Search Results (38)

Prolactin (PRL) is a hormone primarily associated with lactation, but it plays various roles in both men and women. PRL belongs to the family of peptide hormones, including placental lactogen and growth hormone. Interestingly, PRL is a pleiotropic hormone affecting several physiological and pathological conditions, including fertility. Moreover, several pathophysiological roles have been associated with this hormone, including those of the immune system, autoimmune disorders, asthma, and ageing. Additionally, PRL receptors are ubiquitously expressed in tissues, including the mammary gland, gonads, liver, kidney, adrenal gland, brain, heart, lungs, pituitary gland, uterus, skeletal muscle, skin blood cells, and immune system. Therefore, in the present paper, we cover the potential role that PRL may play in asthma by promoting inflammation and modulating immune responses. The detection of its receptor in lung tissue suggests a direct role in airway smooth muscle contractility through activation of signaling pathways such as JAK2-STAT5, MAPK/ERK1/2, and PI3K/Akt, as well as influencing ionic currents that regulate cell contraction, proliferation, and survival. In this sense, this review aims to explore the potential involvement of PRL in asthma pathophysiology by examining its interactions with intracellular signaling pathways and its possible impact on airway smooth muscle contractility and immune modulation. Full article

Although ART leads to viral suppression, people living with HIV (PLWH) still face an increased risk of comorbidities, such as cancer. The HIV-1 Tat protein may contribute to the promotion of chronic inflammation, oxidative stress, and genomic instability. While the presence of anti-Tat antibodies has been associated with slower disease progression, their potential role in modulating DNA damage remains unclear. Assess the effect of anti-Tat antibodies on cytotoxic and DNA damage in PLWH. A cross-sectional study was conducted in 178 PLWH. Serum anti-Tat IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Cytotoxicity and DNA damage were assessed via serum 8-hydroxy-2′-deoxyguanosine (8-OHdG) and nuclear anomalies (Micronucleus cytome assay) in 2000 buccal cells. Statistical significance was considered at p < 0.05. Anti-Tat antibodies were found in 24.2% of participants. Positive individuals had lower CD4+ T cell counts (p = 0.045) and higher levels of pyknosis (p = 0.0001). No differences in 8-OHdG were found, but 8-OHdG correlated positively with CD4+ counts (rho = 0.334, p = 0.006). Pyknosis negatively correlated with CD4+ counts (rho = −0.272, p = 0.027). Anti-Tat antibodies may not prevent DNA damage but could be related to cytotoxic effects in PLWH. Full article

Giardiasis is a common intestinal infection caused by Giardia lamblia. The standard treatment for this parasitic infection involves the administration of nitroimidazoles, albendazoles, and nitrothiazoles. However, in recent years, Giardia lamblia strains resistant to these treatments have been reported. Additionally, the current therapies exhibit considerable side effects, highlighting the need for new compounds that specifically target this parasite. The aim of this study was to evaluate nitrothiazole analogs and assess their impact on the metabolic, redox, and structural gene expression of this parasite. First, the compounds CNZ-7, CNZ-8, FLP-2, FLP-6, and FLP-8 were tested at concentrations ranging from 0 to 50 µM to determine their IC₅₀ in G. lamblia cultures. Subsequently, gene expression changes and structural cell damage in trophozoites were analyzed following incubation with the IC₅₀ of each compound. The giardicidal activity of the compounds was also evaluated in a nitazoxanide-resistant strain. The results showed that FLP-2, FLP-6, and FLP-8 exhibited a stronger effect on trophozoite viability compared to nitazoxanide (NTZ) and metronidazole (MTZ). Both compounds induced an increase in the expression of phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), pyruvate phosphate dikinase (PPDK), and pyruvate:ferredoxin oxidoreductase (PFOR). Additionally, FLP-2 caused ultrastructural alterations in trophozoites. Furthermore, FLP-2, FLP-6, and FLP-8 demonstrated efficacy against drug-resistant strains. These findings suggest that FLP-2, FLP-6, and FLP-8 are promising candidates for the treatment of giardiasis, as they effectively reduce parasite viability, modify gene expression, and exhibit activity against drug-resistant G. lamblia strains. Full article

In this work, cellulose nanocrystals (CNCs) were obtained from the wood of Acacia farnesiana L. Willd (Huizache) via acid hydrolysis; then, they were used to reinforce polyacrylic acid–co-acrylamide (AAc/AAm) hydrogels synthesized in a solution process via in situ free radical photopolymerization. The nanomaterials were characterized using atomic force microscopy, dynamic light scattering (DLS), and the residual charge on the CNCs; the nanohydrogels were characterized using infrared spectroscopy, scanning electron microscopy, swelling kinetics, and Young’s modulus. Soluble-grade cellulose presented 94.6% α-cellulose, 0.5% β-cellulose, and 2.7% γ-cellulose, as well as a viscosity of 8.25 cp and a degree of polymerization (DP) of 706. The CNCs averaged 180 nm in length and 20 nm in width. In the nanohydrogels, it was observed that the swelling kinetic behavior followed the Schott kinetic model, at times lower than 500 h; after that, it became linear. The results show that the hydrogel swelling capacity depended on the crosslinking agent and CNC concentration, as well as the CNC chemical and morphological properties, rather than the CNC source. The hydrogels with CNCs exhibited a decreased swelling degree compared to the hydrogels without CNCs. Young’s modulus increased with CNC presence and depended on the concentration and characteristics of the CNC as a crosslinking agent. Full article

The plays written by Fernando de Zárate, alias of the Crypto-Jewish poet Antonio Enríquez Gómez (1600–1663), appear on the surface to be militantly Catholic. Critics have struggled to reconcile the vision of the ‘Zárate’ plays, written in Seville after Enríquez’s clandestine return from exile (c. 1650), with the poems and treatises he penned in France (1636–1649), which were harshly critical of the Inquisition and Spanish notions of blood purity. One such play, El noble siempre es valiente [The nobleman is always brave], survives in an autograph manuscript from 1660. Written only months before the Inquisition identified and arrested Enríquez, the play became the most popular stage version of the epic hero El Cid in the eighteenth century, when it circulated under the titles El Cid Campeador and Vida y muerte del Cid [Life and death of El Cid]. The work stages the triumph of Spanish Christianity over Islam and appears to advocate an implacably bellicose ethos. This essay, however, interprets the play in the context of Enríquez’s exile writing, with specific focus on the influence of another erstwhile victim of the Inquisition, Fray Luis de León (1527–1591), whose works were found in the private libraries of Crypto-Jewish families. Full article

Microstrip filters are widely used in electronics and communications. Designing these filters requires knowledge in communications, microwave engineering, and radiofrequency systems. Specialized software facilitates the design process, often allowing optimization of results; however, such tools typically require expensive licenses, making them inaccessible to many students. While the literature includes some proposals for microstrip filter design, they generally have the limitation of not addressing parameter optimization. This paper presents a GUI (Graphical User Interface) for microstrip low-pass filter design, offering precise and reliable results at the desired cutoff frequency and attenuation, as demonstrated by experimental tests. The key strategy involves systematically following the steps of the classic design process, while simultaneously varying a specific parameter to analyze its impact on filter development. By exploring the variations in different parameters, various insightful analyses can be conducted. One of the notable achievements is the ability to design an optimal filter with a desired total length, while concurrently maximizing the performance of specific parameters. Additionally, this software is compatible with both MATLAB and Octave platforms, ensuring its usability across multiple environments. Full article

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an enzymopathy that affects approximately 500 million people worldwide. A great number of mutations in the G6PD gene have been described. However, three class A G6PD variants known as G6PD Tomah (C385R), G6PD Kangnam (C385G), and G6PD Madrid (C385W) have been reported to be clinically important due to their associations with severe clinical manifestations such as hemolytic anemia. Therefore, this work aimed to perform, for the first time, biochemical and functional characterizations of these variants. The G6PD variants were cloned and purified for this purpose, followed by analyses of their kinetic parameters and thermal stability, as well as in silico studies. The results showed that the mutations induced changes in the proteins. Regarding the kinetic parameters, it was observed that the three variants showed lower affinities for G6P and NADP⁺, as well as lower thermal stability compared to WT-G6PD. Molecular dynamics simulations showed that C385 mutations induced changes around neighboring amino acids. Metadynamics simulations showed that most remarkable changes account for the binding pocket volumes, particularly in the structural NADP⁺ binding site, with a concomitant loss of affinity for catalytic processes. Full article

Triosephosphate isomerase (TPI) dysfunction is a critical factor in diverse pathological conditions. Deficiencies in TPI lead to the accumulation of toxic methylglyoxal (MGO), which induces non-enzymatic post-translational modifications, thus compromising protein stability and leading to misfolding. This study investigates how specific TPI mutations (E104D, N16D, and C217K) affect the enzyme’s structural stability when exposed to its substrate glyceraldehyde 3-phosphate (G3P) and MGO. We employed circular dichroism, intrinsic fluorescence, native gel electrophoresis, and Western blotting to assess the structural alterations and aggregation propensity of these TPI mutants. Our findings indicate that these mutations markedly increase TPI’s susceptibility to MGO-induced damage, leading to accelerated loss of enzymatic activity and enhanced protein aggregation. Additionally, we observed the formation of MGO-induced adducts, such as argpyrimidine (ARGp), that contribute to enzyme inactivation and aggregation. Importantly, the application of MGO-scavenging molecules partially mitigated these deleterious effects, highlighting potential therapeutic strategies to counteract MGO-induced damage in TPI-related disorders. Full article

T-cell acute lymphoblastic leukemia (T-ALL) is a challenging childhood cancer to treat, with limited therapeutic options and high relapse rates. This study explores deamidated triosephosphate isomerase (dTPI) as a novel therapeutic target. We hypothesized that selectively inhibiting dTPI could reduce T-ALL cell viability without affecting normal T lymphocytes. Computational modeling and recombinant enzyme assays revealed that disulfiram (DS) and curcumin (CU) selectively bind and inhibit dTPI activity without affecting the non-deamidated enzyme. At the cellular level, treatment with DS and CU significantly reduced Jurkat T-ALL cell viability and endogenous TPI enzymatic activity, with no effect on normal T lymphocytes, whereas the combination of sodium dichloroacetate (DCA) with DS or CU showed synergistic effects. Furthermore, we demonstrated that dTPI was present and accumulated only in Jurkat cells, confirming our hypothesis. Finally, flow cytometry confirmed apoptosis in Jurkat cells after treatment with DS and CU or their combination with DCA. These findings strongly suggest that targeting dTPI represents a promising and selective target for T-ALL therapy. Full article

Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis (T. vaginalis) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC₅₀ value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC₅₀ values in the nanomolar range and AGR-2 being the most potent (IC₅₀ 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis, we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes (CK, PFK, TPI, and ENOL) and genes involved in metabolism (G6PD, TKT, TALDO, NADHOX, ACT, and TUB), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis. Full article

There is scarce evidence on sociodemographic and lifestyle characteristics that may explain adherence to different dietary patterns (DPs) during pregnancy. Our aims were to identify dietary patterns in a sample of pregnant Mexican women and to describe their association with selected sociodemographic and lifestyle characteristics. This is a secondary cross-sectional analysis of 252 mothers of children that participated as controls in a hospital-based case–control study of childhood leukemia. We obtained parents’ information about selected sociodemographic characteristics, as well as alcohol and tobacco consumption. We also obtained dietary information during pregnancy. We identified DPs using cluster and factor analyses and we estimated their association with characteristics of interest. We identified two DPs using cluster analysis, which we called “Prudent” and “Non healthy”, as well as three DPs through factor analysis, namely “Prudent”, “Processed foods and fish”, and “Chicken and vegetables”. Characteristics associated with greater adherence to “Prudent” patterns were maternal education, older paternal age, not smoking, and being a government employee and/or uncovered population. Likewise, the “Processed foods and fish” pattern was associated with greater maternal and paternal education, as well as those with less household overcrowding. We did not identify sociodemographic variables related to the “Chicken and Vegetables” pattern. Our results may be useful to identify target populations that may benefit from interventions aimed to improve individual dietary decisions during pregnancy. Full article

The study of the phenomena occurring in the plantar region is remarkably intriguing, especially when performing a normal gait cycle where the foot is under loading conditions. The effects presented in the foot while walking provide relevant indicators regarding clinical means for enhancing regular performance or rehabilitation therapies. Nevertheless, more than traditional methods are needed to biomechanically evaluate foot structural conditions, leading to an incomplete database for determining the patient’s needs so that advanced methodologies provide detailed medical assessment. Therefore, it is necessary to employ technological engineering tools to optimize biomechanical plantar pressure evaluations to reach suitable personalized treatments. This research initially evaluated numerically the pressure points in the foot sole region in each one of the five stance phases in a normal gait cycle. Medical imaging techniques were utilized to construct an anatomically accurate biomodel of the soft tissues of the right foot. The Finite Element Method was employed to predict peak plantar pressure in barefoot conditions for all stance phases; results from this case study presented a close alignment with gait experimental testing implemented to analyze the feasibility and validation of all mechanical considerations for the numerical analyses. Hence, having a solid foundation in the biomechanical behavior from the first case study close estimates, a 3D-printable patient-specific insole was designed and numerically analyzed to observe the mechanical response in the plantar critical zones utilizing a personalized orthotic device. Results from the second case study notably demonstrated a crucial decrement in excessive pressure values. Employing morphological customization orthopedics modeling combined with 3D-printable materials is revolutionizing assistive device design and fabrication techniques. The fundamental contribution of this research relies on deepening the knowledge of foot biomechanics from an interdisciplinary approach by numerically analyzing pressure distribution in critical regions for all five stances phases; thus, based on the methods employed, the results obtained contribute to the advances of patient-specific foot orthopedics. Full article

Diabetic peripheral neuropathy (DPN) is the primary complication in patients with diabetes mellitus, characterized by loss of sensation and function in the lower limbs. Virtual reality (VR) and/or sensory feedback (FB) therapy has shown positive effects in other neurologic conditions such as stroke. However, consensus regarding their effectiveness in the DPN population is lacking. This study aims to analyze existing scientific evidence about the effects of VR and/or FB on improving gait and balance and reducing the risk of falls in patients with DPN (pwDPN). A thorough search was conducted in scientific databases including PubMed, Scopus, and EMBASE, up until November 2023. CMSQ, the PEDro scale, and the Cochrane Collaboration’s tool were used to assess the methodological quality and risk of bias of the studies. A total of 10 studies were selected for qualitative analysis, with three contributing information to the meta-analysis. The combined results suggest a positive trend in favor of VR and FB rehabilitation; however, significant differences were not observed in balance (SMD = −0.81, 95% CI = −1.90, 0.29; p = 0.15; I² = 86%) or gait speed improvements (MD = −1.05, 95% CI = −2.96, 0.85; p = 0.28; I² = 89%). Therefore, further randomized controlled studies are still needed to achieve stronger conclusions regarding the benefits of VR and/or FB in pwDPN. Full article

This paper shows the implementation of the Moth–Flame Optimization algorithm in a Cascade-H multilevel inverter with five and seven levels to determine the optimal switching sequence of the inverter’s semiconductor devices. The algorithm was coded in Matlab software, and the obtained switching sequences were implemented in a Cascade-H multilevel inverter laboratory prototype, where the output voltage waveform was obtained using a digital oscilloscope. The experimental Total Harmonic Distortion was obtained using a power quality analyzer. The experimental results show the improvement of the Total Harmonic Distortion in the voltage output. These results were compared with other papers in the literature with different metaheuristic methods concerning the same modulation. These findings demonstrate the feasibility of employing the Moth–Flame Optimization Algorithm to significantly reduce the Total Harmonic Distortion, obtaining a lower value than most analyzed papers. Full article

The Spanish Golden Age tragedy is assembled around the conflict of passions, which does not find an adequate channel of expression in words because there are feelings that cannot be confessed if one wants to preserve life. However, such intense emotions cannot be hidden for a long time, either. The characters discover that the eyes speak in silence and cannot lie, so they appeal to their sincerity at crucial moments. Such examples can be found in the declarations of love addressed to inaccessible or forbidden women or in the narratives of women who report sexual assault or husbands who believe they have been dishonored. In this article, we will analyze all these circumstances to demonstrate that, if they contradict the lips, the eyes are the windows of the soul, and they speak a language that is as expressive as it is eloquent. Full article