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1.
Int J Biol Macromol ; 267(Pt 1): 131392, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38582483

RESUMO

The main protease (Mpro) of SARS-CoV-2 is critical in the virus's replication cycle, facilitating the maturation of polyproteins into functional units. Due to its conservation across taxa, Mpro is a promising target for broad-spectrum antiviral drugs. Targeting Mpro with small molecule inhibitors, such as nirmatrelvir combined with ritonavir (Paxlovid™), which the FDA has approved for post-exposure treatment and prophylaxis, can effectively interrupt the replication process of the virus. A key aspect of Mpro's function is its ability to form a functional dimer. However, the mechanics of dimerization and its influence on proteolytic activity remain less understood. In this study, we utilized biochemical, structural, and molecular modelling approaches to explore Mpro dimerization. We evaluated critical residues, specifically Arg4 and Arg298, that are essential for dimerization. Our results show that changes in the oligomerization state of Mpro directly affect its enzymatic activity and dimerization propensity. We discovered a synergistic relationship influencing dimer formation, involving both intra- and intermolecular interactions. These findings highlight the potential for developing allosteric inhibitors targeting Mpro, offering promising new directions for therapeutic strategies.

2.
Nucleic Acids Res ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499483

RESUMO

Coronaviruses modify their single-stranded RNA genome with a methylated cap during replication to mimic the eukaryotic mRNAs. The capping process is initiated by several nonstructural proteins (nsp) encoded in the viral genome. The methylation is performed by two methyltransferases, nsp14 and nsp16, while nsp10 acts as a co-factor to both. Additionally, nsp14 carries an exonuclease domain which operates in the proofreading system during RNA replication of the viral genome. Both nsp14 and nsp16 were reported to independently bind nsp10, but the available structural information suggests that the concomitant interaction between these three proteins would be impossible due to steric clashes. Here, we show that nsp14, nsp10, and nsp16 can form a heterotrimer complex upon significant allosteric change. This interaction is expected to encourage the formation of mature capped viral mRNA, modulating nsp14's exonuclease activity, and protecting the viral RNA. Our findings show that nsp14 is amenable to allosteric regulation and may serve as a novel target for therapeutic approaches.

3.
Ginekol Pol ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334336

RESUMO

OBJECTIVES: ABO blood type was hypothesised to be related to a number of infertility processes. There is still an open debate on ABO blood group's incompatibility and infertility. It was associated with ovarian reserve in women with subfertility. There is still not enough information on the influence of blood type and the immunology of follicular fluid (FF). MATERIAL AND METHODS: 78 patients were selected, who underwent in vitro fertilization (IVF) between April 2021 and January 2022. FF samples from each individual patient were taken on the day of ovarian puncture and stored at -80°C until immunological assessment. Concentration of chosen interleukins - IL-1α, IL-2, IL-4, IL-5, IL-6, IL-8 IL-10, IL-15, IL-1ß, IL-18, IFN, LIF, TNFα, GCSF and PIBF-1 were measured using commercially available ELISA kits. RESULTS: All assessed cytokines were present in the FF of exanimated patients. The concentration was compared to the blood type ABO of all women undergoing in vitro fertilization. No statistical relevance was found between blood type ABO and the concentration of GCSF, PIBF1, LIF, IL-15, IL-5, IL-8, IL-1 alfa, IL-1 beta, INF gamma, IL-2HS, IL-4HS, IL-6HS, IL-10HS in the FF obtained during ovarian puncture (p > 0,05). There was no statistically significant correlation between blood type ABO and the quality of embryo, and the positive pregnancy test in patients undergoing IVF/ET. CONCLUSIONS: The blood type ABO does not influence the wide cytokine profile of FF obtained during ovarian puncture in women with infertility of different origin, as well as embryo quality and pregnancy rate.

4.
Int J Immunopathol Pharmacol ; 38: 3946320231223004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38217433

RESUMO

The symptoms of celery allergy are mainly presented as oral allergy symptom, but there are several case reports of patients who experienced anaphylaxis. Defensin (Api g 7), as a novel allergen in celery root, was described in 2022 r. The female patient had a history of several episodes of dyspnea and cough, associated with ingestion of spice mixes containing dried celery. Up to the point of hospitalization, there were no objective tests, either sIgE or skin prick tests, that would confirm celery sensitization. During hospitalization, patient had a positive double-blind placebo-controlled food challenge with cooked celery. The patient was sensitized to mugwort defensin Art v 1. An inhibition assay with celery allergen extract was performed to prove cross-sensitization between Art v 1 and celery allergen responsible for symptoms in the patient. In conclusion, Api g 7 is an important celery allergen that can be responsible for severe reactions. Its cross-reactivity with Art v 1 is characteristic. Negative diagnostic tests with celery do not exclude Api g 7 sensitization.


Assuntos
Anafilaxia , Hipersensibilidade Alimentar , Humanos , Feminino , Anafilaxia/diagnóstico , Hipersensibilidade Alimentar/diagnóstico , Pólen , Proteínas de Plantas/efeitos adversos , Alérgenos , Defensinas , Testes Cutâneos/efeitos adversos
5.
Postepy Dermatol Alergol ; 40(5): 661-669, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38028417

RESUMO

Introduction: The key to the correct diagnosis of shrimp allergy is a qualification to the most efficient diagnostic method and later interpretation of the result. To achieve this, it is necessary to apply a diagnostic strategy relevant to each patient's clinical situation and approach every case individually. Aim: In this study the allergen profile of shrimp-sensitized patients was analysed using ALEX2 Allergy Explorer. Material and methods: This study includes 50 adult patients with positive prick-by-prick tests with tiger shrimp bought from the local eco-market and an elevated concentration of IgE specific to the shrimp allergen extract (ImmunoCap). A total of 35 patients with negative skin prick tests with shrimp and not detectable sIgE shrimp in ImmunoCap were included in the control group. All patients had ALEX2 Allergy Explorer microarray test. Results: In the shrimp-sensitized group, 22 patients were sensitized to at least one allergen component of Penaeus monodon, 20 patients were sensitized to crab, and 20 were sensitized to lobster. Only 15 (30%) patients were sensitized to the Northern prawn (Pandalus borealis) allergen extract in ALEX2 and only 12 (24%) to Shrimp mix (Litopenaeus setiferus, Farfantepenaeus aztecus, Farfantepenaeus dourarum). Conclusions: Sensitization to shrimp tropomyosin in the research group was present only in 34% of cases. There may be other shrimp allergen components, not available in ALEX2, which are responsible for shrimp sensitization.

6.
Antibodies (Basel) ; 12(3)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37753970

RESUMO

Today, the home pregnancy test is the most frequently performed laboratory test for self-diagnosis (home diagnostic test). It is also the first laboratory test that has been adapted for self-use at home. This is probably because women have always wanted to know the answer to the question: "Am I pregnant or not?" and always preferred to know the answer to this question intimately and in a discreet way. The history of the pregnancy test is also an interesting example of how the discovery of antibodies and the development of in vitro diagnostic methods based on the antigen-antibody reaction were important for the development of laboratory and clinical diagnostics. Immunodiagnostic techniques (based on the antigen-antibody reaction) are currently the basis of modern specialist laboratory diagnostics, which is essential in clinical diagnosis. The history of the pregnancy test is an interesting one and dates back to ancient times. A pregnancy test is defined as a procedure intended to reveal the presence or absence of pregnancy. Nowadays, every pregnancy test is based on the detection of human chorionic gonadotropin (hCG) in urine or blood. Human chorionic gonadotropin is secreted by the placenta right after a fertilized egg cell implants in the uterus and can be detected in both the urine and blood of pregnant women. Urine pregnancy tests are convenient for self-use at home. Blood tests are performed in medical laboratories. Specialized laboratory methods not only detect hCG but also determine the concentration of this hormone. However, both of these methods are highly accurate and common. Throughout the ages, many different methods were used to detect pregnancy at the earliest stage. Grain, wine, and various small animals were used as research tools. These were both long-term and often unreliable; most were based on folk beliefs and superstitions. Animal pregnancy tests were the first biological tests used in this field. This was a significant advance in the accurate detection of relatively early pregnancy. Animal tests in modern times are considered cruel and inhumane, no matter how reliable their results can be. Their place is now taken by much more specific, more sensitive, and definitely more ethical immunochemical tests. The pregnancy test and the methods to find out whether a woman is pregnant have gone through massive transformations, from bioassays using plants to bioassays on animals to advanced immunochemical techniques and biosensors. Modern pregnancy tests are not invasive and are very sensitive. Nowadays, it takes only about 3 min to know the answer to the question: "Am I pregnant or not?". However, it was not always as simple as it is today. This manuscript aims to show the important role played by antibodies in the development of laboratory and clinical diagnostics in the example of the interesting history of the pregnancy test.

7.
Curr Issues Mol Biol ; 45(7): 5481-5493, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37504263

RESUMO

Diagnosis of allergic diseases is a complex, multi-stage process. It often requires the use of various diagnostic tools. The in vitro diagnostics (IVD), which includes various laboratory tests, is one of the stages of this process. Standard laboratory tests include the measurement of the serum concentration of specific immunoglobulin E (sIgE) for selected allergens, full allergen extracts and/or single allergen components (molecules). The measurement of IgE sIgE to the allergen components is called molecular allergy diagnosis. During the standard laboratory diagnostic process, various models of immunochemical tests are used, which enable the measurement of sIgE for single allergens (one-parameter tests, singleplex) or IgE specific for many different allergens (multi-parameter tests, multiplex) in one test. Currently, there are many different test kits available, validated for IVD, which differ in the method type and allergen profile. The aim of the manuscript is to present various technical aspects related to modern allergy diagnostics, especially in the area of molecular allergy diagnostics.

8.
Antioxidants (Basel) ; 12(7)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37507897

RESUMO

Color is an important food attribute which increases its attractiveness, thus influencing consumer preferences and acceptance of food products. The characteristic color of fresh, raw food is due to natural dyes present in natural food sources. Food loses its natural color during processing or storage. Loss of natural color (e.g., graying) often reduces the appeal of a product to consumers. To increase the aesthetic value of food, natural or synthetic dyes are added to it. Interestingly, the use of food coloring to enhance food attractiveness and appetizing appearance has been practiced since antiquity. Food coloring can also cause certain health effects, both negative and positive. Dyes added to food, both natural and synthetic, are primarily chemical substances that may not be neutral to the body. Some of these substances have strong antioxidant properties. Thanks to this activity, they can also perform important pro-health functions, including antiallergic ones. On the other hand, as foreign substances, they can also cause various adverse food reactions, including allergic reactions of varying severity and anaphylactic shock. This article discusses food dyes of plant origins with antioxidant properties (anthocyanins, betanins, chlorophylls, carotenoids, and curcumin) and their relationship with allergy, both as sensitizing agents and immunomodulatory agents with potential antiallergic properties.

9.
Life (Basel) ; 13(3)2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36983854

RESUMO

(1) Background: alpha-gal syndrome (AGS) is a serious, potentially life-threatening allergic reaction. This is a type of food allergy to red meat and other mammalian products (e.g., gelatin). In Poland, this problem seems to be rare or, more likely, very underdiagnosed. The diagnosis of AGS is difficult. It seems that the knowledge about this syndrome is insufficient. There are no effective diagnostic tools able to clearly diagnose this cross-reactive allergy. This paper presents the clinical application of a non-standard method in the diagnosis of a cross-reactive allergy using the example of AGS. (2) Methods: standard tests for in vitro allergy diagnostics and the non-standard ImmunoCAP inhibition test(IT) were carried out for serum collected from a patient with a red meat allergy. (3) Results: the serum concentration of anti-α-Gal IgE was very high (302 kUA/L), and IgE antibodies toanti-mammalian-meat allergens were found. The level of IgE antibodies to mammalian meat allergens decreased after blocking on α-GAL-CAP. The concentration of anti-α-Gal IgE decreased after blocking on CAPs coated with various mammalian meat allergens. Blocking with allergens of poultry meat did not affect the concentration of anti-α-Gal IgE. (4) Conclusions: the ImmunoCAP ITseems to be a useful tool in the diagnosis of cross-reactive allergies. Based on their clinical history and test results, the patient was diagnosed with AGS caused by a primary sensitization to α-Gal after a tick bite. This is the second case of AGS described in Poland and the first in Pomerania.

10.
Postepy Dermatol Alergol ; 40(1): 119-125, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36909896

RESUMO

Introduction: Matrix metalloproteinases (MMP) degrade extracellular matrix. Some studies show that MMP9 concentration in follicular fluid (FF) may play a role in oocyte maturation and in vitro fertilization (IVF) success. The immunology of follicular fluid is still not fully understood. Aim: Assessment of RANTES, MIP4A, MMP7, MMP9, MMP14, TIMP 1, TIMP 2 and TIMP 3 concentration in the follicular fluid of patients undergoing in vitro fertilization/embryo transfer procedure. Material and methods: This case-control study included 20 randomly selected patients with a positive pregnancy (PPG) test and 20 patients with a negative pregnancy (NPG) test after IVF/ET. In FF obtained during oocyte retrieval, the concentrations of MIP4A, MMP7, MMP14, TIMP 1, TIMP 2, TIMP 3, RANTES, IL-12p40, and IL-17A were measured. Their effect on the characteristics of follicles, embryos, and the efficiency of IVF and ET were analysed. Results: There was no statistically significant relationship between a positive pregnancy test and the results of the immunoassay performed. The number of COC-1 correlates significantly and positively with RANTES (r = 0.34; p = 0.038) and IP-10 (r = 0.329; p = 0.038). MII correlates significantly and positively with RANTES (r = 0.341, p = 0.031). The number of top-quality embryos correlates significantly and positively with IL-17A (r = 0.451, p = 0.004) and TIMP 1 (r = 0.44, p = 0.005). Conclusions: The concentration of IL-17A and TIMP 1 may predict IVF/ET success. Further studies are required on the influence of the follicular fluid immunological environment on oocyte maturation and quality and, subsequently, embryo development.

11.
Curr Issues Mol Biol ; 45(2): 1168-1182, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36826022

RESUMO

Cross-reactivity of allergens is the cause of various, sometimes unexpected, clinical reactions. There are no standard methods to investigate cross-reactivity. We present an experimental model of a two-sided inhibition test (IT) on ImmunoCAP membranes (CAP). We constructed the described model based on the known cross-allergy syndrome to red meat developing in people bitten by ticks (α-Gal syndrome; AGS). Some individuals who are bitten by ticks develop IgE antibodies specific to the carbohydrate determinant, galactose-α-1,3-galactose (α-Gal), present in the tick's saliva. These antibodies can cross-react with α-Gal molecules expressed on mammalian meat proteins. The well-known property of anti-α-Gal IgE antibodies binding by various sources of this allergen was used by us in the proposed model of the two-sided inhibition test on ImmunoCAP membranes. We expected that anti-α-Gal IgE antibodies bind allergens from mammalian meat and blocking them abolishes this reactivity, and the two-sided inhibition test model we proposed on ImmunoCAP membranes allowed us to observe such a relationship. We conducted the experiment three times on biological material from people with different clinical manifestations of allergy to α-Gal, each time obtaining similar results. In conclusion, the model of bilateral inhibition on ImmunoCAP membranes proposed by us seems to be an attractive, simple tool for direct testing of allergic cross-reactivity.

12.
Postepy Dermatol Alergol ; 39(5): 913-922, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36457677

RESUMO

Introduction: SARS-CoV-2 is responsible for causing the COVID-19 disease, which affected 174 million people worldwide. After vaccines were launched, the focus was on their effectiveness and the degree of their safety. Aim: The authors try to find factors that may affect the response to vaccination. Material and methods: The study was conducted in 47 adults (39 women and 8 men; age: 47.3 ±11.2). Participants were vaccinated with two doses of the Comirnaty mRNA vaccine. Each patient had a medical history taken and the concentration of specific sIgG antibodies against S1 protein and SARS-CoV-2 N protein, as well as of selected cytokines (IL-8, TGF-ß, IFN-γ) was determined before and 3 weeks after the first and second dose of the vaccine. Results: There were 18 convalescents among the respondents. A statistically significant increase in the concentration of specific sIgG S1 in subsequent determinations was observed. Higher levels of sIgG S1 were found after the first dose of the vaccine in COVID-19 convalescents. There was no statistically significant influence of age, body mass index and sex on the increase in the concentration of antibodies and the concentration of the determined cytokines. It was shown that the higher the initial TGF-ß concentration, the greater the increase in sIgG S1 after administration of the vaccine. Conclusions: Vaccination did not increase the levels of IL-8, IFN-ß and TGF-γ. A higher concentration of serum TGF-ß before vaccination correlated with the higher concentration of sIgG S1 antibodies after the first dose of the vaccine.

13.
Int J Mol Sci ; 23(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36232522

RESUMO

The similarity in antigenic structures, including the degree of correspondence between the amino acid sequence and the spatial structure, is not always reflected in the actual cross-reactivity of allergens. Inhibition tests appear to be an invaluable tool for assessing potential cross-reactivity between allergens under natural conditions. In this publication, we present two experimental models of inhibition tests: solid phase (SP-IT) and liquid phase (LP-IT). As an exemplary research model, we used the cross-reactivity between human PSA and anti-Can f 5 IgE antibodies. We performed an SP-IT model using a microplate coated with human PSA. The LP-IT model was based on mixing anti-Can f 5 IgE positive serum with a material containing human PSA. Anti-Can f 5 IgE and PSA concentrations before and after inhibition were measured to evaluate inhibition effectiveness. The results of the performed experiments showed that both proposed models of inhibition tests are an effective tools for studying cross-reactive relationships between antigens. In the SP-IT, the concentration of anti-Can f 5 decreased by 21.6% and, in the LP-IT, it decreased by 34.51%. In turn, the PSA concentration in the SP-IT decreased by 11.25% and, in the LP-IT, it decreased by 15.49%. In conclusion, both the SP-IT and the LP-IT seem to be effective tools for assessing the actual cross-reactivity between different allergens.


Assuntos
Imunoglobulina E , Antígeno Prostático Específico , Alérgenos , Reações Cruzadas , Humanos , Masculino , Modelos Teóricos
14.
J Int Med Res ; 50(9): 3000605221125641, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36138563

RESUMO

OBJECTIVE: Cytokines and enzymes in follicular fluid (FF) may have a crucial role in fertility. This study aimed to analyse the results of in vitro fertilization/embryo transfer (IVF/ET) and compare them with matrix metalloproteinase 9 (MMP-9) and cytokine concentrations in FF. METHODS: This case-control study included 20 randomly selected patients with a positive pregnancy (PPG) test and 20 with a negative pregnancy (NPG) test after IVF/ET. In FF obtained during oocyte retrieval, the concentrations of soluble forms of MMP-9, interleukin 1 (IL-1) alpha, IL-1 beta, interferon gamma, IL-2, IL-4, IL-6, IL-8, and IL-10 were measured. Their effect on the characteristics of follicles, embryos, and the efficiency of IVF and ET were analysed. RESULTS: High-sensitivity IL-4 concentrations were significantly higher in patients with a PPG test than in those with an NPG test (3.15 ± 3.23 vs 1.91 ± 0.35 pg/mL). The number of top-quality embryos achieved was significantly higher in patients with a PPG test than in those with an NPG test (2.6 ± 1.39 vs 1.75 ± 1.21), and they were negatively correlated with IL-8 concentrations in FF. CONCLUSION: Further research on the role of IL-4 and IL-8 in FF is required to establish any clinical benefit of determining their concentrations in FF of infertile women.


Assuntos
Líquido Folicular , Infertilidade Feminina , Estudos de Casos e Controles , Feminino , Fertilização In Vitro/métodos , Humanos , Infertilidade Feminina/terapia , Interferon gama , Interleucina-10 , Interleucina-1beta , Interleucina-2 , Interleucina-4 , Interleucina-6 , Interleucina-8 , Metaloproteinase 9 da Matriz , Gravidez
15.
Int J Immunopathol Pharmacol ; 36: 3946320221111134, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35861194

RESUMO

Introduction: Progesterone is essential for both the initiation and the maintenance of pregnancy. The immunological effects of progesterone are mediated by the progesterone-induced blocking factor (PIBF), which is an immunomodulatory factor with anti-abortive properties. The aim of the research was to establish the cytokine profile and PIBF1 concentration in follicular fluid (FF) of patients undergoing in vitro fertilization (IVF).Methods: Seventy-eight patients who qualified for IVF underwent a detailed medical interview, including the course of fertility treatment and physical, gynecological, and cytological examinations. The concentration of PIBF1, IL-18, IL-2, IL-4, IL-6, IL-10, interferon-γ (IFN-γ), IL-1α, IL-1ß, IL-5, IL-8, and IL-15 in FF during ovarian puncture was measured using commercially available ELISA kits.Results: IL-1 beta concentration was lower in the FF of patients with successful IVF. IL-8 concentration in FF correlated with the number of cumulus-oocyte complexes (COC-1), metaphase II (MII), and top-quality embryos. PIBF1 concentration had a positive correlation with the number of MII and top-quality embryos. IL-2 and IL-6 concentrations were positively correlated with the number of COC-1 and MII. An important parameter in assessing the chances of successful IVF is the number of top-quality embryos achieved.Conclusion: Higher PIBF1 concentration in FF may indicate a greater possibility of successful IVF due to the higher number of top-quality embryos. IL-1 beta concentration was found to be lower in the FF of patients with successful IVF. Therefore, PIBF1 and IL-1 beta in FF could be candidates for a marker of successful IVF.


Assuntos
Líquido Folicular , Infertilidade Feminina , Antígenos de Neoplasias , Feminino , Fertilização In Vitro , Feto , Humanos , Infertilidade Feminina/terapia , Interleucina-1beta , Interleucina-2 , Interleucina-6 , Interleucina-8 , Gravidez , Resultado da Gravidez , Progesterona
16.
Nanotechnology ; 33(43)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35820406

RESUMO

Growing international problem with pathogens acquiring resistance to antibiotics is the reason for the search for bactericidal substances against which microorganisms cannot become resistant. The aim of this study was to synthesize inorganic-organic nanohybrids and obtain materials with antimicrobial effects. Chitosan (CS) was deposited on nanocomposite carriers such as calcium oxide with titanium dioxide (CaO-TiO2), magnesium oxide with titanium dioxide (MgO-TiO2) and copper(II) oxide with titanium dioxide (CuO-TiO2). The efficiency of the process was examined at varying concentrations of chitosan and temperature. The parameters for nanohybrids synthesis were selected based on the highest amount of nano-chitosan deposited on the nanohybrids-for each carrier, the process conditions were as follows: chitosan solution at 5 g l-1and 20 °C. The materials were obtained using these parameters and were used for microbiological tests againstE. coliATCC 25922,S. aureusATCC 25923 andC. albicansATCC 10231. The growth inhibitory activity of the obtained materials was qualitatively defined. These results suggest that the synthesized nanohybrids and nanocomposites exhibit biostatic action. The material with the broadest effect was the CuO-TiO2-CS hybrid, which had biostatic properties against all tested strains at a minimal concentration of 1250µg ml-1. Further research is required to find eco-friendly, non-toxic, and more effective antimicrobials with a broad action to prevent the acquisition of resistance.


Assuntos
Anti-Infecciosos , Quitosana , Nanocompostos , Nanopartículas , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Quitosana/farmacologia , Óxidos , Titânio/farmacologia
17.
Toxins (Basel) ; 14(5)2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35622577

RESUMO

Even cyanobacteria from ecosystems of low biodiversity, such as the Baltic Sea, can constitute a rich source of bioactive metabolites. Potent toxins, enzyme inhibitors, and anticancer and antifungal agents were detected in both bloom-forming species and less commonly occurring cyanobacteria. In previous work on the Baltic Pseudanabaena galeata CCNP1313, the induction of apoptosis in the breast cancer cell line MCF-7 was documented. Here, the activity of the strain was further explored using human dermal fibroblasts, African green monkey kidney, cancer cell lines (T47D, HCT-8, and A549ACE2/TMPRSS2) and viruses (SARS-CoV-2, HCoV-OC43, and WNV). In the tests, extracts, chromatographic fractions, and the main components of the P. galeata CCNP1313 fractions were used. The LC-MS/MS analyses of the tested samples led to the detection of forty-five peptides. For fourteen of the new peptides, putative structures were proposed based on MS/MS spectra. Although the complex samples (i.e., extracts and chromatographic fractions) showed potent cytotoxic and antiviral activities, the effects of the isolated compounds were minor. The study confirmed the significance of P. galeata CCNP1313 as a source of metabolites with potent activity. It also illustrated the difficulties in assigning the observed biological effects to specific metabolites, especially when they are produced in minute amounts.


Assuntos
COVID-19 , Cianobactérias , Animais , Chlorocebus aethiops , Cromatografia Líquida , Ecossistema , Peptídeos/farmacologia , Extratos Vegetais , SARS-CoV-2 , Espectrometria de Massas em Tandem
18.
Postepy Dermatol Alergol ; 38(5): 773-779, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34849123

RESUMO

INTRODUCTION: Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes, conditioning the integrity of skin cells, however, their role in the inflammatory process of atopic dermatitis (AD) and the direct effect on the epidermal barrier parameters remain unexplained. AIM: To assess MMP-1, MMP-2, tissue inhibitors of metalloproteinases (TIMP)-1 concentrations in blood serum in the context of transepidermal water loss (TEWL) and stratum corneum hydration in AD. Moreover, serum levels of MMPs and TIMP-1 were analysed in relation to the Eczema Area and Severity Index (EASI). MATERIAL AND METHODS: Forty-three AD patients and 22 control group subjects have been investigated. Serum concentrations of MMP-1, MMP-2, and TIMP-1 have been evaluated with ELISA. TEWL and stratum corneum hydration have been assessed with a TM300 Tewameter and a CM825 Corneometer. Skin lesions in patients with AD have been evaluated with the Eczema Area and Severity Index. RESULTS: MMP-1 and MMP-2 serum concentrations were significantly higher in the AD group. The results of TIMP-1 serum concentration were similar for both groups. The correlation between the serum concentration and the EASI was demonstrated only for MMP-2 for patients with severe and moderate AD. Patients with AD and TIMP-1 serum concentration greater than MMP-1 presented lower TEWL and higher epidermal hydration. CONCLUSIONS: The results of this study warrant further investigation. The predominance of TIMP-1 over MMP-1 in blood serum can potentially limit TEWL and maintain the proper water content of the epidermis. Future work is necessary to establish how reliable the role of MMP-2 concentration is as an indicator of the severity of AD.

19.
Medicina (Kaunas) ; 57(11)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34833469

RESUMO

A balance within the immune system is necessary for the proper development of ovarian follicles. Numerous cytokines were detected in follicular fluid, the role of which in reproductive physiology seems crucial. They influence the development and maturation of the follicle, ovulation, and corpus luteum formation, as well as embryo implantation and maintenance of pregnancy. The analysis of follicular fluid requires its collection by puncturing of the ovary, which is usually executed in connection with various gynaecological procedures. When interpreting such test results, clinical indications for a given procedure and the method of patient preparation should be taken into account. This review revealed the results of currently available studies on the concentration of pro-inflammatory cytokines in follicular fluid in various forms of infertility. Additionally, it presented cytokines, whose concentration has a significant impact on the size of ovarian follicles, their number, the effectiveness of in vitro fertilisation, development of the embryo, and chances of correct implantation. Despite the many recent publications, the knowledge of follicular fluid immunology in the context of reproductive pathology is superficial and further research is required to extensively understand the roles of individual cytokines in reproductive pathology. In the future, this knowledge may enable patients' individual qualifications to individual methods of infertility treatment, as well as the possible adjustment of the treatment regimen to the patient's immune profile.


Assuntos
Citocinas , Líquido Folicular , Implantação do Embrião , Feminino , Fertilização In Vitro , Humanos , Folículo Ovariano , Gravidez
20.
Allergy Asthma Clin Immunol ; 17(1): 91, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496953

RESUMO

BACKGROUND: An allergy to kiwi is rare in Poland. Most (65-72%) of the patients who are allergic to kiwi report symptoms of an oral allergy syndrome (OAS); however, systemic manifestations (18-28%) have also been reported. CASE REPORT: A 27-year-old male patient, previously not suffering from chronic diseases, exercised in the gym. He began with isometric training and then continued with aerobic exercise on a treadmill. After exercise, he ate 2 kiwi (Actinidia deliciosa) fruits. He experienced a swelling of the lips after eating the fruit, followed by an itchy scalp and a swollen face. Approximately 60 min later, the symptoms worsened: the patient suffered from generalized hives, general weakness and a "rumbling" sensation in ears. The patient's condition improved upon the consumption of antihistamines. However, the swelling of the face persisted for 24 h despite previously eating a kiwi without any side effects. By means of diagnostics based on allergen components, an allergy to grass allergen components, especially timothy grass-Phl p 1, Phl p 2 and Phl p 5, was confirmed. The presence of IgE that is specific for Act d 2 kiwi was also found. The patient had an oral food challenge with kiwi fruit at rest and after exercise provocation test. The challenge was negative at rest and positive after exercise. A food-dependent exercise-induced anaphylaxis gathered with a kiwi sensitization was diagnosed. CONCLUSION: To our knowledge, this case is the first report of a kiwi-allergic patient in whom exercise was a necessary cofactor to induce an anaphylactic reaction.

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