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The Immunogenic Connection of Thermal and Nonthermal Molecular effects in Modulated Electro-Hyperthermia

Open Journal of Biophysics 2023年第4期13卷 103-142页

作者： Attila Marcell Szász Gergö Lóránt András Szász Gyula Szigeti Division of Oncology Department of Internal Medicine and Oncology Semmelweis University Budapest Hungary Biotechnics Department Hungarian University of Agriculture and Life Sciences Budaors Hungary Innovation Center Semmelweis University Budapest Hungary

Hyperthermia in oncology is an emerging complementary therapy. The clinical results depend on multiple conditional factors, like the type of cancer, the stage, the applied treatment device, and the complementary conventional therapy. The molecular effect could also be different depending on the temperature, heating dose, kind of energy transfer, and timing sequences compared to the concomitant treatment. This article examines the molecular impacts of a specific technique used in oncological hyperthermia called modulated electro-hyperthermia (mEHT). What sets mEHT apart is its emphasis on harnessing the combined effects of thermal and nonthermal factors. Nonthermal energy absorption occurs through the excitation of molecules, while the thermal component ensures the ideal conditions for this process. The applied radiofrequency current selects the malignant cells, and the modulation drives the nonthermal effects to immunogenic cell death, helping to develop tumor-specific antitumoral immune reactions. The synergy of the thermal and nonthermal components excites the lipid-assembled clusters of transmembrane proteins (membrane rafts) as the channels of transient receptor potentials (TRPs), the heat-shock proteins (HSPs), the voltage-gated channels, and the voltage-sensitive phosphatases (VSPs). All these transmembrane compartments channeling various ionic species (like calcium and proton) interact with the cytoskeleton and are involved in the apoptotic signal pathways.

关键词： Thermal Nonthermal Membrane Rafts TRP VSP HSP Cytoskeleton Polarization mEHT immune effects Abscopal Effect

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Hygroscopicity measurement of sodium carbonate,β-alanine and internally mixed β-alanine/Na2CO3 particles by ATR-FTIR

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Journal of Environmental Sciences 2020年第1期32卷 250-259页

作者： Ping Yang Hui Yang Na Wang Chunyun Du Shufeng Pang Yunhong Zhang School of Chemistry and Chemical Engineering Beijing Institute of Technology

Water-uptakes of pure sodium carbonate(Na2CO3),pureβ-alanine and internally mixedβ-alanine/Na2CO3 aerosol particles with different mole ratios are first monitored using attenuated total reflectance Fourier transform infrared spectroscopy(ATR-FTIR)*** pure Na2CO3 aerosol particles,combining the absorptions at 877 and 1422 cm-1 with abrupt water loss shows the efflorescence relative humidity(ERH)of 62.9%–51.9%.Upon humidifying,solid Na2CO3 firstly absorbs water to from Na2CO3·H2O crystal at 72.0%RH and then deliquesces at 84.5%RH(DRH).As for pureβ-alanine particles,the crystallization takes place in the range of 42.4%–33.2%RH and becomes droplets at^88.2%***β-alanine is mixed with Na2CO3 at various mole ratios,it shows no efflorescence of Na2CO3 whenβ-alanine to Na2CO3 mole ratio(OIR)is 2:*** 1:1 and 1:2β-alanine/Na2CO3 aerosols,the ERHs of Na2CO3 are 51.8%–42.3%and 57.1%–42.3%,***β-alanine crystal appears from 62.7%RH for 2:1 and 59.4%RH for both 1:1 and 1:2 particles and lasts to driest *** hydration,the DRH is 44.7%–75.2%for Na2CO3 with the OIR of 1:1 and 44.7%–69.0%for 1:2 mixture,and those of β-alanine are 74.8% for 2:1 mixture and 68.9%for two *** the first dehumidification–humidification,all the water contents decrease despite of constituent *** at^92%RH,the remaining water contents are 92%,89%and 82%at^92%RH,corresponding to OIR of 2:1,1:1 and 1:2 mixed system,respectively.

关键词： Sodium carbonate β-Alanine Hygroscopicity Crystallization immune effects Deliquescence

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Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis： perspectives and approaches

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Neural Regeneration Research 2018年第11期13卷 1871-1874页

作者： Francois Grand'Maison Michael Yeung Sarah A. Morrow Liesly Lee Francois Emond Brian J. Ward Pierre Laneuville Robyn Schecter Neuro Rive-Sud Hospital Charles LeMoyne Greenfield Park Quebec Canada Clinical Neurosciences Foothills Medical Centre Calgary Alberta Canada London Health Sciences Center (LHSC) Western University London Ontario Canada Department of Neurology Sunnybrook Health Sciences Centre Toronto Ontario Canada Centre Hospitalier Universitaire de Quebec - hospital de l'Enfant-Jesus Quebec City Quebec Canada Research Institute of the McGill University Health Centre Montreal Quebec Canada Department of Medicine McGill University Montreal Quebec Canada Novartis Pharmaceuticals Canada Inc. Dotal Quebec Canada

Multiple sclerosis（MS） is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies（DMTs） for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this objective requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.

关键词： relapsing multiple sclerosis high efficacy disease-modifying therapies treatment optimization treatment sequencing therapeutic inertia sub-optimal treatment progressive disease immune effects

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