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Infections caused by micro-organisms of the genus Candida are becoming a growing health problem worldwide. These fungi are opportunistic commensals that can produce infections-clinically known as candidiasis-in immunocompromised individuals. The indiscriminate use of different anti-fungal treatments has triggered the resistance of Candida species to currently used therapies. In this sense, propolis has been shown to have potent antimicrobial properties and thus can be used as an approach for the inhibition of Candida species. Therefore, this work aims to evaluate the anti-Candida effects of a propolis extract obtained from the north of Mexico on clinical isolates of Candida species. Candida species were specifically identified from oral lesions, and both the qualitative and quantitative anti-Candida effects of the Mexican propolis were evaluated, as well as its inhibitory effect on C. albicans isolate's germ tube growth and chemical composition. Three Candida species were identified, and our results indicated that the inhibition halos of the propolis ranged from 7.6 to 21.43 mm, while that of the MFC and FC50 ranged from 0.312 to 1.25 and 0.014 to 0.244 mg/mL, respectively. Moreover, the propolis was found to inhibit germ tube formation (IC50 ranging from 0.030 to 1.291 mg/mL). Chemical composition analysis indicated the presence of flavonoids, including pinocembrin, baicalein, pinobanksin chalcone, rhamnetin, and biochanin A, in the Mexican propolis extract. In summary, our work shows that Mexican propolis presents significant anti-Candida effects related to its chemical composition, and also inhibits germ tube growth. Other Candida species virulence factors should be investigated in future research in order to determine the mechanisms associated with antifungal effects against them.
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Candida , Própolis , Antifúngicos/farmacología , Candida albicans , Humanos , México , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Própolis/química , Própolis/farmacologíaRESUMEN
Granulomatous amoebic encephalitis (GAE) is a chronic, difficult to resolve infection caused by amphizoic amoebae of the genus Acanthamoeba, which in most cases occurs in immunosuppressed persons or with chronic diseases such as diabetes. In this study, we describe the early events of A. culbertsoni infection of GAE in diabetic mice model. Diabetes was induced in male BALB/c mice, with a dose of streptozotocin (130 mg/kg). Healthy and diabetic mice were inoculated via intranasal with 1 × 106 trophozoites of A. culbertsoni. Then were sacrificed and fixed by perfusion at 24, 48, 72 and 96 h post-inoculation, the brains and nasopharyngeal meatus were processed to immunohistochemical analysis. Invasion of trophozoites in diabetic mice was significantly greater with respect to inoculated healthy mice. Trophozoites and scarce cysts were immunolocalized in respiratory epithelial adjacent bone tissue, olfactory nerve packets, Schwann cells and the epineurium base since early 24 h post-inoculation. After 48 h, trophozoites were observed in the respiratory epithelium, white matter of the brain, subcortical central cortex and nasopharyngeal associated lymphoid tissue (NALT). At 72 h, cysts and trophozoites were immunolocalized in the olfactory bulb with the presence of a low inflammatory infiltrate characterized by polymorphonuclear cells. Scarce amoebae were observed in the granular layer of the cerebellum without evidence of inflammation or tissue damage. No amoebas were observed at 96 h after inoculation, suggesting penetration to other tissues at this time. In line with this, no inflammatory infiltrate was observed in the surrounding tissues where the amoebae were immunolocalized, which could contribute to the rapid spread of infection, particularly in diabetic mice. All data suggest that trophozoites invade the tissues by separating the superficial cells, penetrating between the junctions without causing cytolytic effect in the adjacent cells and subsequently reaching the CNS, importantly, diabetes increases the susceptibility to amoebae infection, which could favor the GAE development.
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Acanthamoeba/patogenicidad , Amebiasis/etiología , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Encefalitis/parasitología , Acanthamoeba/fisiología , Animales , Encéfalo/parasitología , Encéfalo/patología , Cerebelo/parasitología , Cerebelo/patología , Susceptibilidad a Enfermedades , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos BALB C , Nasofaringe/parasitología , Nasofaringe/patología , Bulbo Olfatorio/parasitología , Bulbo Olfatorio/patología , Pase Seriado , Trofozoítos , VirulenciaRESUMEN
This study was developed in order to describe the early morphological events observed during the invasion of two pathogenic strains of Acanthamoeba (genotype T4); A. castellanii and A. culbertsoni, at the olfactory meatus and cerebral, pulmonary, renal, hepatic and splenic tissues levels, an in vivo invasion study. Histological and immunohistochemical description of the events at 24, 48, 72, and 96 h postintranasal inoculations of BALB/c mice was performed. A. castellanii showed a higher invasion rate than A. culbertsoni, which was only able to reach lung and brain tissue in the in vivo model. The current study supports previous evidence of lack of inflammatory response during the early stages of infection. Acanthamoeba invasion of the CNS and other organs is a slow and contact-dependent process. The early morphological events during the invasion of amoebae include the penetration of trophozoites into different epithelia: olfactory, respiratory, alveolar space, and renal tubule, which resemble the process of amoebae invasion described in corneal tissue. The data suggest that after reaching the nasal epithelium, trophozoites continued invasion, separating and lifting the most superficial cells, then migrating and penetrating between the cell junctions without causing a cytolytic effect on adjacent cells. These results reaffirm the idea that contact-dependent mechanisms are relevant for amoebae of Acanthamoeba genus regardless of the invasion site.
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Acanthamoeba/patogenicidad , Amebiasis/patología , Sistema Nervioso Central/parasitología , Túbulos Renales/parasitología , Mucosa Nasal/parasitología , Mucosa Respiratoria/parasitología , Trofozoítos/metabolismo , Animales , Córnea/parasitología , Modelos Animales de Enfermedad , Genotipo , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB CRESUMEN
The 2016 undergraduate medical degree curriculum at the Facultad de Estudios Superiores Iztacala of the Universidad Nacional Autónoma de México (UNAM) is presented. It is the result of a long institutional reflection and academic dialog process of approximately three years, which culminated in its approval by UNAM's Academic Council for the Biology, Chemistry, and Health Sciences areas on January 25, 2016. Its most relevant characteristics are: modular organization, four knowledge areas (biomedical, methodological, socio-psychological, and humanistic and medical practice), and new modules such as Seminar of socio-psycho-biological integration; Genetics and molecular biology; Biochemistry and cellular biology; Pharmacological basis of therapeutics; Infectious diseases, microbiology and parasitology; Medical ethics; Public health; and Evidence-based medicine - clinical epidemiology. To achieve a more flexible curriculum, optional modules were included. To make possible the curricular change, improving the teaching strategies, innovating the learning assessment methods, supporting the training and updating of the teaching staff, and establishing a curriculum development committee for following up and evaluating the program, are necessary. Curricular changes are difficult and complex processes; they suppose challenges and opportunities. It is mandatory to plan them carefully and sensitively to allow a successful transition and avoid conflicts for the students, the teachers and the institution.
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Curriculum , Educación de Pregrado en Medicina/organización & administración , Docentes Médicos , Humanos , México , Estudiantes de Medicina , Enseñanza/organización & administraciónRESUMEN
PURPOSE: To describe the adhesion properties of Acanthamoeba castellanii trophozoites to silicone hydrogel contact lenses of first generation (lotrafilcon A), second generation (galyfilcon A), and third generation (comfilcon A) and correlate the results with their specific surface characteristics, time of interaction, and suspension media. METHODS: Qualitative and quantitative assessments of the adhesion of 200 trophozoites of A. castellanii on contact lenses in culture medium (Bacto Casitone) and isotonic saline (IS) at different time points (15 minutes and 6 hours) were determined. RESULTS: By scanning electron microscopy, A. castellanii trophozoites were observed firmly adhered to the surface of hydrogel lenses after 15 minutes of interaction. The surface of lotrafilcon A lenses on which amoebae adhere better (16.4±10.2 amoebae/lens section) is rough and folded, which increases the contact surface with trophozoites, allowing acanthopodia to attach firmly. Contrarily, galyfilcon A lenses have a smoother surface, and lower numbers of amoebae were observed adhered to these lenses (4.7±2.9 amoebae/lens section). Even fewer amoebae adhered to the smoother surface of the comfilcon A lens (2.2±1.7 amoebae/lens section). Trophozoites showed similar behavior in both Bacto Casitone medium and IS. CONCLUSION: A rough surface may contribute to better adhesion of amoebae to silicone hydrogel lenses. Although a reduced numbers of trophozoites adhered to smooth lenses, trophozoites are a risk factor for amoebic keratitis. Isotonic saline facilitated trophozoite survival, suggesting that homemade saline solutions may contribute to the persistence of trophozoites, especially when there is no proper hygiene regimen used with the contact lens cases.
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Acanthamoeba castellanii/aislamiento & purificación , Lentes de Contacto Hidrofílicos/microbiología , Hidrogeles , Elastómeros de Silicona , Microscopía Electrónica de Rastreo , Propiedades de Superficie , Factores de Tiempo , TrofozoítosRESUMEN
University students are at high risk of sexually transmitted infections due to the lack of adequate sexual education, as well as multiple associated factors, which lead to risky sexual practices. It is important to update data about sexual behaviors to identify the main factors associated with sexually risky behaviors. The present study aimed to evaluate the current prevalence of sexually risky practices in medical students. A cross-sectional study was conducted among medical students through an anonymous self-administered online questionnaire including demographic characteristics and sexual behaviors. We used descriptive statistics and multivariable regression to analyze the data collected. A total of 1520 undergraduate medical students aged between 18 and 28 years old were included in the study. Sixty percent of the students were sexually active with a higher proportion in men (70%), likewise, they had an earlier sexual debut (16.5 vs 16.9 years old), and a greater number of lifetime sexual partners than women (3.8 vs 2.2). The main sexual activity in both groups was vaginal sex with high use of condoms (75%), however, most of them (67%) reported having unprotected oral sex. Logistic regression analysis showed that condomless sex was associated with having oral sex, anal sex, and being female. The findings of this study showed that medical university students are involved in risky sexual behaviors, the major risk factor was unprotected oral sex. Based on these results, we recommended designing interventions to improve sexual education and preventive approaches from early stages such as in middle school students to mitigate sexually transmitted infections among medical university students.
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Asunción de Riesgos , Conducta Sexual , Estudiantes de Medicina , Humanos , Masculino , Femenino , Estudiantes de Medicina/estadística & datos numéricos , Estudiantes de Medicina/psicología , México/epidemiología , Adolescente , Adulto , Adulto Joven , Conducta Sexual/estadística & datos numéricos , Prevalencia , Estudios Transversales , Encuestas y Cuestionarios , Enfermedades de Transmisión Sexual/epidemiología , Sexo Inseguro/estadística & datos numéricosRESUMEN
Gastric cancer is one of the most common, aggressive, and invasive types of malignant neoplasia. It ranks fifth for incidence and fourth for prevalence worldwide. Products of natural origin, such as propolis, have been assessed for use as new complementary therapies to combat cancer. Propolis is a bee product with antiproliferative and anticancer properties. The concentrations and types of secondary metabolites contained in propolis mainly vary according to the geographical region, the season of the year, and the species of bees that make it. The present study is a systematic review of the main articles related to the effects of propolis against gastric cancer published between 2011 and 2021 in the PubMed and Science Direct databases. Of 1305 articles published, only eight studies were selected; among their principal characteristics was the use of in vitro analysis with cell lines from gastric adenocarcinoma and in vivo murine models of the application of propolis treatments. These studies suggest that propolis arrests the cell cycle and inhibits proliferation, prevents the release of oxidizing agents, and promotes apoptosis. In vivo assays showed that propolis decreased the number of tumors by regulating the cell cycle and the expression of proteins related to apoptosis.
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Several species of Acanthamoeba genus are potential pathogens and etiological agents of several diseases. The pathogenic mechanisms carried out by these amoebae in different target tissues have been documented, evidencing the relevant role of contact-dependent mechanisms. With the purpose of describing the pathogenic processes carried out by these protozoans more precisely, we considered it important to determine the emission of extracellular vesicles (EVs) as part of the contact-independent pathogenicity mechanisms of A. culbertsoni, a highly pathogenic strain. Through transmission electronic microscopy (TEM) and nanoparticle tracking analysis (NTA), EVs were characterized. EVs showed lipid membrane and a size between 60 and 855 nm. The secretion of large vesicles was corroborated by confocal and TEM microscopy. The SDS-PAGE of EVs showed proteins of 45 to 200 kDa. Antigenic recognition was determined by Western Blot, and the internalization of EVs by trophozoites was observed through Dil-labeled EVs. In addition, some EVs biological characteristics were determined, such as proteolytic, hemolytic and COX activity. Furthermore, we highlighted the presence of leishmanolysin in trophozites and EVs. These results suggest that EVs are part of a contact-independent mechanism, which, together with contact-dependent ones, allow for a better understanding of the pathogenicity carried out by Acanthamoeba culbertsoni.
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BACKGROUND: Ellis-van Creveld syndrome (EvCS) is an autosomal recessive ciliopathy with a disproportionate short stature, polydactyly, dystrophic nails, oral defects, and cardiac anomalies. It is caused by pathogenic variants in the EVC or EVC2 genes. To obtain further insight into the genetics of EvCS, we identified the genetic defect for the EVC2 gene in two Mexican patients. METHODS: Two Mexican families were enrolled in this study. Exome sequencing was applied in the probands to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in the parents. Finally, a prediction of the three-dimensional structure of the mutant proteins was made. RESULTS: One patient has a compound heterozygous EVC2 mutation: a novel heterozygous variant c.519_519 + 1delinsT inherited from her mother, and a heterozygous variant c.2161delC (p.L721fs) inherited from her father. The second patient has a previously reported compound heterozygous EVC2 mutation: nonsense mutation c.645G > A (p.W215*) in exon 5 inherited from her mother, and c.273dup (p.K92fs) in exon 2 inherited from her father. In both cases, the diagnostic was Ellis-van Creveld syndrome. Three-dimensional modeling of the EVC2 protein showed that truncated proteins are produced in both patients due to the generation of premature stop codons. CONCLUSION: The identified novel heterozygous EVC2 variants, c.2161delC and c.519_519 + 1delinsT, were responsible for the Ellis-van Creveld syndrome in one of the Mexican patients. In the second Mexican patient, we identified a compound heterozygous variant, c.645G > A and c.273dup, responsible for EvCS. The findings in this study extend the EVC2 mutation spectrum and may provide new insights into the EVC2 causation and diagnosis with implications for genetic counseling and clinical management.
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Síndrome de Ellis-Van Creveld , Proteínas de la Membrana , Humanos , Femenino , Proteínas de la Membrana/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Síndrome de Ellis-Van Creveld/genética , Síndrome de Ellis-Van Creveld/diagnóstico , Linaje , Mutación , Codón sin SentidoRESUMEN
The current pandemic generated by SARS-CoV-2 has led to mass vaccination with different biologics that have shown wide variations among human populations according to the origin and formulation of the vaccine. Studies evaluating the response in individuals with a natural infection before vaccination have been limited to antibody titer analysis and evaluating a few humoral and cellular response markers, showing a more rapid and intense humoral response than individuals without prior infection. However, the basis of these differences has not been explored in depth. In the present work, we analyzed a group of pro and anti-inflammatory cytokines, antibody titers, and cell populations in peripheral blood of individuals with previous SARS-CoV-2 infection using BNT162b2 biologic. Our results suggest that higher antibody concentration in individuals with an earlier disease could be generated by higher production of plasma cells to the detriment of the presence of memory B cells in the bloodstream, which could be related to the high baseline expression of cytokines (IL-6 and IL-10) before vaccination.
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COVID-19 , Vacunas Virales , Vacuna BNT162 , COVID-19/prevención & control , Humanos , Interleucina-10 , Interleucina-6 , Receptores CCR7 , SARS-CoV-2 , VacunaciónRESUMEN
The skin is the main external organ. It protects against different types of potentially harmful agents, such as pathogens, or physical factors, such as radiation. Skin disorders are very diverse, and some of them lack adequate and accessible treatment. The photoaging of the skin is a problem of great relevance since it is related to the development of cancer, while psoriasis is a chronic inflammatory disease that causes scaly skin lesions and deterioration of the lifestyle of people affected. These diseases affect the patient's health and quality of life, so alternatives have been sought that improve the treatment for these diseases. This review focuses on describing the properties and benefits of flavonoids from propolis against these diseases. The information collected shows that the antioxidant and anti-inflammatory properties of flavonoids play a crucial role in the control and regulation of the cellular and biochemical alterations caused by these diseases; moreover, flavones, flavonols, flavanones, flavan-3-ols, and isoflavones contained in different worldwide propolis samples are the types of flavonoids usually evaluated in both diseases. Therefore, the research carried out in the area of dermatology with bioactive compounds of different origins is of great relevance to developing preventive and therapeutic approaches.
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BACKGROUND: Tumor-infiltrating lymphocytes are an important component of the tumor microenvironment (TME) in breast cancer. They have been linked with tumor pathogenesis in advanced stages. However, little is known about their contribution in early phases. In this study, we analyzed the infiltration of leukocytes and cancer stem cells (CSC) in tumors from patients with early breast cancer. METHODS: Samples of blood and tumor tissue from 30 patients with breast cancer were collected, and the number of dendritic cells (DC), T cells, and CSC were analyzed by flow cytometry. RESULTS: Tumor-infiltrating CD4 and CD8 T cells expressed higher levels of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) compared with peripheral T cells. Regulatory T cells (Treg) were enriched in tumors and overexpressed glucocorticoid-induced TNFR-related protein and CTLA-4. Tumor Treg had a positive correlation with the amount of myeloid DC (mDC) and disease progression. The CD8/Treg ratio was associated with lymph node metastasis and tumor stages. The main subset of DC in early breast tumors was mDC, while plasmacytoid DC were almost absent. CSC were present in most tumors with higher frequencies in patients with lymph node metastasis. CSC were also associated with the amount of tumor-infiltrating Treg. CONCLUSION: Early breast cancer has an inflammatory milieu characterized by mDC, Treg, and CSC infiltration. The frequencies of Treg, CSC and CD8/Treg ratio were associated with disease progression. The composition of leukocytes and the presence of CSC in early breast tumors should be considered for the development of new therapeutic approaches.
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Neoplasias de la Mama/patología , Linfocitos T CD8-positivos/inmunología , Metástasis Linfática/inmunología , Células Madre Neoplásicas/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Mama/inmunología , Mama/patología , Neoplasias de la Mama/sangre , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/inmunología , Relación CD4-CD8 , Células Dendríticas/inmunología , Femenino , Humanos , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Linfocitos Infiltrantes de Tumor , Persona de Mediana Edad , Clasificación del Tumor , Microambiente Tumoral/inmunologíaRESUMEN
Amoebae of the genus Acanthamoeba are etiological agents of granulomatous amoebic encephalitis (GAE). Recently, through an in vivo GAE model, Acanthamoeba trophozoites were immunolocalized in contact with the peripheral nervous system (PNS) cells-Schwann cells (SC). In this study, we analyzed in greater detail the in vitro early morphological events (1, 2, 3, and 4 h) during the interaction of A. culbertsoni trophozoites (ATCC 30171) with SC from Rattus norvegicus (ATCC CRL-2941). Samples were processed for scanning and transmission electron microscopy as well as confocal microscopy. After 1 h of interaction, amoebae were observed to be adhered to the SC cultures, emitting sucker-like structures associated with micro-phagocytic channels. In addition, evidence of necrosis was identified since edematous organelles as well as multivesicular and multilamellar bodies characteristics of autophagy were detected. At 2 h, trophozoites migrated beneath the SC culture in which necrosis and autophagy persisted. By 3 and 4 h, extensive lytic zones were observed. SC necrosis was confirmed by confocal microscopy. We reported for the first time the induction of autophagic and necrotic processes in PNS cells, associated in part with the contact-dependent pathogenic mechanisms of A. culbertsoni trophozoites.
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BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a human genetic disorder that affects structures of ectodermal origin such as hair, teeth, and sweat glands. Although there are autosomal recessive and dominant forms, X-linked (XL) is the most frequent form of the disease. This XL-HED phenotype is associated with mutations in the gene encoding the transmembrane protein ectodysplasin-1 (EDA1). We report the clinical and molecular analysis of a novel mutation in exon 1 affecting the transmembrane domain of the protein. METHODS: We have screened 20 members of a family from Yucatán, México, nine men and 11 women, searching clinical and histopathological signs of HED. We searched mutations in EDA1 gene from patients with XL-HED, carriers, and controls. RESULTS: We identified seven men with clinical characteristics of HED showing short toes and plantar hyperkeratosis not reported previously in patients with HED. A mutational study of the EDA1 gene showed that all seven patients with HED carry a novel missense mutation of the nucleotide 409 (c.409T>C) in exon 1, which changes p.Leu56-Pro in the protein amino acid sequence; five women are heterozygous compatible with carrier status. CONCLUSIONS: We found a novel missense mutation in exon 1 of the EDA1 gene in a putative Mayan family from México with XL-HED. We identified in this population some novel clinical signs of HED.
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Displasia Ectodermal Anhidrótica Tipo 1/genética , Ectodisplasinas/genética , Mutación Missense , Exones , Femenino , Heterocigoto , Humanos , Queratodermia Palmoplantar/genética , Masculino , Linaje , Dedos del Pie/anomalíasRESUMEN
The morphological analysis of the cytopathic effect on MDCK cell monolayers and hamster cornea and qualitative and quantitative analyses of conditioned medium and proteases were evaluated and compared between two strains of Acanthamoeba genotype T4. Further than highlighting the biological differences found between both strains, the most important observation in this study was the fact that proteases both in total extracts and in conditioned medium are apparently not determinant in tissue destruction. An interestingly finding was that no lysis of corneal tissue was observed as it was previously suggested. These results, together with previous studies, allow us to conclude that the invasion and disruption of corneal tissue is performed by the penetration of the amoebae through cell junctions, either by the action of proteases promoting cellular separation but not by their destruction and/or a mechanical effect exerted by amoebae. Therefore, contact-dependent mechanisms in Acanthamoeba pathogenesis are more relevant than it has been previously considered. This is supported because the phagocytosis of recently detached cells as well as those attached to the corneal epithelium leads to the modification of the cellular architecture facilitating the migration and destruction of deeper layers of the corneal epithelium.
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Acanthamoeba , Amebiasis , Epitelio Corneal , Péptido Hidrolasas/metabolismo , Proteínas Protozoarias/metabolismo , Acanthamoeba/enzimología , Acanthamoeba/patogenicidad , Acanthamoeba/ultraestructura , Amebiasis/enzimología , Amebiasis/patología , Animales , Cricetinae , Perros , Epitelio Corneal/metabolismo , Epitelio Corneal/parasitología , Epitelio Corneal/ultraestructura , Uniones Intercelulares/metabolismo , Uniones Intercelulares/parasitología , Uniones Intercelulares/ultraestructura , Células de Riñón Canino Madin Darby , Masculino , MesocricetusRESUMEN
The geographical distribution of the metabolic syndrome (MetS) prevalence in young Mexicans (aged 17-24 years) was estimated stepwise starting from its prevalence based on the body mass index (BMI) in a study of 3,176 undergraduate students of this age group from Mexico City. To estimate the number of people with MetS by state, we multiplied its prevalence derived from the BMI range found in the Mexico City sample by the BMI proportions (range and state) obtained from the Mexico 2006 national survey on health and nutrition. Finally, to estimate the total number of young people with MetS in Mexico, its prevalence by state was multiplied by the share of young population in each state according to the National Population and Housing Census 2010. Based on these figures, we estimated the national prevalence of MetS at 15.8%, the average BMI at 24.1 (standard deviation = 4.2), and the prevalence of overweight people (BMI ≥25) of that age group at 39.0%. These results imply that 2,588,414 young Mexicans suffered from MetS in 2010. The Yucatan peninsula in the south and the Sonora state in the north showed the highest rates of MetS prevalence. The calculation of the MetS prevalence by BMI range in a sample of the population, and extrapolating it using the BMI proportions by range of the total population, was found to be a useful approach. We conclude that the BMI is a valuable public health tool to estimate MetS prevalence in the whole country, including its geographical distribution.