scholarly journals Immunomodulatory Effects of Herbal Compounds Quercetin and Curcumin on Cellular and Molecular Functions of Bovine-Milk-Isolated Neutrophils toward Streptococcus agalactiae Infection

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3286
Author(s):  
Purichaya Disbanchong ◽  
Wichayaporn Punmanee ◽  
Anyaphat Srithanasuwan ◽  
Noppason Pangprasit ◽  
Kanruethai Wongsawan ◽  
...  
Keyword(s):  
Streptococcus Agalactiae ◽  
Bovine Milk ◽  
Principal Component ◽  
Cellular Migration ◽  
In Vivo Studies ◽  
Ros Generation ◽  
Bacterial Killing ◽  
Molecular Functions

Herbal phytochemicals featuring active ingredients including quercetin and curcumin have shown potential in treating human and animal diseases. The current study investigated their potential function in vitro for host immunomodulation associated with Streptococcus agalactiae subclinical bovine mastitis via milk-isolated neutrophils. Our results showed a positive influence on cellular migration, reactive oxygen species (ROS) generation, phagocytosis, and bacterial killing as well as neutrophil extracellular traps (NETs) release. This study also highlighted several important molecular aspects of quercetin and curcumin in milk-isolated neutrophils. Gene expression analyses by RT-PCR revealed significant changes in the expression of proinflammatory cytokines (IL1B, IL6, and TNF), ROS (CYBA), phagocytosis (LAMP1), and migration (RAC). The expression levels of apoptotic genes or proteins in either pro-apoptosis (CASP3 and FAS) or anti-apoptosis (BCL2, BCL2L1, and CFLAR) were significantly manipulated by the effects of either quercetin or curcumin. A principal component analysis (PCA) identified the superior benefit of quercetin supplementation for increasing both cellular and molecular functions in combating bacterial mastitis. Altogether, this study showed the existing and potential benefits of these test compounds; however, they should be explored further via in vivo studies.

scholarly journals Once-daily gentamicin therapy for experimental Escherichia coli meningitis.

1997 ◽  
Vol 41 (1) ◽  
pp. 49-53 ◽  
Author(s):  
A Ahmed ◽  
M M París ◽  
M Trujillo ◽  
S M Hickey ◽  
L Wubbel ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Bacterial Killing ◽  
Once Daily ◽  
E Coli ◽  
Aminoglycoside Therapy ◽  
Gentamicin Concentration ◽  
Gentamicin Therapy ◽  
The Impact

In vitro and in vivo studies have demonstrated that the bacteriologic efficacy of once-daily aminoglycoside therapy is equivalent to that achieved with conventional multiple daily dosing. The impact of once-daily dosing for meningitis has not been studied. Using the well-characterized rabbit meningitis model, we compared two regimens of the same daily dosage of gentamicin given either once or in three divided doses for 24 or 72 h. The initial 1 h mean cerebrospinal fluid (CSF) gentamicin concentration for animals receiving a single dose (2.9 +/- 1.7 micrograms/ml) was threefold higher than that for the animals receiving multiple doses. The rate of bacterial killing in the first 8 h of treatment was significantly greater for the animals with higher concentrations in their CSF (-0.21 +/- 0.19 versus -0.03 +/- 0.22 log10 CFU/ml/h), suggesting concentration-dependent killing. By 24h, the mean reduction in bacterial titers was similar for the two regimens. In animals treated for 72 h, no differences in bactericidal activity was noted for 24, 48, or 72 h. Gentamicin at two different dosages was administered intracisternally to a separate set of animals to achieve considerably higher CSF gentamicin concentrations. In these animals, the rate of bacterial clearance in the first 8 h (0.52 +/- 0.15 and 0.58 +/- 0.15 log10 CFU/ml/h for the lower and higher dosages, respectively) was significantly greater than that in animals treated intravenously. In conclusion, there is evidence of concentration-dependent killing with gentamicin early in treatment for experimental E. coli meningitis, and once-daily dosing therapy appears to be at least as effective as multiple-dose therapy in reducing bacterial counts in CSF.

scholarly journals Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation

2018 ◽  
Author(s):  
Vinicius Cruzat ◽  
Marcelo Macedo Rogero ◽  
Kevin Noel Keane ◽  
Rui Curi ◽  
Philip Newsholme
Keyword(s):  
Amino Acid ◽  
The Body ◽  
Glutamine Metabolism ◽  
In Vivo Studies ◽  
Glutamine Supplementation ◽  
Bacterial Killing ◽  
Nutrition Supplementation ◽  
Wide Range

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

High glucose promotes nascent nephron apoptosis via NF-κB and p53 pathways

2011 ◽  
Vol 300 (1) ◽  
pp. F147-F156 ◽  
Author(s):  
Yun-Wen Chen ◽  
Isabelle Chenier ◽  
Shiao-Ying Chang ◽  
Stella Tran ◽  
Julie R. Ingelfinger ◽  
...  
Keyword(s):  
High Glucose ◽  
Nuclear Translocation ◽  
Dominant Negative ◽  
In Vivo Studies ◽  
Ros Generation ◽  
Small Interfering Rnas ◽  
Kidney Size ◽  
P53 Signaling

A hyperglycemic environment in utero reduces kidney size and nephron number due to nascent nephron apoptosis. However, the underlying mechanisms are incompletely understood. The present study investigated whether the nascent nephron apoptosis promoted by high glucose is mediated via the transcription factor NF-κB and p53 signaling pathways. Neonatal mouse kidneys from the offspring of nondiabetic, diabetic, and insulin-treated diabetic dams were used for in vivo studies, and MK4 cells, an embryonic metanephric mesenchymal (MM) cell line, were used for in vitro studies. Neonatal kidneys of the offspring of diabetic mothers exhibited an increased number of apoptotic cells and reactive oxygen species (ROS) generation, enhanced NF-κB activation, and nuclear translocation of its subunits (p50 and p65 subunits) as well as phosphorylation (Ser 15) of p53 compared with kidneys of offspring of nondiabetic mothers. Insulin treatment of diabetic dams normalized these parameters in the offspring. In vitro, high-glucose (25 mM) induced ROS generation and significantly increased MK4 cell apoptosis and caspase-3 activity via activation of NF-κB pathway, with p53 phosphorylation and nuclear translocation compared with normal glucose (5 mM). These changes in a high-glucose milieu were prevented by transient transfection of small interfering RNAs for dominant negative IκBα or IKK or p53. Our data demonstrate that high glucose-induced nascent nephron apoptosis is mediated, at least in part, via ROS generation and the activation of NF-κB and p53 pathways.

scholarly journals Identification of bioactive compounds from Fraxinus angustifolia extracts with anti-NADH oxidase activity of bovine milk xanthine oxidoreductase

2019 ◽  
pp. 133-147 ◽  
Author(s):  
Nadjia AHMANE ◽  
Dina ATMANI-KILANI ◽  
Nassima CHAHER ◽  
Karima AYOUNI ◽  
Meriem RAHMANI-BERBOUCHA ◽  
...  
Keyword(s):  
Oxidase Activity ◽  
Nadh Oxidase ◽  
Bovine Milk ◽  
Ros Generation ◽  
Xanthine Oxidoreductase ◽  
Fraxinus Angustifolia ◽  
Activity Of Enzymes ◽  
Nadh Oxidase Activity

Fraxinus angustifolia leaves and bark are used in traditional medicine against various inflammatory-related pathologies incumbent to reactive oxygen species (ROS) generation by the NADH oxidase activity of enzymes such as xanthine oxidoreductase (XOR). This study was designed to investigate the in vitro and in vivo inhibitory activities of this enzyme by Fraxinus angustifolia extracts. The leaf organic phase of ethyl acetate (LFA) and its bark aqueous counterpart (BFA) showed the strongest anti-NADH oxidase activity in vitro (IC50 = 38.51 and 42.04 μg mL-1, respectively). They consequently suppressed superoxide generation both enzymatically (53% and 19%, respectively) and nonenzymatically (34% and 19%, respectively). These results were corroborated in vivo, with high anti- NADH oxidase potential of the leaves and bark extracts (75.32% and 51.32%, respectively) concomitant with moderate hypouricemic activities (36.84% and 38.59%, respectively). Bio-guided fractionation led to the identification, by LC-DAD-MS/MS, of esculin and calcelarioside in bark and kaempferol glucoside in leaves as the main compounds responsible for the anti-NADH oxidase activity of XOR. These results plead in favor of the use of F. angustifolia as a source of potentially interesting therapeutic substances.

scholarly journals Once-versus thrice-daily netilmicin combined with amoxicillin, penicillin, or vancomycin against Enterococcus faecalis in a pharmacodynamic in vitro model.

1996 ◽  
Vol 40 (10) ◽  
pp. 2258-2261 ◽  
Author(s):  
S Schwank ◽  
J Blaser
Keyword(s):  
Enterococcus Faecalis ◽  
Half Life ◽  
In Vitro Model ◽  
Bacterial Biofilm ◽  
In Vivo Studies ◽  
Bacterial Killing ◽  
Once Daily ◽  
Vitro Model

Several in vitro and in vivo studies as well as clinical trials have demonstrated that once-daily aminoglycoside regimens are as effective as or more effective than multiple daily dosings. However, the most favorable aminoglycoside dosing regimen for treating enterococcal endocarditis remains controversial. The same total dose of netilmicin was administered as once-daily (24-micrograms/ml peaks) and thrice-daily (8 micrograms/ml) regimens in a pharmacodynamic in vitro model simulating exposure of Enterococcus faecalis to human serum kinetics. Netilmicin was administered in combination with continuous infusions of amoxicillin, vancomycin, or penicillin against a bacterial biofilm adhering to glass beads. No significant differences in bacterial killing were found after 24 or 48 h between the once- and thrice-daily regimens. Additional experiments considering animal kinetics (half-life of netilmicin, 20 min) instead of human kinetics (half-life, 2.5 h) in the pharmacodynamic model also revealed similar results. The addition of netilmicin synergistically increased the activity of vancomycin (P < 0.05). In contrast, amoxicillin alone was as effective as the combination with netilmicin. Thus, it could not be established in this model that once-daily dosing of aminoglycosides is contraindicated for treating infections caused by E. faecalis.

scholarly journals CSIG-16. RECONCILING TUMOR HETEROGENEITY IN GLIOBLASTOMA USING A PATHWAY-BASED APPROACH

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi47-vi47
Author(s):  
Alvaro Alvarado ◽  
Riki Kawaguchi ◽  
Giovanni Coppola ◽  
Steven Goldman ◽  
Harley Kornblum
Keyword(s):  
Gene Expression ◽  
Gene List ◽  
Molecular Targets ◽  
Principal Component ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
In Vivo Studies ◽  
Molecular Architecture

Abstract Despite efforts to gain a deeper understanding of its molecular architecture, glioblastoma (GBM) remains uniformly fatal. While genome-based molecular subtyping has revealed that GBMs may be parsed into several distinct molecular categories, this insight has yielded little progress towards extending patient survival. In particular, the great phenotypic heterogeneity of GBM – both inter and intratumorally – has hindered therapeutic efforts. To this end, we interrogated tumor samples using a pathway-based approach to resolve tumoral heterogeneity. Gene set enrichment analysis (GSEA) was applied to gene expression data and used to provide an overview of each sample that was then compared to others, generating sample clusters based on overall patterns of enrichment. The Cancer Genome Atlas (TCGA) samples were clustered using canonical and oncogenic signatures and in both cases the clustering was distinct from the molecular subtypes previously reported. Using principal component analysis (PCA) and other bioinformatics tools, we extracted gene sets to further characterize the pathways contributing to each of these clusters. We generated gene lists of the top common elements and Ingenuity pathway analysis exposed molecular targets that control critical pathways of each identified cluster. Similar analyses were completed in a gene expression database of patient-derived gliomasphere lines and molecular targets were also obtained. We found E2F1 to be a strong target based on gene lists from both databases. A cluster of gliomasphere lines have high enrichment scores for the gene list predicted to depend on E2F1. In vitro genetic perturbation showed decrease stem cell frequency and lower expression of cell cycle progression genes in cell lines from this cluster exclusively. Other cluster-specific targets are being validated and in vivo studies will follow momentarily. Our studies relate intertumoral heterogeneity to critical cellular pathways dysregulated in GBM, with the ultimate goal of establishing a pipeline for patient- and tumor-specific precision medicine.

scholarly journals The Role of Oxidative Stress and Therapeutic Potential of Antioxidants in Graves’ Ophthalmopathy

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1871
Author(s):  
Tzu-Yu Hou ◽  
Shi-Bei Wu ◽  
Hui-Chuan Kau ◽  
Chieh-Chih Tsai
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Ros Generation ◽  
Ocular Motility ◽  
Graves Ophthalmopathy ◽  
Antioxidant Supplements

Graves’ ophthalmopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease. It is characterized initially by an inflammatory process, followed by tissue remodeling and fibrosis, leading to proptosis, exposure keratopathy, ocular motility limitation, and compressive optic neuropathy. The pathogenic mechanism is complex and multifactorial. Accumulating evidence suggests the involvement of oxidative stress in the pathogenesis of GO. Cigarette smoking, a major risk factor for GO, has been shown to induce reactive oxygen species (ROS) generation and oxidative damage in GO orbital fibroblasts. In addition, an elevation in ROS and antioxidant enzymes is observed in tears, blood, and urine, as well as orbital fibroadipose tissues and fibroblasts from GO patients. In vitro and in vivo studies have examined the efficacy of various antioxidant supplements for GO. These findings suggest a therapeutic role of antioxidants in GO patients. This review summarizes the current understanding of oxidative stress in the pathogenesis and potential antioxidants for the treatment of GO.

Natural Products as Potential Agents Against SARS-CoV and SARS-CoV-2

2021 ◽  
Vol 28 ◽  
Author(s):  
Joanda Paolla Raimundo e Silva ◽  
Chonny Alexander Herrera Acevedo ◽  
Thalisson Amorim de Souza ◽  
Renata Priscila Barros de Menezes ◽  
Zoe L. Sessions ◽  
...  
Keyword(s):  
Natural Products ◽  
In Silico ◽  
Principal Component ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Future Research ◽  
Natural Substances ◽  
Effective Drugs

Background: Natural products are useful agents for the discovery of new lead-compounds and effective drugs to combat coronaviruses (CoV). Objective: The present work provides an overview of natural substances, plant extracts, and essential oils as potential antiSARS-CoV agents. In addition, this work evaluates their drug-like properties which are essential in the selection of compounds in order to accelerate the drug development process. Methods: The search was carried out using PubMed, ScienceDirect and SciFinder. Articles addressing plant-based natural products as potential SARS-CoV or SARS-CoV-2 agents within the last seventeen years were analyzed and selected. The descriptors for Chemometrics analyzes were obtained in alvaDesc and the principal component analyzes (PCA) were carried out in SIMCA version 13.0. Results: Based on in vitro assays and computational analyzes, this review covers twenty nine medicinal plant species and more than 300 isolated substances as potential anti-coronavirus agents. Among them, flavonoids and terpenes were the most promising compound classes. In silico analyses of drug-like properties corroborate these findings and indicate promising candidates for in vitro and in vivo studies to validate their activity. Conclusion: This paper highlights the role of ethnopharmacology in drug discovery and simulates the use of integrative (in silico/ in vitro) and chemocentric approaches to strengthen current studies and guide future research in the field of antivirals agents.

scholarly journals Antimicrobial and antibiofilm potentials of cinnamon oil and silver nanoparticles against Streptococcus agalactiae isolated from bovine mastitis: new avenues for countering resistance

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Norhan K. Abd El-Aziz ◽  
Ahmed M. Ammar ◽  
El-sayed Y. M. El-Naenaeey ◽  
Hend M. El Damaty ◽  
Asmaa A. Elazazy ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Streptococcus Agalactiae ◽  
Quantitative Polymerase Chain Reaction ◽  
Bovine Mastitis ◽  
Dairy Farms ◽  
Clinical Mastitis ◽  
In Vivo Studies ◽  
Cinnamon Oil

Abstract Background Streptococcus agalactiae (S. agalactiae) is a contagious pathogen of bovine mastitis. It has financial implications for the dairy cattle industry in certain areas of the world. Since antimicrobial resistance increases in dairy farms, natural antimicrobials from herbal origins and nanoparticles have been given more attention as an alternative therapy. Hence, this study reported the antimicrobial and antibiofilm potentials of cinnamon oil, silver nanoparticles (AgNPs), and their combination against multidrug-resistant (MDR) S. agalactiae recovered from clinical bovine mastitis in Egypt. Results Our findings revealed that 73% (146/200) of the examined milk samples collected from dairy cows with clinical mastitis were infected with Streptococci species. Of these, 9.59% (14/146) were identified as S. agalactiae and categorized as MDR. S. agalactiae isolates expressed four virulence genes (Hyl, cylE, scpB, and lmb) and demonstrated an ability to produce biofilms. Cinnamon oil showed high antimicrobial (MICs ≤0.063 μg /mL) and antibiofilm (MBIC50 = 4 μg/mL) potentials against planktonic and biofilms of S. agalactiae isolates, respectively. However, AgNPs showed reasonable antimicrobial (MICs ≤16 μg/mL) and relatively low antibiofilm (MBIC50 = 64 μg/mL) activities against screened isolates. Synergistic antimicrobial or additive antibiofilm interactions of cinnamon oil combined with AgNPs were reported for the first time. Scanning electron microscope (SEM) analysis revealed that biofilms of S. agalactiae isolates treated with cinnamon oil were more seriously damaged than observed in AgNPs cinnamon oil combination. Moreover, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) showed that cinnamon oil exerted a remarkable down-regulation of pili biosynthesis genes (pilA and pilB) and their regulator (rogB) against S. agalactiae biofilms, meanwhile the AgNPs cinnamon oil combination demonstrated a lower efficacy. Conclusions This is an in vitro preliminary approach that documented the antibiofilm potential of cinnamon oil and the inhibitory activity of cinnamon oil and its combination with AgNPs against MDR S. agalactiae recovered from clinical mastitis. Further in vivo studies should be carried out in animal models to provide evidence of concept for implementing these alternative candidates in the treatment of dairy farms infected by streptococcal mastitis in the future.

scholarly journals Bioactive Tryptophan-Based Copper Complex with Auxiliary β-Carboline Spectacle Potential on Human Breast Cancer Cells: In Vitro and In Vivo Studies

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1606
Author(s):  
Walaa Alharbi ◽  
Iftekhar Hassan ◽  
Rais Ahmad Khan ◽  
Shazia Parveen ◽  
Khadijah H. Alharbi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Human Breast Cancer ◽  
Hek293 Cells ◽  
In Vivo Studies ◽  
Ros Generation ◽  
Human Breast ◽  
Mcf7 Cells

Biocompatible tryptophan-derived copper (1) and zinc (2) complexes with norharmane (β-carboline) were designed, synthesized, characterized, and evaluated for the potential anticancer activity in vitro and in vivo. The in vitro cytotoxicity of both complexes 1 and 2 were assessed against two cancerous cells: (human breast cancer) MCF7 and (liver hepatocellular cancer) HepG2 cells with a non-tumorigenic: (human embryonic kidney) HEK293 cells. The results exhibited a potentially decent selectivity of 1 against MCF7 cells with an IC50 value of 7.8 ± 0.4 μM compared to 2 (less active, IC50 ~ 20 μM). Furthermore, we analyzed the level of glutathione, lipid peroxidation, and visualized ROS generation to get an insight into the mechanistic pathway and witnessed oxidative stress. These in vitro results were ascertained by in vivo experiments, which also supported the free radical-mediated oxidative stress. The comet assay confirmed the oxidative stress that leads to DNA damage. The histopathology of the liver also ascertained the low toxicity of 1.

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