Biology subjects

Liu, H.-H.

Publications and source records attributed to Liu, H.-H..

11 recordsLinked to original sources

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-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↗

bioRxiv2024

Combination of cycling hyperthermia and Echinacoside creates synergistic curing effect on pancreatic cancer PANC-1 cells

Therapy targeting the suppression of human MutT homolog 1 (MTH1) has been gaining ground in recent years, thanks to its resulting significant increase of 8-hydroxy-2-deoxyguanosine triphosphate (8-oxo-dGTP) accumulation in genomic DNA, causing DNA damage and apoptotic cell death. Echinacoside (Ech), a natural phenylethanoid glycoside first extracted from Echinacea angustifolia or desert plant Cistanches is one of a few natural products which are capable of inhibiting the MTH1 function. It, however, is difficult to apply it in clinical trials, due to high cost for effective dosage in need. In the study, we show that combination with thermal-cycling hyperthermia (TC-HT), a novel physical treatment, can amplify the curative effect of Ech, reducing its dosage in need significantly. The combination resulted in a multipronged mechanism targeting multiple key apoptotic regulating proteins such as Bcl-2 and MAPK family proteins. Its effect is expected to be comparable to the treatment strategy containing MTH1, Bcl-2, and ERK inhibitors, posing as new promising approach in cancer treatment.

cancer biology↗

bioRxiv2024

Protective Effects of Lipoxin A4 and B4 Signaling on the Inner Retina in a Mouse Model of Experimental Glaucoma

Glaucoma is a common neurodegenerative disease characterized by progressive degeneration of retinal ganglion cells (RGCs) and the retinal nerve fiber layer (RNFL), resulting in a gradual decline of vision. A recent study by our groups indicated that the levels of lipoxins A4 (LXA4) and B4 (LXB4) in the retina and optic nerve decrease following acute injury, and that restoring their function is neuroprotective. Lipoxins are members of the specialized pro-resolving mediator (SPM) family and play key roles to mitigate and resolve chronic inflammation and tissue damage. Yet, knowledge about lipoxin neuroprotective activity remains limited. Here we investigate the in vivo efficacy of exogenous LXA4 and LXB4 administration on the inner retina in a mouse model of chronic experimental glaucoma. To investigate the contribution of LXA4 signaling we used transgenic knockout (KO) mice lacking the two mouse LXA4 receptors (Fpr2/Fpr3-/-). Functional and structural changes of inner retinal neurons were assessed longitudinally using electroretinogram (ERG) and optical coherence tomography (OCT). At the end of the experiment, retinal samples were harvested for immunohistological assessment. While both lipoxins generated protective trends, only LXB4 treatment was significant, and consistently more efficacious than LXA4 in all endpoints. Both lipoxins also appeared to dramatically reduce Muller glial reactivity following injury. In comparison, Fpr2/Fpr3 deletion significantly worsened inner retinal injury and function, consistent with an essential protective role for endogenous LXA4. Together, these results support further exploration of lipoxin signaling as a treatment for glaucomatous neurodegeneration.

neuroscience↗

bioRxiv2022

Thermal cycling-hyperthermia down-regulates liposaccharide-induced inflammatory response in human whole-blood and helps clear herpes simplex virus type 1 by U-937 macrophages

Infection would lead to temperature increase in the affected region or entire human body, in order to weaken the pathogens, such as virus, or activate the immune system. As an alternative therapy with extensive application for various diseases, hyperthermia (HT) can regulate the release of pro-inflammatory cytokines and the antiviral activity of immune system. However, existing studies have found that overheating impairs healthy tissues and immune cells. The study puts forth a modified HT treatment, thermal cycling-hyperthermia (TC-HT), looking into its effect on immunomodulation and cellular viabilities. It shows that TC-HT can reduce the secretion of pro-inflammatory cytokines, induced by lipopolysaccharide (LPS) both ex vivo and in vitro, and elevate the efficacy of U-937 macrophages in clearing herpes simplex virus type 1 (HSV-1) in vitro. Furthermore, via optimizing its parameters, TC-HT can boost the efficacy of U-937 macrophage in clearing HSV-1, which may be attributed to the enhancement of actin polymerization and phagocytosis activity via TC-HT. In sum, TC-HT outperforms HT in safety and therapeutic effect in immunomodulation, shedding light on its potential in the treatment of immunological diseases.

immunology↗

bioRxiv2022

Thermal cycling-hyperthermia ameliorates cognitive impairment of intracerebroventricular Aβ25-35-induced Alzheimer's disease in C57BL/6 mice

Despite continuation of some controversies, Alzheimers disease (AD), the most common cause of dementia nowadays, has been widely believed to derive mainly from excessive {beta}-amyloid (A{beta}) aggregation, that would increase reactive oxygen species (ROS) and induce neuroinflammation, leading to neuron loss and cognitive impairment. Existing drugs on A{beta} 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 A{beta}25-35, 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 A{beta} 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 A{beta}. In sum, the study proves the potential of TC-HT in AD treatment, which can be put into clinical application with the use of focused ultrasound (FUS).

neuroscience↗

bioRxiv2022

Protection of high-frequency low-intensity pulsed electric fields and brain-derived neurotrophic factor for SH-SY5Y cells against hydrogen peroxide-induced cell damage

Neurodegenerative diseases pose a significant global health threat. In particular, Alzheimers disease, the most common type causing dementia, remains an incurable disease. Alzheimers 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 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) 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 neurodegenerative diseases. Furthermore, BDNF-mimetic drugs combining with non-invasive 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.

neuroscience↗

bioRxiv2022

Thermal cycling hyperthermia sensitizes non-small cell lung cancer A549 cells to EGFR-tyrosine kinase inhibitor Erlotinib

Molecular targeted therapy has emerged as a mainstream treatment for non-small cell lung cancer (NSCLC), the most common lung cancer, which has been the leading cause of cancer death in both genders. Erlotinib (Erl), a targeted therapy inhibiting epidermal growth factor receptor (EGFR) pathways, has been proved to have noticeable response rate for NSCLC cells. However, limited efficacy arises due to intrinsic and acquired resistance among most NSCLC patients. Therefore, sensitizers are required to potentiate the efficacy of Erl in NSCLC treatment. The study proposed a novel thermal therapy, thermal cycling hyperthermia (TC-HT), as a supplement to amplify the effects of Erl. We found that TC-HT remarkably reduced the half-maximal inhibitory concentration (IC50) of Erl to as little as 0.5 M and demonstrated that TC-HT could sensitize A549 NSCLC cells to Erl via the downstream of EGFR signaling cascades. Furthermore, combination treatment induced G2/M cell cycle arrest, and inhibition of cell proliferation and migration. Besides, via raising the high temperature of TC-HT slightly, TC-HT treatment alone can produce excellent antineoplastic effect without hurting the normal cells. The method is expected to be applicable to other combination therapies and may be a starter for more sophisticated, side-effect-free anticancer treatments.

cancer biology↗

bioRxiv2022

One-Step Making of DNA Dumbbells Allows Tunneling of Short-Read Libraries into a Long-Read Format

DNA dumbbells have many applications. For example, they can be templates for rolling-circle amplification to produce highly accurate long-read sequences of single molecules. We have developed a highly efficient and simple method for tunneling short-read Illumina sequencing libraries into long-read dumbbells. A 5-exonuclease used in Gibson Assembly converted fixed Illumina P5/P7 sequences into sticky ends. Self-looping oligonucleotides with complementary 3-overhangs were ligated to form dumbbells. The reaction proceeded in one pot and modified only end nucleotides of input libraries. Resulting dumbbells were ready for Phi29-dependent rolling circle amplification. Demonstrative readouts of full-length 16S rDNA from a standard microbial community, obtained on a Pacific Biosciences (PacBio) platform, confirmed successful tunneling of initially P5/P7-ended sequencing libraries. Twelve fecal samples additionally showed significant correlations between standard and tunneled 16S sequence variants on a PacBio platform.

molecular biology↗

bioRxiv2021

A photo-switchable assay system for dendrite degeneration and repair in Drosophila melanogaster

Neurodegeneration arising from aging, injury or disease has devastating health consequences. Whereas neuronal survival and axon degeneration have been studied extensively, much less is known about how neurodegeneration impacts dendrites. To develop an assay for dendrite degeneration and repair in the Drosophila peripheral nervous system, we used photo-switchable caspase-3 (caspase-LOV) to induce neuronal damage with tunable severity by adjusting illumination duration, thereby revealing cell type-specific responses to caspase-3 induced dendrite degeneration in dendrite arborization (da) neurons. To ask whether mechanisms underlying axon degeneration also govern dendrite degeneration, we tested the involvement of the Wallerian degeneration pathway by examining the effects of expressing the mouse Wallerian degeneration slow (WldS) protein and knockdown of the Drosophila sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein (dSarm1) and Axundead (Axed) in class 4 da neurons. Here we report WldS expression or knockdown of dSarm1 improved dendrite repair following caspase- 3 induced dendrite degeneration. Whereas both dSarm1 and Axed were required for thermal nocifensive behavior in uninjured animals, WldS expression improved the recovery of thermal nocifensive behavior that was impaired by chronic low-level of caspase-LOV activity. By establishing ways to induce graded dendrite degeneration, we uncover a protective role of WldS in caspase-3 induced dendrite degeneration and repair.

neuroscience↗

bioRxiv2017

Role of the Visual Experience-Dependent Nascent Proteome in Neuronal Plasticity

Experience-dependent synaptic plasticity refines brain circuits during development. To identify novel protein synthesis-dependent mechanisms contributing to experience-dependent plasticity, we conducted a quantitative proteomic screen of the nascent proteome in response to visual experience in Xenopus optic tectum using bio-orthogonal metabolic labeling (BONCAT). We identified 83 differentially synthesized candidate plasticity proteins (CPPs). The CPPs form strongly interconnected networks and are annotated to a variety of biological functions, including RNA splicing, protein translation, and chromatin remodeling. Functional analysis of select CPPs revealed the requirement for eukaryotic initiation factor 3 subunit A (eIF3A), fused in sarcoma (FUS), and ribosomal protein s17 (RPS17) in experience-dependent structural plasticity in tectal neurons and behavioral plasticity in tadpoles. These results demonstrate that the nascent proteome is dynamic in response to visual experience and that de novo synthesis of machinery that regulates RNA splicing and protein translation is required for experience-dependent plasticity.\n\nHighlightsO_LIThe nascent proteome changes dynamically in response to visual experience\nC_LIO_LINewly synthesized candidate plasticity proteins were identified using MS/MS\nC_LIO_LIVisual experience induces de novo synthesis of synaptic and cytoskeletal proteins\nC_LIO_LISynthesis of RNA splicing and translation machinery is required for plasticity\nC_LI\n\neTOC BlurbLiu et al. show that the nascent proteome changes dynamically in response to plasticity-inducing visual experience. Functional analysis reveals that visual experience-dependent synthesis of RNA splicing and protein translation machinery is required for plasticity.

neuroscience↗