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1.
Pharmacogenomics J ; 22(3): 180-187, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35361995

RESUMO

The diagnostic process of familial hypercholesterolemia frequently involves the use of genetic studies. Patients are treated with lipid-lowering drugs, frequently statins. Although pharmacogenomic clinical practice guidelines focusing on genotype-based statin prescription have been published, their use in routine clinical practice remains very modest.We have implemented a new NGS strategy that combines a panel of genes related to familial hypercholesterolemia with genomic regions related to the pharmacogenomics of lipid-lowering drugs described in clinical practice guidelines and in EMA and FDA drug labels. A multidisciplinary team of doctors, biologists, and pharmacists creates a clinical report that provides diagnostic and therapeutic findings using a knowledge management and clinical decision support system, as well as an algorithm for treatment selection.For 12 months, a total of 483 genetic diagnostic studies for familial hypercholesterolemia were carried out, of which 221 (45.8%) requested a complementary pharmacogenomic test. Of these 221 patients, 66.5% were carriers of actionable variants in any of the studied pharmacogenomic pathways: 46.6% of patients in one pathway, 19.0% in two pathways, and 0.9% in three pathways. 45.7% of patients could have a response to atorvastatin different from that of the reference population, 45.7% for simvastatin and lovastatin, 29.0% for fluvastatin, and 6.7% patients for pitavastatin.This implementation approach facilitates the incorporation of pharmacogenomic studies in clinical care practice, it does not add complexity nor additional steps to laboratory processes, and improves the pharmacotherapeutic process of patients.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Atorvastatina/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/genética , Farmacogenética , Sinvastatina/uso terapêutico
2.
Parasitol Res ; 121(1): 303-309, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34741218

RESUMO

The infection caused by Entamoeba histolytica is still a serious public health problem, especially in developing countries. The goal of this study was to evaluate the effect of terfenadine against Entamoeba histolytica. The trophozoites were exposed to 1, 2, 3, and 4 µM of terfenadine, for 24 and 48 h. Consequently, the viability of cells was determined by trypan blue exclusion test. The effect of terfenadine on adhesion of Entamoeba histolytica was evaluated in Caco-2 cells. In addition, the effect of terfenadine on the erythrophagocytic capacity of the parasite was investigated. The results show that terfenadine affects the growth and cell viability in a time- and dose-dependent manner. The higher inhibitory effects were observed with 4 µM at 48 h; 91.6% of growth inhibition and only 22.5% of trophozoites were viable. Additionally, we demonstrate that terfenadine is highly selective for the parasite and has low toxicity on Caco-2 cells. Furthermore, adhesion to Caco-2 cells and erythrophagocytic capacity were significantly inhibited. These findings demonstrate that terfenadine exerts significant effects on the virulence of Entamoeba histolytica. This is the first study demonstrating the amoebicidal activity of terfenadine and the results suggest it may be effective in the treatment of amoebiasis.


Assuntos
Entamoeba histolytica , Animais , Células CACO-2 , Reposicionamento de Medicamentos , Humanos , Terfenadina , Trofozoítos
3.
Molecules ; 25(19)2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32992439

RESUMO

Magnetic nanoparticles such as cobalt ferrite are investigated under clinical hyperthermia conditions for the treatment of cancer. Cobalt ferrite nanoparticles (CFNPs) synthesized by the thermal decomposition method, using nonionic surfactant Triton-X100, possess hydrophilic polyethylene oxide chains acting as reducing agents for the cobalt and iron precursors. The monodispersed nanoparticles were of 10 nm size, as confirmed by high-resolution transmission electron microscopy (HR-TEM). The X-ray diffraction patterns of CFNPs prove the existence of cubic spinel cobalt ferrites. Cs-corrected scanning transmission electron microscopy-high-angle annular dark-field imaging (STEM-HAADF) of CFNPs confirmed their multi-twinned crystallinity due to the presence of atomic columns and defects in the nanostructure. Magnetic measurements proved that the CFNPs possess reduced remnant magnetization (MR/MS) (0.86), which justifies cubic anisotropy in the system. Microwave-based hyperthermia studies performed at 2.45 GHz under clinical conditions in physiological saline increased the temperature of the CFNP samples due to the transformation of radiation energy to heat. The specific absorption rate of CFNPs in physiological saline was 68.28 W/g. Furthermore, when triple-negative breast cancer cells (TNBC) in the presence of increasing CFNP concentration (5 mg/mL to 40 mg/mL) were exposed to microwaves, the cell cytotoxicity was enhanced compared to CFNPs alone.


Assuntos
Antineoplásicos , Cobalto , Compostos Férricos , Hipertermia Induzida , Campos Magnéticos , Nanopartículas , Neoplasias de Mama Triplo Negativas/terapia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cobalto/química , Cobalto/farmacologia , Feminino , Compostos Férricos/síntese química , Compostos Férricos/química , Compostos Férricos/farmacologia , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico
4.
J Transl Med ; 17(1): 198, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185999

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) and non-germinal center-like (non-GCB) cell-of-origin groups, entities driven by different oncogenic pathways with different clinical outcomes. DLBCL classification by immunohistochemistry (IHC)-based decision tree algorithms is a simpler reported technique than gene expression profiling (GEP). There is a significant discrepancy between IHC-decision tree algorithms when they are compared to GEP. METHODS: To address these inconsistencies, we applied the machine learning approach considering the same combinations of antibodies as in IHC-decision tree algorithms. Immunohistochemistry data from a public DLBCL database was used to perform comparisons among IHC-decision tree algorithms, and the machine learning structures based on Bayesian, Bayesian simple, Naïve Bayesian, artificial neural networks, and support vector machine to show the best diagnostic model. We implemented the linear discriminant analysis over the complete database, detecting a higher influence of BCL6 antibody for GCB classification and MUM1 for non-GCB classification. RESULTS: The classifier with the highest metrics was the four antibody-based Perfecto-Villela (PV) algorithm with 0.94 accuracy, 0.93 specificity, and 0.95 sensitivity, with a perfect agreement with GEP (κ = 0.88, P < 0.001). After training, a sample of 49 Mexican-mestizo DLBCL patient data was classified by COO for the first time in a testing trial. CONCLUSIONS: Harnessing all the available immunohistochemical data without reliance on the order of examination or cut-off value, we conclude that our PV machine learning algorithm outperforms Hans and other IHC-decision tree algorithms currently in use and represents an affordable and time-saving alternative for DLBCL cell-of-origin identification.


Assuntos
Algoritmos , Perfilação da Expressão Gênica , Centro Germinativo/patologia , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/patologia , Aprendizado de Máquina , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Teorema de Bayes , Árvores de Decisões , Análise Discriminante , Feminino , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/estatística & dados numéricos , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/estatística & dados numéricos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade
5.
Rev Invest Clin ; 70(1): 32-39, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29513299

RESUMO

BACKGROUND: Black bean (Phaseolus vulgaris L.) is a very common legume seed in Mexican diet. Flavonoids and crude extracts from different plants have been reported as effective agents for chemoprevention and cytotoxicity in several cancer cell lines. We investigated the effects of black bean hulls extract (BBE) and its flavonoid fraction (FF) on lymphoma cells. METHODS: BBE and FF were characterized by high-performance liquid chromatography. Viability and flow cytometry assays were carried out. Finally, a mouse model was generated to test the in vivo effect of both fractions. RESULTS: Both BBE and FF inhibited cell proliferation in a dose-dependent way. In addition, cells underwent apoptosis, and the cellular population at S-phase increased after exposure to these fractions. Furthermore, mice treated with BBE or FF increased the overall survival by 5 or 6 days, respectively, in comparison with a placebo group (p = 0.056). DISCUSSION: BBE and FF had cytotoxic action by driving OCI-Ly7 cells into apoptosis as well as blocking progression to G2/M phase. In addition, BBE and FF treatments were effective in xenograft models.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Linfoma/tratamento farmacológico , Phaseolus/química , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Flavonoides/administração & dosagem , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Citometria de Fluxo , Humanos , Masculino , México , Camundongos , Camundongos SCID , Extratos Vegetais/administração & dosagem , Taxa de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Molecules ; 22(5)2017 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-28505094

RESUMO

Giardiasis, a diarrheal disease, is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; unfortunately, all of them have variable efficacies and adverse effects. Bursera fagaroides has been known for its anti-inflammatory and antidiarrheal properties in Mexican traditional medicine. We investigated the in vitro anti-giardial activities of four podophyllotoxin-type lignans from Bursera fagaroides var. fagaroides, namely, 5'-desmethoxy-ß-peltatin-A-methylether (5-DES), acetylpodophyllotoxin (APOD), burseranin (BUR), and podophyllotoxin (POD). All lignans affected the Giardia adhesion and electron microscopy images revealed morphological alterations in the caudal region, ventral disk, membrane, and flagella, to different extents. Only 5-DES, APOD, and POD caused growth inhibition. Using the Caco-2 human cell line as a model of the intestinal epithelium, we demonstrated that APOD displayed direct antigiardial killing activity and low toxicity on Caco-2 cells. This finding makes it an attractive potential starting point for new antigiardial drugs.


Assuntos
Antiprotozoários/farmacologia , Bursera/química , Podofilotoxina/farmacologia , Antiprotozoários/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Podofilotoxina/química
7.
Enferm Infecc Microbiol Clin ; 33(4): 253-6, 2015 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-25444359

RESUMO

INTRODUCTION: Osteoarticular pneumococcal infection is an infrequent complication of pneumococcal bacteremia, due to the advances in antibiotic therapy and in the pattern of immunization. METHODS: A retrospective study was conducted on patients diagnosed with osteoarticular pneumococcal infection between January 2003 and December 2013 in the University Hospital Marqués de Valdecilla in Santander. RESULTS: Five out of 321 patients diagnosed with pneumococcal bacteremia had osteoarticular infection. All of them had at least one chronic underlying disease and had been immunized according to the standard vaccination schedule. Hip and vertebra were the most common joints involved. Outcome was favorable in all cases. CONCLUSIONS: The clinical findings of pneumococcal osteoarticular infection should be borne in mind. Its optimal prevention in high-risk patients should include the 13V conjugate vaccine.


Assuntos
Artrite Infecciosa/epidemiologia , Infecção Hospitalar/epidemiologia , Infecções Oportunistas/epidemiologia , Osteíte/epidemiologia , Infecções Pneumocócicas/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Artrite Infecciosa/microbiologia , Bacteriemia/epidemiologia , Comorbidade , Infecção Hospitalar/microbiologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/microbiologia , Osteíte/microbiologia , Vacinas Pneumocócicas , Estudos Retrospectivos , Espanha/epidemiologia , Vacinação
8.
Salud Publica Mex ; 56(6): 592-602, 2014.
Artigo em Espanhol | MEDLINE | ID: mdl-25604410

RESUMO

OBJECTIVE: To establish the blood lead concentration and associated risk factors in schoolchildren during 1998 and 2008. MATERIALS AND METHODS: A blood lead screening was conducted in schoolchildren of 6-12 years of age, enrolled in 17 elementary schools of the metropolitan area of Monterrey, México, during 1998 and 2008. RESULTS: The mean blood lead level were 9.6 ± 3.0 (µg/dL range of 3.18 to 20.88) in 1998 and 4.5±4.8 µg/dL (range of 3.3 to 53.7) showing a 2.1-times reduction in blood lead levels (p<0.01). CONCLUSIONS: This reduction in blood lead levels demonstrate environmental and industrial control improvements and the benefits of fading out the leaded gasoline during the 1990's.


Assuntos
Chumbo/sangue , Poluentes Atmosféricos/efeitos adversos , Anemia/sangue , Anemia/epidemiologia , Criança , Estudos Transversais , Avaliação Educacional , Exposição Ambiental/estatística & dados numéricos , Feminino , Contaminação de Alimentos , Gasolina , Hematócrito , Humanos , Indústrias , Intoxicação por Chumbo/sangue , Intoxicação por Chumbo/epidemiologia , Intoxicação por Chumbo/etiologia , Masculino , México/epidemiologia , Estudos Prospectivos , Estudos de Amostragem , População Urbana/estatística & dados numéricos , Emissões de Veículos/legislação & jurisprudência , Poluentes Químicos da Água/efeitos adversos
9.
Med Clin (Barc) ; 162(10): 477-482, 2024 05 31.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38342706

RESUMO

BACKGROUND AND PURPOSE: Some studies have shown that influenza vaccination is associated with a lower risk of SARS-CoV-2 infection; in patients with COVID-19 infection, admission to intensive care is reduced, with less need for mechanical ventilation, shorter hospital stays, and reduced mortality. This study aimed to determine if a history of annual influenza vaccination impacts the clinical course of SARS-CoV-2 infection during hospitalization. METHODS: This was an observational, prospective, cohort study of patients older than 65 admitted to the COVID-19 unit from January to June 2021. The history of influenza vaccination over the last 5 years was assessed in each patient during hospitalization. We measured the length of hospital stay, the need for admission to the intensive care unit (ICU), the patient's oxygen requirements, complications during hospitalization, and outcome (medical discharge or death). Patients with a history of vaccination against SARS-CoV-2 were not included. RESULTS: We analyzed 125 patients, 50.4% (n=63) with history of influenza vaccination and 49.6% (n=62) without a history of influenza vaccination. In-hospital mortality was 44.8%, higher in the unvaccinated (54.8%) population (p=0.008). ICU admission was 27% higher in vaccinated (35%) patients (p=0.05). Patients without a history of influenza vaccination had a higher prevalence of cardiac (8% vs. 5%, p=0.04) and renal complications (29% vs. 13%, p=0.02). Patients with a history of vaccination had a greater need for invasive mechanical ventilation (25.4%, p=0.02). CONCLUSION: In this study, a history of influenza vaccination in older adults with SARS-CoV-2 infection was related to lower in-hospital mortality.


Assuntos
COVID-19 , Mortalidade Hospitalar , Hospitalização , Vacinas contra Influenza , Influenza Humana , Humanos , Idoso , COVID-19/prevenção & controle , COVID-19/complicações , COVID-19/mortalidade , COVID-19/epidemiologia , Masculino , Feminino , Estudos Prospectivos , Hospitalização/estatística & dados numéricos , Idoso de 80 Anos ou mais , Influenza Humana/prevenção & controle , Influenza Humana/mortalidade , Influenza Humana/epidemiologia , Influenza Humana/complicações , Tempo de Internação/estatística & dados numéricos , Vacinação , Respiração Artificial/estatística & dados numéricos , Unidades de Terapia Intensiva
10.
Heliyon ; 10(7): e28482, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601514

RESUMO

In recent years, the growth of Internet of Things devices has increased the use of sustainable energy sources. An alternative technology is offered by triboelectric nanogenerators (TENGs) that can harvest green energy and convert it into electrical energy. Herein, we assessed three different nopal powder types that were used as triboelectric layers of eco-friendly and sustainable TENGs for renewable energy harvesting from environmental vibrations and powering electronic devices. These nanogenerators were fabricated using waste and recycled materials with a compact design for easy transportation and collocation on non-homogeneous surfaces of different vibration or motion sources. In addition, these TENGs have advantages such as high output performance, stable output voltage, lightweight, low-cost materials, and a simple fabrication process. These nanogenerators use the contact-separation mode between two triboelectric layers to convert the vibration energy into electrical energy. TENG with the best output performance is based on dehydrated nopal powder, generating an output power density of 2.145 mWm-2 with a load resistance of 39.97 MΩ under 3g acceleration and 25 Hz operating frequency. The proposed TENGs have stable output voltages during 22500 operating cycles. These nanogenerators can light 116 ultra-bright blue commercial LEDs and power a digital calculator. Also, the TENGs can be used as a chess clock connected to a mobile phone app for smart motion sensing. These nanogenerators can harvest renewable vibration energy and power electronic devices, sensors, and smart motion sensing.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38656093

RESUMO

BACKGROUND: COVID-19-induced diabetes is a novel and enigmatic disease. Our aim was to evaluate a possible relationship between post-COVID-19 syndrome (PCS) and increased insulin resistance (IR) in non-diabetic outpatients after mild COVID-19. METHODS: Repeated measures design. Three evaluations [1E (pre-COVID, baseline), 2E (3 months post-COVID) and 3E (21 months post-COVID)] were performed, directed to PCS+ and PCS- subjects. Triglyceride-glucose (TyG) index ≥8.74 was considered IR, and albumin-to-globulin ratio (AGR) <1.50, inflammation. RESULTS: We analyzed 112 individuals (median [IQR] age=44 [20] years, 58% women, 36 PCS+, 76 PCS-). PCS+ with very low basal IR (TyG <7.78, lowest quartile) showed a reduced inflammatory burden (basal AGR=1.81 [0.4] vs. 1.68 [0.2] in 2E; P=0.23), and increased TyG across evaluations (from basal 7.62 [0.2] to 8.29 [0.5]; P=0.018]. Conversely, PCS+ subjects with high basal TyG (TyG ≥8.65, highest quartile) did not show significant variations in TyG, but a greater inflammatory load (basal AGR=1.69 [0.3] vs. 1.44 [0.3] in 2E; P=0.10). In multivariable models addressing groups with reduced basal IR (TyG <8.01), PCS has been a consistent predictor for TyG, after adjusting for confounders. Partial correlation and multivariable analyses showed similarities involving acute polysymptomatic COVID-19 and PCS regarding IR. CONCLUSIONS: PCS was associated with increased IR, being more evident when the baseline degree of IR was very low. PCS and increased IR were separately associated with inflammation. Acute polysymptomatic COVID-19 and PCS could be clinical expressions of underlying inflammatory state, which in turn may also trigger IR.

12.
Mem Inst Oswaldo Cruz ; 108(5): 616-22, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23903978

RESUMO

The humoral immune response plays an important role in the clearance of Giardia lamblia. However, our knowledge about the specific antigens of G. lamblia that induce a protective immune response is limited. The purpose of this study was to identify and characterise the immunogenic proteins of G. lamblia in a mouse model. We generated monoclonal antibodies (moAbs) specific to G. lamblia (1B10, 2C9.D11, 3C10.E5, 3D10, 5G8.B5, 5F4, 4C7, 3C5 and 3C6) by fusing splenocytes derived from infected mice. Most of these moAbs recognised a band of ± 71 kDa (5G8 protein) and this protein was also recognised by serum from the infected mice. We found that the moAbs recognised conformational epitopes of the 5G8 protein and that this antigen is expressed on the cell surface and inside trophozoites. Additionally, antibodies specific to the 5G8 protein induced strong agglutination (> 70-90%) of trophozoites. We have thus identified a highly immunogenic antigen of G. lamblia that is recognised by the immune system of infected mice. In summary, this study describes the identification and partial characterisation of an immunogenic protein of G. lamblia. Additionally, we generated a panel of moAbs specific for this protein that will be useful for the biochemical and immunological characterisation of this immunologically interesting Giardia molecule.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Giardia lamblia/imunologia , Proteínas de Protozoários/imunologia , Animais , Western Blotting , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Giardíase/imunologia , Giardíase/parasitologia , Camundongos
13.
Pharmaceuticals (Basel) ; 16(9)2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37765140

RESUMO

Giardia lamblia is a highly infectious protozoan that causes giardiasis, a gastrointestinal disease with short-term and long-lasting symptoms. The currently available drugs for giardiasis treatment have limitations such as side effects and drug resistance, requiring the search for new antigiardial compounds. Drug repurposing has emerged as a promising strategy to expedite the drug development process. In this study, we evaluated the cytotoxic effect of terfenadine on Giardia lamblia trophozoites. Our results showed that terfenadine inhibited the growth and cell viability of Giardia trophozoites in a time-dose-dependent manner. In addition, using scanning electron microscopy, we identified morphological damage; interestingly, an increased number of protrusions on membranes and tubulin dysregulation with concomitant dysregulation of Giardia GiK were observed. Importantly, terfenadine showed low toxicity for Caco-2 cells, a human intestinal cell line. These findings highlight the potential of terfenadine as a repurposed drug for the treatment of giardiasis and warrant further investigation to elucidate its precise mechanism of action and evaluate its efficacy in future research.

14.
Cureus ; 15(9): e44955, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37701169

RESUMO

Renal cell carcinoma (RCC) is rarely diagnosed during pregnancy and its management represents a challenge as it necessitates considerations for the well-being of both the mother and the developing fetus. Diagnosis can be challenging and is often an incidental finding during routine imaging, which can lead to difficult decision-making. The choice of the ideal imaging study in these cases is a matter of debate. When the tumor is detected at an early stage, radical nephrectomy is indicated. However, there is still controversy regarding whether it should be performed conventionally or laparoscopically, as both techniques have their risks and benefits. In this context, our primary objective was to provide adequate surgical treatment for the patient, while safeguarding fetal health. Here, we present a patient with a history of recurrent miscarriages, in whom a renal tumor was incidentally diagnosed during pregnancy. Adding to the uniqueness of this case, the patient was diagnosed with an eosinophilic variant of chromophobe RCC through histopathological analysis. Our aim is to highlight the controversies surrounding diagnostic and treatment methodologies and to present the surgical techniques employed in this unique situation. This case underscores the importance and need for a multidisciplinary approach, which, in our instance, resulted in favorable outcomes for both maternal and neonatal health.

15.
Nanomaterials (Basel) ; 14(1)2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38202528

RESUMO

This study investigates electrospun fibers of metal-organic frameworks (MOFs), particularly CuBTC and ZIF-8, in polyacrylonitrile (PAN) for the solid-phase extraction (SPE) of Tamoxifen (TAM) and its metabolites (NDTAM, ENDO, and 4OHT) from human blood plasma. The focus is on the isolation, pre-concentration, and extraction of the analytes, aiming to provide a more accessible and affordable breast cancer patient-monitoring technology. The unique physicochemical properties of MOFs, such as high porosity and surface area, combined with PAN's stability and low density, are leveraged to improve SPE efficiency. The study meticulously examines the interactions of these MOFs with the analytes under various conditions, including elution solvents and protein precipitators. Results reveal that ZIF-8/PAN composites outperform CuBTC/PAN and PAN alone, especially when methanol is used as the protein precipitator. This superior performance is attributed to the physicochemical compatibility between the analytes' properties, like solubility and polarity, and the MOFs' structural features, including pore flexibility, active site availability, surface polarity, and surface area. The findings underscore MOFs' potential in SPE applications and provide valuable insights into the selectivity and sensitivity of different MOFs towards specific analytes, advancing more efficient targeted extraction methods in biomedical analysis.

16.
Cancers (Basel) ; 14(9)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35565181

RESUMO

Lymphomas are a highly heterogeneous group of hematological neoplasms. Given their ethiopathogenic complexity, their classification and management can become difficult tasks; therefore, new approaches are continuously being sought. Metabolic reprogramming at the lipid level is a hot topic in cancer research, and sphingolipidomics has gained particular focus in this area due to the bioactive nature of molecules such as sphingoid bases, sphingosine-1-phosphate, ceramides, sphingomyelin, cerebrosides, globosides, and gangliosides. Sphingolipid metabolism has become especially exciting because they are involved in virtually every cellular process through an extremely intricate metabolic web; in fact, no two sphingolipids share the same fate. Unsurprisingly, a disruption at this level is a recurrent mechanism in lymphomagenesis, dissemination, and chemoresistance, which means potential biomarkers and therapeutical targets might be hiding within these pathways. Many comprehensive reviews describing their role in cancer exist, but because most research has been conducted in solid malignancies, evidence in lymphomagenesis is somewhat limited. In this review, we summarize key aspects of sphingolipid biochemistry and discuss their known impact in cancer biology, with a particular focus on lymphomas and possible therapeutical strategies against them.

17.
Pharmaceutics ; 14(8)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36015341

RESUMO

Lung cancer is, currently, one of the main malignancies causing deaths worldwide. To date, early prognostic and diagnostic markers for small cell lung cancer (SCLC) have not been systematically and clearly identified, so most patients receive standard treatment. In the present study, we combine quantitative proteomics studies and the use of magnetic core-shell nanoparticles (mCSNP's), first to identify a marker for lung cancer, and second to functionalize the nanoparticles and their possible application for early and timely diagnosis of this and other types of cancer. In the present study, we used label-free mass spectrometry in combination with an ion-mobility approach to identify 220 proteins with increased abundance in small cell lung cancer (SCLC) cell lines. Our attention was focused on cell receptors for their potential application as mCSNP's targets; in this work, we report the overexpression of Transferrin Receptor (TfR1) protein, also known as Cluster of Differentiation 71 (CD71) up to a 30-fold increase with respect to the control cell. The kinetics of endocytosis, evaluated by a flow cytometry methodology based on fluorescence quantification, demonstrated that receptors were properly activated with the transferrin supported on the magnetic core-shell nanoparticles. Our results are important in obtaining essential information for monitoring the disease and/or choosing better treatments, and this finding will pave the way for future synthesis of nanoparticles including chemotherapeutic drugs for lung cancer treatments.

18.
Nanomaterials (Basel) ; 12(15)2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35893517

RESUMO

Natural sources of green energy include sunshine, water, biomass, geothermal heat, and wind. These energies are alternate forms of electrical energy that do not rely on fossil fuels. Green energy is environmentally benign, as it avoids the generation of greenhouse gases and pollutants. Various systems and equipment have been utilized to gather natural energy. However, most technologies need a huge amount of infrastructure and expensive equipment in order to power electronic gadgets, smart sensors, and wearable devices. Nanogenerators have recently emerged as an alternative technique for collecting energy from both natural and artificial sources, with significant benefits such as light weight, low-cost production, simple operation, easy signal processing, and low-cost materials. These nanogenerators might power electronic components and wearable devices used in a variety of applications such as telecommunications, the medical sector, the military and automotive industries, and internet of things (IoT) devices. We describe new research on the performance of nanogenerators employing several green energy acquisition processes such as piezoelectric, electromagnetic, thermoelectric, and triboelectric. Furthermore, the materials, applications, challenges, and future prospects of several nanogenerators are discussed.

19.
Antibiotics (Basel) ; 11(9)2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36140009

RESUMO

Salmonella spp. is one of the most common food poisoning pathogens and the main cause of diarrheal diseases in humans in developing countries. The increased Salmonella resistance to antimicrobials has led to the search for new alternatives, including natural compounds such as curcumin, which has already demonstrated a bactericidal effect; however, in Gram-negatives, there is much controversy about this effect, as it is highly variable. In this study, we aimed to verify the antibacterial activity of curcumin against the Salmonella enterica serovar Typhimurium growth rate, virulence, and pathogenicity. The strain was exposed to 110, 220 or 330 µg/mL curcumin, and by complementary methods (spectrophotometric, pour plate and MTT assays), we determined its antibacterial activity. To elucidate whether curcumin regulates the expression of virulence genes, Salmonella invA, fliC and siiE genes were investigated by quantitative real-time reverse transcription (qRT-PCR). Furthermore, to explore the effect of curcumin on the pathogenesis process in vivo, a Caenorhabditis elegans infection model was employed. No antibacterial activity was observed, even at higher concentrations of curcumin. All concentrations of curcumin caused overgrowth (35−69%) and increased the pathogenicity of the bacterial strain through the overexpression of virulence factors. The latter coincided with a significant reduction in both the lifespan and survival time of C. elegans when fed with curcumin-treated bacteria. Our data provide relevant information that may support the selective antibacterial effects of curcumin to reconsider the indiscriminate use of this phytochemical, especially in outbreaks of pathogenic Gram-negative bacteria.

20.
Med Clin (Barc) ; 158(7): 308-314, 2022 04 08.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34238580

RESUMO

BACKGROUND AND OBJECTIVE: Diabetic microvascular disease (MVD) has been associated with increased bone fragility. The objective was to analyse the relationship between MVD and trabecular microstructure -assessed by the trabecular bone score (TBS)- in type 2 diabetic (T2D) patients. A second aim was to know the relationship between vitamin D and MVD. PATIENTS AND METHODS: Cross-sectional study, which included men >50 years and postmenopausal women participating in a population-based cohort, diagnosed with T2D. The presence of nephropathy, neuropathy and/or retinopathy was classified as MVD+. Clinical and laboratory variables, TBS, 25(OH)D and BMD by DXA, were evaluated. Bivariate and multivariate analysis were performed. RESULTS: We evaluated 361 patients (51.1% women), 63.8 (9) years old. Of them, 92 were MVD+ and presented poorer metabolic control, longer duration of T2D, lower TBS [1.235 (.1) vs. 1.287 (.1); p=.007] and lower levels of 25(OH)D [18.3 (7) vs. 21.6 (8) ng/ml; p=.0001). There were no differences between MVD+ and MVD- with regard to BMD or P1NP and ß-CTX markers. After adjusting for confounders, including HbA1c and duration of T2D, the TBS value in MVD+ was 1.252 (95% CI 1.230-1.274) vs. 1.281 (95% CI 1.267-1.295) in MVD- (p=.034). MVD was associated with a 25(OH)D level <20 ng ml with an adjusted OR of 1.88 (95% CI 1.06-3.31; p=.028). CONCLUSIONS: The MVD+ patients presented a significantly lower TBS, after adjusting for confounders. Furthermore, multivariable analysis showed a significant relationship between a low 25(OH)D level and a prevalent MVD.


Assuntos
Osso Esponjoso , Diabetes Mellitus Tipo 2 , Absorciometria de Fóton , Densidade Óssea , Calcifediol , Criança , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Vértebras Lombares , Masculino , Vitamina D/análogos & derivados
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