In the previous research, we found that anticancer agent LS-1-2F could cause the vacuolation of tumor cells. Herein we investigated the effect of compound LS-1-2F on the endocytosis of macromolecules, including fluorescence quantum dots, human serum albumin, single-stranded RNA, and monoclonal antibody, into tumor cells. We found that LS-1-2F could accelerate the endocytosis of these large molecules by laser confocal microscope and flow cytometry. The effect of LS-1-2F on the improvement of the internalization efficiency of Herceptin biosimilar was particularly significant. Promoting endocytosis will help increase the efficiency of liquid-phase drug uptake in drug-resistant cancer cells and could potentially facilitate the use of drugs in nanoparticle delivery vehicles. 相似文献
Icariin (ICA) is obtained from Epimedium brevicornu maxim and exploited to remedy miscellaneous cancers. But the role of ICA in medulloblastoma remains hazy. The research delved into the antitumor activity of ICA in medulloblastoma DAOY cells. ICA with diverse concentrations was utilized to stimulate DAOY cells, and the biological functions of ICA in medulloblastoma DAOY cells were examined. Then, the relative SPARC expression was determined in ICA‐managed DAOY cells, and the pc‐SPARC vector was transfected into DAOY cells to further probe the influence of SPARC and JAK1/STAT3 and PI3K/AKT pathways in ICA‐managed DAOY cells. A xenograft model was established to investigate the function of ICA in vivo. ICA restrained cell viability, expedited apoptosis, prohibited cell migration and invasion, and meanwhile affected the associative factors expression in DAOY cells. Additionally, SPARC expression was declined in ICA‐stimulated DAOY cells. Overexpressed SPARC reversed the functions of ICA in above‐involved cell behaviors of DAYO cells and the correlative protein levels. Besides, ICA notably frustrated JAK1/STAT3 and PI3K/AKT activations in DAOY cells. Beyond that, ICA prohibited tumor formation in vivo. The results concluded that ICA exhibited the antitumor activity in DAOY cells via decreasing SPARC and inactivating JAK1/STAT3 and PI3K/AKT pathways. 相似文献
Visceral fat loss in response to four‐cycle ergometer training regimens with explicit differences in exercise intensity and modality was compared. Fifty‐nine obese young women (body fat percentage ≥ 30%) were randomized to a 12‐week intervention consisting of either all‐out sprint interval training (SITall‐out, n = 11); supramaximal SIT (SIT120, 120% O2peak, n = 12); high‐intensity interval training (HIIT90, 90% O2peak, n = 12), moderate‐intensity continuous training (MICT, 60% O2peak, n = 11), or no training (CON, n = 13). The total work done per training session in SIT120, HIIT90, and MICT was confined to 200 kJ, while it was deliberately lower in SITall‐out. The abdominal visceral fat area (AVFA) was measured through computed tomography scans. The whole‐body and regional fat mass were assessed through dual‐energy X‐ray absorptiometry. Pre‐, post‐, and 3‐hour post‐exercise serum growth hormone (GH), and epinephrine (EPI) were measured during selected training sessions. Following the intervention, similar reductions in whole‐body and regional fat mass were found in all intervention groups, while the reductions in AVFA resulting from SITall‐out, SIT120, and HIIT90 (>15 cm2) were greater in comparison with MICT (<3.5 cm2, P < .05). The AVFA reductions among the SITs and HIIT groups were similar, and it was concomitant with the similar exercise‐induced releases of serum GH and EPI. CON variables were unchanged. These findings suggest that visceral fat loss induced by interval training at or above 90% O2peak appeared unresponsive to the change in training intensity. Nonetheless, SITall‐out is still the most time‐efficient strategy among the four exercise‐training regimes for controlling visceral obesity. 相似文献
The ε4 allele of the APOE gene is thought to increase risk from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease. Cognitive decline in the condition is increasingly considered to worsen functional disconnections in brain network composed of gray matter and white matter. Nevertheless, Whether APOEε4 targets specific white matter functional connectivity in patients with aMCI remains mostly unexplored, mainly due to the challenges of detecting BOLD signals in white matter. Here, we applied a novel approach to investigate APOEε4-related specific bundles and cortical area alterations in aMCI subjects, in order to characterize white matter-gray matter functional connectivity differences throughout the brain. We analyzed 75 patients with aMCI and 76 demographically matched normal controls. The aMCI APOEε4 carriers showed decreased functional connectivity located at left corticospinal tract, bilateral posterior limb of internal capsule, and right temporopolaris, which was different from the regions of aMCI-related changes. We further found that recognition scores were positively associated with the right temporopolaris in aMCI APOEε4 carriers. Collectively, the data provide new evidence that APOEε4 genotype exerts a negative impact on neural activity in both gray and white matter in aMCI, which potentially contributes to functional disconnection and memory decline. A novel method provides full-scale measuring effect of disease conditions on functional architecture throughout the brain. Trial registration: https://www.ClinicalTrials.gov (Identifier: NCT02225964). Registered January 2014.