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Acute kidney injury (AKI) is a highly prevalent and a critical complication of cardiac surgery (CS). Serum lactate (sLac) levels have consistently shown an association with morbimortality after CS. We performed a cross-sectional study including 264 adult patients that had a cardiac surgery between January and December 2020. Logistic regression analysis was performed to determine factors associated with AKI development. We measured the postoperative levels of sLac for all participants immediately after CS (T0) and at 4 h (T4) after the surgical intervention. A linear regression model was used to identify the factors influencing both sLac metrics. We identified four risk predictors of AKI; one was preoperative (atrial fibrillation), one intraoperative (cardiopulmonary bypass time), and two were postoperative (length of hospital stay and postoperative sLac). T0 and T4 sLac levels were higher among CS-AKI patients than in Non-CS-AKI patients. Postoperative sLac levels were significant independent predictors of CSA-AKI, and sLac levels are influenced by length of hospital stay, the number of transfused packed red blood cells, and the use of furosemide in CS-AKI patients. These findings may facilitate the earlier identification of patients susceptible to AKI after CS.
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Interleukin-10 (IL-10) is an immunomodulatory cytokine that plays a pivotal role in the pathogenesis of acute coronary syndromes (ACS). Here, we evaluated the role of IL10 promoter variants as markers for ACS susceptibility in Western Mexican patients as well as its association with IL10 mRNA and IL-10 plasma levels. Three promoter variants (- 1082 A > G, - 819 T > C and - 592 A > C) were analyzed in 300 ACS patients and 300 control group (CG) individuals. IL10 relative gene expression was evaluated in peripheral blood mononuclear cells (PBMC) and IL-10 levels were quantified in plasma. The allelic, genotypic and haplotypic frequencies did not show significant differences between groups. ACS patients had sevenfold higher mRNA IL10 level compared to CG (p = 0.0013). Homozygous C/C carriers in both - 819 T > C and - 592 A > C variants had 0.4-fold higher IL10 mRNA expression than heterozygous and polymorphic allele homozygous genotypes (p = 0.0357) in ACS group. There were significant differences in plasma IL-10 levels in CG and ACS group (1.001 vs 1.777 pg/mL, p = 0.0051). The variants were not markers of susceptibility to ACS in Western Mexican individuals. ACS patients showed higher IL10 expression than CG individuals which could be mediated by - 819 T > C and - 592 A > C variants and pharmacotherapy.
Assuntos
Síndrome Coronariana Aguda , Predisposição Genética para Doença , Interleucina-10 , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Humanos , Interleucina-10/genética , Interleucina-10/sangue , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos de Casos e Controles , Genótipo , Alelos , Biomarcadores/sangue , México , Leucócitos Mononucleares/metabolismo , Frequência do Gene , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Skin cancer is one of the most frequent types of cancer, and cutaneous squamous cell carcinoma (cSCC) constitutes 20% of non-melanoma skin cancer (NMSC) cases. PTCH1, a tumor suppressor gene involved in the Sonic hedgehog signaling pathway, plays a crucial role in neoplastic processes. METHODS: An analytical cross-sectional study, encompassing 211 cSCC patients and 290 individuals in a control group (CG), was performed. A subgroup of samples was considered for the relative expression analysis, and the results were obtained using quantitative real-time PCR (qPCR) with TaqMan® probes. The functional, splicing, and disease-causing effects of the proposed variants were explored via bioinformatics. RESULTS: cSCC was predominant in men, especially in sun-exposed areas such as the head and neck. No statistically significant differences were found regarding the rs357564, rs2236405, rs2297086, and rs41313327 variants of PTCH1, or in the risk of cSCC, nor in the mRNA expression between the cSCC group and CG. A functional effect of rs357564 and a disease-causing relation to rs41313327 was identified. CONCLUSION: The proposed variants were not associated with cSCC risk in this Mexican population, but we recognize the need for analyzing larger population groups to elucidate the disease-causing role of rare variants.
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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.
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Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/genética , Estudos Transversais , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , México/epidemiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/genéticaRESUMO
BACKGROUND: Some cytokines are strongly implicated in the development of squamous cell carcinoma (SCC) such as the Macrophage migration inhibitory factor (MIF). The haplotype -794 (CATT)5-8 /-173G>C in MIF gene polymorphisms has been associated with some types of cancer. The aim of this study is to establish the possible association between the presence of this haplotype in the MIF gene and its subsequent soluble levels with the susceptibility of SCC in western Mexican population. METHODS: This study included 175 SCC patients and 175 age-sex-matched individuals as a reference group (RG) from western Mexico. Genomic DNA was extracted from peripheral blood leukocytes. Polymorphisms were genotyped by endpoint PCR and PCR-RFLP, and the determination of MIF serum levels was measured by ELISA. Clinical characteristics were evaluated by a group of dermatologists. RESULTS: Analysis of [-794(CATT)5-8 /-173G>C] MIF gene polymorphisms showed that the 5C (OR = 2.7, p = 0.02) and the 7G (OR = 3.39, p < 0.01) haplotypes are associated with susceptibility in SCC. MIF soluble levels in SCC patients showed a median of 13.93 ng/mL, whereas the reference group showed 6.000 ng/mL. CONCLUSIONS: Our findings suggest that 5C and 7G [-794(CATT)5-8 /-173G>C] MIF gene haplotypes are associated with susceptibility to SCC and that SCC patients present increased soluble levels of MIF.
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Carcinoma de Células Escamosas , Fatores Inibidores da Migração de Macrófagos , Neoplasias Cutâneas , Humanos , Haplótipos , Carcinoma de Células Escamosas/genética , México , Predisposição Genética para Doença , Neoplasias Cutâneas/genética , Polimorfismo Genético , Fatores Inibidores da Migração de Macrófagos/genética , Oxirredutases Intramoleculares/genéticaRESUMO
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.
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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.
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Síndrome Coronariana Aguda , Antígenos CD36 , Dislipidemias , Infarto do Miocárdio com Supradesnível do Segmento ST , Síndrome Coronariana Aguda/genética , Angina Instável/genética , Antígenos CD36/genética , Expressão Gênica , Humanos , RNA Mensageiro/genética , Infarto do Miocárdio com Supradesnível do Segmento ST/genéticaRESUMO
Skin cancer is one of the main types of cancer worldwide, and non-melanoma skin cancer (NMSC) is the most frequent within this group. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common types. Multifactorial features are well-known for cancer development, and new hallmarks are gaining relevance. Genetics and epigenetic regulation play an essential role in cancer susceptibility and progression, as well as the variety of cells and molecules that interact in the tumor microenvironment. In this review, we provide an update on the genetic features of NMSC, candidate genes, and new therapies, considering diverse perspectives of skin carcinogenesis. The global health situation and the pandemic have been challenging for health care systems, especially in the diagnosis and treatment of patients with cancer. We provide innovative approaches to overcome the difficulties in the current clinical dynamics.
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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.
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Síndrome Coronariana Aguda , Síndrome Coronariana Aguda/genética , Apolipoproteínas B/genética , Humanos , México/epidemiologia , Nucleotídeos , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
The current global prevalence of heart failure is estimated at 64.34 million cases, and it is expected to increase in the coming years, especially in countries with a medium-low sociodemographic index where the prevalence of risk factors is increasing alarmingly. Heart failure is associated with many comorbidities and among them, cancer has stood out as a contributor of death in these patients. This connection points out new challenges both in the context of the pathophysiological mechanisms involved, as well as in the quality of life of affected individuals. A hallmark of heart failure is chronic activation of the renin-angiotensin-aldosterone system, especially marked by a systemic increase in levels of angiotensin-II, a peptide with pleiotropic activities. Drugs that target the renin-angiotensin-aldosterone system have shown promising results both in the prevention of secondary cardiovascular events in myocardial infarction and heart failure, including a lower risk of certain cancers in these patients, as well as in current cancer therapies; therefore, understanding the mechanisms involved in this complex relationship will provide tools for a better diagnosis and treatment and to improve the prognosis and quality of life of people suffering from these two deadly diseases.