Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 661
Filtrar
1.
Heart Surg Forum ; 23(1): E063-E069, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32118546

RESUMO

OBJECTIVE: The role of glucose-insulin-potassium (GIK) infusion during cardiac surgery has held interest for so many years without a clear answer. The aim of this meta-analysis was to evaluate the effect of GIK therapy on outcomes in patients undergoing on-pump cardiac surgery. METHODS: A comprehensive online review was performed in The Web of Science, Embase, Medline, PubMed, and The Cochrane Library databases from 2000 to 2019. Eligible studies included randomized controlled trials (RCTs) that compared GIK treatment with placebo or standard care during on-pump cardiac surgery. Risk ratios (RR) were used for binary outcomes and mean difference (MD) was used for continuous variables; both with their 95% confidence intervals (CI). RESULTS: A total of 18 RCTs involving 2,131 patients met the inclusion criteria. Compared with the control group, the GIK treatment significantly reduced in-hospital mortality (RR = 0.56, 95% CI: 0.32-0.97; P = .04), postoperative myocardial infarctions (MI) (RR = 0.71, 95% CI: 0.56-0.91; P = .006), the use of inotropic support (RR = 0.53, 95% CI: 0.45-0.63; P < .00001), and length of stay in the intensive care unit (ICU) (MD = -0.33, 95% CI: -0.52--0.14; P = .0007). Moreover, GIK treatment seemed to be associated with fewer postoperative atrial fibrillation (AF) (RR = 0.81, 95% CI: 0.64-1.03; P = .09). CONCLUSIONS: In patients undergoing on-pump cardiac surgery, GIK infusion has a beneficial role in mortality during hospital stay and demonstrates superior efficacy versus standard care for reduction in postoperative MI, AF, ICU length of stay as well as inotropic agent requirements.

2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(1): 94-98, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32148239

RESUMO

OBJECTIVE: To evaluate the value of lung ultrasound score (LUS) on predicting weaning outcome in patients with intro-abdominal infection (IAI) undergoing mechanical ventilation. METHODS: Patients with IAI undergoing mechanical ventilation admitted to Research Institute of General Surgery of East War Zone Hospital and intensive care unit (ICU) of the First People's Hospital of Lianyungang from January to December in 2018 were included. The patients who satisfied weaning criteria were enrolled in the weaning process, which included spontaneous breathing trial (SBT) and extubation. They were divided into SBT success group and SBT failure group according to whether passed 120-minute SBT or not. LUS scores before and after SBT were compared between the two groups. The patients in the SBT success group were extubated, and they were divided into successful extubation group and failed extubation group for sub-group analysis according to whether re-intubation was needed in 48 hours after extubation. LUS score before extubation (at the end of SBT) and 48 hours after extubation (48 hours after extubation in the successful extubation group or before re-intubation in the failed extubation group) were compared. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of LUS score before SBT for SBT failure and LUS score before extubation for the failure. RESULTS: A total of 76 patients with IAI undergoing mechanical ventilation were included. Twenty-three patients had duration of mechanical ventilation less than 48 hours, severe chronic obstructive pulmonary disease (COPD), tracheotomy or automatic discharge were excluded, and 53 patients were enrolled. SBT was failed in 9 patients, and successfully performed in 44 patients, of whom 23 patients with successful extubation, and 21 with failed extubation. The LUS scores before and after SBT in the SBT failure group were significantly higher than those in the SBT success group (before SBT: 13.22±1.99 vs. 10.79±1.64, t = -3.911, P = 0.000; after SBT: 19.00±1.12 vs. 13.41±1.86, t = -8.665, P = 0.000). ROC curve analysis showed that the area under ROC curve (AUC) of LUS score before SBT for predicting SBT failure was 0.82 [95% confidence interval (95%CI) was 0.67-0.98, P = 0.002]. When the optimum cut-off value was 12.5, the sensitivity was 66.7%, and the specificity was 84.1%. Sub-group analysis showed that the LUS scores before and after extubation in the failed extubation group were significantly higher than those in the successful extubation group (before extubation: 14.19±1.60 vs. 12.69±1.81, t = -2.881, P = 0.006; after extubation: 16.42±1.59 vs. 12.78±1.54, t = -7.710, P = 0.000). ROC curve analysis showed that the AUC of LUS score before extubation for predicting the failure was 0.81 (95%CI was 0.69-0.92, P = 0.000). When the optimum cut-off value was 13.5, the sensitivity was 80.0%, and the specificity was 65.2%. CONCLUSIONS: LUS score can effectively predict SBT outcome, risk of re-intubation after extubation in patients with IAI undergoing mechanical ventilation.

3.
J Asian Nat Prod Res ; : 1-8, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32131631

RESUMO

Two new chlorophenolic glucosides curculigines P (1) and Q (2), together with seven known compounds (3-9), were isolated from the dried rhizomes of Curculigo orchioides. Their structures were determined by spectroscopic methods including 1 D, 2 D NMR and MS. All the isolated compounds were evaluated on 5α-reductase activity by a HaCaT-based bioassay. Compounds 1-9 showed varying degrees of inhibiting activity against 5α-reductase, while compound 1 indicated the most potent inhibitory effect.

4.
Biomater Sci ; 8(6): 1748-1758, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32002530

RESUMO

In this work, we developed multi-shelled hollow nanospheres [RGD@am-ZnO@CuO@Au@DOX HNSs] as multifunctional therapeutic agents to achieve effective and targeted Zn2+/Cu2+ therapy, induced drug delivery under low pH/red-light conditions, and enhanced phototherapy under single red-light. The photothermal and photodynamic performance of am-ZnO@CuO@Au HNSs was enhanced relative to that of am-ZnO nanoparticles (NPs) or am-ZnO@CuO HNSs by utilizing the resonance energy transfer process and broad red-light absorption. The pH-sensitive am-ZnO@CuO@Au HNSs were dissolved to Zn2+/Cu2+ in the acidic endosomes/lysosomes of cancer cells, resulting in a cancer cell killing effect. The release performance of doxorubicin (DOX) from RGD@am-ZnO@CuO@Au@DOX HNSs was evaluated under low pH and red-light-irradiated conditions, and targeting of HNSs was confirmed by dual-modal imaging (magnetic resonance/fluorescence) of the tumor area. Moreover, in vivo synergistic therapy using RGD@am-ZnO@CuO@Au@DOX HNSs was further evaluated in mice bearing human pulmonary adenocarcinoma (A549) cells, achieving a remarkable synergistic antitumor effect superior to that obtained by monotherapy. This study validated that RGD@am-ZnO@CuO@Au@DOX HNSs can be a promising candidate for efficient postoperative cancer therapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32049636

RESUMO

OBJECTIVE: Fetuin-A is a glycoprotein produced by hepatocytes and has been associated with insulin resistance and bone growth in postnatal life. Gestational diabetes mellitus (GDM) is a condition characterized by insulin resistance. It is unclear whether GDM may affect cord blood fetuin-A levels and whether fetuin-A is associated with fetal growth. RESEARCH DESIGN AND METHODS: In a nested case-control study of 153 matched pairs of neonates of mothers with GDM and euglycemic pregnancies in the Shanghai Birth Cohort, we evaluated cord blood fetuin-A in association with GDM and fetal growth. RESULTS: Comparing the newborns of GDM versus euglycemic mothers, cord blood fetuin-A concentrations were similar (mean±SD: 783.6±320.0 vs 754.8±281.9 µg/mL, p=0.53), while insulin-like growth factor (IGF)-I (76.6±27.8 ng/mL vs 68.1±25.1 ng/mL, p=0.008) and IGF-II (195.3±32.5 ng/mL vs 187.5±30.8 ng/mL, p=0.042) concentrations were higher. Cord blood fetuin-A was not correlated with insulin, IGF-I or IGF-II. Cord blood fetuin-A was negatively correlated with birth weight (r=-0.19, p=0.025) and birth length (r=-0.24, p=0.005) z scores in GDM pregnancies, while there were no significant correlations in euglycemic pregnancies (tests for interaction: p=0.014 for birth length, p=0.013 for birth length). Adjusting for maternal and neonatal characteristics, the differential associations remained. CONCLUSIONS: GDM was not associated with cord blood fetuin-A levels. Fetuin-A was negatively associated with fetal growth in GDM but not in euglycemic pregnancies. This novel observation suggests a GDM-conditional negative correlation of fetuin-A with fetal growth.

6.
Biomed Pharmacother ; 125: 109888, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32066039

RESUMO

BACKGROUND: Adipose derived stem cells (ADSCs) have the property to differentiate into neuron-like cells, which may provide a novel insight for the restoration of erectile dysfunction (ED) mainly induced by cavernous nerve injury. Icariside II (ICA II) has been reported to play a key role in the regulation of erectile function via stimulating the differentiation of ADSCs to Schwann Cells (SCs). However, the function and molecular mechanisms of ICA II in ED remains to be further clarified. METHODS: The expression of S100, P75, GDNF and miR-33 was detected by qRT-PCR. And the relative proteins expression was determined by western blot. Cell viability was measured by Cell Counting Kit-8 (CCK-8) assay. Bioinformatics, luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the interaction between miR-33 and GDNF. Intracavernosal pressure (ICP), the ratio of ICP and mean arterial pressure (MAP), as well as nNOS expression were examined to evaluate the erectile function of SD rats with bilateral cavernous nerve injury (BCNI). RESULTS: ICA II and miR-33 respectively promoted and inhibited the differentiation of ADSCs to SCs. MiR-33 could negatively regulate P75 and GDNF expression. ICA II exerted promotion effects on differentiation of ADSCs to SCs via regulating miR-33. GDNF was identified to be a target of miR-33. MiR-33 overexpression abrogated the stimulatory effect of ICA II on ADSCs' differentiation, which was blocked by GDNF overexpression. treated with ICA II recovered the erectile function of BCNI model rats through regulation of miR-33. CONCLUSION: ICA II contributed to the differentiation of ADSCs to SCs viamiR-33/GDNF axis, contributing to the recovery of erectile function in BCNI rats.

7.
Fish Physiol Biochem ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32072342

RESUMO

Autophagy is an important evolutionary conserved process in eukaryotic organisms for the turnover of intracellular substances. Recent studies revealed that autophagy displays circadian rhythms in mice and zebrafish. To date, there is no report focused on the rhythmic changes of autophagy in fish skeletal muscles upon nutritional deprivation. In this study, we examined the circadian rhythms of 158 functional genes in tilapia muscle in response to starvation. We found that 12 genes were involved in autophagy changed their rhythm after starvation. Among these genes, Atg4c, Bnip3la, Lc3a, Lc3b, Lc3c, and Ulk1a exhibited a daily rhythmicity in tilapia muscle, and Atg4b, becn1, bnip3la, bnip3lb, Lc3a, and ulk1b were significantly upregulated in response to starvation. The number of autophagosomes was dramatically increased in fasted fish, indicating that nutritional signals affect not only the muscular clock system but also its autophagy behavior. Administration of GSK4112, an activator of Nr1d1, altered rhythmic expression of both circadian clock genes and autophagy genes in tilapia muscle. Taken together, these findings provide evidence that nutritional deficiency affects both circadian regulation and autophagy activities in skeletal muscle.

8.
Sci Rep ; 10(1): 1927, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024890

RESUMO

In this study, the term "ultrasonic ureteral crossing sign" is defined, and the diagnostic accuracy of this sign in the rapid localization of ureteral calculi is assessed. Between January 2017 and June 2018, 535 patients underwent ultrasound examination for suspected ureteral calculi. The "ultrasonic ureteral crossing sign" was classified as either positive or negative and correlated with the location of ureteral calculi. Of the 451 patients who were ultimately diagnosed with ureteral calculi, 263 patients had a positive sign, of which 258 patients had distal ureteral calculi, and 188 patients had a negative sign, of which 164 patients had proximal ureteral calculi. Eighteen stones were located in the ureter across the iliac vessels. For patients with a positive "ultrasonic ureteral crossing sign", we observed a 91% sensitivity, 97% specificity, 98% PPV, 87% NPV, and AUC of 0.94 for distal ureteral calculi. For patients with a negative "ultrasonic ureteral crossing sign", we observed a 97% sensitivity, 91% specificity, 87% PPV, 98% NPV, and AUC of 0.94 for proximal ureteral calculi. The "ultrasonic ureteral crossing sign" was found to accurately predict the location of ureteral calculi, significantly improve the efficiency of ultrasound examination, and provide a useful basis for follow-up treatment.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32048201

RESUMO

Messenger RNA (mRNA) vaccines have attracted great interest in recent years due to their high potency, safety profile, and potential of rapid development. Although a number of mRNA vaccines have entered clinical trials, there remain several challenges. Inefficient in vivo delivery of mRNA is the foremost one. Here we synthesized a conjugate composed of ß-cyclodextrin (ß-CD) and branched polyethyleneimine (molecular weight 2 kDa, bPEI2k) to deliver an mRNA vaccine. The CD-PEI (CP) conjugate helped the encapsulated mRNA molecules pass through the plasma membranes and escape from the endosomes, which consequently ensured high transfection efficiency. On this basis, we optimized several structural elements of mRNA molecules via synthesizing an advanced cap structure and incorporating untranslated regions (UTRs) and an extended poly(A) tail into the sequence. These modifications led to a higher expression level of encoded proteins, which was expected to induce potent immune responses with a relatively low dosage. We also investigated the relevance of the administration route to the immune responses induced by CP-assisted mRNA vaccines with in vivo evidence, providing a basis for the selection of optimum administration route in specific cases. This CP-based mRNA vaccine platform, with an optimized mRNA structure and administrated in a most appropriate route, holds a promise to be applied to specific antigens in the future. Graphical abstract.

10.
Expert Rev Clin Pharmacol ; : 1-10, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32077347

RESUMO

Background: Inflammation plays a key role in the etiology and pathology of postoperative cognitive dysfunction (POCD). Cyclooxygenase (COX)-2 inhibitor parecoxib is used for the treatment of acute pain due to its potent anti-inflammatory and analgesic effects. Herein, we evaluated the efficacy and safety of parecoxib on early POCD in geriatric patients.Objective: This study was performed to evaluate the efficacy and safety of parecoxib for early postoperative cognitive dysfunction (POCD) in elderly patients.Methods: Comprehensive literature search based on six electronic databases was applied to retrieve all related randomized controlled trials (RCTs). Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. The Cochrane's Tool was applied to evaluate the methodological quality of included studies. RevMan 5.3 was used to conduct meta-analysis.Results: Eight RCTs comprising a total of 1106 subjects prepared for orthopedic surgical operation were selected. All the identified RCTs were conducted in China. The methodological qualities of included studies were judged to be medium to high. The integrated data showed that perioperative intravenous parecoxib could remarkably reduce the incidence of POCD with improved Mini-Mental State Examination (MMSE) score. Parecoxib could significantly reduce the concentrations of interleukin-6, but results regarding the changes in tumor necrosis factor-alpha, C-reactive protein, and S100ß levels remained inconsistent.Conclusion: Perioperative parecoxib administration is effective in reducing the incidence of POCD and improving the MMSE score compared with control. However, the beneficial effect of parecoxib has been tested only in the Chinese population. Future RCTs in western countries with larger-scale and more comprehensive neurological tests are needed.

11.
FASEB J ; 34(2): 2011-2023, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31907997

RESUMO

Src Homology 2-containing Inositol Phosphatase-1 (SHIP-1) is a target of miR-155, a pro-inflammatory factor. Deletion of the SHIP-1 gene in mice caused spontaneous lung inflammation and fibrosis. However, the role and function of endothelial miR-155 and SHIP-1 in lung fibrosis remain unknown. Using whole-body miR-155 knockout mice and endothelial cell-specific conditional miR-155 (VEC-Cre-miR-155 or VEC-miR-155) or SHIP-1 (VEC-SHIP-1) knockout mice, we assessed endothelial-mesenchymal transition (EndoMT) and fibrotic responses in bleomycin (BLM) induced lung fibrosis models. Primary mouse lung endothelial cells (MLEC) and human umbilical vein endothelial cells (HUVEC) with SHIP-1 knockdown were analyzed in TGF-ß1 or BLM, respectively, induced fibrotic responses. Fibrosis and EndoMT were significantly reduced in miR-155KO mice and changes in EndoMT markers in MLEC after TGF-ß1 stimulation confirmed the in vivo findings. Furthermore, lung fibrosis and EndoMT responses were reduced in VEC-miR-155 mice but significantly enhanced in VEC-SHIP-1 mice after BLM challenge. SHIP-1 knockdown in HUVEC cells resulted in enhanced EndoMT induced by BLM. Meanwhile, these changes involved the PI3K/AKT, JAK/STAT3, and SMAD/STAT signaling pathways. These studies demonstrate that endothelial miR-155 plays an important role in fibrotic responses in the lung through EndoMT. Endothelial SHIP-1 is essential in controlling fibrotic responses and SHIP-1 is a target of miR-155. Endothelial cells are an integral part in lung fibrosis.

12.
World Neurosurg ; 136: e542-e552, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31954884

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of an enhanced recovery after surgery (ERAS) program for intraspinal tumors in a single-institutional prospective randomized controlled trial. METHODS: A multimodal and multidisciplinary ERAS protocol for intraspinal tumor surgery was developed. A total of 94 enrolled patients were randomized into 2 groups: 48 were managed following the ERAS protocol (ERAS group), and 46 received conventional perioperative care (control group). The primary end point was postoperative length of stay (LOS). The secondary outcomes included postoperative pain score and pain medication use, urinary catheterization, ambulation, mortality, reoperation/readmission rates, complication rates, patient satisfaction, and overall cost. RESULTS: A significant reduction in LOS was achieved in patients undergoing ERAS protocol compared with the controls (5 vs. 8 days; P < 0.0001). Moreover, patients in the ERAS group had better postoperative pain scores (1.0 ± 1.3 vs. 1.9 ± 1.3; P = 0.007), decreased use of patient-controlled analgesia (4.2% vs. 19.6%; P = 0.020) and oral opioid (37.5% vs. 58.7%; P = 0.040), early urinary catheter removal (58.3% vs. 6.5%; P < 0.0001), greater ambulation (68.8% vs. 17.4%; P < 0.0001), and higher satisfaction scores (91.8 ± 4.4 vs. 88.2 ± 6.8; P = 0.022) than did the control group. There were no deaths or 30-day readmission/reoperation in both groups, nor did the postoperative complication rates differ between groups. CONCLUSIONS: The ERAS protocol for intraspinal tumor surgery seems to be feasible, effective, and safe in shortening postoperative LOS, improving postoperative pain control with reduced opioid use, and accelerating functional recovery without increasing rates of complications or reoperation/readmission. Adoption of spine ERAS programs could be encouraged in practice, although validation with larger-scale multicenter trials is warranted.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31897729

RESUMO

BACKGROUND: In light of the controversies regarding the surgical treatment of adult Chiari malformation type I (CM-I) with syringomyelia, a retrospective study was conducted to evaluate the safety and efficacy of tonsillectomy followed by modified reconstruction of the cisterna magna with or without craniectomy. METHODS: Between 2008 and 2017, 78 adult CM-I patients (36 males and 42 females, mean age 40.6 years old) with syringomyelia were treated with posterior fossa decompression (PFD) with tonsillectomy and modified reconstruction of the cisterna magna. Patients were divided into two study groups: group A (n = 40) underwent cranioplasty with replacement of the bone flap; group B (n = 38) underwent suboccipital craniectomy. Neurological outcomes were evaluated by traditional physician assessment (improved, unchanged, and worsened) and the Chicago Chiari Outcome Scale (CCOS). Syringomyelia outcomes were assessed radiologically. RESULTS: The procedure was successfully performed in all patients, and restoration of normal cerebrospinal fluid (CSF) flow was confirmed by intraoperative ultrasonography. The median postoperative follow-up was 20.3 months (range 18-60 months). Clinical improvement was evident in 66 (84.6%) patients, with no significant differences between the two groups (85.0% vs. 84.2%, P = 0.897). According to the CCOS, 36 patients (90.0%) in group A were labeled as "good" outcome, compared with that of 34 (86.8%) in group B (P = 0.734). Improvement of syringomyelia was also comparable between the groups, which was observed in 35 (87.5%) vs. 33 (86.8%) patients (P = 0.887). The postoperative overall (7.5% vs. 23.7%, P = 0.048) and CSF-related (2.5% vs. 18.4%, P = 0.027) complication rates were significantly lower in group A than group B. CONCLUSIONS: Tonsillectomy with modified reconstruction of the cisterna magna without craniectomy seems to be a safe and effective surgical option to treat adult CM-I patients with syringomyelia, though future well-powered prospective randomized studies are warranted to validate these findings.

14.
Adv Exp Med Biol ; 1232: 409-414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893438

RESUMO

Nakamura et al. examined the evidence, using a discovery and a validation database, that amyloid-ß precursor protein (APP)669-711/amyloid-ß (Aß)1-42 and Aß1-40/Aß1-42 ratios, and composites based on traditional statistics; they concluded that these may be useful as biomarkers of Alzheimer's Disease (AD). We reexamined the same datasets, each of which included cognitively normal individuals (CN), individuals with mild cognitive impairment (MCI) and individuals with AD. We used fractal self-similar analyses and reexamined their data from (1) the Japanese National Center for Geriatrics and Gerontology (NCGG) (discovery database) and (2) the Australian Imaging, Biomarker and Lifestyle Study of Ageing (AIBL) cohort (validation database). Results: Using our methods, the three groups of individuals were found to be self-similar, i.e., they could not be differentiated quantitatively, in contrast to the findings of Nakamura et al. Conclusion: Appropriate biomarkers need further study. Our results suggest that APP669-711/Aß1-42 and Aß1-40/Aß1-42 ratios and their composites may not be valid biomarkers of AD, when reexamined using fractal methods for comparing biomarkers across populations.


Assuntos
Doença de Alzheimer , Biomarcadores , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides , Humanos
15.
J Magn Reson Imaging ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31999388

RESUMO

BACKGROUND: Low-intensity transcranial ultrasound (LITUS) has a therapeutic effect on traumatic brain injury (TBI). Diffusion kurtosis imaging (DKI) might be able to evaluate the effect changes of injured brain microstructure. PURPOSE: To evaluate the therapeutic effect of LITUS in a moderate TBI rat model with DKI parameters. STUDY TYPE: Prospective case-control animal study. ANIMAL MODEL: Forty-five rats were randomly divided into sham control, TBI, and LITUS treatment groups (n = 15). FIELD STRENGTH/SEQUENCE: Single-shot spin echo echo-planar imaging and fast T2 WI sequences at 3.0T. ASSESSMENT: DKI parameters were obtained on days 1, 7, 14, 21, 28, 35, and 42 after TBI. STATISTICAL TESTS: For the mean kurtosis (MK), axial kurtosis (Ka), and radial kurtosis (Kr) values, groups were compared using a two-way analysis of variance (ANOVA). RESULTS: LITUS inhibited TBI and caused MK values to increase significantly during the early stage (LITUS vs. TBI, day 7, adjusted P < 0.0001) and decrease during the late stage (LITUS vs. TBI, day 42, adjusted P = 0.0156) in the damaged cortex. In the thalamus, the MK value of the TBI group began to rise on day 7, with no change observed in the LITUS group. TBI increases Ka value during the early stage in the cortex and decreases during the late stage in the cortex and thalamus. LITUS inhibited these Ka changes (LITUS vs. TBI, day 7, adjusted P = 0.0014; LITUS vs. TBI, day 42, adjusted P = 0.0026 and 0.0478, respectively, for cortex and thalamus). The Kr value increased slightly during the early stage in the cortex (TBI vs. Sham, day 1, adjusted P = 0.0016). DATA CONCLUSION: The DKI parameter, particularly the MK value, evaluates primary cortical injury as well as the secondary brain injury that could not be detected by conventional T2 WI. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020.

16.
Dev Biol ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31904374

RESUMO

Protection of the germline from somatic differentiation programs is crucial for germ cell development. In many animals, whose germline development relies on the maternally inherited germ plasm, such protection in particular at early stages of embryogenesis is achieved by maternally localized global transcriptional repressors, such as PIE-1 of Caenorhabditis elegans, Pgc of Drosophila melanogaster and Pem of ascidians. However, zygotic gene expression starts in later germline cells eventually and mechanisms by which somatic gene expression is selectively kept under repression in the transcriptionally active cells are poorly understood. By using the ascidian species Halocynthia roretzi, we found that H3K27me3, a repressive transcription-related chromatin mark, became enriched in germline cells starting at the 64-cell stage when Pem protein level and its contribution to transcriptional repression decrease. Interestingly, inhibition of H3K27me3 together with Pem knockdown resulted in ectopic expression in germline cells of muscle developmental genes Muscle actin (MA4) and Snail, and of Clone 22 (which is expressed in all somatic but not germline cells), but not of other tissue-specific genes such as the notochord gene Brachyury, the nerve cord marker ETR-1 and a heart precursor gene Mesp, at the 110-cell stage. Importantly, these ectopically expressed genes are normally expressed in the germline sister cells (B7.5), the last somatic lineage separated from the germline. Also, the ectopic expression of MA4 was dependent on a maternally localized muscle determinant Macho-1. Taken together, we propose that H3K27me3 may be responsible for selective transcriptional repression for somatic genes in later germline cells in Halocynthia embryos and that the preferential repression of germline sister-lineage genes may be related to the mechanism of germline segregation in ascidian embryos, where the germline is segregated progressively by successive asymmetric cell divisions during cell cleavage stages. Together with findings from C. elegans and D. melanogaster, our data for this urochordate animal support the proposal for a mechanism, conserved widely throughout the animal kingdom, where germline transcriptional repression is mediated initially by maternally localized factors and subsequently by a chromatin-based mechanism.

17.
Ann N Y Acad Sci ; 1462(1): 128-138, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31583714

RESUMO

The role of spliceosome-associated protein 130 (SAP130) in gut inflammation, particularly in Crohn's disease (CD), remains unclear. The aim of our study was to analyze correlations between serum SAP130 levels and CD severity, and to assess its predictive value for the clinical efficacy of exclusive enteral nutrition (EEN) in CD. Correlations between the SAP130 levels and CD severity were evaluated. SAP130 and its receptor Mincle (macrophage-inducible C-type lectin) in the colon tissue in active CD were measured. Furthermore, the serum SAP130 level was investigated as a predictor of clinical efficacy in patients treated with EEN. The serum SAP130 levels significantly increased in patients with active CD compared with patients in remission for CD (P < 0.001) and control individuals (P < 0.001), and they varied according to clinical activity and significantly correlated with disease severity. In parallel, the expression of both SAP130 and Mincle in colon tissue was elevated in active CD. Additionally, the serum SAP130 level declined in patients with active CD who achieved efficacy at week 8 after EEN therapy. This preliminary evidence shows that SAP130 might be a potential noninvasive biomarker that correlates well with CD severity and the clinical efficacy of EEN in CD.

18.
J Cell Physiol ; 235(4): 3753-3767, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31587299

RESUMO

Apoptosis is the major cause of cardiomyocyte death in myocardial ischemia/reperfusion injury (MI/RI). Increasing evidence suggests that microRNAs (miRNAs) can contribute to the regulation of cardiomyocytes apoptosis by posttranscriptional modulation of gene expression networks. However, the effects of miR-327 in regulating MI/RI-induced cardiomyocytes apoptosis have not been extensively investigated. This study was performed to test whether miR-327 participate in cardiomyocytes apoptosis both in vitro and in vivo, and reveal the potential molecular mechanism of miR-327 regulated MI/RI through targeting apoptosis repressor with caspase recruitment domain (ARC). Sprague-Dawley (SD) rats were subjected to MI/RI by left anterior descending coronary artery occlusion for 30 min and reperfusion for 3 hr. H9c2 cells were exposed to hypoxia for 4 hr and reoxygenation for 12 hr to mimic I/R injury. miRNA-327 recombinant adenovirus vectors were transfected into H9c2 cells for 48 hr and rats for 72 hr before H/R and MI/RI treatment, respectively. The apoptosis rate, downstream molecules of apoptotic pathway, and the target reaction between miRNA-327 and ARC were evaluated. Our results showed that miR-327 was upregulated and ARC was downregulated in the myocardial tissues of MI/RI rats and in H9c2 cells with H/R treatment. Inhibition of miR-327 decreased the expression levels of proapoptotic proteins Fas, FasL, caspase-8, Bax, cleaved caspase-9, cleaved caspase-3, and the release of cytochrome-C, as well as increasing the expression levels of antiapoptotic protein Bcl-2 via negative regulation of ARC both in vivo or vitro. In contrast, overexpression miR-327 showed the reverse effect. Moreover, the results of luciferase reporter assay indicated miR-327 targets ARC directly at the posttranscriptional level. Taken together, inhibition of miR-327 could attenuate cardiomyocyte apoptosis and alleviate I/R-induced myocardial injury via targeting ARC, which offers a new therapeutic strategy for MI/RI.

19.
Acta Pharmacol Sin ; 41(1): 119-128, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31534201

RESUMO

Inefficient diabetic ulcer healing and scar formation remain a challenge worldwide, owing to a series of disordered and dynamic biological events that occur during the process of healing. A functional wound dressing that is capable of promoting ordered diabetic wound recovery is eagerly anticipated. In this study, we designed a silicone elastomer with embedded 20(S)-protopanaxadiol-loaded nanostructured lipid carriers (PPD-NS) to achieve ordered recovery in scarless diabetic ulcer healing. The nanostructured lipid carriers were prepared through an emulsion evaporation-solidification method and then incorporated into a network of silicone elastomer to form a unique nanostructured lipid carrier-enriched gel formulation. Interestingly, the PPD-NS showed excellent in vitro anti-inflammatory and proangiogenic activity. Moreover, in diabetic mice with full-thickness skin excision wound, treatment with PPD-NS significantly promoted in vivo scarless wound healing through suppressing inflammatory infiltration in the inflammatory phase, promoting angiogenesis during the proliferation phase, and regulating collagen deposition in the remodeling phase. Hence, this study demonstrates that the developed PPD-NS could facilitate ordered diabetic wound recovery via multifunctional improvement during different wound-healing phases. This novel approach could be promising for scarless diabetic wound healing.

20.
Magn Reson Imaging ; 67: 79-84, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31278999

RESUMO

OBJECTIVE: To investigate the feasibility of the relative apparent diffusion coefficient (rADC) values based on readout-segmented echo-planar diffusion sequence in evaluation the effects of low-intensity transcranial ultrasound (LIPUS) on ischemic stroke in rat models at different onset times. METHODS: Sixty Sprague-Dawley rats (weight, 250 ±â€¯10 g) were divided randomly into six groups (n = 10) to establish a permanent model of distal middle cerebral artery occlusion (dMCAO). The rats were stimulated with ultrasound for 10 min in the LIPUS groups at 0.5 h, 1 h, 3 h, 6 h, and 9 h after dMCAO (denoted as the LIPUS group (0.5 h), LIPUS group (1 h), LIPUS group (3 h), LIPUS group (6 h), LIPUS group (9 h), and Control group without ultrasound stimulation). Magnetic resonance imaging was acquired at 0.5 h and 1 h after dMCAO and then at 1-hour intervals until 12 h. The rADC values were then measured and calculated. The pathological results from the rat brains were obtained after the experiment. RESULTS: When LIPUS was applied 0.5 h after dMCAO, the rate of decline of rADC values in the early stages were significantly reduced and the final rADC values were significantly increased. When LIPUS were applied at 1 h, 3 h, and 6 h, the final rADC values only increased slightly and did not prevent early declines. No significant difference of ultrasound stimulation at 9 h was found. CONCLUSION: The rADC values demonstrated difference at different time points after dMCAO between with and without LIPUS groups.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA