CONCLUSIONS: We showed that IL-1ß-mediated axon regeneration underlie the mechanism of bFGF for the treatment of HIBD in neonatal rats. Results from this study would provide insights and molecular basis for future therapeutics in treating HIBD.