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1.
J Wound Care ; 32(12): 773-786, 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38060413

RESUMO

OBJECTIVE: To investigate the efficacy and safety of autologous platelet-rich plasma (au-PRP) for diabetic foot ulcer (DFU) treatment. METHOD: We conducted database searches (MEDLINE, EMBASE, evidence-based medicine reviews: CENTRAL, PubMed, and Web of Science) and reference mining for randomised controlled trials from inception to 23 January 2022. Results were scrutinised, data were extracted and research quality was investigated by two independent authors. Primary outcome was the proportion of complete ulcer healing. Secondary outcomes included both the mean time to complete healing and the incidence of adverse events. Statistical analyses were performed in RevMan 5.4 (Cochrane, UK). Kaplan-Meier curves for time to complete healing were pooled in R software (version 4.1.2) (R Foundation, Austria). RESULTS: Of the 231 records identified, 17 studies with a total of 1303 participants (649 randomised to the au-PRP group and 654 to a standard of care (SOC) group) met the eligibility criteria and were included in our study. Compared with SOC, au-PRP appeared to promote the complete healing rate (odds ratio (OR): 2.11; 95% Confidence Interval: 1.55-2.86). Au-PRP also appeared to significantly shorten complete healing time (mean duration: -19.04 days; 95%CI: -20.46--17.61]). There was no significant difference on adverse events. Results were robust on sensitivity analyses. CONCLUSION: Based on the findings of this review and meta-analysis, Au-PRP is an effective and safe adjuvant therapy for DFUs.


Assuntos
Diabetes Mellitus , Pé Diabético , Plasma Rico em Plaquetas , Humanos , Pé Diabético/terapia , Úlcera , Cicatrização , Incidência
2.
Int J Mol Sci ; 24(8)2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37108239

RESUMO

Osteoarthritis (OA) is a degenerative disease that causes pain, cartilage deformation, and joint inflammation. Mesenchymal stem cells (MSCs) are potential therapeutic agents for OA treatment. However, the 2D culture of MSCs could potentially affect their characteristics and functionality. In this study, calcium-alginate (Ca-Ag) scaffolds were prepared for human adipose-derived stem cell (hADSC) proliferation with a homemade functionally closed process bioreactor system; the feasibility of cultured hADSC spheres in heterologous stem cell therapy for OA treatment was then evaluated. hADSC spheres were collected from Ca-Ag scaffolds by removing calcium ions via ethylenediaminetetraacetic acid (EDTA) chelation. In this study, 2D-cultured individual hADSCs or hADSC spheres were evaluated for treatment efficacy in a monosodium iodoacetate (MIA)-induced OA rat model. The results of gait analysis and histological sectioning showed that hADSC spheres were more effective at relieving arthritis degeneration. The results of serological and blood element analyses of hADSC-treated rats indicated that the hADSC spheres were a safe treatment in vivo. This study demonstrates that hADSC spheres are a promising treatment for OA and can be applied to other stem cell therapies or regenerative medical treatments.


Assuntos
Células-Tronco Mesenquimais , Osteoartrite , Ratos , Humanos , Animais , Cálcio/efeitos adversos , Alginatos/efeitos adversos , Osteoartrite/induzido quimicamente , Osteoartrite/terapia , Osteoartrite/patologia , Adipócitos/patologia , Modelos Animais de Doenças
3.
Zhongguo Zhong Yao Za Zhi ; 48(9): 2530-2537, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-37282882

RESUMO

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1ß, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1ß, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.


Assuntos
Interleucina-18 , NF-kappa B , NF-kappa B/genética , NF-kappa B/metabolismo , Interleucina-18/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , Ciclina D1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Músculo Liso Vascular , Proliferação de Células , Transdução de Sinais , Citocinas/metabolismo , Glucose/toxicidade , Glucose/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-36446622

RESUMO

BACKGROUND: There is no criterion on the length of the uniportal video-assisted thoracoscopic surgery (UVATS) incision when performing lobectomy. We aimed to develop a nomogram to assist surgeons in designing incision length for different individuals. METHODS: A cohort consisting of 290 patients were enrolled for nomogram development. Univariate and multivariate logistic regression analyses were performed to identify candidate variables among perioperative characteristics. C-index and calibration curves were utilized for evaluating the performance of the nomogram. Short-term outcomes of nomogram-predicted high-risk patients were compared between long incision group and conventional incision group. RESULTS: Of 290 patients, 150 cases (51.7%) were performed incision extension during the surgery. Age, tumor size, and tumor location were identified as candidate variables related with intraoperative incision extension and were incorporated into the nomogram. C-index of the nomogram was 0.75 (95% confidence interval: 0.6961-0.8064), indicating the good predictive performance. Calibration curves presented good consistency between the nomogram prediction and actual observation. Of high-risk patients identified by the nomogram, the long incision group (n = 47) presented shorter duration of operation (p = 0.03), lower incidence of total complications (p = 0.01), and lower incidence of prolonged air leak (p = 0.03) compared with the conventional incision group (n = 55). CONCLUSION: We developed a novel nomogram for predicting the risk of intraoperative incision extension when performing uniportal video-assisted thoracoscopic lobectomy. This model has the potential to assist clinicians in designing the incision length preoperatively to ensure both safety and minimal invasiveness.

5.
J Asian Nat Prod Res ; 24(9): 860-876, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34698619

RESUMO

The safety evaluation of timosaponin BII (TBII) in beagle dogs with toxicokinetic study was performed. For the acute oral toxicity study, the minimum lethal dose (MLD) of TBII was more than 2000 mg/kg and suggested the characteristics of absorption saturation. For the 28-day repeated dose oral toxicity and toxicokinetic studies, there was no significant effect on all test parameters except for prolonged APTT in the 60 and 180 mg/kg groups, which recovered after withdrawal. The increase of drug exposure of 180 mg/kg group was not proportional to the increase of administration dose, showing the characteristics of absorption saturation.


Assuntos
Toxicocinética , Administração Oral , Animais , Cães , Relação Dose-Resposta a Droga , Estrutura Molecular
6.
J Org Chem ; 86(22): 15886-15896, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33534572

RESUMO

Tunable electrocatalytic annulation reactions of o-arylalkynylanilines have been established, leading to green and divergent syntheses of skeletally diverse indoles by adjusting the electrolytes and the solvents. The presence of ammonium halides as the electrolytes enabled the halogenation of o-arylalkynylanilines to give C3-halogenated indoles whereas naphtho[1',2':4,5]furo[3,2-b]indoles could be obtained by changing the electrolyte from ammonium halides to KI. Interestingly, by combining acetone as the solvent and both NH4I and NH4Cl as the electrolytes, the reaction worked through an intramolecular annulation and [5 + 1] cyclization cascade to form naphtho[1',2':5,6][1,3]oxazino[3,4-a]indoles.


Assuntos
Halogenação , Indóis , Ciclização , Solventes
7.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202717

RESUMO

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1-M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Saponinas/farmacocinética , Esteroides/farmacocinética , Animais , Biotransformação , Masculino , Ratos , Ratos Sprague-Dawley , Saponinas/farmacologia , Esteroides/farmacologia
8.
Zhonghua Nan Ke Xue ; 27(3): 231-235, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-34914305

RESUMO

OBJECTIVE: To investigate the clinical characteristics, diagnosis, treatment and etiology of persistent Müllerian duct syndrome (PMDS). METHODS: A 3-year-old boy was diagnosed with PMDS according to the clinical manifestations and the results of ultrasonography, laboratory examinations and earlier surgical examination. We performed genetic tests for the patient and his family members, removed the infantile uterus by laparoscopic wedge hysterectomy, biopsied and descended the bilateral testes, and ligated the bilateral internal rings, followed by a retrospective analysis and review of relevant literature. RESULTS: The operation was successful. Gonad biopsy revealed testis tissue, and PMDS was confirmed by intraoperative findings and related examinations. Good bilateral testicular blood supply was found during the 6-month follow-up after surgery. Medical exome sequencing showed the AMHR2 gene c.1499G > A (p.Cys500Tyr) mutant homozygote (A/A) in the patient and his sister and mutant heterozygote (G/A) in his parents. CONCLUSIONS: Laparoscopy is definitely effective for the treatment of PMDS. In surgery, the infantile uterus should be removed in case of good blood supply to the testis, and so were the bilateral testes if they cannot be descended. The homozygous mutation in the AMHR2 gene c. 1499G > A (p. Cys500Tyr) can lead to male PMDS. Pedigree investigation may provide some evidence for possible fertility in PMDS patients.


Assuntos
Laparoscopia , Pré-Escolar , Transtorno 46,XY do Desenvolvimento Sexual , Humanos , Masculino , Linhagem , Estudos Retrospectivos
9.
Bioorg Chem ; 99: 103807, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32272364

RESUMO

The design and synthesis of novel multi-substituted benzo-indole pyrazole Schiff base derivatives of potent DNA gyrase inhibitory activity were the main aims of this study. All the novel synthesized compounds were examined for their antibacterial activities against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella. In addition, we selected 20 compounds for the in vitro antibacterial activities assay of 6 drug-resistant bacteria strains. The result revealed compound 8I-w exhibited excellent antibacterial activity against 4 drug-resistant E. coli bacteria strains with IC50 values of 7.0, 17.0, 13.5, and 1.0 µM, respectively. In vitro enzyme inhibitory assay showed that compound 8I-w displayed potent inhibition against DNA gyrase with IC50 values of 0.10 µM. The molecular docking model indicated that compounds 8I-w can bind well to the DNA gyrase by interacting with various amino acid residues. This study demonstrated that the compound 8I-w can act as the most potent DNA gyrase inhibitor in the reported series of compounds and provide valuable information for the commercial DNA gyrase inhibiting bactericides.


Assuntos
Antibacterianos/farmacologia , DNA Girase/metabolismo , Descoberta de Drogas , Indóis/farmacologia , Pirazóis/farmacologia , Inibidores da Topoisomerase II/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Indóis/síntese química , Indóis/química , Listeria monocytogenes/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química , Salmonella/efeitos dos fármacos , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/química
10.
Bioorg Chem ; 100: 103907, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32413631

RESUMO

The design and synthesis of novel coumarin-thiazolyl ester derivatives of potent DNA gyrase inhibitory activity were the main aims of this study. All the novel synthesized compounds were examined for their antibacterial activity against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella. Compound 8p exhibited excellent antibacterial activity against four bacteria strains with MIC values of 0.05, 0.05, 8, and 0.05 µg/mL, respectively. In vitro drug-resistant bacterial inhibition experiments indicated that compound 8p exhibited the best bacteriostatic effect in the selected compounds and four positive control drugs with MIC values of 4 µg/mL. In vitro enzyme inhibitory assay showed that compound 8p exhibited potent inhibition against DNA gyrase with IC50 values of 0.13 µM. The molecular docking model indicated that compounds 8p can bind well to the DNA gyrase by interacting with amino acid residues. This study demonstrated that the compound 8p can act as the most potent DNA gyrase inhibitor in the reported series of compounds and provide valuable information for the commercial DNA gyrase inhibiting bactericides.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/enzimologia , Cumarínicos/química , Cumarínicos/farmacologia , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/farmacologia , Antibacterianos/síntese química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Cumarínicos/síntese química , Desenho de Fármacos , Ésteres/síntese química , Ésteres/química , Ésteres/farmacologia , Humanos , Simulação de Acoplamento Molecular , Tiazóis/síntese química , Tiazóis/química , Tiazóis/farmacologia , Inibidores da Topoisomerase II/síntese química
11.
Pestic Biochem Physiol ; 163: 271-279, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31973867

RESUMO

In this work, a total of 36 novel 5-(nicotinamido)-1-phenyl-1H-pyrazole-4-carboxylic acid derivatives were designed and synthesized successfully by introducing a carboxyl group based on the N-(1-(4-chlorophenyl)-4-cyano-1H-pyrazol-5-yl)-6-methoxynicotinamide. Among them, the growth inhibition assays on agar plates showed that compound 5IV-d(5-(2-chloronicotinamido)-1-(p-tolyl)-1H-pyrazole-4-carboxylic acid) exhibited the significant antifungal activity against four important fruit and main crop disease fungi (i.e., Valsa mali Miyabe et Yamada, Botryosphaeria dothidea, Helminthosporium maydis and Rhizoctonia cerealis) with EC50 values of 22.6, 14.5, 17.6 and 18.2 µM, respectively. In addition, 5IV-d showed the excellent inhibitory effect against SDH enzymes with IC50 values ranging from 9.4 to 15.6 µM. In vivo bioassay and molecular docking were applied to explore the potential in practical application and combination of modified structure and SDH. The results of structure-activity relationships indicates that the methoxy substitution at the benzene ring attached to the pyrazole ring and a wide variety of substituents could be responsible for the promising antifungal efficacy of the designed compounds. This study demonstrated that the compound 5IV-d can act as the most potent SDH inhibitor in the reported series of compounds.


Assuntos
Rhizoctonia , Succinato Desidrogenase , Antifúngicos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
12.
Int J Mol Sci ; 21(6)2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32210196

RESUMO

Ultrasound is a method for enhancing neurite outgrowth because of its thermal effect. In order to reach the working temperature to enhance neurite outgrowth, long-time treatment by ultrasound is necessary, while acknowledging that the treatment poses a high risk of damaging nerve cells. To overcome this problem, we developed a method that shortens the ultrasonic treatment time with a warming biomaterial. In this study, we used Fe3O4 nanoparticle-embedded polycaprolactone (PCL) as a sonosensitized biomaterial, which has an excellent heating rate due to its high acoustic attenuation. With this material, the ultrasonic treatment time for enhancing neurite outgrowth could be effectively shortened. Ultrasonic treatment could also increase neuronal function combined with the warming biomaterial, with more promoter neuronal function than only ultrasound. Moreover, the risk of overexposure can be avoided by the use of the warming biomaterial by reducing the ultrasonic treatment time, providing better effectiveness.


Assuntos
Materiais Biocompatíveis/efeitos da radiação , Crescimento Neuronal/efeitos da radiação , Temperatura , Ondas Ultrassônicas , Acetilcolinesterase/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular , Neurônios/metabolismo , Neurônios/efeitos da radiação , Ratos
13.
Turk J Med Sci ; 50(5): 1444-1453, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32252500

RESUMO

Background/aim: Drynaria fortunei (Gusuibu; GSB) is a popular traditional Chinese medicine used for bone repair. An increasing number of studies have reported that GSB induces osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). These results provide insight into the application of GSB for bone tissue engineering techniques used to repair large bone defects. However, few studies have described the molecular mechanisms of GSB. Materials and methods: In the present study, the effects of GSB and naringin, a marker compound, on the binding of BMP-2 to BMPR and BMP-2-derived signal transduction were investigated using surface plasmon resonance (SPR) and coculturing with BMPR- expressed cell line, C2C12, respectively. Furthermore, naringin was also used to prepare naringin contained scaffolds for bone tissue engineering. The physical and chemical properties of these scaffolds were analysed using scanning electron microscopy (SEM) and highperformance liquid chromatography (HPLC). These scaffolds were cocultured with rabbit BMSCs in vitro and implanted into rabbit calvarial defects for bone repair assessment. Results: The results showed that GSB and naringin affect the binding of BMP and BMPR in SPR experiments. GSB is a subtle BMP modulator that simultaneously inhibits the binding of BMP-2 to BMPR-1A and enhances its binding to BMPR-1B. In contrast, naringin inhibited BMP-2 binding to BMPR-1A. In vitro studies involving the phosphorylation of signals downstream of BMPR and Smad showed that GSB and naringin affected stem cell differentiation by inhibiting BMPR-1A signalling. When using GSB for bone tissue engineering, naringin exhibited a higher capacity for slow and gradual release from the scaffold, which promotes bone formation via osteoinduction. Moreover, control and naringin scaffolds were implanted into rabbit calvarial defects for 4 weeks, and naringin enhanced bone regeneration in vivo significantly. Conclusions: GSB and its marker compound (naringin) could inhibit the binding of BMP-2 and BMPR-1A to control cell differentiation by blocked BMPR-1A signalling and enhanced BMPR-1B signalling. GSB and naringin could be good natural BMP regulators for bone tissue engineering.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Flavanonas/farmacologia , Polypodiaceae/química , Engenharia Tecidual/métodos , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Células Cultivadas , Masculino , Osteogênese/efeitos dos fármacos , Coelhos , Transdução de Sinais/efeitos dos fármacos
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(9): 1001-1006, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-32933634

RESUMO

OBJECTIVE: To study the clinical screening and genetic diagnosis of children suspected of Prader-Willi syndrome (PWS), as well as the differences in the scores of clinical diagnostic criteria among the children with a confirmed diagnosis of PWS. METHODS: A total of 94 children suspected of PWS who were admitted from July 2016 to December 2018 were enrolled as subjects. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to confirm the diagnosis. For the children with a confirmed diagnosis of PWS, the scores of clinical diagnostic criteria were determined, and the perinatal characteristics were analyzed. RESULTS: A total of 11 children with PWS were confirmed by MS-MLPA, with a detection rate of 12%, among whom there were 7 boys and 4 girls, with a median age of 3 years and 4 months (range 25 days to 6 years and 8 months) at the time of confirmed diagnosis. Among the 11 children with PWS, only 5 children (45%) met the criteria for clinical diagnosis. The main perinatal characteristics of the children with PWS were decreased fetal movement (9 cases, 82%), cesarean section birth (11 cases, 100%), hypotonia (11 cases, 100%), feeding difficulties (11 cases, 100%), and weak crying (11 cases, 100%). CONCLUSIONS: Gene testing should be performed as early as possible for children suspected of PWS by clinical screening. PWS may be missed if only based on the scores of clinical diagnostic criteria.


Assuntos
Síndrome de Prader-Willi , Cesárea , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Metilação , Hipotonia Muscular , Gravidez
15.
J Vasc Surg ; 68(6): 1897-1905, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30126782

RESUMO

OBJECTIVE: Erythromelalgia is highly disabling and treatment is often very challenging. There have been solitary case reports that it might benefit from sympathectomy. This study sought to evaluate the short-term and long-term efficacy of chemical lumbar sympathectomy (CLS) for treatment of recalcitrant erythromelalgia and try to identify a CLS-responsive subset. METHODS: Patients with recalcitrant erythromelalgia were recruited from a tertiary hospital over a 10-year period. L3 to L4 CLS was performed using 5% phenol. The pain intensity score (visual analog scale [VAS] 0-10) was assessed before CLS and at 1 day, 1 week, 3 months, 6 months, 1 year, and 2 years after CLS. A VAS decrease of 90%-100% is defined as complete response, 60%-89% as major partial response. Relapse was defined by a return of a VAS score of 5 or higher. SCN9A gene mutations were screened. RESULTS: Thirteen patients were enrolled, with a median age of 15 years. The mean follow-up was 6.2 ± 3.8 years. SCN9A gene mutation was identified in five patients having family histories. The VAS was 8.2 ± 2.0 at baseline; it decreased to 4.9 ± 2.7 at 1 day and 1.9 ± 3.0 at 1 week after CLS. Nine patients (69.2%) achieved complete response at 1 week after CLS, including three patients with SCN9A gene mutation. Among the three complete response patients having the gene mutation, two reverted to major partial response and one relapsed at 2 years after CLS. Among the six complete response patients without mutation, five maintained complete response and one relapsed. Among the four patients who did not achieve complete response, one patient died at 3.5 months and one patient had an amputation performed at 4 months after CLS. CONCLUSIONS: CLS provides a valid option for the treatment of recalcitrant erythromelalgia. It takes about 1 week to achieve full efficacy. Relapse may occur, especially in patients with an SCN9A gene mutation.


Assuntos
Eritromelalgia/terapia , Vértebras Lombares/inervação , Simpatectomia Química/métodos , Adolescente , Amputação Cirúrgica , Criança , Análise Mutacional de DNA , Eritromelalgia/diagnóstico , Eritromelalgia/genética , Eritromelalgia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Medição da Dor , Estudos Prospectivos , Recidiva , Indução de Remissão , Simpatectomia Química/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(7): 549-553, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30022756

RESUMO

OBJECTIVE: To investigate the distribution of adiponectin +45T/G and +276G/T polymorphisms and its association with the development of Kawasaki disease and coronary artery lesion (CAL). METHODS: A total of 81 children with Kawasaki disease (among whom 11 had CAL) and 100 normal children who underwent physical examination (control group) were enrolled in a case-control study. Sequencing was performed to investigate the distribution of adiponectin +45T/G and +276G/T polymorphisms. RESULTS: There were no significant differences between the Kawasaki disease and control groups in the frequencies of TT, TG, and GG genotypes and T/G alleles of +45T/G polymorphism in the adiponectin gene (P>0.05). In the Kawasaki disease group, there were also no significant differences in the genotype and allele frequencies of the +45T/G polymorphism between the children with CAL and those without (P>0.05). There were significant differences between the Kawasaki disease and control groups in the frequencies of GG, GT, and TT genotypes and G/T alleles of +276G/T polymorphism in the adiponectin gene (P<0.05). GG genotype was a risk factor for the development of Kawasaki disease (OR=2.313, P=0.006). In the Kawasaki disease group, there was no significant difference in the genotype distribution of the +276G/T polymorphism between the children with CAL and those without (P>0.05). CONCLUSIONS: The adiponectin +276G/T polymorphism may be associated with the development of Kawasaki disease, but not associated with CAL. The adiponectin +45T/G polymorphism may not be associated with Kawasaki disease or CAL.


Assuntos
Adiponectina/genética , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Criança , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino
17.
Purinergic Signal ; 13(2): 191-201, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27915383

RESUMO

The structure of the human A2A adenosine receptor has been elucidated by X-ray crystallography with a high affinity non-xanthine antagonist, ZM241385, bound to it. This template molecule served as a starting point for the incorporation of reactive moieties that cause the ligand to covalently bind to the receptor. In particular, we incorporated a fluorosulfonyl moiety onto ZM241385, which yielded LUF7445 (4-((3-((7-amino-2-(furan-2-yl)-[1, 2, 4]triazolo[1,5-a][1, 3, 5]triazin-5-yl)amino)propyl)carbamoyl)benzene sulfonyl fluoride). In a radioligand binding assay, LUF7445 acted as a potent antagonist, with an apparent affinity for the hA2A receptor in the nanomolar range. Its apparent affinity increased with longer incubation time, suggesting an increasing level of covalent binding over time. An in silico A2A-structure-based docking model was used to study the binding mode of LUF7445. This led us to perform site-directed mutagenesis of the A2A receptor to probe and validate the target lysine amino acid K153 for covalent binding. Meanwhile, a functional assay combined with wash-out experiments was set up to investigate the efficacy of covalent binding of LUF7445. All these experiments led us to conclude LUF7445 is a valuable molecular tool for further investigating covalent interactions at this receptor. It may also serve as a prototype for a therapeutic approach in which a covalent antagonist may be needed to counteract prolonged and persistent presence of the endogenous ligand adenosine.


Assuntos
Antagonistas do Receptor A2 de Adenosina/síntese química , Antagonistas do Receptor A2 de Adenosina/farmacocinética , Receptor A2A de Adenosina/metabolismo , Triazinas/síntese química , Triazinas/farmacocinética , Triazóis/síntese química , Triazóis/farmacocinética , Antagonistas do Receptor A2 de Adenosina/química , Humanos , Receptor A2A de Adenosina/efeitos dos fármacos , Triazinas/química , Triazóis/química
18.
Phys Chem Chem Phys ; 19(8): 5797-5805, 2017 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-28176989

RESUMO

A gate electrode is usually used to controllably tune the carrier concentrations, further modulating the electrical conductivity and the Seebeck coefficient to obtain the optimum thermoelectric figure of merit (ZT) in two-dimensional materials. On the other hand, it is necessary to investigate how an electric field induced by a gate voltage affects the electronic structures, further determining the thermoelectric properties. Therefore, by using density functional calculations in combination with Boltzmann theory, the thermoelectric properties of bilayer MX2 (M = W, Mo; X = S, Se) with or without a 1 V nm-1 perpendicular electric field are comparatively investigated. First of all, the variations of the electrical conductivity (σ), electron thermal conductivity and Seebeck coefficient (S) with the carrier concentration are studied. Due to the trade-off relationship between S and σ, there is an optimum concentration to obtain the maximum ZT, which increases with the temperature due to the enhancement of the Seebeck coefficient. Moreover, N-type bilayers have larger optimum ZTs than P-type bilayers. In addition, the electric field results in the increase of the Seebeck coefficient in low hole-doped MS2 bilayers and high hole-doped MSe2 bilayers, thus leading to similar variations in ZT. The optimum ZTs are reduced from 2.11 × 10-2, 3.19 × 10-2, 2.47 × 10-2, and 2.58 × 10-2 to 1.57 × 10-2, 1.51 × 10-2, 2.08 × 10-2, and 1.43 × 10-2 for the hole-doped MoS2, MoSe2, and WSe2 bilayers, respectively. For N-type bilayers, the electric field shows a destructive effect, resulting in the obvious reduction of the Seebeck coefficient in the MSe2 layers and the low electron-doped MS2 bilayers. In electron-doped bilayers, the optimum ZTs will decrease from 3.03 × 10-2, 6.64 × 10-2, and 6.69 × 10-2 to 2.81 × 10-2, 3.59 × 10-2, and 4.39 × 10-2 for the MoS2, MoSe2, and WSe2 bilayers, respectively.

19.
Ultrason Imaging ; 39(5): 283-294, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28345418

RESUMO

Ultrasound guidance for epidural block has improved clinical blind-trial problems but the design of present ultrasonic probes poses operating difficulty of ultrasound-guided catheterization, increasing the failure rate. The purpose of this study was to develop a novel ultrasonic probe to avoid needle contact with vertebral bone during epidural catheterization. The probe has a central circular passage for needle insertion. Two focused annular transducers are deployed around the passage for on-axis guidance. A 17-gauge insulated Tuohy needle containing the self-developed fiber-optic-modified stylet was inserted into the back of the anesthetized pig, in the lumbar region under the guidance of our ultrasonic probe. The inner transducer of the probe detected the shallow echo signals of the peak-peak amplitude of 2.8 V over L3 at the depth of 2.4 cm, and the amplitude was decreased to 0.8 V directly over the L3 to L4 interspace. The outer transducer could detect the echoes from the deeper bone at the depth of 4.5 cm, which did not appear for the inner transducer. The operator tilted the probe slightly in left-right and cranial-caudal directions until the echoes at the depth of 4.5 cm disappeared, and the epidural needle was inserted through the central passage of the probe. The needle was advanced and stopped when the epidural space was identified by optical technique. The needle passed without bone contact. Designs of the hollow probe for needle pass and dual transducers with different focal lengths for detection of shallow and deep vertebrae may benefit operation, bone/nonbone identification, and cost.


Assuntos
Cateterismo/métodos , Ultrassonografia de Intervenção/instrumentação , Ultrassonografia de Intervenção/métodos , Animais , Espaço Epidural , Modelos Animais , Suínos
20.
Phys Chem Chem Phys ; 18(40): 28117-28124, 2016 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-27711504

RESUMO

This study is built on density functional calculations in combination with the non-equilibrium Green's function, and we probe the thermoelectric transport mechanisms through C60 molecules anchored to Al nano-electrodes in three different ways, such as, the planar, pyramidal, and asymmetric surfaces. When the electrode is switched from the planar and pyramidal surfaces, the electrical conductance (σ) and electron's thermal conductance (κel) decrease almost two orders of magnitude due to the reduction of the molecule-electrode contact coupling, whereas the Seebeck coefficients (S) are reduced by ∼55%. Furthermore, the maximum electron's thermoelectric figure of merit (ZelT = S2σT/κel, assuming a vanishing phonon's thermal conductance) is about 0.12 in the asymmetric junction. In particular, all σ, S, κel, and ZelT increase along with the average temperature (T) in all C60-junctions, although their growth is really quite negligible in the pyramidal junction because the Fermi level is far away from the frontier orbitals. In addition, when the strain increases from the compressive (-1.0 Å) to tensile (1.0 Å) strain, the Seebeck coefficient in the planar junction increases drastically, while the Seebeck coefficients in the asymmetric and pyramidal junctions reach their maximum values at 0.2 Å tensile and -0.4 Å compressive strains, respectively. This is because the Seebeck coefficient is inversely proportional to the magnitudes and proportional to the slopes of the transmission spectrum around the Fermi level. Finally, it is found that the shift of the Fermi level is an effective scheme to obtain the maximum ZelT of any molecular junction, including fullerene-based junctions.

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