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1.
Int J Mol Sci ; 25(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38396753

RESUMO

Recently, 5-[(4-ethoxyphenyl)imino]methyl-N-(4-fluorophenyl)-6-methyl-2-phenylpyrimidin-4-amine has been synthesized, characterized, and evaluated for its antibacterial activity against Enterococcus faecalis in combination with antineoplastic activity against gastric adenocarcinoma. In this study, new 5-iminomethylpyrimidine compounds were synthesized which differ in the substituent(s) of the aromatic ring attached to the imine group. The structures of newly obtained pyrimidine Schiff bases were established by spectroscopy techniques (ESI-MS, FTIR and 1H NMR). To extend the current knowledge about the features responsible for the biological activity of the new 5-iminomethylpyrimidine derivatives, low-temperature single-crystal X-ray analyses were carried out. For all studied crystals, intramolecular N-H∙∙∙N hydrogen bonds and intermolecular C-H∙∙∙F interactions were observed and seemed to play an essential role in the formation of the structures. Simultaneously, their biological properties based on their cytotoxic features were compared with the activities of the Schiff base (III) published previously. Moreover, computational investigations, such as ADME prediction analysis and molecular docking, were also performed on the most active new Schiff base (compound 4b). These results were compared with the highest active compound III.


Assuntos
Antibacterianos , Bases de Schiff , Simulação de Acoplamento Molecular , Bases de Schiff/farmacologia , Bases de Schiff/química , Espectroscopia de Ressonância Magnética , Antibacterianos/farmacologia , Pirimidinas/farmacologia
2.
Toxicol Appl Pharmacol ; 469: 116541, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37149094

RESUMO

According to some clinical observations, the use of angiotensin-converting enzyme inhibitors (ACEI) may be associated with an increased risk of cancer. The aim of the present study was to screen for the potential carcinogenicity, mutagenicity and genotoxicity of these drugs using in silico methodology. Delapril, enalapril, imidapril, lisinopril, moexipril, perindopril, ramipril, trandolapril, spirapril were thereby analyzed. In parallel, the corresponding degradation impurities, the diketopiperazine (DKP) derivatives, were also investigated. (Q)SAR computer software (VEGA-GUI and Lazar), available in the public domain, was employed. The obtained predictions suggested that none of the compounds tested (from the group of ACE-Is and DKPs) was mutagenic. Moreover, none of the ACE-Is was carcinogenic. The reliability of these predictions was high to moderate. In contrast, in the DKP group, ramipril-DKP and trandolapril-DKP were found to be potentially carcinogenic, but the reliability of this prediction was low. As for the genotoxicity screening, all compounds tested (ACE-I and DKP) were predicted to be active and genotoxic, with moexipril, ramipril, spirapril, and all DKP derivatives within the highest risk group. They were prioritized for experimental verification studies to confirm or exclude their toxic activity. On the other hand, the lowest risk of carcinogenicity was assigned to imidapril and its DKP. Then, a follow-up in vitro micronucleus assay for ramipril was performed. It showed that this drug was genotoxic via aneugenic activity, but only at concentrations exceeding real-life levels. At concentrations found in human blood after standard dose, ramipril was not genotoxic in vitro. Therefore, ramipril was considered safe for human use with a standard dosing regimen. The other compounds of concern (spirapril, moexipril and all DKP derivatives) should be subjected to analogous in vitro studies. We also concluded that the adopted in silico software was applicable for ACE-I toxicity prediction.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Tetra-Hidroisoquinolinas , Humanos , Inibidores da Enzima Conversora de Angiotensina/toxicidade , Carcinógenos/toxicidade , Reprodutibilidade dos Testes , Ramipril/toxicidade
3.
Inorg Chem ; 62(34): 14103-14115, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37582221

RESUMO

Proteolytic degradation of semenogelins, the most abundant proteins from human semen, results in the formation of 26- and 29-amino acid peptides (SgIIA and SgI-29, respectively), which share a common 15 amino acid fragment (Sg-15). All three ligands are effective Zn(II) and Cu(II) binders; in solution, a variety of differently metalated species exist in equilibrium, with the [NH2, 3Nim] donor set prevailing at physiological pH in the case of both metals. For the first time, the Cu(II)-induced antimicrobial activity of Sg-15 against Enterococcus faecalis is shown. In the case of the two native semenogelin fragment metal complexes, the strong local positive charge in the metal-bound HH motif correlates well with their antimicrobial activity. A careful analysis of semenogelins' metal coordination behavior reveals two facts: (i) The histamine-like Cu(II) binding mode of SgI-29 strongly increases the stability of such a complex below pH 6 (with respect to the non-histamine-like binding of SgIIA), while in the case of the SgI-29 Zn(II)-histamine-like species, the stability enhancement is less pronounced. (ii) The HH sequence is a more tempting site for Cu(II) ions than the HXH one.


Assuntos
Anti-Infecciosos , Enterococcus faecalis , Humanos , Cobre/química , Química Bioinorgânica , Zinco/química
4.
Inorg Chem ; 62(48): 19786-19794, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37983127

RESUMO

Shepherin I is a glycine- and histidine-rich antimicrobial peptide from the root of a shepherd's purse, whose antimicrobial activity was suggested to be enhanced by the presence of Zn(II) ions. We describe Zn(II) and Cu(II) complexes of this peptide, aiming to understand the correlation between their metal binding mode, structure, morphology, and biological activity. We observe a logical sequence of phenomena, each of which is the result of the previous one: (i) Zn(II) coordinates to shepherin I, (ii) causes a structural change, which, in turn, (iii) results in fibril formation. Eventually, this chain of structural changes has a (iv) biological consequence: The shepherin I-Zn(II) fibrils are highly antifungal. What is of particular interest, both fibril formation and strong anticandidal activity are only observed for the shepherin I-Zn(II) complex, linking its structural rearrangement that occurs after metal binding with its morphology and biological activity.


Assuntos
Capsella , Antifúngicos/farmacologia , Peptídeos Antimicrobianos , Peptídeos , Zinco/farmacologia
5.
Int J Mol Sci ; 24(14)2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37511545

RESUMO

Microorganisms inhabiting saline environments have been known for decades as producers of many valuable bioproducts. These substances include antimicrobial peptides (AMPs), the most recognizable of which are halocins produced by halophilic Archaea. As agents with a different modes of action from that of most conventionally used antibiotics, usually associated with an increase in the permeability of the cell membrane as a result of a formation of channels and pores, AMPs are a currently promising object of research focused on the investigation of antibiotics with non-standard modes of action. The aim of this study was to investigate antimicrobial activity against multidrug-resistant human pathogens of three peptides, which were synthetised based on sequences identified in metagenomes from saline environments. The investigations were performed against Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. Subsequently, the cytotoxicity and haemolytic properties of the tested peptides were verified. An in silico analysis of the interaction of the tested peptides with molecular targets for reference antibiotics was also carried out in order to verify whether or not they can act in a similar way. The P1 peptide manifested the growth inhibition of E. faecalis at a MIC50 of 32 µg/mL and the P3 peptide at a MIC50 of 32 µg/mL was shown to inhibit the growth of both E. faecalis and S. aureus. Furthermore, the P1 and P3 peptides were shown to have no cytotoxic or haemolytic activity against human cells.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Staphylococcus aureus , Humanos , Peptídeos Antimicrobianos , Antibacterianos/farmacologia , Antibacterianos/química , Peptídeos , Testes de Sensibilidade Microbiana
6.
Inorg Chem ; 60(17): 12730-12734, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34382773

RESUMO

Can a minor difference in the nonmetal binding sequence of antimicrobial clavanins explain the drastic change in the coordination environment and antimicrobial efficiency? This study answers the question with a definite "yes", showing the details of the bioinorganic chemistry of Zn(II) and Cu(II) complexes with clavanins, histidine-rich, antimicrobial peptides from hemocytes of the tunicate Styela clava.


Assuntos
Antibacterianos/farmacologia , Proteínas Sanguíneas/farmacologia , Complexos de Coordenação/farmacologia , Sequência de Aminoácidos , Antibacterianos/química , Antibacterianos/toxicidade , Bactérias/efeitos dos fármacos , Proteínas Sanguíneas/química , Proteínas Sanguíneas/toxicidade , Candida albicans/efeitos dos fármacos , Linhagem Celular , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Cobre/química , Humanos , Testes de Sensibilidade Microbiana , Zinco/química
7.
Int J Mol Sci ; 22(13)2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203496

RESUMO

The antimicrobial activity of surfactant-associated anionic peptides (SAAPs), which are isolated from the ovine pulmonary surfactant and are selective against the ovine pathogen Mannheimia haemolytica, is strongly enhanced in the presence of Zn(II) ions. Both calorimetry and ITC measurements show that the unique Asp-only peptide SAAP3 (DDDDDDD) and its analogs SAAP2 (GDDDDDD) and SAAP6 (GADDDDD) have a similar micromolar affinity for Zn(II), which binds to the N-terminal amine and Asp carboxylates in a net entropically-driven process. All three peptides also bind Cu(II) with a net entropically-driven process but with higher affinity than they bind Zn(II) and coordination that involves the N-terminal amine and deprotonated amides as the pH increases. The parent SAAP3 binds Cu(II) with the highest affinity; however, as shown with potentiometry and absorption, CD and EPR spectroscopy, Asp residues in the first and/or second positions distinguish Cu(II) binding to SAAP3 and SAAP2 from their binding to SAAP6, decreasing the Cu(II) Lewis acidity and suppressing its square planar amide coordination by two pH units. We also show that these metal ions do not stabilize a membrane disrupting ability nor do they induce the antimicrobial activity of these peptides against a panel of human pathogens.


Assuntos
Cobre/metabolismo , Peptídeos/química , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Zinco/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Mannheimia haemolytica/efeitos dos fármacos , Mannheimia haemolytica/patogenicidade , Peptídeos/metabolismo , Termodinâmica
8.
Molecules ; 26(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33921108

RESUMO

Enterococcus faecalis is known as a significant nosocomial pathogen due to its natural resistance to many antibacterial drugs. Moreover, it was found that E. faecalis infection causes inflammation, production of reactive oxygen species, and DNA damage to human gastric cancer cells, which can induce cancer. In this study, we synthesized and tested the biological activity of a new Schiff base, 5-[(4-ethoxyphenyl)imino]methyl-N-(4-fluorophenyl)-6-methyl-2-phenylpyrimidin-4-amine (3), and compared its properties with an analogous amine (2). In the biological investigation, 3 was found to have antibacterial activity against E. faecalis 29212 and far better anticancer properties, especially against gastric adenocarcinoma (human Caucasian gastric adenocarcinoma), than 2. In addition, both derivatives were non-toxic to normal cells. It is worth mentioning that 3 could potentially inhibit cancer cell growth by inducing cell apoptosis. The results suggest that the presence of the -C=N- bond in the molecule of 3 increases its activity, indicating that 5-iminomethylpyrimidine could be a potent core for further drug discovery research.


Assuntos
Pirimidinas/química , Bases de Schiff/química , Adenocarcinoma/metabolismo , Antibacterianos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Neoplasias Gástricas/metabolismo , Relação Estrutura-Atividade
9.
Biol Pharm Bull ; 40(8): 1199-1206, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28769001

RESUMO

The aim of the work was the evaluation of selected biological and physicochemical, applicative properties of ethylated ascorbic acid (AAE) compared to ascorbic acid (AA). Thermogravimetry (TG), differential thermogravimetry (DTG), and differential thermal analysis (DTA) were conducted, followed by the evaluation of AAE decomposition by the UV-Vis spectroscopic method including the influence of temperature and pH. Scavenging, antimicrobial activity and cytotoxicity against L929 fibroblasts were also performed. The difference in mass loss between AA and AAE was 30% via TG. DTA revealed characteristic exothermic and endothermic effects. The AAE solution was more thermally stable than AA. The calculated zero-order rate constants of free-radical scavenging kinetics for AAE were in the range of 4.9×10-3-1.35×10-2 s-1. The activation energy for the process was 11,2281 kJ/mol. AAE was active against Staphylococcus (S.) aureus and Enterococcus (E.) faecalis and acted stronger against Candida (C.) albicans than AA. The concentrations of AA ≥2.5% were cytotoxic, whereas in the case of AAE, a 10% concentration was considered cytotoxic. DTG enables the detailed differentiation between AA and AAE. AAE in aqueous solution is more stable compared to AA. The antioxidant activity of AAE is significant. However, the reaction with 2,2-diphenyl-1-picrylhydrazyl (DPPH) indicates prolonged activity compared to AA. Variability in the antimicrobial activity of AAE may find practical application in the pharmaceutical and cosmetic industries. The potential for applicative aims may be supported by the relatively low in vitro toxicity of AAE.


Assuntos
Ácido Ascórbico/análogos & derivados , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Ácido Ascórbico/química , Ácido Ascórbico/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Compostos de Bifenilo/metabolismo , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Camundongos , Picratos/metabolismo , Termogravimetria
10.
Dalton Trans ; 53(17): 7561-7570, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38606466

RESUMO

This work focuses on the relationship between the coordination chemistry and antimicrobial activity of Zn(II) and Cu(II) complexes of histatin 5 and the products of its hydrolysis: its N-terminal fragment (histatin 5-8) and C-terminal fragment (histatin 8). Cu(II) coordinates in an albumin-like binding mode and Zn(II) binds to up to 3 His imidazoles. The antimicrobial activity of histatins and their metal complexes (i) strongly depends on pH - they are more active at pH 5.4 than at 7.4; (ii) the complexes and ligands alone are more effective in eradicating Gram-positive bacteria than the Gram-negative ones, and (iii) Zn(II) coordination is able to change the structure of the N-terminal region of histatin 5 (histatin 5-8) and moderately increase all of the studied histatins' antimicrobial potency.


Assuntos
Complexos de Coordenação , Cobre , Histatinas , Testes de Sensibilidade Microbiana , Zinco , Histatinas/química , Histatinas/farmacologia , Hidrólise , Concentração de Íons de Hidrogênio , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Cobre/química , Cobre/farmacologia , Zinco/química , Zinco/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Bactérias Gram-Negativas/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química
11.
ACS Infect Dis ; 10(1): 215-231, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38109184

RESUMO

Candida strains as the most frequent causes of infections, along with their increased drug resistance, pose significant clinical and financial challenges to the healthcare system. Some polymeric excipients were reported to interfere with the multidrug resistance mechanism. Bearing in mind that there are a limited number of marketed products with fluconazole (FLU) for the topical route of administration, Pluronic F-127 (PLX)/FLU formulations were investigated in this work. The aims of this study were to investigate (i) whether PLX-based formulations can increase the susceptibility of resistant Candida strains to FLU, (ii) whether there is a correlation between block polymer concentration and the antifungal efficacy of the FLU-loaded PLX formulations, and (iii) what the potential mode of action of PLX assisting FLU is. The yeast growth inhibition upon incubation with PLX formulations loaded with FLU was statistically significant. The highest efficacy of the azole agent was observed in the presence of 5.0 and 10.0% w/v of PLX. The upregulation of the CDR1/CDR2 genes was detected in the investigated Candida strains, indicating that the efflux of the drug from the fungal cell was the main mechanism of the resistance.


Assuntos
Antifúngicos , Fluconazol , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fluconazol/farmacologia , Candida , Poloxâmero , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana
12.
J Inorg Biochem ; 253: 112476, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38171045

RESUMO

The fungal cell wall and cell membrane are an important target for antifungal therapies, and a needle-like cell wall or membrane disruption may be an entirely novel antifungal mode of action. In this work, we show how the coordination of Zn(II) triggers the antifungal properties of shepherin II, a glycine- and histidine-rich antimicrobial peptide from the root of Capsella bursa-pastoris. We analyze Cu(II) and Zn(II) complexes of this peptide using experimental and theoretical methods, such as: mass spectrometry, potentiometry, UV-Vis and CD spectroscopies, AFM imaging, biological activity tests and DFT calculations in order to understand the correlation between their metal binding mode, structure, morphology and biological activity. We observe that Zn(II) coordinates to Shep II and causes a structural change, resulting in fibril formation, what has a pronounced biological consequence - a strong anticandidal activity. This phenomenon was observed neither for the peptide itself, nor for its copper(II) complex. The Zn(II) - shepherin II complex can be considered as a starting point for further anticandidal drug discovery, which is extremely important in the era of increasing antifungal drug resistance.


Assuntos
Candida albicans , Complexos de Coordenação , Candida albicans/metabolismo , Antifúngicos/química , Química Bioinorgânica , Zinco/química , Peptídeos/química , Cobre/química , Complexos de Coordenação/química
13.
Sci Rep ; 14(1): 19286, 2024 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164354

RESUMO

The COVID-19 pandemic has revealed that viruses can have multiple receptor properties, penetrating various tissues and causing mutations in various genes, thus promoting a range of metabolic disorders. The purpose of this study was to investigate the connection between three factors: diabetic status, pre-hospitalization oxygen therapy, and saturation levels, to the values of morphological, inflammatory, and biochemical parameters in the blood serum of COVID-19 patients. The study group consisted of 2139 patients, 1076 women (50.30%) and 1063 men (49.70%), with an average age of 63.73 ± 15.69 years. The population was divided into three groups based on a three-stage scale, taking into account patients with either type 2 diabetes/prediabetes (473 patients), those who received oxygen therapy before hospitalization, and those with a saturation value of below 95% (cut-off value). Among patients who did not receive pre-hospitalization oxygen therapy, those with diabetes and a SpO2 level < 95% had significantly higher levels of D-dimers, procalcitonin, albumin, lymphocytes, RDW-SD ≥ 47, potassium, creatinine, and troponin T when compared to diabetic patients with a SpO2 level ≥ 95%. Similarly, in the same group of patients without pre-hospitalization oxygen therapy, those without diabetes but with a SpO2 level < 95% showed significantly increased levels of IL-6, CRP, albumin, lymphocytes, RDW-SD ≥ 47, glucose, potassium, sodium, creatinine, and ALT, compared to patients without diabetes and with a SpO2 level ≥ 95%. The findings suggest that lower saturation levels may result in increased potassium and glucose levels in patients who did not receive any oxygen therapy before hospitalization due to COVID-19. It is hypothesized that this may be caused by damage to pancreatic ß-cells by SARS-CoV-2, and disturbances in the potassium channel, leading to cell membrane depolarization and insulin secretion.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Oxigenoterapia , Saturação de Oxigênio , Humanos , COVID-19/terapia , COVID-19/sangue , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Oxigenoterapia/métodos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , SARS-CoV-2/isolamento & purificação , Transtornos do Metabolismo de Glucose/terapia , Transtornos do Metabolismo de Glucose/sangue , Hospitalização , Oxigênio/metabolismo
14.
Biomedicines ; 12(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38540218

RESUMO

Due to the molecular mechanisms of action of antidiabetic drugs, they are considered to be effective in the treatment of both COVID-19 and the post-COVID-19 syndromes. The aim of this study was to determine the effect of administering insulin and metformin on the mortality of patients with type 2 diabetes (T2DM) with symptomatic COVID-19 with the use of logistic regression models. The association between death and insulin and metformin was weak and could not be included in the multivariate model. However, the interaction of both drugs with other factors, including remdesivir and low-molecular-weight heparin (metformin), age and hsCRP (insulin), modulated the odds of death. These interactions hint at multifaceted (anti-/pro-) associations of both insulin and metformin with the odds of death, depending on the patient's characteristics. In the multivariate model, RDW-SD, adjusted with low-molecular-weight heparin treatment, age, sex and K+, was associated with mortality among patients with COVID-19 and T2DM. With a 15% increase in RDW-SD, the risk of death increased by 87.7%. This preliminary study provides the foundations for developing further, more personalized models to assess the risk of death in T2DM patients, as well as for identifying patients at an increased risk of death due to COVID-19.

15.
J Genomics ; 11: 14-19, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37066118

RESUMO

Chromohalobacter and Halomonas are genera of bacterial microorganisms belonging to the group of halophiles. They are characterized by high diversity and the ability to produce bioproducts of biotechnological importance, such as ectoine, biosurfactants and carotenoids. Here, we report three draft genomes of Chromohalobacter and two draft genomes of Halomonas isolated from brines. The length of the genomes ranged from 3.6 Mbp to 3.8 Mbp, and GC content was in the 60.11%-66.46% range. None of the analysed genomes has been assigned to any previously known species of the genus Chromohalobacter or Halomonas. Phylogenetic analysis revealed that Chromohalobacter 296-RDG and Chromohalobacter 48-RD10 belonged to the same species, and Chromohalobacter 11-W is more distantly related to the other two analysed strains than to Chromohalobacter canadensis. Halomonas strains 11-S5 and 25-S5 were clustered together and located close to Halomonas ventosae. Functional analysis revealed BGCs related to ectoine production in all genomes analysed. This study increases our overall understanding of halophilic bacteria and is also consistent with the notion that members of this group have significant potential as useful natural product producers.

16.
J Genomics ; 11: 20-25, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37066119

RESUMO

Halophilic Archaea are a unique group of microorganisms living in saline environments. They constitute a complex group whose biodiversity has not been thoroughly studied. Here, we report three draft genomes of halophilic Archaea isolated from brines, representing the genera of Halorubrum, Halopenitus, and Haloarcula. Two of these strains, Boch-26 and POP-27, were identified as members of the genera Halorubrum and Halopenitus, respectively. However, they could not be assigned to any known species because of the excessive difference in genome sequences between these strains and any other described genomes. In contrast, the third strain, Boch-26, was identified as Haloarcula hispanica. Genome lengths of these isolates ranged from 2.7 Mbp to 3.0 Mbp, and GC content was in the 63.77%-68.77% range. Moreover, functional analysis revealed biosynthetic gene clusters (BGCs) related to terpenes production in all analysed genomes and one BGC for RRE (RiPP recognition element)-dependent RiPP (post-translationally modified peptides) biosynthesis. Moreover, the obtained results enhanced the knowledge about the salt mines microbiota biodiversity as a poorly explored environment so far.

17.
Environ Sci Pollut Res Int ; 30(17): 49551-49566, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36780083

RESUMO

The Bochnia Salt Mine is one of the oldest mines in Europe. It was established in the thirteenth century, and actively operated until 1990. The mine has been placed on the UNESCO World Heritage List. Previous research describing Polish salt mines has been focused on bioaerosol characteristics and the identification of microorganisms potentially important for human health. The use of Polish salt mines as inhalation chambers for patients of health resorts has also been investigated. Nevertheless, the biodiversity of salt mines associated with biotechnological potential has not been well characterized. The present study paper examines the biodiversity of microorganisms in the Bochnia Salt Mine based on 16S rRNA gene and shotgun sequencing. Biodiversity studies revealed a significantly higher relative abundance of Chlamydiae at the first level of the mine (3.5%) compared to the other levels (< 0.1%). Patescibacteria microorganisms constituted a high percentage (21.6%) in the sample from site RA6. Shotgun sequencing identified 16 unique metagenome-assembled genomes (MAGs). Although one was identified as Halobacterium bonnevillei, the others have not yet been assigned to any species; it is possible that these species may be undescribed. Preliminary analyses of the biotechnological and pharmaceutical potential of microorganisms inhabiting the mine were also performed, and the biosynthetic gene cluster (BGC) profiles and antimicrobial peptide (AMP) coding genes in individual samples were characterized. Hundreds of BGCs and dozens of AMP coding genes were identified in metagenomes. Our findings indicate that Polish salt mines are promising sites for further research aimed at identifying microorganisms that are producers of potentially important substances with biotechnological and pharmaceutical applications.


Assuntos
Metagenoma , Cloreto de Sódio , Humanos , Polônia , RNA Ribossômico 16S/genética , Bactérias/genética , Cloreto de Sódio na Dieta , Preparações Farmacêuticas , Metagenômica
18.
J Clin Med ; 12(8)2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37109139

RESUMO

BACKGROUND: Sodium imbalance is one of the most common electrolyte disturbances encountered in the medical practice, and it may present with either hyponatremia or hypernatremia. Both sodium abnormalities are related with unfavorable outcomes. OBJECTIVE: Elucidation of the prevalence of dysnatremia among COVID-19 patients and its impact on 30- and 90-day mortality and need for ICU admission was the goal. DESIGN AND PARTICIPANTS: A single-center, retrospective, observational study was conducted. A total of 2026 adult, SARS-CoV-2 positive patients, admitted to Wroclaw University Hospital between 02.2020 and 06.2021, were included. On admission, patients were divided into groups: normonatremic (N), hyponatremic (L), and hypernatremic (H). Acquired data was processed, and Cox hazards regression and logistic regression were implemented. KEY RESULTS: Hyponatremia on admission occurred in 17.47% (n = 354) of patients and hypernatremia occurred in 5.03% (n = 102). Dysnatremic patients presented with more comorbidities, used more drugs, and were statistically more often admitted to the ICU. Level of consciousness was the strongest predictor of ICU admission (OR = 1.21, CI: 1.16-1.27, p < 0.001). Thirty-day mortality was significantly higher in both the L and H groups (28.52%, p = 0.0001 and 47.95%, p < 0.0001, respectively), in comparison to 17.67% in the N group. Ninety-day mortality showed a similar trend in all study groups: 34.37% in the L group (p = 0.0001), 60.27% (p < 0.0001) in the H group, and 23.32% in the N group. In multivariable analyses, hypo- and hypernatremia were found to be independent predictors of 30- and 90-day mortality. CONCLUSIONS: Both hypo- and hypernatremia are strong predictors of mortality and disease severity in COVID-19 patients. Extraordinary care should be taken when dealing with hypernatremic, COVID-positive patients, as this group exhibits the highest mortality rates.

19.
Front Immunol ; 14: 1231813, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37727794

RESUMO

Background: Vitamin D deficiency is a substantial public health problem. The present study evaluated the association between vitamin D concentration and hospitalization and mortality risk in patients with coronavirus disease 19 (COVID-19). Methods: This study used the COronavirus in LOwer Silesia (COLOS) dataset collected between February 2020 and June 2021. The medical records of 474 patients with confirmed severe acute respiratory syndrome 2 (SARS-CoV-2) infection, and whose vitamin D concentration was measured, were analyzed. Results: We determined a significant difference in vitamin D concentration between discharged patients and those who died during hospitalization (p = 0.0096). We also found an effect of vitamin D concentration on the risk of death in patients hospitalized due to COVID-19. As vitamin D concentration increased, the odds ratio (OR) for death slightly decreased (OR = 0.978; 95% confidence interval [CI] = 0.540-0.669). The vitamin D concentration cutoff point was 15.40 ng/ml. In addition, patients with COVID-19 and serum 25-hydroxyvitamin D (25(OH)D) concentrations < 30 ng/ml had a lower survival rate than those with serum 25(OH)D ≥ 30 ng/ml (log-rank test p = 0.0018). Moreover, a Cox regression model showed that patients with an estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 and higher vitamin D concentrations had a 2.8% reduced risk of mortality (hazard ratio HR = 0.972; CI = 0.95-0,99; p = 0.0097). Conclusions: The results indicate an association between 25(OH)D levels in patients with COVID-19 and the final course of hospitalization and risk of death.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Vitamina D , Vitaminas , Hospitalização
20.
J Clin Med ; 12(3)2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36769525

RESUMO

BACKGROUND: Oncology patients are a particularly vulnerable group to the severe course of COVID-19 due to, e.g., the suppression of the immune system. The study aimed to find links between parameters registered on admission to the hospital and the risk of later death in cancer patients with COVID-19. METHODS: The study included patients with a reported history of malignant tumor (n = 151) and a control group with no history of cancer (n = 151) hospitalized due to COVID-19 between March 2020 and August 2021. The variables registered on admission were divided into categories for which we calculated the multivariate Cox proportional hazards models. RESULTS: Multivariate Cox proportional hazards models were successfully obtained for the following categories: Patient data, Comorbidities, Signs recorded on admission, Medications used before hospitalization and Laboratory results recorded on admission. With the models developed for oncology patients, we identified the following variables that registered on patients' admission were linked to significantly increased risk of death. They are: male sex, presence of metastases in neoplastic disease, impaired consciousness (somnolence or confusion), wheezes/rhonchi, the levels of white blood cells and neutrophils. CONCLUSION: Early identification of the indicators of a poorer prognosis may serve clinicians in better tailoring surveillance or treatment among cancer patients with COVID-19.

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