α-Conotoxin RgIA and oligoarginine R8 in the mice model alleviate long-term oxaliplatin induced neuropathy

Biochimie ◽  
2022 ◽  
Author(s):  
I.A. Dyachenko ◽  
Yu A. Palikova ◽  
V.A. Palikov ◽  
Y.V. Korolkova ◽  
V.A. Kazakov ◽  
...  
Keyword(s):  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chengxin Luo ◽  
Li Wang ◽  
Guixian Wu ◽  
Xiangtao Huang ◽  
Yali Zhang ◽  
...  

Abstract Background Mobilization failure may occur when the conventional hematopoietic stem cells (HSCs) mobilization agent granulocyte colony-stimulating factor (G-CSF) is used alone, new regimens were developed to improve mobilization efficacy. Multiple studies have been performed to investigate the efficacy of these regimens via animal models, but the results are inconsistent. We aim to compare the efficacy of different HSC mobilization regimens and identify new promising regimens with a network meta-analysis of preclinical studies. Methods We searched Medline and Embase databases for the eligible animal studies that compared the efficacy of different HSC mobilization regimens. Primary outcome is the number of total colony-forming cells (CFCs) in per milliliter of peripheral blood (/ml PB), and the secondary outcome is the number of Lin− Sca1+ Kit+ (LSK) cells/ml PB. Bayesian network meta-analyses were performed following the guidelines of the National Institute for Health and Care Excellence Decision Support Unit (NICE DSU) with WinBUGS version 1.4.3. G-CSF-based regimens were classified into the SD (standard dose, 200–250 μg/kg/day) group and the LD (low dose, 100–150 μg/kg/day) group based on doses, and were classified into the short-term (2–3 days) group and the long-term (4–5 days) group based on administration duration. Long-term SD G-CSF was chosen as the reference treatment. Results are presented as the mean differences (MD) with the associated 95% credibility interval (95% CrI) for each regimen. Results We included 95 eligible studies and reviewed the efficacy of 94 mobilization agents. Then 21 studies using the poor mobilizer mice model (C57BL/6 mice) to investigate the efficacy of different mobilization regimens were included for network meta-analysis. Network meta-analyses indicated that compared with long-term SD G-CSF alone, 14 regimens including long-term SD G-CSF + Me6, long-term SD G-CSF + AMD3100 + EP80031, long-term SD G-CSF + AMD3100 + FG-4497, long-term SD G-CSF + ML141, long-term SD G-CSF + desipramine, AMD3100 + meloxicam, long-term SD G-CSF + reboxetine, AMD3100 + VPC01091, long-term SD G-CSF + FG-4497, Me6, long-term SD G-CSF + EP80031, POL5551, long-term SD G-CSF + AMD3100, AMD1300 + EP80031 and long-term LD G-CSF + meloxicam significantly increased the collections of total CFCs. G-CSF + Me6 ranked first among these regimens in consideration of the number of harvested CFCs/ml PB (MD 2168.0, 95% CrI 2062.0−2272.0). In addition, 7 regimens including long-term SD G-CSF + AMD3100, AMD3100 + EP80031, long-term SD G-CSF + EP80031, short-term SD G-CSF + AMD3100 + IL-33, long-term SD G-CSF + ML141, short-term LD G-CSF + ARL67156, and long-term LD G-CSF + meloxicam significantly increased the collections of LSK cells compared with G-CSF alone. Long-term SD G-CSF + AMD3100 ranked first among these regimens in consideration of the number of harvested LSK cells/ml PB (MD 2577.0, 95% CrI 2422.0–2733.0). Conclusions Considering the number of CFC and LSK cells in PB as outcomes, G-CSF plus AMD3100, Me6, EP80031, ML141, FG-4497, IL-33, ARL67156, meloxicam, desipramine, and reboxetine are all promising mobilizing regimens for future investigation.


Author(s):  
Azadeh Mesripour ◽  
Neda Rabian ◽  
Afsaneh Yegdaneh

Abstract Background Seaweeds are a famous traditional food resource in some countries containing different types of secondary metabolites. These marine organisms have shown different biological activities. The aim of this study was to investigate the effects of hexane and methanol extracts of Sargassum plagyophylum on depression. Methods Sargassum plagyophylum was collected from Persian Gulf. The plant was extracted by maceration with methanol-ethyl acetate solvent. The extract was evaporated and partitioned by hexane and methanol solvents. The two partitions were administered i.p. to male mice either a single dose or for 7 days. Depression was evaluated by the forced swimming test (FST) which higher immobility time indicates depressive-like behavior. Results The immobility time during FST decreased significantly by all the doses of the hexane partitions (notably 40 mg/kg; 10 s ± 2 vs. 114 s ± 12 control group). However, only the lowest dose (20 mg/kg) of the methanol partition reduced immobility time during FST (23 s ± 8, p<0.001). Following the long term administration both of the partitions reduced the immobility time in FST (hexane 27 s ± 11, methanol 70 s ± 14, p<0.05 vs. control 140 s ± 14). Conclusion The hexane partition showed antidepressant effects not only by long-term administration but also by the single dose during FST. The 7 days therapy with methanol partition also induced antidepressant behavior, but only the lowest single dose reduced immobility in FST. The methanol partitions possibly have certain substance that interfered with behavior in the FST. Therefore, S. plagyophylum should be considered for further antidepressant studies.


2020 ◽  
Vol 36 (2) ◽  
pp. 223-237
Author(s):  
Hojat Anbara ◽  
Mohammad Taghi Sheibani ◽  
Mazdak Razi ◽  
Mehdi Kian

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2431-2431 ◽  
Author(s):  
Tony Peled ◽  
Hadas Shoham ◽  
Dorit Aschengrau ◽  
Dima Yackoubov ◽  
Gabi Frei ◽  
...  

Abstract Abstract 2431 Poster Board II-408 Nicotinamide (NAM), is a form of VitB3 that recognized and inhibits SIRT1, the human ortholog of the yeast Sir2 class III NAD+-dependent histone deacetylase. We have previously demonstrated that NAM inhibits in vitro differentiation and enhances expansion, migration, homing and NOD/SCID engraftment efficacy of cord blood (CB)-derived CD34+ cells cultured with cytokines. In the current study, the in vivo function of ex vivo cultured cells with NAM was tested in a congenic mice model (BALB/C, CD45.1/CD45.2) for BM transplantation. Purified CD117+ BM cells from BALB/C CD45.1 mice were cultured with a combination of 4 cytokines (FLT3, SCF, TPO, IL-6, 50 ng/ml each), with and without 0.5mM NAM for three weeks. Numbers of CFUc, CD117+ and CD117+Lin- cells were significantly (p &lt; 0.05) higher in cultures treated with NAM as compared with cultured treated with cytokines alone. Non-cultured, freshly purified CD117+ cells (1000 and 2500 cells/mice) and their total progeny following expansion with or without NAM were transplanted into ablated (1000 Rad) CD45.2 mice (n = 10/cohort), 24h post irradiation (Fig 1). Three months post transplantation, all the mice in the control group (non-transplanted) died. The percent survival of mice transplanted with cells cultured with cytokines and NAM was remarkably higher over the survival of mice in the cohort transplanted with cells cultured with cytokines alone or non-cultured cells (Fig 1). FACS analysis (CD45.1-donor / CD45.2-host) of peripheral blood from mice transplanted with NAM cultured cells show 80% donor cell chimerism (CD45.1), 3 and 6 months post transplantation. Percent of donor derived Gr-1+ and CD3+ cells were similar in mice transplanted with non-cultured or NAM cultured cells. Percentages of donor cell chimerism (CD45.1) in secondary mice transplanted with total BM cells derived from primary recipients originally transplanted with non-cultured and NAM cultured cells were 47 and 73, respectively, 6 weeks after the secondary transplantation. In a different experiment, to follow time to engraftment during the first month post transplantation, mice transplanted with non-cultured cells or cells cultured with cytokines and NAM (n = 10/cohort) were bled at weekly intervals and peripheral blood samples were counted for WBC and analyzed by the FACS to determine donor cell chimerism and lineage engraftment. The results show accelerated engraftment (Fig 2) and higher levels of donor cell chimerism (Fig 3) in the cohort transplanted with NAM cultured cells relative to the cohort transplanted with non-cultured cells. Number of granulocytes, T, NK and B cells during the first month post transplant were also significantly (p&lt;0.05) higher in mice transplanted with cells cultured with cytokines and NAM relative to their levels in mice transplanted with non-cultured cells. The results obtained in the congenic mice model for BMT suggest that NAM promotes expansion in ex vivo cultures of short and long-term repopulating cells, as demonstrated by accelerated donor derived engraftment during the first month post transplantation, higher survival of mice, sustained donor cell chimerism 6 month post transplantation and successful reconstitution of secondary recipients. NAM is thus a novel molecule that may be used to stimulate and expand hematopoietic repopulating cells, fasten post transplant engraftment and hopefully improve transplantation outcome. Current studies are designed to elucidate NAM mode of action. Fig 1: Three month survival Fig 1:. Three month survival Fig 2: Short-term Engrafoment Fig: 3 Percentage of Donor Chimerism Fig 2:. Short-term Engrafoment Fig: 3 Percentage of Donor Chimerism Disclosures: Peled: Gamida-Cell: Employment, Equity Ownership. Shoham:Gamida Cell: Employment. Aschengrau:Gamida Cell: Employment. Yackoubov:Gamida Cell: Employment. Frei:Gamida Cell: Employment. Nagler:Gamida Cell: Arnon Nagler, Consultancy. Peled:Gamida Cell: Consultancy.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Beibei Zhang ◽  
Xiaoying Wu ◽  
Jing Li ◽  
An Ning ◽  
Bo Zhang ◽  
...  

Abstract Background Hepatic schistosomiasis, a chronic liver injury induced by long-term Schistosoma japonicum (S. japonicum) infection, is characterized by egg granulomas and fibrotic pathology. Hepatic progenitor cells (HPCs), which are nearly absent or quiescent in normal liver, play vital roles in chronic and severe liver injury. But their role in the progression of liver injury during infection remains unknown. Methods In this study, the hepatic egg granulomas, fibrosis and proliferation of HPCs were analyzed in the mice model of S. japonicum infection at different infectious stages. For validating the role of HPCs in hepatic injury, tumor necrosis factor-like-weak inducer of apoptosis (TWEAK) and TWEAK blocking antibody were used to manipulate the proliferation of HPCs in wild-type and IL-33−/− mice infected with S. japonicum. Results We found that the proliferation of HPCs was accompanied by inflammatory granulomas and fibrosis formation. HPCs expansion promoted liver regeneration and inhibited inflammatory egg granulomas, as well as the deposition of fibrotic collagen. Interestingly, the expression of IL-33 was negatively associated with HPCs’ expansion. There were no obvious differences of liver injury caused by infection between wild-type and IL-33−/− mice with HPCs’ expansion. However, liver injury was more attenuated in IL-33−/− mice than wild-type mice when the proliferation of HPCs was inhibited by anti-TWEAK. Conclusions Our data uncovered a protective role of HPCs in hepatic schistosomiasis in an IL-33-dependent manner, which might provide a promising progenitor cell therapy for hepatic schistosomiasis.


2021 ◽  
Author(s):  
Joana I. Gomes ◽  
Joao Jesus ◽  
Renata Macau ◽  
Joana Goncalves-Ribeiro ◽  
Sara Pinto ◽  
...  

It is known that astrocytes, by the Ca2+-dependent release of gliotransmitters, which then act in pre- and post-synaptic receptors, modulate neuronal transmission and plasticity. Thus, hippocampal θ-burst long-term potentiation (LTP), which is a form of synaptic plasticity, can be modulated by astrocytes, since these cells release gliotransmitters that are crucial for the maintenance of LTP. Therefore, in this study, we hypothesized that the facilitatory action of BDNF upon LTP would involve astrocytes. To address that possibility, fEPSP recordings were performed in CA3-CA1 area of hippocampal slices from three different experimental models: Wistar rats where astrocytic metabolism was selectively reduced by a gliotoxin, the DL-fluoricitric acid (FC), IP3R2-/- mice model, which lack IP3R2-mediated Ca2+-signaling in astrocytes and dn-SNARE transgenic mice, in which the SNARE-dependent release of gliotransmitters. For the three models we observed that the astrocytic impairment abolished the excitatory BDNF effect upon hippocampal LTP, only while inducing LTP with a mild θ-burst stimulation paradigm. The present data shows for the first time that astrocytes play an active role in the facilitatory action of BDNF upon LTP, depending on stimulation paradigm.


2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Hwang‐Yong Choi ◽  
Bou‐Hee Kang ◽  
Kyoung‐Soo HA ◽  
Mee Sook Lee ◽  
Young‐Cheul Kim ◽  
...  

2019 ◽  
Vol 65 (5) ◽  
pp. 347-355 ◽  
Author(s):  
Xiangzhi Jiang ◽  
Wei Lin ◽  
Yuanyuan Cheng ◽  
Dongming Wang

Background Glutamatergic system has been known to play a role in the pathogenesis of major depression disorder by inducing N-methyl-d-aspartate receptor-dependent long-term depression (LTD) or metabotropic glutamate receptors (mGluR)-dependent LTD. Here, we characterized the LTD in a chronic social defeat stress (CSDS)-induced depressive mouse model. Methods CSDS was used to induce the depressive-like behaviors in C57BL/6 male mice, which were assessed using sucrose preference test and social interaction test. The synaptic strength including LTD and long-term potentiation (LTP) induced by paired-pulse low frequency stimulation (PP-LFS) was measured using whole-cell recording technique. Results CSDS induced depressive-like behaviors and facilitated PP-LFS-induced LTD in hippocampal CA3-CA1 pathway in the susceptible mice. Interestingly, mGluR5 but not N-methyl-d-aspartate receptor mediated the PP-LFS-induced LTD. In addition, mGluR5 agonist dihydroxyphenylglycine promoted PP-LFS-induced LTD specifically in susceptible mice, which was diminished by activating the BDNF/TrkB signaling pathway. Conclusions Our results suggest that mGluR5-dependent LTD might be responsible for the development of depressive-like behaviors in CSDS-induced depression mice model.


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