Johannsenhyldgaard6118

Breast cancer is the second most common malignancy in women. Current clinical therapy for breast cancer has many disadvantages, including metastasis, recurrence, and poor quality of life. Furthermore, it is necessary to find a new therapeutic drug for breast cancer patients to meet clinical demand. n-Butylidenephthalide (BP) is a natural and hydrophobic compound that can inhibit several tumors. However, BP is unstable in aqueous or protein-rich environments, which reduces the activity of BP. Therefore, we used an LPPC (Lipo-PEG-PEI complex) that can encapsulate both hydrophobic and hydrophilic compounds to improve the limitation of BP. The purpose of this study is to investigate the anti-tumor mechanisms of BP and BP/LPPC and further test the efficacy of BP encapsulated by LPPC on SK-BR-3 cells. BP inhibited breast cancer cell growth, and LPPC encapsulation (BP/LPPC complex) enhanced the cytotoxicity on breast cancer by stabilizing the BP activity and offering endocytic pathways. Additionally, BP and LPPC-encapsulated BP induced cell cycle arrest at the G0/G1 phase and might trigger both extrinsic as well as intrinsic cell apoptosis pathway, resulting in cell death. Moreover, the BP/LPPC complex had a synergistic effect with doxorubicin of enhancing the inhibitory effect on breast cancer cells. Consequently, LPPC-encapsulated BP could improve the anti-cancer effects on breast cancer in vitro. In conclusion, BP exhibited an anti-cancer effect on breast cancer cells, and LPPC encapsulation efficiently improved the cytotoxicity of BP via an acceleration of entrapment efficiency to induce cell cycle block and apoptosis. Furthermore, BP/LPPC exhibited a synergistic effect in combination with doxorubicin.Background Although whole-body cooling has been reported to improve the ischemic/reperfusion injury in hemorrhagic shock (HS) resuscitation, it is limited by its adverse reactions following therapeutic hypothermia. HS affects the experimental and clinical bowel disorders via activation of the brain-gut axis. It is unknown whether selective brain cooling achieves beneficial effects in HS resuscitation via preserving the integrity of the brain-gut axis. Methods Male Sprague-Dawley rats were bled to hypovolemic HS and resuscitated with blood transfusion followed by retrograde jugular vein flush (RJVF) with 4 °C or 36 °C normal saline. The mean arterial blood pressure, cerebral blood flow, and brain and core temperature were measured. The integrity of intestinal tight junction proteins and permeability, blood pro-inflammatory cytokines, and multiple organs damage score were determined. Results Following blood transfusion resuscitation, HS rats displayed gut barrier disruption, increased blood levels of pro-inflammatory cytokines, and peripheral vital organ injuries. Intrajugular-based infusion cooled the brain robustly with a minimal effect on body temperature. This brain cooling significantly reduced the HS resuscitation-induced gut disruption, systemic inflammation, and peripheral vital organ injuries in rats. Conclusion Resuscitation with selective brain cooling achieves peripheral vital organs protection in hemorrhagic shock resuscitation via preserving the integrity of the brain-gut axis.Although accumulating evidence has revealed that metallothioneins (MTs) and its family member MT2A are strongly linked to the risk of various solid tumors, researches on the occurrence and development of acute myeloid leukemia (AML) have rarely been investigated. Here, we constructed a lentiviral vector with MT2A over-expression and the interfering plasmids with MT2A expression inhibition to study the influence of MT2A on the bioactivities of HL60 cells. After cells were infected with a lentiviral vector containing the MT2A gene, both transcription and translation levels of MT2A were significantly increased in the over-expressed group in comparison with control groups. In vitro experiments, all results demonstrated that cell reproductive capacity was inhibited, but cell apoptosis rate was significantly increased. Together, the expression of apoptosis-related protein Bcl2 was remarkably reduced, while a high expression level of Bax protein was detected. Further experiments revealed that up-regulation of MT2A induced cell apoptosis and promoted G2/M phase arrest. The mechanism may be associated with down-regulated p-IκB-α and cyclinD1 expression and up-regulated IκB-α expression in the nuclear factor-kappaB (NF-κB) pathway. On the contrary, MT2A expression was down-regulated by interfering plasmids. We found that cell proliferative potential was notably increased in the interfering group compared with the negative and untreated group. What's more, MT2A may be closely related to AML cell proliferation and function via the NF-κB signal pathway.Objective To investigate the association of a wide QRS-T angle on the surface ECG and late gadolinium enhancement on contrast-enhanced cardiovascular magnetic (CMR) imaging in patients with clinically suspected myocarditis. Background Diagnosis and risk stratification in patients with suspected myocarditis is particularly challenging due to a great spectrum of clinical presentations. Late gadolinium enhancement (LGE) visualizes myocardial necrosis and fibrosis in patients with biopsy-proven myocarditis. The presence or absence of late gadolinium enhancements in these patients is prognostically meaningful. The QRS-T angle from the surface ECG, on the other hand, may serve as a simple and easily available risk marker in suspected myocarditis. Methods We enrolled 97 consecutive patients that were referred to CMR imaging for a clinical suspicion of myocarditis. All patients obtained a standardized digital 12-lead ECG for the calculation of the QRS-T angle and underwent contrast-enhanced CMR imaging. Patients were divided into two groups according to the absence or presence of LGE on CMR. Results 78 of 97 patients with suspected myocarditis had LGE on CMR. Patients with LGE had wider QRS-T angles as compared to the patient group without LGE (53.95-47.5 vs. 26.2-21.2; p less then 0.001). The sensivity, specificity, negative predictive value and positive predictive value for a QRS-T angle above 90 degrees for LGE positive myocarditis were 16.5%, 100%, 24.7%, and 100%, respectively. SAR405838 order Conclusion A wide QRS-T angle of 90 degrees or more is linked to myocardial fibrosis or necrosis (late gadolinium enhancement) in patients with suspected myocarditis.