Laura Jazel Barragan Zuñiga

Vincristine-induced peripheral neuropathy (VIPN) is a common dose-limiting toxicity in pediatric acute lymphoblastic leukemia (ALL), and pharmacogenetic evidence in admixed populations remains limited. We evaluated variants in ABCC1, ABCC2, ABCB1, CYP3A4, CYP3A5, and CEP72 in Mexican pediatric patients with ALL using an ambispective case–control design (n = 43; aged 2–18 years). VIPN was graded using CTCAE v4.0; cases were defined as grade ≥ 2 (n = 11) and controls grade 0–1 (n = 32). Nine single nucleotide variants (SNVs) were genotyped by allele-specific qPCR and analyzed under codominant, dominant, recessive, and log-additive models, including haplotype analyses. VIPN occurred in 25.6% of patients, with 90.9% of cases occurring during induction (p = 0.001). ABCC2 rs11190298 was nominally associated with VIPN under codominant (OR = 0.21; 95% CI: 0.04–0.97), dominant (OR = 0.15; 95% CI: 0.03–0.71), and log-additive (OR = 0.17; 95% CI: 0.04–0.66) models, and ABCC2 haplotypes showed a nominal global association (p = 0.003). These associations did not withstand correction for multiple testing. No significant associations were found for ABCC1, ABCB1, CYP3A4, CYP3A5, or CEP72. Early-onset toxicity may reflect differences in drug exposure or treatment intensity, which pharmacokinetic data could clarify. These hypothesis-generating findings require replication in larger prospective cohorts.

Phytotherapy has emerged as a promising strategy for the management of obesity and related metabolic disorders. In this context, species of the Physalis genus have been widely recognized in traditional medicine for their potential therapeutic effects against these conditions. This study aimed to evaluate the effects of Physalis philadelphica husk infusion on obesity and associated metabolic disturbances such as hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress markers in diet-induced obese rats. Male Wistar rats were allocated into three groups (n = 8): (1) healthy control, (2) obese control group, and (3) intervention group (husk infusion). Obesity was induced using a high-fructose and high-saturated fat diet (~511.1 kcal/100 g), followed by 16 weeks of husk infusion administration. After euthanasia, hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress markers were analyzed. Results showed that rats receiving the husk infusion exhibited a significant reduction in weight gain (~7.2%), serum glucose levels (22.8%), and free fatty acids (26%) compared to the obese control group, while no significant effects on insulin sensitivity, hepatic steatosis, or several lipid-related parameters were observed. Regarding oxidative stress markers, serum nitrite levels decreased by 33%, and malondialdehyde (MDA) levels in the liver (30%) and adipose tissue (38%) were significantly reduced compared to the obese control group. Moreover, treated rats showed a significant increase in catalase (~1.2-fold) and superoxide dismutase (~2.8-fold) activity in the liver. These findings suggest that Physalis philadelphica husk infusion reduces hyperglycemia and improves oxidative stress in obese rats.

The aim of this study was to assess the effect of sertraline on the gene expression of placental transporters for hormones, folates, nutrients and drugs over the course of pregnancy in rats. The studies were conducted on gestational days (GDs) 16 and 20 following oral treatment with 10 mg/kg/day sertraline or the vehicle, administered from weaning onward. The weight and area of the fetuses and placentas were analyzed, and maternal plasma sertraline concentrations were measured. Gene expression of ATP-binding cassette transporter b1a and b1b (Abcb1a and Abcb1b), organic anion-transporting polypeptide 4a1(Slco4A1/Oatp4a1), folate receptor-α (Folr1), reduced folate carrier (Slc19A1/Rfc), and L-type amino acid transporter (Slc7A5/Lat1) was evaluated in the placenta. Sertraline reduced fetal weight (p < 0.001) and fetal area (p < 0.01) at GD 16, while no significant differences were observed in placental weight or area between exposed and unexposed groups. Sertraline concentration was significantly lower at GD20 than at GD16 (p < 0.001). At GD 16, sertraline reduced the expression of Abcb1a (p = 0.027), Abcb1b (p < 0.01), and Oatp4a1 (p = 0.037) compared with controls. Conversely, sertraline induced Folr1 expression in both GDs and increased Rfc expression at GD 20, while Lat1 was not affected. These findings indicate that sertraline alters placental drug transporter gene expression and may impair nutrient transfer to the fetus.

Background/Objectives: Plants and fruits of Physalis philadelphica Lam. Solanacea are commonly used in traditional medicine to improve some illnesses such as diabetes, in North and Central American countries. The aim was to evaluate the effects of aqueous maceration (He-M) and ultrasound-assisted (He-US) extracts of P. philadelphica husk on hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress in obese rats. Methods: The effects of husk extracts on carbohydrate and lipid absorption were evaluated using oral starch and lipid tolerance tests in healthy male Wistar rats. Obesity was then induced using a high-fructose and saturated fat diet, followed by 16 weeks of extract administration. Results: He-US significantly reduced the postprandial glycemic spike, while both extracts lowered serum triglyceride levels (~50%) following lipid loading, compared with the negative control. In obese rats, both extracts reduced body weight gain (~10%) and lowered fasting glucose levels (22% for He-M and 15% for He-US), compared with the obese control. He-US also reduced insulin levels (~32%), insulin resistance (~53%), and free fatty acids (~52%), while He-M improved hepatic steatosis and reduced liver triglycerides (~26%). Both extracts reduced hepatic nitrite levels, although only He-M significantly decreased lipid peroxidation (~32%). Additionally, both treatments enhanced hepatic antioxidant enzyme activity. Conclusions: Husk extracts exerted beneficial effects on hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress markers in obese rats.

Coffee is among the most consumed beverages worldwide and is recognized for its bioactive compounds, which exert diverse physiological effects. This study evaluated the impact of roasting degree on the in vitro antioxidant activity and digestive enzyme inhibition of brews from four Mexican regions, as well as their in vivo effects on carbohydrate and lipid absorption. Antioxidant capacity was assessed through radical scavenging and lipid peroxidation inhibition, while inhibition of lipase, α-amylase, and α-glucosidase was also determined. Oral starch (OSTT) and lipid (OLTT) tolerance tests were conducted in healthy Wistar rats. Antioxidant activity was strongly influenced by region and roasting degree. All coffee samples exhibited radical scavenging activity and lipid peroxidation inhibition. With respect to enzyme inhibition, all coffees showed ~67–70% inhibition of lipase activity. For amylase, unroasted coffee from Oaxaca displayed the highest inhibition (34%, p < 0.001). For glucosidase, unroasted samples showed low inhibition (~6–19%), which increased substantially at the medium roast degree (~55% across all samples) but decreased again at the high roast degree (~27%). In OSTT, serum glucose levels were reduced after 120 min by ~20%, 21%, and 18% in rats treated with unroasted, medium-roast, and high-roast coffee, respectively, compared with the negative control. In OLTT, serum triglycerides decreased by ~26% (Chiapas), ~58% (Colima), ~32% (Oaxaca), and ~54% (Hidalgo). Crop region and roasting degree influence the phytochemical profile and bioactivity of Mexican coffee. Although unroasted coffees had the highest concentration of bioactive compounds, roasting enhanced specific bioactivities, particularly enzyme inhibition and lipid-lowering effects in vivo.

PLAC8, expressed by interstitial extravillous trophoblasts (iEVTs), plays a crucial role in trophoblast invasion, differentiation, and immunotolerance. Its dysregulation may contribute to pregnancy complications, such as preeclampsia. This study investigates the role of PLAC8 in trophoblast invasiveness and endothelial-like differentiation under different oxygen tensions. Swan-71 cells were transiently transfected with PLAC8 overexpression or knockdown plasmids. Invasion was assessed using Matrigel-coated transwells, endothelial-like differentiation through tube formation assays, and vasculogenic marker expression (VEGF, PGF, ANGPT2) by RT-PCR. Hypoxia experiments were performed at different oxygen conditions. PLAC8 overexpression enhanced trophoblast invasion but reduced endothelial-like differentiation, downregulating VEGF and PGF while upregulating ANGPT2. Hypoxia increased PLAC8 expression, indicating oxygen tension as a regulatory factor. PLAC8 manipulation did not affect cell viability. PLAC8 modulates trophoblast behavior by promoting invasion while inhibiting endothelial-like differentiation. Its regulation of vasculogenic and angiogenic factors suggests a critical role in placental homeostasis and potential relevance to pregnancy disorders, such as preeclampsia.

Objective. To describe the prevalence of obesity, diabetes, hypertension, and cardiovascular risk factors in the Indigenous populations of Northwest Mexico. Method. A cross-sectional study was conducted among Indigenous and rural Mestizo populations of Northwest Mexico, including Coras, Huicholes, Mexicaneros, Tarahumaras, and Tepehuanos, and Mestizos. Obesity was defined by a body mass index (BMI) ≥30 kg/m2. The following cardiovascular risk factors were considered: high waist circumference, hyperglycemia or previous diagnosis of diabetes, elevated blood pressure or previous diagnosis of hypertension, hypertriglyceridemia, and low HDL-C. Results. A total of 472 subjects were enrolled in the study, including Mestizos (n = 48), Coras (n = 73), Huicholes (n = 93), Mexicaneros (n = 74), Tarahumaras (n = 81), and Tepehuanos (n = 103). The prevalence of obesity in the overall population was 11.2%, while specifically in Mestizos, Coras, Huicholes, Mexicaneros, Tarahumaras, and Tepehuanos it was 35%, 18%, 7.5%, 9.4%, 7.4%, and 1.9%, respectively. According to the presence of diabetes, the prevalence in the total population was 3.8%, which in Mestizos, Coras, Huicholes, Mexicaneros, Tarahumaras, and Tepehuanos was 2.0%, 7.8%, 0.0%, 4.0%, 9.8%, and 0.0%, respectively. Regarding hypertension, the prevalence in the overall population was 12.7, whilst in Mestizos, Coras, Huicholes, Mexicaneros, Tarahumaras, and Tepehuanos was 39%, 11.8%, 8.6%, 9.4%, 18.5%, and 1.9%, respectively. Conclusion. Our results revealed that Mexican Indigenous groups exhibit a high prevalence of obesity and hypertension, as well as high blood pressure, hypertriglyceridemia, and low HDL-C.