RESUMO
Dimorphic species of Mucor, which are cosmopolitan fungi belonging to subphylum Mucoromycotina, are metabolically versatile. Some species of Mucor are sources of biotechnological products, such as biodiesel from Mucor circinelloides and expression of heterologous proteins from Mucor lusitanicus. Furthermore, Mucor lusitanicus has been described as a model for understanding mucormycosis infections. However, little is known regarding the relationship between Mucor lusitanicus and other soil inhabitants. In this study, we investigated the potential use of Mucor lusitanicus as a biocontrol agent against fungal phytopathogens, namely Fusarium oxysporum f. sp. lycopersici, Fusarium solani, and Alternaria solani, which destroy economically important crops. Results showed that aerobic cell-free supernatants of the culture broth (SS) from Mucor lusitanicus inhibited the growth of the fungal phytopathogens in culture, soil, and tomato fruits. The SS obtained from a strain of Mucor lusitanicus carrying the deletion of rfs gene, which encodes an enzyme involved in the synthesis of siderophore rhizoferrin, had a decreased inhibitory effect against the growth of the phytopathogens. Contrarily, this inhibitory effect was more evident with the SS from an rfs-overexpressing strain compared to the wild-type. This study provides a framework for the potential biotechnological use of the molecules secreted from Mucor lusitanicus in the biocontrol of fungal phytopathogens.
Assuntos
Mucor , Mucormicose , Mucor/genética , Sideróforos , Mucormicose/microbiologia , Doenças das PlantasRESUMO
INTRODUCTION: Despite increasing utilization of spinal cord stimulation (SCS), its effects on chemoefficacy, cancer progression, and chemotherapy-induced peripheral neuropathy (CIPN) pain remain unclear. Up to 30% of adults who are cancer survivors may suffer from CIPN, and there are currently no effective preventative treatments. MATERIALS AND METHODS: Through a combination of bioluminescent imaging, behavioral, biochemical, and immunohistochemical approaches, we investigated the role of SCS and paclitaxel (PTX) on tumor growth and PTX-induced peripheral neuropathy (PIPN) pain development in T-cell-deficient male rats (Crl:NIH-Foxn1rnu) with xenograft human non-small cell lung cancer. We hypothesized that SCS can prevent CIPN pain and enhance chemoefficacy partially by modulating macrophages, fractalkine (CX3CL1), and inflammatory cytokines. RESULTS: We show that preemptive SCS enhanced the antitumor efficacy of PTX and prevented PIPN pain. Without SCS, rats with and without tumors developed robust PIPN pain-related mechanical hypersensitivity, but only those with tumors developed cold hypersensitivity, suggesting T-cell dependence for different PIPN pain modalities. SCS increased soluble CX3CL1 and macrophages and decreased neuronal and nonneuronal insoluble CX3CL1 expression and inflammation in dorsal root ganglia. CONCLUSION: Collectively, our findings suggest that preemptive SCS is a promising strategy to increase chemoefficacy and prevent PIPN pain via CX3CL1-macrophage modulation.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neuralgia , Estimulação da Medula Espinal , Humanos , Ratos , Masculino , Animais , Paclitaxel/efeitos adversos , Paclitaxel/metabolismo , Quimiocina CX3CL1/metabolismo , Quimiocina CX3CL1/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Ratos Sprague-Dawley , Neuralgia/metabolismo , Medula Espinal/patologia , Gânglios Espinais/metabolismoRESUMO
The genus Fusarium can be utilized to produce a great variety of secondary metabolites under specific culture conditions, including pigments of increasing biotechnological interest, such as bikaverin. Such pigments are important due to the biological properties they possess, including antitumor and antibiotic activities, among others. In Fusarium fujikuroi, bik1-bik6 have been identified as the genes that are responsible for the synthesis of bikaverin. Therefore, in this study, we screened for the presence of bik genes and examined changes in mRNA levels of the bik genes under the influence of NH4NO3 (0.024, 0.048, 0.50, 1.0, and 4.60 g L-1) and NH4Cl (0.50 and 1.0 g L-1) as nitrogen sources for the phytopathogen Fusarium oxysporum f. sp. lycopersici. Our results indicated the presence of at least six bik (bik1-bik6) genes and showed increased mRNA levels for bik4, bik5, and bik6 in conditions where NH4NO3 was used at pH 3.0. The characteristic coloration of bikaverin was obtained in 10 out of 16 culture conditions, except when the fungus was grown with higher concentrations of NH4NO3 (1.0 and 4.60 g L-1). The pigment was chloroform-extracted from the culture conditions of NH4NO3 (0.024, 0.048, and 0.50 g L-1) and NH4Cl (0.50 and 1.0 g L-1) with 3 and 9 days of incubation. Analysis via visible spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry were used for the identification of bikaverin.
Assuntos
Fusarium , Xantonas , Fusarium/genética , NitrogênioRESUMO
Infections caused by micro-organisms of the genus Candida are becoming a growing health problem worldwide. These fungi are opportunistic commensals that can produce infections-clinically known as candidiasis-in immunocompromised individuals. The indiscriminate use of different anti-fungal treatments has triggered the resistance of Candida species to currently used therapies. In this sense, propolis has been shown to have potent antimicrobial properties and thus can be used as an approach for the inhibition of Candida species. Therefore, this work aims to evaluate the anti-Candida effects of a propolis extract obtained from the north of Mexico on clinical isolates of Candida species. Candida species were specifically identified from oral lesions, and both the qualitative and quantitative anti-Candida effects of the Mexican propolis were evaluated, as well as its inhibitory effect on C. albicans isolate's germ tube growth and chemical composition. Three Candida species were identified, and our results indicated that the inhibition halos of the propolis ranged from 7.6 to 21.43 mm, while that of the MFC and FC50 ranged from 0.312 to 1.25 and 0.014 to 0.244 mg/mL, respectively. Moreover, the propolis was found to inhibit germ tube formation (IC50 ranging from 0.030 to 1.291 mg/mL). Chemical composition analysis indicated the presence of flavonoids, including pinocembrin, baicalein, pinobanksin chalcone, rhamnetin, and biochanin A, in the Mexican propolis extract. In summary, our work shows that Mexican propolis presents significant anti-Candida effects related to its chemical composition, and also inhibits germ tube growth. Other Candida species virulence factors should be investigated in future research in order to determine the mechanisms associated with antifungal effects against them.
Assuntos
Candida , Própole , Antifúngicos/farmacologia , Candida albicans , Humanos , México , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Própole/química , Própole/farmacologiaRESUMO
Fusarium oxysporum f. sp. lycopersici is an important plant pathogen that has been used to understand the virulence mechanisms that soil inhabiting fungi exhibit during the infection process. In F. oxysporum many of the virulence factors are secreted, and the secretion process requires the formation of vesicles. Arf family members, represented by Arf (ADP- Ribosylation Factor), Arl (Arf-like), and Sar (Secretion-associated and Ras-related) proteins, are involved in the vesicle creation process. In this study we identified the Arf family members in F. oxysporum f. sp. lycopersici, which includes seven putative proteins: Arf1, Arf3, Arl1 through Arl3, Arl8B, and Sar1. Quantification of the mRNA levels of each arf encoding gene revealed that the highest expression corresponds to arf1 in all tested conditions. The phylogenetic analysis revealed that no other Arf1 paralogue, such as Arf2 from yeast, is present in F. oxysporum f. sp. lycopersici. The essential function suggested of Arf1 in F. oxysporum f. sp. lycopersici was corroborated experimentally when, after several attempts, it was impossible to obtain a knockout mutant in arf1. Moreover, arl3 mRNA levels increased significantly when plant tissue was added as a sole carbon source, suggesting that the product of these genes could play pivotal roles during plant infection, the corresponding mutant ∆arl3 was less virulent compared to the wild-type strain. These results describe the role of arl3 as a critical regulator of the virulence in F. oxysporum f. sp. lycopersici and stablish a framework for the arf family members to be studied in deeper details in this phytopathogen.
Assuntos
Fusarium , Solanum lycopersicum , Fusarium/genética , Filogenia , Doenças das Plantas , Virulência/genéticaRESUMO
Amphipterygium adstringens (cuachalalate) contains anacardic acids (AAs) such as 6-pentadecyl salicylic acid (6SA) that show immunomodulatory and antitumor activity with minimal or no secondary adverse effects. By contrast, most chemotherapeutic agents, such as 5-fluorouracil (5-FU) and carboplatin (CbPt), induce myelosuppression and leukopenia. Here, we investigated the myeloprotective and antineoplastic potential of an AA extract or the 6SA as monotherapy or in combination with commonly used chemotherapeutic agents (5-FU and CbPt) to determine the cytoprotective action of 6SA on immune cells. Treatment of Balb/c breast tumor-bearing female mice with an AA mixture or 6SA did not induce the myelosuppression or leukopenia observed with 5-FU and CbPt. The co-administration of AA mixture or isolated 6SA with 5-FU or CbPt reduced the apoptosis of circulating blood cells and bone marrow cells. Treatment of 4T1 breast tumor-bearing mice with the AA mixture or 6SA reduced tumor growth and lung metastasis and increased the survival rate compared with monotherapies. An increased effect was observed in tumor reduction with the combination of 6SA and CbPt. In conclusion, AAs have important myeloprotective and antineoplastic effects, and they can improve the efficiency of chemotherapeutics, thereby protecting the organism against the toxic effects of drugs such as 5-FU and CbPt.
Assuntos
Ácidos Anacárdicos/química , Carboplatina/farmacologia , Fluoruracila/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Anacardiaceae , Ácidos Anacárdicos/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose , Células da Medula Óssea/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Citoproteção , Modelos Animais de Doenças , Feminino , Hexanos/química , Leucócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Casca de Planta/metabolismoRESUMO
Smart conductive materials are developed in regenerative medicine to promote a controlled release profile of charged bioactive agents in the vicinity of implants. The incorporation and the active electrochemical release of the charged compounds into the organic conductive coating is achieved due to its intrinsic electrical properties. The anti-inflammatory drug dexamethasone was added during the polymerization, and its subsequent release at therapeutic doses was reached by electrical stimulation. In this work, a Poly (3,4-ethylenedioxythiophene): κ-carrageenan: dexamethasone film was prepared, and κ-carrageenan was incorporated to keep the electrochemical and physical stability of the electroactive matrix. The presence of κ-carrageenan and dexamethasone in the conductive film was confirmed by µ-Raman spectroscopy and their effect in the topographic was studied using profilometry. The dexamethasone release process was evaluated by cyclic voltammetry and High-Resolution mass spectrometry. In conclusion, κ-carrageenan as a doping agent improves the electrical properties of the conductive layer allowing the release of dexamethasone at therapeutic levels by electrochemical stimulation, providing a stable system to be used in organic bioelectronics systems.
Assuntos
Carragenina/química , Dexametasona/administração & dosagem , Polímeros/química , Polissacarídeos/química , Dexametasona/química , Dexametasona/farmacologia , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Condutividade Elétrica , Técnicas Eletroquímicas , Eletrodos , Análise EspectralRESUMO
Recently, tissue engineering and regenerative medicine studies have evaluated smart biomaterials as implantable scaffolds and their interaction with cells for biomedical applications. Porous materials have been used in tissue engineering as synthetic extracellular matrices, promoting the attachment and migration of host cells to induce the in vitro regeneration of different tissues. Biomimetic 3D scaffold systems allow control over biophysical and biochemical cues, modulating the extracellular environment through mechanical, electrical, and biochemical stimulation of cells, driving their molecular reprogramming. In this review, first we outline the main advantages of using polysaccharides as raw materials for porous scaffolds, as well as the most common processing pathways to obtain the adequate textural properties, allowing the integration and attachment of cells. The second approach focuses on the tunable characteristics of the synthetic matrix, emphasizing the effect of their mechanical properties and the modification with conducting polymers in the cell response. The use and influence of polysaccharide-based porous materials as drug delivery systems for biochemical stimulation of cells is also described. Overall, engineered biomaterials are proposed as an effective strategy to improve in vitro tissue regeneration and future research directions of modified polysaccharide-based materials in the biomedical field are suggested.
Assuntos
Materiais Biocompatíveis/química , Materiais Biomiméticos/química , Polissacarídeos/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Diferenciação Celular , Matriz Extracelular/metabolismo , Humanos , Teste de Materiais , Polímeros/química , Porosidade , Medicina Regenerativa/métodosRESUMO
PURPOSE: Ongoing cancer cachexia trials evaluate sarcopenia by skeletal muscle index (SMI) at the L3 vertebrae level, commonly used as a standard. Routine chest CT institutional protocols widely differ in including L3. We investigated whether SMI at L1 assessment, rather than L3, would be reliable and more practicable for non-small cell lung cancer (NSCLC). METHODS: NSCLC patients with routine CT chest had SMI measurements performed at L1 using Slice-O-Matic software. Accuracy of including L1 level, imaging quality, and ability to detect sarcopenia was collected and correlation of L1 SMI with body mass index (BMI) was performed. RESULTS: Thirty-seven patients with NSCLC (73 CT assessments) were enlisted at three institutions. Characteristics: 47% female; medians: age 59, KPS 80%; BMI 25.49, weight 72.97 kg, SMI 59.24. Sarcopenia was detected in 14.7% of patients; 20% had sarcopenic obesity. Of the 73 CTs, 94.5% included L1 (95% CI 86.6-98.5%). Three images (4%) were difficult to evaluate. Inclusion of L1 was similar among the three participating institutions (90.4 to 96.7% inclusion). BMI correlation with SMI was weak (r = 0.329). CONCLUSIONS: SMI assessment at L1 is achievable in patients with NSCLC receiving routine chest CT, with 96% having acceptable quality evaluations. Similar to results previously reported at L3, BMI showed poor correlation and low sensitivity to detect muscle mass loss. The use of CT at L1 is reliable and presents the opportunity for easier patient evaluation of sarcopenia in patients with lung cancer without the need for additional testing or radiation exposure.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Região Lombossacral/fisiopatologia , Neoplasias Pulmonares/complicações , Músculo Esquelético/patologia , Sarcopenia/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Sarcopenia/diagnóstico por imagem , Sarcopenia/patologiaRESUMO
IntroductionIntracardiac rhabdomyomas can cause severe ventricular dysfunction and outflow tract obstruction.Case reportA term newborn infant with antenatal diagnosis of giant left ventricle rhabdomyoma presented with cardiac failure and duct-dependent systemic circulation after birth. She was treated successfully with everolimus, showing decrease in tumour size and improvement in left ventricular ejection fraction.DiscussionTumour regression rate was 0.32 cm2/day and improved to 0.80 cm2/day with the use of everolimus. Herein we report a newborn with inoperable giant left ventricular cardiac rhabdomyoma and significant regression of the tumour. To our knowledge, this is the largest left ventricular rhabdomyoma reported. A review of the literature was undertaken for comparison. CONCLUSION: Everolimus has proven to be efficacious in size reduction of cardiac rhabdomyomas in cases when surgical resection is not possible.
Assuntos
Antineoplásicos/uso terapêutico , Everolimo/uso terapêutico , Neoplasias Cardíacas/tratamento farmacológico , Rabdomioma/tratamento farmacológico , Ecocardiografia , Feminino , Insuficiência Cardíaca/etiologia , Neoplasias Cardíacas/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Humanos , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal , Rabdomioma/diagnóstico por imagem , Resultado do TratamentoRESUMO
OBJECTIVE: Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI). METHODS: Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND). RESULTS: Mean age was 58 ± 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum. INTERPRETATION: Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life.
Assuntos
Encéfalo/patologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Cognição/fisiologia , Marcha/fisiologia , Adulto , Idoso , Atrofia/patologia , Canadá/epidemiologia , Doenças de Pequenos Vasos Cerebrais/psicologia , Diagnóstico Precoce , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Vigilância da População/métodos , Estudos ProspectivosRESUMO
Brugia malayi (B. malayi) is one of the three causative agents of lymphatic filariasis, a neglected parasitic disease. Current literature suggests that dihydrofolate reductase is a potential drug target for the elimination of B. malayi. Here we report the recombinant expression and purification of a â¼20 kDa B. malayi dihydrofolate reductase (BmDHFR). A His6-tagged construct was expressed in E. coli and purified by affinity chromatography to yield active and homogeneous enzyme for steady-state kinetic characterization and inhibition studies. The catalytic activity kcat was found to be 1.4 ± 0.1 s(-1), the Michaelis Menten constant KM for dihydrofolate 14.7 ± 3.6 µM, and the equilibrium dissociation constant KD for NADPH 25 ± 24 nM. For BmDHFR, IC50 values for a six DHFR inhibitors were determined to be 3.1 ± 0.2 nM for methotrexate, 32 ± 22 µM for trimethoprim, 109 ± 34 µM for pyrimethamine, 154 ± 46 µM for 2,4-diaminoquinazoline, 771 ± 44 µM for cycloguanil, and >20,000 µM for 2,4-diaminopyrimidine. Our findings suggest that antifolate compounds can serve as inhibitors of BmDHFR.
Assuntos
Brugia Malayi/genética , Expressão Gênica , Proteínas de Helminto , Tetra-Hidrofolato Desidrogenase , Animais , Brugia Malayi/enzimologia , Catálise , Proteínas de Helminto/biossíntese , Proteínas de Helminto/química , Proteínas de Helminto/genética , Proteínas de Helminto/isolamento & purificação , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Tetra-Hidrofolato Desidrogenase/biossíntese , Tetra-Hidrofolato Desidrogenase/química , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/isolamento & purificaçãoRESUMO
A new coccidian species (Protozoa: Apicomplexa: Eimeriidae) collected from the red warbler Cardellina rubra (Swainson) is reported from the Nevado de Toluca National Park, Mexico. Isospora cardellinae n. sp. has subspherical oöcysts, measuring on average 26.6 × 25.4 µm, with smooth, bi-layered wall, c.1.3 µm thick. Micropyle, oöcyst residuum, and polar granule are absent. Sporocysts are ovoidal, measuring on average 19.0 × 12.0 µm, with a knob-like Stieda body, a trapezoidal sub-Stieda body and sporocyst residuum composed of scattered spherules of different sizes. Sporozoites are vermiform with one refractile body and a nucleus. This is the fourth description of an isosporoid coccidian infecting a New World warbler.
Assuntos
Isospora/classificação , Isospora/citologia , Aves Canoras/parasitologia , Animais , México , Especificidade da EspécieRESUMO
The Rho1 protein is a GTPase that participates in cell wall biogenesis. We analyzed the transcript levels of laccase genes (lccl, lcc2, lcc3, lcc4, lcc5, and lcc9), and a xylanase gene (xyl3) in Fusarium oxysporum f. sp. lycopersici strain 4287 (wild type) and two mutant strains; rhol::hyg that lacks a functional Rho1, and rho1::hyg + rho1 (G14V) that has a constitutively active Rho1. The transcript levels of lcc2, lcc3, lcc5, and xyl3 differed among the three strains, but those of lcc1 and lcc9 did not. Xylanase activities were higher in rho1::hyg than in both the wild type and rho1::hyg + rho1 (G14V) . Laccase activities were significantly higher in the two mutants than in the wild type. Rho1 thus plays a role in regulating xyl3, lcc2, lcc3, and lcc5 at the transcriptional and/or translational level.
Assuntos
Fusarium/genética , Fusarium/metabolismo , Regulação Fúngica da Expressão Gênica , Lacase/metabolismo , Xilosidases/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Deleção de Genes , Expressão Gênica , Perfilação da Expressão Gênica , Proteínas rho de Ligação ao GTP/genéticaRESUMO
A new coccidian species (Protista: Apicomplexa: Eimeriidae) collected from the rufous-capped brush finch Atlapetes pileatus Wagler in the Nevado de Toluca Natural Protected Area, Mexico. Oöcysts of Eimeria pileata n. sp. are ellipsoidal, measuring on average 16.5 × 14.1 µm, with a smooth, bi-layered wall. Micropyle and oöcyst residuum are absent, but a polar granule is present. Sporocysts are ellipsoidal, measuring on average 9.0 × 5.4 µm. Stieda and sub-Stieda bodies are both present. A sporocyst residuum is present as a compact mass of granules. This is the third description of an eimeriid coccidian infecting passerines.
Assuntos
Eimeria/classificação , Eimeria/citologia , Tentilhões/parasitologia , Animais , México , Oocistos/citologia , Oócitos/citologia , Especificidade da EspécieRESUMO
Lycopene and oleoresin extraction from powder of tomato over-ripe by three agitation methods and four solvents have been evaluated. Also, tomato powder and the oleoresins were characterized biochemically. On average, the moisture content of powder was found to be 4.30, ash 8.90, proteins 11.23 and lipids 4.35 g 100 g(-1). The best oleoresin extraction yield was achieved by combining sonication and acetone at 1.43 g 100 g(-1). The greatest amount of lycopene (65.57 ± 0.33 mg 100 g(-1)) was also obtained using the same treatment. The presence of trans-lycopene was positively confirmed by HPLC and FTIR. In oleoresins, linoleic acid (C18:2n6) was the predominant with 50% of total fatty acids, whereas stearic acid (C18:0) is presented in a smaller proportion (5%). A simple and suitable method for extraction of lycopene from over-ripe tomato was optimized. In industrial applications, tomato by-products are a viable source of analytes, such as lycopene and unsaturated fatty acids.
Assuntos
Carotenoides/isolamento & purificação , Ácidos Graxos Insaturados/isolamento & purificação , Frutas , Extratos Vegetais/isolamento & purificação , Preparações de Plantas/química , Solanum lycopersicum/química , Solventes , Acetona , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Ácido Linoleico/análise , Lipídeos/análise , Licopeno , Extratos Vegetais/química , Pós/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Ácidos Esteáricos/análise , Água/análiseRESUMO
BACKGROUND: Taxanes such as paclitaxel (PTX) induce dose-dependent chemotherapy-induced peripheral neuropathy (CIPN), which is associated with debilitating chronic pain and gait impairment. Increased macrophage-related proinflammatory activities have been reported to mediate the development and maintenance of neuropathic pain. While spinal cord stimulation (SCS) has been used for a number of pain conditions, the mechanisms supporting its use for CIPN remain to be elucidated. Thus, we aimed to examine whether SCS can attenuate Schwann cell-mediated and macrophage-mediated neuroinflammation in the sciatic nerve of Rowlette Nude (RNU) rats with PTX-induced gait impairment and mechanical hypersensitivity. METHODS: Adult male tumor-bearing RNU rats were used for this study examining PTX treatment and SCS. Gait and mechanical hypersensitivity were assessed weekly. Cytokines, gene expression, macrophage infiltration and polarization, nerve morphology and Schwann cells were examined in sciatic nerves using multiplex immunoassay, bulk RNA sequencing, histochemistry and immunohistochemistry techniques. RESULTS: SCS (50 Hz, 0.2 milliseconds, 80% motor threshold) attenuated the development of mechanical hypersensitivity (20.93±0.80 vs 12.23±2.71 grams, p<0.0096) and temporal gait impairment [swing (90.41±7.03 vs 117.27±9.71%, p<0.0076), and single stance times (94.92±3.62 vs 112.75±7.27%, p<0.0245)] induced by PTX (SCS+PTX+Tumor vs Sham SCS+PTX+Tumor). SCS also attenuated the reduction in Schwann cells, myelin thickness and increased the concentration of anti-inflammatory cytokine interleukin (IL)-10. Bulk RNA sequencing revealed differential gene expression after SCS, with 607 (59.2%) genes upregulated while 418 (40.8%) genes were downregulated. Notably, genes related to anti-inflammatory cytokines and neuronal growth were upregulated, while genes related to proinflammatory-promoting genes, increased M2γ polarization and decreased macrophage infiltration and Schwann cell loss were downregulated. CONCLUSION: SCS may attenuate PTX-induced pain and temporal gait impairment, which may be partly attributed to decreases in Schwann cell loss and macrophage-mediated neuroinflammation in sciatic nerves.
RESUMO
Petroleum-based plastics dominate everyday life, necessitating the exploration of natural polymers as alternatives. Starch, abundant and biodegradable, is a promising raw material. However, understanding the molecular mechanisms underlying starch plasticization has proven challenging. To address this, we employ molecular dynamics simulations, focusing on amylose as a model. Our comprehensive evaluation revealed that chain size affects solubility, temperature influenced diffusivity and elastic properties, and oleic acid expressed potential as an alternative plasticizer. Furthermore, blending glycerol or oleic acid with water suggested the enhancement amylose's elasticity. These findings contribute to the design of sustainable and improved biodegradable plastics.
Assuntos
Plásticos Biodegradáveis , Amido , Amilose , Ácido Oleico , Glicerol , Simulação de Dinâmica Molecular , PlásticosRESUMO
INTRODUCTION: a relationship has been observed between elevated levels of liver enzymes and uric acid with the presence of metabolic syndrome (MS) in the pediatric population. OBJECTIVE: to compare serum liver enzyme and uric acid levels between adolescents with and without MS. METHODS: a cross-sectional study was carried out in adolescents with obesity between 10 and 18 years old. Somatometric data, serum insulin, lipid profile, uric acid levels and liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and gamma-glutamyl transferase [GGT]) were analyzed. STATISTICAL ANALYSIS: Student's t test or the Chi-square test was used to evaluate differences between groups. RESULTS: a total of 1095 adolescents with obesity were included (444 with MS and 651 without MS). The group with MS had a higher BMI (with MS 2.28 vs without MS 2.11 p < 0.001), with no difference in body fat (42.9 % vs 42.9 %, p = 0.978). The MS group had significantly higher levels of AST (34.4 vs. 29.5, p = 0.013), ALT (42.2 vs. 34.6, p = 0.003), and uric acid (6.17 vs. 5.74, p = 0.002). comparison to the group without MS. The proportion of ALT (40.5 % vs 29.5 %, p = 0.029) and altered uric acid (58.1 % vs. 45.6 %, p = 0.019) was higher in the MS group. CONCLUSIONS: serum levels of ALT, AST and uric acid in adolescents with obesity and MS were higher compared to those without MS. Altered ALT was a risk factor for SM.
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The application of nanomaterials in the agri-food industry can lead us to the formulation of new sustainable and effective pesticides for the control of fungi such as Fusarium oxysporum f. sp. lycopersici (Fol). This is a fungal plant pathogen for the tomato plant. In this work, silver nanoparticles (AgNPs) were synthesized by a green methodology from Geranium leaf extract as a reducing agent. The poisoned food technique was used to determine the percentage of inhibition of Fol mycelial growth by the action of AgNPs. They were characterized by transmission electron microscopy (TEM, JEOL JEM-2100, Tokyo, Japan) and ultraviolet-visible spectroscopy (UV-VIS, DU 730 Beckman Coulter, Brea, CA, USA). Five different concentrations of AgNPs (10, 20, 40, 75, and 150 mg/L) were evaluated in vitro in order to determine the minimum inhibitory concentration (MIC) as well as the behavior of their antifungal activity in tomato fruit. Nanoparticles with spherical morphology and average diameters of 38.5 ± 18.5 nm were obtained. The maximum percentage of inhibition on the mycelial growth of Fol was 94.6 ± 0.1%, which was obtained using the AgNPs concentration of 150 mg/L and it was determined that the MIC corresponds to 75 mg/L. On the other hand, in a qualitative way, it was possible to observe an external inhibitory effect in the tomato fruit from the concentration of 10 mg/L. Finally, we can conclude that AgNPs are a viable alternative for alternative formulations applied in the agri-food industry as pesticide solutions.