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Pig skeletal muscle-derived stem cells (SK-MSCs) were transplanted onto the common peroneal nerve with a collagen tube as a preclinical large animal experiment designed to address long nerve gaps. In terms of therapeutic usefulness, a human family case was simulated by adjusting the major histocompatibility complex to 50% and 100% correspondences. Swine leukocyte antigen (SLA) class I haplotypes were analyzed and clarified, as well as cell transplantation. Skeletal muscle-derived CD34+/45- (Sk-34) cells were injected into bridged tubes in two groups (50% and 100%) and with non-cell groups. Therapeutic effects were evaluated using sedentary/general behavior-based functional recovery score, muscle atrophy ratio, and immunohistochemistry. The results indicated that a two-Sk-34-cell-transplantation group showed clearly and significantly favorable functional recovery compared to a non-cell bridging-only group. Supporting functional recovery, the morphological reconstitution of the axons, endoneurium, and perineurium was predominantly evident in the transplanted groups. Thus, Sk-34 cell transplantation is effective for the regeneration of peripheral nerve gap injury. Additionally, 50% and 100% SLA correspondences were therapeutically similar and not problematic, and no adverse reaction was found in the 50% group. Therefore, the immunological response to Sk-MSCs is considered relatively low. The possibility of the Sk-MSC transplantation therapy may extend to the family members beyond the autologous transplantation.
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Antígenos de Histocompatibilidad Clase I , Músculo Esquelético , Traumatismos de los Nervios Periféricos , Animales , Porcinos , Traumatismos de los Nervios Periféricos/terapia , Antígenos de Histocompatibilidad Clase I/metabolismo , Regeneración Nerviosa , Recuperación de la Función , Trasplante Homólogo , Trasplante de Células Madre Mesenquimatosas/métodos , Trasplante de Células Madre/métodos , HumanosRESUMEN
Corticotropin-releasing factor (CRF) is mainly secreted from the hypothalamic paraventricular nuclei and plays a crucial role in stress-related responses. Recent studies have reported that CRF is a neuromodulator in the central nervous system. In the cerebellum, CRF is essential for the induction of long-term depression (LTD) at the parallel fiber-Purkinje cell synapses. Given that LTD is thought to be one of the fundamental mechanisms of motor learning, CRF may affect motor learning. However, the role of CRF in motor learning in vivo remains unclear. In this study, we aimed to examine the role of CRF in motor learning. This was achieved through a series of behavioral experiments involving the in vivo administration of CRF and its antagonists. Rats injected with CRF directly into the cerebellum exhibited superior performance on the rotarod test, especially during initial training phases, compared to control subjects. Conversely, rats receiving a CRF receptor antagonist demonstrated reduced endurance on the rotating rod compared to controls. Notably, CRF mRNA expression levels in the cerebellum did not show significant variance between the CRF-injected and control groups. These findings imply a critical role of endogenous CRF in cerebellar motor learning and suggest that exogenous CRF can augment this process. (199 words).
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Cerebelo , Hormona Liberadora de Corticotropina , Aprendizaje , Animales , Hormona Liberadora de Corticotropina/metabolismo , Masculino , Ratas , Aprendizaje/fisiología , Aprendizaje/efectos de los fármacos , Cerebelo/metabolismo , Cerebelo/efectos de los fármacos , Cerebelo/fisiología , Actividad Motora/efectos de los fármacos , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Ratas Sprague-DawleyRESUMEN
The DHCR7 enzyme converts 7-DHC into cholesterol. Mutations in DHCR7 can block cholesterol production, leading to abnormal accumulation of 7-DHC and causing Smith-Lemli-Opitz syndrome (SLOS). SLOS is an autosomal recessive disorder characterized by multiple malformations, including microcephaly, intellectual disability, behavior reminiscent of autism, sleep disturbances, and attention-deficit/hyperactivity disorder (ADHD)-like hyperactivity. Although 7-DHC affects neuronal differentiation in ex vivo experiments, the precise mechanism of SLOS remains unclear. We generated Dhcr7 deficient (dhcr7-/-) zebrafish that exhibited key features of SLOS, including microcephaly, decreased neural stem cell pools, and behavioral phenotypes similar to those of ADHD-like hyperactivity. These zebrafish demonstrated compromised myelination, synaptic anomalies, and neurotransmitter imbalances. The axons of the dhcr7-/- zebrafish showed increased lysosomes and attenuated autophagy, suggesting that autophagy-related neuronal homeostasis is disrupted.
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Axones , Colesterol , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Pez Cebra , Animales , Autofagia , Axones/metabolismo , Colesterol/metabolismo , Lisosomas/metabolismo , Neurogénesis , Neuronas/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/deficiencia , Síndrome de Smith-Lemli-Opitz/metabolismo , Síndrome de Smith-Lemli-Opitz/genética , Síndrome de Smith-Lemli-Opitz/patología , Pez Cebra/metabolismo , Pez Cebra/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative therapy. Enzymatically extracted cells were obtained from green-fluorescence transgenic micro-mini pigs (GFP-Tg MMP) and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN) fractions. The ability to differentiate into skeletal muscle, peripheral nerve, and vascular cell lineages was examined via in vitro cell culture and in vivo cell transplantation into the damaged tibialis anterior muscle and sciatic nerves of nude mice and rats. Protein and mRNA levels were analyzed using RT-PCR, immunohistochemistry, and immunoelectron microscopy. The myogenic potential, which was tested by Pax7 and MyoD expression and the formation of muscle fibers, was higher in Sk-DN cells than in Sk-34 cells but remained weak in the latter. In contrast, the capacity to differentiate into peripheral nerve and vascular cell lineages was significantly stronger in Sk-34 cells. In particular, Sk-DN cells did not engraft to the damaged nerve, whereas Sk-34 cells showed active engraftment and differentiation into perineurial/endoneurial cells, endothelial cells, and vascular smooth muscle cells, similar to the human case, as previously reported. Therefore, we concluded that Sk-34 and Sk-DN cells in pigs are closer to those in humans than to those in mice.
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Células Endoteliales , Fibras Musculares Esqueléticas , Ratones , Humanos , Ratas , Animales , Porcinos , Ratones Desnudos , Porcinos Enanos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Diferenciación Celular/genética , Células Madre/metabolismo , Células Cultivadas , Nervio CiáticoRESUMEN
In cells, mRNA synthesis and decay are influenced by each other, and their balance is altered by either external or internal cues, resulting in changes in cell dynamics. We previously reported that it is important that an array of mRNAs that shape a phenotype are degraded before cellular transitions, such as cellular reprogramming and differentiation. In adipogenesis, the interaction between DDX6 and 4E-T had a definitive impact on the pathway in the processing body (PB). We screened a library of α-helix analogs with an alkaloid-like backbone to identify compounds that inhibit the binding between DDX6 and 4E-T proteins, which occurs between the α-helix of structured and internally disordered proteins. IAMC-00192 was identified as a lead compound. This compound directly inhibited the interaction between DDX6 and 4E-T. IAMC-00192 inhibited the temporal increase in PB formation that occurs during adipogenesis and epithelial-mesenchymal transition (EMT) and significantly suppressed these cellular transitions. In the EMT model, the half-life of preexisting mRNAs in PBs was extended twofold by the compound. The novel inhibitor of RNA decay not only represents a potentially useful tool to analyze in detail the pathological conditions affected by RNA decay and how it regulates the pathological state. The identification of this inhibitor may lead to the discovery of a first-in-class RNA decay inhibitor drug.
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Wnt/ß-catenin is believed to regulate different sets of genes with different coactivators, cAMP response element-binding protein (CREB)-binding protein (CBP) or p300. However, the factors that determine which coactivators act on a particular promoter remain elusive. ICG-001 is a specific inhibitor for ß-catenin/CBP but not for ß-catenin/p300. By taking advantage of the action of ICG-001, we sought to investigate regulatory mechanisms underlying ß-catenin coactivator usage in human pancreatic carcinoma PANC-1 cells through combinatorial analysis of chromatin immunoprecipitation-sequencing and RNA-sequencing. CBP and p300 preferentially bound to regions with the TCF motif alone and with both the TCF and AP-1 motifs, respectively. ICG-001 increased ß-catenin binding to regions with both the TCF and AP-1 motifs, flanking the genes induced by ICG-001, concomitant with the increments of the p300 and AP-1 component c-JUN binding. Taken together, AP-1 possibly coordinates ß-catenin coactivator usage in PANC-1 cells. These results would further our understanding of the canonical Wnt/ß-catenin signaling divergence.
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A total of 42 trisubstituted carboranes categorised into five scaffolds were systematically designed and synthesized by exploiting the different reactivities of the twelve vertices of o-, m-, and p-carboranes to cover all directions in chemical space. Significant inhibitors of hypoxia inducible factor transcriptional activitay were mainly observed among scaffold V compounds (e.g., Vi-m, and Vo), whereas anti-rabies virus activity was observed among scaffold V (Va-h), scaffold II (IIb-g), and scaffold IV (IVb) compounds. The pharmacophore model predicted from compounds with scaffold V, which exhibited significant anti-rabies virus activity, agreed well with compounds IIb-g with scaffold II and compound IVb with scaffold IV. Normalized principal moment of inertia analysis indicated that carboranes with scaffolds I-V cover all regions in the chemical space. Furthermore, the first compounds shown to stimulate the proliferation of the rabies virus were found among scaffold V carboranes.
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The smooth pursuit system has the ability to perform predictive feedforward control of eye movements. This study attempted to examine how stimulus and behavioral histories of past trials affect the control of predictive pursuit of target motion with randomized velocities. We used sequential ramp stimuli where the rightward velocity was fixed at 16 deg/s while the leftward velocity was either fixed (predictable) at one of seven velocities (4, 8, 12, 16, 20, 24, or 28 deg/s) or randomized (unpredictable). As a result, predictive pursuit responses were observed not only in the predictable condition but also in the unpredictable condition. Linear mixed-effects (LME) models showed that both stimulus and behavioral histories of the previous two or three trials influenced the predictive pursuit responses in the unpredictable condition. Intriguingly, the goodness of fit of the LME model was improved when both historical effects were fitted simultaneously rather than when each type of historical data was fitted alone. Our results suggest that predictive pursuit systems allow us to track randomized target motion using weighted averaging of the information of target velocity (stimulus) and motor output (behavior) in past time sequences.
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Fijación Ocular/fisiología , Estimulación Luminosa , Seguimiento Ocular Uniforme/fisiología , Tiempo de Reacción/fisiología , Adulto , Femenino , Humanos , MasculinoRESUMEN
A novel sp3 carbon-rich tricyclic 3D scaffold-based peptide mimetic compound library was constructed to target protein-protein interactions. Tricyclic framework 7 was synthesized from 9-azabicyclo[3,3,1]nonan-3-one (11) via a gold(I)-catalyzed Conia-ene reaction. The electron-donating group on the pendant alkyne of cyclization precursor 12 b-e was the key to forming 6-endo-dig cyclized product 7 with complete regioselectivity. Using the synthetic strategy for regioselective construction of bridged tricyclic framework 7, a diazatricyclododecene 3D-scaffold 8 a, which enables the introduction of substituents into the scaffold to mimic amino acid side chains, was designed and synthesized. The peptide mimetics 21 a-u were synthesized via step-by-step installation of three substituents on diazatricyclododecene scaffold 8 a. Compounds 21 a-h were synthesized as α-helix peptide mimics of hydrophobic ZZxxZ and ZxxZZ sequences (Z=Leu or Phe) and subjected to cell-based assays: antiproliferative activity, HIF-1 transcriptional activity which is considered to affect cancer malignancy, and antiviral activity against rabies virus. Compound 21 a showed the strongest inhibitory activity of HIF-1 transcriptional activity (IC50 =4.1±0.8â µM), whereas compounds 21 a-g showed antiviral activity with IC50 values of 4.2-12.4â µM, suggesting that the 3D-scaffold 8 a has potential as a versatile peptide mimic skeleton.
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Peptidomiméticos , Aminoácidos , Ciclización , Humanos , Péptidos/metabolismoRESUMEN
The purpose of this study was to determine whether smooth pursuit eye movements affect visual motion prediction using a time-to-contact task where observers anticipate the exact instant that a partially occluded target would coincide with a stationary object. Moreover, we attempted to clarify the influence of second-order motion on visual motion prediction during smooth pursuit. One target object moved to another stationary object (6 deg apart) at constant velocity of 3, 4, and 5 deg/s, and then the two objects disappeared 500 ms after the onset of target motion. The observers estimated the moment the moving object would overlap the stationary object and pressed a button. For the pursuit condition, both a Gaussian window and a random dots texture moved in the same direction at the same speed for the first-order motion, whereas a Gaussian window moved over a static background composed of random dots texture for the second-order motion. The results showed that the constant error of the time-to-contact shifted to a later response for the pursuit condition compared to the fixation condition, regardless of the object velocity. In addition, during smooth pursuit, the constant error for the second-order motion shifted to an earlier response compared to the first-order motion when the object velocity was 3 deg/s, whereas no significant difference was found at 4 and 5 deg/s. Therefore, our results suggest that visual motion prediction using a time-to-contact task is affected by both eye movements and motion configuration such as second-order motion.
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Percepción de Movimiento/fisiología , Seguimiento Ocular Uniforme , Anticipación Psicológica , Femenino , Humanos , Masculino , Estimulación Luminosa , Tiempo de Reacción , Visión Binocular , Adulto JovenRESUMEN
Endometriosis exhibits unique characteristics, such as fibrosis, resistance to apoptosis, and promotion of cell proliferation; however, its pathophysiology is not fully understood. Recurrence rates after treatment are high, and the progression risk continues until menopause; hence, more effective therapy for endometriosis is needed. CREB-binding protein (CBP)/ß-catenin signaling inhibitors have demonstrated antifibrogenetic effects in liver, lung, and skin diseases. The present study evaluated the effects of two CBP/ß-catenin signaling inhibitors, ICG-001 and C-82, on the progression of endometriosis using endometriotic cyst stromal cells from the ovary and normal endometrial stromal cells from the uterus. ICG-001 was also evaluated in a mouse model. ICG-001 and C-82 inhibited cell proliferation, fibrogenesis, and cell migration, and promoted apoptosis in vitro. ICG-001 inhibited the growth of endometriotic lesions in the mouse model. CBP/ß-catenin signaling plays an important role in the pathophysiology of endometriosis. Inhibiting the CBP/ß-catenin signal can be a therapeutic target for endometriosis.
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Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Endometriosis/tratamiento farmacológico , Compuestos Heterocíclicos con 2 Anillos/uso terapéutico , Piperazinas/uso terapéutico , Pirimidinonas/uso terapéutico , Transducción de Señal/efectos de los fármacos , beta Catenina/antagonistas & inhibidores , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , beta Catenina/metabolismoRESUMEN
BACKGROUND: The canonical Wnt/ß-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of ß-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether ß-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that ß-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
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Long-term depression (LTD) of AMPA-type glutamate receptor (AMPA receptor)-mediated synaptic transmission has been proposed as a cellular substrate for learning and memory. Although activity-induced AMPA receptor endocytosis is believed to underlie LTD, it remains largely unclear whether LTD and AMPA receptor endocytosis at specific synapses are causally linked to learning and memory in vivo. Here we developed a new optogenetic tool, termed PhotonSABER, which enabled the temporal, spatial, and cell-type-specific control of AMPA receptor endocytosis at active synapses, while the basal synaptic properties and other forms of synaptic plasticity were unaffected. We found that fiberoptic illumination to Purkinje cells expressing PhotonSABER in vivo inhibited cerebellar motor learning during adaptation of the horizontal optokinetic response and vestibulo-ocular reflex, as well as synaptic AMPA receptor decrease in the flocculus. Our results demonstrate that LTD and AMPA receptor endocytosis at specific neuronal circuits were directly responsible for motor learning in vivo. VIDEO ABSTRACT.
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Endocitosis/fisiología , Aprendizaje/fisiología , Depresión Sináptica a Largo Plazo/fisiología , Actividad Motora/fisiología , Optogenética/métodos , Receptores AMPA/fisiología , Animales , Células Cultivadas , Células HEK293 , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Técnicas de Cultivo de Órganos , Células de Purkinje/química , Células de Purkinje/fisiología , Receptores AMPA/análisisRESUMEN
Enhanced root growth is known as the survival strategy of plants under drought. Previous proteome analysis in drought-resistant wild watermelon has shown that Ran GTPase, an essential regulator of cell division and proliferation, was induced in the roots under drought. In this study, two cDNAs were isolated from wild watermelon, CLRan1 and CLRan2, which showed a high degree of structural similarity with those of other plant Ran GTPases. Quantitative RT-PCR and promoter-GUS assays suggested that CLRan1 was expressed mainly in the root apex and lateral root primordia, whereas CLRan2 was more broadly expressed in other part of the roots. Immunoblotting analysis confirmed that the abundance of CLRan proteins was elevated in the root apex region under drought stress. Transgenic Arabidopsis overexpressing CLRan1 showed enhanced primary root growth, and the growth was maintained under osmotic stress, indicating that CLRan1 functions as a positive factor for maintaining root growth under stress conditions.
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Citrullus/enzimología , Citrullus/fisiología , Sequías , Raíces de Plantas/crecimiento & desarrollo , Proteína de Unión al GTP ran/metabolismo , Secuencia de Aminoácidos , Arabidopsis/genética , Citrullus/genética , Citrullus/crecimiento & desarrollo , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica de las Plantas , Presión Osmótica , Plantas Modificadas Genéticamente , ARN Mensajero/genética , ARN Mensajero/metabolismo , Agua/metabolismo , Proteína de Unión al GTP ran/química , Proteína de Unión al GTP ran/genéticaRESUMEN
OBJECTIVE: To develop a bioadhesive phosphorescent particle that can be used as a marker in video-oculography to assess eye movements in the dark without drug treatment. METHODS: The marker was prepared by spray-coating a Sr4Al14O25: Eu2+, Dy3+ phosphor with a carboxyvinyl polymer. The morphologic, luminescent and adhesive properties were assessed. The dynamic properties of VOR measured by the marker were compared with those obtained by tracking the pupil under miotic treatment. RESULTS: Non-aggregated and non-fused particles having diameters of about 5µm could be prepared by polymeric coating of the phosphor, resulting in particles small enough not to restrict eye movement. Although the phosphorescent of the particles decreased with increasing thickness of the coating layer, the coated particles were detectable in the dark for at least 60 min. The thicker the coating layer was, the higher the adhesiveness of the particles obtained. The particles having the thickest coating layer were retained on the corneal surface during VOR measurement and thus performed well as a marker in video-oculography. The dynamic properties of VOR measured by the marker were essentially identical to those obtained by tracking the pupil under miotic treatment. CONCLUSION: Our marker will contribute to understanding the mechanisms underlying motor learning.
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Técnicas de Diagnóstico Oftalmológico , Movimientos Oculares/fisiología , Mediciones Luminiscentes/métodos , Grabación en Video/métodos , Adhesividad , Animales , Biomarcadores/análisis , Córnea , Oscuridad , Ratones Endogámicos C57BL , Tamaño de la Partícula , PolimerizacionRESUMEN
It has been suggested that the DGCR2 gene plays a role in the pathogenesis of 22q11.2 deletion syndrome. To analyze its function, we used our Dgcr2-knock-out/EGFP-knock-in mice (Dgcr2-KO mice). At 20-26 weeks of age, approximately 20% of Dgcr2-KO mice showed gait abnormalities with trembling and difficulty in balancing. Footprint test revealed awkward movements in Dgcr2-KO mice soon after they were placed on the floor. Once they started walking, their stride lengths were not different from wild-type mice. In short-term open field test, Dgcr2-KO mice travelled a significantly shorter distance and walked more slowly than wild-type mice during the initial 5 min after being placed in a new environment. In long-term open field test, Dgcr2-KO mice exhibited reduced cage activity compared to wild-type mice on the first day, but not on later days. Dgcr2-KO mice showed reduced latency to fall in the rotarod test, and the latency was not improved in the 3-day test. Histology revealed sparseness of cerebellar Purkinje cells in Dgcr2-KO mice. Our results suggest that Dgcr2 plays a role in motor control related to Purkinje cell function and that the deficiency of DGCR2 contributes at least to some of the symptoms of patients of 22q11.2 deletion syndrome.
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The combined total annual yield of six major crops (maize, rice, wheat, cassava, soybean, and potato; Solanum tuberosum L.) amounts to 3.1 billion tons. In recent years, staple crops have begun to be used as substitutes for fossil fuel and feedstocks. The diversion of crop products to fuels and industrial feedstocks has become a concern in many countries because of competition for arable lands and increased food prices. These concerns are definitely justified; however, if plant biotechnology succeeds in increasing crop yields to double the current yields, it will be possible to divert the surplus to purposes other than food without detrimental effects. Maize, rice, wheat, and soybean bear their sink organs in the aerial parts of the plant, and potato in the underground parts. Plants with aerial storage organs cannot accumulate products beyond their capacity to support the weight of these organs. In contrast, potato has heavy storage organs that are supported by the soil. In this mini-review, we introduce strategies of intensifying potato productivity and discuss recent advances in this research area.
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INTRODUCTION: An essential complement to molecular-genetic approaches for analyzing the function of the oculomotor circuitry in mice is an understanding of sensory and motor signal processing in the circuit. Although there has been extensive analysis of the signals carried by neurons in the oculomotor circuits of species, such as monkeys, rabbits and goldfish, relatively little in vivo physiology has been done in the oculomotor circuitry of mice. We analyzed the contribution of vestibular and nonvestibular signals to the responses of individual Purkinje cells in the cerebellar flocculus of mice. METHODS: We recorded Purkinje cells in the cerebellar flocculus of C57BL/6 mice during eye movement responses to vestibular and visual stimulation. RESULTS: As in other species, most individual Purkinje cells in mice carried both vestibular and nonvestibular signals, and the most common response across cells was an increase in firing in response to ipsiversive eye movement or ipsiversive head movement. When both the head and eyes were moving, the Purkinje cell responses were approximated as a linear summation of head and eye velocity inputs. Unlike other species, floccular Purkinje cells in mice were considerably more sensitive to eye velocity than head velocity. CONCLUSIONS: The signal content of Purkinje cells in the cerebellar flocculus of mice was qualitatively similar to that in other species. However, the eye velocity sensitivity was higher than in other species, which may reflect a tuning to the smaller range of eye velocities in mice.
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Potenciales de Acción/fisiología , Movimientos Oculares/fisiología , Movimientos de la Cabeza/fisiología , Células de Purkinje/fisiología , Reflejo Vestibuloocular , Animales , Fenómenos Electrofisiológicos/fisiología , Ratones , Ratones Endogámicos C57BL , Nervio Oculomotor/fisiología , Estimulación Luminosa , Estimulación FísicaRESUMEN
The commercial quality of Japanese Angelica radices -- Angelica acutiloba Kitagawa (Yamato-toki) and A. acutiloba Kitagawa var. sugiyama Hikino (Hokkai-toki) -- used in Kampo traditional herbal medicines, was studied by use of omics technologies. Complementary and alternative medical providers have observed in their clinical experience that differences in radix commercial quality reflect the differences in pharmacological responses; however, there has been little scientific examination of this phenomenon. The approach of omics, including metabolomics, transcriptomics, genomics, and informatics revealed a distinction between the radix-quality grades based on their metabolites, gene expression in human subjects, and plant genome sequences. Systems biology, constructing a network of omics data used to analyze this complex system, is expected to be a powerful tool for enhancing the study of radix quality and furthering a comprehensive understanding of all medicinal plants.
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Angelica , Medicamentos Herbarios Chinos/normas , Proyectos de Investigación , Biología de Sistemas , Angelica/genética , Animales , Genómica , Humanos , Informática , Medicina Kampo , Metabolómica , Raíces de Plantas , Plantas Medicinales , TranscriptomaRESUMEN
Metabolic syndrome and the accompanied diabetes mellitus are both important diseases worldwide due to changes of lifestyle and eating habits. The number of patients with diabetes worldwide is estimated to increase to 300 million by 2025 from 150-220 million in 2010. There are two main types of diabetes. In type 1 diabetes, caused by destruction of pancreatic ß-cells resulting in absolute deficiency of intrinsic insulin secretion, the patients require exogenous insulin injections several times a day. In type 2 diabetes, characterized by insulin resistance and abnormal insulin secretion, the patients need exercise, diet control and/or several types of hypoglycemics. The idea of using metal ions for the treatment of diabetes originates from the report in 1899. The research on the role of metal ions that may contribute to the improvement of diabetes began. The orally active metal complexes containing vanadyl (oxidovanadium(iv)) ion and cysteine or other ligands were first proposed in 1990, and a wide class of vanadium, copper and zinc complexes was found to be effective for treating diabetes in experimental animals. We noticed a characteristic compound, allixin, which is a non-sulfur component in dry garlic. Its vanadyl and zinc complexes improved both types of diabetes following oral administration in diabetic animals. We then developed a new zinc complex with thioxoallixin-N-methyl (tanm), which is both a sulfur and N-methyl derivative of allixin, and found that this complex improves not only diabetes but also metabolic syndrome. Furthermore, new zinc complexes inspired from the zinc-tanm were prepared; one of them exceeded the activity of zinc-tanm. The mechanism of such complexes was studied in adipocytes. We describe here the usefulness of the development of metal-based complexes in the context of potential therapeutic application for diabetes and metabolic syndrome.