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1.
Article in English | MEDLINE | ID: mdl-38957959

ABSTRACT

Objective: The purpose of this study was to report a case of herpes simplex virus-1 (HSV-1) keratitis misdiagnosed as fungal keratitis due to its clinical presentation being similar to that of fungal keratitis, ultimately diagnosed by NGS. Patients and Methods: A 59-year-old male presented with reduced vision in the right eye, combined with a history of trauma with vegetative matter. The corneal ulcer was accompanied with feathery infiltration, satellite lesion, and endothelial plaques. In vivo confocal microscopy (IVCM) showed hyper-reflective linear, thin, and branching interlocking structures. Fungal keratitis was diagnosed. Voriconazole 100 mg orally daily, topical tobramycin and 1% voriconazole were initiated empirically right away. The condition was aggravated and penetrating keratoplasty was performed. Anterior segment optical coherence tomography (AS-OCT) demonstrated the presence of plaques with a clear boundary between plaques and endothelium, resembling the AS-OCT images observed in cases of viral keratitis. Next-generation sequencing (NGS) further detected HSV-1 deoxyribonucleic acid, and no fungal component was found. Antifungal agents were discontinued and antiviral treatments were added. Results: We successfully treated a patient with HSV-1 keratitis who was misdiagnosed due to clinical features and IVCM findings similar to fungal keratitis. The patient's infection was controlled. At 2 years after surgery, the cornea recovered well. Conclusions: HSV-1 keratitis with atypical clinical presentation can be easily misdiagnosed. This case report emphasizes the importance of NGS in diagnosing the pathogens of keratitis.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124465, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-38788501

ABSTRACT

Fluorescent probe L-I was synthesized to demonstrate that 1,3,4-thiadiazole is an attractive moiety and could be utilized as positive hydrogen bond acceptor for excited state intramolecular proton transfer (ESIPT) processes, guider of electrons movement for intramolecular charge transfer (ICT) process and identify group for mental ions. Furthermore, dicyanoisophorone framework was employed to improve the fluorescence characteristics and near-infrared (NIR) fluorescent emission at 695 nm accompanied by a Stoke's shift as large as 260 nm was obtained. L-I could selectively detect Cu2+ over other analytes taking advantages of high sensitivity, fast response within 30 s and low detection limit (0.026 µM). More important, L-I exhibited good performance for detection of Cu2+ in actual water samples, food products, traditional Chinese medicine and for cell imaging which demonstrates practical significance in the fields of environmental monitor, food safety and biotechnology.


Subject(s)
Copper , Fluorescent Dyes , Spectrometry, Fluorescence , Thiadiazoles , Thiadiazoles/chemistry , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Copper/analysis , Copper/chemistry , Limit of Detection , Protons , Humans , Spectroscopy, Near-Infrared/methods
3.
Biomolecules ; 14(5)2024 May 16.
Article in English | MEDLINE | ID: mdl-38785996

ABSTRACT

Excitotoxicity is a common pathological process in neurological diseases caused by excess glutamate. The purpose of this study was to evaluate the effect of gypenoside XVII (GP-17), a gypenoside monomer, on the glutamatergic system. In vitro, in rat cortical nerve terminals (synaptosomes), GP-17 dose-dependently decreased glutamate release with an IC50 value of 16 µM. The removal of extracellular Ca2+ or blockade of N-and P/Q-type Ca2+ channels and protein kinase A (PKA) abolished the inhibitory effect of GP-17 on glutamate release from cortical synaptosomes. GP-17 also significantly reduced the phosphorylation of PKA, SNAP-25, and synapsin I in cortical synaptosomes. In an in vivo rat model of glutamate excitotoxicity induced by kainic acid (KA), GP-17 pretreatment significantly prevented seizures and rescued neuronal cell injury and glutamate elevation in the cortex. GP-17 pretreatment decreased the expression levels of sodium-coupled neutral amino acid transporter 1, glutamate synthesis enzyme glutaminase and vesicular glutamate transporter 1 but increased the expression level of glutamate metabolism enzyme glutamate dehydrogenase in the cortex of KA-treated rats. In addition, the KA-induced alterations in the N-methyl-D-aspartate receptor subunits GluN2A and GluN2B in the cortex were prevented by GP-17 pretreatment. GP-17 also prevented the KA-induced decrease in cerebral blood flow and arginase II expression. These results suggest that (i) GP-17, through the suppression of N- and P/Q-type Ca2+ channels and consequent PKA-mediated SNAP-25 and synapsin I phosphorylation, reduces glutamate exocytosis from cortical synaptosomes; and (ii) GP-17 has a neuroprotective effect on KA-induced glutamate excitotoxicity in rats through regulating synaptic glutamate release and cerebral blood flow.


Subject(s)
Cyclic AMP-Dependent Protein Kinases , Glutamic Acid , Gynostemma , Animals , Glutamic Acid/metabolism , Rats , Male , Gynostemma/chemistry , Cyclic AMP-Dependent Protein Kinases/metabolism , Rats, Sprague-Dawley , Synaptosomes/metabolism , Synaptosomes/drug effects , Neuroprotective Agents/pharmacology , Kainic Acid/toxicity , Seizures/chemically induced , Seizures/metabolism , Seizures/drug therapy , Seizures/prevention & control , Synapses/drug effects , Synapses/metabolism , Synaptosomal-Associated Protein 25/metabolism , Synapsins/metabolism , Phosphorylation/drug effects , Calcium/metabolism , Plant Extracts
5.
J Colloid Interface Sci ; 668: 59-67, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38669996

ABSTRACT

Photocatalysis is a green and environmentally friendly method for degrading dangerous and nonbiodegradable pollutants. In this study, a sequence of metal-free triazine-based electronic donor-acceptor (D-A) conjugated polymers Tr-X (X = Th, BT, BTh) were prepared by D-A configuration regulation between triazine (Tr) and monomers containing N and S, such as thiophene (Th), bithiophene (BTh) and benzothiadiazole (BT) units, for the photocatalytic degradation of bisphenol A (BPA) and benzene contaminants in water under visible light. Among these, Tr-BTh exhibited complete photocatalytic degradation owing to its excellent D-A configuration. Moreover, the N and S atoms, which are rich in triazine and thiophene units, serve as highly dispersed reactive sites. The separation and transfer of photogenerated carriers can be further improved by expanding the light-absorption range of polymers. In addition, the polymers showed good adsorption for BPA and other aromatic organic pollutants through π-π interaction and surface hydrogen bonding, which provides a facile strategy for efficient polymer-based photocatalysts for water purification.

7.
Nitric Oxide ; 147: 1-5, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38547960

ABSTRACT

Endotoxin tolerance (ET) is the hyporesponsiveness to lipopolysaccharide (LPS) after prior exposure. It is characterized by the downregulation of pro-inflammatory cytokine levels. Although ET protects against inflammation, its abolishment or recovery is critical for immunity. Nitric oxide (NO) plays various roles in the development of ET; however, its specific role in ET recovery remains unknown. To induce ET, RAW264.7 cells (a murine macrophage cell line) were pre-exposed to LPS (LPS1, 100 ng/mL for 24 h) and subsequently re-stimulated with LPS (LPS2, 100 ng/mL for 24 h). Expression of cytokines, NO, nitrite and inducible NO synthase (iNOS) were measured after 0, 12, 24, and 36 h of resting after LPS1 treatment with or without the iNOS-specific inhibitor, 1400W. LPS2-induced tumor necrosis factor-⍺ (TNF-⍺) and interleukin-6 (IL-6) were downregulated after LPS1 treatment, confirming the development of ET. Notably, TNF-⍺ and IL-6 levels spontaneously rebounded after 12-24 h of resting following LPS1 treatment. In contrast, levles of NO, nitrite and iNOS increased during ET development and decreased during ET recovery. Moreover, 1400W inhibited ET development and blocked the early production of NO (<12 h) during ET recovery. Our findings suggest a negative correlation between iNOS-induced NO and cytokine levels in the abolishment of ET.


Subject(s)
Lipopolysaccharides , Nitric Oxide Synthase Type II , Nitric Oxide , Tumor Necrosis Factor-alpha , Animals , Nitric Oxide/metabolism , Mice , Lipopolysaccharides/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Nitric Oxide Synthase Type II/metabolism , RAW 264.7 Cells , Interleukin-6/metabolism , Endotoxins/pharmacology , Macrophages/drug effects , Macrophages/metabolism
8.
Anal Chim Acta ; 1297: 342379, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38438245

ABSTRACT

Here, 1,3,4-thiadiazole unit was employed as novel excited state intramolecular proton transfer (ESIPT) structure to prepare favorable fluorescent probe. High selectivity and rapid response to Cu2+ was obtained and the settling reaction was also used to recover ESIPT characteristics of probe to achieve sequential detection of H2S. Remarkable color change of solution from colorless to bright yellow and fluorescence emission from green to dark realized the visual detection of Cu2+ by naked eyes and transition of probe into portable fluorescent test strips. As expected, L-E could be utilized to quantitatively sense Cu2+ and H2S in different actual water and food samples including herbs, wine and fruits. The limits of detection for Cu2+ and H2S were as low as 34.5 nM and 38.6 nM. Also, probe L-E achieved real-time, portable, on-site quantitative detection of Cu2+ via a colorimeter and a smartphone platform with limit of detection to 90.3 nM.


Subject(s)
Fluorescent Dyes , Thiadiazoles , Wine , Fruit , Protons
9.
Lancet Reg Health West Pac ; 45: 101032, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38440130

ABSTRACT

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123753, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38091647

ABSTRACT

Two highly sensitive fluorescent triarylimidazole derivatives were synthesized by modifying imidazole with coumarin and large conjugate rigid plane structure. XM-F and XM-L emitted bright yellow-green fluorescent light. Their intense conjugation system generated strong π-π electrostatic interactions with TNP, accompanied by the formation of hydrogen bonds to achieve rapid detection of TNP within 25 s. The detection limits were as low as 0.049 µM and 0.071 µM, respectively. Probes had been successfully applied to rapid detection of TNP in real water samples and manufactured into portable fluorescent test strips. In view of excellent performance of XM-F, it was used to achieve real-time, portable, on-site quantitative detection of TNP by a colorimeter and a smartphone platform. In addition, XM-F also successfully processed into probe-coated TLC plates for efficient detection of fingerprints contaminated with TNP.

11.
ACS Appl Mater Interfaces ; 16(1): 898-906, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38154079

ABSTRACT

Titanium dioxide (TiO2) has been widely used as an alternative anodic material for lithium-ion batteries (LIBs) due to its ultrahigh capacity retention and long cycle lifespan. However, the restriction of lithium insertion, intrinsically poor electronic conductivity, and sluggish lithium ionic kinetics of bulk TiO2 hinder their specific capacity and rate performance. Herein, LiTiO2 nanoparticles (NPs) are synthesized via a facile ball milling method by the reaction of anatase TiO2 with LiH. The as-prepared LiTiO2 NPs have strong structural stability and a "zero strain" effect during the repeated intercalation/deintercalation, even at low potential. As anodic materials for LIBs, LiTiO2 NPs exhibit a superior rate performance of ∼100 mA h g-1 at 10C (3350 mA g-1) with a capacity retention of 100% after 1000 cycles, which is 5 times higher than that of the original commercial anatase TiO2 powder. The higher specific capacity of LiTiO2 NPs is attributed to the increased conversion of Ti3+ to Ti2+ on the porous surface of LiTiO2 NPs, which provides a more capacitive contribution. This study not only provides a new fabrication approach toward Ti-based anodes for ultrafast LIBs but also underscores the potential importance of embedding lithium into transition metal oxides as a strategy for boosting their electrochemical performance.

12.
Sci Rep ; 13(1): 21315, 2023 12 03.
Article in English | MEDLINE | ID: mdl-38044364

ABSTRACT

This study aimed to investigate the value of tissue doppler imaging (TDI) and 4D myocardial strain parameters in evaluating left heart function of pregnant women with hypertension and the association between these parameters and relevant factors. Forty-five pregnant women with hypertensive disorder, including 20 with hypertension, 15 with mild preeclampsia, and 10 with severe preeclampsia, were recruited, and their cardiac functions were compared with those of 30 healthy pregnant women as controls. High Left ventricular end-systolic volume (LVESV), Left atrial volume index (LAVI), E/e were observed in hypertensive disorder, while Mitral peak diastolic velocity(E), Early diastolic peak velocity(e), E/A, Left ventricularglobal longitudinal strain (LVGLS), Left ventricularglobal area strain (LVGAS), and Left atrialglobal longitudinal strain (LAGLS) were decreased; for pre-eclampsia, Left ventricular end-systolic diameter (LVESD), Left atrial anteroposterior diameter (LAD-ap), LVESV, LAVI were significantly increased, LVGLS, LAGLS were significantly decreased, Left ventricular end-diastolic diameter (LVEDD), Left ventricular end-diastolic volume (LVEDV), A peak, E/e were increased, while E peak, E/A, e, Left ventricle global radial strain (LVGRS), Left ventricle global circumferential strain (LVGCS), LVGAS were decreased but not significantly; for severe preeclampsia, Left ventricular end diastolic diameter (LVEDD), LVESD, LAD-ap, Left ventricular end-diastolic volume (LVEDV), LVESV, LAVI, A, and E/e were significantly increased, while LVGLS, LVGRS, LVGCS, LVGAS, LAGLS, E peak, E/A, and e were significantly reduced. TDI combined with 4D myocardial strain parameters can detect early changes in cardiac function of hypertensive disorders in pregnancy, with LVGLS, LVGAS, and LAGLS being the most sensitive indicators for early changes. Such findings provide a basis for effective clinical treatment of these symptoms.


Subject(s)
Hypertension, Pregnancy-Induced , Pre-Eclampsia , Pregnancy , Humans , Female , Hypertension, Pregnancy-Induced/diagnostic imaging , Pre-Eclampsia/diagnostic imaging , Diastole , Heart Ventricles , Heart Atria , Ventricular Function, Left
13.
Light Sci Appl ; 12(1): 186, 2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37495595

ABSTRACT

The purpose of this study is to explore the associations among dry eye disease (DED), air pollution, and meteorological conditions in the cold region of a northeastern Chinese metropolis (i.e., Changchun). Data on ambient air pollutants and meteorological parameters as well as diagnosed DED outpatients during 2015-2021 were collected. The associations between DED and environmental factors were analysed at multiple time scales using various statistical methods (i.e., correlation, regression and machine learning). Among the 10,809 DED patients (21,617 eyes) studied, 64.60% were female and 35.40% were male. A higher frequency of DED was observed in March and April, followed by January, August and October. Individual and multiple factor models showed the positive importance of particles with aerodynamic diameters <10 µm (PM10), carbon monoxide (CO), and ozone (O3) among normal air pollutants and air pressure (AP), air temperature (AT) and wind speed (WS) among normal meteorological parameters. Air pollutants (PM10, nitrogen dioxide: NO2) and meteorological parameters (AT, AP) have combined impacts on DED occurrence. For the first time, we further explored the associations of detailed components of atmospheric particles and DED, suggesting potential emission sources, including spring dust from bare soil and roads and precursor pollutants of summer O3 formation from vehicles and industry in Northeast China. Our results revealed the quantitative associations among air pollutants, meteorological conditions and DED outpatients in cold regions, highlighting the importance of coordinated policies in air pollution control and climate change mitigation.

14.
ACS Appl Mater Interfaces ; 15(26): 31543-31551, 2023 Jul 05.
Article in English | MEDLINE | ID: mdl-37341032

ABSTRACT

Lithium (Li) metal is considered as a promising anode candidate for high-energy-density batteries. However, the high reactivity of Li metal leads to poor air stability, limiting its practical application. Additionally, the interfacial instability, such as dendrite growth and an unstable solid electrolyte interphase layer, further complicates its utilization. Herein, a dense lithium fluoride (LiF)-rich interfacial protective layer is constructed on the Li surface through a simple reaction between Li and fluoroethylene carbonate (denoted as LiF@Li). The LiF-rich interfacial protective layer consists of both organic (ROCO2Li and C-F-containing species, which only exist on the outer layer) and inorganic (LiF and Li2CO3, distribute throughout the layer) components with a thickness of ∼120 nm. Specifically, chemically stable LiF and Li2CO3 play an important role in blocking air and hence improve the air durability of LiF@Li anodes. Notably, LiF with high Li+ diffusivity facilitates uniform Li+ deposition, while organic components with high flexibility relieve volume change upon cycling, thereby enhancing the dendrite inhibition capacity of LiF@Li. Consequently, LiF@Li exhibits remarkable stability and excellent electrochemical performance in both symmetric cells and LiFePO4 full cells. Moreover, LiF@Li maintains its initial color and morphology even after air exposure for 30 min, and the air-exposed LiF@Li anode still retains its superior electrochemical performance, further establishing its outstanding air-defendable capability. This work proposes a facile approach in constructing air-stable and dendrite-free Li metal anodes toward reliable Li metal batteries.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 300: 122904, 2023 Nov 05.
Article in English | MEDLINE | ID: mdl-37229941

ABSTRACT

In this work, three Schiff-based fluorescent probes with aggregation-induced emission (AIE) and excited intramolecular proton transfer (ESIPT) characters were synthesized by grafting 2-aminobenzothiazole group onto 4-substituted salicylaldehydes. More important, a rare tri-responsive fluorescent probe (SN-Cl) was developed by purposeful variation of substituents in the molecule. It could selectively identify Pb2+, Ag+ and Fe3+ in different solvent systems or with the help of masking agent and show complete fluorescence enhancement without interference of other ions. Meanwhile, the other two probes (SN-ON and SN-N) could only recognize Pb2+ in DMSO/Tris-HCl buffer (3: 7, v/v, pH = 7.4). According to Job's plot, density functional theory (DFT) calculations and NMR analysis, coordination between SN-Cl and Pb2+/Ag+/Fe3+ was determined. The LOD values for three ions were as low as 0.059 µM, 0.012 µM and 8.92 µM, respectively. Ideally, SN-Cl showed satisfactory performance in real water samples detection and test paper experiments for three ions. Also, SN-Cl could be used as an excellent imaging agent for Fe3+ in HeLa cells. Therefore, SN-Cl has the ability to be a "single fluorescent probe for three targets".


Subject(s)
Fluorescent Dyes , Protons , Humans , Fluorescent Dyes/chemistry , Lead , Schiff Bases/chemistry , HeLa Cells , Spectrometry, Fluorescence/methods , Ions
16.
Neurochem Int ; 167: 105537, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37164158

ABSTRACT

The purpose of this study was to evaluate the effect of cynarin, a caffeoylquinic acid derivative in artichoke, on glutamate release elicited by 4-aminopyridine (4-AP) in rat cortical nerve terminals (synaptosomes). We observed that cynarin decreased 4-aminopyridine-elicited glutamate release, which was prevented by the removal of external free Ca2+ with ethylene glycol bis (ß-aminoethyl ether)-N,N,N,N-tetraacetic acid (EGTA) or the blockade of P/Q-type calcium channels with ω-agatoxin IVA. Molecular docking also revealed that cynarin formed a hydrogen bond with the P/Q-type Ca2+ channel, indicating a mechanism of action involving Ca2+ influx inhibition. Additionally, the inhibitory effect of cynarin on glutamate release is associated with a change in the available synaptic vesicles, as cynarin decreased 4-AP-elicited FM1-43 release or hypertonic sucrose-evoked glutamate release from synaptosomes. Furthermore, the suppression of protein kinase A (PKA) prevented the effect of cynarin on 4-AP-elicited glutamate release. 4-AP-elicited PKA and synapsin I or synaptosomal-associated protein of 25 kDa (SNAP-25) phosphorylation at PKA-specific residues were also attenuated by cynarin. Our data indicate that cynarin, through the suppression of P/Q-type Ca2+ channels, inhibits PKA activation and attenuates synapsin I and SNAP-25 phosphorylation at PKA-specific residues, thus decreasing synaptic vesicle availability and contributing to glutamate release inhibition in cerebral cortex terminals.


Subject(s)
Cynara scolymus , Glutamic Acid , Rats , Animals , Glutamic Acid/metabolism , Rats, Sprague-Dawley , Cynara scolymus/metabolism , Synaptosomes/metabolism , Synapsins/metabolism , Synapsins/pharmacology , Molecular Docking Simulation , Membrane Potentials , 4-Aminopyridine/pharmacology , Calcium Channels, P-Type/metabolism , Cerebral Cortex/metabolism , Calcium/metabolism , Calcium Channel Blockers/pharmacology , Presynaptic Terminals/metabolism
17.
Eur J Pharmacol ; 950: 175772, 2023 Jul 05.
Article in English | MEDLINE | ID: mdl-37146708

ABSTRACT

Mangiferin is a glucosyl xanthone that has been shown to be a neuroprotective agent against brain disorders involving excess glutamate. However, the effect of mangiferin on the function of the glutamatergic system has not been investigated. In this study, we used synaptosomes from the rat cerebral cortex to investigate the effect of mangiferin on glutamate release and identify the possible underlying mechanism. We observed that mangiferin produced a concentration-dependent reduction in the release of glutamate elicited by 4-aminopyridine with an IC50 value of 25 µM. Inhibition of glutamate release was blocked by removing extracellular calcium and by treatment with the vacuolar-type H+-ATPase inhibitor bafilomycin A1, which prevents the uptake and storage of glutamate in vesicles. Moreover, we showed that mangiferin decreased the 4-aminopyridine-elicited FM1-43 release and synaptotagmin 1 luminal domain antibody (syt1-L ab) uptake from synaptosomes, which correlated with decreased synaptic vesicle exocytosis. Transmission electron microscopy in synaptosomes also showed that mangiferin attenuated the 4-aminopyridine-elicited decrease in the number of synaptic vesicles. In addition, antagonism of Ca2+/calmodulin-dependent kinase II (CaMKII) and protein kinase A (PKA) counteracted mangiferin's effect on glutamate release. Mangiferin also decreased the phosphorylation of CaMKII, PKA, and synapsin I elicited by 4-aminopyridine treatment. Our data suggest that mangiferin reduces PKA and CaMKII activation and synapsin I phosphorylation, which could decrease synaptic vesicle availability and lead to a subsequent reduction in vesicular glutamate release from synaptosomes.


Subject(s)
Glutamic Acid , Xanthones , Rats , Animals , Glutamic Acid/metabolism , Rats, Sprague-Dawley , Synapsins/metabolism , Phosphorylation , Synaptosomes/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Cerebral Cortex , 4-Aminopyridine/pharmacology , Xanthones/pharmacology , Calcium/metabolism
18.
Molecules ; 28(3)2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36770979

ABSTRACT

Inhibiting the excessive release of glutamate in the brain is emerging as a promising therapeutic option and is efficient for treating neurodegenerative disorders. The aim of this study is to investigate the effect and mechanism of plantainoside D (PD), a phenylenthanoid glycoside isolated from Plantago asiatica L., on glutamate release in rat cerebral cortical nerve terminals (synaptosomes). We observed that PD inhibited the potassium channel blocker 4-aminopyridine (4-AP)-evoked release of glutamate and elevated concentration of cytosolic Ca2+. Using bafilomycin A1 to block glutamate uptake into synaptic vesicles and EDTA to chelate extracellular Ca2+, the inhibitory effect of PD on 4-AP-evoked glutamate release was prevented. In contrast, the action of PD on the 4-AP-evoked release of glutamate in the presence of dl-TBOA, a potent nontransportable inhibitor of glutamate transporters, was unaffected. PD does not alter the 4-AP-mediated depolarization of the synaptosomal membrane potential, suggesting that the inhibitory effect of PD on glutamate release is associated with voltage-dependent Ca2+ channels (VDCCs) but not the modulation of plasma membrane potential. Pretreatment with the Ca2+ channel blocker (N-type) ω-conotoxin GVIA abolished the inhibitory effect of PD on the evoked glutamate release, as did pretreatment with the protein kinase C inhibitor GF109203x. However, the PD-mediated inhibition of glutamate release was eliminated by applying the mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 or dantrolene, which inhibits Ca2+ release through ryanodine receptor channels. These data suggest that PD mediates the inhibition of evoked glutamate release from synaptosomes primarily by reducing the influx of Ca2+ through N-type Ca2+ channels, subsequently reducing the protein kinase C cascade.


Subject(s)
4-Aminopyridine , Glutamic Acid , Rats , Animals , Glutamic Acid/metabolism , Rats, Sprague-Dawley , 4-Aminopyridine/pharmacology , Synaptosomes/metabolism , Calcium Signaling , Protein Kinase C/metabolism , Cerebral Cortex/metabolism , Calcium/metabolism , Calcium Channel Blockers/pharmacology
19.
Klin Monbl Augenheilkd ; 240(2): 163-168, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36100251

ABSTRACT

BACKGROUND: This retrospective study aimed to evaluate the effect of intense pulsed light treatment (IPL) combined with meibomian gland expression (MGX) in treating meibomian gland dysfunction (MGD) related dry eye disease (DED) for the first time in Northeast China. METHODS: Thirty-one MGD-related dry eye patients were managed by IPL-MGX from October to December 2019 in The First Hospital of Jilin University. Those patients had single IPL-MGX treatment with one follow-up visit, and no topical eye drops used were included in the study. General checkup and data collection helped in determining the age, sex, diagnosis, status of the MG, first noninvasive tear break-up time (1st NIBUT), average NIBUT, the height of tear film, and additional medical history. RESULTS: There was an improvement in the function of the meibomian gland (MG), with a significant decrease in the MG dropouts in the upper eyelid (Rt eye, p = 0.0047; Lt eye, p = 0.0158) and lower eyelid (Rt eye, p = 0.0017; Lt eye, p = 0.0027) plus the average NIBUT (Rt eye, p = 0.0264) also showed improvement after the IPL-MGX treatment. Though no significant difference was reached with the average NIBUT of the Lt eye (p = 0.5256) and the NIBUT grade (Rt eye, p = 0.0578; Lt eye, p = 0.0588), there was an increased duration of the average NIBUT and improved NIBUT grading. The negative results may be because of the maximum severity of DED and the limited treatment times. CONCLUSIONS: The result suggests that IPL-MGX was effective in treating MGD-related DED.


Subject(s)
Dry Eye Syndromes , Meibomian Gland Dysfunction , Humans , Meibomian Gland Dysfunction/metabolism , Meibomian Gland Dysfunction/therapy , Retrospective Studies , Meibomian Glands/metabolism , Dry Eye Syndromes/therapy , Time Factors , Tears
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