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Ethnopharmacological Relevance. Atopic dermatitis is a chronic inflammatory skin disease. Lagerstroemia ovalifolia Teijsm. & Binn. (LO) has traditionally been used as an herbal medicine for anti-inflammatory diseases. The effect of LO on atopic dermatitis has not been verified scientifically. We investigated the effects of CHCl3 fraction number 5 of LO (LOC) on atopic dermatitis through cell-based experiments. HaCaT cells were treated with tumor necrosis factor-alpha (TNFα)/interferon-gamma (IFNγ) to induce an inflammatory reaction. Proinflammatory cytokines, interleukin- (IL-) 6, IL-8, and IL-1ß and chemokines such as thymus and activation-regulated chemokine (TARC/CCL17), monocyte chemoattractant protein 1 (MCP1/CCL2), and macrophage-derived chemokine (MDC/CCL22) were measured by RT-PCR and ELISA. In addition, the degree of phosphorylation and activation of JAK/STAT1, PI3K/AKT, and nuclear factor-kappa B (NF-κB) were measured by western blot and luciferase assays. The production of inflammatory cytokines and chemokines and activation of the JAK/STAT1, PI3K/AKT, and NF-κB pathways were induced by TNFα/IFNγ in HaCaT cells. Under these conditions, LOC treatment inhibited the production of targeted cytokines and chemokines and decreased the phosphorylation and activation of JAK/STAT1, PI3K/AKT, and NF-κB. These results suggest that LOC reduces the production of proinflammatory cytokines and chemokines by suppressing the JAK/STAT1, PI3K/AKT, and NF-κB pathways. Therefore, LOC may have potential as a drug for atopic dermatitis.
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Background The heterogeneous composition of substantia nigra (SN), including iron, nigrosome-1 substructure, and myelinated white matter, complicates the interpretation of MRI signals. Purpose To investigate R2* and quantitative susceptibility mapping (QSM) in the SN subdivisions of participants with Parkinson disease and healthy control subjects. Materials and Methods In this prospective study conducted from November 2018 to November 2019, participants with Parkinson disease and sex-matched healthy control subjects underwent 3-T MRI. R2* and QSM values were measured and compared in the anterior SN and posterior SN at the rostral (superior) and caudal (inferior) levels. Postmortem MRI and histology correlation of midbrain tissues was evaluated to investigate the effect of myelin and iron in the SN on R2* and QSM values. Results Forty individuals were evaluated: 20 healthy control subjects (mean age, 61 years ± 3 [standard deviation]; 10 men) and 20 participants with Parkinson disease (mean age, 61 years ± 4; 10 men). The R2* values of participants with Parkinson disease were higher in all subdivisions of the SN compared with R2* values in healthy control subjects (all P < .05). For QSM, no evidence of a difference was found in the rostral posterior SN (healthy control subjects, 54.1 ppb ± 21.0; Parkinson disease, 62.2 ppb ± 19.8; P = .49). The combination of rostral R2* and caudal QSM values resulted in an area under the receiver operating characteristic curve of 0.84. R2* values showed higher correlation with QSM values at the caudal level than at the rostral level within each group (all P < .001). Postmortem investigation demonstrated that R2* and QSM values showed weak correlation in the myelin-rich areas (r = 0.22 and r = 0.36, P < .001) and strong correlation in myelin-scanty areas (r ranged from approximately 0.52 to approximately 0.78, P < .001) in the SN. Conclusion Considering the iron and myelin distribution in the substantia nigra subdivisions, the subdivisional analysis of substantia nigra using R2* and quantitative susceptibility mapping might aid in specifically differentiating individuals with Parkinson disease from healthy control subjects. © RSNA, 2021 Online supplemental material is available for this article.
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Hierro/metabolismo , Imagen por Resonancia Magnética/métodos , Vaina de Mielina/metabolismo , Enfermedad de Parkinson/diagnóstico por imagen , Sustancia Negra/diagnóstico por imagen , Sustancia Negra/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/metabolismo , Estudios ProspectivosRESUMEN
OBJECTIVE: The purpose of this study was to conduct a systematic review and meta-analysis of the effects of acupuncture on humeral fractures. METHODS: Randomized controlled trials were searched systematically from inception to January 2020 using the Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and 7 Korean databases. Pain scale and Japanese Orthopaedic Association scores were the primary and secondary measurements. A risk-of-bias assessment and meta-analysis were conducted. RESULTS: Seven randomized controlled trials were included in the systematic review; the quality of the studies was ambiguous. The meta-analysis showed that acupuncture improved the pain severity score compared with conventional therapies (standard mean differenceâ¯=â¯-4.55, 95% confidence interval, -7.48 to -1.61, I2â¯=â¯98%, P < .00001) but did not improve the Japanese Orthopaedic Association score (standard mean differenceâ¯=â¯4.99, 95% confidence interval, -0.31 to 10.30, I2â¯=â¯99%, P < .00001). CONCLUSION: Our meta-analysis shows that acupuncture reduced pain after proximal humeral fracture, in addition to common rehabilitative modalities. However, the conclusion of this review should be cautiously applied in clinical practice owing to the low quality of the included studies.
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Terapia por Acupuntura/métodos , Fracturas del Húmero/rehabilitación , Dolor Musculoesquelético/rehabilitación , China , Humanos , Dimensión del Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de InvestigaciónRESUMEN
In vivo real-time monitoring of neuronal activities in freely moving animals is one of key approaches to link neuronal activity to behavior. For this purpose, an in vivo imaging technique that detects calcium transients in neurons using genetically encoded calcium indicators (GECIs), a miniaturized fluorescence microscope, and a gradient refractive index (GRIN) lens has been developed and successfully applied to many brain structures1 , 2 , 3 , 4 , 5 , 6. This imaging technique is particularly powerful because it enables chronic simultaneous imaging of genetically defined cell populations for a long-term period up to several weeks. Although useful, this imaging technique has not been easily applied to brain structures that locate deep within the brain such as amygdala, an essential brain structure for emotional processing and associative fear memory7. There are several factors that make it difficult to apply the imaging technique to the amygdala. For instance, motion artifacts usually occur more frequently during the imaging conducted in the deeper brain regions because a head-mount microscope implanted deep in the brain is relatively unstable. Another problem is that the lateral ventricle is positioned close to the implanted GRIN lens and its movement during respiration may cause highly irregular motion artifacts that cannot be easily corrected, which makes it difficult to form a stable imaging view. Furthermore, because cells in the amygdala are usually quiet at a resting or anesthetized state, it is hard to find and focus the target cells expressing GECI in the amygdala during baseplating procedure for later imaging. This protocol provides a helpful guideline for how to efficiently target cells expressing GECI in the amygdala with head-mount miniaturized microscope for successful in vivo calcium imaging in such a deeper brain region. It is noted that this protocol is based on a particular system (e.g., Inscopix) but not restricted to it.
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Amígdala del Cerebelo/diagnóstico por imagen , Conducta Animal/fisiología , Calcio/metabolismo , Microscopía/instrumentación , Miniaturización/instrumentación , Estimulación Acústica , Animales , Artefactos , Proteínas de Unión al Calcio/metabolismo , Proteínas Fluorescentes Verdes/metabolismo , Cabeza , Lentes , Ratones Endogámicos C57BL , Movimiento , Neuroimagen , Neuronas/metabolismo , Refractometría , Reproducibilidad de los Resultados , Técnicas EstereotáxicasRESUMEN
Visualizing gradual changes in neuromelanin distribution within the substantia nigra is an important metric used to monitor the progression of Parkinsonism. This study aimed to identify the origin of the mismatch region between magnetic resonance transverse relaxation times (T2 and T2*) in the substantia nigra and investigate its feasibility and implications for in vivo detection of neuromelanin as a clinical biomarker. The relationships between neuromelanin distribution assessed by histological staining and the area of T2 and T2* mismatch determined by high- and low-resolution magnetic resonance relaxometry at 7T were directly compared in two normal and one depigmented substantia nigra collected at postmortem. In vivo feasibility of assessing T2 and T2* mismatch, clinically, was investigated using 3T magnetic resonance imaging. In the normal postmortem substantia nigra tissue, the T2 and T2* mismatch region exhibiting a linear pattern was strongly colocalized with neuromelanin distribution along the dorsal substantia nigra pars compacta, but a negligible amount of dorsal mismatch was observed in the depigmented brain. The regions of T2 and T2* mismatch from MRI, neuromelanin pigments from histology, and elevated iron signals from mass spectrometry were spatially overlapped for a normal postmortem brain. In preliminary in vivo studies, a similar, linear T2 and T2* mismatch region was observed in the dorsal area of the substantia nigra in eight normal subjects; this mismatch was significantly obscured in eight Parkinson's disease patients. The length of the dorsal linear mismatch line based on the T2*-T2 mask was significantly shorter in the Parkinson's disease patients compared to normal controls; this result was corroborated by reduced striatal uptake of [18F] FP-CIT dopamine transporters assessed by positron emission tomography scans. In conclusion, the measurement of T2 and T2* mismatch could serve as a complementary imaging biomarker to visualize the dorsal region of the substantia nigra pars compacta, which contains large amounts of neuromelanin.
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Progresión de la Enfermedad , Imagen por Resonancia Magnética/métodos , Melaninas , Neuroimagen/métodos , Enfermedad de Parkinson/diagnóstico por imagen , Porción Compacta de la Sustancia Negra/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Biomarcadores , Diagnóstico , Estudios de Factibilidad , Femenino , Humanos , Melaninas/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Porción Compacta de la Sustancia Negra/metabolismo , Porción Compacta de la Sustancia Negra/patologíaRESUMEN
Cedrela odorata L. is a native plant of the Amazon region. The bark is used in folk remedies for the treatment of diarrhea, vomiting, fever and inflammation. Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease accompanied by itching. It is a complex disease involving environmental factors and genetic factors. In the present study, the anti-inflammatory and anti-allergic effects of C. odorata L. methanol extract (COEE) on tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated HaCaT keratinocyte cells were investigated. ELISA and RT-PCR analysis revealed that the extract had anti-inflammatory effects, and reduced the interleukin (IL)-6 and IL-8 levels of the HaCaT cells. In addition, COEE exhibited anti-allergic effects, comprising a reduction in the thymus and activation-regulated chemokine and macrophage-derived chemokine levels. In addition, pathway analysis and comparison with Bay11-7082 indicated that these effects are due to the inhibition of nuclear factor (NF)-κB in TNF-α/IFN-γ-induced HaCaT cells. Therefore, the results of the present study suggest that COEE has anti-inflammatory and anti-allergic properties in TNF-α and IFN-γ-stimulated HaCaT cells, which are associated with the inhibition of pro-inflammatory cytokines and chemokines via the NF-κB pathway.
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Rhododendron album Blume (RA) has traditionally been used as an herbal medicine and is considered to have antiinflammatory properties. It is a wellknown medicine for treatment of allergic or atopic diseases. In the present study, the biological effects of an RA methanol extract (RAME) on inflammation were investigated in tumor necrosis factorα (TNFα)/interferonγ (IFNγ)stimulated human keratinocytes. The present study aimed to investigate the potential mechanisms by which RAME inhibited TNFα/IFNγinduced expression of chemokines [thymus and activation-regulated chemokine (TARC) and macrophagederived chemokine (MDC)] and cytokines [interleukin (IL)6 and IL8] through the nuclear factorκB (NFκB) pathway in human keratinocytes. The effects of RAME treatment on cell viability were investigated in TNFα/IFNγstimulated HaCaT cells. The expression of TARC, MDC, IL6 and IL8 was assessed using reverse transcriptionquantitative polymerase chain reaction analysis or ELISA, and its effect on the inhibitory mitogen-activated protein kinase pathway was also studied using western blot analysis. TNFα/IFNγ induced the expression of IL6, IL8, TARC and MDC in a dosedependent manner through NFκB and Janus kinase/signal transducers and activators of transcription (JAK/STAT) activation. Notably, treatment with RAME significantly suppressed TNF-α/IFN-γ-induced expression of IL6, IL8, TARC, and MDC. In addition, RAME treatment inhibited the activation of NFκB and the JAK/STAT pathway in TNFα/IFNγinduced HaCaT cells. These results suggest that RAME decreases the production of chemokines and proinflammatory cytokines by suppressing the NFκB and the JAK/STAT pathways. Consequently, RAME may potentially be used for treatment of atopic dermatitis.
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Interferón gamma/farmacología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Rhododendron/química , Factores de Transcripción STAT/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Electroforesis en Gel de Poliacrilamida , Humanos , Inmunohistoquímica , Extractos Vegetales/químicaRESUMEN
Castanea extracts are known to have antioxidant properties and are used as a traditional medicine in China and Asia. However, the biological activity of Castanea seguinii Dode has remained to be fully elucidated. The present study investigated the anti-inflammatory effects of a Castanea seguinii Dode methanolic extract (CSME) on lipopolysaccharide-induced RAW264.7 macrophage cells. CSME inhibited the production of nitric oxide (NO) and the expression of inducible NO synthase. It also suppressed the production of the pro-inflammatory cytokines inteleukin-6 and tumor necrosis factor-α, as well as chemokine monocyte chemoattractant protein 1. In addition, CSME inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, while also downregulating transcription factor activator protein-1. Furthermore, CSME increased heme oxygenase 1 through the upregulation of NF (erythroid-derived 2)-like-2 (Nrf-2), which directly or indirectly affects inflammation. It also increased the phosphorylation of 5'-adenosine monophosphate-activated protein kinase (AMPK). In conclusion, CSME was demonstrated to exert its anti-inflammatory activities through the inhibition of the NF-κB and the MAPK signaling pathways, as well as the activation of Nrf-2 and AMPK. These results indicated that CSME may be a promising for development as a commercial anti-inflammatory medicine.
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Fagaceae/química , Inflamación/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Quinasas de la Proteína-Quinasa Activada por el AMP , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/genética , Humanos , Inflamación/genética , Inflamación/patología , Ratones , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Factor 2 Relacionado con NF-E2/genética , Extractos Vegetales/química , Proteínas Quinasas/genética , Células RAW 264.7 , Transducción de Señal/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa japonica Thunb. (CJT) is traditionally used as an herbal remedy for the treatment of inflammatory diseases in Korea, China, and Japan. In this study, we evaluated the effects of C. japonica Thunb. (CJT) on the development of COPD using a Cigarette smoke (CS)-induced murine model and cigarette smoke condensate (CSC)-stimulated H292 cells, human pulmonary mucoepidermoid cell line. MATERIAL AND METHODS: C. japonica Thunb. was isolated from the leaves and stem of C. japonica. The methanol extract profile was obtained by UPLC Q-TOF-MS analysis. In in vivo experiment, the mice received 1h of cigarette smoke for 10 days. C. japonica Thunb. was administered to mice by oral gavage 1h before cigarette smoke exposure for 10 days. In in vitro experiment, we evaluated the effect of C. japonica Thunb. on the expression of MUC5AC and proinflammatory cytokines in H292 cells stimulated with CSC. RESULTS: CJT treatment effectively suppressed the infiltration of neutrophils, and decreased the production of ROS and the activity of neutrophil elastase in the bronchoalveolar lavage fluid (BALF) induced by CS. CJT also significantly attenuated production of proinflammatory cytokines such as IL-6 and TNF-α in the BALF, and reduced the infiltration of inflammatory cells and the production of mucus in lung tissue induced by CS. In in vitro experiments, CJT decreased the expression of MUC5AC and proinflammatory cytokines in CSC-stimulated H292 cells. Furthermore, CJT attenuated the phosphorylation of ERK induced by CSC in H292 cells. Taken together, CJT effectively reduced the neutrophil airway inflammation and mucus secretion induced by CS in murine model, and inhibited the expression of MUC5AC in CSC-stimulated H292 human lung cell line. These findings suggest that CJT has a therapeutic potential for the treatment of COPD.
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Callicarpa , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Humo/efectos adversos , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Línea Celular , Línea Celular Tumoral , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Interleucina-6/inmunología , Elastasa de Leucocito/metabolismo , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones Endogámicos C57BL , Moco/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Hojas de la Planta , Tallos de la Planta , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Especies Reactivas de Oxígeno/metabolismo , Nicotiana , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Pentylenetetrazol (PTZ) has been shown to induce seizure-like behavior, learning deficits in passive avoidance response test, and an increase in hsp70 (heat shock protein 70) mRNA expression in the adult zebrafish; PTZ has been increasingly appreciated as an excellent model system for the study of seizures. In this study, we demonstrate that valproic acid (VPA), an antiepileptic drug, suppresses seizure-like behavior and improves learning ability in adult zebrafish treated with PTZ. Pretreatment with VPA significantly reduces rapid involuntary movement and abrupt changes in moving direction in the PTZ-treated zebrafish. PTZ-induced learning impairments were also improved in the zebrafish pretreated with 200 or 500 microM VPA. However, the scopolamine-induced impairments of learning ability were not improved by VPA pretreatment. It is worth noting that while the zebrafish treated with 500 microM VPA for 1-3 weeks learned the passive avoidance response, those treated with 1 or 2mM VPA for 3h didn't. Furthermore, the increased level of hsp70 expression induced by PTZ, a stress marker protein, was significantly reduced in the VPA-pretreated zebrafish brains. Collectively, our data show the antiepileptic effects of VPA in the adult zebrafish, which coincides with reduced hsp70 mRNA expression, rescued learning impairment under PTZ-treated conditions.