AIM: To observe the effect of monoclonal antibody of epidermal growth factor receptor (EGFR) on human colon carcinoma cell lines. METHODS:Cell counting, growth curve measurement and MTT method were applied in this study to examine the proliferation of cultured cells in vitro when different dosage of EGFR McAb is used to treat LST174 colon carcinoma cell lines. RESULT: The proliferation of cultured human colon carcinoma cells could be significantly inhibited in a dose dependent manner by EGFR antibody Compared with the control group, the cell number was decreased by 61 3% and 33 8% respectively when treated with 0 625 mL/L or 2 5 mL/L of EGFR McAb CONCLUSION: EGFR McAb can inhibit cell growth of human colon carcinoma LST174.

OBJECTIVETo investigate the role of p38MAPK and PI3K/AKT pathways in mitomycin (MMC)-induced apoptosis in the liver stem-like cell line WB-F344.

METHODSWB-F344 cells were exposed to MMC and apoptosis was evaluated by flow cytometry and DNA fragmentation. Phospho-MAPK and phospho-PI3K/AKT were detected by western blotting.

RESULTSMMC induced apoptosis in WB-F344 cells at 6h after addition of MMC; the maximum level of apoptosis was reached at 24h after MMC exposure. The apoptosis effects of MMC were concentration dependent and inhibited when the PI3K pathway was abolished by the specific inhibitor LY294002, but not inhibited when the p38MAPK pathway was abolished by inhibitor SB203508.

CONCLUSIONApoptosis of WB-F344 cells can be induced by MMC.Although MMC can activate both the PI3K/AKT and p38MAPK pathways, the apoptosis effect of MMC occurs via a PI3K pathway and is not dependent on the p38MAPK pathway.

Animals ; Apoptosis ; Blotting, Western ; Cell Line ; Chromones ; Flow Cytometry ; Mitomycin ; Morpholines ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Rats ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases

Objective:To explore the effect of joint segmentation model of myocardial-fibrotic region based on deep learning in quantitative analysis of myocardial fibrosis in patients with dilated cardiomyopathy(DCM).Methods:The data of 200 patients with confirmed DCM and myocardial fibrosis in the left ventricle detected by cardiac MR-late gadolinium enhancement (CMR-LGE) in Xuzhou Central Hospital from January 2015 to April 2022 were retrospectively analyzed. Using a complete randomized design, the patients were divided into training set ( n=120), validation set ( n=30) and test set ( n=50). The left ventricle myocardium was outlined and the normal myocardial region was selected by radiologists. Fibrotic myocardium was extracted through calculating the threshold with standard deviation (SD) as a reference standard for left ventricle segmentation and fibrosis quantification. The left ventricular myocardium was segmented by convex prior U-Net network. Then the normal myocardial image block was recognized by VGG image classification network, and the fibrosis myocardium was extracted by SD threshold. The myocardial segmentation effect was evaluated using precision, recall, intersection over union (IOU) and Dice coefficient. The consistency of myocardial fibrosis ratio in left ventricle obtained by joint segmentation model and manual extraction was evaluated with intra-class correlation coefficient (ICC). According to the median of fibrosis rate, the samples were divided into mild and severe fibrosis, and the quantitative effect of fibrosis was compared by Mann-Whitney U test. Results:In the test set, the precision of myocardial segmentation was 0.827 (0.799, 0.854), the recall was 0.849 (0.822, 0.876), the IOU was 0.788 (0.760, 0.816), and the Dice coefficient was 0.832 (0.807, 0.857). The consistency of fibrosis ratio between joint segmentation model and manual extraction was high (ICC=0.991, P<0.001). No statistically significant difference was found in the ratio error between mild and severe fibrosis ( P>0.05). Conclusions:The joint segmentation model realizes the automatic calculation of myocardial fibrosis ratio in left ventricle, which is highly consistent with the results of manual extraction. Therefore, it can accurately realize the automatic quantitative analysis of myocardial fibrosis in patients with dilated cardiomyopathy.

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Siderophores/metabolism* ; Iron/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Cryoelectron Microscopy ; Adenosine Triphosphate/metabolism* ; ATP-Binding Cassette Transporters