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1.
Int J Mol Sci ; 25(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38673804

RESUMO

Throughout its lifecycle, Entamoeba histolytica encounters a variety of stressful conditions. This parasite possesses Heat Shock Response Elements (HSEs) which are crucial for regulating the expression of various genes, aiding in its adaptation and survival. These HSEs are regulated by Heat Shock Transcription Factors (EhHSTFs). Our research has identified seven such factors in the parasite, designated as EhHSTF1 through to EhHSTF7. Significantly, under heat shock conditions and in the presence of the antiamoebic compound emetine, EhHSTF5, EhHSTF6, and EhHSTF7 show overexpression, highlighting their essential role in gene response to these stressors. Currently, only EhHSTF7 has been confirmed to recognize the HSE as a promoter of the EhPgp5 gene (HSE_EhPgp5), leaving the binding potential of the other EhHSTFs to HSEs yet to be explored. Consequently, our study aimed to examine, both in vitro and in silico, the oligomerization, and binding capabilities of the recombinant EhHSTF5 protein (rEhHSTF5) to HSE_EhPgp5. The in vitro results indicate that the oligomerization of rEhHSTF5 is concentration-dependent, with its dimeric conformation showing a higher affinity for HSE_EhPgp5 than its monomeric state. In silico analysis suggests that the alpha 3 α-helix (α3-helix) of the DNA-binding domain (DBD5) of EhHSTF5 is crucial in binding to the major groove of HSE, primarily through hydrogen bonding and salt-bridge interactions. In summary, our results highlight the importance of oligomerization in enhancing the affinity of rEhHSTF5 for HSE_EhPgp5 and demonstrate its ability to specifically recognize structural motifs within HSE_EhPgp5. These insights significantly contribute to our understanding of one of the potential molecular mechanisms employed by this parasite to efficiently respond to various stressors, thereby enabling successful adaptation and survival within its host environment.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Entamoeba histolytica , Regiões Promotoras Genéticas , Proteínas de Protozoários , Sítios de Ligação , Simulação por Computador , Entamoeba histolytica/genética , Entamoeba histolytica/metabolismo , Resposta ao Choque Térmico/genética , Ligação Proteica , Multimerização Proteica , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/química , Elementos de Resposta , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
2.
Perinatol. reprod. hum ; 38(1): 7-11, ene.-mar. 2024. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1569377

RESUMO

Resumen Antecedentes: El incremento seminal de especies reactivas de oxígeno (ERO) se ha vinculado con la oxidación del ADN y anormalidades en la morfología espermática. La enzima 8-oxoguanina ADN glucosilasa 1 (OGG1) repara la oxidación del ADN. Sin embargo, la presencia del polimorfismo en la OGG1 que involucra cambio de citocina (C) por guanina (G), resultando la sustitución de una cisteína por una serina en el codón 326 (Ser326Cis), ha demostrado disminución en la reparación del ADN oxidado. Estudios del polimorfismo Ser326Cis en hombres españoles y asiáticos con infertilidad demostraron que el alelo G(Cis) incrementa las ERO, impactando en la infertilidad y en la teratozoospermia. Objetivo: Conocer la prevalencia del polimorfismo Ser326Cis de OGG1 en pacientes con teratozoospermia. Método: Se analizaron parámetros espermáticos y el polimorfismo Ser326Cis de OGG1 de 81 muestras de semen con teratozoospermia. Resultados: Los genotipos detectados fueron Ser326Ser(CC) 43%, Ser326Cis(CG) 41% y Cis326Cis(GG) 16%. La frecuencia del alelo G(Cis) fue de 0.4, valor mayor a la frecuencia reportada en las bases de datos disponibles para poblaciones americanas (0.21-0.29), los parámetros espermáticos no se relacionaron con el polimorfismo Ser326Cis. Conclusión: El alelo G(Cis) es un factor que contribuye a la infertilidad.


Abstract Background: The increase in seminal reactive oxygen species (ROS) has been linked to DNA oxidation and abnormalities in sperm morphology. The enzyme 8-oxoguanine DNA glycosylase 1 (OGG1) repairs DNA oxidation. However, the presence of the polymorphism in OGG1 that involves a change of cytokine (C) to guanine (G) resulting in the substitution of a cystine for serine at codon 326 (Ser326Cys) has shown a decrease in the repair of oxidized DNA. Studies of the Ser326Cys polymorphism in Spanish and Asian men with infertility demonstrated that the G(Cys) allele increases ROS, impacting infertility and teratozoospermia. Objective: To know the prevalence of the Ser326Cys polymorphism of OGG1 in patients with teratozoospermia. Method: Sperm parameters and the Ser326Cys polymorphism of OGG1 were analyzed from 81 semen samples. Results: The genotypes detected were Ser326Ser(CC) 43%, Ser326Cys(CG) 41%, and yis326Cys(GG) 16%. The frequency of the G allele (Cys) was 0.4, a value higher than the frequency reported in the databases available for American populations (0.21-0.29), the sperm parameters were not related to the Ser326Cys polymorphism. Conclusion: The G (Cys) allele is a factor that contributes to infertility.

3.
Rev. mex. ing. bioméd ; 44(2): 1334, May.-Aug. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1536653

RESUMO

ABSTRACT With an estimated approximately 2 million deaths per year, diabetes is one of the top 5 deadliest noncommunicable diseases globally. Although this disease is not fatal, the degradation of the patient's health due to a bad plan to control their glucose levels can have a fatal outcome. In order to lay the foundations for the development of a device that allows estimating glucose levels in some body fluid, we present the results obtained not only for the estimation of glucose in deionized water, but also describe the development and configuration of the created device. After analyzing 50 signals obtained from 5 different glucose concentrations, the feasibility of using the developed device for the analysis is evident, since, considering the K-Nearest Neighbors (KNN) algorithm, all the signals were associated correctly to the glucose group to which they belong.


RESUMEN Con un estimado de aproximadamente 2 millones de muertes por año, la diabetes es una de las 5 enfermedades no transmisibles más mortales a nivel mundial. Aunque esta enfermedad no es mortal, el deterioro de la salud del paciente por un mal plan para controlar sus niveles de glucosa puede tener un desenlace fatal. Con el fin de sentar las bases para el desarrollo de un dispositivo que permita estimar los niveles de glucosa en algún fluido corporal, presentamos los resultados obtenidos no solo para la estimación de glucosa en agua desionizada, sino que también describimos el desarrollo y configuración del dispositivo creado. Luego de analizar 50 señales obtenidos a partir de 5 concentraciones de glucosa diferentes, se evidencia la factibilidad de utilizar el dispositivo desarrollado para el análisis, ya que, considerando el algoritmo K-Nearest Neighbors (KNN), todas las señales se asociaron correctamente al grupo de glucosa al que pertenecen.

4.
Pharmaceuticals (Basel) ; 16(6)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37375843

RESUMO

Amoebiasis is produced by the parasite Entamoeba histolytica; this disease affects millions of people throughout the world who may suffer from amoebic colitis or amoebic liver abscess. Metronidazole is used to treat this protozoan, but it causes important adverse effects that limit its use. Studies have shown that riluzole has demonstrated activity against some parasites. Thus, the present study aimed, for the first time, to demonstrate the in vitro and in silico anti-amoebic activity of riluzole. In vitro, the results of Entamoeba histolytica trophozoites treated with IC50 (319.5 µM) of riluzole for 5 h showed (i) a decrease of 48.1% in amoeba viability, (ii) ultrastructural changes such as a loss of plasma membrane continuity and alterations in the nuclei followed by lysis, (iii) apoptosis-like cell death, (iv) the triggering of the production of reactive oxygen species and nitric oxide, and (v) the downregulation of amoebic antioxidant enzyme gene expression. Interestingly, docking studies have indicated that riluzole presented a higher affinity than metronidazole for the antioxidant enzymes thioredoxin, thioredoxin reductase, rubrerythrin, and peroxiredoxin of Entamoeba histolytica, which are considered as possible candidates of molecular targets. Our results suggest that riluzole could be an alternative treatment against Entamoeba histolytica. Future studies should be conducted to analyze the in vivo riluzole anti-amoebic effect on the resolution of amebic liver abscess in a susceptible model, as this will contribute to developing new therapeutic agents with anti-amoebic activity.

5.
Ginecol. obstet. Méx ; 91(8): 581-587, ene. 2023. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1520946

RESUMO

Resumen OBJETIVO: Determinar la frecuencia del alelo Ala en una muestra de mujeres mexicanas con diabetes mellitus gestacional y asociar su repercusión en la glucemia. MATERIALES Y MÉTODOS: Estudio ambispectivo, observacional, transversal y correlacional efectuado en una cohorte de pacientes con diabetes gestacional atendidas entre los meses de enero a junio del 2014 en el Hospital Militar de Especialidades de la Mujer y Neonatología de la Secretaría de la Defensa Nacional en la Ciudad de México. Se evaluó el polimorfismo mediante amplificación de un fragmento de ADN mediante la reacción en cadena de la polimerasa (PCR) y su secuenciación. RESULTADOS: Se estudiaron 81 pacientes; 3 de ellas con el alelo Ala, con concentraciones de glucosa menores y antecedente de más abortos en comparación con las mujeres sin el alelo Ala. CONCLUSIONES: La coexistencia del alelo Ala en mujeres embarazadas con diagnóstico de diabetes mellitus gestacional pudiera tener un efecto protector en contra de la hiperglucemia en el embarazo y el riesgo de aborto.


Abstract OBJECTIVE: To determine the frequency of peroxisomal proliferator-activated receptor gamma (PPARg) polymorphism of proline substituted with an alanine in amino acid 12 (Pro12Ala), in women with gestational diabetes mellitus and associate its impact with glycemia. MATERIALS AND METHODS: An ambispective, observational, cross-sectional and correlational study was carried out in a cohort of women with gestational diabetes that included 81 pregnant women treated at the Military Hospital for Women's Specialties and Neonatology of the Ministry of National Defense in the city from Mexico. Polymorphism was evaluated by amplification of a DNA fragment by PCR Polymerase Chain Reaction and its sequencing. RESULTS: The results indicated that 13.5% of the women carriers of the Ala allele also had lower blood glucose values and a history with a higher number of abortions compared to women without the Ala allele. CONCLUSIONS: The presence of the Ala allele in pregnant women with gestational diabetes mellitus could have a protective effect against hyperglycemia in pregnancy and a risk of abortion.

6.
Cells ; 11(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36497139

RESUMO

Various immunopathological events characterize the systemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Moreover, it has been reported that coronavirus disease 2019 (COVID-19) vaccination and infection by SARS-CoV-2 induce humoral immunity mediated by B-cell-derived antibodies and cellular immunity mediated by T cells and memory B cells. Immunoglobulins, cytokines, and chemokines play an important role in shaping immunity in response to infection and vaccination. Furthermore, different vaccines have been developed to prevent COVID-19. Therefore, this research aimed to analyze and compare Fourier-transform infrared (FTIR) spectra of vaccinated people with a positive (V-COVID-19 group) or negative (V-Healthy group) real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) test, evaluating the immunoglobulin and cytokine content as an immunological response through FTIR spectroscopy. Most individuals that integrated the V-Healthy group (88.1%) were asymptomatic; on the contrary, only 28% of the V-COVID-19 group was asymptomatic. Likewise, 68% of the V-COVID-19 group had at least one coexisting illness. Regarding the immunological response analyzed through FTIR spectroscopy, the V-COVID-19 group showed a greater immunoglobulins G, A, and M (IgG, IgA, and IgM) content, as well as the analyzed cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-ɑ), and interleukins 1ß, 6, and 10 (IL-1ß, IL-6, and IL-10). Therefore, we can state that it was possible to detect biochemical changes through FTIR spectroscopy associated with COVID-19 immune response in vaccinated people.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier , Citocinas , Imunidade Humoral
7.
Asian Pac J Cancer Prev ; 23(10): 3253-3259, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36308346

RESUMO

BACKGROUND: Cytochrome P4502E1 (CYP2E1) metabolizes environmental toxins, however, compound metabolism can produce oxidative stress, causing in-cell toxicity and sometimes transformation. AIM: To evaluate CYP2E1 gene expression and its effects in antioxidant defenses, and cell toxicity in printing workers. METHODS: The hierarchical method of health and chemical risk was used to evaluate chemical exposure in workplace. Blood samples and buccal epithelial cells were obtained from printing workers, and workers without any history of occupational exposure to chemicals (control group). Gene expression of CYP2E1, and antioxidant enzymes Superoxide dismutase (SOD) and Catalase (CAT) from leukocytes were evaluated. Hematic analysis and cell-free DNA from plasma were analyzed. Frequencies of cells with micronuclei (MN) and nuclear abnormalities from buccal epithelial cells were explored. RESULTS: Evaluation of chemical exposure in working place demonstrated that ethyl alcohol, isopropyl alcohol, and isophorone represent 91% of the accumulated potential risk. CYP2E1 expression showed a 2.5-fold overexpression in the printing workers compared to the control group. SOD expression showed a 0.5-fold lower level in the printing workers than the control group, and CAT expression showed no differences between groups. Lower red blood cell and platelet values were detected in the printing workers than in the control group, and cell-free DNA plasma concentration was 3-fold higher in the printing workers than in the control group. The printing workers showed a higher frequency of cells with MN and nuclear anomalies than the control group. CONCLUSION: CYP2E1 overexpression triggers antioxidant defenses and toxic cell effects in printing workers.


Assuntos
Ácidos Nucleicos Livres , Exposição Ocupacional , Citocromo P-450 CYP2E1/genética , Antioxidantes/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Estresse Oxidativo/genética , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ácidos Nucleicos Livres/metabolismo , Impressão Tridimensional
8.
Antioxidants (Basel) ; 11(6)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35739948

RESUMO

High-risk human papillomavirus (HR-HPV) infection, followed by chronic inflammation and oxidative stress, is a major risk factor of male infertility. In this study, we explored the potential impact of high-risk (HR) HPV genotypes in single infection (SI) and multiple infections (MI) that promote CYP2E1 expression, oxidative damage and pro-inflammatory cytokines, possibly contributing to sperm damage and male infertility. Semen samples from 101 infertile military men were studied. We analyzed seminal parameters, namely, HPV genotyping, cytochrome P450 2E1 (CYP2E1), oxidative stress biomarkers (total antioxidant capacity (TAC), catalase (CAT) and superoxide dismutase (SOD)), lipid peroxidation (LPO), 8-hydroxiguanosine (8-OHdG) and pro-inflammatory cytokines (IFN-γ, IL-1ß, IL-4, IL-6 and IL-8). Eighty-one men (80.2%, 81/101) were positive for HPV infection, and MI-HR-HPV was higher than SI-HR-HPV (63% vs. 37%). HPV-52 was the most frequently detected type (18.5%), followed by HPV-33 (11.1%), and the most frequent combination of genotypes detected was HPV-33,52 (11.1%), followed by HPV-18,31 (6.2%). The group with infected samples presented lower normal morphology and antioxidant levels compared to non-infected samples. In concordance, the infected group showed high levels of LPO, IFN-γ, IL-1ß, IL-4 and IL-6 and downregulation of CAT and SOD enzymes. Interestingly, changes in motility B, low levels of TAC, overexpression of CYP2E1, LPO and IL-8 levels were higher in MI-HR-HPV than SI-HR-HPV, suggesting that HPV infection promotes a chronic inflammatory process and a toxic and oxidative microenvironment, which increases with MI-HPV infections.

9.
Medicina (Kaunas) ; 57(9)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34577786

RESUMO

Background and Objectives: To investigate the effect of infection with human papillomavirus (HPV) or Chlamydia trachomatis (CT) and HPV + CT coinfection on sperm quality, inflammation, and the state of oxidative stress (OS) in asymptomatic infertile men. Materials and Methods: Semen samples from 84 asymptomatic military infertile men were studied. The polymerase chain reaction (PCR) was used for the molecular detection of HPV and CT. Semen parameters were analyzed according to the World Health Organization guidelines. Inflammation was evaluated by an IL-1ß, IL-6, and IFN-γ enzyme-linked immunosorbent assay (ELISA) and OS by the quantification of lipid peroxidation (LPO), 8-hydroxydeoxyguanosine (8-OHdG), and total antioxidant capacity (TAC). Results: A total of 81 of the 84 (96.4%) samples were positives for the pathogens, with 55/81 (68%) being positive for HPV, 11/81 (13.5%) for CT, and 15/81 (18.5%) for HPV + CT coinfection. Seminal parameters were affected in the infected groups, including pH increases above the normal range in all groups. An abnormal sperm morphology was observed in the HPV and HPV + CT groups. Higher cytokine levels were detected in the HPV group and the highest IL-1ß level was found in the HPV + CT group. No cytokines were detected in the CT group. High LPO and 8-OHdG levels were found in all groups with a lower TAC. Comparisons between groups showed the highest OS state was observed in the HPV group. Conclusions: High HPV infection or coinfection (HVP + CT) in these infertile men suggest compromising male fertility by inducing a proinflammatory state and OS. Infection with CT suggests an alteration of the state of OS by promoting an alkaline pH.


Assuntos
Alphapapillomavirus , Coinfecção , Infertilidade Masculina , Infecções por Papillomavirus , Chlamydia trachomatis , Humanos , Masculino , Estresse Oxidativo , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Espermatozoides
10.
Cent Eur J Immunol ; 46(1): 76-81, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897287

RESUMO

INTRODUCTION: Infection and inflammation of the reproductive tract by Chlamydia trachomatis (CT) are recognized as significant risk factors for male infertility. This study aimed to evaluate CT infection and its effects on seminal parameters and cytokines in asymptomatic patients with teratozoospermia. MATERIAL AND METHODS: Semen samples from one hundred four male patients were collected, and CT detection was performed by polymerase chain reaction (PCR). The quality (volume, sperm concentration, pH, motility, morphology, and leucocytes) of the semen was measured by standard procedures recommended by the World Health Organization (WHO). Pro-inflammatory cytokines [interleukin (IL)-1 ß, IL-6, IL-8, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ)], as well as anti-inflammatory cytokines (IL-4, IL-10), were determined by using enzyme-linked immunosorbent assay (ELISA). The frequency of CT infection was expressed as a percentage. Descriptive statistics were used for comparison of cytokines from infertile men, and then the Mann-Whitney U test was applied for the contrast of seminal parameters and cytokines from CT-infected versus non-CT infected men. RESULTS: A ratio of 33/104 (31.7%) patients were positive for CT infection. The ejaculate of positive CT infection was found to have increased pH (pH = 7.65 in non-CT infected vs. 7.94 CT-infected men; p = 0.026). High levels of pro-inflammatory cytokines were found in the population studied; however, infected males were noted to have high levels of IL-1 ß [184.66 (0-3985.33 pg/ml), p = 0.001] and IL-6 [87.8 (0-1042.8 pg/ml), p = 0.001]. CONCLUSIONS: CT infection increased seminal pH, as well as IL-1 ß and IL-6 cytokines, suggesting a potential role of infection and inflammation in asymptomatic patients with teratozoospermia.

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