Int J Med Sci
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Trastuzumab has proven its effectiveness in gastric cancer with HER-2 gene-amplification, which has now developed resistance while the mechanism of which is not fully elucidated. Our previous studies demonstrated that the activity of GATA6 binding protein 6 (GATA6) enhanced prominently in trastuzumab resistant gastric cancer cell lines (NCI N87R and MKN45R). In the present study, we further confirmed the re-sensitization to trastuzumab and inhibition of mitochondrial functions of GATA6 knockout sublines (NCI N87R/ΔGATA6 and MKN45R/ΔGATA6). ⋯ An integrated proteomics-metabolomics revealed that sub-networks were closely related to TCA cycle, glycolysis, multiple amino acid and nucleotide metabolism. Western blot showed that TCA cycle and glycolysis-related molecules, including PKM, GLS, GLUL and LDHA, were downregulated in GATA6 knockout sublines. Taken together, these findings demonstrate that GATA6 is involved in metabolism reprogramming which might contribute to trastuzumab resistance in gastric cancer.
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Background: In patients with coronavirus disease 2019 (COVID-19) pneumonia, whether new pulmonary lesions will continue to develop after treatment was unknown. This study aimed to determine whether new pulmonary lesions will develop after treatment in patients with COVID-19 pneumonia, and investigate their CT features and outcomes. Methods: This retrospective study included 56 consecutive patients with confirmed COVID-19 pneumonia from January 20 to March 5, 2020. ⋯ The newly developed lesions were usually multiple (38, 90.5%), distributed in the previously involved (39, 92.9%) or uninvolved (27, 64.3%) lobes, and manifested as ground-glass opacities (GGOs) with consolidation (23, 54.8%) or pure GGOs (19, 45.2%). After their occurrence, the new lesions in most patients (32, 76.2%) showed direct absorption, whereas those in some patients (10, 23.8%) progressed before absorption. Conclusion: During treatment, most patients with COVID-19 pneumonia will develop new pulmonary lesions, which usually manifest as multiple GGOs distributed around the primary lesions or in previously uninvolved lobes, and are subsequently absorbed directly.
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MicroRNA-19 (miR-19) is identified as the key oncogenic component of the miR-17-92 cluster. When we explored the functions of the dysregulated miR-19 in lung cancer, microarray-based data unexpectedly demonstrated that some immune and inflammatory response genes (i.e., IL32, IFI6 and IFIT1) were generally down-regulated by miR-19 overexpression in A549 cells, which prompted us to fully investigate whether the miR-19 family (i.e., miR-19a and miR-19b-1) was implicated in regulating the expression of immune and inflammatory response genes in cancer cells. In the present study, we observed that miR-19a or miR-19b-1 overexpression by miRNA mimics in the A549, HCC827 and CNE2 cells significantly downregulated the expression of interferon (IFN)-regulated genes (i.e., IRF7, IFI6, IFIT1, IFITM1, IFI27 and IFI44L). ⋯ The ectopic expression of miR-19a or miR-19b-1 downregulated IL32 expression in the A549 and HCC827 cells and upregulated IL32 expression in CNE2 and HONE1 cells. In addition, enforced miR-19a or miR-19b-1 expression suppressed IL-6 production by lung cancer and nasopharyngeal carcinoma (NPC) cells. Taken together, these findings demonstrate, for the first time, that miR-19 can modulate the expression of IFN-induced genes and MHC class I genes in human cancer cells, suggesting a novel role of miR-19 in linking inflammation and cancer, which remains to be fully characterized.
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Background: Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disorder. It has two pathological subtypes: classical HCL (HCL-C) and HCL-variant (HCL-V). HCL-C and HCL-V are distinct in morphology and immunophenotype. ⋯ CNAs and CN-LOHs were common in both HCL-V and HCL-C but the CNAs were different in them. HCL-C was characterized with the higher ratio of large chromosomal changes but lacked of recurrent CNAs, while HCL-V was presented with the higher incidence of cryptic CNAs and recurrent CNAs involving tumor-associated genes. It is necessary to further investigate the association of the genes, such as NPHP1 and TRAF3 genes, and HCL-V in the future study.
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Comparative Study
Angiotensin II receptor Neprilysin inhibitor (LCZ696) compared to Valsartan attenuates Hepatotoxicity in STZ-induced hyperglycemic rats.
Background and objectives: Although diabetic-induced hepatotoxicity is less common, it can be included in the list of target organ pathologies associated with diabetes. This study aimed to investigate the potential therapeutic role of sacubitril/valsartan (LCZ696) in modulating oxidative and inflammatory injuries and liver fibrosis in STZ-induced hyperglycemic rats in comparison to valsartan alone. Materials and Methods: Following the induction of diabetes using a single dose of streptozotocin (STZ), STZ-induced hyperglycemic animals were administered LCZ696 or valsartan for 6 weeks. ⋯ LCZ696 was superior to valsartan in reducing AST, hepatic fibrosis, tissue IL-1β, TNF-α and NF-κB. In addition, compared with the valsartan group, LCZ696 significantly increased the antioxidant parameters such as GSH, SOD, CAT and GPx. Conclusion: Collectively, our data demonstrated that LCZ696 could suppress the progression of diabetes-induced hepatic fibrosis, correlating with reduced oxidative stress, hepatic inflammation and NF-κB compared with valsartan alone.