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1.
J Neuroinflammation ; 21(1): 32, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38263227

RESUMEN

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain's resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.


Asunto(s)
Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Animales , Humanos , Sistema Inmunológico , Microglía
2.
J Med Primatol ; 53(1): e12663, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37496256

RESUMEN

A free-ranging brown howler monkey (Atelidae: Alouatta guariba clamitans) was necropsied and a mediastinal T-cell lymphoma and esophageal dilation were diagnosed. The case report may contribute to the differential diagnosis of neoplastic and esophageal lesions in non-human primates and highlighted the importance of surveillance of cancer in wildlife.


Asunto(s)
Alouatta , Linfoma de Células T , Animales , Animales Salvajes , Linfoma de Células T/diagnóstico , Linfoma de Células T/veterinaria , Brasil/epidemiología
3.
Chem Biodivers ; : e202401450, 2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39034294

RESUMEN

Three new polyprenylated benzophenone derivatives named burlemarxione G-I (1-3) were isolated from C. burle-marxii trunks (compound 1) and leaves (compounds 2 and 3), along with the known compound burlemarxione F. Burlemarxione G (1) was isolated after methylation with diazomethane and it is the keto-enol tautomeric pair of burlemarxione F. Burlemarxione H (2) derives from burlemarxiones F and G, but it has additional rings due to cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. Burlemarxione I (3) has two additional cyclizations: the first encompasses the cyclization of the former isopentenyl group into an 11,11-dimethyl-six-membered ring, whereas the second produces additional rings due to the cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. All three compounds showed moderate anti-glioma activity. These results show that C. burle-marxii is an important source of sophisticated polyprenylated benzophenone derivatives.

4.
Int J Mol Sci ; 25(2)2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38256111

RESUMEN

Recent discoveries have shown that enteric glial cells play an important role in different neurodegenerative disorders, such as Parkinson's disease (PD), which is characterized by motor dysfunctions caused by the progressive loss of dopaminergic neurons in the substance nigra pars compacta and non-motor symptoms including gastrointestinal dysfunction. In this study, we investigated the modulatory effects of the flavonoid rutin on the behavior and myenteric plexuses in a PD animal model and the response of enteric glia. Adult male Wistar rats were submitted to stereotaxic injection with 6-hydroxydopamine or saline, and they were untreated or treated with rutin (10 mg/kg) for 14 days. The ileum was collected to analyze tissue reactivity and immunohistochemistry for neurons (HuC/HuD) and enteric glial cells (S100ß) in the myenteric plexuses. Behavioral tests demonstrated that treatment with rutin improved the motor capacity of parkinsonian animals and improved intestinal transit without interfering with the cell population; rutin treatment modulated the reactivity of the ileal musculature through muscarinic activation, reducing relaxation through the signaling pathway of nitric oxide donors, and increased the longitudinal contractility of the colon musculature in parkinsonian animals. Rutin revealed modulatory activities on the myenteric plexus, bringing relevant answers regarding the effect of the flavonoid in this system and the potential application of PD adjuvant treatment.


Asunto(s)
Plexo Mientérico , Enfermedad de Parkinson , Masculino , Ratas , Animales , Ratas Wistar , Flavonoides/farmacología , Flavonoides/uso terapéutico , Rutina/farmacología , Rutina/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas
5.
Int J Mol Sci ; 25(5)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38473794

RESUMEN

MicroRNAs (miRs) act as important post-transcriptional regulators of gene expression in glial cells and have been shown to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Here, we investigated the effects of agathisflavone, a biflavonoid purified from the leaves of Cenostigma pyramidale (Tul.), on modulating the expression of miRs and inflammatory mediators in activated microglia. C20 human microglia were exposed to oligomers of the ß-amyloid peptide (Aß, 500 nM) for 4 h or to lipopolysaccharide (LPS, 1 µg/mL) for 24 h and then treated or not with agathisflavone (1 µM) for 24 h. We observed that ß-amyloid and LPS activated microglia to an inflammatory state, with increased expression of miR-146a, miR-155, IL1-ß, IL-6, and NOS2. Treatment with agathisflavone resulted in a significant reduction in miR146a and miR-155 induced by LPS or Aß, as well as inflammatory cytokines IL1-ß, IL-6, and NOS2. In cells stimulated with Aß, there was an increase in p-STAT3 expression that was reduced by agathisflavone treatment. These data identify a role for miRs in the anti-inflammatory effect of agathisflavone on microglia in models of neuroinflammation and AD.


Asunto(s)
Enfermedad de Alzheimer , Biflavonoides , MicroARNs , Humanos , Biflavonoides/farmacología , Microglía/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Citocinas/metabolismo , MicroARNs/genética , Factor de Transcripción STAT3/metabolismo
6.
J Environ Manage ; 368: 122157, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39128349

RESUMEN

With the growing concerns about the protection of ecosystem functions and services, governments have developed public policies and organizations have produced an awesome volume of digital data freely available through their websites. On the other hand, advances in data acquisition through remote sensed sources and processing through geographic information systems (GIS) and statistical tools, allowed an unprecedent capacity to manage ecosystems efficiently. However, the real-world scenario in that regard remains paradoxically challenging. The reasons can be many and diverse, but a strong candidate relates with the limited engagement among the interest parties that hampers bringing all these assets into action. The aim of the study is to demonstrate that management of ecosystem services can be significantly improved by integrating existing environmental policies with environmental big data and low-cost GIS and data processing tools. Using the Upper Rio das Velhas hydrographic basin located in the state of Minas Gerais (Brazil) as example, the study demonstrated how Principal Components Analysis based on a diversity of environmental variables assembled sub-basins into urban, agriculture, mining and heterogeneous profiles, directing management of ecosystem services to the most appropriate officially established conservation plans. The use of GIS tools, on the other hand, allowed narrowing the implementation of each plan to specific sub-basins. This optimized allocation of preferential management plans to priority areas was discussed for a number of conservation plans. A paradigmatic example was the so-called Conservation Use Potential (CUP) devoted to the protection of aquifer recharge (provision service) and control of water erosion (regulation service), as well as to the allocation of uses as function of soil capability (support service). In all cases, the efficiency gains in readiness for plans' implementation and economy of resources were prognosed as noteworthy.

7.
Clin Infect Dis ; 76(3): e360-e366, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35639918

RESUMEN

BACKGROUND: Little is currently known about vaccine effectiveness (VE) for either 2 doses of Oxford-AstraZeneca (ChAdOx1) viral vector vaccine or CoronaVac (Instituto Butantan) inactivated viral vaccine followed by a third dose of mRNA vaccine (Pfizer/BioNTech) among healthcare workers (HCWs). METHODS: We conducted a retrospective cohort study among HCWs (aged ≥18 years) working in a private healthcare system in Brazil from January to December 2021. VE was defined as 1 - incidence rate ratio (IRR), with IRR determined using Poisson models with the occurrence of laboratory-confirmed coronavirus disease 2019 (COVID-19) infection as the outcome, adjusting for age, sex, and job type. We compared those receiving viral vector or inactivated viral primary series (2 doses) with those who received an mRNA booster. RESULTS: A total of 11 427 HCWs met the inclusion criteria. COVID-19 was confirmed in 31.5% of HCWs receiving 2 doses of CoronaVac vaccine versus 0.9% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P < .001) and 9.8% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 1% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P < .001). In the adjusted analyses, the estimated VE was 92.0% for 2 CoronaVac vaccines plus mRNA booster and 60.2% for 2 ChAdOx1 vaccines plus mRNA booster, when compared with those with no mRNA booster. Of 246 samples screened for mutations, 191 (77.6%) were Delta variants. CONCLUSIONS: While 2 doses of ChAdOx1 or CoronaVac vaccines prevent COVID-19, the addition of a Pfizer/BioNTech booster provided significantly more protection.


Asunto(s)
COVID-19 , Vacunas Virales , Humanos , Adolescente , Adulto , Brasil/epidemiología , Estudios Retrospectivos , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Personal de Salud , ARN Mensajero
8.
Cell Mol Neurobiol ; 43(1): 265-281, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34988761

RESUMEN

Studies have suggested aminochrome as an endogenous neurotoxin responsible for the dopaminergic neuron degeneration in Parkinson's disease (PD). However, neuroinflammation, an important alteration in PD pathogenesis, has been strictly induced in vitro by aminochrome. The aim of this study was to characterize the neuroinflammation induced in vivo by aminochrome. Wistar rats (male, 250-270 g) received a unilateral single dose by stereotaxic injection of saline into three sites in the striatum in the negative control group, or 32 nmol 6-hydroxydopamine (6-OHDA) in the positive control, or 6 nmol aminochrome. After 14 days, histological and molecular analyses were performed. We observed by immunofluorescence that aminochrome, as well as 6-OHDA, induced an increase in the number of Iba-1+ cells and in the number of activated (Iba-1+/ CD68+) microglia. An increase in the number of S100b+ cells and in the GFAP expression were also evidenced in the striatum and the SNpc of animals from aminochrome and positive control group. Dopaminergic neuronal loss was marked by reduction of TH+ cells and confirmed with reduction in the number of Nissl-stained neurons in the SNpc of rats from aminochrome and positive control groups. In addition, we observed by qPCR that aminocrhome induced an increase in the levels of IL-1ß, TNF-α, NLRP3, CCL5 and CCR2 mRNA in the SNpc. This work provides the first evidence of microgliosis, astrogliosis and neuroinflammation induced by aminochrome in an in vivo model. Since aminochrome is an endogenous molecule derived from dopamine oxidation present in the targeted neurons in PD, these results reinforce the potential of aminochrome as a useful preclinical model to find anti-inflammatory and neuroprotective drugs for PD. Aminochrome induced dopaminergic neuronal loss, microglial activation, astroglial activation and neuroinflammation marked by an increase in NLRP3, IL1ß, TNF-α, CCL2, CCL5 and CCR2.


Asunto(s)
Fármacos Neuroprotectores , Enfermedad de Parkinson , Ratas , Masculino , Animales , Enfermedad de Parkinson/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/metabolismo , Ratas Wistar , Oxidopamina , Enfermedades Neuroinflamatorias , Dopamina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Neuronas Dopaminérgicas/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/metabolismo , Modelos Animales de Enfermedad , Microglía/metabolismo
9.
Purinergic Signal ; 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-37999896

RESUMEN

Leishmania braziliensis is a pathogenic protozoan parasite that causes American Tegumentary Leishmaniasis (ATL), an important tropical neglected disease. ENTPDases are nucleotidases that hydrolyze intracellular and/or extracellular nucleotides. ENTPDases are known as regulators of purinergic signalling induced by extracellular nucleotides. Leishmania species have two isoforms of ENTPDase, and, particularly, ENTPDase2 seems to be involved in infectivity and virulence. In this study, we conducted the heterologous expression and biochemical characterization of the recombinant ENTPDase2 of L. braziliensis (rLbNTPDase2). Our results show that this enzyme is a canonical ENTPDase with apyrase activity, capable of hydrolysing triphosphate and diphosphate nucleotides, and it is dependent on divalent cations (calcium or magnesium). Substrate specificity was characterized as UDP>GDP>ADP>GTP>ATP=UTP. The enzyme showed optimal activity at a neutral to basic pH and was partially inhibited by suramin and DIDS. Furthermore, the low apparent Km for ADP suggests that the enzyme may play a role in adenosine-mediated signalling. The biochemical characterization of this enzyme can open new avenues for using LbNTPDase2 as a drug target.

10.
Int J Mol Sci ; 24(17)2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37686446

RESUMEN

Tissue engineering for spinal cord injury (SCI) remains a complex and challenging task. Biomaterial scaffolds have been suggested as a potential solution for supporting cell survival and differentiation at the injury site. However, different biomaterials display multiple properties that significantly impact neural tissue at a cellular level. Here, we evaluated the behavior of different cell lines seeded on chitosan (CHI), poly (ε-caprolactone) (PCL), and poly (L-lactic acid) (PLLA) scaffolds. We demonstrated that the surface properties of a material play a crucial role in cell morphology and differentiation. While the direct contact of a polymer with the cells did not cause cytotoxicity or inhibit the spread of neural progenitor cells derived from neurospheres (NPCdn), neonatal rat spinal cord cells (SCC) and NPCdn only attached and matured on PCL and PLLA surfaces. Scanning electron microscopy and computational analysis suggested that cells attached to the material's surface emerged into distinct morphological populations. Flow cytometry revealed a higher differentiation of neural progenitor cells derived from human induced pluripotent stem cells (hiPSC-NPC) into glial cells on all biomaterials. Immunofluorescence assays demonstrated that PCL and PLLA guided neuronal differentiation and network development in SCC. Our data emphasize the importance of selecting appropriate biomaterials for tissue engineering in SCI treatment.


Asunto(s)
Células Madre Pluripotentes Inducidas , Tejido Nervioso , Traumatismos de la Médula Espinal , Regeneración de la Medula Espinal , Animales , Ratas , Humanos , Materiales Biocompatibles/farmacología , Ingeniería de Tejidos , Traumatismos de la Médula Espinal/terapia
11.
Ecol Lett ; 25(3): 581-597, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35199922

RESUMEN

Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species-level information is complete. Here we present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarised as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity.


Asunto(s)
Aves , Ecosistema , Animales , Biodiversidad , Evolución Biológica , Humanos , Filogenia
12.
Cell Mol Neurobiol ; 42(5): 1283-1300, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33387119

RESUMEN

Parkinson's disease (PD) is a neurodegenerative disorder marked primarily by motor symptoms such as rigidity, bradykinesia, postural instability and resting tremor associated with dopaminergic neuronal loss in the Substantia Nigra pars compacta (SNpc) and deficit of dopamine in the basal ganglia. These motor symptoms can be preceded by pre-motor symptoms whose recognition can be useful to apply different strategies to evaluate risk, early diagnosis and prevention of PD progression. Although clinical characteristics of PD are well defined, its pathogenesis is still not completely known, what makes discoveries of therapies capable of curing patients difficult to be reached. Several theories about the cause of idiopathic PD have been investigated and among them, the key role of inflammation, microglia and the inflammasome in the pathogenesis of PD has been considered. In this review, we describe the role and relation of both the inflammasome and microglial activation with the pathogenesis, symptoms, progression and the possibilities for new therapeutic strategies in PD.


Asunto(s)
Inflamasomas , Enfermedad de Parkinson , Humanos , Inflamación/patología , Microglía/patología , Proteína con Dominio Pirina 3 de la Familia NLR , Enfermedad de Parkinson/patología
13.
Plant Cell Rep ; 41(9): 1907-1929, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35833988

RESUMEN

KEY MESSAGE: High pigment mutants in tomato (Solanum lycopersicum L.), a loss of function in the control of photomorphogenesis, with greater pigment production, show altered growth, greater photosynthesis, and a metabolic reprogramming. High pigment mutations cause plants to be extremely responsive to light and produce excessive pigmentation as well as fruits with high levels of health-beneficial nutrients. However, the association of these traits with changes in the physiology and metabolism of leaves remains poorly understood. Here, we performed a detailed morphophysiological and metabolic characterization of high pigment 1 (hp1) and high pigment 2 (hp2) mutants in tomato (Solanum lycopersicum L. 'Micro-Tom') plants under different sunlight conditions (natural light, 50% shading, and 80% shading). These mutants occur in the DDB1 (hp1) and DET1 (hp2) genes, which are related to the regulation of photomorphogenesis and chloroplast development. Our results demonstrate that these mutations delay plant growth and height, by affecting physiological and metabolic parameters at all stages of plant development. Although the mutants were characterized by higher net CO2 assimilation, lower stomatal limitation, and higher carboxylation rates, with anatomical changes that favour photosynthesis, we found that carbohydrate levels did not increase, indicating a change in the energy flow. Shading minimized the differences between mutants and the wild type or fully reversed them in the phenotype at the metabolic level. Our results indicate that the high levels of pigments in hp1 and hp2 mutants represent an additional energy cost for these plants and that extensive physiological and metabolic reprogramming occurs to support increased pigment biosynthesis.


Asunto(s)
Solanum lycopersicum , Carbono/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Solanum lycopersicum/metabolismo , Fotosíntesis/genética , Pigmentación/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Plantas/metabolismo
14.
Oral Dis ; 28(6): 1573-1579, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34289201

RESUMEN

OBJECTIVE: The objective of this observational study was to evaluate telediagnosis of oral lesions using smartphone photography. MATERIALS AND METHODS: Individuals with visible oral lesions composed a convenience sample. The lesions were photographed using a smartphone camera and emailed along with clinical information to three evaluators, who formulated up to two diagnostic hypotheses for each case. A total of 235 photographs from 113 clinical cases were obtained. The evaluators answered questions regarding referral decisions, requests for additional tests, diagnostic difficulties, and image quality. The diagnostic hypotheses were compared to the gold standard by means of percent agreement and kappa coefficient. Consensual face-to-face diagnoses of three specialists-when only a clinical diagnosis was necessary-or histopathological results-when a biopsy was necessary-were considered the gold standard. RESULTS: The telediagnosis was similar to the gold standard in 76% of the cases, and kappa coefficients showed almost perfect agreement (k = 0.817-0.903). The evaluators considered that referrals could have been avoided on an average of 35,4% of the cases. CONCLUSION: Diagnosis of oral lesions using images taken with a smartphone showed almost perfect agreement and diagnostic accuracy comparable to face-to-face diagnosis.


Asunto(s)
Teléfono Inteligente , Telemedicina , Biopsia , Humanos , Fotograbar/métodos , Derivación y Consulta , Telemedicina/métodos
15.
Int J Audiol ; 61(11): 948-955, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-34704862

RESUMEN

OBJECTIVE: To objectively evaluate acoustic sensitivity of the implanted microphone, and maximum stable gain of a totally implantable active middle ear implant. DESIGN: Prospective, single centre evaluation. STUDY SAMPLE: Fourteen adult patients. RESULTS: Microphone sensitivity is approx. 10 dB lower than an externally worn conventional hearing aid, at frequencies up to 4000 Hz, and substantially lower at higher frequencies. The masking level due to microphone noise, which determines the softest test tones that can be detected, is estimated at <20 to <30 dB HL up to 1000 Hz, and <40 dB HL at higher frequencies. Maximum stable effective gain is the maximum amplification achievable without causing feedback whistling. In sensorineural hearing loss (SNHL) cases, it is 30-40 dB at frequencies up to 2000 Hz, allowing to compensate for even the maximum recommended hearing loss (60-70 dB HL). In both SNHL and mixed hearing loss (MHL) cases, maximum stable effective gain is lower (+20 to -30 dB) around 3000-6000 Hz. CONCLUSIONS: Microphone sensitivity is high enough to achieve aided thresholds of 20-40 dB HL. A strong correlation between actuator coupling efficiency and maximum stable effective gain implies that any effort to improve actuator efficiency should also increase the available gain.


Asunto(s)
Sordera , Audífonos , Pérdida Auditiva Sensorineural , Pérdida Auditiva , Prótesis Osicular , Adulto , Humanos , Estudios Prospectivos , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/rehabilitación , Pérdida Auditiva/rehabilitación
16.
Int J Mol Sci ; 23(19)2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-36233069

RESUMEN

Drimys winteri J.R. (Winteraceae) produce drimane sesquiterpenoids with activity against Candida yeast. In this work, drimenol, polygodial (1), isotadeonal (2), and a new drimane α,ß-unsaturated 1,4-dialdehyde, named winterdial (4), were purified from barks of D. winteri. The oxidation of drimenol produced the monoaldehyde drimenal (3). These four aldehyde sesquiterpenoids were evaluated against six Candida species isolated from candidemia patients in Chilean hospitals. Results showed that 1 displays fungistatic activity against all yeasts (3.75 to 15.0 µg/mL), but irritant effects on eyes and skin, whereas its non-pungent epimer 2 has fungistatic and fungicide activities at 1.9 and 15.0 µg/mL, respectively. On the other hand, compounds 3 and 4 were less active. Molecular dynamics simulations suggested that compounds 1-4 are capable of binding to the catalytic pocket of lanosterol 14-alpha demethylase with similar binding free energies, thus suggesting a potential mechanism of action through the inhibition of ergosterol synthesis. According to our findings, compound 2 appears as a valuable molecular scaffold to pursue the future development of more potent drugs against candidiasis with fewer side effects than polygodial. These outcomes are significant to broaden the alternatives to treat fungal infections with increasing prevalence worldwide using natural compounds as a primary source for active compounds.


Asunto(s)
Candidemia , Fungicidas Industriales , Sesquiterpenos , Aldehídos/farmacología , Candida , Chile , Ergosterol , Humanos , Irritantes , Lanosterol , Sesquiterpenos Policíclicos , Sesquiterpenos/química
17.
Int J Mol Sci ; 23(21)2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36361785

RESUMEN

Fungal biotransformation is an attractive synthetic strategy to produce highly specific compounds with chemical functionality in regions of the carbon skeleton that are not easily activated by conventional organic chemistry methods. In this work, Cladosporium antarcticum isolated from sediments of Glacier Collins in Antarctica was used to obtain novel drimane sesquiterpenoids alcohols with activity against Candida yeast from drimendiol and epidrimendiol. These compounds were produced by the high-yield reduction of polygodial and isotadeonal with NaBH4 in methanol. Cladosporium antarcticum produced two major products from drimendiol, identified as 9α-hydroxydrimendiol (1, 41.4 mg, 19.4% yield) and 3ß-hydroxydrimendiol (2, 74.8 mg, 35% yield), whereas the biotransformation of epidrimendiol yielded only one product, 9ß-hydroxyepidrimendiol (3, 86.6 mg, 41.6% yield). The products were purified by column chromatography and their structure elucidated by NMR and MS. The antifungal activity of compounds 1-3 was analyzed against Candida albicans, C. krusei and C. parapsilosis, showing that compound 2 has a MIC lower than 15 µg/mL against the three-pathogenic yeast. In silico studies suggest that a possible mechanism of action for the novel compounds is the inhibition of the enzyme lanosterol 14α-demethylase, affecting the ergosterol synthesis.


Asunto(s)
Alcoholes , Sesquiterpenos , Alcoholes/metabolismo , Candida , Antifúngicos/química , Sesquiterpenos/química , Candida albicans , Biotransformación , Pruebas de Sensibilidad Microbiana
18.
Molecules ; 27(4)2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35208981

RESUMEN

Phenolic compounds (PCs) present in foods are associated with a decreased risk of developing inflammatory diseases. The aim of this study was to extract and characterize PCs from craft beer powder and evaluate their potential benefits in an experimental model of inflammatory bowel disease (IBD). PCs were extracted and quantified from pure beer samples. BALB/c mice received either the beer phenolic extract (BPE) or beer powder fortified with phenolic extract (BPFPE) of PCs daily for 20 days by gavage. Colon samples were collected for histopathological and immunohistochemical analyses. Dextran sodium sulfate (DSS)-induced mice lost more weight, had reduced colon length, and developed more inflammatory changes compared with DSS-induced mice treated with either BPE or BPFPE. In addition, in DSS-induced mice, the densities of CD4- and CD11b-positive cells, apoptotic rates, and activation of NF-κB and p-ERK1/2 MAPK intracellular signaling pathways were higher in those treated with BPE and BPFPE than in those not treated. Pretreatment with the phenolic extract and BPFPE remarkably attenuated DSS-induced colitis. The protective effect of PCs supports further investigation and development of therapies for human IBD.


Asunto(s)
Cerveza , Colitis , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colitis/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Polvos , Dodecil Sulfato de Sodio/toxicidad
19.
Environ Monit Assess ; 194(10): 758, 2022 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36085206

RESUMEN

Trace and potentially toxic elements represent one class of food contaminants that has stimulated research. In markets, two main methods of growing vegetables are generally available: conventional and organic. Conventional farming has been the target of some concerns about the use of agrochemicals, especially the excessive use of pesticides, whereas organic agriculture minimizes the use of agrochemicals. As the main route for potentially toxic elements' absorption by humans is by food intake, it is important to evaluate if the method of cultivation influences their concentrations. This study evaluated the levels of potentially toxic elements and nutrients on four leafy vegetables: curly lettuce, collard greens, escarole, and rocket, cultivated by conventional and organic farming. We found that Al, Ba, Fe, and Sr levels were higher in conventional samples, whereas K, Pb, and Zn were higher in organic. Amongst the elements analysed, values of Fe, Al, and K were around 0.2, 0.3, and 70 g kg-1, respectively, except in collard greens, in which the values were lower. On the other hand, Ba, Sr, and Mn presented higher concentration in collard greens compared to the other vegetables in conventional cultivation (~ 35, 80, and 120 mg kg-1, respectively). The principal component analysis result shows that the samples were grouped according to the type of vegetable, regardless of the type of cultivation. Despite this, the evaluation of the cultivation by different types of farming is important in order to choose the healthiest option.


Asunto(s)
Monitoreo del Ambiente , Verduras , Agroquímicos , Humanos , Lactuca , Hojas de la Planta
20.
Physiol Mol Biol Plants ; 28(6): 1335-1345, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35910437

RESUMEN

Soil contamination by excess heavy metals or trace elements is a global concern, as these elements are highly bioaccumulated in living organisms, migrating throughout the food chain, and causing health problems. Sustainable technologies, using plants, have been increasingly studied and used to contain, reduce, or extract these elements from the soil. In this sense, it is essential to identify plant species that tolerate certain elements, present high biomass production and are resistant to adverse soil conditions. For this reason, we evaluated the biomass production and tolerance of Cajanus cajan in response to different concentrations of copper (30, 60, 120, and 240 mg/dm3, in addition to the control treatment) in the soil, as well as the effect of this metal on photosynthetic pigments and gas exchange. C. cajan was sown in soil previously contaminated with copper sulfate and cultivated in a greenhouse for 60 days after emergence. C. cajan is copper tolerant, approximately 88% copper is accumulated in the roots and therefore there is low copper translocation to the shoot, consequently, the chlorophyll content, the net photosynthesis rate, carbon assimilation, dry biomass, the root system development, and nodulation were not affected by copper. C. cajan can be explored in strategies to improve soil conditions and is a promising species in soil phytoremediation studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01203-6.

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