scholarly journals Pretreatment with Pancaspase Inhibitor (Z-VAD-FMK) Delays but Does Not Prevent Intraperitoneal Heat-Killed Group B Streptococcus-Induced Preterm Delivery in a Pregnant Mouse Model

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Ozlem Equils ◽  
Chantelle Moffatt-Blue ◽  
Tomo-o Ishikawa ◽  
Charles F. Simmons ◽  
Vladimir Ilievski ◽  
...  
Keyword(s):  
Preterm Delivery ◽  
Group B Streptococcus ◽  
Pregnant Mouse ◽  
Tunel Staining ◽  
Pregnant Mice ◽  
Group B ◽  
Induced Apoptosis ◽  
In Vitro Treatment

Caspases and apoptosis are thought to play a role in infection-associated preterm-delivery. We have shown that in vitro treatment with pancaspase inhibitor Z-VAD-FMK protects trophoblasts from microbial antigen-induced apoptosis.Objective. To examine whether in vivo administration of Z-VAD-FMK would prevent infection-induced preterm-delivery.Methods. We injected 14.5 day-pregnant-mice with heat-killed group B streptococcus (HK-GBS). Apoptosis within placentas and membranes was assessed by TUNEL staining. Calpain expression and caspase-3 activation were assessed by immunohistochemistry. Preterm-delivery was defined as expulsion of a fetus within 48 hours after injection.Results. Intrauterine (i.u.) or intraperitoneal (i.p.) HK-GBS injection led to preterm-delivery and induced apoptosis in placentas and membranes at 14 hours. The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta. Treatment with the specific caspase inhibitor Z-VAD-FMK (i.p.) prior to HK-GBS (i.p.) delayed but did not prevent preterm-delivery.Conclusion. Caspase-dependent apoptosis appears to play a role in the timing but not the occurrence of GBS-induced preterm delivery in the mouse.

scholarly journals Periplocin Extracted from Cortex Periplocae Induced Apoptosis of Gastric Cancer Cells via the ERK1/2-EGR1 Pathway

2016 ◽  
Vol 38 (5) ◽  
pp. 1939-1951 ◽  
Author(s):  
Lei Li ◽  
Lian-Mei Zhao ◽  
Su-li Dai ◽  
Wen-Xuan Cui ◽  
Hui-Lai Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Induced Apoptosis

Background/Aims: Periplocin is extracted from the traditional herbal medicine cortex periplocae, which has been reported to suppress the growth of cancer cells. However, little is known about its effect on gastric cancer cells. Methods: Gastric cancer cells were treated with periplocin, and cell viability was assessed using MTS assay. Flow cytometry and TUNEL staining were performed to evaluate apoptosis, and protein expression was examined by western blotting. Microarray analysis was used to screen for changes in related genes. Results: We found that periplocin had an inhibitory effect on gastric cancer cell viability in a dose-dependent manner. Periplocin inhibited cell viability via the ERK1/2-EGR1 pathway to induce apoptosis. Periplocin also inhibited the growth of tumor xenografts and induced apoptosis in vivo. Conclusion: Our results show that periplocin inhibits the proliferation of gastric cancer cells and induces apoptosis in vitro and in vivo, indicating its potential to be used as an antitumor drug.

scholarly journals 767 TYPE 14 PNEUMOCOCCAL ANTISERA IS OPSONIC IN VITRO AND PROTECTIVE IN VIVO FOR GROUP B STREPTOCOCCUS TYPE III

1978 ◽  
Vol 12 ◽  
pp. 491-491 ◽  
Author(s):  
Gerald W Fischer ◽  
George H Lowell ◽  
Martin H Crumrine ◽  
James W Bass
Keyword(s):  
Group B Streptococcus ◽  
Type Iii ◽  
Group B

scholarly journals O-Acetylation of sialic acid on Group B Streptococcus inhibits neutrophil suppression and virulence

2010 ◽  
Vol 428 (2) ◽  
pp. 163-168 ◽  
Author(s):  
Shannon Weiman ◽  
Satoshi Uchiyama ◽  
Feng-Ying C. Lin ◽  
Donald Chaffin ◽  
Ajit Varki ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Group B Streptococcus ◽  
In Vivo Assays ◽  
Group B

GBS (Group B Streptococcus) requires capsular Sia (sialic acid) for virulence and partially modifies this sugar by O-acetylation. In the present paper we describe serotype-specific patterns of GBS Sia O-acetylation that can be manipulated by genetic and biochemical means. In vitro and in vivo assays demonstrate that this subtle modification attenuates GBS Sia-mediated neutrophil suppression and animal virulence.

Abstract 629 Secreted Frizzled Related Protein 2 Protects Cells from Apoptosis by Blocking the Effect of Canonical Wnt3a

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Zhongyan Zhang ◽  
Arjun Deb ◽  
Alok Pachori ◽  
Wei He ◽  
Jian Guo ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Solid Phase ◽  
Tunel Staining ◽  
Beta Catenin ◽  
Related Protein ◽  
Wnt Ligands ◽  
Apoptotic Effect ◽  
Induced Apoptosis

We have demonstrated that mesenchymal stem cells (MSCs) overexpressing the survival gene Akt can confer paracrine protection to ischemic myocytes both in vivo and in vitro through the release of secreted frizzled related protein 2 (Sfrp2). However, the mechanisms mediating these effects of Sfrp2 have not been fully elucidated. In this study, we test the hypothesis that Sfrp2 exerts anti-apoptotic effect by antagonizing pro-apoptotic properties of specific Wnt ligands. To explore this possibility, we studied rat cardiomyoblasts subjected to hypoxia reoxygenation (HR) injury. We examined the effect of Wnt3a and Sfrp2 on HR-induced apoptosis. We choose to study Wnt3a because its expression is up-regulated in response to hypoxia. Wnt3a (3nM) significantly increased cellular caspase activities (35% increase, p<0.05, n=3) and TUNEL staining (38% increase) in response to HR. Sfrp2 attenuated significantly Wnt3a-induced caspase activities in a concentration dependent fashion (0nM, 8.50±0.47; 3nM, 7.28±1.03; 30nM, 7.45±0.49; 300nM, 5.65±0.35), achieving 36% inhibition at a concentration of 300nM. Using a solid phase binding assay, our data demonstrates that Sfrp2 physically binds to Wnt3a. In addition, we observed that 600nM Sfrp2 inhibits 47% of the beta-catenin / TCF transcriptional activities induced by Wnt3a(0.55±0.07 vs 1.03±0.04). Impressively, Dickkopf-1, a protein that binds to the Wnt coreceptor LRP, significantly inhibited the Wnt3a-activated caspase and transcriptional activities by 31% and 77% respectively (caspase activities: 8.62±0.05 vs12.54±0.49; transcriptional activities: 0.41±0.03 vs 1.77±0.01) Similarly, siRNA against beta-catenin inhibited the Wnt3a-activated caspase activities by 59% (6.44±0.92 vs 15.71±0.67). Consistent with this, significantly fewer TUNEL positive cells were observed in siRNA transfected cells than in control cells (43% decrease). Together, our data provide strong evidence to support the notion that Wnt3a is a canonical Wnt with pro-apoptotic action whose cellular activity is prevented by, at least in part, Sfrp2 through direct binding of these molecules. These results can explain the in vivo protective effect of Sfrp2 and highlight its therapeutic potential for the ischemic heart.

scholarly journals Propofol Protects Rat Cardiomyocytes from Anthracycline-Induced Apoptosis by Regulating MicroRNA-181a In Vitro and In Vivo

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Hongwei Zhao ◽  
Xiaobei Zhang ◽  
Ying Zheng ◽  
Yuan Li ◽  
Xiaokun Wang ◽  
...  
Keyword(s):  
Myocardial Cell ◽  
Heart Tissue ◽  
Tunel Staining ◽  
Apoptotic Cells ◽  
Loss Of Function ◽  
Rat Cardiomyocytes ◽  
Direct Target Gene ◽  
Induced Apoptosis

We aimed to evaluate the cardioprotective effect and mechanism of propofol in anthracycline-induced cardiomyocyte apoptosis. We selected the rat myocardial cell line, H9c2, and primary cardiomyocytes for in vitro study. The cardiomyocytes were treated with vehicle, Adriamycin® (ADM), propofol, or a combination of ADM and propofol. The proportion of apoptotic cells and the expression of miR-181a were detected by flow cytometry and real-time PCR, respectively. Luciferase assays were performed to explore the direct target gene of miR-181a. In vivo assay, rats were randomly divided into different treatment groups. The apoptosis index was determined by TUNEL staining, and the expression of miR-181a and STAT3 in heart tissue was detected. The antiproliferative effect of ADM alone was significantly greater than that of ADM plus propofol. A significantly greater decrease in the proportion of apoptotic cells and in miR-181a expression was observed in the combination treatment group compared with that in the ADM groups in vitro and in vivo. The loss-of-function of miR-181a in H9c2 of ADM treatment resulted in increased Bcl-2 and decreased Bax. MiR-181a suppressed Bcl-2 expression through direct targeting of the Bcl-2 transcript. Propofol reduced anthracycline-induced apoptosis in cardiomyocytes via targeting miR-181a/Bcl-2, and a negative correlation between miR-181a and Bcl-2 was observed.

scholarly journals Glucuronoxylomannan, the Major Capsular Polysaccharide of Cryptococcus neoformans, Inhibits the Progression of Group B Streptococcal Arthritis

2004 ◽  
Vol 72 (11) ◽  
pp. 6367-6372 ◽  
Author(s):  
Luciana Tissi ◽  
Manuela Puliti ◽  
Francesco Bistoni ◽  
Paolo Mosci ◽  
Thomas R. Kozel ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cryptococcus Neoformans ◽  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Peritoneal Macrophages ◽  
Type Iv ◽  
Inflammatory Protein ◽  
Group B

ABSTRACT Glucuronoxylomannan (GXM), the principal constituent of the Cryptococcus neoformans capsule, modulates the inflammatory response of human monocytes in vitro. Here we examine the efficacy of GXM as a novel anti-inflammatory compound for use against experimental septic arthritis. Arthritis was induced in mice by the intravenous injection of 8 × 106 CFU of type IV group B streptococcus (GBS). GXM was administered intravenously in different doses (50, 100, or 200 μg/mouse) 1 day before and 1 day after bacterial inoculation. GXM treatment markedly decreased the incidence and severity of articular lesions. Histological findings showed limited periarticular inflammation in the joints of GXM-treated mice, confirming the clinical observations. The amelioration of arthritis was associated with a significant reduction in the local production of interleukin-6 (IL-6), IL-1β, macrophage inflammatory protein 1α (MIP-1α), and MIP-2 and an increase in systemic IL-10 levels. Moreover, peritoneal macrophages derived from GXM-treated mice and stimulated in vitro with heat-inactivated GBS showed a similar pattern of cytokine production. The present study provides evidence for the modulation of the inflammatory response by GXM in vivo and suggests a potential therapeutic use for this compound in pathologies involving inflammatory processes.

scholarly journals Human milk oligosaccharides reduce murine group B Streptococcus vaginal colonization with minimal impact on the vaginal microbiota

2021 ◽  
Author(s):  
Marlyd E Mejia ◽  
Samantha Ottinger ◽  
Alison Vrbanac ◽  
Priyanka Babu ◽  
Jacob Zulk ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Milk ◽  
Biofilm Formation ◽  
Group B Streptococcus ◽  
Human Milk Oligosaccharides ◽  
Vaginal Colonization ◽  
Vaginal Epithelial Cells ◽  
Group B

Group B Streptococcus (GBS) colonizes the vaginal mucosa of a significant percentage of healthy women and is a leading cause of neonatal bacterial infections. Currently, pregnant women are screened in the last month of pregnancy and GBS-positive women are given antibiotics during parturition to prevent bacterial transmission to the neonate. Recently, human milk oligosaccharides (HMOs) isolated from breastmilk were found to inhibit GBS growth and biofilm formation in vitro, and women that make certain HMOs are less likely to be vaginally colonized with GBS. Using in vitro human vaginal epithelial cells and a murine vaginal colonization model, we tested the impact of HMO treatment on GBS burdens and the composition of the endogenous microbiota by 16S rRNA amplicon sequencing. HMO treatment reduced GBS vaginal burdens in vivo with minimal alterations to the vaginal microbiota. HMOs displayed potent inhibitory activity against GBS in vitro, but HMO pretreatment did not alter adherence of GBS or the probiotic Lactobacillus rhamnosus to human vaginal epithelial cells. Additionally, disruption of a putative GBS glycosyltransferase (Δsan_0913) rendered the bacterium largely resistant to HMO inhibition in vitro and in vivo but did not compromise its adherence, colonization, or biofilm formation in the absence of HMOs. We conclude that HMOs are a promising therapeutic bioactive to limit GBS vaginal colonization with minimal impacts on the vaginal microenvironment.

scholarly journals Traditional Chinese Medication Qiliqiangxin Attenuates Diabetic Cardiomyopathy via Activating PPARγ

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaodong Wu ◽  
Ting Zhang ◽  
Ping Lyu ◽  
Mengli Chen ◽  
Gehui Ni ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Neonatal Rat ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Protective Mechanisms ◽  
Rat Cardiomyocytes ◽  
Induced Apoptosis ◽  
Hematoxylin Eosin

Background: Diabetic cardiomyopathy is the primary complication associated with diabetes mellitus and also is a major cause of death and disability. Limited pharmacological therapies are available for diabetic cardiomyopathy. Qiliqiangxin (QLQX), a Chinese medication, has been proven to be beneficial for heart failure patients. However, the role and the underlying protective mechanisms of QLQX in diabetic cardiomyopathy remain largely unexplored.Methods: Primary neonatal rat cardiomyocytes (NRCMs) were treated with glucose (HG, 40 mM) to establish the hyperglycemia-induced apoptosis model in vitro. Streptozotocin (STZ, 50 mg/kg/day for 5 consecutive days) was intraperitoneally injected into mice to establish the diabetic cardiomyopathy model in vivo. Various analyses including qRT-PCR, western blot, immunofluorescence [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining] histology (hematoxylin–eosin and Masson's trichrome staining), and cardiac function (echocardiography) were performed in these mice. QLQX (0.5 μg/ml in vitro and 0.5 g/kg/day in vivo) was used in this study.Results: QLQX attenuated hyperglycemia-induced cardiomyocyte apoptosis via activating peroxisome proliferation-activated receptor γ (PPARγ). In vivo, QLQX treatment protected mice against STZ-induced cardiac dysfunction and pathological remodeling.Conclusions: QLQX attenuates diabetic cardiomyopathy via activating PPARγ.

scholarly journals Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Gang Wang ◽  
Yanan Wang ◽  
Qinzhi Yang ◽  
Chunrong Xu ◽  
Youkun Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Vascular Complications ◽  
Tunel Staining ◽  
Ros Generation ◽  
Dependent Manner ◽  
Diabetic Vascular Complications ◽  
Induced Apoptosis

AbstractMethylglyoxal (MGO) is an active metabolite of glucose and plays a prominent role in the pathogenesis of diabetic vascular complications, including endothelial cell apoptosis induced by oxidative stress. Metformin (MET), a widely prescribed antidiabetic agent, appears to reduce excessive reactive oxygen species (ROS) generation and limit cell apoptosis. However, the molecular mechanisms underlying this process are still not fully elucidated. We reported here that MET prevents MGO-induced apoptosis by suppressing oxidative stress in vitro and in vivo. Protein expression and protein phosphorylation were investigated using western blotting, ELISA, and immunohistochemical staining, respectively. Cell viability and apoptosis were assessed by the MTT assay, TUNEL staining, and Annexin V-FITC and propidium iodide double staining. ROS generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Our results revealed that MET prevented MGO-induced HUVEC apoptosis, inhibited apoptosis-associated biochemical changes such as loss of MMP, the elevation of the Bax/Bcl-2 ratio, and activation of cleaved caspase-3, and attenuated MGO-induced mitochondrial morphological alterations in a dose-dependent manner. MET pretreatment also significantly suppressed MGO-stimulated ROS production, increased signaling through the ROS-mediated PI3K/Akt and Nrf2/HO-1 pathways, and markedly elevated the levels of its downstream antioxidants. Finally, similar results were obtained in vivo, and we demonstrated that MET prevented MGO-induced oxidative damage, apoptosis, and inflammation. As expected, MET reversed MGO-induced downregulation of Nrf2 and p-Akt. In addition, a PI3K inhibitor (LY-294002) and a Nrf2 inhibitor (ML385) observably attenuated the protective effects of MET on MGO-induced apoptosis and ROS generation by inhibiting the Nrf2/HO-1 pathways, while a ROS scavenger (NAC) and a permeability transition pores inhibitor (CsA) completely reversed these effects. Collectively, these findings broaden our understanding of the mechanism by which MET regulates apoptosis induced by MGO under oxidative stress conditions, with important implications regarding the potential application of MET for the treatment of diabetic vascular complications.

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