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BACKGROUND: Cystic fibrosis (CF), an inherited autosomal recessive disorder, is linked with high morbidity and mortality rates due to bacteria, filamentous, yeast and black yeast-like fungi colonisation in the upper respiratory tract. Although Candida species are the most common fungi isolated from CF patients, azole-resistant Aspergillus fumigatus (ARAf) is a big concern for invasive aspergillosis. Notably, the exact prevalences of Aspergillus species and the prevalence of ARAf isolates among Iranian CF patients have yet to be previously reported and are unknown. We aimed to investigate the prevalence of ARAf isolates in CF patients among Iranian populations by focusing on molecular mechanisms of the mutations in the target gene. METHODS: The 1 year prospective study recovered 120 sputum samples from 103 CF patients. Of these, 55.1% (86/156) yielded Aspergillus species, screened for ARAf using plates containing itraconazole (4 mg/L) and voriconazole (1 mg/L). According to the CLSI-M38 guidelines, antifungal susceptibility testing was performed using the broth microdilution method. In all phenotypically resistant isolates, the target of azole agents, the cyp51A gene, was sequenced to detect any possible single nucleotide polymorphisms (SNP) mediating resistance. RESULTS: Of 120 samples, 101 (84.2%) were positive for filamentous fungi and yeast-like relatives, with 156 fungal isolates. The most common colonising fungi were Aspergillus species (55.1%, 86/156), followed by Candida species (39.8%, 62/156), Exophiala species (3.8%, 6/156) and Scedosporium species (1.3%, 2/156). Forty out of 86 (46.5%) were identified for section Fumigati, 36 (41.9%) for section Flavi, 6 (7%) for section Nigri and 4 (4.6%) for section Terrei. Fourteen out of 40 A. fumigatus isolates were phenotypically resistant. The overall proportion of ARAf in total fungal isolates was 9% (14/156). cyp51A gene analysis in resistant isolates revealed that 13 isolates harboured G448S, G432C, T289F, D255E, M220I, M172V, G138C, G54E and F46Y mutations and one isolate carried G448S, G432C, T289F, D255E, M220I, G138C, G54E and F46Y mutations. Additionally, this study detects two novel cyp51A single-nucleotide polymorphisms (I242V and D490E). CONCLUSIONS: This study first investigated ARAf isolates in Iranian CF patients. Due to a resistance rate of up to 9%, it is recommended that susceptibility testing of Aspergillus isolates from CF patients receiving antifungal treatment be a part of the routine diagnostic workup. However, extensive multicentre studies with a high volume of CF patients are highly warranted to determine the impact of ARAf on CF patients.
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Antifúngicos , Aspergillus fumigatus , Azoles , Fibrosis Quística , Sistema Enzimático del Citocromo P-450 , Farmacorresistencia Fúngica , Proteínas Fúngicas , Pruebas de Sensibilidad Microbiana , Humanos , Fibrosis Quística/microbiología , Fibrosis Quística/complicaciones , Irán/epidemiología , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/aislamiento & purificación , Farmacorresistencia Fúngica/genética , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Estudios Prospectivos , Prevalencia , Sistema Enzimático del Citocromo P-450/genética , Azoles/farmacología , Azoles/uso terapéutico , Proteínas Fúngicas/genética , Masculino , Femenino , Aspergilosis/microbiología , Aspergilosis/epidemiología , Aspergilosis/tratamiento farmacológico , Adulto , Niño , Adolescente , Polimorfismo de Nucleótido Simple , Adulto Joven , Esputo/microbiología , Itraconazol/farmacología , Voriconazol/farmacología , Voriconazol/uso terapéutico , Preescolar , MutaciónRESUMEN
Introduction: This study measures the COVID-19 vaccine effectiveness (CVE) against hospital admission and severe COVID-19. Methods: This study is a test-negative case-control design using data from eight provinces in April, 2021 until March, 2022. The individuals were classified as cases and controls based on the results of the RT-PCR test for SARS-CoV-2 and matched based on the timing of the test being conducted as well as the timing of hospital admission. The measure of association was an odds ratio (OR) by univariate and multiple logistic regression. The multiple logistic regression has been carried out to take confounding factors and potential effect modifiers into account. The CVE was computed as CVE = (1 - OR)*100 with 95% confidence interval. Results: Among 19314 admitted patients, of whom 13216 (68.4%) were cases and 6098 (31.6%) were controls, 1313 (6.8%) died. From total, 5959 (30.8%) patients had received the vaccine in which one, two, and booster doses were 2443 (12.6%), 2796 (14.5Ùª), and 720 (3.7Ùª), respectively. The estimated adjusted effectiveness of only one dose, two doses and booter vaccination were 22% (95% CI: 14%-29%), 35% (95% CI: 29%-41%) and 33% (95% CI: 16%-47%), respectively. In addition, the adjusted vaccine effectiveness against severe outcome was 33% (95% CI: 19%- 44%), 34% (95% CI: 20%- 45%) and 20% (95% CI: -29%- 50%) for those who received one, two and booster vaccinations, respectively. Conclusion: Our study concluded that full vaccination, though less effective compared to similar studies elsewhere, decreased hospital admissions and deaths from COVID-19 in Iran, particularly during the Delta variant period, with an observed decline during the Omicron variant dominance.
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Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Eficacia de las Vacunas , Humanos , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/mortalidad , COVID-19/epidemiología , Irán/epidemiología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Masculino , Femenino , Estudios de Casos y Controles , Persona de Mediana Edad , SARS-CoV-2/inmunología , Adulto , Anciano , Hospitalización/estadística & datos numéricos , Vacunación , Adulto Joven , AdolescenteRESUMEN
Introduction: The role of genetic variants in response to chemotherapy has been investigated in several studies. This study aimed to investigate genetic variants associated with response to chemotherapy in breast cancer (BC) patients. Methods: Significant variants (p < 5 × 10-8) associated with response to chemotherapy were obtained from GWA studies. Candidate variants were identified by haplotype analysis (r2 ≥ 0.9, D'≥0.9) using 1000Genome LD data. To determine the effects of the variants on gene expression, expression quantitative trait loci (eQTL) were evaluated. To compare the expression of the identified genes in tumor samples, expression levels were compared between TCGA tumor types and adjacent normal tissues. Results: Six rs3820706, rs147451859, rs4784750, rs17587029, rs16830728, and rs16972207 variants were significantly associated with response to chemotherapy in BC patients (p < 5 × 10-8). Seven novel haplotypic structures were identified to be associated with adverse response to chemotherapy in BC patients. These haplotypes formed two genetic structures associated with neutropenia, leukopenia, chemotherapy-induced cytotoxicity (GAG-TTAT), and chemotherapy-induced alopecia (CC-CAACTCCCGTTGCGG). These variants are located on PPCDC, NLRC5, STAM2, and TNFSF13B genes, and the expression of these genes significantly changed in BC tissues than normal tissues (P ≤ 0.05), also showing gene-gene correlation (P ≤ 0.05). Conclusions: These genetic variants and their associated novel haplotypic structures can predict adverse response to chemotherapy in BC patients and could potentially form BC-associated genetic panel for adverse response to chemotherapy.
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BACKGROUND: Heart failure is a chronic and progressive disease where the heart muscle is unable to pump enough blood and oxygen to meet the body's needs. Oxidative stress and inflammation are key elements in the development and progression of heart failure. Astaxanthin, a carotenoid, has strong anti-inflammatory and antioxidant effects that may protect the cardiovascular system. A study will evaluate the effect of astaxanthin supplementation on inflammatory status, oxidative stress, lipid profile, uric acid levels, endothelial function, quality of life, and disease symptoms in people with heart failure. METHODS: The current study is a double-blind controlled randomized clinical trial for 8 weeks, in which people with heart failure were randomly assigned to two groups: intervention (one capsule containing 20 mg of astaxanthin per day, n = 40) and placebo (one capsule containing 20 mg of maltodextrin per day, n = 40) will be divided. At the beginning and end of the intervention, uric acid, lipid profile, oxidative stress indices, inflammatory markers, blood pressure, nitric oxide, and anthropometric factors will be measured, and questionnaires measuring quality of life, fatigue intensity, shortness of breath, and appetite will be completed. SPSS version 22 software will be used for statistical analysis. DISCUSSION: There is a growing global interest in natural and functional food products. This RCT contributes to the expanding body of research on the potential benefits of astaxanthin in heart failure patients, including its antioxidant, lipid-lowering, and anti-inflammatory effects. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20200429047235N3. Registered on 26 March 2024.
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Biomarcadores , Presión Sanguínea , Suplementos Dietéticos , Insuficiencia Cardíaca , Estrés Oxidativo , Calidad de Vida , Ácido Úrico , Xantófilas , Humanos , Xantófilas/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/sangre , Ácido Úrico/sangre , Método Doble Ciego , Biomarcadores/sangre , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Persona de Mediana Edad , Masculino , Lípidos/sangre , Femenino , Antioxidantes , Anciano , Resultado del Tratamiento , Mediadores de Inflamación/sangre , Adulto , Inflamación/sangre , Antiinflamatorios/uso terapéutico , IránRESUMEN
The continual social and economic impact of infectious diseases on nations has maintained sustained attention on their control and treatment, of which self-medication has been one of the means employed by some individuals. Self-medication complicates the attempt of their control and treatment as it conflicts with some of the measures implemented by health authorities. Added to these complications is the stigmatization of individuals with some diseases in some jurisdictions. This study investigates the co-infection of COVID-19 and malaria and its related deaths and further highlights how self-medication and stigmatization add to the complexities of the fight against these two diseases using Nigeria as a study case. Using a mathematical model on COVID-19 and malaria co-infection, we address the question: to what degree does the impact of the interaction between COVID-19 and malaria amplify infections and deaths induced by both diseases via self-medication and stigmatization? We demonstrate that COVID-19 related self-medication due to misdiagnoses contributes substantially to the prevalence of disease. The control reproduction numbers for these diseases and quantification of model parameters uncertainties and sensitivities are presented.
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COVID-19 , Malaria , Modelos Teóricos , Automedicación , Humanos , Nigeria/epidemiología , COVID-19/psicología , COVID-19/epidemiología , Automedicación/psicología , Automedicación/estadística & datos numéricos , Malaria/tratamiento farmacológico , Malaria/psicología , Coinfección , SARS-CoV-2 , Estigma Social , EstereotipoRESUMEN
Background: According to study on the under-estimation of COVID-19 cases in African countries, the average daily case reporting rate was only 5.37% in the initial phase of the outbreak when there was little or no control measures. In this work, we aimed to identify the determinants of the case reporting and classify the African countries using the case reporting rates and the significant determinants. Methods: We used the COVID-19 daily case reporting rate estimated in the previous paper for 54 African countries as the response variable and 34 variables from demographics, socioeconomic, religion, education, and public health categories as the predictors. We adopted a generalized additive model with cubic spline for continuous predictors and linear relationship for categorical predictors to identify the significant covariates. In addition, we performed Hierarchical Clustering on Principal Components (HCPC) analysis on the reporting rates and significant continuous covariates of all countries. Results: 21 covariates were identified as significantly associated with COVID-19 case detection: total population, urban population, median age, life expectancy, GDP, democracy index, corruption, voice accountability, social media, internet filtering, air transport, human development index, literacy, Islam population, number of physicians, number of nurses, global health security, malaria incidence, diabetes incidence, lower respiratory and cardiovascular diseases prevalence. HCPC resulted in three major clusters for the 54 African countries: northern, southern and central essentially, with the northern having the best early case detection, followed by the southern and the central. Conclusion: Overall, northern and southern Africa had better early COVID-19 case identification compared to the central. There are a number of demographics, socioeconomic, public health factors that exhibited significant association with the early case detection.
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COVID-19 , Humanos , COVID-19/epidemiología , África/epidemiología , Factores Socioeconómicos , SARS-CoV-2 , Salud Pública/estadística & datos numéricosRESUMEN
OBJECTIVE: To assess the impact of self-medication on the transmission dynamics of COVID-19 across different age groups, examine the interplay of vaccination and self-medication in disease spread, and identify the age group most prone to self-medication. METHODS: We developed an age-structured compartmentalized epidemiological model to track the early dynamics of COVID-19. Age-structured data from the Government of Gauteng, encompassing the reported cumulative number of cases and daily confirmed cases, were used to calibrate the model through a Markov Chain Monte Carlo (MCMC) framework. Subsequently, uncertainty and sensitivity analyses were conducted on the model parameters. RESULTS: We found that self-medication is predominant among the age group 15-64 (74.52%), followed by the age group 0-14 (34.02%), and then the age group 65+ (11.41%). The mean values of the basic reproduction number, the size of the first epidemic peak (the highest magnitude of the disease), and the time of the first epidemic peak (when the first highest magnitude occurs) are 4.16499, 241,715 cases, and 190.376 days, respectively. Moreover, we observed that self-medication among individuals aged 15-64 results in the highest spreading rate of COVID-19 at the onset of the outbreak and has the greatest impact on the first epidemic peak and its timing. CONCLUSION: Studies aiming to understand the dynamics of diseases in areas prone to self-medication should account for this practice. There is a need for a campaign against COVID-19-related self-medication, specifically targeting the active population (ages 15-64).
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COVID-19 , Automedicación , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Adolescente , Sudáfrica/epidemiología , Adulto , Persona de Mediana Edad , Adulto Joven , Automedicación/estadística & datos numéricos , Anciano , Niño , Prevalencia , Preescolar , Lactante , Recién Nacido , Modelos Epidemiológicos , SARS-CoV-2 , Factores de Edad , Masculino , Cadenas de Markov , FemeninoRESUMEN
This review investigates the most recent advances in personalized 3D-printed wound dressings and skin scaffolding. Skin is the largest and most vulnerable organ in the human body. The human body has natural mechanisms to restore damaged skin through several overlapping stages. However, the natural wound healing process can be rendered insufficient due to severe wounds or disturbances in the healing process. Wound dressings are crucial in providing a protective barrier against the external environment, accelerating healing. Although used for many years, conventional wound dressings are neither tailored to individual circumstances nor specific to wound conditions. To address the shortcomings of conventional dressings, skin scaffolding can be used for skin regeneration and wound healing. This review thoroughly investigates polysaccharides (e.g., chitosan, Hyaluronic acid (HA)), proteins (e.g., collagen, silk), synthetic polymers (e.g., Polycaprolactone (PCL), Poly lactide-co-glycolic acid (PLGA), Polylactic acid (PLA)), as well as nanocomposites (e.g., silver nano particles and clay materials) for wound healing applications and successfully 3D printed wound dressings. It discusses the importance of combining various biomaterials to enhance their beneficial characteristics and mitigate their drawbacks. Different 3D printing fabrication techniques used in developing personalized wound dressings are reviewed, highlighting the advantages and limitations of each method. This paper emphasizes the exceptional versatility of 3D printing techniques in advancing wound healing treatments. Finally, the review provides recommendations and future directions for further research in wound dressings.
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Vendajes , Polisacáridos , Impresión Tridimensional , Cicatrización de Heridas , Humanos , Cicatrización de Heridas/efectos de los fármacos , Polisacáridos/química , Polisacáridos/uso terapéutico , Andamios del Tejido/química , Piel/efectos de los fármacos , Piel/metabolismo , Polímeros/química , Proteínas/química , Materiales Biocompatibles/química , AnimalesRESUMEN
In microbiome studies, the diversity and types of microbes have been extensively explored; however, the significance of microbial ecology is equally paramount. The comprehension of metabolic interactions among the wide array of microorganisms in the lung microbiota is indispensable for understanding chronic pulmonary disease and for the development of potent treatments. In this investigation, metabolic networks were simulated, and ecological theory was employed to assess the diagnosis of COPD, subsequently suggesting innovative treatment strategies for COPD exacerbation. Lung sputum 16S rRNA paired-end data from 112 COPD patients were utilized, and a supervised machine-learning algorithm was applied to identify taxa associated with sex and mortality. Subsequently, an OTU table with Greengenes 99 % dataset was generated. Finally, the interactions between bacterial species were analyzed using a simulated metabolic network. A total of 1781 OTUs and 1740 bacteria at the genus level were identified. We employed an additional dataset to validate our analyses. Notably, among the more abundant genera, Pseudomonas was detected in females, while Lactobacillus was detected in males. Additionally, a decrease in bacterial diversity was observed during COPD exacerbation, and mortality was associated with the high abundance of the Staphylococcus and Pseudomonas genera. Moreover, an increase in Proteobacteria abundance was observed during COPD exacerbations. In contrast, COPD patients exhibited decreased levels of Firmicutes and Bacteroidetes. Significant connections between microbial ecology and bacterial diversity in COPD patients were discovered, highlighting the critical role of microbial ecology in the understanding of COPD. Through the simulation of metabolic interactions among bacteria, the observed dysbiosis in COPD was elucidated. Furthermore, the prominence of anaerobic bacteria in COPD patients was revealed to be influenced by parasitic relationships. These findings have the potential to contribute to improved clinical management strategies for COPD patients.
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BACKGROUND: Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and bronchiectasis, present significant threats to global health. Recent studies have revealed the crucial role of the lung microbiome in the development of these diseases. Pathogens have evolved complex strategies to evade the immune response, with the manipulation of host cellular epigenetic mechanisms playing a pivotal role. There is existing evidence regarding the effects of Pseudomonas on epigenetic modifications and their association with pulmonary diseases. Therefore, this study aims to directly assess the connection between Pseudomonas abundance and chronic respiratory diseases. We hope that our findings will shed light on the molecular mechanisms behind lung pathogen infections. METHODS: We analyzed data from 366 participants, including individuals with COPD, acute exacerbations of COPD (AECOPD), bronchiectasis, and healthy individuals. Previous studies have given limited attention to the impact of Pseudomonas on these groups and their comparison with healthy individuals. Two independent datasets from different ethnic backgrounds were used for external validation. Each dataset separately analyzed bacteria at the genus level. RESULTS: The study reveals that Pseudomonas, a bacterium, was consistently found in high concentrations in all chronic lung disease datasets but it was present in very low abundance in the healthy datasets. This suggests that Pseudomonas may influence cellular mechanisms through epigenetics, contributing to the development and progression of chronic respiratory diseases. CONCLUSIONS: This study emphasizes the importance of understanding the relationship between the lung microbiome, epigenetics, and the onset of chronic pulmonary disease. Enhanced recognition of molecular mechanisms and the impact of the microbiome on cellular functions, along with a better understanding of these concepts, can lead to improved diagnosis and treatment.
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Bronquiectasia , Microbiota , Enfermedad Pulmonar Obstructiva Crónica , Trastornos Respiratorios , Humanos , Pulmón , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/terapia , Bronquiectasia/genética , Bronquiectasia/terapia , Bacterias , Microbiota/genética , Progresión de la EnfermedadRESUMEN
Until now, only a few comprehensive studies have validated analytical heat stress indices in different conditions. The present study aims to investigate the validity of these indicators in predicting the physiological parameters of workers. This cross-sectional study was conducted with 194 male employees working in warm environments. First, demographic information was collected. After participants rested for 30 min, their heart rate and tympanic temperature were measured. The subjects then performed their routine tasks. At the end of 90 min, their heart rate and tympanic temperature were again measured. Additionally, their metabolism rate and clothing thermal insulation were estimated. Environmental parameters were also measured at 30-, 60-, and 90-min time points. Additional information required to compute the indices was recorded. Then, the values of each of the indices were computed. Finally, the validity of the indices was assessed under different conditions. The results indicated that the highest regression coefficients with tympanic temperature were assigned to modified physiologically equivalent temperature (mPET) (0.7515), predicted heat strain (PHS) (0.7201), and predicted mean vote (PMV) (0.7082), index, respectively. Also, the greatest regression coefficients with heart rate belonged to mPET (0.7773), PMV (0.7624), and PHS (0.6479) index, respectively. Based on the results, the highest diagnostic accuracies of receiver operating characteristic (ROC) curves for tympanic temperature were related to indices of mPET, PHS, and PMV with the area under the ROC curve (AUC) of 0.945, 0.931, and 0.930, respectively. Of the studied indices, it was observed that mPET, PHS, PMV, and PPD showed more validity compared to others.
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Trastornos de Estrés por Calor , Enfermedades Profesionales , Humanos , Masculino , Estudios Transversales , Respuesta al Choque Térmico , Trastornos de Estrés por Calor/diagnóstico , Frecuencia Cardíaca , CalorRESUMEN
Skin substitutes including allografts remain a standard therapeutic approach to promote healing of both acute and chronic large wounds. However, none have resulted in the regrowth of lost and damaged tissues and scarless wound healing. Here, we demonstrate skin allograft chimerism and repair through the mobilization of endogenous bone marrow-derived stem and immune cells in rats and swine. We show that pharmacological mobilization of bone marrow stem cells and immune cells into the circulation promotes host repopulation of skin allografts and restoration of the skin's normal architecture without scarring and minimal contracture. When skin allografts from DA rats are transplanted into GFP transgenic Lewis recipients with a combination of AMD3100 and low-dose FK506 (AF) therapy, host-derived GFP-positive cells repopulate and/or regenerate cellular components of skin grafts including epidermis and hair follicles and the grafts become donor-host chimeric skin. Using AF combination therapy, burn wounds with skin allografts were healed by newly regenerated chimeric skin with epidermal appendages and pigmentation and without contracture in swine.
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Quemaduras , Contractura , Ratas , Animales , Porcinos , Trasplante de Médula Ósea , Médula Ósea , Quimerismo , Ratas Endogámicas Lew , Quemaduras/cirugía , Trasplante de Piel , Aloinjertos , Células Madre , Supervivencia de InjertoRESUMEN
Recently, the early diagnosis of Alzheimer's disease has gained major attention due to the growing prevalence of the disease and the resulting costs imposed on individuals and society. The main objective of this study was to propose an ensemble method based on deep learning for the early diagnosis of AD using MRI images. The methodology of this study consisted of collecting the dataset, preprocessing, creating the individual and ensemble models, evaluating the models based on ADNI data, and validating the trained model based on the local dataset. The proposed method was an ensemble approach selected through a comparative analysis of various ensemble scenarios. Finally, the six best individual CNN-based classifiers were selected to combine and constitute the ensemble model. The evaluation showed an accuracy rate of 98.57, 96.37, 94.22, 99.83, 93.88, and 93.92 for NC/AD, NC/EMCI, EMCI/LMCI, LMCI/AD, four-way and three-way classification groups, respectively. The validation results on the local dataset revealed an accuracy of 88.46 for three-way classification. Our performance results were higher than most reviewed studies and comparable with others. Although comparative analysis showed superior results of ensemble methods against individual architectures, there were no significant differences among various ensemble approaches. The validation results revealed the low performance of individual models in practice. In contrast, the ensemble method showed promising results. However, further studies on various and larger datasets are required to validate the generalizability of the model.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Aprendizaje Profundo , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Diagnóstico PrecozRESUMEN
Ongoing mutations of SARS-CoV-2 present challenges for vaccine development, promising renewed global efforts to create more effective vaccines against coronavirus disease (COVID-19). One approach is to target highly immunogenic viral proteins, such as the spike receptor binding domain (RBD), which can stimulate the production of potent neutralizing antibodies. This study aimed to design and test a subunit vaccine candidate based on the RBD. Bioinformatics analysis identified antigenic regions of the RBD for recombinant protein design. In silico analysis identified the RBD region as a feasible target for designing a recombinant vaccine. Bioinformatics tools predicted the stability and antigenicity of epitopes, and a 3D model of the RBD-angiotensin-converting enzyme 2 complex was constructed using molecular docking and codon optimization. The resulting construct was cloned into the pET-28a (+) vector and successfully expressed in Escherichia coli BL21DE3. As evidenced by sodium dodecyl-polyacrylamide gel electrophoresis and Western blotting analyses, the affinity purification of RBD antigens produced high-quality products. Mice were immunized with the RBD antigen alone or combined with aluminum hydroxide (AlOH), calcium phosphate (CaP), or zinc oxide (ZnO) nanoparticles (NPs) as adjuvants. Enzyme-linked immunosorbent assay assays were used to evaluate immune responses in mice. In-silico analysis confirmed the stability and antigenicity of the designed protein structure. RBD with CaP NPs generated the highest immunoglobulin G titer compared to AlOH and ZnO after three doses, indicating its effectiveness as a vaccine platform. In conclusion, the recombinant RBD antigen administered with CaP adjuvant NPs induces potent humoral immunity in mice, supporting further vaccine development. These results contribute to ongoing efforts to develop more effective COVID-19 vaccines.
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Nanopartículas , Vacunas Virales , Óxido de Zinc , Animales , Ratones , Humanos , Vacunas contra la COVID-19/genética , Anticuerpos Antivirales , Simulación del Acoplamiento Molecular , Vacunas Virales/genética , Modelos Animales , Ratones Endogámicos BALB CRESUMEN
The pathogenesis of antibodies in severe alcoholic hepatitis (SAH) remains unknown. We analyzed immunoglobulins (Ig) in explanted livers from SAH patients (n=45) undergoing liver transplantation and tissues from corresponding healthy donors (HD, n=10) and found massive deposition of IgG and IgA isotype antibodies associated with complement fragment C3d and C4d staining in ballooned hepatocytes in SAH livers. Ig extracted from SAH livers, but not patient serum exhibited hepatocyte killing efficacy. Employing human and Escherichia coli K12 proteome arrays, we profiled the antibodies extracted from explanted SAH, livers with other diseases, and HD livers. Compared with their counterparts extracted from livers with other diseases and HD, antibodies of IgG and IgA isotypes were highly accumulated in SAH and recognized a unique set of human proteins and E. coli antigens. Further, both Ig- and E. coli-captured Ig from SAH livers recognized common autoantigens enriched in several cellular components including cytosol and cytoplasm (IgG and IgA), nucleus, mitochondrion, and focal adhesion (IgG). Except IgM from primary biliary cholangitis livers, no common autoantigen was recognized by Ig- and E. coli-captured Ig from livers with other diseases. These findings demonstrate the presence of cross-reacting anti-bacterial IgG and IgA autoantibodies in SAH livers.
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Hepatitis Alcohólica , Humanos , Escherichia coli , Inmunoglobulina A , Autoanticuerpos , Inmunoglobulina G , Inmunoglobulina MRESUMEN
BACKGROUND: Coxiella burnetii, an intracellular pathogen, serves as the causative agent of zoonotic Q fever. This pathogen presents a significant threat due to its potential for airborne transmission, environmental persistence, and pathogenicity. The current whole-cell vaccine (WCV) utilized in Australia to combat Q fever exhibits notable limitations, including severe adverse reactions and limited regulatory approval for human use. This research employed the reverse vaccinology (RV) approach to uncover antigenic proteins and epitopes of C. burnetii, facilitating the development of more potent vaccine candidates. METHODS: The potential immunogenic proteins derived from C. burnetii RSA493/Nine Mile phase I (NMI) were extracted through manual, automated RV, and virulence factor database (VFDB) methods. Web tools and bioinformatics were used to evaluate physiochemical attributes, subcellular localization, antigenicity, allergenicity, human homology, B-cell epitopes, MHC I and II binding ratios, functional class scores, adhesion probabilities, protein-protein interactions, and molecular docking. RESULTS: Out of the 1850 proteins encoded by RSA493/NMI, a subset of 178 demonstrated the potential for surface or membrane localization. Following a series of analytical iterations, 14 putative immunogenic proteins emerged. This collection included nine proteins (57.1%) intricately involved in cell wall/membrane/envelope biogenesis processes (CBU_0197 (Q83EW1), CBU_0311 (Q83EK8), CBU_0489 (Q83E43), CBU_0939 (Q83D08), CBU_1190 (P39917), CBU_1829 (Q83AQ2), CBU_1412 (Q83BU0), CBU_1414 (Q83BT8), and CBU_1600 (Q83BB2)). The CBU_1627 (Q83B86 ) (7.1%) implicated in intracellular trafficking, secretion, and vesicular transport, and CBU_0092 (Q83F57) (7.1%) contributing to cell division. Additionally, three proteins (21.4%) displayed uncharacterized functions (CBU_0736 (Q83DJ4), CBU_1095 (Q83CL9), and CBU_2079 (Q83A32)). The congruent results obtained from molecular docking and immune response stimulation lend support to the inclusion of all 14 putative proteins as potential vaccine candidates. Notably, seven proteins with well-defined functions stand out among these candidates. CONCLUSIONS: The outcomes of this study introduce promising proteins and epitopes for the forthcoming formulation of subunit vaccines against Q fever, with a primary emphasis on cellular processes and the virulence factors of C. burnetii.
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Coxiella burnetii , Fiebre Q , Humanos , Fiebre Q/prevención & control , Simulación del Acoplamiento Molecular , Vacunas Bacterianas , Factores de Virulencia , EpítoposRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar remodeling. Although the abnormalities are primarily prompted by chronic exposure to inhaled irritants, maladjusted and self-reinforcing immune responses are significant contributors to the development and progression of the disease. The p38 isoforms are regarded as pivotal hub proteins that regulate immune and inflammatory responses in both healthy and disease states. As a result, their inhibition has been the subject of numerous recent studies exploring their therapeutic potential in COPD. MAIN BODY: We performed a systematic search based on the PRISMA guidelines to find relevant studies about P38 signaling in COPD patients. We searched the PubMed and Google Scholar databases and used "P38" AND "COPD" Mesh Terms. We applied the following inclusion criteria: (1) human, animal, ex vivo and in vitro studies; (2) original research articles; (3) published in English; and (4) focused on P38 signaling in COPD pathogenesis, progression, or treatment. We screened the titles and abstracts of the retrieved studies and assessed the full texts of the eligible studies for quality and relevance. We extracted the following data from each study: authors, year, country, sample size, study design, cell type, intervention, outcome, and main findings. We classified the studies according to the role of different cells and treatments in P38 signaling in COPD. CONCLUSION: While targeting p38 MAPK has demonstrated some therapeutic potential in COPD, its efficacy is limited. Nevertheless, combining p38 MAPK inhibitors with other anti-inflammatory steroids appears to be a promising treatment choice. Clinical trials testing various p38 MAPK inhibitors have produced mixed results, with some showing improvement in lung function and reduction in exacerbations in COPD patients. Despite these mixed results, research on p38 MAPK inhibitors is still a major area of study to develop new and more effective therapies for COPD. As our understanding of COPD evolves, we may gain a better understanding of how to utilize p38 MAPK inhibitors to treat this disease. Video Abstract.
We wanted to determine what studies have been done on how a protein called p38 affects a lung disease called COPD. COPD is a condition that makes it hard to breathe and can cause coughing, wheezing, and chest infections. p38 is a protein that helps cells to respond to stress and inflammation, but it may also play a role in causing or worsening COPD. We searched two main online databases for studies that met our criteria. We looked for studies that involved humans, studies that used animals or cells in the lab, studies that reported new findings, studies that were written in English, and studies that focused on p38 and COPD. We did not include studies that were reviews, summaries, opinions, or letters or studies that were not related to p38 or COPD. We found 361 studies that matched our criteria. We read the titles and summaries of these studies and checked the full texts for quality and relevance. We collected information from each study, such as who did it, when and where it was done, how many people were involved, what type of cells were studied, what treatment was given, what outcome was measured, and what the main results were. We grouped the studies based on the type of cells and type of treatment they studied. We found that different types of cells (such as lung cells, immune cells, and blood cells) and different types of treatment can affect how p38 works in COPD.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológicoRESUMEN
Social media contains useful information about people and society that could help advance research in many different areas of health (e.g. by applying opinion mining, emotion/sentiment analysis and statistical analysis) such as mental health, health surveillance, socio-economic inequality and gender vulnerability. User demographics provide rich information that could help study the subject further. However, user demographics such as gender are considered private and are not freely available. In this study, we propose a model based on transformers to predict the user's gender from their images and tweets. The image-based classification model is trained in two different methods: using the profile image of the user and using various image contents posted by the user on Twitter. For the first method a Twitter gender recognition dataset, publicly available on Kaggle and for the second method the PAN-18 dataset is used. Several transformer models, i.e. vision transformers (ViT), LeViT and Swin Transformer are fine-tuned for both of the image datasets and then compared. Next, different transformer models, namely, bidirectional encoders representations from transformers (BERT), RoBERTa and ELECTRA are fine-tuned to recognize the user's gender by their tweets. This is highly beneficial, because not all users provide an image that indicates their gender. The gender of such users could be detected from their tweets. The significance of the image and text classification models were evaluated using the Mann-Whitney U test. Finally, the combination model improved the accuracy of image and text classification models by 11.73 and 5.26% for the Kaggle dataset and by 8.55 and 9.8% for the PAN-18 dataset, respectively. This shows that the image and text classification models are capable of complementing each other by providing additional information to one another. Our overall multimodal method has an accuracy of 88.11% for the Kaggle and 89.24% for the PAN-18 dataset and outperforms state-of-the-art models. Our work benefits research that critically require user demographic information such as gender to further analyze and study social media content for health-related issues.