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A novel halotolerant actinobacterium, designated as RG38T, capable of producing black extracellular melanin pigment on SP2 agar, was isolated from the roots of Tagetes patula. Comparative analysis of the 16S rRNA gene sequence revealed the highest similarity to Streptomyces collinus NBRC 12759T (99.3%). Phylogenetic analysis showed that strain RG38T clustered within the genus Streptomyces forming a monophyletic cluster with its close relatives. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), and amino-acid identity (AAI) values between strain RG38T and related species within the genus Streptomyces were below the standard threshold for prokaryotic species delineation. The DNA G + C content of the strain RG38T was determined to be 73.3%. The genome size measured 7,150,598 bp comprising 17 contigs and encompassed 6,053 protein coding genes. AntiSMASH analysis of the whole genome revealed 35 putative biosynthetic gene clusters (BGCs) responsible for various secondary metabolites. Among these clusters, two gene clusters exhibited 100% similarity to the chromomycin A3, albaflavenone, and anthracimycin, respectively. These compounds were reported to possess significant anticancer and antibacterial activities. LC-MS-based analysis, coupled with further isolation studies, confirmed the production of chromomycins A2 (1), A3 (2), and their derivatives, along with their antibiotic activities. These findings underscore the potential of this novel strain as a novel resource for the discovery of diverse antimicrobial compounds. This study is the first to report an antimicrobial compound producing Streptomyces species isolated from medicinal plant T. patula. Based on a polyphasic study, the strain RG38T isolated from an unexplored habitat with a high potential for new natural products represents a novel species within the genus Streptomyces. Accordingly, we propose the name Streptomyces tagetis sp. nov. for this novel species, with the type strain is RG38T (=KCTC 49624T = TBRC 15113T).
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Ginseng, the roots of Panax species, is an important medicinal herb used as a tonic. As ginsenosides are key bioactive components of ginseng, holistic chemical profiling of them has provided many insights into understanding ginseng. Mass spectrometry has been a major methodology for profiling, which has been applied to realize numerous goals in ginseng research, such as the discrimination of different species, geographical origins, and ages, and the monitoring of processing and biotransformation. This review summarizes the various applications of ginsenoside profiling in ginseng research over the last three decades that have contributed to expanding our understanding of ginseng. However, we also note that most of the studies overlooked a crucial factor that influences the levels of ginsenosides: genetic variation. To highlight the effects of genetic variation on the chemical contents, we present our results of untargeted and targeted ginsenoside profiling of different genotypes cultivated under identical conditions, in addition to data regarding genome-level genetic diversity. Additionally, we analyze the other limitations of previous studies, such as imperfect variable control, deficient metadata, and lack of additional effort to validate causation. We conclude that the values of ginsenoside profiling studies can be enhanced by overcoming such limitations, as well as by integrating with other -omics techniques.
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NMDA receptors (NMDARs) modulate glutamatergic excitatory tone in the brain via two complementary modalities: a phasic excitatory postsynaptic current and a tonic extrasynaptic modality. Here, we demonstrated that the tonic NMDAR-current (I NMDA) mediated by NR2A-containing NMDARs is an efficient biosensor detecting the altered ambient glutamate level in the supraoptic nucleus (SON). I NMDA of magnocellular neurosecretory cells (MNCs) measured by nonselective NMDARs antagonist, AP5, at holding potential (V holding) -70â mV in low concentration of ECF Mg2+ ([Mg2+]o) was transiently but significantly increased 1-week post induction of a DOCA salt hypertensive model rat which was compatible with that induced by a NR2A-selective antagonist, PEAQX (I PEAQX) in both DOCA-H2O and DOCA-salt groups. In agreement, NR2B antagonist, ifenprodil, or NR2C/D antagonist, PPDA, did not affect the holding current (I holding) at V holding -70â mV. Increased ambient glutamate by exogenous glutamate (10â mM) or excitatory amino acid transporters (EAATs) antagonist (TBOA, 50â mM) abolished the I PEAQX difference between two groups, suggesting that attenuated EAATs activity increased ambient glutamate concentration, leading to the larger I PEAQX in DOCA-salt rats. In contrast, only ifenprodil but not PEAQX and PPDA uncovered I NMDA at V holding +40â mV under 1.2â mM [Mg2+]o condition. I ifenprodil was not different in DOCA-H2O and DOCA-salt groups. Finally, NR2A, NR2B, and NR2D protein expression were not different in the SON of the two groups. Taken together, NR2A-containing NMDARs efficiently detected the increased ambient glutamate concentration in the SON of DOCA-salt hypertensive rats due to attenuated EAATs activity.
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Acetato de Desoxicorticosterona , Receptores de N-Metil-D-Aspartato , Ratos , Animais , Receptores de N-Metil-D-Aspartato/metabolismo , N-Metilaspartato/metabolismo , N-Metilaspartato/farmacologia , Ácido Glutâmico/metabolismo , Núcleo Supraóptico/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologiaRESUMO
The objective of this study was to investigate the protective effects of functional nutrients including various functional amino acids, vitamins, and minerals on chicken intestinal epithelial cells (cIECs) treated with oxidative stress. The cIECs were isolated from specific pathogen free eggs. Cells were exposed to 0 mM supplement (control), 20 mM threonine (Thr), 0.4 mM tryptophan (Trp), 1 mM glycine (Gly), 10 µM vitamin C (VC), 40 µM vitamin E (VE), 5 µM vitamin A (VA), 34 µM chromium (Cr), 0.42 µM selenium (Se), and 50 µM zinc (Zn) for 24 h with 6 replicates for each treatment. After 24 h, cells were further incubated with fresh culture medium (positive control, PC) or 1 mM H2O2 with different supplements (negative control, NC and each treatment). Oxidative stress was measured by cell proliferation, whereas tight junction barrier function was analyzed by fluorescein isothiocyanate (FITC)-dextran permeability and transepithelial electrical resistance (TEER). Results indicated that cell viability and TEER values were less (p < 0.05) in NC treatments with oxidative stress than in PC treatments. In addition, FITC-dextran values were greater (p < 0.05) in NC treatments with oxidative stress than in PC treatments. The supplementations of Thr, Trp, Gly, VC, and VE in cells treated with H2O2 showed greater (p < 0.05) cell viability than the supplementation of VA, Cr, Se, and Zn. The supplementations of Trp, Gly, VC, and Se in cells treated with H2O2 showed the least (p < 0.05) cellular permeability. In addition, the supplementation of Thr, VE, VA, Cr, and Zn in cells treated with H2O2 decreased (p < 0.05) cellular permeability. At 48 h, the supplementations of Thr, Trp, and Gly in cells treated with H2O2 showed the greatest (p < 0.05) TEER values among all treatments, and the supplementations of VC and VE in cells treated with H2O2 showed greater (p < 0.05) TEER values than the supplementations of VA, Cr, Se, and Zn in cells treated with H2O2. In conclusion, Thr, Trp, Gly, and VC supplements were effective in improving cell viability and intestinal barrier function of cIECs exposed to oxidative stress.
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Osteoblasts and osteoclasts play crucial roles in bone formation and bone resorption. We found that plum-derived exosome-like nanovesicles (PENVs) suppressed osteoclast activation and modulated osteoblast differentiation. PENVs increased the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells and osteoblasts from mouse bone marrow cultures. Notably, PENVs elevated the expression of osteoblastic transcription factors and osteoblast differentiation marker proteins in MC3T3-E1 cells. Higher levels of phosphorylated BMP-2, p38, JNK, and smad1 proteins were detected in PENV-treated MC3T3-E1 cells. Additionally, the number of TRAP-positive cells was significantly decreased in PENV-treated osteoclasts isolated from osteoblasts from mouse bone marrow cultures. Importantly, osteoclastogenesis of marker proteins such as PPAR-gamma, NFATc1, and c-Fos were suppressed by treatment with PENVs (50 µg/mL). Taken together, these results demonstrate that PENVs can be used as therapeutic targets for treating bone-related diseases by improving osteoblast differentiation and inhibiting osteoclast activation for the first time.
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Doenças Ósseas , Exossomos , Prunus domestica , Animais , Camundongos , Osteoclastos , Osteoblastos , Diferenciação CelularRESUMO
OBJECTIVE: Chemotherapeutic agents such as docetaxel (DTX) can trigger chemotherapy-induced peripheral neuropathy (CIPN), which is characterized by unbearable pain. This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation (LFMNS) on DTX-induced tactile hypersensitivity in mice. METHODS: To produce CIPN, DTX was administered intraperitoneally 4 times, once every 2 d, to male ICR mice. LFMNS was performed on the wrist area, and the pain response was measured using von Frey filaments on both hind paws. Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brain-derived neurotrophic factor (BDNF). RESULTS: Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area. CONCLUSIONS: LFMNS might be an effective non-pharmaceutical option for treating patients suffering from CIPN regulating the expression of peripheral and central BDNF.
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Antineoplásicos , Doenças do Sistema Nervoso Periférico , Ratos , Camundongos , Masculino , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ratos Sprague-Dawley , Nervo Mediano/metabolismo , Camundongos Endogâmicos ICR , Dor , AnalgésicosRESUMO
Metformin as an oral glucose-lowering drug is used to treat type 2 diabetic mellitus. Considering the relatively high incidence of cardiovascular complications and other metabolic diseases in diabetic mellitus patients, a combination of metformin plus herbal supplements is a preferrable way to improve the therapeutic outcomes of metformin. Ginseng berry, the fruit of Panax ginseng Meyer, has investigated as a candidate in metformin combination mainly due to its anti-hyperglycemic, anti-hyperlipidemic, anti-obesity, anti-hepatic steatosis and anti-inflammatory effects. Moreover, the pharmacokinetic interaction of metformin via OCTs and MATEs leads to changes in the efficacy and/or toxicity of metformin. Thus, we assessed how ginseng berry extract (GB) affects metformin pharmacokinetics in mice, specially focusing on the effect of the treatment period (i.e., 1-day and 28-day) of GB on metformin pharmacokinetics. In 1-day and 28-day co-treatment of metformin and GB, GB did not affect renal excretion as a main elimination route of metformin and GB therefore did not change the systemic exposure of metformin. Interestingly, 28-day co-treatment of GB increased metformin concentration in the livers (i.e., 37.3, 59.3% and 60.9% increases versus 1-day metformin, 1-day metformin plus GB and 28-day metformin groups, respectively). This was probably due to the increased metformin uptake via OCT1 and decreased metformin biliary excretion via MATE1 in the livers. These results suggest that co-treatment of GB for 28 days (i.e., long-term combined treatment of GB) enhanced metformin concentration in the liver as a pharmacological target tissue of metformin. However, GB showed a negligible impact on the systemic exposure of metformin in relation to its toxicity (i.e., renal and plasma concentrations of metformin).
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The objective of the current experiment was to investigate the effects of dietary organic or inorganic iron (Fe) concentrations on productive performance, egg quality, blood measurements, and tissue Fe concentrations in aged laying hens. A total of three hundred fifty 60-week-old Hy-Line Brown laying hens were allotted to one of five dietary treatments with seven replicates. Each replicate had 10 consecutive cages. Organic Fe (Fe-Gly) or inorganic Fe (FeSO4 ) was added to the basal diet at the levels of 100 or 200 mg/kg Fe. Diets were fed on an ad libitum basis for 6 weeks. Results indicated that supplementation of organic or inorganic Fe in diets increased (p < 0.05) eggshell color and feather Fe concentrations compared with no supplementation of Fe in diets. An interaction was found (p < 0.05) between Fe sources and supplemental levels in diets for egg weight, eggshell strength, and Haugh unit. Hens fed diets supplemented with organic Fe had greater (p < 0.05) eggshell color and hematocrit than those fed diets supplemented with inorganic Fe. In conclusion, dietary supplementation of organic Fe increases the eggshell color of aged laying hens. High supplemental levels of organic Fe in diets improve egg weight in aged laying hens.
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Galinhas , Ferro , Animais , Feminino , Óvulo , Dieta , Suplementos Nutricionais , Casca de Ovo , Ração Animal/análiseRESUMO
Insomnia is a common health problem that can lead to various diseases and negatively impact quality of life. Pharmacopuncture is a new type of acupuncture that involves applying herbal medicine extracts to acupoints. Korean medicine doctors frequently use it to treat insomnia disorder. However, there is insufficient evidence to support the effectiveness and safety of pharmacopuncture for insomnia disorder. We designed a pragmatic randomized controlled trial to compare the effectiveness of pharmacopuncture and acupuncture for insomnia disorder. This multi-site, randomized, acupuncture-controlled trial will enroll 138 insomnia patients. The subjects will be randomly assigned to one of two groups, pharmacopuncture or acupuncture, at a 2:1 ratio. For 4 weeks, the participants will receive ten sessions of pharmacopuncture or acupuncture treatment and will be followed up for 4 weeks after the treatment ends. The Pittsburgh Sleep Quality Index score is the primary outcome measure. Insomnia severity index score, sleep parameters recorded using actigraphy and sleep diaries, physical symptoms associated with insomnia, emotions, quality of life, medical costs, and safety are the secondary outcome measures. The findings of this trial willprovide evidence that will be useful in clinical decision-making for insomnia treatment strategies.
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Terapia por Acupuntura , Acupuntura , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/terapia , Qualidade de Vida , Terapia por Acupuntura/métodos , Sono , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Traditional East Asian medicine not only serves as a potential source of drug discovery, but also plays an important role in the healthcare systems of Korea, China, and Japan. Tandem mass spectrometry (MS/MS)-based untargeted metabolomics is a key methodology for high-throughput analysis of the complex chemical compositions of medicinal plants used in traditional East Asian medicine. This Data Descriptor documents the deposition to a public repository of a re-analyzable raw LC-MS/MS dataset of 337 medicinal plants listed in the Korean Pharmacopeia, in addition to a reference spectral library of 223 phytochemicals isolated from medicinal plants. Enhanced by recently developed repository-level data analysis pipelines, this information can serve as a reference dataset for MS/MS-based untargeted metabolomic analysis of plant specialized metabolites.
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Medicina Tradicional do Leste Asiático , Plantas Medicinais , Cromatografia Líquida , Metaboloma , Metabolômica , Espectrometria de Massas em TandemRESUMO
Computational approaches such as genome and metabolome mining are becoming essential to natural products (NPs) research. Consequently, a need exists for an automated structure-type classification system to handle the massive amounts of data appearing for NP structures. An ideal semantic ontology for the classification of NPs should go beyond the simple presence/absence of chemical substructures, but also include the taxonomy of the producing organism, the nature of the biosynthetic pathway, and/or their biological properties. Thus, a holistic and automatic NP classification framework could have considerable value to comprehensively navigate the relatedness of NPs, and especially so when analyzing large numbers of NPs. Here, we introduce NPClassifier, a deep-learning tool for the automated structural classification of NPs from their counted Morgan fingerprints. NPClassifier is expected to accelerate and enhance NP discovery by linking NP structures to their underlying properties.
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Produtos Biológicos/química , Produtos Biológicos/classificação , Redes Neurais de Computação , Vias BiossintéticasRESUMO
Plant-based oil inks that imitate the texture and melting behavior of traditional animal fats using 3D printing have been developed. The influence of the incorporation of potato starch and the type of oil on rheology and meltability was investigated. The results showed that the dynamic modulus and hardness of fat analogs increased, whereas fat analog meltability decreased with an increase in potato starch content. Coconut oil and soybean oil-containing fat analogs incorporated with proper potato starch levels exhibited good printability and similar meltability to commercial beef and pork fats. The addition of potato starch suppressed fat analog meltability as it disrupted the inulin matrix. Fat analogs containing coconut oil could be texturized at temperatures lower than those required for their soybean oil counterparts. The fat analogs were solid at room temperature, demonstrated good printability, and imitated the melting behavior of fat contained in real meat throughout the cooking process.
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Emulsões/química , Géis/química , Tinta , Inulina/química , Amido/química , Substâncias Viscoelásticas/química , Animais , Bovinos , Óleo de Coco/química , Módulo de Elasticidade , Gorduras/química , Congelamento , Temperatura Alta , Impressão Tridimensional , Reologia , Solanum tuberosum/química , Óleo de Soja/química , Suínos , ViscosidadeRESUMO
BACKGROUND: Scalding burn injuries can occur in everyday life but occur more frequently in young children. Therefore, it is important to develop more effective burn treatments. OBJECTIVES: This study examined the effects of bee venom (BV) stimulation on scalding burn injury-induced nociception in mice as a new treatment for burn pain. METHODS: To develop a burn injury model, the right hind paw was immersed temporarily in hot water (65°C, 3 seconds). Immediately after the burn, BV (0.01, 0.02, or 0.1 mg/kg) was injected subcutaneously into the ipsilateral knee area once daily for 14 days. A von Frey test was performed to assess the nociceptive response, and the altered walking parameters were evaluated using an automated gait analysis system. In addition, the peripheral and central expression changes in substance P (Sub P) were measured in the dorsal root ganglion and spinal cord by immunofluorescence. RESULTS: Repeated BV treatment at the 2 higher doses used in this study (0.02 and 0.1 mg/kg) alleviated the pain responses remarkably and recovered the gait performances to the level of acetaminophen (200 mg/kg, intraperitoneal, once daily), which used as the positive control group. Moreover, BV stimulation had an inhibitory effect on the increased expression of Sub P in the peripheral and central nervous systems by a burn injury. CONCLUSIONS: These results suggest that a peripheral BV treatment may have positive potency in treating burn-induced pain.
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Venenos de Abelha/uso terapêutico , Queimaduras/terapia , Manejo da Dor , Dor/prevenção & controle , Substância P/biossíntese , Sistema Nervoso Central/metabolismo , Relação Dose-Resposta a Droga , Sistema Nervoso Periférico/metabolismoRESUMO
Numerous biological treatment techniques have been studied for better management of high-strength livestock urine and manure (LUM) but it is still challenging. To gain an advanced option for LUM management, this study proposes a physicochemical process combining microfiltration (MF) and cold plasma (CP). Experimental design applying single CP, single MF, and the integrated system coupling CP and MF (CP + MF) evaluates the performances of the configurations while reducing hydraulic retention time (HRT) from 3 d to 1 d. Results demonstrate that the CP + MF can maximize the removal efficiencies of total nitrogen (72.4 %), total phosphorus (57.8 %), NH4-N (73.3 %), turbidity (99.1 %), dissolved organic carbon (71.3 %), suspended solids (98.7 %) at HRT 3 d. It was verified that CP, even at the lowest HRT (1 d), significantly reduces membrane resistance (0.4 × 1014 m-1) compared to the control (1.5 × 1014 m-1) which leads to lower transmembrane pressure (TMP, 45.6 kPa) and inclined flux (4.4 L/m2/h) than those of the control (45.6 kPa TMP and 2.2 L/m2/h). These results contribute to the advanced treatment of LUM with a cost-effective and environmentally friendly strategy via technical convergence.
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Gases em Plasma , Animais , Reatores Biológicos , Carbono , Gado , Nitrogênio , FósforoRESUMO
Acupuncture is a well-known traditional medical procedure in Korea and is being increasingly used to treat various conditions including pain control, especially among the older generation. However, several problems related to acupuncture have been reported. A 27-year-old woman expressed that she had back pain occurring despite her posture. She received acupuncture therapy 2 months prior. We discovered a needle-shaped foreign material near the T12 vertebra body in the retroperitoneum. We extracted 2 pieces of deteriorated broken needles by laparoscopy. Postoperatively, the woman was discharged within 5 days with no complications. We report a patient that received laparoscopy with a full recovery after having severe back pain caused by a broken needle which was stuck in the retroperitoneum.
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Using molecular networking-guided isolation, three new galloyl ester triterpenoids (1-3), two new hexahydroxydiphenic acid-conjugated triterpenoids (6 and 7), and four known compounds (4, 5, 8, and 9) were isolated from the fruits and leaves of Castanopsis sieboldii. The chemical structures of 1-3, 6, and 7 were elucidated on the basis of interpreting their NMR, HRESIMS, and ECD spectra. All compounds (1-9) were evaluated for their glucose uptake-stimulating activities in differentiated adipocytes using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose as a fluorescent-tagged glucose probe. Compounds 2 and 9 resulted in a 1.5-fold increase in glucose uptake. Among them, compound 2 from the fruits showed an upregulation of p-AMPK/AMPK ratio in differentiated C2C12 myoblasts to support the mechanism proposed of glucose uptake stimulation.
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Fagaceae/química , Glucose/metabolismo , Triterpenos/farmacologia , Células 3T3 , Adipócitos/efeitos dos fármacos , Animais , Dicroísmo Circular , Frutas/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Extratos Vegetais , Folhas de Planta/química , Espectrometria de Massas por Ionização por Electrospray , Estimulação Química , Triterpenos/isolamento & purificaçãoRESUMO
Residual veterinary antibiotics have been detected in livestock wastewater treatment plants. Despite the long retention time, antibiotic treatment efficiency has shown clear limitations. In this study, we evaluated submerged membrane photobioreactors (SMPBR) during sulfonamide antibiotic-containing livestock wastewater treatment under mixotrophic and photoautotrophic conditions. The results showed that microalgal sulfur degradation and consumption under mixotrophic conditions accelerated the biomass concentration increase to 2800 mg VSS/L compared to the 1800 mg VSS/L measured under photoautotrophic conditions. Although microalgal metabolites, such as soluble microbial products and extracellular polymeric substances, might cause membrane fouling in the SMPBR, we proved that microalgae could remove sulfonamide and release degradation-associated sulfur, along with nitrogen and phosphorus. Moreover, this study confirms the statistical correlation between metabolites and sulfonamides. In summary, the results of this study provide promising insights into antibiotic-containing livestock wastewater treatment.
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Fotobiorreatores , Sulfonamidas/metabolismo , Animais , Biomassa , Gado/metabolismo , Microalgas/metabolismo , Nitrogênio/análise , Fósforo/metabolismo , Sulfanilamida , Águas ResiduáriasRESUMO
Docetaxel, a chemotherapeutic agent used to treat breast cancer, produces a robust painful neuropathy that is aggravated by mechanical and thermal stimuli. This study was undertaken to investigate the analgesic effects of electrical stimulation on docetaxel-induced neuropathic pain in mice and to identify associated changes in ultrasound vocalizations. Peripheral neuropathy was induced with intraperitoneally injected docetaxel (5 mg/kg) on 3 times every 2 days in male ICR mice. Electrical wrist stimulation was administered and pain behavior signs were evaluated by von Frey filaments and thermal stimulation on the hind paw. Ultrasound vocalizations were measured using ultrasound microphones, after electrical stimulation. After mice developed docetaxel-induced neuropathic pain behavior, an electrical stimulation temporarily attenuated mechanical allodynia and thermal hyperalgesia. In formalin and NMDA test, pain-induced mice showed increases in 10-30 kHz ultrasound vocalizations, but not in 30-50 and 50-80 kHz vocalizations. Treatment with docetaxel selectively increased 10-30 kHz ultrasound vocalizations, whereas electrical stimulation caused a meaningful decrease. Moreover, electrical stimulation suppressed the docetaxel-enhanced phosphorylation of the NMDA receptor NR2B subunit in the spinal dorsal horn. These results of the analgesic effect of electrical stimulation in chemotherapy-induced neuropathy could potentially provide a new method to treat and manage peripheral neuropathy in patients with cancer.
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Antineoplásicos/toxicidade , Terapia por Estimulação Elétrica/métodos , Neuralgia/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Medula Espinal/metabolismo , Vocalização Animal/fisiologia , Animais , Docetaxel/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neuralgia/induzido quimicamente , Neuralgia/terapia , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Medula Espinal/efeitos dos fármacos , Vocalização Animal/efeitos dos fármacosRESUMO
OBJECTIVE: Isolated rapid eye movement sleep behavior disorder (iRBD) patients are at risk of cognitive impairments, however the underlying mechanism is still unclear. This study aimed to evaluate thalamo-cortical functional connectivity (FC) using resting-state functional magnetic resonance imaging (fMRI) and its correlation with cognitive dysfunction in patients with iRBD. METHODS: A total 37 polysomnographies (PSGs) confirmed iRBD patients and 15 age-sex matched controls underwent resting-state fMRI and comprehensive neuropsychological assessment. Thalamo-cortical FC was evaluated by using seed-to voxel analysis and was compared between the iRBD and controls. Correlation between the average value of significant clusters and cognitive function scores in iRBD were calculated. RESULTS: Compared to the control subjects, patients with iRBD patients showed cognitive decline in word list recognition (p = 0.016), and constructional recall (p = 0.044). The FC analysis showed increased FC between the left thalamus and occipital regions including the right cuneal cortex, left fusiform gyrus and lingual gyrus (cluster level p < 0.05, corrected for false discovery rate). The averaged thalamo-fusiform FC value positively correlated with word list recognition after adjusting for age and sex (adjusted r = 0.347, p = 0.041). CONCLUSION: Thalamic resting state FC is altered in iRBD patients and is associated with the cognitive function. Enhancement of the thalamo-occipital FC may reflect a compensatory mechanism for cognitive impairment in iRBD.
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Disfunção Cognitiva , Transtorno do Comportamento do Sono REM/fisiopatologia , Tálamo/fisiopatologia , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , PolissonografiaRESUMO
Many natural product chemists are working to identify a wide variety of novel secondary metabolites from natural materials and are eager to avoid repeatedly discovering known compounds. Here, we developed liquid chromatography/mass spectrometry (LC/MS) data-processing protocols for assessing high-throughput spectral data from natural sources and scoring the novelty of unknown metabolites from natural products. This approach automatically produces representative MS spectra (RMSs) corresponding to single secondary metabolites in natural sources. In this study, we used the RMSs of Agrimonia pilosa roots and aerial parts as models to reveal the structural similarities of their secondary metabolites and identify novel compounds, as well as isolation of three types of nine new compounds including three pilosanidin- and four pilosanol-type molecules and two 3-hydroxy-3-methylglutaryl (HMG)-conjugated chromones. Furthermore, we devised a new scoring system, the Fresh Compound Index (FCI), which grades the novelty of single secondary metabolites from a natural material using an in-house database constructed from 466 representative medicinal plants from East Asian countries. We expect that the FCIs of RMSs in a sample will help natural product chemists to discover other compounds of interest with similar chemical scaffolds or novel compounds and will provide insights relevant to the structural diversity and novelty of secondary metabolites in natural products.