The effects of methotrexate on the immune responses to the COVID-19 vaccines in the patients with immune-mediated inflammatory disease: A systematic review of clinical evidence.

COVID-19 vaccines exhibit high levels of immunogenicity in the overall population. Data on the effects of immunomodulators on the consequences of COVID-19 in patients with Immune-mediated inflammatory diseases (IMIDs) remains scarce. This systematic review aimed to evaluate the immune responses to the COVID-19 vaccines in IMID patients receiving methotrexate (MTX) compared to healthy individuals. A comprehensive literature search was carried out using electronic databases such as PubMed, Web of Science, Scopus, Google Scholar, and Embase up to August 2022 to identify eligible RCTs evaluating the effect of MTX on immune responses in patients with COVID-19. The PRISMA checklist protocol was applied for the quality assessment of the selected trials. Our findings demonstrated that MTX lowered the responses of T cells and antibodies in IMID patients compared to healthy controls. We also discovered that young age (<60 years) was the main parameter influencing the antibody response after vaccination, while MTX had little effect. Following vaccination, MTX-hold and age were considered the main factors influencing the antibody response. In patients older than 60 years of age, the time point of 10 days of MTX discontinuation was critical to boosting the humoral response to anti-SARS-CoV-2 IgG. Because many IMID patients did not have adequate humoral and cellular responses, our findings highlighted the importance of second or booster doses of vaccine and temporary MTX discontinuation. As a result, it implies that individuals with IMIDs should be subjected to more research, particularly humoral and cellular immunity efficiency trials after COVID-19 vaccination, until credible information is achieved.

Exosomal non-coding RNAs' role in immune regulation and potential therapeutic applications.

Exosomes are now significant players in both healthy and unhealthy cell-to-cell communication. Exosomes can mediate immune activation or immunosuppression, which can influence the growth of tumors. Exosomes affect the immune responses to malignancies in various ways by interacting with tumor cells and the environment around them. Exosomes made by immune cells can control the growth, metastasis, and even chemosensitivity of tumor cells. In contrast, exosomes produced by cancer cells can encourage immune responses that support the tumor. Exosomes carry circular RNAs, long non-coding RNAs, and microRNAs (miRNAs), all involved in cell-to-cell communication. In this review, we focus on the most recent findings concerning the role of exosomal miRNAs, lncRNAs, and circRNAs in immune modulation and the potential therapeutic implications of these discoveries.

Molecular mechanisms of long non-coding RNAs in differentiation of T Helper17 cells.

T helper (Th) 17 cells are one of the most important T cell subsets in a number of autoimmune and chronic inflammatory diseases. During infections, Th17 cells appear to play an important role in the clearance of extracellular pathogens. Th17 cells, on the other hand, are engaged in inflammation and have been linked to the pathophysiology of a number of autoimmune illnesses and human inflammatory disorders. A diverse group of RNA molecules known as lncRNAs serve critical functions in gene expression regulation. They may interact with a wide range of molecules, including DNA, RNA, and proteins, and have a complex structure. LncRNAs, which have restricted or no protein-coding activity, are implicated in a number of illnesses due to their regulatory impact on a variety of biological processes such as cell proliferation, apoptosis, and differentiation. Several lncRNAs have been associated with Th7 cell development in the context of immune cell differentiation. In this article, we cover new studies on the involvement of lncRNAs in Th17 cell differentiation in a variety of disorders, including auto-immune diseases, malignancies, asthma, heart disease, and infections.

miR-199a-3p suppresses neuroinflammation by directly targeting MyD88 in a mouse model of bone cancer pain.

AIMS: Pain is a profoundly debilitating symptom in cancer patients, leading to disability, immobility, and a marked decline in their quality of life. This study aimed to investigate the potential roles of miR-199a-3p in a murine model of bone cancer pain induced by tumor cell implantation in the medullary cavity of the femur. MATERIALS AND METHODS: We assessed pain-related behaviors, including the paw withdrawal mechanical threshold (PWMT) and the number of spontaneous flinches (NSF). To investigate miRNA expression and its targets in astrocytes, we employed a combination of RNA-seq analysis, qRT-PCR, Western blotting, EdU, TUNEL, ChIP, ELISA, and luciferase reporter assays in mice (C3H/HeJ) with bone cancer pain and control groups. KEY FINDINGS: On days 10, 14, 21, and 28 post-surgery, we observed significant differences in PWTL, PWMT, and NSF when compared to the sham group (P < 0.001). qRT-PCR assays and miRNA sequencing results confirmed reduced miR-199a-3p expression in astrocytes of mice with bone cancer pain. Gain- and loss-of-function experiments demonstrated that miR-199a-3p suppressed astrocyte activation and the expression of inflammatory cytokines. In vitro investigations revealed that miR-199a-3p mimics reduced the levels of inflammatory factors in astrocytes and MyD88/NF-κB proteins. Furthermore, treatment with a miR-199a-3p agonist resulted in reduced expression of MyD88, TAK1, p-p65, and inflammatory mediators, along with decreased astrocyte activation in the spinal cord. SIGNIFICANCE: Collectively, these findings demonstrate that upregulation of miR-199a-3p may offer a therapeutic avenue for mitigating bone cancer pain in mice by suppressing neuroinflammation and inhibiting the MyD88/NF-κB signaling pathway.

The protective role of sulforaphane and Homer1a in retinal ischemia-reperfusion injury: Unraveling the neuroprotective interplay.

AIMS: Retinal ischemia/reperfusion (I/R) injury is a common pathological basis for various ophthalmic diseases. This study aimed to investigate the potential of sulforaphane (SFN) and Homer1a in regulating cell apoptosis induced by retinal I/R injury and to explore the underlying regulatory mechanism between them. MATERIALS AND METHODS: In in vivo experiments, C57BL/6J mice and Homer1flox/-/Homer1a+/-/Nestin-Cre+/- mice were used to construct retinal I/R injury models. In vitro experiments utilized the oxygen-glucose deprivation-reperfusion (OGD/R) injury model with primary retinal ganglion cells (RGCs). The effects of Homer1a and SFN on cell apoptosis were observed through pathological analyses, flow cytometry, and visual electrophysiological assessments. KEY FINDINGS: We discovered that after OGD/R injury, apoptosis of RGCs and intracellular Ca2+ activity significantly increased. However, these changes were reversed upon the addition of SFN, and similar observations were reproduced in in vivo studies. Furthermore, both in vivo and in vitro studies confirmed the upregulation of Homer1a after I/R, which could be further enhanced by the administration of SFN. Moreover, upregulation of Homer1a resulted in a reduction in cell apoptosis and pro-apoptotic proteins, while downregulation of Homer1a had the opposite effect. Flash visual evoked potential, oscillatory potentials, and escape latency measurements in mice supported these findings. Furthermore, the addition of SFN strengthened the neuroprotective effects in the OGD/R + H+ group but weakened them in Homer1flox/-/Homer1a+/-/Nestin-Cre+/- mice. SIGNIFICANCE: These results indicate that Homer1a plays a significant role in the therapeutic potential of sulforaphane for retinal I/R injury, thereby providing a theoretical basis for clinical treatment.

A Feature Extraction Using Probabilistic Neural Network and BTFSC-Net Model with Deep Learning for Brain Tumor Classification.

BACKGROUND AND OBJECTIVES: Brain Tumor Fusion-based Segments and Classification-Non-enhancing tumor (BTFSC-Net) is a hybrid system for classifying brain tumors that combine medical image fusion, segmentation, feature extraction, and classification procedures. MATERIALS AND METHODS: to reduce noise from medical images, the hybrid probabilistic wiener filter (HPWF) is first applied as a preprocessing step. Then, to combine robust edge analysis (REA) properties in magnetic resonance imaging (MRI) and computed tomography (CT) medical images, a fusion network based on deep learning convolutional neural networks (DLCNN) is developed. Here, the brain images' slopes and borders are detected using REA. To separate the sick region from the color image, adaptive fuzzy c-means integrated k-means (HFCMIK) clustering is then implemented. To extract hybrid features from the fused image, low-level features based on the redundant discrete wavelet transform (RDWT), empirical color features, and texture characteristics based on the gray-level cooccurrence matrix (GLCM) are also used. Finally, to distinguish between benign and malignant tumors, a deep learning probabilistic neural network (DLPNN) is deployed. RESULTS: according to the findings, the suggested BTFSC-Net model performed better than more traditional preprocessing, fusion, segmentation, and classification techniques. Additionally, 99.21% segmentation accuracy and 99.46% classification accuracy were reached using the proposed BTFSC-Net model. CONCLUSIONS: earlier approaches have not performed as well as our presented method for image fusion, segmentation, feature extraction, classification operations, and brain tumor classification. These results illustrate that the designed approach performed more effectively in terms of enhanced quantitative evaluation with better accuracy as well as visual performance.

Factores de riesgo y parasitosis intestinal en niños menores de 10 años de la olla común / Risk factors and intestinal parasitosis in children under 10 years of age from the common pot

Diversos factores de riesgos pueden condicionar las prevalencias de parasitosis intestinales en niños. Como objetivo se propuso determinar los factores de riesgo y parasitosis intestinal en niños menores de 10 años de la Olla Común ubicada en Villa Mara del Triunfo-Perú durate el año 2022. La investigación fue descriptiva-experimental y correlativa con una muestra de 160 niños <10 años de ambos sexos. Como instrumento de recolección se aplicó un cuestionario con preguntas dicotómicas para conocer las prácticas de higiene de los niños y se efectuó la recolección y procesamiento de muestras con técnicas de Solución Salina S.S.F al 85%, Lugol, Método de Kato y Método de concentración-Flotación de Faust. Para analizar los datos se utilizó Microsoft Excel y el software SPSS, estadística descriptica y hallar tablas de frecuencias y porcentajes y Prueba de correlación entre los elementos de riesgo y la frecuencia de signos de los parásitos. Como resultado, el cálculo estadístico con el método de Spearman mostró una concordancia positiva con el coeficiente de correlación 0,725 y con un valor de 0,001<0,05; donde los niveles de factores de riesgo en los infantes mostraron que el 31,3% se encontraban en riesgo bajo con un nivel bajo de síntomas y sin evidencia de parásitos intestinales, el 18,8% en riesgo medio y el 12,5% en riesgo alto y un nivel alto de síntomas y parasitosis intestinal confirmado; la mayoría de los niños se encuentran en un entorno de bajo riesgo. Se hace necesario e indispensable continuar con invesigaciones en zonas adyacentes(AU)

Various risk factors can condition the prevalence of intestinal parasitosis in children. The objective was to determine the risk factors and intestinal parasitosis in children under 10 years of age from the Common Pot located in Villa Mara del Triunfo-Peru during the year 2022. The research was descriptive-experimental and correlative with a sample of 160 children <10 years of both sexes. As a collection instrument, a questionnaire with dichotomous questions was applied to know the hygiene practices of the children and the collection and processing of samples was carried out with techniques of Saline Solution S.S.F at 85%, Lugol's, Kato's Method and Concentration-Flotation Method. of Faust. To analyze the data, Microsoft Excel and the SPSS software were used, descriptive statistics and finding tables of frequencies and percentages and a correlation test between the risk elements and the frequency of signs of the parasites. As a result, the statistical calculation with the Spearman method showed a positive agreement with the correlation coefficient 0.725 and with a p value of 0.001<0.05; where the levels of risk factors in infants showed that 31.3% were at low risk with a low level of symptoms and no evidence of intestinal parasites, 18.8% at medium risk and 12.5% at high risk and a high level of symptoms and confirmed intestinal parasitism; most children are in a low-risk environment. It is necessary and essential to continue with investigations in adjacent areas(AU)