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1.
Anal Biochem ; : 113609, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032545

RESUMO

Intracellular pH plays an important role in various biological processes; abnormal pH changes in the intracellular compartment leads to the production of free radicals, the disruption of membrane contractility, inappropriate apoptosis, and necrosis, resulting in serious illness. Although fluorescent probes have widely been used to detect pH levels owing to their high sensitivity and specificity, there is still a demand for near-infrared (NIR) fluorescent probes with high Stokes shift. Here, a NIR fluorescent probe, PipDC, comprising N-ethyl piperazine (response unit) and naphthyl dicyanoisophorone (fluorophore), was designed for pH sensing. The probe has an extremely large Stokes shift (290 nm), and its fluorescence intensity at 730 nm sharply increases when the environment changes from basic to acidic owing to the protonation of piperazine, which results in the quenching of the photoinduced electron transfer effect. It exhibited a specific response to acidic microenvironments regardless of other interfering substances. In addition, PipDC operates well in the lysosome environment in living cells and displays an off-on fluorescence response with pH alterations. Together, these results suggest that PipDC is a promising fluorescent probe for intracellular pH sensing.

2.
Dev Biol ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32007453

RESUMO

In Drosophila, the deposition of the germ plasm at the posterior pole of the oocyte is essential for the abdomen and germ cell formation during embryogenesis. To assemble the germ plasm, oskar (osk) mRNA, produced by nurse cells, should be localized and anchored on the posterior cortex of the oocyte. Processing bodies (P-bodies) are cytoplasmic RNA granules responsible for the 5'-3' mRNA degradation. Evidence suggests that the components of P-bodies, such as Drosophila decapping protein 1 and Ge-1, are involved in the posterior localization of osk. However, whether the decapping core enzyme, Drosophila decapping protein 2 (dDcp2), is also involved remains unclear. Herein, we generated a dDcp2 null allele and showed that dDcp2 was required for the posterior localization of germ plasm components including osk. dDcp2 was distributed on the oocyte cortex and was localized posterior to the osk. In the posterior pole of dDcp2 mutant oocytes, osk was mislocalized and colocalized with F-actin detached from the cortex; moreover, considerably fewer F-actin projections were observed. Using the F-actin cosedimentation assay, we proved that dDcp2 interacted with F-actin through its middle region. In conclusion, our findings explored a novel function of dDcp2 in assisting osk localization by modulating the formation of F-actin projections on the posterior cortex.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32041882

RESUMO

The pathogenesis of bipolar disorder (BD) has remained enigmatic, largely because genetic animal models based on identified susceptible genes have often failed to show core symptoms of spontaneous mood cycling. However, pedigree and induced pluripotent stem cell (iPSC)-based analyses have implicated that dysfunction in some key signaling cascades might be crucial for the disease pathogenesis in a subpopulation of BD patients. We hypothesized that the behavioral abnormalities of patients and the comorbid metabolic abnormalities might share some identical molecular mechanism. Hence, we investigated the expression of insulin/synapse dually functioning genes in neurons derived from the iPSCs of BD patients and the behavioral phenotype of mice with these genes silenced in the hippocampus. By these means, we identified synaptotagmin-7 (Syt7) as a candidate risk factor for behavioral abnormalities. We then investigated Syt7 knockout (KO) mice and observed nocturnal manic-like and diurnal depressive-like behavioral fluctuations in a majority of these animals, analogous to the mood cycling symptoms of BD. We treated the Syt7 KO mice with clinical BD drugs including olanzapine and lithium, and found that the drug treatments could efficiently regulate the behavioral abnormalities of the Syt7 KO mice. To further verify whether Syt7 deficits existed in BD patients, we investigated the plasma samples of 20 BD patients and found that the Syt7 mRNA level was significantly attenuated in the patient plasma compared to the healthy controls. We therefore concluded that Syt7 is likely a key factor for the bipolar-like behavioral abnormalities.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32043188

RESUMO

In the present work, we used systematic engineering at transport and transcription levels to significantly enhance alkaline α-amylase production in Bacillus subtilis 168M. Signal peptide YwbN' proved to be optimal. Alkaline α-amylase production was elevated by deleting a putative peptide segment of YwbN'. Insertion of arginine (R) between residues 5 and 6 of YwbN'∆p further increased the protein yield. Enhancing positive charges at sites 4 and 10 and decreasing the hydrophobicity of the H-region of YwbN'∆p were critical for improving alkaline α-amylase production in B. subtilis 168M. PHpaII was the optimal promoter, and deleting - 27T or - 31A from PHpaII enhanced the transcription of the target gene. Using a single-pulse feeding-based fed-batch system, alkaline α-amylase activity of B. subtilis 168M P∆-27T was increased by 250.6-fold, compared with B. subtilis 168M A1.

5.
Int J Mol Sci ; 21(3)2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32046264

RESUMO

Interleukin (IL)-33 is a member of the IL-1 family, which acts as an alarmin. Several studies suggested that IL-33 inhibited osteoclastogenesis and bone resorption. Tumor necrosis factor-α (TNF-α) is considered a direct inducer of osteoclastogenesis. However, there has been no report regarding the effect of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. The objective of this study is to investigate the role of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. In an in vitro analysis of osteoclastogenesis, osteoclast precursors, which were derived from bone marrow cells, were treated with or without IL-33 in the presence of TNF-α. Tartrate-resistant acid phosphatase (TRAP) staining solution was used to assess osteoclast formation. In an in vivo analysis of mouse calvariae, TNF-α with or without IL-33 was subcutaneously administrated into the supracalvarial region of mice daily for 5 days. Histological sections were stained for TRAP, and osteoclast numbers were determined. Using micro-CT reconstruction images, the ratio of bone destruction area on the calvariae was evaluated. The number of TRAP-positive cells induced by TNF-α was significantly decreased with IL-33 in vitro and in vivo. Bone resorption was also reduced. IL-33 inhibited IκB phosphorylation and NF-κB nuclear translocation. These results suggest that IL-33 inhibited TNF-α-induced osteoclastogenesis and bone resorption.

6.
Chemosphere ; 244: 125493, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32050327

RESUMO

Zearalenone (ZEA), as a contaminant commonly found in our daily diet, has been widely studied for its toxicity. However, the exact mechanism underlying ZEA induced reproduction disorders remains unclear. Our study aimed to elucidate the underlying relationship between aberrations in the gut microbiota and the degeneration of the ovarian reserve following exposure to ZEA. Four-week-old mice were treated with different doses (0, 20, 40 µg/kg bw/day) of ZEA for 2 weeks and it was found that the primordial follicles were dramatically decreased when compared to untreated controls. Moreover, we applied metagenomic shotgun sequencing to investigate the effects of ZEA exposure on the population composition and function of gut microbiota. The results showed that the abundance of three susceptible bacterial strains, parabacteroides, bacteroides and lachnospiraceae were increased in a dose-dependent manner after ZEA exposure, whereas the bacterial glycerophospholipid metabolism pathway was greatly suppressed. Of note, utilizing LC/MS we found lysophosphatidylcholines (LPCs), important metabolites in the process of glycerophospholipid metabolism, were markedly decreased in the plasma of the ZEA treated mice. In conclusion, our findings here provide evidences that the dysfunction in gut microbiome after ZEA exposure may affect the ovarian reserve.

7.
Cell Death Differ ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051546

RESUMO

Rab5 is a master regulator for endosome biogenesis and transport while its in vivo physiological function remains elusive. Here, we find that Rab5a is upregulated in several in vivo and in vitro myogenesis models. By generating myogenic Rab5a-deficient mice, we uncover the essential roles of Rab5a in regulating skeletal muscle regeneration. We further reveal that Rab5a promotes myoblast differentiation and directly interacts with insulin receptor substrate 1 (IRS1), an essential scaffold protein for propagating IGF signaling. Rab5a interacts with IRS1 in a GTP-dependent manner and this interaction is enhanced upon IGF-1 activation and myogenic differentiation. We subsequently identify that the arginine 207 and 222 of IRS1 and tyrosine 82, 89, and 90 of Rab5a are the critical amino acid residues for mediating the association. Mechanistically, Rab5a modulates IRS1 activation by coordinating the association between IRS1 and the IGF receptor (IGFR) and regulating the intracellular membrane targeting of IRS1. Both myogenesis-induced and IGF-evoked AKT-mTOR signaling are dependent on Rab5a. Myogenic deletion of Rab5a also reduces the activation of AKT-mTOR signaling during skeletal muscle regeneration. Taken together, our study uncovers the physiological function of Rab5a in regulating muscle regeneration and delineates the novel role of Rab5a as a critical switch controlling AKT-mTOR signaling by activating IRS1.

8.
J Ren Nutr ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32063457

RESUMO

OBJECTIVE: The in-hospital mortality rate of patients with end-stage renal disease (ESRD) is 6-8 times greater than that of the general population. A large fraction of patients with ESRD are frail, which further exacerbates this poor outcome. This study aimed to determine the impact of frailty on in-hospital outcomes of patients with ESRD. DESIGN AND METHODS: This population-based, retrospective study used data from the Nationwide Inpatient Sample (NIS), the largest all-payer US inpatient care database. Data of 1,424,026 hospitalized patients on maintenance dialysis between 2005 and 2014 were included. Patients were classified with respect to frailty status. Primary endpoints were all-cause in-hospital mortality, discharge disposition, length of hospital stay, and hospital costs. Patient characteristics included age, sex, race, income, insurance status, and Charlson's comorbidity index. Logistic regression and linear regression analyses were conducted to evaluate the associations between frailty and clinical outcomes. RESULTS: After adjustment for the confounders, hospitalized patients with frailty on maintenance dialysis were at double the risk of in-hospital mortality, 3 times the risk of discharge to long-term facilities, had hospital stays 5 days longer, and incurred $40,000 more in-hospital costs than those without frailty. The impact of frailty on all these in-hospital outcomes was greater among patients aged <65 years than among older adults. CONCLUSION: For hospitalized patients on maintenance dialysis, frailty independently predicts worse in-hospital outcomes, with stronger effects on younger patients. The development of adequate interventions for frailty in patients with ESRD and vigilance in treating this subgroup during hospitalization are highly warranted.

9.
Gene ; 737: 144411, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32006596

RESUMO

Long non-coding RNAs (lncRNAs) have been identified in cerebral ischemia-reperfusion (I/R) injury nowadays. Herein, we uncovered the function and underlying mechanism of the lncRNA Rian in cerebral I/R injury. The oxygen-glucose deprivation model in N2a cells was offered to mimic cerebral I/R injury in vitro. Trypan blue staining, reactive oxygen species (ROS) production, and caspase-3 activity were used to evaluate cell apoptosis. Then, middle cerebral artery occlusion was conducted to evaluate the function of lncRNA Rian in mice. Real-time PCR and western blotting were performed to determine the expression of lncRNA Rian, miR-144-3p, GATA binding protein 3 (GATA3), caspase-3, Bax, and Bcl-2. The results showed that both Rian and GATA3 were downregulated, and miR-144-3p was upregulated in cerebral I/R injury in vitro and in vivo. Overexpression of Rian could inhibit the cell apoptosis induced by oxygen-glucose deprivation. Furthermore, overexpression of Rian distinctly reduced the infarct size, and it also improved the neurological score. Overexpression of Rian could abolish miR-144-3p-mediated I/R injury in vitro and in vivo. Besides, GATA3 was the target of miR-144-3p and GATA3 could be regulated co-operatively by miR-144-3p and Rian. Consequently, these findings showed that the Rian/miR-144-3p/GATA3 axis is an essential signaling in cerebral I/R injury. The lncRNA Rian may serve as a potential target for novel treatment in patients with ischemic stroke.

10.
Anal Chim Acta ; 1103: 32-48, 2020 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-32081187

RESUMO

In recent years, layered double hydroxides (LDHs) have garnered a lot of attention in analytical chemistry, due to their advantages such as relatively simple synthesis, low cost, possession of large specific surface area and high catalytic activity, and biocompatibility. The most common applications of LDH in analytical chemistry such as sorbents in sample extraction, electrode materials in electrochemical sensing and color indicators in colorimetric detection have been well reported. Generally, the LDHs are prepared as composites with nanomaterials, or constructed with specific three-dimensional structures, befitting the applications desired for them. However, the applications of LDHs (as extraction sorbents, color indicators and in electrochemical sensing) are usually limited in these scenarios. To help address these challenges, future trends and developmental prospects of LDHs materials in analytical chemistry are discussed in this article. Besides, the strategies associated with the design of LDHs, including the structural aspects, for potential analytical applications are presented and reviewed.

11.
Environ Pollut ; 261: 114007, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-32036198

RESUMO

Zearalenone (ZEA), an estrogen-like mycotoxin, is commonly detected in animal feeds including improperly stored grains. It has been well demonstrated that ovarian granulosa cells (GCs) perform vital roles during follicular development, however, the competing endogenous RNA (ceRNA) network in GCs after ZEA exposure remains to be well described. Here, for the first time, we adopted whole-transcriptome sequence technology to explore the molecular mechanism of ZEA toxicology on porcine GCs. The results provide evidence that the cell cycle of porcine GCs is arrested in the G2/M phase after exposure to ZEA. Furthermore, bioinformation analysis found that cell cycle arrest related genes were perturbed, including CDK1, CCNB1, CDC25A, and CDC25C, which was consistent with the results of RT-qPCR, immunofluorescence, and Western Blotting. Based on the whole-transcriptome sequence data, by constructing ceRNA networks related to cell cycle arrest, we observed that ZEA exposure arrested cell cycle progression at the G2/M phase in porcine GCs, and non-coding RNAs (ncRNAs) played an important role in this process via regulating the expressions of cell cycle arrest related genes. Taken together, our data here provides strong data to support that the toxicological mechanism regarding the widely distributed toxicant ZEA acts through ceRNA networks in porcine granulosa cells.

12.
RNA Biol ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32070191

RESUMO

RNA secondary structure elements in the mRNA 3'-untranslated regions (3'UTR) play important roles in post-transcriptional regulation. RNA structure elements in the viral RNA provide valuable model for studying diverse regulation mechanisms. Herpesvirus genomes are double-stranded DNA with GC-rich sequences, which can be transcribed into abundant GC-rich RNAs. It is valuable to explore the structures and function of those GC-rich RNAs. We identified a G2-quadruplex-forming sequence named PQS18-1 in the 3'UTR of the unique immediate early gene of Pseudorabies virus (PRV), an important member of alphaherpesvirus subfamily. The RNA PQS18-1 was folded into parallel G-quadruplex structure, enhancing gene expression. Both non-G-quadruplex mutant and G3-quadruplex mutant in the 3'UTR showed lower gene expression level than the wildtype G2-quadruplex. A chemical compound destroyed PQS18-1 G2-quadruplex and suppressed gene expression, accordingly reducing PRV replication by one titre in the PK15 cells at 24 hours post infection. Our findings indicated that the RNA G2-quadruplex in 3'UTR was essential for high expression of IE180 gene, and it could be a specific post-transcription regulation element in response to small molecules or other macromolecules. This study discovers a novel RNA G2-quadruplex in the 3'UTR of an immediate early gene of alphaherpesvirus, and provides a new nucleic acid target for anti-virus drug design.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32095885

RESUMO

PURPOSE: Stereotactic body radiotherapy (SBRT) is the primary treatment method for early-stage non-small cell lung cancer (NSCLC) considered inoperable due to medical comorbidities. However, the application of SBRT in patients aged ≥ 75 years has not been adequately studied. This retrospective study aimed to investigate the effectiveness and safety of SBRT in early-stage NSCLC patients aged ≥ 75 years, and the impact of treatment on nutritional status and self-care ability. METHODS: Histopathologically confirmed early-stage (T1-3N0M0) NSCLC patients aged ≥ 75 years treated with SBRT between 2013 and 2018 at our center were identified from the electronic database. Treatment efficacy, treatment toxicities, impact of treatment on nutritional status, and self-care ability were retrospectively analyzed. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Event (CTCAE) (Common 2010) version 4.0. Nutritional status was assessed by Nutritional Risk Screening 2002 criteria, and self-care ability by Barthel index and fall risk index. RESULTS: A total of 68 patients were enrolled. Median follow-up duration was 46.3 (3.9-80.1) months. The 1-, 3-, and 5-year overall survival rates were 92.6%, 77.2%, and 59.1%, respectively, and the 1-year, 3-year and 5-year local control rates were 95.6%, 88.9% and 85.6%, respectively. Grade 1-2 and grade 3 radiation pneumonitis occurred in 60/68 (96.8%) and 1/68 (1.5%) patients, respectively. Fall risk at 3 months after treatment was not significantly different from that before treatment (P = 0.22). Barthel index increased significantly after treatment (P < 0.001). CONCLUSIONS: SBRT appears to be effective and safe for NSCLC patients aged ≥ 75 years, with no adverse impact on nutritional status and self-care ability.

14.
Pediatr Neonatol ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31964590

RESUMO

BACKGROUND: The study of genetic polymorphisms of surfactant-lipids related genes can help to understand individual variability in the susceptibility to development of pulmonary pathologies. The purpose of this study was to evaluate the association of polymorphisms of surfactant-lipids related genes (LPCAT1, CHPT1 and PCYT1B) with the risk/severity of respiratory distress syndrome (RDS) in preterm neonates among the Chinese Han population in Southern China. METHODS: Four hundred and forty-six preterm neonates were enrolled in a case-control study. Six polymorphisms of 3 genes were analyzed by PCR amplification of genomic DNA and genotyping was performed using an improved multiplex ligation detection reaction (iMLDR) technique based on LDR. RESULTS: The GG genotype and G allele of LPCAT1-rs9728 were found less frequently in the RDS group than in the controls (11.5% vs. 22.0% and 38.3% vs. 48.2%, respectively) (p < 0.05). CONCLUSION: This report is the first study to evaluate a direct genetic association between polymorphisms of LPCAT1 and RDS development in Chinese Han preterm infants. Our study raises the possibility that a genetic variation of LPCAT1 could be implicated in the pathophysiology of RDS in preterm neonates. GG genotype and G allele of rs9728 are protective factors for the development of RDS in preterm infants.

16.
Oncol Rep ; 43(2): 662-670, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894344

RESUMO

Cullin 4A (CUL4A) is a member of the cullin family of proteins and has been demonstrated to be abnormally expressed in various types of malignancies. However, the function of CUL4A in metastasis of lung adenocarcinoma to the bone has rarely been reported. The aim of present of the study was to explore the biological functions and potential underlying molecular mechanisms of CUL4A in lung adenocarcinoma, highlighting a novel therapeutic target for the diagnosis and treatment of patients with lung adenocarcinoma. A549­CUL4A, H1299­CUL4A and H460­shCUL4A cells were created using lentiviral infection. The efficiency of knockdown or overexpression was assessed using reverse transcription­quantitative PCR and western blotting. The effects of CUL4A on proliferation, migration and invasion of lung adenocarcinoma cells in vitro and metastasis to the bone in vivo were determined using an MTT assay, colony formation assay, wound­healing assay, Transwell assay and a mouse model of bone metastasis. The relationship between CUL4A and the EMT­activator zinc finger E­box binding homeobox 1 (ZEB1) were detected by western blotting. The results showed that overexpression of CUL4A in lung adenocarcinoma cells increased proliferation, migration and invasion, and increased metastasis of A549 to the bones in vivo. Silencing of CUL4A expression in lung adenocarcinoma cells reduced proliferation, migration and invasion in vitro. Mechanistically, CUL4A transcriptionally upregulated expression of ZEB1 which resulted in epithelial­mesenchymal transition, which in turn promoted metastasis of lung adenocarcinoma to the bones. Taken together, these results suggest that CUL4A may serve an important regulatory role in the development of metastasis of lung adenocarcinoma to the bone.

17.
Carbohydr Polym ; 230: 115639, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887964

RESUMO

A novel, cost-effective and biomass-derived adsorbent was fabricated by coating polydopamine on lanthanum-chitosan hydrogel (La-CS@PDA), which were endowed with a plentiful of amine groups. The diffusion structure of channel-network of La-CS@PDA made it well used in phosphate removal in wastewater treatment. The Langmuir isotherm delivered the maximal adsorption capacity about 195.3 mg/g, which was superior to most reported phosphate removal materials. More significantly, in the presence of competitive anions Cl-, SO42-, HCO3-, NO3-, F- and HCrO4-, the resultant La-CS@PDA still conducted distinct selectivity for phosphate, which could be attributed to the selective binding sites of La species in the composite. Under continuous adsorption, the dynamic experimental data fitted well with Thomas model which imitates industrial practical application. By virtue of more fortes of high efficiency, ease of separation and expectable mechanical strength, as-prepared La-CS@PDA might be a promising candidate of dephosphorizing sorbent.

18.
Mucosal Immunol ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900405

RESUMO

Worldwide the incidence of cancer has been continuing increasing. Mucositis of the gastrointestinal tract is a common side effect in patients under chemotherapy. Anticancer drug busulfan, used for treating chronic myeloid leukemia especially in pediatric patients, causes mucositis of the gastrointestinal tract. Alginate oligosaccharides (AOS) are natural products with attractive pharmaceutical potentials. We aimed to investigate, at the single-cell level, AOS preventing small intestine mucositis induced by busulfan. We found that busulfan disturbed the endoplasmic reticulum and mitochondria of cells in the small intestine, damaged cell membranes especially cell junctions, and disrupted microvilli; all of which were rescued by AOS. Single-cell RNA sequencing analysis and functional enrichment analysis showed that AOS could recover small intestinal function. Deep analysis found that AOS improved the expression of transcriptional factors which explained AOS regulating gene expression to improve small intestine function. Further investigation in IPEC-J2 cells found that AOS acts its function through mannose receptor signaling pathway. Moreover, the improved blood metabolome confirmed small intestinal function was recovered by AOS. As a natural product with many advantages, AOS could be developed to assist in the recovery of intestinal functions in patients undergoing anticancer chemotherapy or other treatments.

19.
Development ; 147(3)2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31988187

RESUMO

The strength of Notch signaling contributes to pleiotropic actions of Notch; however, we do not yet have a full understanding of the molecular regulation of Notch-signaling strength. We have investigated the mode of Notch activation in binary fate specification in the Drosophila spermathecal linage, where Notch is asymmetrically activated across three divisions to specify different cell fates. Using clonal analysis, we show that Delta (Dl) serves as the ligand for Notch in the first and second divisions. Dl and Serrate (Ser) function redundantly in the third division. Compared with the third division, cell-fate decision in the second division requires a lower level of Suppressor of Hairless protein, and, consequently, a lower level of Notch signaling. Several Notch endosomal trafficking regulators differentially regulate Notch signaling between the second and third divisions. Here, we demonstrate that cell differentiation in spermathecae involves different Notch-activation modes, Notch-signaling strengths and Notch-trafficking regulations. Thus, the Drosophila spermathecal lineage is an exciting model for probing the molecular mechanisms that modulate the Notch signaling pathway.

20.
FASEB J ; 34(2): 2541-2553, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31908023

RESUMO

Brain-derived neurotrophic factor precursor (proBDNF) has been reported to strengthen the dysfunction of monocytes/macrophages in animal studies. However, it is still unknown the roles of proBDNF in the dysfunction of monocytes in the inflammatory diseases in humans. In the present study, we showed that proBDNF and pan neurotrophic receptor p75 were significantly upregulated in monocytes from healthy donors (HD) after lipopolysaccharide treatment. Exogenous proBDNF treatment upregulated CD40 and proinflammatory cytokines expression in monocytes including interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. In Stanford type-A acute aortic dissection (AAD) patients, proBDNF was upregulated in CD14+ CD163+ CX3CR1+ M2- but not CD14+ CD68+ CCR2+ M1-like monocytes. In addition, sera from AAD patients activated gene expression of proinflammatory cytokines in cultured PBMCs from HD, which was attenuated by proBDNF monoclonal antibody (Ab-proB) treatment. These findings suggested that upregulation of proBDNF in M2-like monocytes may contribute to the proinflammatory response in the AAD.

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