A 59-year-old man was admitted to our hospital with a diagnosis of hypopharyngeal carcinoma. During gastroscopy, a mass was identified in the descending part of the duodenum, and biopsy results indicated the presence of low grade intraepithelial neoplasia. An enhanced computed tomography of the upper abdomen demonstrated that the wall of the descending part of the duodenum was markedly thickened, exhibiting a local mass-like convexity into the lumen, which was markedly and homogeneously enhanced ([Fig. 1]), with mesenteric arterial blood supply. Additionally, the local lumen of the duodenum was narrowed, and the surrounding fat space was clear. Following the exclusion of contraindications, a decision was taken to proceed with endoscopic submucosal dissection (ESD).
Mycobacterium tuberculosis (Mtb) infection has been regional outbreak, recently. The traditional focus on the patterns of "reductionism" which was associated with single molecular changes has been unable to meet the demand of early diagnosis and clinical application when current tuberculosis infection happened. In this study, we employed a systems biology approach to collect large microarray data sets including mRNAs and microRNAs (miRNAs) to identify the differentially expressed mRNAs and miRNAs in the whole blood of TB patients. The aim was to identify key genes associated with the immune response in the pathogenic process of tuberculosis by analyzing the co-regulatory network that was consisted of transcription factors and miRNAs as well as their target genes. The network along with their co-regulatory genes was analyzed utilizing Transcriptional Regulatory Element Database (TRED) and Database for Annotation, Visualization and Integrated Discovery (DAVID). We got 21 (19 up-regulated and 2 down-regulated) differentially expressed genes that were co-regulated by transcription factors and miRNAs. KEGG pathway enrichment analysis showed that the 21 differentially expressed genes were predominantly involved in Tuberculosis signaling pathway, which may play a major role in tuberculosis biological process. Quantitative real-time PCR was performed to verify the over expression of co-regulatory genes (FCGR1A and CEBPB). The genetic expression was correlated with clinicopathological characteristics in TB patients and inferences drawn. Our results suggest the TF-miRNA gene co-regulatory network may help us further understand the molecular mechanism of immune response to tuberculosis and provide us a new angle of future biomarker and therapeutic targets.
Abstract Extracellular cytokines are enriched in the tumor microenvironment and regulate various important properties of cancers, including autophagy. However, the precise molecular mechanisms underlying the link between autophagy and extracellular cytokines remain to be elucidated. In the present study, we demonstrate that IL-6 activates autophagy through the IL-6/JAK2/BECN1 pathway and promotes chemotherapy resistance in colorectal cancer (CRC). Mechanistically, IL-6 triggers the interaction between JAK2 and BECN1, where JAK2 phosphorylates BECN1 at Y333. We demonstrate that BECN1 Y333 phosphorylation is crucial for BECN1 activation and IL-6-induced autophagy by regulating PI3KC3 complex formation. Furthermore, we investigate BECN1 Y333 phosphorylation as a predictive marker for poor CRC prognosis and chemotherapy resistance. Combination treatment with autophagy inhibitors or pharmacological agents targeting the IL-6/JAK2/BECN1 signaling pathway may represent a potential strategy for CRC cancer therapy.
Objective:To assess the value of MSCT and CTA in diagnosing pulmonary sequestration.Methods:CT images of seven patients with pathologically confirmed pulmonary sequestration were analyzed retrospectively.All patients underwent MSCT contrasts scanning.The post-processed images of volume rendering,maximum intensity projection,and multi-planar reconstruction were analyzed retrospectively.Results:All patients were diagnosed correctly.Lesions were located in the posterior basa lsegment or interior basal segment of the lower lobe and characteristic abnormall supplying artery could be seen in al1 7 cases(from descending aorta).Reconstructed images displayed the origin,courser,branches and distribution of lesions clearly.Conclusion:Mluti-slice spiral CT is an ideal noninvasive and effective modality for diagnosing pulmonary sequestration and postprocessing techniques can provide more useful information for evaluation and making preoperative planning.
Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: MYCN is a member of the MYC proto-oncogene family that also includes MYC and MYCL. Overexpression of MYCN is frequent in several solid cancers and associated with poor prognosis. However, the role of MYCN in acute myeloid leukemia (AML) remains poorly understood. Aims: To investigate the mechanism of MYCN in maintenance of malignant characteristic of leukemia cells. Methods: The expression of MYC family was analyzed in 542 AML patients, 76 chronic myeloid leukemia (CML) patients and 74 non-leukemia/healthy controls from Microarray Innovations in Leukemia (MILE) study. Lentivirus-mediated MYCN knockdown was performed to investigate its biological function in leukemia cell lines. The mechanism of MYCN in leukemia development was investigated by functional experiments. Results: We found that MYCN, not MYC or MYCL, was up-regulated in the AML patients compared with CML or non-leukemia controls. In vitro experiments, knockdown of MYCN impaired growth capacity, elevated autonomously cell apoptosis and increased apoptosis sensitivity to cytotoxic agent. Gene microarray and bioinformatic analysis suggested that MYCN plays a critical role in transcription regulation and apoptosis pathway. Correlation analysis and functional experiments revealed that MSI2 is a target of MYCN. Knockdown of MYCN inhibited the expression of MSI2. Mechanistically, MYCN could directly bind at the promoter of MSI2 and promote its transcription. Summary/Conclusion: MYCN oncogene contributes to the malignant characteristics of leukemia cells through activation of MSI2 in AML. MYCN is required for maintaining an oncogenic characteristics of leukemia cells in acute myeloid leukemia This study was supported by the National Natural Science Foundation of China (Grant No. 81770120 and 81770122) The authors declare no competing financial interests. Keywords: Acute myeloid leukemia, MYC, Oncogene
Cerebral amyloid angiopathy (CAA), a prevalent cerebral small vessel disease in the elderly and a common comorbidity of Alzheimer's disease, is characterized by cerebral vascular amyloid accumulation, cerebral infarction, microbleeds, and intracerebral hemorrhages and is a prominent contributor to vascular cognitive impairment and dementia. Here, we investigate proteome changes associated with specific pathological features in several brain regions of rTg-DI rats, a preclinical model of CAA. Whereas varying degrees of microvascular amyloid and associated neuroinflammation are found in several brain regions, the presence of microbleeds and occluded small vessels is largely restricted to the thalamic region of rTg-DI rats, indicating different levels of CAA and associated pathologies occur in distinct brain regions in this model. Here, using SWATHLC-MS/MS, we report specific proteomic analysis of isolated brain regions and employ pathway analysis to correlate regionally specific proteomic changes with uniquely implicated molecular pathways. Pathway analysis suggested common activation of tumor necrosis factor α (TNFα), abnormal nervous system morphology, and neutrophil degranulation in all three regions. Activation of transforming growth factor-β1 (TGF-β1) was common to the hippocampus and thalamus, which share high CAA loads, while the thalamus, which uniquely exhibits thrombotic events, additionally displayed activation of thrombin and aggregation of blood cells. Thus, we present significant and new insight into the cerebral proteome changes found in distinct brain regions with differential CAA-related pathologies of rTg-DI rats and provide new information on potential pathogenic mechanisms associated with these regional disease processes.
Exercise has been shown to be protective against the risk of dementias, including Alzheimer’s disease (AD). Intervention studies have demonstrated its ability to mitigate cognitive and behavioral impairments and reduce disease in both humans and animals. However, information is lacking in regard to the volume and intensity, as well as timing of exercise onset with respect to disease stage, which produces optimal benefits. Here, utilizing the Tg2576 mouse, a model of AD-like parenchymal amyloid pathology and cognitive impairment, we sought to understand the effects of different lengths of daily access to a running wheel on advanced stage disease. This study is the first to determine the benefits of long-term exercise (4 months of voluntary running) and different periods of daily access to a running wheel (0 h, 1 h, 3 h, and 12 h running wheel access) beginning in 14-month-old Tg2576 mice, an age with significant amyloid pathology. We found that exercising Tg2576 animals showed lower levels of some aspects of AD pathology and reduced behavioral dysfunction compared to sedentary Tg2576 animals. High intensity exercise, rather than high volume exercise, was generally most beneficial in reducing amyloid pathology. Our results suggest that engaging in vigorous exercise programs, even after living a sedentary life, may lead to a measurable reduction in AD pathology and preservation of some cognitive abilities.
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