Inhibiting circ_0000673 blocks the progression of colorectal cancer through downregulating CPSF6 via targeting miR-548b-3p.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers, and its progression is regulated by several factors, including circular RNA (circRNA). OBJECTIVES: The objective of this study was to determine the role, or roles, of circ_0000673 in CRC. MATERIAL AND METHODS: We used quantitative real-time polymerase chain reaction (qPCR) to detect the expression of circ_0000673, miR-548b-3p and cleavage and polyadenylation specific factor 6 (CPSF6) in DLD-1 and RKO cells. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to determine circ_0000673 roles in proliferation. Wound healing and transwell assays were used to detect cell migration and invasion abilities. Expression of CPSF6 protein and stem cell-associated proteins were examined using western blot. The putative relationship between miR-548b-3p and circ_0000673 or CPSF6 was verified with dual-luciferase reporter assay. The role of circ_0000673 in CRC was also investigated in a tumor xenograft assay in nude mice. RESULTS: Circ_0000673 expression was increased in CRC tissues and cancer cells. Silencing circ_0000673 reduced tumor cell proliferation, migration and invasion, while also decreasing cell stemness. MiR-548b-3p was found to be a target of circ_0000673, while CPSF6 was a downstream target of miR-548b-3p. The tumor-regulatory effects of si-circ_0000673, anti-miR-548b-3p and oe-CPSF6 were partially reversed by anti-miR-548b-3p, si-CPSF6 and si-circ_0000673, respectively, in rescue assays. Downregulation of circ_0000673 reduced solid tumor growth in vivo. CONCLUSIONS: Circ_0000673 inhibition reduced CPSF6 expression by targeting miR-548b-3p, thereby blocking proliferation, migration and invasion of CRC tumor cells.

The value of lymphocyte count in determining the severity of COVID-19 and estimating the time for nucleic acid test results to turn negative.

Peripheral blood lymphocyte count is shown to be decreased in patients with COVID-19 in the early stage of the disease. The degree of lymphocyte count reduction is related to COVID-19 severity and could be used as an indicator to reflect the disease severity. Our aim was to investigate the value of lymphocyte count in determining COVID-19 severity and estimating the time for SARS-CoV-2 nucleic acid test results to turn negative. We retrospectively analyzed clinical data of 201 patients with severe and critical COVID-19. The patients were admitted to the West Campus of Union Hospital of Tongji Medical College of Huazhong University of Science and Technology. The data included age, gender, chronic disease, lymphocyte count, and SARS-CoV-2 nucleic acid test results. The age of patients in critically ill group was higher than in severely ill group (p = 0.019). The lymphocyte count of critically ill patients was lower than of severely ill patients. The cutoff value of lymphocyte count to distinguish between the critically ill and the severely ill was 0.735 × 109/L (p = 0.001). The cutoff value of lymphocyte count for SARS-CoV-2 nucleic acid test results turning negative in severely and critically ill patients with chronic diseases (hypertension, diabetes, and coronary heart disease) was 0.835 × 109/L (p = 0.017). The cutoff value of lymphocyte count for SARS-CoV-2 nucleic acid test results turning negative in severely and critically ill male patients was 0.835 × 109/L (p < 0.0001). Lymphocyte count could be an effective indicator to predict COVID-19 severity. It may also be useful in determining the time for nucleic acid test results to turn negative in COVID-19 patients with underlying chronic diseases or male COVID-19 patients with severe and critical conditions.

Clinical characteristics of patients with COVID-19 presenting with gastrointestinal symptoms as initial symptoms: Retrospective case series.

BACKGROUND: A large number of pneumonia cases due to coronavirus disease 2019 (COVID-19) have been first reported in China. Meanwhile, the virus is sweeping all around the world and has infected millions of people. Fever and pulmonary symptoms have been noticed as major and early signs of infection, whereas gastrointestinal symptoms were also observed in a significant portion of patients. The clinical investigation of disease onset was underestimated, especially due to the neglection of cases presenting with gastrointestinal symptoms. AIM: To characterize the clinical features of coronavirus-infected patients with gastrointestinal symptoms as initial symptoms. METHODS: This is a retrospective, single-center case series of the general consecutive hospitalized patients with confirmed COVID-19 at Wuhan Union Hospital from February 2, 2020 to February 13, 2020. According to their initial symptoms, these patients were classified into two groups. Patients in group one presented with pulmonary symptoms (PS) as initial symptoms, and group two presented with gastrointestinal symptoms (GS). Epidemiological, demographic, clinical, laboratory, and treatment data were collected for analysis. RESULTS: Among the 50 patients recruited, no patient has been admitted to intensive care units, and no patient died during the study. The duration of hospitalization was longer in the GS group than in the PS group (12.13 ± 2.44 vs 10.00 ± 2.13, P < 0.01). All of the 50 patients exhibited decreased lymphocytes. However, lymphocytes in the GS group were significantly lower compared to those in the PS group (0.94 ± 0.06 vs 1.04 ± 0.15, P < 0.01). Procalcitonin and hs-CRP were both significantly higher in the GS group than in the PS group. Accordingly, the duration of viral shedding was significantly longer in the GS group compared to the PS group (10.22 ± 1.93 vs 8.15 ± 1.87, P < 0.01). CONCLUSION: COVID-19 patients presenting with gastrointestinal symptoms as initial symptoms need more days of viral shedding and hospitalization than the patients presenting with pulmonary symptoms.

Clinical application of intra-aortic balloon pump in patients with cardiogenic shock during the perioperative period of cardiac surgery.

Intra-aortic balloon pumps (IABP) have saved many patients with cardiogenic shock during the perioperative period of cardiac surgery. However, the ideal insertion timing is controversial. In the present study, we aimed to optimize the insertion timing, in order to increase the survival rate of the patients. A total of 197 patients with cardiogenic shock during the perioperative period of cardiac surgery and implemented IABP from January 2011 to October 2015 were selected for the study. Patients were divided into five groups on the basis of application timing of IABP: 0-60, 61-120, 121-180, 181-240 and >240 min. The 30-day mortality, application rate of continuous renal replacement therapy (CRRT), duration of mechanical ventilation, duration of hospital stay and hospitalization charges were analyzed in the above groups. The risk factors related to mortality and the occurrence of IABP complications were also analyzed. The mortality in the 0-60, 61-120, 121-180, 181-240 and >240 min groups were 42.17, 36.6, 77.3, 72.7 and 79.3%, respectively. Earlier IABP insertion resulted in less patients receiving CRRT from acute renal failure and less daily hospitalization charges. However, the IABP application timing had no effect on indexes such as hospitalization duration, duration of mechanical ventilation and total hospitalization charges. Multifactor logistic regression analysis indicated that the independent risk factors of death in patients with cardiogenic shock during cardiac surgery were related to IABP support timing and vasoactive-inotropic score (VIS) before balloon insertion. In the first 120 min of cardiogenic shock during the perioperative period of cardiac surgery, IABP application decreased 30-day mortality. Mortality was related with VIS score of patients, which can be used to predict the prognosis of patients with cardiogenic shock.

Endoplasmic reticulum stress mediates the arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells.

Arsenic trioxide has been proven to trigger apoptosis in human hepatocellular carcinoma cells. Endoplasmic reticulum stress has been known to be involved in apoptosis through the induction of CCAAT/enhancer-binding protein homologous protein. However, it is unknown whether endoplasmic reticulum stress mediates arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells. Our data showed that arsenic trioxide significantly induced apoptosis in human hepatocellular carcinoma cells. Furthermore, arsenic trioxide triggered endoplasmic reticulum stress, as indicated by endoplasmic reticulum dilation, upregulation of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein. We further found that 4-phenylbutyric acid, an inhibitor of endoplasmic reticulum stress, alleviated arsenic trioxide-induced expression of CCAAT/enhancer-binding protein homologous protein. More important, knockdown of CCAAT/enhancer-binding protein homologous protein by siRNA or inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid alleviated apoptosis induced by arsenic trioxide. Consequently, our results suggested that arsenic trioxide could induce endoplasmic reticulum stress-mediated apoptosis in hepatocellular carcinoma cells, and that CCAAT/enhancer-binding protein homologous protein might play an important role in this process.

Arsenic trioxide induces G2/M arrest in hepatocellular carcinoma cells by increasing the tumor suppressor PTEN expression.

Arsenic trioxide (As(2)O(3)), an effective agent against acute promyelocytic leukemia, has been reported to inhibit the viability of solid tumors cell lines recently. The detailed molecular mechanism underlying the As(2)O(3)-induced inactivation of the cdc2 and possible functional role of PTEN in the observed G2/M arrest has yet to be elucidated. Here, we assessed the role of PTEN in regulation of As(2)O(3)-mediated G2/M cell cycle arrest in Hepatocellular carcinoma cell lines (HepG2 and SMMC7721). After 24 h following treatment, As(2)O(3) induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. The sustained G2/M arrest by As(2)O(3) is associated with decreased cdc2 protein and increased phospho-cdc2(Tyr15). As(2)O(3) treatment increased Wee1 levels and decreased phospho-Wee1(642). Moreover, As(2)O(3) substantially decreased the Ser473 and Thr308 phosphorylation of Akt and upregulated PTEN expression. Downregulation of PTEN by siRNA in As(2)O(3) -treated cells increased phospho-Wee1(Ser642) while decreased phospho-cdc2(Tyr15), resulting in decreased the G2/M cell cycle arrest. Therefore, induction of G2/M cell cycle arrest by As(2)O(3) involved upregulation of PTEN.