Anti-hepatitis B virus activity of food nutrients and potential mechanisms of action.

Hepatitis B virus (HBV) is endemic in many parts of the world and is a significant cause of chronic liver damage and hepatocellular carcinoma. HBV therapeutics vary according to the disease stage. The best therapeutic option for patients with end-stage liver disease is liver transplantation, while for chronic patients, HBV infection is commonly managed using antivirals (nucleos(t)ides analogs or interferons). However, due to the accessibility issues and the high cost of antivirals, most HBV patients do not have access to treatment. These complications have led researchers to reconsider treatment approaches, such as nutritional therapy. This review summarizes the nutrients reported to have antiviral activity against HBV and their possible mechanism of action. Recent studies suggest resveratrol, vitamin E, lactoferrin, selenium, curcumin, luteolin-7-O-glucoside, moringa extracts, chlorogenic acid, and epigallocatechin-3-gallate may be beneficial for patients with hepatitis B. The anti-HBV effect of most of these nutrients has been analyzed in vitro and in animal models. Different antiviral and hepatoprotective mechanisms have been proposed for these nutrients, such as the activation of antioxidant and anti-inflammatory pathways, regulation of metabolic homeostasis, epigenetic control, activation of the p53 gene, inhibition of oncogenes, inhibition of virus entry, and induction of autophagosomes. In conclusion, scientific evidence indicates that HBV replication, transcription, and expression of viral antigens can be affected directly by nutrients. In the future, these nutrients may be considered to develop appropriate nutritional management for patients with hepatitis B.

Immunometabolic Effect of Cholesterol in Hepatitis C Infection: Implications in Clinical Management and Antiviral Therapy.

Hepatitis C virus (HCV) is a lipid-enveloped virion particle that causes infection to the liver, and as part of its life cycle, it disrupts the host lipid metabolic machinery, particularly the cholesterol synthesis pathway. The innate immune response generated by liver resident immune cells is responsible for successful viral eradication. Unfortunately, most patients fail to eliminate HCV and progress to chronic infection. Chronic infection is associated with hepatic fat accumulation and inflammation that triggers fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Despite that the current direct-acting antiviral agents have increased the cure rate of HCV infection, viral genotype and the host genetic background influence both the immune response and lipid metabolism. In this context, recent evidence has shown that cholesterol and its derivatives such as oxysterols might modulate and potentialize the hepatic innate immune response generated against HCV. The impairment of the HCV life cycle modulated by serum cholesterol could be relevant for the clinical management of HCV-infected patients before and after treatment. Alongside, cholesterol levels are modulated either by genetic variations in IL28B, ApoE, and LDLR or by dietary components. Indeed, some nutrients such as unsaturated fatty acids have demonstrated to be effective against HCV replication. Thus, cholesterol modifications may be considered as a new adjuvant strategy for HCV infection therapy by providing a biochemical tool that guides treatment decisions, an improved treatment response and favoring viral clearance. Herein, the mechanisms by which cholesterol contributes to the immune response against HCV infection and how genetic and environmental factors may affect this role are reviewed.

Expression of WNT genes in cervical cancer-derived cells: Implication of WNT7A in cell proliferation and migration.

According to the multifactorial model of cervical cancer (CC) causation, it is now recognized that other modifications, in addition to Human papillomavirus (HPV) infection, are necessary for the development of this neoplasia. Among these, it has been proposed that a dysregulation of the WNT pathway might favor malignant progression of HPV-immortalized keratinocytes. The aim of this study was to identify components of the WNT pathway differentially expressed in CC vs. non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A expression was found strongly downregulated in cell lines and biopsies derived from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviral gene delivery system or after adding a recombinant human protein decreases cell proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly accelerates proliferation. Decreased WNT7A expression was due to hypermethylation at particular CpG sites. To our knowledge, this is the first study reporting reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration.

Personalized medicine and nutrition in hepatology for preventing chronic liver disease in Mexico.

Chronic liver disease is a global health issue. Patients with chronic liver disease require a fresh approach that focuses on the genetic and environmental factors that contribute to disease initiation and progression. Emerging knowledge in the fields of Genomic Medicine and Genomic Nutrition demonstrates differences between countries in terms of genetics and lifestyle risk factors such as diet, physical activity, and mental health in chronic liver disease, which serves as the foundation for the implementation of Personalized Medicine and Nutrition (PerMed-Nut) strategies. Most of the world's populations have descended from various ethnic groupings. Mexico's population has a tripartite ancestral background, consisting of Amerindian, European, and African lineages, which is common across Latin America's regional countries. The purpose of this review is to discuss the genetic and environmental components that could be incorporated into a PerMed-Nut model for metabolic-associated liver disease, viral hepatitis B and C, and hepatocellular carcinoma in Mexico. Additionally, the implementation of the PerMed-Nut approach will require updated medicine and nutrition education curricula. Training and equipping future health professionals and researchers with new clinical and investigative abilities focused on preventing liver illnesses in the field of genomic hepatology globally is a vision that clinicians and nutritionists should be concerned about.

Combination of enteral and parenteral nutrition in the acute phase of critical illness: An updated systematic review and meta-analysis.

BACKGROUND: Uncertainty remains about the best route and timing of medical nutrition therapy in the acute phase of critical illness. Early combined enteral nutrition (EN) and parenteral nutrition (PN) may represent an attractive option to achieve recommended energy and protein goals in select patient groups. This meta-analysis aims to update and summarize the current evidence. METHODS: This systematic review and meta-analysis includes randomized controlled trials (RCTs) targeting the effect of EN alone vs a combination of EN with PN in the acute phase of critical illness in adult patients. Assessed outcomes include mortality, intensive care unit (ICU) and hospital length of stay (LOS), ventilation days, infectious complications, physical recovery, and quality-of-life outcomes. RESULTS: Twelve RCTs with 5543 patients were included. Treatment with a combination of EN with PN led to increased delivery of macronutrients. No statistically significant effect of a combination of EN with PN vs EN alone on any of the parameters was observed: mortality (risk ratio = 1.0; 95% CI, 0.79-1.28; P = .99), hospital LOS (mean difference, -1.44; CI, -5.59 to 2.71; P = .50), ICU LOS, and ventilation days. Trends toward improved physical outcomes were observed in two of four trials. CONCLUSION: A combination of EN with PN improved nutrition intake in the acute phase of critical illness in adults and was not inferior regarding the patients' outcomes. Large, adequately designed trials in select patient groups are needed to answer the question of whether this nutrition strategy has a clinically relevant treatment effect.

Venous tortuosity as a novel biomarker of rupture risk in arteriovenous malformations: ARI score.

BACKGROUND: Risk of rupture in arteriovenous malformations (AVMs) varies considerably among series. Hemodynamic factors, especially within the venous side of the circuit, seem to be responsible but are not yet well defined. We analyzed tortuosity in the draining vein as a potential new marker of rupture in AVMs, and propose a simple index to predict AVM bleeding. METHODS: A retrospective analysis of the venous angioarchitecture of brain AVMs was carried out at our center from 2013 to 2021, with special attention to venous tortuosity. After univariate analysis, the features of interest were combined to construct several predictive models using multivariate logistic regression. The best model proposed was the new AVM rupture index (ARI), which was then validated in an independent cohort. RESULTS: 68 AVMs were included in the first step and 32 in the validation cohort. Venous tortuosity, expressed as at least one curve >180°, was a significant predictor of rupture (p=0.023). The proposed bleeding index consisted of: venous tortuosity (any curve of >180°), single draining vein, and paraventricular/infratentorial location. It seems to be a robust evaluation tool, with an area under the receiver operating characteristic (AUROC) curve of 0.806 (95% CI 0.714 to 0.899), consistently replicated in the independent sample (AUROC 0.759 (95% CI 0.607 to 0.911)), and with an inter-rater kappa coefficient of 0.81 . CONCLUSIONS: Venous tortuosity may serve as a predictor of bleeding in AVMs that warrants further investigation. This likely new marker was one of the three elements of the proposed ARI. ARI outperformed the predictive accuracy of previous scores, and remained consistent in an independent cohort.

Impacts of Pesticides on Oral Cavity Health and Ecosystems: A Review.

Pesticides are chemical substances used to control, prevent, or destroy agricultural, domestic, and livestock pests. These compounds produce adverse changes in health, and they have been associated with the development of multiple chronic diseases. This study aimed to present a detailed review of the effect of pesticides on the oral cavity and the oral microbiome. In the oral cavity, pesticides alter and/or modify tissues and the microbiome, thereby triggering imbalance in the ecosystem, generating an inflammatory response, and activating hydrolytic enzymes. In particular, the imbalance in the oral microbiome creates a dysbiosis that modifies the number, composition, and/or functions of the constituent microorganisms and the local response of the host. Pesticide exposure alters epithelial cells, and oral microbiota, and disrupts the homeostasis of the oral environment. The presence of pesticides in the oral cavity predisposes the appearance of pathologies such as caries, periodontal diseases, oral cancer, and odontogenic infections. In this study, we analyzed the effect of organochlorines, organophosphates, pyrethroids, carbamates, bipyridyls, and triazineson oral cavity health and ecosystems.

Association of Apolipoprotein e2 Allele with Insulin Resistance and Risk of Type 2 Diabetes Mellitus Among an Admixed Population of Mexico.

PURPOSE: This study aimed to analyze the association of the apolipoprotein E (ApoE) polymorphisms with type 2 diabetes mellitus (T2DM) among the admixed population of West Mexico. PATIENTS AND METHODS: ApoE genotypes were determined in 168 T2DM patients and 449 non-diabetic control subjects from the general admixed population of West Mexico. The non-diabetic subjects were stratified according to body mass index (BMI) in normal weight (n=186), overweight (n=138), and obesity (n=125). ApoE genotypes were assessed by using a TaqMan allelic discrimination assay, insulin resistance (IR) by HOMA-IR, and biochemistry with a dry chemistry assay. RESULTS: The rate of dyslipidemias and IR increased by BMI category among the control subjects. The greater shift in the prevalence of dyslipidemia was observed from normal weight (51.4%) to overweight (76.6%), p<0.01. Normal weight or obese e4 allele carriers had a higher level of total cholesterol and hypercholesterolemia than non-e4 carriers. Among the T2DM patients, the e2 carriers had abnormal HOMA-IR value than the non-e2 carriers (p=0.002). Comparatively, between the T2DM patients vs non-diabetics, the e2e3 genotype or e2 allele conferred a higher risk for T2DM (adjusted OR= 2.36, 95% CI 1.28-4.34, p=0.006 and adjusted OR=2.1, 95% Cl 1.20-3.79, p=0.009, respectively). CONCLUSION: The ApoE e2 allele was associated with IR and the risk of T2DM in subjects from the general admixed population of West Mexico.

Wilkie's syndrome as a cause of bowel obstruction in adults: A case report.

BACKGROUND: The superior mesenteric artery (SMA) syndrome, also known as Wilkie's syndrome, is one of the rarest causes of small bowel obstruction. CLINICAL CASE: A 36-year-old female patient, with a medical history of diabetes mellitus type 2, arrived at the emergency department with upper intestinal obstruction; a study protocol is made, integrating the diagnosis of Wilkie's syndrome. We performed a laparoscopic duodenojejunostomy, the patient did well in the post-operative period. CONCLUSIONS: Laparoscopic duodenojejunostomy is a practical option to treat Wilkie's syndrome. It provides definitive treatment with the advantages and benefits of minimally invasive surgery.

ANTECEDENTES: El síndrome de la arteria mesentérica superior o síndrome de Wilkie es una de las causas más raras de obstrucción del intestino Delgado. CASO CLÍNICO: Mujer de 36 años, con antecedente de diabetes mellitus tipo 2, que llegó al servicio de urgencias con un cuadro de oclusión intestinal alta. Se realizó protocolo de estudio, integrando el diagnóstico de síndrome de Wilkie. Se realizó anastomosis duodenoyeyunal laparoscópica y la paciente cursó con adecuada evolución posquirúrgica. CONCLUSIONES: La anastomosis duodenoyeyunal laparoscópica es una opción práctica en el tratamiento del síndrome de Wilkie, con las ventajas y beneficios de la cirugía de mínima invasión.

Comparison between surgical techniques in gallstone ileus and outcomes.

INTRODUCTION: Gallstone ileus is a rare cause of mechanical bowel obstruction, generally found in elderly patients who often have other significant medical conditions. OBJECTIVE: The objective of the study was to determine the prevalence of gallstone ileus and the number of postsurgical complications and outcomes depending on what type of surgical management is performed. METHOD: Cohort, retrospective, observational, and comparative study was conducted, which included 31 patients undergoing surgery for gallstone ileus. Three groups were integrated according to the type of surgical procedure: Group 1: enterotomy and stone extraction alone,. Group 2: enterotomy and cholecystectomy with fistula closure, and Group 3: bowel resection alone. RESULTS: A total of 31 patients were analyzed. Gallstone ileus represented the 1.44% of all cases of bowel obstruction. Complication rates were similar between three groups. Mortality rate was lower in Group A, especially when compared to Group B, with a statistically significant difference (p < 0.05). CONCLUSIONS: Surgery is the pillar in treatment of gallstone ileus. Enterotomy with stone extraction alone appears to be associated with a lower mortality rate and better outcomes when compared to more extensive techniques.

ANTECEDENTES: El íleo biliar es una causa rara de obstrucción intestinal mecánica, que se presenta generalmente en pacientes ancianos que a menudo tienen otras afecciones médicas importantes. OBJETIVO: Determinar la prevalencia del íleo biliar, el número de complicaciones y los resultados según el tipo de tratamiento quirúrgico que se realice. MÉTODO: Estudio de cohorte, retrospectivo, observacional y comparativo, que incluyó 31 pacientes sometidos a cirugía por íleo biliar. Se integraron tres grupos según el tipo de procedimiento quirúrgico: grupo 1, enterotomía y extracción de cálculos únicamente; grupo 2, enterotomía y colecistectomía con cierre de fístula; y grupo 3, resección intestinal únicamente. RESULTADOS: Se analizaron 31 pacientes. El íleo biliar representó el 1.44% de todos los casos de obstrucción intestinal. Las tasas de complicaciones fueron similares en los tres grupos. La tasa de mortalidad fue menor en el grupo 1, en especial cuando se comparó con el grupo 2, con una diferencia estadísticamente significativa (p < 0.05). CONCLUSIONES: La cirugía es el pilar en el tratamiento del íleo biliar. La enterotomía con extracción de cálculos parece asociarse con una menor tasa de mortalidad y mejores resultados en comparación con técnicas más extensas.

Exogenous Expression of WNT7A in Leukemia-Derived Cell Lines Induces Resistance to Chemotherapeutic Agents.

BACKGROUND: Dysregulations of the WNT pathway are implicated in the malignant transformation of different types of neoplasia. WNT7A is expressed in normal peripheral lymphocytes, but is decreased in the tumoral counterpart. Furthermore, the treatment of leukemic cells with recombinant WNT7A decreases proliferation, suggesting its possible use as a therapeutic biomolecule. This study aimed to evaluate the concomitant action of WNT7A and different chemotherapeutic agents over proliferation and cell death of leukemia/ lymphoma derived cell lines. METHODS: Ectopic expression of WNT7A was induced in CEM and BJAB cell lines by using a lentiviral system. RNA expression was analyzed by microarrays and qPCR, and protein expression was determined by Western Blot. Cell proliferation was measured by cell counting, metabolic activity by WST-1 assay, cell death and DNA content by flow cytometry. RESULTS: WNT7A ectopic expression was shown to decrease cell proliferation, but the apoptosis rate of leukemic cells was not altered. Moreover, these cells acquired resistance to doxorubicin, vincristine and MG-132. Cell cycle analysis reveals a decrease in G1 and an increase in S and G2 phases with a further upregulation of senescence- associated genes. Microarray analysis reveals that most gene expression changes were related to cancer and metabolic associated pathways. All those changes appear to be independent of the WNT canonical pathway regulation. CONCLUSION: WNT7A negatively regulates cell proliferation in leukemic cell lines and promotes resistance to chemotherapeutic agents by inducing a senescence-like phenotype independently of the WNT canonical pathway.

Effectiveness of Hyperbaric Oxygenation Versus Normobaric Oxygenation Therapy in Carbon Monoxide Poisoning: A Systematic Review.

Carbon monoxide (CO) is a gas product of combustion, considered highly poisonous. Prolonged CO exposure is responsible for more than half of fatal poisonings and is also one of the leading causes of poisoning in Western countries. We aimed to compare the effectiveness of therapy with hyperbaric oxygen (HBO) versus normobaric oxygen (NBO) in the setting of carbon monoxide poisoning (COP). We independently searched the National Library of Medicine's Medline (PubMed™), ScienceDirect™, and Scielo™ for any relevant studies published from 1989 to 2017, using the following keywords: hyperbaric therapy, hyperbaric oxygenation, normobaric therapy, carbon monoxide poisoning, carboxyhemoglobin, Haldane effect. We analyzed the studies that suggested the effectiveness of HBO or NBO. Also, we searched for studies related to COP; including history, epidemiology (risk factors, incidence, demographics), pathophysiology, clinical manifestations, diagnosis, and treatment. Sixty-eight articles were found, sixteen of which dealt with either HBO or NBO or both. Twelve suggested HBO as the treatment of choice in COP; four studies indicated that NBO was an adequate treatment due to its cost-effectiveness and availability in the emergency department (ED). HBO has been shown in several studies to be effective in moderate to high-risk COP situations, being the therapy of choice to avoid sequelae, especially neurologically. NBO can be considered as a reasonable alternative due to its cost-effectiveness. The availability and understanding of different therapeutic interventions are critical in the management of patients with COP in ED and the Critical Care unit.

Hepatitis C virus clearance and less liver damage in patients with high cholesterol, low-density lipoprotein cholesterol and APOE ε4 allele.

BACKGROUND: Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus (HCV). APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection. The relationship between cholesterol, APOE alleles, and the outcome of HCV infection has not been evaluated in the admixed population of Mexico. AIM: To investigate the role of APOE -ε2, -ε3, and -ε4 alleles and the metabolic profile in the outcome of HCV infection. METHODS: A total of 299 treatment-naïve HCV patients were included in this retrospective study. Patients were stratified in chronic hepatitis C (CHC) (n = 206) and spontaneous clearance (SC) (n = 93). A clinical record was registered. Biochemical tests were assessed by dry chemistry assay. APOE genotypes were determined using a Real-Time polymerase chain reaction assay. RESULTS: Total cholesterol, low-density lipoprotein cholesterol (LDL-c), triglycerides, and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOE ε4 allele (12.4% vs 7.3%). SC patients were overweight (54.8%). The ε4 allele was associated with SC (OR = 0.55, 95%CI: 0.31-0.98, P = 0.042) and mild fibrosis (F1-F2) in CHC patients (OR 0.091, 95%CI 0.01-0.75, P = 0.020). LDL-c ≥ 101.5 mg/dL (OR = 0.20, 95%CI: 0.10-0.41, P < 0.001) and BMI ≥ 26.6 kg/m2 (OR= 0.37, 95%CI: 0.18-0.76, P < 0.001) were associated with SC status; while ALT ≥ 50.5 IU/L was negatively associated (OR = 5.67, 95%CI: 2.69-11.97, P < 0.001). CONCLUSION: In SC patients, the APOE ε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.

Williams-Beuren syndrome in Mexican patients confirmed by FISH and assessed by aCGH.

Williams-Beuren syndrome (WBS) has a prevalence of 1/7500-20000 live births and results principally from a de novo deletion in 7q11.23 with a length of 1.5 Mb or 1.8 Mb. This study aimed to determine the frequency of 7q11.23 deletion, size of the segment lost, and involved genes in 47 patients with a clinical diagnosis of WBS and analysed by fluorescence in situ hybridization (FISH); among them, 31 had the expected deletion. Micro-array comparative genomic hybridization (aCGH) confirmed the loss in all 18 positive-patients tested: 14 patients had a 1.5 Mb deletion with the same breakpoints at 7q11.23 (hg19: 72726578-74139390) and comprising 24 coding genes from TRIM50 to GTF2I. Four patients showed an atypical deletion: two had a 1.6 Mb loss encompassing 27 coding genes, from NSUN5 to GTF2IRD2; another had a 1.7 Mb deletion involving 27 coding genes, from POM121 to GTF2I; the remaining patient presented a deletion of 1.2 Mb that included 21 coding genes from POM121 to LIMK1. aCGH confirmed the lack of deletion in 5/16 negative-patients by FISH. All 47 patients had the characteristic facial phenotype of WBS and 45 of 47 had the typical behavioural and developmental abnormalities. Our observations further confirm that patients with a classical deletion present a typical WBS phenotype, whereas those with a high (criteria of the American Association of Pediatrics, APP) clinical score but lacking the expected deletion may harbour an ELN point mutation. Overall, the concomitant CNVs appeared to be incidental findings.

Enteral nutritional support in non-ICU hospitalized patients: current practice in Mexico.

BACKGROUND AND OBJECTIVES: Patients receiving >=80% of their energy requirements by enteral nutrition (EN) have better clinical outcomes; unfortunately, there are discrepancies between the amount prescribed and amount received. The aim of this study was to explore the nutritional clinical practice, determine the adequacy and identify reasons for underfeeding. METHODS AND STUDY DESIGN: A retrospective study was conducted in hospitalized, non-intensive care unit, adult patients receiving EN for >=72 h. The following data were recorded: the prescribed target of energy and protein per day, daily energy intake, and the percentage of adequacy of the energy and protein requirement up to hospital day seven. Complications during administration or reasons for interruption and the proportion of patients who received >=80% of the energy goals on days four and seven were also recorded. RESULTS: In total, 52 patients were included (61.5% women), with a median age of 57.5 years; 20.4% and 6.1% of the patients received >=80% of their energy and protein goals, respectively, on day four, which improved to 28% (p<0.005) and 19% (p<0.001), respectively, on day seven. During the first seven days, a statistically significant (p<0.001) difference was observed between the amount of prescribed and administered energy over 24 h. The patients who received <80% of their total energy requirement remained hospitalized for 29 days (IQR 16.5-45.5), while those who received >=80% were hospitalized for 18 days (IQR 13.3-28.8) (p<0.05). CONCLUSIONS: Significant energy and protein deficits were documented. Furthermore, it is necessary to use strategies such as the implementation of an algorithm to optimize EN.

[HPV genotypes prevalence in México and worldwide detected by Linear Array]. / Prevalencia de genotipos de VPH en México y en el mundo detectados mediante Linear Array.

Infection with human papillomavirus (HPV) is the main factor associated with the development of cervical cancer (CC). Knowing about the prevalence of HPVs at different stages in the development of CC is important for determining the HPV oncogenic risk, the development of screening strategies, the evaluation of prevention programs, and also for vaccine designing. This paper is a meta-analysis of HPV prevalence worldwide and in Mexico from studies using the Linear Array® HPV Genotyping Test as a diagnostic test (it is the commercial test that, up to date, identifies the largest number of HPV genotypes in a single sample) in DNA of cervical samples from women with normal cytology, with low grade squamous intraepithelial lesions (LGSIL), with high grade squamous intraepithelial lesions (HGSIL) and with CC. The most prevalent genotypes after HPV-16 and -18 in women with CC varies depending on geographic region, which supports the need to develop detection and prevention strategies according to the characteristics of the population.

La infección por el virus de papiloma humano (VPH) es el principal factor asociado al desarrollo de cáncer cervicouterino (CaCU). Conocer la prevalencia de los diversos VPH en distintas etapas del desarrollo del CaCU es relevante para determinar los VPH de riesgo oncogénico, establecer el desarrollo de estrategias de tamizaje y la evaluación de programas de prevención, así como para el diseño de vacunas. El presente trabajo es un metaanálisis sobre prevalencia de VPH a nivel mundial y en México de estudios que hayan utilizado el Linear Array® HPV Genotyping Test como prueba diagnóstica (prueba comercial que a la fecha identifica la mayor cantidad de genotipos de VPH en una sola muestra), en ADN de raspados cervicales de mujeres con diagnóstico citológico normal, con lesión intraepitelial escamosa de bajo grado (LIEBG), con lesión intraepitelial escamosa de alto grado (LIEAG) y con CaCU. En mujeres con este tipo de cáncer, los genotipos más prevalentes después de los VPH-16 y -18 varían dependiendo de la región geográfica, lo que soporta la necesidad de desarrollar estrategias de detección y prevención acordes a las características de la población.

Expression of transcription factor grainyhead-like 2 is diminished in cervical cancer.

The transcription factor grainyhead-like 2 (GRHL2) is evolutionarily conserved in many different species, and is involved in morphogenesis, epithelial differentiation, and the control of the epithelial-mesenchymal transition. It has also recently been implicated in carcinogenesis, but its role in this remains controversial. Expression of GRHL2 has not previously been reported in cervical cancer, so the present study aimed to characterize GRHL2 expression in cervical cancer-derived cell lines (CCCLs) and cervical tissues with different grades of lesions. Microarray analysis found that the expression of 58 genes was down-regulated in CCCLs compared to HaCaT cells (non-tumorigenic human epithelial cell line). The expression of eight of these genes was validated by quantitative real-time PCR (qPCR), and GRHL2 was found to be the most down-regulated. Western blot assays corroborated that GRHL2 protein levels were strongly down-regulated in CCCLs. Cervical cells from women without cervical lesions were shown to express GRHL2, while immunohistochemistry found that positivity to GRHL2 decreased in cervical cancer tissues. In conclusion, a loss or strong reduction in GRHL2 expression appears to be a characteristic of cervical cancer, suggesting that GRHL2 down-regulation is a necessary step during cervical carcinogenesis. However, further studies are needed to delineate the role of GRHL2 in cervical cancer and during malignant progression.

Distribution of CYP2D6 and CYP2C19 polymorphisms associated with poor metabolizer phenotype in five Amerindian groups and western Mestizos from Mexico.

BACKGROUND: The distribution of polymorphisms in the CYP2D6 and CYP2C19 genes allows inferring the potential risk for specific adverse drug reactions and lack of therapeutic effects in humans. This variability shows differences among human populations. The aim of this study was to analyze single-nucleotide polymorphisms related to a poor metabolizer (PM) phenotype in nonpreviously studied Amerindian groups and Mestizos (general admixed population) from Mexico. METHODS: We detected by SNaPshot(®) different polymorphisms located in CYP2D6 (*3, *4, *6, *7, and *8) and CYP2C19 (*2, *3, *4 and *5) in western Mestizos (n=145) and five Amerindian groups from Mexico: Tarahumaras from the North (n=88); Purépechas from the Center (n=101); and Tojolabales (n=68), Tzotziles (n=88), and Tzeltales (n=20) from the Southeast. Genotypes were observed by capillary electrophoresis. The genetic relationships among these populations were estimated based on these genes. RESULTS AND DISCUSSION: The wild-type allele (*1) of both genes was predominant in the Mexican populations studied. The most widely observed alleles were CYP2C19*2 (range, 0%-31%) and CYP2D6*4 (range, 1.2%-7.3%), whereas CYP2D6*3 was exclusively detected in Mestizos. Conversely, CYP2C19*4 and *5, as well as CYP2D6*3, *6, *7, and *8, were not observed in the majority of the Mexican populations. The Tarahumaras presented a high frequency of the allele CYP2C19*2 (31%) and of homozygotes *2/*2 (10.7%), which represent a high frequency of potentially PM phenotypes in this Amerindian group. The genetic distances showed high differentiation of Tarahumaras (principally for CYP2C19 gene). In general, a relative proximity was observed between most of the Amerindian, Mexican-Mestizo, and Latin-American populations. CONCLUSION: In general, the wild-type allele (*1) predominates in Mexican populations, outlining a relatively homogeneous distribution for CYP2C19 and CYP2D6. The exception is the Tarahumara group that displays a potentially increased risk for adverse reactions to CYP2C19-metabolized drugs.