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13 result(s) for "Almanza-Reyes, Horacio"
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Evaluation of silver nanoparticles for the prevention of SARS-CoV-2 infection in health workers: In vitro and in vivo
SARS-CoV-2 infection in hospital areas is of a particular concern, since the close interaction between health care personnel and patients diagnosed with COVID-19, which allows virus to be easily spread between them and subsequently to their families and communities. Preventing SARS-CoV-2 infection among healthcare personnel is essential to reduce the frequency of infections and outbreaks during the pandemic considering that they work in high-risk areas. In this research, silver nanoparticles (AgNPs) were tested in vitro and shown to have an inhibitory effect on SARS-CoV-2 infection in cultured cells. Subsequently, we assess the effects of mouthwash and nose rinse with ARGOVIT ® silver nanoparticles (AgNPs), in the prevention of SARS-CoV-2 contagion in health workers consider as high-risk group of acquiring the infection in the General Tijuana Hospital, Mexico, a hospital for the exclusive recruitment of patients diagnosed with COVID-19. We present a prospective randomized study of 231 participants that was carried out for 9 weeks (during the declaration of a pandemic). The \"experimental\" group was instructed to do mouthwash and nose rinse with the AgNPs solution; the \"control\" group was instructed to do mouthwashes and nose rinse in a conventional way. The incidence of SARS-CoV-2 infection was significantly lower in the \"experimental\" group (two participants of 114, 1.8%) compared to the \"control\" group (thirty-three participants of 117, 28.2%), with an 84.8% efficiency. We conclude that the mouth and nasal rinse with AgNPs helps in the prevention of SARS-CoV-2 infection in health personnel who are exposed to patients diagnosed with COVID-19.
Mitochondrial Dysfunction Induced by Zinc Oxide Nanoparticles
The constant evolution and applications of metallic nanoparticles (NPs) make living organisms more susceptible to being exposed to them. Among the most used are zinc oxide nanoparticles (ZnO-NPs). Therefore, understanding the molecular effects of ZnO-NPs in biological systems is extremely important. This review compiles the main mechanisms that induce cell toxicity by exposure to ZnO-NPs and reported in vitro research models, with special attention to mitochondrial damage. Scientific evidence indicates that in vitro ZnO-NPs have a cytotoxic effect that depends on the size, shape and method of synthesis of ZnO-NPs, as well as the function of the cells to which they are exposed. ZnO-NPs come into contact with the extracellular region, leading to an increase in intracellular [Zn2+] levels. The mechanism by which intracellular ZnO-NPs come into contact with organelles such as mitochondria is still unclear. The mitochondrion is a unique organelle considered the “power station” in the cells, participates in numerous cellular processes, such as cell survival/death, multiple biochemical and metabolic processes, and holds genetic material. ZnO-NPs increase intracellular levels of reactive oxygen species (ROS) and, in particular, superoxide levels; they also decrease mitochondrial membrane potential (MMP), which affects membrane permeability and leads to cell death. ZnO-NPs also induced cell death through caspases, which involve the intrinsic apoptotic pathway. The expression of pro-apoptotic genes after exposure to ZnO-NPs can be affected by multiple factors, including the size and morphology of the NPs, the type of cell exposed (healthy or tumor), stage of development (embryonic or differentiated), energy demand, exposure time and, no less relevant, the dose. To prevent the release of pro-apoptotic proteins, the damaged mitochondrion is eliminated by mitophagy. To replace those mitochondria that underwent mitophagy, the processes of mitochondrial biogenesis ensure the maintenance of adequate levels of ATP and cellular homeostasis.
Impact of CYP3A5 1 and 3 single nucleotide variants on tacrolimus pharmacokinetics and graft rejection risk in pediatric kidney transplant patients
Tacrolimus, a calcineurin inhibitor, is widely used to prevent allograft rejection in kidney transplant recipients. Its metabolism is predominantly mediated by the cytochrome P450 3A5 (CYP3A5) enzyme, and single nucleotide variants (SNVs) within intron 3 of the CYP3A5 gene are strongly associated with interindividual variability in enzyme expression and activity. These SNVs can generate a cryptic splice site, resulting in either preserved enzymatic function classified as expressers ( CYP3A5 *1/*1 and *1/*3) or loss of function, classified as non-expressers ( CYP3A5 *3/*3). Differential expression of CYP3A5 contributes to variability in tacrolimus pharmacokinetics and clinical outcomes, including graft rejection and therapeutic efficacy. In this study, we evaluated three pharmacokinetic parameters: trough concentration (TAC-C 0 ), weight-adjusted daily dose (TAC-D, mg/kg), and dose-normalized trough concentration (TAC-C 0 /D). One-way ANOVA was used to assess differences in these parameters between CYP3A5 expressers and non-expressers. Additionally, Poisson regression was performed to examine associations between clinical/genetic variables and the incidence rate of acute rejection events. Genotyping was conducted in 45 pediatric kidney transplant recipients. The CYP3A5 *3/*3 genotype was most prevalent (66.7%), followed by *1/*3 (26.7%) and *1/*1 (6.7%). During the 6-month post-transplant period, CYP3A5 expressers required significantly higher tacrolimus doses to achieve target trough levels. Increased drug exposure was associated with a higher incidence of rejection events, whereas CYP3A5 expression correlated with a reduced rate of rejection. These findings underscore the clinical utility of CYP3A5 genotyping for optimizing tacrolimus dosing strategies. Carriers of functional CYP3A5 alleles (*1/*3 or *1/*1) benefit from individualized dose adjustments to achieve therapeutic concentrations and reduce the risk of graft rejection.
Evaluation of the Efficacy and Safety of Silver Nanoparticles in the Treatment of Non-Neurological and Neurological Distemper in Dogs: A Randomized Clinical Trial
Canine distemper is caused by canine distemper virus (CDV), a multisystemic infectious disease with a high morbidity and mortality rate in dogs. Nanotechnology represents a development opportunity for new molecules with antiviral effects that may become effective treatments in veterinary medicine. This study evaluated the efficacy and safety of silver nanoparticles (AgNPs) in 207 CDV, naturally infected, mixed-breed dogs exhibiting clinical signs of the non-neurological and neurological phases of the disease. Group 1a included 52 dogs (experimental group) diagnosed with non-neurologic distemper treated with 3% oral and nasal AgNPs in addition to supportive therapy. Group 1b included 46 dogs (control group) diagnosed with non-neurological distemper treated with supportive therapy only. Group 2a included 58 dogs with clinical signs of neurological distemper treated with 3% oral and nasal AgNPs in addition to supportive therapy. Group 2b included 51 dogs (control group) diagnosed with clinical signs of neurological distemper treated with supportive therapy only. Efficacy was measured by the difference in survival rates: in Group 1a, the survival rate was 44/52 (84.6%), versus 7/46 in Group 1b (15.2%), while both showed clinical signs of non-neurological distemper. The survival rate of dogs with clinical signs of neurological distemper in Group 2a (38/58; 65.6%) was significantly higher than those in Control Group 2b (0/51; 0%). No adverse reactions were detected in experimental groups treated with AgNPs. AgNPs significantly improved survival in dogs with clinical signs of neurological and non-neurological distemper. The use of AgNPs in the treatment of neurological distemper led to a drastic increase in the proportion of dogs recovered without sequels compared to dogs treated without AgNPs. The evidence demonstrates that AgNP therapy can be considered as a targeted treatment in dogs severely affected by canine distemper virus.
Impact of single-nucleotide variants and individual characteristics on adverse events of L-asparaginase in children with acute lymphoblastic leukemia
L-Asparaginase (L-Asp) is a key drug in the treatment of acute lymphoblastic leukemia (ALL); however, it is commonly associated with the occurrence of adverse events (AE). Risk factors such as age, sex, nutritional status, and some single nucleotide variants (SNVs) in specific genes could be related to hypersensitivity reactions to L-Asp. The objective of this study was to identify the influence of individual characteristics and three SNVs in the and genes on the occurrence of the most significant adverse events caused by the use of L-Asp in Mexican children with ALL. Eighty-five children from ages 0-17 years old diagnosed with ALL were included. The patients were treated at two hospital centers in Mexico. The SNV genotypes of the and genes studied were examined using real-time qPCR. The evaluation of AE was carried out according to the Common Terminology Criteria for adverse events, and the determination of anti-L-Asp antibodies was conducted using Western blot immunoassay. Homozygosity (AA) of the rs4958351 SNV was significantly associated with the occurrence of AE with the use of L-Asp (OR = 4.05; 95% CI = 1.06 to 15.40, = 0.04) and was strongly associated with the development of anti-L-Asp antibodies (OR = 3.4375, 95% CI = 1.04 to 11.25, = 0.04). With this, we found a significant risk association for the SNV rs4958351 of the gene. On the other hand, we did not find significant risk associations for the rs6889909 and rs6021191 SNVs, although other populations have shown a significant risk. Our study has some limitations, such as the small sample size, the heterogeneity in adverse events due to the patients' different regions of origin, and the limited ability to conduct a more detailed follow-up on pancreatitis. Additionally, since no significant associations were found between the rs6021191 and rs6889909 SNVs and the development of adverse events or the presence of antibodies due to the use of L-Asp, it is necessary to investigate new specific SNVs that may improve the efficacy and safety of treatment in Mexican children with ALL.
Effects of IGF1 rs6214 Polymorphism and Milk Consumption on Serum Levels of IGF-1 and GH and Body Composition
Milk and dairy are rich in insulin-like growth factor 1 (IGF-1), a protein secreted through the action of growth hormone (GH) and implicated in growth and metabolism. Objective: This study aimed to investigate the roles of milk intake and body composition and identify the presence of the single nucleotide variant (SNV) rs6214 in the insulin-like growth factor 1 gene (IGF1) and its effects on the serum IGF-1 and GH levels and body composition. Methods: We analyzed 110 volunteers with and without a history of milk intake. Through a case–control study with one hundred ten healthy volunteers, serum IGF-1 and GH levels were measured using the ELISA technique, the body composition was determined with bio-electrical impedance equipment, genotyping of the rs6214 SNV was carried out using real-time PCR, and a dietary questionnaire was administered to assess milk intake, with or without consumption. Results: The results showed that the highest levels of IGF-1 were found in people who regularly consumed milk, along with a lower body mass index (BMI) and percentage of fat. A lower BMI and fat percentage were associated with higher levels of IGF-1, lean mass, and SNV presence. Lower levels of BMI and percentages of subcutaneous and visceral fat were found in regular milk consumers. Conclusions: Our study suggests that dairy intake and the IGF1 gene rs6214 SNV are associated with higher levels of IGF-1, high levels of lean mass, a low BMI, a low % fat, and low visceral fat.
Genotype Analysis of ABCC1, NCF4 and CBR3 Polymorphism and the Association With Childhood Acute Lymphoblastic Leukemia in Mexican Childhood Population
Background: The identification of genetic risk factors for Acute Lymphoblastic Leukemia (ALL), are increasingly urgent and necessary. Objective: The purpose of this study is to determine the association of the genetic polymorphisms ABCC1 rs3743527, NCF4 rs1883112 and CBR3 rs1056892 with ALL. Methods: DNA samples were obtained in 71 children with ALL (from 2 to 18 years) and in 71 controls without ALL, to determine the polymorphisms by real-time polymerase chain reaction (qPCR), using specific TaqMan probes in a StepOne ® thermal cycler (Applied Biosystems, United States). Results: The results of the Odds Ratio analysis show that in the rs1883112 polymorphism of the NCF4 gene, the heterozygous allele has a risk effect for ALL (OR = 3.1870, CI = 1.8880–7.9383 and p = 0.0002), in turn the mutated genotype (AA) is associated with a protective effect (OR = 0.26, 0.1248 to 0.5434 and p = 0.0003). On the other hand, the CBR3 rs1056892 polymorphism shows a significant association of risk to ALL, in the presence of the HT genotype (OR = 2.77, IC = 1.3837 to 5.5651 and p = 0.004) and the mutated genotype of this polymorphism has a significant association with protection to ALL in the HM genotype (OR = 0.52, IC = 0.2639 to 1.0304 and p = 0.05). While the inheritance models of the polymorphisms let us see that of the rs1883112 polymorphism of the NCF4 polymorphism; the HT genotype of the codominant model shows a protective effect against ALL (OR = 0.4117, IC = 0.1718 to 0.9866 and p = 0.04), the recessive model shows us and confirms what we already saw in table number 3, being that there is an association with protective effect in the HM genotype (OR = 0.2604, IC = 0.1248 to 0.5434 and p = 0.0003). In the polymorphism rs1056892 of the CBR3 gene, a protection association was found in the heterozygous allele of the codominant model (OR = 0.3448, IC = 0.1375 to 0.8896 and p = 0.0274). In addition, the recessive inheritance model for the HM genotype shows a protective effect to ALL, (OR = 0.52, CI = 0.9919 to 3.8638 and p = 0.05). Conclusion: There is an evident impact of the NCF4 rs1883112 and CBR3 rs1056892 polymorphisms with an increased risk of susceptibility to ALL; Likewise, through the codominant inheritance model, the effect of the variation of the CBR3 rs1056892 gene as a protective factor against ALL was evaluated.
Using Respiratory Gas Analyzers to Determine Resting Metabolic Rate in Adults: A Systematic Review of Validity Studies
Background: Correct assessment of resting metabolic rate (RMR) is fundamental for estimating total energy expenditure in both clinical nutrition and sports sciences research. Various methods have been proposed for RMR determination, including predictive equations, isotopic dilution techniques, and indirect calorimetry. Over the past two decades, portable gas analyzers have emerged as promising alternatives, offering more accessible and cost-effective solutions for metabolic assessment. However, evidence regarding their validity remains inconsistent, particularly across diverse populations and varying metabolic assessment protocols. Methods: This systematic review was conducted in May 2025 using the PubMed, Web of Science, and EBSCO databases, following the PRISMA-DTA guidelines, and included observational studies with the objective of examining the available evidence regarding the validity of portable gas analyzers to determine RMR in humans. The methodological quality of each study was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: From an initial pool of 230 studies, 16 met the eligibility criteria. The findings revealed notable variability in measurement validity among devices, mainly influenced by device model, population characteristics, and methodological factors. While portable analyzers such as FitMate and Q-NRG exhibited high validity, MedGem exhibited systematic biases, particularly in individuals with higher adiposity, leading to RMR overestimations. Conclusions: The main results demonstrated the critical need for rigorous validation of portable gas analyzers before their implementation in clinical and research settings to ensure their applicability across diverse populations and metabolic assessments.
Impacto de polimorfismos genéticos de la vía metabólica del metotrexato sobre la sobrevida de niños mexicanos con leucemia linfoblástica aguda (LLA)
Antecedentes: La leucemia linfoblástica aguda (LLA) es un padecimiento oncológico importante en la población pediátrica mexicana, cuya base genética pudiera modificar la efectividad de la quimioterapia del antifolato metotrexato (MTX) y el tiempo de sobrevida libre de enfermedad y la sobrevida total. Objetivos: Determinar la asociación de 10 polimorfismos genéticos de la vía del folato: en transportadores celulares (COL18A1, SLC19A1, ABCB1 y ABCC5) y las enzimas folilpoliglutamil sintetasa (FPGS) y xantina oxidasa (XO), con la sobrevida de los niños con leucemia linfoblástica aguda. Métodos: En el Centro Estatal de Cancerología de Durango- México, se estudiaron 39 niños con leucemia linfoblástica aguda tratados con MTX y 102 controles sin la enfermedad, a quienes mediante qPCR, se les determinaron 10 polimorfismos en la vía del folato. Durante 5 años de seguimiento se determinó la sobrevida libre de enfermedad y la sobrevida total, y su relación con su genotipo. Resultados: Cuatro polimorfismos no estuvieron en equilibrio de Hardy-Weinberg COL18A1(rs2274808), ABCC5(rs9838667 y rs3792585) y XO(rs17011368). Únicamente el rs17011368 de XO se asoció con riesgo de estar presente en los pacientes con leucemia linfoblástica aguda cuyo OR fue 9.771(IC95% 4.974-19.196, p=0,001). El FPGS(rs1544105) afectó la sobrevida libre de enfermedad y la sobrevida total (Log Rank p<0.05). Conclusiones: El polimorfismo (rs17011368) de la XO presentó riesgo para leucemia linfoblástica aguda; así mismo, se encontró una asociación importante entre los portadores del polimorfismo FPGS(rs1544105) que modificaría la sobrevidas de los pacientes tratados con MTX.
Association of ABCB1, ABCC5 and xanthine oxidase genetic polymorphisms with methotrexate adverse reactions in Mexican pediatric patients with ALL
Background: Acute lymphoblastic leukemia (ALL) is one of the most frequent oncological disorders in pediatric populations. To date, the drug of choice for the treatment of ALL is methotrexate, a drug associated with a high risk of adverse reactions (ADRs). The xanthine oxidase ([XO]) polymorphisms, [1936A>G] and [2107A>G], as well as the polymorphic variants derived from ATP-binding cassette transporter gene subfamilies, [ABCB1] and [ABCC5], of drug resistant codifying genes, are implicated as precursors of drug-related neurologic, hepatic, and renal toxicities. Our aim was to determine whether the mentioned polymorphisms are risk or protective factors for the development of adverse reactions by methotrexate in our pediatric population with ALL. Methods: A total of 35 Mexican children from Centro Estatal de Cancerología-Durango, Mexico, with ALL and the previously noted polymorphisms as determined qPCR were studied. At the same time, a 12-month drug monitoring program was conducted in accordance with WHO-PAHO guidelines for pharmacovigilance. Results: The [ABCB11936A>G] and [2107A>G] and [ABCC5 3414+434A>C] polymorphisms were not associated with methotrexate ADRs. Single nucleotide polymorphisms (SNPs) of [ABCB1] 1236C>T (OR 0.19, 95% CI: 0.03-0.9, p<0.05) and [ABCC5 3933+313T>C] (OR 0.12, 95% CI: 0.027-0.58, p<0.05) were associated with methotrexate ADRs. Conclusions: SNPs [1236C>T] of [ABCB1] and [ABCC5 3933+313T>C] are not associated with the development of typical ADRs by methotrexate, rather, they showed a protective factor for myelosuppression in the studied sick population.