scholarly journals Co-Existence of Hypertensive and Anti-Hypertensive Constituents, Synephrine, and Nobiletin in Citrus unshiu Peel

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1197 ◽  
Author(s):  
Jung-Joon Kim ◽  
Keunyoung Kim ◽  
Ye-Ryeon Jung ◽  
Yiying Bian ◽  
Thien Ngo ◽  
...  
Keyword(s):  
Plant Extract ◽  
Response Pattern ◽  
Contractile Activity ◽  
Activity Patterns ◽  
Citrus Unshiu ◽  
Response Patterns ◽  
Acorus Gramineus ◽  
Citrus Unshiu Peel ◽  
Insight Into

A single herb can contain multiple constituents with diverse bioactivities. We found that the extract of Citrus unshiu peel (CUP), induced abnormal vasoconstriction responses on the freshly isolated rat aortic rings in vitro. CUP stimulated the vasoconstriction alone, and it suppressed the phenylephrine-stimulated vasoconstriction. We studied the reasons behind this abnormal vasoconstriction pattern. Major constituents of CUP were determined and evaluated for their vaso-activities. Notably, synephrine, a contractile agonist, and nobiletin, newly identified to have anti-contractile activity co-existed in CUP. Synephrine and nobiletin competitively blocked or activated the same contractile targets resulting in contradicting and abnormal vasoconstriction responses. Accordingly, the vasoconstriction pattern varies significantly depending on the relative contents of synephrine and nobiletin in CUP. Interestingly, this response pattern could be observed with another plant extract, Acorus gramineus Sol. Collectively, we demonstrated that active ingredients with contradicting bioactivities could co-exist in a single plant extract, interact and produce abnormal response patterns in bioassay, which would give an important insight into the interpretation of unusual activity patterns induced by plant extracts.

In vitro and in vivo evaluation of systemic and genetic toxicity of Citrus unshiu peel

2018 ◽  
Vol 215 ◽  
pp. 120-123 ◽  
Author(s):  
Hwayong Park ◽  
Youn-Hwan Hwang ◽  
Jang-Gi Choi ◽  
Jin Yeul Ma
Keyword(s):  
Citrus Unshiu ◽  
In Vivo Evaluation ◽  
Genetic Toxicity ◽  
Citrus Unshiu Peel

scholarly journals Citrus unshiu peel suppress the metastatic potential of murine melanoma B16F10 cells in vitro and in vivo

2019 ◽  
Vol 33 (12) ◽  
pp. 3228-3241 ◽  
Author(s):  
Eun Ok Choi ◽  
Hyesook Lee ◽  
Hyun HwangBo ◽  
Da Hye Kwon ◽  
Min Yeong Kim ◽  
...  
Keyword(s):  
Metastatic Potential ◽  
Citrus Unshiu ◽  
Murine Melanoma ◽  
B16f10 Cells ◽  
Melanoma B16f10 ◽  
Citrus Unshiu Peel

Stimulus Ratio Effects on Speech Discrimination by Children and Adults

1991 ◽  
Vol 34 (3) ◽  
pp. 671-678 ◽  
Author(s):  
Joan E. Sussman
Keyword(s):  
Discrimination Task ◽  
Response Pattern ◽  
Response Patterns ◽  
Speech Discrimination ◽  
Adult Group ◽  
Discrimination Accuracy ◽  
Formant Frequency ◽  
Response Strategies ◽  
Place Of Articulation ◽  
Adults And Children

This investigation examined the response strategies and discrimination accuracy of adults and children aged 5–10 as the ratio of same to different trials was varied across three conditions of a “change/no-change” discrimination task. The conditions varied as follows: (a) a ratio of one-third same to two-thirds different trials (33% same), (b) an equal ratio of same to different trials (50% same), and (c) a ratio of two-thirds same to one-third different trials (67% same). Stimuli were synthetic consonant-vowel syllables that changed along a place of articulation dimension by formant frequency transition. Results showed that all subjects changed their response strategies depending on the ratio of same-to-different trials. The most lax response pattern was observed for the 50% same condition, and the most conservative pattern was observed for the 67% same condition. Adult response patterns were most conservative across condition. Differences in discrimination accuracy as measured by P(C) were found, with the largest difference in the 5- to 6-year-old group and the smallest change in the adult group. These findings suggest that children’s response strategies, like those of adults, can be manipulated by changing the ratio of same-to-different trials. Furthermore, interpretation of sensitivity measures must be referenced to task variables such as the ratio of same-to-different trials.

scholarly journals Stochastic activation and bistability in a Rab GTPase regulatory network

2020 ◽  
Vol 117 (12) ◽  
pp. 6540-6549
Author(s):  
Urban Bezeljak ◽  
Hrushikesh Loya ◽  
Beata Kaczmarek ◽  
Timothy E. Saunders ◽  
Martin Loose
Keyword(s):  
Regulatory Network ◽  
Regulatory Networks ◽  
Membrane Surface ◽  
Activity Patterns ◽  
Small Gtpases ◽  
Signaling Networks ◽  
Rab Gtpase ◽  
Endomembrane System ◽  
In Vitro Reconstitution

The eukaryotic endomembrane system is controlled by small GTPases of the Rab family, which are activated at defined times and locations in a switch-like manner. While this switch is well understood for an individual protein, how regulatory networks produce intracellular activity patterns is currently not known. Here, we combine in vitro reconstitution experiments with computational modeling to study a minimal Rab5 activation network. We find that the molecular interactions in this system give rise to a positive feedback and bistable collective switching of Rab5. Furthermore, we find that switching near the critical point is intrinsically stochastic and provide evidence that controlling the inactive population of Rab5 on the membrane can shape the network response. Notably, we demonstrate that collective switching can spread on the membrane surface as a traveling wave of Rab5 activation. Together, our findings reveal how biochemical signaling networks control vesicle trafficking pathways and how their nonequilibrium properties define the spatiotemporal organization of the cell.

The in vitro neonatal rat spinal cord preparation: a new insight into mammalian locomotor mechanisms

2004 ◽  
Vol 190 (5) ◽  
pp. 343-357 ◽  
Author(s):  
F. Clarac ◽  
E. Pearlstein ◽  
J. F. Pflieger ◽  
L. Vinay
Keyword(s):  
Spinal Cord ◽  
Neonatal Rat ◽  
Rat Spinal Cord ◽  
Insight Into

scholarly journals Plant-Derived Extracellular Vesicles: Current Findings,Challenges, and Future Applications

Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 411
Author(s):  
Nader Kameli ◽  
Anya Dragojlovic-Kerkache ◽  
Paul Savelkoul ◽  
Frank R. Stassen
Keyword(s):  
Human Health ◽  
Extracellular Vesicles ◽  
Preliminary Results ◽  
In Vivo Experiments ◽  
Health And Disease ◽  
Conducting Research ◽  
Protocol Standardization ◽  
Insight Into

In recent years, plant-derived extracellular vesicles (PDEVs) have gained the interest of many experts in fields such as microbiology and immunology, and research in this field has exponentially increased. These nano-sized particles have provided researchers with a number of interesting findings, making their application in human health and disease very promising. Both in vitro and in vivo experiments have shown that PDEVs can exhibit a multitude of effects, suggesting that these vesicles may have many potential future applications, including therapeutics and nano-delivery of compounds. While the preliminary results are promising, there are still some challenges to face, such as a lack of protocol standardization, as well as knowledge gaps that need to be filled. This review aims to discuss various aspects of PDEV knowledge, including their preliminary findings, challenges, and future uses, giving insight into the complexity of conducting research in this field.

scholarly journals GRAding of functional and anatomical response to DExamethasone implant in patients with Diabetic Macular Edema: GRADE-DME Study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patricio J. Rodríguez-Valdés ◽  
Matus Rehak ◽  
Dinah Zur ◽  
Anna Sala-Puigdollers ◽  
Samantha Fraser-Bell ◽  
...  
Keyword(s):  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Response Pattern ◽  
Observational Cohort Study ◽  
Response Patterns ◽  
Dexamethasone Implant ◽  
Central Subfield Thickness ◽  
Treatment Naïve ◽  
Observational Cohort ◽  
Stable Improvement

AbstractTo analyze functional and anatomical response patterns to dexamethasone (DEX) implant in diabetic macular edema (DME), to describe proportion of responders and non-responders, and to propose a new DME grading system. Retrospective, multicenter, observational cohort study. Naïve and non-naïve DME patients were treated with DEX, with visual acuity (VA) ≥ 0.2 logMAR and central subfield thickness (CST) of ≥ 300 µm. Functional and anatomical responses were graded after 2 and 4 months, and categorized as early and stable improvement, early and progressive improvement, pendular response, delayed improvement, and persistent non-response. 417 eyes were included (175 treatment naïve eyes). Compared to non-naïve eyes, naïve eyes showed a very good functional response (VA gain ≥ 10 letters) more frequently after 2 and 4 months (56% and 57% [naïve] vs. 33% and 28% [non-naïve], p < 0.001). A VA gain < 5 letters (non-response) after 2 and 4 months was seen in 18% and 16% of naïve eyes, and in 49% and 53% of non-naïve eyes (p < 0.001). A lack of anatomical response was rare in both groups, but more frequently in non-naïve eyes (12% vs. 4%, p = 0.003). Functionally and anatomically, naïve eyes showed most frequently an early and stable improvement (functionally: 77/175 44%; anatomically: 123/175 eyes, 70%). Most non-naïve eyes experienced no significant improvement functionally (97/242 eyes, 40%), despite a mostly early and stable improvement anatomical response pattern (102/242 eyes, 42%). Functional but not anatomical response patterns were influenced by baseline VA. Naïve and non-naïve eyes show different functional and anatomical response patterns to DEX implant. Functional non-responders are rare in naïve eyes, whereas anatomical non-response is unusual in both groups.

scholarly journals Cryo-EM structure of amyloid fibrils formed by the entire low complexity domain of TDP-43

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiuye Li ◽  
W. Michael Babinchak ◽  
Witold K. Surewicz
Keyword(s):  
Amyloid Fibrils ◽  
Low Complexity ◽  
Structural Features ◽  
Protein Fragments ◽  
Hydrophobic Residues ◽  
Backbone Conformation ◽  
Hydrophobic Amino Acids ◽  
Insight Into ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis and several other neurodegenerative diseases are associated with brain deposits of amyloid-like aggregates formed by the C-terminal fragments of TDP-43 that contain the low complexity domain of the protein. Here, we report the cryo-EM structure of amyloid formed from the entire TDP-43 low complexity domain in vitro at pH 4. This structure reveals single protofilament fibrils containing a large (139-residue), tightly packed core. While the C-terminal part of this core region is largely planar and characterized by a small proportion of hydrophobic amino acids, the N-terminal region contains numerous hydrophobic residues and has a non-planar backbone conformation, resulting in rugged surfaces of fibril ends. The structural features found in these fibrils differ from those previously found for fibrils generated from short protein fragments. The present atomic model for TDP-43 LCD fibrils provides insight into potential structural perturbations caused by phosphorylation and disease-related mutations.

scholarly journals Peptide drugs for photopharmacology: how much of a safety advantage can be gained by photocontrol?

2020 ◽  
Vol 2 (1) ◽  
pp. FDD28 ◽  
Author(s):  
Oleg Babii ◽  
Sergii Afonin ◽  
Tim Schober ◽  
Liudmyla V Garmanchuk ◽  
Liudmyla I Ostapchenko ◽  
...  
Keyword(s):  
Chemotherapeutic Agent ◽  
In Vitro Cytotoxicity ◽  
Pharmacokinetic Parameters ◽  
Cancer Model ◽  
Pharmacokinetic Properties ◽  
Insight Into ◽  
Safety Advantage ◽  
Murine Cancer Model

Aim: To verify whether photocontrol of biological activity could augment safety of a chemotherapeutic agent. Materials & methods: LD50 values for gramicidin S and photoisomeric forms of its photoswitchable diarylethene-containing analogs were determined using mice. The results were compared with data obtained from cell viability measurements taken for the same compounds. Absorption, Distribution, Metabolism, and Elimination (ADME) tests using a murine cancer model were conducted to get insight into the underlying reasons for the observed in vivo toxicity. Results: While in vitro cytotoxicity values of the photoisomers differed substantially, the differences in the observed LD50 values were less pronounced due to unfavorable pharmacokinetic parameters. Conclusion: Despite unfavorable pharmacokinetic properties as in the representative case studied here, there is an overall advantage to be gained in the safety profile of a chemotherapeutic agent via photocontrol. Nevertheless, optimization of the pharmacokinetic parameters of photoisomers is an important issue to be addressed during the development of photopharmacological drugs.

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