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DENV infection outcomes depend on the host's variable expression of immune receptors and mediators, leading to either resolution or exacerbation. While the NS3 protein is known to induce robust immune responses, the specific impact of its protease region epitopes remains unclear. This study investigated the effect of recombinant NS3 protease region proteins from all four DENV serotypes on splenocyte activation in BALB/c mice (n = 5/group). Mice were immunized with each protein, and their splenocytes were subsequently stimulated with homologous antigens. We measured the expression of costimulatory molecules (CD28, CD80, CD86, CD152) by flow cytometry, along with IL-2 production, CD25 expression, and examined the antigen-specific activation of CD4 + and CD8 + T cells. Additionally, the expression of IL-1, IL-10, and TGF-ß1 in splenocytes from immunized animals was assessed. Apoptosis was evaluated using Annexin V/PI staining and DNA fragmentation analysis. Stimulation of splenocytes from immunized mice triggered apoptosis (phosphatidylserine exposure and caspase 3/7 activation) and increased costimulatory molecule expression, particularly CD152. Low IL-2 production and low CD25 expression, as well as sustained expression of the IL-10 gene. These results suggest that these molecules might be involved in mechanisms by which the NS3 protein contributes to viral persistence and disease pathogenesis.

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Metal-Organic Frameworks (MOFs) have been shown to enhance the activity of encapsulated compounds by facilitating their passage across cell membranes, thereby enabling controlled and selective release. This study investigates the efficacy of BNZ@Zn-MOFs against the acute phase of Trypanosoma cruzi infection in a mouse model. The particles were synthesized by electroelution (EL), doped with BZN via mechanochemistry, and characterized using scanning electron microscopy (SEM), infrared spectroscopy (FTIR), and X-ray diffraction (XRD). BNZ@Zn-MOFs released 80% of the encapsulated BZN within 3 h, demonstrating no cytotoxicity in NIH-3T3 and HeLa cells. Furthermore, in a model of acute experimental T. cruzi-infection in BALB/c mice, the delivery system exhibited antiparasitic activity at a significantly lower BZN concentration compared to free BZN treatment. PCR analysis of treated mice revealed no parasite DNA in their tissues, and hematoxylin-eosin staining showed no apparent damage to tissue architecture. Additionally, serum levels of liver function enzymes remained unchanged, indicating no adverse effects on liver function. This delivery system, utilizing suboptimal BZN doses, enables the preservation of drug activity while potentially facilitating a substantial decrease in side effects associated with Chagas disease treatment.

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Introduction: Breast milk contains both nutritional and non-nutritional components for the newborn, with some of the latter exhibiting marked diurnal variations in concentration. This study aimed to analyze the circadian behavior of specific immune cell populations and proinflammatory cytokines present in the transitional milk of premature infants. Methods: The study quantified cellular components, including stem and immune cells, using flow cytometry. Additionally, ELISA assays were employed to measure proinflammatory cytokine concentrations. Results: Flow cytometry analyses revealed a diurnal rise in the percentage of CD23+, CD32+, CD36+, CD2+, and Tγδ cell populations. Conversely, nocturnal increases were observed in the percentage of CD16+, CD19+, and CD4+ populations. Notably, CD3+ and CD8+ populations did not exhibit any rhythmic variations. Proinflammatory cytokine concentrations were found to be higher in daytime milk samples compared to those collected at night. Conclusion: This study demonstrates rhythmic fluctuations in both immune cell populations and proinflammatory cytokine concentrations within the transitional milk of premature mothers.

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In the Yucatan Peninsula, Mexico, Triatoma dimidiata is the main vector of Chagas disease. This is a native species in the region that principally inhabits sylvatic habitats. Nevertheless, it shows a tolerant behavior to anthropogenic disturbance, with adult bugs frequently infesting human dwellings, principally during the warm and dry season. Yet, whether the temporal variation of abundance is independent of the habitat and how this is related to the infection rate with Trypanosoma cruzi in Yucatan is still poorly understood. The objective of this study was to simultaneously analyze the temporal variations of T. dimidiata abundance and infection with T. cruzi in domestic and sylvatic habitats from two localities of rural Yucatan (Sudzal, 20°52'19″N, 88°59'20″W and Teya, 21°02'55″N, 89°04'25″W) to help for the further improvement of locally adapted strategies aimed at controlling T. cruzi vector transmission. Using community participation and a combination of different trapping techniques, we collected T. dimidiata bugs during 29 consecutive months within domestic and sylvatic habitats. We then assessed by PCR the infection of the bugs with T. cruzi. Generalized linear models were used to evaluate the effect of climatic variables on the abundance of T. dimidiata and the effect of bug sex, season and habitat on the prevalence of infection with T. cruzi. Overall, 3640 specimens of T. dimidiata were collected. We clearly observed peaks of maximum abundance in both habitats during the warm and dry season and found a negative association of bug abundance with relative humidity. The overall prevalence of infection of the bugs with T. cruzi was 15.2 %. Additionally, bugs collected in domestic habitats displayed a significantly higher prevalence of infection than sylvatic bugs (19.6% vs. 6.1 %, respectively), suggesting an increased risk of T. cruzi transmission related with anthropogenic disturbance. Our study is the first to describe the annual pattern of abundance of T. dimidiata in sylvatic habitats of rural Yucatan and constitutes a contribution to the knowledge of T. dimidiata ecology and of T. cruzi transmission cycle dynamics in the region. In Yucatan, where the use of mosquito nets has shown to be effective to limit human dwelling infestation by T. dimidiata, reinforcing the awareness of local residents about the increased risk of T. cruzi transmission during the warm and dry season when realizing activities in the sylvatic ambient should be, among others, also considered to improve control strategies and limit the risk of vector transmission.

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Chagas disease, considered a neglected disease, was initially confined to rural localities in endemic areas; however, in recent years through the process of urbanization and migration of infected people, the disease is gaining importance in urban environments. The presence of the vector in urban areas in most cases is due to the passive transport of vectors, but recently, its presence seems to be linked to vector adaptation processes associated with climate change. This paper reports the occurrence of an infected triatomine in the peridomicile of a house in an urban area of Córdoba, Veracruz, Mexico, where the species found is described, the molecular characteristics and resistance to BZN and NFX of the Trypanosoma cruzi isolate obtained, as well as serological data of the dwelling inhabitants. These urban disease scenarios make it possible to generate new scientific knowledge and enable the creation of new control strategies for Chagas disease vectors.

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OBJECTIVE: To evaluate the presence of cross-reactivity by anti-severe acute respiratory syndrome coronavirus 2 antibodies induced by the Pfizer-BioNTech vaccine against Trypanosoma cruzi proteins in a screening test. METHODS: Forty-three serum samples were obtained from personnel at the Hospital General Naval de Alta Especialidad in Mexico City who received one or two doses of the vaccine and were tested for T. cruzi infection using four tests: two 'in house' enzyme-linked immunosorbent assays (ELISAs), a commercial ELISA diagnostic kit and an immunoblot test. RESULTS: IgG antibodies against the T. cruzi proteins were present in the serum of unvaccinated subjects and subjects who had received one or two doses of the vaccine. The positivity of the samples against T. cruzi was ruled out by means of a Western Blot assay, where all samples were negative for T. cruzi. CONCLUSION: The data suggest that people convalescing from coronavirus disease 2019 and those who received the Pfizer-BioNTech vaccine exhibit cross-reactive antibodies against T. cruzi antigens in ELISA assays.

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Zika virus (ZIKV) infection in pregnancy is associated with birth and developmental alterations in infants. In this study, clinical records of 47 infants whose mothers had Zika during pregnancy or clinical manifestations compatible with Zika were reviewed. A description of the infants' anomalies was established, and a neurodevelopmental assessment was performed on 18 infants, using the Evaluation of Infant Development (EDI for its initialism in Spanish) and DDST-II (Denver Developmental Screening Test II) tests. From his sample, 74.5% of the infants evaluated had major anomalies and 51.9% had minor anomalies. The incidence of major anomalies, related to trimester of pregnancy, was 84.2% for the first trimester, 77.8% for the second trimester, and 37.5% in the third trimester. A similar trend was observed in the frequency of infants without anomalies and was less evident in the incidence of minor anomalies (p = 0.016). Through neurodevelopmental assessments, EDI identified 27.8% of infants as having normal development, while 55.5% of affected infants had developmental delay, and 16.7% were at risk for developmental delay. The DDSST-II showed that 77.7% infants had delay in the gross motor and language area, 88.8% in the fine-adaptative motor area, and 72.2% in the personal-social area. In this work, children of mothers with ZIKV infection during pregnancy may have major or minor anomalies regardless of the trimester of pregnancy in which the infection occurred. The neurodevelopmental assessment shows that ZIKV can cause a developmental delay in infants with the fine-adaptative motor area being the most affected.

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PURPOSE: The objective of this study was to molecularly characterize Mexican isolates of T. cruzi obtained from infected triatomine bugs (the vectors of T. cruzi) and to evaluate their susceptibility to Nifurtimox (NFX). METHODS: Three isolates obtained from Triatoma dimidiata (collected in the State of Veracruz) and one isolate obtained from Triatoma bassolsae (collected in the State of Puebla) were molecularly characterized and the expression of genes associated with natural resistance to NFX was analyzed by qPCR. RESULTS: Molecular characterization by PCR showed that isolates Zn3, Zn5, and SRB1 belong to the DTU TcI, while isolate Sum3 belongs to TcIV. The latter was also confirmed by sequencing of mitochondrial genes. Isolate Zn5 was the most sensitive to treatment with NFX (IC50, 6.8 µM), isolates SRB1 and Zn3 were partially resistant (IC50, 12.8 µM and 12.7 µM) and isolate Sum3 showed a high degree of resistance to NFX (IC50, 21.4 µM). We also found an association between decreased NTR1 or OYE gene expression with NFX resistance. CONCLUSION: Our results also evidenced a high variability in the susceptibility to NFX of these T. cruzi isolates Central and Southeastern Mexico, suggesting the presence of naturally resistant isolates circulating in the country. These results have important implications for defining treatment policies for patients with Chagas disease.

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During pregnancy the human fetus receives timed cues from the circadian rhythms of temperature, metabolites, and hormones from the mother. This influence is interrupted after parturition, the infant does not secrete melatonin and their circadian rhythms are still immature. However, evolution provided the solution to this problem. The newborn can continue receiving the mother's timed cues through breastmilk. Colostrum, transitional, and mature human milk are extraordinary complex biofluids that besides nutrients, contain an array of other non-nutritive components. Upon birth the first milk, colostrum, is rich in bioactive, immunological factors, and in complex oligosaccharides which help the proper establishment of the microbiome in the gut, which is crucial for the infants' health. Hormones, such as glucocorticoids and melatonin, transfer from the mother's plasma to milk, and then the infant is exposed to circadian cues from their mother. Also, milk components of fat, proteins, amino acids, and endogenous cannabinoids, among others, have a markedly different concentration between day and night. In the present review, we give an overview of nutritive and non-nutritive components and their daily rhythms in human milk and explore their physiological importance for the infant. Finally, we highlight some interventions with a circadian approach that emphasize the importance of circadian rhythms in the newborn for their survival, proper growth, and development. It is estimated that ~600,000 deaths/year are due to suboptimal breastfeeding. It is advisable to increase the rate of exclusive breastfeeding, during the day and night, as was established by the evolution of our species.

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Cutaneous leishmaniasis is the most common form of leishmaniasis in humans, factors such as poverty, poor housing, inadequate domestic hygiene, malnutrition, mobility, and occupational exposure are risk factors associated with the condition, however, there are few studies focused on determining the immune mechanism involved in the resolution of cutaneous leishmaniasis caused by the species Leishmania mexicana, as well as possible environmental factors such as solar radiation, which could contribute to its establishment. through mechanisms immunosuppressants, of which to date is unknown. In this study, the effect of UV-B light was evaluated as a risk factor affecting components of the innate immune response 3 days after infection with L. mexicana. A delayed-type hypersensitivity reaction (DTH) was used to evaluate immunosuppression induced by UV-B light. Through a histological analysis, the skin lesions of the mice (Hematoxylin & Eosin) were evaluated, the presence of mast cells and their level of degranulation (toluidine blue staining), the presence of IL-10+ and MOMA2+ cells were analyzed by immunohistochemistry and finally, the cytokine profile was evaluated by qPCR in the skin lesions tissue. An alteration in the architecture of the tissue was observed, as well as a greater number of mast cells, both complete and degranulated, as well as an increase in IL-10+ and MOMA2+ cells in the skin lesions of the mice that were irradiated and subsequently infected, when compared with the lesions of infected mice (P> 0.0001), immunomodulation was also observed in the profile of cytokines expressed between both groups analyzed. This is the first study to demonstrate the effects of UV-B radiation on components of the innate immune response at short times of infection by L. mexicana.

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Triatoma dimidiata is the main vector of Trypanosoma cruzi parasites in Veracruz, Mexico, and its association with human housing appears variable. Also, in spite of a high seroprevalence of T. cruzi infection in humans, parasite transmission remains poorly understood. Therefore, we aimed to identify T. dimidiata blood feeding sources and its parasite and microbial diversity to reconstruct T. cruzi parasite transmission ecology in central Veracruz, Mexico, within a One Health/Ecohealth framework. We used a metabarcoding and deep sequencing approach of specific markers for the simultaneous identification of T. dimidiata haplogroup (ITS-2), vertebrate blood meals (12 s gene), T. cruzi parasites (mini-exon gene), and gut microbiota (bacterial 16 s). Twelve species of domestic/synanthropic animals and humans were identified as blood sources, with multiple feeding on 4.2 ± 0.4 hosts per bug. The feeding/parasite transmission network was strongly centered on humans, emphasizing a significant risk of infection. We also unambiguously confirmed the presence of TcI, TcII, TcV and TcVI DTUs in T. dimidiata, and sequences from Veracruz tended to cluster apart from parasites from other regions, suggesting some level of local differentiation. Analysis of T. dimidiata microbiota suggested that several bacterial families may be associated with the presence/absence of T. cruzi, and some of these associations may also be parasite DTU-specific. Such integrative approaches within the EcoHealth/One Health framework provide key insights on T. cruzi transmission and potential novel strategies for disease control.

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OBJECTIVE: To analyse the ecological and social factors involved in infestation of houses by Triatoma dimidiata in a rural locality of Veracruz, Mexico, where active transmission of the parasite is occurring. METHODS: A survey was applied to the households of the locality to obtain sociodemographic data. In parallel, T. dimidiata insects were collected during one year through community participation. Using PCR, the insects were genotyped, their infection status was assessed, and parasite genotypes infecting the insects were identified. The vector's blood meal sources were identified using a polymerase-heteroduplex chain reaction assay. RESULTS: Seasonal variations in the patterns of infestation by T. dimidiata were observed. An overall infestation rate of 19.46%, a colonisation index of 9.09%, a dispersion rate of 22.15% and a synanthropy index of 80.6% were found. The collected insects were identified as ITS-2 group 2 insects, and a natural infection with T. cruzi of 54.35% was found. TcI and no-TcI genotypes of T. cruzi were found in infected insects. Factors such as rain (P = 0.0006) and temperature (P < 0.0001) were associated with infestation. Analysis of the blood meal sources indicated frequent feeding upon humans and mice. Furthermore, house materials and peridomiciles were found to play an important role in the dynamics of infestation. CONCLUSIONS: The contribution of this study is important for understanding the epidemiology of Chagas disease in rural areas of the state of Veracruz and will help to the establishment of an entomological surveillance system and implementation of prevention and control measures in accordance with the reality of the area.

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PURPOSE: Leishmaniasis is an infectious disease transmitted by insects that proliferate mainly in impoverished environments of tropical climates. In the absence of an effective vaccine, pharmacological treatment is the main tool to combat this disease. The objective of this work was to analyze the anti-leishmanial activity of 2-chloro-N-[4-(4-chlorophenyl)-2-thiazolyl] acetamide (AT) in promastigotes of Leishmania mexicana. METHODS: The biological activity of the compound was evaluated using a sulphorhodamine B cytotoxicity test and the integrity of the erythrocytes was evaluated by a lysis test. The anti-trypanosomatid activity was evaluated in vitro, a cell death assay was performed by flow cytometry (IP/Annexin V stain) and a parasite growth recovery assay was performed. RESULTS: The AT showed a CC50 value of 0.031 µM for HeLa cells after 24 h of exposure, which did not induce erythrocyte lysis. On the other hand, the AT showed an IC50 value of 0.086 µM for L. mexicana (promastigote form) after 24 h of interaction. The compound was capable of inducing apoptosis in the parasites and did not allow recovery after 24 h of exposure. CONCLUSION: This study provides valuable information with the objective of developing new drugs for the treatment of this disease, although more research on this molecule is needed to improve its biological activity.

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Triatoma dimidiata is considered one of the most important vectors in the spread of Chagas disease in Mesoamerica. Hematophagous insects may deposit faeces contaminated or not with Trypanosoma cruzi on the surface of the skin during the feeding process. In endemic areas humans can be in contact several times to this fluid before get infection. Due to limited work on the of immune response to insect's fluids in mammals. In this work, we explored the early response of chemokine and cytokines of skin tissue at the inoculation site against faeces from T. dimidiata contaminated or not with T. cruzi in murine model, also we explored the in vitro response of epitheloid cells line "HeLa cells" to this fluid. Mice were exposed intradermically to faeces free of metacyclic trypomastigotes, oneor multiple times along the experiment before challenged with faeces contaminated with metacyclic trypomastigotes, mimicking natural conditions. In in vitro assay with HeLa cells only one exposure was carried out. It was observed that mice multiexposed to faeces, induced the strong response of TNF-α and CXCL3 expression at the inoculation site; but faeces contaminated with metacyclic trypomastigotes lower the response of TNF-α, and CXCL3. In in vitro assay with HeLa cell line, the faeces induced a strong response of CXCL8 and IL-6, but the presence of faeces contaminated with metacyclic trypomastigotes lower the response of CXCL8. In contrast, to in vivo model null response of TNF α and IL-1-α was observed in HeLa cells. In conclusion, Triatoma dimidiata faeces induces at the inoculation site chemokines that mediate preferentially chemotaxis of neutrophils and macrophages but the presence of metacyclic trypomastigotes moderate their induction. Epithelial cells act as efficient sentinels producing chemokines that may recruit neutrophils and monocytes.

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BACKGROUND: Chagas disease caused by the parasite Trypanosoma cruzi is considered a neglected disease in several countries. One of the main problems about this disease is the lack of an effective treatment and the absence of adverse effects. T. cruzi, like most pathogenic fungi and yeasts, require specific sterols to maintain viability and proliferative capacity during their life cycle. However, the oxidation of this molecule to ergosterol peroxide has shown several biological effects, including its trypanocidal activity. METHODS: We have synthesized MOFs nanoparticles as carrier system coupled to ergosterol peroxide (MOFs-EP) and we have studied its effect on the circulating forms of the T. cruzi parasite. RESULTS: MOFs-EP possess an efficient trypanocidal activity at much lower inhibitory concentrations (ng/mL) that the concentrations shown by ergosterol peroxide (µg/mL) when administered unconjugated form. CONCLUSION: Our results open a new possibility in the biomedical application of MOFs and ergosterol peroxide in the search for new options for the treatment of Chagas disease.

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PURPOSE: The state of Veracruz, Mexico, is a well-recognized endemic region for Chagas disease, but congenital transmission has not been extensively studied. We estimated here the prevalence and the risk of congenital transmission of Trypanosoma cruzi in pregnant women from 27 municipalities of central Veracruz. METHODS: 528 sera from pregnant women were analyzed by ELISA and IFA assays for the detection of IgG antibodies against T. cruzi. RESULTS: The presence of anti-T. cruzi antibodies was identified in women from 17 municipalities, obtaining an overall seroprevalence of 17.0%. A higher seropositivity was observed in the municipalities of Orizaba (25.2%), Nogales (13.6%), and Río Blanco (10.5%). The results suggest that there is a high risk of congenital transmission of T. cruzi in the region. CONCLUSION: There are currently limited actions for the surveillance and control of congenital transmission of Chagas disease in Veracruz.

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BACKGROUND: Adjuvants have been obtained empirically by trial and error experiments and today, there is a tendency to the rational design of adjuvants candidates, which will increasingly achieve effective and safe products. The aim of this work was to design and evaluate the compound IMR-23 derived from nitroimidazole as an immunomodulatory molecule. MATERIALS AND METHODS: The IMR-23 molecule was obtained by a condensation reaction, cytotoxicity was tested by the sulforhodamine B assay. Adjuvanticity was evaluated in vivo and in vitro in J774A.1 cells and in the mouse model, respectively. RESULTS: IMR-23 that did not show cytotoxicity on HeLa, Vero cells and macrophages J774A.1, was able to induce the production of molecules involved in the inflammatory process, such as cytokines and chemokines determined by ELISA, to induce the production of antibodies and to generate antigenspecific cells to ovalbumin and against the antigen GST-L1b. CONCLUSION: These results open the possibility of further studies to obtain a proper balance of immunogenicity- toxicity in the use of IMR-23 as an adjuvant molecule.

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Trypanosoma cruzi, which causes Chagas disease, is a significant health threat in many countries and affects millions of people. Given the magnitude of this disease, a broader understanding of trypanocidal mechanisms is needed to prevent and treat infection. Natural endoperoxides, such as ergosterol peroxide, have been shown to be toxic to parasites without causing harm to human cells or tissues. Although prior studies have demonstrated the trypanocidal activity of ergosterol peroxide, the cellular and molecular mechanisms remain unknown. The results of this study indicate that a free-radical reaction occurs in T. cruzi following ergosterol peroxide exposure, leading to cell death. Using a combination of biochemical, microscopic and in silico experimental approaches, we have identified, for the first time, the cellular and molecular cytotoxic mechanism of an ergosterol peroxide obtained from Pleurotus ostreatus (Jacq) P. Kumm. f. sp. Florida.

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Female sex workers (FSWs) have been considered a key population for sexually transmitted infections (STIs); therefore, they are periodically screened as a requirement to obtain a work card. However, there is insufficient epidemiological data on STIs among FSWs in Mexico. The detection of Trichomonas vaginalis is limited to microscopic studies and the molecular screening of Human papillomavirus (HPV) is only done to women 35 years of age and older. The objective of this study was to determine the prevalence of T. vaginalis and HPV infections in FSWs in the city of Orizaba, Veracruz, Mexico. Samples from 105 FSWs were obtained by cervical swab and analyzed. The identification of T. vaginalis and HPV was performed by molecular methods. HPV DNA was identified in 5.71% of the samples with the presence of HPV16, HPV18, and HPV58. A percentage of 25.7% samples were positive for T. vaginalis for optical microscopy and 23.8% for PCR. The results of the study indicate the need to incorporate more sensitive methods for the timely diagnosis of STIs as well as comprehensive health promotion programs directed to the most vulnerable groups among FSWs.

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Compounds showing pharmacological activity on the immune system are of interest because of their therapeutic potential in the treatment of many diseases. However, data from primary human immune cells and in vivo studies are limited. The aim of this study was to analyze the ability to induce the expression of Toll-like receptors (TLRs) and proinflammatory molecules on cells involved in the immune system using the compound ergosta-7,22-dien-3- one, isolated from a wild Mexican strain of Ganoderma oerstedii. According to our study, ergosta-7,22-dien-3-one did not present any cytotoxic effect on HeLa or J774A.1 cells, and it was able to stimulate nitric oxide production, induce the expression of genes, and induce the production of TLRs, cytokines, chemokines, and cellular adhesion molecules in J774A.1 cells, based on reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Here we report a new pro-inflammatory property of ergosta-7,22-dien-3-one, which should be considered as a possible adjuvant property in view of its biological activity.

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