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CD2-Associated protein (CD2AP) is a candidate susceptibility gene for Alzheimer's disease, but its role in the mammalian central nervous system remains largely unknown. We show that CD2AP protein is broadly expressed in the adult mouse brain, including within cortical and hippocampal neurons, where it is detected at pre-synaptic terminals. Deletion of Cd2ap altered dendritic branching and spine density, and impaired ubiquitin-proteasome system activity. Moreover, in mice harboring either one or two copies of a germline Cd2ap null allele, we noted increased paired-pulse facilitation at hippocampal Schaffer-collateral synapses, consistent with a haploinsufficient requirement for pre-synaptic release. Whereas conditional Cd2ap knockout in the brain revealed no gross behavioral deficits in either 3.5- or 12-month-old mice, Cd2ap heterozygous mice demonstrated subtle impairments in discrimination learning using a touchscreen task. Based on unbiased proteomics, partial or complete loss of Cd2ap triggered perturbation of proteins with roles in protein folding, lipid metabolism, proteostasis, and synaptic function. Overall, our results reveal conserved, dose-sensitive requirements for CD2AP in the maintenance of neuronal structure and function, including synaptic homeostasis and plasticity, and inform our understanding of possible cell-type specific mechanisms in Alzheimer's Disease.
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Background: The interaction between pyroptosis-a form of programmed cell death-and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in cancer: it can both promote tumor development and counteract it by activating immune responses that inhibit tumor evasion and encourage cell death. Current tumor immunotherapy strategies, notably CAR-T cell therapy and immune checkpoint inhibitors (ICIs), alongside the potential of certain traditional Chinese medicinal compounds, highlight the intricate relationship between pyroptosis and cancer immunity. As research delves deeper into pyroptosis mechanisms within tumor therapy, its application in enhancing tumor immune responses emerges as a novel research avenue. Purpose: This review aims to elucidate the mechanisms underlying pyroptosis, its impact on tumor biology, and the advancements in tumor immunotherapy research. Methods: A comprehensive literature review was conducted across PubMed, Embase, CNKI, and Wanfang Database from the inception of the study until August 22, 2023. The search employed keywords such as "pyroptosis", "cancer", "tumor", "mechanism", "immunity", "gasdermin", "ICB", "CAR-T", "PD-1", "PD-L1", "herbal medicine", "botanical medicine", "Chinese medicine", "traditional Chinese medicine", "immunotherapy", linked by AND/OR, to capture the latest findings in pyroptosis and tumor immunotherapy. Results: Pyroptosis is governed by a complex mechanism, with the Gasdermin family playing a pivotal role. While promising for tumor immunotherapy application, research into pyroptosis's effect on tumor immunity is still evolving. Notably, certain traditional Chinese medicine ingredients have been identified as potential pyroptosis inducers, meriting further exploration. Conclusion: This review consolidates current knowledge on pyroptosis's role in tumor immunotherapy. It reveals pyroptosis as a beneficial factor in the immunotherapeutic landscape, suggesting that leveraging pyroptosis for developing novel cancer treatment strategies, including those involving traditional Chinese medicine, represents a forward-looking approach in oncology.
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Imunoterapia , Neoplasias , Piroptose , Piroptose/imunologia , Piroptose/efeitos dos fármacos , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Imunoterapia/métodos , Animais , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacosRESUMO
Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase (RTK) primarily expressed in hematopoietic stem cells and dendritic cells (DCs). While FLT3 plays a critical role in the proliferation, development and maintenance of DCs, thus influencing immune responses under both normal and pathological conditions, there also exists some evidence that FLT3+DC may be involved with immune responses in liver transplantation (LT). In this study, results from single-cell sequencing data analysis revealed a clear relationship between FLT3+DCs and Regulatory T cells (Tregs) in liver tissue of LT recipients. In peripheral blood samples of LT patients, levels of FLT3+DCs were decreased post-LT-surgery, while Tregs were increased. In a LT mouse model, levels of FLT3+DCs in the liver and bone marrow exhibited an initial time-dependent decrease followed by an increase after LT surgery. Results as obtained with co-culture experiments using mature BMDCs and CD4+ T cells revealed fluctuations in Tregs in response to FLT3 inhibitors and the FLT3 ligand. These findings suggest that FLT3+DCs could emerge as a novel target for mitigating immune rejection in LT.
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Células Dendríticas , Rejeição de Enxerto , Transplante de Fígado , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores , Tirosina Quinase 3 Semelhante a fms , Linfócitos T Reguladores/imunologia , Animais , Células Dendríticas/imunologia , Tirosina Quinase 3 Semelhante a fms/metabolismo , Humanos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Masculino , Camundongos , Fígado/imunologia , Feminino , Técnicas de Cocultura , Pessoa de Meia-Idade , Células Cultivadas , Camundongos Endogâmicos BALB C , Proteínas de MembranaRESUMO
Background: Quercetin, a widespread polyphenolic flavonoid, is known for its extensive health benefits and is commonly found in the plant kingdom. The natural occurrence and extraction methods of quercetin are crucial due to its bioactive potential. Purpose: This review aims to comprehensively cover the natural sources of quercetin, its extraction methods, bioavailability, pharmacokinetics, and its role in various cell death pathways and liver fibrosis. Methods: A comprehensive literature search was performed across several electronic databases, including PubMed, Embase, CNKI, Wanfang database, and ClinicalTrials.gov, up to 10 February 2024. The search terms employed were "quercetin", "natural sources of quercetin", "quercetin extraction methods", "bioavailability of quercetin", "pharmacokinetics of quercetin", "cell death pathways", "apoptosis", "autophagy", "pyroptosis", "necroptosis", "ferroptosis", "cuproptosis", "liver fibrosis", and "hepatic stellate cells". These keywords were interconnected using AND/OR as necessary. The search focused on studies that detailed the bioavailability and pharmacokinetics of quercetin, its role in different cell death pathways, and its effects on liver fibrosis. Results: This review details quercetin's involvement in various cell death pathways, including apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis, with particular attention to its regulatory influence on apoptosis and autophagy. It dissects the mechanisms through which quercetin affects these pathways across different cell types and dosages. Moreover, the paper delves into quercetin's effects on liver fibrosis, its interactions with hepatic stellate cells, and its modulation of pertinent signaling cascades. Additionally, it articulates from a physical organic chemistry standpoint the uniqueness of quercetin's structure and its potential for specific actions in the liver. Conclusion: The paper provides a detailed analysis of quercetin, suggesting its significant role in modulating cell death mechanisms and mitigating liver fibrosis, underscoring its therapeutic potential.
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Purpose: This research investigated the impact of the COVID-19 pandemic on the mental well-being and sleep quality of students in higher vocational colleges in Sichuan, China, identifying key factors influencing their psychological health during this period. Methods: Between January and February 2022, a comprehensive survey was conducted among students from several higher vocational colleges in Sichuan, utilizing a randomized selection approach to involve 3,300 participants. Data were collected through direct interviews executed by skilled interviewers. Results: Out of 3,049 valid responses, a significant number reported experiencing symptoms of poor mental health, anxiety, depression, and insomnia, with prevalence rates of 21.2%, 9.7%, 14.1%, and 81.9%, respectively. Factors contributing positively to mental health and sleep included a higher family economic status, reduced stress from the pandemic, and decreased online activity. Conversely, lack of physical activity post-pandemic, disruptions to education and employment, and deteriorating relationships emerged as negative influencers. Interestingly, a lack of pre-pandemic mental health knowledge acted as a protective factor against insomnia. Conclusion: The ongoing management of COVID-19 has notably influenced the psychological and sleep health of vocational college students, driven by economic, emotional, lifestyle, and educational factors. The findings underscore the necessity for targeted interventions to address these challenges effectively.
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COVID-19 , Saúde Mental , Distúrbios do Início e da Manutenção do Sono , Qualidade do Sono , Estudantes , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , China/epidemiologia , Masculino , Estudantes/psicologia , Feminino , Universidades , Adulto Jovem , Adulto , Inquéritos e Questionários , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Depressão/epidemiologia , Ansiedade/epidemiologia , Adolescente , SARS-CoV-2 , PrevalênciaRESUMO
Xenotransplantation is emerging as a vital solution to the critical shortage of organs available for transplantation, significantly propelled by advancements in genetic engineering and the development of sophisticated immunosuppressive treatments. Specifically, the transplantation of kidneys from genetically engineered pigs into human patients has made significant progress, offering a potential clinical solution to the shortage of human kidney supply. Recent trials involving the transplantation of these modified porcine kidneys into deceased human bodies have underscored the practicality of this approach, advancing the field towards potential clinical applications. However, numerous challenges remain, especially in the domains of identifying suitable donor-recipient matches and formulating effective immunosuppressive protocols crucial for transplant success. Critical to advancing xenotransplantation into clinical settings are the nuanced considerations of anesthesia and surgical practices required for these complex procedures. The precise genetic modification of porcine kidneys marks a significant leap in addressing the biological and immunological hurdles that have traditionally challenged xenotransplantation. Yet, the success of these transplants hinges on the process of meticulously matching these organs with human recipients, which demands thorough understanding of immunological compatibility, the risk of organ rejection, and the prevention of zoonotic disease transmission. In parallel, the development and optimization of immunosuppressive protocols are imperative to mitigate rejection risks while minimizing side effects, necessitating innovative approaches in both pharmacology and clinical practices. Furthermore, the post-operative care of recipients, encompassing vigilant monitoring for signs of organ rejection, infectious disease surveillance, and psychological support, is crucial for ensuring post-transplant life quality. This comprehensive care highlights the importance of a multidisciplinary approach involving transplant surgeons, anesthesiologists, immunologists, infectiologists and psychiatrists. The integration of anesthesia and surgical expertise is particularly vital, ensuring the best possible outcomes of those patients undergoing these novel transplants, through safe procedural practices. As xenotransplantation moving closer to clinical reality, establishing consensus guidelines on various aspects, including donor-recipient selection, immunosuppression, as well as surgical and anesthetic management of these transplants, is essential. Addressing these challenges through rigorous research and collective collaboration will be the key, not only to navigate the ethical, medical, and logistical complexities of introducing kidney xenotransplantation into mainstream clinical practice, but also itself marks a new era in organ transplantation.
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Anestesia , Transplante de Órgãos , Animais , Humanos , Suínos , Transplante Heterólogo/efeitos adversos , Zoonoses , Rim , ImunossupressoresRESUMO
In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of xenotransplantation research. It begins by examining the mechanisms through which xenotransplantation activates both the classical and alternative complement pathways. It then assesses the current landscape of xenotransplantation from donor pigs, with a particular emphasis on the innovative strides made in genetically engineering pigs to evade complement system activation. These modifications are critical in mitigating the discordance between pig endogenous retroviruses and human immune molecules. Additionally, the review discusses pharmacological interventions designed to support transplantation. By exploring the intricate relationship between the complement system and xenotransplantation, this retrospective analysis not only underscores the scientific and clinical importance of this field but also sheds light on the potential pathways to overcoming one of the major barriers to the success of xenografts. As such, the insights offered here hold significant promise for advancing xenotransplantation from a research concept to a viable clinical reality.
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Ativação do Complemento , Rejeição de Enxerto , Animais , Humanos , Suínos , Transplante Heterólogo , Animais Geneticamente Modificados , Estudos Retrospectivos , Rejeição de Enxerto/prevenção & controle , Proteínas do Sistema ComplementoRESUMO
Emerging research into metabolic dysfunction-associated steatotic liver disease (MASLD) up until January 2024 has highlighted the critical role of cuproptosis, a unique cell death mechanism triggered by copper overload, in the disease's development. This connection offers new insights into MASLD's complex pathogenesis, pointing to copper accumulation as a key factor that disrupts lipid metabolism and insulin sensitivity. The identification of cuproptosis as a significant contributor to MASLD underscores the potential for targeting copper-mediated pathways for novel therapeutic approaches. This promising avenue suggests that managing copper levels could mitigate MASLD progression, offering a fresh perspective on treatment strategies. Further investigations into how cuproptosis influences MASLD are essential for unraveling the detailed mechanisms at play and for identifying effective interventions. The focus on copper's role in liver health opens up the possibility of developing targeted therapies that address the underlying causes of MASLD, moving beyond symptomatic treatment to tackle the root of the problem. The exploration of cuproptosis in the context of MASLD exemplifies the importance of understanding metal homeostasis in metabolic diseases and represents a significant step forward in the quest for more effective treatments. This research direction lights path for innovative MASLD management and reversal.
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Apoptose , Cobre , Fígado Gorduroso , Animais , Humanos , Cobre/metabolismo , Fígado Gorduroso/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Fígado/metabolismo , Fígado/patologia , Doenças Metabólicas/metabolismoRESUMO
Ginsenoside Rh2 is one of the major bioactive ginsenosides in Panax ginseng. Although Rh2 is known to enhance immune cells activity for treatment of cancer, its anti-inflammatory and neuroprotective effects have yet to be determined. In this study, we investigated the effects of Rh2 on spared nerve injury (SNI)-induced neuropathic pain and elucidated the potential mechanisms. We found that various doses of Rh2 intrathecal injection dose-dependently attenuated SNI-induced mechanical allodynia and thermal hyperalgesia. Rh2 also inhibited microglia and astrocyte activation in the spinal cord of a murine SNI model. Rh2 treatment inhibited SNI-induced increase of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1 and IL-6. Expression of miRNA-21, an endogenous ligand of Toll like receptor (TLR)8 was also decreased. Rh2 treatment blocked the mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting of phosphorylated extracellular signal-regulated kinase expression. Finally, intrathecal injection of TLR8 agonist VTX-2337 reversed the analgesic effect of Rh2. These results indicated that Rh2 relieved SNI-induced neuropathic pain via inhibiting the miRNA-21-TLR8-MAPK signaling pathway, thus providing a potential application of Rh2 in pain therapy.
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Ginsenosídeos , MicroRNAs , Neuralgia , Fármacos Neuroprotetores , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , MAP Quinases Reguladas por Sinal Extracelular , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Hiperalgesia/tratamento farmacológico , Interleucina-6 , Ligantes , Camundongos , MicroRNAs/genética , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptor 8 Toll-Like , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: This study aimed to investigate the direct monosynaptic projections from cortical functional regions to the cerebrospinal fluid (CSF)-contacting nucleus for understanding the functions of the CSF-contacting nucleus. METHODS: The Sprague-Dawley rats received cholera toxin B subunit (CB) injections into the CSF-contacting nucleus. After 7-10 days of survival time, the rats were perfused, and the whole brain and spinal cord were sliced under a freezing microtome at 40 µm. All sections were treated with the CB immunofluorescence reaction. The retrogradely labeled neurons in different cortical areas were revealed under a confocal microscope. The distribution features were further illustrated under 3D reconstruction. RESULTS: The retrogradely labeled neurons were identified in the olfactory, orbital, cingulate, insula, retrosplenial, somatosensory, motor, visual, auditory, association, rhinal, and parietal cortical areas. A total of 12 functional areas and 34 functional subregions showed projections to the CSF-contacting nucleus in different cell intensities. CONCLUSION: According to the connectivity patterns, we conclude that the CSF-contacting nucleus participates in cognition, emotion, pain, visceral activity, etc. The present study firstly reveals the cerebral cortexâCSF-contacting nucleus connections, which implies the multiple functions of this special nucleus in neural and body fluid regulations.
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Objective: To identify the novel projections received by the cerebrospinal fluid (CSF)-contacting nucleus from the subcortex and limbic system to understand the biological functions of the nucleus. Methods: The cholera toxin subunit B (CB), a retrograde tracer, was injected into the CSF-contacting nucleus in Sprague-Dawley rats. After 7-10 days, the surviving rats were perfused, and the whole brain and spinal cord were sliced for CB immunofluorescence detection. The CB-positive neurons in the subcortex and limbic system were observed under a fluorescence microscope, followed by 3D reconstructed with the imaris software. Results: CB-positive neurons were found in the basal forebrain, septum, periventricular organs, preoptic area, and amygdaloid structures. Five functional areas including 46 sub-regions sent projections to the CSF-contacting nucleus. However, the projections had different densities, ranging from sparse to moderate, to dense. Conclusions: According to the projections from the subcortex and limbic system, we hypothesize that the CSF-contacting nucleus participates in emotion, cognition, homeostasis regulation, visceral activity, pain, and addiction. In this study, we illustrate the novel projections from the subcortex and limbic system to the CSF-contacting nucleus, which underlies the diverse and complicated circuits of the nucleus in body regulations.
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BACKGROUND: There is a unique nucleus (CSF-contacting nucleus) in the brain of rat. It has been demonstrated in our previous research. The extraordinary feature of this nucleus is that it is not connected to any parenchymal organ but to the CSF. In primates, however, the presence or absence of this nucleus has not been proven. Confirmation of the presence of this nucleus in primates will provide the structural basis for brain-CSF communication and help to understand the neurohumoral regulatory mechanisms in humans. METHODS: The tracer cholera toxin B subunit conjugated to horseradish peroxidase (CB-HRP) was injected into the CSF in the lateral ventricle (LV) of primate rhesus monkeys. After 48 h, the monkeys were perfused and the brain was dissected out, and sectioned for CB-HRP staining. The CB-HRP positive structures were observed under confocal and electron microscopy. The three-dimensional (3D) structure of the CB-HRP positive neurons cluster was reconstructed by computer software. RESULTS: (1) CB-HRP labeling is confined within the ventricle, but not leakage into the brain parenchyma. (2) From the midbrain inferior colliculus superior border plane ventral to the aqueduct to the upper part of the fourth ventricle (4V) floor, a large number of CB-HRP positive neurons are consistently located, form a cluster, and are symmetrically located on both sides of the midline. (3) 3D reconstruction shows that the CB-HRP positive neurons cluster in the monkey brain occupies certain space. The rostral part is large and caudal part is thin appearing a "rivet"-like shape. (4) Under electron microscopy, the CB-HRP positive neurons show different types of synaptic connections with the non-CSF-contacting structures in the brain. Some of the processes stretch directly into the ventricle cavity. CONCLUSION: Same as we did in rats, the CSF-contacting nucleus is also existed in the primate brain parenchyma. We also recommend listing it as the XIII pair of cranial nucleus, which is specialized in the communications between the brain and the CSF. It is significant to the completing of innervation in the organism.
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Objective: To investigate whether the CSF-contacting nucleus receives brainstem and spinal cord projections and to understand the functional significance of these connections. Methods: The retrograde tracer cholera toxin B subunit (CB) was injected into the CSF-contacting nucleus in Sprague-Dawley rats according the previously reported stereotaxic coordinates. After 7-10 days, these rats were perfused and their brainstem and spinal cord were sliced (thickness, 40 µm) using a freezing microtome. All the sections were subjected to CB immunofluorescence staining. The distribution of CB-positive neuron in different brainstem and spinal cord areas was observed under fluorescence microscope. Results: The retrograde labeled CB-positive neurons were found in the midbrain, pons, medulla oblongata, and spinal cord. Four functional areas including one hundred and twelve sub-regions have projections to the CSF-contacting nucleus. However, the density of CB-positive neuron distribution ranged from sparse to dense. Conclusion: Based on the connectivity patterns of the CSF-contacting nucleus receives anatomical inputs from the brainstem and spinal cord, we preliminarily conclude and summarize that the CSF-contacting nucleus participates in pain, visceral activity, sleep and arousal, emotion, and drug addiction. The present study firstly illustrates the broad projections of the CSF-contacting nucleus from the brainstem and spinal cord, which implies the complicated functions of the nucleus especially for the unique roles of coordination in neural and body fluids regulation.
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Tronco Encefálico/química , Líquido Cefalorraquidiano/química , Conectoma/métodos , Imageamento Tridimensional/métodos , Medula Espinal/química , Núcleo do Nervo Abducente/química , Núcleo do Nervo Abducente/citologia , Núcleo do Nervo Abducente/fisiologia , Animais , Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Aqueduto do Mesencéfalo/química , Aqueduto do Mesencéfalo/citologia , Aqueduto do Mesencéfalo/fisiologia , Líquido Cefalorraquidiano/fisiologia , Vias Neurais/química , Vias Neurais/citologia , Vias Neurais/fisiologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia , Medula Espinal/fisiologia , Núcleos Vestibulares/química , Núcleos Vestibulares/citologia , Núcleos Vestibulares/fisiologiaRESUMO
Objective: To investigate the projections the cerebrospinal fluid-contacting (CSF-contacting) nucleus receives from the diencephalon and to speculate on the functional significance of these connections. Methods: The retrograde tracer cholera toxin B subunit (CB) was injected into the CSF-contacting nucleus in SD rats according to the experimental formula of the stereotaxic coordinates. Animals were perfused 7-10 days after the injection, and the diencephalon was sliced at 40 µm with a freezing microtome. CB-immunofluorescence was performed on all diencephalic sections. The features of CB-positive neuron distribution in the diencephalon were observed with a fluorescence microscope. Results: The retrograde labeled CB-positive neurons were found in the epithalamus, subthalamus, and hypothalamus. Three functional diencephalic areas including 43 sub-regions revealed projections to the CSF-contacting nucleus. The CB-positive neurons were distributed in different density ranges: sparse, moderate, and dense. Conclusion: Based on the connectivity patterns of the CSF-contacting nucleus that receives anatomical inputs from the diencephalon, we preliminarily assume that the CSF-contacting nucleus participates in homeostasis regulation, visceral activity, stress, emotion, pain and addiction, and sleeping and arousal. The present study firstly illustrates the broad projections of the CSF-contacting nucleus from the diencephalon, which implies the complicated functions of the nucleus especially for the unique roles of coordination in neural and body fluids regulations.
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In this paper, we expound the origin and development of special acupuncture needle tools for cutaneous region, and discuss its mechanisms from modern medical theory. By consulting related acupuncture books and literature and in combination with needles used in clinical practice, we conclude that acupuncture needle tools can be divided into skin massage needle (digital pressing, spoon needle, etc.), cutaneous pricking blood needle (shear needle, three-edged needle, plum blossom needle, etc.), subcutaneous shallow puncture needle (intradermal needle, superficial needle, subcutaneous in-dwelling needle), etc. The skin-brain axis is the core of skin stimulation therapy. Mechanical pressure exerted on the skin surface induced by acupuncture stimulation or pressing, microcirculation changes and drug superposition are probably the underlying mechanisms of special skin acupuncture needle tools for treatment of various clinical disorders.
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Terapia por Acupuntura , Pontos de Acupuntura , Humanos , Microcirculação , Agulhas , PeleRESUMO
By analyzing the evolution of reinforcing-reducing manipulation achieved by lifting and thrusting the needle recorded in ancient literature of traditional Chinese medicine, it is found that the main contents of reinforcing-reducing manipulation by lifting and thrusting the needle include manipulating speed change, manual amplitude, insertion layer, gender, the direction to the acupuncture receiver, forenoon and afternoon and relevant quantity. Among them, gender, the direction to the acupuncture receiver, forenoon and afternoon and relevant quantity are the unnecessary parameters, while the manipulating speed change, manual amplitude and insertion layer are the indispensable parameters. The manipulating speed change is the core of the necessary parameters for the reinforcing-reducing manipulation achieved by lifting and thrusting the needle. Combined with the manual amplitude, the manipulating speed of needle determines the volume of needling stimulation. The insertion layer is decided on the base of the clinical demand. In the core technique of reinforcing-reducing manipulation by lifting and thrusting the needle, the reinforcing is achieved by thrusting the needle forcefully and quickly and then lifting the needle body slowly and evenly back to the original layer. The reducing is achieved by lifting the needle forcefully and quickly and then thrusting the needle body slowly and evenly back to the original layer. The manipulating speed and manual amplitude of needling are the parameters to quantize acupuncture manipulation. In association with the acupuncture effects in human body, these parameters contribute to the interpretation of the dose-effect relationship of acupuncture and the improvement of clinical effects.
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Terapia por Acupuntura , Remoção , Humanos , Medicina Tradicional Chinesa , AgulhasRESUMO
A unique nucleus, the cerebrospinal fluid (CSF)-contacting nucleus, has recently been recognized in the brain parenchyma. The outstanding feature of this nucleus is that the neural somas are located in the parenchyma, but their processes stretch into the CSF, implying that it may be a key structure bridging the nervous and body fluids-regulating systems and may play a pivotal role in modulating physiological activities. However, the true biological significance of this nucleus needs to be uncovered. The morphology of a nucleus is one of the most important parameters for neuroscience studies. For this reason, a common experimental animal, Sprague-Dawley (SD) rats, was chosen. The position, adjacent structures, neuronal distribution, size, three-dimensional reconstruction, and core coordinates of the CSF-contacting nucleus in SD rats of different weights (90-400 g) were illustrated for the first time. Furthermore, the formulas for calculating the core coordinates of the CSF-contacting nucleus in rats of different weights were revealed. Finally, the possible biological functions uncovered by past research are reviewed in this paper. This study provides an indispensable methodology and a significant reference for researchers interested in this unique nucleus.
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To establish an entirely cerebrospinal fluid (CSF)-contacting nucleus-deficient model animal, we used cholera toxin B subunit (CB)- saporin (SAP), which is an analog of CB-HRP that specifically labels the CSF-contacting nucleus, to exclusively damage the nucleus. The effectiveness and specificity of the ablation were evaluated upon days 1-10 after CB-SAP microinjection into the brain ventricular system. The vital status, survival, and common physiological parameters of the model animals were also assessed during the experimental period. The results demonstrated that CB-SAP damaged only the CSF-contacting nucleus, but not other functional structures, in the brain. The complete ablation occurred by day 7 after CB-SAP microinjection. A model animal that had no CSF-contacting nucleus was established after survival beyond that time point. No obvious effects were observed in the vital status of the model animals, and their survival was ensured. The common physiological parameters of model animals were stable. The present study provides a method to establish a CSF-contacting nucleus "knockout" model animal, which is similar to a gene knockout model animal for studying this particular nucleus in vivo.
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BACKGROUND: The activation of mitogen-activated protein kinases (MAPKs) have been observed in synaptic plasticity processes of learning and memory in neuropathic pain. Cerebrospinal fluid-contacting nucleus (CSF-CN) has been identified with the onset and persistence of neuropathic pain. However, whether extracellular signal-regulated protein kinase 5 (ERK5), a member of MAPKs, in CSF-CN participates in neuropathic pain has not been studied yet. OBJECTIVE: The aim of the present study was to identify the role of ERK5 in CSF-CN on the formation and development of neuropathic pain, and to investigate its possible mechanism. STUDY DESIGN: Controlled animal study. SETTING: University laboratory. METHODS: After a chronic constriction injury (CCI) model was produced, BIX02188 was dissolved in 1% DMSO and injected into the lateral ventricles LV in a volume of 3 µl with different doses (0.1 µg, 1 µg, 10 µg). Mechanical allodynia and thermal hypersensitivity behavioral test, immunofluorescence, and western blot technique were used in this research. RESULT: Following CCI, mechanical allodynia and thermal hypersensitivity were developed within a day, peaked at 14 days, and persisted for 21 days. ERK5 was remarkably activated by CCI in CSF-CN. Moreover, selective inhibiting of p-ERK5 expression in CSF-CN by BIX02188 could significantly relieve CCI-induced mechanical allodynia and thermal hypersensitivity, accompanying with the decreased phosphorylation of cAMP response-element binding protein (CREB) in CSF-CN. LIMITATIONS: More underlying mechanism(s) of the role of ERK5 in CSF-CN on the formation and development of neuropathic pain will be needed to explore in future research. CONCLUSION: These findings suggest activation of ERK5 in CSF-CN might contribute to the onset and development of neuropathic pain and its role might be partly accomplished by p-CREB.