Selective retina therapy and thermal stimulation of the retina: different regenerative properties - implications for AMD therapy

Background Selective Retina Therapy (SRT), a photodisruptive micropulsed laser modality that selectively destroys RPE cells followed by regeneration, and Thermal Stimulation of the Retina (TSR), a stimulative photothermal continuous wave laser modality that leads to an instant sublethal temperature increase in RPE cells, have shown therapeutic effects on Age-related Macular Degeneration (AMD) in mice. We investigate the differences between both laser modalities concerning RPE regeneration. Methods For PCR array, 6 eyes of murine AMD models, apolipoprotein E and nuclear factor erythroid-derived 2- like 2 knock out mice respectively, were treated by neuroretina-sparing TSR or SRT. Untreated litter mates were controls. Eyes were enucleated either 1 or 7 days after laser treatment. For morphological analysis, porcine RPE/choroid organ cultures underwent the same laser treatment and were examined by calcein vitality staining 1 h and 1, 3 or 5 days after irradiation. Results TSR did not induce the expression of cell-mediators connected to cell death. SRT induced necrosis associated cytokines as well as inflammation 1 but not 7 days after treatment. Morphologically, 1 h after TSR, there was no cell damage. One and 3 days after TSR, dense chromatin and cell destruction of single cells was seen. Five days after TSR, there were signs of migration and proliferation. In contrast, 1 h after SRT a defined necrotic area within the laser spot was seen. This lesion was closed over days by migration and proliferation of adjacent cells. Conclusions SRT induces RPE cell death, followed by regeneration within a few days. It is accompanied by necrosis induced inflammation, RPE proliferation and migration. TSR does not induce immediate RPE cell death; however, migration and mitosis can be seen a few days after laser irradiation, not accompanied by necrosis-associated inflammation. Both might be a therapeutic option for the treatment of AMD.

Hsp70 Promotes SUMO of HIF-1α and Promotes Lung Cancer Invasion and Metastasis

Objective. This study aims to investigate the effect of heat shock protein-70 (Hsp70) on epithelial-mesenchymal transition (EMT) of lung cancer cells under heat stimulation and to explore its possible molecular mechanism. Methods. qRT-PCR and immunohistochemistry assay were used to detect the expression of Hsp70 in lung cancer tissues and adjacent tissues. EdU assay was used to detect the cell activity. The effect of Hsp70 on the migration and invasion of A549 and NCI-H446 cells was detected by the wound-healing assay and Transwell assay. A tumor transplantation animal model was established to detect the effect of overexpression of Hsp70 on proliferation and metastasis of lung cancer cells. Western blot assay was used to detect the effect of thermal stimulation and overexpression of Hsp70 on SUMO modification of HIF-1α. Results. The wound-healing rate of A549 and NCI-H446 cells under Hsp70 stimulation was significantly higher than blank control group. At the same time, the number of cells passing through the membrane increased significantly. Hypodermic tumor transplantation in nude mice proved that knockout Hsp70 can inhibit proliferation and metastasis of lung cancer cells. Thermal stimulation upregulated the expression of Hsp70 and promoted SUMO modification of HIF-1α, ultimately promoting the proliferation and metastasis of lung cancer. Inhibition of Hsp70 reverses the effect of thermal stimulation on lung cancer by reducing the SUMO modification of HIF-1α. Conclusion. Thermal stimulation can promote EMT in A549 and NCI-H446 cells and promote cell migration and invasion in vitro and in vivo by upregulation of Hsp70. This process is associated with the promotion of SUMO modification of HIF-1α.

Effectiveness of Thermal Stimulation of Superplasticizers on Fresh Properties of Cement Mortar

Polycarboxylic acid-based superplasticizers are used in various types of concrete work. Wide variations in environmental temperatures are known to affect how well chemical admixtures perform as superplasticizers, influencing the properties of the concrete. However, little has been reported on changes in performance caused by thermal variations. Previous studies have reported that heating superplasticizers change the polymer structure, improving and sustaining cement particles' dispersibility. Moreover, the improved fluidity from thermal stimulation is not temporary. The effect has been observed to remain for about seven days, with the residual characteristics differing depending on the superplasticizers used. Therefore this study evaluates mortar stiffness when using thermally stimulated superplasticizers and evaluates how the stimulation affects construction performance using measures such as the flow and rheological properties (plastic viscosity) of fresh mortar, vane shear tests, blade viscometer tests, and mortar vibration box tests. Mortar's fluidity was found to improve by about 25% when using thermally stimulated additives, with plastic viscosity dropping by up to 45% and the stress likely to be needed for pumping also being reduced by about 16%. Filling speed was also found to increase by about 26%. Thus, thermal stimulation improves mortar and concrete construction performance, and it may be possible in the future to carry out the construction with fewer workers utilizing this technology’s benefits. The study indicates a need for further investigation of how thermal stimulation affects polymer molecules’ adsorption efficiency with cement to elucidate the mechanism at full scale and propose ways to adopt thermal stimulation at actual construction sites.

Emotional Response to Vibrothermal Stimuli

Emotional response to haptic stimuli is a widely researched topic, but the combination of vibrotactile and thermal stimuli requires more attention. The purpose of this study is to investigate emotional response to vibrothermal stimulation by combining spatiotemporal vibrotactile stimulus with dynamic thermal stimulus (hot or cold). The vibrotactile and thermal stimuli were produced using the Haptic Chair and the Embr wave thermal bracelet, respectively. The results show that spatiotemporal vibrotactile patterns and their duration, and dynamic thermal stimulation, have an independent effect on the emotional response. Increasing duration generally increases the valence and arousal of emotional response. Shifting the dynamic temperature from cold to hot generally decreases the valence of emotional response but has no significant effect on arousal. Nevertheless, certain spatiotemporal patterns do exhibit unique responses to changes in dynamic temperature, although no interaction effects were found. The results show the potential of designing affective haptic interfaces using multimodal vibrothermal feedback.

Transcranial photobiomodulation and thermal stimulation induce distinct topographies of EEG alpha and beta power changes in healthy humans

Our recent study demonstrated that prefrontal transcranial photobiomodulation (tPBM) with 1064-nm laser enables significant changes in EEG rhythms, but these changes might result from the laser-induced heat rather than tPBM. This study hypothesized that tPBM-induced and heat-induced alterations in EEG power topography were significantly distinct. We performed two sets of measurements from two separate groups of healthy humans under tPBM (n = 46) and thermal stimulation (thermo_stim; n = 11) conditions. Each group participated in the study twice under true and respective sham stimulation with concurrent recordings of 64-channel EEG before, during, and after 8-min tPBM at 1064 nm or thermo_stim with temperature of 33–41 °C, respectively. After data preprocessing, EEG power spectral densities (PSD) per channel per subject were quantified and normalized by respective baseline PSD to remove the power-law effect. At the group level for each group, percent changes of EEG powers per channel were statistically compared between (1) tPBM vs light-stimulation sham, (2) thermo_stim vs heat-stimulation sham, and (3) tPBM vs thermo_stim after sham exclusion at five frequency bands using the non-parametric permutation tests. By performing the false discovery rate correction for multi-channel comparisons, we showed by EEG power change topographies that (1) tPBM significantly increased EEG alpha and beta powers, (2) the thermal stimulation created opposite effects on EEG power topographic patterns, and (3) tPBM and thermal stimulations induced significantly different topographies of changes in EEG alpha and beta power. Overall, this study provided evidence to support our hypothesis, showing that the laser-induced heat on the human forehead is not a mechanistic source causing increases in EEG power during and after tPBM.

Problems of Active Dynamic Thermography Measurement Standardization in Medicine

Reliability of thermographic diagnostics in medicine is an important practical problem. In the field of static thermography, a great deal of effort has been made to define the conditions for thermographic measurements, which is now the golden standard for such research. In recent years, there are more and more reports on dynamic tests with external stimulation, such as Active Dynamic Thermography, Thermographic Signal Reconstruction or Thermal Tomography. The subject of this report is a discussion of the problems of standardization of dynamic tests, the choice of the method of thermal stimulation and the conditions determining the credibility of such tests in medical diagnostics. Typical methods of thermal stimulation are discussed, problems concerning accuracy and control of resulting distributions of temperature are commented. The best practices to get reliable conditions of measurements are summarized.

Performance Change in Superplasticizers after Thermal Stimulation

Polycarboxylic acid-based superplasticizers are used for all types of concrete, but it is not well known that their fundamental performance changes with heating. Previous research confirmed that the superplasticizer storage environment changes its physical properties, which in turn changes the fluidity and workability of concrete or mortar. Therefore, this study confirmed the thermal stimulation effect on polycarboxylic acid-based and other superplasticizers and also confirmed the mechanism of polymer “entanglement” using superplasticizers that were centrifuged to simulate long-term storage. Based on the results, it was confirmed that the change in physical properties due to the change in environmental temperature is specific to polycarboxylic acid-based superplasticizers. It was also confirmed that centrifugal treatment of the superplasticizer slightly decreased its performance but increased the effect of thermal stimulation.