scholarly journals Effect ofLactobacillus reuterion intestinal microflora and immune parameters: involvement of sex differences

2018 ◽  
Author(s):  
Jiayi He ◽  
Lingyi Wu ◽  
Zhen Wu ◽  
Daodong Pan ◽  
Yuxing Guo ◽  
...  
Keyword(s):  
Relative Abundance ◽  
Dose Group ◽  
Low Dose ◽  
Probiotic Strain ◽  
Fecal Microbiota ◽  
Shannon Index ◽  
Control Group ◽  
Immune Parameters

AbstractProbiotic candidateL. reuteriwas screened out forin vivoexperiments based on a relatively higher gastrointestinal tolerance and moderate adhesiveness. As results shown inin-vivoexperiments, a significantly higher level of IL-12 at low-dose group was found both in females and males. Higher levels of T-lymphocytes were also observed in females compared to control group, however, males displayed a reduction expcept for CD8-positive cells in ileum. In comparison to the control group, the relative abundance of phylotypes in the phylumBacteroidetes(genus ofBacteroides,Prevotella) andFirmicutes(genus ofClostridiumIV) exihibited a reserve shift between sexes afterL. reuteriintervened. Meanwhile, the relative abundance of several taxa (Acetobacteroides,Lactobcaillus,bacillus) also differed markedly in sexes at low-dose group, together with microbiota diversity, as indicated by Shannon index.ImportanceSexual dimorphism has triggered researchers’ attention. However, the relationship between immune parameters and gut microbiota caused byLactobacillusat different dosage are not fully elucidated. In present research, the possible probiotic role ofL. reuteriDMSZ 8533 on immunomodulation and effect on fecal microbiota composition were investigated. Our findings demonstrate the importance of L. reuteri DMSZ 8533 as a potential probiotic strain with an immunomodulatory effect, which also alters the microflora composition depending on the sex of the host.

scholarly journals Preliminary Study of Quercetin Affecting the Hypothalamic-Pituitary-Gonadal Axis on Rat Endometriosis Model

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Yang Cao ◽  
Meng-fei Zhuang ◽  
Ying Yang ◽  
Shu-wu Xie ◽  
Jin-gang Cui ◽  
...  
Keyword(s):  
Western Blot ◽  
Dose Group ◽  
Low Dose ◽  
Control Group ◽  
Expression Levels ◽  
Model Control ◽  
Model Control Group ◽  
Preliminary Study ◽  
Ectopic Endometrium

In this study, the endometriosis rats model was randomly divided into 6 groups: model control group, ovariectomized group, Gestrinone group, and quercetin high/medium/low dose group. Rats were killed after 3 weeks of administration. The expression levels of serum FSH and LH were detected by ELISA. The localizations and quantities of ERα, ERβ, and PR were detected by immunohistochemistry and western blot. The results showed that the mechanism of quercetin inhibiting the growth of ectopic endometrium on rat endometriosis model may be through the decreasing of serum FSH and LH levels and then reducing local estrogen content to make the ectopic endometrium atrophy. Quercetin can decrease the expression of ERα, ERβ, and PR in hypothalamus, pituitary, and endometrium, thereby inhibiting estrogen and progesterone binding to their receptors to play the role of antiestrogen and progesterone.

scholarly journals Exogenous Fecal Microbial Transplantation Alters Fearfulness, Intestinal Morphology, and Gut Microbiota in Broilers

2021 ◽  
Vol 8 ◽  
Author(s):  
Chao Yan ◽  
Jinlong Xiao ◽  
Zhiwei Li ◽  
Hao Liu ◽  
Xinjie Zhao ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Behavioral Plasticity ◽  
Fecal Microbiota Transplantation ◽  
Muscle Layer ◽  
Fecal Microbiota ◽  
Intestinal Morphology ◽  
Control Group ◽  
Muscularis Mucosa

Fecal microbiota transplantation (FMT) documented transplanting a donor fecal sample to a receipt individual for a desired physiologic effect. However, whether the gut microbiota construction, intestinal maturation, and behavioral plasticity are modulated by FMT during the early life of broilers is waiting for verification. To evaluate the role of transfer of fecal microbiota from aged broilers donor (BD) to another individual, 96 birds were equally divided into a check (CK, control) group and a broiler recipient (BR) group. FMT was conducted daily from 5 to 12 days of age to determine the future impact on body weight, behavior, intestinal development, and gut microbiota. Results indicated that fearfulness in the CK group was higher than the BR group in both the behavioral tests (p < 0.05). The muscularis mucosa, thickness of muscle layer, and thickness of serous membrane layer in the BR group were higher compared with those of the CK group in the jejunum (p < 0.05). In the gut microbiota, Shannon diversity showed no difference, while beta diversity presented a difference in principal coordination analysis (PCoA) between the CK and BR groups. At the phylum level, the relative abundance of Lentisphaerae in the CK group was lower than the BR (p = 0.052) and BD (p = 0.054) groups. The relative abundance of Tenericutes in the BD group was higher than that in the CK and BR groups (p < 0.05). At the genus level, Megamonas in the CK group was higher than the BR (p = 0.06) and BD (p < 0.05) groups. In the BR group, the functional capabilities of microbial communities analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were increased in the glutamatergic synapse and N-glycan biosynthesis pathways in comparison with the CK and BD groups (p < 0.05). Some characteristics of gut microbiota in the donor chickens could be transferred to recipient chickens by FMT. In conclusion, exogenous FMT as a probiotic-like administration might be an efficient way to improve the physiology and behavior of chickens. Notably, the role of microbiota for various individuals and periods remains undefined, and the mechanism of microbiota on behaviors still needs further investigation.

scholarly journals Impacts of Ceftriaxone Exposure During Pregnancy on Maternal Gut and Placental Microbiota and Its Influence on Maternal and Offspring Immunity in Mice (OR01-04-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ruyue Cheng ◽  
Fang He
Keyword(s):  
Relative Abundance ◽  
Inflammatory Responses ◽  
Fecal Microbiota ◽  
Control Group ◽  
Funding Sources ◽  
Clone Sequencing ◽  
Rrna Sequencing ◽  
Viable Bacteria ◽  
Exposure During Pregnancy

Abstract Objectives This study aimed to investigate whether antibiotic exposure during pregnancy could alter maternal gut and placental microbiota, and consequently affect the immunity of both mother and offspring. Methods Pregnant BALB/c mice (n = 24) were gavaged with ceftriaxone from gestation day 13 to delivery. Both dams and pups were then sacrificed immediately after delivery. Spleen, placental, and fecal samples were collected from the tested dams, and blood samples were collected from both the dams and their pups. The microbiota in the feces and placenta of the dams were comprehensively analyzed using16S rRNA sequencing. Furthermore, viable bacteria in the placentas of dams were also isolated by plate cultivation then taxonomically identified in detail by clone sequencing. Serum cytokines collected from dams and pups were quantitatively profiled using Luminex. Results The maternal spleen index was significantly lower and the offspring serum interleukin-6 (IL-6) levels were significantly higher in ceftriaxone-treated mice compared with the control group. The diversity of maternal fecal microbiota was significantly lower in ceftriaxone-treated mice. The relative abundance of Bacteriodetes was significantly lower, while the relative abundance of Tenericutes was significantly higher in ceftriaxone-treated mothers. However, no significant differences in placental microbiota communities or metagenomic activity were found between the control group and the ceftriaxone-treated mice. Conclusions These results indicated that ceftriaxone exposure in pregnancy could dramatically alter maternal intestinal microbiota, which affected the immunity of the mothers and their offspring, characteristically by enhanced pro-inflammatory responses. The results from the present study also indicated that the placenta might harbor its own microbes, which may not be affected by environmental factors, such as oral administration of ceftriaxone during pregnancy. Further studies should be focused on the role of these microbes in the health of the fetus and infants. Funding Sources This work was supported by the National Natural Science Foundation of China (Grant number 81372982).

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

scholarly journals Spatio-temporal biodistribution of 89Zr-oxine labeled huLym-1-A-BB3z-CAR T-cells by PET imaging in a preclinical tumor model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naomi S. Sta Maria ◽  
Leslie A. Khawli ◽  
Vyshnavi Pachipulusu ◽  
Sharon W. Lin ◽  
Long Zheng ◽  
...  
Keyword(s):  
T Cells ◽  
Real Time ◽  
Pet Imaging ◽  
Dose Group ◽  
Low Dose ◽  
High Dose ◽  
Car T Cells ◽  
Nsg Mice ◽  
Car T

AbstractQuantitative in vivo monitoring of cell biodistribution offers assessment of treatment efficacy in real-time and can provide guidance for further optimization of chimeric antigen receptor (CAR) modified cell therapy. We evaluated the utility of a non-invasive, serial 89Zr-oxine PET imaging to assess optimal dosing for huLym-1-A-BB3z-CAR T-cell directed to Lym-1-positive Raji lymphoma xenograft in NOD Scid-IL2Rgammanull (NSG) mice. In vitro experiments showed no detrimental effects in cell health and function following 89Zr-oxine labeling. In vivo experiments employed simultaneous PET/MRI of Raji-bearing NSG mice on day 0 (3 h), 1, 2, and 5 after intravenous administration of low (1.87 ± 0.04 × 106 cells), middle (7.14 ± 0.45 × 106 cells), or high (16.83 ± 0.41 × 106 cells) cell dose. Biodistribution (%ID/g) in regions of interests defined over T1-weighted MRI, such as blood, bone, brain, liver, lungs, spleen, and tumor, were analyzed from PET images. Escalating doses of CAR T-cells resulted in dose-dependent %ID/g biodistributions in all regions. Middle and High dose groups showed significantly higher tumor %ID/g compared to Low dose group on day 2. Tumor-to-blood ratios showed the enhanced extravascular tumor uptake by day 2 in the Low dose group, while the Middle dose showed significant tumor accumulation starting on day 1 up to day 5. From these data obtained over time, it is apparent that intravenously administered CAR T-cells become trapped in the lung for 3–5 h and then migrate to the liver and spleen for up to 2–3 days. This surprising biodistribution data may be responsible for the inactivation of these cells before targeting solid tumors. Ex vivo biodistributions confirmed in vivo PET-derived biodistributions. According to these studies, we conclude that in vivo serial PET imaging with 89Zr-oxine labeled CAR T-cells provides real-time monitoring of biodistributions crucial for interpreting efficacy and guiding treatment in patient care.

scholarly journals Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Pure Water ◽  
Intervention Group ◽  
Control Group ◽  
High Dose ◽  
Endocrine Glands ◽  
Blood Samples ◽  
High Doses ◽  
The Brain

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

Acute adenosine preconditioning is mediated by p38 MAPK activation in discrete subcellular compartments

2005 ◽  
Vol 288 (3) ◽  
pp. H1359-H1366 ◽  
Author(s):  
Cherry Ballard-Croft ◽  
Gentian Kristo ◽  
Yukihiro Yoshimura ◽  
Easton Reid ◽  
Byron J. Keith ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Adenosine Receptor ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fraction ◽  
Control Group ◽  
Mapk Activation ◽  
Subcellular Compartments ◽  
Sb 203580

Although acute adenosine preconditioning (PC) is well established, the signaling pathways mediating this cardioprotection remain unclear. Because adenosine receptor agonists activate p38 MAPK and this kinase has been implicated in ischemic and pharmacological PC, the purpose of this study was to determine the role of p38 MAPK in acute adenosine receptor PC. The role of p38 MAPK activation in discrete subcellular compartments during ischemia-reperfusion was also determined. The following groups were used in an in vivo rat ischemia-reperfusion model: 1) control (10% DMSO iv), 2) the A1/A2a adenosine receptor AMP-579 (50 μg/kg iv), 3) AMP-579 + the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 μg/kg iv), 4) AMP-579 + the p38 MAPK inhibitor SB-203580 (1 mg/kg iv), and 5) SB-203580 alone. p38 MAPK activation was measured by Western blot analysis in cytosolic, mitochondrial, membrane, and nuclear/myofilament fractions obtained from hearts at preischemic, ischemic, and reperfusion time points. A significant reduction in infarct size was observed with AMP-579 PC, an effect blocked by DPCPX or SB-203580 pretreatment. AMP-579 treatment was associated with a significant increase in p38 MAPK activation in the nuclear/myofilament fraction before ischemia, whereas no activation of this kinase occurred during ischemia or reperfusion. In contrast, p38 MAPK was activated in the mitochondrial fraction by ischemia and in the cytosolic, mitochondrial, and membrane fractions by reperfusion in the control group. SB-203580 blocked the AMP-579-induced increase in phosphorylation of the downstream p38 substrate activating transcription factor-2. These results suggest a role for p38 MAPK activation in discrete subcellular compartments in acute adenosine A1 receptor PC.

scholarly journals Comparison of the in-vivo Effect of Two Tranexamic Acid Doses on Fibrinolysis Parameters in Adults Undergoing Valvular Cardiac Surgery with Cardiopulmonary Bypass - A Pilot Investigation

2020 ◽  
Author(s):  
Zhen-feng ZHOU ◽  
Wen Zhai ◽  
Li-na YU ◽  
Kai SUN ◽  
Li-hong SUN ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Placebo Group ◽  
Cardiopulmonary Bypass ◽  
Plasminogen Activator ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
Pai 1

Abstract Background: The blood saving efficacy of TXA in cardiac surgery has been proved in several studies, but TXA dosing regimens were varied in those studies. Therefore, we performed this study to investigate if there is a dose dependent in-vivo effect of TXA on fibrinolysis parameters by measurement of fibrinolysis markers in adults undergoing cardiac surgery with CPB, which has not been systematically elucidated.Methods: A double-blind, randomized, controlled prospective trial was conducted from February 11, 2017 to May 05, 2017. Thirty patients undergoing cardiac valve surgery were identified and randomly divided into a placebo group, low-dose group and high-dose group by 1: 1: 1. Fibrinolysis parameters were measured by plasma levels of D-Dimers, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), plasmin-antiplasmin complex (PAP), tissue plasminogen activator (tPA) and thrombomodulin (TM). Those proteins were measured at five different sample times: preoperatively before the TXA injection (T1), 5 min after the TXA bolus (T2), 5 min after the initiation of CPB (T3), 5 min before the end of CPB (T4) and 5 min after the protamine administration (T5). A Thrombelastography (TEG) and standard coagulation test were also performed.Results: Compared with the control group, the level of the D-Dimers decreased in the low-dose and high-dose groups when the patients arrived at the ICU and on the first postoperative morning. Over time, the concentrations of PAI-1, TAFI, and TM, but not PAP and tPA, showed significant differences between the three groups (p <0.05). Compared with the placebo group, the plasma concentrations of PAI-1 and TAFI decreased significantly at the T3 and T4 (p <0.05); TAFI concentrations also decreased at the T5 in low-dose group (p <0.05). Compared with the low-dose group, the concentration of TM increased significantly at the T4 in high-dose group. No significant differences were observed in the levels of the coagulation proteins at any points between the groups.Conclusions: The vivo effect of low dose TXA is equivalent to high dose TXA on fibrinolysis parameters in adults undergoing valvular cardiac surgery with cardiopulmonary bypass, and we recommend a low dose TXA regimen for those patients.Clinical trial number and registry URL: ChiCTR-IPR-17010303; http://www.chictr.org.cn, Principal investigator: Zhen-feng ZHOU, Date of registration: January 1, 2017.

scholarly journals The Role of Serotonin in MDMA Self-administration in Rats

2021 ◽  
Author(s):  
◽  
Sarah Bradbury
Keyword(s):  
Negative Impact ◽  
Primary Objective ◽  
Repeated Exposure ◽  
Lesion Group ◽  
Control Group ◽  
Self Administration ◽  
Initial Exposure ◽  
Abstinence Period

<p>Rationale: The profile of acquisition for MDMA self-administration differs from that of amphetamine and cocaine self-administration in that fewer rats meet an acquisition criterion and the latency to acquisition is longer. These characteristics of MDMA self-administration may be because it preferentially stimulates serotonin (5HT) release whereas self-administration has generally been attributed to enhanced dopamine (DA) neurotransmission. Because 5HTergic agonists are not self-administered and increased synaptic 5HT decreased self-administration of other drugs, MDMA self-administration may be initially inhibited by the pronounced 5HT response. Accordingly, the acquisition of MDMA self-administration might proceed as a result of deficits in 5HT neurotransmission and a corresponding disinhibition of DA neurotransmission.  Objective: The primary objective was to determine the role of 5HT in the acquisition and maintenance of MDMA self-administration.  Methods: MDMA-induced increases of extracellular 5HT and DA and their primary metabolites were measured in the DA terminal regions of the nucleus accumbens (NAc) using in vivo microdialysis, prior to the commencement of MDMA self-administration. The relationship between MDMA-induced increases of neurotransmitter levels and the acquisition of MDMA self-administration was assessed. A subsequent study depleted brain 5HT by administering the neurotoxin, 5,7 – DHT, or vehicle into the lateral ventricle of the left hemisphere, prior to the commencement of MDMA self-administration. The proportion of subjects that acquired MDMA self-administration and the latency to acquire MDMA self-administration was compared for the two groups. In order to determine effects of MDMA self-administration on 5HT and DA responses, behaviours that reflect 5HT and/or DA neurotransmission were measured 5 or 14 days after self-administration of 165 mg/kg MDMA, or 14 days after vehicle self-administration. These time periods were chosen because they reflect a period of 5HT deficits (5 days) and recovery (14 days). Finally, the effect of abstinence on MDMA self-administration was measured.  Results: The MDMA-induced increase of extracellular 5HT was significantly lower for the group that subsequently acquired MDMA self-administration but the MDMA-induced increase in DA was not different from the group that failed to acquire self-administration. 5, 7-DHT administration significantly decreased tissue levels of 5HT, but not DA. MDMA self-administration was facilitated by the lesion; 100% of the lesion group acquired MDMA self-administration, whereas only 50% of the control group acquired self-administration. Five days following the last MDMA self-administration session, DAergic behaviours were enhanced and 5HTergic behaviours were reduced relative to the control group. These differences in 5HTergic mediated behaviours were not apparent 14 days after self-administration but the DAergic behaviours remained elevated. The pattern of self-administration did not differ as a function of the length of the abstinence period.  Conclusions: The variability in acquisition of MDMA self-administration was related to the magnitude of the 5HT response evoked by initial exposure to MDMA. These findings suggested that predisposing differences in the 5HT response might explain differences in the variability in acquisition of MDMA self-administration. The negative impact of 5HT on the acquisition of MDMA self-administration was clearly demonstrated following a 5, 7-DHT lesion. Thus, 5HT limits the development of MDMA self-administration. With repeated exposure to self-administered MDMA, behavioural responses indicative of 5HT activation were reduced whereas behavioural indices of DA activation were increased. The maintenance of MDMA self-administration was comparable regardless of whether there was a forced abstinence period or not. These data are consistent with the hypotheses that 5HT is inhibitory to the acquisition, but not the maintenance, of MDMA self-administration. Rather, the maintenance of self-administration might reflect sensitised DA responses that became apparent following repeated exposure.</p>

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