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1.
J Org Chem ; 88(21): 15311-15317, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37873929

RESUMO

A route for cycloaddition reaction of alkenes and tert-butyl nitrite to synthesize Δ2-isoxazolines has been developed. The overall process involves the formation of multiple chemical bonds without the use of a catalyst. This methodology features mild reaction conditions and good functional group tolerance, providing a direct approach for the preparation of isoxazolines.

2.
Clin Neurol Neurosurg ; 231: 107849, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37385126

RESUMO

BACKGROUND: Ultrasound (US)-guided injections for chronic pain has multiple advantages over traditional radiologic method. The study was performed to exam the clinical outcomes of lumbar transforaminal epidural injection (LTFEI) between US and fluoroscopy (FL) guidance for lumbar radiculopathy (LRP). METHODS: A total of 164 patients with LRP were randomly assigned into US and FL group to receive LTFEI in a 1:1 ratio. Pain relief and functional disability were assessed by numeric rating scale (NRS) and Modified Oswestry Disability Questionnaire (MODQ) scores before treatment, 1 month and 3 months post-intervention. Contrast spread pattern, fluoroscopic image number and complications were also recorded. The primary outcome was accurate rate of contrast dispersing into lumbar epidural space, and non-inferiority margin was predefined at -15 %. RESULTS: The accuracy of LTFEI was 90.2 % and 91.5 % in US and FL group, and the lower limit of the 95 %CI of mean difference between two modalities (-4.9 % (95 %CI: -12.8 %, 3.1 %)) was above the non-inferiority margin. Procedure time in US group (531.90 ± 67.12 s) was shorter than FL group (904.20 ± 120.20 s) (p < 0.05), while radiation dosage in the US group was lower than in the FL group (3047.20 ± 569.53 vs. 8807.50 ± 1039.10 µGy m2, p < 0.001). Both groups didn't differ in pain reduction (F = 1.050, p = 0.306) and functional improvement (F = 0.103, p = 0.749) during follow-up period. No severe complications occurred in both groups. CONCLUSIONS: US-guided LTFEI confirmed by FL was not inferior to conventional FL method in terms of accurate rate of lumbar epidural contrast dispersion. Effective pain relief and functional ability improvement were comparable between two modalities, and US technique had advantages of less radiation exposure and possible facilitation of avoiding critical vessels around intervertebral foramen.


Assuntos
Dor Lombar , Radiculopatia , Humanos , Resultado do Tratamento , Radiculopatia/diagnóstico por imagem , Radiculopatia/tratamento farmacológico , Dor Lombar/diagnóstico por imagem , Dor Lombar/tratamento farmacológico , Injeções Epidurais , Ultrassonografia de Intervenção , Fluoroscopia/métodos , Vértebras Lombares/diagnóstico por imagem
3.
Anesth Analg ; 135(4): 837-844, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35426836

RESUMO

BACKGROUND: Because it is traditionally difficult and time-consuming to identify the foramen ovale (FO) with fluoroscopy, we recently developed the H-figure method to acquire fluoroscopic view of FO with shorter procedure time and less radiation. However, the impact of such an H-figure approach on the clinical outcomes of trigeminal ganglion radiofrequency thermocoagulation (RFT) in treating idiopathic trigeminal neuralgia (ITN) remains unclear. METHODS: In a 12-month follow-up retrospective cohort study, patients with ITN had fluoroscopy-guided RFT of trigeminal ganglion via either classic approach (n = 100) or H-figure approach (n = 136) to identify FO. Data of continuous variables were analyzed with a Shapiro-Wilk test for normality and subsequently with a Mann-Whitney test, and the binary data were analyzed with a χ 2 test. The primary outcome was the facial pain measured by a Visual Analog Scale (VAS) 1 year after the treatment. The secondary outcomes included the quality of the fluoroscopic FO views, the threshold voltage to provoke paresthesia, the procedure time, the number of fluoroscopic images, and the facial numbness VAS. RESULTS: Compared with the classic approach group, the H-figure approach group was associated with better long-term pain relief after the procedure, with significantly fewer patients had pain 3 months (6.6% vs 17.0%, P = .012) and 12 months (21.3% vs 38.0%, P = .005) after the procedure, and among patients who had pain after the procedure, patients in the H-figure group had significantly less pain 6 months after the procedure (VAS median [interquartile range (IQR)]: 3 [2-6] vs 6 [4-7], P < .001). Moreover, compared to the classic approach, the H-figure approach provided better fluoroscopic view of FO, lower threshold voltage to elicit paresthesia (median [IQR]: 0.2 [0.2-0.3] vs 0.4 [0.4-0.5] V, P < .0001), with shorter procedure time (median [IQR]: 7.5 [6.0-9.0] vs 14.0 [10.0-18.0] min, P < .0001), and required fewer fluoroscopic images (median [IQR]: 4.0 [3.0-5.0] vs 8.0 [6.0-10.0], P < .0001). CONCLUSIONS: RFT of the trigeminal ganglion using the H-figure approach is associated with superior longer term clinical pain relief than the classic approach in treating ITN.


Assuntos
Forame Oval , Neuralgia do Trigêmeo , Dor Facial , Fluoroscopia , Humanos , Parestesia , Estudos Retrospectivos , Resultado do Tratamento , Neuralgia do Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/terapia
4.
Reg Anesth Pain Med ; 46(4): 350-353, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33328267

RESUMO

BACKGROUND AND OBJECTIVES: Access through the foramen ovale (FO) is essential in performing trigeminal ganglion injection, glycerol rhizolysis, balloon compression, and radiofrequency thermocoagulation (RFT) to treat idiopathic trigeminal neuralgia (ITN). However, identification of the FO under fluoroscopy can be difficult and time-consuming, and thus exposes patients to increased radiation and procedure risks. Here we present the 'H-figure' as a novel fluoroscopic landmark to quickly visualize the FO. METHODS: The H-figure landmark can be recognized as the medial border of the mandible and the lateral edge of the maxilla as the two vertical lines, and the superior line of petrous ridge of temporal bone (S-P-T line) as the horizontal line, and the FO fluoroscopic view is then optimized at the center of the H-figure immediately above the S-P-T line. We applied this landmark in a clinical cohort of 136 patients with ITN who underwent fluoroscopy-guided RFT of the trigeminal ganglion. We also compared the H-figure method with the traditional method. The primary outcome was the total number of fluoroscopic images required to visualize the FO (as a proxy of radiation exposure). Secondary measures included the procedure time required to finalize the FO view and the sensory testing voltage for paresthesia. RESULTS: With the H-figure approach we were able to view the FO with an average of 4.2 fluoroscopic shots at an average time of 6.8 min. When compared with the non-H-figure traditional technique, the H-figure method required almost half the fluoroscopic shots in nearly half the procedure duration time, and paresthesia was evoked with half of the voltage. CONCLUSION: The H-figure is an easy fluoroscopic landmark that can help to view the FO with less radiation and procedure time, and the needles placed with this approach can be closer to the target for the RFT treatment of patients with ITN.


Assuntos
Forame Oval , Neuralgia do Trigêmeo , Eletrocoagulação , Fluoroscopia , Humanos , Gânglio Trigeminal
5.
FEBS Lett ; 594(3): 497-508, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31626714

RESUMO

The voltage-gated sodium channels (VGSCs) are aberrantly expressed in a variety of tumors and play an important role in tumor growth and metastasis. Here, we show that VGSCs auxiliary ß3 subunit, encoded by the SCN3B gene, promotes proliferation and suppresses apoptosis in HepG2 cells by promoting p53 degradation. ß3 significantly increases HepG2 cell proliferation, promotes tumor growth in mouse xenograft models, and suppresses senescence and apoptosis. We found that ß3 knockdown stabilizes p53 protein, leading to potentiation of p53-induced cell cycle arrest, senescence, and apoptosis. Mechanistic studies revealed that ß3 could bind to p53, promoting p53 ubiquitination and degradation by stabilizing the p53/MDM2 complex. Our results suggest that ß3 is a novel negative regulator of p53 and a potential oncogenic factor.


Assuntos
Carcinogênese , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteólise , Proteína Supressora de Tumor p53/metabolismo , Subunidade beta-3 do Canal de Sódio Disparado por Voltagem/metabolismo , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Proliferação de Células , Senescência Celular , Técnicas de Silenciamento de Genes , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Ubiquitinação , Subunidade beta-3 do Canal de Sódio Disparado por Voltagem/deficiência , Subunidade beta-3 do Canal de Sódio Disparado por Voltagem/genética
6.
J Int Med Res ; 47(2): 783-790, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30477369

RESUMO

OBJECTIVE: To investigate the value of serum galactomannan antigen (GM) testing combined with chest computed tomography (CT) as a noninvasive method for early diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancies with febrile neutropenia after antifungal drug treatment. METHODS: We retrospectively analyzed the data of 376 patients with febrile neutropenia from January 2015 to August 2017. All patients were given broad-spectrum antibiotics and divided into the control group (effective antibiotic treatment, no antifungal drugs given) and the observational group (ineffective antibiotic treatment, antifungal drugs given). The serum GM testing, chest CT, and microbiological examination findings were compared between the two groups. RESULTS: The false-positive rates of GM testing for IPA in the control and observational groups were 4.04% and 8.65%, respectively, and the false-negative rates in the two groups were 1.10% and 9.62%, respectively. Sixty-five patients in the observational group and 11 in the control group had typical features of CT imaging. CONCLUSION: Clinical weekly screening of serum GM and chest CT may be an effective combined approach to the early diagnosis of IPA in patients with febrile neutropenia, even if they have undergone antifungal treatment.


Assuntos
Antifúngicos/efeitos adversos , Neutropenia Febril/tratamento farmacológico , Neoplasias Hematológicas/complicações , Aspergilose Pulmonar Invasiva/diagnóstico , Mananas/sangue , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Aspergillus/isolamento & purificação , Diagnóstico Precoce , Neutropenia Febril/etiologia , Feminino , Seguimentos , Galactose/análogos & derivados , Humanos , Aspergilose Pulmonar Invasiva/induzido quimicamente , Aspergilose Pulmonar Invasiva/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
7.
Org Lett ; 20(16): 5040-5043, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-30063140

RESUMO

A novel Rh(I)-catalyzed sequential C-C coupling and redox isomerization between allylic alcohols and 1,3-dienes has been accomplished. This versatile protocol provides expeditious access to a broad range of polysubstituted α,ß-unsaturated ketones with excellent atom economy and regioselectivity.

8.
Tumour Biol ; 37(3): 3033-41, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26419595

RESUMO

Analgesic-antitumor peptide (AGAP), one of the scorpion toxin polypeptides, has been shown to have an antitumor activity. Recombinant AGAP (rAGAP) was shown to affect the migration and invasion of HepG2 cells via a voltage-gated sodium channel (VGSC) ß1 subunit. The VGSC ß1 subunit was validated as a cell adhesion molecule (CAM) in human hepatocellular carcinoma (HCC) cell lines. rAGAP suppresses the migration and invasion of HepG2 cells but has no significant effect of human liver HL7702 cells without ß1 subunit expression. rAGAP inhibits the migration and invasion of the cells when the VGSC ß1 subunit is overexpressed in HL7702 cells. To explain these findings, VGSC ß1 subunit messenger RNA (mRNA) and protein levels were measured. The ß1 subunit protein level was upregulated in a dose-dependent manner following treatment with rAGAP while there was no significant change in the mRNA level, so rAGAP might be an active component of the VGSC ß1 subunit.


Assuntos
Antineoplásicos/farmacologia , Peptídeos/farmacologia , Venenos de Escorpião/farmacologia , Subunidade beta-1 do Canal de Sódio Disparado por Voltagem/fisiologia , Movimento Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Invasividade Neoplásica , Proteínas Recombinantes/farmacologia , Subunidade beta-1 do Canal de Sódio Disparado por Voltagem/análise
9.
Peptides ; 31(6): 995-1000, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20307602

RESUMO

In this study, an effective Escherichia coli expression system was used to study the role of residues in the antitumor-analgesic peptide from Chinese scorpion Buthus martensii Karsch (BmKAGAP). To evaluate the extent to which residues of the toxin core contribute to its analgesic activity, nine mutants of BmKAGAP were obtained by PCR. Using site-directed mutagenesis, all of these residues were individually substituted by one amino acid. These were then subjected to a circular dichroism analysis, and an analgesic activity assay in mice. This study represents a thorough mapping and elucidation of the epitopes that underlie the molecular basis of the analgesic activity. The three-dimensional structure of BmKAGAP was established by homology modeling. Our results revealed large mutant-dependent differences that indicated important roles for the studied residues. With our ongoing efforts for establishing the structure and analgesic activity relationship of BmKAGAP, we have succeeded in pinpointing which residues are important for the analgesic activity.


Assuntos
Analgésicos/química , Analgésicos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Peptídeos/química , Peptídeos/farmacologia , Venenos de Escorpião/química , Venenos de Escorpião/farmacologia , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Dicroísmo Circular , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Peptídeos/genética , Estrutura Secundária de Proteína , Venenos de Escorpião/genética , Escorpiões , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Relação Estrutura-Atividade
10.
Ai Zheng ; 24(6): 657-62, 2005 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-15946473

RESUMO

BACKGROUND & OBJECTIVE: Most multiple myeloma (MM) patients could not be cured by high-dose chemotherapy and bone marrow transplantation. This study was designed to investigate in vitro killing effect of tumor-specific cytotoxic T lymphocytes (CTLs) stimulated by idiotype protein (Id)-pulsed dendritic cells (DCs) on autologous MM cells. METHODS: DCs were generated from peripheral blood monocytes of 6 MM patients using interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). After cultured for 5 days, immature DCs were pulsed with Idû tumor necrosis factor-alpha (TNF-alpha) was added at the 7th day. Id-pulsed DCs were cocultured with autologous T cells for 3 days to induce tumor-specific CTLs. MTT assay was used to detect proliferation of autologous T cells, and evaluate killing effect of CTLs on autologous MM cells. RESULTS: Mature DCs were successfully induced. Id-pulsed DCs markedly increased proliferation of autologous T cells in a dose-dependent manner; stimulation index (SI) of Id-pulsed DCs was the highest [(39.1+/-6.0)%] when the radio of DCs to T cells was 10:1, which was significantly higher than those of unpulsed mature DCs [(19.3+/-7.7)%], Id-pulsed immature DCs [(15.9+/-6.1)%], and unpulsed immature DCs [(11.4+/-4.9)%] (P < 0.01). Id-pulsed DCs induced anti-MM activity of CTLs in a dose-dependent manner. Unpulsed mature DCs also induced cytotoxicity of CTLs against autologous MM cellsû however, when DC:T was 30:1, killing rate of MM cells was significantly higher in Id-pulsed mature DCs group than in unpulsed mature DCs group [(70.1+/-7.9)% vs. (40.8+/-7.8)%,P < 0.05]. KRN7000-pulsed mature DCs stimulated proliferation of allogeneic T cells in a dose-dependent manner; when DC:T was 1:10, SI was significantly higher in KRN7000-pulsed mature DCs group than in unpulsed mature DCs group [(38.5+/-5.7)% vs. (20.2+/-5.7)%, P < 0.05]. CONCLUSIONS: Mature DCs could be induced and Id with biological activity could be extracted from peripheral blood of MM patients. Id-pulsed DCs could induce antitumor immune response. KRN7000 could improve the immune function of in vitro cultured DCs.


Assuntos
Células Dendríticas/fisiologia , Idiótipos de Imunoglobulinas/farmacologia , Mieloma Múltiplo/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T/citologia , Adulto , Idoso , Proliferação de Células , Citotoxicidade Imunológica , Células Dendríticas/citologia , Relação Dose-Resposta a Droga , Feminino , Galactosilceramidas/administração & dosagem , Galactosilceramidas/farmacologia , Humanos , Idiótipos de Imunoglobulinas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia
11.
Zhonghua Xue Ye Xue Za Zhi ; 26(10): 593-7, 2005 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-16532967

RESUMO

OBJECTIVE: To investigate the specific antitumor immune response induced by idiotype protein (Id)-pulsed dendritic cells (DC) in vitro. METHODS: DC was generated from peripheral blood monocytes of the multiple myeloma (MM) patients using GM-CSF, IL-4, and TNF-alpha. The DCs were pulsed with idiotypic fragment, the F(ab')2 fragment of M protein from MM patient at the immature stage. The morphologic characteristics of the cells were observed with light and electron microscopes. The phenotypic features were analyzed with FACS, MTT assay was employed to evaluate the proliferation of autologous T cells and the inhibition rate of MM cells. RESULTS: DC precursors in peripheral blood could be induced to typical mature DC in medium containing GM-CSF, IL-4 and TNF-alpha. Mature DC with Id could increase the proliferation of the autologous T cells and activate naive T cells to become tumor specialized cytotoxic T lymphocytes (CTL). The CTL at different doses showed significant inhibition on or killing ability to autologous MM cells in vitro. CONCLUSIONS: In a suitable cytokine environment, the DC precursors from peripheral blood of MM patients could be induced to functional DC, and vaccination of Id-pulsed DC could induce active antitumor immune response.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Mieloma Múltiplo/imunologia , Adulto , Idoso , Células Cultivadas , Feminino , Humanos , Imunoterapia Ativa , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Linfócitos T Citotóxicos/imunologia
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