In vivo ketogenic diet treatment attenuates pathologic sharp waves and high frequency oscillations in in vitro hippocampal slices from epileptic Kv1.1α knockout mice

The hippocampus is thought to be a good experimental model for investigating epileptogenesis in and/or antiepileptic therapy for temporal lobe epilepsy. The hippocampus is also a useful target for researching the ketogenic diet. This chapter focuses on electrophysiological recordings using hippocampal slices and introduces their use for studying the anticonvulsant effects underlying ketogenic diets. The major difficulty in using hippocampal slices is the inability to precisely reproduce the in vivo condition of ketogenic diet feeding in this in vitro preparation. Three different approaches are reported to reproduce diet effects in the hippocampal slices: (1) direct application of ketone bodies, (2) mimicking the ketogenic diet condition with whole-cell patch-clamp technique, and (3) hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods. These three approaches are useful tools to elucidate the underlying anticonvulsant mechanisms of the ketogenic diet.

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High-frequency oscillations and seizure-like discharges in the entorhinal cortex of the in vitro isolated guinea pig brain

Epilepsy Research ◽

10.1016/j.eplepsyres.2017.01.001 ◽

2017 ◽

Vol 130 ◽

pp. 21-26 ◽

Cited By ~ 2

Author(s):

Laura Uva ◽

Davide Boido ◽

Massimo Avoli ◽

Marco de Curtis ◽

Maxime Lévesque

Keyword(s):

Guinea Pig ◽

Entorhinal Cortex ◽

High Frequency ◽

High Frequency Oscillations ◽

Pig Brain ◽

Guinea Pig Brain

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Region-specific effects of early-life status epilepticus on the adult hippocampal ca3 – medial entorhinal cortex circuitry in vitro: focus on interictal spikes and concurrent high-frequency oscillations

Neuroscience ◽

10.1016/j.neuroscience.2021.04.030 ◽

2021 ◽

Author(s):

Christos Panagiotis Lisgaras ◽

Apostolos Mikroulis ◽

Caterina Psarropoulou

Keyword(s):

Status Epilepticus ◽

Entorhinal Cortex ◽

High Frequency ◽

Early Life ◽

Interictal Spikes ◽

Medial Entorhinal Cortex ◽

Specific Effects ◽

High Frequency Oscillations ◽

Hippocampal Ca3

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Selective elimination of immunosuppressive T cells in patients with multiple myeloma

Leukemia ◽

10.1038/s41375-021-01172-x ◽

2021 ◽

Author(s):

Mohamed H. S. Awwad ◽

Abdelrahman Mahmoud ◽

Heiko Bruns ◽

Hakim Echchannaoui ◽

Katharina Kriegsmann ◽

...

Keyword(s):

Multiple Myeloma ◽

T Cells ◽

Immune Responses ◽

High Frequency ◽

Surface Markers ◽

Selective Elimination ◽

Related Transcription Factor ◽

Cell Membrane Protein

AbstractElimination of suppressive T cells may enable and enhance cancer immunotherapy. Here, we demonstrate that the cell membrane protein SLAMF7 was highly expressed on immunosuppressive CD8+CD28-CD57+ Tregs in multiple myeloma (MM). SLAMF7 expression associated with T cell exhaustion surface markers and exhaustion-related transcription factor signatures. T cells from patients with a high frequency of SLAMF7+CD8+ T cells exhibited decreased immunoreactivity towards the MART-1aa26–35*A27L antigen. A monoclonal anti-SLAMF7 antibody (elotuzumab) specifically depleted SLAMF7+CD8+ T cells in vitro and in vivo via macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). Anti-SLAMF7 treatment of MM patients depleted suppressive T cells in peripheral blood. These data highlight SLAMF7 as a marker for suppressive CD8+ Treg and suggest that anti-SLAMF7 antibodies can be used to boost anti-tumoral immune responses in cancer patients.

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Sirt1 deacetylates and stabilizes p62 to promote hepato-carcinogenesis

Cell Death and Disease ◽

10.1038/s41419-021-03666-z ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Lifeng Feng ◽

Miaoqin Chen ◽

Yiling Li ◽

Muchun Li ◽

Shiman Hu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cell Growth ◽

Knockout Mice ◽

Liver Tumors ◽

Underlying Mechanism ◽

Carcinoma Cells ◽

Conditional Knockout

Abstractp62/SQSTM1 is frequently up-regulated in many cancers including hepatocellular carcinoma. Highly expressed p62 promotes hepato-carcinogenesis by activating many signaling pathways including Nrf2, mTORC1, and NFκB signaling. However, the underlying mechanism for p62 up-regulation in hepatocellular carcinoma remains largely unclear. Herein, we confirmed that p62 was up-regulated in hepatocellular carcinoma and its higher expression was associated with shorter overall survival in patients. The knockdown of p62 in hepatocellular carcinoma cells decreased cell growth in vitro and in vivo. Intriguingly, p62 protein stability could be reduced by its acetylation at lysine 295, which was regulated by deacetylase Sirt1 and acetyltransferase GCN5. Acetylated p62 increased its association with the E3 ligase Keap1, which facilitated its poly-ubiquitination-dependent proteasomal degradation. Moreover, Sirt1 was up-regulated to deacetylate and stabilize p62 in hepatocellular carcinoma. Additionally, Hepatocyte Sirt1 conditional knockout mice developed much fewer liver tumors after Diethynitrosamine treatment, which could be reversed by the re-introduction of exogenous p62. Taken together, Sirt1 deacetylates p62 at lysine 295 to disturb Keap1-mediated p62 poly-ubiquitination, thus up-regulating p62 expression to promote hepato-carcinogenesis. Therefore, targeting Sirt1 or p62 is a reasonable strategy for the treatment of hepatocellular carcinoma.

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Further pharmacological evaluation of a novel synthetic peptide bradykinin B2 receptor agonist

Biological Chemistry ◽

10.1515/hsz-2012-0295 ◽

2013 ◽

Vol 394 (3) ◽

pp. 353-360 ◽

Cited By ~ 9

Author(s):

Martin Savard ◽

Julie Labonté ◽

Céléna Dubuc ◽

Witold Neugebauer ◽

Pedro D’Orléans-Juste ◽

...

Keyword(s):

Knockout Mice ◽

Synthetic Peptide ◽

Receptor Agonist ◽

Rabbit Lung ◽

Hypotensive Action ◽

Duration Of Action ◽

Selective Agonist ◽

Comparable Magnitude

Abstract We recently identified a novel human B2 receptor (B2R) agonist [Hyp3,Thi5,NChg7,Thi8]-bradykinin (NG291) with greater in vitro and in vivo potency and duration of action than natural bradykinin (BK). Here, we further examined its stability and selectivity toward B2R. The hypotensive, antithrombotic, and profibrinolytic functions of NG291 relative to BK and its analogue ([Hyp3,Thi5,(4-Me)Tyr8(ΨCH2NH)Arg9]-BK) (RMP-7) were also tested. Contraction assays using isolated mouse stomachs (containing kinin B1R, B2R, and kininase I- and II-like activities) showed that NG291 is a more potent contractant than BK and is inhibited by HOE-140 (B2R antagonist) but unaffected by R954 (B1R antagonist), whereas both decreased the potency of BK. In stomach tissues from B2R knockout mice, BK maintained its activity via B1R, whereas NG291 had no contractile effect, indicating that it was selective for B2R. Unlike BK, NG291 was not degraded by rabbit lung ACE. Comparing intravenously administered BK and NG291 revealed that NG291 exhibited more potent and prolonged hypotensive action and greater antithrombotic and profibrinolytic activities. These effects were of comparable magnitude to RMP-7 and were absent in B2R knockout mice. We concluded that NG291 is a novel biostable B2R-selective agonist that may prove suitable for investigating the (pre)clinical cardioprotective efficacy of B2R activation.

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Effect of Common Anesthetics on Dendritic Properties in Layer 5 Neocortical Pyramidal Neurons

Journal of Neurophysiology ◽

10.1152/jn.01126.2007 ◽

2008 ◽

Vol 99 (3) ◽

pp. 1394-1407 ◽

Cited By ~ 28

Author(s):

Sarah Potez ◽

Matthew E. Larkum

Keyword(s):

High Frequency ◽

Pyramidal Neurons ◽

Animal Experiments ◽

Apical Dendrite ◽

Network Activity ◽

Calcium Spikes ◽

Firing Properties ◽

The Impact

Understanding the impact of active dendritic properties on network activity in vivo has so far been restricted to studies in anesthetized animals. However, to date no study has been made to determine the direct effect of the anesthetics themselves on dendritic properties. Here, we investigated the effects of three types of anesthetics commonly used for animal experiments (urethane, pentobarbital and ketamine/xylazine). We investigated the generation of calcium spikes, the propagation of action potentials (APs) along the apical dendrite and the somatic firing properties in the presence of anesthetics in vitro using dual somatodendritic whole cell recordings. Calcium spikes were evoked with dendritic current injection and high-frequency trains of APs at the soma. Surprisingly, we found that the direct actions of anesthetics on calcium spikes were very different. Two anesthetics (urethane and pentobarbital) suppressed dendritic calcium spikes in vitro, whereas a mixture of ketamine and xylazine enhanced them. Propagation of spikes along the dendrite was not significantly affected by any of the anesthetics but there were various changes in somatic firing properties that were highly dependent on the anesthetic. Last, we examined the effects of anesthetics on calcium spike initiation and duration in vivo using high-frequency trains of APs generated at the cell body. We found the same anesthetic-dependent direct effects in addition to an overall reduction in dendritic excitability in anesthetized rats with all three anesthetics compared with the slice preparation.

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High Frequency Plant Regeneration of Musa paradisiaca cv. Karibale Monthan

International Journal of Applied Sciences and Biotechnology ◽

10.3126/ijasbt.v3i2.12536 ◽

2015 ◽

Vol 3 (2) ◽

pp. 202-209 ◽

Cited By ~ 1

Author(s):

R. Shashi Kumar ◽

V. Krishna ◽

. Venkatesh

Keyword(s):

Plant Regeneration ◽

High Frequency ◽

Synergetic Effect ◽

Multiple Shoot ◽

Coconut Water ◽

Morphological Variations ◽

Musa Paradisiaca ◽

Shoot Initiation

High frequency plant regeneration protocol has been standardized from banana cultivar Musa paradisiaca cv. Karibale Monthan, an endemic cultivar of Malnad region of Karnataka. The fruits are used as glomerular protective to solve kidney problems. To minimize the microbial contamination and to promote healthy growth, explants were treated with 70 % absolute alcohol for 6 min, 0.1 % Mercuric chloride for 10 min and 0.2 % for 10 min, 1 % Sodium hypochlorite for 15 min, 0.1 % Cefotaxime for 5 min and 0.05 % Gentamicin for 5 min. The high frequency shoot initiation (93.33 %) was recorded at 5 mg/l BAP. The synergetic effect of BAP (4 to 6 mg/l), TDZ (0.1 to 1.2 mg/l) and coconut water (0.1 to 0.9 ml/l) induced multiple shoot buds and it was optimized at the concentration of 5 mg/l BAP, 0.5 mg/l TDZ and 0.5 ml/l coconut water with 15.90 ± 1.66 frequency of shoots per propagule. Supplementation of 1.0 mg/l IBA induced 5.33 ± 1.21 numbers of roots with a mean root length of 7.50 ± 1.87 roots. The 99% of plantlets with distinct roots and shoots were successfully acclimatized in the green house and transferred to the field to evaluate the agro-morphological variations. The weight of the bunch (kg), number of hands in a bunch, number of fingers in a hand, length of the finger (cm), girth of the finger (cm) and girth of the pseudostem (cm) exhibited by in vitro plants were higher than the in vivo plants.Int J Appl Sci Biotechnol, Vol 3(2): 202-209 DOI: http://dx.doi.org/10.3126/ijasbt.v3i2.12536

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JAZF1 heterozygous knockout mice show altered adipose development and metabolism

Cell & Bioscience ◽

10.1186/s13578-021-00625-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jain Jeong ◽

Soyoung Jang ◽

Song Park ◽

Wookbong Kwon ◽

Si-Yong Kim ◽

...

Keyword(s):

Adipose Tissue ◽

Knockout Mice ◽

Metabolic Disorders ◽

Adipocyte Differentiation ◽

Zinc Finger Protein ◽

Tissue Mass ◽

In Vivo Models ◽

Brown Adipose

Abstract Background Juxtaposed with another zinc finger protein 1 (JAZF1) is associated with metabolic disorders, including type 2 diabetes mellitus (T2DM). Several studies showed that JAZF1 and body fat mass are closely related. We attempted to elucidate the JAZF1 functions on adipose development and related metabolism using in vitro and in vivo models. Results The JAZF1 expression was precisely regulated during adipocyte differentiation of 3T3-L1 preadipocyte and mouse embryonic fibroblasts (MEFs). Homozygous JAZF1 deletion (JAZF1-KO) resulted in impaired adipocyte differentiation in MEF. The JAZF1 role in adipocyte differentiation was demonstrated by the regulation of PPARγ—a key regulator of adipocyte differentiation. Heterozygous JAZF1 deletion (JAZF1-Het) mice fed a normal diet (ND) or a high-fat diet (HFD) had less adipose tissue mass and impaired glucose homeostasis than the control (JAZF1-Cont) mice. However, other metabolic organs, such as brown adipose tissue and liver, were negligible effect on JAZF1 deficiency. Conclusion Our findings emphasized the JAZF1 role in adipocyte differentiation and related metabolism through the heterozygous knockout mice. This study provides new insights into the JAZF1 function in adipose development and metabolism, informing strategies for treating obesity and related metabolic disorders.

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