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Introduction: Sarcopenia, an age-related disease, has become a major public health concern, threatening muscle health and daily functioning in older adults around the world. Changes in the gut microbiota can affect skeletal muscle metabolism, but the exact association is unclear. The richness of gut microbiota refers to the number of different species in a sample, while diversity not only considers the number of species but also the evenness of their abundances. Alpha diversity is a comprehensive metric that measures both the number of different species (richness) and the evenness of their abundances, thereby providing a thorough understanding of the species composition and structure of a community. Methods: This meta-analysis explored the differences in intestinal microbiota diversity and richness between populations with sarcopenia and non-sarcopenia based on 16 s rRNA gene sequencing and identified new targets for the prevention and treatment of sarcopenia. PubMed, Embase, Web of Science, and Google Scholar databases were searched for cross-sectional studies on the differences in gut microbiota between sarcopenia and non-sarcopenia published from 1995 to September 2023 scale and funnel plot analysis assessed the risk of bias, and performed a meta-analysis with State v.15. 1. Results: A total of 17 randomized controlled studies were included, involving 4,307 participants aged 43 to 87 years. The alpha diversity of intestinal flora in the sarcopenia group was significantly reduced compared to the non-sarcopenia group: At the richness level, the proportion of Actinobacteria and Fusobacteria decreased, although there was no significant change in other phyla. At the genus level, the abundance of f-Ruminococcaceae; g-Faecalibacterium, g-Prevotella, Lachnoclostridium, and other genera decreased, whereas the abundance of g-Bacteroides, Parabacteroides, and Shigella increased. Discussion: This study showed that the richness of the gut microbiota decreased with age in patients with sarcopenia. Furthermore, the relative abundance of different microbiota changed related to age, comorbidity, participation in protein metabolism, and other factors. This study provides new ideas for targeting the gut microbiota for the prevention and treatment of sarcopenia. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=475887, CRD475887.
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Microneedle (MNs), as a novel dermal drug delivery formulation, have drawn a lot of attention in recent years. Drug release and diffusion behavior in dermal interstitial fluid (ISF) determines the pharmacokinetics and effectiveness of MNs, which have not been clearly elucidated until now. Herein, we develop surface-enhanced Raman scattering (SERS)-based detection MNs (D-MNs) for the sensitive analysis of model drugs in ISF. The surface of the D-MNs was deposited with a high density of hotspot-rich core-satellite gold nanoparticles, which would generate a sensitive SERS signal of a model drug (3,3'-diethylthiatricarbocyanine, DTTC) released by therapeutic MNs (T-MNs). Furthermore, the D-MNs produced an internal-standard signal for drug signal calibration, increasing the accuracy of detection. Taking advantage of the D-MNs, the release and diffusion behavior of the drug from T-MNs in the ISF of living mice was systematically studied. It was found that DTTC diffused without directional preference in ISF up to a distance of 1.5 cm. The intensities at diffusion sites decreased sharply with increasing distance from the release site (less than 0.3% at 1.5 cm). These results indicated that drug concentration gradient rather than ISF fluidity was a major driving force for the diffusion. Moreover, the application of water-soluble MN polymers, hydrophilic model drugs in T-MNs, as well as a heating or cupping treatment of mouse skin, enhanced drug diffusion in ISF. This work provides a new tool for in situ and real-time detection of molecules in ISF, which would be beneficial for the development and evaluation of MN-based therapeutic systems.
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Líquido Extracelular , Nanopartículas Metálicas , Camundongos , Animais , Ouro , Liberação Controlada de Fármacos , Análise Espectral RamanRESUMO
OBJECTIVES: The goal of this study was to determine whether electro-acupuncture (EA) stimulation might protect the motor endplate, minimize muscle atrophy in the hind limbs, and enhance functional recovery of rats with spinal cord injury (SCI). METHODS: Sprague-Dawley adult female rats (n = 30) were randomly assigned into Sham, SCI, and EA + SCI groups (n = 10 each). Rats in the Sham and SCI groups were bound in prone position only for 30 min, and rats in the EA + SCI group were treated with electro-acupuncture. The EA was conducted from the first day after surgery, lasted for 30 mins, once every day for 28 consecutive days. RESULTS: EA significantly prevented motor endplate degeneration, improved electrophysiological function, and ameliorated hindlimb muscle atrophy after SCI. Meanwhile, EA upregulated Tuj-1 expression, downregulated GFAP expression, and reduced glial scar formation. Additionally, after 4 weeks of EA treatment, the serum of SCI rats exhibited a reduced inflammatory response. CONCLUSION: These findings suggest that EA can preserve the motor endplate and reduce muscular atrophy. In addition, EA has been shown to improve the function of upper and lower neurons, reduce glial scar formation, suppress systemic inflammation, and improve axon regeneration.
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OBJECTIVE: Physical factors have been used to address disuse osteoporosis, but their effects and mechanism remain unclear. The purpose of this study was to determine the effects of pulsed electromagnetic field (PEMF) and whole-body vibration (WBV) on disuse osteoporosis to increase knowledge about treating osteoporosis. METHODS: A disuse osteoporosis rat model was developed by hind-limb unloading (HU) for 6 weeks. Forty 4-month-old female Sprague-Dawley rats were divided into 5 groups and given the following interventions: HU, HU treated with PEMF (HUP), HU treated with WBV (HUW), HU treated with both PEMF and WBV (HUPW), and no intervention (controls). After 8 weeks of intervention, measurements were taken. RESULTS: HU induced a decrease in bone mineral density (BMD), whereas HUP, HUW, and HUPW increased it. Moreover, the bone resorption markers tartrate-resistant acid phosphatase (TRAP) and C-terminal peptide of type 1 collagen in the HU group significantly increased, whereas the osteogenesis markers osteocalcin and N-terminal propeptide of type 1 procollagen significantly decreased. The markers osteocalcin and N-terminal propeptide of type 1 procollagen significantly increased, but TRAP and C-terminal peptide of type 1 collagen significantly decreased in the HUPW, HUP, and HUW groups compared with the HU group. In particular, HUPW effectively increased osteocalcin and decreased TRAP compared with HUP and WBV. Microcomputed tomography analysis of the femur indicated that HUPW improved trabecular number, bone volume over total volume, bone surface over bone volume, trabecular separation, and the structure model index compared with HUP and that it improved bone surface over bone volume, trabecular separation, and structure model index compared with HUW. The HUPW group showed a significant increase in maximum load compared with the HUW group and a significant increase in elastic modulus compared with the HUP group. CONCLUSION: PEMF, WBV, and their combination all attenuated bone resorption and enhanced osteogenesis. WBV and the combination of treatments have great potential to improve osteogenesis compared with PEMF. In addition, HUPW significantly attenuated bone resorption compared with HUW and HUP. IMPACT: The results of this study indicated that HUPW could effectively improve disuse osteoporosis compared with HUP, given that trabecular number and bone volume over total volume are associated with disuse osteoporosis. Moreover, BMD recovered well with HUP, HUW, and HUPW but the bone structure-especially mechanical performance-did not, indicating that osteoporosis should be evaluated with BMD and mechanical performance, not with BMD in isolation.
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Reabsorção Óssea , Osteoporose , Ratos , Feminino , Animais , Campos Eletromagnéticos , Microtomografia por Raio-X , Osteocalcina , Colágeno Tipo I , Vibração/uso terapêutico , Fosfatase Ácida Resistente a Tartarato , Pró-Colágeno , Ratos Sprague-Dawley , Osteoporose/terapia , Densidade Óssea , PeptídeosRESUMO
Stroke is the most common cerebrovascular disease with high morbidity and mortality around the world. However, the underlying mechanisms involved in nerve injury and cerebral ischaemia/reperfusion (I/R) during cerebrovascular disease are still not completely clear. In the present study, we investigate the role of kinesin family member 2 (KIF2) in the neuroprotection after cerebral I/R injury. KIF2 was aberrantly expressed in the cerebral tissues from middle cerebral artery occlusion (MCAO) rat model in a time dependent manner. A similar changing pattern was found in the cultured hypoxic neurons as well as SK-N-SH cells in vitro. Compared to the control, KIF2 inhibition significantly increased the level of malonic dialdehyde (MDA), and reduced the level of superoxide dismutase (SOD) as well as glutathione peroxidase (GSH-px) activity in cerebral tissues of MCAO rat model. The reactive oxygen species (ROS) level was also up-regulated after KIF2 siRNA knockdown in cultured hypoxic SK-N-SH cells. The apoptosis rates of hypoxic neurons and SK-N-SH cells as well as activated-caspase-3 level were obviously increased after KIF2 silencing. Furthermore, we found that the nuclear factor-kappa B (NF-κB) pathway was involved in KIF2-mediated neuroprotection after cerebral I/R injury, and induced apoptosis of hypoxic SK-N-SH cells by KIF2 silencing could be attenuated by the specific inhibitor BAY11-7082 of NF-κB. In conclusion, we demonstrate that KIF2 could mediate the neuroprotection in cerebral I/R injury by inhibiting activation of NF-κB pathway. This might provide a novel therapeutic target for cerebral I/R injury.
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Isquemia Encefálica/metabolismo , Cinesinas/biossíntese , NF-kappa B/metabolismo , Neuroproteção/fisiologia , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/fisiologia , Animais , Isquemia Encefálica/prevenção & controle , Linhagem Celular Tumoral , Humanos , Masculino , NF-kappa B/antagonistas & inibidores , Neuroproteção/efeitos dos fármacos , Nitrilas/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Sulfonas/farmacologiaRESUMO
Salvia miltiorrhiza Bunge (Lamiaceae), one of the most commonly used traditional Chinese herbs, is widely used for the treatment of cardiovascular disease, cerebrovascular disease, Alzheimer's disease, and Parkinson's disease in clinical practice. Salvianolic acid B (Sal B, C36H30O16, FW = 718.62) is the main water-soluble active ingredient of Salvia miltiorrhiza Bunge, which performs prophylactic and therapeutic activities against neurodegenerative diseases. So far, numerous studies have proved that multiple factors and mechanisms are involved in the pathological process of neurodegenerative diseases, including amyloid ß (Aß) aggregation and fibril formation, hyperphosphorylation of tau protein, neuroinflammation, oxidative-stress damage, mitochondrial dysfunction, and neuron apoptosis. This study is aimed at reviewing experimental studies and describing the possible mechanisms of Sal B on neurodegenerative diseases.
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Benzofuranos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Doenças Neurodegenerativas/terapia , Benzofuranos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , HumanosRESUMO
BACKGROUD: Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. To date, SCI treatment is still a significant challenge in clinic and research around the world. Danshen (dried roots and rhizomes of Salvia miltiorrhiza), a commonly used Chinese medicinal herb, has been attracting attention in SCI treatment. PURPOSE: Aim of this study was to evaluate the potential beneficial effects of danshen extract in a SCI rat model, as well as investigate possible mechanism of action and potential biomarkers. METHODS: Here, a rat SCI model was established with weight-drop method, and danshen extract was administered by oral gavage (12.5â¯g/kg). Recovery of motor function and histomorphological changes were evaluated by Basso, Beattie and Bresnahan score and hematoxylin-eosin staining, respectively. In addition, neurofilament 200 (NF-H), brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP) and CD11b expressions were assayed by immunofluorescence and western blot analysis. Furthermore, a metabolomics analysis based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was conducted. RESULTS: The results demonstrated that danshen extract could significantly ameliorated histopathology changes and improved recovery of motor function after SCI. Moreover, NF-H, BDNF and CD11b expression were progressively increased until 4 weeks post-injury after administrated danshen extract. Furthermore, a good separation was observed among different groups using OPLS-DA. Trajectory analysis showed the gradual shift from position of model group toward normal group with increasing time after administration of danshen extract. Meanwhile, 51 significantly altered metabolites were identified, while metabolic pathway analysis suggested that 6 metabolic pathways were disturbed by the altered metabolites. CONCLUSION: In summary, this study provides an overview of neuroprotective effects and investigates possible mechanism of danshen extract in SCI treatment. However, further research is needed to uncover its regulatory mechanisms more clearly.
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Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Fármacos Neuroprotetores/farmacologia , Salvia miltiorrhiza/química , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Cromatografia Líquida , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , Rizoma/química , Espectrometria de Massas em TandemRESUMO
Chinese medicinal herbs danshen and huangqin have attracted attention in spinal cord injury (SCI) treatment. Purpose of this study was to investigate and compare the pharmacokinetic characteristics of 4 phenolic acids and 4 flavonoids in SCI rat plasma after orally administrate danshen, huangqin and combined extract of these two herbs (CDH). Thus, a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneously quantitative determination of tanshinol, protocatechualdehyde, protocatechuic acid, salvianolic acid A, baicalein, baicalin, wogonin and wogonoside. After inducing a contusion injury by a weight-drop device, SCI rats were orally administrated a single dose (12.5 g/kg) of danshen, huangqin and CDH extracts, respectively. Then, blood samples at different time points were collected and analyzed. In CDH group, Cmax and AUC of tanshinol, protocatechualdehyde and protocatechuic acid significantly declined, while those of salvianolic acid A enhanced. These changes were beneficial for danshen to treat SCI. As for flavonoids, double peaks were observed in huangqin group, while this phenomenon disappeared in CDH group. Concomitantly, Cmax and AUC declined after administrated CDH. These alterations were due to influence of danshen active constituents on absorption and transportation process of flavonoids. Therefore, danshen and huangqin significantly influenced pharmacokinetic profile and parameters of each other, thus exert synergistic therapeutic effect in SCI treatment.
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Medicamentos de Ervas Chinesas/farmacocinética , Salvia miltiorrhiza/química , Scutellaria baicalensis/química , Traumatismos da Medula Espinal/tratamento farmacológico , Administração Oral , Animais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Combinação de Medicamentos , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Flavonoides/sangue , Humanos , Hidroxibenzoatos/sangue , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/etiologia , Espectrometria de Massas em TandemRESUMO
Objective: This study aimed to evaluate the efficacy and adverse events of vortioxetine for Chinese patients with major depressive disorder (MDD) over 10 weeks.Methods: A total of 120 patients with MDD were randomly assigned to two groups that received vortioxetine 20 mg or placebo for 10 weeks. The outcomes were the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impressions-Improvement (CGI-I) scale, Sheehan Disability Scale (SDS) at Week 10, and the presence of adverse events.Results: A total of 113 patients completed the study. Vortioxetine showed greater efficacy than the placebo in improving MADRS, HAM-A, CGI-I, and SDS scores at Week 10. However, no significant differences were found between the groups for any treatment-emergent adverse events. No suicide related to vortioxetine treatment was recorded.Conclusions: In summary, the results of this study showed that 10 weeks of vortioxetine treatment was efficacious and well-tolerated in patients with MDD.
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Transtorno Depressivo Maior/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Vortioxetina/farmacologia , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Vortioxetina/administração & dosagem , Vortioxetina/efeitos adversosRESUMO
Osteoporosis is a common orthopedic disease which is associated with hyper-activated osteoclastogenesis. Daphnetin is a natural coumarin derivative isolated from Genus Daphne, which possesses antiarthritis effect. However, the role of daphnetin in osteoclastogenesis has not been illustrated. This study aimed to investigate the effects of daphnetin on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in vitro. Our results showed that the osteoclast formation was significantly suppressed by daphnetin treatment in bone marrow-derived macrophages (BMMs), which was illustrated by reduced number of tartrate-resistant acid phosphatase positive multinucleated osteoclasts and decreased expression levels of tumor necrosis factor receptor-associated factors (TRAF6), c-Fos, nuclear factor of activated T cells c1, and cathepsin K. RANKL caused significant induction effects in reactive oxygen species (ROS) generation and nicotinamide adenine dinucleotide phosphate oxidase activity, whereas the induction was dramatically reduced after pretreatment with daphnetin. In addition, daphnetin prevented the RANKL-induced activation of NF-κB and Akt/GSK-3ß pathways in BMMs. These findings indicated that daphnetin exhibited an inhibitory effect on RANKL-induced osteoclastogenesis in vitro. The effect of daphnetin might be mediated by inhibiting ROS signal transduction, as well as preventing the activation of NF-κB and Akt/GSK-3ß signaling pathways. These findings indicated that daphnetin might be considered as a new therapeutic approach for the osteoporosis treatment.
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Fatty acid (FA) composition is closely associated with tumorigenesis and neoplasm metastasis. This study was designed to investigate the differences of phospholipid FA (PLFA) composition in erythrocyte and platelet cell membranes in both gastrointestinal (GI) tumor patients and healthy controls.In this prospective study, 50 GI tumor patients and 33 healthy volunteers were recruited between the years 2013 and 2015. Blood samples were collected from healthy volunteers and patients, and FA composition was assessed using gas chromatography-mass spectrometer (GC-MS), and data were analyzed by multifactor regression analysis.Compared with healthy controls, the percentages of C18:0 (stearic acid, SA), C22:6 (docosahexaenoic acid, DHA), and n-3 polyunsaturated FAs (n-3 PUFA) were significantly increased, while C18:1 (oleic acid, OA), C18:2 (linoleic acid, LA), and monounsaturated FAs (MUFA) decreased in erythrocyte membranes of GI tumor patients. Also, patient's platelets revealed higher levels of C20:4 (arachidonic acid, AA) and DHA, and lower levels of OA and MUFA.Our study displayed a remarkable change in the FA composition of erythrocyte and platelet membranes in GI tumor patients as compared with healthy controls. The octadeca-carbon FAs (SA, OA, and LA) in erythrocyte membranes could serve as a potential indicator for GI tumor detection.
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Membrana Eritrocítica/metabolismo , Ácidos Graxos/metabolismo , Neoplasias Gastrointestinais/sangue , Fosfolipídeos/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Análise de Regressão , Adulto JovemRESUMO
The Casimir force, originating from vacuum zero-point energy, is one of the most intriguing purely quantum effects. It has attracted renewed interests in current field of nanomechanics, due to the rapid size decrease of on-chip devices. Here we study the optomechanically-induced transparency (OMIT) with a tunable Casimir force. We find that the optical output rate can be significantly altered by the vacuum force, even terminated and then restored, indicating a highly-controlled optical switch. Our result addresses the possibility of designing exotic optical nano-devices by harnessing the power of vacuum.
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Antitumor-analgesic peptide (AGAP) is a novel recombinant polypeptide. The primary study showed that AGAP 1.0 mg/kg exhibited strong analgesic and antitumor effects. The tail vein administration of AGAP potently reduced pain behaviors in mice induced by intraplantar injection of formalin or intraperitoneal injection of acetic acid, without affecting basal pain perception. To further assess the mechanisms of AGAP, the effects of AGAP on sodium channels were assessed using the whole-cell patch clamp recordings in dorsal root ganglia (DRG) neurons. The results showed that AGAP (3-1000 nM) inhibited the sodium currents in small-diameter DRG neurons in a dose-dependent manner. 1000 nM AGAP could inhibit the current density-voltage relationship curve of sodium channels in a voltage-dependent manner and negatively shift the activation curves. 1000 nM AGAP could reduce the tetrodotoxin-resistant (TTX-R) sodium currents by 42.8% in small-diameter DRG neurons. Further analysis revealed that AGAP potently inhibited NaV1.8 currents by 59.4%, and negatively shifted the activation and inactivation kinetics. 1000 nM AGAP also reduced the NaV1.9 currents by 33.7%, but had no significant effect on activation and inactivation kinetics. Thus, our results demonstrated that submicromolar concentrations of AGAP inhibited TTX-R sodium channel in rat small-diameter DRG neurons. It is concluded that these new results may better explain, at least in part, the analgesic properties of this polypeptide.
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Neuropathic pain is a global medical concern, characterized by spontaneous pain, heat hyperalgesia and mechanical allodynia. The condition has been associated with alterations in the voltagegated sodium channels, Nav1.8 and Nav1.9, in nociceptive neurons termed nociceptors. However, an explanation for the contribution of these channels to the phenotype observed in neuropathic pain remains to be elucidated. The changes induced by chronic constriction injury (CCI) to Nav1.8 and Nav1.9 mRNA and protein levels, as well as electrical currents in injured and contralateral noninjured dorsal root ganglion (DRG) neurons are described in the present study. A marked downregulation was observed for each Nav isoform transcript and protein expressed in injured neurons with the exception of the Nav1.9 protein, which exhibited no change, while in contralateral noninjured neurons, the levels of protein and mRNA remained unchanged. Nav isoform functional analysis was then performed in L(46) DRG neurons 14 days after CCI. The Nav1.8 current density was markedly decreased in injured DRG neurons following CCI. The voltagedependent activation of the Nav1.8 channel in these neurons was shifted to depolarized potentials by 5.3 mV, while it was shifted to hyperpolarized potentials by 10 mV for inactivation. The electrophysiological function of Nav1.9 was not affected by CCI. The present study demonstrated that ectopic discharge following CCI, which was likely induced by a positive shift in the Nav1.8 current inactivation curve in injured neurons, enhanced the excitability of the neurons by facilitating tetrodotoxinresistant sodium channels into the fast inactivation state and did not occur as a result of a compensatory redistribution in the contralateral uninjured neurons.
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Gânglios Espinais/patologia , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Neuralgia/metabolismo , Neuralgia/patologia , Neurônios/patologia , Potenciais de Ação , Animais , Constrição , Gânglios Espinais/metabolismo , Hiperalgesia/etiologia , Masculino , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Canal de Sódio Disparado por Voltagem NAV1.9/genética , Canal de Sódio Disparado por Voltagem NAV1.9/metabolismo , Neuralgia/complicações , Neuralgia/genética , Neurônios/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Sprague-DawleyRESUMO
Intracellular calcium transient ([Ca(2+)]i transient) induced by fluid shear stress (FSS) plays an important role in osteoblastic mechanotransduction. Changes of membrane potential usually affect [Ca(2+)]i level. Here, we sought to determine whether there was a relationship between membrane potential and FSS-induced [Ca(2+)]i transient in osteoblasts. Fluorescent dyes DiBAC4(3) and fura-2AM were respectively used to detect membrane potential and [Ca(2+)]i. Our results showed that FSS firstly induced depolarization of membrane potential and then a transient rising of [Ca(2+)]i in osteoblasts. There was a same threshold for FSS to induce depolarization of membrane potential and [Ca(2+)]i transients. Replacing extracellular Na(+) with tetraethylammonium or blocking stretch-activated channels (SACs) with gadolinium both effectively inhibited FSS-induced membrane depolarization and [Ca(2+)]i transients. However, voltage-activated K(+) channel inhibitor, 4-Aminopyridine, did not affect these responses. Removing extracellular Ca(2+) or blocking of L-type voltage-sensitive Ca(2+) channels (L-VSCCs) with nifedipine inhibited FSS-induced [Ca(2+)]i transients in osteoblasts too. Quantifying membrane potential with patch clamp showed that the resting potential of osteoblasts was -43.3mV and the depolarization induced by FSS was about 44mV. Voltage clamp indicated that this depolarization was enough to activated L-VSCCs in osteoblasts. These results suggested a time line of Ca(2+) mobilization wherein FSS activated SACs to promote Na(+) entry to depolarize membrane that, in turn, activated L-VSCCs and Ca(2+) influx though L-VSCCs switched on [Ca(2+)]i response in osteoblasts.
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Canais de Cálcio Tipo L/metabolismo , Cálcio/metabolismo , Mecanotransdução Celular , Potenciais da Membrana , Osteoblastos/metabolismo , Células 3T3 , Animais , Fura-2/análogos & derivados , Camundongos , Nifedipino , Estresse MecânicoRESUMO
A previous study showed that antitumor-analgesic peptide (AGAP), a novel recombinant polypeptide, which had been expressed in Escherichia coli, exhibits analgesic and antitumor effects in mice. In the present study, we investigated the underlying analgesic mechanism of AGAP. The effect of AGAP on voltage-gated calcium channels (VGCCs) was assessed in acutely isolated rat dorsal root ganglia (DRG) neurons using the whole-cell patch clamp technique. The results showed that AGAP potently inhibited VGCCs, especially high-voltage activated (HVA) calcium channels. AGAP inhibited HVA and T-type calcium currents in a dose-dependent manner, but had no significant effect on their dynamic functions in rat small-diameter DRG neurons. AGAP inhibited N- and L-type calcium currents at 78.2% and 57.3%, respectively. Thus, the present study demonstrates that AGAP affects calcium currents through the inhibition of N-, L- and T-type channels in DRG neurons, explaining the potential mechanisms of antinociception.
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Canais de Cálcio Tipo T/efeitos dos fármacos , Gânglios Espinais/efeitos dos fármacos , Ativação do Canal Iônico/efeitos dos fármacos , Venenos de Escorpião/toxicidade , Animais , Canais de Cálcio Tipo T/fisiologia , Gânglios Espinais/fisiologia , RatosRESUMO
OBJECTIVE: To explore the effects of five-element music therapy on elderly patients with seasonal affective disorder in a Chinese nursing home. METHODS: The patients (n = 50) were recruited from a Shijingshan district nursing home in Beijing, China. They were randomly assigned to two groups, a treatment group and a control group, with 25 participants in each group. The patients received music therapy for 1-2 h each week over an 8-week period. The music therapy involved four phases: introduction, activities, listening to the Chinese five-element music, and a concluding phase. The participants in the control group did not listen to the five-element music. This study consisted of two parts: (a) a qualitative study that used focus groups to understand the feelings of the patients with seasonal affective disorder; (b) a quantitative study that involved administration of the self-rating depression scale (SDS) and Hamilton depression scale (HAMD) before and after treatment. RESULTS: (a) Qualitative analysis results: strength derived from the five-element group music therapy and emotional adjustment. The five-element group music therapy can reduce patients' psychological distress and let them feel inner peace and enhance their life satisfaction. (b) No significant difference in SDS and HAMD scores was found between the two groups (P > 0.05) prior to treatment. After treatment, the mean SDS score of the control group was 49.9 +/- 18.8, while the treatment group's score was 40.2 +/- 18.1. The HAMD score of the control group was 11.2 +/-3.1, and the treatment group's score was 8.8 +/- 4.9. Following 8 weeks of music therapy, the SDS and HAMD scores of the treatment group were significantly lower than those for the control group (P < 0.05). CONCLUSION: Five-element music therapy alleviated the symptoms of seasonal affective disorder in the elderly patients.
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Musicoterapia , Transtorno Afetivo Sazonal/terapia , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Casas de Saúde/estatística & dados numéricos , Transtorno Afetivo Sazonal/psicologiaRESUMO
OBJECTIVE: To evaluate the curative effects of manipulative reduction for children's type III humeral supracondylar fracture and the preventions of ischemic contracture of forearm in the early period. METHODS: From September 2008 to September 2011, 38 patients with humeral supracondylar fractures were treated with manipulative reduction and plaster stabilization, including 20 males and 18 females with an average age of 7.5 years (ranged, 2 to 13 years); the average time from injury to visit was 1.8 days(ranged,0.5 h to 6 d). There were 21 cases in straighten-ulnar deviation type and 17 cases in straighten-radial deviation type, 1 case in flexion type,all of them without vascular nerve injury. It was important to process swelling correctly in early stage of fracture. To decide fixed position according to the original displacement, and make a regular X-ray review, if found another displacement to correct it in 1-2 weeks after injury in time. Dismantle the plaster on the basis of bone healing and guide the functional exercise of elbow joint. According to Dodgt standard to evaluate clinical effects. RESULTS: All patients were followed up from 3 months to 1 year with an average of 7 months. All fractures healed. According to Dodgt standard, 14 patients got an excellent results, 19 good, 4 fair and 1 poor. The excellent and good rate was 86.84%. CONCLUSION: It can obtain satisfactory clinical effects to treat humeral supracondylar fracture in children with closed manipulative reduction and plaster stabilization, while without vascular nerve injury. Early correct processing swelling and paying attention to gypsous angle can effectively prevent the ischemic contracture of forearm.
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Antebraço/irrigação sanguínea , Fraturas do Úmero/terapia , Contratura Isquêmica/prevenção & controle , Adolescente , Moldes Cirúrgicos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Manipulação OrtopédicaRESUMO
INTRODUCTION: The copper(I)-catalyzed 1,3-dipolar cycloaddition of alkynes and azides to form 1,2,3-triazoles is the most popular reaction in click chemistry. This reaction is also near-perfect, in terms of its robustness, due to the high degree of reliability and complete specificity. Furthermore, this reaction has been used increasingly in drug discovery, because the formed 1,2,3-triazole can act as both a bioisostere and a linker. AREAS COVERED: This review provides an overview of a most important click reaction, 1,3-dipolar cycloadditions of alkynes and azides, in the drug discovery. EXPERT OPINION: Click chemistry is a very powerful tool, in the drug discovery, because it is very efficient in the creation of compound libraries through combinatorial methodology. However, the 1,2,3-triazole ring itself is not a commonly used pharmacophore and has rarely been found in marketed drugs, demonstrating that there are still some limitations during the use of 1,2,3-triazole in the molecules of drug candidates. Hopefully, in the next decade, we will witness the emergence of 1,2,3-triazole-bearing drugs on the market as this click reaction is used more and more widely in the drug discovery.