Differential expression of PSMC4, SKP1, and HSPA8 in Parkinson's disease: insights from a Mexican mestizo population.

Parkinson's disease (PD) is a complex neurodegenerative condition characterized by alpha-synuclein aggregation and dysfunctional protein degradation pathways. This study investigates the differential gene expression of pivotal components (UBE2K, PSMC4, SKP1, and HSPA8) within these pathways in a Mexican-Mestizo PD population compared to healthy controls. We enrolled 87 PD patients and 87 controls, assessing their gene expression levels via RT-qPCR. Our results reveal a significant downregulation of PSMC4, SKP1, and HSPA8 in the PD group (p = 0.033, p = 0.003, and p = 0.002, respectively). Logistic regression analyses establish a strong association between PD and reduced expression of PSMC4, SKP1, and HSPA8 (OR = 0.640, 95% CI = 0.415-0.987; OR = 0.000, 95% CI = 0.000-0.075; OR = 0.550, 95% CI = 0.368-0.823, respectively). Conversely, UBE2K exhibited no significant association or expression difference between the groups. Furthermore, we develop a gene expression model based on HSPA8, PSMC4, and SKP1, demonstrating robust discrimination between healthy controls and PD patients. Notably, the model's diagnostic efficacy is particularly pronounced in early-stage PD. In conclusion, our study provides compelling evidence linking decreased gene expression of PSMC4, SKP1, and HSPA8 to PD in the Mexican-Mestizo population. Additionally, our gene expression model exhibits promise as a diagnostic tool, particularly for early-stage PD diagnosis.

Risk Factors Associated with COVID-19 Mortality in the State of Durango, Mexico.

The coronavirus disease 2019 (COVID-19) has caused over six million deaths worldwide since its emergence in Wuhan China, factors associated with COVID-19 mortality, such as comorbidities, age, and observed symptomatology still remain a major subject of study. In the present work, a total of 16,345 SARS-CoV-2 positive cases from Durango Mexico diagnosed from May 2020 to December 2021 were analyzed to establish an association of COVID-19 mortality with clinical and demographic variables in a case-control study. Selected variables include patient age, smoking status, sex, presence of comorbidities such as hypertension, diabetes and obesity, as well as patient symptomatology such as fever, dyspnea, abdominal pain and diarrhea. Results indicate that among analyzed data, the median age was 43 years; 54% were female, with a mortality rate of 5.66%. Multivariate regression analysis indicated that the comorbidities associated with the highest risk factor were advanced age (>60) with an odds ratio of 4.127 (IC 95%, 3.37-5.05), hypertension with 1.961 (IC 95%, 1.57-2.45), diabetes with 1.753 (IC 95%, 1.39-2.20) and obesity with 1.413 (IC 95%, 1.11-1.78) respectively. On the other hand, the symptom associated with the highest risk factor was dyspnea with an odds ratio of 18.369 (IC 95%, 14.42-23.39). Our data suggests an association between hypertension and old age with COVID-19 mortality. Other findings include the prevalence of dyspnea, polypnea and cyanosis as a major predictor for COVID-19 mortality, as well as lower mortality risks among health workers.

Association between the expression of TLR4, TLR2, and MyD88 with low-grade chronic inflammation in individuals with metabolically healthy obesity.

BACKGROUND: Among the Toll-like receptors (TLR) that are dependent of myeloid response protein (MyD88), the TLR4 and TLR2 are directly associated with low-grade chronic inflammation; however, they are not been investigated in subjects with metabolically healthy obesity (MHO). Thus, the objective of this study was to determine the association between the expression of TLR4, TLR2, and MyD88 with low-grade chronic inflammation in individuals with MHO. METHODS AND RESULTS: Men and women with obesity aged 20 to 55 years were enrolled in a cross-sectional study. Individuals with MHO were allocated into the groups with and without low-grade chronic inflammation. Pregnancy, smoking, alcohol consumption, intense physical activity or sexual intercourse in the previous 72 h, diabetes, high blood pressure, cancer, thyroid disease, acute or chronic infections, renal impairment, and hepatic diseases, were exclusion criteria. The MHO phenotype was defined by a body mass index (BMI ≥ 30 kg/m2) plus one or none of the following cardiovascular risk factors: hyperglycemia, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol. A total of 64 individuals with MHO were enrolled and allocated into the groups with (n = 37) and without (n = 27) inflammation. The multiple logistic regression analysis indicated that TLR2 expression is significantly associated with inflammation in individuals with MHO. In the subsequent analysis adjusted by BMI, TLR2 expression remained associated with inflammation in individuals with MHO. CONCLUSION: Our results suggest that overexpression of TLR2, but not TLR4 and MyD88, is associated with low-grade chronic inflammation in subjects with MHO.

Differential expression of HTR2A and MAOA genes in the prefrontal cortex and hypothalamus of suicide victims from Mexican population.

OBJECTIVE: The main aim of the current study was to investigate whether the expression levels of the HTR2A and MAOA genes are altered in the postmortem brain of suicide victims from Mexican population. METHODS: On the basis of a case- control study, we examined the expression levels of HTR2A and MAOA genes in the postmortem prefrontal cortex (Brodmann area 8/9) and hypothalamus (ventromedial nucleus) tissues from 20 suicide victims and 20 control subjects from a Mexican population. Gene-expression profile quantification was carried out by qPCR and determined by the 2-ΔΔCt method. RESULTS: In suicide victims, the expression levels of the HTR2A gene were significantly higher in the prefrontal cortex. In contrast, the expression of the MAOA gene in the hypothalamus of the suicide victims was significantly higher than in the control subjects. These results were consistent regardless of age, sex, postmortem interval, or pH of brain tissue. CONCLUSION: The evidence suggests that the pattern of differential expression of HTR2A and MAOA genes in the brain may be involved in suicide, providing a possible molecular basis for the brain abnormalities in suicide victims.

Epigenetic marks in suicide: a review.

Suicide is a complex phenomenon and a global public health problem that involves several biological factors that could contribute to the pathophysiology of suicide. There is evidence that epigenetic factors influence some psychiatric disorders, suggesting a predisposition to suicide or suicidal behavior. Here, we review studies of molecular mechanisms of suicide in an epigenetic perspective in the postmortem brain of suicide completers and peripheral blood cells of suicide attempters. Besides, we include studies of gene-specific DNA methylation, epigenome-wide association, histone modification, and interfering RNAs as epigenetic factors. This review provides an overview of the epigenetic mechanisms described in different biological systems related to suicide, contributing to an understanding of the genetic regulation in suicide. We conclude that epigenetic marks are potential biomarkers in suicide, and they could become attractive therapeutic targets due to their reversibility and importance in regulating gene expression.

α-syn and SNP rs356219 as a potential biomarker in blood for Parkinson's disease in Mexican Mestizos.

Clinical criteria diagnose Parkinson's disease (PD), therefore, it is crucial to find biological elements that could support diagnosis or even act as prognostic tools of PD. The SNCA gene codifies a protein called α - synuclein; several studies associate genetic and biochemical factors of SNCA with PD, including transcript and plasmatic protein levels, however, contradictory evidence indicates inconclusive results. We aim to compare SNCA mRNA expression, plasmatic α-syn protein and rs356219 SNP between PD cases and a control group, and to identify a potential biomarker in Mexican mestizos', focusing on these three components determined in blood. We included 88 PD patients and 88 age-matched controls. We observed higher α-syn protein and decreased SNCA mRNA levels in PD subjects, compared to control group (p = 0.044 and p < 0.001, respectively). A statistically significant difference was found in allelic and genotypic frequencies of SNP rs356219 between PD patients and normal subjects (p = 0.006 and p = 0.023, respectively). Logistic regression analysis determined as optimal predictors of PD the GG genotype of SNP rs356219 (OR 2.49; p = 0.006) in a recessive model and α-syn protein (OR 1.057; p = 0.033). Furthermore, the G allele of SNP rs356219 was associated with higher plasmatic α-syn and mRNA levels in PD subjects. The receiver operating curves (ROC) distinguished PD from healthy controls with good sensitivity and specificity considering the plasmatic α-syn protein (AUC = 0.693, Sensitivity = 66.7 %, Specificity = 63.9 %) or a predictive probability of plasmatic α-syn protein and SNP rs356219 in a single model (AUC = 0.692, Sensitivity = 62.3 %, Specificity = 62.5 %). The performance of this classifier model in PD at early stage (n = 31) increase the discriminant power in both, plasmatic α-syn protein (AUC = 0.779, Sensitivity = 72.7 %, Specificity = 73.9 %) and predictive probability (AUC = 0.707, Sensitivity = 63.6 %, Specificity = 62.5 %). We propose that α-syn protein and SNP rs356219 together may work as a good signature of PD, and they can be suggested as a non-invasive biomarker of PD risk.

rs3764435 Associated With Parkinson's Disease in Mexican Mestizos: Case-Control Study Reveals Protective Effects Against Disease Development and Cognitive Impairment.

Parkinson's disease (PD) is the second most common movement disorder. Genetic risk factors provide information about the pathophysiology of PD that could potentially be used as biomarkers. The ALDH1A1 gene encodes for the aldehyde dehydrogenase enzyme, which is involved in the disposal of toxic metabolites of dopamine. Due to the cytotoxic nature of aldehydes, their detoxification is essential for cellular homeostasis. It has been reported that ALDH1A1 expression levels and activity are decreased in PD patients. A deficit in ALDH1A1 activity in the substantia nigra, may lead to the accumulation of neurotoxic aldehydes and eventually the cell death seen in PD. One of the single nucleotide polymorphisms (SNP) that may modulate ALDH1A1 activity levels is rs3764435 (A/C). To investigate whether a statistical association exists between PD and the SNP rs3764435, we carried out a population-based Case-Control association study (120 PD patients and 178 non-PD subjects) in Mexican mestizos. DNA was extracted from blood samples and genotyped for rs3764435 using real-time PCR. A significant difference was found between PD cases and controls in both allelic and genotypic frequencies. The calculated OR showed that the C/C genotype is a protective factor under the codominant and recessive models of inheritance. However, after stratifying by sex, the protective role of this genotype is conserved only in men. Also, under the codominant and dominant models, rs3764435 appears to exert a protective effect against cognitive impairment in PD patients. Here for the first time, we show an association between PD and rs3764435 in a Mexican mestizo population, suggesting it confers neuroprotection for dementia in PD and is neuroprotective against developing PD in the males of this population. While analysis of the SNP looks favorable, replication of our study in cell lines or rs3764435 KO mice is required to validate these results.