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1.
J Affect Disord ; 296: 26-34, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34587546

RESUMO

BACKGROUND: Previous studies have shown that psilocybin has antidepressant effects. In the current study, we aim to explore the dose effects of psilocybin on primary (major depression patients) and secondary depression (depressed cancer patients). METHODS: Published studies concerning psilocybin for depression were retrieved. In accordance with PRISMA guidelines, 6 databases (PubMed, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov 2.3 and WanFang database) were searched for research studies published or still in progress from inception to 30 November, 2020, with language restricted to English and Chinese. Hedges' g of Beck Depression Inventory (BDI) score changes was calculated as the primary outcome. RESULTS: 7 articles were finally included, with a total of 136 participants. In terms of efficacy, Hedges' g was 1.289 (95%CI=[1.020, 1.558], heterogeneity I2=50.995%, p<0.001). As psilocybin dose increases within a certain range, the antidepressive effect declines and then increases, with 30-35 mg/70 kg achieving the optimal therapeutic effect. Subgroup analysis suggested that the antidepressive effect of psilocybin was extremely significant at a relatively high dose (30-35mg/70kg: Hedges' g=3.059, 95%CI=[2.269, 3.849], p<0.001), long-term (>1month: Hedges' g=1.123, 95%CI=[0.861, 1.385], p<0.001) and when used in primary depression patients (Hedges' g=2.190, 95%CI=[1.423, 2.957], p<0.001). LIMITATIONS: Only a small number of studies can be identified of variable quality, thus our conclusions remain preliminary. CONCLUSIONS: Our preliminary results have shown that psilocybin exerts a rapid effect in reducing depressive symptom on primary and secondary depression. The optimal dose of psilocybin may be 30-35mg/70kg or higher; future clinical trials are warranted for further evaluation on its effect.

2.
Environ Res ; 203: 111802, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34343555

RESUMO

Anaerobic ammonium oxidation coupled to Fe(III) reduction, known as Feammox, is a newly discovered nitrogen-cycling process, which serves an important role in the pathways of nitrogen loss in the environment. However, the specific types of microorganisms involved in Feammox currently remain unclear. In this study, we selected two groups of soil samples (paddy and mine), from considerably different habitats in South China, to acclimate Feammox colonies. The Paddy Group had a shorter lag period than the Mine Group, while the ammonium transformation rate was nearly equal in both groups in the mature period. The emergence of the Feammox activity was found to be associated with the increased abundance of iron-reducing bacteria, especially Clostridium_sensu_stricto_12, Desulfitobacterium, Thermoanaerobaculum, Anaeromyxobacter and Geobacter. Ammonium oxidizing archaea and methanogens were dominant among the known archaea. These findings extend our knowledge of the microbial community composition of the potential Feammox microbes from soils under different environmental conditions, which broadens our understanding of this important Fe/N transformation process.

3.
Bioresour Technol ; 343: 126108, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34637911

RESUMO

Types of microbial aggregates have essential effects on bacterial communities' characteristics, thus affecting the pollutants removal. An up-flow biofilm reactor was used to study the different performances of S2-/NO2- removal and functional genes in suspended sludge and biofilms. The metabolic pathways of sulfurous and nitrogenous pollutants in the desulfurization-denitrification process were proposed. The results showed that S0 formation dominated the reactor with a high S2- concentration. Autotrophic Sulfurovum responsible for S2-/S0 oxidation was the only dominant bacteria in suspended sludge. Heterotrophic Desulfocapsa responsible for SO42- reduction coexisted with Sulfurovum and dominated in biofilms. S2- oxidation to S0 was catalyzed via fccA/B and sqr genes in suspended sludge. S32-/S0 oxidation to SO42- was catalyzed via dsrA/B gene in biofilms. SO42- and NO2- were removed via the dissimilatory sulfate reduction and denitrification pathway, respectively. This work provides a fundamental and practical basis for optimizing suspended sludge/biofilm systems for S2-/NO2- removal.


Assuntos
Desnitrificação , Esgotos , Bactérias/genética , Biofilmes , Reatores Biológicos , Nitrogênio , Enxofre
4.
Chemosphere ; 287(Pt 2): 132137, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34496335

RESUMO

Uranium extraction and recovery play a critical role in guaranteeing the sustainable nuclear energy supply and protecting the environmental safety. The ideal uranium sorbents possess high adsorption capacity, excellent selectivity and reusability, as well as outstanding antimicrobial property, which are greatly desired for the real application of uranium extraction from seawater. To address this challenge, a novel magnetic core-shell adsorbent was designed and fabricated by a facile method. The obtained amidoximed Fe3O4@TiO2 particles (Fe3O4@TiO2-AO) achieved equilibrium in 2 h and the maximum adsorption capacity calculated from Langmuir model is 217.0 mg/g. The adsorption kinetics followed the pseudo-second-order model. Meanwhile, the Fe3O4@TiO2-AO exhibited great selectivity when competitive metal ions and anions coexisted. In addition, the magnetic Fe3O4@TiO2-AO could be conveniently separated and collected by an external magnetic field, the regeneration efficiency maintained at 78.5% even after ten adsorption-desorption cycles. In natural seawater, the uranium uptake reached 87.5 µg/g in 33 days. Furthermore, the TiO2 contained adsorbent showed effective photo induced bactericidal properties against both E. coli and S. aureus. The Fe3O4@TiO2-AO with great U(VI) adsorption performance is highly promising in uranium extraction and reclamation.


Assuntos
Urânio , Adsorção , Antibacterianos , Escherichia coli , Oximas , Água do Mar , Staphylococcus aureus , Titânio
5.
Ultrasound Med Biol ; 48(1): 3-9, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34706844

RESUMO

Precise positioning of the left or right main bronchus is a prerequisite for effective lung isolation in thoracic surgeries. This study aimed to clarify the ability of lung ultrasound to detect tracheal and mainstem intubation. Studies that investigated the ability of lung ultrasound to detect tracheal and mainstem intubation were searched from PubMed and ScienceDirect databases from their inception to March 2021. The pooled accuracy of this method and its sensitivity and specificity were computed with a fixed-effects model using Stata 14.0. Nine eligible articles that involved a total of 617 participants were included in this systematic review and meta-analysis. Overall, the accuracy of lung ultrasound in detecting tracheal and mainstem intubation was 86.7%, with a sensitivity of 93.0% and a specificity of 75.0%. Subgroup analysis revealed that the accuracy remained high regardless of patient age, ultrasonic method, sample size, study design or ultrasonic skills training. Sensitivity analysis indicated that the results were stable. Deeks' test showed no publication bias. These findings imply that lung ultrasound is an effective method for detecting tracheal and mainstem intubation.

6.
Anal Chim Acta ; 1189: 339259, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34815053

RESUMO

Owing to the ubiquitous occurrence and chemotoxicity of BTEX (benzene, toluene, ethylbenzene and xylene), the development of stable and accurate analysis methods that can assess environment risks and can generate monitoring data rapidly is urgent. In this work, a new strategy was proposed for efficient detection of BTEX. By creatively utilizing thermal deposition method, a robust SPME fiber was fabricated, where the γCD-MOF acted as the adsorbent, while PDMS functionalized as the adhesive and protective coating. Benefiting from the protection of PDMS, the γCD-MOF fiber presented significantly better extraction performance and exhibited long-term structural stabilities in aqueous or methanol samples up to a week. The stable and improved properties of γCD-MOF demonstrated that the PDMS protected the MOF components from the adverse effects of solvent. The detection limits of PDMS modified γCD-MOF fiber for BTEX was as low as 0.13-0.29 ng L-1 that accompanied with wide linear range of 1-1000 ng L-1, which was significantly superior to commercial PDMS fiber and other MOF-based fibers. Besides, the feasibility of the proposed method was verified by the quantitative determination of BTEX in real water samples. This work presents an effective strategy for creating ultrasensitive and stable SPME fibers based on γCD-MOF for applications in aqueous samples or other poor solvent.


Assuntos
Microextração em Fase Sólida , Poluentes Químicos da Água , Benzeno/análise , Tolueno/análise , Poluentes Químicos da Água/análise , Xilenos/análise
7.
Sci Total Environ ; 805: 150303, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34537702

RESUMO

Accumulating research evidence has revealed that harmful algal blooms (HABs) can substantially affect the community structures of phytoplankton and heterotrophic bacteria in marine ecosystems. However, little is known about their species-specific interactions between phytoplankton and heterotrophic bacteria during the HABs period and about their interaction shifts in response to blooms. From this perspective, we investigated the co-occurrence of chromophytic phytoplankton and Vibrio during Phaeocystis globosa blooms in the Beibu Gulf. The results showed that Vibrio communities were distinct during the blooms, and P. globosa blooms resulted in a decline in phytoplankton alpha diversity, revealing that the blooms could affect their community compositions. The regression lines between the Shannon indices and Bray-Curtis distances of phytoplankton and Vibrio showed positive correlations with each other (p < 0.001), suggesting that they may have intrageneric symbiotic interactions overall. In addition, network analysis further demonstrated that relationships between phytoplankton and Vibrio were dominated by positive correlations, and more interaction modules were observed during the blooms, revealing that the blooms intensified synergistic association and mutual symbiotic interactions between them. Environmental factors (SiO32-, NH4+, NO3- and TN,) and P. globosa density more deeply affected network interactions between phytoplankton and Vibrio during the periods of P. globosa blooms than those before the blooms and after the blooms. This study provided new insight to elucidate community structure and interaction relationships between phytoplankton and Vibrio in response to P. globosa blooms and their ecological effects in marine ecosystems.


Assuntos
Haptófitas , Vibrio , Ecossistema , Proliferação Nociva de Algas , Fitoplâncton
8.
J Hazard Mater ; 423(Pt A): 127034, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34481393

RESUMO

A glassy carbon electrode (GCE) modified by a hybrid, macroporous carbon (MPC) functionalized with triazine bridged covalent organic polycalix[4]arenes (CalCOP) (CalCOP-MPC), has been fabricated and utilized for simultaneous detection of nitrophenols (NP). The obtained CalCOP-MPC were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS), which confirmed that MPC had functionalized with CalCOP successfully. Benefiting from the synergistic supramolecular effect of macrocyclic receptor of CalCOP and the excellent electrical properties of MPC, the anodic peaks of o-nitrophenol (o-NP), m-nitrophenol (m-NP), and p-nitrophenol (p-NP) in their mixture can be well separated by the prepared electrode. Differential pulse voltammetry (DPV) measurements at CalCOP-MPC/GCE revealed that the linear ranges of NP isomers were all 1-400 µM, and the detection limit limits were 0.383 µM, 0.122 µM, and 0.212 µM for o-NP, m-NP, and p-NP, respectively. Moreover, the prepared modified electrodes showed a relatively good selectivity and stability, implying the prospect for detecting NP in real environmental samples.

9.
Eur J Med Chem ; 227: 113871, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34638033

RESUMO

The ubiquitination of the hypoxia-inducible factor-1α (HIF-1α) is mediated by interacting with the von Hippel-Lindau protein (VHL), and is associated with cancer, chronic anemia, and ischemia. VHL, an E3 ligase, has been reported to degrade HIF-1 for decades, however, there are few successful inhibitors currently. Poor understanding of the binding pocket and a lack of in-depth exploration of the interactions between two proteins are the main reasons. Hence, we developed an effective strategy to identify and design new inhibitors for protein-protein interaction targets. The hydroxyproline (Hyp564) of HIF-1α contributed the key interaction between HIF-1α and VHL. In this study, detailed information of the binding pocket were explored by alanine scanning, site-directed mutagenesis and molecular dynamics simulations. Interestingly, we found the interaction(s) between Y565 and H110 played a key role in the binding of VHL/HIF-1α. Based on the interactions, 8 derivates of VH032, 16a-h, were synthesized by introducing various groups bounded to H110. Further assay on protein and cellular level exhibited that 16a-h accessed higher binding affinity to VHL and markable or modest improvement in stabilization of HIF-1α or HIF-1α-OH in HeLa cells. Our work provides a new orientation for the modification or design of VHL/HIF-1α protein-protein interaction inhibitors.

10.
Neuropharmacology ; 203: 108871, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742928

RESUMO

Ghrelin is a circulating peptide hormone that promotes feeding and regulates metabolism in humans and rodents. The action of ghrelin is mediated by the growth hormone secretagogue receptor type 1a (GHSR-1a) that is widely distributed in the brain, including the hippocampus. Studies have demonstrated the critical role of hippocampal ghrelin/GHS-R1a signaling in synaptic physiology and memory. However, those findings are controversial, and the mechanism underlying ghrelin modulation of learning and memory is uncertain. Here, we report that micro-infusion of ghrelin in the CA1 region of the dorsal hippocampus during training specifically impairs memory acquisition. The activation of GHS-R1a and the subsequent PI3K/Akt/GSK3ß signaling cascades are involved in this process. Moreover, we report that bath application of ghrelin suppresses the intrinsic excitability of dCA1 pyramidal neurons through activating GHS-R1a, and PI3K inhibitor LY294002 blocks ghrelin's effect. However, LY294002 fails to rescue ghrelin-induced LTP impairment. Our findings support an adverse effect of ghrelin-dependent activation of GHS-R1a on memory acquisition, and suggest that PI3K/Akt/GSK3ß signaling-dependent repression of neuronal intrinsic excitability is an important novel mechanism underlying memory inhibition of ghrelin in the hippocampus.

11.
Int J Biol Macromol ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34852260

RESUMO

Resveratrol (RSV) is a lipophilic polyphenol susceptible to photo- and thermal degradation, and strategies are to be studied to enable its distribution in food matrices, prevent its degradation during storage, and increase its bioaccessibility during digestion. In this study, the porous matrix of natural starch, in the form of milled freeze-dried potato microparticles (FDPMs), was studied as an absorbent to load RSV. The binary solvent of ethanol and polyethylene glycol 400 (40:60 v/v) was used to dissolve 30% w/v RSV for diffusion into FDPMs. After ethanol was evaporated, the loading capacity was 112 mg RSV/g FDPMs and was maintained at 104 mg RSV/g FDPMs (92.9% retention) after 110-day ambient storage. The RSV stability under UV irradiation at 253 nm was improved by 32% due to shielding effect of FDPMs, and the ferric reducing power was 25% higher than the pristine RSV. The release of RSV in FDPMs was significantly higher than pristine RSV during simulated gastric and intestinal digestions (82.3% vs 51.4% bioaccessibility). The increased reducing power and bioaccessibility were supported by the amorphous state of RSV in FDPMs. The present study illustrates the potential of porous vegetable microparticles as natural matrices to load lipophilic bioactive compounds in functional foods.

12.
Front Oncol ; 11: 714948, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858808

RESUMO

Purpose: The aim of this study was to evaluate the clinical value of simultaneous positron emission tomography/computed tomography (PET/CT) and abdominal positron emission tomography/magnet resonance imaging (PET/MRI) in the detection of liver metastases and extrahepatic disease (EHD) in patients with potentially resectable colorectal liver metastases (CLM). Methods: Fifty-six patients with CLM underwent conventional imaging (chest and abdomen CT, liver contrast-enhanced CT or MRI) and PET imaging [fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT and subsequent liver PET/MRI] for staging or restaging. Diagnostic ability of PET imaging was compared with conventional imaging. Abnormal findings were correlated with follow-up imaging and/or histology. The influence of the PET imaging findings was categorized for each patient in relation to operability and other significant findings. The clinical management included three modalities (surgery for resectable CLM, unresectable CLM with conversion treatment, and systemic therapy). The clinical impact of the imaging modality was analyzed. The operative histopathological analysis and/or imaging follow-up were performed as the standard of reference. Results: This study enrolled a total of 56 patients (median age 60 years, 62.5% were male, 36 with colon cancer and 20 with rectal cancer). For EHD detection, PET/CT detected more EHD than conventional imaging (60.7% vs. 46.4%). PET/CT had different findings in 19 (33.9%) patients, including downstaging in 4 (7.1%) patients and upstaging in 15 (26.8%) patients. For liver lesion detection, PET/MRI showed comparable detection ability with CE-MRI and CE-CT (99.5%, 99.4%, and 86.5%, respectively) based on lesion analysis, much higher than PET/CT (47.5%). PET imaging had a major impact in 10/56 (17.9%) patients (4 from unresectable to resectable, 6 from resectable to unresectable) and a minor impact in 4/56 (7.1%) patients for changing the surgery extent. The therapeutic strategies had been altered in a total of 14/56 patients (25%) after PET/CT and PET/MRI scans. Conclusion: The results of this study indicate that simultaneous 18F-FDG PET/CT and abdominal PET/MRI scans can provide accurate information regarding CLM status and EHD, and can affect the management of 25% of the patients by changing the therapeutic strategies determined by conventional imaging. This new modality may serve as a new one-stop method in patients with potentially resectable CLM.

13.
Neurosurg Rev ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34859335

RESUMO

Whether surgical revascularization can prevent recurrent hemorrhage in hemorrhagic moyamoya disease (HMD) patients remains a matter of debate. This study mainly aims at the comparison of treatment effect between surgical revascularization and conservative treatment of adult HMD patients. We retrospectively enrolled 322 adult HMD patients, including 133 in revascularization group and 189 in conservative group. The revascularization group included patients who underwent combined (n = 97) or indirect revascularization alone (n = 36). Ninety-two and forty-one patients underwent unilateral and bilateral revascularization respectively. The modified Rankin scale (mRS) was used to assess the functional status. The comparison was made based on initial treatment paradigm among two categories: (1) revascularization vs. conservative, (2) unilateral vs. bilateral revascularization. The rebleeding rate was significantly lower in revascularization group than that in conservative group (14.3% vs. 27.0%, P = 0.007). As for the functional outcomes, the average mRS was significantly better in revascularization group (1.7 ± 1.5) than that in conservative group (2.8 ± 1.9) (P < 0.001). The death rate in revascularization group was 8.3% (11/133), comparing to 20.1% (38/189) in conservative group (P = 0.004). While comparing between unilateral and bilateral revascularization within the revascularization group, the result demonstrated lower annual rebleeding rate in bilateral group (0.5%/side-year) than that in unilateral group (3.3%/side-year) (P = 0.001). This study proved the better treatment efficacy of surgical revascularization than that of conservative treatment in HMD patients, regarding both in rebleeding rate and mortality rate. Furthermore, bilateral revascularization seems more effective in preventing rebleeding than unilateral revascularization.

14.
Front Neurol ; 12: 747958, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777218

RESUMO

Objective: The study was conducted to summarize the treatment outcomes of newly diagnosed epilepsy (NDE) and analyse the risk factors for refractory epilepsy (RE) in Northeast China. Methods: A total of 466 adult patients with NDE were consecutively enrolled in this programme. Clinical data were collected at baseline and each follow-up. Several scales concerning recognition and mood were also completed at the first visit. Results: Seizure-free status was achieved by 52% (n = 244) of the patients; however, 15% (n = 68) manifested RE. A total of 286 (61%) patients continued with the first ASM as monotherapy, among which 186 (40%) patients became seizure-free. Fifteen (22%) patients with RE became seizure-free following ASM adjustment and 34 patients (14%) had breakthrough seizures after being classified as seizure-free. One patient developed RE after attaining seizure-free status. Breakthrough seizures during the first expected interictal interval [Odds ratio (OR) = 5.81, 95% CI: 2.70-12.50], high seizure frequency at baseline (OR = 1.24, 95% CI: 1.04-1.49), younger age of onset (OR = 1.42, 95% CI: 1.12-1.79), and male sex (OR = 2.64, 95% CI: 1.26-5.53) were risk factors for RE. Significance: Treatment outcomes of the majority of NDE cases are good. New risk factors could help physicians more promptly and accurately identify patients who are likely to develop RE. Seizure-free state is not long enough to commence the withdrawal of ASMs. RE is not permanent and seizure-free may be achieved subsequently by appropriate drug adjustment.

15.
Oral Dis ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34739175

RESUMO

The folate-mediated one-carbon metabolism pathway is thought to play an important role in the etiology of non-syndromic oral clefts (NSOFC), although none of the genes in this pathway has shown significant signals in genome-wide association studies (GWAS). Recent evidence indicated that enhanced understanding could be gained by aggregating multiple SNPs effect simultaneously into polygenic risk score (PRS) to assess its association with disease risks. This study is aimed to assess the association between the genetic effect of folate-mediated one-carbon metabolism pathway and NSOFC risks using PRS based on a case-parent trio design. A total of 297 SNPs mapped from 18 genes in the folate-mediated one-carbon metabolism pathway were aggregated from a GWAS of 2458 case-parent trios recruited from an international consortium. We found a PRS based on the folate-mediated one-carbon metabolism pathway was significant among all NSOFC trios (OR = 1.95, 95% CI: 1.66-2.28, p = 2.39 × 10-16 ), as well as two major subtypes, non-syndromic cleft lip with or without cleft palate (NSCL/P) trios (OR = 1.71, 95% CI: 1.50-1.96, p = 7.66 × 10-15 ) and non-syndromic cleft palate only (NSCPO) trios (OR = 1.51, 95% CI: 1.36-1.68, p = 2.1 × 10-14 ). Similar results were also observed in further subgroup analyses stratified into Asian and European trios. The averaged PRS of the folate-mediated one-carbon metabolism pathway varied between the NSOFC case group and its comparison group (p < 0.05) with higher average PRS in the cases. Moreover, the top 5% pathway PRS group had 2.25 (95% CI: 1.85-2.73) times increased NSOFC risk, also 3.09 (95% CI: 2.50-3.81) and 2.06 (95% CI: 1.39-3.02) times increased risk of NSCL/P and NSCPO compared to the remainder of the distribution. The results of our study confirmed the folate-mediated one-carbon metabolism pathway was important in controlling risk to NSOFC and this study enhanced evidence towards understanding the genetic risks of NSOFC.

16.
Int J Mol Sci ; 22(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34769364

RESUMO

Alzheimer's disease (AD) is an intractable neurodegenerative disease that leads to dementia, primarily in elderly people. The neurotoxicity of amyloid-beta (Aß) and tau protein has been demonstrated over the last two decades. In line with these findings, several etiological hypotheses of AD have been proposed, including the amyloid cascade hypothesis, the oxidative stress hypothesis, the inflammatory hypothesis, the cholinergic hypothesis, et al. In the meantime, great efforts had been made in developing effective drugs for AD. However, the clinical efficacy of the drugs that were approved by the US Food and Drug Association (FDA) to date were determined only mild/moderate. We recently adopted a vanadium compound bis(ethylmaltolato)-oxidovanadium (IV) (BEOV), which was originally used for curing diabetes mellitus (DM), to treat AD in a mouse model. It was shown that BEOV effectively reduced the Aß level, ameliorated the inflammation in brains of the AD mice, and improved the spatial learning and memory activities of the AD mice. These finding encouraged us to further examine the mechanisms underlying the therapeutic effects of BEOV in AD. In this review, we summarized the achievement of vanadium compounds in medical studies and investigated the prospect of BEOV in AD and DM treatment.

18.
Ultrasound Med Biol ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34789402

RESUMO

The objective of this study was to evaluate the correlation between contrast-enhanced ultrasound (CEUS) parameters and histopathological features in patients with diabetic nephropathy (DN). Sixty-two patients with DN (44 men, mean age: 52.61 ± 10.63 y) were enrolled. They underwent renal biopsy for DN at the Department of Ultrasound, PLA Hospital, between May 2017 and February 2020. Renal tissue was obtained by ultrasound-guided percutaneous needle biopsy. CEUS was performed, and time-intensity curves (TICs) and renal perfusion parameters were analyzed. Differences in CEUS parameters were analyzed according to the glomerular classification and interstitial fibrosis-tubular atrophy (IFTA) score. Continuous variables were evaluated using the analysis of variance or Mann-Whitney U-test. Discontinuous variables were compared with the χ2-test. Spearman correlation analyses evaluated associations among quantitative ultrasound perfusion parameters and histopathological characteristics. Peak enhancement (PE), wash-in rate (WiR), wash-in perfusion index (WiPI) and wash-out rate (WoR) of the cortex, and their cortex/medulla ratios, decreased with increasing glomerular classification grade (p < 0.05). The fall time (FT) of the cortex, and their cortex/medulla ratios, increased with increasing glomerular classification grade (p < 0.05). There were no significant differences in the CEUS parameters for different IFTA scores. The perfusion volume-relevant parameters (such as PE, WiR and WiPI) had a negative correlation (p < 0.05), while the perfusion time-relevant parameters (such as RT and FT) had a positive correlation (p < 0.05), with the severity of glomerular lesions, glomerulosclerosis rate and number of Kimmelstiel-Wilson lesions. The CEUS parameters of the cortex could reflect pathological characteristics, especially changes in glomerular lesions.

19.
Cancer Res ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764205

RESUMO

Metabolic reprogramming by oncogenic signaling is a hallmark of cancer. Hyperactivation of Wnt/ß-catenin signaling has been reported in hepatocellular carcinoma (HCC). However, the mechanisms inducing hyperactivation of Wnt/ß-catenin signaling and strategies for targeting this pathway are incompletely understood. In this study, we find nucleoside diphosphate kinase 7 (NME7) to be a positive regulator of Wnt/ß-catenin signaling. Upregulation of NME7 positively correlated with the clinical features of HCC. Knockdown of NME7 inhibited HCC growth in vitro and in vivo, while overexpression of NME7 cooperated with c-Myc to drive tumorigenesis in a mouse model and promote the growth of tumor-derived organoids. Mechanistically, NME7 bound and phosphorylated serine 9 of GSK3ß to promote ß-catenin activation. Furthermore, MTHFD2, the key enzyme in one-carbon metabolism, was a target gene of ß-catenin and mediated the effects of NME7. Tumor-derived organoids with NME7 overexpression exhibited increased sensitivity to MTHFD2 inhibition. Additionally, expression levels of NME7, ß-catenin and MTHFD2 correlated with each other and with poor prognosis in HCC patients. Collectively, this study emphasizes the crucial roles of NME7 protein kinase activity in promoting Wnt/ß-catenin signaling and one-carbon metabolism, suggesting NME7 and MTHFD2 as potential therapeutic targets for HCC.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34745284

RESUMO

The purpose of this study is to design a flower-shaped lactose loaded curcumin solid lipid nanoparticles dry powder inhaler and characterize it to improve the solubility and dissolution rate of curcumin in lung. Curcumin solid lipid nanoparticles (Cur-SLNs) were prepared by solvent evaporation method, and then they were micronized by freeze-drying technology. Finally, Cur-SLN micropowder obtained by freeze-drying was mixed with flower-shaped lactose (FL) at a ratio of 2 : 1 and then passed through a 200-mesh sieve to obtain Cur-SLN-FL powder. Tween-80 was selected as the surfactant to inhibit the aggregation of drug solid lipid nanoparticles. Under the optimum conditions, the solid lipid nanoparticles (SLN) were relatively spherical, with an average particle size of 14.7 nm, narrow distribution, Zeta potential of -22.5 mV, encapsulation efficiency of 90.21%, and drug loading of 8.56%. According to the particle size, PI, Zeta potential, drug loading (LC%), encapsulation efficiency (EE%), morphology, and in vitro release characteristics, the prescription of solid lipid nanoparticles was screened. Dry powder inhaler (DPI) was characterized by differential scanning calorimetry, scanning electron microscopy, particle size, density, and in vitro release performance. Its cytotoxicity to mouse fibroblasts (L929) and human normal lung epithelial cells (BEAS-2B) in vitro was investigated, and its safety for pulmonary inhalation was preliminarily determined. FTIR analysis shows that the micronized Cur-SLN-FL has the same chemical structure as FL. FTIR and DSC analysis confirmed that the characteristic absorption peak of curcumin was not found in Cur-SLN-FL, showing similar structure to SLN and FL. In addition, curcumin was coated in solid lipid nanoparticles to make powder mist, which increased its drug loading, kept its aerodynamic particle size (4.03 ± 0.40) µm, and significantly improved its drug release performance in artificial lung fluid. In vitro cytotoxicity test results confirmed that Cur-SLN-FL was less toxic to BEAS-2B cells than L929 cells. Therefore, curcumin was prepared into solid lipid nanoparticles by emulsion evaporation-low temperature solidification method and then micronized and mixed with FL to prepare curcumin solid lipid nanoparticle powder mist loaded with flower-shaped lactose. The process is simple and feasible, and it has better safety performance for lung cells, which is expected to become a safe and effective delivery system for pulmonary inhalation drugs.

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