Effect of initial foot angle (IFA) on kinematics and dynamics of body during sit-to-stand transfer.

Sit-to-stand (STS) is considered the most common functional activities in daily life and the basis for other activities. The elderly and patients with lower limb disorders could not complete the STS motion very well due to limb pain and muscle weakness. Physiotherapist find that specific STS transfer strategies can make patients more easily to complete this task. However, few researchers pay attention to the effect of initial foot angle (IFA) on STS motion. Twenty-six healthy subjects were randomly selected to perform STS transfer experiment. The motion characteristic parameters of subjects under 4 different IFAs (nature, 0°, 15°, and 30°) were obtained, including the percentage of duration in each phase, the velocity of joints, rotation angle and angular velocity of joints (shoulder, hip and knee), center of gravity (COG) trajectory. the change of plantar pressure parameters, and dynamic margin of stability. By comparing the motion characteristic parameters obtained under different IFAs and carrying out statistical analysis, the influence of different IFAs on body kinematics and dynamics during STS task was further explored. The kinematic parameters obtained under different IFAs are significantly different. The percentage of duration in each phase of the STS transfer was different with different IFA, the main differences were in phase I and phase II. The phase I of U15 took 24.5% T, while phase I of N, U0 and U30 took about 20% T, and the maximum difference was (U15-U0) 5.4%. The phase II of U15 took the least time, about 30.8% T. When the IFA is nature (N) and 15°(U15), the trajectories of COG are basically in coincidence; when the IFA is 0°(U0) and 30°(U30), the displacement of COG in anterior-posterior direction is larger. The larger the IFA, the smaller the plantar pressure parameter. When the IFA is 15°, the COG is close to the center of limits of stability, which can provide a better stability. This paper summarizes the influence under 4 different experimental conditions of IFAs on STS transfer, so as to provide a starting point and bases for clinicians to develop rehabilitation training protocols and STS motion strategies for patient.

Cancer-Targeted Selenium Nanoparticles Sensitize Cancer Cells to Continuous γ Radiation to Achieve Synergetic Chemo-Radiotherapy.

Cancer radiotherapy with 125 I seeds demonstrates higher long-term efficacy and fewer side effects than traditional X-ray radiotherapy owing to its low-dose and continuous radiation but is still limited by radioresistance in clinical applications. Therefore, the design and synthesis of sensitizers that could enhance the sensitivity of cancer cells to 125 I seeds is of great importance for future radiotherapy. Selenium nanoparticles (SeNPs) have been found to exhibit high potential in cancer chemotherapy and as drug carriers. In this study, we found that, based on the Auger-electron effect and Compton effect of Se atoms, cancer-targeted SeNPs in combination with 125 I seeds achieve synergetic effects to inhibit cancer-cell growth and colony formation through the induction of cell apoptosis and cell cycle arrest. Detailed studies on the action mechanisms reveal that the combined treatments effectively activate intracellular reactive oxygen species (ROS) overproduction to regulate p53-mediated DNA damage apoptotic signaling pathways and mitogen-activated protein kinase (MAPK) phosphorylation and to prevent the self-repair of cancer cells simultaneously. Taken together, the combination of SeNPs with 125 I seeds could be further exploited as a safe and effective strategy for next-generation cancer chemo-radiotherapy in clinical applications.

Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy.

Rational design and construction of delivery nanosystems for anticancer metal complexes is a crucial strategy to improve solubility under physiological conditions and permeability and retention behavior in tumor cells. Therefore, in this study, we designed and synthesize a transferrin (Tf)-conjugated nanographene oxide (NGO) nanosystem as a cancer-targeted nanocarrier of Pt complexes (Tf-NGO@Pt). This nanodelivery system exhibited good solubility under physiological conditions. Moreover, Tf-NGO@Pt showed higher anticancer efficacy against MCF human breast cancer cells than the free Pt complex, and effectively inhibited cancer-cell migration and invasion, with involvement of reactive oxygen species overproduction. In addition, nanolization also enhanced the penetration ability and inhibitory effect of the Pt complex toward MCF7 breast cancer-cell tumor spheroids. The enhancement of anticancer efficacy was positively correlated with increased cellular uptake and cellular drug retention. This study provides a new strategy to facilitate the future application of metal complexes in cancer therapy.

Phycocyanin-based nanocarrier as a new nanoplatform for efficient overcoming of cancer drug resistance.

Resistance to chemotherapy remains the primary obstacle for the successful treatment of cancers. Nanotechnology-based studies have developed many smart nanomedicines and efficient strategies to overcome multidrug resistance (MDR), which have brought new horizons to cancer therapy. Among them, protein-based nanomedicine represents an appealing drug delivery platform to realize safe and superior therapeutic effects due to its paramount biocompatibility with minimized toxicity. Herein we describe the rational design and construction of a novel protein-based nanocarrier using the naturally-occurring protein phycocyanin (PC) as the base material, to achieve safe and tumor-specific drug delivery. This cancer-targeting nanosystem (FA-PCNP@DOX) with bio-responsive properties exhibits positive targeting accumulation in resistant cancer cells and overcomes drug efflux by enhancing cellular uptake and retention time. Specifically, FA-PCNP@DOX inhibits the function of pumping proteins of the ABC family and triggers ROS-mediated apoptotic signaling pathways, thereby attaining highly efficient anticancer efficacy and overcoming drug resistance. Pharmaceutical studies demonstrate that FA-PCNP@DOX overwhelms DOX by sustained release in the blood, which verifies its prolonged circulation in vivo. Moreover, FA-PCNP@DOX efficiently accumulates in tumors and strengthens the tumor inhibitory effect of DOX by enhanced tumoral penetration. Importantly, FA-PCNP@DOX effectively reduces the hepatic, pulmonary, renal and cardiac toxicity caused by DOX. Therefore, as a new nanocarrier, this novel nanosystem could be further exploited as a safe and versatile nanoplatform for next-generation cancer therapy.

A multifunctional DNA origami as carrier of metal complexes to achieve enhanced tumoral delivery and nullified systemic toxicity.

The use of metal complexes in cancer treatment is hampered by the insufficient accumulation in tumor regions and observable systemic toxicity due to their nonspecificity in vivo. Herein we present a cancer-targeted DNA origami as biocompatible nanocarrier of metal complexes to achieve advanced antitumor effect. The formation of unique tetrahedral nanostructure of DNA cages effectively enhances the interaction between ruthenium polypyridyl complexes (RuPOP) and the cages, thus increasing the drug loading efficacy. Conjugation of biotin to the DNA-based nanosystem (Bio-cage@Ru) enhances its specific cellular uptake, drug retention and cytotoxicity against HepG2 cells. Different from free RuPOP and the cage itself, Bio-cage@Ru translocates to cell nucleus after internalization, where it undergoes self-immolative cleavage in response to DNases, leading to triggered drug release and induction of ROS-mediated cell apoptosis. Moreover, in the nude mice model, the nanosystem specifically accumulates in tumor sites, thus exhibits satisfactory in vivo antitumor efficacy, and alleviates the damage of liver, kidney, lung and heart function of nude mice induced by RuPOP and tumor xenografts. Collectively, this study demonstrates a strategy for construction of biocompatible and cancer-targeted DNA origami with enhanced anticancer efficacy and reduced toxicity for next-generation cancer therapy.

Dual-Functional Nanographene Oxide as Cancer-Targeted Drug-Delivery System to Selectively Induce Cancer-Cell Apoptosis.

Construction of bioresponsive drug-delivery nanosystems could enhance the anticancer efficacy of anticancer agents and reduce their toxic side effects. Herein, by using transferrin (Tf) as a surface decorator, we constructed a cancer-targeted nanographene oxide (NGO) nanosystem for use in drug delivery. This nanosystem (Tf-NGO@HPIP) drastically enhanced the cellular uptake, retention, and anticancer efficacy of loaded drugs but showed much lower toxicity to normal cells. The nanosystem was internalized through receptor-mediated endocytosis and triggered pH-dependent drug release in acidic environments and in the presence of cellular enzymes. Moreover, Tf-NGO@HPIP effectively induced cancer-cell apoptosis through activation of superoxide-mediated p53 and MAPK pathways along with inactivation of ERK and AKT. Taken together, this study demonstrates a good strategy for the construction of bioresponsive NGO drug-delivery nanosystems and their use as efficient anticancer drug carriers.