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1.
Biomed Pharmacother ; 122: 109700, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918273

RESUMO

Hypoxia induces cardiomyocytes injury, which further triggers the occurrence and development of cardiovascular diseases. There is a paucity of specific treatment options available with proven efficacy. Chinese patented pharmaceutical product Salidroside (Sal) has potent efficacy on treating hypoxic injury. However, the molecular mechanism remains obscure. In the present study, a UPLC-QTOFMS-based metabolomic method combined with cell viability and apoptosis assays were established to explore the therapeutic mechanisms of Sal against hypoxic injury. Significant protective effects of Sal against inhibited cell viability and apoptosis induced by hypoxic injury were observed in the pharmacodynamic evaluation. Moreover, 40 significantly changed metabolites related to hypoxic injury were identified, of which, 26 can be significantly regulated by Sal. Metabolic pathway enrichment analysis revealed that the mechanisms of Sal against hypoxic injury may be attributed to modulating the disordered homeostasis of energy and lipid metabolism. The present study provides new experimental information on the pathogenesis of hypoxia, unravels the potential targeted metabolic pathways of Sal against hypoxia on the whole metabolic network and highlights the importance of metabolomics as a potential tool for deciphering drug-targeted metabolic pathways.

2.
Biosci Rep ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904088

RESUMO

Parietal cells of the gastric mucosa contain a complex and extensive secretory membrane system that harbors gastric H+, K+-adenosine triphosphatase, the enzyme primarily responsible for gastric lumen acidification. Here, we describe the characterization of mice deficient in the H+, K+-ATPase α subunit (Atp4a-/-) to determine the role of this protein in the biosynthesis of this membrane system and the biology of the gastric mucosa. Wild-type and Atp4a-/- mice, paired for age, were examined at 10, 12, 14 and 16 weeks for histopathology, and the expression of MUC2, AMACR, Ki-67, and p53 proteins was analyzed by immunohistochemistry. For further information, PI3K, AKT, mTOR, HIF-1α, LDHA, and SIRT6 were detected by western blotting. Compared to the WT mice,  Atp4a-/- mice developed parietal cell atrophy and significant antral inflammation and intestinal metaplasia with elevated MUC2 expression. Areas of dysplasia in the Atp4a-/- mouse stomach showed increased AMACR and Ki-67 expression. Consistent with elevated antral proliferation, tissue isolated from Atp4a-/- mice showed elevated p53 expression. The expression of P-PI3K, P-AKT, P-mTOR, HIF-1α, LDHA, and SIRT6 was significantly higher in tissue from the Atp4a-/- mice compared with the WT mice. The H+, K+-ATPase α subunit is required for acid-secretory activity of parietal cells in vivo, the normal development and cellular homeostasis of the gastric mucosa, and attainment of the normal structure of the secretory membranes. Chronic achlorhydria and hypergastrinemia in aged Atp4a-/- mice produced progressive hyperplasia and mucolytic and intestinal metaplasia and activated the Warburg effect via PI3K/AKT/mTOR signaling.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31913004

RESUMO

The high-resolution technique transmission electron microscopy (TEM), with OsO4 as the traditional fixative, is an essential tool for cell biology and medicine. Although OsO4 has been extensively used, it is far from perfect because of its high volatility and toxicity. Os(II) polypyridyl complexes like [Os(phen)2(dppz)]2+ (phen = 1,10-phenanthroline; dppz = dipyridophenazine) are not only the well-known molecular DNA "light-switches" but also the potential ideal candidates for TEM studies. Here, we report that the cell-impermeable cationic [Os(phen)2(dppz)]2+ can be preferentially delivered into the live-cell nucleus through ion-pairing with chlorophenolate counter-anions, where it functions as an unparalleled enantioselective nuclear DNA imaging reagent especially suitable for correlative light and electron microscopy (CLEM) studies in both living and fixed cells, which can clearly visualize chromosome aggregation and decondensation during mitosis simultaneously. We propose that the chiral Os(II) polypyridyl complexes can be used as a distinctive group of enantioselective high-resolution CLEM imaging probes for live-cell nuclear DNA studies.

4.
Fitoterapia ; : 104470, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31917300

RESUMO

Phytochemical investigations on Physalis. alkekengi L. var. franchetii, a widespread traditional Chinese medicine, led to the isolation and identification of three new sesquiterpenoids physalisitins A-C (1-3). Their structures were elucidated by NMR and HRESIMS analysis, and their absolute configurations were determined by quantum chemical NMR and ECD calculations, as well as by comparing their optical rotation values with those known analogues. All of the isolated compounds were evaluated for their cyclooxygenase-2 (COX-2) inhibitory activity. Compounds 1-3 dose-dependently inhibited the COX-2 enzyme with IC50 values of 3.22 ±â€¯0.25, 6.35 ±â€¯0.84, and 11.13 ±â€¯1.47 µM, respectively.

5.
Brain Imaging Behav ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898093

RESUMO

Cerebral microbleeds (CMBs) in dialysis patients have recently attracted much attention, and the different locations of CMBs indicate different pathological processes. Previous studies on the relationship between CMBs and cognitive impairment (CI) in the general population and in dialysis patients have reported controversial results. A total of 180 chronic dialysis patients were enrolled in our study. Based on brain magnetic resonance imaging (MRI) analysis of CMBs, the patients were divided into 4 groups (without-CMBs group, strictly lobar group, strictly deep group, and mixed group). A wide range of cognitive tests was administered to evaluate cognitive function. The risk factors for CMBs were explored, and the correlation between CMB distribution and CI was investigated by regression analysis. The prevalence of CMBs was 32.8% in the total study population, 36.1% in the haemodialysis (HD) subgroup and 26.2% in the peritoneal dialysis (PD) PD subgroup. Sixteen subjects (8.9%) were classified as the lobar group, 12 subjects (6.7%) as the mixed group, and 31 subjects (17.2%) as the deep group. A significant association was shown between deep CMBs and impaired cognitive function, involving overall cognitive function, memory, language ability and executive function. Deep CMBs were significantly associated with dialysis vintage, mean arterial pressure (MAP) and lacunar infarcts number, while deep CMBs showed no correlation with dialysis modality and current heparin medication. Deep CMBs are closely associated with global and specific CI in dialysis patients. Blood pressure control may prevent deep CMBs and their associated CI.

6.
J Neurosurg ; : 1-10, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899871

RESUMO

OBJECTIVE: Cushing's disease (CD) involves brain impairments caused by excessive cortisol. Whether these impairments are reversible in remitted CD after surgery has long been controversial due to a lack of high-quality longitudinal studies. In this study the authors aimed to assess the reversibility of whole-brain changes in remitted CD after transsphenoidal surgery (TSS), and its correlations with clinical and hormonal parameters, in the largest longitudinal study cohort to date for CD patient brain analysis. METHODS: Fifty patients with pathologically diagnosed CD and 36 matched healthy controls (HCs) were enrolled in a tertiary comprehensive hospital and national pituitary disease registry center in China. 3-T MRI studies were analyzed using an artificial intelligence-assisted web-based autosegmentation tool to quantify 3D brain volumes. Clinical parameters as well as levels of serum cortisol, adrenocorticotrophic hormone (ACTH), and 24-hour urinary free cortisol were collected for the correlation analysis. All CD patients underwent TSS and 46 patients achieved remission. All clinical, hormonal, and MRI parameters were reevaluated at the 3-month follow-up after surgery. RESULTS: Widespread brain volume loss was observed in active CD patients compared with HCs, including total gray matter (p = 0.003, with false discovery rate [FDR] correction) and the frontal, parietal, occipital, and temporal lobes; insula; cingulate lobe; and enlargement of lateral and third ventricles (p < 0.05, corrected with FDR). All affected brain regions improved significantly after TSS (p < 0.05, corrected with FDR). In patients with remitted CD, total gray matter and most brain regions (except the frontal and temporal lobes) showed full recovery of volume, with volumes that did not differ from those of HCs (p > 0.05, corrected with FDR). ACTH and serum cortisol changes were negatively correlated with brain volume changes during recovery (p < 0.05). CONCLUSIONS: This study demonstrates the rapid reversal of total gray matter loss in remitted CD. The combination of full recovery areas and partial recovery areas after TSS is consistent with the incomplete recovery of memory and cognitive function observed in CD patients in clinical practice. Correlation analyses suggest that ACTH and serum cortisol levels are reliable serum biomarkers of brain recovery for clinical use after surgery.

7.
J Enzyme Inhib Med Chem ; 35(1): 330-343, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31856607

RESUMO

Cholinesterase inhibitor plays an important role in the treatment of patients with Alzheimer's disease (AD). Herein, we report the medicinal chemistry efforts leading to a new series of 1,3-dimethylbenzimidazolinone derivatives. Among the synthesised compounds, 15b and 15j showed submicromolar IC50 values (15b, eeAChE IC50 = 0.39 ± 0.11 µM; 15j, eqBChE IC50 = 0.16 ± 0.04 µM) towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Kinetic and molecular modelling studies revealed that 15b and 15j act in a competitive manner. 15b and 15j showed neuroprotective effect against H2O2-induced oxidative damage on PC12 cells. This effect was further supported by their antioxidant activity determined in a DPPH assay in vitro. Morris water maze test confirmed the memory amelioration effect of the two compounds in a scopolamine-induced mouse model. Moreover, the hepatotoxicity of 15b and 15j was lower than tacrine. In summary, these data suggest 15b and 15j are promising multifunctional agents against AD.

8.
Prostate ; 80(3): 256-266, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31856338

RESUMO

BACKGROUND: Because androgen receptor (AR) signaling is essential for prostate cancer (PCa) initiation and progression, castration is the main approach for treatment. Unfortunately, patients tend to enter a stage called castration-resistant prostate cancer (CRPC) despite the initial response to castration. For various reasons, AR signaling is reactivated in CRPC. As such, AR signaling inhibitors, such as enzalutamide, has been approved by the Food and Drug Administration to treat CRPC in the clinic. However, the limited success of these new drugs suggests an immediate unmet need to understand the underlying mechanisms for resistance so novel targets can be identified to enhance their efficacy. METHODS: An unbiased bioinformatics analysis was performed with the existing human patient dataset and RNA-seq results of in-house PCa cell lines to identify new targets to overcome enzalutamide resistance. Cell viability and growth were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and colony formation assay. Cell invasion and migration were detected by transwell assay. Protein levels were detected by Western blot or immunofluorescence. RESULTS: We found that the noncanonical Wnt signaling was activated in enzalutamide-resistant PCa cells and that the activation of noncanonical Wnt signaling was correlated with AR expression and disease progression. This was validated by the elevated expression of noncanonical Wnt pathway members such as Wnt5a, RhoA, and ROCK in enzalutamide-resistant PCa cells in comparison to their enzalutamide-sensitive counterparts. And, both Y27632, an inhibitor of ROCK, and depletion of ROCK enhanced the efficacy of enzalutamide in enzalutamide-resistant PCa cells. Of significance, a combination of Y27632 and enzalutamide inhibited 22RV1-derived xenograft tumor growth synergistically. Finally, ROCK depletion plus enzalutamide treatment inhibited invasion and migration of enzalutamide-resistant PCa cells via inhibition of epithelial-mesenchymal transition. CONCLUSIONS: The noncanonical Wnt pathway is activated in enzalutamide-resistant PCa and inhibition of noncanonical Wnt pathway overcomes enzalutamide resistance and enhances its efficacy in CRPC.

9.
Bioorg Med Chem Lett ; 30(2): 126853, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31859162

RESUMO

Oxidative stress plays vital roles in virous neurodegenerative diseases including Alzheimer's disease. Activation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), the key regulator of oxidative stress, may provide a new therapeutic strategy for these diseases. Herein we synthesized and evaluated a series of 1,3,4-oxa/thiadiazole core Nrf2 activators as neuroprotective agents. The representative compound 8 exhibited cytoprotective and Nrf2 activation effects in a neuron-like PC-12 cells. Additionally, compound 8 showed good membrane permeability, indicating this compound could penetrate blood-brain barrier (BBB) to reach central nervous system (CNS) as a neuro-protective agent. These results indicated that these Nrf2 activators with 1,3,4-oxa/thiadiazole core could serve as a new chemotype against oxidative stress in neurodegenerative diseases.

10.
Pituitary ; 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31838612

RESUMO

BACKGROUND: Ectopic ACTH-secreting pituitary adenoma (EAPA) are a rare cause of Cushing's disease. Due to the lack of consensus and experience in terms of the diagnosis and treatment of EAPAs, preoperative identification and optimal treatment remain challenging. PURPOSE: To investigate the characteristics of EAPAs and offer some proposals for the diagnosis and management of this uncommon disease, the EAPA patients admitted to our center and all of the EAPA cases reported in the literature were reviewed. METHODS: In a retrospective electronic medical chart review, 6 patients (0.39%) with EAPAs were identified from 1536 consecutive patients who were admitted to our hospital with a diagnosis of Cushing's syndrome between January 2000 and August 2019. A literature review was performed on the online databases PubMed and EMBASE, and 52 cases conformed to the criteria. The data regarding biochemical tests, imaging examinations and follow-ups were analyzed. RESULTS: The mean age of patients with EAPAs was 37.7 years old, and an obvious female predominance (3.5: 1) was demonstrated. The most common location of EAPAs was the cavernous sinus (34.5%), followed by the sphenoid sinus (31.0%) and the suprasellar region (20.7%). No significant differences in the biochemical test results were found among tumors in different locations. Except for sex, no risk factors related to remission were found. Although no significant differences among different locations were found, the tumors in the cavernous sinus had a relatively higher rate of invisibility in terms of imaging and a higher non-remission rate than tumors in other locations. CONCLUSIONS: In patients with negative intrasellar findings, the uncommon disease of EAPA should be considered. Due to the endocrine similarity between intrasellar pituitary corticotrophin adenoma and EAPA, the preoperative identification of EAPA depends on a careful review of the imaging examinations. Locations such as the cavernous sinus, sphenoid sinus and suprasellar region should be considered first. Tumor resection is recommended when the diagnosis is confirmed.

11.
J Magn Reson Imaging ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808980

RESUMO

BACKGROUND: Whether men with a prostate-specific antigen (PSA) level of 4-10 ng/mL should be recommended for a biopsy is clinically challenging. PURPOSE: To develop and validate a radiomics model based on multiparametric MRI (mp-MRI) in patients with PSA levels of 4-10 ng/mL to predict prostate cancer (PCa) preoperatively and reduce unnecessary biopsies. STUDY TYPE: Retrospective. SUBJECTS: In all, 199 patients with PSA levels of 4-10 ng/mL. FIELD STRENGTH/SEQUENCE: 3T, T2 -weighted, diffusion-weighted, and dynamic contrast-enhanced MRI. ASSESSMENT: Lesion regions of interest (ROIs) from T2 -weighted, diffusion-weighted, and dynamic contrast-enhanced MRI were annotated by two radiologists. A total of 2104 radiomic features were extracted from the ROI of each patient. A random forest classifier was used to build the radiomics model for PCa in the primary cohort. A combined model was constructed using multivariate logistic regression by incorporating the radiomics signature and clinical-radiological risk factors. STATISTICAL TESTS: For continuous variables, variance equality was assessed by Levene's test and Student's t-test, and Welch's t-test was used to assess between-group differences. For categorical variables, Pearson's chi-square test, Fisher's exact test, or the approximate chi-square test was used to assess between-group differences. P < 0.05 was considered statistically significant. RESULTS: The combined model incorporating the multi-imaging fusion model, age, PSA density (PSAD), and the PI-RADS v2 score yielded area under the curve (AUC) values of 0.956 and 0.933 on the primary (n = 133) and validation (n = 66) cohorts, respectively. Compared with the clinical-radiological model, the combined model performed better on both the primary and validation cohorts (P < 0.05). Furthermore, the use of the combined model to predict PCa could identify more negative PCa patients than the use of the clinical-radiological model by 18.4%. DATA CONCLUSION: The combined model was developed and validated to provide potential preoperative prediction of PCa in men with PSA levels of 4-10 ng/mL and might aid in treatment decision-making and reduce unnecessary biopsies. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019.

12.
J Pharm Biomed Anal ; 179: 112938, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31816471

RESUMO

Sennoside B is a specific dianthrone compound extracted from senna, which is widely used as a stimulant laxative but has potential side effects. This study aimed to obtain the metabolic and pharmacokinetic data of sennoside B. The metabolic profiles of sennoside B were obtained from rat plasma, urine, bile and feces by an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). As a result, 14 metabolites were structurally identified and the proposed metabolic pathways of sennoside B included hydrolysis to aglycones, release of rhein-type anthrone, and extensive conjugation. As the only compound detected in the plasma samples after intravenous and intragastric administrations, the prototype was selected as the plasma marker in the pharmacokinetic study. A simple and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the quantitation of sennoside B in rat plasma. The linear range of sennoside B was 5-1000 ng/mL (R2 ≥ 0.991) and the lowest limit of quantification (LLOQ) was 5 ng/mL. The intra- and inter- precisions of the assay were less than 10%, whereas accuracy ranged from 85.80% to 103.80%. The extraction recovery, matrix effect and stability of sennoside B were within acceptable limits. The established method was well validated and successfully applied to the pharmacokinetic study of sennoside B. The oral absolute bioavailability of sennoside B was calculated as 3.60% and the value apparent volume of distribution of intravenous and intragastric administrations were 32.47 ±â€¯10.49 L/kg and 7646 ±â€¯1784 L/kg, respectively. The maximum plasma concentrations were 212.6 ±â€¯50.9 µg/L and 14.06 ±â€¯2.73 µg/L for intravenous and intragastric dosing groups, respectively. According to the current results of pharmacokinetic and metabolic profiling studies, metabolites with high abundance in tissues would be the next object in the pharmacokinetic study of sennoside B.

14.
Cancer Imaging ; 19(1): 90, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864408

RESUMO

PURPOSE: To compare the diagnostic accuracy of biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) for prostate cancer (PCa) and clinically significant prostate cancer (csPCa) and to explore the application value of dynamic contrast-enhanced (DCE) MRI in prostate imaging. METHODS AND MATERIALS: This study retrospectively enrolled 235 patients with suspected PCa in our hospital from January 2016 to December 2017, and all lesions were histopathologically confirmed. The lesions were scored according to the Prostate Imaging Reporting and Data System version 2 (PI-RADS V2). The bpMRI (T2-weighted imaging [T2WI], diffusion-weighted imaging [DWI]/apparent diffusion coefficient [ADC]) and mpMRI (T2WI, DWI/ADC and DCE) scores were recorded to plot the receiver operating characteristic (ROC) curves. The area under the curve (AUC), accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for each method were calculated and compared. The patients were further stratified according to bpMRI scores (bpMRI ≥3, and bpMRI = 3, 4, 5) to analyse the difference in DCE MRI between PCa and non-PCa lesions (as well as between csPCa and non-csPCa). RESULTS: The AUC values for the bpMRI and mpMRI protocols for PCa were comparable (0.790 [0.732-0.840] and 0.791 [0.733-0.841], respectively). The accuracy, sensitivity, specificity, PPV and NPV of bpMRI for PCa were 76.2, 79.5, 72.6, 75.8, and 76.6%, respectively, and the values for mpMRI were 77.4, 84.4, 69.9, 75.2, and 80.6%, respectively. The AUC values for the bpMRI and mpMRI protocols for the diagnosis of csPCa were similar (0.781 [0.722-0.832] and 0.779 [0.721-0.831], respectively). The accuracy, sensitivity, specificity, PPV and NPV of bpMRI for csPCa were 74.0, 83.8, 66.9, 64.8, and 85.0%, respectively; and 73.6, 87.9, 63.2, 63.2, and 87.8%, respectively, for mpMRI. For patients with bpMRI scores ≥3, positive DCE results were more common in PCa and csPCa lesions (both P = 0.001). Further stratification analysis showed that for patients with a bpMRI score = 4, PCa and csPCa lesions were more likely to have positive DCE results (P = 0.003 and P < 0.001, respectively). CONCLUSION: The diagnostic accuracy of bpMRI is comparable with that of mpMRI in the detection of PCa and the identification of csPCa. DCE MRI is helpful in further identifying PCa and csPCa lesions in patients with bpMRI ≥3, especially bpMRI = 4, which may be conducive to achieving a more accurate PCa risk stratification. Rather than omitting DCE, we think further comprehensive studies are required for prostate MRI.

15.
Metabolism ; : 154050, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31863780

RESUMO

BACKGROUND AND OBJECTIVES: Cushing's disease (CD) patients have metabolic abnormalities in the brain caused by excessive exposure to endogenous cortisol. However, the reversibility of brain metabolism of CD patients after treatment remains largely unknown. METHODS: This study recruited 50 CD patients seeking treatment and 34 matched normal controls (NCs). The patients were treated with Transsphenoidal Adenomectomy (TSA) and reexamined 3 months later. Cerebral blood flow (CBF) of the patients were assessed using 3D pseudo-continuous arterial spin labelling (PCASL) imaging before the treatment and at the 3-month follow-up and were compared with CBF measures of the NCs using a whole-brain voxelwise group comparison method. For remitted patients, their CBF measures and hormone level measures, including adrenocorticotropic hormone (ACTH), 24-h urinary free cortisol (24hUFC) and serum cortisol, were compared before and after the treatment. Finally, a correlation analysis was carried out to explore the relationship between changes of CBF and hormone level measures of the remitted CD patients. RESULTS: After the treatment, 45 patients reached remission. Compared with the NCs, the CD patients before the treatment exhibited significantly reduced CBF in cortical regions, including occipital lobe, parietal lobe, superior/middle/inferior temporal gyrus, superior/middle/inferior frontal gyrus, orbitofrontal cortex, precentral gyrus, middle/posterior cingulate gyrus, and rolandic operculum, as well as significantly increased CBF in subcortical structures, including caudate, pallidum, putamen, limbic lobe, parahippocampal gyrus, hippocampus, thalamus, and amygdala (p < .01, false discovery rate corrected). For the remitted patients, the change in CBF before and after the treatment displayed a spatial pattern similar to the difference between the NCs and the CD patients before the treatment, and no significant difference in CBF was observed between the NCs and the remitted CD patients after the treatment. The changes of 24hUFC were significantly correlated with the changes of averaged CBF within the subcortical region in the remitted patients (p = .01). CONCLUSIONS: Our findings demonstrate that the brain metabolic abnormalities of CD patients are reversible when their hormone level changes towards normal after surgery treatment.

16.
Brain Res ; : 146512, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31706953

RESUMO

Vascular dementia (VaD) is widely recognized as the second most common type of dementia, yet effective treatments are still lacking. Traditional Chinese medicine Yi-Gan San (YGS) has potent efficacy on treating VaD in clinical practice. However, the underlying mechanism is still unclear. In the present study, a UPLC-QTOFMS-based metabolomic method was established to explore the therapeutic mechanisms of YGS on VaD. Experimental VaD model was induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2-VO]) in rats. Cognitive function, pathological changes and oxidative stress condition in the brains of VaD rats were assessed using Morris water maze tests, hematoxylin-eosin staining and antioxidant assays (MDA, SOD, GSH and GSH-Px), respectively. UPLC-QTOFMS combined with computational systems analysis were conducted to study the changes of metabolic networks in serum of rats. The results indicated that VaD model was established successfully and 2-VO caused a decline in spatial learning and memory and hippocampal histopathological abnormalities of rats. YGS significantly improved the cognitive impairment induced by 2VO and attenuated hippocampal histopathological abnormalities. The inducement of 2-VO significantly elevated the level of MDA, and reduced SOD and GSH-Px activities, and YGS can significantly regulate the levels. We have identified 34 significantly changed metabolites related to 2-VO-induced VaD, and YGS can significantly regulate the abnormalities of 24 metabolites. Metabolic pathway enrichment analysis revealed that the mechanisms of YGS against 2-VO-induced VaD may be attributed to modulating the metabolic disorders of arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study provides new experimental information on the pathogenesis of VaD, unravels the potential targeted metabolic pathways of YGS against VaD on the whole metabolic network and highlights the importance of metabolomics as a potential tool for deciphering drug-targeted metabolic pathways.

17.
J Surg Oncol ; 120(8): 1379-1385, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31691290

RESUMO

BACKGROUND: Open surgery for hilar cholangiocarcinoma (HCCA) has already been widely reported and analyzed. However, the laparoscopic technique for treating HCCA remains controversial because of the lack of radicality and poor assessment of the resectability of hilar structures without direct palpation. The aim of this study was to provide detailed surgical procedures and photographs of this technically demanding operation, describe our experience in assessing resectability before and during surgery, and confirm the radicality of laparoscopic resection of Bismuth type III and IV HCCA. METHODS: From November 2016 to November 2018, nine patients received laparoscopic resection of Bismuth type III or IV HCCA in our department. RESULTS: Laparoscopic right hepatectomy was performed in four patients, and laparoscopic left hepatectomy was performed in five patients. Negative margins were achieved in all patients. Complications were found in two (22.22%) patients, with bile leakage and hepatic insufficiency each in one patient. The patient developing hepatic insufficiency had persistent and ongoing liver failure and finally expired. CONCLUSION: The radicality of laparoscopic resection for Bismuth type III and IV HCCA can be technically improved through extended lymphadenectomy, visual assessment of hilar structures, and frozen section techniques.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Hepatectomia/métodos , Tumor de Klatskin/cirurgia , Laparoscopia/métodos , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Transfusão de Eritrócitos , Feminino , Humanos , Tumor de Klatskin/patologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Seleção de Pacientes , Complicações Pós-Operatórias
18.
Artigo em Inglês | MEDLINE | ID: mdl-31703056

RESUMO

STUDY DESIGN: A prospective randomized controlled study. OBJECTIVE: To clarify whether percutaneous transforaminal endoscopic discectomy (PTED) has better clinical outcomes and less surgical trauma compared with microendoscopic discectomy (MED). SUMMARY OF BACKGROUND DATA: Two kinds of minimally invasive spine surgeries, PTED and MED, are now widely used for the treatment of lumbar disc herniation (LDH). It is still a controversial issue to choose the proper surgical approach. METHODS: In this single-center, open-label, randomized controlled trial, patients were included if they had persistent signs and symptoms of radiculopathy with corresponding imaging-confirmed LDH, and were randomly allocated to PTED or MED group. The primary outcome was the score of Oswestry Disability Index (ODI) and the secondary outcomes included the score of Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain (SF36-BP) and physical function (SF36-PF) scales, European Quality of Life-5 Dimensions (EQ-5D), Visual Analogue Scales for back pain (VAS-back) and leg pain (VAS-leg). RESULTS: 250 participants were randomly assigned to two treatment groups, 241 of that received the specific surgical procedure. 222 patients (92.1%) have completed the 2-year follow-up. Both the primary and secondary outcomes did not differ significantly between the two treatment groups at each prespecified follow-up time (P > 0.05). For PTED, the postoperative improvement of ODI score in the median herniation subgroup was less compared with paramedian subgroup. For MED, less improvement of ODI score was found in far-lateral herniation subgroup compared with paramedian subgroup. Total complication rate over the course of 2 year was 13.44% in PTED group and 15.57% in MED group (P = 0.639). 10 cases (8.40%) in PTED group and 5 cases (4.10%) in MED group suffered from residue/recurrence of herniation, for which reoperation was required. CONCLUSION: Over the 2-year follow-up period, PTED did not show superior clinical outcomes and did not appear to be safer procedure for LDH patients compared with MED. PTED had inferior results for median disc herniation, while MED did not appear to be the best option for far-lateral disc herniation. LEVEL OF EVIDENCE: 2.

19.
Nat Commun ; 10(1): 5047, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31695035

RESUMO

Plants associate with beneficial arbuscular mycorrhizal fungi facilitating nutrient acquisition. Arbuscular mycorrhizal fungi produce chitooligosaccharides (COs) and lipo-chitooligosaccharides (LCOs), that promote symbiosis signalling with resultant oscillations in nuclear-associated calcium. The activation of symbiosis signalling must be balanced with activation of immunity signalling, which in fungal interactions is promoted by COs resulting from the chitinaceous fungal cell wall. Here we demonstrate that COs ranging from CO4-CO8 can induce symbiosis signalling in Medicago truncatula. CO perception is a function of the receptor-like kinases MtCERK1 and LYR4, that activate both immunity and symbiosis signalling. A combination of LCOs and COs act synergistically to enhance symbiosis signalling and suppress immunity signalling and receptors involved in both CO and LCO perception are necessary for mycorrhizal establishment. We conclude that LCOs, when present in a mix with COs, drive a symbiotic outcome and this mix of signals is essential for arbuscular mycorrhizal establishment.

20.
Front Neurosci ; 13: 1134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695595

RESUMO

Background: The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis plays an important role in brain structure and maintenance of brain function. There is a close correlation between serum GH and IGF1 levels and age-related cognitive function. The effects of childhood-onset growth hormone deficiency (GHD)on brain morphology are underestimated so far. Methods: In this cross-sectional study, T1-weighted magnetic resonance imaging was assessed in 17 adult males with childhood-onset GHD and 17 age and gender-matched healthy controls. The cortical thickness was analyzed and compared between the two groups of subjects. Effects of disease status and hormone levels on cortical thickness were also evaluated. Results: Although there was no difference in whole brain volume or gray matter volume between the two groups, there was decreased cortical thickness in the parahippocampal gyrus, posterior cingulate gyrus and occipital visual syncortex in the adult growth hormone deficiency (AGHD) group, and increased cortical thickness in a partial area of the frontal lobe, parietal lobe and occipital visual syncortex in AGHD group. Cortical thickness of the posterior cingulum gyrus was prominently associated with FT3 serum levels only in control group after adjusting of IGF-1 levels. Conclusion: These results suggest that young adult male patients with childhood-onset GHD have alterations in cortical thickness in different brain lobes/regions.

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