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Background/Objectives: Coronavirus Disease 2019 (COVID-19) can cause liver injury and a deterioration of hepatic function. The Model for End-Stage Liver Disease (MELD) score is a good predictor for poor prognosis of hospitalized COVID-19 patients in the United States, Egypt and Turkey. Nevertheless, the best cut-off value for the MELD score to predict mortality in the Mexican population has yet to be established. Methods: A total of 234 patients with COVID-19 were studied in a tertiary-level hospital. Patients were stratified into survivors (n = 139) and non-survivors (n = 95). Receiver operating characteristic curves, Cox proportional hazard models, Kaplan-Meier method, and Bonferroni corrections were performed to identify the predictors of COVID-19 mortality. Results: MELD score had an area under the curve of 0.62 (95% CI: 0.56-0.68; p = 0.0009), sensitivity = 53.68%, and specificity = 73.38%. Univariate Cox proportional hazard regression analysis suggested that the leukocytes > 10.6, neutrophils > 8.42, neutrophil-to-lymphocyte ratio (NLR) > 8.69, systemic immune-inflammation index (SII) > 1809.21, MELD score > 9, and leukocyte glucose index (LGI) > 2.41 were predictors for mortality. However, the multivariate Cox proportional hazard model revealed that only the MELD score >9 (Hazard Ratio [HR] = 1.83; 95% confidence interval [CI]: 1.2-2.8; Pcorrected = 0.03) was an independent predictor for mortality of COVID-19. Conclusions: Although the MELD score is used for liver transplantation, we suggest that a MELD score >9 could be an accurate predictor for COVID-19 mortality at admission to ICU requiring mechanical ventilation.
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OBJECTIVES: To identify the predictive factors of first hospitalization and associated variables to the main causes of hospitalizations in lupus patients from a Latin American cohort. METHODS: The first hospitalization after entry into the cohort during these patients' follow-up due to either lupus disease activity and/or infection was examined. Clinical and therapeutic variables were those occurring prior to the first hospitalization. Descriptive statistical tests, multivariable logistic, and Cox regression models were performed. RESULTS: 1341 individuals were included in this analysis; 1200 (89.5%) were women. Their median and interquartile range (IQR) age at diagnosis were 27 (20-37) years and their median and IQR follow up time were 27.5 (4.7-62.2) months. A total of 456 (34.0%) patients were hospitalized; 344 (75.4%), 85 (18.6%) and 27 (5.9%) for disease activity, infections, or both, respectively. The predictors of the first hospitalization regardless of its cause were: medium (HR 2.03(1.27-3.24); p = 0.0028) and low (HR 2.42(1.55-3.79); p < 0.0001) socioeconomic status, serosal (HR 1.32(1.07-1.62); p = 0.0074) and renal (HR 1.50(1.23-1.82); p < 0.0001) involvement. Antimalarial (AM) use (HR 0.61(0.50-0.74); p < 0.0001) and achieving remission (HR 0.80(0.65-0.97); p = 0.0300) were negative predictors. CONCLUSIONS: The first hospitalization was associated with worse socioeconomic status and serosal and renal involvement. Conversely, AM use and achieving remission were associated with a lower risk of hospitalizations.
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Nuclear bodies are structures in eukaryotic cells that lack a plasma membrane and are considered protein condensates, DNA, or RNA molecules. Known nuclear bodies include the nucleolus, Cajal bodies, and promyelocytic leukemia nuclear bodies. These bodies are involved in the concentration, exclusion, sequestration, assembly, modification, and recycling of specific components involved in the regulation of ribosome biogenesis, RNA transcription, and RNA processing. Additionally, nuclear bodies have been shown to participate in cellular processes such as the regulation of transcription of the cell cycle, mitosis, apoptosis, and the cellular stress response. The dynamics and functions of these bodies depend on the state of the cell. It is now known that both DNA and RNA viruses can direct their proteins to nuclear bodies, causing alterations in their composition, dynamics, and functions. Although many of these mechanisms are still under investigation, it is well known that the interaction between viral and nuclear body proteins is necessary for the success of the viral infection cycle. In this review, we concisely describe the interaction between viral and nuclear body proteins. Furthermore, we focus on the role of the nucleolus in RNA virus infections. Finally, we discuss the possible implications of the interaction of viral proteins on cellular transcription and the formation/degradation of non-coding RNAs.
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Nucléolo Celular , Proteínas Virales , Nucléolo Celular/metabolismo , Nucléolo Celular/virología , Humanos , Proteínas Virales/metabolismo , AnimalesRESUMEN
The New World screwworm, Cochliomyia hominivorax Coquerel (Diptera: Calliphoridae), was officially eliminated from Costa Rica in 2000, but it was reintroduced in 2023. A myiasis by C. hominivorax in a 71-year-old man with a 4-month history of foot hyperkeratosis and interdigital ulcers is reported. The myiasis was detected before sampling for bacterial culture. Approximately 160 first- and second-instar larvae were recovered and identified as C. hominivorax. Morphological identification was based mainly on characteristics of the cephalopharyngeal skeleton, spiracles, and pigmented dorsal tracheal trunks. Sequencing of a cytochrome c oxidase subunit I gene fragment confirmed the identity. The ulcers healed after extraction of the larvae and ciprofloxacin treatment of a concurrent Staphylococcus aureus and Pseudomonas aeruginosa infection. Given the reintroduction of C. hominivorax in Costa Rica and the risk of northward expansion, this report highlights its impact on public health and calls for awareness among clinicians and healthcare practitioners.
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Viral RNA and miRNAs released by immune cells contribute to inflammation in COVID-19 patients. Here, we investigated the role of SARS-CoV2 RNA and host miRNAs carried within extracellular vesicles (EVs) in modulating inflammation. EVs were classified as positive or negative depending on their viral RNA cargo. To assess the function of viral RNA, EVs, and LPS were used to stimulate whole blood samples from healthy subjects, and the secretion of 27 serum analytes was measured. EVs alone did not induce cytokines, chemokines, or growth factors. However, under LPS stimulation, (SARS-CoV2+) EVs increased IL-12 and decreased IL-13 secretion, while (SARS-CoV2-) EVs increased MIP-1α and IL-1ß secretion. Host miR-19a-3p, -192-5p, -let-7c-5p, and -92b-3a were differentially expressed in association with viral RNA. EVs from COVID-19 patients exhibited differences in viral RNA and miRNA expression profiles that modulate LPS responses. This knowledge sheds light on the immunopathology of COVID-19.
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Dengue, caused by the dengue virus (DENV), is a global health threat transmitted by Aedes mosquitoes, resulting in 400 million cases annually. The disease ranges from mild to severe, with potential progression to hemorrhagic dengue. Current research is focused on natural antivirals due to challenges in vector control. This study evaluates the antiviral potential of peptides derived from the microalgae Phaeodactylum tricornutum, known for its bioactive compounds. Microalgae were cultivated under controlled conditions, followed by protein extraction and hydrolysis to produce four peptide fractions. These fractions were assessed for cytotoxicity via the MTT assay and antiviral activity against DENV serotype 2 using flow cytometry and plaque formation assays. The 10-30 kDa peptide fraction, at 150 and 300 µg/mL concentrations, demonstrated no cytotoxicity and significantly reduced the percentage of infected cells and viral titers. These findings suggest that peptides derived from Phaeodactylum tricornutum exhibit promising antiviral activity against dengue virus serotype 2, potentially contributing to developing new therapeutic approaches for dengue.
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Antivirales , Virus del Dengue , Microalgas , Virus del Dengue/efectos de los fármacos , Antivirales/farmacología , Antivirales/química , Animales , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/química , Dengue/tratamiento farmacológico , Dengue/virología , Péptidos/farmacología , Péptidos/química , Serogrupo , Chlorocebus aethiops , Humanos , Aedes/efectos de los fármacos , Células VeroRESUMEN
Electrophoretic deposition is a straightforward method for synthesizing high-quality photoanodes. We present a protocol for synthesizing a TiO2-modified boron-doped diamond photoanode (BDD/TiO2) via electrophoretic deposition, detailing the chemical and electrochemical treatments applied to the bare BDD electrode prior to use. We provide a step-by-step guide for performing photoelectrochemical characterization under both dark and light conditions and describe an optical technique for investigating band-gap energy. For complete details on the use and execution of this protocol, please refer to Quilumbaquin et al.1.
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Boro , Diamante , Técnicas Electroquímicas , Electrodos , Titanio , Titanio/química , Boro/química , Diamante/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Procesos Fotoquímicos , Electroforesis/métodosRESUMEN
Pseudomonas aeruginosa is an opportunistic pathogen in HAIs with two facets: the most studied is the high rate of antimicrobial resistance, and the less explored is the long list of virulence factors it possesses. This study aimed to characterize the virulence genes carried by strains as well as the profile of cytokines related to inflammation, according to the resistance profile presented. This study aims to identify the virulence factors associated with MDR strains, particularly those resistant to carbapenems, and assess whether there is a cytokine profile that correlates with these characteristics. As methodology species were identified by classical microbiological techniques and confirmed by molecular biology, resistance levels were determined by the minimum inhibitory concentration and identification of MDR strains. Virulence factor genotyping was performed using PCR. In addition, biofilm production was assessed using crystal violet staining. Finally, the strains were cocultured with PBMC, and cell survival and the cytokines IL-1ß, IL-6, IL-10, IL-8, and TNF-α were quantified using flow cytometry. Bacteremia and nosocomial pneumonia in adults are the most frequent types of infection. In the toxigenic aspect, genes corresponding to the type III secretion system were present in at least 50% of cases. In addition, PBMC exposed to strains of four different categories according to their resistance and toxicity showed a differential pattern of cytokine expression, a decrease in IL-10, IL-6, and IL-8, and an over-secretion of IL-1b. In conclusion, the virulence genes showed a differentiated appearance for the two most aggressive exotoxins of T3SS (exoU and exoS) in multidrug-resistant strains. Moreover, the cytokine profile displays a low expression of cytokines with anti-inflammatory and proinflammatory effects in strains carrying the exoU gene.
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Several risk factors were associated with mortality in patients with coronavirus disease 2019 (COVID-19) infection in intensive care units (ICU). We assessed the effect of risk factors related to the characteristics and clinical history of the population, laboratory test results, drug management, and type of ventilation on the probability of survival/discharge from the ICU. A retrospective cohort multicentric study of adults with COVID-19 admitted to the ICU between March 2020 and December 2021. Data were collected from 6 hospitals in 5 cities in Ecuador. The primary outcome was ICU survival/discharge. Survival analysis was conducted using semi-parametric Cox proportional hazards models. Of those admitted to the ICU with COVID-19, (nâ =â 991), mean age was 56.76â ±â 13.14, and 65.9% were male. Regarding the primary outcome, 51.1% (nâ =â 506) died and 48.9% (nâ =â 485) survived. Of the group that died, their mean age was higher than the survivors (60.7 vs 52.60 years, respectively), and they had a higher prevalence of comorbidities such as arterial hypertension (37.2% vs 20.4%, respectively) and diabetes mellitus (26.9% vs 15.7%, respectively), with Pâ <â .001. In ventilatory management, 32.7% of patients used noninvasive ventilation and high-flow nasal cannula, and 67.3% required invasive ventilatory support. After adjusting for confounders, Cox regression analysis showed that patients were less likely to be discharged alive from the ICU if they met the following conditions: arterial hypertension (hazard ratio [HR]â =â 0.83 95% CI 0.723-0.964), diabetes mellitus (HRâ =â 0.80 95% CI 0.696-0.938), older than 62 years (HRâ =â 0.86 95% CI 0.790-0.956), obese (body mass indexâ ≥â 30) (HRâ =â 0.78 95% CI 0.697-0.887), 1 unit increase in SOFA score (HRâ =â 0.94 95% CI 0.937-0.961), PaO2/FiO2 ratio <100 mm Hg (HRâ =â 0.84 95% CI 0.786-0.914), and the use of invasive mechanical ventilation (HRâ =â 0.68 95% CI 0.614-0.769). Risk factors associated with increased mortality were older age, obesity, arterial hypertension, and diabetes. Factors such as male gender, chronic obstructive pulmonary disease, acute kidney injury, and cancer reported in other investigations did not have the same effect on mortality in our study.
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COVID-19 , Unidades de Cuidados Intensivos , Humanos , Masculino , COVID-19/mortalidad , COVID-19/epidemiología , Persona de Mediana Edad , Femenino , Ecuador/epidemiología , Estudios Retrospectivos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Factores de Riesgo , Anciano , Adulto , Comorbilidad , Mortalidad Hospitalaria , SARS-CoV-2 , Respiración Artificial/estadística & datos numéricos , Modelos de Riesgos ProporcionalesRESUMEN
Disease severity and drought due to climate change present significant challenges to orchard productivity. This study examines the effects of spring inoculation with Pseudomonas syringae pv. syringae (Pss) on sweet cherry plants, cvs. Bing and Santina with varying defense responses, assessing plant growth, physiological variables (water potential, gas exchange, and plant hydraulic conductance), and the levels of abscisic acid (ABA) and salicylic acid (SA) under two summer irrigation levels. Pss inoculation elicited a more pronounced response in 'Santina' compared to 'Bing' at 14 days post-inoculation (dpi), and those plants inoculated with Pss exhibited a slower leaf growth and reduced transpiration compared to control plants during 60 dpi. During differential irrigations, leaf area was reduced 14% and 44% in Pss inoculated plants of 'Bing' and 'Santina' respectively, under well-watered (WW) conditions, without changes in plant water status or gas exchange. Conversely, water-deficit (WD) conditions led to gas exchange limitations and a 43% decrease in plant biomass compared to that under WW conditions, with no differences between inoculation treatments. ABA levels were lower under WW than under WD at 90 dpi, while SA levels were significantly higher in Pss-inoculated plants under WW conditions. These findings underscore the influence on plant growth during summer in sweet cherry cultivars that showed a differential response to Pss inoculations and how the relationship between ABA and SA changes in plant drought level responses.
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RATIONALE: Conjugation sites are a quality attribute of conjugate vaccines. Proteolysis of bioconjugates synthesized by maleimide-thiol chemistry generates type 2 peptides with a hydrolyzed thiosuccinimide linker containing information on the conjugation sites. A mass spectrometry (MS)-cleavable linker could make the identification of conjugation sites by MS more reliable. METHODS: Four synthetic type 2 peptides with a hydrolyzed thiosuccinimide linker were analyzed by matrix-assisted laser desorption ionization (MALDI) MS/MS with and without collision gas. These peptides were also partially labeled with 18O in the linker to confirm the proposed fragmentation mechanism. A conjugate vaccine with the hydrolyzed thiosuccinimide linker was reduced and S-alkylated, digested with trypsin and analyzed by liquid chromatography-MS/MS using collision-induced dissociation (CID) and higher-energy collisional dissociation (HCD) fragmentation methods at a normalized collision energy of 30. RESULTS: A metastable fragmentation preferentially cleaves the newly formed pseudopeptide bond within the hydrolyzed thiosuccinimide linker of type 2 peptides to yield P + 71 and C + 98 ions. These ions make the assignment of conjugation sites more reliable. Partial 18O-labeling and MS/MS analysis confirmed the proposed structures. CID produces these ions as the two most intense signals more favorably than HCD. The latter also yields these ions, guarantees better sequence coverage and promotes other fragmentations in the linker. CONCLUSIONS: Hydrolyzed thiosuccinimide linker is cleavable in MALDI and electrospray ionization MS/MS analysis by a gas-phase metastable fragmentation. The resulting fragment ions (P + 71 and C + 98) make the identification of conjugation sites more reliable. These results could be extended to self-hydrolyzing maleimides, which efficiently stabilize the thiosuccinimide linker upon hydrolysis, in antibody-drug conjugates.
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Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Succinimidas , Espectrometría de Masas en Tándem , Vacunas Conjugadas , Succinimidas/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Espectrometría de Masas en Tándem/métodos , Vacunas Conjugadas/química , Péptidos/química , HidrólisisRESUMEN
Anterior cruciate ligament (ACL) instability poses a considerable challenge in traumatology and orthopedic medicine, demanding precise diagnostics for optimal treatment. The pivot-shift test, a pivotal assessment tool, relies on subjective interpretation, emphasizing the need for supplementary imaging. This study addresses this limitation by introducing a machine learning classification algorithm integrated into a mobile application, leveraging smartphones' built-in inertial sensors for dynamic rotational stability assessment during knee examinations. Orthopedic specialists conducted knee evaluations on a cohort of 52 subjects, yielding valuable insights. Quantitative analyses, employing the Intraclass Correlation Coefficient (ICC), demonstrated robust agreement in both intraobserver and interobserver assessments. Specifically, ICC values of 0.94 reflected strong concordance in the timing between maneuvers, while signal amplitude exhibited consistency, with the ICC ranging from 0.71 to 0.66. The introduced machine learning algorithms proved effective, accurately classifying 90% of cases exhibiting joint hypermobility. These quantifiable results underscore the algorithm's reliability in assessing knee stability. This study emphasizes the practicality and effectiveness of implementing machine learning algorithms within a mobile application, showcasing its potential as a valuable tool for categorizing signals captured by smartphone inertial sensors during the pivot-shift test.
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Non-tuberculosis infections in immunocompromised patients represent a cause for concern, given the increased risks of infection, and limited treatments available. Herein, we report that molecules for binding to the catalytic site of histone deacetylase (HDAC) inhibit its activity, thus increasing the innate immune response against environmental mycobacteria. The action of HDAC inhibitors (iHDACs) was explored in a model of type II pneumocytes and macrophages infection by Mycobacterium aurum. The results show that the use of 1,3-diphenylurea increases the expression of the TLR-4 in M. aurum infected MDMs, as well as the production of defb4, IL-1ß, IL-12, and IL-6. Moreover, we observed that aminoacetanilide upregulates the expression of TLR-4 together with TLR-9, defb4, CAMP, RNase 6, RNase 7, IL-1ß, IL-12, and IL-6 in T2P. Results conclude that the tested iHDACs selectively modulate the expression of cytokines and antimicrobial peptides that are associated with reduction of non-tuberculous mycobacteria infection.
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Citocinas , Reposicionamiento de Medicamentos , Inhibidores de Histona Desacetilasas , Inmunidad Innata , Infecciones por Mycobacterium no Tuberculosas , Inmunidad Innata/efectos de los fármacos , Humanos , Infecciones por Mycobacterium no Tuberculosas/inmunología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Inhibidores de Histona Desacetilasas/farmacología , Citocinas/metabolismo , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/microbiología , Micobacterias no Tuberculosas/efectos de los fármacos , Micobacterias no Tuberculosas/inmunología , Mycobacterium/inmunología , Mycobacterium/efectos de los fármacosRESUMEN
Species are expected to migrate to higher latitudes as warming intensifies due to anthropogenic climate change since physiological mechanisms have been adapted to maximize fitness under specific temperatures. However, literature suggests that upwellings could act as thermal refugia under climate warming protecting marine ecosystem diversity. This research aimed to predict the effects of climate warming on commercial and non-commercial fish species reported in official Mexican documents (>200 species) based on their thermal niche to observe if upwellings can act as potential thermal refugia. Present (2000-2014) and Representative Concentration Pathway (6.0 and 8.5) scenarios (2040-2050 and 2090-2100) have been considered for this work. Current and future suitability patterns, species distribution, richness, and turnover were calculated using the minimum volume ellipsoids as algorithm. The results in this study highlight that beyond migration to higher latitudes, upwelling regions could protect marine fishes, although the mechanism differed between the innate characteristics of upwellings. Most modeled species (primarily tropical fishes) found refuge in the tropical upwelling in Northern Yucatan. However, the highest warming scenario overwhelmed this region. In contrast, the Baja California region lies within the Eastern Boundary Upwelling Systems. While the area experiences an increase in suitability, the northern regions have a higher upwelling intensity acting as environmental barriers for many tropical species. Conversely, in the southern regions where upwelling is weaker, species tend to congregate and persist even during elevated warming, according to the turnover analysis. These findings suggest that tropicalization in higher latitudes may not be as straightforward as previously assumed. Nevertheless, climate change affects numerous ecosystem features, such as trophic relationships, phenology, and other environmental variables not considered here. In addition, uncertainty still exists about the assumption of increasing intensity of upwelling systems.
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Cambio Climático , Peces , Animales , Peces/fisiología , Refugio de Fauna , México , Ecosistema , Calentamiento Global , TemperaturaRESUMEN
High-density lipoprotein cholesterol (HDL-c) removes cholesterol, an essential component in lipid rafts, and this cholesterol removal can regulate protein attachment to lipid rafts, modulating their functionality in the immune cell response. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can alter the lipid profile, there is little information on the role of HDL-c and other lipids in prognostic of the coronavirus disease 2019 (COVID-19) in Mexican population. This study aims to evaluate the predictive value of HDL-c and lipid profile on severity and survival of 102 patients infected with SARS-CoV-2 during the COVID-19 first wave. Our findings, derived from univariate and multivariate Cox proportional hazards regression models, highlighted age and hypertension as significant predictors of survival (HR = 1.04, p = 0.012; HR = 2.78, p = 0.027), while gender, diabetes, and obesity showed no significant impact. Triglycerides and HDL-c levels notably influenced mortality, with elevated triglycerides and lower HDL-c associated with higher mortality risk (p = 0.032). This study underscores the importance of lipid profiles alongside traditional risk factors in assessing COVID-19 risk and outcomes. It contributes to the understanding of COVID-19 patient management and emphasizes the need for further investigation into the role of dyslipidemia in influencing COVID-19 prognosis, potentially aiding in refined risk stratification and therapeutic strategies.
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COVID-19 , HDL-Colesterol , SARS-CoV-2 , Humanos , COVID-19/mortalidad , COVID-19/sangre , Masculino , Femenino , Persona de Mediana Edad , HDL-Colesterol/sangre , Adulto , Anciano , SARS-CoV-2/aislamiento & purificación , Factores de Riesgo , Triglicéridos/sangre , Pronóstico , Lípidos/sangre , México/epidemiología , Dislipidemias/sangre , Modelos de Riesgos Proporcionales , Hipertensión/sangreRESUMEN
To compare 2 different graft preparation techniques to determine biomechanical strength and resultant tissue trauma evaluated by histology. Twelve common flexors of the finger's tendons were prepared with either tubulization (SpeedTrap™) or transtendon stiches (Orthocord™). The stiffness, resistance and energy at maximum load were tested for biomechanical assessment in both groups. After load testing, Samples were stained with hematoxylin and eosin (HE) to evaluate histological damage. We observe that the time to prepare tendons with SpeedTrap™ was 8.3 times faster (1:25 min) than traditional ones (15:02 min). In all cases, the mean values for SpeedTrap™ were higher in terms of strength, stiffness and energy at maximum load than for traditional suture but without significant difference (p > 0.05). The Krackow stitch produces greater structural damage to the collagen fibers while SpeedTrap™ maintains better organized arrangement of the fibers after tubulization preparation. With the results obtained, we can conclude that the tubulization technique allows faster graft preparation with less structural damage to the manipulated tissue without altering the biomechanical resistance provided by the transtendon suture technique.
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Técnicas de Sutura , Suturas , Tendones , Fenómenos Biomecánicos , Tendones/fisiología , Humanos , Resistencia a la TracciónRESUMEN
PDZ (PSD-95/Dlg/ZO-1) domain-containing proteins constitute a large family of scaffolds involved in a wide range of cellular tasks, and mainly studied in polarity functions. Diverse host PDZ proteins can be targeted by viral pathogens which express proteins containing PDZ-binding motifs (PDZbm). Previously, we have identified host PDZ-based interactions with the SARS-CoV-2 E protein (2E) in human monocytes. Here, we deepen the study of these interactions by docking and molecular dynamics analyses to identify the most favorable PDZ-PDZbm interaction of seven host PDZ proteins with the PDZbm of 2E. In addition, we analyzed changes in the expression of three of the PDZ proteins identified as 2E interactors in monocytes (syntenin, ZO-2, and IL-16), in human monocyte-derived macrophages (MΦ) and in dendritic cells (DCs) upon stimulation. Our results suggest that these PDZ proteins may have important functions in professional antigen-presenting cells (APCs), and their targeting by the PDZbm of 2E, a central virulence determinant of SARS-CoV-2, support the hypothesis that such PDZ-dependent interaction in immune cells may constitute a viral evasion mechanism. Inhibitor design based on the PDZbm of 2E in the development of drugs against a variety of diseases is discussed.
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During the COVID-19 pandemic, a considerable proportion of patients developed a severe condition that included respiratory failure, shock, or multiple organ dysfunction. Acute Kidney Injury (AKI) has been recognized as a possible cause of severe COVID-19 development. Given this, this study investigates the occurrence and consequences of AKI in Mexican patients to contribute to better knowledge and management of this problem. Methods: Using a retrospective observational cohort methodology, we investigated 313 cases from a cohort of 1019 patients diagnosed with COVID-19 at the IMSS Zacatecas General Hospital of Zone No. 1 in 2020. The prevalence of AKI was determined using the AKIN criteria based on serum creatinine levels and a detailed review of demographic characteristics, medical history, comorbidities, and clinical development. Results: The data showed a 25.30% prevalence of AKI among patients infected with severe COVID-19. Remarkably, these patients with AKI exhibited an advanced age (>65 years), arterial hypertension, a higher number of white blood cells during admission and the hospital stay, and elevated levels of C-reactive protein, serum creatinine, and blood urea nitrogen (BUN). Clinically, patients with AKI had signs of prostration, pneumonia, and the requirement for ventilatory assistance when compared to those without AKI. Finally, those diagnosed with AKI and COVID-19 had a 74% death rate. Relative risk analyses indicated that age (>65 years), arterial hypertension, high creatinine levels, endotracheal intubation, and pneumonia are associated with the development of AKI. On the other hand, among the protective factors against AKI, high hemoglobin levels and the consumption of statins during COVID-19 were found. Conclusions: The findings of this study underscore the significance of promptly identifying and effectively managing AKI to potentially alleviate the negative consequences of this complication within the Mexican population during COVID-19.
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Identifying and evaluating potential vaccine candidates has become one of the main objectives to combat tuberculosis. Among them, mannosylated Apa antigen from Mycobacterium tuberculosis and the non-mannosylated protein expressed in Escherichia coli, have been studied. Although both proteins can induce a protective response in mice, it has been considered that native protein can be dispensed. In this work, we study the protective response induced by Apa expressed in E. coli and in Streptomyces lividans. The latter, like native is secreted as a double band of 45/47 kDa, however, only its 47 kDa band is mannosylated. Both antigens and BCG were intranasal administrated in mice, and animals were then challenged by aerosol with M. tuberculosis H37Rv. The results showed that both, Apa from S. lividans and E. coli conferred statistically significantly protection to animals compared to controls. The cytokine immune response was studied by an immunoassay after animals' immunization, revealing that Apa from S. lividans induced a statistically significant proliferation of T cell, as well as the expression of IFN-γ, IL-1ß, IL-17 and IL-10. In contrast, non-proliferation was obtained with non-mannosylated protein, but induction of IL-12 and IL-17 was observed. Together, these results demonstrate that both proteins were able to modulate a specific immune response against M. tuberculosis, that could be driven by different mechanisms possibly associated with the presence or not of mannosylation. Furthermore, stimulation of cells from BCG-vaccinated animals with the proteins could be an important tool, to help define the use of a given subunit-vaccine after BCG vaccination.
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Administración Intranasal , Citocinas , Mycobacterium tuberculosis , Streptomyces lividans , Tuberculosis , Animales , Ratones , Aerosoles , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/genética , Antígenos Bacterianos/administración & dosificación , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/administración & dosificación , Citocinas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Ratones Endogámicos BALB C , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/administración & dosificación , Streptomyces lividans/genética , Streptomyces lividans/inmunología , Tuberculosis/prevención & control , Tuberculosis/inmunología , Vacunas contra la Tuberculosis/inmunología , Vacunas contra la Tuberculosis/administración & dosificación , Vacunas contra la Tuberculosis/genéticaRESUMEN
Bacterial canker is an important disease of sweet cherry plants mainly caused by Pseudomonas syringae pv. syringae (Pss). Water deficit profoundly impairs the yield of this crop. Nitric oxide (NO) is a molecule that plays an important role in the plant defense mechanisms. To evaluate the protection exerted by NO against Pss infection under normal or water-restricted conditions, sodium nitroprusside (SNP), a NO donor, was applied to sweet cherry plants cv. Lapins, before they were exposed to Pss infection under normal or water-restricted conditions throughout two seasons. Well-watered plants treated with exogenous NO presented a lower susceptibility to Pss. A lower susceptibility to Pss was also induced in plants by water stress and this effect was increased when water stress was accompanied by exogenous NO. The lower susceptibility to Pss induced either by exogenous NO or water stress was accompanied by a decrease in the internal bacterial population. In well-watered plants, exogenous NO increased the stomatal conductance and the net CO2 assimilation. In water-stressed plants, NO induced an increase in the leaf membranes stability and proline content, but not an increase in the CO2 assimilation or the stomatal conductance.