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1.
BMC Musculoskelet Disord ; 21(1): 730, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172443

RESUMO

PURPOSE: Muscle strength training is a common strategy for treating chronic ankle instability (CAI), but the effectiveness decreases for mechanical ankle instability (MAI) patients with initial severe ligament injuries. The purpose of this study was to investigate the characteristics and the potential predictors of muscle strength deficit in MAI patients, with a view to proposing a more targeted muscle strength training strategy. METHODS: A total of 220 MAI patients with confirmed initial lateral ankle ligament rupture and a postinjury duration of more than 6 months were included. All patients underwent a Biodex isokinetic examination of the ankle joints of both the affected and unaffected sides. Then, the associations between the limb symmetry index (LSI) (mean peak torque of the injury side divided by that of the healthy side) and the patients' sex, body mass index, postinjury duration, presence of intra-articular osteochondral lesions, presence of osteophytes and ligament injury pattern (i.e., isolated anterior talofibular ligament (ATFL) injury or combined with calcaneofibular ligament injury) were analysed. RESULTS: There was significantly weaker muscle strength on the affected side than on the unaffected side in all directions (p < 0.05). The LSI in plantar flexion was significantly lower than that in dorsiflexion at 60°/s (0.87 vs 0.98, p < 0.001). A lower LSI in eversion was significantly correlated with female sex (0.82 vs 0.94, p = 0.016) and isolated ATFL injury (0.86 vs 0.95, p = 0.012). No other factors were found to be associated with muscle strength deficits. CONCLUSION: MAI patients showed significant muscle strength deficits on the affected side, especially in plantar flexion. There were greater strength deficits in eversion in females and individuals with an isolated ATFL injury. Thus, a muscle strength training programme for MAI patients was proposed that focused more on plantar flexion training and eversion training for females and those with an isolated ATFL injury.

2.
Chem Commun (Camb) ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185210

RESUMO

A highly chemoselective as well as enantioselective fluorescent probe has been discovered for the recognition of the acidic amino acids, including glutamic acid and aspartic acid. This study has established a novel amino acid recognition mechanism by an aldehyde-based fluorescent probe.

3.
Biomed Pharmacother ; 131: 110764, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152927

RESUMO

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is thought to be a risk factor for endometrial hyperplasia, but potential links between the two diseases are unknown. This study aims to evaluate the role of T2DM in the progression of endometrial hyperplasia. METHODS: Female Sprague-Dawley rats were randomly divided into normal (N) group, endometrial hyperplasia (NH) group, T2DM (T) group, and endometrial hyperplasia with T2DM (TH) group. Proteomics analysis was performed to determine the protein profile of endometrial tissues. Proliferation, migration, and invasion of cells with/without GLANT2-knockdown were assessed. Immunohistochemical staining and ELISA were used to examine the expression of GALNT2 in endometrial tissues and serum of clinical samples. RESULTS: The highest uterus index and endometrial thickness were observed in TH group, with the expression of proliferation marker PCNA increased significantly, indicating that T2DM facilitates the progress of endometrial hyperplasia. Proteomics analysis showed that there were significant differences in protein profiles among groups and differential proteins were mainly enriched in metabolic pathways. Further verification by molecular biology analysis indicated that GALNT2 is the key target for T2DM facilitating endometrial hyperplasia. The expression of GALNT2 was significantly decreased in high glucose environment. T2DM could synergize the proliferative function of GALNT2 aberration by activating EGFR/AKT/ERK pathway. The decreased expressions of GALNT2 in clinical samples were associated with worse subtypes of endometrial hyperplasia. CONCLUSION: T2DM promoted the progression of endometrial hyperplasia by regulating the GALNT2-mediated phosphorylation of EGFR and enhancing cell proliferation. GALNT2 has the potential to be a novel biomarker in the treatment of endometrial hyperplasia.

4.
Int Orthop ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230605

RESUMO

BACKGROUND: The objective was to analyze the long-term clinical outcome of terrible triad injury of the elbow following surgical intervention with a single lateral approach. METHOD: We treated twenty-five patients with terrible triad injury of the elbow from July 1, 2017, to June 30, 2020, and performed post hoc analysis. All patients underwent standardized surgery which entailed: plate fixation for the ulnar coronoid process, fixation or replacement of the radial head, and repair of the lateral ligament but not the medial collateral ligament. RESULTS: We followed up each patient for an average of 22.9 months (range, 12 to 36 months) after surgery. Patients had an average angle scope of elbow flexion and extension that ranged from 8° to 120°. Average pronation of the elbow was 75° (range, 10°-85°), and average supination was 72° (range, 25°-80°). Patient-reported outcome measures were excellent: the DASH and Mayo elbow performance score (MEPS) were 96%. We were unable to follow-up one patient (4%). Among the remaining 24 patients, one patient (4%) presented with heterotopic ossification and stiffness following arthrolysis in the elbow one year after the initial surgery. We did not observe any joint dislocation, subluxation, or joint instability in the elbow after surgery. DISCUSSION: The single lateral approach, a sequential surgery for terrible triad injury of the elbow, can improve initial stability of the elbow. Patients are able to perform rehabilitative exercises sooner in their recovery, which helps to reduce stiffness. Heterotopic ossification is also reduced.

5.
Acta Biomater ; 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33130305

RESUMO

Although various biodegradable materials have been investigated for ligament reconstruction fixation in the past decades, only few of them possess a combination of high mechanical properties, appropriate degradation rate, good biocompatibility, and osteogenic effect, thus limiting their clinical applications. A high-strength Zn-0.8Mn-0.4Mg alloy (i.e., Zn08Mn04Mg) with yield strength of 317 MPa was developed to address this issue. The alloy showed good biocompatibility and promising osteogenic effect in vitro. The degradation effects of Zn08Mn04Mg interference screws on the interface between soft tissue and bone were investigated in anterior cruciate ligament (ACL) reconstruction in rabbits. Compared to Ti6Al4V, the Zn alloy screws significantly accelerated the formation of new bone and further induced partial tendon mineralization, which promoted tendon-bone integration. The newly developed screws are believed to facilitate early joint function recovery and rehabilitation training and also avoid screw breakage during insertion, thereby contributing to an extensive clinical prospect.

6.
Sci Total Environ ; : 143036, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33131876

RESUMO

Dihydroxylated polybrominated diphenyl ethers (diOH-PBDEs) appear to be natural products or metabolites of PBDEs in some marine organisms, yet its toxicity is still largely unknown. With a newly lab-synthesized diOH-PBDE, 6,6'-dihydroxy-2,2',4'4'-tetrabromodiphenyl ether (6,6'-diOH-BDE-47) in hand, the present study has provided the first data set to compare 6-hydroxy-2,2',4'4'- tetrabromodiphenyl ether (6-OH-BDE-47) and 6,6'-diOH-BDE-47 for their acute toxicity and accumulation, and thyroid hormone levels in treated zebrafish larvae. By real time-PCR technique, transcripts of hypothalamic-pituitary-thyroid axis associated genes were also investigated in developing larvae at 96 h post fertilization (96 hpf). Apparently, 6,6'-diOH-BDE-47 was less toxic than that of 6-OH-BDE-47: 1) the 96-h LC50 (96-h median lethal concentration) of 6-OH-BDE-47 and 6,6'-diOH-BDE-47 were 235 nM and 516 nM, respectively; 2) although severe developmental delays and morphological deformities were observed in zebrafish larvae in high exposure doses, at the exposure concentration of 1-50 nM, the accumulated 6-OH-BDE-47 and 6,6'-diOH-BDE-47 is ranged between 226-2279 nmol/g and 123-539 nmol/g in treated larvae; and 3) for 6-OH-BDE-47, its bioconcentration factor (BCF) were 1.83- to 4.30-fold more than that of 6,6'-diOH-BDE-47, suggesting that the lower internal exposure concentration of 6,6'-diOH-BDE-47 may lead to lower toxicity. The increased thyroid hormone levels were recorded for 1 nM of 6-OH-BDE-47 and 20 nM of 6,6'-diOH-BDE-47, and the exposures both significantly increased thyroid gland-specific transcription of thyroglobulin gene, indicating an adverse effect associated with the HPT axis. Therefore, 6,6'-diOH-BDE-47, with lower toxicity compared to that of 6-OH-BDE-47, still possesses hazards and environmental risk.

7.
Sci Total Environ ; : 143555, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33189387

RESUMO

BACKGROUND: Limited evidence is available on the associations of long-term exposure to various fine particulate matter (PM2.5) constituents with sub-clinical outcomes of cardiovascular disease (CVD) in China. OBJECTIVES: We aimed to explore the associations of PM2.5 and its constituents with blood pressure (BP), fasting glucose, and cardiac electrophysiological (ECG) properties based on a national survey of 5852 Chinese adults, who participated in the Sub-Clinical Outcome of Polluted Air study, from July 2017 to March 2019. METHODS: Annual residential exposure to PM2.5 and its constituents of each subject was predicted by a satellite-based mode. We assessed the associations between five main constituents [organic matter (OM), black carbon (BC), sulfate (SO42-), nitrate (NO3-), ammonium (NH4+)] of PM2.5 and systolic BP (SBP), diastolic BP (DBP), fasting glucose, and ECG measurements (PR, QRS, QT, and QTc interval) using multivariable linear regression models. RESULTS: Long-term PM2.5 exposure was significantly associated with increased levels of fasting glucose, DBP, and ECG measurements. An IQR increase in OM (8.2 µg/m3) showed considerably stronger associations with an elevated fasting glucose of 0.39 mmol/L (95%CI confidence interval: 0.28, 0.49) compared with other PM2.5 constituents. Meanwhile, an IQR increase in NO3-, NH4+ and OM had stronger associations with DBP and ECG parameters compared with BC and SO42-. CONCLUSIONS: This nationwide multi-center study in China indicated that some constituents (i.e., OM, NO3-, and NH4+) might be mainly responsible for the association of PM2.5 with sub-clinical outcomes of CVD including BP, fasting glucose, and ECG measurements.

8.
Chemosphere ; : 128713, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33162156

RESUMO

The sharp redox gradient at soil-water interfaces (SWI) plays a key role in controlling arsenic (As) translocation and transformation in paddy soils. When Eh drops, As is released to porewater from solid iron (Fe) and manganese (Mn) minerals and reduced to arsenite. However, the coupling or decoupling processes operating within the redox gradient at the SWI in flooded paddy soils remain poorly constrained due to the lack of direct evidence. In this paper, we reported the mm-scale mapping of Fe, As and other associated elements across the redox gradient in the SWI of five different paddy soils. The results showed a strong positive linear relationship between dissolved Fe, Mn, As, and phosphorus (P) in 4 out of the 5 paddy soils, indicating the general coupling of these elements. However, decoupling of Fe, Mn and As was observed in one of the paddy soils. In this soil, distinct releasing profiles of Mn, As and Fe were observed, and the releasing order followed the redox ladder. Further investigation of As species showed the ratio of arsenite to total As dropped from 100% to 75.5% and then kept stable along depth of the soil profile, which indicates a dynamic equilibrium between arsenite oxidization and arsenate reduction. This study provides direct evidence of multi-elements' interaction along redox gradient of SWI in paddy soils.

9.
Phytomedicine ; 80: 153356, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33039729

RESUMO

BACKGROUND: Using natural polysaccharides from Traditional Chinese Medicine as nanodrug delivery systems have considerable potential for tumor diagnostics and therapeutics. PURPOSE: On the basis of targeted therapy and combining the advantages of natural polysaccharides (angelica polysaccharide, APS) and natural Chinese medicine (curcumin, Cur) to design functionalized nanoparticles to improve the therapeutic through cell membrane encapsulation and immunotherapy. STUDY DESIGN AND METHODS: Cur-loaded, glycyrrhetic acid (GA)-APS-disulfide bond (DTA)-Cur nanomicelle (GACS-Cur), which were prepared by the dialysis method. GACS-Cur was encapsulated with the membranes from red blood cells (RBCm) termed GACS-Cur@RBCm, which were prepared by the principle of extrusion using a miniature extruder. The developed formulations were subjected to various in vitro and in vivo evaluation tests. RESULTS: The resulting APS nanocarriers supported a favorable drug-loading capacity, biocompatibility, and enhanced synergistic anti-hepatoma effects both in vitro and in vivo. After administration in mice, in vivo imaging results showed that the GACS-Cur and RBCm-coated groups had an obvious stronger tumor tissue targeting ability than the control treatment groups. Additionally, the immunomodulatory effect increased IL-12, TNF-α and IFN-γ expression and CD8+ T cell infiltration (1.9-fold) than that of the saline group. Notably, in comparison with hyaluronic acid (HA) nanocarriers, APS nanocarriers possess higher anti-hepatoma efficiency and targeting capabilities and, thus, should be further studied for a wide range of anti-cancer applications. CONCLUSION: Our data demonstrated that APS nanocarriers encapsulated with erythrocyte membrane mighty be a promising clinical method in the development of efficacy, safety and targeting of liver cancer therapy.

10.
Anat Rec (Hoboken) ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33015956

RESUMO

The cognitive dysfunction associated with type 2 diabetes mellitus (T2DM) has been widely studied, and many structures in the hippocampus, such as neurons and synapses, have been shown to play a crucial role in the cognitive decline. However, the mechanism of these changes remains unknown. To further explore this issue, we investigated the changes in the blood supply of the hippocampus in transgenic T2DM mice. In the current study, histochemistry, immunohistochemistry, and unbiased stereological methods were utilized to research the effects of T2DM on hippocampal capillaries of transgenic db/db mice. Twenty (Leprdb ) mut/mut mice and twenty (Leprdb ) wt/wt mice were used in this study. The learning and memory ability was appraised by Morris water maze test.

11.
Asia Pac Psychiatry ; : e12427, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33089622

RESUMO

INTRODUCTION: China has been severely affected by coronavirus disease 2019 (COVID-19) since December 2019. Military healthcare workers in China have experienced many pressures when combating COVID-19. This study aimed to investigate the current psychological status and associated risk factors among military healthcare workers. METHODS: We collected data from 194 military healthcare workers from three inpatient wards in two specialized COVID-19 hospitals using a web-based cross-sectional survey. The survey covered demographic information, the patient health questionnaire-9, the Generalized Anxiety Disorder-7, and the patient health questionnaire-15. Hierarchical regression analysis was used to explore potential risk factors for mental health problems. RESULTS: The overall prevalence rates of depressive, generalized anxiety, and somatic symptoms were 37.6%, 32.5%, and 50%, respectively. Rates of severe depression, generalized anxiety, and somatic symptoms were 5.2%, 3.6%, and 15.5%, respectively. In 22.7% of cases, comorbidities existed between depression, generalized anxiety, and somatization. A junior-grade professional title was associated with depression, older age was associated with generalized anxiety and somatization, and short sleep duration and poor sleep quality were associated with all three symptoms. DISCUSSION: The prevalence of depression, generalized anxiety, and somatic symptoms among military healthcare workers in specialized COVID-19 hospitals is high during the current COVID-19 outbreak. A junior-grade professional title, older age, short sleep duration, and poor sleep quality significantly affect military healthcare workers' mental health. Continuous surveillance and monitoring of the psychological consequences of the COVID-19 outbreak should be routine to promote mental health among military healthcare workers.

12.
Pharmacol Ther ; 216: 107698, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33039419

RESUMO

The contribution of natural products (NPs) to cardiovascular medicine has been extensively documented, and many have been used for centuries. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Over the past 40 years, approximately 50% of newly developed cardiovascular drugs were based on NPs, suggesting that NPs provide essential skeletal structures for the discovery of novel medicines. After a period of lower productivity since the 1990s, NPs have recently regained scientific and commercial attention, leveraging the wealth of knowledge provided by multi-omics, combinatorial biosynthesis, synthetic biology, integrative pharmacology, analytical and computational technologies. In addition, as a crucial part of complementary and alternative medicine, Traditional Chinese Medicine has increasingly drawn attention as an important source of NPs for cardiovascular drug discovery. Given their structural diversity and biological activity NPs are one of the most valuable sources of drugs and drug leads. In this review, we briefly described the characteristics and classification of NPs in CVDs. Then, we provide an up to date summary on the therapeutic potential and the underlying mechanisms of action of NPs in CVDs, and the current view and future prospect of developing safer and more effective cardiovascular drugs based on NPs.

14.
Acta Biochim Biophys Sin (Shanghai) ; 52(10): 1071-1080, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33085761

RESUMO

Circular RNAs (circRNAs) have good stability and long half-life in blood and other body fluid, and possess regulatory effects on various biological processes as miRNA/RNA-binding protein sponges, or by competing endogenous RNA, indicating their great potential as biomarkers or targets of cancer therapy. In this study, we mainly explored the role and mechanism of circular RNA SMARCA5 (circsSMARCA5) in non-small cell lung cancer (NSCLC). Quantitative RT-PCR was applied to measure the expression levels of genes, and then, the relationships among circsSMARCA5, microRNA-670-5p (miR-670-5p), and RBM24 were further analyzed. Animal and cell experiments were performed to explore the functions of circsSMARCA5 in NSCLC cells. The results showed that circsSMARCA5 was expressed at low level in NSCLC tissues and cells, while miR-670-5p had high level in NSCLC tissues. Dual luciferase reporter assay verified that miR-670-5p was the target of circsSMARCA5, and RBM24 has the binding site of miR-670-5p. Further analysis showed that circsSMARCA5 could negatively regulate miR-670-5p and had positive relationship with RBM24. Moreover, circsSMARCA5 obviously inhibited tumor growth in vivo, reduced cell proliferation and increased cell apoptosis in vitro, while miR-670-5p mimic or RBM24 knockdown could reverse these effects. Thus, circsSMARCA5 may serve as an NSCLC suppressor by regulating the miR-670-5p/RBM24 axis, and it may have the potential to be a biomarker or therapeutic target for NSCLC.

15.
Exp Neurol ; 335: 113504, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33058889

RESUMO

BACKGROUND: Survivors of sepsis must often endure significant cognitive and behavioral impairments after discharge, but research on the relevant mechanisms and interventions remains lacking. TGR5, a member of the class A GPCR family, plays an important role in many physiological processes, and recent studies have shown that agonists of TGR5 show neuroprotective effects in a variety of neurological disorders. To date, no studies have assessed the effects of TGR5 on neuroinflammatory, cognitive, or behavioral changes in sepsis models. METHODS: A total of 267 eight-week-old male Sprague-Dawley rats were used in this study. Sepsis was induced via cecal ligation and puncture (CLP). All animals received volume resuscitation. The rats were given TGR5 CRISPR oligonucleotide intracerebroventricularly 48 h before CLP surgery. INT-777 was administered intranasally 1 h after CLP, and the cAMP inhibitor, SQ22536, was administered intracerebroventricularly 1 h after CLP. Survival rate, bodyweight change, and clinical scores were assessed, and neurobehavioral tests, western blot, and immunofluorescence staining were performed. The cognitive function of rats was measured using the Morris water maze during 15-20 days after CLP. RESULTS: The expression of TGR5 in the rat hippocampus was upregulated, and peaked at 3 days after CLP. The survival rate of rats after CLP was less than 50%, and the growth rate, in terms of weight, was significantly decreased. While INT-777 treatment did not improve these changes, the treatment did reduce the clinical scores of rats at 24 h after CLP. On day 15 and later, the surviving mice completed a series of behavioral tests. CLP rats showed spatial and memory deficits and anxiety-like behaviors, but INT-777 treatment significantly improved these effects. Mechanistically, immunofluorescence analysis showed that INT-777 treatment reduced the number of microglia in the hippocampus, neutrophilic infiltration, and the expression of inflammatory factors after CLP in rats. Moreover, INT-777 treatment significantly increased the expression of TGR5, cAMP, p-PKA, and p-CREB, but downregulated the expression of IL-1ß, IL-6, and TNF-α. CRISPR-mediated TGR5 knockdown and SQ22536 treatment abolished the neuroprotective effects of TGR5 activation after CLP. CONCLUSION: This study demonstrates that INT-777 treatment reduced neuroinflammation and microglial cell activation, but improved cognitive impairment in the experimental sepsis rats. TGR5 has translational potential as a therapeutic target to improve neurological outcomes in sepsis survivors.

16.
Eur J Clin Invest ; : e13446, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33128454

RESUMO

BACKGROUND: Noninvasive methods have been used for the assessment of hepatic steatosis in patients with nonalcoholic fatty liver disease(NAFLD). The aim was to assess the efficacy and accuracy of both magnetic resonance imaging(MRI) and transient elastography(TE) for the evaluation of hepatic steatosis. MATERIALS AND METHODS: The PubMed, Cochrane Library, Embase, MEDLINE and Web of Science databases were searched to retrieve studies examining the accuracy of MRI-proton density fat fraction(PDFF) and TE-controlled attenuation parameter(CAP) for evaluating the grading of steatosis(S0-S3) diagnosed by liver biopsy in NAFLD. We compared the sensitivity, specificity, hierarchical summary receiver operating characteristic curves(HSROC) and clinical utility of these methods. RESULTS: Twenty-four articles with a total of 2979 patients with NAFLD were included. The steatosis distribution was 8.1%/35.1%/32.2%/24.6% for S0/S1/S2/S3. For the diagnostic accuracy of MRI-PDFF, the HSROCs were 0.97 for ≥ S1, 0.91 for ≥ S2, and 0.90 for ≥ S3. For the diagnostic accuracy of TE-based CAP, the HSROCs were 0.85 for ≥ S1, 0.83 for ≥ S2, and 0.79 for ≥ S3. Following a "positive" measurement (over the threshold value) for ≥S1, the corresponding posttest probabilities of PDFF and CAP for the presence of steatosis were 82% and 61%, respectively, when the pretest probability was 24%. If the values were below these thresholds ("negative" results), the posttest probabilities were 3% and 7%. CONCLUSION: MRI-PDFF and TE-CAP both provide highly accurate noninvasive approaches for quantifying and staging hepatic steatosis in NAFLD. Compared with TE-CAP, MRI-PDFF is significantly more accurate for evaluating dichotomized grades of steatosis.

17.
Bioorg Med Chem ; 28(23): 115785, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33099182

RESUMO

ADCs based on the natural product maytansine have been successfully employed clinically. In a previous report, ADCs based on hydrophilic non-cell permeable maytansinoids was presented. The authors in this report further explore the maytansine scaffold to develop tubulin inhibitors capable of cell permeation. The research resulted in amino-benzoyl-maytansinoid payloads that were further elaborated with linkers for conjugating to antibodies. This approach was applied to MUC16 tumor targeting antibodies for ovarian cancers. A positive control ADC was evaluated alongside the amino-benzoyl-maytansinoid ADC and the efficacy observed was equivalent while the isotype control ADCs had no effect.

18.
Sci Total Environ ; 746: 141860, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33027873

RESUMO

Tralopyril, an antifouling biocide, widely used in antifouling systems to prevent underwater equipment from biological contamination, which can pose a potential risk to aquatic organisms and human health. However, there is little information available on the toxicity of tralopyril to aquatic organisms. Herein, zebrafish (Danio rerio) were used to investigate the toxicity mechanisms of tralopyril and a series of developmental indicators, thyroid hormones, gene expression and metabolomics were measured. Results showed that tralopyril significantly decreased the heart-beat and body length of zebrafish embryos-larvae exposed to 4.20 µg/L or higher concentrations of tralopyril and also induced developmental defects including pericardial hemorrhage, spine deformation, pericardial edema, tail malformation and uninflated gas bladder. Tralopyril decreased the thyroid hormone concentrations in embryos and changed the transcriptions of the related genes (TRHR, TSHß, TSHR, Nkx2.1, Dio1, TRα, TRß, TTR and UGT1ab). Additionally, metabolomics analysis showed that tralopyril affected the metabolism of amino acids, energy and lipids, which was associated with regulation of thyroid system. Furthermore, this study demonstrated that alterations of endogenous metabolites induced the thyroid endocrine disruption in zebrafish following the tralopyril treatment. Therefore, the results showed that tralopyril can induce adverse developmental effects on zebrafish embryos by disrupting the thyroid system and metabolism.


Assuntos
Glândula Tireoide , Peixe-Zebra , Animais , Pirróis , Hormônios Tireóideos
19.
Curr Med Chem ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33019919

RESUMO

In recent years, due to the shortcomings of conventional chemotherapy, such as poor bioavailability, low treatment index and unclear side effects, the focus of cancer research has shifted to new nanocarriers of chemotherapeutic drugs. By using biodegradable materials, nanocarriers generally have the advantages of good biocompatibility, low side effects, targeting, controlled release profile, and improved efficacy. And more to the point, nanocarrier based anti-cancer drug delivery systems clearly show the potential to overcome the problems associated with conventional chemotherapy. In order to promote the deepening of research and development in this field, we herein summarized and analyzed various nanocarrier based drug delivery systems for cancer therapy, including the concepts, types, characteristics and preparation methods. The active and passive targeting mechanisms of cancer therapy were also included, along with a brief introduction of the research progress of nanocarriers used for anti-cancer drug delivery in the past decade.

20.
J Mol Model ; 26(11): 300, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052478

RESUMO

The thermal decomposition of pure nitromethane (NM) and NM/nano-aluminum (Al) composites was simulated by reactive molecular dynamics with ReaxFF-lg corrected force field parameters. The initial decomposition pathway of NM molecules in pure NM is C-N bond rupture. However, NM is decomposed early by the initial pathway of N-O bond rupture when it mixes with nano-Al because of the strong attraction of Al to O. The decomposition process of NM/nano-Al can be divided into three stages: adsorption, slow decomposition, and rapid decomposition. The addition of nano-Al particles decreases the energy barrier in decomposition, increases the released energy, and reduces the decomposition temperature of NM. Adding 3% Al to the explosive can make the detonation pressure 3.083% higher than that of pure system. Compared with pure NM, the energy barrier of 16% Al composite is 25.63 kcal/mol lower and the energy released is 22.99 kcal/mol more. There is an optimal amount of Al contents being added to the NM composite by which the largest total numbers of gaseous products (N2, H2O, and CO2) are released. The effect of Al additives on CO2 production is the most obvious. The maximum detonation pressure can be achieved by adding an appropriate amount of nano-Al, which is similar to the experimental results. Graphical abstract.

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