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1.
J Pharm Pharmacol ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836050

RESUMO

OBJECTIVES: To evaluate the anticancer effects of lupeol in retinoblastoma cells. METHODS: WERI-Rb-1 and Y-79 cell lines were used to evaluate the anticancer effect of lupeol. After lupeol treatment, the viability, proliferation, apoptosis, cancer stem-like properties, autophagy and in vivo tumour xenograft formation were detected. KEY FINDINGS: In this study, lupeol decreased cell viability in both WERI-Rb-1 and Y-79 cell lines. Lupeol could also inhibit proliferation and induce apoptosis of RB cells, with increased Bax level and decreased Ki67, survivin and Bcl-2 levels. Furthermore, lupeol could suppress the spheroid formation and stem-like properties of RB cells. Moreover, LC3 II/LC3 I ratio and the levels of Beclin1 and ATG7 were increased after lupeol treatment, indicating that lupeol could induce autophagy in RB cells. Next, the inhibitory effect of lupeol on the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway was observed. In tumour-bearing mice, lupeol suppressed tumour growth, and this might relate to its role in cell apoptosis, autophagy and stem-like properties. CONCLUSIONS: Lupeol suppressed proliferation and cancer stem-like properties, and promoted autophagy and apoptosis of RB cells by restraining the PI3K/AKT/mTOR pathway.

2.
Nat Plants ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33833418

RESUMO

Beneficial interactions between plant roots and rhizosphere microorganisms are pivotal for plant fitness. Nevertheless, the molecular mechanisms controlling the feedback between root architecture and microbial community structure remain elusive in maize. Here, we demonstrate that transcriptomic gradients along the longitudinal root axis associate with specific shifts in rhizosphere microbial diversity. Moreover, we have established that root-derived flavones predominantly promote the enrichment of bacteria of the taxa Oxalobacteraceae in the rhizosphere, which in turn promote maize growth and nitrogen acquisition. Genetic experiments demonstrate that LRT1-mediated lateral root development coordinates the interactions of the root system with flavone-dependent Oxalobacteraceae under nitrogen deprivation. In summary, these experiments reveal the genetic basis of the reciprocal interactions between root architecture and the composition and diversity of specific microbial taxa in the rhizosphere resulting in improved plant performance. These findings may open new avenues towards the breeding of high-yielding and nutrient-efficient crops by exploiting their interaction with beneficial soil microorganisms.

3.
Anal Chem ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33834764

RESUMO

Cardiovascular disease is one of the main causes of death in the world, which is closely associated with dyslipidemia. Dyslipidaemia is usually manifested as a relatively higher level of low-density lipoprotein (LDL) and lower level of high-density lipoprotein (HDL). Thus, the quantitative detection of the LDL and HDL particles is of great importance to predict the risk of cardiovascular diseases. However, the traditional methods can only indirectly reflect the HDL/LDL particle concentrations by detecting the cholesterol or proteins in HDL/LDL particles and are always laborious and time-consuming. Thus, the accurate and efficient approach for the detection of intact HDL and LDL particles is still lacking so far. We developed an enzyme- and isolation-free method to measure the concentration of HDL and LDL based on DNAzyme and hybridization chain reaction (HCR)-based signal amplification. This method can be used to directly and accurately detect the concentration of "actual" HDL and LDL particles instead of the cholesterol in HDL and LDL, with limits of detection of 10 and 30 mg/dL, respectively, which also satisfied the lipoprotein analysis in clinical samples. Therefore, this autocatalytic HCR-DNAzyme platform has great potential in clinical applications and health management.

4.
J Ethnopharmacol ; 274: 114043, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33753143

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Kushen Injection (CKI) is a widely used TCM formula for treatment of carcinomatous pain and tumors of digestive system including hepatocellular carcinoma (HCC). However, the potential mechanisms of CKI for treatment of HCC have not been systematically and deeply studied. AIM OF STUDY: A metabolic data-driven systems pharmacology approach was utilized to investigate the potential mechanisms of CKI for treatment of HCC. MATERIALS AND METHODS: Based on phenotypic data generated by metabolomics and genotypic data of drug targets, a propagation model based on Dijkstra program was proposed to decode the effective network of key genotype-phenotype of CKI in treating HCC. The pivotal pathway was predicted by target propagation mode of our proposed model, and was validated in SMMC-7721 cells and diethylnitrosamine-induced rats. RESULTS: Metabolomics results indicated that 12 differential metabolites, and 5 metabolic pathways might be involved in the anti-HCC effect of CKI. A total of 86 metabolic related genes that affected by CKI were obtained. The results calculated by propagation model showed that 6475 shortest distance chains might be involved in the anti-HCC effect of CKI. According to the results of propagation mode, EGFR was identified as the core target of CKI for the anti-HCC effect. Finally, EGFR and its related pathway EGFR-STAT3 signaling pathway were validated in vivo and in vitro. CONCLUSION: The proposed method provides a methodological reference for explaining the underlying mechanism of TCM in treating HCC.

5.
Molecules ; 26(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33672038

RESUMO

Our previous study found that desmethylxanthohumol (1) inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol (2) and its dimer analogue rottlerone (3) exhibited more potent α-glucosidase inhibitory activity than 1. The aim of this study was to synthesize a series of rottlerone analogues and evaluate their α-glucosidase and DPP-4 dual inhibitory activity. The results showed that compounds 4d and 5d irreversibly and potently inhibited α-glucosidase (IC50 = 0.22 and 0.12 µM) and moderately inhibited DPP-4 (IC50 = 23.59 and 26.19 µM), respectively. In addition, compounds 4d and 5d significantly promoted glucose consumption, with the activity of 5d at 0.2 µM being comparable to that of metformin at a concentration of 1 mM.


Assuntos
Inibidores da Dipeptidil Peptidase IV/farmacologia , Flavonoides/síntese química , Flavonoides/farmacologia , Glucose/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Propiofenonas/síntese química , Propiofenonas/farmacologia , Dipeptidil Peptidase 4/metabolismo , Flavonoides/química , Células Hep G2 , Humanos , Cinética , Propiofenonas/química , alfa-Glucosidases/metabolismo
6.
J Orthop Surg Res ; 16(1): 198, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731155

RESUMO

BACKGROUND: Cement mantle penetration and the cement-bone interface strength were critical to a successful primary total knee arthroplasty (TKA). It remained unclear whether decreased blood and fat in the cancellous bone achieved with the use of a tourniquet increases tibial cement mantle penetration in different zones on AP and lateral view in TKA according to criteria defined by the Knee Society Scoring System (KSS). The purpose of this study was to determine whether tourniquet use influences tibial cement mantle penetration in different zones on AP and lateral view in TKA according to KSS. METHODS: We conducted a meta-analysis to identify studies involving the impact of tourniquet use and no tourniquet use on tibial bone cement penetration in primary TKA in electronic databases, including Web of Science, Embase, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, VIP, Wanfang database, up to January 2021. Finally, we identified 1231 patients (1231 knees) assessed in twelve studies. RESULTS: Tourniquet use increases the cumulative cement mantle penetration (P < 0.00001), mean cement mantle penetration (P = 0.004), and cement mantle in zone 3(P < 0.0001) on AP view. However, there were no significant differences in cement mantle in zone 1(P = 0.5), zone 2(P =0 .54), zone 4(P = 0.07) on AP view, and zone 1(P = 0.32), zone 2(P = 0.38) on lateral view between two groups. There were also no significant differences in length of surgery(P = 0.7), change in hemoglobin(P = 0.4), transfusion rates(P = 0.47), and complications such as muscular calf vein thrombosis(P = 0.21), superficial infection (P = 0.72), and deep vein thrombosis (P = 0.66) between two groups. CONCLUSION: The application of a tourniquet increases the thickness of the tibial bone cement penetration-the increase in the thickness of bone cement penetration mainly located in zone 3 on the anteroposterior (AP) view.

7.
Zool Res ; 42(2): 246-249, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33709636

RESUMO

Somatic mutations are a large category of genetic variations, which play an essential role in tumorigenesis. Detection of somatic single nucleotide variants (SNVs) could facilitate downstream analysis of tumorigenesis. Many computational methods have been developed to detect SNVs, but most require normal matched samples to differentiate somatic SNVs from the normal state, which can be difficult to obtain. Therefore, developing new approaches for detecting somatic SNVs without matched samples are crucial. In this work, we detected somatic mutations from individual tumor samples based on a novel machine learning approach, svmSomatic, using next-generation sequencing (NGS) data. In addition, as somatic SNV detection can be impacted by multiple mutations, with germline mutations and co-occurrence of copy number variations (CNVs) common in organisms, we used the novel approach to distinguish somatic and germline mutations based on the NGS data from individual tumor samples. In summary, svmSomatic: (1) considers the influence of CNV co-occurrence in detecting somatic mutations; and (2) trains a support vector machine algorithm to distinguish between somatic and germline mutations, without requiring normal matched samples. We further tested and compared svmSomatic with other common methods. Results showed that svmSomatic performance, as measured by F1-score, was significantly better than that of others using both simulation and real NGS data.


Assuntos
Aprendizado de Máquina , Mutação/genética , Neoplasias/genética , Algoritmos , Animais , Biologia Computacional/métodos , Variações do Número de Cópias de DNA , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Neoplasias/metabolismo
8.
Environ Res ; 197: 111007, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33716032

RESUMO

Antibiotic resistance has gained increasing attention worldwide, and wastewater treatment plants have been regarded as hotspots for antibiotic-resistant bacteria and antibiotic-resistant genes (ARGs). In this study, we evaluated the removal of tetracycline-resistant Escherichia coli and its related genes through ultrasound (US) treatment with different input levels of US-specific energy combined with ultraviolet light emitting diodes (UV-LEDs). Simultaneous US with UV-LEDs effectively eliminated tetracycline-resistant E. coli with the normal suggested UV-LEDs dosage (below 30 mJ/cm2). The removal efficiency increased with the addition of US (specific input energy of 8-16 kJ/L), and simultaneous US treatment with UV-LEDs was relatively more effective than US pretreatment. Analyses of cell damage by K+ leakage and flow cytometry showed that the cell wall kept its integrity during the applied treatment conditions. Consequently, the removal efficiencies of 16 S rRNA, tet M, and tet Q were unsatisfactory because less than 1 log reduction was achieved. Increasing the US energy remarkably damaged the cell wall and potentially promoted the reaction. The removal of ARGs increased four times when using US-specific input energy at 330 kJ/L with 5 mJ/cm2 compared with UV-LEDs alone. The US treatment combined with UV-LEDs is a novel process that does not require chemicals. Results of this research can provide theoretical support for the removal of ARGs.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33719413

RESUMO

As a promising candidate in various fields, including energy conversion and electronics, layered van der Waals metal phosphorus trichalcogenides (MPX3) have been widely explored. In addition to the layered structures, MPX3 comprising post-transition metals (i.e., Sn and Pb) are known to form a unique 3D framework with nonlayered structure. However, the nonlayered two-dimensional (2D) crystals of this family have remained unexplored until now. Herein, we successfully synthesized 2D nonlayered tin thiohypodiphosphate (Sn2P2S6) nanosheets, having an indirect bandgap of 2.25 eV and a thickness down to ∼10 nm. The as-obtained nanosheets demonstrate promising photocatalytic water splitting activity to generate H2 in pure water under simulated solar light (AM 1.5G). Moreover, the ultrathin Sn2P2S6 catalyst shows auspicious performance and stability with a continuous operation of 40 h. This work is not only an expansion of the MPX3 family, but it is also a major milestone in the search for new materials for future energy conversion.

10.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(2): 131-138, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33729128

RESUMO

The epidemic of coronavirus disease 2019 (COVID-19) puts higher demands on critical care medicine. Lots of studies have been conducted to solve COVID-19-related problems. Therefore, we reviewed the annual progress for COVID-19-related issues including antivirals threapies, respiratory support and immunomodulatory therapies and other critical issues, including the effect of antibiotic on mitochondrial damage and its relationship with sepsis, the goal and direction of antimicrobial de-escalation, drug prophylaxis of constipation, bleeding in gastrointestinal disorders and management of critical illness in the informalization era and so on. We hope to provide reference for clinical and scientific research work of the intensivists.


Assuntos
Cuidados Críticos , Estado Terminal , Humanos
11.
Eur J Med Chem ; 217: 113372, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33744689

RESUMO

Diabetes mellitus is one of the most challenging threats to global public health. To improve the therapy efficacy of antidiabetic drugs, numerous drug delivery systems have been developed. Polyethylene glycol (PEG) is a polymeric family sharing the same skeleton but with different molecular weights which is considered as a promising material for drug delivery. In the delivery of antidiabetic drugs, PEG captures much attention in the designing and preparation of sustainable and controllable release systems due to its unique features including hydrophilicity, biocompatibility and biodegradability. Due to the unique architecture, PEG molecules are also able to shelter delivery systems to decrease their immunogenicity and avoid undesirable enzymolysis. PEG has been applied in plenty of delivery systems such as micelles, vesicles, nanoparticles and hydrogels. In this review, we summarized several commonly used PEG-contained antidiabetic drug delivery systems and emphasized the advantages of stimuli-responsive function in these sustainable and controllable formations.

12.
BMC Urol ; 21(1): 48, 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33773582

RESUMO

PURPOSE: to describe the methodology of transurethral seminal vesiculoscopy and the anatomy of the area of the verumontanum, and to determine the safety of this procedure, especially in terms of postoperative complications. METHODS: This retrospective observational study enrolled 144 patients with intractable hematospermia from May 2011 and August 2019. A 4.5/6.5-Fr vesiculoscope was inserted into the seminal vesicle to deal with the positive findings. The solution of quinolones was used to rinse each seminal vesicle. RESULTS: In this study, Transurethral seminal vesiculoscopy was successfully performed in 139 patients (96.53%). Hematospermia was alleviated or disappeared in 116 (80.56%) patients by less than half a year after surgery. Common intraoperative manifestations were hemorrhage, stones, utricle polyps and cysts. The surgical approach in our study were categorized into four types, including 24 (16.7%), 73 (50.7%), 42 (29.2%), and 5 (3.5%) cases in Type A (natural opening of the ejaculatory duct), B (trans-duct fenestration), C (trans-utricle fenestration), and D (not founded), respectively. Sexual function change was recorded in 12 patients of 111 patients, all by the method of trans-utricle fenestration, including 8 (7.21%), 3 (2.70%), and 1 (0.90%) patients in shorter intravaginal ejaculatory latency time, worse erection hardness and loss of orgasm, respectively. CONCLUSION: Transurethral seminal vesiculoscopy is an effective and safe procedure for the management of hematospermia. The anatomy of the distal seminal tract should be understood more deeply and Wu'method (uncover-curtain method) needs to be promoted to verify its universality and safety. Besides, the complications of the function dysfunction should be discussed in the future in multi-center clinical trials.

13.
Sci Rep ; 11(1): 4993, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654211

RESUMO

Compared with traditional craniotomy, the expanded endoscopic endonasal approach (EEEA) may have some advantages for tuberculum sellae meningioma (TSM) treatment. We described our experience of the therapeutic effect of endoscopic TSM treatment. From August 2015 to December 2019, 40 patients with a TSM were treated by the EEEA in our institution. EEEA outcome in TSM treatment was analyzed. Among 39 patients with visual impairment, 38 (97.4%) improved their visual function to some extent after the EEEA, and one case had no significant change in visual acuity. Among all patients, 38 (95.0%) achieved gross total resection (GTR) and 2 (5.0%) achieved near-total resection (NTR). Cerebrospinal fluid (CSF) leakage occurred in three patients (7.5%) and meningitis (post-CSF leakage) in two patients (5.0%). Eight patients (20.0%) suffered postoperative hyposmia, three of whom developed long-term hyposmia. One patient (2.5%) suffered from bleeding of the branch of the anterior cerebral artery intraoperatively leading to postoperative acute cerebral infarction. The EEEA is a safe and reliable minimally invasive method for TSM removal. Compared with traditional craniotomy, the EEEA may have better visual outcomes and a higher prevalence of GTR, but carries the risk of CSF leakage.

14.
Medicine (Baltimore) ; 100(8): e24591, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663069

RESUMO

BACKGROUND: Thyroid nodules (TN) are discrete lesions within the thyroid gland and are a common clinical problem detected in 19% to 68% of people. TN are more common as age increases and occur more frequently in women. TN can cause pressure symptoms, cosmetic complaints, and thyroid dysfunction. Treatment for benign thyroid nodules includes thyroid hormone therapy, surgery, radioiodine treatment, percutaneous ethanol injection therapy, and laser or radiofrequency treatment to shrink nodules. In China and many other countries, doctors use Chinese herbal medicines (CHM) to treat TN. However, systematic review and meta-analysis has not been found to assess the effects and safety of CHM in curing TN at present. Hence, the systematic review is conducted to scientifically and methodically evaluate the value of its effectiveness and safety of CHM on TN. METHODS: Literatures related to CHM for TN from the establishment of the database to November 2020 will be retrieved from the following databases: PubMed, Excerpta Medica Database (EMBASE), MEDLINE, Web of Science, Cochrane Library, SpringerLink, WHO International Clinical Trials Registry Platform (ICTRP), Wanfang Database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP). There are no language restrictions for retrieving literatures. Case reports, animal studies, editorials, expert opinions, reviews without original data, and studies on pediatric population were excluded. Eligible randomized clinical trials (RCTs) evaluating the effectiveness and safety of CHM in TN patients will be put in the study including nodule volume reduction ≥50%, pressure symptoms, cosmetic complaints, quality of life, and adverse events. By scanning the titles, abstracts and full texts, 2 reviewers will independently select studies, extract data, and assess the quality of study. Meta-analysis of RCTs will be conducted using Review Manager 5.1 software. The results will be presented as risk ratio for dichotomous data, and standardized or weighted mean difference for continuous data. RESULT: This study will provide high-quality available evidence for the treatment of TN with CHM based on nodule volume reduction ≥50%, pressure symptoms, cosmetic complaints, quality of life, and adverse events. CONCLUSION: The systematic review will to evaluate the efficacy of CHM in treating benign thyroid nodules in adults and provide evidence for clinicians. INPLASY REGISTRATION NUMBER: INPLASY2020120093.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Nódulo da Glândula Tireoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Testes de Função Tireóidea
15.
Cell Death Dis ; 12(4): 302, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753726

RESUMO

Expression of kinesin family member 18B (KIF18B), an ATPase with key roles in cell division, is deregulated in many cancers, but its involvement in prostate cancer (PCa) is unclear. Here, we investigated the expression and function of KIF18B in human PCa specimens and cell lines using bioinformatics analyses, immunohistochemical and immunofluorescence microscopy, and RT-qPCR and western blot analyses. KIF18B was overexpressed in PCa specimens compared with paracancerous tissues and was associated with poorer disease-free survival. In vitro, KIF18B knockdown in PCa cell lines promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, while KIF18B overexpression had the opposite effects. In a mouse xenograft model, KIF18B overexpression accelerated and promoted the growth of PCa tumors. Bioinformatics analysis of control and KIF18B-overexpressing PCa cells showed that genes involved in the PI3K-AKT-mTOR signaling pathway were significantly enriched among the differentially expressed genes. Consistent with this observation, we found that KIF18B overexpression activates the PI3K-AKT-mTOR signaling pathway in PCa cells both in vitro and in vivo. Collectively, our results suggest that KIF18B plays a crucial role in PCa via activation of the PI3K-AKT-mTOR signaling pathway, and raise the possibility that KIF18B could have utility as a novel biomarker for PCa.

16.
Org Lett ; 23(6): 2279-2284, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33667106

RESUMO

We disclose herein a Au(I)-catalyzed domino cyclization of 1,6-diynes incorporated with indole. This protocol enabled the diastereoselective buildup of indole-fused azabicyclo[3.3.1]nonanes from linear precursors. Density functional theory calculations showed that the reaction proceeded via an unprecedented cascade dearomatization/rearomatization/dearomatization process. Independent gradient model analysis revealed that a noncovalent attractive interaction between the distal alkyne and the Au/proximal complex was responsible for the chemoselectivity of the first spirocyclization step.

17.
Hepatology ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33638162

RESUMO

The dynamic N6-methyladenosine (m6 A) mRNA modification is essential for acute stress response and cancer progression. Sublethal heat stress from insufficient radiofrequency ablation (IRFA) has been confirmed to promote hepatocellular carcinoma (HCC) progression, however, whether m6 A machinery is involved in IRFA-induced HCC recurrence remains unknown. Using IRFA HCC orthotopic mouse model, we detected higher level of m6 A reader YTHDF1 in the sublethal-heat-exposed transitional zone close to the ablation center than that in the farther area. In addition, we validated the increased m6 A modification and elevated YTHDF1 protein level in sublethal-heat-treated HCC cell lines, HCC patient-derived xenograft (PDX) mouse model and patients' HCC tissues. Functionally, gain-/loss-of function assays showed that YTHDF1 promotes HCC cell viability and metastasis. Knockdown of YTHDF1 drastically restrains the tumor metastasis evoked by sublethal heat treatment in tail vein injection lung metastasis and orthotopic HCC mouse models. Mechanistically, we found that sublethal heat treatment increases EGFR m6 A modification in the vicinity of 5'UTR region and promotes its binding with YTHDF1, which enhances the translation of EGFR mRNA. The sublethal heat induced up-regulation of EGFR level was further confirmed in IRFA HCC PDX mouse model and patients' tissues. Combination of YTHDF1 silencing and EGFR inhibition suppressed the malignancies of HCC cells synergically. CONCLUSION: The m6 A-YTHDF1-EGFR axis promotes HCC progression after IRFA, supporting the rationale for targeting m6 A machinery in combined with EGFR inhibitors to suppress HCC metastasis after RFA.

18.
Arthroscopy ; 37(3): 862-870, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33524479

RESUMO

PURPOSE: To investigate the change in muscle volume around the hip in patients with femoroacetabular impingement (FAI) after arthroscopy and evaluate other factors related to muscle change. METHODS: We performed a retrospective review of magnetic resonance imaging data of patients with FAI who underwent hip arthroscopy. Magnetic resonance imaging was obtained pre- and postoperatively. The cross-sectional area (CSA) of muscles were determined on axial images. The Wilcoxon signed-rank test was used to determine the differences between pre- and postoperative hip muscle CSA. The correlations of change in muscle CSA with age, sex, body mass index, pain level, preoperative symptom duration, follow-up time, and multiple validated patient-reported outcomes were also analyzed with a Spearman rank correlation test. RESULTS: Fifty-one patients with a mean age of 36.5 ± 5.6 years were included and analyzed. The follow-up was 26.6 ± 0.5 months (range, 24-40 months), and 27 (52.9%) were women. Patients with FAI showed increased hip muscle CSA of gluteus maximus (P = .002) and gluteus minimus (P = .001). Post- compared with preoperative, the value for the change in medius CSA was underpowered, and no differences in other hip muscle CSAs were observed. The increased muscle CSA of the gluteus maximus was significantly correlated with the improvement of modified Harris Hip Score (ρ = 0.404; P = .003). The increased muscle CSA of the gluteus minimus was significantly correlated with the improvement of pain Visual Analog Scale (ρ = 0.452; P = .001). Age, body mass index, sex, symptom duration, and follow-up time were not significantly correlated with change in muscle CSA. CONCLUSIONS: Patients with FAI have a significantly increased postoperative muscle CSA of the gluteus maximus (7.8%) and the gluteus minimus (11.6%) compared with preoperative values. The increased muscle CSA of the gluteus maximus and gluteus minimus was significantly correlated with improvement in modified Harris Hip Score and pain Visual Analog Scale, respectively. The increase of muscle volume may be associated with the improvement of subjective function and pain relief. LEVELS OF EVIDENCE: Level IV, therapeutic case series.

19.
ACS Chem Neurosci ; 12(4): 756-765, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33539063

RESUMO

Demyelination, the loss of the protecting sheath of neurons, contributes to disability in many neurological diseases. In order to fully understand its role in different diseases and to monitor treatments aiming at reversing this process, it would be valuable to have PET radiotracers that can detect and quantify molecular changes involved in demyelination such as the uncovering and upregulation of the axonal potassium channels Kv1.1 and Kv1.2. Carbon-11 labeled radiotracers present the advantage of allowing for multiple scans on the same subject in the same day. Here, we describe [11C]3MeO4AP, a novel 11C-labeled version of the K+ channel tracer [18F]3F4AP, and characterize its imaging properties in two non-human primates including a monkey with a focal brain injury sustained during a surgical procedure 3 years prior to imaging. Our findings show that [11C]3MeO4AP is brain permeable, metabolically stable and has high plasma availability. When compared with [18F]3F4AP, [11C]3MeO4AP shows very high correlation in volumes of distribution (VT), confirming a common target. [11C]3MeO4AP shows slower washout than [18F]3F4AP, suggesting stronger binding. Finally, similar to [18F]3F4AP, [11C]3MeO4AP is highly sensitive to the focal brain injury. All these features make it a promising radioligand for imaging demyelinated lesions.

20.
Brain Res ; 1757: 147328, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33539795

RESUMO

Sevoflurane (Sev), a commonly used volatile anesthetic, could induce nerve damage and cognitive deficiency. Oxidative stress induced by iron overload promotes nerve damage and cell apoptosis in the brain. This study revealed a new toxic mechanism of Sev to the brain occurred through the dysfunction of iron metabolism. Twelve-month-old C57BL/6 mice were randomly assigned to the following three groups: control group; 2% Sev (6 h) group; and Sev plus iron deficiency group. Iron levels and iron metabolism-related proteins and apoptosis-related factors in hippocampus and cortex tissues were detected by using synchrotron radiation micro-X-ray fluorescence (µ-XRF) and western blotting. Our results showed that a decline in cognitive function was observed in mice treated with Sev. Sev significantly induced iron accumulation through upregulating ferritin and downregulating transferrin receptor 1 which involved in ferroportin1 (Fpn1)/hepcidin pathway and increasing reactive oxygen species (ROS) and malondialdehyde (MDA) content of hippocampus and cortex. Sev aggravated BACE1 expression and Aß accumulation. Changes in the ratio of Bcl2/Bax and Tau/p-Tau intensified the cell apoptosis in hippocampus and cortex tissues. Interestingly, the cognitive deficiency and neurotoxicity induced by Sev could be ameliorated significantly by feeding a low-iron diet to mice prior to anesthesia. The data uncovered a new lesion mechanism of Sev from the role of iron metabolism. This study also suggested that the reduction in iron levels could protect the brain against neurological damage induced by Sev.

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