Association between the FAAH C385A variant (rs324420) and obesity-related traits: a systematic review.

BACKGROUND: Overweight and obesity are the consequence of a sustained positive energy balance. Twin studies show high heritability rates pointing to genetics as one of the principal risk factors. By 2022, genomic studies led to the identification of almost 300 obesity-associated variants that could help to fill the gap of the high heritability rates. The endocannabinoid system is a critical regulator of metabolism for its effects on the central nervous system and peripheral tissues. Fatty acid amide hydrolase (FAAH) is a key enzyme in the inactivation of one of the two endocannabinoids, anandamide, and of its congeners. The rs324420 variant within the FAAH gene is a nucleotide missense change at position 385 from cytosine to adenine, resulting in a non-synonymous amino acid substitution from proline to threonine in the FAAH enzyme. This change increases sensitivity to proteolytic degradation, leading to reduced FAAH levels and increased levels of anandamide, associated with obesity-related traits. However, association studies of this variant with metabolic parameters have found conflicting results. This work aims to perform a systematic review of the existing literature on the association of the rs324420 variant in the FAAH gene with obesity and its related traits. METHODS: A literature search was conducted in PubMed, Web of Science, and Scopus. A total of 645 eligible studies were identified for the review. RESULTS/CONCLUSIONS: After the identification, duplicate elimination, title and abstract screening, and full-text evaluation, 28 studies were included, involving 28 183 individuals. We show some evidence of associations between the presence of the variant allele and higher body mass index, waist circumference, fat mass, and waist-to-hip ratio levels and alterations in glucose and lipid homeostasis. However, this evidence should be taken with caution, as many included studies did not report a significant difference between genotypes. These discordant results could be explained mainly by the pleiotropy of the endocannabinoid system, the increase of other anandamide-like mediators metabolized by FAAH, and the influence of gene-environment interactions. More research is necessary to study the endocannabinoidomic profiles and their association with metabolic diseases.

Pharmacomicrobiomics and Drug-Infection Interactions: The Impact of Commensal, Symbiotic and Pathogenic Microorganisms on a Host Response to Drug Therapy.

Microorganisms have a close relationship with humans, whether it is commensal, symbiotic, or pathogenic. Recently, it has been documented that microorganisms may influence the response to drug therapy. Pharmacomicrobiomics is an emerging field that focuses on the study of how variations in the microbiome affect the disposition, action, and toxicity of drugs. Two additional sciences have been added to complement pharmacomicrobiomics, namely toxicomicrobiomics, which explores how the microbiome influences drug metabolism and toxicity, and pharmacoecology, which refers to modifications in the microbiome as a result of drug administration. In this context, we introduce the concept of "drug-infection interaction" to describe the influence of pathogenic microorganisms on drug response. This review analyzes the current state of knowledge regarding the relevance of microorganisms in the host's response to drugs. It also highlights promising areas for future research and proposes the term "drug-infection interaction" as an extension of pharmacomicrobiomics.

Chronic Administration of Diethylnitrosamine and 2-Acetylaminofluorene Induces Hepatocellular Carcinoma in Wistar Rats.

This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a hepatocarcinogenesis model induced by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Thirteen rats weighing 180 to 200 g were divided into two groups: control and treated. Rats in the treated group were administered an intraperitoneal (i.p.) injection of DEN (50 mg/kg/week) and an intragastric (i.g.) dose of 2-AAF (25 mg/kg/week) for 18 weeks. The treated group had significant increases in their total cholesterol, HDL-C, AST, ALT, ALKP, and GGT levels. Furthermore, a histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa that were distributed between the portal triads and collagen fibers through the hepatic sinusoids. The gene expressions of 24 genes related to fibrosis, inflammation, apoptosis, cell growth, angiogenesis, lipid metabolism, and alpha-fetoprotein (AFP) were analyzed; only TGFß, COL1α1, CYP2E1, CAT, SOD, IL6, TNF-α, and ALB showed significant differences when both groups were compared. Additionally, lung histopathological alterations were found in the treated group, suggesting metastasis. In this model, the chronic administration of DEN+2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats without AFP gene expression changes, highlighting different signatures in hepatocellular carcinoma heterogeneity.

A comparison of opioid-containing anesthesia versus opioid-free anesthesia using the Cortínez-Sepúlveda model on differential cytokine responses in obese patients undergoing gastric bypass surgery: a randomized controlled trial.

BACKGROUND: Opioid anesthetic agents can modulate the impaired immune response in obese patients through mechanisms that involve the expression and release of cytokines. For this reason, anesthetic care for obese patients remains controversial. Therefore, the aim of the study was to compare the effect of opioid-containing anesthesia (OCA) vs opioid-free anesthesia (OFA) using the Cortínez-Sepúlveda model on IL-6, IL-1ß and TNF-α serum levels before and after surgery in obese patients undergoing bypass surgery. METHODS: This randomized cross-sectional study conducted among 40 unrelated obese adults was performed in the Civil Hospital of Guadalajara "Dr. Juan I. Menchaca". Before undergoing laparoscopic Roux-en-Y gastric bypass, patients were randomly assigned to two anesthesia groups: OCA (n = 20) or OFA (n = 20). Fentanyl was the opioid used in the OCA group. The Cortínez-Sepúlveda pharmacokinetic model was used to characterize the disposition of intravenous propofol for the target-controlled infusion technique in obese patients. Body mass was determined to the nearest 0.05 kg using a balance scale (Seca 703; Seca, Hamburg, Germany). Blood samples were taken before and immediately after surgery and cytokine concentrations were determined by ELISA. Pain was assessed using a numerical pain rating scale. Adverse effects were collected within the first 24 h after surgery. RESULTS: A total of 6 men and 34 women were included (37.9 ± 10.6 years). Pre-surgery IL-6 and TNF-α serum levels were not detected in study subjects. However, IL-1ß levels significantly decreased after surgery (49.58 pg/mL (18.50-112.20)-before surgery vs 13 pg/mL (5.43-22)-after surgery, p = 0.019). IL-6 concentrations were significantly higher in subjects who received OCA (with fentanyl) compared to subjects with OFA (224.5 pg/mL (186.3-262.8) vs 99.5 pg/mL (60.8-138.2), respectively, p < 0.001; adjusted by age, gender, and BMI). In addition, the use of opioids confers an increased risk for higher IL-6 levels in obese patients (OR = 2.95, 95% CI: 1.2-7.2, p = 0.010). A linear regression model showed that the operative time (in hours) of bypass surgery and anesthetic technique were positively correlated with IL-6 levels. CONCLUSION: Anesthesia with opioids correlated positively with IL-6 serum levels in obese patients undergoing bypass surgery. This finding could have clinical relevance when an appropriate anesthetic management plan is selected for bariatric surgical patients. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov Identification Number: NCT04854252, date 22/04/2021.

The ACTN3 R577X polymorphism is associated with metabolic alterations in a sex-dependent manner in subjects from western Mexico.

BACKGROUND: The ACTN3 gene is primarily expressed in fast skeletal muscle fibres. A common nonsense polymorphism in this gene is ACTN3 R577X (rs1815739), which causes an absolute deficiency of α-actinin-3 protein and alterations in muscle metabolism. Considering metabolic alterations are influenced by nutrition and genetic factors, as well as lifestyle factors, we hypothesise a possible association of the ACTN3 R577X polymorphism with metabolic alterations. METHODS: In this cross-sectional study, 397 adults met the inclusion criteria. Body composition was measured by electrical bioimpedance. Dietary data were analysed using Nutritionist Pro™ software. Biochemical variables were determined by dry chemistry. Genomic DNA was extracted from peripheral leukocytes and genotyping of the ACTN3 R577X polymorphism was determined by allelic discrimination using TaqMan probes. The statistical analyses were performed using SPSS statistical software. p < 0.05 was considered statistically significant. RESULTS: The ACTN3 577XX genotype was associated with high glucose, triglyceride and very low density lipoprotein-cholesterol levels and a higher frequency of hypertriglyceridaemia and insulin resistance in women. In males, the genetic variant showed a trend towards significance for insulin resistance. CONCLUSIONS: The ACTN3 R577X polymorphism was associated with metabolic alterations in women and a tendency was observed in men variant carriers. Thus, this common genetic variant could be implicated in the development of chronic metabolic diseases.

Association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to psoriasis and psoriatic arthritis: a meta-analysis.

BACKGROUND: Psoriasis (Ps) is a chronic dermatosis characterized by erythematous-squamous plaques derived from an inflammatory response. The effect of polymorphisms in the genes that encode the members of the IL-17 family and their receptors has been studied to find an association with the susceptibility to Ps. However, the findings have not been conclusive. OBJECTIVES: To describe the association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to Ps. METHOD: A systematic review was conducted using the PubMed and Scopus databases to identify studies that evaluated the association between IL-17A, IL-17F, and IL-17RA gene polymorphisms and Ps susceptibility. This meta-analysis included reports published until June 2021. Heterogeneity was assessed using Cochran's Q-statistic test and I2 statistics. The associations between polymorphisms and Ps susceptibility were determined by pooled OR with a 95% CI. RESULTS: Fifteen studies were included. The frequency of the T allele of the IL-17F rs763780 polymorphism was significantly lower in patients with vulgar Ps (OR = 0.732, p = 0.026). The TT genotype of the IL-17F rs763780 polymorphism was significantly associated with a decreased frequency in individuals with Ps and psoriatic arthritis (PsA) (TT:TC + CC OR = 0.664, p = 0.046). Regarding IL-17RA polymorphisms, the AG genotype of the rs4819554 polymorphism showed a near-significant decrease in psoriasis risk compared to the GG genotype (AG:GG OR = 0.604, p = 0.050). Other polymorphisms in IL-17A, IL-17F and IL-17RA showed no association with Ps. CONCLUSIONS: The T allele and TT genotype of the IL-17F rs763780 polymorphism may be associated with a decreased risk of psoriasis. Therefore, the implications of this variant on psoriasis pathogenesis and treatment require further investigation.

Association between rs662 (A > G) and rs854560 (A > T) polymorphisms in PON1 gene and the susceptibility for psoriasis in mestizo population of Western Mexico.

Psoriasis is a chronic, autoimmune skin disease. In psoriasis, PON1 activity is diminished and peroxidation biomarkers are elevated. The most studied PON1 polymorphisms are rs662 (A > G) and rs854560 (A > T), which have been associated with the antioxidant activity of PON1, risk of cardiovascular diseases and psoriasis development. The aim of this study, was to determine the association of rs662 (A > G) and rs854560 (A > T) PON1 polymorphisms with psoriasis susceptibility in Western Mexico population. In this case-control study, we included 104 psoriasis patients and 124 control subjects. The genotyping of polymorphisms rs662 (A > G) and rs854560 (A > T) of PON1 was carried out by PCR-RFLPs. The lipid profiles were quantified by enzymatic colorimetric method, and PON1 activity was determined by spectrophotometry. The lipid profile levels, except HDL-C and atherogenic index, were higher in patients vs. controls. Patients presented lower paraoxonase and arylesterase activity. The G allele of rs662 (A > G) is associated with risk for psoriasis, while the T allele of rs854560 (A > T) is associated with low susceptibility to psoriasis. The AG haplotype was more frequent within the patient group (p < 0.05). The AA and AG genotypes of rs662 (A > G) and TT and AA genotypes of rs854560 (A > T) are associated with lower PONase and ARE activity in patients vs. controls. Patients with the G allele of rs662 (G > A) and T alleles of rs854560 (A > T) show significant differences in the lipid levels in comparison to controls. These results suggest that carriers of G allele of rs662 (A > G) present a greater susceptibility to psoriasis.

Association between the TAP1 gene polymorphisms and recurrent respiratory papillomatosis in patients from Western Mexico: A pilot study.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a respiratory tract disease that affects children and adults and is characterized by the recurrent proliferation of multiple papillomas. The etiologic agent is the human papillomavirus, mainly genotypes 6 and 11. Furthermore, polymorphisms in TAP1 appear to influence the selection of antigenic peptides and the transport process to the rough endoplasmic reticulum, for their subsequent presentation to T lymphocytes, an essential process against viral diseases and tumor processes. Previous studies have shown that individuals with those polymorphisms are susceptible to immune, infectious, and tumor-related diseases. The present study aimed to determine the association between the TAP1 rs1057141 (c.1177A>G) and rs1135216 (c.2090A>G) single nucleotide polymorphisms (SNPs) and RRP. METHODS: A case-control study was carried out on a group of 70 individuals (35 controls and 35 patients). RRP diagnosis, HPV genotyping, and viral load were determined through histology and PCR. SNPs rs1057141 and rs1135216 were identified through allelic discrimination, using real-time PCR. The haplotypic analyses were performed using the Arlequin 3.5 program. RESULTS: HPV-6 and HPV-11 were the genotypes found in the samples. In the polymorphism analysis, rs1057141 showed no significant differences (p = 0.049, CI = 0.994-7.331). In contrast, a significant difference was found in rs1135216 (p = 0.039, OR = 2.4) in the allelic analysis, as well as in the dominant (p = 0.027, OR = 3.06), codominant (p = 0.033, OR = 3.06), and additive model (p = 0.043, OR = 2.505) in subjects with the G allele. CONCLUSION: The G allele in rs1135216 was associated with a genetic risk of susceptibility for RRP in a population in Western Mexico.

Leu72Met polymorphism of GHRL gene decreases susceptibility to type 2 diabetes mellitus in a Mexican population.

BACKGROUND: Type 2 diabetes mellitus (T2D) is the most frequent type of diabetes. It has a multifactorial etiology, affecting millions of people worldwide. Ghrelin gene (GHRL) encodes the ghrelin peptide, which promotes food intake, induces body weight and adipogenesis. Several single nucleotide polymorphisms (SNPs) in GHRL gene have been associated with metabolic diseases. A protective effect of the Leu72Met (rs696217) polymorphism has been described for T2D in some populations, but this effect seems to depend on the ethnicity of the patients studied. METHODS: The aim of this study was to investigate the association between the GHRL Leu72Met (rs696217) SNP with the development of T2D and serum ghrelin levels in a Western Mexican population. We performed a case-control study in which we included 284 subjects (159 with previous T2D diagnosis and 125 control subjects (CS)). Leu72Met SNP was genotyped by using PCR-RFLPs technique. Serum ghrelin levels were measured using a commercial enzyme immunoassay. Genotypic and allelic distributions were compared using Chi square test. Student T-test and Mann-Whitney U test were used to compare quantitative variables. Odds ratio (OR) was used to evaluate the association between alleles or genotypes and T2D. Multiple and logistic regression models were performed for adjustment. A two-tailed p-value ≤0.05 was considered statistically significant. RESULTS: Leu72Leu genotype was more frequent among T2D compared to CS (p < 0.05). After adjusting for age and body composition, there was a significant protective effect of the 72Met allele for T2D development (OR 0.40 IC 95% 0.23-0.70; p ≤ 0.001). Fasting serum ghrelin levels were lower in T2D than CS (p ≤ 0.0001) irrespective of age, body weight and BMI. No associations were found between genotypes and ghrelin serum levels in our population. CONCLUSIONS: The GHRL 72Met allele decreases susceptibility for T2D development in a Western Mexican population. Serum ghrelin levels are lower in T2D independently of Leu72Met polymorphism genotype.

Development of an effective and rapid qPCR for identifying human ChREBPα/ß isoforms in hepatic and adipose tissues.

Most quantitative real-time PCR (qPCR) detection methods use two types of chemistries to measure the expression levels of ChREBP isoforms, hydrolysis probes for ChREBPα and SYBR Green for ChREBPß. Hydrolysis probes are not available to determine the ChREBPß isoform. The aim of this study was to develop a qPCR assay based only on hydrolysis probes for both ChREBP isoforms. Liver and adipose tissue biopsies from patients undergoing elective cholecystectomy surgery were used to perform qPCR. To validate this assay, the results were compared with sequencing and High Resolution Melting (HRM) PCR assays. Direct sequencing was used to determine the sequence showing site where ChREBPß presents its specific splicing (1 b exon/2 exon) in order to design the primers and the probe. We developed a qPCR assay to determine the ChREBP isoforms expression based on hydrolysis probes. It assays showed good efficiency (95.50%, on average), high reproducibility, and a strong linear correlation (R2 ≥ 0.99) for tissues tested. HRM analysis confirmed the specificity of the primers and the result of this assay matched (100%) with the outcomes obtained by sequencing and qPCR. Also, we obtained the ChREBPß sequence showing exon 1b spliced to exon 2, bypassing exon 1a, and retaining the remainder of the ChREBPα exons. Based on the use of hydrolysis probes, our method can efficiently identify the expression of both ChREBP isoforms. Thus, the comparability of the qPCR results using a single chemistry (hydrolysis probes) to discriminate between both ChREBP isoforms was possible.

Association of A-604G ghrelin gene polymorphism and serum ghrelin levels with the risk of obesity in a mexican population.

Obesity is a metabolic disorder that has a multifactorial etiology and affects millions of people worldwide. Ghrelin, a hormone coded by the GHRL gene, plays a role in human body composition and appetite. Single nucleotide polymorphisms (SNPs) of the GHRL gene have been associated with obesity and metabolic disorders. To evaluate the association of A-604G SNP of GHRL promoter region with serum ghrelin levels and the risk of obesity in a Mexican population. Two hundred and fifty individuals were enrolled and classified as obese or control subjects (CS) according to BMI. DNA samples, anthropometric measurements and biochemical parameters were obtained from all subjects. The A-604G SNP was genotyped using PCR-RFLPs technique. Ghrelin levels were measured using a commercial enzyme immunoassay. The G/G genotype was more frequent among obese individuals (p < 0.0001) when compared to CS. The G/A genotype and A allele were associated with protection against obesity (OR 0.29, p < 0.0001; OR 0.39, p < 0.0001 respectively), the A allele remained significant after adjusting for age and gender (OR: 0.25, p < 0.0001). Serum ghrelin levels were higher in obese patients (p = 0.004) than in CS, however, significance was lost after adjustment for age (p = 0.088). The G/G genotype was associated with higher levels of serum ghrelin (p = 0.02) independently of the effect of age. The G/G genotype of the A-604G SNP in the GHRL gene is associated with altered serum ghrelin levels and obesity. The A allele was also associated with protection against obesity in this study.

High Prevalence of ITPA Alleles Associated with Ribavirin-Induced Hemolytic Anemia Among Mexican Population.

BACKGROUND: The prevalence of two functional polymorphisms (rs1127354 and rs7270101) of the inosine triphosphatase (ITPA) gene associated with ribavirin-induced hemolytic anemia (RIHA) during antiviral therapy for hepatitis C virus (HCV) infection varies by ethnicity. In Mexico, the distribution of these polymorphisms among Native Amerindians (NA) and admixed population (Mestizos) is unknown. This study aimed to determine the prevalence of the ITPA polymorphisms among healthy NA and Mestizos, as well as in HCV patients from West Mexico. MATERIAL AND METHODS: In a cross-sectional study, 600 unrelated subjects (322 Mestizos, 100 NA, and 178 treatment-naïve, HCV-infected Mestizos patients) were enrolled. A medical history was registered. ITPA genotype was determined by Real-Time PCR. Fst-values and genetic relatedness between study and reference populations were assessed. RESULTS: The frequency of the risk genotypes rs1127354CC and rs7270101AA was higher among NA (98-100%) than in Mestizos (87-92.9%), (p &lt; 0.05). The NA presented the highest prevalence of the rs1127354CC genotype reported worldwide. The Fst-values revealed a genetic relatedness among Mexican NA, South Americans and African populations (p &gt; 0.05). The frequency of the predicted risk for RIHA was higher among NA (98%) than in Mestizos (80.5%) and HCV-infected patients (81.5%) (p &lt; 0 .01). The CC/AA alleles were associated with lower values of total bilirubin, aspartate/alanine aminotransferases, and aspartate-to-platelet-ratio-index score among HCV-patients. CONCLUSION: A high prevalence of the ITPA polymorphisms associated with RIHA was found in Mexican NA. These polymorphisms could be a useful tool for evaluating potential adverse effects and the risk or benefit of antiviral therapy in Mexicans and other admixed populations.

Antifungal activity of caspofungin in experimental infective endocarditis caused by Candida albicans.

BACKGROUND: Infective endocarditis is a disease characterised by heart valve lesions, which exhibit extracellular matrix proteins that act as a physical barrier to prevent the passage of antimicrobial agents. The genus Candida has acquired clinical importance given that it is increasingly being isolated from cases of nosocomial infections. OBJECTIVE: To evaluate the activity of caspofungin compared to that of liposomal amphotericin B against Candida albicans in experimental infective endocarditis. METHODS: Wistar rats underwent surgical intervention and infection with strains of C. albicans to develop infective endocarditis. Three groups were formed: the first group was treated with caspofungin, the second with liposomal amphotericin B, and the third received a placebo. In vitro sensitivity was first determined to further evaluate the effect of these treatments on a rat experimental model of endocarditis by semiquantitative culture of fibrinous vegetations and histological analysis. FINDINGS: Our semiquantitative culture of growing vegetation showed massive C. albicans colonisation in rats without treatment, whereas rats treated with caspofungin showed significantly reduced colonisation, which was similar to the results obtained with liposomal amphotericin B. CONCLUSIONS: The antifungal activity of caspofungin is similar to that of liposomal amphotericin B in an experimental model of infective endocarditis caused by C. albicans.

Association of a novel TAS2R38 haplotype with alcohol intake among Mexican-Mestizo population.

BACKGROUND: Alcohol intake has been associated with the bitter taste receptor T2R38. TAS2R38 gene expresses two common haplotypes: PAV and AVI. It has been reported that AVI homozygotes consume more alcohol than heterozygotes and PAV homozygotes. The aim of this study was to determine the prevalence of the TAS2R38 haplotypes among Mexican-Mestizo population and to analyze its association with alcohol intake. MATERIAL AND METHODS: In a cross-sectional study, a total of 375 unrelated Mestizo individuals were genotyped for TAS2R38 polymorphisms (A49P, V262A and I296V) by a Real-Time PCR System (TaqMan). Haplotype frequencies were calculated. Association of TAS2R38 haplotypes with alcohol intake was estimated in drinkers (DRS) and nondrinkers (NDRS). RESULTS: Two haplotypes accounted for over 96% of all haplotypes(AVV, 60%, and PAI, 36.5%). The frequency of AVV homozygotes was significantly higher in DRS than NDRS(47.2 vs. 32.2%, respectively; p < 0.05). Additionally, the AVV/AVV genotype was associated with alcohol intake when compared with heterozygotes and PAI homozygotes (OR = 1.79, 95% CI 1.13-2.84, p < 0.05 and OR = 2.23, 95% CI 1.11-4.48; p < 0.05, respectively). CONCLUSIONS: In conclusion, two TAS2R38 haplotypes(AVV and PAI) prevailed in Mexican-Mestizo population. The novel AVV haplotype was associated with alcohol intake. The high prevalence of this allelic profile in our population could help to explain, at least in part, the preference for alcohol among the Mexicans.

Influence of ApoE and FABP2 polymorphisms and environmental factors in the susceptibility to gallstone disease.

BACKGROUND: Gallstone disease (GSD) is a common chronic disease in the Western hemisphere, yet environmental and genetic factors may be responsible for the variations in the prevalence of GSD among populations. AIM: To analyze the relationship of the ApoE and FABP2 polymorphisms with diet, physical activity and emotional health in patients with GSD from West Mexico. MATERIAL AND METHODS: A total of 120 patients with GSD and 370 healthy subjects were enrolled. Anthropometric, biochemical, nutritional, clinical and physical activity parameters were measured. ApoE and FABP2 genotypes were assesed by PCR-RFLPs assays. RESULTS: ApoE E3/E4 genotype and the ApoE E4 allele was highly prevalent among the GSD patients compared to the controls (32% vs. 12.0% and 22% vs. 8.4% respectively p < 0.01). Patients with the Apo E4 allele showed an upward trend of cholesterol levels compared to non-Apo E4 allele carriers (E4 186 ± 30 mg/dL; E3 143 ± 37 mg/dL; E2 129 ± 34 mg/dL). High triglyceride levels were associated with patients that were FABP2 Thr54 allele carriers (p < 0.05) but lacked association with GSD. This may be due to changes in dietary fats after GSD diagnosis, masking the clinical course of the disease. Sedentary lifestyle and negative emotions were detected in 83% and 63% of patients, respectively. CONCLUSION: These data suggest that the Apo E4 allele could confer genetic susceptibility for the development of GSD among the Mexican population. The Ala54Thr polymorphism of FABP2 was associated with high triglycerides levels, but not to GSD; suggesting that environmental factors modulate such susceptibility.

SCCmec types and pvl gene in methicillin-resistant Staphylococcus aureus strains from children hospitalized in a tertiary care hospital in Mexico.

BACKGROUND: The aim of this study was to determine the prevalence, SCCmec types, presence of the Panton-Valentine leukocidin (PVL) gene, and susceptibility to antibiotics of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from hospitalized children. METHODS: From August 2009 to September 2011, 291 S. aureus strains were isolated from normally sterile body sites, of which 190 (65%) were MRSA. One hundred and two of the MRSA strains were genetically evaluated. SCCmec genotypes were identified by M-PCR and the PVL gene (pvl) by end-point PCR. Resistance to erythromycin, rifampicin, clindamycin, and trimethoprim-sulfamethoxazole (SXT) was assessed by Kirby-Bauer disk diffusion method in accordance with the Clinical and Laboratory Standards Institute guidelines of 2012. RESULTS: Of the 102 strains evaluated, 97 (95%) were SCCmec type II, 5 (5%) were SCCmec type IVa, and all (100%) were pvl-negative. Resistance to erythromycin, clindamycin, rifampicin, and SXT was 97%, 95%, 0%, and 0%, respectively. CONCLUSIONS: The prevalence of hospital-acquired MRSA was high. SCCmec type II was predominant and the pvl gene appeared not to play any role in the virulence of the MRSA strains from hospitalized children.

FTO rs9939609: T>A Variant and Physical Inactivity as Important Risk Factors for Class III Obesity: A Cross-Sectional Study.

BACKGROUND: The prevalence of obesity has been increasing worldwide. It has been reported that physiological and environmental factors such as diet, culture, physical activity, and genetics are the principal factors related to obesity. The fat mass and obesity-associated (FTO) gen variant (rs9939609: T>A) has been associated with class III obesity. The A variant has been correlated with anthropometric and metabolic alterations. Therefore, the purpose of this study was to analyze the association of the FTO rs9939609: T>A variant and environmental factors with clinical, anthropometric, and biochemical variables in subjects with class III obesity. RESULTS: The A variant frequency was higher in the class III obesity group compared with the normal weight group (44% vs. 25%, p < 0.001). Subjects with the AA genotype had a higher body mass index (BMI) than those with the AT genotype (35.46 kg/m2 (31-39.8) vs. 26.91 kg/m2 (23.7-30), p = 0.005). Women with the AA genotype showed higher waist circumferences than the AT group (101.07 cm (90.9-111.1) vs. 85.45 cm (77-93.8) p = 0.047). The FTO A variant increases the risk by 3.54 times and physical inactivity increases the risk by 6.37 times for class III obesity. CONCLUSIONS: Our results suggest that among the studied variables, those most related to class III obesity were the FTO risk genotype (A allele) and physical inactivity.

The Role of Diet and Physical Activity in Shaping COVID-19 Severity: Design, Validation, and Application of a Retrospective Questionnaire.

After the global challenges posed by COVID-19, researchers strived to identify risk factors for severe cases, which lead to various complications-including death. Lifestyle modifications, such as implementing a healthy diet and recommended physical activity, have been shown to be protective against severe COVID-19 cases. Despite an association of a plant-based diet with reduced COVID-19 severity, specific dietary characteristics have not been identified. Also, the methodology for measuring physical activity is variable, with studies overlooking the intensity or the habit components of physical activity. To bridge this gap, our study designed, validated, and applied a retrospective questionnaire with aims of exploring the relationship between lifestyle factors, specifically diet and physical activity, and severe COVID-19. We considered the intensity and years of physical activity habit, which is a limitation of other questionnaires. Results reveal associations of age and BMI with severe COVID-19. An excessive sugar diet was found to be associated with severe COVID-19 and increased symptom duration. We also observed an inverse relationship pattern of moderate- and vigorous-intensity physical activity across case severity, which is absent in walking physical activity. This study lays a foundation for research aiming to identify lifestyle factors that prevent severe COVID-19 cases.

Pirfenidone Reverts Global DNA Hypomethylation, Promoting DNMT1/UHRF/PCNA Coupling Complex in Experimental Hepatocarcinoma.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in the carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-Acetylaminofluorene (2-AAF). The HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, ß-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.