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Cervical medial branch block (CMBB) has been recognized as an effective treatment for cervicogenic pain. Previous studies mostly used ultrasound-guided out-of-plane puncture for CMBB, while this prospective study was designed to investigate the efficacy of ultrasound-guided in-plane puncture, specifically focusing on the new target of CMBB for cervical pain. This study includes two parts: the accuracy study (N = 15, CMBB was completed by ultrasound and confirmed by computed tomography [CT], in which a good distribution percentage of the analgesic solution was observed) and the efficacy study (N = 40, CMBB was completed by ultrasound or CT, while the proportion of pain relief (numerical rating scale) decrease by more than 50% postoperatively was analyzed). The results showed that the good distribution percentage of the analgesic solution was 97.8%. Furthermore, in the early period (30 min and 2 h postoperatively), the proportion of patients with pain relief was lower in the ultrasound group than that in the CT group, especially at 2 h postoperatively (52% vs. 94%). However, at 24 h postoperatively and later, the proportion of patients with pain relief gradually stabilized to about 60%-70%, and lasted for about 2 weeks to 1 month. Therefore, the new target for CMBB, guided by ultrasound in-plane, offers high visibility and accuracy. A single CMBB performed under ultrasound guidance resulted in pain relief comparable to that of a CT-guided procedure (1 day to 1 month postoperatively). This study indicated that CMBB guided by ultrasound in-plane could be regarded as a promising approach for treatment of cervicogenic pain.
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This study aimed to elucidate the opioid mechanisms underlying dexamethasone-induced pain antihypersensitive effects in neuropathic rats. Dexamethasone (subcutaneous and intrathecal) and membrane-impermeable Dex-BSA (intrathecal) administration dose-dependently inhibited mechanical allodynia and thermal hyperalgesia in neuropathic rats. Dexamethasone and Dex-BSA treatments increased expression of dynorphin A in the spinal cords and primary cultured microglia. Dexamethasone specifically enhanced dynorphin A expression in microglia but not astrocytes or neurons. Intrathecal injection of the microglial metabolic inhibitor minocycline blocked dexamethasone-stimulated spinal dynorphin A expression; intrathecal minocycline, the glucocorticoid receptor antagonist Dex-21-mesylate, dynorphin A antiserum, and κ-opioid receptor antagonist GNTI completely blocked dexamethasone-induced mechanical antiallodynia and thermal antihyperalgesia. Additionally, dexamethasone elevated spinal intracellular cAMP levels, leading to enhanced phosphorylation of PKA, p38 MAPK and CREB. The specific adenylate cyclase inhibitor DDA, PKA inhibitor H89, p38 MAPK inhibitor SB203580 and CREB inhibitor KG-501 completely blocked dexamethasone-induced anti-neuropathic pain and increased microglial dynorphin A exprression. In conclusion, this study reveal that dexamethasone mitigateds neuropathic pain through upregulation of dynorphin A in spinal microglia, likely involving the membrane glucocorticoid receptor/cAMP/PKA/p38 MAPK/CREB signaling pathway.
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Proteínas Quinasas Dependientes de AMP Cíclico , AMP Cíclico , Dexametasona , Dinorfinas , Microglía , Neuralgia , Ratas Sprague-Dawley , Transducción de Señal , Médula Espinal , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Microglía/metabolismo , Microglía/efectos de los fármacos , AMP Cíclico/metabolismo , Médula Espinal/metabolismo , Médula Espinal/efectos de los fármacos , Masculino , Neuralgia/metabolismo , Neuralgia/tratamiento farmacológico , Dinorfinas/metabolismo , Ratas , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Dexametasona/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Hiperalgesia/metabolismo , Hiperalgesia/tratamiento farmacológicoRESUMEN
Purpose: To compare the effectiveness of azvudine and nirmatrelvir/ritonavir for the treatment of coronavirus disease (COVID-19). Patients and Methods: We conducted a retrospective analysis of data from 576 patients with COVID-19, comprising 195 patients without antiviral therapy, 226 patients treated with azvudine, 114 patients treated with nirmatrelvir/ritonavir, and 41 patients were treated with azvudine and nirmatrelvir/ritonavir concurrently. We compared their symptoms, mortality rates, and the length and cost of hospitalization. Results: The incidence of symptoms was similar in patients treated with azvudine and in those treated with nirmatrelvir/ritonavir. However, among patients experiencing weakness, the duration of weakness was significantly shorter in the azvudine group than in the nirmatrelvir/ritonavir group (P=0.029). Mortality did not differ significantly between the azvudine group and the nirmatrelvir/ritonavir group (18.14% vs.10.53%, P=0.068). Among "severe patients", the mortality rate was markedly lower in patients treated with nirmatrelvir/ritonavir than in patients treated with azvudine (16.92% vs.32.17%, P=0.026). In patients with hepatic insufficiency, those treated with nirmatrelvir/ritonavir had substantially lower mortality than those treated with azvudine (15.09% vs.34.25%, P=0.016). In addition, patients treated with nirmatrelvir/ritonavir had longer hospital stays (P=0.002) and higher hospital costs (P<0.001) than those receiving azvudine. Compared with patients treated with nirmatrelvir/ritonavir or azvudine alone, patients taking nirmatrelvir/ritonavir and azvudine concurrently had no significant improvement in survival (P>0.05), length of stay (P>0.05), or hospital costs (P>0.05). Conclusion: Azvudine is recommended for patients with non-severe COVID-19 with weakness. Nirmatrelvir/ritonavir is recommended for patients with severe COVID-19, to reduce mortality, and it could be the best choice for patients with hepatic insufficiency. The concurrent use of nirmatrelvir/ritonavir and azvudine in patients with COVID-19 could be not recommended.
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A novel high-speed multi-frame photographic system is presented in this paper. The system demonstrates exceptional compactness and flexibility, requiring only the introduction of a cavity comprising multiple beam-splitters in the optical path to enable multi-frame imaging of sub-nanosecond events. The number and temporal delay of frames can be easily adjusted by adjusting the distance and angle between beam-splitters. These capabilities are demonstrated by observing the laser ablation process, highlighting the great potential for application in capturing ultrafast time-evolving events such as optical breakdown, the evolution of laser-produced plasmas, and the propagation of shock waves.
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Holography, which can provide the information of phase as well as amplitude of a laser probe, could be a powerful method to diagnose the electron density and temperature of a plasma simultaneously. In this paper, digital holography with an ultrashort laser pulse is applied to diagnose laser-produced aluminum plasmas. Detailed analyses show that the reconstruction of the wave amplitude could be profoundly affected by the difference between the phase and group velocity of the ultrashort laser pulse in the plasma, which makes it a challenge to accurately reconstruct the amplitude in the case when ultrashort laser pulses are utilized for high-temporal resolution of holography.
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OBJECTIVE: To compare the clinical effect between heat-sensitive moxibustion and mild moxibustion for migraine without aura. METHODS: A total of 54 patients with migraine without aura were randomized into an observation group (27 cases, 2 cases dropped off) and a control group (27 cases, 2 cases dropped off). The basic western medication treatment was adopted in the two groups. In the control group, mild moxibustion was applied at Shuaigu (GB 8), Fengchi (GB 20) and Yanglingquan (GB 34) on the affected side. In the observation group, the frequent acupoint areas of the affected side i.e. Shuaigu (GB 8), Fengchi (GB 20), Taiyang (EX-HN 5), Taichong (LR 3), Yanglingquan (GB 34) were determined, 3 acupoints with strong heat-sensitive sensation were selected each time and mild moxibustion was adopted. The treatment was given once a day, 5 times of treatment was as one course and 2 courses were required in the two groups. Before and after treatment, the scores of migraine symptom, visual analogue scale (VAS), migraine specific quality of life questionnaire (MSQ) were observed, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the scores of migraine symptom and VAS were decreased compared with those before treatment (P<0.01), while the MSQ scores were increased compared with those before treatment (P<0.01) in the two groups. After treatment, the scores of migraine symptom and VAS in the observation group were lower than those in the control group (P<0.05), while the MSQ score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 92.0% (23/25) in the observation group, which was superior to 72.0% (18/25) in the control group (P<0.05). CONCLUSION: Both heat-sensitive moxibustion and mild moxibustion can effectively alleviate the clinical symptoms, improve the headache degree and life quality in patients with migraine without aura, the clinical efficacy of heat-sensitive moxibustion is superior to that of mild moxibustion.
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Terapia por Acupuntura , Migraña sin Aura , Moxibustión , Humanos , Migraña sin Aura/terapia , Calor , Calidad de Vida , Puntos de Acupuntura , Resultado del TratamientoRESUMEN
The purpose of this study was to analyse the clinical characteristics of patients with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) PCR re-positivity after recovering from coronavirus disease 2019 (COVID-19). Patients (n = 1391) from Guangzhou, China, who had recovered from COVID-19 were recruited between 7 September 2021 and 11 March 2022. Data on epidemiology, symptoms, laboratory test results and treatment were analysed. In this study, 42.7% of recovered patients had re-positive result. Most re-positive patients were asymptomatic, did not have severe comorbidities, and were not contagious. The re-positivity rate was 39%, 46%, 11% and 25% in patients who had received inactivated, mRNA, adenovirus vector and recombinant subunit vaccines, respectively. Seven independent risk factors for testing re-positive were identified, and a predictive model was constructed using these variables. The predictors of re-positivity were COVID-19 vaccination status, previous SARs-CoV-12 infection prior to the most recent episode, renal function, SARS-CoV-2 IgG and IgM antibody levels and white blood cell count. The predictive model could benefit the control of the spread of COVID-19.
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COVID-19 , Humanos , SARS-CoV-2 , Vacunas contra la COVID-19 , Prueba de COVID-19 , Reacción en Cadena de la PolimerasaRESUMEN
Panax notoginseng (Chinese ginseng, Sanqi), one of the major ginseng species, has been traditionally used to alleviate different types of chronic pain. The raw P. notoginseng powder is commonly available in China as a non-prescription drug to treat various aliments including arthritic pain. However, strong scientific evidence is needed to illustrate its pain antihypersensitive effects, effective ingredients and mechanism of action. The oral P. notoginseng powder dose-dependently alleviated formalin-induced tonic hyperalgesia, and its total ginsenosides remarkably inhibited neuropathic pain hypersensitivity. Ginsenoside Rb1, the most abundant ginsenoside of P. notoginseng, dose-dependently produced neuropathic pain antihypersensitivity. Conversely, ginsenosides Rg1, Re and notoginseng R1, the other major saponins from P. notoginseng, failed to inhibit formalin-induced tonic pain or mechanical allodynia in neuropathic pain. Ginsenoside Rb1 metabolites ginsenosides Rg3, Compound-K and protopanaxadiol also had similar antineuropathic pain efficacy to ginsenoside Rb1. Additionally, intrathecal ginsenoside Rb1 specifically stimulated dynorphin A expression which was colocalized with microglia but not neurons or astrocytes in the spinal dorsal horn and primary cultured cells. Pretreatment with microglial metabolic inhibitor minocycline, dynorphin A antiserum and specific κ-opioid receptor antagonist GNTI completely blocked Rb1-induced mechanical antiallodynia in neuropathic pain. Furthermore, the specific glucocorticoid receptor (GR) antagonist Dex-21-mesylate (but not GPR30 estrogen receptor antagonist G15) also entirely attenuated ginsenoside Rb1-related antineuropathic pain effects. All these results, for the first time, show that P. notoginseng alleviates neuropathic pain and ginsenoside Rb1 is its principal effective ingredient. Furthermore, ginsenoside Rb1 inhibits neuropathic pain by stimulation of spinal microglial dynorphin A expression following GR activation.
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Ginsenósidos , Neuralgia , Panax notoginseng , Ginsenósidos/metabolismo , Ginsenósidos/farmacología , Ginsenósidos/uso terapéutico , Dinorfinas/metabolismo , Dinorfinas/farmacología , Dinorfinas/uso terapéutico , Panax notoginseng/metabolismo , Microglía/metabolismo , Polvos/metabolismo , Polvos/farmacología , Polvos/uso terapéutico , Hiperalgesia/metabolismo , Neuralgia/tratamiento farmacológicoRESUMEN
Astragalus polysaccharide(APS), one of the main active components of Astragali Radix, plays an anti-tumor effect by regulating the inflammatory microenvironment of tumors. Exosomes are small extracellular vesicles with a diameter ranging from 50 to 200 nm and carry several biological components from parental cells such as nucleic acids and proteins. When combined with recipient cells, they play an important role in intercellular communication and immune response. In this study, exosomes released from H460 cells at the inflammatory state or with APS addition activated by Toll-like receptor 4(TLR4) were extracted by ultracentrifugation and characterized by Western blot, transmission electron microscopy, and nanoparticle tracking analysis. The exosomal proteins derived from H460 cells in the three groups were further analyzed by label-free proteomics, and 897, 800, and 911 proteins were identified in the three groups(Con, LPS, and APS groups), 88% of which belonged to the ExoCarta exosome protein database. Difference statistical analysis showed that the expression of 111 proteins was changed in the LPS group and the APS group(P<0.05). The biological information analysis of the differential proteins was carried out. The molecular functions, biological processes, and signaling pathways related to the differential proteins mainly involved viral processes, protein binding, and bacterial invasion of proteasome and epithelial cells. Key differential proteins mainly included plasminogen activator inhibitor-1, laminin α5, laminin α1, and CD44, indicating that tumor cells underwent systemic changes in different states and were reflected in exosomes in the inflammatory microenvironment. The analysis results also suggested that APS might affect the inflammatory microenvironment through the TLR4/MyD88/NF-κB signaling pathway or the regulation of the extracellular matrix. This study is conducive to a better understanding of the mechanism of tumor development in the inflammatory state and the exploration of the anti-inflammatory effect of APS at the exosome level.
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Planta del Astrágalo , Exosomas , Neoplasias Pulmonares , Humanos , Exosomas/metabolismo , Proteómica , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Lipopolisacáridos , Planta del Astrágalo/química , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Polisacáridos/farmacología , Polisacáridos/metabolismo , Microambiente TumoralRESUMEN
Dexmedetomidine, a highly selective α2-adrenoceptor agonist, has been recently reported to alleviate systemic inflammatory response induced by lipopolysaccharide (LPS), in addition to its sedative, analgesic, bradycardic and hypotensive properties. This study aimed to illustrate the molecular mechanisms underlying dexmedetomidine-induced anti-inflammation. In the LPS-pretreated mice, subcutaneous injection of dexmedetomidine reduced the spleen weight as well as serum and spleen expression of proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß, and increased serum and spleen expression of IL-10, a known anti-inflammatory cytokine. In addition, dexmedetomidine-attenuated proinflammatory cytokine reduction was entirely inhibited by selective α7 nicotinic acetylcholine receptor (nAChR) antagonist methyllycaconitine but not α2-adrenoceptor antagonist yohimbine. Dexmedetomidine also increased macrophageal IL-10 expression in the presence and absence of LPS, which was also attenuated by methyllycaconitine but not yohimbine. Furthermore, the stimulatory effect of dexmedetomidine on the expression of IL-10 was also reduced by the α7 nAChR gene silencer siRNA/α7 nAChR. Lastly, pretreatment with the IL-10 neutralizing antibody reversed dexmedetomidine-supressed expression of proinflammatory cytokines. Our findings illustrate that dexmedetomidine-induced anti-inflammation is through macrophageal expression of IL-10 following activation of α7 nAchRs but not α2-adrenoceptors.
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Dexmedetomidina , Lipopolisacáridos , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Citocinas/metabolismo , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Ratones , Receptores Adrenérgicos/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/metabolismoRESUMEN
Adzuki bean (Vigna angularis), also called red bean, is a legume of Fabaceae (Leguminosae) family. This crop is native to East Asia and is also commercially available in other parts of the world. It is becoming a research focus owing to its distinct nutritional properties (e.g., abundant in polyphenols). The diverse health benefits and multiple utilization of this pulse are associated with its unique composition. However, there is a paucity of reviews focusing on the nutritional properties and potent applications of adzuki beans. This review summarizes the chemical compositions, physicochemical properties, health benefits, processing, and applications of adzuki beans. Suggestions on how to better utilize the adzuki bean are also provided to facilitate its development as a functional grain. Adzuki bean and its components can be further developed into value-added and nutritionally enhanced products.
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Fabaceae , Vigna , Fabaceae/química , Polifenoles , Vigna/químicaRESUMEN
Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neurodevelopmental disorders. However, the neuropathogenesis remains largely elusive due to a lack of informative animal models. In this study, we developed a congenital murine CMV (cMCMV) infection mouse model with high survival rate and long survival period that allowed long-term follow-up study of neurodevelopmental disorders. This model involves in utero intracranial injection and mimics many reported clinical manifestations of cCMV infection in infants, including growth restriction, hearing loss, and impaired cognitive and learning-memory abilities. We observed that abnormalities in MRI/CT neuroimaging were consistent with brain hemorrhage and loss of brain parenchyma, which was confirmed by pathological analysis. Neuropathological findings included ventriculomegaly and cortical atrophy associated with impaired proliferation and migration of neural progenitor cells in the developing brain at both embryonic and postnatal stages. Robust inflammatory responses during infection were shown by elevated inflammatory cytokine levels, leukocyte infiltration, and activation of microglia and astrocytes in the brain. Pathological analyses and CT neuroimaging revealed brain calcifications induced by cMCMV infection and cell death via pyroptosis. Furthermore, antiviral treatment with ganciclovir significantly improved neurological functions and mitigated brain damage as shown by CT neuroimaging. These results demonstrate that this model is suitable for investigation of mechanisms of infection-induced brain damage and long-term studies of neurodevelopmental disorders, including the development of interventions to limit CNS damage associated with cCMV infection.
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Infecciones por Citomegalovirus , Modelos Animales de Enfermedad , Neuroimagen , Animales , Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/diagnóstico por imagen , Infecciones por Citomegalovirus/fisiopatología , Infecciones por Citomegalovirus/terapia , Femenino , Estudios de Seguimiento , Ratones , Ratones Endogámicos ICR , EmbarazoRESUMEN
There are many trillions of bacteria in the gastrointestinal microbiome (GM). Their ecological dysregulation can contribute to the development of certain neurodegenerative diseases, including Alzheimer's disease (AD). AD is common dementia and its incidence is increasing year by year. However, the relationship between GM and AD is unclear. Therefore, this review discusses the relationship between GM and AD, elaborates on the possible factors that can affect this relationship through the inflammation of the brain induced by blood-brain damage and accumulation of amyloid deposit, and proposes feasible ways to treat AD through GM-related substances, such as probiotics, Mega-3, and gut hormones, including their shortcomings as well.
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Interrupted aortic arch (IAA) is a rare complex congenital heart disease characterized by interrupted continuity between ascending aorta and descending aorta. Prenatal diagnosis of IAA by echocardiography is not uncommonly reported despite its rarity. However, employing four-dimensional ultrasound HD-flow imaging and spatiotemporal image correlation (STIC) in diagnosis of this condition has seldom been reported. We report a case of fetal IAA prenatally diagnosed by two-dimensional echocardiography and HD-flow STIC.
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Ecocardiografía Tetradimensional , Cardiopatías Congénitas , Aorta Torácica/diagnóstico por imagen , Femenino , Corazón Fetal/diagnóstico por imagen , Cardiopatías Congénitas/diagnóstico por imagen , Humanos , Embarazo , Diagnóstico Prenatal , Ultrasonografía PrenatalRESUMEN
Background: Public health measures (such as wearing masks, physical distancing, and isolation) have significantly reduced the spread of the coronavirus disease-2019 (COVID-19), but the impact of public health measures on other respiratory infectious diseases is unclear. Objective: To assess the correlation between public health measures and the incidence of respiratory infectious diseases in China during the COVID-19 pandemic. Methods: We collected the data from the National Health and Construction Commission in China on the number of patients with six respiratory infectious diseases (measles, tuberculosis, pertussis, scarlet fever, influenza, and mumps) from 2017 to 2020 and assessed the correlation between public health measures and the incidence of respiratory infectious diseases. Finally, we used the data of the six respiratory infectious diseases in 2021 to verify our results. Results: We found public health measures significantly reduced the incidence of measles (p = 0.002), tuberculosis (p = 0.002), pertussis (p = 0.004), scarlet fever (p = 0.002), influenza (p = 0.034), and mumps (p = 0.002) in 2020, and prevented seasonal peaks. Moreover, the effects of public health measures were most marked during the peak seasons for these infections. Of the six respiratory infectious diseases considered, tuberculosis was least affected by public health measures. Conclusion: Public health measures were very effective in reducing the incidence of respiratory infectious diseases, especially when the respiratory infectious diseases would normally have been at their peak.
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COVID-19 , Enfermedades Transmisibles , Enfermedades Transmisibles/epidemiología , Humanos , Pandemias , Salud Pública , SARS-CoV-2RESUMEN
Thalidomide is an antiinflammatory, antiangiogenic and immunomodulatory agent which has been used for the treatment of erythema nodosum leprosum and multiple myeloma. It has also been employed in treating complex regional pain syndromes. The current study aimed to reveal the molecular mechanisms underlying thalidomide-induced pain antihypersensitive effects in neuropathic pain. Thalidomide gavage, but not its more potent analogs lenalidomide and pomalidomide, inhibited mechanical allodynia and thermal hyperalgesia in neuropathic pain rats induced by tight ligation of spinal nerves, with ED50 values of 44.9 and 23.5 mg/kg, and Emax values of 74% and 84% MPE respectively. Intrathecal injection of thalidomide also inhibited mechanical allodynia and thermal hyperalgesia in neuropathic pain. Treatment with thalidomide, lenalidomide and pomalidomide reduced peripheral nerve injury-induced proinflammatory cytokines (TNFα, IL-1ß and IL-6) in the ipsilateral spinal cords of neuropathic rats and LPS-treated primary microglial cells. In contrast, treatment with thalidomide, but not lenalidomide or pomalidomide, stimulated spinal expressions of IL-10 and ß-endorphin in neuropathic rats. Particularly, thalidomide specifically stimulated IL-10 and ß-endorphin expressions in microglia but not astrocytes or neurons. Furthermore, pretreatment with the IL-10 antibody blocked upregulation of ß-endorphin in neuropathic rats and cultured microglial cells, whereas it did not restore thalidomide-induced downregulation of proinflammatory cytokine expression. Importantly, pretreatment with intrathecal injection of the microglial metabolic inhibitor minocycline, IL-10 antibody, ß-endorphin antiserum, and preferred or selective µ-opioid receptor antagonist naloxone or CTAP entirely blocked thalidomide gavage-induced mechanical antiallodynia. Our results demonstrate that thalidomide, but not lenalidomide or pomalidomide, alleviates neuropathic pain, which is mediated by upregulation of spinal microglial IL-10/ß-endorphin expression, rather than downregulation of TNFα expression.
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Interleucina-10/biosíntesis , Microglía/metabolismo , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Talidomida/uso terapéutico , betaendorfina/biosíntesis , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Interleucina-10/agonistas , Masculino , Microglía/efectos de los fármacos , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Talidomida/farmacología , betaendorfina/agonistasRESUMEN
Cynandione A, an acetophenone isolated from Cynanchum Wilfordii Radix, attenuates inflammation. The present study aimed to study the mechanisms underlying cynandione A-induced antiinflammation. Treatment with cynandione A and the specific α7 nicotinic acetylcholine receptor (α7 nAChR) agonist PHA-543613 remarkably reduced overexpression of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß in lipopolysaccharide (LPS)-treated RAW264.7 cells and primary peritoneal macrophages, and endotoxemic mice. Both cynandione A and PHA-543613 also stimulated IL-10 expression in naïve and LPS-treated macrophages and endotoxemic mice. Cynandione A- and PHA-543613-inhibited proinflammatory cytokine expression was completely blocked by the α7 nAChR antagonist methyllycaconitine and the IL-10 antibody. The stimulatory effect of cynandione A and PHA-543613 on IL-10 expression were suppressed by methyllycaconitine and knockdown of α7 nAChRs using siRNA/α7 nAChR. Cynandione A significantly stimulated STAT3 phosphorylation, which was attenuated by methyllycaconitine and the IL-10 neutralizing antibody. The STAT3 activation inhibitor NSC74859 also blocked cynandione A-inhibited proinflammatory cytokine expression. Taken together, our results, for the first time, demonstrate that cynandione A and PHA-543613 inhibit inflammation through macrophageal α7 nAChR activation and subsequent IL-10 expression.
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Compuestos de Bifenilo/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Mediadores de Inflamación/antagonistas & inhibidores , Interleucina-10/agonistas , Macrófagos/efectos de los fármacos , Quinuclidinas/farmacología , Receptor Nicotínico de Acetilcolina alfa 7/agonistas , Animales , Compuestos de Bifenilo/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Células Cultivadas , Cynanchum , Relación Dosis-Respuesta a Droga , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Interleucina-10/biosíntesis , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Quinuclidinas/uso terapéutico , Células RAW 264.7 , Receptor Nicotínico de Acetilcolina alfa 7/metabolismoRESUMEN
Gabapentinoids are recommended first-line treatments for neuropathic pain. They are neuronal voltage-dependent calcium channel α2δ-1 subunit ligands and have been suggested to attenuate neuropathic pain via interaction with neuronal α2δ-1 subunit. However, the current study revealed their microglial mechanisms underlying antineuropathic pain. Intrathecal injection of gabapentin, pregabalin and mirogabalin rapidly inhibited mechanical allodynia and thermal hyperalgesia, with projected ED50 values of 30.3, 6.2 and 1.5 µg (or 176.9, 38.9 and 7.2 nmol) and Emax values of 66%, 61% and 65% MPE respectively for mechanical allodynia. Intrathecal gabapentinoids stimulated spinal mRNA and protein expression of IL-10 and ß-endorphin (but not dynorphin A) in neuropathic rats with the time point parallel to their inhibition of allodynia, which was observed in microglia but not astrocytes or neurons in spinal dorsal horns by using double immunofluorescence staining. Intrathecal gabapentin alleviated pain hypersensitivity in male/female neuropathic but not male sham rats, whereas it increased expression of spinal IL-10 and ß-endorphin in male/female neuropathic and male sham rats. Treatment with gabapentin, pregabalin and mirogabalin specifically upregulated IL-10 and ß-endorphin mRNA and protein expression in primary spinal microglial but not astrocytic or neuronal cells, with EC50 values of 41.3, 11.5 and 2.5 µM and 34.7, 13.3 and 2.8 µM respectively. Pretreatment with intrathecal microglial metabolic inhibitor minocycline, IL-10 antibody, ß-endorphin antiserum or µ-opioid receptor antagonist CTAP (but not κ- or δ-opioid receptor antagonists) suppressed spinal gabapentinoids-inhibited mechanical allodynia. Immunofluorescence staining exhibited specific α2δ-1 expression in neurons but not microglia or astrocytes in the spinal dorsal horns or cultured primary spinal cells. Thus the results illustrate that gabapentinoids alleviate neuropathic pain through stimulating expression of spinal microglial IL-10 and consequent ß-endorphin.
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Gabapentina/farmacología , Interleucina-10 , Microglía/metabolismo , Neuralgia , betaendorfina , Animales , Femenino , Hiperalgesia/tratamiento farmacológico , Interleucina-10/metabolismo , Masculino , Neuralgia/tratamiento farmacológico , Ratas , Ratas Wistar , Médula Espinal , betaendorfina/metabolismoRESUMEN
Graphitic carbon nitride (g-C3N4) has been identified as a promising material for photocatalytic hydrogen (H2) production, but it shows a low activity. Herein, g-C3N4 doped with a benzene ring (B-CNx) was synthesized via a simple thermal polycondensation method, exhibits 5.4 times higher H2 evolution rate than the pristine one, and achieves a high apparent quantum yield of 4.11% at 420 nm.
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Vascular ring and sling are congenital anomalies of the vascular structure in the thorax with a prevalence of 2.4/10,000 live births. Double aortic arch (DAA), right aortic arch with left ductus arteriosus and aberrant left subclavian artery (RAA-ALSA), and pulmonary artery sling (PAS) are the three common types of vascular ring and sling. These anomalies can be isolated or accompanied by intracardiac malformation. The presence of both vascular ring and PAS is extremely rare. Here, we report a fetus who was prenatally diagnosed with PAS and RAA-ALS, and developed symptoms due to esophageal and airway compression after birth.