Objective: The aim of the present study was to investigate the mechanisms responsible for the radiation-sensitizing effect of antennapedia proteins, ANTP-SMACN7, on lung cancer cells treated with accelerated carbon and Fe particle irradiation. Methods: The ANTP-SMACN7 fusion peptide was synthesized and linked to fluorescein isothiocyanate to determine its ability to penetrate cells. A549 and NCI-H460 cells, human non-small cell lung cancer (NSCLC) cell lines, were irradiated with X-ray or high linear energy transfer (LET) irradiation with or without ANTP-SMACN7 treatment. Cellular survival, apoptosis, and protein expression were studied by colony formation assays, flow cytometry, and western blot analyses, respectively. Results: ANTP-SMACN7 fusion proteins entered the cells and promoted A549 and NCI-H460 cell high LET irradiation radiosensitization. High LET irradiation was more efficient for clonogenic cell killing and the induction of apoptosis (P < 0.05). Treatment with ANTP-SMACN7 significantly reduced the A549 and NCI-H460 cell clone-forming percentages and increased apoptosis through inhibition of the X-linked inhibitor of apoptosis protein and the activation of caspase-3 and caspase-9. Conclusions: Regarding pharmaceutical radiosensitization, these findings provided a way to improve high-LET clinical radiotherapy for NSCLC patients.
Summary Rice bread is an essential component of a healthy diet. However, due to the poor processing properties of rice protein and starch, it is difficult to form an effective gel network structure, resulting in poor quality of rice breads. This research investigated the impacts of soy protein isolate (SPI) on the physicochemical properties of rice dough and the quality of rice bread. The results suggested that adding SPI could refine the thermal stability of mixtures and delay the aging of starch compared with pure rice flour, indicating that adding SPI reduced the amylose concentration and inhibited starch interaction in the mixed rice powder system. The rheology and SEM analysis of doughs showed that the appropriate addition of SPI increased the elasticity, and reached the highest fermentation height and gas retention coefficient at 9% SPI content, which increased by 115.38% and 8.39%, respectively. In contrast, excessive SPI led to protein aggregation and weakened the structural strength of the dough. When adding 9% SPI improved the hardness, chewiness and specific volume of rice bread, significantly reduced the brightness and baking loss rate, and refined the performance and quality of rice bread. This study confirms that SPI can be used as an improver for good gluten‐free bread (GFB) through its good functional properties and action on starch and provides some basis for further investigation of the interaction between SPI as an improver and rice starch.
In-stent restenosis (ISR) and its associated inflammation remains a significant concern for long-term patient outcomes following stent implantation in percutaneous coronary intervention (PCI). The problem is intricately associated with endothelial injury, excessive endothelialization, hyperproliferation of smooth muscle cells, and the infiltration of inflammatory molecules. However, commonly employed imaging techniques encounter challenges in simultaneously acquiring both vascular structural information and functional data related to inflammation. Here, we presented a novel Tri modality intravascular imaging system capable of simultaneous optical coherence tomography (OCT), near-infrared fluorescence (NIRF), ultrasound (US) imaging, and fabricated the OCT-NIRF-US catheter which outer diameter is 0.75 mm, aiming to provide a more comprehensive diagnostic tool for ISR and its associated inflammation. Experiments were conducted on atherosclerotic rabbits implanted with a scaffold, divided into two groups (n=3 each group) for assessment on the first and twenty-eighth day, respectively. Primary results demonstrated that the integrated OCT-NIRF-US intravascular system enables complementary structural imaging and functional imaging of inflammation. The system presents the potential to offer a more accurate assessment, providing with valuable insights into the ISR processing and assisting in the development of more precise clinical strategies.
Pregnant adult C57BL/6J mice, randomly assigned to 1 of 4 groups, 3 of them were irradiated with β-rays from tritiated water(HTO) by a single intraperitoneal injection on the 12.5th day of gestation. Their offspring received cumulative doses of 0, 5, 10 or 30 cGy in utero. Male pups were trained and examined using a set of behavioral tests that included avoidance acquisition and avoidance maintenance, open field test, hole-board dipping, a water maze, and a food labyrinth. Results were found for most parameters in the 10 and 30 cGy groups that differed significantly from results for the controls, indicating that the behavioral teratogenic effect of prenatal exposure to chronic β-ray radiation from HTO may be greater than the same dose of acute X- or γ-irradiation and that 10 cGy may be the lowest detectable dose level at which behavioral changes is detactable under the conditions used in this experiment.
To evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of mavrilimumab, a human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, in subjects with rheumatoid arthritis (RA).
Methods
A randomised, double-blind, placebo-controlled, dose-escalating phase I study in subjects with RA who received stable methotrexate treatment for ≥3 months before enrolment. Subjects received single intravenous escalating doses of mavrilimumab (0.01–10.0 mg/kg) or placebo.
Results
32 subjects were enrolled in this study (1 unblinded subject at 0.01 mg/kg and another at 0.03 mg/kg were followed by five sequential double-blinded cohorts, n=6 each, treated with 0.1, 0.3, 1.0, 3.0 and 10.0 mg/kg, respectively). Adverse events were mild or moderate and were reported with similar frequency across all treatment cohorts. One subject (10.0 mg/kg) experienced moderate face and neck urticaria during infusion that resolved with symptomatic treatment. Systemic clearance of mavrilimumab approached that of endogenous IgG at doses >1.0 mg/kg; pharmacodynamic activity was confirmed in the 1.0 and 3.0 mg/kg cohorts by suppression of suppressor of cytokine signalling 3 mRNA transcripts. In exploratory analyses, reductions of acute phase reactants were observed in subjects with elevated C-reactive protein (>5 mg/l) and erythrocyte sedimentation rate (≥20.0 mm/h) at baseline. No significant change in Disease Activity Score 28-joint assessment (DAS28) was seen in any of the cohorts. In mavrilimumab-treated subjects (n=15) with baseline DAS28 >3.2, mean disease activity (DAS28) was significantly reduced at 4 weeks.
Conclusion
In this first-in-human study, mavrilimumab showed preliminary evidence of pharmacodynamic activity. Importantly, the safety and pharmacokinetic profiles of mavrilimumab support further clinical studies in RA. Trial registration number: NCT00771420.
Sialic acid (N-acetylneuraminic acid), a component of gangliosides and sialylglycoproteins, may be a conditional nutrient in early life because endogenous synthesis is limited. The aim of this study was to investigate the metabolic fate of intravenously administrated N-acetylneuraminic acid-6-14C (sialic acid) in piglets.Three-day-old male domestic piglets (Sus scrofa) were injected via the jugular vein with 5 microCi (11-12 x 10(6) cpm) of N-acetylneuraminic acid-6-14C (specific activity of 55 mCi/mmol). Blood samples were collected at regular intervals over the next 120 min. The organs were then removed and the urine collected for determination of residual radioactivity.Within 2 min of injection, 80% of the activity was removed from the blood and by 120 min the remaining activity approached 8%. At 120 min, the brain contained significantly more radioactivity (cpm/g tissue) than the liver, pancreas, heart and spleen, but less than the kidneys. Within the brain, the percentage of total injected activity was highest in the cerebrum (0.175 +/-0.008) followed by the cerebellum (0.0295 +/-0.006, p=0.00006) and the thalamus (0.029 +/- 0.006, p =0.00003).An exogenous source of sialic acid is capable of crossing the blood-brain barrier and being taken up into various tissues. The findings suggest that dietary sources of sialic acid may contribute to early brain development in newborn mammals.
The aim of this study was to evaluate, in adults, the immunogenicity of six hepatitis B vaccines with different doses or different manufacturers in the Chinese market and to provide evidence to support adult hepatitis B vaccination. Participants were randomly divided into six groups (I–VI). Six vaccines (4 at 10 μg/dose and 2 at 20 μg/dose) were administered intramuscularly to healthy adults at 0, 1 and 6 month intervals. All participants (16–50 years) who were negative for any hepatitis B virus serological markers were vaccinated. Anti-HBs levels were assessed 1 month and 1 year after the third vaccination. The anti-HBs seroconversion rate (anti-HBs >10mIU/ml) was 99.4 % (99.9 % for 10 μg dose groups and 97.9 % for 20 μg dose groups) 1 month after the third vaccination, and the anti-HBs seroreversion rate was 77.0 % (75.3 and 82.6 %) 1 year after the third vaccination (n = 1036). One month after completing the vaccinations, the seroconversion rates were not significantly different (100.0, 100.0, 99.6, 100.0 %) for the four 10 μg dose and two 20 μg dose groups (99.1, 96.9 %). One year after the third vaccination, the group II positive rate was significantly higher than the other three 10 μg dose groups, and the group VI positive rate was significantly higher than the other 20 μg dose group. Groups II and VI showed a significantly higher positive rate and anti-HBs geometric mean titer (GMT) than the other groups. The anti-HBs level declined with increasing age, and the seroreversion rate and GMT decreased over time. All six vaccines had high anti-HBs seroconversion rates and good immunization effects. The 10 μg dose vaccine (Dalian High-Tech) and the 20 μg dose vaccine (GlaxoSmithKline) are recommended for adults.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)