When infection occurs, the temperature in the infected region or in the whole body will be elevated in order to weaken the infectious pathogens such as virus, or to promote the activity of immune systems. As a clinical alternative treatment, hyperthermia (HT) has been widely used in various diseases, which is also capable of regulating the release of pro-inflammatory cytokines and antiviral activity of immune systems. However, studies have also indicated that overheating impairs the health tissues as well as the immune cells. In this study, we provide a modified HT method-thermal cycling-hyperthermia (TC-HT) and investigate its effects on immunomodulation and cellular viabilities, showing that TC-HT could reduce the secretion of pro-inflammatory cytokines induced by lipopolysaccharide (LPS) ex vivo, and elevate the efficacy of U-937 macrophages for clearing herpes simplex virus type 1 (HSV-1) in vitro. Furthermore, the efficacy of U-937 macrophage for clearing HSV-1 could be further boosted up via optimizing the parameter of TC-HT. Collectively, we prove that TC-HT is a more promising and safer thermal treatment with stronger therapeutic effects in immunomodulation than HT, shedding light on the development of the therapy in immunological diseases.

No abstract

Neurodegenerative diseases have been a major threat to public health worldwide nowadays. In particular, Alzheimer's disease is the most common type causing dementia which has remained an incurable disease, despite improvement of the symptoms via some therapies. The pathogenic mechanism of Alzheimer's disease is deemed to be related to the aggregation of beta-amyloid peptide (Aβ), a major cause for amyloid plaques, resulting in neuronal death via the generation of reactive oxygen species (ROS). Scientists have regarded oxidative stress as a potential treatment target in the development of novel remedies. In the study, human neural cell line SH-SY5Y was used in probing the effect of combining non-invasive high-frequency low-intensity pulsed electric field (H-LIPEF) and brain-derived neurotrophic factor (BDNF) in protection against hydrogen peroxide (H2O2)-induced neuron damage. Our result finds that the combination approach has intensified the neuroprotective effect significantly, perhaps due to H-LIPEF and BDNF synergistically increasing the expression level of the phosphorylated epidermal growth factor receptor (p-EGFR), which induces the survival-related mitogen-activated protein kinases (MAPK) proteins. The study confirmed the activation of extracellular signal-regulated kinase (ERK), a member of MAPK family, and the downstream pro-survival and antioxidant proteins as the mechanism underlying neuron protection. These findings have highlighted the potential of H-LIPEF combining with BDNF in the treatment of neurodegenerative diseases. Furthermore, the application of BDNF-mimetic drugs and non-invasive H-LIPEF to patients is a promising approach worthy of further research, and this points to strategies and mechanisms for selecting drugs or compounds to cooperate with electric fields in the treatment of neurodegenerative disorders.

Neurodegenerative diseases (NDDs) pose a significant global health threat. In particular, Alzheimer disease, the most common type causing dementia, remains an incurable disease. Alzheimer disease is thought to be associated with an imbalance of reactive oxygen species (ROS) in neurons, and scientists considered ROS modulation as a promising strategy for novel remedies. In the study, human neural cell line SH-SY5Y was used in probing the effect of combining noninvasive high-frequency low-intensity pulsed electric field (H-LIPEF) and brain-derived neurotrophic factor (BDNF) in protection against hydrogen peroxide (H2O2)-induced neuron damage. Our result finds that the combination approach has intensified the neuroprotective effect significantly, perhaps due to H-LIPEF and BDNF synergistically increasing the expression level of the phosphorylated epidermal growth factor receptor (p-EGFR), which induces the survival-related mitogen-activated protein kinases (MAPK) proteins. The study confirmed the activation of extracellular signal-regulated kinase (ERK) and the downstream pro-survival and antioxidant proteins as the mechanism underlying neuron protection. These findings highlighted the potential of H-LIPEF combined with BDNF in the treatment of NDDs. Furthermore, BDNF-mimetic drugs combining with noninvasive H-LIPEF to patients is a promising approach worthy of further research. This points to strategies for selecting drugs to cooperate with electric fields in treating neurodegenerative disorders.

Despite continuation of some controversies, Alzheimer's disease (AD), the most common cause of dementia nowadays, has been widely believed to derive mainly from excessive β-amyloid (Aβ) aggregation, that would increase reactive oxygen species (ROS) and induce neuroinflammation, leading to neuron loss and cognitive impairment. Existing drugs on Aβ have been ineffective or offer only temporary relief at best, due to blood-brain barrier or severe side effects. The study employed thermal cycling-hyperthermia (TC-HT) as an alternative AD therapy and compared its effect with continuous hyperthermia (HT) in vivo. It established an AD mice model via intracerebroventricular (i.c.v.) injection of Aβ25-35, proving that TC-HT is much more effective in alleviating its performance decline in Y-maze and NOR test, in comparison with HT. In addition, TC-HT also exhibits a better performance in decreasing the hippocampal Aβ and BACE1 expressions as well as the neuroinflammation markers Iba-1 and GFAP levels. Furthermore, the study finds that TC-HT can elevate more protein expressions of IDE and antioxidative enzyme SOD2 than HT. Besides, after establishment of neuroprotective mechanism, removal of TC-HT-induced ROS can further augment protection of neural cells against Aβ. In sum, the study proves the potential of TC-HT in AD treatment, which can be put into clinical application with the use of high-intensity focused ultrasound (HIFU).