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1.
J Cell Mol Med ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845833

RESUMO

Vascular Ehlers-Danlos syndrome (vEDS) is a rare and severe hereditary connective tissue disease arising from a mutation in the type III collagen alpha I chain (COL3A1) gene, with a poor prognosis due to exceptional vascular ruptures and premature death. Herein, starting from a 36-year-old Chinese male patient with a complaint of upper abdominal pain, we collected clinical data of and performed a genetic analysis of a total of 20 family members. We identified two closely spaced COL3A1 missense variants in cis, p.Leu734Phe (c.2199_2200TC>AT) and p.Gly741Ser (c.2221G>A), as the cause of vEDS in this family. p.Gly741Ser, a glycine substitution mutation, has been previously reported, whereas p.Leu734Phe, a non-glycine substitution mutation, is novel. We analysed their independent and combined effects on the COL3A1 level in transfected skin fibroblast cells by means of Western blotting. We found that both variants independently led to a reduced COL3A1 level and, when combined, led to an even more reduced COL3A1 level compared to the wild type. Thus, each missense variant can be independently classified as a pathogenic variant, albeit with a synergetic effect when occurring together. Moreover, our genetic findings provide an explanation for four previous sudden deaths and identified two high-risk carriers in the family.

2.
J Cardiothorac Surg ; 16(1): 334, 2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34802435

RESUMO

OBJECTIVE: This retrospective study sought to evaluate the efficacy of transit time flow measurement (TTFM) as a means of predicting bypass graft patency as assessed by coronary artery angiography upon 5-year follow-up. METHODS: Of 311 patients undergone isolated off-pump coronary artery bypass graft surgery from January 2014 through December 2014, 202 (65%) underwent both intraoperative TTFM and angiography at follow-up. 610 grafts, 202 left internal mammary artery grafts and 408 saphenous vein grafts were checked. Any grafts that exhibited Fitzgibbon type B or O lesions upon angiographic evaluation were considered to be failing. Receiver operating characteristic curves were used to identify the optimal TTFM values for predicting graft patency. RESULTS: A total of 610 grafts were included in this analysis, including 202 LIMA grafts and 408 SV grafts, of which 107, 129, 129, and 43 anastomosed to DIAG, OM, PDA, and PLA, respectively. LIMA, DIAG, OM, PDA, and PLA bypass grafts had overall patency rates of 95.0%, 74.8%, 73.6%, 71.5%, and 74.4%, respectively, upon 5-year follow up. No significant differences in TTFM values (MGF, PI, and DF) were observed when comparing outcomes associated with individual or sequential SV grafting. MGF was found to be predictive of graft failure regardless of the target vessel (P < 0.05). While PI was found to predict LIMA, OM, and PDA graft failure (P < 0.05), it was not associated with the failure of grafts associated with DIAG and PLA vessels. Similarly, DF was found to predict OM and PDA graft failure (P < 0.05), but was not significantly associated with the failure of grafts associated with LIMA, DIAG, or PLA vessels. CONCLUSION: LIMA bypass grafts were associated with better 5-year graft patency relative to SV bypass grafts. Similar graft patency rates were observed for both individual and sequential bypass grafts. MGF was able to predict bypass graft failure in patients that underwent off-pump CABG surgery.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Angiografia Coronária , Ponte de Artéria Coronária , Seguimentos , Humanos , Estudos Retrospectivos , Veia Safena/diagnóstico por imagem , Resultado do Tratamento , Grau de Desobstrução Vascular
3.
Clin Res Cardiol ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34761309

RESUMO

BACKGROUND: Left bundle branch pacing (LBBP) is a novel near-physiological pacing method that still lacks quantitative criteria to guide the selection of lead-implanted sites to enhance the success likelihood of lead deployments. This study aimed to quantitatively analyze the relationships of LBBP success likelihood to the distribution of lead-implanted sites and the lead-localization-pacing electrocardiographic (ECG) features. METHODS: All the lead-implanted sites in patients with finally successful LBBP were enrolled for analysis, including successful and failed sites. A novel coordinate system was invented to describe the sites' distribution as longitudinal distance (longit-dist) and lateral distance (lat-dist). Corrected distance parameters were generated to eliminate the cardiac dimension variations. The lead-localization-pacing ECG parameters were also collected, such as paced QRS duration (locat-QRSd), left ventricular activation time (locat-LVAT), LVAT/QRSd ratio (locat-LVAT/QRSd), and QRS directions. RESULTS: A total of 94 patients with 105 successful sites and 93 failed sites were enrolled. Longit-dist and corrected longit-dist of successful sites were significantly longer, while locat-QRSd and locat-LVAT were shorter and locat-LVAT/QRSd was lower than failed sites. There was a positive dose-response relationship between LBBP success likelihood and corrected longit-dist with a cut-off of 26.95 mm, whereas there were negative dose-response relationships of LBBP success likelihood to locat-QRSd, locat-LVAT, and locat-LVAT/QRSd with the cut-offs of 142 ms, 92 ms, and 64.7%, respectively. Downward QRS direction in II/III ECG leads was also associated with successful LBBP. CONCLUSION: Longit-dist, locat-QRSd, locat-LVAT, and locat-LVAT/QRSd were quantitative parameters to guide the selection of lead-implanted sites during LBBP implantation. Quantitative distance and electrocardiographic parameters for lead-implanted site selection to enhance the success likelihood of left bundle branch pacing. LBBP, left bundle branch pacing; Longit-dist, longitudinal distance; CL-apex-dist, distance from contraction line to apex; LBBB, left bundle branch block; IVCD, intraventricular conduction delay; Locat-QRSd, lead-localization-pacing QRS duration; Locat-LVAT, lead-localization-pacing left ventricular activation time; Locat-LVAT/QRSd, lead-localization-pacing LVAT/QRSd ratio.

4.
BMC Pregnancy Childbirth ; 21(1): 762, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758779

RESUMO

INTRODUCTION: Postpartum hemorrhage is a serious complication of childbirth and is still the leading cause of maternal death worldwide. Lower uterine segment hemorrhage during cesarean section is an important cause of postpartum hemorrhage. Our objective is to expore the efficacy and safety of King's combined uterine suture for hemostasis during cesarean section. METHODS: We examined 48 cases: 16 cases of pernicious placenta previa (including one case of twins), 11 cases of central placenta previa (including one case of twins), 18 cases of uterine scarring (including two cases of twins), as well as one case of twin pregnancy, two cases of breech presentation, and one case of pulmonary hypertension. The "King's combined uterine suture" method for hemostasis was used in patients with lower uterine segment hemorrhage during cesarean section. RESULTS: The results showed that all patients had successful hemostasis during surgery, and there were no cases of hysterectomy. CONCLUSION: We have concluded that King's combined uterine suture is a fast and safe hemostasis method for cesarean section that can effectively reduce blood loss and restore the normal shape of the lower uterine segment. Furthermore, this suture method can reduce postpartum hemorrhage and hysterectomy rate, as well as improve maternal prognosis.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Cesárea , Hemostasia Cirúrgica/métodos , Hemorragia Pós-Parto/prevenção & controle , Técnicas de Sutura , Adulto , Feminino , Humanos , Gravidez
5.
Front Neurosci ; 15: 711528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759789

RESUMO

Objective: To investigate the profiles of brain volumetric measurements in children with attention deficit hyperactivity disorder (ADHD), and the consistency of these brain volumetric measurements derived from the synthetic and conventional T1 weighted MRI (SyMRI and cT1w MRI). Methods: Brain SyMRI and cT1w images were prospectively collected for 38 pediatric patients with ADHD and 38 healthy children (HC) with an age range of 6-14 years. The gray matter volume (GMV), white matter volume (WMV), cerebrospinal fluid (CSF), non-WM/GM/CSF (NoN), myelin, myelin fraction (MYF), brain parenchyma volume (BPV), and intracranial volume (ICV) were automatically estimated from SyMRI data, and the four matching measurements (GMV, WMV, BPV, ICV) were extracted from cT1w images. The group differences of brain volumetric measurements were performed, respectively, using analysis of covariance. Pearson correlation analysis and interclass correlation coefficient (ICC) were applied to evaluate the association between synthetic and cT1w MRI-derived measurements. Results: As for the brain volumetric measurements extracted from SyMRI, significantly decreased GMV, WMV, BPV, and increased NON volume (p < 0.05) were found in the ADHD group compared with HC; No group differences were found in ICV, CSF, myelin volume and MYF (p > 0.05). With regard to GMV, WMV, BPV, and ICV estimated from cT1w images, the group differences between ADHD and HC were consistent with the results estimated from SyMRI. And these four measurements showed noticeable correlation between the two approaches (r = 0.692, 0.643, 0.898, 0.789, respectively, p < 0.001; ICC values are 0.809, 0.782, 0.946, 0.873, respectively). Conclusion: Our study demonstrated a global brain development disability, but normal whole-brain myelination in children with ADHD. Moreover, our results demonstrated the high consistency of brain volumetric indices between synthetic and cT1w MRI in children, which indicates the high reliability of SyMRI in the child-brain volumetric analysis.

6.
Phys Rev E ; 104(4-1): 044137, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34781450

RESUMO

We study the mutual information between two lattice blocks in terms of von Neumann entropies for one-dimensional infinite lattice systems. Quantum q-state Potts model and transverse-field spin-1/2 XY model are considered numerically by using the infinite matrix product state approach. As a system parameter varies, block-block mutual information exhibit singular behaviors that enable us to identify the critical points for the quantum phase transitions. As happens with von Neumann entanglement entropy of single block, at critical points, block-block mutual information for two adjacent blocks show a logarithmic leading behavior with increasing the size of the blocks, which yields the central charge c of the underlying conformal field theory, as it should be. It seems that two disjoint blocks show a similar logarithmic growth of the mutual information as a characteristic property of critical systems but the proportional coefficients of the logarithmic term are very different from the central charges. As the separation between the two lattice blocks increases, the mutual information reveals a consistent power-law decaying behavior for various truncation dimensions and lattice-block sizes. The critical exponent of block-block mutual information in the thermodynamic limit is estimated by extrapolating the exponents of power-law decaying regions for finite truncation dimensions. For a given lattice-block size ℓ, the critical exponents for the same universality classes seem to have very close values each other. Whereas the critical exponents have different values to a degree of distinction for the different universality classes. As the lattice-block size becomes bigger, the critical exponent becomes smaller. We discuss a relation between the exponents of block-block mutual information and correlation with the Shatten one-norm of block-block correlation.

7.
Toxicol Rep ; 8: 1783-1791, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722163

RESUMO

Ovatodiolide is a bioactive cembrane-type diterpenoid isolated from Anisomeles indica (L.) Kuntze. It has been proven that ovatodiolide is anti-inflammatory, anti-tumorigenic, anti-melanogenic and attenuates asthma by regulating signaling pathways. The aim of this study was to evaluate the safety of ovatodiolide by conducting genotoxicity tests and 28-day oral toxicity tests in rats. Genotoxicity assays were conducted by using a bacterial reverse mutation test and mammalian chromosomal aberration test to assess whether ovatodiolide causes reverse mutations and mutagenicity with or without metabolism activation. For the in vivo mammalian erythrocyte micronucleus test, mice were administered a single dose of 0, 250, 500 or 1000 mg/kg b.w. ovatodiolide by single gavage. In the acute oral toxicity test, rats were given a single dose of ovatodiolide 1000 mg/kg b.w. by single gavage. In the 28-day oral toxicity test, groups were divided into a control, ovatodiolide 10, 25 and 50 mg/kg b.w. The results showed that there was no mutagenicity in the bacterial reverse mutation test or the mammalian chromosomal aberration test with or without S9 fraction. Ovatodiolide did not produce an increase in micronucleated reticulocytes in the micronucleus test. The results revealed that the acute oral toxicity of ovatodiolide is over 1000 mg/kg b.w. in rats. Moreover, 10, 25 and 50 mg/kg b.w. of ovatodiolide did not cause a significant effect in rats. According to the results of the genotoxicity and oral toxicity studies in rats, ovatodiolide did not produce any adverse effects, and the tested doses can serve as clinical references.

8.
BMC Pregnancy Childbirth ; 21(1): 744, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732155

RESUMO

INTRODUCTION: A retrospective study was conducted to investigate the effectiveness and feasibility of fibroid enucleation in the anterior wall of the uterus by transverse uterine incision during cesarean section. METHODS: The medical history, surgical data, preoperative and postoperative changes in the blood system, and complications of 90 pregnant women who underwent myomectomy of the anterior uterine wall during cesarean section at the second Department of Maternal and Child Health Hospital of Fujian Province were analyzed retrospectively. RESULTS: No significant differences were noted in the leiomyoma number, pathological type, preoperative and postoperative hemoglobin level, perioperative bleeding incidence, blood transfusion frequency, postoperative fever incidence, and duration of lochia between the study and control groups. The proportion of large fibroids was slightly higher in the study group than in the control group (p < 0.05), and the operation time and average hospitalization time were slightly longer in the study group than in the control group (p < 0.05). The distribution of type III-V fibroids was slightly more in the study group than in the control group (p < 0.05), and the distribution of type VI fibroids in the study group was less than that in the control group (p < 0.05). CONCLUSION: Fibroid enucleation is safe and effective in the anterior wall of the uterus through the lower uterine transverse incision in cesarean section. It has the potential to reduce the risk of pelvic and intrauterine adhesions in the future.

9.
Pain Physician ; 24(8): 495-506, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34793634

RESUMO

BACKGROUND: Chronic musculoskeletal pain (CMP) management is a major global public health goal owing to increased social and economic burdens. However, the risk of CMP in smokers compared with nonsmokers remains uncertain. OBJECTIVES: This study aims to determine the magnitude and importance of the relationship between cigarette smoking and risk of CMP. STUDY DESIGN: A meta-analysis of the CMP risk of cigarette smokers. METHODS: We systematically searched PubMed, Embase, and Cochrane library databases from inception to August 2020. Data extraction and quality assessment were performed by 2 independent reviewers using a standardized extraction checklist. Data were pooled using a random-effects model. RESULTS: In this meta-analysis of 32 studies involving 296,109 participants, current smoking was associated with increased CMP risk (OR: 1.23, 95% CI: 1.09-1.40), whereas ever and past smoking did not show such an association (OR: 1.14, 95% CI: 0.95-1.37; OR: 1.06, 95% CI: 0.83-1.35, respectively). Stratified analyses showed that there was a marked significance in almost all strata of current smokers compared with non-smokers, except for mean age (>= 50 years), location of pain (neck pain, sacral pain, and knee pain), smoking frequency (occasionally), study design (cross-sectional), mean follow-up (< 10 years), and adjustment for confounding factors (>= 6). Interestingly, there was statistically negative association between cigarette smoking and knee pain risk in current smokers, ever smokers, and past smokers. LIMITATIONS: The major limitation of this meta-analysis relates to the heterogeneities across included studies. CONCLUSIONS: Cigarette smoking was associated with increased risk of CMP. In view of the high prevalence of smoking in many countries and the increasing number of CMP patients worldwide, reducing tobacco use should be an important public health strategy to prevent and control the global epidemic of CMP. Future research should attempt to establish whether this association is causal and clarify its mechanisms.

10.
World J Clin Cases ; 9(26): 7653-7670, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34621817

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a refractory intestinal disease with alternating onset and remission and a long disease course, which seriously affects the health and quality of life of patients. The goal of treatment is to control clinical symptoms, induce and maintain remission, promote mucosal healing, and reduce recurrence. Clinical trials have shown unsatisfactory clinical response rates. As a supplementary alternative medicine, traditional Chinese medicine has a rich history and has shown good results in the treatment of UC. Because of the quality of herbal medicine and other factors, the curative effect of traditional Chinese medicine is not stable enough. The mechanism underlying the effect of Jianpi Qingchang Huashi Recipe (JPQCHSR) on inducing UC mucosal healing is not clear. AIM: To investigate the potential mechanism of JPQCHSR for the treatment of UC based on network pharmacology and molecular docking. METHODS: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to extract the active components and action targets of JPQCHSR, and the target names were standardized and corrected through UniProt database. The related targets of UC were obtained through GeneCards database, and the intersection targets of drugs and diseases were screened by jvenn online analysis tool. The visual regulatory network of "Traditional Chinese medicine-active components-target-disease" was constructed using Cytoscape software, the protein interaction network was constructed using STRING database, and enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways was conducted through R software. At last, the active components were docked with the core target through SYBYL-X 2.1.1 software. RESULTS: Through database analysis, a total of 181 active components, 302 targets and 205 therapeutic targets were obtained for JPQCHSR. The key compounds include quercetin, luteolin, kaempferol, etc. The core targets involved STAT3, AKT1, TP53, MAPK1, MAPK3, JUN, TNF, etc. A total of 2861 items were obtained by GO enrichment analysis, and 171 items were obtained by KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis. The results of molecular docking showed that the key active components in JPQCHSR had certain affinity with the core target. CONCLUSION: The treatment of UC with JPQCHSR is a complex process of multi-component, multi-target and multi-pathway regulation. The mechanism of this Recipe in the treatment of UC can be predicted through network pharmacology and molecular docking, so as to provide theoretical reference for it to better play its therapeutic role.

11.
Brain Imaging Behav ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491528

RESUMO

To investigate the quantitative profiles of brain grey matter (GM) in pediatric drug-naïve ADHD patients using synthetic magnetic resonance imaging (SyMRI). A total of 37 drug-naïve pediatric ADHD and 27 age- and gender-matched healthy controls (HC) were enrolled in this study. Each subject underwent both SyMRI and conventional 3D T1-FSPGR scans. Quantitative parameters, T1 and T2 maps, were extracted from the SyMRI data. Between-group quantitative maps were compared using a general linear model analysis. Pearson correlation analysis was conducted to assess the association between significantly altered MR indices and clinical measurements in ADHD. Compared with the HC group, altered T1 and T2 relaxometry times in the ADHD group were mainly distributed in GM regions of the cerebellum, attention and execution control network, default mode network, and limbic areas. Moreover, the T1 value of the right cerebellum 8 was negatively correlated with the attention concentration level in ADHD (R = 0.140, P = 0.0225). With regards to T2 map, the associations were observed between the attention level of ADHD patients and left fusiform gyrus (R = 0.251, P = 0.0016), and right cerebellum crus2 (R = 0.142, P = 0.0214). Altered T1, T2 values found in specific regions of GM, including cerebellum, attention and execution control network, default mode network, and limbic areas, may reveal widespread micromorphology changes, i.e., brain iron deficiency, low myelin content, and enlarged vascular interstitial space in ADHD patients. Thus, T1, T2 values might be promising imaging markers for future ADHD studies.

12.
Front Cardiovasc Med ; 8: 739889, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552968

RESUMO

Background: Night-time heart rate (HR) is expected to reflect more accurately the cardiac autonomic function of modulating cardiovascular activity. Few studies have been conducted on the predictive values of night-time HR in relation to cardioverter-defibrillator therapies. Aims: To explore the associations of night-time HR with the ventricular tachyarrhythmias (VTAs), appropriate and inappropriate implantable cardioverter-defibrillator (ICD) shocks. Methods: Patients from the SUMMIT registry receiving ICD or cardiac resynchronization therapy with defibrillator (CRT-D) implantation were retrospectively analyzed using archived home monitoring data. Night-time HR was recorded from 2:00 am to 6:00 am during the first 30 to 60 days after implantation. VTA events and ICD shocks were identified using the intracardiac electrograms by two independent physicians. Restricted cubic splines and smooth curve fitting were conducted to address the non-linear associations between night-time HR and adjusted hazards for clinical outcomes. Results: Over a mean follow-up duration of 55.8 ± 22.7 months, 187 deaths were observed among 730 patients. VTAs, appropriate and inappropriate ICD shocks were observed in 422 (57.8%), 293 (40.1%), and 72 (10.0%) patients, respectively. Apparent U-shaped non-linear associations of night-time HR with VTAs (P for non-linearity = 0.007), appropriate ICD shocks (P for non-linearity = 0.003) and inappropriate ICD shocks (P for non-linearity = 0.014) were detected. When night-time HR was beyond 60 bpm, every 1 bpm increase in night-time HR could result in 3.2, 3.3, and 4.9% higher risks of VTAs and appropriate and inappropriate ICD shocks, respectively; when night-time HR was lower than 60 bpm, every 1 bpm increase in night-time HR could result in 6.0 and 10.7% lower risks of appropriate and inappropriate ICD shocks. Compared to night-time HR of ≤ 50 or ≥70 bpm, night-time HR of 50-70 bpm was associated with 24.9, 30.2, 63.5, and 31.5% reduced incidences of VTA events, appropriate ICD shocks, inappropriate ICD shocks, and all-cause mortality, respectively. Conclusion: Apparent non-linear associations of night-time HR with VTAs and ICD shocks were detected. An increasing incidence of VTAs and ICD shocks was observed at both low and high levels of night-time HR. Night-time HR of 50-70 bpm might be the optimal therapeutics target for the management of ICD/CRT-D recipients.

13.
Front Cardiovasc Med ; 8: 693458, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513943

RESUMO

Background: Changes in physical activity (PA) after implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillators (CRT-D) implantation were unknown. The association of PA changes with new-onset atrial fibrillation (AF), cardiac death and all-cause mortality was unclear in patients at high risk of sudden cardiac death. Methods: Patients receiving ICD/CRT-D implantation from SUMMIT registry were retrospectively analyzed. Changes in PA were considered from baseline status to 1 year after implantation. New-onset AF was defined as the first atrial high-rate episode ≥1% of the daily AF burden detected after implantation. Results: Over a mean follow-up of 50.3 months, 124 new-onset AF events (36.2%), 61 cardiac deaths (17.8%), and 87 all-cause deaths (25.4%) were observed in 343 patients with ICD/CRT-D implantation. PA at 1 year after implantation was increased compared with PA at baseline (11.97 ± 5.83% vs. 10.82 ± 5.43%, P = 0.008), and PA at 1 year was improved in 210 patients (61.2%). Per 1% decrease in PA was associated with 12.4, 18.3, and 14.3% higher risks of new-onset AF, cardiac death and all-cause mortality, regardless of different baseline characteristics. Patients with decreased PA had 2-fold risks of new-onset AF (hazard ratio [HR] = 1.972, 95% confidence interval [CI]: 1.352-2.877, P < 0.001) as high as those with unchanged/increased PA. Decreased PA was an independent risk factor for cardiac death (HR = 3.358, 95% CI: 1.880-5.996, P < 0.001) and all-cause mortality (HR = 2.803, 95% CI:1.732-4.535, P < 0.001). Conclusion: PA decrease after ICD/CRT-D implantation is associated with a higher incidence of new-onset AF, resulting in worsened outcomes in cardiac death and all-cause mortality.

14.
Acta Pharmacol Sin ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34522005

RESUMO

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP2, and PIP3. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.

15.
Int J Behav Nutr Phys Act ; 18(1): 128, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544427

RESUMO

BACKGROUND: High levels of physical activity (PA) and heart rate variability (HRV) are associated with cardiovascular benefits in patients with cardiovascular diseases. HRV, representing cardiac autonomic function, is positively associated with PA. However, the impacts of PA and cardiac autonomic function on cardiovascular outcomes were not analysed in the same study population. This lack of evidence supported our hypothesis that PA might contribute to cardiovascular benefits via enhanced cardiac autonomic function. METHODS: Patients with implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy defibrillator (CRT-D) implantation were included from the SUMMIT registry. HRV and PA values were assessed during the first 30-60 days post device implantation using a continuous home monitoring system. Causal mediation analysis was conducted to explore the possible mediation function of HRV in the association of PA with long-term cardiac death and all-cause mortality in patients at a high risk of sudden cardiac death. RESULTS: Over a mean follow-up period of 47.7 months, 63 cardiac deaths (18.9%) and 85 all-cause death events (25.5%) were observed among 342 patients with ICD/CRT-D implantation. A positive linear association between HRV and PA was demonstrated and the ß value of HRV was 0.842 (95% confidence interval [CI]: 0.261-1.425, P = 0.005) in the multiple linear regression analysis. Multivariable Cox proportional hazards analysis revealed that high levels of PA (≥11.0%) and HRV (≥75.9 ms) were independent protective factors against cardiac death (PA: hazard ratio [HR] = 0.273; 95% CI, 0.142-0.526, P < 0.001; HRV: HR = 0.224; 95% CI, 0.103-0.489, P < 0.001) and all-cause mortality (PA: HR = 0.299; 95% CI, 0.177-0.505, P < 0.001; HRV: HR = 0.394; 95% CI, 0.231-0.674, P = 0.001). Causal mediation analysis demonstrated partial mediation effects of PA that were mediated through HRV on cardiac death (mediation proportion = 12.9, 95%CI: 2.2-32.0%, P = 0.006) and all-cause mortality (mediation proportion = 8.2, 95%CI: 1.6-20.0%, P = 0.006). CONCLUSIONS: HRV might be a modest mediator in the association between high levels of PA and the reduced risks of cardiac death and all-cause mortality in ICD/CRT-D recipients. This finding supports that enhanced cardiac autonomic function might be one of the underlying mechanisms by which regular PA contributes to cardiovascular benefits.


Assuntos
Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Estudos de Coortes , Morte Súbita Cardíaca/prevenção & controle , Exercício Físico , Insuficiência Cardíaca/terapia , Humanos
16.
Cell Death Dis ; 12(10): 881, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580283

RESUMO

Podocytes are known to play a determining role in the progression of proteinuric kidney disease. N6-methyladenosine (m6A), as the most abundant chemical modification in eukaryotic mRNA, has been reported to participate in various pathological processes. However, its role in podocyte injury remains unclear. In this study, we observed the elevated m6A RNA levels and the most upregulated METTL14 expression in kidneys of mice with adriamycin (ADR) and diabetic nephropathy. METTL14 was also evidently increased in renal biopsy samples from patients with focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy and in cultured human podocytes with ADR or advanced glycation end product (AGE) treatment in vitro. Functionally, we generated mice with podocyte-specific METTL14 deletion, and identified METTL14 knockout in podocytes improved glomerular function and alleviated podocyte injury, characterized by activation of autophagy and inhibition of apoptosis and inflammation, in mice with ADR nephropathy. Similar to the results in vivo, knockdown of METTL14 facilitated autophagy and alleviated apoptosis and inflammation in podocytes under ADR or AGE condition in vitro. Mechanically, we identified METTL14 knockdown upregulated the level of Sirt1, a well-known protective deacetylase in proteinuric kidney diseases, in podocytes with ADR or AGE treatment. The results of MeRIP-qPCR and dual-luciferase reporter assay indicated METTL14 promoted Sirt1 mRNA m6A modification and degradation in injured podocytes. Our findings suggest METTL14-dependent RNA m6A modification contributes to podocyte injury through posttranscriptional regulation of Sirt1 mRNA, which provide a potential approach for the diagnosis and treatment of podocytopathies.

17.
J Plant Physiol ; 266: 153527, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34563791

RESUMO

Agrobacterium-mediated plant transformation has been widely used for introducing transgene(s) into a plant genome and plant breeding. However, our understanding of T-DNA integration into rice genome remains limited relative to that in the model dicot Arabidopsis. To better elucidate the T-DNA integration into the rice genome, we investigated extensively the T-DNA ends and their flanking rice genomic sequences from two transgenic rice plants carrying Cowpea Trypsin Inhibitor (CpTI)-derived gene Signal-CpTI-KDEL (SCK) and Bacillus thuringiensis (BT) gene, respectively, by TAIL-PCR method. Analysis of the junction sequences between the T-DNA ends and rice genome DNA indicated that there were three joining patterns of microhomology, filler DNA sequences, and exact joining, and both the T-DNA ends tend to adopt identical manner to join the rice genome. After T-DNA integration, there were several variations of rice genomic sequences, including small deletions at the integration sites, superfluous DNA inserted between T-DNA and genome, and translocation of genomic DNA in the flanking regions. The translocation block could be from a noncontiguous region in the same chromosome or different chromosomes at the integration sites, and the originating position of the translocated block resulted in comparable deletion based on a cut/paste mechanism rather than a replication mechanism. Our study may lead to a better understand of T-DNA integration mechanism and facilitate functional genomic studies and further crop improvement.

18.
J Nanobiotechnology ; 19(1): 244, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34391417

RESUMO

BACKGROUND: Macromoleculization of nitroxides has been an effective strategy to improve low relaxivities and poor in vivo stability, however, nitroxides-based metal-free magnetic resonance imaging (MRI) macromolecular contrast agents (mCAs) are still under-performed. These mCAs do not possess a high nitroxides content sufficient for a cumulative effect. Amphiphilic nanostructures in these mCAs are not stable enough for highly efficient protection of nitroxides and do not have adequate molecular flexibility for full contact of the paramagnetic center with the peripheral water molecules. In addition, these mCAs still raise the concerns over biocompatibility and biodegradability due to the presence of macromolecules in these mCAs. RESULTS: Herein, a water-soluble biodegradable nitroxides-based mCA (Linear pDHPMA-mPEG-Ppa-PROXYL) was prepared via covalent conjugation of a nitroxides (2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl, PROXYL) onto an enzyme-sensitive linear di-block poly[N-(1, 3-dihydroxypropyl) methacrylamide] (pDHPMA). A high content of PROXYL up to 0.111 mmol/g in Linear pDHPMA-mPEG-Ppa-PROXYL was achieved and a stable nano-sized self-assembled aggregate in an aqueous environment (ca. 23 nm) was formed. Its longitudinal relaxivity (r1 = 0.93 mM- 1 s- 1) was the highest compared to reported nitroxides-based mCAs. The blood retention time of PROXYL from the prepared mCA in vivo was up to ca. 8 h and great accumulation of the mCA was realized in the tumor site due to its passive targeting ability to tumors. Thus, Linear pDHPMA-mPEG-Ppa-PROXYL could provide a clearly detectable MRI enhancement at the tumor site of mice via the T1WI SE sequence conventionally used in clinical Gd3+-based contrast agents, although it cannot be compared with DTPA-Gd in the longitudinal relaxivity and the continuous enhancement time at the tumor site of mice. Additionally, it was demonstrated to have great biosafety, hemocompatibility and biocompatibility. CONCLUSIONS: Therefore, Linear pDHPMA-mPEG-Ppa-PROXYL could be a potential candidate as a substitute of metal-based MRI CAs for clinical application.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34388085

RESUMO

Two pairs of aerobic, Gram-stain-positive, rod-shaped strains (HY164T/HY044, HY168T/HY211) were isolated from bat faecal samples. Strains HY164T and HY044 were motile with a polar flagellum, and had 16S rRNA gene similarity of 95.1-98.6 % to Haloactinobacterium album YIM 93306T and Haloactinobacterium glacieicola T3246-1T; strains HY168T and HY211 were most similar to Ruania albidiflava DSM 18029T (96.6 %). Phylogenetic trees based on 16S rRNA gene and whole genome sequences revealed affiliation of strains HY164T and HY168T to the family Ruaniaceae, representing novel lineages in the genera Haloactinobacterium and Ruania, respectively, which was also supported by the results for average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH). For all isolates, the principal cellular fatty acids were anteiso-C15 : 0 and iso-C14 : 0. HY164T and HY168T had MK-8(H4) as the predominant isoprenoid quinone, diphosphatidylglycerol, phosphatidylglycerol, several unidentified phospholipids and glycolipids as common polar lipids while the latter strain additionally contained one unidentified aminophospholipid and one unidentified phosphoglycolipid. Besides sharing alanine, glutamic acid and lysine with HY164T, HY168T additionally contained 2,4-diaminobutyric acid in the cell-wall peptidoglycan. The whole-cell sugars of HY164T were ribose and rhamnose, while HY168T only included the latter. The DNA G+C contents of HY164T and HY168T were 71.0 and 69.1 mol%, respectively. Combining the polyphasic taxonomic data, HY164T (=CGMCC 4.7606T=JCM 33464T) is classified as representing a novel species of the genus Haloactinobacterium with the proposed name Haloactinobacterium kanbiaonis sp. nov., and HY168T (=CGMCC 1.16970T=JCM 33465T) is proposed to represent a novel species of the genus Ruania with the name Ruania zhangjianzhongii sp. nov.


Assuntos
Actinobacteria/classificação , Quirópteros , Filogenia , Actinobacteria/isolamento & purificação , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , Quirópteros/microbiologia , DNA Bacteriano/genética , Ácidos Graxos/química , Fezes/microbiologia , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
20.
Front Oncol ; 11: 709210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367994

RESUMO

Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells via receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP+ macrophages and C5_IFIT1+ macrophages were found to regulate regulatory T cells and participate in CD8+ T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8+ T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.

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