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1.
Artigo em Inglês | MEDLINE | ID: mdl-38648003

RESUMO

Under laboratory conditions, the toxicological effects of pesticides tend to be less variable and realistic than under field conditions, limiting their usefulness in environmental risk assessment. In the current study, the earthworm Eisenia fetida was selected as a bioindicator for assessing glyphosate toxic effects in two different trials to solve this dilemma. In Trial 1, the worms were exposed for 7 and 14 days to concentrations of a commercial glyphosate formulation (1 to 500 mg a.i. kg-1) currently used in the field. In Trial 2, the worms were kept in nine soils collected from different plots with crops for 14 days of exposure. In both experiments, glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and acetylcholinesterase (AChE) activities and contents of lipid peroxidation (LPO) were evaluated. In T1, the glyphosate formulation produced a 40% inhibition of AChE activity and a significant increase in GST, SOD, CAT, and GPx activities and LPO contents in E. fetida on day 7. In T2, higher concentrations of glyphosate were detected in the soils of soybean, papaya, and corn (0.92, 0.87, and 0.85 mg kg-1), which induced a positive correlation between the levels of glyphosate residues with GST, SOD, CAT, GPx, and LPO and a negative correlation with AChE. These findings indicate that crop soils polluted with glyphosate elicited higher oxidative stress than under laboratory conditions, confirmed by IBRv2, PCA, and AHC analyses.

2.
Front Med (Lausanne) ; 11: 1363977, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476442

RESUMO

Introduction: Currently, there is only scarce evidence of a causal association between risk of malnutrition (RM) by the mini-nutritional assessment (MNA) and the incidence of sarcopenia. This study was designed to assess such an association at 4.2 years of follow-up in community-dwelling subjects over 60 years old. Methods: The data used were from the FraDySMex cohort study. The exposition variables were RM diagnosed by the long forma of the MNA (MNA-LF) and short form (MNA-SF). The last one included the body mass index and calf circumference at baseline, while sarcopenia was diagnosed by the EWGSOP2 at follow-up and taken as the response variable. Several covariates involved in the association were also considered. A multiple logistic regression analysis was performed to test the association. Results: At baseline, 27.0 and 37.9% of subjects had RM by the MNA-LF and MNA-SF, respectively. The incidence of sarcopenia was 13.7%. The fat mass variable significantly modified the association, so it was tested in each stratum. Two independent models showed that subjects with RM by the MNA-LF in the normal fat mass stratum were at a higher risk for developing sarcopenia at follow-up than those without RM (OR 9.28; IC 95% 1.57-54.76) after adjusting for age, sex, and waist circumference. No association was found for the excess fat mass stratum subjects. Subjects with RM by the MNA-SF in the excess fat mass stratum were more likely to develop sarcopenia at follow-up than those without RM by the MNA-SF (OR 3.67; IC 95% 1.29-10.43). This association was not found in the subjects in the normal fat mass stratum. Conclusion: The association was dependent on the variable fat mass. The two forms of the MNA should not be applied indistinctly with older adults. Based on these results, it is clear that the risk of malnutrition precedes the onset of sarcopenia.

3.
Neurobiol Aging ; 138: 28-35, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38522384

RESUMO

Astrocytes play an important role in neuroinflammation by producing proinflammatory molecules. In response to various stressful stimuli, astrocytes can become senescent or reactive, both are present in age-associated cognitive impairment and other neurodegenerative diseases, and contribute to neuroinflammation. However, there are no studies that compare the cytokines secreted by these types of astrocytes in the brain during aging. Hence, we aimed to broaden the picture of the secretory profiles and to differentiate the variability between them. Therefore, a systematic review was conducted following the guidelines of the "Reporting Items for Systematic Review and Meta-Analyses". Only three studies that met the inclusion terms evaluated age-related cytokine secretion, however, no evaluation of senescence or gliosis was performed. Consequently, to increase the spectrum of the review, studies where those phenotypes were induced and cytokines determined were included. Although some cytokines were common for gliosis and senescence, some interesting differences were also found. The dissimilarities in cytokines secretion between these phenotypes could be studied in the future as potential markers.


Assuntos
Astrócitos , Senescência Celular , Humanos , Senescência Celular/fisiologia , Gliose , Doenças Neuroinflamatórias , Citocinas
4.
Aquat Toxicol ; 268: 106868, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38387248

RESUMO

Worldwide production of alkyl phenols and ethoxylated alkyl phenols is high due to their broad industrial uses. It has been widely documented that they are endocrine disruptors, and it has been suggested that they could exert neurotoxic effects. However, a lack of information about the neurotoxic effects of APs and APEs prevails. In this study, the bisphenol A (BPA), 4-nonylphenol (NP), and 3­tert-butylphenol (tertBP) effects on brain and spinal cord of Nile tilapia exposed to environmental concentrations were evaluated by assessing acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and carboxylesterases (CES) activities, and γ-aminobutyric acid (GABA) levels and their effects were evaluated by molecular docking. BPA and NP, tertBP behave as agonists and antagonists of AChE, BuChE, CES, and GABA, with notable differences among organs. However, none of these compounds or their metabolites interact with the enzymes' catalytic triad, suggesting an indirect alteration of enzymatic activities. While inhibiting these enzymes stand out hydrophobic interactions with the peripheral anion site, contacts with the inner face of the active site and blocking the mouth of the gorge of the active site, and steric hindrance in the enzyme pocket of glutamate decarboxylase (GAD). In contrast, inductions probably are by homotropic pseudo-cooperative phenomenon, where APEs behave as anchors favoring the active site to remain open and interactions that confer a conservative stabilization of the regulatory domain. Although the results of this study are complex, with notable differences between organs and toxicants, they are some of the first evidence of the neurotoxicity of alkylphenols and their ethoxylated derivatives.


Assuntos
Ciclídeos , Hominidae , Poluentes Químicos da Água , Animais , Butirilcolinesterase/metabolismo , Ciclídeos/metabolismo , Fenol , Acetilcolinesterase/metabolismo , Simulação de Acoplamento Molecular , Poluentes Químicos da Água/toxicidade , Fenóis/toxicidade , Compostos Benzidrílicos/toxicidade , Hominidae/metabolismo , Ácido gama-Aminobutírico
5.
Nutrients ; 15(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37892494

RESUMO

BACKGROUND AND AIMS: Only one cohort study exists on the incidence of the risk of malnutrition (RM) in older adults, though numerous cross-sectional reports, identified several risk factors associated with the prevalence and incidence of this condition. However, alterations in body composition and impaired physical performance as exposition variables of RM have not been explored. This study assessed the incidence of RM and determined its association with excess fat mass, low total lean tissue, gait speed, and handgrip strength as exposition variables for RM in community-dwelling older adults. METHODS: This is a secondary analysis of older adults (≥60 years) derived from the study "Frailty, dynapenia, and sarcopenia in Mexican adults (FraDySMex)", a prospective cohort project conducted from 2014 to 2019 in Mexico City. At baseline, volunteers underwent body composition analysis and physical performance tests. Several covariates were identified through comprehensive geriatric assessment. At baseline and follow-up, RM was assessed using the long form of the mini nutritional assessment (MNA-LF) scale. Associations between the exposition variables and RM were assessed by multiple logistic regression. RESULTS: The cohort included 241 subjects. The average age was 75.6 ± 7.8 years, and 83.4% were women. The mean follow-up period was 4.1 years, during which 28.6% of subjects developed RM. This condition was less likely to occur in those with an excess fat mass, even after adjusting for several covariates. Regarding total lean tissue, the unadjusted model showed that RM was more likely to occur in men and women with a low TLT by the TLTI classification, compared to the normal group. However, after adjusting for several covariates (models 1 and 2), the association lost significance. Results on the association between gait speed and RM showed that this condition was also more likely to occur in subjects with low gait speed, according to both the unadjusted and adjusted models. Similar results were found for RM in relation to low handgrip strength; however, after adjusting for the associated covariates, models 1 and 2 no longer reached the level of significance. CONCLUSIONS: RM diagnosed by MNA-LF was significantly less likely to occur among subjects with excess fat mass, and a significant association emerged between low gait speed and RM after 4.1 years of follow-up in these community-dwelling older adults. These results confirm the association between some alterations of body composition and impaired physical performance with the risk of malnutrition and highlight that excess fat mass and low gait speed precede the risk of malnutrition, not vice versa.


Assuntos
Desnutrição , Sarcopenia , Masculino , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Vida Independente , Velocidade de Caminhada , Estudos de Coortes , Força da Mão , Estudos Prospectivos , Incidência , Estudos Transversais , Desnutrição/complicações , Desnutrição/epidemiologia , Sarcopenia/epidemiologia , Sarcopenia/diagnóstico , Avaliação Geriátrica/métodos
6.
Pharmaceuticals (Basel) ; 16(10)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37895943

RESUMO

The involvement of NK and other cytotoxic cells is considered the first defense line against cancer. However, a significant lack of information prevails on the possible roles played by factors considered characteristic of primitive cells, such as c-kit and Sca-1, in activating these cells, particularly in melanoma models subjected to treatments with substances under investigation, such as the case of norcantharidin. In this study, B16F1 murine melanoma cells were used to induce tumors in DBA/2 mice, estimating the proportions of NK and iNKT cells; the presence of activation (CD107a+) and primitive/activation (c-kit+/Lya6A+) markers and some tumor parameters, such as the presence of mitotic bodies, nuclear factor area, NK and iNKT cell infiltration in the tumor, infiltrated tumor area, and infiltrating lymphocyte count at 10x and 40x in specimens treated with pentoxifylline, norcantharidin, and the combination of both drugs. Possible correlations were estimated with Pearson's correlation analysis. It should be noted that, despite having demonstrated multiple correlations, immaturity/activation markers were related to these cells' activation. At the tumor site, iNKT cells are the ones that exert the cytotoxic potential on tumor cells, but they are confined to specific sites in the tumor. Due to the higher number of interactions of natural killer cells with tumor cells, it is concluded that the most effective treatment was PTX at 60 mg/kg + NCTD at 0.75 mg/kg.

7.
Front Endocrinol (Lausanne) ; 14: 1192236, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37635955

RESUMO

Introduction: Sarcopenia is a highly prevalent disease associated with adverse outcomes such as falls, disability, and death. The current international consensuses agree that muscle strength, muscle mass, and gait speed must be included in the definition. However, these proposed criteria require objective measurements that are not available for most populations. Since the timely identification of sarcopenia is a priority, several subjective screening scales have been developed; however, they have some limitations due to their low sensitivity. The objective of this work was to develop and validate SARCO-GS, a new short scale to screen sarcopenia that is affordable, easy, and accessible for all clinical care settings. Methods and materials: The development of the SARCO-GS included four stages: (1) Review and analysis of documentary sources, (2) Contextualization of the theoretical model of sarcopenia, (3) Scale conformation, and (4) Reliability and validity analyses. SARCO-GS was validated in the FraDySMex study, which is a longitudinal cohort of community-dwelling adults. Results: In the studied population (n=852), the average age was 68.9 years (SD 10.21) and 80.1% of the participants were women. SARCO-GS is a seven-item scale with an innovative structure that included five subjective questions (gait speed, muscular strength, muscle mass) and two measurements of muscular strength and muscle mass (Chair stand test and calf circumference). The results regarding criterion validity showed that the cut-off point ≥ 3 had good sensitivity (77.68%) versus the EWGSOP2 consensus, with an adequate Area Under the Receiver Operating Characteristic (AUC) (0.73), in addition to showing higher values of sensitivity and AUC than SARC-F and SARC-CalF using as reference the same consensus. Furthermore, SARCO-GS presented good predictive validity for functional dependence (HR=2.22, p=0.046) and acceptable correlation with other related measurements (construct validity). Regarding reliability, the scale showed acceptable internal reliability (correlation between items and total score: 0.50 to 0.70). After the validation analysis, the scale was adapted to English. Conclusions: The SARCO-GS is a novel scale to screen sarcopenia with high sensitivity, good construct, predictive validity, and internal reliability that may be useful for health professionals in different clinical settings and for clinical research.


Assuntos
Sarcopenia , Adulto , Humanos , Feminino , Idoso , Masculino , Sarcopenia/diagnóstico , Reprodutibilidade dos Testes , Força Muscular , Consenso , Pessoal de Saúde
9.
Bull Cancer ; 110(9): 912-936, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37277266

RESUMO

Cutaneous melanoma is an aggressive and highly metastatic skin cancer. In recent years, immunotherapy and targeted small-molecule inhibitors have improved the overall survival of patients. Unfortunately, most patients in advanced stages of disease exhibit either intrinsically resistant or rapidly acquire resistance to these approved treatments. However, combination treatments have emerged to overcome resistance, and novel treatments based on radiotherapy (RT) and targeted radionuclide therapy (TRT) have been developed to treat melanoma in the preclinical mouse model, raising the question of whether synergy in combination therapies may motivate and increase their use as primary treatments for melanoma. To help clarify this question, we reviewed the studies in preclinical mouse models where they evaluated RT and TRT in combination with other approved and unapproved therapies from 2016 onwards, focusing on the type of melanoma model used (primary tumor and or metastatic model). PubMed® was the database in which the search was performed using mesh search algorithms resulting in 41 studies that comply with the inclusion rules of screening. Studies reviewed showed that synergy with RT or TRT had strong antitumor effects, such as tumor growth inhibition and fewer metastases, also exhibiting systemic protection. In addition, most studies were carried out on antitumor response for the implanted primary tumor, demonstrating that more studies are needed to evaluate these combined treatments in metastatic models on long-term protocols.


Assuntos
Melanoma , Neoplasias Cutâneas , Animais , Camundongos , Melanoma/tratamento farmacológico , Melanoma/radioterapia , Melanoma/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/radioterapia , Terapia Combinada , Imunoterapia/métodos , Radioisótopos/uso terapêutico
10.
Front Aging Neurosci ; 15: 1162747, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37139092

RESUMO

Being overweight and obesity are world health problems, with a higher prevalence in women, defined as abnormal or excessive fat accumulation that increases the risk of chronic diseases. Excess energy leads to adipose expansion, generating hypertrophic adipocytes that produce various pro-inflammatory molecules. These molecules cause chronic low-intensity inflammation, affecting the organism's functioning and the central nervous system (CNS), inducing neuroinflammation. The neuroinflammatory response during obesity occurs in different structures of the CNS involved in memory and learning, such as the cortex and the hippocampus. Here we analyzed how obesity-related peripheral inflammation can affect CNS physiology, generating neuroinflammation and promoting cellular senescence establishment. Since some studies have shown an increase in senescent cells during aging, obesity, and neurodegenerative diseases, we proposed that cellular senescence participation may contribute to the cognitive decline in an obesity model of middle-aged female Wistar rats. The inflammatory state of 6 and 13 months-old female Wistar rats fed with a hypercaloric diet was measured in serum and CNS (cortex and hippocampus). Memory was evaluated using the novel object recognition (NOR) test; the presence of senescent markers was also determined. Our data suggest that the systemic inflammation generated by obesity induces a neuroinflammatory state in regions involved in learning and memory, with an increase in senescent markers, thus proposing senescence as a potential participant in the negative consequences of obesity in cognition.

11.
Photodiagnosis Photodyn Ther ; 43: 103596, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37148952

RESUMO

BACKGROUND: Melanoma is a highly metastatic skin cancer with limited response to current therapies in advanced patients. To overcome resistance, novel treatments based on photodynamic and photothermal therapies (PDT and PTT, respectively) have been developed to treat melanoma in preclinical murine models. Despite success inhibiting implanted tumors' growth, there has been limited evaluation of their long-term effectiveness in preventing metastasis, recurrence, or improving survival rates. METHODS: Combined and multidrug therapies based on PDT and/or PTT to treat cutaneous malignant melanoma in the preclinical mouse model were reviewed from 2016 onwards. PubMed® was the database in which the search was performed using mesh search algorithms resulting in fifty-one studies that comply with strict inclusion rules of screening. RESULTS: B16 melanoma-bearing C57BLACK6 mice model was the most used to evaluate immunotherapies, chemotherapies, and targeted therapies in combination with PDT and/or PTT. Combined therapies demonstrated a synergistic effect, resulting in intense antitumor activity. The most extensively studied protocol for developing metastatic models involved the intravenous administration of malignant cells, with some combined therapies being tested. Furthermore, the review presents the composition of the nanostructures utilized for delivering the drugs and light-responsive agents and the treatment plans for each combined approach. CONCLUSIONS: The identified mechanisms to simulate metastatic melanoma models and the therapeutic combinations may aid in evaluating the systemic protection of combined PDT and PTT-based therapies, particularly in conducting short-term preclinical experiments. Such simulations could have relevance to clinical studies.


Assuntos
Melanoma Experimental , Fotoquimioterapia , Camundongos , Animais , Fotoquimioterapia/métodos , Terapia Fototérmica , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Fototerapia , Modelos Animais de Doenças , Melanoma Experimental/tratamento farmacológico , Linhagem Celular Tumoral
12.
Pharmaceuticals (Basel) ; 16(4)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37111258

RESUMO

Melanoma is a highly lethal type of cancer that has had an increase in incidence in the last decades. Nevertheless, current therapies lack effectiveness and have highly disabling side effects, which calls for new therapeutic strategies. Norcantharidin (NCTD) is an acid derivative with potential antitumor activity isolated from natural blister beetles. However, its solubility limitations restrict its use. To address this issue, we developed an oil-in-water nanoemulsion using commonly available cosmetic ingredients, which increased NCTD solubility 10-fold compared to water. The developed nanoemulsion showed a good droplet size and homogeneity, with adequate pH and viscosity for skin application. In vitro drug release studies showed a sustained release profile, ideal for prolonged therapeutic effects. Accelerated stability studies proved that the formulation was reasonably stable under stress conditions, with particle separation fingerprints, instability index, particle size, and sedimentation velocity analyses being conducted. To assess the therapeutic potential of the developed formulation, in vitro studies were conducted on melanoma B16F1 cells; results showed an IC50 of 1.026 +/- 0.370 mg/kg, and the cells' metabolic activity decreased after exposure to the NCTD nanoemulsion. Hence, a new "easy-to-make" nanoformulation with therapeutic potential on melanoma cells was developed, as a possible adjuvant for future melanoma treatment.

13.
Naunyn Schmiedebergs Arch Pharmacol ; 396(1): 99-108, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36184699

RESUMO

Norcantharidin (NCTD) is the demethylated analog of cantharidin, with allegedly reduced toxicity. However, there is still limited information regarding its posology and potential risk in its use in cancer treatment. Healthy BDF1 mice were intraperitoneally administered with norcantharidin (0, 3, 6, 12, and 25 mg/kg) every 24 h for 6 days. Survivor mice were euthanized, and the brain, lungs, kidneys, spleen, and liver were procured for enzymatic and histopathological analysis in the liver and kidney. DL50 were 8.86 mg/kg for females and 11.77 mg/kg for males. The treatments with 3.0 mg/kg and 6.0 mg/kg significantly modified the phosphorylase, alanine transaminase, and γ-glutamyl transferase activities; however, an organ-specific response was detected. A significant dose-dependent decrease was observed in the kidney for ROS, while the liver had the opposite effect. Histopathological analysis revealed a significant elevation in hepatocytes' nuclei average size and total area (3 mg/kg), as well as centrilobular vein and adjacent sinusoidal capillaries showed a significant difference. The portal triad presented a significant difference in veins and capillarity count in 6 mg/kg. Renal samples showed cortex convoluted tubules' average size significantly augmented in both doses' groups, and tubule count was found augmented in 6 mg/kg. These physiological effects of NCTD can be exploited as treatment strategies if able to operate in an established posology and proper testing.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Rim , Masculino , Feminino , Camundongos , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/toxicidade
14.
Arch Gerontol Geriatr ; 105: 104856, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36399890

RESUMO

Osteosarcopenic obesity (OSO) has been associated with increase immobility, falls, fractures, and other dysfunctions, which could increase mortality risk during aging. However, its etiology remains unknown. Recent studies revealed that sedentarism, fat gain, and epigenetic regulators are critical in its development. One effective intervention to prevent and treat OSO is exercise. Therefore, in the present study, by keeping rats in conditions of sedentarism and others under a low-intensity exercise routine, we established an experimental model of OSO. We determined the degree of sarcopenia, obesity, and osteopenia at different ages and analyzed the miRNA expression during the lifespan using miRNA microarrays from gastrocnemius muscle. Interestingly microarrays results showed that there is a set of miRNAs that changed their expression with exercise. The pathway enrichment analysis showed that these miRNAs are strongly associated with immune regulation. Further inflammatory profiles with IL-6/IL-10 and TNF-α/IL-10 ratios showed that exercised rats presented a lower pro-inflammatory profile than sedentary rats. Also, the body fat gain in the sedentary group increased the inflammatory profile, ultimately leading to muscle dysfunction. Exercise prevented strength loss over time and maintained skeletal muscle functionality over time. Differential expression of miRNAs suggests that they might participate in this process by regulating the inflammatory response associated with aging, thus preventing the development of OSO.


Assuntos
Envelhecimento , Doenças Ósseas Metabólicas , Imunidade , MicroRNAs , Obesidade , Condicionamento Físico Animal , Sarcopenia , Animais , Ratos , Interleucina-10/genética , Interleucina-10/metabolismo , MicroRNAs/metabolismo , Obesidade/imunologia , Obesidade/prevenção & controle , Sarcopenia/imunologia , Sarcopenia/prevenção & controle , Doenças Ósseas Metabólicas/imunologia , Doenças Ósseas Metabólicas/prevenção & controle , Músculo Esquelético/metabolismo , Inflamação/imunologia , Inflamação/prevenção & controle , Comportamento Sedentário , Modelos Animais de Doenças , Citocinas/genética , Citocinas/metabolismo
15.
Front Immunol ; 13: 1021828, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569901

RESUMO

Introduction: The anti-CD20 antibody rituximab (RTX) has substantially improved outcomes of patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing lymphomas. An approach to increase the clinical effectiveness of anti-tumor therapy is the use of antibody-cytokine fusion proteins (immunocytokines (ICKs)) to deliver at the tumor site the antibody effector functions and cytokines that trigger anti-tumor activities. In particular, IL-2-based ICKs have shown significant results in preclinical studies but not in clinical trials due to the toxicity profile associated to high doses IL-2 and the undesired expansion of Tregs. Methods: To improve the efficacy of RTX therapy, we fused a murine (mIgG2a) or a human (hIgG1) version of RTX to a mutated IL-2 (no-alpha mutein), which has a disrupted affinity for the high affinity IL-2 receptor (IL-2R) to prevent the stimulation of Tregs and reduce the binding to endothelial cells expressing CD25, the α chain of high affinity IL-2R. Characterization of anti-CD20-IL2no-alpha ICKs was performed by SDS-PAGE, Western-blotting and SEC-HPLC and also by several functional in vitro techniques like T-cell proliferation assays, apoptosis, CDC and ADCC assays. The in vivo activity was assessed by using murine tumor cells expressing huCD20 in C57/Bl6 mice. Results: Both ICKs exhibited similar in vitro specific activity of their IL2no-alpha mutein moieties and kept CD20-binding capacity. Anti-CD20-IL2no-alpha (hIgG1) retained antibody effector functions as complement-dependent cytotoxicity and enhanced direct apoptosis, NK cell activation and antibody-dependent cellular cytotoxicity relative to RTX. In addition, both ICKs demonstrated a higher antitumor efficacy than parental molecules or their combination in an EL4-huCD20 tumor model in immunocompetent mice. Anti-CD20-IL2no-alpha (hIgG1) strongly expanded NK and CD8+ T cells but not Tregs in tumor-bearing mice. Discussion: These findings suggest that anti-CD20-IL2no-alpha could represent an alternative treatment for B cell lymphoma patients, mainly those refractory to RTX therapy.


Assuntos
Interleucina-2 , Linfoma de Células B , Humanos , Camundongos , Animais , Células Endoteliais/patologia , Recidiva Local de Neoplasia , Rituximab/farmacologia , Rituximab/uso terapêutico , Anticorpos/uso terapêutico
16.
Dose Response ; 20(3): 15593258221130752, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325182

RESUMO

Neurodegenerative diseases have increased worldwide in recent years. Their relationship with oxidative stress has motivated the research to find therapies and medications capable of suppressing oxidative damage and therefore slowing the progression of these diseases. Glutathione (GSH) is the most important cellular antioxidant in living beings and is responsible for regulating the cellular redox state. However, GSH cannot be administered by any route of administration, so molecules that increase its levels by activating Nrf2-ARE signaling pathway are explored; since Nrf2 regulates the main genes involved in GSH de novo synthesis and recycling. Astrocytes are the most important cell-type in the antioxidant cell response and are responsible for providing GSH and other substrates for neurons to have an efficient antioxidant response. Methotrexate (MTX) is an anti-inflammatory agent that has different cellular effects when administered at low or high concentrations. So in this study, we used MTX different concentrations and exposure times to induce a hormetic antioxidant response in rat primary astrocytes. Our results showed that 20 nM MTX pre-conditioning for 12 h augmented the GSH/GSSG ratio and protected cellular viability against a toxic MTX and H2O2 insult, which was abrogated when Nrf2 was inhibited by brusatol. Hence, MTX subsequent studies as a drug to counteract the progression of some stress-associated neurodegenerative diseases are suggested.

17.
Ecotoxicology ; 31(8): 1241-1253, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36112299

RESUMO

Soil contamination with petroleum hydrocarbons affects plants and rhizospheric microorganisms. Microbial activity participates in important biochemical processes that stimulate, together with plants, the modification of toxic compounds for organisms. A nine-month experiment was set up to study the effect over time of oil on plant height (cm), formation of new plants, plant matter production (gravimetry), and population of rhizospheric microorganisms (serial dilution) in the sedge Eleocharis palustris. Removal of total petroleum hydrocarbons (soxhlet and gravimetry) from the soil was also evaluated. The means of the evaluated variables registered significant statistical differences (Duncan, p < 0.05) regarding the age of the plant and the amount of crude oil. There was a high correlation between oil and plant height (0.848) and with new plants (0.994). 60 mg oil dose promoted the greatest statistical difference in the amounts of roots and plant biomass (p < 0.05). E. palustris exposed to 60 and 75 mg of oil stimulated high densities of microalgae, actinomycetes, fungi, hydrocarbonoclastic bacteria and Pseudomonas spp; the overall ratio was 2:1 relative to natural attenuation. Plant and microorganism variables evaluated registered physiological and microbiological hormetic indices ≥1, showing a positive linear relationship. Natural attenuation was more efficient in removing crude oil. We conclude that E. palustris is tolerant to oil exposure. It is suggested to combine it with natural attenuation for the optimization of soils contaminated with crude oil.


Assuntos
Eleocharis , Petróleo , Poluentes do Solo , Biodegradação Ambiental , Argila , Hormese , Hidrocarbonetos , Petróleo/toxicidade , Plantas , Solo/química , Microbiologia do Solo , Poluentes do Solo/química , Poluentes do Solo/toxicidade
18.
Salud Publica Mex ; 64(5, sept-oct): 515-521, 2022 Aug 26.
Artigo em Espanhol | MEDLINE | ID: mdl-36130355

RESUMO

OBJETIVO: Analizar el rol de los factores socioeconómicos y culturales en la vulnerabilidad a la obesidad en madres y sus hijos menores de dos años, en localidades del Sur de Morelos, México. Material y métodos. Se realizó trabajo de campo y observación no participativa. Durante 2019, se aplicaron 17 entrevistas semiestructuradas a una submuestra de una cohorte. Los datos fueron ordenados y analizados con apoyo del software Atlas-Ti v. 7, usando 18 códigos libres. RESULTADOS: Factores sociales como los ingresos del hogar y los roles de género, combinados con la influencia de la parentela y las creencias sobre la preferencia de la niñez por productos ultraprocesados, predisponen la disponibilidad de bebidas y alimentos calóricos que generan vulnerabilidad a la obesidad durante la infancia temprana. La actividad eco-nómica de las madres, la participación de los padres y evitar influencia de parientes puede predisponer una mejor calidad de los alimentos y mayor actividad física. CONCLUSIONES: La baja disponibilidad de alimentos saludables, los riesgos de inseguridad alimentaria y los factores familiares y culturales, que se presentan en contextos de vulnerabilidad económica y social, incrementan la vulnerabilidad del binomio madre-hijo a la obesidad.


Assuntos
Sobrepeso , Humanos , México , Sobrepeso/epidemiologia , Estudos Retrospectivos
19.
Biogerontology ; 23(5): 587-613, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35960458

RESUMO

Aging is a complex and detrimental process, which disrupts most organs and systems within the organisms. The nervous system is morphologically and functionally affected during normal aging, and oxidative stress has been involved in age-related damage, leading to cognitive decline and neurodegenerative processes. Sulforaphane (SFN) is a hormetin that activates the antioxidant and anti-inflammatory responses. So, we aimed to evaluate if SFN long-term treatment was able to prevent age-associated cognitive decline in adult and old female and male rats. Memory was evaluated in adult (15-month-old), and old (21-month-old) female and male Wistar rats after three months of SFN treatment. Young rats (4-month-old) were used as age controls. The antioxidant response induction, the redox state (GSH/GSSG), and oxidative damage were determined in the brain cortex (Cx) and hippocampus (Hc). Our results showed that SFN restored redox homeostasis in the Cx and Hc of adult rats, thus preventing cognitive decline in both sexes; however, the redox responses were not the same in males and females. Old rats were not able to recover their redox state as adults did, but they had a mild improvement. These results suggest that SFN mainly prevents rather than reverts neural damage; though, there might also be a range of opportunities to use hormetins like SFN, to improve redox modulation in old animals.


Assuntos
Antioxidantes , Disfunção Cognitiva , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Disfunção Cognitiva/prevenção & controle , Feminino , Homeostase , Isotiocianatos , Masculino , Oxirredução , Estresse Oxidativo , Ratos , Ratos Wistar , Sulfóxidos
20.
BMC Geriatr ; 22(1): 388, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505279

RESUMO

BACKGROUND: Aging is an independent risk factor for deterioration in functional capacity. Some studies have reported that physical activity (PA) improves functional capacity and physical performance among older adults (OA). Thus the objective of the present study was to assess the longitudinal association between PA and functional and physical performance in non-institutionalized OA. METHODS: A longitudinal analysis using data from the Frailty, Dynapenia and Sarcopenia in Mexican adults (FRADYSMEX, by its Spanish acronym) cohort study was conducted. PA was assessed through the Community Healthy Activities Model Program for Seniors (CHAMPS) instrument. Functionality was measured with the Barthel index and the Lawton and Brody scale, while physical performance was measured with the Short Physical Performance Battery (SPPB). To evaluate the association between the level of PA and physical and functional performance as a continuous variable, a linear regression of mixed effects was performed. To assess PA and dependence in basic activities of the daily life (BADL), instrumental activities of the daily life (IADL), and low physical performance (PP), generalized estimation equation models [to compute odds ratios (OR) and 95% confidence intervals (95%CI)] were computed. RESULTS: Older people who performed moderate to vigorous-intensity PA had a lower risk of dependence in IADL (OR = 0.17; 95%CI: 0.10, 0.80) and lower risk of low PP (OR = 0.18; 95%CI: 0.11, 0.58) compared to those in lower categories of PA. CONCLUSIONS: Older adults living in the community who perform PA of moderate to vigorous intensity have a lower risk of dependence in BADL and IADL and have a lower risk of low PP.


Assuntos
Fragilidade , Sarcopenia , Idoso , Estudos de Coortes , Exercício Físico , Humanos , Desempenho Físico Funcional
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