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1.
Int J Mol Sci ; 25(8)2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38674101

RESUMEN

Betulonic acid (B(O)A) is a pentacyclic lupane-type triterpenoid that widely exists in plants. There are scientific reports indicating anticancer activity of B(O)A, as well as the amides and esters of this triterpenoid. In the first step of the study, the synthesis of novel amide derivatives of B(O)A containing an acetylenic moiety was developed. Subsequently, the medium-soluble compounds (EB171 and EB173) and the parent compound, i.e., B(O)A, were investigated for potential cytotoxic activity against breast cancer (MCF-7 and MDA-MB-231) and melanoma (C32, COLO 829 and A375) cell lines, as well as normal human fibroblasts. Screening analysis using the WST-1 test was applied. Moreover, the lipophilicity and ADME parameters of the obtained derivatives were determined using experimental and in silico methods. The toxicity assay using zebrafish embryos and larvae was also performed. The study showed that the compound EB171 exhibited a significant cytotoxic effect on cancer cell lines: MCF-7, A-375 and COLO 829, while it did not affect the survival of normal cells. Moreover, studies on embryos and larvae showed no toxicity of EB171 in an animal model. Compared to EB171, the compound EB173 had a weaker effect on all tested cancer cell lines and produced less desirable effects against normal cells. The results of the WST-1 assay obtained for B(O)A revealed its strong cytotoxic activity on the examined cancer cell lines, but also on normal cells. In conclusion, this article describes new derivatives of betulonic acid-from synthesis to biological properties. The results allowed to indicate a promising direction for the functionalization of B(O)A to obtain derivatives with selective anticancer activity and low toxicity.


Asunto(s)
Amidas , Antineoplásicos , Ácido Betulínico , Ácido Oleanólico , Pez Cebra , Humanos , Animales , Amidas/química , Amidas/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos/farmacocinética , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacología , Ácido Oleanólico/química , Ácido Oleanólico/síntesis química , Ácido Oleanólico/farmacocinética , Línea Celular Tumoral , Simulación por Computador , Células MCF-7 , Supervivencia Celular/efectos de los fármacos
2.
Molecules ; 29(18)2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39339403

RESUMEN

There are scientific studies indicating that the attachment of an indole moiety to the triterpene scaffold can lead to increased anticancer potential. Lipophilicity is one of the factors that may influence biological properties and is therefore an important parameter to determine for newly obtained compounds as drug candidates. In the present study, previously synthesized 3 and/or 28-indole-betulin derivatives were evaluated for lipophilicity by reversed-phase thin-layer chromatography. The experimental values of lipophilicity (logPTLC) were then subjected to correlation analysis with theoretical values of logP, as well as for selected physicochemical and pharmacokinetic parameters and anticancer activity. A toxicity test using zebrafish embryos and larvae was also conducted. High correlation was observed between the experimental and theoretical values of lipophilicity. We presented correlation equations and statistical parameters describing the relationships between logPTLC and several physicochemical and ADME parameters. We also revealed the lack of correlation between the experimental values of lipophilicity and anticancer activity. Moreover, experiments on zebrafish have confirmed no toxicity of the tested compounds, which was consistent with the results of the in silico toxicity analysis. The results demonstrated, using the example of indole derivatives of betulin, the utility of lipophilicity values in the context of predicting the biological activity of new compounds.


Asunto(s)
Indoles , Triterpenos , Pez Cebra , Animales , Triterpenos/química , Triterpenos/farmacología , Indoles/química , Indoles/farmacología , Interacciones Hidrofóbicas e Hidrofílicas , Larva/efectos de los fármacos , Antineoplásicos/química , Antineoplásicos/farmacología , Embrión no Mamífero/efectos de los fármacos , Estructura Molecular , Ácido Betulínico
3.
Int J Mol Sci ; 24(16)2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37628760

RESUMEN

Notch1 signalling plays a multifaceted role in tissue development and homeostasis. Currently, due to the pivotal role of Notch1 signalling, the relationship between NOTCH1 expression and the development of health disorders is being intensively studied. Nevertheless, Notch1 signalling is not only controlled at the transcriptional level but also by a variety of post-translational events. First is the ligand-dependent mechanical activation of NOTCH receptors and then the intracellular crosstalk with other signalling molecules-among those are long non-coding RNAs (lncRNAs). In this review, we provide a detailed overview of the specific role of lncRNAs in the modulation of Notch1 signalling, from expression to activity, and their connection with the development of health disorders, especially cancers.


Asunto(s)
Fenómenos Biológicos , Neoplasias , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Transducción de Señal/genética , Neoplasias/genética , Reacciones Cruzadas
4.
Int J Mol Sci ; 24(17)2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-37685853

RESUMEN

Psoriasis is an important issue in daily dermatological practice. Not only is it an aesthetic defect but it is also a matter of decreased life quality and economic burden. However frequent, the pathogenesis of psoriasis remains uncertain despite numerous investigations. Gasdermins are a family of six proteins. Gasdermin D (GSDMD) is the best-studied from this group and is involved in the processes of inflammation, proliferation, and death of cells, especially pyroptosis. GSDMD has never been studied in psoriatic sera or urine before. Our study involved 60 patients with psoriasis and 30 volunteers without dermatoses as controls. Serum and urinary GSDMD concentrations were examined by ELISA. The tissue expression of GSDMD was assessed by immunohistochemistry. The serum-GSDMD concentration was insignificantly higher in the patients than controls. There were no differences in the urinary-GSDMD concentrations between the patients and controls. Strong tissue expression of GSDMD was significantly more prevalent in psoriatic plaque than in the non-lesional skin and healthy skin of the controls. There was no correlation between the serum-GSDMD concentrations and the psoriasis severity in PASI, age, or disease duration. Taking into consideration the documented role of gasdermins in cell proliferation and death, the increased expression of GSDMD in psoriatic skin may demonstrate the potential involvement of this protein in psoriasis pathogenesis. Neither serum, nor urinary GSDMD can be currently considered a psoriasis biomarker; however, future studies may change this perspective.


Asunto(s)
Líquidos Corporales , Psoriasis , Humanos , Gasderminas , Piel , Psoriasis/genética , Proliferación Celular , Proteínas de Unión a Fosfato/genética , Proteínas Citotóxicas Formadoras de Poros
5.
Molecules ; 28(5)2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36903645

RESUMEN

In the last few decades, there has been a growing interest in Bruton's tyrosine kinase (BTK) and the compounds that target it. BTK is a downstream mediator of the B-cell receptor (BCR) signaling pathway and affects B-cell proliferation and differentiation. Evidence demonstrating the expression of BTK on the majority of hematological cells has led to the hypothesis that BTK inhibitors (BTKIs) such as ibrutinib can be an effective treatment for leukemias and lymphomas. However, a growing body of experimental and clinical data has demonstrated the significance of BTK, not just in B-cell malignancies, but also in solid tumors, such as breast, ovarian, colorectal, and prostate cancers. In addition, enhanced BTK activity is correlated with autoimmune disease. This gave rise to the hypothesis that BTK inhibitors can be beneficial in the therapy of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), Sjögren's syndrome (SS), allergies, and asthma. In this review article, we summarize the most recent findings regarding this kinase as well as the most advanced BTK inhibitors that have been developed to date and their clinical applications mainly in cancer and chronic inflammatory disease patients.


Asunto(s)
Enfermedades Autoinmunes , Neoplasias , Humanos , Agammaglobulinemia Tirosina Quinasa/metabolismo , Enfermedades Autoinmunes/tratamiento farmacológico , Transducción de Señal , Neoplasias/tratamiento farmacológico
6.
Molecules ; 27(13)2022 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-35807468

RESUMEN

A thorough understanding of cancer pathogenesis is a necessary step in the development of more effective and safer therapy. However, due to the complexity of the process and intricate interactions, studying tumor development is an extremely difficult and challenging task. In bringing this issue closer, different scientific models with various advancement levels are helpful. Cell cultures is a system that is too simple and does not allow for multidirectional research. On the other hand, rodent models, although commonly used, are burdened with several limitations. For this reason, new model organisms that will allow for the studying of carcinogenesis stages and factors reliably involved in them are urgently sought after. Danio rerio, an inconspicuous fish endowed with unique features, is gaining in importance in the world of scientific research. Including it in oncological research brings solutions to many challenges afflicting modern medicine. This article aims to illustrate the usefulness of Danio rerio as a model organism which turns out to be a powerful and unique tool for studying the stages of carcinogenesis and solving the hitherto incomprehensible processes that lead to the development of the disease.


Asunto(s)
Neoplasias , Pez Cebra , Animales , Carcinogénesis , Modelos Animales de Enfermedad , Neoplasias/patología
7.
J Enzyme Inhib Med Chem ; 36(1): 535-548, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33522320

RESUMEN

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in men and in women. The impact of the new pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide (MM-129) was evaluated against human colon cancer in vitro and in zebrafish xenografts. Our results show that this new synthesised compound effectively inhibits cell survival in BTK-dependent mechanism. Its effectiveness is much higher at a relatively low concentration as compared with the standard chemotherapy used for CRC, i.e. 5-fluorouracil (5-FU). Flow cytometry analysis after annexin V-FITC and propidium iodide staining revealed that apoptosis was the main response of CRC cells to MM-129 treatment. We also found that MM-129 effectively inhibits tumour development in zebrafish embryo xenograft model, where it showed a markedly synergistic anticancer effect when used in combination with 5-FU. The above results suggest that this novel heterofused 1,2,4-triazine derivative may be a promising candidate for further evaluation as chemotherapeutic agent against CRC.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Triazinas/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Relación Estructura-Actividad , Triazinas/síntesis química , Triazinas/química , Células Tumorales Cultivadas , Pez Cebra
8.
J Enzyme Inhib Med Chem ; 35(1): 1697-1711, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32912025

RESUMEN

Recombinant human erythropoietin (Epo) is an effective and convenient treatment for cancer-related anaemia. In our study for the first time, we evaluated the effect of simultaneous use of Epo and Bruton's tyrosine kinase (BTK) inhibitor LFM-A13 on the viability and tumour development of breast cancer cells. The results demonstrated that Epo significantly intensifies the anticancer activity of LFM-A13 in MCF-7 and MDA-MB-231. The featured therapeutic scheme efficiently blocked the tumour development in zebrafish experimental cancer model. Epo and LFM-A13 administered together resulted in effective cell killing, accompanied by attenuation of the BTK signalling pathways, loss of mitochondrial membrane potential (MMP), accumulation of apoptotic breast cancer cells with externalised PS, a slight increase in phase G0/G1 and a reduction in cyclin D1 expression. Simultaneous use of Epo with LFM-A13 inhibited early stages of tumour progression. This therapeutic scheme may be rationale for further possible research.


Asunto(s)
Amidas/farmacología , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Eritropoyetina/antagonistas & inhibidores , Nitrilos/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Amidas/química , Antineoplásicos/química , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Eritropoyetina/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Estructura Molecular , Nitrilos/química , Relación Estructura-Actividad , Células Tumorales Cultivadas
9.
Molecules ; 25(12)2020 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-32575817

RESUMEN

Novel transition metal complexes (Au, Pd, Pt) with berenil and 2-(1-methyl-5-nitroimidazol-2-yl)ethanol were obtained through two-step synthesis. The cytotoxicity assay against MCF-7 and MDA-MB-231 breast cancer cells revealed that novel platinum and palladium complexes cause a reduction on the viability of MCF-7 and MDA-MB-231 breast cancer cells to a greater extent than cisplatin. The complexes showed lower cytotoxicity on normal MCF-10A human breast epithelial cells than on tumor cells. Furthermore, we observed that these complexes selectively concentrate in tumor cell mitochondria due to the characteristic for these cells increased membrane potential that may explain their increased proapoptotic activity. The activity of the synthesized compounds against topoisomerase type IIα and their increased impact on DNA defragmentation also were documented. The novel complexes also induced autophagosome changes and inhibited tumor growth in xenograft models (established using breast cancer cells).


Asunto(s)
Antineoplásicos/farmacología , Autofagosomas/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Complejos de Coordinación/farmacología , Diminazeno/análogos & derivados , Nitroimidazoles/química , Compuestos Organometálicos/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cisplatino/farmacología , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , ADN/efectos de los fármacos , ADN/metabolismo , ADN-Topoisomerasas de Tipo II/metabolismo , Diminazeno/química , Femenino , Oro/farmacología , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Paladio/farmacología , Platino (Metal)/farmacología , Elementos de Transición/química , Ensayos Antitumor por Modelo de Xenoinjerto , Pez Cebra
10.
Int J Mol Sci ; 19(4)2018 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-29690619

RESUMEN

The Bruton’s tyrosine kinase (BTK) inhibitor LFM-A13 has been widely employed as an antileukemic agent, but applications in solid cancer have been found recently. The compound promotes apoptosis, has an antiproliferative effect, and increases cancer cell sensitivity to chemotherapy drugs. We decided to assess the impact of the simultaneous use of erythropoietin (Epo) and LFM-A13 on signal transduction in colon DLD-1 and HT-29 cells, as well as in tumor xenografts. The induction of apoptosis by Epo and LFM-A-13 in the cells was confirmed by phosphatidylserine externalization, loss of mitochondrial membrane potential, and modulation of the expression of apoptotic protein BAX and antiapoptotic protein BCL-2 in colon adenocarcinoma cells. Nude mice were inoculated with adenocarcinoma cells and treated with Epo and LFM-A13 in order to evaluate the degree of tumor regression. The simultaneous use of Epo and LFM-A13 severely inhibited cell growth, activated apoptosis, and also inhibited tumor growth in xenografts. The addition of Epo to LFM-A13 intensified the antiproliferative effect of LFM-A13, confirmed by the loss of mitochondrial membrane potential and the accumulation of apoptotic colon cancer cells with externalized phosphatidylserine (PS). These preclinical results suggest that the combination of Epo and LFM-A13 has a high proapoptotic activity and should be tested in the clinic for the treatment of solid tumors such as colon cancer.


Asunto(s)
Amidas/farmacología , Neoplasias Colorrectales/metabolismo , Eritropoyetina/farmacología , Nitrilos/farmacología , Animales , Apoptosis/efectos de los fármacos , Células HT29 , Humanos , Ratones , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Front Mol Biosci ; 11: 1382069, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38693919

RESUMEN

Psoriasis is one of the most common skin diseases and a crucial issue to manage in contemporary dermatology. The search for the details of its pathogenesis, markers and treatment is continuously ongoing. Our aim was to investigate the role of gasdermin B (GSDMB) in psoriasis, the second protein from the gasdermin family, involved in cell death and proliferation. GSDMB serum and urinary concentrations have never been studied in psoriatics, neither tissue expression of GSDMB by immunohistochemistry. The study included 60 psoriatic patients and 30 volunteers without dermatoses as controls. The serum and urinary GSDMB were evaluated by ELISA. Tissue expression of GSDMB was analyzed by immunohistochemistry. The serum and absolute urine concentrations of GSDMB were significantly higher in psoriatic patients than controls without skin diseases (p = 0.0137, p = 0.039 respectively). Urinary GSDMB/creatinine concentration ratio was significantly lower in patients compared to controls (p = 0.0241). The expression of GSDMB in the dermis and epidermis was significantly more prevalent in psoriatic plaque compared to the non-lesional skin and healthy skin of controls (p = 0.0012, p = 0.017, respectively). Serum GSDMB correlated positively with the age of patients (R = 0.41; p = 0.001). Our study adds to the current state of knowledge about psoriasis concerning the potential involvement of GSDMB. Possibly it could be engaged in keratinocytes migration, which requires further research. Elevated serum GSDMB and decreased urinary GSDMB/creatinine concentration ratio could potentially be investigated as psoriasis biomarkers. GSDMB could be investigated in the future as a potential therapeutic target.

12.
Dermatol Pract Concept ; 14(3)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39122519

RESUMEN

INTRODUCTION: Psoriasis is a frequent and incurable skin disease that is an important issue in contemporary dermatology, although its pathogenesis is still uncertain. Gasdermin A (GSDMA) is a member of the gasdermin protein family which are able to cause pore formation in cellular membranes leading to cell death called pyroptosis. OBJECTIVE: Our aim was to investigate the role of GSDMA in psoriatic patients. METHOD: The study enrolled 60 patients with active plaque-type psoriasis and 30 sex- and age-matched volunteers without dermatoses. GSDMA concentration was assessed in serum and urine samples of all participants using ELISA. GSDMA tissue expression was assessed by immunohistochemistry. RESULTS: GSDMA serum concentration was significantly higher in patients compared to controls, whereas urinary GSDMA/creatinine ratio was insignificantly lower. GSDMA tissue expression was more prominent in psoriatic plaque compared to non-lesional patients' skin and healthy skin of subjects without dermatoses. There was a strong negative correlation between GSDMA serum concentration and ALT activity. GSDMA did not correlate with PASI or psoriasis duration. CONCLUSIONS: Obtained results point to the probable involvement of GSDMA in psoriasis. GSDMA overexpression may probably lead to keratinocytes hyperproliferation and be responsible for triggering inflammation in psoriatic skin. Serum GSDMA could become psoriasis biomarker, whereas urinary GSDMA, not at this point.

13.
Biomolecules ; 13(10)2023 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-37892153

RESUMEN

Psoriasis is a complex disease that nowadays is considered not only a dermatosis but a kind of systemic disorder associated with many accompanying diseases. Metabolic complications leading to cardiovascular incidences are the cause of increased mortality in psoriatic patients. Galectins (gal) are beta-galactoside-binding lectins that exert different functions, including engagement in metabolic processes. Our aim was to assess the concentrations of gal-1, 2 and 12 in psoriatics, to establish their potential clinical implications, including in metabolic complications. Plasma galectins were assessed by ELISA in 60 psoriatic patients and 30 controls without dermatoses and a negative family history of psoriasis. Plasma concentrations of all galectins were significantly higher in patients than controls (gal-1 with p < 0.001, gal-2 and 12 with p < 0.05). There were no correlations between galectins concentrations and psoriasis severity in PASI or disease duration (p > 0.05). Gal-1 and 12 were significantly negatively correlated with GFR (p < 0.05, p < 0.01, respectively) and gal-2 with HDL (p < 0.05). Gal-2 was significantly positively correlated with CRP (p < 0.05) and gal-12 with fasting glucose (p < 0.01). Based on the results and given the reported role of galectins in metabolic disorders we may conclude that gal-1, 2 and 12 could be potentially engaged in metabolic complications in psoriatics, most probably in atherosclerosis. Gal-2 could be perhaps further investigated as a marker of metabolically induced inflammation in psoriasis, gal-1 and gal-12 as predictors of renal impairment in psoriatics due to metabolic disorders. Potentially, gal-12 could be considered in the future as a marker of carbohydrate metabolism disorders in psoriatics.


Asunto(s)
Enfermedades Metabólicas , Psoriasis , Humanos , Galectina 3/metabolismo , Galectinas/metabolismo , Galectina 2
14.
J Clin Med ; 12(18)2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37763041

RESUMEN

BACKGROUND: This study aims to investigate the prevalence of hand eczema, its association with disinfectant usage during the COVID-19 pandemic, and potential correlations with age and dermatological history on hand symptoms in the Polish female population. METHODS: A personalized online questionnaire was administered from January to March 2021 to 142 participants, including individuals with hand eczema. The questionnaire addressed demographics, dermatological history, disinfectant usage, and symptoms experienced during the pandemic. RESULTS: The prevalence of hand eczema was higher in younger adults (aged 18-35), with significant exacerbations reported due to increased disinfectant usage. Respondents with a dermatological history were more susceptible to new skin symptoms during the pandemic. The quality of life was substantially impacted, particularly in individuals with hand skin dermatoses. CONCLUSIONS: The COVID-19 pandemic had a considerable influence on hand eczema, affecting prevalence, symptoms, and quality of life. Disinfectant usage emerged as a key factor in exacerbating hand skin lesions. Further research is warranted to explore the influence of specific disinfecting agents and improve treatment guidelines for personalized management of hand eczema. Despite limitations in the online survey method, these findings highlight the importance of proactive healthcare support for individuals with hand eczema during challenging times.

15.
Cells ; 12(17)2023 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-37681881

RESUMEN

Psoriasis is a frequent and incurable skin disease whose pathogenesis is still not fully understood. It is characterized by immune disturbances leading to hyperproliferation and improper differentiation of keratinocytes. Gasdermin E (GSDME) is a protein from the gasdermin family involved in the processes of inflammation and cell death based on apoptosis, necroptosis and pyroptosis. It has never been studied in psoriatics' sera or urine before. Our study enrolled 60 patients with psoriasis and 30 volunteers without dermatoses as controls. Serum and urinary GSDME concentrations were examined by ELISA and tissue expression of GSDME by immunohistochemistry. Serum GSDME concentration was significantly higher in patients than controls (p < 0.05). There were no differences in urinary GSDME concentrations between patients and controls. GSDME expression was significantly higher in the psoriatic plaque than non-lesional patients' skin and compared to controls (both p < 0.001). There was no correlation between serum GSDME or its lesional expression and psoriasis severity, age or disease duration. GSDME serum concentration was significantly negatively correlated with BMI, triglycerides and glucose concentrations. The obtained results suggest the engagement of GSDME in psoriasis pathogenesis. It could potentially become a new non-invasive psoriasis marker. Considering its pro-apoptotic influence, GSDME could be compensatively elevated to direct cells towards apoptosis, whereas under other circumstances, it may lead to pyroptosis and sustain inflammation. GSDME may exert a protective influence on the metabolic complications in psoriasis which requires further studies.


Asunto(s)
Líquidos Corporales , Psoriasis , Humanos , Gasderminas , Piel , Inflamación
16.
Cancers (Basel) ; 16(1)2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38201550

RESUMEN

(1) Background: The purpose of the given study was to examine the antitumor activity of the simultaneous administration of MM-129, a 1,2,4-triazine derivative, and indoximod (IND), the kynurenine pathway inhibitor, toward colon cancer. (2) Methods: The efficiency of the co-administration of the studied compounds was assessed in xenografted zebrafish embryos. Then, the effects of the combined administration of compounds on cellular processes such as cell viability, apoptosis, and intracellular signaling pathways were evaluated. In vitro studies were performed using two colorectal cancer cell lines, namely, DLD-1 and HT-29. (3) Results: The results indicated that the simultaneous application of MM-129 and indoximod induced a stronger inhibition of tumor growth in zebrafish xenografts. The combination of these compounds intensified the process of apoptosis by lowering the mitochondrial potential, enhancing the externalization of phosphatidylserine (PS) and activation of caspases. Additionally, the expression of protein kinase B (AKT) and indoleamine 2,3-dioxygenase-(1IDO1) was disrupted under the applied compound combination. (4) Conclusions: Simultaneous targeting of ongoing cell signaling that promotes tumor progression, along with inhibition of the kynurenine pathway enzyme IDO1, results in the enhancement of the antitumor effect of the tested compounds against the colon cancer cells.

17.
J Clin Med ; 12(1)2022 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-36614996

RESUMEN

During the COVID-19 pandemic, disinfection became an integral part of everybody's life in order to avoid spreading the coronavirus. In 2021, an original anonymous online survey was carried out. The questions concerned the usage of disinfectants. The study population included 56 subjects diagnosed by a physician with hand eczema (HE-derm group) and 114 subjects with no hand skin disease diagnosed by a specialist (non-derm). The HE and non-HE groups were distinguished. Nearly 80% of the HE group, and 10% of the non-HE group, experienced worsening of hand skin lesions caused by increased skin disinfection. HE-group respondents more often declared the occurrence of new hand skin symptoms, over 80% of the subjects of this group had more than 1 new symptom (compared to nearly 40% of the non-HE group). Exacerbations of the skin disease were more frequently observed by the HE group during the pandemic. There was a statistically significant decrease of the quality of life in the HE group compared to the non-HE group during the pandemic. The COVID-19 pandemic caused an increase in the prevalence of hand skin symptoms and deterioration of the skin condition. Education on appropriate disinfection techniques and skincare, as well as early dermatological intervention, might allow us to limit the development of hand skin diseases.

18.
Metabolites ; 12(9)2022 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-36144281

RESUMEN

Psoriasis, vitiligo and lichen planus (LP) are autoimmune skin diseases associated with metabolic syndrome. Angiopoietin-like 4 (ANGPTL4) is a member of angiopoietin-like proteins, which play an important role in lipid metabolism, and its serum concentration has been proposed as a biomarker of cardiometabolic complications, especially coronary artery disease (CAD). The study involved 56 patients with abovementioned dermatoses and 29 sex- and age-matched volunteers without dermatoses. ANGPTL4 serum concentration was measured by ELISA. ANGPTL4 concentration was statistically significantly higher in patients with LP compared to the control group (p < 0.01); moreover, it was significantly higher than in patients with psoriasis and vitiligo (p < 0.001, p < 0.01, respectively). There was no statistically significant difference in ANGPTL4 concentration between patients with psoriasis or vitiligo and controls. There was no correlation between ANGPTL4 concentration and age or BMI in all study groups. There was a positive correlation between ANGPTL4 concentration and fasting glucose (R = 0.43) and AST activity (R = 0.39) in psoriatic patients and ALT activity in patients with vitiligo (R = 0.44). ANGPTL4 could be a potential marker of metabolic complications in patients with LP, especially CAD. Perhaps patients with LP are more prone to CAD compared to the other two dermatoses, which requires further research.

19.
J Clin Med ; 11(17)2022 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-36078974

RESUMEN

Psoriasis is one of the most common dermatoses, which shortens patients' lives because of the wide comorbidity. However, little is known about its association with neurodegenerative diseases (NDs). We aimed to investigate whether psoriatics are at increased risk of NDs. Sixty patients with plaque-type psoriasis were enrolled into the study. Serum concentrations of tau protein (MAPT), neuronal cell adhesion molecule (NrCAM) and neprilysin (NEP), which are NDs biomarkers and have been hardly studied in psoriasis before, were measured before and after 12 weeks of treatment with acitretin or methotrexate. NrCAM and NEP concentrations were significantly lower in patients than controls, whereas MAPT higher (all p < 0.05). There was no association between these markers and psoriasis severity, BMI or disease duration. After the treatment the concentration of NrCAM and NEP significantly increased and MAPT decreased (p < 0.001, p < 0.05, p < 0.01, respectively). Methotrexate had significant influence on the concentrations of all markers, hence it seems to have neuroprotective properties. Psoriasis severity and duration do not seem to affect the risk of neurodegenerative process. Our results suggest that NDs could be considered as another comorbidity of psoriasis and that further research are needed in order to establish their definite association.

20.
J Clin Med ; 11(9)2022 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-35566558

RESUMEN

Psoriasis and neurodegenerative diseases (NDs) are important medical, social and economic issues. The possible relationship of psoriasis and NDs has not been established yet. This study involved 60 patients with plaque-type psoriasis. Serum concentrations of fatty acid-binding protein 7 (FABP-7), glutamic acid (GA) and neurofilament light chain (NFL), which have been hardly studied in psoriasis before, were measured by ELISA before and after 12 weeks of treatment with acitretin or methotrexate. The concentration of FABP-7 and NFL in patients before the treatment was significantly higher than in the controls (p < 0.01, p < 0.001, respectively). After the treatment their concentration decreased, although FABP-7 did so insignificantly. The concentration of GA did not differ significantly between patients and controls and before and after the treatment but we found its negative correlation with CRP (p < 0.05). The duration of psoriasis does not seem to directly affect the risk of neurodegeneration and the severity only in patients with worse skin condition. Elevated FABP-7 and NFL, which are present in the brain, may be considered as potential indicators of NDs development in psoriatics, although it surely requires further research. GA might correspond with neuroinflammation in psoriasis. Systemic antipsoriatic therapy could be studied in order to improve cognitive impairment through lowering NDs biomarkers in some cases.

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