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Journal of Agricultural and Food... Jun 2024We investigated the protective effect of walnut peptides and YVPFPLP (YP-7) on scopolamine-induced memory impairment in mice and β-amyloid (Aβ)-induced excitotoxic...
Walnut-Derived Peptides Ameliorate Scopolamine-Induced Memory Impairments in a Mouse Model via Activation of Peroxisome Proliferator-Activated Receptor γ-Mediated Excitotoxicity.
We investigated the protective effect of walnut peptides and YVPFPLP (YP-7) on scopolamine-induced memory impairment in mice and β-amyloid (Aβ)-induced excitotoxic injury in primary hippocampal neurons, respectively. Additionally, the protective mechanism of YP-7 on neuronal excitotoxicity was explored. Mouse behavioral and hippocampal slice morphology experiments indicate that YP-7 improves the learning and memory abilities of cognitively impaired mice and protects synaptic integrity. Immunofluorescence, western blotting, and electrophysiological experiments on primary hippocampal neurons indicate that YP-7 inhibits neuronal damage caused by excessive excitation of neurons induced by Aβ. HT-22 cell treatment with peroxisome proliferator-activated receptor γ (PPARγ) activators and inhibitors showed that YP-7 activates PPARγ expression and maintains normal neuronal function by forming stable complexes with PPARγ to inhibit the extracellular regulated protein kinase pathway. Therefore, YP-7 can ameliorate glutamate-induced excitotoxicity and maintain neuronal signaling. This provides a theoretical basis for active peptides to ameliorate excitotoxicity and the development of functional foods.
Topics: Animals; Scopolamine; Mice; Memory Disorders; PPAR gamma; Juglans; Hippocampus; Male; Peptides; Neurons; Disease Models, Animal; Humans; Memory; Plant Proteins; Amyloid beta-Peptides
PubMed: 38785039
DOI: 10.1021/acs.jafc.4c01058 -
Journal of Yeungnam Medical Science May 2024This case report is a unique case of solar retinopathy following antidepressant-induced mydriasis and highlights the need for comprehensive ophthalmic evaluation in...
This case report is a unique case of solar retinopathy following antidepressant-induced mydriasis and highlights the need for comprehensive ophthalmic evaluation in patients treated with medications having mydriatic effects. A 49-year-old female patient who had received long-term antidepressant therapy presented with bilateral visual impairment after prolonged sun exposure. Fundoscopy confirmed solar retinopathy, which was attributed to drug-induced mydriasis. Medication adjustments and sun protection strategies led to full visual recovery, underscoring the importance of interdisciplinary awareness. This case emphasizes the challenges associated with the simultaneous management of psychiatric and ophthalmic conditions and highlights the need for routine ophthalmic evaluation of patients prescribed antidepressants with reported ocular side effects.
PubMed: 38778720
DOI: 10.12701/jyms.2024.00213 -
The British Journal of Ophthalmology May 2024Ophthalmic quality of life (OQoL) has been investigated in selected parts of general populations and in patients with ocular disease, but OQoL in unselected general...
BACKGROUND
Ophthalmic quality of life (OQoL) has been investigated in selected parts of general populations and in patients with ocular disease, but OQoL in unselected general populations has not been studied in detail. The present study reports OQoL obtained from a representative sample of the adult Danish population 2020-2022.
METHODS
The FORSYN study invited 10 350 citizen representatives for the adult Danish population for a non-mydriatic eye examination and answer the National Eye Institute Visual Function Questionnaire with 39 items in the validated Danish translation. The results from the 3384 (32.7%) persons who participated in the study were weighted on the basis of relevant socio-economic factors, and data were projected to represent the total population. Binocular visual acuity was below 0.1 corresponding to legal blindness in 0.22% of this population.
RESULTS
OQoL was positively correlated with binocular visual acuity up to better than 93 ETDRS letters, negatively correlated with age for persons younger than 60 years of age and again positively correlated with age for persons older than 60 years. OQoL was negatively correlated with increasing ametropia and refractive error above 1 dioptre and encompassed more OQoL parameters for hyperopic than for myopic persons.
CONCLUSIONS
The study underlines the benefits of improving visual acuity even within the normal range and of adjusting uncorrected refraction errors in the general population. OQoL is positively correlated with age in older persons independently of visual acuity, sex, refractive power and previous cataract surgery.
PubMed: 38777390
DOI: 10.1136/bjo-2023-324414 -
Toxicology and Applied Pharmacology Jul 2024Soman produces excitotoxic effects by inhibiting acetylcholinesterase in the cholinergic synapses and neuromuscular junctions, resulting in soman-induced sustained...
Seizure suppression and neuroprotection in soman-exposed rats following delayed intramuscular treatment of adenosine A receptor agonist as an adjunct to standard medical treatment.
Soman produces excitotoxic effects by inhibiting acetylcholinesterase in the cholinergic synapses and neuromuscular junctions, resulting in soman-induced sustained status epilepticus (SSE). Our previous work showed delayed intramuscular (i.m.) treatment with A adenosine receptor agonist N-bicyclo-[2.2.1]-hept-2-yl-5'-chloro-5'-deoxyadenosine (ENBA) alone suppressed soman-induced SSE and prevented neuropathology. Using this same rat soman seizure model, we tested if delayed therapy with ENBA (60 mg/kg, i.m.) would terminate seizure, protect neuropathology, and aid in survival when given in conjunction with current standard medical countermeasures (MCMs): atropine sulfate, 2-PAM, and midazolam (MDZ). Either 15- or 30-min following soman-induced SSE onset, male rats received atropine and 2-PAM plus either MDZ or MDZ + ENBA. Electroencephalographic (EEG) activity, physiologic parameters, and motor function were recorded. Either 2- or 14-days following exposure surviving rats were euthanized and perfused for histology. All animals treated with MDZ + ENBA at both time points had 100% EEG seizure termination and reduced total neuropathology compared to animals treated with MDZ (2-day, p = 0.015 for 15-min, p = 0.002 for 30-min; 14-day, p < 0.001 for 15-min, p = 0.006 for 30-min), showing ENBA enhanced MDZ's anticonvulsant and neuroprotectant efficacy. However, combined MDZ + ENBA treatment, when compared to MDZ treatment groups, had a reduction in the 14-day survival rate regardless of treatment time, indicating possible enhancement of MDZ's neuronal inhibitory effects by ENBA. Based on our findings, ENBA shows promise as an anticonvulsant and neuroprotectant in a combined treatment regimen following soman exposure; when given as an adjunct to standard MCMs, the dose of ENBA needs to be adjusted.
Topics: Animals; Soman; Male; Adenosine A1 Receptor Agonists; Rats; Rats, Sprague-Dawley; Injections, Intramuscular; Seizures; Neuroprotective Agents; Anticonvulsants; Electroencephalography; Adenosine; Atropine; Status Epilepticus; Midazolam
PubMed: 38777098
DOI: 10.1016/j.taap.2024.116970 -
Brazilian Journal of Medical and... 2024Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced...
Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway.
Topics: Animals; Male; Phenylephrine; Rats, Wistar; Arthritis, Experimental; Nitric Oxide; Vasoconstriction; Endothelium, Vascular; Vasoconstrictor Agents; Rats; Aorta
PubMed: 38775546
DOI: 10.1590/1414-431X2024e13304 -
Pharmaceutical Biology Dec 2024The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown.
Network pharmacology integrated with experimental validation to elucidate the mechanisms of action of the Guizhi-Gancao Decoction in the treatment of phenylephrine-induced cardiac hypertrophy.
CONTEXT
The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown.
OBJECTIVE
This study explores the mechanisms of GGD against cardiac hypertrophy.
MATERIALS AND METHODS
Network pharmacology analysis was carried out to identify the potential targets of GGD. experiments, C57BL/6J mice were divided into Con, phenylephrine (PE, 10 mg/kg/d), 2-chloroadenosine (CADO, the stable analogue of adenosine, 2 mg/kg/d), GGD (5.4 g/kg/d) and GGD (5.4 g/kg/d) + CGS15943 (a nonselective adenosine receptor antagonist, 4 mg/kg/d). experiments, primary neonatal rat cardiomyocytes (NRCM) were divided into Con, PE (100 µM), CADO (5 µM), GGD (10 g/mL) and GGD (10 g/mL) + CGS15943 (5 µM). Ultrasound, H&E and Masson staining, hypertrophic genes expression and cell surface area were conducted to verify the GGD efficacy. Adenosine receptors (ADORs) expression were tested real-time polymerase chain reaction (PCR), western blotting and immunofluorescence analysis.
RESULTS
Network pharmacology identified ADORs among those of the core targets of GGD. experiments demonstrated that GGD attenuated PE-induced increased surface area (with an EC of 5.484 × 10 g/mL). data shown that GGD attenuated PE-induced ventricular wall thickening. and data indicated that GGD alleviated PE-induced hypertrophic gene expression (e.g., ANP, BNP and MYH7/MYH6), A1AR over-expression and A2aAR down-expression. Moreover, CADO exerts effects similar to GGD, whereas CGS15943 eliminated most effects of GGD.
DISCUSSION AND CONCLUSIONS
Our findings suggest the mechanism by which GGD inhibits cardiac hypertrophy, highlighting regulation of ADORs as a potential therapeutic strategy for HF.
Topics: Animals; Drugs, Chinese Herbal; Phenylephrine; Cardiomegaly; Mice, Inbred C57BL; Mice; Male; Rats; Myocytes, Cardiac; Network Pharmacology; Rats, Sprague-Dawley; Cells, Cultured; Disease Models, Animal; Medicine, Chinese Traditional
PubMed: 38773737
DOI: 10.1080/13880209.2024.2354335 -
Veterinary Ophthalmology May 2024To determine the mydriatic effect of topical 10% phenylephrine with 10 mg/mL rocuronium bromide and compare this protocol with and without pretreatment with proparacaine.
OBJECTIVE
To determine the mydriatic effect of topical 10% phenylephrine with 10 mg/mL rocuronium bromide and compare this protocol with and without pretreatment with proparacaine.
ANIMALS STUDIED
Ten client-owned pet adult eastern box turtles (Terrapene carolina carolina).
PROCEDURES
All turtles were sedated with 8 mg/kg alfaxalone intramuscularly. One group of four turtles received four 20 μL drops of 10% phenylephrine and four 20 μL drops of rocuronium bromide in the right eye. Another group of four turtles received one standard drop of proparacaine followed by four 20 μL drops of 10% phenylephrine and four 20 μL drops of rocuronium bromide in the right eye. Two control group turtles received four 20 μL drops of saline in the right eye. The left eye was untreated in all turtles. Drops of the same type were separated by 2 min while drops of different types were separated by 5 min. Pupil size was recorded at 0, 15, 30, 60, 90, 120, 180, 240, and 360 min after administration of the final drop.
RESULTS
Treatment with 10% phenylephrine and rocuronium bromide resulted in pupil diameter changes from baseline that were statistically significant from zero at 60, 90, and 120 min in the non-proparacaine group and 90 min in the proparacaine group. The time to peak effect was 90 min in the proparacaine group and 75 min in the non-proparacaine group. Saline-treated pupils in the control group decreased in diameter over the study period. Overall, the treated eyes of the proparacaine group and non-proparacaine group were not different from each other, but both dilated more than the control group.
CONCLUSIONS
Rocuronium bromide and 10% phenylephrine can produce effective and safe mydriasis in eastern box turtles, but there was wide interindividual variation in effectiveness. Proparacaine did not improve the mydriatic effect.
PubMed: 38760319
DOI: 10.1111/vop.13229 -
Medicine May 2024This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to... (Observational Study)
Observational Study
This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to measure refractive error accurately by paralyzing accommodation. However, effects on axial length (AL), anterior chamber depth (ACD), keratometry (Km), and white-to-white distance (WTW) are not well studied in this population. This retrospective study examined 797 patients (1566 eyes) undergoing cycloplegic refraction at a Samsung Kangbuk hospital pediatric ophthalmology clinic from 2010 to 2023. Ocular biometry was measured before and after instilling 1% cyclopentolate and 0.5% phenylephrine/0.5% tropicamide. Patients were categorized by strabismus diagnosis, age, refractive error and amblyopia status. Differences in AL, ACD, Km, WTW, and refractive error pre- and post-cycloplegia were analyzed using paired t tests. ACD (3.44 ± 0.33 vs 3.58 ± 0.29 mm, P < .05) and WTW (12.09 ± 0.42 vs 12.30 ± 0.60 mm, P < .05) increased significantly after cycloplegia in all groups except other strabismus subgroup (Cs) in both parameters and youngest subgroup (G1) in ACD. Refractive error demonstrated a hyperopic shift from -0.48 ± 3.00 D to -0.06 ± 3.32 D (P < .05) in overall and a myopic shift from -6.97 ± 4.27 to -8.10 ± 2.26 in high myopia (HM). Also, AL and Km did not change significantly. In conclusion, cycloplegia impacts ocular biometrics in children with strabismus and amblyopia, significantly increasing ACD and WTW. Refractive error shifts hyperopically in esotropia subgroup (ET) and myopically in high myopia subgroup (HM), eldest subgroup (G3) relating more to anterior segment changes than AL/Km. Understanding cycloplegic effects on biometry is important for optimizing refractive correction in these patients.
Topics: Humans; Amblyopia; Strabismus; Retrospective Studies; Male; Female; Child; Biometry; Mydriatics; Child, Preschool; Refraction, Ocular; Cyclopentolate; Refractive Errors; Adolescent; Anterior Chamber; Axial Length, Eye
PubMed: 38758890
DOI: 10.1097/MD.0000000000038143 -
Bratislavske Lekarske Listy 2024In the present study, two structurally similar alkaloids from trees of Cinchona genus, chloroquine and cinchonine, were examined for their vasorelaxant effects in...
BACKGROUND
In the present study, two structurally similar alkaloids from trees of Cinchona genus, chloroquine and cinchonine, were examined for their vasorelaxant effects in a model of phenylephrine-induced smooth muscle contractions.
METHODS
Potential mechanisms of action associated with endothelial vasorelaxant compounds, voltage-gated Ca2+ channels (LTCCs), and inositol triphosphate receptors were examined in isolated rat aortic rings. Also, an in silico approach was used to predict the activity of the two test compounds.
RESULTS
Experimental results revealed that both chloroquine and cinchonine significantly decrease phenylephrine-induced smooth muscle contractions, although to a different extent. Evaluated mechanisms of action indicate that endothelium is not involved in the vasorelaxant action of the two tested alkaloids. On the other hand, voltage-gated Ca2+ channels were found to be the dominant way of action associated with the vasorelaxant action of chloroquine and cinchonine. Finally, IP3R is found to have only a small impact on the observed activity of the tested compounds.
CONCLUSION
Molecular docking studies predicted that chloroquine possesses a significant activity toward a suitable model of LTCCs, while cinchonine does not. The results of the present study point to the fact that great caution should be paid while administering chloroquine to vulnerable patients, especially those with cardiovascular disorders (Tab. 3, Fig. 3, Ref. 28).
Topics: Animals; Chloroquine; Rats; Muscle, Smooth, Vascular; Molecular Docking Simulation; Calcium Channels; Vasodilator Agents; Muscle Tonus; Male; Rats, Wistar; Computer Simulation; Phenylephrine
PubMed: 38757591
DOI: 10.4149/BLL_2024_53 -
Food & Function Jun 2024protein hydrolysates are known for their abundant amino acids and excellent developmental values. This study aimed to identify and screen neuroprotective peptides from...
protein hydrolysates are known for their abundant amino acids and excellent developmental values. This study aimed to identify and screen neuroprotective peptides from protein hydrolysates and validate the protective effects of YVYAETY on memory impairment in scopolamine-induced mice. The protein was hydrolyzed by simulated gastrointestinal digestion, followed by purification through ultrafiltration and gel chromatography. The fraction exhibiting the strongest neuroprotective activity was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main identified peptides (SDLKPADF, WNDHYY, YVYAETY, and WFHPLF) effectively mitigated excessive ROS production by increasing SOD and GSH-px activities while inhibiting cell apoptosis and mitochondrial membrane potential (MMP) collapse against oxidative stress in Aβ-induced HT22 cells. By molecular docking, the interaction between peptides and the active site of the Keap1-Kelch domain reveals their capacity to regulate the Keap1/Nrf2/HO-1 pathway. , the peptide YVYAETY had the best effect and can be further validated . The behavioral tests showed that YVYAETY improved scopolamine-induced cognitive impairment in mice. YVYAETY also alleviated neuron damage including neuron vacuolation and pyknotic nuclei in the hippocampus. Furthermore, it significantly inhibited oxidative stress and suppressed the activation of the Nrf2 pathway. Therefore, this study revealed that YVYAETY had the potential to serve as a novel neuroprotective agent.
Topics: Animals; Mice; Scopolamine; Neuroprotective Agents; Cognitive Dysfunction; Protein Hydrolysates; Flammulina; Male; Oxidative Stress; Peptides; Molecular Docking Simulation; Hippocampus; Apoptosis
PubMed: 38757389
DOI: 10.1039/d4fo00871e