Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke.

We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357-395 of C X3 C motif chemokine ligand 1 (CX3CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3CL1 (comprising amino acids 357-395 of CX3CL1) disrupts the interaction between postsynaptic density-93 and CX3CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3CL1 (357-395aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3CL1. Furthermore, the a disintegrin and metalloprotease domain 17 (ADAM17) inhibitor GW280264x, which inhibits metalloprotease activity and prevents CX3CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3CL1 formation. Additionally, Tat-CX3CL1 (357-395aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31-34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3CL1 (357-395aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3CL1 (357-395aa) is a potential therapeutic agent for ischemic stroke.

[Effect of Dimethyl Fumarate (DMF) on T-cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore the effect and possible mechanism of dimethyl fumarate (DMF) on T-cell acute lymphoblastic leukemia (T-ALL), and provide experimental and theoretical basis for the clinical treatment of T-ALL. METHODS: Jurkat cells were treated with different concentrations of DMF for 24 hours, and then the proportion and absolute count of Ki67-positive Jurkat cells were analyzed by flow cytometry. Meanwhile, the protein levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and E3 ubiquitin ligase HACE1 in Jurkat cells treated with DMF for 24 hours were evaluated by Western blot. Nrf2 proteins were co-immunoprecipitated in Jurkat cells, and then HACE1 protein was assessed by Western blot. Plasmids of Flag-Nrf2 and different gradients of Flag-HACE1 were transfected into HEK293T cells, and the levels of Flag-Nrf2 were detected by Western blot after 48 hours. RESULTS: DMF could significantly inhibit the proportion and absolute count of Ki67-positive Jurkat cells, and DMF inhibited the proliferation of Jurkat cells in a dose-dependent manner (r=0.9595, r=0.9054). DMF could significantly up-regulate the protein levels of Nrf2 and E3 ubiquitin ligase HACE1 in Jurkat cells (P<0.01, P<0.01). HACE1 physically interacted with Nrf2 in Jurkat cells. Overexpression of Flag-HACE1 significantly increased the protein level of Flag-Nrf2 in a dose-dependent manner (r=0.9771). CONCLUSION: DMF inhibits the proliferation of T-cell acute lymphoblastic leukemia cell. The mechanism may be that, DMF significantly up-regulates the protein levels of Nrf2 and E3 ubiquitin ligase HACE1, and HACE1 interacts with Nrf2 and positively regulates Nrf2 protein level.

Anxiety and depression in parents of sick neonates: a hospital-based study.

AIMS AND OBJECTIVES: To investigate the prevalence of anxiety and depression in parents of hospitalised neonates and to analyse their relationship with other factors such as stress and social support, to provide evidence for targeted clinical interventions. BACKGROUND: The perinatal period, a special susceptibility to negative emotions, is a period that women and their spouses have to face. In this time, the fact that the neonates have to be hospitalised is no doubt a huge psychological stress to their parents. Little understanding of the hospitalisation environment, lacking awareness of neonatal diseases as well as concerns about the neonates' safety, can easily lead to negative emotions in parents. Under the influence of negative mood, parents could become irritable and vulnerable, which may do harm to their physical and mental health, impact family harmony and even result in ineffective communication with doctors, affecting the care of neonates. DESIGN: This study applied a cross-sectional study design. METHODS: The psychological status of 600 parents (400 fathers and 200 mothers) was assessed in the first week of the hospitalisation of neonates, using the Self-Rating Anxiety Scale, Self-Rating Depressive Scale, Social Support Rating Scale and Perceived Stress Scale. RESULTS: The results of the cross-sectional survey showed that 20% of fathers and 24% of mothers had symptoms of anxiety, while 30.8% of fathers and 35% of mothers had depressive symptoms. The total scores for anxiety and depression in these parents were significantly higher than the normal population (p<0.01). The level of social support and perceived stress were the most important factors relating to parental anxiety and depression. CONCLUSION: Parents of hospitalised neonates are more prone to suffer from negative emotions than normal population. Anxiety and depression are common emotions in these parents. However, the social support they receive is far from satisfactory, so timely and effective nursing interventions are essential. RELEVANCE TO CLINICAL PRACTICE: Health professionals should understand the mental health of parents with hospitalised neonates and take measures to reduce their psychological pressure so as to improve their care of the neonates, and help to maintain the harmony and stability of families and the whole society.

microRNA expression profiling of the developing mouse heart.

microRNAs (miRNAs) play an important role in regulating normal organ physiology and development. Many miRNAs show spatially and temporally restricted expression patterns during embryogenesis and organogenesis. This study aimed to characterize the miRNA profile of the fetal mouse heart at 4 key time-points [embryonic day (E)12.5, E14.5, E16.5 and E18.5] in its development, by performing a sequencing by oligonucleotide ligation and detection (SOLiD) miRNA screen. The 4 time-points were designated as groups M1 (E18.5), M2 (E16.5), M3 (E14.5) and M4 (E12.5). miRNAs found to have consistent fold-changes of >2.0) between the 4 time-points were selected for further analysis. Ten miRNAs (mmu-miR-23b, mmu-miR-24, mmu-miR-23a, mmu-miR-375, mmu-miR-29a, mmu-miR-93, mmu-miR-21, mmu-miR-25, mmu-let-7b and mmu-miR-27b) that were the most highly expressed in the 4 groups, including the percentage >1% of total read counts, were identified. No miRNA was consistently downregulated or upregulated. There were 16 differentially expressed miRNAs between the later development group (M1+M2) and the early development group (M3+M4), which were validated by quantitative real-time PCR. Several members of the let-7 miRNA cluster (mmu-let-7a/7d/7e/7f) were upregulated in the later development group compared with the early development group. A network analysis of the predicted targets of mmu-let-7a/7d/7e/7f identified 5 target genes (FOXP1, TBX5, HAND1, AKT2 and PPARGC1A), known to be involved in cardiac development. Therefore, this study identified several miRNAs that are abundantly expressed in the developing heart, several of which are differentially expressed in the 4 time-points studied. Findings of this analysis may thus clarify the mechanisms of normal heart development and provide a physiological basis for future studies on congenital heart disease.

[Causes and countermeasure of complications in operative management of intra - articular fracture of calcaneus].

OBJECTIVE: To discuss the probable causes of the post-surgery complications with the intra-artcular fracture of calcaneus, the proper steps for prevention and solution. METHODS: Seventy-one patients (76 injured feet) included 49 males and 22 females aged from 19 to 56 years old (mean 35.6 years). According to Sanders' classification, 23 cases (24 injuried feet) belonged to type II, 36 (38 injured feet) were type III, the remain 12 (14 injured feet) met the criteria of type IV. All the patients received the operation of open reduction, autogenous bone grafting and internal fixation with stainless steel plates. RESULTS: Thirteen injuried feet developed early complications. Two injuried feet got the superficial layer of the wound disrupted and infected, I had the deep layer of the wound disrupted and infected. Cutaneous necrosis at the pointed end of the wound occurred in 7 cases. Another 1 developed osteomyelitis. Two cases suffered from sural nerve damage. Two injuried feet developed late complications, both of them suffered from arthritis of talocalcaneal joint. All the patients were followed up at least 6 months (ranged from 6 to 42 months, mean 19 months). According to Kerr's post-surgery evaluation criteria, 34 injuried feet were excellent, 32 were fine, 9 were acceptable, only 1 was bad. CONCLUSION: If proper measures are taken, the post-surgery complications of intra-articular fracture of calcaneus will be reduced. This requires us to be strict in selecting operation indication, to make a good plan and preparation, to select a right time for operation, to improve surgical skills and pay more attention to peri-surgery nursing. If complications happen, according measures should be taken in order to get a better outcome.