MiR-140 Resensitizes Cisplatin-Resistant NSCLC Cells to Cisplatin Treatment Through the SIRT1/ROS/JNK Pathway.

BACKGROUND: Although cisplatin is an effective chemotherapeutic drug that is commonly used for non-small-cell lung cancer (NSCLC) treatment, the drug resistance usually occurs during the long-term use of it. It is urgent to develop strategies to reduce the resistance of NSCLC cells to cisplatin. METHODS: Cisplatin-resistant NSCLC cell lines (PC9/R and A549/R) were acquired through long-term exposure of PC9 and A549 cells to cisplatin. QRT-PCR analysis was performed to compare the expression of miR-140 between routine NSCLC cells and cisplatin-resistant NSCLC cells. CCK-8 assay was used to evaluate the effect of miR-140 on the sensitivity of PC9/R and A549/R to cisplatin. Western blot assay and luciferase reporter assay were used to confirm the regulation of miR-140 on SIRT1. Western blot and flow cytometry analysis were performed to evaluate the effect of miR-140 on the apoptosis pathway induced by cisplatin. RESULTS: PC9/R and A549/R exhibited obviously lower sensitivity compared to their parental PC9 and A549 cells, respectively. Furthermore, PC9/R and A549/R cells expressed significantly lower levels of miR-140 compared to their parental PC9 and A549 cells, respectively. However, transfection with miR-140 mimics significantly resensitized the PC9/R and A549/R to cisplatin-induced cytotoxicity. In the mechanism research, we confirmed that SIRT1 was overexpressed and was targeted by miR-140 in PC9/R and A549/R. Furthermore, overexpression of SIRT1 was responsible for the resistance to cisplatin in PC9/R and A549/R cells. Transfection with miR-140 was able to inhibit the expression of SIRT1 and thus inhibited the SIRT1/ROS/JNK pathway. As a result, the PC9/R and A549/R cells restored the sensitivity to cisplatin-induced apoptosis. CONCLUSION: MiR-140 resensitizes cisplatin-resistant NSCLC cells to cisplatin treatment through the SIRT1/ROS/JNK pathway.

Potential killer in the ICU-severe tuberculosis combined with hemophagocytic syndrome: A case series and literature review.

Hemophagocytic syndrome (HPS) is a life-threatening clinical syndrome that has various presentations, shows rapid progression and is associated with a high mortality. Clinical reports about pulmonary tuberculosis combined with respiratory failure accompanied by HPS are rare.HPS has no special clinical manifestations, and the main presentations include persistent fever, hepatosplenomegaly, hematocytopenia, and rash. In the Intensive Care Unit (ICU), the clinical manifestations of severe infection and secondary HPS overlap, thus there is often a delay in the diagnosis and treatment of HPS.HPS is not an independent disease but represents an excessive inflammatory response due to immune dysfunction induced by various causes such as infection and tumor.The 2 cases in this report show that tuberculosis-associated hemophagocytic syndrome is not easy to find, especially in ICU. There are few clinical reports of pulmonary tuberculosis combined with respiratory failure and HPS. Here, we describe 2 such clinical cases and review the relevant literature in order to deepen our understanding of this disease.

Histopathological findings in a critically ill patient with avian influenza A (H7N9).

To date, data regarding the pulmonary histopathology of human H7N9 disease are scarce. We herein describe a patient with a severe case of avian influenza A (H7N9). A chest computerized tomography (CT) scan showed diffuse ground-glass opacities and consolidation throughout the lungs. A resection of pulmonary bullae in the right middle lobe was performed by video-assisted thoracic surgery (VATS) based on the extracorporeal membrane oxygenation (ECMO) supportive technique on the 23(rd) day after the onset of symptoms because of a right pneumothorax persistent air leak. The histopathological findings of the resected lung tissue revealed pneumocyte hyperplasia and fibroproliferative changes along with diffuse alveolar damage. Bronchoalveolar lavage fluid (BALF) specimens for influenza A (H7N9) virus were continuously positive for more than three weeks, despite oseltamivir treatment, and continuous viral replication significantly prolonged the course of the disease. The patient's clinical status continuously deteriorated, with the development of refractory hypoxemia due to progressive and rapid lung fibrosis, which was confirmed by the final histological changes observed from a limited post-mortem biopsy of lung tissue. Pre-terminally, he developed multi-organ failure and died on the 39(th) day after symptom onset, despite corticosteroid treatment.