scholarly journals MicroRNA-210 regulates the metabolic and inflammatory status of primary human astrocytes

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Nicholas W. Kieran ◽  
Rahul Suresh ◽  
Marie-France Dorion ◽  
Adam MacDonald ◽  
Manon Blain ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Stress Conditions ◽  
Potential Candidate ◽  
Vitro Assay ◽  
Control Tissue ◽  
Inflammatory Status ◽  
Human Astrocytes ◽  
Anti Inflammatory ◽  
In Vitro Stress

Abstract Background Astrocytes are the most numerous glial cell type with important roles in maintaining homeostasis and responding to diseases in the brain. Astrocyte function is subject to modulation by microRNAs (miRs), which are short nucleotide strands that regulate protein expression in a post-transcriptional manner. Understanding the miR expression profile of astrocytes in disease settings provides insight into the cellular stresses present in the microenvironment and may uncover pathways of therapeutic interest. Methods Laser-capture microdissection was used to isolate human astrocytes surrounding stroke lesions and those from neurological control tissue. Astrocytic miR expression profiles were examined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Primary human fetal astrocytes were cultured under in vitro stress conditions and transfection of a miR mimic was used to better understand how altered levels of miR-210 affect astrocyte function. The astrocytic response to stress was studied using qPCR, enzyme-linked immunosorbent assays (ELISAs), measurement of released lactate, and Seahorse. Results Here, we measured miR expression levels in astrocytes around human ischemic stroke lesions and observed differential expression of miR-210 in chronic stroke astrocytes compared to astrocytes from neurological control tissue. We also identified increased expression of miR-210 in mouse white matter tissue around middle cerebral artery occlusion (MCAO) brain lesions. We aimed to understand the role of miR-210 in primary human fetal astrocytes by developing an in vitro assay of hypoxic, metabolic, and inflammatory stresses. A combination of hypoxic and inflammatory stresses was observed to upregulate miR-210 expression. Transfection with miR-210-mimic (210M) increased glycolysis, enhanced lactate export, and promoted an anti-inflammatory transcriptional and translational signature in astrocytes. Additionally, 210M transfection resulted in decreased expression of complement 3 (C3) and semaphorin 5b (Sema5b). Conclusions We conclude that miR-210 expression in human astrocytes is modulated in response to ischemic stroke disease and under in vitro stress conditions, supporting a role for miR-210 in the astrocytic response to disease conditions. Further, the anti-inflammatory and pro-glycolytic impact of miR-210 on astrocytes makes it a potential candidate for further research as a neuroprotective agent.

scholarly journals Ethosomes and Transethosomes for Mangiferin Transdermal Delivery

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 768
Author(s):  
Maddalena Sguizzato ◽  
Francesca Ferrara ◽  
Supandeep Singh Hallan ◽  
Anna Baldisserotto ◽  
Markus Drechsler ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Radical Scavenging ◽  
Human Keratinocytes ◽  
Antioxidant Response ◽  
Correlation Spectroscopy ◽  
Inflammatory Status ◽  
Transmission Electron ◽  
Anti Inflammatory

Mangiferin is a natural glucosyl xanthone with antioxidant and anti-inflammatory activity, making it suitable for protection against cutaneous diseases. In this study ethosomes and transethosomes were designed as topical delivery systems for mangiferin. A preformulation study was conducted using different surfactants in association with phosphatidylcholine. Vesicle dimensional distribution was monitored by photon correlation spectroscopy, while antioxidant capacity and cytotoxicity were respectively assessed by free radical scavenging analysis and MTT on HaCaT keratinocytes. Selected nanosystems were further investigated by cryogenic transmission electron microscopy, while mangiferin entrapment capacity was evaluated by ultracentrifugation and HPLC. The diffusion kinetics of mangiferin from ethosomes and transethosomes evaluated by Franz cell was faster in the case of transethosomes. The suitability of mangiferin-containing nanovesicles in the treatment of skin disorders related to pollutants was investigated, evaluating, in vitro, the antioxidant and anti-inflammatory effect of ethosomes and transethosomes on human keratinocytes exposed to cigarette smoke as an oxidative and inflammatory challenger. The ability to induce an antioxidant response (HO-1) and anti-inflammatory status (IL-6 and NF-kB) was determined by RT-PCR and immunofluorescence. The data demonstrated the effectiveness of mangiferin loaded in nanosystems to protect cells from damage. Finally, to gain insight into the keratinocytes’ uptake of ethosome and transethosome, transmission electron microscopy analyses were conducted, showing that both nanosystems were able to pass intact within the cells.

Curcumin: Natural Antimicrobial and Anti Inflammatory Agent

2021 ◽  
pp. 1-8
Author(s):  
Pehlivanović Belma ◽  
Čaklovica Kenan ◽  
Lagumdžija Dina ◽  
Omerović Naida ◽  
Žiga Smajić Nermina ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Protein Denaturation ◽  
Dose Range ◽  
In Vitro Assays ◽  
Natural Antimicrobial ◽  
In Vivo Models ◽  
Vitro Assay ◽  
Inflammatory Agent ◽  
Anti Inflammatory

The pursuance of novel antimicrobial and anti-inflammatory agents has been expanding due to a significant need for more efficient pharmacotherapy of various infections and chronic diseases. During the last decade, pharmacokinetics, pharmacodynamics and pharmacological properties of curcumin have been extensively studied. The aim of the present study was to evaluate the antibacterial activity of curcumin against both Gram-positive and Gram-negative bacteria as well as its antifungal activity by using in vitro agar well diffusion assay. Moreover, the anti-inflammatory activity of curcumin was determined with in vitro assay of inhibition of protein denaturation. Results demonstrated wide antimicrobial activity of curcumin upon all of the test bacteria and fungi. The strongest activity of curcumin was observed at a concentration of 0.50 mg/ml against S. aureus, L. monocytogenes, E. coli, P. aeruginosa and C. albicans, resulting in a maximum zone of inhibition of 14.7 mm, 14.3 mm, 13.7 mm, 10.7 mm and 10.7 mm, respectively. Findings suggested that the antimicrobial activity of curcuminis dependent upon the concentrations. Furthermore, results demonstrated high effectiveness of curcumin compared to standard acetylsalicylic acid in inhibiting heat-induced protein denaturation, which activity is also depended upon the concentrations. The present study emphasises the potential application of curcumin as a natural antimicrobial and anti-inflammatory agent. However, findings of this study are restricted to in vitro assays and consideration should be given to conducting a study involving wider dose range test substances as well as including further research on in vivo models.

scholarly journals The anti-inflammatory peptide Ac-SDKP is released from thymosin-β4 by renal meprin-α and prolyl oligopeptidase

2016 ◽  
Vol 310 (10) ◽  
pp. F1026-F1034 ◽  
Author(s):  
Nitin Kumar ◽  
Pablo Nakagawa ◽  
Branislava Janic ◽  
Cesar A. Romero ◽  
Morel E. Worou ◽  
...  
Keyword(s):  
Amino Acids ◽  
Rat Kidney ◽  
Plasma Concentrations ◽  
Potential Candidate ◽  
Thymosin Β4 ◽  
Wild Type ◽  
Prolyl Oligopeptidase ◽  
Anti Inflammatory

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural tetrapeptide with anti-inflammatory and antifibrotic properties. Previously, we have shown that prolyl oligopeptidase (POP) is involved in the Ac-SDKP release from thymosin-β4 (Tβ4). However, POP can only hydrolyze peptides shorter than 30 amino acids, and Tβ4 is 43 amino acids long. This indicates that before POP hydrolysis takes place, Tβ4 is hydrolyzed by another peptidase that releases NH2-terminal intermediate peptide(s) with fewer than 30 amino acids. Our peptidase database search pointed out meprin-α metalloprotease as a potential candidate. Therefore, we hypothesized that, prior to POP hydrolysis, Tβ4 is hydrolyzed by meprin-α. In vitro, we found that the incubation of Tβ4 with both meprin-α and POP released Ac-SDKP, whereas no Ac-SDKP was released when Tβ4 was incubated with either meprin-α or POP alone. Incubation of Tβ4 with rat kidney homogenates significantly released Ac-SDKP, which was blocked by the meprin-α inhibitor actinonin. In addition, kidneys from meprin-α knockout (KO) mice showed significantly lower basal Ac-SDKP amount, compared with wild-type mice. Kidney homogenates from meprin-α KO mice failed to release Ac-SDKP from Tβ4. In vivo, we observed that rats treated with the ACE inhibitor captopril increased plasma concentrations of Ac-SDKP, which was inhibited by the coadministration of actinonin (vehicle, 3.1 ± 0.2 nmol/l; captopril, 15.1 ± 0.7 nmol/l; captopril + actinonin, 6.1 ± 0.3 nmol/l; P < 0.005). Similar results were obtained with urinary Ac-SDKP after actinonin treatment. We conclude that release of Ac-SDKP from Tβ4 is mediated by successive hydrolysis involving meprin-α and POP.

scholarly journals RNA atlas of human bacterial pathogens uncovers stress dynamics linked to infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kemal Avican ◽  
Jehad Aldahdooh ◽  
Matteo Togninalli ◽  
A. K. M. Firoj Mahmud ◽  
Jing Tang ◽  
...  
Keyword(s):  
Stress Responses ◽  
Large Scale ◽  
Bacterial Pathogens ◽  
Stress Conditions ◽  
Altered Expression ◽  
Online Resource ◽  
Species Specific ◽  
In Vitro Stress

AbstractBacterial processes necessary for adaption to stressful host environments are potential targets for new antimicrobials. Here, we report large-scale transcriptomic analyses of 32 human bacterial pathogens grown under 11 stress conditions mimicking human host environments. The potential relevance of the in vitro stress conditions and responses is supported by comparisons with available in vivo transcriptomes of clinically important pathogens. Calculation of a probability score enables comparative cross-microbial analyses of the stress responses, revealing common and unique regulatory responses to different stresses, as well as overlapping processes participating in different stress responses. We identify conserved and species-specific ‘universal stress responders’, that is, genes showing altered expression in multiple stress conditions. Non-coding RNAs are involved in a substantial proportion of the responses. The data are collected in a freely available, interactive online resource (PATHOgenex).

A Novel in vitro Assay for Anti-Inflammatory Agents Based on Stabilization of Erythrocytes

1967 ◽  
Vol 125 (3) ◽  
pp. 837-843 ◽  
Author(s):  
J. H. Brown ◽  
H. K. Mackey ◽  
D. A. Riggilo
Keyword(s):  
In Vitro Assay ◽  
Vitro Assay ◽  
Anti Inflammatory

scholarly journals Neuroprotective and Angiogenesis Effects of Levetiracetam Following Ischemic Stroke in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiang Yao ◽  
Wenping Yang ◽  
Zhendong Ren ◽  
Haoran Zhang ◽  
Dafa Shi ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Hypoxia Inducible Factor ◽  
Neuronal Cell ◽  
Anti Inflammatory

Objective: The present study explored whether levetiracetam (LEV) could protect against experimental brain ischemia and enhance angiogenesis in rats, and investigated the potential mechanisms in vivo and in vitro.Methods: The middle cerebral artery was occluded for 60 min to induce middle cerebral artery occlusion (MCAO). The Morris water maze was used to measure cognitive ability. The rotation test was used to assess locomotor function. T2-weighted MRI was used to assess infarct volume. The neuronal cells in the cortex area were stained with cresyl purple. The anti-inflammatory effects of LEV on microglia were observed by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISA) were used to measure the production of pro-inflammatory cytokines. Western blotting was used to detect the levels of heat shock protein 70 (HSP70), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) in extracts from the ischemic cortex. Flow cytometry was used to observe the effect of LEV on neuronal cell apoptosis.Results: LEV treatment significantly increased the density of the surviving neurons in the cerebral cortex and reduced the infarct size (17.8 ± 3.3% vs. 12.9 ± 1.4%, p &lt; 0.01) after MCAO. Concurrently, the time required to reach the platform for LEV-treated rats was shorter than that in the saline group on day 11 after MCAO (p &lt; 0.01). LEV treatment prolonged the rotarod retention time on day 14 after MCAO (84.5 ± 6.7 s vs. 59.1 ± 6.2 s on day 14 compared with the saline-treated groups, p &lt; 0.01). It also suppressed the activation of microglia and inhibited TNF-α and Il-1β in the ischemic brain (135.6 ± 5.2 pg/ml vs. 255.3 ± 12.5 pg/ml, 18.5 ± 1.3 pg/ml vs. 38.9 ± 2.3 pg/ml on day 14 compared with the saline-treated groups, p &lt; 0.01). LEV treatment resulted in a significant increase in HIF-1α, VEGF, and HSP70 levels in extracts from the ischemic cerebral cortex. At the same time, LEV reduced neuronal cell cytotoxicity and apoptosis induced by an ischemic stroke (p &lt; 0.01).Conclusion: LEV treatment promoted angiogenesis and functional recovery after cerebral ischemia in rats. These effects seem to be mediated through anti-inflammatory and antiapoptotic activities, as well as inducing the expression of HSP70, VEGF, and HIF-1α.

scholarly journals Anti-periodontal Pathogen and Anti-inflammatory Activities of Oxyresveratrol

2013 ◽  
Vol 8 (5) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Waranyoo Phoolcharoen ◽  
Sireerat Sooampon ◽  
Boonchoo Sritularak ◽  
Kittisak Likhitwitayawuid ◽  
Jintakorn Kuvatanasuchati ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Pathogenic Bacteria ◽  
Biological Activities ◽  
Mrna Level ◽  
Periodontal Pathogen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Minimal Bactericidal Concentration ◽  
Potential Candidate ◽  
Anti Inflammatory

Oxyresveratrol, a compound in the heartwood of Artocarpus lakoocha Roxb and other medicinal plants, has been shown to have various biological activities. However, these have not been studied in periodontal research. In this study, we investigated whether oxyresveratrol has antibacterial activity against the predominant perio-pathogenic bacteria Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Moreover, the anti-inflammatory properties of oxyresveratrol were studied in LPS-stimulated human periodontal ligament (hPDL) cells. The antibacterial activity of oxyresveratrol on P. gingivalis and A. actinomycetemcomitans was initially evaluated using a disc diffusion test. The anti-bacterial strength of oxyresveratrol was then assessed in vitro by determining the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC). Furthermore, the effects of oxyresveratrol on the LPS-induced production of inflammatory mediators were measured in hPDL cells. The levels of cytokine mRNA and protein expression were determined using reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that oxyresveratrol exhibited antibacterial activities against P. gingivalis with MIC and MBC values of 0.07 mg/mL and 0.16 mg/mL, respectively. The MIC and MBC values against A. actinomycetemcomitans were 0.08 mg/mL and 0.16 mg/mL, respectively. When examining inflammatory stimulation, LPS treatment strongly induced the expression of pro-inflammatory cytokines in hPDL cells. However, pre-treatment with oxyresveratrol significantly inhibited the expression of IL-6 and IL-8 at both the mRNA and protein levels. The IL-1β mRNA level was suppressed by oxyresveratrol, but the level of secreted IL-1β protein was not detectable using ELISA. The results of the present study indicate that oxyresveratrol is a potential candidate for use as an anti-periodontitis agent because of its anti-bacterial activity against the main oral pathogens related to periodontal disease and its anti-inflammatory activity in LPS-stimulated hPDL cells.

scholarly journals Evaluation of Anti-inflammatory, Anti-pyretic, Analgesic, and Hepatoprotective Properties of Terminalia macroptera

2020 ◽  
Vol 07 (02) ◽  
pp. e58-e67
Author(s):  
Mahamane Haïdara ◽  
Adama Dénou ◽  
Mohamed Haddad ◽  
Aïssata Camara ◽  
Korotoumou Traoré ◽  
...  
Keyword(s):  
Traditional Medicine ◽  
High Resolution Mass Spectrometry ◽  
Biological Activities ◽  
Traditional Healers ◽  
Potential Candidate ◽  
Murine Models ◽  
Leaf Extracts ◽  
Anti Inflammatory

AbstractIn Mali, improved traditional medicines [“Médicaments Traditionnels Améliorés”] are prepared from traditionally used medicinal plants. Recently, the Department of Traditional Medicine has identified Terminalia macroptera Guill. & Perr. (Combretaceae) as a potential candidate for an improved traditional medicine. T. macroptera is a West African medicinal plant used in Mali against various health disorders, with more than 30 different indications mentioned by traditional healers, including hepatitis, gonorrhea, fever, pain relief, and various infectious diseases (Helicobacter pylori-associated diseases). To date, validation of most of the biological activities of has been mainly carried out in vitro, except for antimalarial activities. In this study, the potential anti-inflammatory, antipyretic, analgesic, and hepatoprotective properties of T. macroptera were investigated in different murine models. Administration of T. macroptera ethanolic root and leaf extracts in rats significantly reduced pyrexia, pain, inflammation, and hepatic marker enzymes such as alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in the different murine models used (p<0.05). A phytochemical screening of T. macroptera revealed the presence of tannins, flavonoids, saponins, anthracene derivatives, sterols, triterpenes, and sugars in both leaf and root extracts as the main phytochemical compounds. This was confirmed by qualitative analysis, liquid chromatography coupled with high-resolution mass spectrometry. T. macroptera extracts demonstrated interesting in vivo antipyretic, analgesic, anti-inflammatory, and hepatoprotective activities. Therefore, T. macroptera should be proposed and further evaluated as a potential improved traditional medicine for the treatment of liver-related disorders and for the relief of pain and fever.

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