ABSTRACT
In recent decades, bacteriocins have received substantial attention as antimicrobial compounds. Although bacteriocins have been predominantly exploited as food preservatives, they are now ...receiving increased attention as potential clinical antimicrobials and as possible immune-modulating agents. Infections caused by antibiotic-resistant bacteria have been declared as a global threat to public health. Bacteriocins represent a potential solution to this worldwide threat due to their broad- or narrow-spectrum activity against antibiotic-resistant bacteria. Notably, despite their role in food safety as natural alternatives to chemical preservatives, nisin remains the only bacteriocin legally approved by regulatory agencies as a food preservative. Moreover, insufficient data on the safety and toxicity of bacteriocins represent a barrier against the more widespread use of bacteriocins by the food and medical industry. Here, we focus on the most recent trends relating to the application of bacteriocins, their toxicity and impacts.
Antimicrobial activity, gastrointestinal bihaviour and toxicity of bacteriocins.
Bacteriocins and reuterin are promising antimicrobials for application in food, veterinary, and medical sectors. In the light of their high potential for application in hand sanitizer, we ...investigated the skin toxicity of reuterin, microcin J25, pediocin PA-1, bactofencin A, and nisin Z in vitro using neutral red and LDH release assays on NHEK cells. We determined their skin sensitization potential using the human cell line activation test (h-CLAT). Their skin irritation potential was measured on human epidermal model EpiDerm™. We showed that the viability and membrane integrity of NHEK cells remained unaltered after exposure to bacteriocins and reuterin at concentrations up to 400 µg/mL and 80 mg/mL, respectively. Furthermore, microcin J25 and reuterin showed no skin sensitization at concentrations up to 100 µg/mL and 40 mg/mL, respectively, while pediocin PA-1, bactofencin A, and nisin Z caused sensitization at concentrations higher than 100 µg/mL. Tissue viability was unaffected in presence of bacteriocins and reuterin at concentrations up to 200 µg/mL and 40 mg/mL, respectively, which was confirmed by measuring cytokine IL-1α and IL-8 levels and by histological analysis. In conclusion, the current study provides scientific evidence that some bacteriocins and reuterin, could be safely applied topically as sanitizers at recommended concentrations.
Zusammenfassung
Die neuen Leitlinien der European Society of Cardiology (ESC) für die Diagnose und Therapie der akuten und der chronischen Herzinsuffizienz beinhalten eine neue Benennung der ...Herzinsuffizienz mit mild reduzierter Ejektionsfraktion (HFmrEF, EF: 41–49 %, früher „mid-range“, jetzt „mildly reduced“); für diese Form der Herzinsuffizienz gibt es erstmals Empfehlungen zur Therapie mit den Standardmedikamenten, die auch bei HFrEF eingesetzt werden. Neu ist ebenso eine Klasse-I-Empfehlung für die Behandlung mit SGLT2(„sodium-glucose linked transporter 2“)-Inhibitoren (SGLT2i) bei Patienten mit HFrEF unabhängig vom Vorliegen eines Diabetes mellitus. Hervorzuheben ist, dass alle HFrEF-Patienten mit einer 4‑fach-Kombination aus Angiotensinrezeptor-Neprilysininhibitor (ARNI) bzw. ACE(„angiotensin-converting enzyme“)-Hemmer, Betablocker, Mineralokortikoidrezeptorantagonist (MRA) und SGLT2i behandelt werden sollen; es kann auch eine Primärtherapie mit ARNI erwogen werden ohne vorherige Gabe eines ACE-Hemmers. Bezüglich der Indikation zur primärprophylaktischen ICD(implantierbarer Kardioverter-Defibrillator)-Implantation besteht bei Patienten mit einer EF von 35 % oder weniger wie bisher eine Klasse-I-Indikation bei ischämischer, jedoch eine IIa-Indikation bei nichtischämischer Genese. Diese und weitere wichtige Neuerungen werden unter Einbeziehung der zugrunde liegenden klinischen Studien zusammengefasst.
Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM ...are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.
Bacteriocins are receiving increased attention as potent candidates in food preservation and medicine. Although the inhibitory activity of bacteriocins has been studied widely, little is known about ...their gastrointestinal stability and toxicity toward normal human cell lines. The aim of this study was to evaluate the gastrointestinal stability and activity of microcin J25, pediocin PA-1, bactofencin A and nisin using
models. In addition cytotoxicity and hemolytic activity of these bacteriocins were investigated on human epithelial colorectal adenocarcinoma cells (Caco-2) and rat erythrocytes, respectively. Pediocin PA-1, bactofencin A, and nisin were observed to lose their stability while passing through the gastrointestinal tract, while microcin J25 is only partially degraded. Besides, selected bacteriocins were not toxic to Caco-2 cells, and integrity of cell membrane was observed to remain unaffected in presence of these bacteriocins at concentrations up to 400 μg/mL. In hemolysis study, pediocin PA-1, bactofencin A, and nisin were observed to lyse rat erythrocytes at concentrations higher than 50 μg/mL, while microcin J25 showed no effect on these cells. According to data indicating gastrointestinal degradation and the absence of toxicity of pediocin PA-1, bactofencin A, and microcin J25 they could potentially be used in food or clinical applications.
In this research, zeolite ZSM-12 with Si/Al ratio = 80 was synthesized by hydrothermal method. The synthesized zeolite ZSM-12 was modified using Fe and Ga metals and a combination of these two ...metals, 1 % iron metals (Z80-Fe) and 1 % gallium metals(Z80-Ga), and a 2 % combination of these two metals (Z80-Fe-Ga). The physicochemical properties of synthesized zeolites were evaluated and compared by XRD, EDX-dot-mapping, NH3-TPD, BET, FT-IR, and TGA analyses. The catalytic assessment of synthesized zeolites in the HTO (n-hexane to olefins) process in a fixed bed reactor under atmospheric pressure and Weight hourly space velocity (WHSV) equal to 4 h−1 at 550 °C was evaluated. Various parameters such as selectivity towards light olefins, propylene to ethylene (P/E ratio), production of light alkanes, and aromatic compounds (BTX) were investigated. The results show that using metals led to the improvement and adjustment of the acid sites of zeolite, and the highest amount of light olefin and the lowest amount of coke were obtained. The result of the n-hexane to olefin process showed that the yield of light olefins was significantly improved in all modified catalysts compared to parent zeolite MTW. Compared to other modified zeolites, Z80-Fe-Ga zeolite has the highest yield of light olefins, equal to 59 %. This zeolite performs better due to the presence of gallium and iron metals and shows the highest propylene selectivity (P/E = 2.4). In addition, according to the results of the TGA analysis, the content of coke on the Z80-Fe-Ga catalyst after the catalytic reaction is much less than that of other catalysts after the catalytic reactor test.
Bacteria-derived natural antimicrobial compounds such as bacteriocins, reruterin, and organic acids have recently received substantial attention as food preservatives or therapeutic alternatives in ...human or animal sectors. This study aimed to evaluate the antimicrobial activity of different bacteria-derived antimicrobials, alone or in combination, against a large panel of Gram-negative and Gram-positive bacteria. Bacteriocins, including microcin J25, pediocin PA-1, nisin Z, and reuterin, were investigated alone or in combination with lactic acid and citric acid, using a checkerboard assay. Concentrations were selected based on predetermined MICs against Salmonella enterica subsp.
serovar Newport ATCC 6962 and Listeria ivanovii HPB28 as Gram-negative and Gram-positive indicator strains, respectively. The results demonstrated that the combination of microcin J25 + citric acid + lactic acid; microcin J25 + reuterin + citric acid; and microcin J25 + reuterin + lactic acid tested against
Newport ATCC 6962 showed synergistic effects (FIC index = 0.5). Moreover, a combination of pediocin PA-1 + citric acid + lactic acid; and reuterin + citric acid + lactic acid against
HPB28 showed a partially synergistic interactions (FIC index = 0.75). Nisin Z exerted a partially synergistic effect in combination with acids (FIC index = 0.625 -0.75), whereas when it was combined with reuterin or pediocin PA-1, it showed additive effects (FIC index = 1) against
HPB28. The inhibitory activity of synergetic consortia were tested against a large panel of Gram-positive and Gram-negative bacteria. According to our results, combining different antimicrobials with different mechanisms of action led to higher potency and a broad spectrum of inhibition, including multidrug-resistance pathogens.
Reuterin and bacteriocins, including microcin J25, pediocin PA-1, nisin were produced and purified with >90% purity. Using the broth-based checkerboard assay the interaction between these compounds (synergetic, additive, or antagonistic) was assessed. By combining different natural antimicrobials with different modes of action and structure (reuteirn, microcin J25, pediocin PA-1, and organic acids), we successfully developed five different synergetic consortia with improved antimicrobial activity and a broad spectrum of inhibition. These consortia were shown to be effective against a large panel of pathogenic and spoilage microorganisms as well as clinically important multidrug-resistance bacteria. Moreover, because the lower concentrations of bacteriocins and reuterin are used in the synergetic consortia, there is a limited risk of toxicity and resistance development for these compounds.
Over the last 15–20 years, remarkable developments of heart failure (HF) pharmacotherapies have been achieved. However, HF remains a global healthcare challenge with more than 64 million patients ...worldwide. Optimization of guideline‐directed chronic HF medical therapy is highly recommended with every patient visit to improve outcomes in patients with HF with reduced ejection fraction. However, the majority of patients in real‐world settings are treated with doses that are lower than those with proven efficacy in clinical trials, which might be due to concerns of adverse effects and inertia of physicians. Likewise, a significant proportion of patients still do not receive all drug classes that could improve their prognosis. The recent European Society of Cardiology guidelines do not provide detailed recommendations on how these drug classes should be implemented in the treatment of inpatients to allow for both safety and a high likelihood of efficacy. We therefore propose a practical approach algorithm to support physicians to treat HF patients in their daily practice.
Mobile health technologies are gaining importance in clinical decision-making. With the capability to monitor the patient's heart rhythm, they have the potential to reduce the time to confirm a ...diagnosis and therefore are useful in patients eligible for screening of atrial fibrillation as well as in patients with symptoms without documented symptom rhythm correlation. Such is crucial to enable an adequate arrhythmia management including the possibility of a catheter ablation. After ablation, wearables can help to search for recurrences, in symptomatic as well as in asymptomatic patients. Furthermore, those devices can be used to search for concomitant arrhythmias and have the potential to help improving the short- and long-term patient management. The type of wearable as well as the adequate technology has to be chosen carefully for every situation and every individual patient, keeping different aspects in mind. This review aims to describe and to elaborate a potential workflow for the role of wearables for cardiac rhythm monitoring regarding detection and management of arrhythmias before and after cardiac electrophysiological procedures.
PDF
