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1.
Molecules ; 29(16)2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39202874

RESUMEN

American trypanosomiasis or Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects approximately 6-7 million people worldwide. However, its pharmacological treatment causes several uncomfortable side effects, causing patients' treatment abandonment. Therefore, there is a need for new and better treatments. In this work, the molecular docking of nine hundred twenty-four FDA-approved drugs on three different sites of trypanothione reductase of T. cruzi (TcTR) was carried out to find potential trypanocidal agents. Finally, biological evaluations in vitro and in vivo were conducted with the selected FDA-approved drugs. Digoxin, alendronate, flucytosine, and dihydroergotamine showed better trypanocidal activity than the reference drugs benznidazole and nifurtimox in the in vitro evaluation against the trypomastigotes form. Further, these FDA-approved drugs were able to reduce 20-50% parasitemia in a short time in an in vivo model, although with less efficiency than benznidazole. Therefore, the results suggest a combined therapy of repurposed and canonical drugs against T. cruzi infection.


Asunto(s)
Enfermedad de Chagas , Simulación del Acoplamiento Molecular , NADH NADPH Oxidorreductasas , Tripanocidas , Trypanosoma cruzi , Tripanocidas/farmacología , Tripanocidas/química , NADH NADPH Oxidorreductasas/antagonistas & inhibidores , NADH NADPH Oxidorreductasas/química , NADH NADPH Oxidorreductasas/metabolismo , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/enzimología , Enfermedad de Chagas/tratamiento farmacológico , Animales , Humanos , United States Food and Drug Administration , Aprobación de Drogas , Evaluación Preclínica de Medicamentos , Estados Unidos , Ratones
2.
J Med Entomol ; 61(5): 1105-1114, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38995691

RESUMEN

Triatomine bugs are vectors for the Trypanosoma cruzi Chagas parasites, the etiological agent for Chagas disease. This study evaluated 6 epidemiologically significant behaviors (development time, number of blood meals required for molting to the next instar, mortality rate, aggressiveness, feeding duration, and defecation delay) across 4 populations of Triatoma mexicana Herrich-Schaeffer (Heteroptera: Reduviidae), a major T. cruzi vector in Central Mexico. We collected triatomines from areas characterized by high (HP), medium (MP), medium-high (MHP), and low (LP) prevalence of human T. cruzi infection. The MHP population had the shortest development time, <290 days. Both the HP and MP populations required the most blood meals to molt to the next instar, with a median of 13. Mortality rates varied across all populations, ranging from 44% to 52%. All of the tested populations showed aggressive behavior during feeding. All populations shared similar feeding durations, with most exceeding 13 min and increasing with each instar. Quick defecation, during feeding, immediately after or less than 1 min after feeding, was observed in most nymphs (78%-90%) from the MP and MHP populations and adults (74%-92%) from HP, MP, and MHP populations. Though most parameters suggest a low potential for T. mexicana to transmit T. cruzi, unique feeding and defecation behaviors in 3 populations (excluding the LP group) could elevate their epidemiological importance. These population-specific differences may contribute to the varying prevalence rates of T. cruzi infection in areas where T. mexicana is found.


Asunto(s)
Triatoma , Animales , Triatoma/fisiología , Triatoma/crecimiento & desarrollo , Triatoma/parasitología , México/epidemiología , Rasgos de la Historia de Vida , Ninfa/crecimiento & desarrollo , Ninfa/fisiología , Femenino , Conducta Alimentaria , Masculino , Insectos Vectores/fisiología , Defecación , Enfermedad de Chagas/transmisión
3.
Med Chem ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39082172

RESUMEN

BACKGROUND: Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of Trypanosoma cruzi (α-TcCA) has emerged as an interesting target for the design of new antiparasitic compounds due to its crucial role in parasite processes. OBJECTIVE: The aim of this study was to identify potential α-TcCA inhibitors with trypanocide activity. METHOD: A maximum common substructure (MCS) and molecular docking were used to carry out a ligand- and structure-based virtual screening of ZINC20 and MolPort databases. The compounds selected were evaluated in an in vitro model against the NINOA strain of Trypanosoma cruzi, and cytotoxicity was determined in a murine model of macrophage cells J774.2. RESULTS: Five sulfonamide derivatives (C7, C9, C14, C19, and C21) had the highest docking scores (-6.94 to -8.31 kcal/mol). They showed key residue interactions on the active site of the α-TcCA and good biopharmaceutical and pharmacokinetic properties. C7, C9, and C21 had half-maximal inhibitory concentration (IC50) values of 26, 61.6, and 49 µM, respectively, against NINOA strain epimastigotes of Trypanosoma cruzi. CONCLUSION: Compounds C7, C9, and C21 showed trypanocide activity; therefore, these results encourage the development of new trypanocidal agents based on their scaffold.

4.
Int J Mol Sci ; 25(11)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38892424

RESUMEN

Parasitic diseases, predominantly prevalent in developing countries, are increasingly spreading to high-income nations due to shifting migration patterns. The World Health Organization (WHO) estimates approximately 300 million annual cases of giardiasis. The emergence of drug resistance and associated side effects necessitates urgent research to address this growing health concern. In this study, we evaluated over eleven thousand pharmacological compounds sourced from the FDA database to assess their impact on the TATA-binding protein (TBP) of the early diverging protist Giardia lamblia, which holds medical significance. We identified a selection of potential pharmacological compounds for combating this parasitic disease through in silico analysis, employing molecular modeling techniques such as homology modeling, molecular docking, and molecular dynamics simulations. Notably, our findings highlight compounds DB07352 and DB08399 as promising candidates for inhibiting the TBP of Giardia lamblia. Also, these compounds and DB15584 demonstrated high efficacy against trophozoites in vitro. In summary, this study identifies compounds with the potential to combat giardiasis, offering the prospect of specific therapies and providing a robust foundation for future research.


Asunto(s)
Antiprotozoarios , Giardia lamblia , Giardiasis , Simulación del Acoplamiento Molecular , United States Food and Drug Administration , Giardiasis/tratamiento farmacológico , Giardia lamblia/efectos de los fármacos , Antiprotozoarios/farmacología , Antiprotozoarios/química , Estados Unidos , Humanos , Proteínas Protozoarias/química , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/antagonistas & inhibidores , Simulación de Dinámica Molecular
5.
Foods ; 13(12)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38928782

RESUMEN

The amount of by-products/waste in the fish industry is roughly 50%. Fish bones could be used to produce nanoparticles, which may have potential use in the food industry as a novel calcium source and at the same time, contribute to reduce waste production. The objective of this study was to evaluate the bioavailability of nano-size salmon fish bone particles compared to micro-size salmon fish bone particles, and calcium carbonate. The study was carried out in 21-28-day-old C57BL/6 male mice fed for 21 days with the experimental diets. The groups were as follows: CaCO3 0.5% Ca (CN 0.5); CaCO3 1.0% Ca (CN 1.0); salmon fish bone (SFB) microparticles 0.5% Ca (MP 0.5); SFB microparticles 1.0% Ca (MP 1.0); SFB nanoparticles 0.5% Ca (NP 0.5); and SFB nanoparticles 1.0% Ca (NP 1.0). Calcium bioavailability, defined as the percent calcium in femur showed an increasing trend from CN 0.5 to NP 1.0 group. According to ANCOVA, the greatest Ca content was observed in the NP 1.0 group compared with all groups but NP 0.5. In conclusion, in a murine model, salmon fish bone nanoparticles present higher calcium bioavailability than salmon fish bone microparticles, and both, in turn, have better bioavailability than calcium carbonate.

6.
Arch. cardiol. Méx ; 94(2): 127-132, Apr.-Jun. 2024. graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1556908

RESUMEN

Abstract Objective: Analyze sex hormone's influence during Chagas disease. Methods: Male and female BALB/c mice were divided into six groups, four experimental (sham, orchiectomized, orchiectomized and supplemented with estradiol, orchiectomized supplemented with testosterone, oophorectomized, oophorectomized and supplemented with estradiol, and oophorectomized and supplemented with testosterone), and two control (healthy and intraperitoneally with T. cruzi strain NINOA infected). Clinical data were recorded daily, parasitemia was evaluated using a Neubauer chamber during the infection, and heart histopathological analysis was performed using the paraffin embedding technique. To analyze parasitemia curves and the area under the parametric curves, two-way ANOVA test was performed to correlate groups' data. P-values < 0.05 were considered statistically significant. Results: Higher mortality rates, cardiomegaly, hepatomegaly, ascites, edema, higher parasitemia levels, more amastigote nests, and more severe inflammatory infiltrate were found in higher testosterone concentration mice, whereas in higher estradiol concentration groups, paresia, prostration, edema, and necrosis were found. Conclusions: Our results showed that testosterone increased infection severity, whereas estradiol had the opposite effect. This research improves the understanding of sex hormones´ infuence upon this infection to contribute with the handling of Chagas´ disease.


Resumen Objetivo: Analizar la influencia de las hormonas durante la enfermedad de Chagas. Métodos: Se separaron grupos de ratones macho y hembras BALB/c, todos infectados con T. cruzi (cepa NINOA), 4 grupos experimentales de machos (Sham, orquidectamizados, orquidectimezados y suplementados con estradiol, orquidectamizaos y suplementados con testosterona). 4 grupos experimentales de hembras (oforectomizadas, oforectomizadas y suplementadas con estradiol, oforectomizadas y suplementadas con testosterona y sham), and y dos grupos control para cada sexo (sin infección e infectados intraperitonealmente con T. cruzi (cepa NINOA). Los datos clínicos fueron registrados diariamente, la parasitemia fue evaluada durante toda la infección utilizando una cámara de Neubauer y el análisis histopatológico del corazón fue realizada con la técnica de inclusión en parafina. Para el análisis de las curvas de parasitemia y el área bajo la curva, se realizó una prueba de ANOVA de dos vías, p < 0.05 fueron considerados estadísticamente diferentes. Resultados: Las mayores tasas de mortalidad, cardiomegalia, hepatomegalia y mayor infiltrado inflamatorio, se encontró en los ratones con una mayor concentración de testosterona. En contraste los ratones con mayor concentración de estradiol presentaron paresia, postración edema y necrosis. Conclusiones: Nuestros resultados ponen en manifiesto que la testosterona incrementa la severidad del curso de la enfermedad de Chagas, mientras que el estradiol tuvo el efecto opuesto. Este trabajo mejora el entendimiento del rol que juegan las hormonas sexuales en esta infección para contribuir en un mejor manejo de la enfermedad de Chagas.

7.
Acta Trop ; 256: 107259, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38821148

RESUMEN

In Mexico, more than 30 species of triatomines, vectors of Trypanosoma cruzi, the etiological agent of Chagas disease, have been collected. Among them, Triatoma pallidipennis stands out for its wide geographical distribution, high infection rates and domiciliation. Local populations of triatomines have shown notable biological and behavioral differences, influencing their vectorial capacity. Six behaviors of epidemiological importance, namely, egg-to-adult development time, median number of blood meals to molt to the next instar, instar mortality rates, aggressiveness (delay in initiating a meal), feeding time and defecation delay, were evaluated in this study for six populations of T. pallidipennis. Those populations from central, western and southern Mexico were arranged by pairs with a combination of high (HP) and medium (MP) of Trypanosoma cruzi human infection and most (MFC) and low (CLF) collection frequencies: HP/MFC, HP/CLF, and MP/MFC. The development time was longer in HP/CLF populations (> 220 days). The median number of blood meals to molt was similar (7-9) among five of the six populations. Mortality rates were greater (> 40 %) in HP/CLF and one MP/MFC populations. All studied populations were aggressive but exhibited slight differences among them. The feeding times were similar (≥ 10 min) for all studied populations within instars, increasing as instars progressed. An irregular pattern was observed in defecation behaviors, with marked differences even between the two populations from the same pair. High percentages of young (57.3-87.9 %), and old (62.4-89.8 %) nymphs, of female (61.1-97.3 %) and male (65.7-93.1 %) of all the studied populations defecated quickly (while eating, immediately after finishing feeding or < 1 min postfeeding). Our results indicate that the HP/MFC populations are potentially highly effective vectors for transmitting T. cruzi infections, while HP/CLF populations are potentially less effective vectors T. cruzi infections.


Asunto(s)
Enfermedad de Chagas , Insectos Vectores , Triatoma , Trypanosoma cruzi , Animales , Triatoma/parasitología , Triatoma/fisiología , Enfermedad de Chagas/transmisión , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/parasitología , México/epidemiología , Femenino , Trypanosoma cruzi/fisiología , Insectos Vectores/parasitología , Insectos Vectores/fisiología , Humanos , Masculino , Conducta Alimentaria , Prevalencia , Defecación/fisiología
8.
Int J Mol Sci ; 25(7)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38612484

RESUMEN

Twenty 2-(4-alkyloxyphenyl)-imidazolines and 2-(4-alkyloxyphenyl)-imidazoles were synthesized, with the former being synthesized in two steps by using MW and ultrasonication energy, resulting in good to excellent yields. Imidazoles were obtained in moderate yields by oxidizing imidazolines with MnO2 and MW energy. In response to the urgent need to treat neglected tropical diseases, a set of 2-(4-alkyloxyphenyl)- imidazolines and imidazoles was tested in vitro on Leishmania mexicana and Trypanosoma cruzi. The leishmanicidal activity of ten compounds was evaluated, showing an IC50 < 10 µg/mL. Among these compounds, 27-31 were the most active, with IC50 values < 1 µg/mL (similar to the reference drugs). In the evaluation on epimastigotes of T. cruzi, only 30 and 36 reached an IC50 < 1 µg/mL, showing better inhibition than both reference drugs. However, compounds 29, 33, and 35 also demonstrated attractive trypanocidal activities, with IC50 values < 10 µg/mL, similar to the values for benznidazole and nifurtimox.


Asunto(s)
Antiprotozoarios , Enfermedad de Chagas , Imidazolinas , Leishmania mexicana , Trypanosoma cruzi , Humanos , Imidazoles/farmacología , Compuestos de Manganeso , Óxidos , Antiprotozoarios/farmacología
9.
J Med Entomol ; 61(2): 309-317, 2024 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-38339860

RESUMEN

Chagas disease is one of the most significant vector-borne diseases in Mexico. The presence of "sylvatic" triatomine vectors of Trypanosoma cruzi (Chagas) inside human dwellings necessitates estimating their vectorial capacity. To estimate this capacity in Triatoma protracta nahuatlae (Ryckman), Triatoma sinaloensis (Ryckman), and their laboratory hybrids, 6 biological parameters were examined. Triatoma sinaloensis exhibited the shortest development time (155 days), with a median of 12 blood meals. Mortality rates varied from 35% to 45% in the 3 studied cohorts. All 3 cohorts were aggressive, initiating feeding within 0.5-1 min, and had similar feeding periods ranging from 10 to 18 min. A majority (75.3-97.9%) of the hybrids defecated when feeding, immediately after feeding, or in less than 1 min post-feeding. In contrast, only 7-42% of nymphs of T. sinaloensis defecated during the same period. Our results regarding the 6 parameters studied confirm the potential role of T. p. nahuatlae as an efficient vector of T. cruzi. Triatoma sinaloensis, on the other hand, exhibited limited vectorial capacity primarily due to its poor defecation behavior. Continued surveillance of these "sylvatic" triatomine populations is necessary to prevent an epidemiological problem.


Asunto(s)
Enfermedad de Chagas , Triatoma , Trypanosoma cruzi , Humanos , Animales , Ninfa , Laboratorios , Conducta Alimentaria
10.
Arch Cardiol Mex ; 94(2): 127-132, 2024 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-38377617

RESUMEN

OBJECTIVE: Analyze sex hormone's influence during Chagas´ Disease. METHODS: Male and female BALB/c mice were divided into six groups, four experimental (sham, orchiectomized, orchiectomized and supplemented with estradiol, orchiectomized supplemented with testosterone, oophorectomized, oophorectomized and supplemented with estradiol, and oophorectomized and supplemented with testosterone), and two control (healthy and intraperitoneally with T. cruzi strain NINOA infected). Clinical data were recorded daily, parasitemia was evaluated using a Neubauer chamber during the infection, and heart histopathological analysis was performed using the paraffin embedding technique. To analyze parasitemia curves and the area under the parametric curves, two-way ANOVA test was performed to correlate groups´ data. P-values <0.05 were considered statistically significant. RESULTS: Higher mortality rates, cardiomegaly, hepatomegaly, ascites, edema, higher parasitemia levels, more amastigote nests, and more severe inflammatory infiltrate were found in higher testosterone concentration mice, whereas in higher estradiol concentration groups, paresia, prostration, edema, and necrosis were found. CONCLUSIONS: Our results showed that testosterone increased infection severity, whereas estradiol had the opposite effect. This research improves the understanding of sex hormones´infuence upon this infection to contribute with the handling of Chagas´disease.

11.
Arch Med Res ; 55(2): 102958, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38290200

RESUMEN

BACKGROUND: Chagas disease and cutaneous leishmaniasis, two parasitic diseases caused by Trypanosoma cruzi (T. cruzi) and Leishmania mexicana (L. mexicana), respectively, have a major global impact. Current pharmacological treatments for these diseases are limited and can cause severe side effects; thus, there is a need for new antiprotozoal drugs. METHODS: Using molecular docking, this work describes a structure-based virtual screening of an FDA-approved drug library against Trypanosoma cruzi and Leishmania mexicana glycolytic enzyme triosephosphate isomerase (TIM), which is highly conserved in these parasites. The selected compounds with potential dual inhibitory activity were tested in vitro to confirm their biological activity. RESULTS: The study showed that five compounds: nilotinib, chlorhexidine, protriptyline, cyproheptadine, and montelukast, were more active against T. cruzi, than the reference drugs, nifurtimox and benznidazole while chlorhexidine and protriptyline were the most active against L. mexicana. CONCLUSIONS: The analysis of these compounds and their structural characteristics may provide the basis for the development of new antiprotozoal agents.


Asunto(s)
Antiprotozoarios , Enfermedad de Chagas , Leishmaniasis Cutánea , Trypanosoma cruzi , Humanos , Simulación del Acoplamiento Molecular , Clorhexidina/farmacología , Clorhexidina/uso terapéutico , Protriptilina/farmacología , Protriptilina/uso terapéutico , Enfermedad de Chagas/tratamiento farmacológico , Leishmaniasis Cutánea/tratamiento farmacológico , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Antiprotozoarios/química
12.
Int J Mol Sci ; 25(1)2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38203832

RESUMEN

Chemotherapy currently available for leishmaniasis treatment has many adverse side effects and drug resistance. Therefore, the identification of new targets and the development of new drugs are urgently needed. Previously, we reported the synthesis of a N-(2-methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, named compound 8, with an IC50 value in the micromolar range against L. mexicana, it also inhibited 68.27% the activity of recombinant L. mexicana arginase. Herein, we report studies carried out to characterize the mechanism of action of compound 8, as well as its in vivo leishmanicidal activity. It was shown in our ultrastructural studies that compound 8 induces several changes, such as membrane blebbing, the presence of autophagosomes, membrane detachment and mitochondrial and kinetoplast disorganization, among others. Compound 8 triggers the production of ROS and parasite apoptosis. It reduced 71% of the parasite load of L. mexicana in an experimental model of cutaneous leishmaniasis in comparison with a control. Altogether, the data obtained suggest the potential use of compound 8 in the treatment of cutaneous leishmaniasis.


Asunto(s)
Leishmania mexicana , Leishmaniasis Cutánea , Humanos , Leishmaniasis Cutánea/tratamiento farmacológico , Apoptosis , Arginasa , Bencimidazoles/farmacología , Aminas
13.
Iberoam. j. med ; 6(1): 23-27, 2024. ilus
Artículo en Inglés | IBECS | ID: ibc-229287

RESUMEN

Pulmonary lophomoniasis is a rare infection produced by a multiflagellated and anaerobic pyriform or oval protozoan belonging to the family of Lophomonadidae. The study aimed learn the differential diagnosis of lophomoniasis in patients with COVID-19 in northern Mexico. Clinical case of a 37-years-old male patient diagnosed with pneumonia, respiratory syndrome, hemoptysis, and fever, which suggested pulmonary tuberculosis. Bronchial lavage was performed, and laboratory tests were requested, an RT-PCR test to search for SARS-CoV-2, which was positive. The results for TB and KOH for fungi were negative. In addition to the protocol, a fresh examination was performed by placing a drop from the sample on a glass slide and observing it with a 10X objective, then 40X searching for clinically structural elements. As a result, multiflagellated cellular elements in the continuous movement were observed that morphologically correspond to the genus Lophomonas spp concluding the bacteriological protocol of bronchial secretions should consider fresh examination to search for trophozoites of Lophomonas spp. Medical and laboratory personnel are unaware of the protozoa Lophomonas spp, since the fresh examination in the analysis protocol is not considered. This paper reports the first case of Lophomonas infection in a patient caused by chronic lung disease. (AU)


La lofomoniasis pulmonar es una infección rara producida por un protozoo piriforme u ovalado multiflagelado y anaeróbico perteneciente a la familia de los Lophomonadidae. El estudio tuvo como objetivo conocer el diagnóstico diferencial de lofomoniasis en pacientes con COVID-19 en el norte de México. Caso clínico de un paciente masculino de 37 años con diagnóstico de neumonía, síndrome respiratorio, hemoptisis y fiebre, que sugería tuberculosis pulmonar. Se realizó lavado bronquial y se solicitaron pruebas de laboratorio, prueba RT-PCR para búsqueda de SARS-CoV-2, la cual resultó positiva. Los resultados de TB y KOH para hongos fueron negativos. Además del protocolo, se realizó un nuevo examen colocando una gota de la muestra en un portaobjetos de vidrio y observándola con un objetivo de 10X, luego 40X en busca de elementos clínicamente estructurales. Como resultado se observaron elementos celulares multiflagelados en movimiento continuo que morfológicamente corresponden al género Lophomonas spp, por lo que el protocolo bacteriológico de secreciones bronquiales debe considerar examen en fresco para búsqueda de trofozoítos de Lophomonas spp. El personal médico y de laboratorio desconoce la presencia del protozoo Lophomonas spp, ya que en el protocolo de análisis no se considera el examen en fresco. Este artículo reporta el primer caso de infección por Lophomonas en un paciente causado por una enfermedad pulmonar crónica. (AU)


Asunto(s)
Humanos , Masculino , Adulto , Enfermedades Pulmonares/complicaciones , Infecciones por Protozoos , México/epidemiología , Enfermedad Crónica
14.
Biosystems ; 234: 105066, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37898397

RESUMEN

Trypanosoma cruzi is the causal agent of American Trypanosomiasis or Chagas Disease in humans. The current drugs for its treatment benznidazole and nifurtimox have inconveniences of toxicity and efficacy; therefore, the search for new therapies continues. Validation through genetic strategies of new drug targets against the parasite metabolism have identified numerous essential genes. Target validation can be further narrowed by applying Metabolic Control Analysis (MCA) to determine the flux control coefficients of the pathway enzymes. That coefficient is a quantitative value that represents the degree in which an enzyme/transporter determines the flux of a metabolic pathway; those with the highest coefficients can be promising drug targets. Previous studies have demonstrated that cysteine (Cys) is a key precursor for the synthesis of trypanothione, the main antioxidant metabolite in the parasite. In this research, MCA was applied in an ex vivo system to the enzymes of the reverse transsulfuration pathway (RTP) for Cys synthesis composed by cystathionine beta synthase (CBS) and cystathionine gamma lyase (CGL). The results indicated that CGL has 90% of the control of the pathway flux. Inhibition of CGL with propargylglycine (PAG) decreased the levels of Cys and trypanothione and depleted those of glutathione in epimastigotes (proliferative stage in the insect vector); these metabolite changes were prevented by supplementing with Cys, suggesting a compensatory role of the Cys transport (CysT). Indeed, Cys supplementation (but not PAG treatment) increased the activity of the CysT in epimastigotes whereas in trypomastigotes (infective stage in mammals) CysT was increased when they were incubated with PAG. Our results suggested that CGL could be a potential drug target given its high control on the RTP flux and its effects on the parasite antioxidant defense. However, the redundant Cys supply pathways in the parasite may require inhibition of the CysT as well. Our findings also suggest differential responses of the Cys supply pathways in different parasite stages.


Asunto(s)
Quistes , Trypanosoma cruzi , Humanos , Animales , Antioxidantes/metabolismo , Cisteína/metabolismo , Cistationina gamma-Liasa/genética , Cistationina gamma-Liasa/metabolismo , Mamíferos
15.
Data Brief ; 50: 109525, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37701711

RESUMEN

This data article introduces a dataset comprising 1630 alkali-activated concrete (AAC) mixes, compiled from 106 literature sources. The dataset underwent extensive curation to address feature redundancy, transcription errors, and duplicate data, yielding refined data ready for further data-driven science in the field of AAC, where this effort constitutes a novelty. The carbon footprint associated with each material used in the AAC mixes, as well as the corresponding CO2 footprint of every mix, were approximated using two published articles. Serving as a foundation for future expansions and rigorous data applications, this dataset enables the characterization of AAC properties through machine learning algorithms or as a benchmark for performance comparison among different formulations. In summary, the dataset provides a resource for researchers focusing on AAC and related materials and offers insights into the environmental benefits of substituting traditional Portland concrete with AAC.

16.
J Med Entomol ; 60(5): 998-1007, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37459050

RESUMEN

Chagas disease is an important vector-borne disease endemic in Mexico. Of the 33 triatomine species found in Mexico, Triatoma longipennis (Usinger) is considered among the most important because of its infection indices, capacity for transmitting Trypanosoma cruzi (Chagas), and its distribution areas. Here, we describe the results of a reproductive isolation analysis among 5 populations of T. longipennis collected from representative areas of Mexico. Fertility and segregation of morphological characteristics were examined in two generations of hybrids. The percentage of pairs with (fertile) offspring varied from 30% to 100% in the parental crosses, while these values varied from 0 to 100% in the intersite crosses. Our results indicate partial reproductive isolation among these populations. These findings shed light on the potential presence of a cryptic species complex of T. longipennis in Mexico.


Asunto(s)
Enfermedad de Chagas , Triatoma , Triatominae , Trypanosoma cruzi , Animales , Triatoma/genética , Aislamiento Reproductivo , México/epidemiología
17.
Pharmaceuticals (Basel) ; 16(4)2023 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37111300

RESUMEN

Protozoan parasite diseases cause significant mortality and morbidity worldwide. Factors such as climate change, extreme poverty, migration, and a lack of life opportunities lead to the propagation of diseases classified as tropical or non-endemic. Although there are several drugs to combat parasitic diseases, strains resistant to routinely used drugs have been reported. In addition, many first-line drugs have adverse effects ranging from mild to severe, including potential carcinogenic effects. Therefore, new lead compounds are needed to combat these parasites. Although little has been studied regarding the epigenetic mechanisms in lower eukaryotes, it is believed that epigenetics plays an essential role in vital aspects of the organism, from controlling the life cycle to the expression of genes involved in pathogenicity. Therefore, using epigenetic targets to combat these parasites is foreseen as an area with great potential for development. This review summarizes the main known epigenetic mechanisms and their potential as therapeutics for a group of medically important protozoal parasites. Different epigenetic mechanisms are discussed, highlighting those that can be used for drug repositioning, such as histone post-translational modifications (HPTMs). Exclusive parasite targets are also emphasized, including the base J and DNA 6 mA. These two categories have the greatest potential for developing drugs to treat or eradicate these diseases.

18.
Molecules ; 28(6)2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36985426

RESUMEN

Aedes aegypti is a vector for the arbovirus responsible for yellow fever, Zika and Chikungunya virus. Essential oils and their constituents are known for their larvicidal properties and are strong candidates for mosquito control. This work aimed to develop a quantitative structure-activity study and molecular screening for the search and design of new larvicidal agents. Twenty-five monoterpenes with previously evaluated larvicidal activity were built and optimized using computational tools. QSAR models were constructed through genetic algorithms from the larvicidal activity and the calculation of theoretical descriptors for each molecule. Docking studies on acetylcholinesterase (AChE) and sterol carrier protein (SCP-2) were also carried out. Results demonstrate that the epoxide groups in the structure of terpenes hinder larvicidal activity, while lipophilicity plays an important role in enhancing biological activity. Larvicidal activity correlates with the interaction of the sterol-carrier protein. Of the 25 compounds evaluated, carvacrol showed the highest larvicidal activity with an LC50 of 8.8 µg/mL. The information included in this work contributes to describing the molecular, topological, and quantum mechanical properties related to the larvicidal activity of monoterpenes and their derivatives.


Asunto(s)
Aedes , Insecticidas , Aceites Volátiles , Infección por el Virus Zika , Virus Zika , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/química , Terpenos , Relación Estructura-Actividad Cuantitativa , Acetilcolinesterasa , Insecticidas/farmacología , Insecticidas/química , Monoterpenos , Larva , Proteínas Portadoras , Esteroles
19.
Acta Parasitol ; 68(2): 334-343, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36920591

RESUMEN

BACKGROUND AND OBJECTIVES: The head louse Pediculus humanus capitis is a cosmopolitan ectoparasite that causes pediculosis. In the study of human lice, little research focuses on embryonic development. Currently, external markers of embryonic development represent a new approach in the evaluation of ovicidal drugs. The objective of this work was to update the morphology of embryonic development and propose novel external markers to differentiate between early, medium, or late P. h. capitis eggs. METHODS: Using stereoscopic light microscopy, we describe the morphological characteristics of P. h. capitis eggs with a special focus on embryonic development. RESULTS: The morphological analysis of the eggs revealed the presence of an operculum with ten aeropyles, although no micropyles were observed. For the first time, the presence of defective eggs that were non-viable due to the apparent absence of yolk granules was documented. The early eggs presented yolk granules and developing germ bands, while the medium eggs presented an embryonic rudiment and the outlines of the eyes and limbs. In late eggs, the head with eyes and antennae, the thorax with three pairs of legs, and the abdomen with six pairs of spiracles were observed as formed structures. At the end of this stage, the embryos acquired the morphology of the nymph I stage. CONCLUSION: We propose novel biomarkers (e.g., the presence of spiracles and antennae, the proportion of the egg occupied by the embryo) to facilitate the differentiation between the developmental stages. The updated morphological characteristics of P. h. capitis eggs facilitate the standardization of toxicological tests in the quest for ovicidal drugs.


Asunto(s)
Insecticidas , Infestaciones por Piojos , Pediculus , Animales , Humanos , Desarrollo Embrionario , Microscopía
20.
Med Vet Entomol ; 37(1): 124-131, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36315043

RESUMEN

Chagas disease is one of the most important vector-borne diseases in Latin America, including Mexico. Triatoma pallidipennis (Stål) (Hemiptera: Reduviidae) is a Mexican triatomine vector commonly associated with different hosts. The influence of six blood meals (rabbits, rats, mice, dogs, cats and chickens) on six biological parameters of the biology of T. pallidipennis was evaluated. A significant difference was found in the period of egg-to-adult development between the five mammalian feeds (mean 195 days) and the chicken feed (221 days). The probability of survival was significantly lower in the chicken cohort (0.285). The total number of blood meals to moult from the first instar to the adult stage was the highest in the chicken cohort (10-15). This cohort had the significantly highest rate of females at the end cycle. The mean number of eggs laid per female and the egg eclosion rate were similar among the six food sources. Most results seemed to be influenced by the higher nutritional quality of the mammalian blood compared to the bird's blood and the increased energy expenditure required for the digestion of bird blood. These results clearly show that T. pallidipennis, unlike other triatomine species, has a high reproductive capacity when feeding on different hosts.


Asunto(s)
Enfermedad de Chagas , Enfermedades de los Perros , Heterópteros , Triatoma , Triatominae , Trypanosoma cruzi , Animales , Femenino , Ratas , Ratones , Conejos , Perros , México , Pollos , Insectos Vectores , Enfermedad de Chagas/veterinaria , Comidas , Mamíferos
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