Objective: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity. Methods: We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients. Methods: We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients. Results: RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p = 0.032 OR = 1.59, C.I. 1.02–2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p = 0.026). The RA patients showed higher sCD28 serum levels than HS (p = 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p = 0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272; p = 0.016), was found. Conclusion: The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients.

Prolactin (PRL) is a hormone produced by the pituitary gland and multiple non-pituitary sites, vital in several physiological processes such as lactation, pregnancy, cell growth, and differentiation. However, PRL is nowadays known to have a strong implication in oncogenic processes, making it essential to delve into the mechanisms governing these actions. PRL and its receptor (PRLR) activate a series of effects such as survival, cellular proliferation, migration, invasion, metastasis, and resistance to treatment, being highly relevant in developing certain types of cancer. Because women produce high levels of PRL, its influence in gynecological cancers is herein reviewed. It is interesting that, other than the 23 kDa PRL, whose mechanism of action is endocrine, other variants of PRL have been observed to be produced by tumoral tissue, acting in a paracrine/autocrine manner. Because many components, including PRL, surround the microenvironment, it is interesting to understand the hormone’s modulation in cancer cells. This work aims to review the most important findings regarding the PRL/PRLR axis in cervical, ovarian, and endometrial cancers and its molecular mechanisms to support carcinogenesis.

BackgroundNKG2D, an activating immunoreceptor, is primarily restricted to NK cells and CD8+ T cells. The existence of an atypical cytotoxic CD4+NKG2D+ T cell population has also been found in patients with autoimmune dysfunctions. Nonetheless, contradictory evidence has categorized this population with a regulatory rather than cytotoxic role in other situations. These confounding data have led to the proposal that two distinct CD4+NKG2D+ T cell subsets might exist. The immune response elicited in cervical cancer has been characterized by apparent contradictions concerning the role that T cells, in particular T-helper cells, might be playing in the control of the tumor growth. Interestingly, we recently reported a substantial increase in the frequency of CD4+NKG2D+ T cells in patients with cervical intraepithelial neoplasia grade-1. However, whether this particular population is also found in patients with more advanced cervical lesions or whether they express a distinctive phenotype remains still to be clarified. In this urgent study, we focused our attention on the immunophenotypic characterization of CD4+NKG2D+ T cells in patients with well-established cervical carcinoma and revealed the existence of at least two separate CD4+NKG2D+ T cell subsets defined by the co-expression or absence of CD28.ResultsPatients with diagnosis of invasive cervical carcinoma were enrolled in the study. A group of healthy individuals was also included. Multicolor flow cytometry was used for exploration of TCR alpha/beta, CD28, CD158b, CD45RO, HLA-DR, CD161, and CD107a. A Luminex-based cytokine kit was used to quantify the levels of pro- and anti-inflammatory cytokines. We found an increased percentage of CD4+NKG2D+ T cells in patients with cervical cancer when compared with controls. Accordingly with an increase of CD4+NKG2D+ T cells, we found decreased CD28 expression. The activating or degranulation markers HLA-DR, CD161, and CD107a were heterogeneously expressed. The levels of IL-1beta, IL-2, TNF-alpha, and IL-10 were negatively correlated with the percentages of CD4+NKG2D+ T cells in patients with cervical carcinoma.ConclusionsTaken together, our results reveal the existence of two separate CD4+NKG2D+ T cell subsets defined by the co-expression or absence of CD28, the latter more likely to be present in patients with cervical cancer.

Estrogens are hormones that have been extensively presented in many types of cancer such as breast, uterus, colorectal, prostate, and others, due to dynamically integrated signaling cascades that coordinate cellular growth, differentiation, and death which can be potentially new therapeutic targets. Despite the historical use of estrogens in the pathogenesis of prostate cancer (PCa), their biological effect is not well known, nor their role in carcinogenesis or the mechanisms used to carry their therapeutic effects of neoplastic in prostate transformation. The expression and regulation of the estrogen receptors (ERs) ERα, ERβ, and GPER stimulated by agonists and antagonists, and related to prostate cancer cells are herein reviewed. Subsequently, the structures of the ERs and their splice variants, the binding of ligands to ERs, and the effect on PCa are provided. Finally, we also assessed the contribution of molecular simulation which can help us to search and predict potential estrogenic activities.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the pathogen agent causing coronavirus disease (COVID)-19, which was declared a global pandemic in 2020. The spike protein of this virus and the angiotensin-converter enzyme (ACE)-2 in host cells in humans play a vital role in infection and in COVID-19 pathogenesis. Estradiol is known to modulate the actions of immune cells, and, therefore, the antiviral mechanisms of these cells could also be modified by this hormone stimulus. Even though estradiol is not considered a protective factor, evidence shows that women with high levels of this hormone have a lower risk of developing severe symptoms and an even a lower incidence of death. Understanding the mechanism of action of estradiol with regard to viral infections and COVID-19 is essential for the improvement of therapeutic strategies. This review aims to describe the effects that estradiol exerts on immune cells during viral infections and COVID-19.

Aim Intestinal dysfunction in cirrhosis patients is linked to death by bacterial infections. Currently, there is no effective therapy for this complication. This study aims to evaluate butyrate, a novel postbiotic, on the intestinal inflammatory response, tight junction proteins and the microbiota in the cholestasis model. Methods and Results Wistar rats underwent 15 days of bile duct ligation (BDL). We administered butyrate at a concentration of 1%. The BDL group did not receive treatment. The results showed that butyrate could significantly reduce pro‐inflammatory cytokines (IL‐17A, IFN‐γ, TNF‐α) in the ileum and colon while promoting IL‐10 expression in the colon. Moreover, it significantly promotes tight junction protein (cld‐1, occludin and ZO‐1) expression in the ileum. A similar effect was observed in the colon except for ZO‐1. Additionally, butyrate limited taxa diversity loss and promoted probiotic genera expansion such as Lachnospira, Prevotella and Lactobacillus. The increase in Turicibacter and Clostridiaceae distinguished the BDL group. Conclusions Butyrate is effective in regulating the inflammatory response, tight junction proteins and limits bacterial diversity loss. Significance and Impact of the Study This research reveals that butyrate could represent an interesting postbiotic metabolomic intervention for intestinal epithelium dysfunction in liver disease.

Due to the COVID-19 pandemic, the rapid development of vaccines against SARS-CoV-2 has been promoted. BNT162b2 is a lipid-nanoparticle mRNA vaccine with 95% efficacy and is the most administered vaccine globally. Nevertheless, little is known about the cellular immune response triggered by vaccination and the immune behavior over time. Therefore, we evaluated the T-cell immune response against the SARS-CoV-2 spike protein and neutralization antibodies (nAbs) in naïve and SARS-CoV-2 previously infected subjects vaccinated with BTN162b2. Methods: Forty-six BTN162b2 vaccinated subjects were included (twenty-six naïve and twenty SARS-CoV-2 previously infected subjects vaccinated with BTN162b2). Blood samples were obtained at basal (before vaccination), 15 days after the first dose, and 15 days after the second dose, to evaluate cellular immune response upon PBMC’s stimulation and cytokine levels. The nAbs were determined one and six months after the second dose. Results: SARS-CoV-2 previously infected subjects vaccinated with BTN162b2 showed the highest proportion of nAbs compared to naïve individuals one month after the second dose. However, women were more prone to lose nAbs percentages over time significantly. Furthermore, a diminished CD154+ IFN-γ+ CD4+ T-cell response was observed after the second BTN162b2 dose in those with previous SARS-CoV-2 infection. In contrast, naïve participants showed an overall increased CD8+ IFN-γ+ TNF-α+ T-cell response to the peptide stimulus. Moreover, a significant reduction in IP-10, IFN-λI, and IL-10 cytokine levels was found in both studied groups. Additionally, the median fluorescence intensity (MFI) levels of IL-6, IFNλ-2/3, IFN-𝛽, and GM-CSF (p < 0.05) were significantly reduced over time in the naïve participants. Conclusion: We demonstrate that a previous SARS-CoV-2 infection can also impact cellular T-cell response, nAbs production, and serum cytokine concentration. Therefore, the study of T-cell immune response is essential for vaccination scheme recommendations; future vaccine boost should be carefully addressed as continued stimulation by vaccination might impact the T-cell response.

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