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1.
mBio ; : e0142622, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913157

RESUMO

Aspergillus fumigatus is a devastating opportunistic fungal pathogen causing hundreds of thousands of deaths every year. Phosphoglucose isomerase (PGI) is a glycolytic enzyme that converts glucose-6-phosphate to fructose-6-phosphate, a key precursor of fungal cell wall biosynthesis. Here, we demonstrate that the growth of A. fumigatus is repressed by the deletion of pgi, which can be rescued by glucose and fructose supplementation in a 1:10 ratio. Even under these optimized growth conditions, the Δpgi mutant exhibits severe cell wall defects, retarded development, and attenuated virulence in Caenorhabditis elegans and Galleria mellonella infection models. To facilitate exploitation of A. fumigatus PGI as an antifungal target, we determined its crystal structure, revealing potential avenues for developing inhibitors, which could potentially be used as adjunctive therapy in combination with other systemic antifungals. IMPORTANCE Aspergillus fumigatus is an opportunistic fungal pathogen causing deadly infections in immunocompromised patients. Enzymes essential for fungal survival and cell wall biosynthesis are considered potential drug targets against A. fumigatus. PGI catalyzes the second step of the glycolysis pathway, linking glycolysis and the pentose phosphate pathway. As such, PGI has been widely considered as a target for metabolic regulation and therefore a therapeutic target against hypoxia-related diseases. Our study here reveals that PGI is important for A. fumigatus survival and exhibit pleiotropic functions, including development, cell wall glucan biosynthesis, and virulence. We also solved the crystal structure of PGI, thus providing the genetic and structural groundwork for the exploitation of PGI as a potential antifungal target.

2.
J Minim Access Surg ; 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35915531

RESUMO

Objectives: The meta-analysis was conducted to systematically assess the efficacy and safety of generic stent-graft/bare-stent combination compared with Fluency stent alone in transjugular intrahepatic portosystemic shunt procedure for refractory variceal bleeding. Methods: PubMed, EMBASE, Scopus, Web of Science and the Cochrane Database were searched for relevant studies from January 1990 to September 2020; outcome measures studied were primary patency, hepatic encephalopathy, survival, re-bleeding and portal venous pressure. Results: Four studies (1 randomised controlled trial and 3 retrospective studies) with 449 subjects (157 patients in the combined stent group and 292 patients in the covered stent group) were included. No significant difference was observed in the incidence of mortality (hazard ratio [HR] = 1.069, 95% confidence interval [CI] [0.524, 2.178]), hepatic encephalopathy (odds ratio [OR] = 0.860, 95% CI [0.341, 2.169], P = 0.750) and re-bleeding (OR = 1.049, 95% CI [0.226, 4.881], P = 0.951). Compared with Fluency stent alone, combination therapy was associated with moderate decrease in outcomes on the post-operative portal venous pressure (standard mean difference [SMD] -0.210, 95% CI [-0.418, -0.001], P = 0.049) and was not associated with significant decrease in outcomes on the pre-operative portal venous pressure (SMD - 0.129, 95% CI [-0.336, 0.078], P = 0.223). The primary patency was significantly lower in the Fluency/bare-stent combination group (HR = 0.473, 95% CI [0.288, 0.776]). Conclusions: Generic stent-graft/bare-stent combination therapy was associated with significantly lower primary patency compared to Fluency stent alone.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35929499

RESUMO

Efficient and large-scale expansion of mesenchymal stem/stromal cells (MSCs) has always been a formidable challenge to researchers in cell-based therapies and regenerative medicine. To reconcile major drawbacks of 2D planar culturing system, we innovatively developed an automated closed industrial scale cell production (ACISCP) platform based on GMP-grade microcarrier for culture of umbilical cord-mesenchymal stem/stromal cells (UCMSCs), in accordance with the criteria of stem cell bank. ACISCP system is a fully closed system, which employs different models of vivaSPIN bioreactors (CytoNiche Biotech, China) for scale-up cell culture and vivaPREP (CytoNiche Biotech, China) for automated cell harvesting and cell dosage preparation. To realize industrial scale expansion of UCMSCs, a three-stage expansion was conducted with 1 L, 5 and 15 L vivaSPIN bioreactors. Using 3D TableTrix® and ACISCP system, we inoculated 1.5 × 107 of UCMSCs into 1 L vivaSPIN bioreactor and finally scaled to two 15 L bioreactor. A final yield of 2.09 × 1010 cells with an overall expansion factor of 1975 within 13 days. The cells were harvested, concentrated, washed and prepared automatically with vivaPREP. The entire process was realized with ACISCP platform and was totally enclosed. Critical quality attributes (CQA) assessments and release tests of MSCs, including sterility, safety, purity, viability, identity, stability and potency were performed accordingly. The quality of cells harvested from 3D culture on the ACISCP and conventional 2D planar culture counterpart has no significant difference. This study provides a bioprocess engineering platform, harnessing GMP-grade 3D TableTrix® microcarriers and ACISCP to achieve industrial-scale manufacturing of clinical-grade hMSCs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35922261

RESUMO

The aim of this study was to compare modified partial superficial parotidectomy (MPSP) with conventional partial superficial parotidectomy (CPSP) in a retrograde approach, and to determine whether MPSP can reduce the risk of injury to the MMB of the facial nerve and the rate of postoperative facial palsy. Patients with benign parotid gland tumors of the superficial lobe were included retrospectively in two groups: one group was treated with CPSP; the other group was treated with MPSP, in which the MMB was dissected in an anterograde direction or not dissected. The patients' sex and age, location of tumor, size of tumor (maximum tumor diameter), histopathological distribution, operative time, and incidence of postoperative facial nerve weakness were compared. There was no significant difference in operative time between the two groups (p = 0.913). There was a significant difference (p = 0.008) in postoperative facial nerve weakness, with temporary facial nerve weakness observed in 19 and five patients in the CPSP and MPSP groups, respectively. Furthermore, there was a significant difference (p = 0.009) in MMB weakness, with temporary MMB weakness observed in 15 and three patients in the CPSP and MPSP groups, respectively. There was no significant difference (p = 0.564) in the weakness of other branches between the two groups. All cases of paresis scored ≤3 on the House-Brackmann scale, and all cases of temporary facial nerve weakness resolved within 6 months of surgery. No patient developed permanent paralysis. Within the limitations of the study, it seems that modified partial superficial parotidectomy (MPSP) should be preferred over conventional partial superficial parotidectomy (CPSP) whenever appropriate.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35924861

RESUMO

BACKGROUND: Although the association between Helicobacter pylori (H. pylori) infection and hepatic encephalopathy (HE) has been confirmed through some research, the results of these relevant studies still remain controversial. We conducted an updated meta-analysis based on published studies to address this issue. METHODS: A systematic search was conducted, reviewing all studies about the association between H. pylori infection and HE, through November 2021. The outcome measures were presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In total, 13 studies provided data from 2784 subjects. H. pylori infection increased the risk of HE by 32% (OR = 2.32, 95% CI: 1.78-3.04). The effect became greater after hepatic encephalopathy was divided into overt HE and minimal hepatic encephalopathy (MHE) (HE OR = 2.66, 95% CI: 2.01-3.51, MHE OR = 1.74, 95% CI: 1.10-2.76). After H. pylori eradication, the risk of HE was reduced by 64%. CONCLUSIONS: H. pylori infection is significantly associated with HE, and the infection rate of H. pylori also increases with the severity of HE. Eradication of H. pylori has a protective effect on HE. Therefore, it is necessary to eradicate H. pylori in HE treatments.

6.
Antimicrob Agents Chemother ; : e0065822, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35924925

RESUMO

TBI-166, derived from riminophenazine analogues, shows more potent anti-TB activity than clofazimine and is being assessed against tuberculosis (TB) in a phase IIa clinical trial in China. Preclinical regimen studies containing TBI-166 will support the phase IIb clinical trials of TBI-166. In the present study, we compared the efficacy in three murine TB models of an all-oral drug-resistant TB drug regimen of TBI-166 with bedaquiline (BDQ) and pyrazinamide (PZA) with the first-line regimen of isoniazid (INH) with rifampin (RFP) and PZA (HRZ regimen), the most effective reported TBI-166-containing regimen of TBI-166 with BDQ and linezolid (LZD), and the Nix-TB clinical trial regimen of BDQ with pretomanid and LZD (BPaL regimen). In the C3HeB/FeJ murine TB model, for the TBI-166+BDQ+PZA regimen, the lungs of mice were culture negative at 4 weeks, and there were no relapses at 8 weeks of treatment. The reduction in bacterial burden and relapse rate were greater than those of the HRZ regimen and the TBI-166+BDQ+LZD regimen. Compared with the BPaL regimen, the TBI-166+BDQ+PZA regimen had similar or stronger early bactericidal activity, bactericidal activity, and sterilizing activity in the BALB/c murine TB model. The bacterial burden in the TBI-166+BDQ+PZA regimen group decreased significantly more than that in the BPaL regimen group and was almost or totally relapse free (<13.33% after 8 weeks). In conclusion, oral short-course three-drug regimens, including TBI-166 with high efficacy, were identified. The TBI-166+BDQ+PZA regimen is recommended for further study in a TBI-166 phase IIb clinical trial.

7.
Artigo em Inglês | MEDLINE | ID: mdl-35925804

RESUMO

Developing artificial microsystems based on liquid-liquid phase separation (LLPS) to mimic cellular dynamic compartmentalization has gained increasing attention. However, limitations including complicated components and laborious fabrication techniques have hindered their development. Herein, we describe a new single-component dynamic compartmentalization system using peptide-oligonucleotide conjugates (POCs) produced from short elastin-like polypeptides (sELPs) and oligonucleotides (ONs), which can perform thermoreversible phase transition between a nanovesicle and a microdroplet. The phase transition of sELP-ONs is thoroughly investigated, of which the transition temperature can be controlled by concentration, length of sELPs and ONs, base sequences, and salt. Moreover, the sELP-ON microcompartment can enrich a variety of functional molecules including small molecules, polysaccharides, proteins, and nucleic acids. Two sELP-ON compartments are used as nano- and microreactors for enzymatic reactions, separately, in which chemical activities are successfully regulated under different-scaled confinement effects, demonstrating their broad potential application in matter exchange and artificial cells.

8.
Neural Plast ; 2022: 6472475, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35915650

RESUMO

Low-intensity focused ultrasound (LIFU) is a potential noninvasive method to alleviate allodynia by modulating the central nervous system. However, the underlying analgesic mechanisms remain unexplored. Here, we assessed how LIFU at the anterior cingulate cortex (ACC) affects behavior response and central plasticity resulting from chronic constrictive injury (CCI). The safety of LIFU stimulation was assessed by hematoxylin and eosin (H&E) and Fluoro-Jade C (FJC) staining. A 21-day ultrasound exposure therapy was conducted from day 91 after CCI surgery in mice. We assessed the 50% mechanical withdrawal threshold (MWT50) using Von Frey filaments (VFFs). The expression levels of microtubule-associated protein 2 (MAP2), growth-associated protein 43 (GAP43), and tau were determined via western blotting (WB) and immunofluorescence (IF) staining to evaluate the central plasticity in ACC. The regions of ACC were activated effectively and safely by LIFU stimulation, which significantly increased the number of c-fos-positive cells (P < 0.05) with no bleeding, coagulative necrosis, and neuronal loss. Under chronic neuropathic pain- (CNP-) induced allodynia, MWT50 decreased significantly (P < 0.05), and overexpression of MAP2, GAP43, and tau was also observed. After 3 weeks of treatment, significant increases in MWT50 were found in the CCI+LIFU group compared with the CCI group (P < 0.05). WB and IF staining both demonstrated a significant reduction in the expression levels of MAP2, GAP43, and tau (P < 0.05). LIFU treatment on ACC can effectively attenuate CNP-evoked mechanical sensitivity to pain and reverse aberrant central plasticity.


Assuntos
Hiperalgesia , Neuralgia , Animais , Giro do Cíngulo/metabolismo , Hiperalgesia/metabolismo , Hiperalgesia/terapia , Camundongos , Neuralgia/metabolismo , Neuralgia/terapia , Plasticidade Neuronal , Ratos , Ratos Sprague-Dawley
9.
J Med Chem ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35915958

RESUMO

In this work, pyrrole-2-carboxamides were designed with a structure-guided strategy based on the crystal structure of MmpL3 and a pharmacophore model. The structure-activity relationship studies revealed that attaching phenyl and pyridyl groups with electron-withdrawing substituents to the pyrrole ring and attaching bulky substituents to the carboxamide greatly improved anti-TB activity. Most compounds showed potent anti-TB activity (MIC < 0.016 µg/mL) and low cytotoxicity (IC50 > 64 µg/mL). Compound 32 displayed excellent activity against drug-resistant tuberculosis, good microsomal stability, almost no inhibition of the hERG K+ channel, and good in vivo efficacy. Furthermore, the target of the pyrrole-2-carboxamides was identified by measuring their potency against M. smegmatis expressing wild-type and mutated variants of the mmpL3 gene from M. tuberculosis (mmpL3tb) and determining their effect on mycolic acid biosynthesis using a [14C] acetate metabolic labeling assay. The present study provides new MmpL3 inhibitors that are promising anti-TB agents.

10.
Int J Ophthalmol ; 15(7): 1157-1164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35919332

RESUMO

AIM: To evaluate the vision status and sociodemographic associations of visual acuity (VA) in an urban and rural population in a coastal province of southern China. METHODS: The Fujian Eye Study, a population-based cross-sectional study, was performed from May 2018 to October 2019. Totally 10 044 participants over 50 years old from all nine cities in Fujian Province were enrolled, and underwent a questionnaire and a series of standard physical and ocular examinations. VA was measured by E Standard Logarithmic Visual Acuity Chart (GB 11533-1989). Data was double entered with EpiData v3.1 for data collation and Stata/SE statistical software v15.1 was used to analyze the data. RESULTS: Totally 8211 (81.8%) participants were finally included and were divided into urban populations (4678 subjects), rural populations (n=3533), coastal residents (n=6434), and inland residents (1777 subjects); 4836 participants were female. The mean age was 64.39±8.87y (median 64y; range 50-98y). The mean presenting VA was 0.61±0.30 (0.23±0.27 logMAR), and the mean best corrected visual acuity (BCVA) was 0.82±0.28 (0.08±0.19 logMAR). In the multiple regression analysis, BCVA was significantly correlated with several socioeconomic and biologic factors, including age (P<0.001), education level (P<0.001), income (P=0.005), rural residency (P<0.001), inland residency (P=0.001) and refractive error (P<0.001), while sex (P=0.194) was independent with BCVA. CONCLUSION: Accessible services and eye health policies targeting the elderly, people with high myopia and people living in rural or inland areas are needed.

11.
BMJ Open ; 12(8): e059029, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922113

RESUMO

OBJECTIVE: To investigate the existing barriers and recommendations of real-world data (RWD) standardisation for clinical research through a qualitative study on different stakeholders. DESIGN: This qualitative study involved five types of stakeholders based on five interview outlines. The data analysis was performed using the constructivist grounded theory analysis process. SETTING: Eight hospitals, four hospital system vendors, three big data companies, six medical products companies and four regulatory institutions were included. PARTICIPANTS: In total, 62 participants from 25 institutions were interviewed through purposive sampling. RESULTS: The findings showed that the lack of clinical applicability in existing terminology standards, lack of generalisability in existing research databases, and lack of transparency in existing data standardisation process were the barriers of data standardisation of RWD for clinical research. Enhancing terminology standards by incorporating locally used clinical terminology, reducing burden in the usage of terminology standards, improving generalisability of RWD for research by using clinical data models, and improving traceability to source data for transparency might be feasible suggestions for solving the current problems. CONCLUSIONS: Efficient and reliable data standardisation of RWD for clinical research can help generate better evidence used to support regulatory evaluation of medical products. This research suggested enhancing terminology standards by incorporating locally used clinical terminology, reducing burden in the usage of terminology standards, improving generalisability of RWD for research by using clinical data models, and improving traceability to source data for transparency to guide efforts in data standardisation in the future.


Assuntos
Hospitais , Projetos de Pesquisa , China , Humanos , Pesquisa Qualitativa , Padrões de Referência
12.
Front Bioeng Biotechnol ; 10: 916615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928958

RESUMO

DNA is a natural storage medium with the advantages of high storage density and long service life compared with traditional media. DNA storage can meet the current storage requirements for massive data. Owing to the limitations of the DNA storage technology, the data need to be converted into short DNA sequences for storage. However, in the process, a large amount of physical redundancy will be generated to index short DNA sequences. To reduce redundancy, this study proposes a DNA storage encoding scheme with hidden addressing. Using the improved fountain encoding scheme, the index replaces part of the data to realize hidden addresses, and then, a 10.1 MB file is encoded with the hidden addressing. First, the Dottup dot plot generator and the Jaccard similarity coefficient analyze the overall self-similarity of the encoding sequence index, and then the sequence fragments of GC content are used to verify the performance of this scheme. The final results show that the encoding scheme indexes with overall lower self-similarity, and the local thermodynamic properties of the sequence are better. The hidden addressing encoding scheme proposed can not only improve the utilization of bases but also ensure the correct rate of DNA storage during the sequencing and decoding processes.

13.
Fitoterapia ; : 105260, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35931289

RESUMO

Twelve sesquiterpenoids with seven different carbon skeletons, including four isodaucanes (1-4), an aromadendrane (5), a guaiane (6), a cadalane (7), two eudesmanes (8 and 9), two bisabolanes (10 and 11), and a megastigmane (12), were isolated from the twigs and leaves of Aglaia lawii (Wight) C. J. Saldanha et Ramamorthy. Of these compounds, amouanglienoids A (1) and B (2) are new isodaucane sesquiterpenoids. This is the first report of isodaucanes from the genus Aglaia, and amouanglienoid A (1) represents the first isodaucane containing a Δ7(8) double bond. Their structures were discerned from extensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison of the experimental and calculated ECD data. In in vitro bioassays, compounds 1, 10, and 11 showed potent inhibitory effects against lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells, while compound 11 exhibited considerable inhibition of PTP1B with an IC50 value of 16.05 ±â€¯1.09 µM.

14.
Front Nutr ; 9: 957778, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35938100

RESUMO

To prepare peptides with high angiotensin-converting enzyme (ACE) inhibitory (ACEi) activity, Alcalase was screened from five proteases and employed to prepare protein hydrolysate (TMH) of skipjack tuna (Katsuwonus pelamis) milts. Subsequently, 10 novel ACEi peptides were isolated from the high-ACEi activity TMH and identified as Tyr-Asp-Asp (YDD), Thr-Arg-Glu (TRE), Arg-Asp-Tyr (RDY), Thr-Glu-Arg-Met (TERM), Asp-Arg-Arg-Tyr-Gly (DRRYG), Ile-Cys-Tyr (ICY), Leu-Ser-Phe-Arg (LSFR), Gly-Val-Arg-Phe (GVRF), Lys-Leu-Tyr-Ala-Leu-Phe (KLYALF), and Ile-Tyr-Ser-Pro (IYSP) with molecular weights of 411.35, 404.41, 452.45, 535.60, 665.69, 397.48, 521.61, 477.55, 753.91, and 478.53 Da, respectively. Among them, the IC50 values of ICY, LSFR, and IYSP on ACE were 0.48, 0.59, and 0.76 mg/mL, respectively. The significant ACEi activity of ICY, LSFR, and IYSP with affinities of -7.0, -8.5, and -8.3 kcal/mol mainly attributed to effectively combining with the ACEi active sites through hydrogen bonding, electrostatic force, and hydrophobic interaction. Moreover, ICY, LSFR, and IYSP could positively influence the production of nitric oxide (NO) and endothelin-1 (ET-1) secretion in human umbilical vein endothelial cells (HUVECs) and weaken the adverse impact of norepinephrine (NE) on the production of NO and ET-1. In addition, ICY, LSFR, and IYSP could provide significant protection to HUVECs against H2O2 damage by increasing antioxidase levels to decrease the contents of reactive oxide species and malondialdehyde. Therefore, the ACEi peptides of ICY, LSFR, and IYSP are beneficial functional molecules for healthy foods against hypertension and cardiovascular diseases.

15.
Front Cell Dev Biol ; 10: 906042, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35938155

RESUMO

Background: Cataract is the leading cause of blindness worldwide. In order to achieve large-scale cataract screening and remarkable performance, several studies have applied artificial intelligence (AI) to cataract detection based on fundus images. However, the fundus images they used are original from normal optical circumstances, which is less impractical due to the existence of poor-quality fundus images for inappropriate optical conditions in actual scenarios. Furthermore, these poor-quality images are easily mistaken as cataracts because both show fuzzy imaging characteristics, which may decline the performance of cataract detection. Therefore, we aimed to develop and validate an antiinterference AI model for rapid and efficient diagnosis based on fundus images. Materials and Methods: The datasets (including both cataract and noncataract labels) were derived from the Chinese PLA general hospital. The antiinterference AI model consisted of two AI submodules, a quality recognition model for cataract labeling and a convolutional neural networks-based model for cataract classification. The quality recognition model was performed to distinguish poor-quality images from normal-quality images and further generate the pseudo labels related to image quality for noncataract. Through this, the original binary-class label (cataract and noncataract) was adjusted to three categories (cataract, noncataract with normal-quality images, and noncataract with poor-quality images), which could be used to guide the model to distinguish cataract from suspected cataract fundus images. In the cataract classification stage, the convolutional-neural-network-based model was proposed to classify cataracts based on the label of the previous stage. The performance of the model was internally validated and externally tested in real-world settings, and the evaluation indicators included area under the receiver operating curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE). Results: In the internal and external validation, the antiinterference AI model showed robust performance in cataract diagnosis (three classifications with AUCs >91%, ACCs >84%, SENs >71%, and SPEs >89%). Compared with the model that was trained on the binary-class label, the antiinterference cataract model improved its performance by 10%. Conclusion: We proposed an efficient antiinterference AI model for cataract diagnosis, which could achieve accurate cataract screening even with the interference of poor-quality images and help the government formulate a more accurate aid policy.

16.
Front Aging Neurosci ; 14: 909738, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912084

RESUMO

Objectives: The relationship between preoperative serum uric acid (SUA) and cerebrospinal fluid (CSF) Alzheimer-related biomarkers were investigated to determine whether high SUA is a potential risk factor for postoperative delirium (POD) and to evaluate its predictive efficacy. Methods: The participants were selected from the Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) study and the Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE) study. The logistic regression equation was used to analyze the risk factors and protective factors of POD. The interaction term (SUA × Sex) was introduced into the linear model to explore the potential modification effects of sex on the identified correlations. We analyzed the mediating effects of Alzheimer-related biomarkers. Finally, we constructed the receiver operating characteristic (ROC) curve and the nomogram model to evaluate the efficacy of SUA and Alzheimer-related biomarkers in predicting POD. Results: Patients with POD had elevated SUA level (PNDRFAP: p = 0.002, PNDABLE: p < 0.001). Preoperative SUA level was positively correlated with CSF phosphorylated tau (P-tau) (p = 0.027) and ß-amyloid42 (Aß42)/P-tau (p = 0.023). Interaction analysis did not find any modification effect of sex. The relationship between SUA and POD was partially mediated by CSF P-tau (15.3%). ROC curve showed that the model combining SUA and Alzheimer-related biomarkers had better performance in predicting POD [area under the curve (AUC) = 0.880; p < 0.001], and the predictive model is accurate. Conclusions: High SUA may enhance CSF P-tau level, thus increasing the risk of POD, and the model combining SUA and Alzheimer-related biomarkers can accurately predict the occurrence of POD.

17.
J Chromatogr A ; 1678: 463361, 2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35914408

RESUMO

In this study, an on-tissue chemical labeling - matrix assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) method was developed for visualization of the distribution of three catecholamine (CA) compounds (dopamine, epinephrine and norepinephrine) in porcine adrenal gland. Commercially available pyrene-1-boronic acid (PBA) was employed as an effective in situ derivatizing reagent dissolved in acetonitrile containing 0.1% pyridine for the chemical labeling and the matrix coating. Without extra matrix coating, the tissue section was directly analyzed by MALDI-MS. The detection specificity and sensitivity were greatly improved with the on-tissue PBA labeling and successful imaging of the three CAs in porcine adrenal gland was achieved. Compared with previously reported methods for MALDI-MSI of the CAs, the analytical strategy proposed in the study provided a robust, easy-to-use and low-cost on-tissue chemical derivatization method that facilitated simultaneous molecular imaging of the three compounds.

18.
Front Immunol ; 13: 932152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935951

RESUMO

Neurological disorders (NDs) are one of the leading causes of global death. A sustained neuroinflammatory response has been reported to be associated with the pathogenesis of multiple NDs, including Parkinson's disease (PD), multiple sclerosis (MS), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and major depressive disorder (MDD). Accumulating evidence shows that the recruitment of abundant lymphocytes in the central nervous system may contribute to promoting the development and progress of inflammation in neurological disorders. As one subset of T lymphocytes, CD4+ T cells have a critical impact on the inflammation of neurological disorders. T helper (Th) 17 is one of the most studied CD4+ Th subpopulations that produces cytokines (e.g., IL-17A, IL-23, IL-21, IL-6, and IFN-γ), leading to the abnormal neuroinflammatory response including the excessive activation of microglia and the recruitment of other immune cell types. All these factors are involved in several neurological disorders. However, the possible mechanisms of Th17 cells and their associated cytokines in the immunopathology of the abovementioned neurological disorders have not been clarified completely. This review will summarize the mechanisms by which encephalitogenic inflammatory Th17 cells and their related cytokines strongly contribute to chronic neuroinflammation, thus perpetuating neurodegenerative processes in NDs. Finally, the potential therapeutic prospects of Th17 cells and their cytokines in NDs will also be discussed.

19.
Front Pharmacol ; 13: 905547, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784704

RESUMO

Aims: To evaluate the utility of fasudil in a rat model of contrast-associated acute kidney injury (CA-AKI) and explore its underlying mechanism through multiparametric renal magnetic resonance imaging (mpMRI). Methods: Experimental rats (n = 72) were grouped as follows: controls (n = 24), CA-AKI (n = 24), or CA-AKI + Fasudil (n = 24). All animals underwent two mpMRI studies (arterial spin labeling, T1 and T2 mapping) at baseline and post iopromide/fasudil injection (Days 1, 3, 7, and 13 respectively). Relative change in renal blood flow (ΔRBF), T1 (ΔT1) and T2 (ΔT2) values were assessed at specified time points. Serum levels of cystatin C (CysC) and interleukin-1ß (IL-1ß), and urinary neutrophil gelatinase-associated lipocalin (NGAL) concentrations were tested as laboratory biomarkers, in addition to examining renal histology and expression levels of various proteins (Rho-kinase [ROCK], α-smooth muscle actin [α-SMA]), hypoxia-inducible factor-1α (HIF-1α), and transforming growth factor-ß1 (TGF-ß1) that regulate renal fibrosis and hypoxia. Results: Compared with the control group, serum levels of CysC and IL-1ß, and urinary NGAL concentrations were clearly increased from Day 1 to Day 13 in the CA-AKI group (all p < 0.05). There were significant reductions in ΔT2 values on Days 1 and 3, and ΔT1 reductions were significantly more pronounced at all time points (Days 1-13) in the CA-AKI + Fasudil group (vs. CA-AKI) (all p < 0.05). Fasudil treatment lowered expression levels of ROCK-1, and p-MYPT1/MYPT1 proteins induced by iopromide, decreasing TGF-ß1 expression and suppressing both extracellular matrix accumulation and α-SMA expression relative to untreated status (all p < 0.05). Fasudil also enhanced PHD2 transcription and inhibition of HIF-1α expression after CA-AKI. Conclusions: In the context of CA-AKI, fasudil appears to reduce renal hypoxia, fibrosis, and dysfunction by activating (Rho/ROCK) or inhibiting (TGF-ß1, HIF-1α) certain signaling pathways and reducing α-SMA expression. Multiparametric MRI may be a viable noninvasive tool for monitoring CA-AKI pathophysiology during fasudil therapy.

20.
Front Surg ; 9: 875040, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784942

RESUMO

Background: Femoral neck fracture (FNF) is a commonly encountered injury in orthopedic practice, and many studies have been conducted in this field. However, no bibliometric studies regarding the global research trend concerning FNF have been performed. This study aims to analyze the knowledge framework, research hotspots, and theme trends in the field of FNF research. Methods: The scientific outputs related to FNF from 1994 to 2021 were retrieved from the Web of Science Core Collection. Three bibliometric tools were used for this study. The main analyses include publication and citation counts, contributions of countries, institutions, authors, funding agencies and journals, and clustering of keywords. Results: In total, 3,553 articles were identified. The annual publication counts of FNF showed an ascending tendency as a whole. The United States has the most prominent contributions, with the most number of publications and the highest H-index. Karolinska Institutet devoted the most in this domain. Professors Bhandari M, Schemitsch EH, Frihagen F, Parker MJ, and Rogmark C were the core authors in this field. The most productive journal was Injury International Journal of the Care of the Injured. Keywords were divided into four clusters: epidemiology and mortality, fracture prevention, internal-fixation and risk factors, and hip replacement. A trend of balanced and diversified development existed in these clusters. Keywords with the ongoing bursts, including "outcome," "reoperation," "complication," "revision," "displaced intracapsular," "fracture," and "adult," are considered as the research hotspots in the future and deserve more attention. Conclusions: The management of FNF in young patients is drawing more attention from orthopedic surgeons, and it is expected that these research topics may continue to be the research hotspots and focus in the near future.

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