Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.995
Filtrar
1.
Methods Mol Biol ; 2147: 125-135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32840815

RESUMO

Nano- and micro-scaled fibers have been incorporated in a number of applications in biofabrication and tissue cultures, providing a cell interfacing structure with extracellular matrix-mimicking topography and adhesion sites, and further supporting localized drug release. Here, we describe the low-voltage electrospinning patterning (LEP) protocol, which allows direct and continuous patterning of sub-micron fibers in a controlled fashion. The processable polymers range from protein (e.g., gelatin) to thermoplastic (e.g., polystyrene) polymers, with flexible selections of collecting substrates. The operation voltage for fiber fabrication can be as low as 50 V, which brings the benefits of reducing costs and mild-processing.

2.
Food Chem ; 337: 127798, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32799166

RESUMO

In this study, polysaccharides (BPSs) were obtained from fresh bitter gourd (Momordica charantia L.) by room temperature extraction techniques, including three-phase partitioning (TPP) and ultrasonic-assisted extraction (UAE) performed in different solvents. The results showed that the extraction methods had significant influence on the extraction yield, chemical composition, weight-average molecular weight (Mw), monosaccharide composition, preliminary structural characterization and microstructure of the BPSs. The BPS-W sample obtained from the bitter gourd residue via UAE in distilled water had a higher uronic acid content (24.22%) and possessed stronger antioxidant capacities and α-amylase and α-glycosidase inhibitory activities than BPS-C extracted with UAE in citric acid, BPS-A extracted with UAE in 1.25 mol/L NaOH/0.05% NaBH4, and BPS-J extracted from bitter gourd juice by TPP. Moreover, BPS-A, which had the lowest Mws, showed the best bile acid-binding capacity among the four BPSs. This study had great potentials for the preparation of bioactive polysaccharides from fresh vegetables.

3.
Cancer Med ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33047873

RESUMO

BACKGROUND: Positive peritoneal cytology (PCY) indicates metastasis (M1) in gastric cancer (GC) patients; both the American and Chinese guidelines recommend laparoscopic peritoneal lavage (LPL) for cytology. However, relatively high costs impair the widespread use of LPL in some resource-limited regions in China, and the cost-effectiveness of PCY testing remains unclear. Therefore, we performed a decision analysis to evaluate the cost-effectiveness of PCY testing by comparing the guideline-recommended intraoperative LPL, a newly proposed preoperative percutaneous peritoneal lavage (PPL), and a third strategy of exploratory laparotomy with no cytology testing (ELNC) among GC patients. METHODS: We developed a decision-analytic Markov model of the aforementioned three strategies for a hypothetical cohort of GC patients with curative intent after initial imaging, from the perspective of Chinese society. We estimated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) as primary outcomes; we also conducted one-way and probabilistic sensitivity analyses to investigate the model's robustness. RESULTS: We found that ELNC was dominated (i.e., more expensive and less effective) by PPL and LPL. LPL was the most cost-effective method with an ICER of US$17,200/QALY compared to PPL, which was below the Chinese willingness-to-pay (WTP) threshold of US$29,313 per QALY gained. In sensitivity analyses, PPL was more likely to be cost-effective with a lower WTP threshold. CONCLUSIONS: Cytology testing through either LPL or PPL was less expensive and more effective than ELNC among GC patients. Moreover, LPL was the most cost-effective modality at the current WTP threshold, while PPL could potentially be cost-effective in lower-income areas.

4.
Sci Rep ; 10(1): 16632, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024251

RESUMO

This study aims to investigate the relationship between key physicochemical parameters related to composting process and bioavailability of Cd, As and Cr during swine manure composting through regulating different initial carbon to nitrogen (C/N) ratios (15:1, 20:1, 25:1) and bulking agent types (straw, green waste). Results showed that higher initial C/N ratio of 20:1 or 25:1 and straw as bulking agent were optimal to reduce the bioavailability of Cd, As and Cr (62.4%, 20.6% and 32.2% reduction, respectively). Redundancy analysis implied that the bioavailability of Cd was significantly associated with total phosphorus and total nitrogen, deducing the formation of phosphate precipitation and biosorption might participated in the reaction process, while that of As and Cr were mainly influenced by organic matter (OM), cation exchange capacity (CEC) and OM, CEC, electric conductivity, respectively. A total of 48.5%, 64.6% and 62.2% of Cd, As and Cr redistribution information could be explained by the above parameters. Further correlation analysis revealed that bioavailable As and Cr were negatively correlated with humic acid to fulvic acid ratio. In summary, this study confirms that the mechanisms of phosphate precipitation, biosorption and humification played critical role in reducing Cd, As and Cr bioavailability during swine manure composting.

5.
Mediators Inflamm ; 2020: 1719279, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029103

RESUMO

Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators were involved in the pathogenesis of atherosclerosis. This study sought to investigate the effects of proatherogenic inflammatory and antiatherogenic inflammatory mediators on the proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations. We measured the expression levels of proatherogenic inflammatory/antiatherogenic inflammatory cytokines. This included interleukin-1 ß (IL-1 ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-10 (IL-10), interleukin-17 (IL-17), interleukin-13 (IL-13), and interleukin-37 (IL-37) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions after coronary stent implantations. Levels of IL-1 ß, IL-6, IL-8, TNF-α, and hs-CRP were remarkably increased (P < 0.001), and levels of IL-10, IL-17, IL-13, and IL-37 were remarkably lowered (P < 0.001) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions. Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators may be involved in the formation and progression of proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations.

6.
Anal Biochem ; : 113982, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035460

RESUMO

A novel and facile electrochemical immunosensor based on self-assembled gold nanorods modified glassy carbon electrode was developed for label-free and sensitive detection of Staphylococcus aureus (S. aureus). The gold nanorods were firstly assembled on the electrode surface by using poly-(diallyldimethylammonium chloride) (PDDA) and poly-(styrenesulfonate) (PSS) as the linkers, followed by the functionlization of anti-S. aureus antibodies. The immobilized antibodies on self-assembled gold nanorods could efficiently capture S. aureus to the modified electrode by the specific immune reaction, which clearly blocked the electron transfer of electrochemical probes on the electrode surface due to the resistance of S. aureus. Atomic force microscopy and electrochemical impedance spectroscopy were used to verify the stepwise assembly of the immunosensor fabrication. The immunosensor could detect S. aureus in a linear range from 1.8×103 to 1.8×107 CFU mL-1 with a low detection limit of 2.4×102 CFU mL-1. Furthermore, the designed electrochemical immunosensor was successfully applied to determine S. aureus in milk samples with acceptable results. The proposed immunosensor, obviating the complicated sample preparation, could be further expanded to sensitive detection other pathogens with the addition of specific antibodies.

7.
Nanomaterials (Basel) ; 10(10)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33036403

RESUMO

Wearable electronics, such as sensors, actuators, and supercapacitors, have attracted broad interest owing to their promising applications. Nevertheless, practical problems involving their sensitivity and stretchability remain as challenges. In this work, efforts were devoted to fabricating a highly stretchable and sensitive strain sensor based on dip-coating of graphene onto an electrospun thermoplastic polyurethane (TPU) nanofibrous membrane, followed by spinning of the TPU/graphene nanomembrane into an intertwined-coil configuration. Owing to the intertwined-coil configuration and the synergy of the two structures (nanoscale fiber gap and microscale twisting of the fiber gap), the conductive strain sensor showed a stretchability of 1100%. The self-inter-locking of the sensor prevents the coils from uncoiling. Thanks to the intertwined-coil configuration, most of the fibers were wrapped into the coils in the configuration, thus avoiding the falling off of graphene. This special configuration also endowed our strain sensor with an ability of recovery under a strain of 400%, which is higher than the stretching limit of knees and elbows in human motion. The strain sensor detected not only subtle movements (such as perceiving a pulse and identifying spoken words), but also large movements (such as recognizing the motion of fingers, wrists, knees, etc.), showing promising application potential to perform as flexible strain sensors.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33058942

RESUMO

Mammalian cells contain an elaborate network of organelles and molecular machines that orchestrate essential cellular processes. Visualization of this network at a molecular level is vital for understanding these cellular processes. Here we present a model system based on nerve growth factor (NGF)-differentiated PC12 cells (PC12+) and suitable for high resolution imaging of organelles and molecular machines in situ. We detail an optimized imaging pipeline that effectively combines correlative light and electron microscopy (CLEM), cryo-focused ion beam (cryo-FIB), cryo-electron tomography (cryo-ET), and sub-tomogram averaging to produce three-dimensional and molecular resolution snapshots of organelles and molecular machines in near-native cellular environments. Our studies demonstrate that cryo-ET imaging of PC12+ systems provides an accessible and highly efficient avenue for dissecting specific cellular processes in mammalian cells at high resolution.

10.
Neural Plast ; 2020: 8850653, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029119

RESUMO

As the global population ages, the incidence of neurodegenerative diseases has risen. Furthermore, it has been suggested that depression, especially in elderly people, may also be an indication of latent neurodegeneration. Stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) are usually accompanied by depression. The urgent challenge is further enforced by psychiatric comorbid conditions, particularly the feeling of despair in these patients. Fortunately, as our understanding of the neurobiological substrates of maladies affecting the central nervous system (CNS) has increased, more therapeutic options and novel potential biological mechanisms have been presented: (1) Neurodegenerative diseases share some similarities in their pathological characteristics, including changes in neuron structure or function and neuronal plasticity. (2) MicroRNAs (miRNAs) are small noncoding RNAs that contribute to the pathogenesis of diverse neurological disease. (3) One ubiquitous neurotrophin, brain-derived neurotrophic factor (BDNF), is crucial for the development of the nervous system. Accumulating data have indicated that miRNAs not only are related to BDNF regulation but also can directly bind with the 3'-UTR of BDNF to regulate BDNF and participate in neuroplasticity. In this short review, we present evidence of shared biological substrates among stroke, AD, PD, and depression and summarize the possible influencing mechanisms of acupuncture on the neuroplasticity of these diseases. We discuss neuroplasticity underscored by the roles of miRNAs and BDNF, which might further reveal the potential biological mechanism of neurodegenerative diseases and depression by acupuncture.

11.
Aging (Albany NY) ; 12(19): 19083-19094, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33041262

RESUMO

BACKGROUND: Apathy is common in Alzheimer's disease (AD) patients. However, its relation with other clinical symptoms in AD and brain structural changes in magnetic resonance imaging is unclear. RESULTS: Compared with AD with no apathy group, cognitive function and activities of daily living were significantly impaired and neuropsychiatric symptoms were obviously presented in AD with apathy group (P<0.05). The frequency of Apolipoprotein E genotypes was not significantly different (P>0.05). Correlation analyses and multiple linear analyses revealed that thickness of left temporal pole and volume of posterior corpus callosum were significantly and negatively correlated with Modified Apathy Estimation Scale score in AD patients (P<0.05). CONCLUSIONS: Apathy with AD is positively correlated with cognitive impairment, neuropsychiatric symptoms and poor activities of daily living. Atrophy of left temporal pole and posterior corpus callosum presented by MRI is positively related with apathy of AD. METHODS: In this study, 137 AD patients were recruited and divided into AD with apathy group and AD with no apathy group according to Modified Apathy Estimation Scale score. We evaluated patients' cognitive function, neuropsychiatric symptoms and activities of daily living, detected the frequency of Apolipoprotein E genotypes and measured cortical thickness and volume by magnetic resonance imaging (MRI).

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1605-1610, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067961

RESUMO

OBJECTIVE: To investigate the effect and possible mechanism of up-regulation of p-Akt by doxycycline (DOX) on myeloma cell line H929. METHODS: Multiple myeloma cell line H929 was treated with DOX at different concentrations for different times, and cell proliferation rate was measured by CCK-8 assay. The protein expression level of p-Akt, PTEN, p-PDK1, p-mTOR, p-GSK-3ß, and p-BAD was analyzed by Western blot. The mRNA levels of mTOR, BCL-2, and NF-κB was analyzed by RT-PCR. PI3K inhibitor Wortmannin was used to antagonize the up-regulation of p-Akt, and the cell proliferation and p-Akt protein expression level were analyzed by CCK-8 assay and Western blot respectively. RESULTS: DOX could inhibit the proliferation of H929 cells and up-regulate the expression of p-Akt at the same time. The protein levels of both p-PDK1 and PTEN in H929 cells did not alter significantly during DOX treatment. The expressions of p-BAD and p-GSK-3ß were up-regulated in H929 cells after treated with DOX, but the expression of p-mTOR was not altered. The mRNA levels of mTOR, BCL-2, and NF-κB in H929 were all down-regulated in H929 cells during DOX treatment. The effect up-regulating p-Akt level by DOX was suppressed when DOX combined with PI3K inhibitor Wortmannin and Wortmannin could enhance the inhibitory effect of DOX in H929 cells. CONCLUSION: DOX can activate PI3K/Akt signaling pathway in H929 cells, and antagonizing this effect of DOX may enhance its cytotoxicity to myeloma cells.


Assuntos
Mieloma Múltiplo , Apoptose , Linhagem Celular Tumoral , Doxiciclina/farmacologia , Glicogênio Sintase Quinase 3 beta , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Regulação para Cima
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1762-1768, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067987

RESUMO

OBJECTIVE: To investigate the effect of dasatinib on the expansion of NK cells in vitro, as well as the subsets, receptor expression and cytotoxic function of NK cells. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy adult volunteers and cultured with SCGM added IL-2 and IL-15 for expansion of NK cells. In this culture system, dasatinib of different concentrations were added. Cell counting and phenotyping by flow cytometry were used to evaluate the amplification efficiency of NK cells. FCM was used to detect the expression of receptors on the surface of NK cells and the distribution of subsets. Subsequently, degranulation assay and CFSE/7AAD based cytotoxicity assay were used to detect the effects of dasatinib on NK cytotoxicity against leukemia cell line K562 cells. RESULTS: The expansion efficiency of NK cells in vitro could be increased by dasatinib at the concentration range of 5-50 nmol/L, and the expansion efficiency of NK cells reached the peak at 20 nmol/L of dasatinib. The NK cytotoxicity against K562 cells in dasatinib cultured group at the concentration of 20 nmol/L was significantly higher than that in control group. For the cells cultured by disatinib in vitro, the MFI of CD226, NKP46 and NKG2D was up-regulated; the ratio of NKG2A+CD57- subset was down-regulated, while the ratio of NKG2A-CD57+ subset was up-regulated.The degranulation response of NKG2A-CD57+ NK cells to K562 cells was stronger than that of NKG2A+CD57- NK cells. CONCLUSION: The results shows that appropriate dose of dasatinib(20 nmol/L) can increases the amplification efficiency of NK cells, simultaneously up-regulates the expression of NK activating receptors and increases the NKG2A-CD57+ subset, which lead to the enhancement of NK cytotoxicty against leukemia cell lines.


Assuntos
Antineoplásicos , Leucócitos Mononucleares , Adulto , Antineoplásicos/farmacologia , Dasatinibe/farmacologia , Humanos , Células K562 , Células Matadoras Naturais
14.
Med Sci Monit ; 26: e923680, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068389

RESUMO

BACKGROUND Asthma is a chronic disease with high morbidity rates. Brain-derived neurotrophic factor (BDNF) has been proven to induce airway hyper-responsiveness, but the function of BDNF in the wound-healing process of asthmatic human airway epithelial cells (HAECs) remains unclear. This study investigated the effects of BDNF in asthmatic children with injured HAECs. MATERIAL AND METHODS HAECs were obtained from healthy children and asthmatic children through bronchoscopy, and then cultured in air-liquid (ALI) interface with or without BDNF. A mechanical injury model was established for the wound-healing assay. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to measure BDNF mRNA expressions, while western blot assay was used for the measurement of BDNF and CCND1 protein expressions. Cell proliferation of impaired HAECs was assayed in a ³H-thymidine incorporation experiment. RESULTS The mRNA and protein levels of BDNF were overexpressed, and the wound-healing ability of HAECs decreased in asthma samples. Also, the cell proliferation of HAECs was suppressed in the asthmatic injury model and the injury-induced increase of CCND1 protein expressions was inhibited in asthma. Although mRNA and protein expressions of BDNF remained unchanging in healthy HAECs, there was an increase in impaired asthmatic HAECs. Upregulating BDNF led to a decrease in wound-healing ability of HAECs in both healthy children and children with asthma. Simultaneously, overexpressed BDNF reduced the CCND1 protein expressions in healthy HAECs, but had little impact on asthmatic HAECs. CONCLUSIONS Brain-derived neurotrophic factor (BDNF) inhibited wound-healing and cell proliferative ability of human airway epithelial cells (HAECs) in asthmatic children.

15.
Int J Biol Sci ; 16(15): 2853-2867, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061801

RESUMO

MicroRNAs (miRNAs) and N6-methyladenosine (m6A) are known to serve as key regulators of acute myeloid leukemia (AML). Our previous microarray analysis indicated miR-550-1 was significantly downregulated in AML. The specific biological roles of miR-550-1 and its indirect interactions and regulation of m6A in AML, however, remain poorly understood. At the present study, we found that miR-550-1 was significantly down-regulated in primary AML samples from human patients, likely owing to hypermethylation of the associated CpG islands. When miR-550-1 expression was induced, it impaired AML cell proliferation both in vitro and in vivo, thus suppressing tumor development. When ectopically expressed, miR-550-1 drove the G0/1 cell cycle phase arrest, differentiation, and apoptotic death of affected cells. We confirmed mechanistically that WW-domain containing transcription regulator-1 (WWTR1) gene was a downstream target of miR-550-1. Moreover, we also identified Wilms tumor 1-associated protein (WTAP), a vital component of the m6A methyltransferase complex, as a target of miR-550-1. These data indicated that miR-550-1 might mediate a decrease in m6A levels via targeting WTAP, which led to a further reduction in WWTR1 stability. Using gain- and loss-of-function approaches, we were able to determine that miR-550-1 disrupted the proliferation and tumorigenesis of AML cells at least in part via the direct targeting of WWTR1. Taken together, our results provide direct evidence that miR-550-1 acts as a tumor suppressor in the context of AML pathogenesis, suggesting that efforts to bolster miR-550-1 expression in AML patients may thus be a viable clinical strategy to improve patient outcomes.

16.
Disabil Rehabil ; 42(22): 3243-3249, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33084443

RESUMO

Purpose: To demonstrate the validity and reliability of a smartphone app to measure ROM after stroke.Materials and methods: Twenty-one stroke survivors with a diagnosis of stroke that affected the motor cortex or subcortical motor pathways and were hospital inpatients at one of two metropolitan hospitals were recruited. A within-session test-retest design was used to compare ROM measurements taken using the GetMyROM app for iPhone to those taken by a digital inclinometer. Torque-controlled passive elbow and wrist extension were collected and statistical analysis of concurrent validity and test-retest reliability performed.Results: GetMyROM app was valid when compared to the digital inclinometer for measuring passive ROM of the elbow (r = .98, p = .0001, ICC = 0.97) and wrist (r = .97, p = .0001, ICC = 0.96) in individuals with acute stroke. Both the GetMyROM app and inclinometer demonstrated excellent test-retest reliability: ICC values are 0.84 to 0.93, and standard error of measurement between 6° to 10°.Conclusion: The GetMyROM app may be implemented in a clinical setting similar to that where the study was conducted, enabling rehabilitation physicians and therapists to use a smartphone to take precise measurements of ROM in daily clinical practice.Implications for rehabilitationApproximately half of all stroke survivors experience reduced passive upper limb range of movement.Accurate measurement of passive upper limb range of movement using validated assessments and/or instruments is paramount.This study demonstrates that the GetMyROM app is valid and reliable compared to the gold standard comparison (digital inclinometer), and is therefore appropriate to use in clinical settings to take precise measurements.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33085741

RESUMO

MicroRNAs (miRNAs) play an important role in cardiac function and metabolism. However, whether they regulate insulin resistance (IR) of cardiomyocytes remains unclear. The aim of the present study was to shed light on this issue with a focus on miR-150. We found here that miR-150 level was elevated in myocardium of type 2 diabetes mellitus (T2DM) rat model and in insulin-resistant cardiomyocytes induced by high glucose (25 mM) and high insulin (1 µM). Deregulation of miR-150 downregulated the protein and mRNA levels of glucose transporter 4 (GLUT4) as assessed by western blot, real-time polymerase chain reaction (qPCR), and immunofluorescence assays. Overexpression of miR-150 inhibited glucose utilization in cardiomyocytes as detected by 2-deoxyglucose transport and glucose consumption assays. In contrast, knockdown of miR-150 significantly increased glucose uptake in cardiomyocytes. Moreover, GLUT4 translocation was increased after transfection of miR-150 inhibitor (AMO-150). Collectively, miR-150 reduced glucose utilization by directly decreasing the expression and translocation of GLUT4 in the cardiomyocytes with IR and therefore might be a new therapeutic target for metabolic diseases such as T2DM.

18.
J Mater Chem B ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006351

RESUMO

Enzyme mimics have been developed by imitating and incorporating specific features of native enzymes to achieve catalytic activity, and are expectedly comparable to that of native enzymes. Here, inspired by the "catalytic triad" in serine proteases, a series of peptide-based enzyme mimics were designed to follow the rational design principle of peptides via self-assembly, and were further applied in the degradation of di(2-ethylhexyl)phthalate (DEHP). The relationship of the structure of enzyme mimics with their degradation activity was analyzed by transmission electron microscopy, fluorescence spectroscopy, circular dichroism, Raman spectroscopy, X-ray diffraction spectroscopy, and computational modeling. These results show that the hydrophobic skeleton, amino acid sequence, species, and periodic distribution have important effects on the structure of the peptide sequence and the number of hydrogen bonds; in addition, pH can also affect the self-assembly characteristics of peptides and the formation of stable fibers, which are all closely linked to the catalytic activity of the enzyme mimics. The self-assembled peptides had a stable fibrous morphology and secondary structure after the DEHP degradation assay. The enzyme mimics with high catalytic activity constructed from the self-assembled peptides may provide guidance for the future degradation of DEHP in food packaging or water treatment, and also give insights into the design of enzyme mimics in other related fields.

19.
Hum Brain Mapp ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030795

RESUMO

Subjective cognitive decline (SCD) is a high-risk yet less understood status before developing Alzheimer's disease (AD). This work included 76 SCD individuals with two (baseline and 7 years later) neuropsychological evaluations and a baseline T1-weighted structural MRI. A machine learning-based model was trained based on 198 baseline neuroimaging (morphometric) features and a battery of 25 clinical measurements to discriminate 24 progressive SCDs who converted to mild cognitive impairment (MCI) at follow-up from 52 stable SCDs. The SCD progression was satisfactorily predicted with the combined features. A history of stroke, a low education level, a low baseline MoCA score, a shrunk left amygdala, and enlarged white matter at the banks of the right superior temporal sulcus were found to favor the progression. This is to date the largest retrospective study of SCD-to-MCI conversion with the longest follow-up, suggesting predictable far-future cognitive decline for the risky populations with baseline measures only. These findings provide valuable knowledge to the future neuropathological studies of AD in its prodromal phase.

20.
J Neuroinflammation ; 17(1): 295, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036632

RESUMO

BACKGROUND: Spinal cord injury (SCI) favors a persistent pro-inflammatory macrophages/microglia-mediated response with only a transient appearance of anti-inflammatory phenotype of immune cells. However, the mechanisms controlling this special sterile inflammation after SCI are still not fully elucidated. It is known that damage-associated molecular patterns (DAMPs) released from necrotic cells after injury can trigger severe inflammation. High mobility group box 1(HMGB1), a ubiquitously expressed DNA binding protein, is an identified DAMP, and our previous study demonstrated that reactive astrocytes could undergo necroptosis and release HMGB1 after SCI in mice. The present study aimed to explore the effects and the possible mechanism of HMGB1on macrophages/microglia polarization, as well as the neuroprotective effects by HMGB1 inhibition after SCI. METHODS: In this study, the expression and the concentration of HMGB1 was determined by qRT-PCR, ELISA, and immunohistochemistry. Glycyrrhizin was applied to inhibit HMGB1, while FPS-ZM1 to suppress receptor for advanced glycation end products (RAGE). The polarization of macrophages/microglia in vitro and in vivo was detected by qRT-PCR, immunostaining, and western blot. The lesion area was detected by GFAP staining, while neuronal survival was examined by Nissl staining. Luxol fast blue (LFB) staining, DAB staining, and western blot were adopted to evaluate the myelin loss. Basso-Beattie-Bresnahan (BBB) scoring and rump-height Index (RHI) assay was applied to evaluate locomotor functional recovery. RESULTS: Our data showed that HMGB1 can be elevated and released from necroptotic astrocytes and HMGB1 could induce pro-inflammatory microglia through the RAGE-nuclear factor-kappa B (NF-κB) pathway. We further demonstrated that inhibiting HMGB1 or RAGE effectively decreased the numbers of detrimental pro-inflammatory macrophages/microglia while increased anti-inflammatory cells after SCI. Furthermore, our data showed that inhibiting HMGB1 or RAGE significantly decreased neuronal loss and demyelination, and improved functional recovery after SCI. CONCLUSIONS: The data implicated that HMGB1-RAGE axis contributed to the dominant pro-inflammatory macrophages/microglia-mediated pro-inflammatory response, and inhibiting this pathway afforded neuroprotection for SCI. Thus, therapies designed to modulate immune microenvironment based on this cascade might be a prospective treatment for SCI.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA