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1.
Sci Total Environ ; 923: 171475, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38453063

RESUMO

Climbazole is an azole biocide that has been widely used in formulations of personal care products. Climbazole can cause developmental toxicity and endocrine disruption as well as gut disturbance in aquatic organisms. However, the mechanisms behind gut toxicity induced by climbazole still remain largely unclear in fish. Here, we evaluate the gut effects by exposing grass carp (Ctenopharyngodon idella) to climbazole at levels ranging from 0.2 to 20 µg/L for 42 days by evaluating gene transcription and expression, biochemical analyses, correlation network analysis, and molecular docking. Results showed that climbazole exposure increased cyp1a mRNA expression and ROS level in the three treatment groups. Climbazole also inhibited Nrf2 and Keap1 transcripts as well as proteins, and suppressed the transcript levels of their subordinate antioxidant molecules (cat, sod, and ho-1), increasing oxidative stress. Additionally, climbazole enhanced NF-κB and iκBα transcripts and proteins, and the transcripts of NF-κB downstream pro-inflammatory factors (tnfα, and il-1ß/6/8), leading to inflammation. Climbazole increased pro-apoptosis-related genes (fadd, bad1, and caspase3), and decreased anti-apoptosis-associated genes (bcl2, and bcl-xl), suggesting a direct reaction to apoptosis. The molecular docking data showed that climbazole could form stable hydrogen bonds with CYP1A. Mechanistically, our findings suggested that climbazole can induce inflammation and oxidative stress through CYP450s/ROS/Nrf2/NF-κB pathways, resulting in cell apoptosis in the gut of grass carp.


Assuntos
Carpas , Suplementos Nutricionais , Imidazóis , Animais , Suplementos Nutricionais/análise , Dieta , NF-kappa B , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Imunidade Inata , Azóis/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Inflamação/induzido quimicamente , Inflamação/veterinária , Estresse Oxidativo , Apoptose , Carpas/metabolismo
2.
J Neurophysiol ; 130(2): 380-391, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37435647

RESUMO

Electroacupuncture (EA) is well documented to treat irritable bowel syndrome (IBS). However, the mechanism of the central nervous system related to IBS and acupuncture stimulation is still not well known. In this study, a rat model of IBS was established by cold-restraint comprehensive stresses for 15 days, and it was found that the levels of corticotropin-releasing hormone (CRH), corticosterone (CORT), and adrenocorticotropic hormone (ACTH) in the peripheral serum were increased; the visceral sensitivity was enhanced; and the intestinal motility was accelerated, specifically, there was an enhancement in the discharge frequency of neurons in the paraventricular nucleus (PVN). EA treatment for 3 days, 20 min/day, alleviated the increase in the levels of CRH, CORT, and ACTH in the peripheral serum of rats, reduced the visceral sensitivity of IBS rats, and inhibited colon movement and discharge frequency of the neurons in the PVN. In addition, EA could reduce the excitability of CRH neurons and the expression of corticotropin-releasing hormone receptor 1 (CRHR1) and corticotropin-releasing hormone receptor 2 (CRHR2) in PVN. At the same time, the expression of CRH, CRHR1, and CRHR2 in the peripheral colon was decreased. Taken together, EA appears to regulate intestinal functional activity through the central CRH nervous system, revealing the central regulation mechanism of EA in IBS rats, and providing a scientific research basis for the correlation among the meridians, viscera, and brain.NEW & NOTEWORTHY The purpose of this research was to determine the central regulatory mechanism of electroacupuncture (EA) in rats with irritable bowel syndrome (IBS). Our results showed that combined with the serum changes in corticotropin-releasing hormone (CRH), corticosterone (CORT), and adrenocorticotropic hormone (ACTH), the improvement of IBS by EA was related to them. Furthermore, EA could regulate intestinal functional activity through the central CRH+ nervous system.


Assuntos
Eletroacupuntura , Síndrome do Intestino Irritável , Ratos , Animais , Hormônio Liberador da Corticotropina/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Síndrome do Intestino Irritável/terapia , Corticosterona , Eletroacupuntura/métodos , Ratos Sprague-Dawley , Hormônio Adrenocorticotrópico/metabolismo , Neurônios/metabolismo
3.
J Ethnopharmacol ; 302(Pt B): 115934, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36414216

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zhi-zi-chi decoction (ZZCD), from "Treatise on Febrile Diseases", is a typical traditional Chinese medicine herb pair, which consists of Gardeniae Fructus (GF) and Semen Sojae Praeparatu (SSP). In clinical research, ZZCD was widely used to fight depression, remove annoyance. Many studies have reported that gut microbiota is critical target for the influence of depress through gut-brain axis, and our previously studies have found that ZZCD exhibiting antidepressant effect was through the gut-brain axis. However, the specific mechanism by which gut microbiota mediates the pharmacokinetics parameters of active compounds from ZZCD during the process of depression treatment has not yet been studied. AIM OF THE STUDY: To explore the differences in pharmacokinetics characters of bioactive iridoids from ZZCD and study the changes of gut microbiota at different stages of depression with the personalized medicine of ZZCD. MATERIALS AND METHODS: A new strategy exploring the relationship among disease phenotypes (D), intestinal microbiota (I), enzymes (E) and traits of metabolism (T) named as "DIET" was established. Firstly, a fast, selective and sensitive ultra-performance liquid chromatography coupled with tandem mass spectrometer (UPLC-MS/MS) was established and validated to quality the main bioactive compounds from ZZCD and compare the pharmacokinetics and bioavailability of different iridoids prototypes and metabolites from ZZCD between normal and chronic unpredictable mild stress rats. Subsequently, the activity of corresponding metabolic enzymes of anti-depressive compounds, ß-glucosidases and sulfotransferases, were analyzed by ρ-nitrophenyl-ß -D-glucopyranoside and sulfotransferases ELISA kits, respectively. Finally, 16S rRNA gene sequencing was adopt to analyze intestinal bacteria composition for the treatment of depression by ZZCD. RESULTS: The antidepressant effect of ZZCD was promoted due to the increased exposures and reduced eliminations of anti-depressive compounds, especially geniposide and genipin 1-gentiobioside, under the depression state. With the ZZCD treatment, the depression was improved, but the exposures of anti-depressive compounds from ZZCD gradually decreased. Meanwhile, there were the corresponding decreased trends on the activity of ß-glucosidases and sulfotransferases. With the consumption of ZZDC and the improvement of depression, the exposures of anti-depressive iridoid glycosides decreased and the activity of metabolism enzymes restored. Meanwhile, the dysbiosis of pathogenic bacteria (Bacteroidota) induced by depression was ameliorated and the probiotics (Firmicutes) at the phylum and genus level raised, the two phyla are closely related to the production of ß-glucosidase and sulfotransferases. CONCLUSIONS: It is the first proposed that ZZCD could personalized to treat depression at different stages targeting gut microbiota and gut microbiome could emerged as a potential diagnostic and therapeutic biomarker in depression.


Assuntos
Celulases , Depressão , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Animais , Ratos , Cromatografia Líquida , Depressão/tratamento farmacológico , Iridoides , Medicina de Precisão , RNA Ribossômico 16S , Espectrometria de Massas em Tandem , Medicamentos de Ervas Chinesas/farmacologia
4.
BMJ Open ; 12(10): e062494, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36288843

RESUMO

INTRODUCTION: Lower limb dysfunction is among the common sequelae of patients who had a poststroke and often results in the reduction of the quality of life. This study aims to assess the short and interim-term efficacy of dry needling (DN) intervention on lower extremity function, balance and gait in lower limb dysfunction after stroke. METHODS AND ANALYSIS: This protocol entails an assessor and statistician-blinded, single-centre study with a randomised controlled trial. Forty-four patients who had a poststroke will be randomly allocated (1:1) to either the conventional treatment group (n=22) or the DN group (n=22). The conventional treatment group will receive conventional rehabilitation treatment once a day for 40 min each time. The treatment will be performed five times a week for 2 weeks. In the DN group, participants will be treated with DN on the basis of the conventional treatment. The intervention will be performed thrice a week for 2 weeks. The primary outcome that determines the efficacy of lower limb dysfunction will be the change in the Fugl-Meyer Assessment of Lower Extremity scale. The secondary indicators include the range of motion of knee and ankle joints, limits of stability, modified Clinical Test of Sensory Interaction on Balance, Timed Up and Go test, Modified Ashworth Scale and Barthel Index. Results will be evaluated at baseline, at 24 hours after intervention, at 2 weeks after intervention and at 3-month follow-up. Data will be released after the completion of the study. Adverse events will be reported. ETHICS AND DISSEMINATION: The experiment was approved by the Ethical Committee of Shanghai Tong Ren Hospital in October 2021 (approval number: 202105702). The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000040754.


Assuntos
Agulhamento Seco , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Qualidade de Vida , Equilíbrio Postural , Resultado do Tratamento , Estudos de Tempo e Movimento , China , Acidente Vascular Cerebral/terapia , Extremidade Inferior , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Ann Palliat Med ; 11(8): 2695-2708, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36064360

RESUMO

BACKGROUND: Ischaemic stroke is a common neurological disease and a leading cause of severe disability and death in developed countries. In most cases, stroke is thought to be a multifactorial disorder or complex trait for which classic patterns of inheritance cannot be shown. Xuesaitong is one of the most commonly used medicines for treating ischemic stroke in China. However, compared to the conventional therapy, the effectiveness and safety of Xuesaitong for ischemic stroke needs to be further systematically reviewed and determined. METHODS: Relevant randomized controlled trials (RCTs) examining the use of the Xuesaitong soft capsule in the treatment of patients with ischemic stroke were identified from databases, including the China National Knowledge Infrastructure, Wanfang, PubMed, Embase, and Web of Science databases. Next, 2 researchers independently extracted information from the included studies, analyzed the data using STATA 15.0 software, and evaluated the quality of the included studies using RevMan 5.3. RESULTS: A total of 17 RCTs (comprising 1,942 patients with ischemic stroke) were included in the meta-analysis. The meta-analysis results showed that the Xuesaitong soft capsule treatment increased patients' total effective rate compared to conventional or other drug treatments, and improved patients' Clinical Severity Score (CSS scores) or Barthel index (BI) score. A further subgroup analysis stratified by different treatment times showed that Xuesaitong soft capsule treatment at 4 and 8 weeks improved CSS scores more than treatment at 2 weeks in patients with ischemic stroke. Additionally, the Xuesaitong soft capsule also significantly improved plasma viscosity, whole-blood viscosity at high and low shear rates, fibrinogen, hematocrit, and the effect on traditional Chinese medicine (TCM) single symptoms or signs in patients with ischemic stroke. DISCUSSION: In summary, compared to conventional or other drug treatments, the Xuesaitong soft capsule treatment was beneficial in improving patients' TCM symptoms (e.g., crooked mouth and tongue, and dizziness) and various indicators. Further, Xuesaitong soft capsule may be a safe and effective drug for the treatment of ischemic stroke. And large-scale randomized clinical trials are needed to further confirm our findings.


Assuntos
Medicamentos de Ervas Chinesas , AVC Isquêmico , Saponinas , Acidente Vascular Cerebral , Cápsulas/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Saponinas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico
7.
Neuropsychiatr Dis Treat ; 17: 2599-2611, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413646

RESUMO

OBJECTIVE: Postoperative cognitive dysfunction (POCD) after anesthesia and surgery (AS) is a common complication in the elderly population. A cholinergic-dependent signal, the alpha7-nicotinic acetylcholine receptor (α7-nAChR), has been suggested to regulate cognitive processes in a variety of neurologic diseases. In the current study, we determined whether electroacupuncture (EA) pretreatment ameliorates AS-induced POCD in aged rats, as well as the underlying mechanism. METHODS: Male Sprague-Dawley rats (20 months old) were randomly assigned to the following 5 groups (n=12): vehicle; POCD (tibial fracture surgery); EA plus POCD; EA plus POCD and alpha-bungarotoxin (α-BGT); and POCD plus α-BGT groups. Alpha-bungarotoxin (1 µg/kg), a selective antagonist of α7-nAChR, was administrated via intraperitoneal injection before EA. Thirty days post-AS, the Morris water maze and a novel objective recognition test were used to evaluate cognitive function. Neuronal amount, apoptosis, microglial activation, percentage of high mobility group box 1 (HMGB1)- and nuclear factor-κB (NF-κB)-positive microglia, and levels of HMGB-1 downstream factors, including NF-κB, interleukin-6 (IL-6), and IL-1ß, were detected by Nissl staining, immunofluorescence, and Western blot assays. RESULTS: EA pretreatment significantly increased crossing platform times and elevated the time with a novel object, restored the quantity of neurons, decreased TUNEL-positive neurons, alleviated activation of microglia, downregulated expression of HMGB1 and NF-κB in the microglia, and reduced levels of phosphor-NF-κB, IL-6, and IL-1ß 35 days after AS, while α-BGT partially reversed these changes. CONCLUSION: EA pretreatment improved AS-induced POCD in aged rats, and the underlying mechanism may be associated with inhibition of HMGB1-NF-κB via an α7-nAChR signal in the microglia.

8.
Fitoterapia ; 153: 104989, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34252513

RESUMO

Ten new nortriterpenes, euphorbiumrins A-J (1-10), together with three known analogues (11-13) were isolated from the latex of Euphorbia resinifera. Their structures were established on the basis of extensive spectroscopic analyses (IR, UV, HRESIMS, 1D and 2D NMR). Their inhibitions on tomato yellow leaf curl virus (TYLCV) were evaluated and compound 5 exhibited significant anti-TYLCV activity with an inhibition rate of 71.7% at concentration of 40 µg/mL.


Assuntos
Begomovirus/efeitos dos fármacos , Euphorbia/química , Doenças das Plantas/prevenção & controle , Triterpenos/farmacologia , China , Látex/química , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Doenças das Plantas/virologia , Nicotiana/virologia , Triterpenos/isolamento & purificação
9.
Clin Interv Aging ; 16: 757-765, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33976542

RESUMO

BACKGROUND: Postoperative cognitive decline (POCD) in the old ages seriously delays the rapid recovery. Here, we aimed to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) against POCD in elderly patients undergoing laparoscopic radical colon cancer surgery, as well as the potential mechanism. METHODS: A prospective, single-center, parallel-group, randomized trial was designed. A total of 100 patients (age ≥65 years) undergoing laparoscopic radical resection of colon cancer were involved and randomly divided into TEAS (Group T) and control (Group C) groups. The patients in Group T were performed with percutaneous acupoint electrical stimulation in bilateral Hegu, Neiguan and Zusanli points from 30 minutes before anesthesia induction to the end of surgery. A Z-score based on Mini-Mental State Exam (MMSE) was used to assess the incidence of POCD. The levels of serum IL-6, hs-CRP, CGRP at 0 min before TEAS (T0), 1 h after beginning of surgery (T1) and the end of surgery (T2) were evaluated. RESULTS: Our data showed that the cumulative duration of POCD on postoperative day 2 and 3 in Group T was significantly decreased compared to Group C (P < 0.05). Compared with T0, the levels of serum IL-6, hs-CRP, and CGRP in both Group T and C were statistically elevated at T1 and T2 (P < 0.05). Moreover, the levels of serum IL-6 and hs-CRP were decreased, but the level of CGRP was increased in Group T compared to Group C at T1 and T2 (P < 0.05). CONCLUSION: TEAS is associated with a lower cumulative duration of POCD in elderly patients undergoing laparoscopic radical colon cancer surgery, which may be related to the regulation of inflammatory factors and neuropeptides interacted with gut-brain axis.


Assuntos
Pontos de Acupuntura , Transtornos Cognitivos/terapia , Complicações Pós-Operatórias/terapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Idoso , Proteína C-Reativa/análise , Neoplasias do Colo/cirurgia , Comorbidade , Feminino , Humanos , Interleucina-6/sangue , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Duração da Cirurgia , Projetos Piloto , Estudos Prospectivos
10.
Carbohydr Polym ; 235: 115949, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32122485

RESUMO

Photodynamic antifungal therapy is a promising treatment for increasing drug-resistant fungi. However, low physiological solubility and low fungi-affinity of most potential photosensitizers limits their therapeutic efficacy. To improve the water-solubility and photodynamic antifungal activity of zinc(II) phthalocyanine, two molecular-weight carboxymethyl chitosans (CMC1,50 kDa; CMC2,170 kDa) were herein respectively conjugated with 1-[4-(2-aminoethyl)phenoxy] zinc(II) phthalocyanine (ZnPcN) and further quaternized, and eight novel conjugates were obtained and characterized. Their photophysical and photochemical properties, cellular uptakes and in vitro photodynamic antifungal activities against Candida albicans have also been investigated. All the conjugates are less aggregated in water than ZnPcN. The low-molecular-weight CMC1-conjugated ZnPcN is more readily ingested and highly photoactive. Mainly due to its highest uptake by Candida cells, a conjugate of CMC1 and ZnPcN shows the highest photocytotoxicity with an IC90 value down to 0.72 µM. Further quaternization decreases the photocytotoxicity. Additionally, the conjugates show special affinity to the mitochondria of C. albicans.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Quitosana/análogos & derivados , Indóis/farmacologia , Compostos Organometálicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Candida albicans/citologia , Quitosana/química , Quitosana/farmacologia , Indóis/química , Isoindóis , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Organometálicos/química , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Propriedades de Superfície , Compostos de Zinco
11.
Front Pharmacol ; 10: 1446, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849686

RESUMO

Traditional Chinese medicines (TCMs) represent one form of complementary and alternative medicine. The popularity and complexity in production make them attractive and vulnerable to adulteration in stages ranging from planting to production. Adulteration refers to the addition of extraneous, improper, or inferior ingredients that should not be present in TCMs. To detect and combat adulterated TCMs, supplementary testing methods (STMs), which expand the capability of routine testing standards, have been applied in China since 2003. From 2003 to 2017, a total of 184 STMs for TCMs were approved by the Chinese national drug regulatory authority. By assessing these STMs, this research intends to identify those TCMs vulnerable to adulteration, to list common adulterants, and to characterize the techniques of analysis. The results show that adulteration of TCMs can be classified into three main categories: the addition of undeclared drugs/chemical substances, substitution with non-drug components, and the addition of foreign non-drug materials. The top five therapeutic areas of TCMs vulnerable to adulteration are diabetes, calm and sleep, sexual dysfunction, pain relief, and rheumatism. A total of 166 adulterants were detected in the adulterated TCM preparations and herbal products studied here, with 158 adulterants in TCM preparations and 43 in herbal products, with 35 adulterants in common. Each STM consists of different pharmaceutical analysis techniques, including tests for physical-chemical properties, chromatography, spectroscopic techniques, and mass spectrometry. The analytical methodology of STMs relies on the combination of these techniques, with HPLC ranking the highest percentage (76.1%) and physical-chemical techniques the lowest percentage (11.4%). This research shows that STMs have played a crucial role in combating adulterated TCMs. However, STMs represent merely a product testing-centered regulatory strategy. The inspection of cultivation and manufacturing processes should also be strengthened. More importantly, the awareness and self-discipline of TCM manufacturers in implementing good manufacturing practices and regulating the planting and cultivation of raw materials should be improved.

12.
J Crit Care ; 50: 287-295, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30673625

RESUMO

PURPOSE: In the critically ill, sarcopenia is associated with a variety of adverse outcomes however there is no consensus regarding its management. This study aimed to systematically review the evidence for interventions for the management and prevention of sarcopenia in critically ill patients. MATERIALS AND METHODS: Bibliographic databases were searched according to pre-specified criteria (PROSPERO-CRD42018086271). Randomised controlled trials (RCTs) investigating interventions to preserve muscle mass and/or function in critically ill patients were included. Two independent authors selected the articles and assessed bias using the Cochrane Risk of Bias Tool. RESULTS: Twenty-two eligible RCTs were identified comprising 2792 patients. Three main groups of interventions were implemented in these trials: neuromuscular electrical stimulation (NMES), exercise-based and nutritional. Both the interventions and outcomes measured varied significantly between studies. NMES was most frequently studied as an intervention to preserve muscle mass whilst exercise-based treatments were evaluated as interventions to preserve muscle function. There was significant variation in the efficacy of the interventions on sarcopenia markers and secondary outcomes. CONCLUSIONS: NMES and exercise-based interventions may preserve muscle mass and function in patients with critical illness. There is a lack of consistency seen in the effects of these interventions. Further, large, high quality RCTs are required.


Assuntos
Estado Terminal , Sarcopenia/terapia , Terapia por Estimulação Elétrica , Exercício Físico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sarcopenia/prevenção & controle
13.
J Pain Res ; 11: 2797-2808, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30510442

RESUMO

PURPOSE: Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, with chronic pain as its typical symptom. Although studies have shown that an activated peripheral CB2 receptor can reduce acute pain, whether the CB2 receptor is involved in electroacupuncture (EA) inhibiting chronic pain and the involved mechanism remains unclear. The aim of this study was to investigate whether EA may strengthen peripheral CB2 receptor-inhibited chronic pain in a mouse model of KOA. MATERIALS AND METHODS: KOA was induced by intra-articular injection of monosodium iodoacetate (MIA) into the left knee joint of mice. Thermal hyperalgesia was tested with the hot plate test, and mechanical allodynia was quantified using von Frey filaments. The expression of CB2 receptor and IL-1ß were quantified by using immunofluorescence labeling. RESULTS: EA treatment at 2 Hz+1 mA significantly increased the expression of CB2 receptor in fibroblasts and decreased the expression of IL-1ß in the menisci compared with that in the KOA group. However, EA had no effect on the expression of IL-1ß in CB2-/- mice. At 2 Hz+1 mA, EA significantly increased mechanical threshold, thermal latency, and weight borne after KOA modeling. However, knockout of the CB2 receptor blocked these effects of EA. After 2 Hz+1 mA treatment, EA significantly reduced the Osteoarthritis Research Society International (OARSI) score after KOA modeling. However, EA had no significant effect on the OARSI score in CB2-/- mice. CONCLUSION: EA reduced the expression of IL-1ß by activating the CB2 receptor, thus inhibiting the chronic pain in the mouse model of KOA.

14.
Medicine (Baltimore) ; 97(52): e13814, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30593173

RESUMO

Transcutaneous electrical acupoint stimulation (TEAS) is a emerging treatment which combines transcutaneous electrical nerve stimulation with traditional acupoint therapy. The present study was aimed to evaluate the effect of TEAS on the effective concentration (EC50) of remifentanil suppressing tracheal extubation response in elderly patients.Fifty-three patients undergoing spine surgery were randomly divided into 2 groups: control group (group C, n = 26) and transcutaneous electrical acupoint stimulation group (group TEAS, n = 27). The EC50 values for remifentanil TCI were determined using sequential method and probit analysis.The remifentanil EC50 of that suppressed responses to extubation during anesthetic emergence was 1.20 ng/mL in group TEAS, a value that was significantly lower than the 1.64 ng/mL needed by patients in group C.The TEAS can enhance the efficacy of remifentanil on suppressing responses to tracheal extubation in elderly patients, the EC50 of remifentanil can reduce approximately 27% compared with group C.


Assuntos
Analgesia por Acupuntura/métodos , Pontos de Acupuntura , Extubação/métodos , Analgésicos Opioides/administração & dosagem , Remifentanil/administração & dosagem , Estimulação Elétrica Nervosa Transcutânea/métodos , Idoso , Idoso de 80 Anos ou mais , Extubação/efeitos adversos , Período de Recuperação da Anestesia , Terapia Combinada , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
15.
Clin Interv Aging ; 13: 2127-2134, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425466

RESUMO

PURPOSE: This study aims to investigate the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative delirium (POD) in elderly patients with silent lacunar infarct and preliminarily to determine the relationship among TEAS, blood-brain barrier (BBB), neuroinflammation, and POD. PATIENTS AND METHODS: Sixty-four-old patients with silent lacunar infarct were randomly divided into two groups: group TEAS and control group (group C). Patients in the group TEAS received TEAS (disperse-dense waves; frequency, 2/100 Hz) on acupoints Hegu and Neiguan of both sides starting from 30 minutes before induction of anesthesia until the end of surgery, and the intensity was the maximum current that could be tolerated. In group C, electrodes were placed on the same acupoints before anesthesia induction, but no current was given. At 0 minute before the treatment of TEAS, 30 minutes after skin incision, and after completion of surgery (T1-3), blood samples were extracted to detect the concentration of serum tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), and S100ß. We assessed patients for delirium and coma twice daily in the first 3 postoperative days using the Confusion Assessment Method for the intensive care unit and the Richmond Agitation-Sedation Scale. RESULTS: This study preliminarily suggests that TEAS can reduce the development of POD in elderly patients with silent lacunar infarction (6.3% vs 25.0%; P=0.039). Compared with the baseline value at T1, the serum concentrations of IL-6, TNF-α, MMP-9, and S100ß were significantly increased at T2-3 in both the groups (P<0.05). Compared with group TEAS, serum levels of TNF-α and IL-6 were higher at T2-3 and serum levels of MMP-9 and S100ß were higher at T3 in group C (P<0.05). The intraoperative anesthetic consumptions were less in group TEAS than group C. CONCLUSION: TEAS can alleviate POD in older patients with silent lacunar infarction and may be related to reduce the neuroinflammation by lowering the permeability of BBB.


Assuntos
Pontos de Acupuntura , Delírio/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Acidente Vascular Cerebral Lacunar/complicações , Estimulação Elétrica Nervosa Transcutânea/métodos , Idoso , Barreira Hematoencefálica/fisiologia , Delírio/fisiopatologia , Feminino , Finlândia , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Complicações Pós-Operatórias/fisiopatologia , Cuidados Pré-Operatórios , Fatores de Risco , Acidente Vascular Cerebral Lacunar/fisiopatologia
16.
Crit Care Med ; 46(12): e1128-e1135, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30222631

RESUMO

OBJECTIVES: Observational studies suggest an association between vitamin D deficiency and adverse outcomes of critical illness and identify it as a potential risk factor for the development of lung injury. To determine whether preoperative administration of oral high-dose cholecalciferol ameliorates early acute lung injury postoperatively in adults undergoing elective esophagectomy. DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: Three large U.K. university hospitals. PATIENTS: Seventy-nine adult patients undergoing elective esophagectomy were randomized. INTERVENTIONS: A single oral preoperative (3-14 d) dose of 7.5 mg (300,000 IU; 15 mL) cholecalciferol or matched placebo. MEASUREMENTS AND MAIN RESULTS: Primary outcome was change in extravascular lung water index at the end of esophagectomy. Secondary outcomes included PaO2:FIO2 ratio, development of lung injury, ventilator and organ-failure free days, 28 and 90 day survival, safety of cholecalciferol supplementation, plasma vitamin D status (25(OH)D, 1,25(OH)2D, and vitamin D-binding protein), pulmonary vascular permeability index, and extravascular lung water index day 1 postoperatively. An exploratory study measured biomarkers of alveolar-capillary inflammation and injury. Forty patients were randomized to cholecalciferol and 39 to placebo. There was no significant change in extravascular lung water index at the end of the operation between treatment groups (placebo median 1.0 [interquartile range, 0.4-1.8] vs cholecalciferol median 0.4 mL/kg [interquartile range, 0.4-1.2 mL/kg]; p = 0.059). Median pulmonary vascular permeability index values were significantly lower in the cholecalciferol treatment group (placebo 0.4 [interquartile range, 0-0.7] vs cholecalciferol 0.1 [interquartile range, -0.15 to -0.35]; p = 0.027). Cholecalciferol treatment effectively increased 25(OH)D concentrations, but surgery resulted in a decrease in 25(OH)D concentrations at day 3 in both arms. There was no difference in clinical outcomes. CONCLUSIONS: High-dose preoperative treatment with oral cholecalciferol was effective at increasing 25(OH)D concentrations and reduced changes in postoperative pulmonary vascular permeability index, but not extravascular lung water index.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Colecalciferol/administração & dosagem , Esofagectomia/métodos , Idoso , Biomarcadores , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Água Extravascular Pulmonar/metabolismo , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Reino Unido , Vitamina D/sangue
17.
Nanomedicine ; 14(7): 2283-2294, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29981460

RESUMO

Tumor angiogenesis is a key step in the process of tumor development, and antitumor angiogenesis has a profound influence on tumor growth. Herein we report a dual-function drug delivery system comprising a Near-infrared (NIR) dye and an anti-angiogenic drug within liposomes (Lip-IR780-Sunitinib) for enhanced antitumor therapy. The hydrophobic NIR dye IR780 was loaded into the liposome phospholipid bilayer, and the bilayer would be disrupted by laser irradiation so that anti-angiogenic drug sunitinib release would be activated remotely at the tumor site. The released hydrophilic sunitinib could potentially target multiple VEGF receptors on the tumor endothelial cell surface to inhibit angiogenesis. Meanwhile, IR780-loaded liposomes kill the cancer cells by photothermal therapy. Lip-IR780-Sunitinib exhibited enhanced anti-tumor and anti-angiogenic effects in vitro and in vivo. This system facilitates easy and controlled release of cargos to achieve anti-tumor angiogenesis and photothermal therapy.


Assuntos
Neoplasias da Mama/terapia , Hipertermia Induzida , Indóis/química , Lipossomos/administração & dosagem , Neovascularização Patológica/terapia , Fototerapia , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Apoptose , Neoplasias da Mama/patologia , Movimento Celular , Proliferação de Células , Terapia Combinada , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Indóis/administração & dosagem , Lasers , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/patologia , Espectroscopia de Luz Próxima ao Infravermelho , Sunitinibe/química , Sunitinibe/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Nat Prod ; 81(5): 1209-1218, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29667820

RESUMO

The phytochemical study of Euphorbia resinifera afforded 18 structurally diverse diterpenoids, including 14 new ingol-type diterpenoids, euphorblins A-N (1-14), a new rhamnofolane diterpenoid, euphorblin O (15), and three known analogues (16-18). The structures of these compounds were deduced using 2D NMR spectroscopy and NOE experiments. The structure of compound 1 was confirmed by single-crystal X-ray crystallography. The abilities of the compounds to enhance lysosomal biosynthesis were evaluated through LysoTracker Red staining. Among the 10 active compounds, compounds 2, 4, and 18 showed remarkable immunofluorescence strength, and their LysoTracker staining intensities were 155.9%, 143.5%, and 140.7%, respectively, greater than that of the control. A series of lysosomal genes were also found to be upregulated by these compounds, which further confirms their ability to induce lysosome biosynthesis and suggests that these diterpenoids have potential as lead compounds for the development of drugs for the treatment of lysosome-related diseases.


Assuntos
Diterpenos/química , Diterpenos/farmacologia , Euphorbia/química , Lisossomos/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Cristalografia por Raios X/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética/métodos , Ressonância Magnética Nuclear Biomolecular/métodos
19.
Front Mol Neurosci ; 11: 112, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29681797

RESUMO

Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA) is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC) function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA). EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG) level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG) can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG)-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.

20.
Brain Behav Immun ; 67: 91-100, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28782714

RESUMO

The therapeutic effect of electroacupuncture (EA) on inflammatory pain has been well recognized clinically. The inflammasome promotes the maturation of the inflammatory cytokines, and EA can stimulate cannabinoid CB2 receptors in inflamed tissues. In this study we investigated whether EA inhibits NLRP3 inflammasome activation through CB2 receptors and thus relieving inflammatory pain. Assay of Caspase-1 activity and western blotting revealed that complete Freund's adjuvant (CFA) injection activated the NLRP3 inflammasome in the skin tissue in rats, which was attenuated by EA treatment. Immunofluorescence labeling showed that NLRP3 inflammasome elicited by CFA in the skin macrophages were decreased by EA. Nociceptive behavioral tests demonstrated that in CB2 receptor knockout mice, the EA effects on NLRP3 inflammasomes were largely attenuated. In addition, in vitro studies in a macrophage cell line showed that CB2 receptor stimulation inhibited the NLRP3 inflammasome activation. Thus, our results suggest a novel signaling pathway through which CB2 receptors are involved in the analgesic effect of EA on inflammatory pain. Stimulation of CB2 receptors inhibits NLRP3 inflammasome activation in inflamed skin tissues. These results suggest that EA reduces the inflammatory pain by inhibiting the activation of NLRP3 inflammasome through CB2 receptors. Our findings provide novel information about the mechanisms through which EA and CB2 receptor activation reduce inflammatory pain.


Assuntos
Eletroacupuntura , Inflamassomos/metabolismo , Inflamação/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Dor/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Animais , Linhagem Celular , Inflamação/complicações , Inflamação/prevenção & controle , Masculino , Camundongos , Dor/complicações , Dor/prevenção & controle , Limiar da Dor , Ratos Sprague-Dawley , Receptor CB2 de Canabinoide/genética , Pele/metabolismo
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