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The SARS-CoV-2 outbreak has provoked more than 6 million deaths worldwide. The scarcity of effective treatments and its virulence converted the vaccines into an essential tool to face it. The most used vaccines were the mRNA, adenovirus vector, and inactivated whole-virus. However, nowadays, infants aged < 6 months are not eligible for any vaccines against COVID-19, and their immunization relies on passive immunity. In this research, we investigated the humoral and cellular immune response generated on newborns of SARS-CoV-2 vaccinated mothers with mRNA or viral vector (VV) vaccine employing Fourier transformed infrared (FTIR) spectroscopy in saliva samples. For this purpose, saliva samples of newborns and their mothers were collected; the population was divided into two groups, VV and mRNA, which were subdivided into three subgroups: before pregnancy (BP), at the first (FTP) and second (STP) trimesters of pregnancy. The samples were analyzed using FTIR spectroscopy, and the bands associated with the humoral and cellular immune responses, such as IgG, IgA, and IFN-γ were analyzed. The integrated areas were calculated and compared to elucidate the quantity of those immunoglobins and the cytokine. Likewise, the correlation of the humoral and cellular immune response between the newborns and their mothers and the correlation between cellular and humoral immune response was also evaluated. The VV vaccine produced a significant humoral and cellular immune response in newborns and their mothers when they received it at the STP compared with the mRNA vaccine, evidencing statistical significance. However, no correlation was observed between newborns and their mothers when the vaccine was applied in this trimester of pregnancy. When administered BP, the mRNA vaccine generated more humoral immunity in newborns and their mothers. Nevertheless, compared with the VV vaccine, it only showed statistical significance in the mothers, highlighting that IgG showed a moderate positive correlation between the newborns and their mothers.
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Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunación , Humanos , Femenino , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Recién Nacido , COVID-19/prevención & control , COVID-19/inmunología , Embarazo , Vacunación/métodos , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Adulto , Madres , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/análisis , Inmunidad Humoral , Saliva/inmunología , Inmunidad Celular , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina A/análisis , Interferón gamma/metabolismo , Vacunas de ARNm/inmunologíaRESUMEN
There is a growing trend in using saliva for SARS-CoV-2 detection with reasonable accuracy. We have studied the responses of IgA, IgG, and IgM in human saliva by directly comparing disease with control analyzing two-trace two-dimensional correlation spectra (2T2D-COS) employing Fourier transform infrared (FTIR) spectra. It explores the molecular-level variation between control and COVID-19 saliva samples. The advantage of 2T2D spectra is that it helps in discriminating remarkably subtle features between two simple pairs of spectra. It gives spectral information from highly overlapped bands associated with different systems. The clinical findings from 2T2D show the decrease of IgG and IgM salivary antibodies in the 50, 60, 65, and 75-years COVID-19 samples. Among the various COVID-19 populations studied the female 30-years group reveals defense mechanisms exhibited by IgM and IgA. Lipids and fatty acids decrease, resulting in lipid oxidation due to the SARS-CoV-2 in the samples studied. Study shows salivary thiocyanate plays defense against SARS-CoV-2 in the male population in 25 and 35 age groups. The receiver operation characteristics statistical method shows a sensitivity of 98% and a specificity of 94% for the samples studied. The measure of accuracy computed as F score and G score has a high value, supporting our study's validation. Thus, 2T2D-COS analysis can potentially monitor the progression of immunoglobulin's response function to COVID-19 with reasonable accuracy, which could help diagnose clinical trials. KEY MESSAGES: The molecular profile of salivary antibodies is well resolved and identified from 2T2D-COS FTIR spectra. The IgG antibody plays a significant role in the defense mechanism against SARS-CoV-2 in 25-40 years. 2T2D-COS reveals the absence of salivary thiocyanate in the 40-75 years COVID-19 population. The receiver operation characteristic (ROC) analysis validates our study with high sensitivity and specificity.
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COVID-19 , Masculino , Humanos , Femenino , COVID-19/diagnóstico , SARS-CoV-2 , Tiocianatos , Espectroscopía Infrarroja por Transformada de Fourier , Análisis de Fourier , Inmunoglobulina G , Inmunoglobulina M , Inmunidad , Inmunoglobulina ARESUMEN
Introduction: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes. Methods: To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity). Results: According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02). Discussion: Our data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.
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COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , COVID-19/genética , Serina Proteasas , SARS-CoV-2 , Estudios TransversalesRESUMEN
Diabetes is a chronic degenerative disease that carries multiple complications. One of the most important complications is the diabetic cutaneous complications, such as skin lesions, ulcerations, and diabetic foot, which are present in 30%-70% of the patients. Currently, the treatments for wound healing include growth factors and cytokines, skin substitutes, hyperbaric oxygen therapy, and skin grafts. However, these treatments are ineffective due to the complex mechanisms involved in developing unhealed wounds. Considering the aforementioned complications, regenerative medicine has focused on this pathology using stem cells to improve these complications. However, it is essential to mention that there is a poor biomolecular understanding of diabetic skin and the effects of treating it with stem cells. For this reason, herein, we investigated the employment of pluripotent stem cells (PSC) in the wound healing process by carrying out morphometric, histological, and Fourier-transform infrared microspectroscopy (FTIRM) analysis. The morphometric analysis was done through a photographic follow-up, measuring the lesion areas. For the histological analysis, hematoxylin & eosin and picrosirius red stains were used to examine the thickness of the epidermis and the cellularity index in the dermis as well as the content and arrangement of collagen type I and III fibers. Finally, for the FTIRM analysis, skin cryosections were obtained and analyzed by employing a Cassegrain objective of 16× of an FTIR microscope coupled to an FTIR spectrometer. For this purpose, 20 mice were divided into two groups according to the treatment they received: the Isotonic Salt Solution (ISS) group and the PSCs group (n = 10). Both groups were induced to diabetes, and six days after diabetes induction, an excisional lesion was made in the dorsal area. Furthermore, using microscopy and FTIRM analysis, the skin healing process on days 7 and 15 post-skin lesion excision was examined. The results showed that the wound healing process over time, considering the lesion size, was similar in both groups; however, the PSCs group evidenced hair follicles in the wound. Moreover, the histological analysis evidenced that the PSCs group exhibited granulation tissue, new vessels, and better polarity of the keratinocytes. In addition, the amount of collagen increased with a good deposition and orientation, highlighting that type III collagen fibers were more abundant in the PSCs. Finally, the FTIR analysis evidenced that the PSCs group exhibited a faster wound healing process. In conclusion, the wounds treated with PSCs showed a more rapid wound healing process, less inflammatory cellular infiltration, and more ordered structures than the ISS group.
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Outdoor air pollution is responsible for the exacerbation of respiratory diseases in humans. Particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) is one of the main components of outdoor air pollution, and solvent extracted organic matter (SEOM) is adsorbed to the main PM2.5 core. Some of the biological effects of black carbon and polycyclic aromatic hydrocarbons, which are components of PM2.5, are known, but the response of respiratory cell lineages to SEOM exposure has not been described until now. The aim of this study was to obtain SEOM from PM2.5 and analyze the molecular and proteomic effects on human type II pneumocytes. PM2.5 was collected from Mexico City in the wildfire season and the SEOM was characterized to be exposed on human type II pneumocytes. The effects were compared with benzo [a] pyrene (B[a]P) and hydrogen peroxide (H2O2). The results showed that SEOM induced a decrease in surfactant and deregulation in the molecular protein and lipid pattern analyzed by reflection-Fourier transform infrared (ATR-FTIR) spectroscopy on human type II pneumocytes after 24 h. The molecular alterations induced by SEOM were not shared by those induced by B[a]P nor H2O2, which highlights specific SEOM effects. In addition, proteomic patterns by quantitative MS analysis revealed a downregulation of 171 proteins and upregulation of 134 proteins analyzed in the STRING database. The deregulation was associated with positive regulation of apoptotic clearance, removal of superoxide radicals, and positive regulation of heterotypic cell-cell adhesion processes, while ATP metabolism, nucleotide process, and cellular metabolism were also affected. Through this study, we conclude that SEOM extracted from PM2.5 exerts alterations in molecular patterns of protein and lipids, surfactant expression, and deregulation of metabolic pathways of type II pneumocytes after 24 h of exposure in absence of cytotoxicity, which warns about apparent SEOM silent effects.
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Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Células Epiteliales Alveolares/química , Peróxido de Hidrógeno/análisis , Proteómica , Monitoreo del Ambiente/métodos , Contaminación del Aire/análisis , Material Particulado/toxicidad , Material Particulado/análisis , Tensoactivos/análisisRESUMEN
Diabetes is one of the top 5 non-communicable diseases that occur worldwide according to the World Health Organization. Despite not being a fatal disease, a late diagnosis as well as poor control can cause a fatal outcome, because of that, several studies have been carried out with the aim of proposing additional techniques to the gold standard to assist in the diagnosis and control of this disease in a non-invasive way. Considering the above, and in order to provide a solid starting point for future researches, we share a primary research dataset with 1040 saliva samples obtained by Fourier Transform Infrared Spectroscopy considering the Attenuated Total Reflectance method. Database include: gender, age, individuals (patients) with/without diabetes, the glucose value, and the result to the A1C test for the diabetic population. We believe that sharing dataset as is could increase experimentation, research, and analysis of spectra through different strategies broaden its range of applicability by chemists, doctors, physicists, computer scientists, among others, to identify the effects that the virus causes in the body and to propose possible clinical treatments as well as to develop devices that allow us to assist in the characterization of possible carriers.
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Titanium dioxide food grade (E171) is one of the most used food additives containing nanoparticles. Recently, the European Food Safety Authority indicated that E171 could no longer be considered safe as a food additive due to the possibility of it being genotoxic and there is evidence that E171 administration exacerbates colon tumor formation in murine models. However, less is known about the effects of E171 accumulation once the exposure stopped, then we hypothesized that toxic effects could be detected even after E171 removal. Therefore, we investigated the effects of E171 exposure after being removed from colon cell cultures. Human colon cancer cell line (HCT116) was exposed to 0, 1, 10 and 50 µg/cm2 of E171. Our results showed that in the absence of cytotoxicity, E171 was accumulated in the cells after 24 of exposure, increasing granularity and reactive oxygen species, inducing alterations in the molecular pattern of nucleic acids and lipids, and causing nuclei enlargement, DNA damage and tubulin depolymerization. After the removal of E171, colon cells were cultured for 48 h more hours to analyze the ability to restore the previously detected alterations. As we hypothesized, the removal of E171 was unable to revert the alterations found after 24 h of exposure in colon cells. In conclusion, exposure to E171 causes alterations that cannot be reverted after 48 h if E171 is removed from colon cells.
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Nanopartículas , Titanio , Animales , Colon , Aditivos Alimentarios/toxicidad , Humanos , Ratones , Nanopartículas/toxicidad , Titanio/toxicidadRESUMEN
The World Health Organization has declared that diabetes is one of the four leading causes of death attributable to non-communicable diseases. Currently, many devices allow monitoring blood glucose levels for diabetes control based mainly on blood tests. In this paper, we propose a novel methodology based on the analysis of the Fourier Transform Infrared (FTIR) spectra of saliva using machine learning techniques to characterize controlled and uncontrolled diabetic patients, clustering patients in groups of a low, medium, and high glucose levels, and finally performing the point estimation of a glucose value. After analyzing the obtained results with Support Vector Machines (SVM), Artificial Neural Networks (ANN), and Linear Regression (LR), we found that using ANN, it is possible to carry out the characterizations mentioned above efficiently since it allowed us to identify correctly the 540 spectra that make up our database studying the region 4000-2000 cm-1.
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Diabetes Mellitus Tipo 2 , Saliva , Diabetes Mellitus Tipo 2/diagnóstico , Análisis de Fourier , Humanos , Aprendizaje Automático , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
The coronavirus disease 2019 (COVID-19) is the latest biological hazard for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though numerous diagnostic tests for SARS-CoV-2 have been proposed, new diagnosis strategies are being developed, looking for less expensive methods to be used as screening. This study aimed to establish salivary vibrational modes analyzed by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy to detect COVID-19 biological fingerprints that allow the discrimination between COVID-19 and healthy patients. Clinical dates, laboratories, and saliva samples of COVID-19 patients (N = 255) and healthy persons (N = 1209) were obtained and analyzed through ATR-FTIR spectroscopy. Then, a multivariate linear regression model (MLRM) was developed. The COVID-19 patients showed low SaO2, cough, dyspnea, headache, and fever principally. C-reactive protein, lactate dehydrogenase, fibrinogen, D-dimer, and ferritin were the most important altered laboratory blood tests, which were increased. In addition, changes in amide I and immunoglobulin regions were evidenced in the FTIR spectra analysis, and the MLRM showed clear discrimination between both groups. Specific salivary vibrational modes employing ATR-FTIR spectroscopy were established; moreover, the COVID-19 biological fingerprint in saliva was characterized, allowing the COVID-19 detection using an MLRM, which could be helpful for the development of new diagnostic devices.
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Prueba de COVID-19/métodos , COVID-19/diagnóstico , Saliva/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Adulto , Anciano , Femenino , Humanos , Inmunoglobulinas/análisis , Masculino , Persona de Mediana Edad , Oxígeno/análisis , SARS-CoV-2/aislamiento & purificaciónRESUMEN
BACKGROUND: Inhaled nanoparticles (NPs) challenges mobile and immobile barriers in the respiratory tract, which can be represented by type II pneumocytes (immobile) and monocytes (mobile) but what is more important for biological effects, the cell linage, or the type of nanoparticle? Here, we addressed these questions and we demonstrated that the type of NPs exerts a higher influence on biological effects, but cell linages also respond differently against similar type of NPs. DESIGN: Type II pneumocytes and monocytes were exposed to tin dioxide (SnO2) NPs and titanium dioxide (TiO2) NPs (1, 10 and 50 µg/cm2) for 24 h and cell viability, ultrastructure, cell granularity, molecular spectra of lipids, proteins and nucleic acids and cytoskeleton architecture were evaluated. RESULTS: SnO2 NPs and TiO2 NPs are metal oxides with similar physicochemical properties. However, in the absence of cytotoxicity, SnO2 NPs uptake was low in monocytes and higher in type II pneumocytes, while TiO2 NPs were highly internalized by both types of cells. Monocytes exposed to both types of NPs displayed higher number of alterations in the molecular patterns of proteins and nuclei acids analyzed by Fourier-transform infrared spectroscopy (FTIR) than type II pneumocytes. In addition, cells exposed to TiO2 NPs showed more displacements in FTIR spectra of biomolecules than cells exposed to SnO2 NPs. Regarding cell architecture, microtubules were stable in type II pneumocytes exposed to both types of NPs but actin filaments displayed a higher number of alterations in type II pneumocytes and monocytes exposed to SnO2 NPs and TiO2 NPs. NPs exposure induced the formation of large vacuoles only in monocytes, which were not seen in type II pneumocytes. CONCLUSIONS: Most of the cellular effects are influenced by the NPs exposure rather than by the cell type. However, mobile, and immobile barriers in the respiratory tract displayed differential response against SnO2 NPs and TiO2 NPs in absence of cytotoxicity, in which monocytes were more susceptible than type II pneumocytes to NPs exposure.
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Células Epiteliales Alveolares/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Monocitos/efectos de los fármacos , Citoesqueleto de Actina/metabolismo , Células Epiteliales Alveolares/química , Células Epiteliales Alveolares/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Nanopartículas del Metal/química , Monocitos/química , Monocitos/metabolismo , Espectroscopía Infrarroja por Transformada de Fourier , Compuestos de Estaño/química , Compuestos de Estaño/farmacología , Compuestos de Estaño/toxicidad , Titanio/química , Titanio/farmacología , Titanio/toxicidad , Vacuolas/metabolismoRESUMEN
The Organisation for Economic Co-operation and Development has listed thirteen engineered nanomaterials (ENM) in order to investigate their toxicity on human health. Silicon dioxide (SiO2) and titanium dioxide (TiO2) are included on that list and we added indium tin oxide (ITO) nanoparticles (NPs) to our study, which is not listed on OECD suggested ENM to be investigated, however ITO NPs has a high potential of industrial production. We evaluate the physicochemical properties of SiO2 NPs (10-20 nm), TiO2 nanofibers (NFs; 3 µm length) and ITO NPs (<50 nm) and the impact of protein-corona formation on cell internalization. Then, we evaluated the toxicity of uncoated ENM on human lung epithelial cells exposed to 10 and 50 µg/cm2 for 24 h. TiO2 NFs showed the highest capability to adsorb proteins onto the particle surface followed by SiO2 NPs and ITO NPs after acellular incubation with fetal bovine serum. The protein adsorption had no impact on Alizarin Red S conjugation, intrinsic properties for reactive oxygen (ROS) formation or cell uptake for all types of ENM. Moreover, TiO2 NFs induced highest cell alterations in human lung epithelial cells exposed to 10 and 50 µg/cm2 while ITO NPs induced moderated cytotoxicity and SiO2 NPs caused even lower cytotoxicity under the same conditions. DNA, proteins and lipids were mainly affected by TiO2 NFs followed by SiO2 NPs with toxic effects in protein and lipids while limited variations were detected after exposure to ITO NPs on spectra analyzed by Fourier Transform Infrared Spectroscopy.
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Nanoestructuras/química , Nanoestructuras/toxicidad , Corona de Proteínas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Células A549 , Tamaño de la Célula , Gránulos Citoplasmáticos/metabolismo , Gránulos Citoplasmáticos/ultraestructura , Células Epiteliales/metabolismo , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Mucosa Respiratoria/citología , Mucosa Respiratoria/metabolismo , Dióxido de Silicio/química , Dióxido de Silicio/metabolismo , Dióxido de Silicio/toxicidad , Propiedades de Superficie , Titanio/química , Titanio/metabolismo , Titanio/toxicidad , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Una célula madre (CM) es capaz de dividirse indefinidamente y diferenciarse en distintos tipos de células especializadas, no sólo morfológicamente sino también de forma funcional. A finales del siglo XX los histoembriólogos Boveri y Haeckel acuñaron el término de células madre (CM). Atendiendo a su origen, las CM se clasifican en embrionarias y adultas, en tanto que de acuerdo a su potencial y capacidad de diferenciación se clasifican en: totipotenciales, pluripotenciales, multipotenciales y unipotenciales. Dentro de las características principales de las CM se encuentran a) autorrenovación, debida a la actividad de la telomerasa; b) potencialidad, que es la capacidad de diferenciarse en otro tipo celular; c) baja inmunogenicidad, debido a una baja expresión del complejo principal de histocompatibilidad I (MHC I) y carencia de la expresión de MHC II. Las principales investigaciones que se han desarrollado con CM han sido con la finalidad de diferenciarlas in vitro hacia otros tejidos como: páncreas, condrocitos y cardiomiocitos, entre otros, con el objetivo de llegar a ser una fuente de reemplazo celular. Sin embargo, tienen otras aplicaciones, como el vehículo terapéutico de genes para enfermedades monogénicas o como vehículo de terapias antitumorales, además de la tecnología de CM pluripotentes inducidas (iPSC) que ha permitido evaluar la toxicidad en diversos fármacos.
A stem cell (SC) is capable to divide indefinitely and differentiate into several specialized cell types, not only morphologically but also functionally. The term of SC emerged at the late twentieth century, by histologists and embryologist Boveri and Haecker. According to their origin the SC are classified in embryonic and adult, while according to their potential and differentiation capacity, they are classified in: totipotential, pluripotential, multipotential and unipotential. The main SC features are: a) self-renewal, which is due to the telomerase activity; b) pluripotentiallity, which is their ability to differentiate into other cell types; c) low immunogenicity, due to the low expression of the major histocompatibility complex I (MHC I) and lack expression of MHCII. The major SC works have been developed with aimed to differentiate the SC in vitro to other tissues such as pancreas, chondrocytes and cardiomyocytes among others, in other to become a cell replacement source; however, there are other applications such as gene therapy vehicle for monogenic diseases, or as a vehicle for antitumor therapies. In additions, the induced pluripotent stem cells (iPSC) technology has allowed human toxicity evaluation of various drugs.