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Chen, W.-T.

Publications and source records attributed to Chen, W.-T..

At least 19 recordsLinked to original sources

The sex determination gene fruitless is essential for male Aedes aegypti mosquito swarming and attraction to female flight sounds

Aggregating male mosquitoes locate females by showing strong and innate attraction to female flight sounds, with these behaviors forming the basis of mating in the worlds deadliest animal. In contrast, females do not show aggregation or sound attraction behaviors. Despite being documented for almost a century, the molecular underpinnings of these behavioral dimorphisms remain unknown. Here, we found that by disrupting the male-specific isoform of the key sex determination gene fruitless (referred to as fruM) in Aedes aegypti, mutant males behave like females. fruM mutant males show complete abolition of aggregation and sound attraction behaviors, resulting in failure to locate females for mating. We identified strong fruitless expression in control male ears, with the loss of FruM severely disrupting mutant male ability to amplify female flight sounds compared to control males. fruM mutant male ears propagate frequency-specific, sound-evoked electrical signals at about one-sixth the magnitude of control males, significantly reducing the amount of auditory information relayed to the brain. fruitless thus plays a significant role in determining proper male peripheral hearing function, which enables male hearing behaviors essential for mating. Transcriptomic analyses of mosquito ears enabled identification of essential hearing genes under the transcriptional influence of FruM. We propose that FruM fine-tunes the masculinization of mosquito ears through shaping male-specific hearing cellular machineries that support male attraction to female flight sounds. We conclude that FruM is the master regulator of male-specific reproductive behaviors in mosquitoes and propose fruitless, as well as fruitless-dependent genes, as novel targets for control strategies. HighlightsO_LIFruM is the master regulator of male swarming and attraction to female flight sounds C_LIO_LIFruM in male ears is essential for male amplification of female flight sounds C_LIO_LIFruM in male ears modulates sound-evoked electrical signal propagation to the brain C_LIO_LIFruM regulates essential hearing gene expression C_LI

neuroscience↗

Rediscovery of the Enigmatic Paroxygraphis in Xizang, China: Phylogenetic Evidence for its Reclassification Within Oxygraphis (Ranunculaceae)

The enigmatic monotypic genus Paroxygraphis (Ranunculaceae, trib. Ranunculeae), represented solely by P. sikkimensis, has long posed taxonomic uncertainties due to its rarity. Through field rediscovery in southern Xizang province, China, and comprehensive molecular phylogenetic analyses combining nrITS and four plastid regions, we resolve its phylogenetic position within the Oxygraphis clade, with an estimated divergence time of about 3.73 Ma (95% HPD: 1.98-5.77 Ma) from its sister clade. Morphological and ecological characteristics, including small herb with a rosette of basal simple leaves, longitudinally ribbed achenes, and its alpine adaptations, further support this relationship. Furthermore, the results showed that persistent sepals and unisexual flowers in trib. Ranunculeae reflects multiple independent evolutionary origins. We propose the new combination Oxygraphis sikkimensis and highlight its critically endangered status due to habitat vulnerability. Lectotypification of P. sikkimensis is also made. This study provides new data for the floristic research of China and resolves the long-standing taxonomic controversy of this problematic genus within trib. Ranunculeae.

evolutionary biology↗

cAMP-related second messenger pathways modulate hearing function in Aedes aegypti mosquitoes

The powerful ears of male Aedes aegypti mosquitoes facilitate identification and localization of mating partners via detection of female flight tones. Male hearing function is modulated by the efferent release of neurotransmitters, though the secondary mechanisms underlying this modulation remain unclear. Here, we investigated these mechanisms using octopamine as a model, as octopamine modulates hearing function and the erection status of fibrillar hairs lining male ears. We found that pharmacological interference with octopamine receptors alters hearing function at multiple levels and identified the second messenger cAMP as likely mediating these changes. Furthermore, the erection status of male ear fibrillar hairs could be altered by targeting specific sub-types of octopamine receptors, but these changes were not linked to changes in ear frequency tuning. Finally, we suggest that octopamine 2 receptors linked to fibrillar hair erection may not always produce functional proteins across species, with downstream implications for hearing behaviors. HighlightsO_LIOctopamine and its receptors are found throughout Aedes aegypti mosquito ears C_LIO_LIPharmacological interference with octopamine receptors modulates hearing function C_LIO_LIModulating levels of the second messenger cAMP also alters hearing function C_LIO_LIEar frequency tuning does not correlate with the erection of hairs lining male ears C_LI

neuroscience↗

A robust benchmark for detecting low-frequency variants in the HG002 Genome In A Bottle NIST reference material.

Somatic mosaicism is an important cause of disease, but mosaic and somatic variants are often challenging to detect because they exist in only a fraction of cells. To address the need for benchmarking subclonal variants in normal cell populations, we developed a benchmark containing mosaic variants in the Genome in a Bottle Consortium (GIAB) HG002 reference material DNA from a large batch of a normal lymphoblastoid cell line. First, we used a somatic variant caller with high coverage (300x) Illumina whole genome sequencing data from the Ashkenazi Jewish trio to detect variants in HG002 not detected in at least 5% of cells from the combined parental data. These candidate mosaic variants were subsequently evaluated using >100x BGI, Element, and PacBio HiFi data. High confidence candidate SNVs with variant allele fractions above 5% were included in the HG002 draft mosaic variant benchmark, with 13/85 occurring in medically relevant gene regions. We also delineated a 2.45 Gbp subset of the previously defined germline autosomal benchmark regions for HG002 in which no additional mosaic variants >2% exist, enabling robust assessment of false positives. The variant allele fraction of some mosaic variants is different between batches of cells, so using data from the homogeneous batch of reference material DNA is critical for benchmarking these variants. External validation of this mosaic benchmark showed it can be used to reliably identify both false negatives and false positives for a variety of technologies and detection algorithms, demonstrating its utility for optimization and validation. By adding our characterization of mosaic variants in this widely-used cell line, we support extensive benchmarking efforts using it in simulation, spike-in, and mixture studies.

bioinformatics↗

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↗

Applying high-resolution spatial transcriptomics to characterise the amyloid plaque cell niche in Alzheimer's Disease

The amyloid plaque cell niche is a pivotal hallmark of Alzheimers disease (AD). Where early spatial transcriptomics (ST) technologies have provided valuable information on transcriptomic alterations in the small tissue domains overlaying with amyloid plaques, they lacked cellular resolution. Here we compare two novel high-resolution ST platforms, CosMx and Stereo-seq, in their ability to characterize the cellular response in the amyloid plaque niche in an AD mouse model. Combining the results from both techniques empowered us to survey the highly variable microglial-astrocytic response across the amyloid plaque micro-environment and provided a first insight into how these responses could relate to neuronal transcriptomic alterations. This pilot study demonstrates the great potential of high-resolution ST, while simultaneously highlighting limitations that, when addressed, will unleash the full power of these techniques to map the progression of molecular and cellular changes in the brains of AD patients.

neuroscience↗

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↗

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↗

α-synuclein over expression, NRF2 suppression, and enhanced ferroptosis creates a vicious cycle of neuronal loss in Parkinson's disease

Parkinsons disease (PD) is the second most common neurodegenerative disorder, affecting millions each year. Most PD cases ([~]90%) are sporadic, resulting from the age-dependent accumulation of pathogenic effects. One key pathological hallmark of PD progression is the accumulation of alpha-synuclein (-syn), which has been shown to negatively affect neuronal function and viability. Here, using 3- and 6-month-old Nrf2+/+ and Nrf2-/- mice overexpressing human -syn (PD model), we show that loss of NRF2 increases markers of ferroptosis across PD-relevant brain regions. Increased ferroptosis was associated with an age- and genotype-dependent increase in -syn pathology and behavioral deficits. Finally, we demonstrate that -syn overexpression sensitizes neuronal cells and ex vivo brain slices to ferroptosis induction, which may be due to -syn suppression of NRF2 at the protein level. Altogether, these results indicate that NRF2 is a critical anti-ferroptotic mediator of neuronal survival, and that the vicious cycle of -syn overexpression and NRF2 suppression, leading to enhanced neuronal ferroptotic cell death, could represent a targetable and currently untapped means of preventing PD onset and progression.

neuroscience↗

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↗

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↗

Long noncoding RNA MEG3 activates neuronal necroptosis in Alzheimer's disease

Abstract/SummaryNeuronal cell loss is a defining feature of Alzheimers disease (AD), but it remains unclear how neurons die and how this relates to other defining characteristics of the disease1. Existing in vivo AD models only partially recapitulate the neuropathology of AD with very mild or no neuronal cell loss. Here we demonstrate that human neurons xenografted in mouse brain exposed to amyloid pathology develop sarkosyl-insoluble tau filaments, positive Gallyas silver staining, release phosphorylated tau (P-tau181) into the blood, and display considerable neuronal cell loss, providing a model for the induction of full Tau pathology by simple exposure to amyloid pathology in AD. The alterations are specific to human neurons and contrast with the mild effects exhibited in mouse neurons. A core transcriptional program in the human neurons is characterized by strong upregulation of MEG3, a neuron-specific long noncoding RNA. MEG3 is also strongly upregulated in neurons from AD patients in situ. MEG3 expression alone is sufficient to induce necroptosis in human neurons in vitro. Orally administered small molecule receptor-interacting protein (RIP) kinase -1 and -3 inhibitors rescued the neuronal cell loss in this novel AD model. Thus, xenografted human neurons are uniquely sensitive to amyloid pathology, recapitulate all the defining neuropathological features of AD, and ultimately die by necroptosis.

neuroscience↗

Analysis of single-cell RNA-sequencing data to identify quiescent and proliferating neural cell populations in Glioblastoma

BackgroundDiffuse Glioblastoma (GBM) has high mortality and remains one of the most challenging type of cancer to treat. Identifying and characterizing the cells populations driving tumor growth and therapy resistance has been particularly difficult owing to marked inter and intra tumoral heterogeneity observed in these tumors. These tumorigenic populations contain long lived cells associated with latency, immune evasion and metastasis. MethodsHere, we analyzed the single-cell RNA-sequencing data of high grade glioblastomas from four different studies using integrated analysis of gene expression patterns, cell cycle stages and copy number variation to identify gene expression signatures associated with quiescent and cycling neuronal tumorigenic cells. ResultsThe results show that while cycling and quiescent cells are present in GBM of all age groups, they exist in a much larger proportion in pediatric glioblastomas. These cells show similarities in their expression patterns of a number of pluripotency and proliferation related genes. Upon unbiased clustering, these cells explicitly clustered on their cell cycle stage. Quiescent cells in both the groups specifically overexpressed a number of genes for ribosomal protein, while the cycling cells were enriched in the expression of high-mobility group and heterogeneous nuclear ribonucleoprotein group genes. A number of well-known markers of quiescence and proliferation in neurogenesis showed preferential expression in the quiescent and cycling populations identified in our analysis. Through our analysis, we identify ribosomal proteins as key constituents of quiescence in glioblastoma stem cells. ConclusionsThis study identifies gene signatures common to adult and pediatric glioblastoma quiescent and cycling stem cell niches. Further research elucidating their role in controlling quiescence and proliferation in tumorigenic cells in high grade glioblastoma will open avenues in more effective treatment strategies for glioblastoma patients.

cancer biology↗

Study on the effect of a triple cancer treatment of propolis, thermal cycling-hyperthermia, and low-intensity ultrasound on PANC-1 cells

BackgroundPancreatic cancer is a deadly cancer around the world. To reduce side effects and enhance treatment efficacy, study on combination therapy for pancreatic cancer has gained much attention in recent years. MethodsIn this paper, we propose a novel triple treatment combining propolis and two physical stimuli-thermal cycling-hyperthermia (TC-HT) and low-intensity ultrasound (US) on a human pancreatic cancer cell line PANC-1. MTT assay was used to determine the viability of PANC-1 cells. Flow cytometry was used to detect apoptosis, mitochondrial membrane potential (MMP) loss, and intracellular reactive oxygen species (ROS) levels. Western blot analysis was further performed to measure protein expression and phosphorylation. ResultsThe experiments found that, after the triple treatment, the cell viability of the PANC-1 cells decreased to a level 80% less than the control, without affecting the normal pancreatic cells. Another result was excessive accumulation of ROS after the triple treatment, leading to the amplification of apoptotic pathway through the mitogen-activated protein kinase (MAPK) family and mitochondrial dysfunction. Moreover, the combination of TC-HT and US also promotes the anticancer effect of the heat-sensitive chemotherapy drug cisplatin on PANC-1 cells. ConclusionThis study, to the best of our knowledge, is the first attempt to combine TC-HT, US and a nature compound in cancer treatment. We demonstrate that physical stimuli could augment the therapeutical effect of anticancer agents. It is expected that optimized parameters for different agents and different types of cancer will expand the methodology on oncological therapy in a safe manner.

cancer biology↗

Melanin Concentrating Hormone- and sleep-dependent synaptic downscaling is impaired in Alzheimer's Disease

In Alzheimers disease (AD), pathophysiological changes in the hippocampus cause deficits in episodic memory formation, leading to cognitive impairment 1,2. Neuronal hyperactivity is observed early in AD 3,4. Here, we find that homeostatic mechanisms transiently counteract increased neuronal activity in the hippocampal CA1 region of the AppNL-G-F humanized knock-in mouse model for AD 5, but ultimately fail to maintain neuronal activity at set-point. Spatial transcriptomic analysis in CA1 during the homeostatic response identifies the Melanin-Concentrating Hormone (MCH)-encoding gene. MCH is expressed in sleep-active lateral hypothalamic neurons that project to CA1 and modulate memory 6. We show that MCH regulates synaptic plasticity genes and synaptic downscaling in hippocampal neurons. Furthermore, MCH-neuron activity is impaired in AppNL-G-F mice, disrupting sleep-dependent homeostatic plasticity and stability of neuronal activity in CA1. Finally, we find perturbed MCH-axon morphology in CA1 early in AppNL-G-F mice and in AD patients. Our work identifies dysregulation of the MCH-system as a key player in aberrant neuronal activity in the early stages of AD.

neuroscience↗

Correlation between cancer stem cells, inflammation and malignant transformation in a DEN-induced model of hepatic carcinogenesis

AimsChronic inflammation and cancer stem cells are known risk factors for tumorigenesis. The aetiology of hepatocellular carcinoma (HCC) involves a multistep pathological process characterised by chronic inflammation and hepatocyte damage but the correlation between HCC, inflammation and cancer stem cell remains unclear. In this study, we examined the role of hepatic progenitor cells in a mouse model of chemical-induced hepatocarcinogenesis to elucidate the relationship between inflammation, malignant transformation and cancer stem cells. Methods and resultsWe used diethylnitrosamine (DEN) to induce liver tumour and scored for H&E and reticulin staining, and also immunohistochemistry staining for OV-6 expression and analysed the statistical correlation between each other. DEN progressively induced inflammation at 7 week 7 (40%, 2/5), week 27 (75%, 6/8), week 33 (62.5%, 5/8) and week 50 (100%, 12/12). DEN progressively induced malignant transformation at week 7 (0%, 0/5), week 27 (87.5%, 7/8), week 33 (100%, 8/8) and week 50 (100%, 12/12). Data obtained showed that DEN progressively induced high-levels of OV-6 expression at week 7 (20%, 1/5), week 27 (37.5%, 3/8), week 33 (50%, 4/8) and week 50 (100%, 12/12). DEN-induced inflammation, malignant transformation and high-level OV-6 expression in hamster liver as shown above and applying Spearmans correlation to the data showed that expression of OV-6 was significantly correlated to inflammation (p = 0.001) and malignant transformation (p < 0.001) ConclusionsThere was a significant correlation between number of cancer stem cells, inflammation and malignant transformation in a DEN-induced model of hepatic carcinogenesis in the hamster.

cancer biology↗

Effect of high frequency and low intensity pulsed electric field on protecting SH-SY5Y cells against hydrogen peroxide and β-amyloid-induced cell injury via ERK pathway

As the most common type of neurodegenerative diseases (NDDs), Alzheimers disease (AD) is thought to be caused mainly by the excessive aggregation of {beta}-amyloid protein (A{beta}). However, a growing number of studies have found that reactive oxygen species (ROS) play a key role in the onset and progression of AD. The present study aimed to probe the neuroprotective effect of high-frequency low-intensity pulsed electric field (H-LIPEF) for SH-SY5Y cells against hydrogen peroxide (H2O2) and A{beta}-induced cytotoxicity. By looking in a systematic way into the frequency- and amplitude-dependent neuroprotective effect of pulsed electric field (PEF), the study finds that H-LIPEF at 200 Hz produces the optimal protective effect for SH-SY5Y cells. The underlying mechanisms were confirmed to be due to the activation of extracellular signal-regulated kinase (ERK) pathway and the downstream prosurvival and antioxidant proteins. Because the electric field can be modified to focus on specific area in a non-contact manner, the study suggests that H-LIPEF holds great potential for treating NDDs, whose effect can be further augmented with the administering of drugs or natural compounds at the same time.

neuroscience↗

Thermal cycling protects SH-SY5Y cells against hydrogen peroxide and -amyloid-induced cell injury through stress response mechanisms involving Akt pathway

Neurodegenerative diseases (NDDs) are becoming a major threat to public health, according to the World Health Organization (WHO). The most common form of NDDs is Alzheimers disease (AD), boasting 60-70% share. Excessive aggregation of {beta}-amyloid protein (A{beta}) and neurofibrillary tangles has been deemed the major cause for the pathogenesis of AD. A growing number of evidences from studies, however, have suggested that reactive oxygen species (ROS) also play a key role in the onset and progression of AD. Although scientists have had some understanding of the pathogenesis of AD, the disease still cannot be cured, with existing treatment only capable of providing a temporary relief at best, partly due to the obstacle of blood-brain barrier (BBB). The study was aimed to ascertain the neuroprotective effect of thermal cycle hyperthermia (TC-HT) against hydrogen peroxide (H2O2) and A{beta}-induced cytotoxicity in SH-SY5Y cells. Treating cells with this physical stimulation beforehand significantly improved the cell viability and decreased the ROS content. The underlying mechanisms were confirmed to be due to the activation of Akt pathway and the downstream antioxidant and prosurvival proteins. The findings manifest significant potential of TC-HT in neuroprotection, via inhibition of oxidative stress and cell apoptosis. It is believed that coupled with the use of drugs or natural compounds, this methodology can be even more effective in treating NDDs.

neuroscience↗