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1.
Brain ; 146(7): 2957-2974, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37062541

RESUMO

Reactive astrogliosis is a hallmark of Alzheimer's disease (AD). However, a clinically validated neuroimaging probe to visualize the reactive astrogliosis is yet to be discovered. Here, we show that PET imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. To investigate the alterations of acetate and glucose metabolism in the diseased brains and their impact on the AD pathology, we adopted multifaceted approaches including microPET imaging, autoradiography, immunohistochemistry, metabolomics, and electrophysiology. Two AD rodent models, APP/PS1 and 5xFAD transgenic mice, one adenovirus-induced rat model of reactive astrogliosis, and post-mortem human brain tissues were used in this study. We further curated a proof-of-concept human study that included 11C-acetate and 18F-FDG PET imaging analyses along with neuropsychological assessments from 11 AD patients and 10 healthy control subjects. We demonstrate that reactive astrocytes excessively absorb acetate through elevated monocarboxylate transporter-1 (MCT1) in rodent models of both reactive astrogliosis and AD. The elevated acetate uptake is associated with reactive astrogliosis and boosts the aberrant astrocytic GABA synthesis when amyloid-ß is present. The excessive astrocytic GABA subsequently suppresses neuronal activity, which could lead to glucose uptake through decreased glucose transporter-3 in the diseased brains. We further demonstrate that 11C-acetate uptake was significantly increased in the entorhinal cortex, hippocampus and temporo-parietal neocortex of the AD patients compared to the healthy controls, while 18F-FDG uptake was significantly reduced in the same regions. Additionally, we discover a strong correlation between the patients' cognitive function and the PET signals of both 11C-acetate and 18F-FDG. We demonstrate the potential value of PET imaging with 11C-acetate and 18F-FDG by visualizing reactive astrogliosis and the associated neuronal glucose hypometablosim for AD patients. Our findings further suggest that the acetate-boosted reactive astrocyte-neuron interaction could contribute to the cognitive decline in AD.


Assuntos
Doença de Alzheimer , Camundongos , Humanos , Ratos , Animais , Doença de Alzheimer/metabolismo , Fluordesoxiglucose F18/metabolismo , Astrócitos/metabolismo , Radioisótopos de Carbono/metabolismo , Gliose/diagnóstico por imagem , Encéfalo/patologia , Tomografia por Emissão de Pósitrons/métodos , Ácido gama-Aminobutírico/metabolismo
2.
J Dairy Sci ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825137

RESUMO

This study characterized the sleep activity, sleep mechanism, and active peptides of whey protein hydrolysates selected through behavioral analysis of fruit-flies (Drosophila melanogaster). Sleep-inducing whey protein (WP) hydrolysate was selected through fruit fly behavior analysis, and sleep activity was measured using a pentobarbital model and electroencephalographic analysis. The mechanism of action was confirmed using a γ-aminobutyric acid (GABA) receptor antagonist, and the active peptide was identified using liquid chromatography-mass spectroscopy. Whey protein hydrolysate, prepared using Alcalase and Prozyme (WP-AP), increased sleep time in a dose-dependent manner. WP-AP significantly increased not only sleep time but also slow-wave sleep and showed an insomnia-alleviating effect in a caffeine-induced insomnia mouse model. In addition, the gene and protein expression levels of GABA sub-type A (GABAA) receptors increased in the brains of mice orally administered with WP-AP. Through peptide analysis, the mixture of DIQK, VPPF peptide, and GABA contained in WP-AP was estimated to exhibit sleep activity, and due to its high content, DIQK was speculated to be the main sleep -inducing ingredient. These results indicate that WP-AP has the potential to be used as a new ingredient to improve sleep quality.

3.
Molecules ; 29(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38893346

RESUMO

Photosensitizers cause oxidative damages in various biological systems under light. In this study, the method for analyzing photosensitizing activity of various dietary and medicinal sources was developed using 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (thiazolyl blue formazan; MTT-F) as a probe. Significant and quantitative decolorization of MTT-F was observed in the presence of photosensitizers used in this study under light but not under dark conditions. The decolorization of MTT-F occurred irradiation time-, light intensity-, and photosensitizer concentration-dependently. The decolorized MTT-F was reversibly reduced by living cells; the LC-MS/MS results indicated the formation of oxidized products with -1 m/z of base peak from MTT-F, suggesting that MTT-F decolorized by photosensitizers was its corresponding tetrazolium. The present results indicate that MTT-F is a reliable probe for the quantitative analysis of photosensitizing activities, and the MTT-F-based method can be an useful tool for screening and evaluating photosensitizing properties of various compounds used in many industrial purposes.


Assuntos
Formazans , Fármacos Fotossensibilizantes , Sais de Tetrazólio , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Humanos , Sais de Tetrazólio/química , Formazans/química , Espectrometria de Massas em Tandem/métodos , Tiazóis/química , Luz , Cromatografia Líquida/métodos , Corantes/química
4.
Med Princ Pract ; 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37549659

RESUMO

Background The relationship between overweight or obesity and low back pain (LBP) has previously been investigated. Several recent studies have focused on the relationship between other indicators of obesity, particularly indicators of fat and the risk of LBP. However, the results of body composition and LBP have been inconsistent. Methods All data for the present retrospective, cross-sectional study was extracted from the Korea National Health and Nutrition Examination Survey (KNHANES) versions V-1 and 2 conducted in 2010 and 2011 by the Korean Centers for Disease Control and Prevention. In KNHANES V-1 (2010) and V-2 (2011), those over 50 years of age completed the surveys on LBP, body weight, and body composition assessed using dual-energy X-ray absorptiometry (DXA) were included. The multivariable logistic regression analysis was used to examine the relationship between the presence of chronic LBP and body composition adjusting for confounders. Results We analyzed 3,579 persons who completed the question. In the multivariable analyses adjusting for age and sex, none of the variables, including fat mass and fat-free mass, remained positively or negatively associated with LBP. Additionally, when depression, smoking, alcohol intake, physical activity, diabetes mellitus, and fat or lean tissue mass were included in the multivariable logistic model, no significant associations were found between all measures of fat mass, fat-free mass, and LBP Conclusion This study is contrary to previous studies that concluded that there is a correlation between obesity and fat mass and LBP. LBP is not associated with increased levels of obesity and fat mass.

5.
Biochem Biophys Res Commun ; 619: 110-116, 2022 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-35753218

RESUMO

Chemotherapy induces tumor cell death and inhibits tumor progression, but the accompanying immune responses in the surrounding dying tissue cause significant inflammation. These responses, such as excessive neutrophil infiltration into tumor tissue, are the main causes of resistance to anticancer treatment. The development of drugs that reduce neutrophil infiltration into tumors is necessary to increase the anticancer effect of chemotherapy. Here, we show that the antitumor effect of the chemotherapy AC regimen (Adriamycin and cyclophosphamide) was increased by 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) cotreatment in the MDA-MB-231 triple-negative breast cancer xenograft mouse model. Tumor growth was inhibited up to 56% in mice treated with AC and inhibited up to 94% in mice cotreated with AC and PLAG. Side effects of chemotherapy, such as a reduction in body weight, were alleviated in mice cotreated with AC and PLAG. Excessive neutrophil infiltration caused by the AC regimen was successfully cleared in mice cotreated with AC and PLAG. We conclude that PLAG inhibits excessive neutrophil infiltration that aids tumor growth. Reduced neutrophils and increased lymphocytes in PLAG-treated mice can maximize the antitumor effect of the AC regimen and inhibit tumor growth.


Assuntos
Doxorrubicina , Neoplasias de Mama Triplo Negativas , Animais , Linhagem Celular Tumoral , Ciclofosfamida/uso terapêutico , Modelos Animais de Doenças , Doxorrubicina/uso terapêutico , Xenoenxertos , Humanos , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
6.
BMC Cancer ; 22(1): 727, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35787261

RESUMO

BACKGROUND: The PD-L1 antibody is an immune checkpoint inhibitor (ICI) attracting attention. The third-generation anticancer drug has been proven to be very effective due to fewer side effects and higher tumor-specific reactions than conventional anticancer drugs. However, as tumors produce additional resistance in the host immune system, the effectiveness of ICI is gradually weakening. Therefore, it is very important to develop a combination therapy that increases the anticancer effect of ICI by removing anticancer resistance factors present around the tumor. METHODS: The syngeneic model was used (n = 6) to investigate the enhanced anti-tumor effect of PD-L1 antibody with the addition of PLAG. MB49 murine urothelial cancer cells were implanted into the C57BL/6 mice subcutaneously. PLAG at different dosages (50/100 mpk) was daily administered orally for another 4 weeks with or without 5 mpk PD-L1 antibody (10F.9G2). PD-L1 antibody was delivered via IP injection once a week. RESULTS: The aPD-L1 monotherapy group inhibited tumor growth of 56% compared to the positive group, while the PLAG and aPD-L1 co-treatment inhibited by 89%. PLAG treatment effectively reduced neutrophils infiltrating localized in tumor and converted to a tumor microenvironment with anti-tumor effective T-cells. PLAG increased tumor infiltration of CD8 positive cytotoxic T-cell populations while effectively inhibiting the infiltration of neoplastic T-cells such as CD4/FoxP3. Eventually, neutrophil-induced tumor ICI resistance was resolved by restoring the neutrophil-to-lymphocyte ratio to the normal range. In addition, regulation of cytokine and chemokine factors that inhibit neutrophil infiltration and increase the killing activity of cytotoxic T cells was observed in the tumors of mice treated with PLAG + aPD-L1. CONCLUSIONS: PLAG effectively turned the tumor-promoting microenvironment into a tumor-suppressing microenvironment. As a molecule that increases the anti-tumor effectiveness of aPD-L1, PLAG has the potential to be an essential and effective ICI co-therapeutic agent.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Animais , Camundongos , Antígeno B7-H1 , Carcinoma de Células de Transição/tratamento farmacológico , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos , Microambiente Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico
7.
Adv Funct Mater ; 31(1)2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34764824

RESUMO

Accurately replicating and analyzing cellular responses to mechanical cues is vital for exploring metastatic disease progression. However, many of the existing in vitro platforms for applying mechanical stimulation seed cells on synthetic substrates. To better recapitulate physiological conditions, a novel actuating platform is developed with the ability to apply tensile strain on cells at various amplitudes and frequencies in a high-throughput multi-well culture plate using a physiologically-relevant substrate. Suspending fibrillar fibronectin across the body of the magnetic actuator provides a matrix representative of early metastasis for 3D cell culture that is not reliant on a synthetic substrate. This platform enables the culturing and analysis of various cell types in an environment that mimics the dynamic stretching of lung tissue during normal respiration. Metabolic activity, YAP activation, and morphology of breast cancer cells are analyzed within one week of cyclic stretching or static culture. Further, matrix degradation is significantly reduced in breast cancer cell lines with metastatic potential after actuation. These new findings demonstrate a clear suppressive cellular response due to cyclic stretching that has implications for a mechanical role in the dormancy and reactivation of disseminated breast cancer cells to macrometastases.

8.
Can J Physiol Pharmacol ; 97(9): 857-862, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31251888

RESUMO

Acute physical exercise increases reactive oxygen species in skeletal muscle, leading to tissue damage and fatigue. Molecular hydrogen (H2) acts as a therapeutic antioxidant directly or indirectly by inducing antioxidative enzymes. Here, we examined the effects of drinking H2 water (H2-infused water) on psychometric fatigue and endurance capacity in a randomized, double-blind, placebo-controlled fashion. In Experiment 1, all participants drank only placebo water in the first cycle ergometer exercise session, and for comparison they drank either H2 water or placebo water 30 min before exercise in the second examination. In these healthy non-trained participants (n = 99), psychometric fatigue judged by visual analogue scales was significantly decreased in the H2 group after mild exercise. When each group was divided into 2 subgroups, the subgroup with higher visual analogue scale values was more sensitive to the effect of H2. In Experiment 2, trained participants (n = 60) were subjected to moderate exercise by cycle ergometer in a similar way as in Experiment 1, but exercise was performed 10 min after drinking H2 water. Endurance and fatigue were significantly improved in the H2 group as judged by maximal oxygen consumption and Borg's scale, respectively. Taken together, drinking H2 water just before exercise exhibited anti-fatigue and endurance effects.


Assuntos
Água Potável/química , Fadiga/psicologia , Hidrogênio , Resistência Física/efeitos dos fármacos , Adulto , Idoso , Método Duplo-Cego , Fadiga/metabolismo , Feminino , Humanos , Hidrogênio/metabolismo , Masculino , Pessoa de Meia-Idade , Placebos , Psicometria , Adulto Jovem
9.
IEEE Sens J ; 19(4): 1373-1378, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31579395

RESUMO

Indwelling catheters are used widely in medicine to treat various chronic medical conditions. However, chronic implantation of catheters often leads to a premature failure due to biofilm accumulation. Previously we reported on the development of a self-clearing catheter by integrating polymer-based microscale magnetic actuators. The microactuator provides an active anti-biofouling mechanism to disrupt and remove adsorbed biofilm on demand using an externally applied stimulus. During an in vivo evaluation of self-clearing catheter, we realized that it is important to periodically monitor the performance of implanted microactuators. Here we integrate gold-based piezoresistive strain-gauge on our magnetic microactuators to directly monitor the device deflection with good sensitivity (0.035%/Deg) and linear range (±30°). With the integrated strain-gauge, we demonstrate the multi-functional capabilities of our magnetic microactuators that enable device alignment, flow-rate measurement, and obstruction detection and removal towards the development of chronically implantable self-clearing smart catheter.

10.
AAPS PharmSciTech ; 20(3): 96, 2019 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-30694397

RESUMO

Transdermal drug delivery has advantages of topical drug administration compared to the other conventional administration methods. However, the skin penetration of drugs is limited by the barrier properties of stratum corneum. The combinational strategy has been investigated to improve the skin permeability of the drug. For this study, we devised an improved device that can perform not only the single application of sonophoresis or iontophoresis but also the simultaneous application. The enhancement effect of sonophoresis was evaluated for various cosmeceutical drugs using a Franz diffusion cell. The enhancement ratio of niacinamide and retinol with sonophoresis was increased to 402% and 292%, respectively. The relationship was found between the enhancement effect of sonophoresis and the physicochemical properties of drugs. In particular, the simultaneous treatment of sonophoresis and iontophoresis enhanced skin penetration of glutamic acid to 240% using the fabricated device. The simultaneous application showed significantly higher enhancement ratio than application of sonophoresis or iontophoresis alone. Moreover, the improved device achieved skin penetration enhancement of various cosmeceutical drugs with lower intensity and a short application time. This combined strategy of transdermal physical enhancement methods is advantageous in terms of decline in energy density, thereby reducing the skin irritation. The miniaturized device with sonophoresis and iontophoresis is a promising approach due to enhanced transdermal drug delivery and feasibility of self-administration in cosmetic and therapeutic fields.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Iontoforese/métodos , Pele/metabolismo , Ondas Ultrassônicas , Administração Cutânea , Animais , Difusão , Desenho de Equipamento , Ácido Glutâmico/administração & dosagem , Interações Hidrofóbicas e Hidrofílicas , Iontoforese/instrumentação , Miniaturização , Permeabilidade/efeitos dos fármacos , Preparações Farmacêuticas/administração & dosagem , Farmacocinética , Absorção Cutânea
11.
Sens Actuators B Chem ; 273: 1694-1704, 2018 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34276138

RESUMO

Here we report on the development of polyimide-based flexible magnetic actuators for actively combating biofouling that occurs in many chronically implanted devices. The thin-film flexible devices are microfabricated and integrated into a single-pore silicone catheter to demonstrate a proof-of-concept for a self-clearing smart catheter. The static and dynamic mechanical responses of the thin-film magnetic microdevices were quantitatively measured and compared to theoretical values. The mechanical fatigue properties of these polyimide-based microdevices were also characterized up to 300 million cycles. Finally, the biofouling removal capabilities of magnetically powered microdevices were demonstrated using bovine serum albumin and bioconjugated microbeads. Our results indicate that these thin-film microdevices are capable of significantly reducing the amount of biofouling. At the same time, we demonstrated that these microdevices are mechanically robust enough to withstand a large number of actuation cycles during its chronic implantation.

12.
Neuromodulation ; 21(2): 117-125, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28782181

RESUMO

OBJECTIVE: The Shannon model is often used to define an expected boundary between non-damaging and damaging modes of electrical neurostimulation. Numerous preclinical studies have been performed by manufacturers of neuromodulation devices using different animal models and a broad range of stimulation parameters while developing devices for clinical use. These studies are mostly absent from peer-reviewed literature, which may lead to this information being overlooked by the scientific community. We aimed to locate summaries of these studies accessible via public regulatory databases and to add them to a body of knowledge available to a broad scientific community. METHODS: We employed web search terms describing device type, intended use, neural target, therapeutic application, company name, and submission number to identify summaries for premarket approval (PMA) devices and 510(k) devices. We filtered these records to a subset of entries that have sufficient technical information relevant to safety of neurostimulation. RESULTS: We identified 13 product codes for 8 types of neuromodulation devices. These led us to devices that have 22 PMAs and 154 510(k)s and six transcripts of public panel meetings. We found one PMA for a brain, peripheral nerve, and spinal cord stimulator and five 510(k) spinal cord stimulators with enough information to plot in Shannon coordinates of charge and charge density per phase. CONCLUSIONS: Analysis of relevant entries from public regulatory databases reveals use of pig, sheep, monkey, dog, and goat animal models with deep brain, peripheral nerve, muscle and spinal cord electrode placement with a variety of stimulation durations (hours to years); frequencies (10-10,000 Hz) and magnitudes (Shannon k from below zero to 4.47). Data from located entries indicate that a feline cortical model that employs acute stimulation might have limitations for assessing tissue damage in diverse anatomical locations, particularly for peripheral nerve and spinal cord simulation.


Assuntos
Bases de Dados Factuais/normas , Aprovação de Equipamentos/legislação & jurisprudência , Aprovação de Equipamentos/normas , Terapia por Estimulação Elétrica , Neurotransmissores , Animais , Encéfalo/fisiologia , Bases de Dados Factuais/legislação & jurisprudência , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Terapia por Estimulação Elétrica/normas , Humanos
13.
Biomed Microdevices ; 16(1): 153-61, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24077662

RESUMO

The mechanical robustness of microfabricated torsional magnetic actuators in withstanding the strong static fields (7 T) and time-varying field gradients (17 T/m) produced by an MR system was studied in this investigation. The static and dynamic mechanical characteristics of 30 devices were quantitatively measured before and after exposure to both strong uniform and non-uniform magnetic fields. The results showed no statistically significant change in both the static and dynamic mechanical performance, which mitigate concerns about the mechanical stability of these devices in association with MR systems under the conditions used for this assessment. The MR-induced heating was also measured in a 3-T/128-MHz MR system. The results showed a minimal increase (1.6 °C) in temperature due to the presence of the magnetic microactuator array. Finally, the size of the MR-image artifacts created by the magnetic microdevices were quantified. The signal loss caused by the devices was approximately four times greater than the size of the device.


Assuntos
Imageamento por Ressonância Magnética/métodos , Microtecnologia/instrumentação , Próteses e Implantes , Artefatos , Desenho de Equipamento , Campos Magnéticos , Magnetismo/instrumentação
14.
J Microelectromech Syst ; 23(4): 795-802, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29151776

RESUMO

Here, we report on the development and evaluation of novel unobstructing magnetic microactuators for maintaining the patency of implantable ventricular catheters used in hydrocephalus application. The treatment of hydrocephalus requires chronic implantation of a shunt system to divert excess cerebrospinal fluid from the brain. These shunt systems suffer from a high failure rate (>40%) within the first year of implantation, often due to biological accumulation. Previously, we have shown that magnetic microactuators can be used to remove biological blockage. The new cantilever-based magnetic microactuator presented in this paper improves upon the previous torsional design using a bimorph to induce a postrelease out-of-plane deflection that will prevent the device from occluding the pore at rest. The mechanical evaluations (i.e., postrelease deflection, static and dynamic responses) of fabricated devices are reported and compared with theoretical values.

15.
Microsyst Nanoeng ; 10: 16, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38264708

RESUMO

The vagus nerve (VN) plays an important role in regulating physiological conditions in the gastrointestinal (GI) tract by communicating via the parasympathetic pathway to the enteric nervous system (ENS). However, the lack of knowledge in the neurophysiology of the VN and GI tract limits the development of advanced treatments for autonomic dysfunctions related to the VN. To better understand the complicated underlying mechanisms of the VN-GI tract neurophysiology, it is necessary to use an advanced device enabled by microfabrication technologies. Among several candidates including intraneural probe array and extraneural cuff electrodes, microchannel electrode array devices can be used to interface with smaller numbers of nerve fibers by securing them in the separate channel structures. Previous microchannel electrode array devices to interface teased nerve structures are relatively bulky with thickness around 200 µm. The thick design can potentially harm the delicate tissue structures, including the nerve itself. In this paper, we present a flexible thin film based microchannel electrode array device (thickness: 11.5 µm) that can interface with one of the subdiaphragmatic nerve branches of the VN in a rat. We demonstrated recording evoked compound action potentials (ECAP) from a transected nerve ending that has multiple nerve fibers. Moreover, our analysis confirmed that the signals are from C-fibers that are critical in regulating autonomic neurophysiology in the GI tract.

16.
IEEE Trans Biomed Circuits Syst ; 18(2): 396-407, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37938943

RESUMO

Opioid-induced overdose is one of the leading causes of death among the US population under the age of 50. In 2021 alone, the death toll among opioid users rose to a devastating number of over 80,000. The overdose process can be reversed by the administration of naloxone, an opioid antagonist that rapidly counteracts the effects of opioid-induced respiratory depression. The idea of a closed-loop opioid overdose detection and naloxone delivery has emerged as a potential engineered solution to mitigate the deadly effects of the opioid epidemic. In this work, we introduce a wrist-worn wearable device that overcomes the portability issues of our previous work to create a closed-loop drug-delivery system, which includes (1) a Near-Infrared Spectroscopy (NIRS) sensor to detect a hypoxia-driven opioid overdose event, (2) a MOSFET switch, and (3) a Zero-Voltage Switching (ZVS) electromagnetic heater. Using brachial artery occlusion (BAO) with human subjects (n = 8), we demonstrated consistent low oxygenation events. Furthermore, we proved our device's capability to release the drug within 10 s after detecting a hypoxic event. We found that the changes in the oxyhemoglobin, deoxyhemoglobin and oxygenation saturation levels ( SpO2) were different before and after the low-oxygenation events ( 0.001). Although additional human experiments are needed, our results to date point towards a potential tool in the battle to mitigate the effects of the opioid epidemic.


Assuntos
Overdose de Drogas , Overdose de Opiáceos , Humanos , Analgésicos Opioides/uso terapêutico , Overdose de Opiáceos/tratamento farmacológico , Antagonistas de Entorpecentes/uso terapêutico , Naloxona/uso terapêutico , Overdose de Drogas/tratamento farmacológico
17.
CNS Neurosci Ther ; 30(5): e14740, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38715318

RESUMO

AIMS: γ-aminobutyric acid (GABA) from reactive astrocytes is critical for the dysregulation of neuronal activity in various neuroinflammatory conditions. While Scutellaria baicalensis Georgi (S. baicalensis) is known for its efficacy in addressing neurological symptoms, its potential to reduce GABA synthesis in reactive astrocytes and the associated neuronal suppression remains unclear. This study focuses on the inhibitory action of monoamine oxidase B (MAO-B), the key enzyme for astrocytic GABA synthesis. METHODS: Using a lipopolysaccharide (LPS)-induced neuroinflammation mouse model, we conducted immunohistochemistry to assess the effect of S. baicalensis on astrocyte reactivity and its GABA synthesis. High-performance liquid chromatography was performed to reveal the major compounds of S. baicalensis, the effects of which on MAO-B inhibition, astrocyte reactivity, and tonic inhibition in hippocampal neurons were validated by MAO-B activity assay, qRT-PCR, and whole-cell patch-clamp. RESULTS: The ethanolic extract of S. baicalensis ameliorated astrocyte reactivity and reduced excessive astrocytic GABA content in the CA1 hippocampus. Baicalin and baicalein exhibited significant MAO-B inhibition potential. These two compounds downregulate the mRNA levels of genes associated with reactive astrogliosis or astrocytic GABA synthesis. Additionally, LPS-induced aberrant tonic inhibition was reversed by both S. baicalensis extract and its key compounds. CONCLUSIONS: In summary, baicalin and baicalein isolated from S. baicalensis reduce astrocyte reactivity and alleviate aberrant tonic inhibition of hippocampal neurons during neuroinflammation.


Assuntos
Astrócitos , Flavanonas , Flavonoides , Lipopolissacarídeos , Neurônios , Extratos Vegetais , Scutellaria baicalensis , Ácido gama-Aminobutírico , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Flavanonas/farmacologia , Scutellaria baicalensis/química , Camundongos , Ácido gama-Aminobutírico/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Masculino , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Monoaminoxidase/metabolismo , Inibição Neural/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo
18.
ACS Sens ; 9(2): 662-673, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38300847

RESUMO

Self-healing hydrogels are in high demand for wearable sensing applications due to their remarkable deformability, high ionic and electrical conductivity, self-adhesiveness to human skin, as well as resilience to both mechanical and electrical damage. However, these hydrogels face challenges such as delayed healing times and unavoidable electrical hysteresis, which limit their practical effectiveness. Here, we introduce a self-healing hydrogel that exhibits exceptionally rapid healing with a recovery time of less than 0.12 s and an ultralow electrical hysteresis of less than 0.64% under cyclic strains of up to 500%. This hydrogel strikes an ideal balance, without notable trade-offs, between properties such as softness, deformability, ionic and electrical conductivity, self-adhesiveness, response and recovery times, durability, overshoot behavior, and resistance to nonaxial deformations such as twisting, bending, and pressing. Owing to this unique combination of features, the hydrogel is highly suitable for long-term, durable use in wearable sensing applications, including monitoring body movements and electrophysiological activities on the skin.


Assuntos
Hidrogéis , Dispositivos Eletrônicos Vestíveis , Humanos , Eletricidade , Condutividade Elétrica , Movimento
19.
ACS Appl Mater Interfaces ; 16(20): 26613-26623, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38728055

RESUMO

Strain gauges, particularly for wearable sensing applications, require a high degree of stretchability, softness, sensitivity, selectivity, and linearity. They must also steer clear of challenges such as mechanical and electrical hysteresis, overshoot behavior, and slow response/recovery times. However, current strain gauges face challenges in satisfying all of these requirements at once due to the inevitable trade-offs between these properties. Here, we present an innovative method for creating strain gauges from spongy Ag foam through a steam-etching process. This method simplifies the traditional, more complex, and costly manufacturing techniques, presenting an eco-friendly alternative. Uniquely, the strain gauges crafted from this method achieve an unparalleled gauge factor greater than 8 × 103 at strains exceeding 100%, successfully meeting all required attributes without notable trade-offs. Our work includes systematic investigations that reveal the intricate structure-property-performance relationship of the spongy Ag foam with practical demonstrations in areas such as human motion monitoring and human-robot interaction. These breakthroughs pave the way for highly sensitive and selective strain gauges, showing immediate applicability across a wide range of wearable sensing applications.

20.
PNAS Nexus ; 3(5): pgae156, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38715730

RESUMO

The increasing need for precise dietary monitoring across various health scenarios has led to innovations in wearable sensing technologies. However, continuously tracking food and fluid intake during daily activities can be complex. In this study, we present a machine-learning-powered smart neckband that features wireless connectivity and a comfortable, foldable design. Initially considered beneficial for managing conditions such as diabetes and obesity by facilitating dietary control, the device's utility extends beyond these applications. It has proved to be valuable for sports enthusiasts, individuals focused on diet control, and general health monitoring. Its wireless connectivity, ergonomic design, and advanced classification capabilities offer a promising solution for overcoming the limitations of traditional dietary tracking methods, highlighting its potential in personalized healthcare and wellness strategies.

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