Post-Coronavirus Disease 2019 Syndrome in Japan: An Observational Study Using a Medical Database.

Introduction: In Japan, the clinical information on post-COVID-19 syndrome, including nursing care requirements, is limited. The present study investigated the incidence of acute and post-COVID-19 symptoms, including nursing care requirements, when different SARS-CoV2 strains were prevalent and vaccination statuses changed to mass vaccination programs in Japan. Methods: Electronic health records of 122,045 patients diagnosed with COVID-19 between January 1, 2020, and June 30, 2022, were obtained from the Tokushukai Group Medical Database. Patient data was divided into three observation periods. Using the International Statistical Classification of Diseases and Related Health Problems 10 codes, typical symptoms of acute (within two weeks after diagnosis) and post-COVID-19 (2-12 weeks after diagnosis) were extracted. Moreover, the nursing care requirements of patients who visited the hospital before and after the COVID-19 diagnosis were examined. Results: Original and alpha strains were prevalent in Period 1, wherein most of the population was unvaccinated. The delta strain was prevalent in Period 2, wherein approximately 70% of the population was vaccinated. The omicron strain was prevalent in Period 3, wherein approximately 70% of the population completed the two vaccination doses. Headache, malaise/fatigue, depression, and disuse syndrome were detected in acute and post-COVID-19. The incidence of depression and disuse syndrome in post-COVID-19 increased with age, with the highest incidence in the 60-85-year group. Moreover, increased high-level nursing care requirements were observed after COVID-19 in the 60-85-year-age group. Conclusions: A lower incidence of acute and post-COVID-19 symptoms in Japan is linked to increased population vaccination coverage. However, differences in viral strains may be involved. Moreover, a reduction in long-term quality of life exists in older adult patients after COVID-19. These data provide fundamental information for preventing and treating post-COVID-19 syndrome in Japan.

19n01, a broadly neutralizing antibody against omicron BA.1, BA.2, BA.4/5, and other SARS-CoV-2 variants of concern.

This study reports the isolation and characterization of a human monoclonal antibody (mAb) called 19n01. This mAb was isolated by using single-cell RNAseq of B cells from donors infected with the ancestral strain. This mAb possesses a potent and broad capacity to bind and neutralize all previously circulating variants of concern (VOCs), including Omicron sublineages BA.1, BA.2, and BA.4/5. The pseudovirus neutralization assay revealed robust neutralization capacity against the G614 strain, BA.1, BA.2, and BA.4/5, with inhibitory concentration (IC50) values ranging from 0.0035 to 0.0164 µg/mL. The microneutralization assay using the G614 strain and VOCs demonstrated IC50 values of 0.013-0.267 µg/mL. Biophysical and structural analysis showed that 19n01 cross-competes with ACE2 binding to the receptor-binding domain (RBD) and the kinetic parameters confirmed the high affinity against the Omicron sublineages (KD of 61 and 30 nM for BA.2 and BA.4/5, respectively). These results suggest that the 19n01 is a remarkably potent and broadly reactive mAb.

Construction of a T cell receptor signaling range for spontaneous development of autoimmune disease.

Thymic selection and peripheral activation of conventional T (Tconv) and regulatory T (Treg) cells depend on TCR signaling, whose anomalies are causative of autoimmunity. Here, we expressed in normal mice mutated ZAP-70 molecules with different affinities for the CD3 chains, or wild type ZAP-70 at graded expression levels under tetracycline-inducible control. Both manipulations reduced TCR signaling intensity to various extents and thereby rendered those normally deleted self-reactive thymocytes to become positively selected and form a highly autoimmune TCR repertoire. The signal reduction more profoundly affected Treg development and function because their TCR signaling was further attenuated by Foxp3 that physiologically repressed the expression of TCR-proximal signaling molecules, including ZAP-70, upon TCR stimulation. Consequently, the TCR signaling intensity reduced to a critical range generated pathogenic autoimmune Tconv cells and concurrently impaired Treg development/function, leading to spontaneous occurrence of autoimmune/inflammatory diseases, such as autoimmune arthritis and inflammatory bowel disease. These results provide a general model of how altered TCR signaling evokes autoimmune disease.

CD36 gene polymorphism -31118 G > A (rs1761667) is associated with overweight and obesity but not with fat preferences in Mexican children.

CD36 glycoprotein is a candidate receptor involved in the gustatory detection of lipids and emerging evidence has suggested that genetic variations in CD36 may modulate the oral perception threshold to fatty acids. Here, we analyzed the association of -31118 G > A polymorphism in CD36 gene with nutritional status and preferences for fatty foods in Mexican children. Genotyping of SNP rs1761667 was performed in school-age children (n = 63) in addition to sensory tests evaluating the preference and satisfaction score assigned to oil-based sauces of different fatty acid composition. The G allele was associated with high BMI z-score in children (OR = 2.43, 95% (CI 1.02-5.99); p = 0.02) but CD36 genotypes (AA, GA, and GG) did not show significant association with the preference and satisfaction scores assigned to oil-based sauces. The BMI z-score showed no association with the preference to oil-based sauces; however, children with normal weight gave higher satisfaction scores to sauces with a high content of unsaturated fatty acids than to sauces rich in saturated fatty acids (0.56 ± 1.26 vs. 0.06 ± 1.22; p = 0.02). Therefore, the G allele of -31118 G > A SNP in CD36 gene is associated with overweight and obesity in Mexican children but do not appear to modulate the preferences and satisfaction scores to fat.

Troublesome friends within us: the role of gut microbiota on rheumatoid arthritis etiopathogenesis and its clinical and therapeutic relevance.

The role of gut microbiota on immune regulation and the development of autoimmune diseases such as rheumatoid arthritis (RA) is an emerging research topic. Multiple studies have demonstrated alterations on gut microbiota composition and/or function (referred to as dysbiosis) both in early and established RA patients. Still, research delineating the molecular mechanisms by which gut microorganisms induce the loss of immune tolerance or contribute to disease progression is scarce. Available data indicate that gut microbiota alterations are involved in RA autoimmune response by several mechanisms including the post-translational modification of host proteins, molecular mimicry between bacterial and host epitopes, activation of immune system and polarization toward inflammatory phenotypes, as well as induction of intestinal permeability. Therefore, in this review we analyze recent clinical and molecular evidence linking gut microbiota with the etiopathogenesis of RA. The potential of the gut microbiota as a diagnostic or severity biomarker is discussed, as well as the opportunity areas for the development of complementary therapeutic strategies based on the modulation of gut microbiota in the rheumatic patient.

Methods for sequence and structural analysis of B and T cell receptor repertoires.

B cell receptors (BCRs) and T cell receptors (TCRs) make up an essential network of defense molecules that, collectively, can distinguish self from non-self and facilitate destruction of antigen-bearing cells such as pathogens or tumors. The analysis of BCR and TCR repertoires plays an important role in both basic immunology as well as in biotechnology. Because the repertoires are highly diverse, specialized software methods are needed to extract meaningful information from BCR and TCR sequence data. Here, we review recent developments in bioinformatics tools for analysis of BCR and TCR repertoires, with an emphasis on those that incorporate structural features. After describing the recent sequencing technologies for immune receptor repertoires, we survey structural modeling methods for BCR and TCRs, along with methods for clustering such models. We review downstream analyses, including BCR and TCR epitope prediction, antibody-antigen docking and TCR-peptide-MHC Modeling. We also briefly discuss molecular dynamics in this context.

Leu72Met polymorphism of GHRL gene decreases susceptibility to type 2 diabetes mellitus in a Mexican population.

BACKGROUND: Type 2 diabetes mellitus (T2D) is the most frequent type of diabetes. It has a multifactorial etiology, affecting millions of people worldwide. Ghrelin gene (GHRL) encodes the ghrelin peptide, which promotes food intake, induces body weight and adipogenesis. Several single nucleotide polymorphisms (SNPs) in GHRL gene have been associated with metabolic diseases. A protective effect of the Leu72Met (rs696217) polymorphism has been described for T2D in some populations, but this effect seems to depend on the ethnicity of the patients studied. METHODS: The aim of this study was to investigate the association between the GHRL Leu72Met (rs696217) SNP with the development of T2D and serum ghrelin levels in a Western Mexican population. We performed a case-control study in which we included 284 subjects (159 with previous T2D diagnosis and 125 control subjects (CS)). Leu72Met SNP was genotyped by using PCR-RFLPs technique. Serum ghrelin levels were measured using a commercial enzyme immunoassay. Genotypic and allelic distributions were compared using Chi square test. Student T-test and Mann-Whitney U test were used to compare quantitative variables. Odds ratio (OR) was used to evaluate the association between alleles or genotypes and T2D. Multiple and logistic regression models were performed for adjustment. A two-tailed p-value ≤0.05 was considered statistically significant. RESULTS: Leu72Leu genotype was more frequent among T2D compared to CS (p < 0.05). After adjusting for age and body composition, there was a significant protective effect of the 72Met allele for T2D development (OR 0.40 IC 95% 0.23-0.70; p ≤ 0.001). Fasting serum ghrelin levels were lower in T2D than CS (p ≤ 0.0001) irrespective of age, body weight and BMI. No associations were found between genotypes and ghrelin serum levels in our population. CONCLUSIONS: The GHRL 72Met allele decreases susceptibility for T2D development in a Western Mexican population. Serum ghrelin levels are lower in T2D independently of Leu72Met polymorphism genotype.

Serum ghrelin and obestatin levels in HIV-infected patients: Effect of 36 weeks of antiretroviral treatment / Niveles séricos de Ghrelina y Obestatina en pacientes infectados con VIH: efecto de 36 semanas de tratamiento antirretroviral

Introduction: Patients with HIV+ often present lipid disturbances. The role of ghrelin and obestatin in these lipid disturbances is not clear. The effect of antiretroviral (ART) drugs on those molecules is also unknown. This study measured ghrelin and obestatin levels, as well as metabolic markers, in patients with HIV+ before and after 36 weeks of ART. Material and methods: Twenty HIV-positive, ART-naïve patients who started a scheme consisting of tenofovir/emtricitabine+lopinavir/ritonavir were enrolled. Plasma samples were collected before and after 36 weeks of treatment. Serum ghrelin and obestatin levels were quantitated by ELISA; glucose, cholesterol, and triglyceride levels were measured by colorimetric and enzymatic methods, and cardiovascular risk was calculated by the atherogenic index of plasma (AIP). Results: All patients completed 36 weeks of ART. Total cholesterol (p<0.001), LDL-C (p=0.019), HDL-C (p=0.003), VLDL-C (p=0.002), and triglyceride levels (p=0.021) significantly increased after treatment. AIP revealed increased cardiovascular risk at baseline, which remained high after treatment. There was a statistically significant increase in obestatin level in the unpaired and paired analyses, while ghrelin levels only showed a trend to increase. Changes in ghrelin and obestatin levels positively correlated, but no correlation was seen with any metabolic parameter. Conclusion: After 36 weeks of ART, patients showed an altered lipid profile, but there were no significant changes in cardiovascular risk. Ghrelin and obestatin levels increased after 36 weeks of ART, but the increase was only significant for obestatin. Changes in ghrelin and obestatin positively correlate

Introducción: Los pacientes con VIH+ frecuentemente presentan alteraciones del perfil lípidico. El papel de ghrelina y obestatina en estas complicaciones no está claro. El efecto del tratamiento antirretroviral (TAR) en dichas moléculas es desconocido. Este estudio determinó los niveles de ghrelina y obestatina, así como los parámetros metabólicos en pacientes VIH+ antes y después de 36 semanas del TAR. Material y métodos: Participaron 20 pacientes VIH+, vírgenes a TAR, que iniciaron con un esquema de tenofovir/emtricitabina + lopinavir/ritonavir. Se tomaron muestras de plasma antes y después de 36 semanas de tratamiento. Los niveles séricos de ghrelina y obestatina fueron cuantificados por ELISA, los parámetros bioquímicos fueron determinados por métodos colorimétricos, se evaluó el riesgo cardiovascular por medio del índice aterogénico del plasma (AIP). Resultados: Los pacientes completaron 36 semanas del TAR. Los niveles de colesterol total (p<0,001), c-LDL (p=0,019), c-HDL (p=0,003), c-VLDL (p=0,002) y triglicéridos (p=0,021) mostraron un incremento estadísticamente significativo posterior al tratamiento. El AIP reveló un riesgo cardiovascular alto. Los niveles de obestatina se incrementaron significativamente en el análisis pareado y no pareado; y ghrelina solo mostró tendencia al incremento. Los cambios en ghrelina y obestatina correlacionaron positivamente, sin embargo no correlacionaron con los parámetros metabólicos. Conclusión: Los pacientes VIH+ mostraron un perfil lipídico alterado después de 36 semanas del TAR. Los niveles de ghrelina y obestatina se incrementaron tras 36 semanas del TAR. El riesgo cardiovascular es persistente. Los cambios en ghrelina y obestatina mostraron una correlación positiva

Serum ghrelin and obestatin levels in HIV-infected patients: Effect of 36 weeks of antiretroviral treatment.

INTRODUCTION: Patients with HIV+ often present lipid disturbances. The role of ghrelin and obestatin in these lipid disturbances is not clear. The effect of antiretroviral (ART) drugs on those molecules is also unknown. This study measured ghrelin and obestatin levels, as well as metabolic markers, in patients with HIV+ before and after 36 weeks of ART. MATERIAL AND METHODS: Twenty HIV-positive, ART-naïve patients who started a scheme consisting of tenofovir/emtricitabine+lopinavir/ritonavir were enrolled. Plasma samples were collected before and after 36 weeks of treatment. Serum ghrelin and obestatin levels were quantitated by ELISA; glucose, cholesterol, and triglyceride levels were measured by colorimetric and enzymatic methods, and cardiovascular risk was calculated by the atherogenic index of plasma (AIP). RESULTS: All patients completed 36 weeks of ART. Total cholesterol (p<0.001), LDL-C (p=0.019), HDL-C (p=0.003), VLDL-C (p=0.002), and triglyceride levels (p=0.021) significantly increased after treatment. AIP revealed increased cardiovascular risk at baseline, which remained high after treatment. There was a statistically significant increase in obestatin level in the unpaired and paired analyses, while ghrelin levels only showed a trend to increase. Changes in ghrelin and obestatin levels positively correlated, but no correlation was seen with any metabolic parameter. CONCLUSION: After 36 weeks of ART, patients showed an altered lipid profile, but there were no significant changes in cardiovascular risk. Ghrelin and obestatin levels increased after 36 weeks of ART, but the increase was only significant for obestatin. Changes in ghrelin and obestatin positively correlate.

Functional MIF promoter haplotypes modulate Th17-related cytokine expression in peripheral blood mononuclear cells from control subjects and rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17, and macrophage migration inhibitory factor (MIF). MIF induces IL-17 secretion and MIF promoter polymorphisms influence the expression of selected downstream mediators. The aim of this study was to investigate the relationship between known functional MIF haplotypes and Th17-related cytokine secretion profile in peripheral blood mononuclear cells (PBMC) from control subjects (CS) and RA patients stimulated with lipopolysaccharide (LPS) and recombinant human MIF (rhMIF). The -794 CATT5-8 and -173G > C polymorphisms of the MIF gene were determined by conventional PCR and PCR-RFLP, respectively. The most frequent haplotypes of the MIF polymorphism and PBMC were identified from three subjects homozygous for each haplotype and in both study groups, the PBMC were obtained and stimulated with LPS or rhMIF. The secretion of cytokines related to the Th17 profile was determined by a multiplex immunoassay (MAGPIX). LPS stimulation induced the secretion of cytokines related to the Th17 profile in PBMC from CS and RA patients, whereas, rhMIF only stimulated this response in PBMC from RA patients. PBMC from CS carriers of the MIF 7C haplotype showed more IL-17A, IL-17F, IL-22, and IL-23 secretion than non-7C carriers after LPS stimulation. In the case of rhMIF stimulation, the PBMC from CS carriers of the 7C haplotype secreted more IL-17A and IL-23 than non-7C carriers. In conclusion, genetic variants of the MIF promoter modulate the secretion of cytokines related to the Th17 profile in PBMC from CS inducing a differential response in comparison to PBMC from RA patients.

PTPN22 1858C>T polymorphism is associated with increased CD154 expression and higher CD4+ T cells percentage in rheumatoid arthritis patients.

BACKGROUND: CD40 is a costimulatory molecule for B cells, and CD154 is a marker of CD4+ T cells activation. CD40-CD154 interaction promotes pro-inflammatory cytokines secretion and autoantibodies production. PTPN22 gene encodes LYP protein, an inhibitor of T- and B-cell activation. PTPN22 1858C>T polymorphism confers rheumatoid arthritis (RA) susceptibility. Hence, we evaluate the relationship between 1858C>T polymorphism with CD40 and CD154 expression and IFN-γ secretion in RA patients. METHODS: PTPN22 1858C>T polymorphism was genotyped in 315 RA patients and 315 control subjects (CS) using PCR-RFLP method. Later, we selected only ten anti-CCP-positive RA patients, naïve to disease-modifying antirheumatic drugs and ten CS, all with known 1858C>T PTPN22 genotype. The CD40 and CD154 membrane expressions were determined by flow cytometry in peripheral B and T cells, correspondingly. RESULTS: The B cells percentage and mCD40 expression were similar between RA and CS (P > 0.05) and we did not find an association between these variables and the 1858C>T polymorphism. The CD4+ T cells percentage was higher in RA patients than CS (P = 0.003), and in the RA group, the CD4+ T cells percentage and mCD154 expression were higher in the 1858 T allele carriers (P = 0.008 and P = 0.032, respectively). The IFN-γ levels were lower in RA patients carrying the PTPN22 risk allele (P = 0.032). CONCLUSION: The PTPN22 1858 T risk allele is associated with increased CD4+ T cells percentage and high mCD154 expression in RA patients, which could favor the pro-inflammatory cytokine release and the establishment of the inflammatory response at the seropositive RA.

Polimorfismos de los genes APOA1 y APOB y concentraciones de sus apolipoproteínas como biomarcadores de riesgo en el síndrome coronario agudo: relación con la efectividad del tratamiento hipolipemiante / APOA1 and APOB polymorphisms and apolipoprotein concentrations as biomarkers of risk in acute coronary syndrome: Relationship with lipid-lowering therapy effectiveness

Antecedentes y objetivo: Las alteraciones en el metabolismo de los lípidos contribuyen al síndrome coronario agudo (SCA). Se ha demostrado que los polimorfismos rs670, rs5070 y rs693 modifican el riesgo de enfermedad cardiovascular. La apolipoproteína A-I (ApoA-I) desempeña un papel principal en el transporte inverso del colesterol; la apolipoproteína B (ApoB) contribuye a la acumulación de colesterol en la placa. El objetivo de este estudio fue investigar la asociación entre los polimorfismos rs670 y rs5070 de APOA1 y el polimorfismo rs693 de APOB con SCA y los niveles circulantes de estas proteínas, e investigar si ApoB/ApoA-I podría introducirse como parámetro independiente predictor de riesgo de la enfermedad cardiovascular y como biomarcador del tratamiento de reducción de lípidos en la población mexicana. Métodos: Se incluyó a 300 pacientes con SCA y 300 sujetos control (SC). Resultados: Ni las frecuencias genotípicas ni las alélicas de los polimorfismos rs670, rs5070 y rs693 reflejaron diferencias estadísticamente significativas entre los grupos. Los niveles séricos de ApoA-I (195 frente a 161,4mg/dl; p<0,001) y ApoB (167 frente a 136,9mg/dl; p<0,001) fueron significativamente superiores en los SC en comparación con los SCA; sin embargo, no existió asociación genética. Los pacientes con angina inestable reflejaron los niveles más elevados de ApoA-I (varones: 176,3mg/dl; mujeres: 209,1mg/dl). Conclusión: Los polimorfismos rs670, rs5070 y rs693 no constituyen factores de susceptibilidad genética para SCA en la población de México y no tienen efecto sobre las concentraciones de sus apolipoproteínas. En nuestra población, ApoA-I, ApoB y c-HDL podrían constituir unos mejores biomarcadores del riesgo cardiovascular, y podrían indicar si las dosis de estatinas reducen debidamente las partículas aterogénicas

Background and objective: Lipid metabolism alterations contribute to acute coronary syndrome (ACS). rs670, rs5070 and rs693 polymorphisms have shown to modify the risk of cardiovascular disease. Apolipoprotein A-I (ApoA-I) plays a major role in reverse cholesterol transport; apolipoprotein B (ApoB) contributes to accumulation of cholesterol in the plaque. The aim of this study was to investigate the association of rs670 and rs5070 polymorphisms of APOA1 and rs693 polymorphism of APOB with ACS and circulating levels of its proteins and find if ApoB/ApoA-I could be implemented as an independent parameter of risk for cardiovascular disease and as a biomarker of lipid-lowering therapy effectiveness in Mexican population. Methods: Three hundred patients with ACS and 300 control subjects (CS) were included. Results: Neither genotype nor allele frequencies of rs670, rs5070 and rs693 polymorphisms showed statistical differences between groups. Serum levels of ApoA-I (195 vs. 161.4mg/dL; P<.001) and ApoB (167 vs. 136.9mg/dL; P<.001) were significantly higher in CS compared with ACS; however, there was no genetic association. Unstable angina patients showed the highest ApoA-I levels (males: 176.3mg/dL; females: 209.1mg/dL). Conclusion: The rs670, rs5070 and rs693 polymorphisms are not genetic susceptibility factors for ACS in Mexican population and had no effect on their apolipoprotein concentrations. In our population, ApoA-I, ApoB and HDL-C could be better biomarkers of cardiovascular risk and could indicate if statins doses reduce atherogenic particles properly

Clinical and immunological aspects of anti-peptidylarginine deiminase type 4 (anti-PAD4) autoantibodies in rheumatoid arthritis.

Rheumatoid arthritis (RA) is the most common rheumatic autoimmune disease worldwide, which causes progressive joint damage and can lead to functional disability. Despite prominent advances in RA diagnosis and treatment during the last 20years, there is still a need for novel biomarkers that aid in diagnosis and prognosis of this heterogeneous disease. Citrullination is a key post-translational modification implicated on anti-citrullinated protein/peptide antibodies (ACPA) production in RA, catalyzed by human peptidylarginine deiminases (PADs). Among these enzymes, PAD4 has been recognized as an important player in RA pathogenesis and the enzyme itself is a target of autoantibodies (anti-PAD4) in a subgroup of RA patients. Accumulating evidence suggests that anti-PAD4 autoantibodies may be useful as a severity biomarker in RA and recent studies have also shed light on the functional significance of these autoantibodies. This review summarizes the evidence on anti-PAD4 autoantibodies in RA, and addresses its usefulness for disease diagnosis and prognosis. Novel immunological aspects of anti-PAD4 antibodies and their relevance to RA pathogenesis are also discussed.

APOA1 and APOB polymorphisms and apolipoprotein concentrations as biomarkers of risk in acute coronary syndrome: Relationship with lipid-lowering therapy effectiveness. / Polimorfismos de los genes APOA1 y APOB y concentraciones de sus apolipoproteínas como biomarcadores de riesgo en el síndrome coronario agudo: relación con la efectividad del tratamiento hipolipemiante.

BACKGROUND AND OBJECTIVE: Lipid metabolism alterations contribute to acute coronary syndrome (ACS). rs670, rs5070 and rs693 polymorphisms have shown to modify the risk of cardiovascular disease. Apolipoprotein A-I (ApoA-I) plays a major role in reverse cholesterol transport; apolipoprotein B (ApoB) contributes to accumulation of cholesterol in the plaque. The aim of this study was to investigate the association of rs670 and rs5070 polymorphisms of APOA1 and rs693 polymorphism of APOB with ACS and circulating levels of its proteins and find if ApoB/ApoA-I could be implemented as an independent parameter of risk for cardiovascular disease and as a biomarker of lipid-lowering therapy effectiveness in Mexican population. METHODS: Three hundred patients with ACS and 300 control subjects (CS) were included. RESULTS: Neither genotype nor allele frequencies of rs670, rs5070 and rs693 polymorphisms showed statistical differences between groups. Serum levels of ApoA-I (195 vs. 161.4mg/dL; P<.001) and ApoB (167 vs. 136.9mg/dL; P<.001) were significantly higher in CS compared with ACS; however, there was no genetic association. Unstable angina patients showed the highest ApoA-I levels (males: 176.3mg/dL; females: 209.1mg/dL). CONCLUSION: The rs670, rs5070 and rs693 polymorphisms are not genetic susceptibility factors for ACS in Mexican population and had no effect on their apolipoprotein concentrations. In our population, ApoA-I, ApoB and HDL-C could be better biomarkers of cardiovascular risk and could indicate if statins doses reduce atherogenic particles properly.

Association of A-604G ghrelin gene polymorphism and serum ghrelin levels with the risk of obesity in a mexican population.

Obesity is a metabolic disorder that has a multifactorial etiology and affects millions of people worldwide. Ghrelin, a hormone coded by the GHRL gene, plays a role in human body composition and appetite. Single nucleotide polymorphisms (SNPs) of the GHRL gene have been associated with obesity and metabolic disorders. To evaluate the association of A-604G SNP of GHRL promoter region with serum ghrelin levels and the risk of obesity in a Mexican population. Two hundred and fifty individuals were enrolled and classified as obese or control subjects (CS) according to BMI. DNA samples, anthropometric measurements and biochemical parameters were obtained from all subjects. The A-604G SNP was genotyped using PCR-RFLPs technique. Ghrelin levels were measured using a commercial enzyme immunoassay. The G/G genotype was more frequent among obese individuals (p < 0.0001) when compared to CS. The G/A genotype and A allele were associated with protection against obesity (OR 0.29, p < 0.0001; OR 0.39, p < 0.0001 respectively), the A allele remained significant after adjusting for age and gender (OR: 0.25, p < 0.0001). Serum ghrelin levels were higher in obese patients (p = 0.004) than in CS, however, significance was lost after adjustment for age (p = 0.088). The G/G genotype was associated with higher levels of serum ghrelin (p = 0.02) independently of the effect of age. The G/G genotype of the A-604G SNP in the GHRL gene is associated with altered serum ghrelin levels and obesity. The A allele was also associated with protection against obesity in this study.

A cut-point value of uncarboxylated to carboxylated index is associated with glycemic status markers in type 2 diabetes.

BACKGROUND: The uncarboxylated osteocalcin (ucOC) has been described as a regulator of glucose metabolism in mice, and it is decreased in human type 2 diabetes mellitus (T2D). Although inversely correlated with serum glucose, insulin, and glycated hemoglobin, it is unclear if ucOC decrement is caused by diabetes or plays a role in the pathogenesis and/or progression of the disease. Whatever the case may be, diabetes affects osteoblast gene expression, and possibly the proportion of ucOC over carboxylated OC (cOC). The association of ucOC/cOC index with glycemic status markers in patients with T2D has not been described before. OBJECTIVE: The objective of this study was to assess the ucOC/cOC index and its relationship with glycemic status markers in patients with T2D. METHODS: The ucOC/cOC index was determined by the quotient of ucOC and cOC serum levels in 80 T2D patients and 160 healthy subjects. The relationship between the ucOC/cOC index and glycemic status markers was evaluated. RESULTS: The ucOC/cOC index was low and negatively correlated to fasting plasma glucose and homeostasis assessment-insulin resistance model in T2D patients. The odds ratio for T2D patients with an ucOC/cOC index below the cut-point obtained by receiver operating characteristic analysis was 12.64 (confidence interval, 5.75-27.77; P < 0.001). CONCLUSIONS: A value of ucOC/cOC index less than 0.3 is associated with markers of poor metabolic control in patients with T2D.

Rectal Plasmablastic Lymphoma in HIV/AIDS: Two Cases.

Plasmablastic lymphoma is an aggressive variant of large B-cells lymphoma in which the infection by Human Immunodeficiency Virus and Epstein-Barr herpesvirus are involved. This recently denominated neoplasia has a special tropism through the oral cavity. However, its presence has been reported in the digestive tract, abdominal cavity and retroperitoneum. We describe two Human Immunodeficiency Virus infected patient cases with rectal presentation of PL in the HIV service of the Hospital Civil de Guadalajara.

Serum levels of macrophage migration inhibitory factor are associated with rheumatoid arthritis course.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unknown etiology. Many cytokines have been found to be associated with RA pathogenesis and among them is macrophage migration inhibitory factor (MIF). The aim of this study was to determine whether MIF serum levels are associated with RA course, clinical activity, and clinical biomarkers of the disease. MIF levels were determined in serum samples of 54 RA patients and 78 healthy subjects (HS) by enzyme-linked immunosorbent assay (ELISA). Disease activity was evaluated using the DAS28 score. Patients were subgrouped according to disease activity and years of evolution of disease. Statistical analysis was carried out by SPSS 10.0 and GraphPad Prism 5 software. RA patients presented increased levels of MIF as compared to HS. MIF levels were raised on early stages of RA and tend to decrease according to years of evolution. Moreover, MIF levels positively correlated with rheumatoid factor in RA patients and with C reactive protein in all individuals studied. Our findings suggest that MIF plays a role in early stages of RA.

Increased CD28 serum levels are not associated with specific clinical activity in systemic lupus erythematosus.

CD28 is one of the main activator receptors involved in systemic lupus erythematosus (SLE) pathogenesis, and its expression and serum levels are significantly higher in patients with SLE and other autoimmune diseases than in healthy controls (HC). However, it is unknown whether this increase is associated with specific organ damage. Therefore, our objective was to measure the CD28 levels in serum from SLE and HC groups to confirm the CD28 serum levels increase, as reported previously, and to determine whether this increase was associated with specific organ activity and the SLE Disease Activity Index (SLEDAI). Forty SLE patients and 40 matched HC were included, and the age, disease duration, SLEDAI and Mexican SLEDAI were recorded for the SLE group. CD28 serum levels were measured by ELISA. There was a statistically significant increase in the CD28 serum levels of SLE patients compared to controls (p = 0.039); however, we did not find any significant correlation with disease activity indices or organ involvement, although we found a significant but low correlation with C3. Our results and a review of the literature suggest that the increase in CD28 serum levels may be the result of CD28 gene overexpression, which could be related to the decrease in CD28+ T cells, T-cell hyporesponsiveness and immune impairment that occurs in SLE.

Plasminogen activator inhibitor-1 polymorphisms (-844 G>A and HindIII C>G) in systemic lupus erythematosus: association with clinical variables.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of autoantibodies against nuclear autoantigens as well as cytoplasmic and circulating proteins. Recent studies have demonstrated mechanisms responsible for modulation of the immune response by the plasminogen activator inhibitor-1 (PAI-1). Furthermore, the endogenous PAI-1 has shown to promote a Th2 immune response. We assessed the -844 G>A and HindIII C>G PAI-1 polymorphisms in SLE. In a case-control study of 71 SLE patients classified according to ACR criteria and 71 healthy subjects (HS). The A allele of -844 PAI-1 polymorphism showed a significant difference in SLE patients (41%) when compared with HS (27%) [P = 0.01; OR = 1.8, 95%, CI = 1.1-3.0]. In addition, the -844 G>A PAI-1 polymorphism was associated with increased risk for SLE in a dominant genetic model (G/G vs. G/A + A/A; OR = 2.3, 95% CI = 1.14-4.44). Also, anti-RNP positive antibodies in SLE were associated with G/G -844 PAI-1 genotype. The HindIII polymorphism did not show any differences. The haplotype analysis showed that the AC haplotype confers susceptibility to SLE (OR = 3.1, 95% CI, 1.45-6.52; P = 0.003). The AC haplotype of the -844 and HindIII PAI-1 polymorphism might be an additional susceptibility factor to SLE in Mexicans.