The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

<p>Abstract</p> <p>Background</p> <p>High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo.</p> <p>Methods</p> <p>1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed.</p> <p>Results</p> <p>The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P < 0.05). The tumor grow delay of groups with prolonged delivery time 30 min was longer than that of groups with prolonged delivery time 60 min P < 0.05). There was no significant difference between groups with same delivery time (P > 0.05). Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min.</p> <p>Conclusions</p> <p>The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time.</p

Interferon regulatory factor-1 together with reactive oxygen species promotes the acceleration of cell cycle progression by up-regulating the cyclin E and CDK2 genes during high glucose-induced proliferation of vascular smooth muscle cells

BACKGROUND: The high glucose-induced proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development of diabetic vascular diseases. In a previous study, we confirmed that Interferon regulatory factor-1 (Irf-1) is a positive regulator of the high glucose-induced proliferation of VSMCs. However, the mechanisms remain to be determined. METHODS: The levels of cyclin/CDK expression in two cell models involving Irf-1 knockdown and overexpression were quantified to explore the relationship between Irf-1 and its downstream effectors under normal or high glucose conditions. Subsequently, cells were treated with high glucose/NAC, normal glucose/H(2)O(2), high glucose/U0126 or normal glucose/H(2)O(2)/U0126 during an incubation period. Then proliferation, cyclin/CDK expression and cell cycle distribution assays were performed to determine whether ROS/Erk1/2 signaling pathway was involved in the Irf-1-induced regulation of VSMC growth under high glucose conditions. RESULTS: We found that Irf-1 overexpression led to down-regulation of cyclin D1/CDK4 and inhibited cell cycle progression in VSMCs under normal glucose conditions. In high glucose conditions, Irf-1 overexpression led to an up-regulation of cyclin E/CDK2 and an acceleration of cell cycle progression, whereas silencing of Irf-1 suppressed the expression of both proteins and inhibited the cell cycle during the high glucose-induced proliferation of VSMCs. Treatment of VSMCs with antioxidants prevented the Irf-1 overexpression-induced proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression in high glucose conditions. In contrast, under normal glucose conditions, H(2)O(2) stimulation and Irf-1 overexpression induced cell proliferation, up-regulated cyclin E/CDK2 expression and promoted cell cycle acceleration. In addition, overexpression of Irf-1 promoted the activation of Erk1/2 and when VSMCs overexpressing Irf-1 were treated with U0126, the specific Erk1/2 inhibitor abolished the proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression under high glucose or normal glucose/H(2)O(2) conditions. CONCLUSIONS: These results demonstrate that the downstream effectors of Irf-1 are cyclin E/CDK2 during the high glucose-induced proliferation of VSMCs, whereas they are cyclin D1/CDK4 in normal glucose conditions. The Irf-1 overexpression-induced proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression are associated with ROS/Erk1/2 signaling pathway under high glucose conditions

Visible-Light-Driven Rotation of Molecular Motors in Discrete Supramolecular Metallacycles

The organization of molecular motors in supramolecular assemblies to allow the amplification and transmission of motion and collective action is an important step toward future responsive systems. Metal-coordination-driven directional self-assembly into supramolecular metallacycles provides a powerful strategy to position several motor units in larger structures with well-defined geometries. Herein, we present a pyridyl-modified molecular motor ligand (MPY) which upon coordination with geometrically distinct di-Pt(II) acceptors assembles into discrete metallacycles of different sizes and shapes. This coordination leads to a red-shift of the absorption bands of molecular motors, making these motorized metallacycles responsive to visible light. Photochemical and thermal isomerization experiments demonstrated that the light-driven rotation of the motors in the metallacycles is similar to that in free MPY in solution. CD studies show that the helicity inversions associated with each isomerization step in the rotary cycle are preserved. To explore collective motion, the trimeric motor-containing metallacycle was aggregated with heparin through multiple electrostatic interactions, to construct a multi-component hierarchical system. SEM, TEM, and DLS measurements revealed that the photo- and thermal-responsive molecular motor units enabled selective manipulation of the secondary supramolecular aggregation process without dissociating the primary metallacycle structures. These visible-light-responsive metallacycles, with intrinsic multiple rotary motors, offer prospects for cooperative operations, dynamic hierarchical self-assembled systems, and adaptive materials

The botanical origin and antioxidant, anti-BACE1 and antiproliferative properties of bee pollen from different regions of South Korea

Abstract Background Bee pollen (BP) has been used as a traditional medicine and food diet additive due to its nutritional and biological properties. The potential biological properties of bee pollen vary greatly with the botanical and geographical origin of the pollen grains. This study was conducted to characterize the botanical origin and assess the antioxidant effects of ethanol extracts of 18 different bee pollen (EBP) samples from 16 locations in South Korea and their inhibitory activities on human β-amyloid precursor cleavage enzyme (BACE1), acetylcholinesterase (AChE), human intestinal bacteria, and 5 cancer cell lines. Methods The botanical origin and classification of each BP sample was evaluated using palynological analysis by observing microscope slides. We measured the biological properties, including antioxidant capacity, inhibitory activities against human BACE1, and AChE, and antiproliferative activities toward five cancer cell lines, of the 18 EBPs. In addition, the growth inhibitory activities on four harmful intestinal bacteria, six lactic acid-producing bacteria, two nonpathogenic bacteria, and an acidulating bacterium were also assessed. Results Four samples (BP3, BP4, BP13 and BP15) were found to be monofloral and presented four dominant pollen types: Quercus palustris, Actinidia arguta, Robinia pseudoacacia, and Amygdalus persica. One sample (BP12) was found to be bifloral, and the remaining samples were considered to be heterofloral. Sixteen samples showed potent antioxidant activities with EC50 from 292.0 to 673.9 μg mL− 1. Fourteen samples presented potent inhibitory activity against human BACE1 with EC50 from 236.0 to 881.1 μg mL− 1. All samples showed antiproliferative activity toward the cancer cell lines PC-3, MCF-7, A549, NCI-H727 and AGS with IC50 from 2.7 to 14.4 mg mL− 1, 0.9 to 12.7 mg mL− 1, 5.0 to > 25 mg mL− 1, 2.7 to 17.7 mg mL− 1, and 2.4 to 8.7 mg mL− 1, respectively. In addition, total phenol and flavonoid contents had no direct correlation with antioxidant, anti-human BACE1, or antiproliferative activities. Conclusion Fundamentally, Korean bee pollen-derived preparations could be considered a nutritional addition to food to prevent various diseases related to free radicals, neurodegenerative problems, and cancers. The botanical and geographical origins of pollen grains could help to establish quality control standards for bee pollen consumption and industrial production

Online state of charge estimation for the aerial lithium-ion battery packs based on the improved extended Kalman filter method.

An effective method to estimate the integrated state of charge (SOC) value for the lithium-ion battery (LIB) pack is proposed, because of its capacity state estimation needs in the high-power energy supply applications, which is calculated by using the improved extended Kalman filter (EKF) method together with the one order equivalent circuit model (ECM) to evaluate its remaining available power state. It is realized by the comprehensive estimation together with the discharging and charging maintenance (DCM) process, implying an accurate remaining power estimation with low computational calculation demand. The battery maintenance and test system (BMTS) equipment for the aerial LIB pack is developed, which is based on the proposed SOC estimation method. Experimental results show that, it can estimate SOC value of the LIB pack effectively. The BMTS equipment has the advantages of high detection accuracy and stability and can guarantee its power-supply reliability. The SOC estimation method is realized on it, the results of which are compared with the conventional SOC estimation method. The estimation has been done with an accuracy rate of 95% and has an absolute root mean square error (RMSE) of 1.33% and an absolute maximum error of 4.95%. This novel method can provide reliable technical support for the LIB power supply application, which plays a core role in promoting its power supply applications

The effective on intradermal acupuncture based on changes in biological specificity of acupoints for major depressive disorder: study protocol of a prospective, multicenter, randomized, controlled trial

BackgroundAntidepressants still have some side effects in treating major depressive disorder (MDD), and acupuncture therapy is a complementary therapy of research interest for MDD. Acupoints are sensitive sites for disease response and stimulation points for acupuncture treatment. Prior studies suggest that the biological specificity of acupoints is altered in physiological and pathological situations. Therefore, we hypothesize that the biological specificity of acupoints is associated with the diagnosis of MDD and that stimulating acupoints with significant biological specificity can achieve a better therapeutic effect than clinical common acupoints. This study aims to investigate the efficacy and safety of intradermal acupuncture (IA) treatment for MDD based on changes in the biological specificity of acupoints.MethodsThe first part of the study will enroll 30 MDD patients and 30 healthy control (HC) participants to assess pain sensitivity and thermal specificity of MDD-related acupoints using a pressure pain threshold gauge (PTG) and infrared thermography (IRT). The potentially superior acupoints for treating MDD will be selected based on the results of PTG and IRT tests and referred to as pressure pain threshold strong response acupoints (PSA) and temperature strong response acupoints (TSA).The second part of the study will enroll 120 eligible MDD patients randomly assigned to waiting list (WL) group, clinical common acupoint (CCA) group, TSA group, and PSA group in a 1:1:1:1 ratio. The change in the Patient Health Questionnaire-9 Items (PHQ-9), the MOS item short-form health survey (SF-36), pressure pain threshold, temperature of acupoints, and adverse effects will be observed. The outcomes of PHQ-9 and SF-36 measures will be assessed before intervention, at 3 and 6 weeks after intervention, and at a 4-week follow-up. The biological specificity of acupoint measures will be assessed before intervention and at 6 weeks after intervention. All adverse effects will be assessed.DiscussionThis study will evaluate the therapeutic effect and safety of IA for MDD based on changes in the biological specificity of acupoints. It will investigate whether there is a correlation between the biological specificity of MDD-related acupoints and the diagnosis of MDD and whether stimulating strong response acupoints is superior to clinical common acupoints in the treatment of MDD. The study’s results may provide insights into the biological mechanisms of acupuncture and its potential as a complementary therapy for MDD.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT05524519