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1.
Nat Commun ; 15(1): 2000, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38448437

ABSTRACT

Bioresorbable neural implants based on emerging classes of biodegradable materials offer a promising solution to the challenges of secondary surgeries for removal of implanted devices required for existing neural implants. In this study, we introduce a fully bioresorbable flexible hybrid opto-electronic system for simultaneous electrophysiological recording and optogenetic stimulation. The flexible and soft device, composed of biodegradable materials, has a direct optical and electrical interface with the curved cerebral cortex surface while exhibiting excellent biocompatibility. Optimized to minimize light transmission losses and photoelectric artifact interference, the device was chronically implanted in the brain of transgenic mice and performed to photo-stimulate the somatosensory area while recording local field potentials. Thus, the presented hybrid neural implant system, comprising biodegradable materials, promises to provide monitoring and therapy modalities for versatile applications in biomedicine.


Subject(s)
Absorbable Implants , Central Nervous System Depressants , Animals , Mice , Optogenetics , Artifacts , Brain , Electronics , Mice, Transgenic
2.
Antioxidants (Basel) ; 13(2)2024 Feb 03.
Article in English | MEDLINE | ID: mdl-38397793

ABSTRACT

Photoaging refers to the accumulation of skin damage which includes wrinkle formation, loss of elasticity, and epidermal thickening due to repeated ultraviolet (UV) irradiation. The present study investigated the protective effects of Elaeagnus umbellata fruit extract (Elaea) on UV-mediated photoaged skin of SKH1 hairless mice and compared the effects of Elaea with ascorbic acid. Although there was no difference in body weight between groups during experimental period, oral administration of 50-200 mg/kg Elaea once daily for 15 weeks significantly prevented an increase in skin weight, epithelial thickening of epidermis, and apoptosis caused by UV irradiation. Skin replica and histopathological analyses revealed that Elaea dose-dependently decreased wrinkle and microfold formation. In addition, Elaea administration restored UV-mediated reduction in type I collagen and hyaluronan through the inhibition of matrix metalloproteinases and p38 mitogen-activated protein kinase expression. Moreover, Elaea suppressed UV-dependent increases in superoxide anion production, fatty acid oxidation, and protein nitration by up-regulating antioxidant system. Furthermore, Elaea alleviated infiltration of inflammatory cells in UV-irradiated skin. The preventive effects of 100 mg/kg Elaea administration against UV-induced photoaging were similar to those by 100 mg/kg ascorbic acid. Collectively, the present study suggests that the E. umbellata fruit is a promising edible candidate to prevent skin photoaging.

3.
Vet Sci ; 11(2)2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38393114

ABSTRACT

With the increase in the number of households raising dogs and the reports of human-to-dog transmission of oral bacteria, concerns about dogs' oral health and the need for oral hygiene management are increasing. In this study, the owners' perceptions about their dogs' oral health and the frequency of oral hygiene were determined along with the analysis of dog dental plaque bacteria through metagenomic amplicon sequencing so as to support the need for oral hygiene management for dogs. Although the perception of 63.2% of the owners about their dogs' oral health was consistent with the veterinarian's diagnosis, the owners' oral hygiene practices regarding their dogs were very poor. The calculi index (CI) and gingiva index (GI) were lower in dogs who had their teeth brushed more than once a week (57.89%) than in dogs brushed less than once a month (42.10%); however, the difference was nonsignificant (CI: p = 0.479, GI: p = 0.840). Genomic DNA was extracted from dental plaque bacteria removed during dog teeth scaling, and metagenomic amplicons were sequenced. The 16S amplicons of 73 species were identified from among the plaque bacteria of the dogs. These amplicons were of oral disease-causing bacteria in humans and dogs. The 16S amplicon of Streptococcus mutans matched that of the human S. mutans, with type c identified as the main serotype. This result suggests that human oral bacteria can be transmitted to dogs. Therefore, considering the high frequency of contact between dogs and humans because of communal living and the current poor oral health of dogs, owners must improve the oral hygiene management of their dogs.

4.
Food Sci Biotechnol ; 33(4): 945-954, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38371695

ABSTRACT

This study evaluated zinc, manganese, copper, and magnesium intake levels in Koreans using the Korean Total Diet Study, targeting 92-93% of the Korean diet. Representative foods were collected from 9 cities, resulting in 1344-1368 samples. Results showed adequate intake for most minerals, but high proportions of adults and adolescents didn't meet recommended levels. Infants had high levels of zinc and manganese intake, posing possible health concerns. This is the first comprehensive assessment of these nutrients in Korea and is significant for considering all age groups, including infants, by analyzing nutrient content for table-ready (cooked) samples of foods. It is hoped that the Korean Total Diet Survey will be expanded to assess a wider range of nutrients for better nutrient intake assessment in Korea. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01394-y.

5.
Glia ; 72(4): 748-758, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38200694

ABSTRACT

Implantable neural probes have been extensively utilized in the fields of neurocircuitry, systems neuroscience, and brain-computer interface. However, the long-term functionality of these devices is hampered by the formation of glial scar and astrogliosis at the surface of electrodes. In this study, we administered KDS2010, a recently developed reversible MAO-B inhibitor, to mice through ad libitum drinking in order to prevent glial scar formation and astrogliosis. The administration of KDS2010 allowed long-term recordings of neural signals with implantable devices, which remained stable over a period of 6 months and even restored diminished neural signals after probe implantation. KDS2010 effectively prevented the formation of glial scar, which consists of reactive astrocytes and activated microglia around the implant. Furthermore, it restored neural activity by disinhibiting astrocytic MAO-B dependent tonic GABA inhibition induced by astrogliosis. We suggest that the use of KDS2010 is a promising approach to prevent glial scar formation around the implant, thereby enabling long-term functionality of neural devices.


Subject(s)
Astrocytes , Gliosis , Mice , Animals , Gliosis/drug therapy , Gliosis/prevention & control , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase/pharmacology , Macrophages
6.
Polymers (Basel) ; 16(2)2024 Jan 07.
Article in English | MEDLINE | ID: mdl-38256976

ABSTRACT

Recent environmental concerns have increased demand for renewable polymers and sustainable green resource usage, such as biomass-derived components and carbon dioxide (CO2). Herein, we present crosslinked polyurethanes (CPUs) fabricated from CO2- and biomass-derived monomers via a facile solvent-free ball milling process. Furan-containing bis(cyclic carbonate)s were synthesized through CO2 fixation and further transformed to tetraols, denoted FCTs, by aminolysis and utilized in CPU synthesis. Highly dispersed polyurethane-based hybrid composites (CPU-Ag) were also manufactured using a similar ball milling process. Due to the malleability of the CPU matrix, enabled by transcarbamoylation (dynamic covalent chemistry), CPU-based composites are expected to present very low interfacial thermal resistance between the heat sink and heat source. The characteristics of the dynamic covalent bond (i.e., urethane exchange reaction) were confirmed by the results of dynamic mechanical thermal analysis and stress relaxation analysis. Importantly, the high thermal conductivity of the CPU-based hybrid material was confirmed using laser flash analysis (up to 51.1 W/m·K). Our mechanochemical approach enables the facile preparation of sustainable polymers and hybrid composites for functional application.

7.
Stem Cells Int ; 2023: 3320211, 2023.
Article in English | MEDLINE | ID: mdl-37810631

ABSTRACT

Brain organoids have been considered as an advanced platform for in vitro disease modeling and drug screening, but numerous roadblocks exist, such as lack of large-scale production technology and lengthy protocols with multiple manipulation steps, impeding the industrial translation of brain organoid technology. Here, we describe the high-speed and large-scale production of midbrain organoids using a high-throughput screening-compatible platform within 30 days. Micro midbrain organoids (µMOs) exhibit a highly uniform morphology and gene expression pattern with minimal variability. Notably, µMOs show dramatically accelerated maturation, resulting in the generation of functional µMOs within only 30 days of differentiation. Furthermore, individual µMOs display highly consistent responsiveness to neurotoxin, suggesting their usefulness as an in vitro high-throughput drug toxicity screening platform. Collectively, our data indicate that µMO technology could represent an advanced and robust platform for in vitro disease modeling and drug screening for human neuronal diseases.

8.
Sci Adv ; 9(39): eadi8918, 2023 09 29.
Article in English | MEDLINE | ID: mdl-37756405

ABSTRACT

Numerous wireless optogenetic systems have been reported for practical tether-free optogenetics in freely moving animals. However, most devices rely on battery-powered or coil-powered systems requiring periodic battery replacement or bulky, high-cost charging equipment with delicate antenna design. This leads to spatiotemporal constraints, such as limited experimental duration due to battery life or animals' restricted movement within specific areas to maintain wireless power transmission. In this study, we present a wireless, solar-powered, flexible optoelectronic device for neuromodulation of the complete freely behaving subject. This device provides chronic operation without battery replacement or other external settings including impedance matching technique and radio frequency generators. Our device uses high-efficiency, thin InGaP/GaAs tandem flexible photovoltaics to harvest energy from various light sources, which powers Bluetooth system to facilitate long-term, on-demand use. Observation of sustained locomotion behaviors for a month in mice via secondary motor cortex area stimulation demonstrates the notable capabilities of our device, highlighting its potential for space-free neuromodulating applications.


Subject(s)
Optogenetics , Wireless Technology , Mice , Animals , Optogenetics/methods , Movement , Electric Power Supplies
9.
Proc Natl Acad Sci U S A ; 120(28): e2219231120, 2023 07 11.
Article in English | MEDLINE | ID: mdl-37399389

ABSTRACT

Real-time monitoring of various neurochemicals with high spatial resolution in multiple brain regions in vivo can elucidate neural circuits related to various brain diseases. However, previous systems for monitoring neurochemicals have limitations in observing multiple neurochemicals without crosstalk in real time, and these methods cannot record electrical activity, which is essential for investigating neural circuits. Here, we present a real-time bimodal (RTBM) neural probe that uses monolithically integrated biosensors and multiple shanks to study the connectivity of neural circuits by measuring multiple neurochemicals and electrical neural activity in real time. Using the RTBM probe, we demonstrate concurrent measurements of four neurochemicals-glucose, lactate, choline, and glutamate without cross-talking each other-and electrical activity in real time in vivo. Additionally, we show the functional connectivity between the medial prefrontal cortex and mediodorsal thalamus through the simultaneous measurement of chemical and electrical signals. We expect that our device will contribute to not only elucidating the role of neurochemicals in neural circuits related to brain functions but also developing drugs for various brain diseases related to neurochemicals.


Subject(s)
Brain Diseases , Brain , Humans , Brain/physiology , Electrophysiological Phenomena , Glutamic Acid , Electrophysiology
10.
Front Pharmacol ; 14: 1095955, 2023.
Article in English | MEDLINE | ID: mdl-37153778

ABSTRACT

As our previous study revealed that N-benzyl-N-methyldecan-1-amine (BMDA), a new molecule originated from Allium sativum, exhibits anti-neoplastic activities, we herein explored other functions of the compound and its derivative [decyl-(4-methoxy-benzyl)-methyl-amine; DMMA] including anti-inflammatory and anti-oxidative activities. Pretreatment of THP-1 cells with BMDA or DMMA inhibited tumor necrosis factor (TNF)-α and interleukin (IL)-1ß production, and blocked c-jun terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), MAPKAP kinase (MK)2 and NF-κΒ inflammatory signaling during LPS stimulation. Rectal treatment with BMDA or DMMA reduced the severity of colitis in 2,4-dinitrobenzenesulfonic acid (DNBS)-treated rat. Consistently, administration of the compounds decreased myeloperoxidase (MPO) activity (representing neutrophil infiltration in colonic mucosa), production of inflammatory mediators such as cytokine-induced neutrophil chemoattractant (CINC)-3 and TNF-α, and activation of JNK and p38 MAPK in the colon tissues. In addition, oral administration of these compounds ameliorated collagen-induced rheumatoid arthritis (RA) in mice. The treatment diminished the levels of inflammatory cytokine transcripts, and protected connective tissues through the expression of anti-oxidation proteins such as nuclear factor erythroid-related factor (Nrf)2 and heme oxygenase (HO)1. Additionally, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels did not differ between the BMDA- or DMMA-treated and control animals, indicating that the compounds do not possess liver toxicity. Taken together, these findings propose that BMDA and DMMA could be used as new drugs for curing inflammatory bowel disease (IBD) and RA.

11.
Adv Sci (Weinh) ; 10(20): e2301787, 2023 07.
Article in English | MEDLINE | ID: mdl-37170679

ABSTRACT

Axis formation and related spatial patterning are initiated by symmetry breaking during development. A geometrically confined culture of human pluripotent stem cells (hPSCs) mimics symmetry breaking and cell patterning. Using this, polarized spinal cord organoids (pSCOs) with a self-organized dorsoventral (DV) organization are generated. The application of caudalization signals promoted regionalized cell differentiation along the radial axis and protrusion morphogenesis in confined hPSC colonies. These detached colonies grew into extended spinal cord-like organoids, which established self-ordered DV patterning along the long axis through the spontaneous expression of polarized DV patterning morphogens. The proportions of dorsal/ventral domains in the pSCOs can be controlled by the changes in the initial size of micropatterns, which altered the ratio of center-edge cells in 2D. In mature pSCOs, highly synchronized neural activity is separately detected in the dorsal and ventral side, indicating functional as well as structural patterning established in the organoids. This study provides a simple and precisely controllable method to generate spatially ordered organoids for the understanding of the biological principles of cell patterning and axis formation during neural development.


Subject(s)
Body Patterning , Pluripotent Stem Cells , Humans , Spinal Cord , Morphogenesis , Organoids
12.
Healthcare (Basel) ; 11(7)2023 Mar 30.
Article in English | MEDLINE | ID: mdl-37046917

ABSTRACT

BACKGROUND: There are various therapeutic options for the conservative management of lower back pain (LBP). A combination of two or more treatment options may be more effective in the clinical management of non-specific LBP. In this study, we compared the effects of simultaneous heat massage with conventional physical therapy in patients with subacute LBP. METHODS: A single-center randomized controlled trial in which 40 participants with LBP were allocated to one of two groups: a heat massage group (HMG) and physical therapy group (PTG). The HMG received simultaneous heat massage therapy using a mechanical device (CGM MB-1401, Ceragem, Republic of Korea). The PTG received conventional physical therapy. Both groups received 40 min of therapy once daily, five times a week, for a total of four weeks. Changes in serum cortisol, epinephrine (EP), and norepinephrine (NE) were assessed. The outcomes were measured using the pain numeric rating scale (PNRS), the Oswestry disability index (ODI), the Roland-Morris disability questionnaire (RMDQ), the short-form McGill pain questionnaire (SF-MPQ), the multidimensional fatigue inventory (MFI-20), the Beck depression inventory (BDI), surface EMG (sEMG), and sympathetic skin response (SSR) at baseline (PRE), at 2 (2 W) and 4 weeks (4 W) following the intervention. RESULTS: The serum EP and NE levels in the HMG decreased after treatment. The PNRS, ODI, RMDQ, and SF-MPQ scores improved without significance in both groups. The BDI score showed improvement in the HMG before the PTG. The MFI-20 score improved in both groups, but the results were better in the HMG than in the PTG at 4 W. All the activities of sEMG were significantly decreased in both groups. However, the improvement of the %MVIC in the HMG was better than that in the PTG at 4 W. The SSR latency on sEMG decreased while the amplitude increased in the HMG at 2 W and 4 W, respectively. CONCLUSIONS: Following 4 weeks of combined therapies, heat massage was not superior to conventional physical therapy alone. Both treatments were shown to be effective in improving LBP and pain-related disability. However, heat massage was shown to have a better effect on the control of autonomic nerve function and underlying moods.

13.
Antioxidants (Basel) ; 12(4)2023 Apr 13.
Article in English | MEDLINE | ID: mdl-37107297

ABSTRACT

Adenophora stricta Miq. (Campanulaceae family) is a traditional herb used for relieving cough and phlegm in East Asia. This study explored the effects of A. stricta root extract (AsE) in ovalbumin (OVA)-induced allergic asthma and lipopolysaccharide (LPS)-stimulated macrophages. Administration of 100-400 mg/kg AsE dose-dependently decreased pulmonary congestion and suppressed the reduction of alveolar surface area in mice with OVA-mediated allergic asthma. Histopathological analysis of lung tissue and cytological analysis of bronchioalveolar lavage fluid showed that AsE administration significantly attenuated inflammatory cell infiltration into the lungs. In addition, AsE also alleviated OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5 production, which are essential for OVA-dependent activation of T helper 2 lymphocytes. In Raw264.7 macrophage cells, AsE significantly blocked nitric oxide, tumor necrosis factor-α, IL-1ß, IL-6, and monocyte chemoattractant factor-1 production in response to LPS. Results from an immunoblot assay revealed that AsE inhibited the phosphorylation of c-jun N-terminal kinase, inhibitory-κB kinase α/ß, and p65 in LPS-stimulated cells. Furthermore, 2-furoic acid, 5-hydroxymethylfurfural, and vanillic acid 4-ß-D-glucopyranoside in AsE were shown to inhibit the production of proinflammatory mediators by LPS. Taken together, the present results suggest that A. stricta root will be a useful herb for relieving allergic asthma through managing airway inflammation.

14.
Sci Adv ; 9(10): eadf0925, 2023 03 10.
Article in English | MEDLINE | ID: mdl-36897938

ABSTRACT

Anisotropically organized neural networks are indispensable routes for functional connectivity in the brain, which remains largely unknown. While prevailing animal models require additional preparation and stimulation-applying devices and have exhibited limited capabilities regarding localized stimulation, no in vitro platform exists that permits spatiotemporal control of chemo-stimulation in anisotropic three-dimensional (3D) neural networks. We present the integration of microchannels seamlessly into a fibril-aligned 3D scaffold by adapting a single fabrication principle. We investigated the underlying physics of elastic microchannels' ridges and interfacial sol-gel transition of collagen under compression to determine a critical window of geometry and strain. We demonstrated the spatiotemporally resolved neuromodulation in an aligned 3D neural network by local deliveries of KCl and Ca2+ signal inhibitors, such as tetrodotoxin, nifedipine, and mibefradil, and also visualized Ca2+ signal propagation with a speed of ~3.7 µm/s. We anticipate that our technology will pave the way to elucidate functional connectivity and neurological diseases associated with transsynaptic propagation.


Subject(s)
Brain , Collagen , Animals , Brain/physiology
15.
Medicina (Kaunas) ; 59(2)2023 Feb 20.
Article in English | MEDLINE | ID: mdl-36837620

ABSTRACT

Background and Objectives: The anterolateral ligament (ALL) could be the potential anatomical structure responsible for rotational instability after anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to investigate the anatomical and biomechanical characteristics of the ALL in Korean cadaveric knee joints. Materials and Methods: Twenty fresh-frozen cadaveric knees were dissected and tested. Femoral and tibial footprints of the ALL were recorded. Pivot shift and Lachman tests were measured with KiRA. Results: The prevalence of ALL was 100%. The average distance of the tibial footprint to the tip of the fibular head was 19.85 ± 3.41 mm; from the tibial footprint to Gerdy's tubercle (GT) was 18.3 ± 4.19 mm; from the femoral footprint to the lateral femoral epicondyle was 10.25 ± 2.97 mm. ALL's footprint distance was the longest at 30° of flexion (47.83 ± 8.05 mm, p < 0.01) in a knee with intact ALL-ACL and neutral rotation. During internal rotation, the footprint distance was the longest at 30° of flexion (50.05 ± 8.88 mm, p < 0.01). Internal rotation produced a significant increase at all three angles after ACL-ALL were transected (p = 0.022), where the footprint distance was the longest at 30° of flexion (52.05 ± 7.60 mm). No significant difference was observed in KiRA measurements between intact ALL-ACL and ALL-transected knees for pivot shift and Lachman tests. However, ACL-ALL-transected knees showed significant differences compared to the intact ALL-ACL and ALL-transected knees (p < 0.01). Conclusions: The ALL was identified as a distinct ligament structure with a 100% prevalence in this cadaveric study. The ALL plays a protective role in internal rotational stability. An isolated ALL transection did not significantly affect the ALL footprint distances or functional stability tests. Therefore, the ALL is thought to act as a secondary supportive stabilizer for rotational stability of the knee joint in conjunction with the ACL.


Subject(s)
Anterior Cruciate Ligament Injuries , Joint Instability , Humans , Anterior Cruciate Ligament Injuries/surgery , Biomechanical Phenomena , Joint Instability/surgery , Cadaver , Knee Joint , Ligaments , Range of Motion, Articular , Accelerometry , Republic of Korea
16.
Article in English | WPRIM (Western Pacific) | ID: wpr-1002127

ABSTRACT

Objectives@# Based on the results from the Korean Total Diet Study (KTDS), the sodium (Na) and potassium (K) intake of Koreans were estimated and compared with intake estimates from the Food & Nutrient Database (FNDB), as in the Korea National Health and Nutrition Examination Survey (KNHANES) to verify the validity of these estimates. @*Methods@# One hundred and thirty-four representative foods (RFs) covering 92.5% of the total food intake of Koreans were selected, and 228 pairs of corresponding ‘RF x representative cooking method’ were derived by reflecting the methods used mainly in terms of frequency and quantity in their cooking.RF samples were collected from three cities with a larger population size in three regions (nine cities) nationwide, and six composite samples were made for each RF, considering its regional and/or seasonal characteristics. One thousand three hundred and sixty-eight ‘RF x representative cooking method’ pair samples were prepared, and the Na and K contents were assessed using inductively coupled plasma atomic emission spectrometry (ICP-MS). The Na and K intake of the Korean population was estimated by linking the content with the food intake data from the 7th KNHANES. @*Results@# The mean Na and K intake of Koreans were 2,807.4 mg and 2,335.0 mg per person per day, respectively. A comparison with the Na and K intake from KNHANES, including only RFs of KTDS, showed comparable results with less than 5% variation. While the contribution and ranking of food items to Na intake were similar between KNHANES and KTDS, there were differences in K intake.This was attributed to the large discrepancies in the K content of rice and coffee between KTDS results and the values in the 9th Revision of the National Food Composition Table used in KNHANES. @*Conclusions@# The Na and K intake of Koreans estimated based on the KTDS, which performed nutrient analysis on samples prepared to a ‘table-ready’ state using foods of the representative collection, was similar and comparable with that of KNHANES. This supports the validity and usefulness of FNDB-based nutrient intake estimation at the population level. The list of nutrients studied in KTDS is expected to be expanded, allowing for intake estimation of nutrients with currently insufficient or absent information in the FNDBs in use.

17.
Free Radic Biol Med ; 193(Pt 2): 620-637, 2022 11 20.
Article in English | MEDLINE | ID: mdl-36370962

ABSTRACT

Ferroptosis is a widely known regulator of cell death in connection with the redox state as a consequence of the depletion of glutathione or accumulation of lipid peroxidation. Hepatic stellate cells (HSCs) play a pivotal role in the progression of hepatic fibrosis by increasing the production and secretion of the extracellular matrix. However, the role of ferroptosis in HSC activation and liver fibrogenesis has not been clearly elucidated. The ferroptosis inducer RAS-selective lethal 3 (RSL3) or erastin treatment in HSCs caused cell death. This effect was suppressed only after exposure to ferroptosis inhibitors. We observed induction of ferroptosis by RSL3 treatment in HSCs supported by decreased glutathione peroxidase 4, glutathione deficiency, reactive oxygen species generation, or lipid peroxidation. Interestingly, RSL3 treatment upregulated the expression of plasminogen activator inhibitor-1, a representative fibrogenic marker of HSCs. In addition, treatment with ferroptosis-inducing compounds increased c-JUN phosphorylation and activator protein 1 luciferase activity but did not alter Smad phosphorylation and Smad-binding element luciferase activity. Chronic administration of iron dextran to mice causes ferroptosis of liver in vivo. The expression of fibrosis markers, such as alpha-smooth muscle actin and plasminogen activator inhibitor-1, was increased in the livers of mice with iron accumulation. Hepatic injury accompanying liver fibrosis was observed based on the levels of alanine aminotransferase, aspartate aminotransferase, and hematoxylin and eosin staining. Furthermore, we found that both isolated primary hepatocyte and HSCs undergo ferroptosis. Consistently, cirrhotic liver tissue of patients indicated glutathione peroxidase 4 downregulation in fibrotic region. In conclusion, our results suggest that ferroptosis contribute to HSC activation and the progression of hepatic fibrosis.


Subject(s)
Ferroptosis , Hepatic Stellate Cells , Mice , Animals , Ferroptosis/genetics , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Liver/metabolism , Liver Cirrhosis/metabolism , Glutathione/metabolism , Iron/metabolism , Luciferases/metabolism
18.
Article in English | MEDLINE | ID: mdl-36317105

ABSTRACT

Objectives: A powerful analgesic called Morphine causes addiction behaviors and immune suppression as a potential oxidative stressor. Acupuncture showed to inhibit oxidative stress-induced hepatic damage, regulate reactive oxygen species, and attenuate morphine addiction behaviors. Therefore, we investigated the potential effects of acupuncture on morphine-induced immune suppression. Materials and Methods: Rats received morphine intravenously through implanted catheters for 3, 7, or 21 days to determine the optimal condition for morphine-induced immune suppression. Second, we examined whether intravenous (iv.) or intraperitoneal (ip.) administration produced different results. Third, the effects of acupuncture in rats who received morphine for 21 days were investigated. Spleen and submandibular lymph node (S-LN) weights and natural killer (NK) cell activity were measured, and the white pulp diameter, total and cortical spleen thicknesses, and the number of lymphoid follicles in S-LNs were examined. The number of immunoreactive cells was also measured. Results: Decreased organ weights and increased atrophic changes were observed as morphine-induced immune suppression. However, dose-dependent increased immune suppression was not observed between 5.0 mg/kg and 10.0 mg/kg of morphine. And, 3-day withdrawal did not affect. Similar histopathological findings were observed in 5.0 and 10.0 ip. rats when compared to equal dosages of iv., respectively. The morphine induced-immune suppression evidenced by spleen and left S-LN weights, splenic NK cell activities, histopathological findings, and the immunoreactive cell number were normalized by acupuncture. Conclusion: These results indicate that acupuncture inhibits morphine-induced immune suppression, maybe via antioxidative action.

19.
IEEE Trans Biomed Circuits Syst ; 16(6): 1044-1056, 2022 12.
Article in English | MEDLINE | ID: mdl-36191109

ABSTRACT

This article presents a CMOS microelectrode array (MEA) system with a reconfigurable sub-array multiplexing architecture using the time-division multiplexing (TDM) technique. The system consists of 24,320 TiN electrodes with 17.7 µm-pitch pixels and 380 column-parallel readout channels including a low-noise amplifier, a programmable gain amplifier, and a 10-b successive approximation register analog to digital converter. Readout channels are placed outside the pixel for high spatial resolution, and a flexible structure to acquire neural signals from electrodes selected by configuring in-pixel memory is realized. In this structure, a single channel can handle 8 to 32 electrodes, guaranteeing a temporal resolution from 5 kS/s to 20 kS/s for each electrode. A 128 × 190 MEA system was fabricated in a 110-nm CMOS process, and each readout channel consumes 81 µW at 1.5-V supply voltage featuring input-referred noise of 1.48 µVrms without multiplexing and 5.4 µVrms with multiplexing at the action-potential band (300 Hz-10 kHz).


Subject(s)
Amplifiers, Electronic , Microelectrodes , Action Potentials
20.
Nat Commun ; 13(1): 5521, 2022 09 21.
Article in English | MEDLINE | ID: mdl-36130965

ABSTRACT

Assessing the neurological and behavioral effects of drugs is important in developing pharmacological treatments, as well as understanding the mechanisms associated with neurological disorders. Herein, we present a miniaturized, wireless neural probe system with the capability of delivering drugs for the real-time investigation of the effects of the drugs on both behavioral and neural activities in socially interacting mice. We demonstrate wireless drug delivery and simultaneous monitoring of the resulting neural, behavioral changes, as well as the dose-dependent and repeatable responses to drugs. Furthermore, in pairs of mice, we use a food competition assay in which social interaction was modulated by the delivery of the drug, and the resulting changes in their neural activities are analyzed. During modulated food competition by drug injection, we observe changes in neural activity in mPFC region of a participating mouse over time. Our system may provide new opportunities for the development of studying the effects of drugs on behaviour and neural activity.


Subject(s)
Central Nervous System Depressants , Neuropharmacology , Animals , Brain/physiology , Cardiac Electrophysiology , Central Nervous System Depressants/pharmacology , Mice , Neurons/physiology
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