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Breast cancer is the most common cancer and a frequent cause of cancer-related deaths among women wordlwide. As therapeutic strategies for breast cancer have limitations, novel chemotherapeutic reagents and treatment strategies are needed. In this study, we investigated the anti-cancer effect of synthetic homoisoflavane derivatives of cremastranone on breast cancer cells. Homoisoflavane derivatives, SH-17059 and SH-19021, reduced cell proliferation through G2/M cell cycle arrest and induced caspase-independent cell death. These compounds increased heme oxygenase-1 (HO-1) and 5-aminolevulinic acid synthase 1 (ALAS1), suggesting downregulation of heme. They also induced reactive oxygen species (ROS) generation and lipid peroxidation. Furthermore, they reduced expression of glutathione peroxidase 4 (GPX4). Therefore, we suggest that the SH-17059 and SH-19021 induced the caspase-independent cell death through the accumulation of iron from heme degradation, and the ferroptosis might be one of the potential candidates for caspase-independent cell death.
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Background and Objectives@#Embryonic stem (ES) cells have the capacity to self-renew and generate all types of cells.MUC1-C, a cytoplasmic subunit of MUC1, is overexpressed in various carcinomas and mediates signaling pathways to regulate intracellular metabolic processes and gene expression involved in the maintenance of cancer cells. However, the functional role of MUC1-C in ES cells is not well understood. In this study, we investigated the role of MUC1-C on growth, survival,: and differentiation of mouse ES (mES) cells. @*Methods@#and Results: Undifferentiated mES cells expressed the MUC1-C protein and the expression level was decreased during differentiation. Inhibition of MUC1-C, by the specific inhibitor GO201, reduced proliferation of mES cells.However, there was no prominent effect on pluripotent markers such as Oct4 expression and STAT3 signaling, and MUC1-C inhibition did not induce differentiation. Inhibition of MUC1-C increased the G1 phase population, decreased the S phase population, and increased cell death. Furthermore, inhibition of MUC1-C induced disruption of the ROS balance in mES cells. @*Conclusions@#These results suggest that MUC1-C is involved in the growth and survival of mES cells.
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Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Signaling pathways that are essential for virus production have potential as therapeutic targets against COVID-19. In this study, we investigated cellular responses in two cell lines, Vero and Calu-3, upon SARS-CoV-2 infection and evaluated the effects of pathway-specific inhibitors on virus production. SARS-CoV-2 infection induced dephosphorylation of STAT1 and STAT3, high virus production, and apoptosis in Vero cells. However, in Calu-3 cells, SARS-CoV-2 infection induced long-lasting phosphorylation of STAT1 and STAT3, low virus production, and no prominent apoptosis. Inhibitors that target STAT3 phosphorylation and dimerization reduced SARS-CoV-2 production in Calu-3 cells, but not in Vero cells. These results suggest a necessity to evaluate cellular consequences upon SARS-CoV-2 infection using various model cell lines to find out more appropriate cells recapitulating relevant responses to SARS-CoV-2 infection in vitro.
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Background and Objectives@#Embryonic stem (ES) cells have the capacity to self-renew and generate all types of cells.MUC1-C, a cytoplasmic subunit of MUC1, is overexpressed in various carcinomas and mediates signaling pathways to regulate intracellular metabolic processes and gene expression involved in the maintenance of cancer cells. However, the functional role of MUC1-C in ES cells is not well understood. In this study, we investigated the role of MUC1-C on growth, survival,: and differentiation of mouse ES (mES) cells. @*Methods@#and Results: Undifferentiated mES cells expressed the MUC1-C protein and the expression level was decreased during differentiation. Inhibition of MUC1-C, by the specific inhibitor GO201, reduced proliferation of mES cells.However, there was no prominent effect on pluripotent markers such as Oct4 expression and STAT3 signaling, and MUC1-C inhibition did not induce differentiation. Inhibition of MUC1-C increased the G1 phase population, decreased the S phase population, and increased cell death. Furthermore, inhibition of MUC1-C induced disruption of the ROS balance in mES cells. @*Conclusions@#These results suggest that MUC1-C is involved in the growth and survival of mES cells.
ABSTRACT
Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Signaling pathways that are essential for virus production have potential as therapeutic targets against COVID-19. In this study, we investigated cellular responses in two cell lines, Vero and Calu-3, upon SARS-CoV-2 infection and evaluated the effects of pathway-specific inhibitors on virus production. SARS-CoV-2 infection induced dephosphorylation of STAT1 and STAT3, high virus production, and apoptosis in Vero cells. However, in Calu-3 cells, SARS-CoV-2 infection induced long-lasting phosphorylation of STAT1 and STAT3, low virus production, and no prominent apoptosis. Inhibitors that target STAT3 phosphorylation and dimerization reduced SARS-CoV-2 production in Calu-3 cells, but not in Vero cells. These results suggest a necessity to evaluate cellular consequences upon SARS-CoV-2 infection using various model cell lines to find out more appropriate cells recapitulating relevant responses to SARS-CoV-2 infection in vitro.
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OBJECTIVE: To investigate whether an audible cracking sound during shoulder manipulation following distention arthrography is clinically significant in patients with adhesive capsulitis of the shoulder. METHODS: A total of 48 patients (31 women, 17 men) with primary adhesive capsulitis of the shoulder completed the study. All participants underwent C-arm-guided arthrographic distention of the glenohumeral joint with injections of a corticosteroid and normal saline. After distention, we performed flexion and abduction manipulation of the shoulder. The patients were grouped into sound and non-sound groups based on the presence or absence, respectively, of an audible cracking sound during manipulation. We assessed shoulder pain and disability based on a Numeric Rating Scale (NRS), the Shoulder Pain and Disability Index (SPADI), and passive range of motion (ROM) measurements (flexion, abduction, internal and external rotation) before the procedure and again at 3 weeks and at 6 weeks after the intervention. RESULTS: The patients were divided into two groups: 21 were included in the sound group and 27 in the non-sound group. In both groups, the results of the NRS, SPADI, and ROM assessments showed statistically significant improvements at both 3 and 6 weeks after the procedure. However, there were no significant differences between the two groups except with respect to external rotation at 6 weeks, at which time the sound group showed a significant improvement in external rotation when compared with the non-sound group (p<0.05). CONCLUSION: These findings showed that manipulation following distention arthrography was effective in decreasing pain and increasing shoulder range of motion. In addition, the presence of an audible cracking sound during manipulation, especially on external rotation, was associated with better shoulder range of motion.
Subject(s)
Female , Humans , Adhesives , Arthrography , Bursitis , Range of Motion, Articular , Shoulder Joint , Shoulder Pain , ShoulderABSTRACT
OBJECTIVE: To verify the utility of the lateral femoral cutaneous nerve (LFCN) ultrasound-guided conduction technique compared to that of the conventional nerve conduction technique. METHODS: Fifty-eight legs of 29 healthy participants (18 males and 11 females; mean age, 42.7+/-14.9 years) were recruited. The conventional technique was performed bilaterally. The LFCN was localized by ultrasound. Cross-sectional area (CSA) of the LFCN and the distance between the anterior superior iliac spine (ASIS) and the LFCN was measured. The nerve conduction study was repeated with the corrected cathode location. Sensory nerve action potential (SNAP) amplitudes of the LFCN were recorded and compared between the ultrasound-guided and conventional techniques. RESULTS: Mean body mass index of the participants was 23.7+/-3.5 kg/m2, CSA was 4.2+/-1.9 mm2, and the distance between the ASIS and LFCN was 5.6+/-1.7 mm. The mean amplitude values were 6.07+/-0.52 microV and 6.66+/-0.54 microV using the conventional and ultrasound-guided techniques, respectively. The SNAP amplitude of the LFCN using the ultrasound-guided technique was significantly larger than that recorded using the conventional technique. CONCLUSION: Correcting the stimulation position using the ultrasound-guided technique helped obtain increased SNAP amplitude.