Association between rs662 (A > G) and rs854560 (A > T) polymorphisms in PON1 gene and the susceptibility for psoriasis in mestizo population of Western Mexico.

Psoriasis is a chronic, autoimmune skin disease. In psoriasis, PON1 activity is diminished and peroxidation biomarkers are elevated. The most studied PON1 polymorphisms are rs662 (A > G) and rs854560 (A > T), which have been associated with the antioxidant activity of PON1, risk of cardiovascular diseases and psoriasis development. The aim of this study, was to determine the association of rs662 (A > G) and rs854560 (A > T) PON1 polymorphisms with psoriasis susceptibility in Western Mexico population. In this case-control study, we included 104 psoriasis patients and 124 control subjects. The genotyping of polymorphisms rs662 (A > G) and rs854560 (A > T) of PON1 was carried out by PCR-RFLPs. The lipid profiles were quantified by enzymatic colorimetric method, and PON1 activity was determined by spectrophotometry. The lipid profile levels, except HDL-C and atherogenic index, were higher in patients vs. controls. Patients presented lower paraoxonase and arylesterase activity. The G allele of rs662 (A > G) is associated with risk for psoriasis, while the T allele of rs854560 (A > T) is associated with low susceptibility to psoriasis. The AG haplotype was more frequent within the patient group (p < 0.05). The AA and AG genotypes of rs662 (A > G) and TT and AA genotypes of rs854560 (A > T) are associated with lower PONase and ARE activity in patients vs. controls. Patients with the G allele of rs662 (G > A) and T alleles of rs854560 (A > T) show significant differences in the lipid levels in comparison to controls. These results suggest that carriers of G allele of rs662 (A > G) present a greater susceptibility to psoriasis.

Recombinant p40 Protein Promotes Expression of Occludin in HaCaT Keratinocytes: A Brief Communication.

The ability of epithelial barriers to perform as the first defense line against external damage derives from tight junctions, protein complexes that block microorganisms through the paracellular space. Indeed, disturbances of barrier permeability caused by bacterial metabolites and other inflammatory stimuli are the consequence of changes in protein expression in these complexes. Postbiotics, molecules derived from bacteria with beneficial effects on the host, improve barrier function through the activation of survival pathways in epithelial cells. Lacticaseibacillus rhamnosus GG secretes the muramidase p40, which protects intestinal barriers through an EGFR-dependent pathway. In this work, we cloned, expressed, and purified the recombinant p40 protein from L. rhamnosus GR-1 to evaluate its effect on cell viability, cell cytotoxicity, TEER, and protein levels of tight junctions, as well as EGFR activation via Western blot on HaCaT keratinocytes subjected to LPS. We found a novel mutation at residue 368 that does not change the structure of p40. Our protein also reduces the LPS-induced increase in cell cytotoxicity when it is added prior to this stimulus. Furthermore, although LPS did not cause changes in barrier function, p40 increased TEER and occludin expression in HaCaT, but unlike previous work with p40 from LGG, we found that recombinant p40 did not activate EGFR. This suggests that recombinant p40 enhances epithelial barrier function through distinct signaling pathways.

Association of SNP rs5069 in APOA1 with Benign Breast Diseases in a Mexican Population.

Breast cancer (BCa) is the most common type of cancer affecting women worldwide. Some histological subtypes of benign breast disease (BBD) are considered risk factors for developing BCa. Single nucleotide polymorphisms (SNPs) in the genes encoding apolipoproteins A-I (APOA1) and B (APOB) have been associated with BCa in Tunisian, Chinese, and Taiwanese populations. The objective of this pilot study is to evaluate the possible contribution of APOA1 and APOB polymorphisms to BCa and BBD in the Mexican population. We analyzed the association of 4 SNPs in genes encoding apolipoproteins: rs670 and rs5069 in the APOA1 gene, and rs693 and rs1042031 in the APOB gene, by performing PCR-RFLP with DNA extracted from the biopsy tissue of Mexican women with BCa or BBD and whole blood samples obtained from the general population (GP). Our results showed an association between the CT + TT genotypes of the SNP rs5069 and BBD (p = 0.03201). In the A-T haplotype, the frequency of the SNPs rs670 and rs5069 differed significantly between the BBD group and the GP and BCa groups (p = 0.004111; p = 0.01303). In conclusion, the SNP rs5069 is associated with BBD but not with BCa in the Mexican population.

Probiotics: Protecting Our Health from the Gut.

The gut microbiota (GM) comprises billions of microorganisms in the human gastrointestinal tract. This microbial community exerts numerous physiological functions. Prominent among these functions is the effect on host immunity through the uptake of nutrients that strengthen intestinal cells and cells involved in the immune response. The physiological functions of the GM are not limited to the gut, but bidirectional interactions between the gut microbiota and various extraintestinal organs have been identified. These interactions have been termed interorganic axes by several authors, among which the gut-brain, gut-skin, gut-lung, gut-heart, and gut-metabolism axes stand out. It has been shown that an organism is healthy or in homeostasis when the GM is in balance. However, altered GM or dysbiosis represents a critical factor in the pathogenesis of many local and systemic diseases. Therefore, probiotics intervene in this context, which, according to various published studies, allows balance to be maintained in the GM, leading to an individual's good health.

To Trap a Pathogen: Neutrophil Extracellular Traps and Their Role in Mucosal Epithelial and Skin Diseases.

Neutrophils are the most abundant circulating innate immune cells and comprise the first immune defense line, as they are the most rapidly recruited cells at sites of infection or inflammation. Their main microbicidal mechanisms are degranulation, phagocytosis, cytokine secretion and the formation of extracellular traps. Neutrophil extracellular traps (NETs) are a microbicidal mechanism that involves neutrophil death. Since their discovery, in vitro and in vivo neutrophils have been challenged with a range of stimuli capable of inducing or inhibiting NET formation, with the objective to understand its function and regulation in health and disease. These networks composed of DNA and granular components are capable of immobilizing and killing pathogens. They comprise enzymes such as myeloperoxidase, elastase, cathepsin G, acid hydrolases and cationic peptides, all with antimicrobial and antifungal activity. Therefore, the excessive formation of NETs can also lead to tissue damage and promote local and systemic inflammation. Based on this concept, in this review, we focus on the role of NETs in different infectious and inflammatory diseases of the mucosal epithelia and skin.

Cytokines and nervous system: relationship with schizophrenia / Citocinas y sistema nervioso: relación con la esquizofrenia

Schizophrenia is a heterogeneous disorder of mental symptoms and alterations, characterized by presenting abnormal ideas and perceptions, in which the individual loses contact with reality as a result of a complex neuropsychological disorganization, which affects the affective, intellectual and behavioral functioning; as well as inducing a significant social dysfunction. The etiology of schizophrenia is extremely complex, and is not very clear yet; it is believed to be the result of the combination of genetic factors and the environment. Numerous neurotransmitters have been implicated in this disease, as is the case of dopamine, serotonin and glutamate. The role of the inflammatory process in the pathogenesis of schizophrenia has been postulated, where a prenatal immune "challenge" during the second trimester of pregnancy can be key to the development of the disease. Some of the pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) play a key role in the processes of modulation of the nervous system functions related to affective, emotional and social alterations in subjects with schizophrenia. The mechanisms associated with inflammation and the anti-inflammatory defense system that may be associated with the development of schizophrenia are still unknown. This review was intended to address schizophrenia, in regards to the mechanisms associated with inflammation and the anti-inflammatory defense system in its development.

La esquizofrenia es un trastorno heterogéneo de síntomas y alteraciones mentales, caracterizadas por presentar ideas y percepciones anormales, en el que el individuo pierde contacto con la realidad a consecuencia de una compleja desorganización neuropsicológica, lo cual afecta el funcionamiento afectivo, intelectual y de comportamiento; asimismo, conlleva una disfunción social significativa. La etiología de la esquizofrenia aún no está establecida con claridad. Numerosos neurotransmisores han sido implicados en esta enfermedad, como es el caso de la dopamina, la serotonina y el glutamato. Se ha postulado el papel del proceso inflamatorio en la patogenia de la esquizofrenia, donde un "desafío" inmune prenatal durante el segundo trimestre de la gestación puede ser clave para el desarrollo de la enfermedad. Algunas de las citocinas proinflamatorias (TNF-alfa, IL-1beta e IL-6) juegan un papel clave en los procesos de modulación de las funciones del sistema nervioso relacionadas con alteraciones afectivas, emocionales y sociales en los sujetos con esquizofrenia. Aún se desconocen los mecanismos asociados con la inflamación y el sistema de defensa antiinflamatorio que pudieran intervenir en el desarrollo de la esquizofrenia. Esta revisión tuvo el propósito de tratar sobre la esquizofrenia, en lo que respecta a los mecanismos asociados con la inflamación y el sistema de defensa antiinflamatorio en su desarrollo.

Microbiota and Its Role on Viral Evasion: Is It With Us or Against Us?

Viruses are obligate intracellular pathogens that require the protein synthesis machinery of the host cells to replicate. These microorganisms have evolved mechanisms to avoid detection from the host immune innate and adaptive response, which are known as viral evasion mechanisms. Viruses enter the host through skin and mucosal surfaces that happen to be colonized by communities of thousands of microorganisms collectively known as the commensal microbiota, where bacteria have a role in the modulation of the immune system and maintaining homeostasis. These bacteria are necessary for the development of the immune system and to prevent the adhesion and colonization of bacterial pathogens and parasites. However, the interactions between the commensal microbiota and viruses are not clear. The microbiota could confer protection against viral infection by priming the immune response to avoid infection, with some bacterial species being required to increase the antiviral response. On the other hand, it could also help to promote viral evasion of certain viruses by direct and indirect mechanisms, with the presence of the microbiota increasing infection and viruses using LPS and surface polysaccharides from bacteria to trigger immunosuppressive pathways. In this work, we reviewed the interaction between the microbiota and viruses to prevent their entry into host cells or to help them to evade the host antiviral immunity. This review is focused on the influence of the commensal microbiota in the viruses' success or failure of the host cells infection.