Randruppollard4655

The underlying mechanism for protective effects of CARMP in pathological hypertrophy was determined by using a NF-κB agonist together with rCRAMP (rat homolog for human LL-37) in AngII or PE treated neonatal rat cardiomyocytes (NRCMs). Results Serum levels of LL-37 were significantly decreased in acute HF patients (area under the curve (AUC) of 0.616), and negatively correlated with NT-proBNP. We further confirmed that mCRAMP was decreased in both heart and serum samples of TAC- and ISO-induced HF mice models. Moreover, in PE and AngII-induced NMCMs hypertrophic models, both intracellular and secreted mCRAMP levels were reduced. Functionally, mCRAMP could attenuate TAC, ISO, and AngII-induced HF in mice while CRAMP deficiency exacerbated HF. Mechanistically, the anti-hypertrophy effects of CRAMP were mediated by NF-κB signaling. Conclusions Collectively, serum LL-37 is associated with acute HF and increasing CRAMP is protective against deleterious NF-κB signaling in the rodent.Reduced hepatic Na+/K+-ATPase (NKA) activity and NKAα1 expression are engaged in the pathologies of metabolism diseases. The present study was designed to investigate the potential roles of NKAα1 in hepatic gluconeogenesis and glycogenesis in both hepatocytes and obese diabetic mice. Methods Insulin resistance was mimicked by glucosamine (GlcN) in either human hepatocellular carcinoma (HepG2) cells or primary mouse primary hepatocytes. Obese diabetic mice were induced by high-fat diet (HFD) feeding for 12 weeks. Results We found that both NKA activity and NKAα1 protein level were downregulated in GlcN-treated hepatocytes and in the livers of obese diabetic mice. Pharmacological inhibition of NKA with ouabain worsened, while activation of NKAα1 with an antibody against an extracellular DR region of NKAα1 subunit (DR-Ab) prevented GlcN-induced increase in gluconeogenesis and decrease in glycogenesis. Likewise, the above results were also corroborated by the opposite effects of genetic knockout/overexpression of NKAα1 on both gluconeogenesis and glycogenesis. In obese diabetic mice, hepatic activation or overexpression of NKAα1 stimulated the PI3K/Akt pathway to suppress hyperglycemia and improve insulin resistance. More importantly, loss of NKA activities in NKAα1+/- mice was associated with more susceptibility to insulin resistance following HFD feeding. Conclusions Our findings suggest that NKAα1 is a physiological regulator of glucose homoeostasis and its DR-region is a novel target to treat hepatic insulin resistance.Background The exact identification of tumor boundaries and related liver segments is especially important for liver tumor surgery. This study aimed to evaluate a new approach for vascular boundary assessment and surgical navigation based on fiber-optic microscopy and microvascular fluorescence labeling. Methods Antibody clones with fast binding ability were identified and selected using immunofluorescence. We evaluated the endothelial capture efficacy for an anti-mouse CD31 antibody labeled with different fluorophores and different degrees of labeling ex vivo. Segment boundary identification and navigation potential using endothelial capture were explored by two different fiber-optic microscopy systems. Finally, microvasculature labeling and fiber-optic microscopy were used to identify and treat microscopic liver tumors in vivo. Results The following monoclonal antibodies were selected anti-mouse CD31 (clone 390), anti-mouse CD54 (YN1/1.7.4), anti-human CD31 (WM59), and anti-human CD54 (HA58). These clones showed fast binding to endothelial cells and had long half-lives. The fluorophore choice and the degree of antibody labeling did not significantly affect capture efficacy in an isolated liver perfusion model. The microvascular system was clearly identified with wide-field fiber-optic microscopy after labeling the endothelium with low doses of specific antibodies, and the specifically labeled liver segment could be microscopically dissected. Olaparib mouse High antibody doses were required for confocal laser endomicroscopy. After microscopically identifying the vascular margin in vivo, tumor thermoablation strongly reduced tumor size or totally eliminated tumors. Conclusions We demonstrated that vascular boundaries of liver tumors and locally perfused liver segments were accurately identified and surgical micronavigation was facilitated with fiber-optic microscopy and selected endothelium-specific antibodies.EGFR TKI therapy has become a first-line regimen for non-small cell lung cancer (NSCLC) patients with EGRF mutations. However, there are two big challenges against effective therapy--the secondary EGFR mutation-associated TKI resistance and brain metastasis (BMs) of lung cancer. The BMs is a major cause of death for advanced NSCLC patients, and the treatment of BMs with TKI resistance remains difficult. Methods Tumor-associated macrophages (TAM) is a promising drug target for inhibiting tumor growth, overcoming drug resistance, and anti-metastasis. TAM also plays an essential role in regulating tumor microenvironment. We developed a dual-targeting liposomal system with modification of anti-PD-L1 nanobody and transferrin receptor (TfR)-binding peptide T12 for codelivery of simvastatin/gefitinib to treat BMs of NSCLC. Results The dual-targeting liposomes could efficiently penetrate the blood-brain barrier (BBB) and enter the BMs, acting on TAM repolarization and reversal of EGFRT790M-associated drug resistance. The treatment mechanisms were related to the elevating ROS and the suppression of the EGFR/Akt/Erk signaling pathway. Conclusion The dual-targeting liposomal codelivery system offers a promising strategy for treating the advanced EGFRT790M NSCLC patients with BMs.Rationale To retrospectively analyze serial chest CT and clinical features in patients with coronavirus disease 2019 (COVID-19) for the assessment of temporal changes and to investigate how the changes differ in survivors and nonsurvivors. Methods The consecutive records of 93 patients with confirmed COVID-19 who were admitted to Wuhan Union Hospital from January 10, 2020, to February 22, 2020, were retrospectively reviewed. A series of chest CT findings and clinical data were collected and analyzed. The serial chest CT scans were scored on a semiquantitative basis according to the extent of pulmonary abnormalities. Chest CT scores in different periods (0 - 5 days, 6 - 10 days, 11 - 15 days, 16 - 20 days, and > 20 days) since symptom onset were compared between survivors and nonsurvivors, and the temporal trend of the radiographic-clinical features was analyzed. Results The final cohort consisted of 93 patients 68 survivors and 25 nonsurvivors. Nonsurvivors were significantly older than survivors. For both survivors and nonsurvivors, the chest CT scores were not different in the first period (0 - 5 days) but diverged afterwards.