Faculty Opinions recommendation of Oxytocin pretreatment decreases oxytocin-induced myometrial contractions in pregnant rats in a concentration-dependent but not time-dependent manner.

The novelty of this project is to describe how chronic diabetes altered the haematological and uterine indicators in a time dependent-manner that were reversed by camel milk (CM) therapy in pregnant and non-pregnant rat models. Fifty-four female rats were divided into three groups: Placebo (N), diabetic control (DC) and diabetic treated (DT) with CM at 40 ml/kg/24 h for 90 days. A single intact male was introduced into every group for mating at day 60 of the experiment. The sample collection was undertaken at day 30 and 60 of the non-pregnant rats and at day 90 immediately after parturition for the pregnant rats. At every collection, the dam’s blood, as well as the uteri and neonatal kidneys were collected and subjected to a paraffin tissue preparation technique for a histological evaluation. The data revealed that at day 30, the uterine endo- and myometrium remained unaffected by diabetes, but at day 60, a significant reduction in the uterine indicators from diabetes was observed. However, the CM restored the uterine histology in the DT. At 90 day, chronic diabetes showed (P < 0.05) a harmful effect on the pregnant uterus which was reversed (P < 0.05) by the CM. The RBC (red blood cell) indices, platelets, and leucocyte counts were severely affected by the diabetes and protected by the CM at every point of collection. The kidney tissues of the neonate rats, delivered by the dams, in the DC presented a significant (P < 0.05) shrinkage in the cortex and glomeruli while the CM potentially reversed these changes. These results will help to understand the chronic diabetes effects on the uterus and neonate’s renal genesis, and the role of camel milk in the management of chronic pre-gestational diabetes.

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Oxytocin pre-treatment decreases oxytocin-induced myometrial contractions in pregnant rats in a dose but not time-dependent manner

Canadian Journal of Anesthesia/Journal canadien d anesthésie ◽

10.1007/bf03016473 ◽

2008 ◽

Vol 55 (S1) ◽

pp. 4753191-4753192

Author(s):

Mrinalini Balki ◽

Joyce Magalhaes ◽

Robert Parkes ◽

John Kingdom ◽

Yonge Li ◽

...

Keyword(s):

Time Dependent ◽

Dependent Manner ◽

Pregnant Rats ◽

Pre Treatment

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Conflicting Nongenomic Effects of Progesterone in the Myometrium of Pregnant Rats

International Journal of Molecular Sciences ◽

10.3390/ijms22042154 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2154

Author(s):

Katsuhiko Yasuda ◽

Aya Yoshida ◽

Hidetaka Okada

Keyword(s):

Calcium Channels ◽

Saline Solution ◽

Contractile Activity ◽

Time Dependent ◽

Dependent Manner ◽

Pregnant Rats ◽

Voltage Dependent ◽

Voltage Dependent Calcium Channels ◽

Nongenomic Effects

Recently, it has been suggested that progesterone affects the contractile activity of pregnant myometrium via nongenomic pathways; therefore, we aimed to clarify whether progesterone causes and/or inhibits pregnant myometrial contractions via nongenomic pathways. Our in vitro experiments using myometrial strips obtained from rats at 20 days of gestation revealed that progesterone caused myometrial contractions in a concentration- and time-dependent manner at concentrations up to 5 × 10−7 M; however, this effect decreased at concentrations higher than 5 × 10−5 M. Similarly, progesterone enhanced oxytocin-induced contractions up to 5 × 10−7 M and inhibited contractions at concentrations higher than 5 × 10−5 M. Conversely, progesterone did not enhance high-KCl-induced contractions but inhibited contractions in a concentration- and time-dependent manner at concentrations higher than 5 × 10−7 M. We also found that RU486 did not affect progesterone-induced contractions or the progesterone-induced inhibition of high-KCl-induced contractions; however, progesterone-induced contractions were blocked by calcium-free phosphate saline solution, verapamil, and nifedipine. In addition, FPL64176, an activator of L-type voltage-dependent calcium channels, enhanced high-KCl-induced contractions and rescued the decrease in high-KCl-induced contractions caused by progesterone. Together, these results suggest that progesterone exerts conflicting nongenomic effects on the contractions of pregnant myometrium via putative L-type voltage-dependent calcium channels.

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The Natural Flavonoid Naringenin Inhibits the Cell Growth of WilmsTumorinChildren by Suppressing TLR4/NF-κB Signaling

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620999200818155814 ◽

2020 ◽

Vol 20 ◽

Author(s):

Hongtao Li ◽

Peng Chen ◽

Lei Chen ◽

Xinning Wang

Keyword(s):

Cell Growth ◽

Western Blot ◽

Wilms Tumor ◽

Critical Role ◽

Time Dependent ◽

Luciferase Assay ◽

Dependent Manner ◽

Tlr4 Expression ◽

Protein Levels

Background: Nuclear factor kappa B (NF-κB) is usually activated in Wilms tumor (WT) cells and plays a critical role in WT development. Objective: The study purpose was to screen a NF-κB inhibitor from natural product library and explore its effects on WT development. Methods: Luciferase assay was employed to assess the effects of natural chemical son NF-κB activity. CCK-8 assay was conducted to assess cell growth in response to naringenin. WT xenograft model was established to analyze the effect of naringenin in vivo. Quantitative real-time PCR and Western blot were performed to examine the mRNA and protein levels of relative genes, respectively. Results: Naringenin displayed significant inhibitory effect on NF-κB activation in SK-NEP-1 cells. In SK-NEP-1 and G-401 cells, naringenin inhibited p65 phosphorylation. Moreover, naringenin suppressed TNF-α-induced p65 phosphorylation in WT cells. Naringenin inhibited TLR4 expression at both mRNA and protein levels in WT cells. CCK-8 staining showed that naringenin inhibited cell growth of the two above WT cells in dose-and time-dependent manner, whereas Toll-like receptor 4 (TLR4) over expression partially reversed the above phenomena. Besides, naringenin suppressed WT tumor growth in dose-and time-dependent manner in vivo. Western blot found that naringenin inhibited TLR4 expression and p65 phosphorylation in WT xenograft tumors. Conclusion: Naringenin inhibits WT development viasuppressing TLR4/NF-κB signaling

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Synthesis and Evaluation of the Antitumor Activity of Novel 1-(4-Substituted phenyl)-2-ethyl Imidazole Apoptosis Inducers In Vitro

Molecules ◽

10.3390/molecules25184293 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4293

Author(s):

Zhen-Wang Li ◽

Chun-Yan Zhong ◽

Xiao-Ran Wang ◽

Shi-Nian Li ◽

Chun-Yuan Pan ◽

...

Keyword(s):

Antitumor Activity ◽

Tumor Cells ◽

Antiproliferative Activity ◽

Antitumor Agent ◽

Positive Control ◽

Selectivity Index ◽

Time Dependent ◽

Potential Candidate ◽

Dependent Manner

Novel imidazole derivatives were designed, prepared, and evaluated in vitro for antitumor activity. The majority of the tested derivatives showed improved antiproliferative activity compared to the positive control drugs 5-FU and MTX. Among them, compound 4f exhibited outstanding antiproliferative activity against three cancer cell lines and was considerably more potent than both 5-FU and MTX. In particular, the selectivity index indicated that the tolerance of normal L-02 cells to 4f was 23–46-fold higher than that of tumor cells. This selectivity was significantly higher than that exhibited by the positive control drugs. Furthermore, compound 4f induced cell apoptosis by increasing the protein expression levels of Bax and decreasing those of Bcl-2 in a time-dependent manner. Therefore, 4f could be a potential candidate for the development of a novel antitumor agent.

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Moxifloxacin Activates the SOS Response in Mycobacterium tuberculosis in a Dose- and Time-Dependent Manner

Microorganisms ◽

10.3390/microorganisms9020255 ◽

2021 ◽

Vol 9 (2) ◽

pp. 255

Author(s):

Angelo Iacobino ◽

Giovanni Piccaro ◽

Manuela Pardini ◽

Lanfranco Fattorini ◽

Federico Giannoni

Keyword(s):

Gene Expression ◽

Mycobacterium Tuberculosis ◽

Physiological State ◽

Transcriptional Response ◽

Sos Response ◽

Resistant Mutant ◽

Time Dependent ◽

Dependent Manner ◽

Gyra Gene ◽

Drug Concentrations

Previous studies on Escherichia coli demonstrated that sub-minimum inhibitory concentration (MIC) of fluoroquinolones induced the SOS response, increasing drug tolerance. We characterized the transcriptional response to moxifloxacin in Mycobacterium tuberculosis. Reference strain H37Rv was treated with moxifloxacin and gene expression studied by qRT-PCR. Five SOS regulon genes, recA, lexA, dnaE2, Rv3074 and Rv3776, were induced in a dose- and time-dependent manner. A range of moxifloxacin concentrations induced recA, with a peak observed at 2 × MIC (0.25 μg/mL) after 16 h. Another seven SOS responses and three DNA repair genes were significantly induced by moxifloxacin. Induction of recA by moxifloxacin was higher in log-phase than in early- and stationary-phase cells, and absent in dormant bacilli. Furthermore, in an H37Rv fluoroquinolone-resistant mutant carrying the D94G mutation in the gyrA gene, the SOS response was induced at drug concentrations higher than the mutant MIC value. The 2 × MIC of moxifloxacin determined no significant changes in gene expression in a panel of 32 genes, except for up-regulation of the relK toxin and of Rv3290c and Rv2517c, two persistence-related genes. Overall, our data show that activation of the SOS response by moxifloxacin, a likely link to increased mutation rate and persister formation, is time, dose, physiological state and, possibly, MIC dependent.

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Class I HDAC inhibition improves object recognition memory consolidation through BDNF/TrkB pathway in a time-dependent manner

Neuropharmacology ◽

10.1016/j.neuropharm.2021.108493 ◽

2021 ◽

Vol 187 ◽

pp. 108493

Author(s):

Gerardo Ramirez-Mejia ◽

Elvi Gil-Lievana ◽

Oscar Urrego-Morales ◽

Ernesto Soto-Reyes ◽

Federico Bermúdez-Rattoni

Keyword(s):

Object Recognition ◽

Recognition Memory ◽

Memory Consolidation ◽

Time Dependent ◽

Class I ◽

Dependent Manner ◽

Hdac Inhibition ◽

Object Recognition Memory

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NF-κB and FosB mediate inflammation and oxidative stress in the blast lung injury of rats exposed to shock waves

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmaa179 ◽

2021 ◽

Author(s):

Hong Wang ◽

Wenjuan Zhang ◽

Jinren Liu ◽

Junhong Gao ◽

Le Fang ◽

...

Keyword(s):

Oxidative Stress ◽

Lung Injury ◽

Shock Waves ◽

Time Dependent ◽

Inflammatory Factors ◽

Control Group ◽

Dependent Manner ◽

Total Antioxidant ◽

Blast Lung Injury ◽

And Oxidative Stress

Abstract Blast lung injury (BLI) is the major cause of death in explosion-derived shock waves; however, the mechanisms of BLI are not well understood. To identify the time-dependent manner of BLI, a model of lung injury of rats induced by shock waves was established by a fuel air explosive. The model was evaluated by hematoxylin and eosin staining and pathological score. The inflammation and oxidative stress of lung injury were also investigated. The pathological scores of rats’ lung injury at 2 h, 24 h, 3 days, and 7 days post-blast were 9.75±2.96, 13.00±1.85, 8.50±1.51, and 4.00±1.41, respectively, which were significantly increased compared with those in the control group (1.13±0.64; P<0.05). The respiratory frequency and pause were increased significantly, while minute expiratory volume, inspiratory time, and inspiratory peak flow rate were decreased in a time-dependent manner at 2 and 24 h post-blast compared with those in the control group. In addition, the expressions of inflammatory factors such as interleukin (IL)-6, IL-8, FosB, and NF-κB were increased significantly at 2 h and peaked at 24 h, which gradually decreased after 3 days and returned to normal in 2 weeks. The levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase were significantly decreased 24 h after the shock wave blast. Conversely, the malondialdehyde level reached the peak at 24 h. These results indicated that inflammatory and oxidative stress induced by shock waves changed significantly in a time-dependent manner, which may be the important factors and novel therapeutic targets for the treatment of BLI.

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Influences of advanced glycosylation end products on the inner blood–retinal barrier in a co-culture cell model in vitro

Open Life Sciences ◽

10.1515/biol-2020-0067 ◽

2020 ◽

Vol 15 (1) ◽

pp. 619-628

Author(s):

Chen Yuan ◽

Ya Mo ◽

Jie Yang ◽

Mei Zhang ◽

Xuejun Xie

Keyword(s):

Electrical Resistance ◽

Cell Model ◽

Polyclonal Antibodies ◽

Time Dependent ◽

Dependent Manner ◽

Blood Retinal Barrier ◽

Advanced Glycosylation End Products ◽

End Products ◽

Advanced Glycosylation

AbstractAdvanced glycosylation end products (AGEs) are harmful factors that can damage the inner blood–retinal barrier (iBRB). Rat retinal microvascular endothelial cells (RMECs) were isolated and cultured, and identified by anti-CD31 and von Willebrand factor polyclonal antibodies. Similarly, rat retinal Müller glial cells (RMGCs) were identified by H&E staining and with antibodies of glial fibrillary acidic protein and glutamine synthetase. The transepithelial electrical resistance (TEER) value was measured with a Millicell electrical resistance system to observe the leakage of the barrier. Transwell cell plates for co-culturing RMECs with RMGCs were used to construct an iBRB model, which was then tested with the addition of AGEs at final concentrations of 50 and 100 mg/L for 24, 48, and 72 h. AGEs in the in vitro iBRB model constructed by RMEC and RMGC co-culture led to the imbalance of the vascular endothelial growth factor (VEGF) and pigment epithelial derivative factor (PEDF), and the permeability of the RMEC layer increased because the TEER decreased in a dose- and time-dependent manner. AGEs increased VEGF but lowered PEDF in a dose- and time-dependent manner. The intervention with AGEs led to the change of the transendothelial resistance of the RMEC layer likely caused by the increased ratio of VEGF/PEDF.

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