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

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.

The Capacitive Coupling Modalities for Oncological Hyperthermia

The local-regional oncological hyperthermia has various electromagnetic methods for energy-transfer. The differences involve conceptual considerations and technical solutions. The most frequently applied energy transfer is capacitive coupling, concentrating the electric field to be the active heating component. The realization of the capacitive coupling set-up is divided into two different categories based on their goals for heating: 1) the homogeneous (conventional) heating, using isothermal conditions for dosing, and 2) the selective heterogeneous heating, using cellularly absorbed energy for dosing. The homogeneous heating utilizes plane-wave matching, absorbing the wave for energy transfer. The heterogenic heating uses impedance matching, selecting the malignant cells by their electromagnetic specialties, like their heterogenic impedance, higher membrane-raft density, and different spatio-temporal (pathologic pattern) arrangements. This article’s objective is to compare and discuss the details of the two kinds of capacitive coupling techniques.

Dynamic spatial reorganization of BSK1 complexes in the plasma membrane underpins signal-specific activation for growth and immunity

Growth and immunity are opposing processes that compete for cellular resources,and proper resource allocation is crucial for plant survival.BSK1 plays a key role in the regulation of both growth and immunity by associating with BRI1 and FLS2,respectively.However,it remains unclear how two antagonistic signals co-opt BSK1 to induce signal-specific activation.Here we show that the dynamic spatial reorganiization of BSK1 within the plasma membrane underlies the mechanism of signal-specific activation for growth or immunity.Resting BSK1 localizes to membrane rafts as complexes.Unlike BSK1-associated FLS2 and BRI1,flg22 or exogenous brassinosteroid(BR)treatment did not decrease BSK1 levels at the plasma membrane(PM)but rather induced BSK1 multimerization and dissociation from FLS2/BSK1 or BRI1/BSK1,respectively.Moreover,flg22-activated BSK1 translocated from membrane rafts to non-membrane-raft regions,whereas BR-activated BSK1 remained in membrane rafts.When applied together with flg22,BR suppressed various flg22-induced BSK1 activities such as BSK1 dissociation from FLS2/BSK1,BSK1 interaction with MAPKKK5,and BSK translocation together with MAPKKK5.Taken together,this study provides a unique insight into how the precise control of BSK1 spatiotemporal organization regulates the signaling specificity to balance plant growth and immunity.