Biology subjects

Kung, Y.

Publications and source records attributed to Kung, Y..

5 recordsLinked to original sources

bioRxiv2026

Epigallocatechin gallate and thermal cycling-stimulation synergistically promote apoptosis in A549 cells via endoplasmic reticulum stress-induced calcium ion dysregulation and oxidative stress

Non-small cell lung cancer (NSCLC), as the predominant subtype of lung cancer, presents a considerable clinical challenge due to its high rates of recurrence and the significant adverse effects associated with conventional therapeutic modalities. In response to these challenges, this study explored the new combined anticancer effects of epigallocatechin gallate (EGCG) together with thermal cycling-stimulation (TCS). The findings demonstrated that the combination of EGCG and TCS synergistically decreased the viability of A549 and NCI-H460 NSCLC cells, while exhibiting minimal cytotoxic effects on IMR-90 normal lung fibroblasts. Further investigation revealed that EGCG mitigated the TCS-induced upregulation of heat shock proteins HSP70 and HSP105 and concurrently diminished the expression levels of proteasome subunits. This combined effect disrupted proteostasis, resulting in pronounced endoplasmic reticulum (ER) stress. Subsequently, a positive feedback mechanism was established between inositol 1,4,5-trisphosphate receptor (IP3R)-mediated ER Ca2+ release and excessive reactive oxygen species (ROS) production, ultimately leading the cells to undergo mitochondrial apoptosis. This combined treatment reduces the necessary dosage of EGCG, thereby overcoming limitations related to its poor bioavailability and systemic toxicity, while also preventing the development of thermotolerance induced by TCS. Consequently, this method offers a new and potentially practical therapeutic strategy for treating NSCLC.

Cancer Biology↗

bioRxiv2025

Reduction of Aβ25-35-Induced Cognitive Impairments in C57BL/6 Mice Through Focused Ultrasound Thermal-Cycling Stimulation

Hyperthermia (HT) is recognized across various medical disciplines for its capacity to modulate specific protein expressions. In efforts to improve Alzheimers disease (AD), HT has the potential to regulate heat shock proteins (HSPs) and antioxidant enzymes, which helps decrease the aberrant accumulation of {beta}-amyloid (A{beta}) protein and oxidative stress. Nonetheless, the precise delivery of mild hyperthermia to the brain remains a significant challenge. To apply mild hyperthermia targeted to the brain and evaluate its impact on cognitive improvement, this study used focused ultrasound (FUS) to administer localized mild hyperthermia to the brains of AD mouse induced by intracerebroventricular (i.c.v.) injection of A{beta}25-35. For considerations of safety and therapeutic efficacy, a thermal cycling-hyperthermia (TC-HT) protocol was adapted into a focused ultrasound-mediated thermal cycling stimulation (FUS-TCS), which was compared with the continuous focused ultrasound-mediated hyperthermia stimulation (FUS-HTS). The findings revealed that the FUS-TCS treatment group exhibited a significant improvement in cognitive performance, as evidenced by enhanced outcomes in the Y-maze and novel object recognition (NOR) tests. Furthermore, this group demonstrated increased expression of A{beta}-degrading enzymes and antioxidant proteins, including heat shock protein 70 (HSP70), neprilysin (NEP), insulin degrading enzyme (IDE), sirtuin 1 (SIRT1), and superoxide dismutase 2 (SOD2). These results suggest that localized mild hyperthermia targeting the brain using FUS-TCS treatment represents a promising strategy for ameliorating cognitive deficits associated with AD.

neuroscience↗

bioRxiv2025

Thermal cycling stimulation via nasal inhalation attenuates Aβ25-35-induced cognitive deficits in C57BL/6 mice

Alzheimers disease (AD) continues to pose a significant public health challenge, with current treatments demonstrating limited effectiveness, partly due to the difficulty of delivering therapeutics across the blood-brain barrier (BBB). The nose-to-brain (N-2-B) pathway offers a promising alternative, enabling pharmacological agents to circumvent the BBB. However, to date, no drugs have been successfully implemented in clinical settings for the treatment of AD via this route, underscoring the necessity for additional research in this area. Mild stress is thought to activate intrinsic protective mechanisms against neurodegeneration, but traditional methods of inducing stress often lack both specificity and practicality. To address this limitation, we propose the inhalation of mildly heated air as a form of thermal stimulation, which utilizes the N-2-B pathway to induce mild stress and stimulate cerebral activity. This study employs the method of thermal cycling-hyperthermia (TC-HT) technique [Chao C.Y. et al., U.S. patent 11753634, 2023 & Chao C.Y. et al., U.S. patent Appl. No. 18/864192, 2024] into a new treatment, adapted as thermal cycling-stimulation via nasal inhalation (TCSNI), which provides cyclic stimulation to maintain pathway activity while minimizing thermal injury. In this study, we assessed the health and olfactory effects of TCSNI in C57BL/6 mice and found no adverse effects. In experimental groups administered with {beta}-amyloid (A{beta}), TCSNI treatment resulted in significant enhancements in cognitive performance as evidenced by Y-maze and novel object recognition (NOR) assessments, suggesting an improvement in cognitive function. Protein analyses conducted on the hippocampus of the mice indicated a reduction in A{beta} accumulation, alongside increased expression of heat shock protein 70 (HSP70) and insulin-degrading enzyme (IDE) expression, as well as elevated levels of phosphorylated Akt (p-Akt). These results suggest that N-2-B-delivered TCSNI effectively modulates protein expression and enhances cognitive function, highlighting its potential for further exploration in AD treatment.

neuroscience↗

bioRxiv2025

Thermal cycling-hyperthermia attenuates rotenone-induced cell injury in SH-SY5Y cells through heat-activated mechanisms

Parkinsons disease (PD) is the second most prevalent neurodegenerative disease. It is characterized by mitochondrial dysfunction, increased reactive oxygen species (ROS), -synuclein (-syn) and phosphorylated-tau protein (p-tau) aggregation, and dopaminergic neuron cell death. Current drug therapies only provide temporary symptomatic relief and fail to stop or reverse disease progression due to the severe side effects or the blood-brain barrier. This study aimed to investigate the neuroprotective effects of thermal cycling-hyperthermia (TC-HT) in an in vitro PD model using rotenone (ROT)-induced human neural SH-SY5Y cells. Our results revealed that TC-HT pretreatment conferred neuroprotective effects in the ROT-induced in vitro PD model using human SH-SY5Y neuronal cells, including reducing ROT-induced mitochondrial apoptosis and ROS accumulation in SH-SY5Y cells. In addition, TC-HT also inhibited the expression of -syn and p-tau through heat-activated pathways associated with sirtuin 1 (SIRT1) and heat-shock protein 70 (Hsp70), involved in protein chaperoning, and resulted in the phosphorylation of Akt and glycogen synthase kinase-3{beta} (GSK-3{beta}), which inhibit p-tau formation. These findings underscore the potential of TC-HT as an effective treatment for PD in vitro, supporting its further investigation in in vivo models or potentially in human trials, with focused ultrasound (FUS) as a feasible heat-delivery approach.

neuroscience↗

bioRxiv2023

Enhancing glymphatic function with very low-intensity ultrasound via the transient receptor potential vanilloid-4-aquaporin-4 pathway

Recently, the glymphatic system has been proposed as a mechanism for waste clearance from the brain parenchyma. Glymphatic dysfunction has been associated with several neurological diseases such as Alzheimers disease, traumatic brain injury, and stroke. Therefore, it may be an important target for therapeutic interventions. In this study, we demonstrated that very low intensity ultrasound (VLIUS) (center frequency = 1 MHz; pulse repetition frequency = 1 kHz; duty factor = 1%, and spatial peak temporal average intensity [Ispta] = 3.68 mW/cm2; duration = 5 min) could significantly enhance the influx of cerebrospinal fluid tracers into the perivascular spaces of the brain and also facilitate interstitial substance clearance from the brain parenchyma. Notably, no evidence of brain damage was observed after VLIUS stimulation. We also demonstrated that VLIUS enhanced the glymphatic influx via the transient receptor potential vanilloid-4-aquaporin-4 pathway in the astrocytes. This mechanism may provide insights into VLIUS-regulated glymphatic function that modifies the natural course of central nervous system disorders related to waste clearance dysfunction. One Sentence SummaryVery low-intensity ultrasound enhances glymphatic influx via the TRPV4-AQP4 pathway in the astrocytes, without observable brain damage.

neuroscience↗