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1.
Brain Imaging Behav ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31468373

RESUMO

As a relay center between the cerebral cortex and various subcortical brain areas, the thalamus is repeatedly associated with the dysfunction of brain-gut interaction in patients with irritable bowel syndrome (IBS). However, the regional morphological alterations of the thalamus in IBS are not well defined. We acquired structural magnetic resonance data from 34 patients with IBS and 34 demographically similar healthy subjects. Data processing was performed using FMRIB's Integrated Registration and Segmentation Tool (FIRST). Volumetric analysis and surface-based vertex analysis were both carried out to characterize the morphology of the thalamus and other subcortical structures. Our results suggested that the majority (31 cases) of the patients with IBS had diarrhea-predominant symptoms. Volumetric analysis revealed a larger normalized volume of the right thalamus and left caudate nucleus in patients with IBS than in healthy controls. Surface analysis indicated that the difference arose mainly from the laterodorsal nucleus of the right thalamus, and the body of the left caudate nucleus. In addition, patients with IBS had different hemispheric asymmetries of the thalamus (rightward) and caudate nucleus (leftward) from controls (leftward for the thalamus and rightward for the caudate nucleus). In general, our results indicated that patients with diarrhea-predominant IBS had enlarged thalamus and caudate nucleus volumes, as well as altered hemispheric asymmetries of these two structures, compared with healthy controls. The neuroimaging evidence of these structural alterations helps clarify the underlying pathophysiology of diarrhea-predominant IBS.

2.
Small ; : e1902811, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31373758

RESUMO

Tin diselenide (SnSe2 ) nanosheets as novel 2D layered materials have excellent optical properties with many promising application prospects, such as photoelectric detectors, nonlinear optics, infrared photoelectric devices, and ultrafast photonics. Among them, ultrafast photonics has attracted much attention due to its enormous advantages; for instance, extremely fast pulse, strong peak power, and narrow bandwidth. In this work, SnSe2 nanosheets are fabricated by using solvothermal treatment, and the characteristics of SnSe2 are systemically investigated. In addition, the solution of SnSe2 nanosheets is successfully prepared as a fiber-based saturable absorber by utilizing the evanescent field effect, which can bear a high pump power. 31st-order subpicosecond harmonic mode locking is generated in an Er-doped fiber laser, corresponding to the maximum repetition rate of 257.3 MHz and pulse duration of 887 fs. The results show that SnSe2 can be used as an excellent nonlinear photonic device in many fields, such as frequency comb, lasers, photodetectors, etc.

3.
Medicine (Baltimore) ; 98(32): e16592, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393358

RESUMO

RATIONALE: Refractory nasopharyngeal carcinoma is challenging to treat and at present there is no standard treatment or any good choice. PATIENT CONCERNS: Although the three patients in our case reports had already underwent multiple treatments before, they still suffered from disease recurrence of nasopharyngeal carcinoma. DIAGNOSIS: They were diagnosed as refractory nasopharyngeal carcinoma. INTERVENTIONS: A continuous infusion of Endostar, an antiangiogenic agent, combined with chemotherapy and radiation therapy was given to treat the patients. OUTCOMES: Patients showed complete or partial response to the combined therapy as evidenced by regression of tumors and decrease in plasma Epstein-Barr virus (EBV) DNA load. LESSONS: Continuous infusions of Endostar in combination with chemotherapy and/or radiation therapy showed promising efficacy and safety. The combination therapy indicates a new approach to treat refractory nasopharyngeal carcinoma.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Endostatinas/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Adulto , Quimiorradioterapia/métodos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia
4.
Inflammation ; 42(5): 1630-1640, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31102125

RESUMO

Spinal cord injury (SCI) involves both primary and secondary damages. After the phase of primary injury, a series of inflammatory responses initiate, which belong to the secondary injury. There has been little investigation into the cellular inflammatory response of the spleen to SCI. To disclose the impact of SCI on the spleen, we examined the inflammatory reactions of the spleen during the acute phase of SCI in rat. Adult rats were used as experimental animals and divided into un-injured, sham, and SCI groups (n = 36). Contusion injuries were produced at the T3 vertebral level. Spinal cords were harvested 6 h, 24 h, 48 h, 72 h, 120 h, and 168 h after surgery and were prepared for immunohistochemistry. Spleen wet weight was measured. Blood and spleens were prepared for quantitative analyses. The spleen index was significantly decreased in the SCI groups. Immunohistochemical results showed an increase of the infiltrating cells in the spinal cord tissues from SCI rats at all time points, peaking in 72 h post injury. In the blood, T and B lymphocytes significantly decreased in the SCI group as compared with the sham group, while monocyte increased. Surprisingly, in the SCI group, neutrophil initially decreased and subsequently tended to return toward baseline levels, then remained elevated until the end of the study. Spleen analyses revealed a significant increase in monocyte and neutrophil but a minor (not statistically significant) reduction in T and B lymphocytes. Our data show that the four most prevalent inflammatory cells infiltrate the spinal cord after injury. Increased levels of inflammatory cells (monocyte and neutrophil) in the blood and spleen appear to be very sensitive to SCI. The spleen plays a critical role in the acute phase of SCI.

5.
Nanotechnology ; 30(35): 354002, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31082808

RESUMO

The ultrafast photonics of different conventional two-dimensional (2D) materials have been studied intensively. Few-layer structure bismuthene has been reported as a new type of 2D material with high efficient electronics, strong mechanics and outstanding photonics properties. In this paper, a robust ultrafast pulse generation in communications-Band (C-Band) based on few-layer bismuthene has been reported. The characteristics and the ultrafast optical nonlinear properties of few-layer bismuthene have been investigated experimentally. The optical induced deposition method is employed to fabricate the saturable absorber based on bismuthene (BiSA). Most importantly, we also utilize BiSA for the ultrafast photonics, which demonstrates that a high-splitting-threshold robust ultrafast fiber laser with 1.3-ps pulse duration at 1531 nm has been obtained in the experiments. Even though we increase the pump power from the self-starting threshold (i.e. 86 mW) to 314 mW, the soliton pulse does not split. Moreover, the high-splitting-threshold laser operation can be achieved stably even if the lasers are exposed in air for at least half a year. It is demonstrated that the proposed bismuthene nonlinear components can be potentially applied to the optical communications with C-Band (i.e. 1530-1565 nm wavelength) to broaden the communications window.

6.
Chem Biodivers ; 16(6): e1900052, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30946516

RESUMO

One new racemic mixture, penicilliode A (1) and four pairs of enantiomeric polyketides, penicilliode B and C (2 and 3) and coniochaetone B and C (4 and 5), were obtained from the starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2. Interestingly, the strain GGF16-1-2 can produce enantiomers. The absolute configuration of 1 was determined by X-ray diffraction (XRD) analysis, and the absolute configurations of 2-4 were determined by the optical rotation (OR) values and electronic circular dichroism (ECD) calculations. Compounds 1-5 were firstly isolated from the marine-derived fungus Penicillium as racemates, and 2-5 were separated by HPLC with a chiral stationary phase. All the compounds were evaluated for their antibacterial, cytotoxic and inhibitory activities against PDE4D2.


Assuntos
Penicillium/metabolismo , Policetídeos/química , Estrelas-do-Mar/microbiologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Conformação Molecular , Penicillium/química , Policetídeos/isolamento & purificação , Policetídeos/farmacologia , Estereoisomerismo , Simbiose
7.
Vascul Pharmacol ; 117: 35-44, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30610955

RESUMO

High mobility group box 1 (HMGB1), a critical nonclassical inflammatory cytokine, has been found up-regulated in patients with idiopathic pulmonary arterial hypertension (IPAH), but its role in vascular remodeling of pulmonary hypertension (PH) is still unknown. In present study, we demonstrated that the plasma level of inflammatory cytokine including HMGB1, interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were elevated in hypoxia-induced pulmonary hypertension rats model. Moreover, expressions of HMGB1 and Toll like receptor-4 (TLR4) in pulmonary arteries were obviously up-regulated accompanied with down-regulation of bone morphogenetic protein receptor 2 (BMPR2) signaling, characterized by decline of phosphorylated Smad1/5/8 (p-Smsd1/5/8) and inhibitor of differention 1 (Id1) expression. In cultured primary pulmonary arterial smooth muscle cells (PASMCs), we found that HMGB1 incubation significantly promoted proliferation and migration of PASMCs, down-regulated p-Smsd1/5/8 and Id1 expression, which can be abrogated by HMGB1 inhibitors saquinavir, glycyrrhizn and TLR4 inhibitors TAK-242. Furthermore, saquinavir, glycyrrhizn and TAK-242 treatment significantly attenuated the development of PH in rats by recovering homodynamic parameters, pulmonary vascular remodeling and BMPR2 signaling pathway. In summary, our results suggest that HMGB1/TLR4 signaling promotes hypoxia-induced pulmonary hypertension via suppressing BMPR2 signaling.

8.
Eur J Pharmacol ; 843: 96-103, 2018 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-30352200

RESUMO

It has been documented cardiac fibroblasts as the predominant cell population undergoing senescence in heart. Calcitonin gene-related peptide (CGRP) exhibits a wide range of cardiovascular protective effects. Whether CGRP protects against cardiac fibroblasts senescence in cardiac fibrosis remains unknown. Here, we detected the down-regulation of CGRP concomitant with senescence in fibrotic myocardium, both hypertension- induced left ventricular fibrosis in SHR rats and hypoxia-induced right ventricular fibrosis in pulmonary artery hypertension rats. Exogenous CGRP inhibited the cardiac fibroblasts senescence and senescence-associated secretory phenotype (SASP) induced by TGF-ß1, which was abolished by CGRP8-37, a selective CGRP receptor antagonist. Moreover, the expression of klotho, an anti-senescence protein, was down-regulated in fibrotic myocardium, and CGRP up-regulated the klotho expression in TGF-ß1-treated cardiac fibroblasts. Klotho knockdown by siRNA reversed the inhibition of CGRP on senescence and SASP induced by TGF-ß1 in cardiac fibroblasts. These results suggested that CGRP inhibited the cardiac fibroblasts senescence and SASP in cardiac fibrosis via up-regulating klotho expression.

9.
Zhongguo Gu Shang ; 31(9): 824-828, 2018 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-30332875

RESUMO

OBJECTIVE: To discuss clinical outcomes of accordion operation for the Ilizarov technique in treating tibial bone defects. METHODS: From January 2014 to June 2016, 22 patients with tibial bone defects were treated by Ilizarov bone-transport technique, including 19 males and 3 females with an average age of 44.04 years old ranging from 23 to 60 years old;the length of the bone defects before the bone transport was 5 to 11 cm with an average 7.68 cm; Cause of injury invlved traffic accidents in 14 cases, fall injury in 3, smashing injury in 4, high drop injury in 1; 6 cases were on the left and 16 cases were on the right. The patients were divided into two groups: 11 cases in accordion group were treated by "accordion operation" after bone transport was completed;11 cases in control group were treated by the external fixator locked waiting for bone consolidation after bone transport was completed. All patients were followed up for 18 to 36 months with an average time of 27.9 months. There was no statistical significance between two groups, such as sex, age, length of bone defect(P>0.05). Analysis of healing time, healing index and other indicators, and Paley's criterion was used to evaluate the healing effect of bone healing and function recovery of the limb. RESULTS: The result of X-ray evaluation was all patients achieved bone healing. In accordion group, the bone healing time was (365±91) days, the bone healing index was (46.2±3.5) d/cm; in control group, the bone healing time was(435±108) days, the bone healing index was (57.8±3.5) d/cm. There was no statistical significance in the bone healing time between the two groups(t=1.648, P=0.115);There was statistical significance in the bone healing index between the two groups(t=7.754, P=0.000). At the final follow-up, according to Paley's criterion, the result in accordion group was excellent in 9 cases, good in 2 cases; in control group, excellent in 8 cases, good in 3 cases. Score was not statistically significant(z=-0.479, P=0.619). Complications involved nail infection (9 cases in accordion group, 10 cases in control group);local traction pain (2 cases in accordion group, 1 case in control group); axial malalignment>10°(4 cases in accordion group, 3 cases in control group);location difference of the junction of bone defects (3 cases in accordion group, 2 cases in control group);Complications were not statistically significant(P>0.05). CONCLUSIONS: Accordion operation for the Ilizarov technique in treating tibial bone defects can shorten the treatment time and consolidation time, and improve the healing index.

10.
Neural Regen Res ; 13(12): 2191-2199, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30323152

RESUMO

Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury (SCI); however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the autophagy inhibitor 3-methyladenine (3-MA) in a rat model of SCI. The rats were randomly assigned to the SCI, lithium, 3-MA and sham groups. In the 3-MA group, rats were intraperitoneally injected with 3-MA (3 mg/kg) 2 hours before SCI. In the lithium and 3-MA groups, rats were intraperitoneally injected with lithium (LiCl; 30 mg/kg) 6 hours after SCI and thereafter once daily until sacrifice. At 2, 3 and 4 weeks after SCI, neurological function and diffusion tensor imaging indicators were remarkably improved in the lithium group compared with the SCI and 3-MA groups. The Basso, Beattie and Bresnahan locomotor rating scale score and fractional anisotropy values were increased, and the apparent diffusion coefficient value was decreased. Immunohistochemical staining showed that immunoreactivities for Beclin-1 and light-chain 3B peaked 1 day after SCI in the lithium and SCI groups. Immunoreactivities for Beclin-1 and light-chain 3B were weaker in the 3-MA group than in the SCI group, indicating that 3-MA inhibits lithium-induced autophagy. Furthermore, NeuN+ neurons were more numerous in the lithium group than in the SCI and 3-MA groups, with the fewest in the latter. Our findings show that lithium reduces neuronal damage after acute SCI and promotes neurological recovery by inducing autophagy. The neuroprotective mechanism of action may not be entirely dependent on the enhancement of autophagy, and furthermore, 3-MA might not completely inhibit all autophagy pathways.

11.
Acta Pharmacol Sin ; 2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30038339

RESUMO

Pulmonary arterial hypertension (PAH) is the most common form of pulmonary hypertension. Pulmonary arterial remodeling is closely related to the abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs), which leads to the thickening of the medial layer of muscular arteries and then results in the narrowing or occlusion of the precapillary arterioles and PAH. However, the mechanisms underlying the abnormal proliferation of PASMCs remain unclear. In this study, we established rat primary PAH models using monocrotaline (MCT) injection or hypoxic exposure, then investigated the expression patterns of seven miRNAs associated with multiple pathogenic pathways central to pulmonary hypertension, and further explored the roles and the possible mechanisms of miR-135a during the development of PAH. In the rat primary PAH models, we observed that the expression of miR-135a-5p in lungs was drastically decreased at the initial stage of PAH development after MCT administration or hypoxic exposure, but it increased by 12-fold or 10-fold at the later stage. In vitro study in PASMCs showed a similar pattern of miR-135a-5p expression, with downregulation at 6 h but upregulation at 18, 24, and 48 h after hypoxic exposure. Early, but not late, administration of a miR-135a-5p mimic inhibited hypoxia-induced proliferation of PASMCs. The protective role of early miR-135a-5p agomir in the PAH rat model further supported the hypothesis that the early decrease in the expression of miR-135a-5p contributes to the proliferation of PASMCs and development of PAH, as early administration of miR-135a-5p agomir (10 nM, i.v.) reversed the elevated mean pulmonary arterial pressure and pulmonary vascular remodeling in MCT-treated rats. We revealed that miR-135a-5p directly bound to the 3'-UTR sequence of rat transient receptor potential channel 1 (TRPC1) mRNA and decreased TRPC1 protein expression, thus inhibiting PASMC proliferation. Collectively, our data suggest that dysregulation of miR-135a-5p in PASMCs contributes to the abnormal proliferation of PASMCs and the pathogenesis of PAH. Increasing miR-135a-5p expression at the early stage of PAH is a potential new avenue to prevent PAH development.

12.
Cancer Imaging ; 18(1): 22, 2018 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-29941018

RESUMO

BACKGROUND: To identify location and number of insulinomas before operation is very important for improving the cure rate. The objective of the study was to assess performance of CT during celiac artery angiography for preoperative localization of clinically suspected small insulinomas (< 2 cm in diameter). METHODS: From January 2013 to November 2016, 42 patients with hypoglycemic symptoms underwent celiac artery angiography, superior mesenteric artery angiography and CT during celiac artery angiography by a combined CT/digital subtraction angiography system, MIYABI Angio CT plus an Artiszeeceiling (SIEMENS, Germany). Patient group consisted of 13 males and 29 females, age 17-69 years (average, 45.4 ± 13.5 y). After diagnosis, all 42 patients were operated. Obtained images were retrospectively analyzed and compared with findings from post-operation pathology. RESULTS: All interventional radiology procedures were performed successfully with no complications. Sensitivity of angiography alone for insulinoma was 76.1% (32/42), at combined CT/digital subtraction angiography, 4 more nodules were found (sensitivity, 85.7%, 36/42), while 6 false-negatives were observed (all false negative lesions were less than 2 cm). A total of 64 ml to 80 ml contrast media was used per patient. CONCLUSION: CT during celiac artery angiography is a sensitive diagnostic procedure for localizing insulinomas. Combined with angiography, it can prioritize the pancreatic region for exploration and guide a pancreatic resection. TRIAL REGISTRATION: Ethical approval was obtained from the Hospital Research Ethics Committee. Informed consent was obtained from all patients included in the study. Duan Feng, Bai Yan-hua and Cui Li are co-first authors.


Assuntos
Angiografia Digital/métodos , Artéria Celíaca/diagnóstico por imagem , Insulinoma/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Angiografia Digital/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/normas
13.
Biomed Rep ; 8(6): 535-539, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29774144

RESUMO

The aim of the present study was to evaluate the effects of passage and cryopreservation of choroid plexus epithelial cells on their secretion of neurotrophic factors. Choroid plexus epithelial cells were cryopreserved and thawed following primary culture or passage cultured for up to two passages. The supernatant of primary, first/second passage and cryopreserved-thawed choroid plexus epithelial cells was collected when cells reached 80-90% confluence. ELISA was used to quantify brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) levels in the cell supernatant. First passage and cryopreserved-thawed cells secreted less BDNF and CNTF compared with primary cultured cells and increased levels of these two factors compared with second passage cells, and increased levels of GDNF and NGF compared with primary cultured and second passage cells (all P<0.05). Therefore, first passage culture decreased BDNF and CNTF secretion but increased NGF and GDNF compared with primary culture; second passage culture diminished neurotrophic factor secretion compared with first passage culture; and cryopreservation did not weaken the function of choroid plexus epithelial cells in secreting BDNF, GDNF, NGF and CNTF. The current study demonstrates that first passage and cryopreserved-thawed choroid plexus epithelial cells have an enhanced function to secrete neurotrophic factors including BDNF, GDNF, NGF and CNTF.

14.
Opt Express ; 26(8): 9893-9900, 2018 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-29715934

RESUMO

A supercontinuum source based on a figure-eight Er-doped fiber ring cavity has been experimentally demonstrated with low repetition rate. The proposed configuration of the experiment is a figure-eight fiber laser grounded in Nonlinear Optical Loop Mirror (NOLM) technique. A broad spectrum of approximately 410 nm spanning the range 1315-1725 nm at the level of 30 dB can be obtained at a given average power of 2.6 mW and without any amplifier. Such wide spectrum can be directly achieved in the fiber resonator, which makes the structure compact and robust. By changing the pump power, the temporal pulse width can be adjusted accordingly. The pulse width is about 4 ns at the pump power of around 240 mW. The broadband spectrum was generated directly from the fiber resonator, which can be easily applied in numerous areas, such as the optical frequency metrology, optical spectroscopy, optical coherence tomography, optical communications, and medical sciences.

15.
J Cancer ; 9(5): 797-806, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29581758

RESUMO

Background: To establish a prognostic score based on clinical routine factors to stratify nasopharyngeal carcinoma patients with bone metastasis into risk groups with different survival rates. Materials and Methods: Total 276 patients from multicenter were retrospectively analyzed. Kaplan-Meier method and Cox regression were used to confirm independent risk factors, which were checked for internal validity by bootstrapping method. The prognostic score, deriving from the corresponding regression coefficients in Cox model, classified patients into low and high risk groups. Finally, two independent cohorts were used for external validation. Results: In development cohort, six risk factors were identified: age>46 year-old (point=1), N>0 stage (point=2), anemia (point=2), bone metastasis free interval≤12 months (point=1), without radiotherapy to primary sites (point=1), and without radiotherapy to first metastasis sites (point=1). The derived prognostic score divided patients into low (score, 0-4) and high (score, 5-8) risk groups, with highly significant differences of 5-year overall survival rates (high vs. low risk: 24.6% vs. 58.2%, HR 3.47, P<0.001). Two external validations presented congruent results. Conclusion: A feasible and applicative prognostic score was successfully established and validated to discriminate bone metastatic nasopharyngeal carcinoma into low/high risk groups, which will be useful for individual treatment.

16.
Bioorg Med Chem Lett ; 28(4): 737-741, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29395981

RESUMO

Isothiocyanates 7a and 7b have poor stability and aqueous solubility. To address these problems, prodrugs 8a and 8b were synthesized. Prodrugs 8a and 8b were stable in HEPES buffer at pH 4.4, but released the active compounds 7a and 7b in HEPES buffer at pH 7.4 and in mouse plasma, respectively. Compound 8a and especially compound 8b showed anti-inflammatory effects. Compound 8b demonstrated significant efficacy in animal models of traumatic inflammation, acute inflammation and rheumatoid arthritis. Compound 8b also did not cause appreciable toxicity in mice after 5 weeks at a daily dose of 200 mg/kg.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Isotiocianatos/uso terapêutico , Pró-Fármacos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/toxicidade , Peso Corporal/efeitos dos fármacos , Meia-Vida , Isotiocianatos/síntese química , Isotiocianatos/farmacocinética , Isotiocianatos/toxicidade , Camundongos , Neutrófilos/efeitos dos fármacos , Pró-Fármacos/síntese química , Pró-Fármacos/farmacocinética , Pró-Fármacos/toxicidade , Ratos Sprague-Dawley , Ratos Wistar , Peixe-Zebra
17.
Med Sci Monit ; 24: 114-148, 2018 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-29306956

RESUMO

BACKGROUND The explosive increase in medical literature has changed therapeutic strategies, but it is challenging for physicians to keep up-to-date on the medical literature. Scientific literature data mining on a large-scale of can be used to refresh physician knowledge and better improve the quality of disease treatment. MATERIAL AND METHODS This paper reports on a reformulated version of a data mining method called MedRank, which is a network-based algorithm that ranks therapy for a target disease based on the MEDLINE literature database. MedRank algorithm input for this study was a clear definition of the disease model; the algorithm output was the accurate recommendation of antihypertensive drugs. Hypertension with diabetes mellitus was chosen as the input disease model. The ranking output of antihypertensive drugs are based on the Joint National Committee (JNC) guidelines, one through eight, and the publication dates, ≤1977, ≤1980, ≤1984, ≤1988, ≤1993, ≤1997, ≤2003, and ≤2013. The McNemar's test was used to evaluate the efficacy of MedRank based on specific JNC guidelines. RESULTS The ranking order of antihypertensive drugs changed with the date of the published literature, and the MedRank algorithm drug recommendations had excellent consistency with the JNC guidelines in 2013 (P=1.00 from McNemar's test, Kappa=0.78, P=1.00). Moreover, the Kappa index increased over time. Sensitivity was better than specificity for MedRank; in addition, sensitivity was maintained at a high level, and specificity increased from 1997 to 2013. CONCLUSIONS The use of MedRank in ranking medical literature on hypertension with diabetes mellitus in our study suggests possible application in clinical practice; it is a potential method for supporting antihypertensive drug-prescription decisions.


Assuntos
Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus/patologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Estatística como Assunto , Guias como Assunto , Humanos , Resultado do Tratamento
18.
Br J Pharmacol ; 175(8): 1157-1172, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28631302

RESUMO

BACKGROUND AND PURPOSE: Vascular inflammation, including the expression of inflammatory cytokines in endothelial cells, plays a critical role in hyperhomocysteinaemia-associated vascular diseases. Cathepsin V, specifically expressed in humans, is involved in vascular diseases through its elastolytic and collagenolytic activities. The aim of this study was to determine the effects of cathepsin V on l-homocysteine-induced vascular inflammation. EXPERIMENTAL APPROACH: A high methionine diet-induced hyperhomocysteinaemic mouse model was used to assess cathepsin V expression and vascular inflammation. Cultures of HUVECs were challenged with l-homocysteine and the cathepsin L/V inhibitor SID to assess the pro-inflammatory effects of cathepsin V. Transfection and antisense techniques were utilized to investigate the effects of cathepsin V on the dual-specificity protein phosphatases (DUSPs) and MAPK pathways. KEY RESULTS: Cathepsin L (human cathepsin V homologous) was increased in the thoracic aorta endothelial cells of hyperhomocysteinaemic mice; l-homocysteine promoted cathepsin V expression in HUVECs. SID suppressed the activity of cathepsin V and reversed the up-regulation of inflammatory cytokines (IL-6, IL-8 and TNF-α), adhesion and chemotaxis of leukocytes and vascular inflammation induced by l-homocysteine in vivo and in vitro. Increased cathepsin V promoted the degradation of DUSP6 and DUSP7, phosphorylation and subsequent nuclear translocation of ERK1/2, phosphorylation of STAT1 and expression of IL-6, IL-8 and TNF-α. CONCLUSIONS AND IMPLICATIONS: This study has identified a novel mechanism, which shows that l-homocysteine-induced upregulation of cathepsin V mediates vascular endothelial inflammation under high homocysteine condition partly via ERK1/2 /STAT1 pathway. This mechanism could represent a potential therapeutic target in hyperaemia-associated vascular diseases. LINKED ARTICLES: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

20.
Medicine (Baltimore) ; 96(46): e8513, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29145254

RESUMO

Traditional Chinese Medicine Constitution (TCMC) theory states that individuals with a biased TCMC are more likely to suffer from specific diseases. However, little is known regarding the influence of TCMC on susceptibility to hypertension. The aim of this study is to examine the possible relationship between TCMC and hypertension. Retrospective evaluation and observation were performed using the STROBE guidelines checklist. A large community-based cross-sectional study was conducted between 2009 and 2013 in Changsha, China. TCMC was assessed using a questionnaire that included 68 items. TCMC distributions and the associations of different TCMCs with hypertension risk were analyzed. In total, 144,439 subjects underwent evaluations of TCMC and blood pressure (BP). There were significant differences in the hypertension prevalence among the various TCMC groups (P < .01). An adjusted logistic regression model indicated that those with phlegm wetness, yin deficiency, blood stasis, or qi deficiency were more likely to have hypertension. Analysis of the clinical characteristics related to TCMC indicated that different TCMCs corresponded to different hypertension classifications using Western medicine criteria; for example, phlegm wetness with hypertension was similar to obesity-related hypertension. Our results suggest that phlegm wetness, yin deficiency, blood stasis, and qi deficiency have different effects on the prevalence of hypertension. More attention should be paid to TCMCs associated with susceptibility to hypertension, and corresponding preventive and therapeutic treatments should be developed according to different TCMCs.


Assuntos
Constituição Corporal , Hipertensão/epidemiologia , Medicina Tradicional Chinesa , Adolescente , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Humanos , Hipertensão/prevenção & controle , Pessoa de Meia-Idade , Medicina de Precisão , Estudos Retrospectivos , Adulto Jovem
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