Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population.

BACKGROUND: Cholesterol has been associated as a risk factor for cardiovascular disease. Recently, however, there is growing evidence about crucial requirement of neuron membrane cholesterol in the organization and function of the 5-HT1A serotonin receptor. For this, low cholesterol level has been reported to be associated with depression and suicidality. However there have been inconsistent reports about this finding and the exact relationship between these factors remains controversial. Therefore, we investigated the link between serum cholesterol and its fractions with depression disorder and suicide attempt in 467 adult subjects in Mexican mestizo population. METHODS: Plasma levels of total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) were determined in 261 MDD patients meeting the DSM-5 criteria for major depressive disorder (MDD), 59 of whom had undergone an episode of suicide attempt, and 206 healthy controls. RESULTS: A significant decrease in total cholesterol, LDL-cholesterol, VLDL-cholesterol and triglyceride serum levels was observed in the groups of MDD patients and suicide attempt compared to those without suicidal behavior (p < 0.05). After adjusting for covariates, lower cholesterol levels were significantly associated with MDD (OR 4.229 CI 95% 2.555 - 7.000, p<.001) and suicide attempt (OR 5.540 CI 95% 2.825 - 10.866, p<.001) CONCLUSIONS: These results support the hypothesis that lower levels of cholesterol are associated with mood disorders like MDD and suicidal behavior. More mechanistic studies are needed to further explain this association.

Arsenic exposure and risk of preeclampsia in a Mexican mestizo population.

BACKGROUND: Exposure to arsenic in drinking water has been associated with various complications of pregnancy including fetal loss, low birth weight, anemia, gestational diabetes and spontaneous abortion. However, to date, there are no studies evaluating its possible association with preeclampsia. METHODS: This case-control study involved 104 preeclamptic and 202 healthy pregnant women. The concentrations of arsenic in drinking water and urine were measured using a Microwave Plasma-Atomic Emission Spectrometer. RESULTS: We found relatively low levels of arsenic in household tap water (range of 2.48-76.02 µg/L) and in the urine of the participants (7.1 µg/L vs 6.78 µg/L in cases and controls, respectively). CONCLUSIONS: The analysis between groups showed for the first time that at these lower levels of exposure there is no association with preeclampsia.

Polymorphisms in DNA repair genes (APEX1, XPD, XRCC1 and XRCC3) and risk of preeclampsia in a Mexican mestizo population.

Variations in genes involved in DNA repair systems have been proposed as risk factors for the development of preeclampsia (PE). We conducted a case-control study to investigate the association of Human apurinic/apyrimidinic (AP) endonuclease (APEX1) Asp148Glu (rs1130409), Xeroderma Pigmentosum group D (XPD) Lys751Gln (rs13181), X-ray repair cross-complementing group 1 (XRCC) Arg399Gln (rs25487) and X-ray repair cross-complementing group 3 (XRCC3) Thr241Met (rs861539) polymorphisms with PE in a Mexican population. Samples of 202 cases and 350 controls were genotyped using RTPCR. Association analyses based on a χ2 test and binary logistic regression were performed to determine the odds ratio (OR) and a 95% confidence interval (95% CI) for each polymorphism. The allelic frequencies of APEX1 Asp148Glu polymorphism showed statistical significant differences between preeclamptic and normal women (p = 0.036). Although neither of the polymorphisms proved to be a risk factor for the disease, the APEX1 Asp148Glu polymorphism showed a tendency of association (OR: 1.74, 95% CI = 0.96-3.14) and a significant trend (p for trend = 0.048). A subgroup analyses revealed differences in the allelic frequencies of APEX1 Asp148Glu polymorphism between women with mild preeclampsia and severe preeclampsia (p = 0.035). In conclusion, our results reveal no association between XPD Lys751Gln, XRCC Arg399Gln and XRCC3 Thr241Met polymorphisms and the risk of PE in a Mexican mestizo population; however, the results in the APEX1 Asp148Glu polymorphism suggest the need for future studies using a larger sample size.

Characterization of the complete chloroplast genome sequence of Agave durangensis (Asparagales: Asparagaceae: Agavoideae).

Agave durangensis commonly known as agave cenizo, is an endemic Agave species in Mexico used for mescal production, yet its taxonomic delimitation is still controversial. This study aimed to enhance taxonomic clarity by characterizing its chloroplast genome. Chloroplast DNA was isolated from 2-year-old A. durangensis leaves. The complete chloroplast genome size was 156,441 bp, comprising a large single-copy region (LSC), a pair of inverted repeat regions (IR), and a small single-copy region (SSC). Annotation revealed 87 protein-coding genes, 38 tRNAs, and 8 rRNAs, with notable gene inversions. Phylogenetic analysis suggests, A. durangensis forms a separate lineage within the Agave genus.

Genetic variation in oxidative stress and DNA repair genes in a Mexican population.

BACKGROUND: Oxidative stress has been associated with several complex diseases. Effects generated as a result of oxidative stress may be modulated by various genes. Variation in these genes, particularly when located within coding or regulating regions, may be the primary cause of this modulation. The aim of this work was to determine the allelic and genotypic frequencies of CAT C-262T, SOD3 Ala58Thr, APEX1 Asp148Glu, XPD Lys751Gln and XRCC3 Thr241Met genetic markers in a northern Mexican population. SUBJECTS AND METHODS: This study analysed 250 unrelated individuals by RT-PCR. RESULTS: A high allele mutant frequency was found in SOD3 Ala58Thr and APEX1 Asp148Glu genetic markers (0.395 and 0.38, respectively). A correspondence analysis showed that northern Mexicans are close to European populations. A linkage disequilibrium test between XPD Lys751Gln and CAT C-262T and XPD Lys751Gln and SOD3 Ala58Thr genetic markers was significant (p = 0.000). CONCLUSION: The genetic markers described in this work will be a valuable resource for future functional studies in the northern Mexican population to explore comprehensively their role in the aetiology of human diseases. Furthermore, it will be necessary to replicate these studies in other regions of Mexico due to differences between Mexican sub-populations.

The rs7208505 Polymorphism and Differential Expression of the SKA2 Gene in the Prefrontal Cortex of Suicide Victims from the Mexican Population.

OBJECTIVE: The main aim of the current study was to investigate whether SKA2 gene expression in the postmortem brain of rs7208505 genotype are altered in suicide victims from a Mexican population. METHODS: In this study, we report a genetic analysis of expression levels of the SKA2 gene in the prefrontal cortex of the postmortem brain of suicidal subjects (n = 22) compared to subjects who died of causes other than suicide (n = 22) in a Mexican population using RT-qPCR assays. Additionally, we genotyped the rs7208505 polymorphism in suicide victims (n = 98) and controls (n = 88) and we evaluate the association of genotypes for the SNP rs7208505 with expression level of SKA2. RESULTS: The results showed that the expression of the SKA2 gene was significantly higher in suicide victims compared to control subjects (p = 0.044). Interestingly, we observed a greater proportion of allele A of the rs7208505 in suicide victims than controls. Even though there was no association between the SNP with suicide in the study population we found a significative association of the expression level from SKA2 with the allele A of the rs7208505 and suicide. CONCLUSION: The evidence suggests that the expression of SKA2 in the prefrontal cortex may be a critical factor in the etiology of suicidal behavior.

HighlightsSuicide victims have a higher level of SKA2 gene expression in the brain's prefrontal cortex than control subjects.The SKA2 rs7208505 is not associated with suicide in the Mexican population studied.Allele frequencies for G are higher than allele frequencies for A in our study population.The allele A of the rs7208505 affects the expression values of the SKA2 gene.

Design of a Whole-Cell Biosensor Based on Bacillus subtilis Spores and the Green Fluorescent Protein To Monitor Arsenic.

A green fluorescent protein (GFP)-based whole-cell biosensor (WCB-GFP) for monitoring arsenic (As) was developed in Bacillus subtilis. To this end, we designed a reporter gene fusion carrying the gfpmut3a gene under the control of the promoter/operator region of the arsenic operon (Pars::gfpmut3a) in the extrachromosomal plasmid pAD123. This construct was transformed into B. subtilis 168, and the resultant strain was used as a whole-cell biosensor (BsWCB-GFP) for the detection of As. The BsWCB-GFP was specifically activated by inorganic As(III) and As(V), but not by dimethylarsinic acid [DMA(V)], and exhibited high tolerance to the noxious effects of arsenic. Accordingly, after 12 h exposure, B. subtilis cells carrying the Pars::gfpmut3a fusion exhibited 50 and 90% lethal doses (LD50 and LD90) to As(III) of 0.89 mM and As 1.71 mM, respectively. Notably, dormant spores from the BsWCB-GFP were able to report the presence of As(III) in a concentration range from 0.1 to 1,000 µM 4 h after the onset of germination. In summary, the specificity and high sensitivity for As, as well as its ability to proliferate under concentrations of the metal that are considered toxic in water and soil, makes the B. subtilis biosensor developed here a potentially important tool for monitoring environmental samples contaminated with this pollutant. IMPORTANCE Arsenic (As) contamination of groundwater is associated with serious worldwide health risks. Detection of this pollutant at concentrations that are established as permissible for water consumption by WHO is a matter of significant interest. Here, we report the generation of a whole-cell biosensor for As detection in the Gram-positive spore former B. subtilis. This biosensor reports the presence of inorganic As, activating the expression of the green fluorescent protein (GFP) under the control of the promoter/operator of the ars operon. The biosensor can proliferate under concentrations of As(III) that are considered toxic in water and soil and detect this ion at concentrations as low as 0.1 µM. Of note, spores of the Pars-GFP biosensor exhibited the ability to detect As(III) following germination and outgrowth. Therefore, this novel tool has the potential to be directly applied to monitor As contamination in environmental samples.

Alternative excision repair of ultraviolet B- and C-induced DNA damage in dormant and developing spores of Bacillus subtilis.

The nucleotide excision repair (NER) and spore photoproduct lyase DNA repair pathways are major determinants of Bacillus subtilis spore resistance to UV radiation. We report here that a putative ultraviolet (UV) damage endonuclease encoded by ywjD confers protection to developing and dormant spores of B. subtilis against UV DNA damage. In agreement with its predicted function, a His(6)-YwjD recombinant protein catalyzed the specific incision of UV-irradiated DNA in vitro. The maximum expression of a reporter gene fusion to the ywjD opening reading frame occurred late in sporulation, and this maximal expression was dependent on the forespore-specific RNA polymerase sigma factor, σ(G). Although the absence of YwjD and/or UvrA, an essential protein of the NER pathway, sensitized developing spores to UV-C, this effect was lower when these cells were treated with UV-B. In contrast, UV-B but not UV-C radiation dramatically decreased the survival of dormant spores deficient in both YwjD and UvrA. The distinct range of lesions generated by UV-C and UV-B and the different DNA photochemistry in developing and dormant spores may cause these differences. We postulate that in addition to the UvrABC repair system, developing and dormant spores of B. subtilis also rely on an alternative excision repair pathway involving YwjD to deal with the deleterious effects of various UV photoproducts.

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.

Maternal and umbilical cord procalcitonin, high-sensitivity C-reactive protein, and interleukin-6 levels in preeclamptic and normotensive patients: A cross-sectional study.

OBJECTIVES: To report maternal and umbilical vein levels of procalcitonin (PCT) in patients with preeclampsia (PE) compared to controls. As secondary aims, we measured high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6). Moreover, correlation analyses were performed between the inflammatory biomarkers and mean arterial pressure (MAP). STUDY DESIGN: This was a single center, cross-sectional study. MAIN OUTCOME MEASURES: After Institutional Review Board approval and written informed consent, patients with or without PE were enrolled. PCT, hs-CRP, and IL-6 levels were compared between groups using multiple linear regression models. We calculated the adjusted ratios of geometric means (aRGM) for the comparison of patients with and without PE. Correlation analysis between the inflammatory biomarkers and MAP was performed using Spearman's method. RESULTS: A total of 156 participants were enrolled, yielding 156 venous blood samples and umbilical venous blood samples. Seventy-six patients were in the PE group, and 80 patients were in the control group. Maternal plasma and serum concentrations of PCT (aRGM 3.35 (95% confidence interval [CI]: 2.26, 4.95; p < 0.001)), hs-CRP (aRGM 1.85 (95% CI: 1.30, 2.63; p = 0.003)), and IL-6 (aRGM 1.49 (95% CI: 1.08, 2.04; p = 0.045)) were higher in the PE group. In umbilical venous samples, the concentrations of PCT (aRGM 2.54 (95% CI: 1.46, 4.44; p = 0.003)) and hs-CRP (aRGM 1.45 (95% CI: 1.13, 1.87; p = 0.012)) in the PE group were higher than the controls. No difference in umbilical venous IL-6 concentrations were detected between PE vs. control groups (aRGM 1.46; 95% CI: 1.07, 1.98; p = 0.051). There was positive correlation for both PCT and hs-CRP with MAP in maternal and umbilical venous samples. However, there was no correlation between IL and 6 and MAP in maternal or umbilical venous samples. CONCLUSIONS: PCT levels were elevated in maternal and umbilical venous samples of patients with PE, and correlated with disease severity.

A Quest for New Cancer Diagnosis, Prognosis and Prediction Biomarkers and Their Use in Biosensors Development.

Traditional techniques for cancer diagnosis, such as nuclear magnetic resonance, ultrasound and tissue analysis, require sophisticated devices and highly trained personnel, which are characterized by elevated operation costs. The use of biomarkers has emerged as an alternative for cancer diagnosis, prognosis and prediction because their measurement in tissues or fluids, such as blood, urine or saliva, is characterized by shorter processing times. However, the biomarkers used currently, and the techniques used for their measurement, including ELISA, western-blot, polymerase chain reaction (PCR) or immunohistochemistry, possess low sensitivity and specificity. Therefore, the search for new proteomic, genomic or immunological biomarkers and the development of new noninvasive, easier and cheaper techniques that meet the sensitivity and specificity criteria for the diagnosis, prognosis and prediction of this disease has become a relevant topic. The purpose of this review is to provide an overview about the search for new cancer biomarkers, including the strategies that must be followed to identify them, as well as presenting the latest advances in the development of biosensors that possess a high potential for cancer diagnosis, prognosis and prediction, mainly focusing on their relevance in lung, prostate and breast cancers.

YwqL (EndoV), ExoA and PolA act in a novel alternative excision pathway to repair deaminated DNA bases in Bacillus subtilis.

DNA deamination generates base transitions and apurinic/apyrimidinic (AP)-sites which are potentially genotoxic and cytotoxic. In Bacillus subtilis uracil can be removed from DNA by the uracil DNA-glycosylase through the base excision repair pathway. Genetic evidence suggests that B. subtilis YwqL, a homolog of Endonuclease-V (EndoV), acts on a wider spectrum of deaminated bases but the factors that complete this pathway have remained elusive. Here, we report that a purified His6-YwqL (hereafter BsEndoV) protein had in vitro endonuclease activity against double-stranded DNAs containing a single uracil (U), hypoxanthine (Hx), xanthine (X) or an AP site. Interestingly, while BsEndoV catalyzed a single strand break at the second phosphodiester bond towards the 3'-end of the U and AP lesions, there was an additional cleavage of the phosphodiester bond preceding the Hx and X lesions. Remarkably, the repair event initiated by BsEndoV on Hx and X, was completed by a recombinant B. subtilis His6-DNA polymerase A (BsPolA), but not on BsEndoV-processed U and AP lesions. For the latter lesions a second excision event performed by a recombinant B. subtilis His6-ExoA (BsExoA) was necessary before completion of their repair by BsPolA. These results suggest the existence of a novel alternative excision repair pathway in B. subtilis that counteracts the genotoxic effects of base deamination. The presence of this novel pathway in vivo in B. subtilis was also supported by analysis of effects of single or multiple deletions of exoA, endoV and polA on spontaneous mutations in growing cells, and the sensitivity of growing wild-type and mutant cells to a DNA deaminating agent.

Oxidative stress equilibrium during obstetric event in normal pregnancy.

OBJECTIVE: The aim of this study was to determine malondialdehyde (MDA) concentration as an oxidative stress marker and total antioxidant capacity (TAC) in pregnancy before and after perinatal event. METHODS: This study was performed on 200 healthy full-term pregnant women admitted to pregnancy resolution in Maternal-Child Hospital of Durango, Mexico. Oxidative stress and TAC were assessed through detection of lipid peroxidation by quantitation of thiobarbituric acid-reactive substances (TBARS) and TAC through ferric reducing ability of the plasma (FRAP). RESULTS: Our results showed increased levels of MDA after vaginal delivery (VD). TAC was also increased after obstetric event, but it did not differ between VD and caesarean section. CONCLUSIONS: We demonstrated that MDA concentrations are increased two hours after obstetric event, and this increase correlates with VD. The TAC was increased as a compensatory mechanism during obstetric event. Another important finding is that women receiving analgesia administration in VD, as well as dexamethasone administration in caesarean section, experienced a protector effect that decreased MDA levels.

Lower uric Acid linked with cognitive dysfunction in the elderly.

Uric acid has been associated as a risk factor for cardiovascular disease. Recently, however, there is growing evidence that uric acid plays a role as antioxidant in the brain. In cognitive dysfunction, vascular and oxidative stress mechanisms play a role, but the link remains unknown. Therefore, we investigated the link between serum uric acid-levels and cognitive function in 62 elderly subjects. The statistical analysis was adjusted to age, sex and cardiovascular risk factors. Here, we found that lower serum uric acid levels are linked to cognitive dysfunction. In a Mexican population, higher levels of uric acid are associated with a decreased risk of dementia.

Association of COMT G675A and MTHFR C677T polymorphisms with hypertensive disorders of pregnancy in Mexican mestizo population.

OBJECTIVE: To investigate the relationship between COMT G675A and MTHFR C677T polymorphisms and hypertension disorders of pregnancy (HDP) in a Mexican mestizo population. DESIGN AND METHODS: This case-control study involved 194 HDP and 194 normoevolutive pregnant women. The polymorphisms were genotyped by real time PCR. RESULTS: Our results showed that the COMT AA genotype increases the risk to HDP (OR: 2.67; 95% CI 1.33-5.35), preeclampsia (OR: 2.69; 95% CI 1.00-7.22) and gestational hypertension (OR: 3.87; 95% CI 1.25-12.0). Furthermore, the double mutant genotype (COMTAA/MTHFRTT) potency the risk to HDP more than two times (OR: 5.21; 95% CI 1.12-24.3, p=0.019). CONCLUSION: Our work provides evidence that COMT 675AA genotype is a risk factor for HDP and that this risk is increased by the presence of MTHFR 677TT genotype in a Mexican mestizo population.

Effects of forespore-specific overexpression of apurinic/apyrimidinic endonuclease Nfo on the DNA-damage resistance properties of Bacillus subtilis spores.

The effects of overexpression of the apurinic/apyrimidinic DNA endonuclease Nfo on wet and dry heat and UV-C (254 nm) resistance of Bacillus subtilis spores with or without alpha/beta-type small, acid-soluble spore proteins (SASP) were determined. Results revealed that overexpression of Nfo > or =50-fold in spores increased the wet heat resistance of exoA nfo B. subtilis spores (termed alpha(-)beta(-)) that lack most alpha/beta-type SASP, but had no effect on these spores' UV-C resistance. Nfo overexpression also increased these spores' dry heat resistance, and to levels slightly greater than that of wild-type spores. These results are consistent: (1) with wet and dry heat (but not UV-C) generating abasic sites in alpha(-)beta(-) spore DNA; (2) with dry heat generating some of these lesions in spores that retain alpha/beta-type SASP; and (3) indicate that Nfo can repair these abasic lesions following spore germination.