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Objective: To introduce MexOMICS, a Mexican Consortium focused on establishing electronic databases to collect, cross-reference, and share health-related and omics data on the Mexican population. Methods: Since 2019, the MexOMICS Consortium has established three electronic-based registries: the Mexican Twin Registry (TwinsMX), Mexican Lupus Registry (LupusRGMX), and the Mexican Parkinson's Research Network (MEX-PD), designed and implemented using the Research Electronic Data Capture web-based application. Participants were enrolled through voluntary participation and on-site engagement with medical specialists. We also acquired DNA samples and Magnetic Resonance Imaging scans in subsets of participants. Results: The registries have successfully enrolled a large number of participants from a variety of regions within Mexico: TwinsMX (n = 2,915), LupusRGMX (n = 1,761) and MEX-PD (n = 750). In addition to sociodemographic, psychosocial, and clinical data, MexOMICS has collected DNA samples to study the genetic biomarkers across the three registries. Cognitive function has been assessed with the Montreal Cognitive Assessment in a subset of 376 MEX-PD participants. Furthermore, a subset of 267 twins have participated in cognitive evaluations with the Creyos platform and in MRI sessions acquiring structural, functional, and spectroscopy brain imaging; comparable evaluations are planned for LupusRGMX and MEX-PD. Conclusions: The MexOMICS registries offer a valuable repository of information concerning the potential interplay of genetic and environmental factors in health conditions among the Mexican population.

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Microorganism lipid droplet small regulator (MLDSR) is a transcriptional regulator of the major lipid droplet (LD)-associated protein MLDS in Rhodococcus jostii RHA1 and Rhodococcus opacus PD630. In this study, we investigated the role of MLDSR on lipid metabolism and triacylglycerol (TAG) accumulation in R. jostii RHA1 at physiological and molecular levels. MLDSR gene deletion promoted a significant decrease of TAG accumulation, whereas inhibition of de novo fatty acid biosynthesis by the addition of cerulenin significantly repressed the expression of the mldsr-mlds cluster under nitrogen-limiting conditions. In vitro and in vivo approaches revealed that MLDSR-DNA binding is inhibited by fatty acids and acyl-CoA residues through changes in the oligomeric or conformational state of the protein. RNAseq analysis indicated that MLDSR not only controls the expression of its own gene cluster but also of several genes involved in central, lipid, and redox metabolism, among others. We also identified putative MLDSR-binding sites on the upstream regions of genes coding for lipid catabolic enzymes and validated them by EMSA assays. Overexpression of mldsr gene under nitrogen-rich conditions promoted an increase of TAG accumulation, and further cell lysis with TAG release to the culture medium. Our results suggested that MLDSR is a fatty acid-responsive regulator that plays a dual role in cells by repression or activation of several metabolic genes in R. jostii RHA1. MLDSR seems to play an important role in the fine-tuning regulation of TAG accumulation, LD formation, and cellular lipid homeostasis, contributing to the oleaginous phenotype of R. jostii RHA1 and R. opacus PD630.

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The current study provides a comprehensive look of the adsorption process of Candida rugosa lipase (CRL) on Ca2Fe2O5 iron oxide nanoparticles (NPs). Protein-support interactions were identified across a broad range of pH and ionic strengths (mM) through a response surface methodology, surface charge determination, and spectroscopic and in silico analyses. The maximum quantity of immobilized protein was achieved at an ionic strength of 50 mM and pH 4. However, this condition did not allow for the greatest hydrolytic activity to be obtained. Indeed, it was recorded at acidic pH, but at 150 mM, where evaluation of the recovered activity revealed hyperactivation of the enzyme. These findings were supported by adsorption isotherms performed under different conditions. Based on zeta potential measurements, electrostatic interactions contributed differently to protein-support binding under the conditions tested, showing a strong correlation with experimentally determined immobilization parameters. Raman spectra revealed an increase in hydrophobicity around tryptophan residues, whereas the enzyme immobilization significantly reduced the phenylalanine signal in CRL. This suggests that this residue was involved in the interaction with Ca2Fe2O2 and molecular docking analysis confirmed these findings. Fluorescence spectroscopy showed distinct behaviors in the CRL emission patterns with the addition of Ca2Fe2O5 at pH 4 and 7. The calculated thermodynamic parameters indicated that the contact would be mediated by hydrophobic interactions at both pHs, as well as by ionic ones at pH 4. In this approach, this work adds to our understanding of the design of biocatalysts immobilized in iron oxide NPs.

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Introducción: el lupus eritematoso sistémico (LES) es una enfermedad sistémica que se ha asociado a mayor severidad con la infección por SARS-CoV-2. Particularmente la alta actividad de la enfermedad y algunos inmunosupresores se han vinculado a peores desenlaces. Objetivos: describir las características por SARS-CoV-2 en pacientes con LES en Argentina del registro SAR-COVID y establecer los factores asociados a peor desenlace de la misma. Materiales y métodos: estudio observacional. Se incluyeron pacientes con diagnóstico de LES con infección confirmada por SARS-CoV-2 (RT-PCR y/o serología positiva) del registro SAR-COVID. Los datos se recolectaron desde agosto de 2020 hasta marzo de 2022. El desenlace de la infección se midió mediante la escala ordinal de la Organización Mundial de la Salud (EO-OMS). Se definió COVID-19 severo con un valor EO-OMS ≥5. Análisis descriptivo, test T de Student, test de Mann Whitney U, ANOVA, chi2 y Fisher. Regresión logística múltiple. Resultados: se incluyeron 399 pacientes, el 93% de sexo femenino, con una edad media de 40,9 años (DE 12,2). El 39,6% tenía al menos una comorbilidad. Al momento de la infección, el 54,9% recibía glucocorticoides, el 30,8% inmunosupresores y el 3,3% agentes biológicos. La infección por SARS-CoV-2 fue leve en la mayoría de los casos, mientras que un 4,6% tuvo curso severo y/o falleció. Estos últimos presentaban comorbilidades, usaban glucocorticoides y tenían síndrome antifosfolipídico (SAF) con mayor frecuencia y mayor actividad de la enfermedad al momento de la infección. En el análisis multivariado, la hipertensión arterial, el diagnóstico de SAF y el uso de glucocorticoides se asociaron a hospitalización severa y/o muerte por COVID-19 (EO-OMS ≥5). Conclusiones: en esta cohorte de pacientes con LES con infección por SARS-CoV-2 confirmada, la mayoría cursó de manera sintomática, un 22,1% fue hospitalizado y un 5% requirió ventilación mecánica. La mortalidad fue cercana al 3%. El diagnóstico de SAF, tener hipertensión arterial y el uso de glucocorticoides se asociaron significativamente con COVID-19 severo.

Introduction: systemic lupus erythematosus (SLE) is a systemic disease that has been associated with greater severity with SARS-CoV-2 infection. Particularly high disease activity and some immunosuppressants have been linked to worse outcomes. Objectives: to describe the characteristics due to SARS-CoV-2 in patients with SLE in Argentina from the SAR-COVID registry and to establish the factors associated with a worse outcome of the same. Materials and methods: observational study. Patients diagnosed with SLE with confirmed SARS-CoV-2 infection (RT-PCR and/or positive serology) from the SAR-COVID registry were included. Data was collected from August 2020 to March 2022. The outcome of the infection was measured using the World Health Organization - ordinal scale (WHO-OS). Severe COVID-19 was defined as an WHO-OS value ≥5. Descriptive analysis, Student's T test, Mann Whitney U, ANOVA, chi2 and Fisher. Multiple logistic regression. Results: a total of 399 patients were included, 93% female, with a mean age of 40.9 years (SD 12.2), 39.6% had at least one comorbidity. At the time of infection, 54.9% were receiving glucocorticoids, 30.8% immunosuppressants, and 3.3% biological agents. SARS-CoV-2 infection was mild in most cases, while 4.6% had a severe course and/or died. The latter had comorbidities, used glucocorticoids and had antiphospholipid syndrome (APS) more frequently and higher disease activity at the time of infection. In the multivariate analysis, high blood pressure, the diagnosis of APS, and the use of glucocorticoids were associated with severe hospitalization and/or death from COVID-19 (WHO-EO ≥5). Conclusions: in this cohort of SLE patients with confirmed SARS-CoV-2 infection, most had a symptomatic course, 22.1% were hospitalized, and 5% required mechanical ventilation. Mortality was close to 3%. The diagnosis of APS, having high blood pressure, and the use of glucocorticoids were significantly associated with severe COVID-19.

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The production of bioethanol and sugar from sugarcane is an important economic activity in several countries. Sugarcane is susceptible to different phytopathogens. Over the last years, the red stripe disease caused by the bacterium Acidovorax avenae subsp. avenae produced significant losses in sugarcane crops. Bio-nanotechnology emerged as an eco-friendly alternative to the biosynthesis of antimicrobial molecules. The aims of this study were to (a) produce extracellular silver nanoparticles using the heavy metal resistant strain Amycolatopsis tucumanensis, (b) evaluate their antibacterial in vitro effect and (c) determine the potential of silver nanoparticles to protect sugarcane against red stripe disease. Amycolatopsis tucumanensis synthesized spherical silver nanoparticles with an average size of 35 nm. Nanoparticles were able to control the growth of A. avenae subsp. avenae in in vitro assays. In addition, in vivo assays in sugarcane showed a control upon the red stripe disease when silver nanoparticles were applied as preventive treatment. The Disease Severity Index was 28.94% when silver nanoparticles were applied 3 days before inoculation with A. avenae subsp. a venae. To our knowledge, this is the first report of silver nanoparticles extracellularly synthesized by an Amycolatopsis strain that were able to inhibited the growth of A. avenae subsp. avenae and control the red stripe disease in sugarcane.

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BACKGROUND: Vitamin D (VD) has been classically associated with calcium homeostasis and bone mineral density since it has a key role on mineralization and resorption. Immunomodulatory effects have been attributable to VD; low concentrations of VD have been associated with elevation of inflammatory markers. Inflammatory autoimmune diseases, such as multiple sclerosis (MS), a chronic neurodegenerative suffering, whose etiology is still unknown, is directly related to an increase in pro-inflammatory cytokines such as interleukin 17 and interleukin 1ß who play an important role in this physiopathology. Nowadays, even though additional studies have linked MS's clinical signs with low VD concentration, there is scarce information of this association in people from regions with sufficient sun exposure. The aim of this study was to evaluate serum VD and cytokine concentrations, and bone density, in Mexican people with MS. METHODS: Vitamin D (25OHD), interleukin 1ß, interleukin 6 and interleukin 17 concentrations of twenty-five volunteers with MS were determined by enzyme-linked immunosorbent assay. Bone mineral density and body composition assessment was performed by dual energy X-Ray absorptiometry. RESULTS: A mean concentration of 17.3 ± 4.6 ng/ml of 25OHD was obtained, in a range of 5.15 to 25.71 ng/ml; when international advisory bodies thresholds were applied 76% of the participants exhibited some degree of VD inadequacy. Pro-inflammatory markers were detectable among the participants: interleukin 1ß in 100%, interleukin 6 in 64%, whereas interleukin 17 was found in 24% of the volunteers. Bone mineral density below the expected for the age was found in 8% of the participants, with lumbar spine as the most affected anatomic region. Non-significant correlations were found between VD and bone mineral density (Z-score) or pro-inflammatory markers. CONCLUSION: Although non-significant correlations were found between VD and bone mineral density or cytokines, it is important to highlight that an important percentage of our participants exhibited some degree of VD inadequacy, an unknown fact for them, since these are not included in routine clinical evaluations. The low concentrations of VD among this sample regardless of annual UVB sun exposure may suggest the involvement of endogenous and not environmental factors. Further works are needed in order to deepen the physiological causes and effects of VD deficiency in people with MS.

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OBJECTIVES: To elucidate the molecular mechanisms involved in the substrate interaction of the bile salt hydrolase of Lactobacillus reuteri CRL 1098 (LrBSH) with bile acids (BAs) and to evaluate potential enzyme inhibitors based on computer and in vitro modeling assays. RESULTS: Asp19, Asn79, and Asn171 participated in the LrBSH interaction with all BAs tested while Leu56 and Glu 222 played an important role in the interaction with glyco- and tauro-conjugated BAs, respectively. A great percentage of hydrophobic and polar interactions were responsible for the binding of LrBSH with glyco- and tauro-conjugated BAs, respectively. Remarkably, the four binding pocket loops participated in the substrate binding site of LrBSH unlike most of the reported BSHs. Inhibition assays showed that ascorbic acid, citric acid, penicillin G, and ciprofloxacin decreased LrBSH activity by 47.1%, 40.14%, 28.8%, and 9%, respectively. Docking analysis revealed that tetracycline and caffeic acid phenethyl ester had the low binding energy (-7.32 and -7.19 kcal/mol, respectively) and resembled the interaction pattern of GDCA (-6.88 kcal/mol) while penicillin (-6.25 kcal/mol) and ascorbic acid (-5.98 kcal/mol) interacted at a longer distance. CONCLUSION: This study helps to delve into the molecular mechanisms involved in the recognition of substrates and potential inhibitors of LrBSH.

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3,4,3',4'-tetrachloroazobenzene known as TCAB is an unwanted product derivate from the degradation of propanil herbicide. In this work UV-visible and infrared spectroscopies were used to experimentally explore the impact of pH and temperature changes of TCAB in aqueous and ethanol solutions. Two isomeric forms, cis and trans, are present in solution. The density functional theory (DFT) with PCM methodology was used to analyze the stability of each isomer in solution phase by the evaluation of solvation energy and frontier orbital energies of TCBA at 25 and 40 °C. This compound has been studied from room temperature to 50 °C, revealing the weakening of trans form with an increment of cis form in ethanol and high temperature. Interestingly, under acid conditions the protonated azo compound was evidenced in solution. We found that the cis form is predominant in aqueous solution at 40 °C and 30 min. Finally, FTIR studies show that the increasing of the temperature promote irreversible structural changes via a trans to cis interconversion process. The derivative results from this study may contributed to understanding of transformation of TCAB in aqueous solution by pH and temperature changes.

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BACKGROUND: Multiple sclerosis (MS) is one of the principal causes of non-traumatic neurological disability among young adults. The unpredictable and progressive evolution of multiple sclerosis is associated with a decline in physical and psychological health, affecting quality of life, which may be influenced by additional physical and psycho-social factors. OBJECTIVE: The present investigation aims to evaluate the quality of life (QoL), use of coping strategies and their relationship with other physical and psycho-social factors among 26 Mexican persons with MS. METHODS: Eight questionnaires were administrated for evaluation of the additional psycho-social and physical factors, including quality of life, coping strategies, social support system, family functionality, depression and anxiety prevalence. RESULTS: Results showed that the use of positive coping strategies (84.6% of our population) improve QoL perception (r = 0.396, p = 0.045) and the following domains: physical health (r = 0.514, p = 0.009), psychological health (r = 0.516, p = 0.008), social relationships (r = 0.654, p = 0.000) and environment (r = 0.600, p = 0.002). Negative correlations were observed between QoL and the presence of symptoms of both depression (r = -0.557, p = 0.003) and anxiety (r = -0.517, p = 0.007). A multiple linear regression model showed that QoL can be explained by physical and psycho-social factor in 54.6% of the cases that were evaluated. CONCLUSION: The use of positive coping strategies in conjunction with a suitable psycho-social environment and good physical health result in a better perception of QoL in Mexican patients living with MS. Still, the negative factors are ineffectively diagnosed and hence generally under treated in medical MS monitoring. An interdisciplinary evaluation will provide the adequate tools to confront the diagnosis and the uncertainty of multiple sclerosis evolution, benefiting the QoL of Mexican patients with MS.

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Fluoroquinolones (FQs) constitute an important class of biologically active broad-spectrum antibacterial drugs that are which are in contact with many biological fluids under different acidity conditions. We studied the reactivity of ciprofloxacin (Cpx) and levofloxacin (Lev) and their interaction with lysozyme (Lyz) at different pH values, using UV-visible absorption, fluorescence, infrared spectroscopies supported by DFT calculation and docking. In addition, by antimicrobial assays, the biological consequences of the interaction were evaluated. DFT calculation predicted that the FQ cationic species present at acid pH have lower stabilization energies, with an electric charge rearrangement because of their interactions with solvent molecules. NBO and frontier orbital calculations evidenced the role of two charged centers, NH2⁺ and COO-, for interactions by electronic delocalization effects. Both FQs bind to Lyz via a static quenching with a higher interaction in neutral medium. The interaction induces a structural rearrangement in ß-sheet content while in basic pH a protective effect against the denaturation of Lyz was inferred. The analysis of thermodynamic parameters and docking showed that hydrophobic, electrostatic forces and hydrogen bond are the responsible of Cpx-Lyz and Lev-Lyz associations. Antimicrobial assays evidenced an antagonist effect of Lyz in acid medium while in neutral medium the FQs' activities were not modified by Lyz.

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