scholarly journals Antiseptic Effect of Ps-K18: Mechanism of Its Antibacterial and Anti-Inflammatory Activities

2019 ◽  
Vol 20 (19) ◽  
pp. 4895 ◽  
Author(s):  
Mihee Jang ◽  
Jieun Kim ◽  
Yujin Choi ◽  
JeongKyu Bang ◽  
Yangmee Kim
Keyword(s):  
Septic Shock ◽  
Antibacterial Activity ◽  
Bioactive Peptides ◽  
Liver Toxicity ◽  
Inflammatory Responses ◽  
Lung Damage ◽  
Peptide Antibiotic ◽  
Gram Negative ◽  
Innate Defense ◽  
Anti Inflammatory

Recently, bioactive peptides have attracted attention for their therapeutic applications in the pharmaceutical industry. Among them, antimicrobial peptides are candidates for new antibiotic drugs. Since pseudin-2 (Ps), isolated from the skin of the paradoxical frog Pseudis paradoxa, shows broad-spectrum antibacterial activity with high cytotoxicity, we previously designed Ps-K18 with a Lys substitution for Leu18 in Ps, which showed high antibacterial activity and low toxicity. Here, we examined the potency of Ps-K18, aiming to develop antibiotics derived from bioactive peptides for the treatment of Gram-negative sepsis. We first investigated the antibacterial mechanism of Ps-K18 based on confocal micrographs and field emission scanning electron microscopy, confirming that Ps-K18 targets the bacterial membrane. Anti-inflammatory mechanism of Ps-K18 was investigated by secreted alkaline phosphatase reporter gene assays and RT-PCR, which revealed that Ps-K18 activates innate defense via Toll-like receptor 4-mediated nuclear factor-kappa B signaling pathways. Moreover, we investigated the antiseptic effect of Ps-K18 using a lipopolysaccharide or Escherichia coli K1-induced septic shock mouse model. Ps-K18 significantly reduced bacterial growth and inflammatory responses in the septic shock model. Ps-K18 showed low renal and liver toxicity and attenuated lung damage effectively. This study suggests that Ps-K18 is a potent peptide antibiotic that could be applied therapeutically to Gram-negative sepsis.

scholarly journals Effectiveness of steroid treatment for SARS-CoV-2 pneumonia with COP-like reaction: a case report

2020 ◽  
pp. 1-13
Author(s):  
Taehwa Kim ◽  
Eunjeong Son ◽  
Doosoo Jeon ◽  
Su Jin Lee ◽  
Seungjin Lim ◽  
...  
Keyword(s):  
Case Report ◽  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Responses ◽  
Clinical Course ◽  
Steroid Treatment ◽  
Lung Damage ◽  
Organizing Pneumonia ◽  
Cryptogenic Organizing Pneumonia ◽  
Steroid Administration ◽  
Anti Inflammatory

Abstract Several studies on the treatment of coronavirus disease (COVID-19) are being conducted, and various drugs are being tried; however, the results have not been uniform. Steroids have been widely used in the treatment of COVID-19, but their effects are controversial. As immunosuppressive and anti-inflammatory agents, steroids are considered to reduce lung damage by regulating various inflammatory responses. We report a case of severe acute respiratory syndrome coronavirus-2 pneumonia manifesting as a cryptogenic organizing pneumonia-like reaction and discuss its treatment, clinical course, and favorable outcomes after steroid administration.

scholarly journals Host-Directed Therapies: Modulating Inflammation to Treat Tuberculosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Stefanie Krug ◽  
Sadiya Parveen ◽  
William R. Bishai
Keyword(s):  
Immune Response ◽  
Inflammatory Responses ◽  
Lung Damage ◽  
Tb Treatment ◽  
Inflammatory Processes ◽  
Clinical Models ◽  
Human Immune Response ◽  
Human Immune ◽  
Anti Inflammatory ◽  
Microbiological Cure

Following infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), most human hosts are able to contain the infection and avoid progression to active TB disease through expression of a balanced, homeostatic immune response. Proinflammatory mechanisms aiming to kill, slow and sequester the pathogen are key to a successful host response. However, an excessive or inappropriate pro-inflammatory response may lead to granuloma enlargement and tissue damage, which may prolong the TB treatment duration and permanently diminish the lung function of TB survivors. The host also expresses certain anti-inflammatory mediators which may play either beneficial or detrimental roles depending on the timing of their deployment. The balance between the timing and expression levels of pro- and anti-inflammatory responses plays an important role in the fate of infection. Interestingly, M. tuberculosis appears to manipulate both sides of the human immune response to remodel the host environment for its own benefit. Consequently, therapies which modulate either end of this spectrum of immune responses at the appropriate time may have the potential to improve the treatment of TB or to reduce the formation of permanent lung damage after microbiological cure. Here, we highlight host-directed TB therapies targeting pro- or anti-inflammatory processes that have been evaluated in pre-clinical models. The repurposing of already available drugs known to modulate these responses may improve the future of TB therapy.

scholarly journals Implications of Statin Use on Vasopressor Therapy in the Setting of Septic Shock

2018 ◽  
Vol 53 (3) ◽  
pp. 152-156
Author(s):  
Chelsey M. McPheeters ◽  
Jennifer A. Wiedmar ◽  
Christina M. Pinkston ◽  
Kyle A. Weant
Keyword(s):  
Septic Shock ◽  
Inflammatory Responses ◽  
Control Group ◽  
Vasopressor Therapy ◽  
Statin Group ◽  
Improved Outcomes ◽  
Anti Inflammatory ◽  
Time Of Admission ◽  
Statin Use

Background: Pleiotropic anti-inflammatory and immunomodulatory effects of statins have been associated with improved outcomes in the critically ill population. Objective: To evaluate the implications of prior statin use on the duration of vasopressor therapy in the setting of septic shock. Methods: This was a retrospective, multicenter study of adult patients who were diagnosed with septic shock. Patients were included if they were treated with any vasopressor for greater than 6 hours from the time of admission. The primary outcome was to compare the duration of vasopressor therapy in patients with septic shock with and without previous statin exposure. Results: A total of 88 statin-exposed cases and 205 unexposed controls were included in the analysis. Despite 92% of statin-exposed patients being reinitiated on therapy within 24 hours, the duration of vasopressors did not differ between groups (44 hours, statin group vs 53 hours, control group, P = .51). There were also no mortality differences between the statin group and the controls (40% vs 47%, P = .27). Conclusions: Long-term statin exposure does not impact the duration of vasopressor therapy in septic shock. The lack of differences in clinical outcomes supports the concept that sepsis involves pro- and anti-inflammatory pathways as well as other nonimmunologic pathways. Results lend further credence to the recent conceptualization of sepsis, with complications leading to organ dysfunction caused not primarily due to inflammatory responses but by a dysregulated response to infection.

Pro- and anti-inflammatory responses are regulated simultaneously from the first moments of septic shock

2011 ◽  
Vol 22 (2) ◽  
pp. 82-87 ◽  
Author(s):  
Eduardo Tamayo ◽  
Ana Fernández ◽  
Raquel Almansa ◽  
Elena Carrasco ◽  
María Heredia ◽  
...  
Keyword(s):  
Septic Shock ◽  
Inflammatory Responses ◽  
Anti Inflammatory

scholarly journals A Novel Thiazolyl Schiff Base: Antibacterial and Antifungal Effects and In Vitro Oxidative Stress Modulation on Human Endothelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Cristian Cezar Login ◽  
Ioana Bâldea ◽  
Brînduşa Tiperciuc ◽  
Daniela Benedec ◽  
Dan Cristian Vodnar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antibacterial Activity ◽  
Schiff Base ◽  
Cell Cultures ◽  
Gram Negative ◽  
Colorimetric Measurement ◽  
Anti Inflammatory ◽  
Experimental Findings ◽  
Antibacterial And Antifungal

Schiff bases (SBs) are chemical compounds displaying a significant pharmacological potential. They are able to modulate the activity of many enzymes involved in metabolism and are found among antibacterial, antifungal, anti-inflammatory, antioxidant, and antiproliferative drugs. A new thiazolyl-triazole SB was obtained and characterized by elemental and spectral analysis. The antibacterial and antifungal ability of the SB was evaluated against Gram-positive and Gram-negative bacteria and against three Candida strains. SB showed good antibacterial activity against L. monocytogenes and P. aeruginosa; it was two times more active than ciprofloxacin. Anti-Candida activity was twofold higher compared with that of fluconazole. The effect of the SB on cell viability was evaluated by colorimetric measurement on cell cultures exposed to various SB concentrations. The ability of the SB to modulate oxidative stress was assessed by measuring MDA, TNF-α, SOD1, COX2, and NOS2 levels in vitro, using human endothelial cell cultures exposed to a glucose-enriched medium. SB did not change the morphology of the cells. Experimental findings indicate that the newly synthetized Schiff base has antibacterial activity, especially on the Gram-negative P. aeruginosa, and antifungal activity. SB also showed antioxidant and anti-inflammatory activities.

scholarly journals A Novel Peptide Antibiotic, Pro10-1D, Designed from Insect Defensin Shows Antibacterial and Anti-Inflammatory Activities in Sepsis Models

2020 ◽  
Vol 21 (17) ◽  
pp. 6216
Author(s):  
Manigandan Krishnan ◽  
Joonhyeok Choi ◽  
Ahjin Jang ◽  
Yangmee Kim
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Cell ◽  
Film Formation ◽  
Systemic Infection ◽  
Nuclear Factor Κb ◽  
Peptide Antibiotic ◽  
Gram Negative Bacteria ◽  
Peptide Antibiotics ◽  
Gram Negative ◽  
Cell Selectivity

Owing to the challenges faced by conventional therapeutics, novel peptide antibiotics against multidrug-resistant (MDR) gram-negative bacteria need to be urgently developed. We had previously designed Pro9-3 and Pro9-3D from the defensin of beetle Protaetia brevitarsis; they showed high antimicrobial activity with cytotoxicity. Here, we aimed to develop peptide antibiotics with bacterial cell selectivity and potent antibacterial activity against gram-negative bacteria. We designed 10-meric peptides with increased cationicity by adding Arg to the N-terminus of Pro9-3 (Pro10-1) and its D-enantiomeric alteration (Pro10-1D). Among all tested peptides, the newly designed Pro10-1D showed the strongest antibacterial activity against Escherichia coli, Acinetobacter baumannii, and MDR strains with resistance against protease digestion. Pro10-1D can act as a novel potent peptide antibiotic owing to its outstanding inhibitory activities against bacterial film formation with high bacterial cell selectivity. Dye leakage and scanning electron microscopy revealed that Pro10-1D targets the bacterial membrane. Pro10-1D inhibited inflammation via Toll Like Receptor 4 (TLR4)/Nuclear factor-κB (NF-κB) signaling pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Furthermore, Pro10-1D ameliorated multiple-organ damage and attenuated systemic infection-associated inflammation in an E. coli K1-induced sepsis mouse model. Overall, our results suggest that Pro10-1D can potentially serve as a novel peptide antibiotic for the treatment of gram-negative sepsis.

scholarly journals Bactericidal Effect and Anti-Inflammatory Activity of Cassia garettiana Heartwood Extract

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Sumalee Panthong ◽  
Arunporn Itharat ◽  
Suchada Naknarin ◽  
Pranporn Kuropakornpong ◽  
Buncha Ooraikul ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Chemical Constituents ◽  
Ethanolic Extract ◽  
Antibacterial Activities ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Inhibiting Effect ◽  
Anti Inflammatory ◽  
Time Kill

Natural products are used as alternative drugs in traditional medicine to treat infection and inflammation and relieve pain. Heartwood of Cassia garettiana Craib has been investigated as an ingredient in Thai traditional medicine for anti-HIV protease, but there is no report on its antibacterial and anti-inflammatory activities. The objectives of this study were to investigate the anti-inflammatory and antibacterial activities, time-kill profile, and main active constituents of an ethanolic extract of C. garettiana heartwood. The study followed the generally accepted experimental design. All tests were investigated in triplicate. The heartwood of C. garettiana was extracted by maceration with 95% EtOH. The antibacterial activity of the extract and its chemical constituents were determined by their MIC values using resazurin as an indicator. Time-kill profile was determined at 0, 2, 4, 6, 8, 10, 12, and 24 hrs and expressed as log CFU/mL. The anti-inflammatory activity of the extract and its chemical components was investigated by their inhibiting effect on IL-6 and TNF-α production by ELISA. The ethanolic extract was analyzed for its chemical constituents by HPLC technique. The ethanolic extract showed both dose- and time-dependent bactericidal effects against Staphylococcus aureus, methicillin-resistance Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Salmonella Typhi, Salmonella Typhimurium, Klebsiella pneumoniae, and Shigella dysenteriae with MIC values of 312.5, 312.5, 312.5, 1,250, 2,500, 625, 625, 2,500, and 625 μg/mL, respectively. It showed an inhibiting effect on IL-6 production at concentrations of 12.5 to 100 μg/mL. The main active chemical constituent of C. garettiana was piceatannol that showed antibacterial activity against all test bacteria except P. aeruginosa. C. garettiana showed a broad spectrum of antibacterial activity against both Gram-negative and Gram-positive bacteria. Piceatannol and resveratrol from the plant strongly inhibited IL-6 production. Based on these results, we concluded that the ethanolic extract of C. garettiana showed both an antibacterial activity and inhibition of IL-6. Piceatannol is the active constituent of the extract and showed anti-inflammatory and antibacterial activities against Gram-negative and Gram-positive bacteria.

scholarly journals Syk/Src Pathway-Targeted Inhibition of Skin Inflammatory Responses by Carnosic Acid

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Jueun Oh ◽  
Tao Yu ◽  
Soo Jeong Choi ◽  
Yanyan Yang ◽  
Heung Soo Baek ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Carnosic Acid ◽  
Prostaglandin E ◽  
Lauryl Sulfate ◽  
Akt Inhibitor ◽  
Gram Positive ◽  
Gram Negative ◽  
Anti Inflammatory ◽  
Targeted Inhibition

Carnosic acid (CA) is a diterpene compound exhibiting antioxidative, anticancer, anti-angiogenic, anti-inflammatory, anti-metabolic disorder, and hepatoprotective and neuroprotective activities. In this study, the effect of CA on various skin inflammatory responses and its inhibitory mechanism were examined. CA strongly suppressed the production of IL-6, IL-8, and MCP-1 from keratinocyte HaCaT cells stimulated with sodium lauryl sulfate (SLS) and retinoic acid (RA). In addition, CA blocked the release of nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin E2(PGE2) from RAW264.7 cells activated by the toll-like receptor (TLR)-2 ligands, Gram-positive bacterium-derived peptidoglycan (PGN) and pam3CSK, and the TLR4 ligand, Gram-negative bacterium-derived lipopolysaccharide (LPS). CA arrested the growth of dermatitis-inducing Gram-positive and Gram-negative microorganisms suchPropionibacterium acnes, Pseudomonas aeruginosa, andStaphylococcus aureus. CA also blocked the nuclear translocation of nuclear factor (NF)-κB and its upstream signaling including Syk/Src, phosphoinositide 3-kinase (PI3K), Akt, inhibitor of κBα (IκBα) kinase (IKK), and IκBα for NF-κB activation. Kinase assays revealed that Syk could be direct enzymatic target of CA in its anti-inflammatory action. Therefore, our data strongly suggest the potential of CA as an anti-inflammatory drug against skin inflammatory responses with Src/NF-κB inhibitory properties.

scholarly journals Transduced PEP-1-Heme Oxygenase-1 Fusion Protein Attenuates Lung Injury in Septic Shock Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Xue-Tao Yan ◽  
Xiang-Hu He ◽  
Yan-Lin Wang ◽  
Zong-Ze Zhang ◽  
Jun-Jiao Tang
Keyword(s):  
Oxidative Stress ◽  
Septic Shock ◽  
Lung Injury ◽  
Fusion Protein ◽  
Heme Oxygenase ◽  
Cecal Ligation ◽  
Protective Role ◽  
Lung Damage ◽  
Heme Oxygenase 1 ◽  
Anti Inflammatory

Oxidative stress and inflammation have been identified to play a vital role in the pathogenesis of lung injury induced by septic shock. Heme oxygenase-1 (HO-1), an effective antioxidant and anti-inflammatory and antiapoptotic substance, has been used for the treatment of heart, lung, and liver diseases. Thus, we postulated that administration of exogenous HO-1 protein transduced by cell-penetrating peptide PEP-1 has a protective role against septic shock-induced lung injury. Septic shock produced by cecal ligation and puncture caused severe lung damage, manifested in the increase in the lung wet/dry ratio, oxidative stress, inflammation, and apoptosis. However, these changes were reversed by treatment with the PEP-1-HO-1 fusion protein, whereas lung injury in septic shock rats was alleviated. Furthermore, the septic shock upregulated the expression of Toll-like receptor 4 (TLR4) and transcription factor NF-κB, accompanied by the increase of lung injury. Administration of PEP-1-HO-1 fusion protein reversed septic shock-induced lung injury by downregulating the expression of TLR4 and NF-κB. Our study indicates that treatment with HO-1 protein transduced by PEP-1 confers protection against septic shock-induced lung injury by its antioxidant, anti-inflammatory, and antiapoptotic effects.

scholarly journals Mesenchymal Stem Cells Impact on COVID-19 Patients Immune System, an Ex Vivo Study

2021 ◽  
Author(s):  
Raedeh Saraei ◽  
kosar malekpour ◽  
Ali Hazrati ◽  
Hamed Valizadeh ◽  
Behnam Hashemi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Methylation Status ◽  
Lung Damage ◽  
Th2 Cells ◽  
Regulatory Function ◽  
Anti Inflammatory

Abstract Current clinical management approaches for COVID-19 patients are generally based on supportive treatment, which mainly includes respiratory support and restricted fluid input, which is currently a subject of much debate. Systemic Inflammation caused by SARS-CoV-2 may be related to various extrapulmonary comorbidities such as cytokine-mediated neuroinflammation leading to both non-neuronal and neurological consequences in COVID-19. Mesenchymal stem cells (MSCs) are adult stem cells with multipotent properties suitable for medical applications that have been reported as potential therapies in the setting of lung diseases. The immunosuppressive properties of MSCs provide a strong rationale to explore their potential beneficial effects on immune events in COVID-19. Multiple in vivo studies have demonstrated the capability of MSCs to prevent inflammatory responses and reduce lung damage. Recently, the use of MSCs in treating COVID-19 disease has improved long-term pulmonary function, but the specific mechanisms by which MSCs inhibit the severe inflammatory response induced by SARS-CoV-2 have not been elucidated. To the best of our knowledge, this is the first work describing the regulatory effects of MSCs on peripheral blood mononuclear cells (PBMCs) derived from patients with COVID-19 by measuring the pro-inflammatory and anti-inflammatory cytokines expression and secretion. We also examined the effects on the methylation of genes normally suppressed by DNA methylation in PBMCs. Our result showed that MSCs exerted an immune regulatory function on PBMCs in culture, skewing toward a type-2 response. This occurs by a mechanism consistent with a reduction in inflammatory factors (TNF-α, IL-1β, IL-6, IL-18, and IFNγ) protein and mRNA expression levels. In contrast, the anti-inflammatory cytokines (IL-4 and IL-10) increased following co-culture with MSCs. Consistent with these findings, the DNA methylation status of these immune genes seemed relevant to their expression pattern, except for GATA3, IL-1β, and IFNγ genes which showed no significant differences in methylation level between PBMCs with and without MSC exposure. Moreover, in co-culture interaction, MSCs modulated the Th1/Th2 cells in PBMCs compared to unstimulated PBMCs. These data demonstrate that MSCs can exert important immunomodulatory functions that affect virus-associated cytokine storms in pulmonary tissue during the severe respiratory stage.

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