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1.
Neural Regen Res ; 17(5): 1023-1033, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34558529

RESUMO

The formation of nerve bundles, which is partially regulated by neural cell adhesion molecule 1 (NCAM1), is important for neural network organization during peripheral nerve regeneration. However, little is known about how the extracellular matrix (ECM) microenvironment affects this process. Here, we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrix-gel, Matrigel, laminin 521, collagen I, and collagen IV, and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment. We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon. A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation. Collagen VI interacted with NCAM1 by directly binding to the FNIII domain, thereby increasing the stability of NCAM1 at the axolemma. Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/mL Matrigel and 20 µg/mL collagen VI. These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation. This study was approved by the Animal Ethics Committee of Guangzhou Medical University (approval No. GY2019048) on April 30, 2019.

2.
Bioact Mater ; 9: 157-167, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34820563

RESUMO

The integration of photothermal therapy (PTT) with gene therapy (GT) in a single nanoscale platform demonstrates great potential in cancer therapy. Porous iron oxide nanoagents (PIONs) are widely used as magnetic nanoagents in the drug delivery field and also serve as a photothermal nanoagent for photothermal therapy. However, the therapeutic efficacy of PIONs-mediated GT has not been studied. The long noncoding RNA (lncRNA) CRYBG3 (LNC CRYBG3), a lncRNA induced by heavy ion irradiation in lung cancer cells, has been reported to directly bind to globular actin (G-actin) and cause degradation of cytoskeleton and blocking of cytokinesis, thus indicating its potential for use in GT by simulating the effect of heavy ion irradiation and functioning as an antitumor drug. In the present study, we investigated the possibility of combining PIONs-mediated PTT and LNC CRYBG3-mediated GT to destroy non-small cell lung cancer (NSCLC) cells both in vitro and in vivo. The combination therapy showed a high cancer cell killing efficacy, and the cure rate was better than that achieved using PTT or GT alone. Moreover, as a type of magnetic nanoagent, PIONs can be used for magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) both in vitro and in vivo. These findings indicate that the new combination therapy has high potential for cancer treatment.

3.
Sci Total Environ ; 803: 150083, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34525679

RESUMO

Understanding the spatio-temporal heterogeneous effects of socioeconomic and meteorological factors on CO2 emissions from combinations of different district heating systems with "Coal-to-Gas" transition can contribute to the development of future low-carbon energy systems that are efficient and effective. This work downscales city-level CO2 emissions to a 3 × 3 km2 gridded level in northern China during 2012 to 2018. By employing the Geographically and Temporally Weighted Regression (GTWR) model, nighttime light (NTL) data are adopted as a proxy of the level of urbanization, and the Temperature-Humidity-Wind (THW) Index is used as a proxy of meteorological factors in the downscaling model. The results show that, for more than 85% of the cities, urbanization significantly enhances the CO2 emissions of district heating systems, while the THW Index shows negative impacts on CO2 emissions. Significant spatial and temporal heterogeneity exists. The grids with the highest CO2 emissions from coal-fired boilers (grids with annual variation >0.59 Gg CO2/year) are mainly located in nonurban areas of the two megacities Beijing and Tianjin and also in the capital cities of each province. Urbanization has larger effects on the CO2 emissions of natural gas-fired boilers than of coal-fired boilers and combined heat and power (CHP). The average growth rate of CO2 emissions of gas-fired boilers in the urban areas of the study regions was approximately 4.7 times that of nonurban areas. The spatio-temporal heterogeneous impacts of urbanization on CO2 emissions should therefore be considered in future discussions of clean heating policies and climate response strategies.


Assuntos
Dióxido de Carbono , Calefação , Dióxido de Carbono/análise , China , Carvão Mineral , Urbanização
5.
Int J Low Extrem Wounds ; : 15347346211055972, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34747262

RESUMO

BACKGROUND: Diabetic foot infections (DFIs) are the most complex and challenging pathological state, characterized by high complexity of management, morbidity, and mortality. Empirical antimicrobial administration is needed before the identification of the causative organisms. Microbiological profile of the diabetic foot patients is the basis of the antibiotic choice for clinicians. METHODS: 76 patients visiting the Diabetic Foot Center of our Hospital for having ulcers with Wagner 3 to 5 were retrospectively surveyed for the bacterium infected. Antimicrobial susceptibility testing (AST) was implemented and the results were interpreted on the basis of the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: A total of 92 isolates were obtained, of which 47 strains of gram-negative bacilli (GNB) accounted for 51.1%, 41 strains of gram-positive cocci (GPC) accounted for 44.6%, and 4 strains of fungi accounted for 4.3%. Species of Enterobacteriaceae and Staphylococcus are the two predominant strains. The top 4 most frequently isolated strains were Staphylococcus aureus (22.8%), enterococcus faecalis (9.8%), Pseudomonas aeruginosa (9.8%), Escherichia coli (5.4%). The rate of resistance to methicillin was 33.3% for S. aureus. The rate of extended-spectrum ß-lactamases (ESBLs) production among E. coli was 60%. 50% of Klebsiella pneumoniae were resistant to carbapenems. P. aeruginosa showed high sensitivity to commonly used antibiotics. There was one isolate of Acinetobacter spp. resistant to most antimicrobials except tigecycline and aminoglycosides. CONCLUSION: Enterobacteriaceae and Staphylococcus are the two predominant species. The resistance to antibiotics of S. aureus and P. aeruginosa showed optimistic results. However, the high prevalence of CRKP imposed a challenging issue for clinical physicians.

6.
Child Dev ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748214

RESUMO

Dialogic reading, when children are read a storybook and engaged in relevant conversation, is a powerful strategy for fostering language development. With the development of artificial intelligence, conversational agents can engage children in elements of dialogic reading. This study examined whether a conversational agent can improve children's story comprehension and engagement, as compared to an adult reading partner. Using a 2 (dialogic reading or non-dialogic reading) × 2 (agent or human) factorial design, a total of 117 three- to six-year-olds (50% Female, 37% White, 31% Asian, 21% multi-ethnic) were randomly assigned into one of the four conditions. Results revealed that a conversational agent can replicate the benefits of dialogic reading with a human partner by enhancing children's narrative-relevant vocalizations, reducing irrelevant vocalizations, and improving story comprehension.

7.
Front Microbiol ; 12: 739569, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745041

RESUMO

Aspergillus oryzae, commonly known as koji mold, has been widely used for the large-scale production of food products (sake, makgeolli, and soy sauce) and can accumulate a high level of lipids. In the present study, we showed the dynamic changes in A. oryzae mycelium growth and conidia formation under nitrogen and phosphorus nutrient stress. The fatty acid profile of A. oryzae was determined and the content of unsaturated fatty acid was found increased under nitrogen and phosphorus limitation. Oleic acid (C18:1), linoleic acid (C18:2), and γ-linolenic acid (C18:3) production were increased on five nitrogen and phosphorus limitation media, especially on nitrogen deep limitation and phosphorus limitation group, showing a 1. 2-, 1. 6-, and 2.4-fold increment, respectively, compared with the control. Transcriptomic analysis showed the expression profile of genes related to nitrogen metabolism, citrate cycle, and linoleic acid synthesis, resulting in the accumulation of unsaturated fatty acid. qRT-PCR results further confirmed the reliability and availability of the differentially expressed genes obtained from the transcriptome analysis. Our study provides a global transcriptome characterization of the nitrogen and phosphorus nutrient stress adaptation process in A. oryzae. It also revealed that the molecular mechanisms of A. oryzae respond to nitrogen and phosphorus stress. Our finding facilitates the construction of industrial strains with a nutrient-limited tolerance.

8.
World J Gastrointest Surg ; 13(10): 1202-1215, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34754388

RESUMO

BACKGROUND: Immunoinflammatory markers such as the peripheral blood neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have gained considerable attention as prognostic markers in gastrointestinal stromal tumors (GISTs). AIM: To assess the prognostic value of Onodera's Prognostic Nutritional Index (OPNI) for GISTs. METHODS: All patients who had undergone surgical resection for a primary, localized GIST from 2009 to 2016 at our cancer center were initially and retrospectively identified. Recurrence-free survival (RFS) was calculated by the Kaplan-Meier method and compared by the log-rank test. We used multivariate Cox proportional hazard regression models to identify associations with outcome variables. RESULTS: A total of 235 GISTs were identified and included for analysis under our inclusion criteria. Univariate and multivariate analyses both identified the OPNI as an independent prognostic marker, and the OPNI was associated with the primary site, tumor size, mitotic index, tumor rupture, necrosis, and modified NIH risk classification. Low OPNI (< 51.30; hazard ratio = 5.852; 95% confidence interval: 1.072-31.964; P = 0.0414) was associated with worse RFS. The 2- and 5-year RFS rates of the patients with a low OPNI were 92.83% and 76.22%, respectively, whereas 100% and 98.41% were achieved by the patients with a high OPNI. CONCLUSION: The preoperative OPNI is a novel and useful prognostic marker for GISTs.

9.
Cell Mol Biol Lett ; 26(1): 48, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34794379

RESUMO

BACKGROUND: Intestinal mucositis is a common side effect of chemotherapy and radiotherapy. Very few drugs can efficiently ameliorate it. Tertiary butylhydroquinone (TBHQ) is a widely used food preservative with known immunomodulatory activity. Whether it has an effect on intestinal mucositis remains unknown. In this study, we investigated the role and mechanism of action of TBHQ on 5-fluorouracil-induced (5-FU-induced) human intestinal epithelial cell (HIEC) injury and intestinal mucositis in mice. METHODS: We established a cell model of HIEC injury and a mouse model of intestinal mucositis via treatment with 5-FU. Cell death, Cell Counting Kit-8, and lactate dehydrogenase (LDH) release were assessed for the HIECs. Diarrhea, body weight, intestinal length, mucosal damage, and the levels of IL-6, TNF-α, IL-1ß, glutathione, reactive oxygen species, and malondialdehyde were determined for the mice. Additionally, we performed immunohistochemical analysis, immunofluorescence, western blotting, quantitative real-time PCR, and ELISA to examine the effects of TBHQ. Finally, HIECs were transfected with an Nrf2 gene silencer to verify its role in ferroptosis. All data were analyzed using one-way analysis of variance or paired t-tests. RESULTS: TBHQ markedly decreased LDH release and cell death and improved the proliferative ability of 5-FU-treated HIECs. The TBHQ-treated mice showed reduced weight loss, a lower diarrhea score, and longer colons than the 5-FU-treated mice. The in vivo expressions of IL-1ß, IL-6, and TNF-α were suppressed by TBHQ treatment. Ferroptosis was shown to be involved in 5-FU-induced intestinal mucositis, and TBHQ markedly hampered its activation. Mechanistically, TBHQ activated Nrf2 effectively and selective Nrf2 knockdown significantly reduced the anti-ferroptotic functions of TBHQ in 5-FU-treated HIECs. CONCLUSIONS: TBHQ attenuates ferroptosis in 5-FU-induced intestinal mucositis, making it a potential novel protective agent against intestinal mucositis.

10.
Cancer Manag Res ; 13: 8411-8423, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34785949

RESUMO

Purpose: Long non-coding RNAs (lncRNAs) have diverse roles in modulating gene expression on both transcriptional and translational levels, but their involvement in osteosarcoma (OS) metastasis remains unknown. Patients and Methods: Transcriptional and clinical data were downloaded from TARGET datasets. A total of seven lncRNAs screened by univariate cox regression, lasso regression, and multivariate cox regression analysis were used to establish the OS metastasis model. The area under the receiver operating characteristic curve (AUC) was used to evaluate the model. Results: The established model showed exceptional predictive performance (1 year: AUC = 0.92, 95% Cl = 0.83-0.99; 3 years: AUC = 0.87, 95% Cl = 0.79-0.96; 5 years: AUC = 0.86, 95% Cl = 0.76-0.96). Patients in the high group had a poor survival outcome than those in the low group (p < 0.0001). GSEA analysis revealed that "NOTCH_SIGNALING" and "WNT_BETA_CATENIN_SIGNALING" were significantly enriched and that resting dendritic cells were associated with AL512422.1, AL357507.1, and AC006033.2 (p < 0.05). Conclusion: Based on seven prognosis-related lncRNAs, we constructed a novel model with high reliability and accuracy for predicting metastasis in OS patients.

11.
Int J Syst Evol Microbiol ; 71(11)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34788209

RESUMO

A novel symbiotic bacterium, designated strain XY-114T, was isolated from the cerata of an Onchidium marine invertebrate species collected in the South China Sea. Strain XY-114T was an aerobic, Gram-stain-negative, non-motile and short rod-shaped bacterium (0.5-0.8 µm wide and 1.0-1.5 µm long) without flagellum. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain XY-114T belonged to the genus Algibacter with the highest similarity of 97.2 % to the closest phylogenetic relative Algibacter aestuarii KYW371T. Cells grew at 15-37 °C (optimum, 30 °C), at pH 5.5-9.0 (optimum 7.0-8.0) and at NaCl concentrations of 0.5-5.0 % (w/v; optimum 1.5-3.0 %). The major fatty acids (>10 %) were summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c), iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The predominant polar lipid was phosphatidylethanolamine. The predominant respiratory quinone was MK-6. Flexirubin-type pigments were absent. The genome size of strain XY-114T was 3.4 Mbp, with 34.9 mol% of DNA G+C content. The average nucleotide identity, digital DNA-DNA hybridization and amino acid identity values between strain XY-114T and A. aestuarii KYW371T were 74.5 %, 17.0±1.8 % and 73.9 %. Characterization based on phylogenetic, phenotypic, chemotaxonomic and genomic evidence demonstrated that strain XY-114T represents a novel species of the genus Algibacter, for which the name Algibacter onchidii sp. nov. is proposed. The type strain is XY-114T (=KCTC 72217T=MCCC 1K03606T).


Assuntos
Ácidos Graxos , Gastrópodes , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae , Hibridização de Ácido Nucleico , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
12.
PLoS One ; 16(11): e0260108, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34788347

RESUMO

In this paper we introduce a system of partial differential equations that is capable of modeling a variety of dynamic processes in soft tissue cellular populations and their microenvironments. The model is designed to be general enough to simulate such processes as tissue regeneration, tumor growth, immune response, and many more. It also has built-in flexibility to include multiple chemical fields and/or sub-populations of cells, interstitial fluid and/or extracellular matrix. The model is derived from the conservation laws for mass and linear momentum and therefore can be classified as a continuum multi-phase model. A careful choice of state variables provides stability in solving the system of discretized equations defining advective flux terms. A concept of deviation from normal allows us to use simplified constitutive relations for stresses. We also present an algorithm for computing numerical approximations to the solutions of the system and discuss properties of these approximations. We demonstrate several examples of applications of the model. Numerical simulations show a significant potential of the model for simulating a variety of processes in soft tissues.

13.
J Autism Dev Disord ; 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34800227

RESUMO

Autism Spectrum Disorder (ASD) is a serious neurodevelopmental disorder with no clinical biomarker. This study used untargeted metabolomic analysis to identify metabolic characteristics in plasma that can distinguish ASD children. 29 boys with ASD (3.02 ± 0.67 years) and 30 typically developing (TD) boys (3.13 ± 0.46 years) were recruited. Developmental and behavioral assessments were conducted in ASD group. Samples of plasma were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The association between metabolite concentration and scale score was assessed by Spearman rank correlation. Altered metabolic characteristics were found in boys with ASD. In Receiver Operating Characteristic (ROC) analysis, ornithine had the highest AUC (Area under ROC) value. Furthermore, the concentration of choline and ornithine was negatively correlated with ABC-language score in ASD group.

14.
Inorg Chem ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822250

RESUMO

Constructing robust adsorbents for SO2 removal remains a challenging issue. Herein, a U-Co bimetallic-organic framework, namely, ECUT-123, showing a helical 1D pore decorated by abundant -CH3 groups, enables ultrahigh stability under acid, base, and water. This merit further supports its big potential for the removal of trace SO2.

15.
Transl Androl Urol ; 10(10): 3837-3851, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804826

RESUMO

Background: The interferon-inducible transmembrane (IFITM) proteins are localized in the endolysosomal and plasma membranes, conferring cellular immunity to various infections. However, the relationship with carcinogenesis remains poorly elucidated. In the present study, we investigated the role of IFITM in kidney renal clear cell carcinoma (KIRC). Methods: We utilized the online databases of Oncomine, UALCAN and Human Protein Atlas to analyze the expression of IFITMs and validate their levels in human KIRC cells by qPCR and western blot. Furthermore, we evaluated prognostic significance with the Gene Expression Profiling Interactive Analysis tool (Kaplan-Meier (KM) Plotter) and delineated the immune cell infiltration profile related to IFITMs with the TIMER2.0 database. Results: IFITMs were overexpressed in KIRC and varied in subtypes and tumor grades. High expression of IFITMs indicated a poor prognosis and more immune cell infiltration, especially endothelial cells and cancer-associated fibroblasts. IFITMs were associated with immune genes, which correlated with poor prognosis of renal clear cell carcinoma. We also explored the enriched network of IFITMs co-occurrence genes and their targeted transcription factors and miRNA. The expression of IFITMs correlated with hub mutated genes of KIRC. Conclusions: IFITMs play a crucial role in the oncogenesis of KIRC and could be a potential surrogate marker for treatment response to targeted therapies.

16.
Opt Express ; 29(24): 39241-39248, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809292

RESUMO

An electro-optic method based on a self-referenced pilot operation is proposed for simultaneously characterizing electro-absorption modulation optoelectronic transceivers with a shared setup. Through inserting and extracting the self-referenced pilot, the frequency responses of electro-absorption modulated lasers (EMLs) and photodetectors (PDs) are independently obtained in a single measurement, and any extra optical-to-electrical or electrical-to-optical calibration is avoided. Specifically, the relative frequency response of the EML at fm is determined through the extracted difference-frequency pilot at fp (close to DC), realizing the low-frequency analysis for an EML. The relative frequency response of PD at 2fm+fp is obtained from the amplitude ratio of the extracted sum- and difference-frequency pilots at 2fm+fp and fp under the microwave driving signal at fm, verifying the doubled measuring frequency range. In the proof-of-concept demonstration, the frequency response of an electro-absorption modulation transceiver is measured up to 40 GHz. Thereinto, the frequency response of the EML is obtained by detecting the fixed low-frequency pilot of 10 kHz, and the frequency response of the PD is extracted with frequency-swept modulation to 20 GHz. The experiment results are compared with those obtained with the electro-optic frequency sweeping method to check for accuracy.

17.
Bioresour Technol ; : 126421, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34838961

RESUMO

This study presents an approach for developing periphytic biofilm with N-acyl-homoserine-lactones (AHLs) stimulation and lanthanum (La, a rare earth element) loading, to achieve highly efficient and stable phosphorus (P) recovery from wastewater. AHLs stimulated biofilm growth and formation, also improved stable P entrapment by enhancing extracellular polymeric substance (EPS) production and optimizing P-entrapment bacterial communities. Periphytic biofilms loading La is based on ligand exchanges, and La loading achieved initial rapid P entrapment by surface adsorption. The combination of AHLs stimulation and La loading achieved 99.0% P entrapment. Interestingly, the enhanced EPS production stimulated by AHLs protected biofilms against La. Moreover, a method for P and La separately recovery from biofilms was developed, achieving 89-96% of P and 88-93% of La recovery. This study offers a promising biotechnology to reuse La from La-rich wastewater and recover P by biofilm doped with La, which results in a win-win situation for resource sustainability.

18.
Drug Deliv ; 28(1): 2415-2426, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34763595

RESUMO

Koumine (KME) is an active alkaloid extracted from Gelsemium elegans, and its diverse bioactivities have been studied for decades. However, KME exhibits poor solubility and low oral bioavailability, which hampers its potential therapeutic exploitation. This work aimed to develop optimized inclusion complexes to improve the bioavailability of KME. The KME/hydroxypropyl-ß-cyclodextrin (KME/HP-ß-CD) inclusion complexes were prepared by the solvent evaporation method and later optimized using the Box-Behnken design. The optimal KME/HP-ß-CD was characterized by scanning electron microscopy, Fourier transforms infrared spectroscopy, differential scanning calorimetry, and nuclear magnetic resonance spectroscopy. The physicochemical characterization results revealed that the crystalline state of KME was transformed into an amorphous form, forming KME/HP-ß-CD inclusion complexes. Compared with KME, the solubility and in vitro release rate of KME/HP-ß-CD was significantly enhanced by 52.34- and 1.3-fold, respectively. Further research was performed to investigate the intestinal absorption characteristics and in vivo bioavailability in rats. The optimal KME/HP-ß-CD showed enhanced absorptive permeability and relative bioavailability increased more than two-fold compared to that of raw KME. These results indicate that the optimal KME/HP-ß-CD can be used as an effective drug carrier to improve the solubility, intestinal absorption, and bioavailability of KME.

19.
Dement Geriatr Cogn Disord ; : 1-6, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34775383

RESUMO

INTRODUCTION: Little is known about the role of inflammation in the process of small vessel vascular dementia (VaD). Recently, the notion that small vessel VaD is caused solely by vascular pathology has been challenged by new evidence of concomitant breakdown of the blood-brain barrier and dysregulation of neuroinflammation in the white matter. METHODS: We examined selected inflammatory cytokines and chemokines in the plasma from patients with small vessel VaD (n = 41) and from age-matched controls (n = 131) using multiplex bead-based assays. Participants were recruited from a memory disorder clinic and from a hospital or community. RESULTS: When compared to controls, patients with small vessel VaD had a highly significant increase in the plasma interferon-γ-inducible protein 10 (IP-10) level (p < 0.0001) and a highly significant decrease in plasma macrophage inflammatory protein 1-beta (MIP-1ß) level (p < 0.0001). We also observed a significant increase in patients' levels of interleukin-10 (IL-10) (p = 0.022) as well as decreases in interleukin-8 (IL-8) (p = 0.004) and interleukin-7 (IL-7) (p = 0.011) when compared to age-matched controls. CONCLUSION: Both IP-10 and MIP-1ß are macrophage-related chemokines. The significant differences between cases and controls suggest a potential role for macrophages in small vessel VaD neuroinflammation. Although it remains unclear whether there is a causal effect of their alteration for small vessel VaD, a better understanding of these molecules in the pathogenesis of small vessel VaD may lead to improved diagnosis and future treatment outcomes against this disease.

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