Visual EMDR stimulation mitigates acute varied stress effects on morphology of hippocampal neurons in male Wistar rats.

Introduction: Stress is a pervasive health concern known to induce physiological changes, particularly impacting the vulnerable hippocampus and the morphological integrity of its main residing cells, the hippocampal neurons. Eye Movement Desensitization and Reprocessing (EMDR), initially developed to alleviate emotional distress, has emerged as a potential therapeutic/preventive intervention for other stress-related disorders. This study aimed to investigate the impact of Acute Variable Stress (AVS) on hippocampal neurons and the potential protective effects of EMDR. Methods: Rats were exposed to diverse stressors for 7 days, followed by dendritic morphology assessment of hippocampal neurons using Golgi-Cox staining. Results: AVS resulted in significant dendritic atrophy, evidenced by reduced dendritic branches and length. In contrast, rats receiving EMDR treatment alongside stress exposure exhibited preserved dendritic morphology comparable to controls, suggesting EMDR's protective role against stressinduced dendritic remodeling. Conclusions: These findings highlight the potential of EMDR as a neuroprotective intervention in mitigating stress-related hippocampal alterations.

PTCH1 gene variants rs357564, rs2236405, rs2297086 and rs41313327, mRNA and tissue expression in basal cell carcinoma patients from Western Mexico.

BACKGROUND: Basal cell carcinoma (BCC) represents about 80% of all cases of skin cancer. The PTCH1 is a transmembrane protein of the Sonic Hedgehog signaling pathway that regulates cell proliferation. Genetic variants in PTCH1 gene have been previously described in association with BCC development. In addition, PTCH1 mRNA and protein expression analysis are also significant to understand its role in skin cancer physiopathology. METHODS: An analytical cross-sectional study was performed, and a total of 250 BCC patients and 290 subjects from the control group (CG) were included, all born in western Mexico. The genotypes and relative expression of the mRNA were determined by TaqMan® assay. The protein expression was investigated in 70 BCC paraffin-embedded samples with PTCH1 antibodies. Semi-quantitative analysis was performed to determine the expression level in the immunostained cells. RESULTS: We did not find evidence of an association between PTCH1 rs357564, rs2297086, rs2236405, and rs41313327 genetic variants and susceptibility to BCC. Likewise, no statistically significant differences were found in the comparison of the mRNA level expression between BCC and CG (p > 0.05). The PTCH1 protein showed a low expression in 6 of the analyzed samples and moderate expression in 1 sample. No association was found between genetic variants, protein expression, and demographic-clinical characteristics (p > 0.05). CONCLUSION: The studied PTCH1 variants may not be associated with BCC development in the Western Mexico population. The PTCH1 mRNA levels were lower in patients with BCC compared to the control group, but its protein was underexpressed in the tissue samples.

Human Monkeypox: A Comprehensive Overview of Epidemiology, Pathogenesis, Diagnosis, Treatment, and Prevention Strategies.

Monkeypox virus (MPXV) is an emerging zoonotic virus that belongs to the Orthopoxvirus genus and presents clinical symptoms similar to those of smallpox, such as fever and vesicular-pustular skin lesions. However, the differential diagnosis between smallpox and monkeypox is that smallpox does not cause lymphadenopathy but monkeypox generates swelling in the lymph nodes. Since the eradication of smallpox, MPXV has been identified as the most common Orthopoxvirus to cause human disease. Despite MPXV being endemic to certain regions of Africa, the current MPXV outbreak, which began in early 2022, has spread to numerous countries worldwide, raising global concern. As of the end of May 2023, over 87,545 cases and 141 deaths have been reported, with most cases identified in non-endemic countries, primarily due to human-to-human transmission. To better understand this emerging threat, this review presents an overview of key aspects of MPXV infection, including its animal reservoirs, modes of transmission, animal models, epidemiology, clinical and immunological features, diagnosis, treatments, vaccines, and prevention strategies. The material presented here provides a comprehensive understanding of MPXV as a disease, while emphasizing the significance and unique characteristics of the 2022 outbreak. This offers valuable information that can inform future research and aid in the development of effective interventions.

Targeting inflammasome-dependent mechanisms as an emerging pharmacological approach for osteoarthritis therapy.

Arthritic diseases have attracted enormous scientific interest because of increased worldwide prevalence and represent a significant socioeconomic burden. Osteoarthritis (OA) is the most prevalent form of arthritis. It is a disorder of the diarthrodial joints, characterized by degeneration and loss of articular cartilage associated with adjacent subchondral bone changes. Chronic and unresolving inflammation has been identified as a critical factor driving joint degeneration and pain in OA. Despite numerous attempts at therapeutic intervention, no effective disease-modifying agents targeting OA inflammation are available to the patients. Inflammasomes are protein complexes known to play a critical role in the inflammatory pathology of several diseases, and their roles in OA pathogenesis have become evident over the last decade. In this sense, it is relevant to evaluate the vital role of inflammasomes as potential modulators of pathogenic features in OA. This review will provide an overview and perspectives on why understanding inflammasome activation is critical for identifying effective OA therapies. We elaborate on the contribution of extracellular mediators from the circulatory system and synovial fluid as well as intracellular activators within the synovial fibroblasts and articular chondrocytes toward invoking the inflammasome in OA. We further discuss the merits of emerging inflammasome targeting therapies and speculate on the potential strategies for inflammasome blockade for OA therapy.

APOA1 (-75 G>A and 83 C>T) and APOB (2488 C>T) polymorphisms and their association with myocardial infarction, lipids and apolipoproteins in patients with type 2 diabetes mellitus.

Introduction: The increased risk of myocardial infarction (MI) in type 2 diabetes mellitus (T2DM) is well documented. Polymorphisms in APOA1 and APOB genes allow us to identify new genetic markers in the Mexican population with T2DM and MI. Material and methods: We studied 135 patients with DMT2 and MI (DI); another 85 non-infarcted diabetic individuals with DMT2 but without previous ischemic events (NID) and 242 healthy subjects (HS). All three groups were selected with the aim to investigate the association between the polymorphisms and infarction when T2DM is present or absent. Results: -75 G>A polymorphism: Differences were found in genotype distribution between DI and NID individuals (OR = 2.01, 95% CI: 1.117-3.623, p = 0.019) with an increased risk for A in the dominant model (OR = 1.77, 95% CI: 1.020-3.084, p = 0.042); also concentrations of ApoA-I for A/A were lower in comparison with G/A (p = 0.038) and LDL-C and HDL-C levels were lower in G/A compared to G/G carriers. 83 C>T polymorphism of APOA1: For DI individuals, HDL-C was lower in T/T compared to C/C and triglyceride levels were lower in C/T compared to C/C carriers. Conclusions: The -75 G>A APOA1 polymorphism could be considered as a susceptibility factor for myocardial infarction in individuals with T2DM and 2488 C>T APOB polymorphism is associated with changes in HDL-C and LDL-C and triglycerides in the same group.

Role of Bcl-2, p53, and Ki-67 expression in basal cell carcinoma and their association with aggressive and non-aggressive histological phenotypes.

Introduction: There is increasing evidence that immunohistochemical expression of p53, Ki-67, and Bcl-2 is associated with aggressive (aBCC) and less aggressive (nBCC) histological subtypes and may have a prognostic role. Aim: To investigate the clinicopathological features and immunohistochemical expressions of p53, Ki-67, and Bcl-2 in cutaneous basal cell carcinoma focusing on histological subtypes. Their roles and possible interactions in the development and progression of BCC are discussed. Material and methods: A total of 50 BCC samples from 50 patients from Western Mexico between June 2018 and June 2019 were included. Paraffin-embedded samples were immunostained with p53, Ki-67, and Bcl-2 antibodies. Semi-quantitative analysis was performed to determine the intensity and positivity of immunostained cells. Parametrical and non-parametrical tests were performed according to the sample's distribution. Results: Samples included 21 nBCC and 29 aBCC. The statistical analysis showed statistical association when grouped as non-aggressive and aggressive subtypes for p53 (p = 0.04) and Bcl-2 (p < 0.01). An inverse negative correlation was found between age and Bcl-2 expression. No statistical association was found between Ki-67 immunoreactivity and any of the other variables. Conclusions: We found that a high expression of Bcl-2 and a low expression of p53 was associated with more indolent histopathological features of BCC and therefore better outcomes. These findings suggest that examination of p53 and Bcl-2 expression in BCC patients may provide valuable prognostic information. These biomarkers may play a role in the development and progression of some cases of BCC.

Genetic variants, gene expression, and soluble CD36 analysis in acute coronary syndrome: Differential protein concentration between ST-segment elevation myocardial infarction and unstable angina.

BACKGROUND: Atherosclerosis plays an important role in the pathophysiology of acute coronary syndrome (ACS). CD36 is a scavenger receptor involved in lipid metabolism. Some single-nucleotide variants in the non-coding region could indirectly alter the expression and the function of the protein. OBJECTIVE: The aim of this study was to investigate the gene and protein expression associated with CD36 variants (rs1194182;C > G; rs1049654;C > A, rs1334512;G > T, and rs3211892;G > A) in ACS patients from the western Mexican population. METHODS: We recruited 310 ACS patients and 308 subjects in the control group (CG). Genotyping was determined by TaqMan SNP genotyping assays. CD36 expression at the mRNA level was quantified by TaqMan gene expression assays. Soluble CD36 (sCD36) was measured by enzyme-linked immunosorbent assay. RESULTS: We show that rs1194182G > C variant provides a protective effect with a 1.7-fold lower susceptibility to develop ACS (p  = 0.03); however, this association was masked by diabetes and dyslipidemia. We observed a higher sCD36 concentration in patient with ST-segment elevation myocardial infarction (STEMI) compared with patients with unstable angina (UA) (p  = 0.038). Likewise, in diabetic patients versus non-diabetic (p < 0.001). We observed in patients an increase in CD36 mRNA expression (1.91 times higher) than in the CG (p  = 0.02). CONCLUSION: The rs1194182 seems to be associated with diabetes in a risky manner, in ACS patients and protective for dyslipidemia in both groups. The concentration of sCD36 seems to be associated with the clinical spectrum of the ACS patients and the presence of diabetes, since patients with STEMI present significantly elevated level compared with UA.

Analysis of the APOB Gene and Apolipoprotein B Serum Levels in a Mexican Population with Acute Coronary Syndrome: Association with the Single Nucleotide Variants rs1469513, rs673548, rs676210, and rs1042034.

Apolipoprotein B (APOB) is associated with the development of atherosclerosis and consequently in the acute coronary syndrome (ACS) physiopathology. Single number variants (SNVs) in apolipoprotein B gene (APOB) influence over the susceptibility for this syndrome. The aim of this study was to determine the impact of the rs1469513, rs673548, rs676210, and rs1042034 SNVs and serum levels of APOB in the risk of ACS in a population from western Mexico. We included 300 patients in the group of cases (ACSG) and 300 individuals in the control group (CG). APOB levels were evaluated by immunonephelometry, and SNVs were genotyped with TaqMan probes. We found significant allelic and genotypic differences between groups for rs673548 and rs676210 (OR = 1.33, p=0.030, OR = 2.69, p < 0.001) and rs1042034 (OR = 0.50, p=0.037) SNVs. We found a risk haplotype TAGT (OR: 2.14, IC 1.50-3.04, p < 0.001). Our findings support a significant risk association between rs673548 and rs676210 variants for ACS; meanwhile, rs1042034 could be considered protective factor in a western Mexican population. Also, in this population, haplotype TAGT may confer 2.14 times a higher risk. APOB serum levels were compared by genotype variants in both groups without any significant statistical difference.

The Genetic Variants -717T>C (rs2794521), 1444G>A (rs1130864), and 1846 C > T (rs1205) of CRP Gene, Their Haplotypes, and Their Association with Serum CRP Levels, Acute Coronary Syndrome, and Diabetes in Patients from Western Mexico.

Background: C-reactive protein (CRP) is involved in inflammatory pathways that are associated with the onset and progression of type 2 diabetes mellitus (T2DM) as well as an increased risk of an acute coronary syndrome (ACS). This research aimed to evaluate the potential association of the genetic variants -717T>C, 1444G>A, and 1846 C > T of CRP gene on CRP levels, ACS, and T2DM in participants from Western Mexico. Methods: Six hundred three participants were studied: (1) control group (CG); (2) ACS participants classified as unstable angina (UA), myocardial infarction without ST-segment elevation (NSTEMI), and myocardial infarction with ST-segment elevation (STEMI); (3) T2DM Participants; and (4) ACS plus T2DM participants (ACS+T2DM). Genetic variants were genotyped using allelic discrimination with TaqMan® probes, and high-sensitivity CRP (hs-CRP) was measured by Turbidimetry. Results: TAC haplotype frequency was significantly higher in ACS+T2DM versus CG and versus ACS participants (odds ratio [OR] = 2.774, P = 0.017 and OR = 3.479, P = 0.020, respectively). hs-CRP levels were especially higher for ACS and for ACS+T2DM participants with respect to CG and T2DM (with P < 0.0001). We observed higher hs-CRP levels in NSTEMI and STEMI versus UA in ACS scenario (P = 0.001, P = 0.027, respectively) and for ACS+T2DM scenario (P = 0.0001, P = 0.002, respectively). Conclusion: hs-CRP level fluctuations are related to the presence of T2DM and the presence and severity of ACS. Very high levels (>10 mg/L) are a risk marker of cardiovascular complications. Our results demonstrate a possible relationship between TAC haplotype and an increased risk for T2DM and ACS.

Cytokine profiles and clinical characteristics in primary Sjögren´s syndrome patient groups.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups. METHODS: Ninety-nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K-mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal-Wallis test and the Bonferroni test. RESULTS: Higher IFN-γ, IL-17F, IL-21, IL-23, IL-4, and IL-31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity. CONCLUSION: Cluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach.

Haplotypes of (-794(CATT)5-8/-173G>C) MIF gene polymorphisms and its soluble levels in basal cell carcinoma in western Mexican population.

Basal cell carcinoma (BCC) is the most common dermatological neoplasms in Caucasian populations. In Mexico, a prevalence of 3.9 per 1000 habitants is estimated. Recently, the macrophage migration inhibitory factor (MIF) has been related to different types of cancer. Therefore, this study aimed to investigate the genetic association of haplotypes of [-794(CATT)5-8/-173G>C]MIF gene polymorphisms and its soluble levels in BCC. A total of 360 individuals were recruited for the study, that is, 180 of the total amounts were patients with BCC histologically confirmed and the remaining 180 individuals were identified as control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP (restriction fragment length polymorphism), and MIF serum levels were measured by ELISA kit. A borderline difference was found between the 55 genotype and the susceptibility to BCC (5.6% vs 1.7% in BCC and CS, respectively, OR=3.7 and p=0.04). Furthermore, the haplotype 7G showed a significant association with BCC (p=0.02, OR=1.99). Concerning MIF soluble levels, patients with BCC showed a media of 2.1 ng/mL and CS showed 4.4 ng/mL, the comparison between groups was significant (p<0.01). Our findings suggest that the 55 genotype and the haplotype 7G are associated with the susceptibility to BCC; furthermore, a significant difference was found between MIF soluble levels in both study groups.

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

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.

Influence of haplotypes, gene expression and soluble levels of L-selectin on the risk of acute coronary syndrome.

BACKGROUND: L-selectin gene (SELL) is a candidate gene for the development of acute coronary syndrome (ACS) that contributes to endothelial dysfunction. The -642C>T (rs2205849) and 725C>T (rs2229569) polymorphisms have been associated with changes in gene expression, ligand affinity and increased risk of cardiovascular disease. The aim of this study was to investigate the association between the haplotypes constructed with the -642C>T and 725C>T polymorphisms of the SELL gene, the expression levels of its mRNA and the serum levels of soluble L-selectin with ACS. METHODS: We recruited 615 individuals of Mexican origin matched by age, including 342 patients with ACS and 273 individuals without personal history of ischemic cardiopathy as control group (CG). Genotyping was performed by PCR-RFLP. The qPCR technique was used to analyze the expression of mRNA using TaqMan® UPL probes. The levels of soluble L-selectin were measured with ELISA. RESULTS: The allele variants in both polymorphisms were over-represented in the CG compared to the ACS (OR range: 0.371-0.716, p<0.006). The CT and TT haplotypes had a protective effect against the development of ACS (OR=0.401, p<0.0001; OR=0.628, p<0.0001, respectively). SELL expression was 3.076 times higher in the ACS group compared to CG (p<0.001). The levels of soluble L-selectin were similar between ACS and CG. CONCLUSIONS: Both polymorphisms had no effect on mRNA expression and soluble protein levels. The polymorphisms -642C>T and 725C>T of the SELL gene are protective factors against the development of ACS. There is an increased gene expression of L-selectin in ACS compared to CG in the population of Western Mexico.