Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of Capsicum plants (chili peppers), which are grown as food and for medicinal purposes since ancient times, and is responsible for ...the pungency of their fruit. Besides its multiple pharmacological and physiological properties (pain relief, cancer prevention, and beneficial cardiovascular, and gastrointestinal effects) capsaicin has recently attracted considerable attention because of its antimicrobial and anti-virulence activity. This is the first study of its in vitro antibacterial and anti-virulence activity against Streptococcus pyogenes (Group A streptococci, GAS), a major human pathogen. The test strains were previously characterized, erythromycin-susceptible (n = 5) and erythromycin-resistant (n = 27), cell-invasive pharyngeal isolates. The MICs of capsaicin were 64-128 μg/mL (the most common MIC was 128 μg/mL). The action of capsaicin was bactericidal, as suggested by MBC values that were equal or close to the MICs, and by early detection of dead cells in the live/dead assay. No capsaicin-resistant mutants were obtained in single-step resistance selection studies. Interestingly, growth in presence of sublethal capsaicin concentrations induced an increase in biofilm production (p ≤ 0.05) and in the number of bacteria adhering to A549 monolayers, and a reduction in cell-invasiveness and haemolytic activity (both p ≤ 0.05). Cell invasiveness fell so dramatically that a highly invasive strain became non-invasive. The dose-response relationship, characterized by opposite effects of low and high capsaicin doses, suggests a hormetic response. The present study documents that capsaicin has promising bactericidal activity against erythromycin-resistant, cell-invasive pharyngeal GAS isolates. The fact that sublethal concentrations inhibited cell invasion and reduced haemolytic activity, two important virulence traits of GAS, is also interesting, considering that cell-invasive, erythromycinresistant strains can evade β-lactams by virtue of intracellular location and macrolides by virtue of resistance, thus escaping antibiotic treatment. By inhibiting intracellular invasion and haemolytic activity, capsaicin could thus prevent both formation of a difficult to eradicate intracellular reservoir, and infection spread to deep tissues.
•Polyphenols (PPs) are key mediators of the beneficial effects of the Mediterranean Diet.•Dietary PPs can affect glucose and lipid homeostasis through multiple mechanisms.•Clinical trials exploring ...the effects of PPs on type 2 diabetes and dyslipidemia are affected by multiple sources of bias.•Long-term trials to evaluate the association between PPs and the incidence of type 2 diabetes are needed.
Epidemiological evidence from observational studies suggests that dietary polyphenols (PPs) – phytochemicals found in a variety of plant-based foods – can reduce the risk of developing type 2 diabetes mellitus (T2DM). Clinical trials have also indicated that PPs may help manage the two key features of T2DM, hyperglycemia and dyslipidemia. Since the incidence of T2DM is dramatically increasing worldwide, identifying food-based approaches that can reduce the risk of developing it and help manage its main risk factors in early-stage disease has clinical and socioeconomic relevance.
After a brief overview of current epidemiological data on the incidence of T2DM in individuals consuming PP-rich diets, we review the evidence from clinical trials investigating PP-enriched foods and/or PP-based nutraceutical compounds, report their main results, and highlight the knowledge gaps that should be bridged to enhance our understanding of the role of PPs in T2DM development and management.
Skin and chronic wound infections are an increasing and urgent health problem worldwide. Their management is difficult and the development of antibiotic resistance by both planktonic and ...biofilm-associated bacteria necessitates the use of alternative treatments. The purpose of this study was to compare the antimicrobial activity of four honeys from different floral and geographical origins:
honey (Cuba) and three
honeys Manuka honey (New Zealand),
honey (Cuba), and African honey (Kenya). The physicochemical parameters were within the ranges reported for these honeys and
honey stood out due to its acidic character. An agar incorporation technique was used to determine the minimum active dilution of each honey against 52 clinical isolates (34 Gram-positive, 17 Gram-negative, and 1
). The antibiofilm activity of honeys was tested by assessing their ability to inhibit biofilm formation and to disrupt preformed biofilms. Overall,
honey had the highest antimicrobial and antibiofilm activity, although a marked disruption in preformed biofilms was shared by all tested honeys. Structural changes induced by
honey on
and
cells were observed by transmission electron microscopy suggesting that this honey has a potent antimicrobial action and may be an excellent candidate for the development of topical preparations for the treatment of infected wounds.
Anti-virulence strategies are being explored as a novel approach to combat pathogens. Such strategies include inhibition of surface adhesion, tissue invasion, toxin production, and/or interference ...with the gene regulation of other virulence traits.
, the causative agent of listeriosis, is a facultative intracellular food pathogen characterized by a wide distribution in the environment. Its ability to persist within biofilms and to develop resistance to sanitizers is the cause of significant problems in food processing plants and of steep costs for the food industry. In humans, the treatment of listeriosis is hampered by the intracellular location of listeriae and the poor intracellular penetration of some antibiotics. Eleven
isolates from patients who were diagnosed with invasive listeriosis in Italy in 2014-2016 were studied. This
and
study explored the antibacterial and anti-virulence properties of a steam-distilled essential oil of
L., which is being intensively investigated for its high content in powerful bioactive phytochemicals. Susceptibility experiments demonstrated a moderate bactericidal activity of the essential oil (Minimum Bactericidal Concentration > 2048 μg/mL). Assessment of the effects of sublethal concentrations of the essential oil on
virulence traits demonstrated a significant action on motility. Listeriae were non-motile after exposure to the essential oil. Light and scanning electron microscopy documented aggregates of listeriae with the flagella trapped inside the cluster. Real-time RT-PCR experiments showed downregulation of flagellar motility genes and of the regulatory gene
. The ability to form biofilm and to invade Caco-2 cells was also significantly reduced.
larvae infected with
grown in presence of sublethal concentrations of the essential oil showed much higher survival rates compared with controls, suggesting that the extract inhibited tissue invasion. Food contamination with
is a major concern for the food industry, particularly for plants making ready-to-eat and processed food. The present work provides a baseline in the study of the anti-virulence properties of the
essential oil against
. Further studies are needed to understand if it could be used as an alternative agent for the control of
in food processing plants.
The neuro-immune axis has a crucial function both during physiological and pathological conditions. Among the immune cells, myeloid-derived suppressor cells (MDSCs) exert a pivotal role in regulating ...the immune response in many pathological conditions, influencing neuroinflammation and neurodegenerative disease progression. In chronic neuroinflammation, MDSCs could lead to exacerbation of the inflammatory state and eventually participate in the impairment of cognitive functions. To have a complete overview of the role of MDSCs in neurodegenerative diseases, research on PubMed for articles using a combination of terms made with Boolean operators was performed. According to the search strategy, 80 papers were retrieved. Among these, 44 papers met the eligibility criteria. The two subtypes of MDSCs, monocytic and polymorphonuclear MDSCs, behave differently in these diseases. The initial MDSC proliferation is fundamental for attenuating inflammation in Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), but not in amyotrophic lateral sclerosis (ALS), where MDSC expansion leads to exacerbation of the disease. Moreover, the accumulation of MDSC subtypes in distinct organs changes during the disease. The proliferation of MDSC subtypes occurs at different disease stages and can influence the progression of each neurodegenerative disorder differently.
Several studies have demonstrated that stigmas of
contain several bioactive compounds with potential health-promoting properties. However, during the processing of stigmas, large amounts of floral ...bio-residues are normally discarded as by-products. In this study, using untargeted metabolomics, the comprehensive phytochemical composition of
stigma and tepals was investigated. Moreover, the antibacterial and anti-biofilm properties of the extracts of
stigmas and tepals were compared. The study was carried out using two methicillin-resistant staphylococcal reference strains (i.e.,
ATCC 43300 and Staphylococcus epidermidis ATCC 35984), representing important Gram-positive biofilm-forming human pathogens. The antibacterial properties were correlated with total polyphenol content, total terpenoid content, and
antioxidant properties of tepals and stigmas. The results demonstrated that stigma and tepal extracts, at the sub-toxic concentrations, were able to interfere with biofilm formation by ATCC 43300 and ATCC 35984. Besides, the higher antibacterial activity of tepals than stigmas was associated with higher levels of phycompounds. Therefore, our results demonstrated that
stigmas and bio-residues, such as tepals, are potential antioxidant sources and good candidates as antibacterial agents to prevent biofilm formation. Taken together, these findings showed that
could be used as functional ingredient by the food and pharmaceutical industries.
H-Ras oncogene requires deregulation of additional oncogenes or inactivation of tumor suppressor proteins to increase cell proliferation rate and transform cells. In fact, the expression of the ...constitutively activated H-RasV12 induces cell growth arrest and premature senescence, which act like barriers in pre-neoplastic lesions. In our experimental model, human fibroblasts transfected with H-RasV12 show a dramatic modification of morphology. H-RasV12 expressing cells also show premature senescence followed by cell death, induced by autophagy and apoptosis. In this context, we provide evidence that in H-RasV12 expressing cells, the premature senescence is associated with cellular redox imbalance as well as with altered post-translation protein modification. In particular, redox imbalance is due to a strong reduction of total antioxidant capacity, and significant decrease of glutathione level. As the reversible addition of glutathione to cysteinyl residues of proteins is an important post-translational regulative modification, we investigated S-glutathionylation in cells expressing active H-Ras. In this contest we observed different S-glutathionylation patterns in control and H-RasV12 expressing cells. Particularly, the GAPDH enzyme showed S-glutathionylation increase and significant enzyme activity depletion in H-Ras V12 cells. In conclusion, we proposed that antioxidant defense reduction, glutathione depletion and subsequent modification of S-glutathionylation of target proteins contribute to arrest cell growth, leading to death of fibroblasts expressing constitutively active H-Ras oncogene, thus acting as oncogenic barriers that obstacle the progression of cell transformation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Non-Small Cell Lung Cancer (NSCLC) represents ∼85% of all lung cancers and ∼15–20% of them are characterized by mutations affecting the Epidermal Growth Factor Receptor (EGFR). For several years now, ...a class of tyrosine kinase inhibitors was developed, targeting sensitive mutations affecting the EGFR (EGFR-TKIs). To date, the main burden of the TKIs employment is due to the onset of resistance mutations. This scoping review aims to resume the current situation about the cell line models employed for the in vitro evaluation of resistance mechanisms induced by EGFR-TKIs in oncogene-addicted NSCLC. Adenocarcinoma results the most studied NSCLC histotype with the H1650, H1975, HCC827 and PC9 mutated cell lines, while Gefitinib and Osimertinib the most investigated inhibitors. Overall, data collected frame the current advancement of this topic, showing a plethora of approaches pursued to overcome the TKIs resistance, from RNA-mediated strategies to the innovative combination therapies.
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•228 original articles have been collected from 1999 to March 2023.•H1650, H1975, HCC827 and PC9 are the most employed NSCLC mutated cell lines.•Afatinib, Erlotinib, Gefitinib and Osimertinib are the most investigated EGFR-TKIs.•Knockdown and combined approaches were pursued to overcome the TKIs resistance.
Carvacrol (CAR), a natural monoterpene particularly abundant in plants belonging to the Lamiaceae family, has recently attracted much attention for its many biological properties (antioxidant, ...anti-inflammatory, neuroprotective, antitumour, antibacterial, and several others). However, CAR has poor chemical-physical properties (low water solubility and high volatility), which hamper its potential pharmacological uses.
In this paper, the synthesis and antimicrobial evaluation of 23 carvacrol derivatives (WSCP1-23) against a panel of selected gram-positive and gram-negative bacteria are reported. Using the prodrug approach, CAR hydrophilic (WSCP1-17) and lipophilic prodrugs (WSCP18–23) were prepared. Notably, CAR water solubility was increased by using polar neutral groups (such as natural amino acids) with the aim of improving oral drug delivery. On the other hand, CAR lipophilic prodrugs, obtained by prenylation of CAR hydroxyl group, were designed to promote membrane permeation and oral absorption.
Our results revealed that WSCP1-3, showing the highest water solubility (>1700-fold compared to that of CAR), possessed good antibacterial activity against gram-negative bacteria with MIC values comparable to those of CAR and antifungal properties against different species of Candida. WSCP18–19 were the most promising prodrugs, showing good antibacterial profiles against gram-positive bacteria by interfering with the biofilm formation of Staphylococcus aureus and Staphylococcus epidermidis. Moreover, WSCP18–19 resulted more stable in simulated fluids and human plasma than WSCP1-3. Toxicity studies performed on human erythrocytes and HaCaT cells revealed that all WSCPs were not toxic at the tested concentrations.
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•Synthesis of novel carvacrol prodrugs.•Carvacrol prodrugs as potential antibacterial agents.•Antibiofilm activity of WSCP18 against S. aureus.
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