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1.
EMBO Rep ; 25(6): 2635-2661, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38730210

RESUMEN

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function.


Asunto(s)
Interleucinas , Obesidad , Linfocitos T Reguladores , Termogénesis , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Interleucinas/metabolismo , Obesidad/metabolismo , Ratones , Humanos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Inflamación/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados
2.
Am J Med Genet A ; 194(2): 328-336, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37846940

RESUMEN

Mesomelic skeletal dysplasia is a heterogeneous group of skeletal disorders that has grown since the molecular basis of these conditions is in the process of research and discovery. Here, we report a Brazilian family with eight affected members over three generations with a phenotype similar to mesomelic Kantaputra dysplasia. This family presents marked shortening of the upper limbs with hypotrophy of the lower limbs and clubfeet without synostosis. Array-based CNV analysis and exome sequencing of four family members failed to show any region or gene candidate. Interestingly, males were more severely affected than females in this family, suggesting that gender differences could play a role in the phenotypic expressivity of this condition.


Asunto(s)
Disgenesia Gonadal , Osteocondrodisplasias , Masculino , Femenino , Humanos , Factores Sexuales , Osteocondrodisplasias/genética , Familia , Fenotipo
3.
Extremophiles ; 28(2): 25, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664270

RESUMEN

We surveyed the presence of perchlorate-reducing microorganisms in available metagenomic data of halite environments from the Atacama Desert, an extreme environment characterized by high perchlorate concentrations, intense ultraviolet radiation, saline and oxidizing soils, and severe desiccation. While the presence of perchlorate might suggest a broad community of perchlorate reducers or a high abundance of a dominant taxa, our search reveals a scarce presence. In fact, we identified only one halophilic species, Salinibacter sp003022435, carrying the pcrA and pcrC genes, represented in low abundance. Moreover, we also discovered some napA genes and organisms carrying the nitrate reductase nasB gene, which hints at the possibility of cryptic perchlorate reduction occurring in these ecosystems. Our findings contribute with the knowledge of perchlorate reduction metabolism potentially occurring in halites from Atacama Desert and point towards promising future research into the perchlorate-reducing mechanism in Salinibacter, a common halophilic bacterium found in hypersaline ecosystems, whose metabolic potential remains largely unknown.


Asunto(s)
Clima Desértico , Ambientes Extremos , Oxidación-Reducción , Percloratos , Percloratos/metabolismo , Metagenoma , Microbiota
4.
Int J Mol Sci ; 25(14)2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39062809

RESUMEN

The study evaluated the effects of Arthrospira maxima phycobiliproteins (PBPs), rosiglitazone (RSG), and 17ß-estradiol (E) on the differentiation process of 3T3-L1 cells and on their regulation of lipogenic and inflammatory gene expression at different stages of the process. The results showed that phycobiliproteins promoted cell proliferation after 24 h of treatment. Furthermore, for all three treatments, the regulation of the highest number of markers occurred on days 6 and 12 of differentiation, regardless of when the treatment was applied. Phycobiliproteins reduced lipid droplet accumulation on days 3, 6, 10, and 13 of the adipogenic process, while rosiglitazone showed no differences compared to the control. On day 6, both phycobiliproteins and rosiglitazone positively regulated Acc1 mRNA. Meanwhile, all three treatments negatively regulated Pparγ and C/ebpα. Phycobiliproteins and estradiol also negatively regulated Ucp1 and Glut4 mRNAs. Rosiglitazone and estradiol, on the other hand, negatively regulated Ppara and Il-6 mRNAs. By day 12, phycobiliproteins and rosiglitazone upregulated Pparγ mRNA and negatively regulated Tnfα and Il-1ß. Additionally, phycobiliproteins and estradiol positively regulated Il-6 and negatively regulated Ppara, Ucp2, Acc1, and Glut4. Rosiglitazone and estradiol upregulate C/ebpα and Ucp1 mRNAs. The regulation exerted by phycobiliproteins on the mRNA expression of the studied markers was dependent on the phase of cell differentiation. The results of this study highlight that phycobiliproteins have an anti-adipogenic and anti-inflammatory effect by reducing the expression of adipogenic, lipogenic, and inflammatory genes in 3T3-L1 cells at different stages of the differentiation process.


Asunto(s)
Células 3T3-L1 , Adipocitos , Adipogénesis , Diferenciación Celular , Estradiol , Ficobiliproteínas , Rosiglitazona , Animales , Ratones , Estradiol/farmacología , Rosiglitazona/farmacología , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/citología , Diferenciación Celular/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Adipogénesis/genética , Ficobiliproteínas/farmacología , Ficobiliproteínas/metabolismo , Ficobiliproteínas/genética , Regulación de la Expresión Génica/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Lipogénesis/genética , PPAR gamma/metabolismo , PPAR gamma/genética , Proliferación Celular/efectos de los fármacos , Inflamación/metabolismo , Inflamación/genética , Spirulina
5.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38474283

RESUMEN

Excessive or insufficient gestational weight gain (GWG) leads to diverse adverse maternal and neonatal outcomes. There is evidence that pregestational body mass index (pBMI) plays a role in GWG, but no genetic cause has been identified. In this review, we aim to analyze genotype variants associated with GWG. Results: We identified seven genotype variants that may be involved in GWG regulation that were analyzed in studies carried out in Brazil, Romania, the USA, Turkey, Ukraine, and Canada. Some genetic variants were only associated with GWG in certain races or depending on the pBMI. In women who were obese or overweight before gestation, some genetic variants were associated with GWG. Environmental and genetic factors together showed a greater association with GWG than genetic factors alone; for example, type of diet was observed to have a significant influence. Conclusions: We found little scientific evidence of an association between genotype variants in countries with a high prevalence of women of reproductive age who are overweight and obese, such as in Latin America. GWG may be more dependent on environmental factors than genetic variants. We suggest a deeper study of genetic variants, cytokines, and their possible association with GWG, always with the respective control of potential cofounding factors, such as pBMI, diet, and race.


Asunto(s)
Ganancia de Peso Gestacional , Sobrepeso , Recién Nacido , Femenino , Humanos , Masculino , Embarazo , Sobrepeso/complicaciones , Aumento de Peso/fisiología , Obesidad/complicaciones , Dieta , Índice de Masa Corporal , Resultado del Embarazo
6.
Int J Mol Sci ; 25(2)2024 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-38279319

RESUMEN

Entamoeba histolytica (E. histolytica) exhibits a remarkable capacity to respond to thermal shock stress through a sophisticated genetic regulation mechanism. This process is carried out via Heat Shock Response Elements (HSEs), which are recognized by Heat Shock Transcription Factors (EhHSTFs), enabling fine and precise control of gene expression. Our study focused on screening for HSEs in the promoters of the E. histolytica genome, specifically analyzing six HSEs, including Ehpgp5, EhrabB1, EhrabB4, EhrabB5, Ehmlbp, and Ehhsp100. We discovered 2578 HSEs, with 1412 in promoters of hypothetical genes and 1166 in coding genes. We observed that a single promoter could contain anywhere from one to five HSEs. Gene ontology analysis revealed the presence of HSEs in essential genes for the amoeba, including cysteine proteinases, ribosomal genes, Myb family DNA-binding proteins, and Rab GTPases, among others. Complementarily, our molecular docking analyses indicate that these HSEs are potentially recognized by EhHSTF5, EhHSTF6, and EhHSTF7 factors in their trimeric conformation. These findings suggest that E. histolytica has the capability to regulate a wide range of critical genes via HSE-EhHSTFs, not only for thermal stress response but also for vital functions of the parasite. This is the first comprehensive study of HSEs in the genome of E. histolytica, significantly contributing to the understanding of its genetic regulation and highlighting the complexity and precision of this mechanism in the parasite's survival.


Asunto(s)
Entamoeba histolytica , Entamoeba histolytica/genética , Entamoeba histolytica/metabolismo , Simulación del Acoplamiento Molecular , Regiones Promotoras Genéticas , Respuesta al Choque Térmico/genética , Regulación de la Expresión Génica
7.
Int J Mol Sci ; 25(8)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38673804

RESUMEN

Throughout its lifecycle, Entamoeba histolytica encounters a variety of stressful conditions. This parasite possesses Heat Shock Response Elements (HSEs) which are crucial for regulating the expression of various genes, aiding in its adaptation and survival. These HSEs are regulated by Heat Shock Transcription Factors (EhHSTFs). Our research has identified seven such factors in the parasite, designated as EhHSTF1 through to EhHSTF7. Significantly, under heat shock conditions and in the presence of the antiamoebic compound emetine, EhHSTF5, EhHSTF6, and EhHSTF7 show overexpression, highlighting their essential role in gene response to these stressors. Currently, only EhHSTF7 has been confirmed to recognize the HSE as a promoter of the EhPgp5 gene (HSE_EhPgp5), leaving the binding potential of the other EhHSTFs to HSEs yet to be explored. Consequently, our study aimed to examine, both in vitro and in silico, the oligomerization, and binding capabilities of the recombinant EhHSTF5 protein (rEhHSTF5) to HSE_EhPgp5. The in vitro results indicate that the oligomerization of rEhHSTF5 is concentration-dependent, with its dimeric conformation showing a higher affinity for HSE_EhPgp5 than its monomeric state. In silico analysis suggests that the alpha 3 α-helix (α3-helix) of the DNA-binding domain (DBD5) of EhHSTF5 is crucial in binding to the major groove of HSE, primarily through hydrogen bonding and salt-bridge interactions. In summary, our results highlight the importance of oligomerization in enhancing the affinity of rEhHSTF5 for HSE_EhPgp5 and demonstrate its ability to specifically recognize structural motifs within HSE_EhPgp5. These insights significantly contribute to our understanding of one of the potential molecular mechanisms employed by this parasite to efficiently respond to various stressors, thereby enabling successful adaptation and survival within its host environment.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Entamoeba histolytica , Regiones Promotoras Genéticas , Proteínas Protozoarias , Sitios de Unión , Simulación por Computador , Entamoeba histolytica/genética , Entamoeba histolytica/metabolismo , Respuesta al Choque Térmico/genética , Unión Proteica , Multimerización de Proteína , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/química , Elementos de Respuesta , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/química , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo
8.
Molecules ; 29(7)2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38611719

RESUMEN

Cancer is one of the leading causes of death worldwide, making the search for alternatives for its control a critical issue. In this context, exploring alternatives from natural sources, such as certain vegetables containing a variety of secondary metabolites with beneficial effects on the body and that play a crucial role in the fight against cancer, is essential. Among the compounds with the greatest efficacy in controlling this disease, those with antioxidant activity, particularly phenolic com-pounds, stand out. A remarkable example of this group is protocatechuic acid (PCA), which has been the subject of various revealing research on its activities in different areas. These studies sustain that protocatechuic acid has anti-inflammatory, antimutagenic, antidiabetic, antiulcer, antiviral, antifibrogenic, antiallergic, neuroprotective, antibacterial, anticancer, antiosteoporotic, anti-aging, and analgesic properties, in addition to offering protection against metabolic syndrome and con-tributing to the preservation of hepatic, renal, and reproductive functionality. Therefore, this paper aims to review the biological activities of PCA, focusing on its anticancer potential and its in-volvement in the control of various molecular pathways involved in tumor development, sup-porting its option as a promising alternative for cancer treatment.


Asunto(s)
Hidroxibenzoatos , Neoplasias , Humanos , Hidroxibenzoatos/farmacología , Hidroxibenzoatos/uso terapéutico , Neoplasias/tratamiento farmacológico , Fenoles
9.
Medicina (Kaunas) ; 60(7)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39064575

RESUMEN

Background and Objectives: Congenital thyroid dyshormonogenesis is caused by alterations in the synthesis of thyroid hormones in a newborn. Additionally, 10 to 20% of these cases are hereditary, caused by defects in proteins involved in hormonal synthesis. One of the most common causes is mutations in the thyroid peroxidase (TPO) enzyme gene, an autosomal recessive disease. We aimed to detect mutations of the TPO gene in 12 Chilean patients with congenital hypothyroidism due to dyshormonogenesis (CHD) and to characterize these patients clinically and molecularly. Materials and Methods: Twelve patients under 20 years of age with CHD, controlled at San Juan de Dios Hospital in Santiago, Chile, were selected according to the inclusion criteria: elevated neonatal TSH, persistent hypothyroidism, and thyroid normotopic by imaging study. Those with deafness, Down syndrome, and central or transient congenital hypothyroidism were excluded. Blood samples were taken for DNA extraction, and the 17 exons and exon-intron junctions of the TPO gene were amplified by PCR. The PCR products were sequenced by Sanger. Results: Two possibly pathogenic mutations of the TPO gene were detected: c.2242G>A (p.Val748Met) and c.1103C>T (p.Pro368Leu). These mutations were detected in 2 of 12 patients (16.6%): 1 was compound heterozygous c.1103C>T/c.2242G>A, and the other was heterozygous for c.2242G>A. In the diagnostic confirmation test, both patients presented diffuse hyper-uptake goiter on thyroid scintigraphy and high TSH in venous blood (>190 uIU/mL). Conclusions: The frequency of patients with possibly pathogenic mutations in TPO with CHD was 16.6%. Its study would allow for genetic counseling to be offered to the families of affected patients.


Asunto(s)
Hipotiroidismo Congénito , Yoduro Peroxidasa , Proteínas de Unión a Hierro , Mutación , Humanos , Hipotiroidismo Congénito/genética , Hipotiroidismo Congénito/sangre , Chile , Yoduro Peroxidasa/genética , Femenino , Masculino , Proteínas de Unión a Hierro/genética , Autoantígenos/genética , Lactante , Niño , Adolescente , Preescolar , Recién Nacido , Disgenesias Tiroideas/genética , Disgenesias Tiroideas/complicaciones , Disgenesias Tiroideas/sangre
10.
FASEB J ; 36(3): e22190, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35147994

RESUMEN

We demonstrated that serpinA3c/k relocates from the cytoplasm to the apical tubular membrane (ATM) in chronic kidney disease (CKD), suggesting its secretion in luminal space in pathophysiological contexts. Here, we studied serpinA3c/k expression and secretion under different stressful conditions in vitro and in vivo. HEK-293 cells were transfected with a FLAG-tagged serpinA3c/k clone and exposed to H2 O2 or starvation. Both stressors induced serpinA3c/k secretion but with a higher molecular weight. Glycanase treatment established that serpinA3c/k is glycosylated. Site-directed mutagenesis for each of the four glycosylation sites was performed. During cellular stress, serpinA3c/k secretion increased with each mutant except in the quadruple mutant. In rats and patients suffering acute kidney injury (AKI), an atypical urinary serpinA3c/k excretion (uSerpinA3c/k) was observed. In rats with AKI, the greater the induced kidney damage, the greater the uSerpinA3 c/k, together with relocation toward ATM. Our findings show that: (1) serpinA3c/k is glycosylated and secreted, (2) serpinA3c/k secretion increases during cellular stress, (3) its appearance in urine reveals a pathophysiological state, and (4) urinary serpinA3 excretion could become a potential biomarker for AKI.


Asunto(s)
Lesión Renal Aguda/metabolismo , Estrés Fisiológico , alfa 1-Antiquimotripsina/metabolismo , Lesión Renal Aguda/orina , Animales , Glicosilación , Células HEK293 , Humanos , Masculino , Mutación , Ratas , alfa 1-Antiquimotripsina/genética , alfa 1-Antiquimotripsina/orina
11.
J Org Chem ; 88(4): 2174-2189, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36735858

RESUMEN

Three new diboronic acid-substituted bisquinolinium salts were synthesized, structurally described by single-crystal X-ray diffraction, and studied in-depth as fluorescent receptors for six monosaccharides and two open-chain polyols in water at physiological pH. The dicationic pyridine-2,6-dicarboxamide-based receptors contain two N-quinolinium rings as the fluorescent units covalently linked to three different isomers of phenylboronic acid (ortho, 2; meta, 3; and para, 4) as chelating binding sites for polyols. Additions of glucose/fructose in the micromolar concentration range to receptors 2 and 3 induce significant fluorescence changes, but in the presence of arabinose, galactose, mannose, and xylose, only modest optical changes are observed. This optical change is attributed to a static photoinduced electron transfer mechanism. The meta-diboronic receptor 3 exhibited a high affinity/selectivity toward glucose (K = 3800 M-1) over other monosaccharides including common interfering species such as fructose and mannitol. Based on multiple spectroscopic tools, electrospray ionization high-resolution mass spectrometry, crystal structures, and density functional theory calculations, the binding mode between 3 and glucose is proposed as a 1:1 complex with the glucofuranose form involving a cooperative chelating diboronate binding. These results demonstrate the usefulness of a new set of cationic fluorescent diboronic acid receptors with a strong ability for optical recognition of glucose in the sub-millimolar concentration range.

12.
Mol Biol Rep ; 50(1): 719-730, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36372816

RESUMEN

BACKGROUND: Streptomyces strains degrade many complex organic compounds and produce secondary metabolites. In aerobic organisms such as Streptomyces species, the tricarboxylic acid (TCA) cycle represents an indispensable central carbon metabolic pathway for energy generation and metabolic intermediary replenishment. Although various precursors for antibiotic biosynthesis are derived from this cycle, relatively few studies have focused on determining how a single carbon source can impact this metabolic pathway at different growth phases. In this study, we identified chromosomal genes involved in the TCA cycle in Streptomyces coelicolor and determined their mRNA levels. METHODS AND RESULTS: We searched the genes involved in the TCA cycle in S. coelicolor through bioinformatic analysis. Growth, glucose concentration quantification and RNA isolation were made from cultures of S. coelicolor grown on minimal medium with glucose along 72 h. mRNA levels of all identified genes were obtained by RT-qPCR. Five enzymes encoded by a single gene each were found, while for the rest at least two genes were found. The results showed that all the genes corresponding to the TCA enzymes were transcribed at very different levels and some of them displayed growth-phase dependent expression. CONCLUSION: All TCA cycle-associated genes, including paralog genes, were differentially transcribed in S. coelicolor grown in minimal medium with glucose as carbon source. Some of them, such as succinyl-CoA synthetase and succinate dehydrogenase, have low mRNA levels, which could limit the carbon flux through the TCA cycle. Our findings suggest that the genetic expansion of TCA cycle genes could confer to S. coelicolor the ability to adapt to diverse nutritional conditions and metabolic changes through different paralog genes expression.


Asunto(s)
Streptomyces coelicolor , Streptomyces , Ciclo del Ácido Cítrico/genética , Streptomyces coelicolor/genética , Streptomyces coelicolor/metabolismo , Glucosa/metabolismo , Redes y Vías Metabólicas/genética , Streptomyces/metabolismo , Carbono/metabolismo
13.
Mar Drugs ; 21(3)2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36976231

RESUMEN

The process by which cancer cells evade or inhibit apoptosis is considered one of the characteristics of cancer. The ability of cancer cells to escape apoptosis contributes to tumor proliferation and promotes metastasis. The discovery of new antitumor agents is essential for cancer treatment due to the lack of selectivity of drugs and cellular resistance to anticancer agents. Several studies showed that macroalgae produce various metabolites with different biological activities among marine organisms. This review discusses multiple metabolites extracted from macroalgae and their pro-apoptotic effects through regulating apoptosis signaling pathway target molecules and the structure-activity relationship. Twenty-four promising bioactive compounds have been reported, where eight of these compounds exhibited values of maximum inhibitory concentration (IC50) of less than 7 µg/mL. Fucoxanthin was the only carotenoid reported that induced apoptosis in HeLa cells with an IC50 below 1 µg/mL. Se-PPC (a complex of proteins and selenylated polysaccharides) is the magistral compound because it is the only one with an IC50 of 2.5 µg/mL which regulates the primary proteins and critical genes of both apoptosis pathways. Therefore, this review will help provide the basis for further studies and the development of new anticancer drugs, both as single agents and adjuvants, decreasing the aggressiveness of first-line drugs and offering patients better survival and quality of life.


Asunto(s)
Antineoplásicos , Algas Marinas , Humanos , Células HeLa , Calidad de Vida , Antineoplásicos/farmacología , Relación Estructura-Actividad , Apoptosis , Proliferación Celular , Línea Celular Tumoral
14.
Enferm Infecc Microbiol Clin ; 41(6): 329-334, 2023.
Artículo en Español | MEDLINE | ID: mdl-34931102

RESUMEN

Introduction: The generalization of treatment with dexamethasone or other immunosuppressants in patients with SARS-CoV-2 infection may increase the risk of occurrence of severe forms of strongyloidiasis. A nationwide survey was conducted to better understand the diagnostic and therapeutic situation of strongyloidiasis in SARS-CoV-2 co-infected patients in Spain. Materials and methods: A survey was designed and sent to all SEIMC members during February and March 2021. Responses were exported for computer processing to Microsoft Excel 2017 and statistically processed with the free software PSPP. Results: 189 responses were received, of which 121 (64%) were selected for further processing. Eighty-four centers (69.5%) had no specific strongyloidiasis screening protocol. Forty-two centers (34.7%) had serological techniques available in their laboratories and the rest were sent to a reference laboratory. Only 22 centers (18%) screened for strongyloidiasis in SARS-CoV-2 infected patients. A total of 227 cases of strongyloidiasis were diagnosed in patients with SARS-CoV-2 infection. In four cases patients developed a massive hyperinfestation syndrome leading to the death of one patient. Conclusion: COVID-19 has highlighted the need to unify screening and treatment protocols for imported pathologies such as strongyloidiasis. Efforts to disseminate knowledge are needed to ensure that this potentially fatal disease is adequately treated in patients with the highest risk of complications, such as those with COVID-19.

15.
Molecules ; 28(11)2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37298837

RESUMEN

Cancer is a disease with the highest mortality and morbidity rate worldwide. First-line drugs induce several side effects that drastically reduce the quality of life of people with this disease. Finding molecules to prevent it or generate less aggressiveness or no side effects is significant to counteract this problem. Therefore, this work searched for bioactive compounds of marine macroalgae as an alternative treatment. An 80% ethanol extract of dried Caulerpa sertularioides (CSE) was analyzed by HPLS-MS to identify the chemical components. CSE was utilized through a comparative 2D versus 3D culture model. Cisplatin (Cis) was used as a standard drug. The effects on cell viability, apoptosis, cell cycle, and tumor invasion were evaluated. The IC50 of CSE for the 2D model was 80.28 µg/mL versus 530 µg/mL for the 3D model after 24 h of treatment exposure. These results confirmed that the 3D model is more resistant to treatments and complex than the 2D model. CSE generated a loss of mitochondrial membrane potential, induced apoptosis by extrinsic and intrinsic pathways, upregulated caspases-3 and -7, and significantly decreased tumor invasion of a 3D SKLU-1 lung adenocarcinoma cell line. CSE generates biochemical and morphological changes in the plasma membrane and causes cell cycle arrest at the S and G2/M phases. These findings conclude that C. sertularioides is a potential candidate for alternative treatment against lung cancer. This work reinforced the use of complex models for drug screening and suggested using CSE's primary component, caulerpin, to determine its effect and mechanism of action on SKLU-1 in the future. A multi-approach with molecular and histological analysis and combination with first-line drugs must be included.


Asunto(s)
Caulerpa , Neoplasias Pulmonares , Humanos , Caulerpa/química , Calidad de Vida , Extractos Vegetales/farmacología , Extractos Vegetales/química , Puntos de Control del Ciclo Celular , Neoplasias Pulmonares/metabolismo , Apoptosis , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular
16.
Molecules ; 28(9)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37175211

RESUMEN

Obesity is characterized by the excessive accumulation of fat, which triggers a low-grade chronic inflammatory process. Currently, the search for compounds with anti-obesogenic effects that help reduce body weight, as well as associated comorbidities, continues. Among this group of compounds are plant extracts and flavonoids with a great diversity of action mechanisms associated with their beneficial effects, such as anti-inflammatory effects and/or as signaling molecules. In the bark of Tabebuia rosea tree, there are different classes of metabolites with anti-inflammatory properties, such as quercetin. Therefore, the present work studied the effect of the ethanolic extract of T. rosea and quercetin on the mRNA of inflammation markers in obesity compared to the drugs currently used. Total RNA was extracted from epididymal adipose tissue of high-fat diet-induced obese Wistar rats treated with orlistat, phentermine, T. rosea extract, and quercetin. The rats treated with T. rosea and quercetin showed 36 and 31% reductions in body weight compared to the obese control, and they likewise inhibited pro-inflammatory molecules: Il6, Il1b, Il18, Lep, Hif1a, and Nfkb1 without modifying the expression of Socs1 and Socs3. Additionally, only T. rosea overexpressed Lipe. Both T. rosea and quercetin led to a reduction in the expression of pro-inflammatory genes, modifying signaling pathways, which led to the regulation of the obesity-inflammation state.


Asunto(s)
Fármacos Antiobesidad , Tabebuia , Ratas , Animales , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Ratas Wistar , Quercetina/metabolismo , Extractos Vegetales/uso terapéutico , Obesidad/etiología , Obesidad/inducido químicamente , Tejido Adiposo/metabolismo , Peso Corporal , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Dieta Alta en Grasa/efectos adversos
17.
Molecules ; 28(22)2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38005324

RESUMEN

Nowadays, bee products are commended by consumers for their medicinal and dietary properties. This study aimed to differentiate between monofloral bee pollens originating from Portugal using phenolic and volatile profiles and investigate their antioxidant and cytotoxic activity. Total phenolic and flavonoid compounds were recorded between 2.9-35.8 mg GAE/g and 0.7-4.8 mg QE/g, respectively. The LC/DAD/ESI-MSn analytical results allowed us to identify and quantify a total of 72 compounds, including phenolic and phenylamide compounds, whereas GC-MS results revealed the presence of 49 different compounds, mostly ketones, aldehydes, esters, hydrocarbons, and terpenes. The highest DPPH• radical scavenging activity, EC50: 0.07 mg/mL, was recorded in the sample dominated by Castanae sp. pollen, whereas the Rubus sp. (1.59 mM Trolox/mg) and Cistaceae sp. (0.09 mg GAE/g) pollen species exhibited the highest antioxidant activity in ABTS•+ and reducing power assays, respectively. Regarding the anti-carcinogenic activity, only Carduus sp. showed remarkable cytotoxic potential against MCF-7.


Asunto(s)
Antioxidantes , Fenoles , Abejas , Animales , Portugal , Fenoles/análisis , Antioxidantes/farmacología , Flavonoides , Polen/química
18.
Molecules ; 29(1)2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38202766

RESUMEN

Green tomato (Physalis ixocarpa) is a specie native to Mexico, and it is known as "tomatillo" or "husk tomato". The fruit contains vitamins, minerals, phenolic compounds, and steroidal lactones, presenting antimicrobial activity and antinarcotic effects. Therefore, it is not only used in traditional Mexican cuisine, but also in traditional medicine to relieve some discomforts such as fever, cough, and amygdalitis. However, it is a perishable fruit whose shelf life is very short. As a part of the peel, cuticle, and epicuticular waxes represent the most important part in plant protection, and the specific composition and structural characterization are significant to know how this protective biopolymer keeps quality characteristics in fresh fruits. P. ixocarpa cutin was obtained by enzymatic treatments (cellulase, hemicellulose, and pectinase) and different concentrations of TFA, and studied through Cross Polarization Magic Angle Spinning Nuclear Magnetic Resonance (CPMAS 13C NMR), Ultra-High Performance Liquid Chromatography coupled to Mass Spectrometry (UHPLC-MS), and was morphologically characterized by Confocal Laser Scanning Microscopy (CLSM) and Scanning Electron Microscopy (SEM). The main constituents identified under the basis of UHPLC-MS analysis were 9,10,18-trihydroxy-octadecanoic acid and 9,10-epoxy-18-hydroxy-octadecanoic acid with 44.7 and 37.5%, respectively. The C16 absence and low occurrence of phenolic compounds, besides the presence of glandular trichomes, which do not allow a continuous layer on the surface of the fruit, could be related to a lower shelf life compared with other common fruits such as tomato (Solanum lycopersicum).


Asunto(s)
Lípidos de la Membrana , Physalis , Solanum lycopersicum , Frutas , México , Fenoles
19.
Molecules ; 28(2)2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36677892

RESUMEN

Bee pollen is frequently characterized as a natural source of bioactive components, such as phenolic compounds, which are responsible for its pharmaceutical potential and nutritional properties. In this study, we evaluated the bioactive compound contents of mono- and polyfloral bee pollen samples using spectroscopic and chromatographic methods and established links with their antioxidant and antitumor activity. The findings demonstrated that the botanical origin of bee pollen has a remarkable impact on its phenolic (3-17 mg GAE/g) and flavonoid (0.5-3.2 mg QE/g) contents. Liquid chromatography-mass spectrometry analysis revealed the presence of 35 phenolic and 13 phenylamide compounds in bee pollen, while gas chromatography-mass spectrometry showed its richness in volatiles, such as hydrocarbons, fatty acids, alcohols, ketones, etc. The concentration of bioactive compounds in each sample resulted in a substantial distinction in their antioxidant activity, DPPH (EC50: 0.3-0.7 mg/mL), ABTS (0.8-1.3 mM Trolox/mg), and reducing power (0.03-0.05 mg GAE/g), with the most bioactive pollens being the monofloral samples from Olea europaea and Ononis spinosa. Complementarily, some samples revealed a moderate effect on cervical carcinoma (GI50: 495 µg/mL) and breast adenocarcinoma (GI50: 734 µg/mL) cell lines. This may be associated with compounds such as quercetin-O-diglucoside and kaempferol-3-O-rhamnoside, which are present in pollens from Olea europaea and Coriandrum, respectively. Overall, the results highlighted the potentiality of bee pollen to serve health-promoting formulations in the future.


Asunto(s)
Antioxidantes , Flavonoides , Animales , Abejas , Antioxidantes/química , Flavonoides/química , Cromatografía de Gases y Espectrometría de Masas , Espectrometría de Masas , Fenoles/química , Polen/química
20.
Int J Environ Health Res ; 33(12): 1664-1675, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36031859

RESUMEN

The impact of contamination of water drainage ditches in the development of antibiotic-resistant bacteria has been scarcely studied in Mexico. In this regard, 101 isolates of E. coli were obtained from water samples from a ditch in Sinaloa, during one year. The antimicrobial resistant profiles, the presence of the class 1 integron and evolutionary relationship of intI1 sequences were determined. The 47.5% of strains were resistant and 5.9% multidrug resistant (MDR) with an average multiple antibiotic resistance index value of 0.45. The highest resistance was registered with ß-lactam (39.6%) and quinolone (9.9%). The intI1 gene was detected in 11.9% of the isolates, and no association with MDR was found. Sequence were associated with human and animal host isolates. MDR E. coli isolates with intI1 gene highlight the potential risk of the ditch's water to human health. An attenuation effect of MDR E. coli isolates in the outlet water was observed.


Asunto(s)
Infecciones por Escherichia coli , Escherichia coli , Animales , Humanos , Integrones/genética , Farmacorresistencia Bacteriana Múltiple/genética , Antibacterianos/farmacología , Infecciones por Escherichia coli/microbiología , Pruebas de Sensibilidad Microbiana
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