Perineuronal Nets Alterations Contribute to Stress-Induced Anxiety-Like Behavior.

Anxiety disorder is one of the most common mental disorders worldwide, affecting nearly 30% of adults. However, its underlying molecular mechanisms are still unclear. Here we subjected mice to chronic restraint stress (CRS), a paradigm known to induce anxiety-like behavior in mice. CRS mice exhibited anxiety-like behavior and reduced synaptic transmission in the medial prefrontal cortex (mPFC). Notably, Wisteria Floribunda agglutinin (WFA) staining showed a reduction of perineuronal nets (PNNs) expression in the mPFC of CRS mice. And the mRNA and protein levels of aggrecan (ACAN), a core component of PNNs, were also reduced. Parallelly, enzymatic digestion of PNNs in the mPFC by injecting Chondroitinase ABC (chABC) resulted in anxiety-like behavior in mice. Fluoxetine (FXT) is a clinically prescribed antidepressant/anxiolytic drug. FXT treatment in CRS mice not only ameliorated their deficits in behavior and synaptic transmissions, but also prevented CRS-induced reduction of PNNs and ACAN expressions. This study demonstrates that proper PNNs level is critical to brain functions, and their decline may serve as a pathological mechanism of anxiety disorders.

Enriched Environment Enhances Sociability Through the Promotion of ESyt1-Related Synaptic Formation in the Medial Prefrontal Cortex.

Sociability stands as a crucial factor in the evolutionary success of all mammalian species. Notably, enriched environment (EE) housing has been shown to enhance sociability in mice. However, the precise underlying molecular mechanism remains elusive. In this study, we established an EE paradigm, housing mice for a 14-day period. Both enhanced sociability and an increased spine density in the medial prefrontal cortex (mPFC) of mice subjected to EE were detected. To elucidate the potential molecular pathway, we conducted high-performance liquid chromatography tandem mass spectrometry (HPLC-MS) analysis of the entire mPFC from both EE and home-caged (HC) housed mice. Our analysis identified 16 upregulated and 20 downregulated proteins in the EE group. Among them, Extended Synaptotagmin 1 (ESyt1), an activity-dependent endoplasmic reticulum (ER)-plasma membrane (PM) tethering protein associated with synaptic function and growth, emerged as a potentially key player in the increased synapse formation and enhanced sociability observed in EE-housed mice. Further investigation, involving the knockdown of ESyt1 expression via sh ESyt1 lentivirus in the mPFC, revealed that ESyt1 is crucial for increased spine density of mPFC and enhanced sociability of mice in an enriched environment but not in normal condition. Overall, our findings uncover a novel mechanistic insight into the positive influence of environmental enrichment on social behavior via ESyt1-mediated pathways.

Perineuronal Nets: From Structure to Neurological Disorders.

Perineuronal nets (PNN) is condensed extracellular matrix (ECM) in the central nervous system (CNS), which surrounds cell soma, axon initial segments, and synapses. In the brain, most neurons surrounded by PNN are interneurons, especially the parvalbumin-expressing interneurons (PVI). The formation of PNN is involved in the PVI maturation as well as the onset and closure of critical periods for developmental plasticity end. Dysfunction of PVI can lead to some neurological disorders, such as schizophrenia, bipolar depression, and Alzheimer's disease. Similarly, PNN assembling abnormalities are often observed in human patients and animal disease models. PNN is thought to have a neuroprotective effect and interact with signaling molecules to regulate synaptic plasticity and neuronal activity. In this review, we provide an overview of the composition, structure, and functions of PNN. In addition, we highlight abnormal changes in PNN components in pathological conditions. Understanding the roles of different components of PNN will bring us a new perspective on brain plasticity and neurological disorders.

Effect of buried vs. exposed Kirschner wire osteosynthesis on phalangeal, metacarpal and distal radial fractures: A systematic review and meta-analysis.

BACKGROUND: During Kirschner wire osteosynthesis for phalangeal, metacarpal and distal radial fractures, a key clinical decision is whether to leave a Kirschner wire exposed or bury it beneath the skin. Therefore, we conducted a meta-analysis to evaluate the clinical effect of buried and exposed Kirschner wire osteosynthesis on phalangeal, metacarpal and distal radial fractures. METHODS: PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched and clinical trials that evaluated buried and exposed Kirschner wire osteosynthesis for phalangeal, metacarpal and distal radial fractures were identified. Methodological qualities of studies were assessed by using the Cochrane Collaboration tool and Newcastle-Ottawa Scale. Publication bias was detected using Begg's test and Egger's test. Sensitivity analyses were performed by excluding one study at a time to determine whether overall results were reliable. RESULTS: Two randomized controlled trials (RCT) and five case-controlled studies involving 1446 patients were included in the analysis. Sensitivity analyses indicated that the results of each study were statistically robust. Begg's test or Egger's test revealed no significant publication bias. Our meta-analysis indicated that exposed Kirschner wire osteosynthesis had a significantly higher infection rate than its buried counterpart. Additionally, buried Kirschner wire osteosynthesis resulted in a significantly higher rate of Kirschner wire removal in operating room than the exposed one. Our meta-analysis exhibited no statistical differences between the two procedures in the rate of early pin removal. CONCLUSIONS: Meta-analysis of available RCTs and case-controlled studies demonstrated that buried Kirschner wire osteosynthesis had a lower infection rate but tended to lead to more frequent Kirschner wire removal in the operating room as compared to its exposed counterpart. TRIAL REGISTRATION: PROSPERO (CRD42018105249).

The protective effect of WKYMVm peptide on inflammatory osteolysis through regulating NF-κB and CD9/gp130/STAT3 signalling pathway.

The balance between bone formation and bone resorption is closely related to bone homeostasis. Osteoclasts, originating from the monocyte/macrophage lineage, are the only cell type possessing bone resorption ability. Osteoclast overactivity is thought to be the major reason underlying osteoclast-related osteolytic problems, such as Paget's disease, aseptic loosening of prostheses and inflammatory osteolysis; therefore, disruption of osteoclastogenesis is considered a crucial treatment option for these issues. WKYMVm, a synthetic peptide, which is a potent FPR2 agonist, exerts an immunoregulatory effect. This peptide inhibits the production of inflammatory cytokines, such as (IL)-1ß and TNF-α, thus regulating inflammation. However, there are only few reports on the role of WKYMVm and FPR2 in osteoclast cytology. In the current study, we found that WKYMVm negatively regulates RANKL- and lipopolysaccharide (LPS)-induced osteoclast differentiation and maturation in vitro and alleviates LPS-induced osteolysis in animal models. WKYMVm down-regulated the expression of osteoclast marker genes and resorption activity. Furthermore, WKYMVm inhibited osteoclastogenesis directly through reducing the phosphorylation of STAT3 and NF-kB and indirectly through the CD9/gp130/STAT3 pathway. In conclusion, our findings demonstrated the potential medicinal value of WKYMVm for the treatment of inflammatory osteolysis.

Interleukin-27 prevents LPS-induced inflammatory osteolysis by inhibiting osteoclast formation and function.

Osteolysis is a serious complication of several chronic inflammatory diseases and is closely associated with a local chronic inflammatory reaction with a variety of causes. Inflammatory factors and osteoclastogenesis can enhance bone erosion. Interleukin-27 (IL-27) is speculated to play an important role in the physiological immune response. However, there are few studies on its effects on osteoclastogenesis. In this study, IL-27 was shown to inhibit receptor activator nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. The gene expression levels of osteoclast (OC)-specific genes, such as nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and C-FOS, which are essential for OC differentiation and bone resorption, were significantly reduced. Further investigating the underlying mechanism, we found that IL-27 significantly reduced RANKL-induced osteoclastogenesis by inhibiting the phosphorylation of IκB and phosphorylation of nuclear factor κB (NF-κB) p65. Furthermore, IL-27 was shown to inhibit lipopolysaccharide (LPS)-induced osteolysis in vivo. Collectively, these results indicate that IL-27 may be a potential candidate for the treatment of osteolytic diseases.

Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesis via NF-κB-NFATc1 signal pathway.

Skeletal homeostasis is closely effectuated by the regulation of bone formation and bone resorption. Osteoclasts are multinuclear giant cells responsible for bone resorption. Overactivated osteoclasts and excessive bone resorption result in various lytic bone diseases, such as osteoporosis, osteoarthritis, periprosthetic infection, and inflammatory aseptic loosening of orthopedic implants. In consideration of the severe side effects caused by the currently available drugs, exploitation of novel drugs has gradually attracted attention. Because of its anti-inflammatory, antioxidant, and antitumor capacities, diallyl disulfide (DADS), a major oil-soluble organosulfur ingredient compound derived from garlic, has been widely researched. However, the effects of DADS on osteoclasts and lytic bone diseases are still unknown. In this study, we investigated the effects of DADS on receptor activator of NF-κB ligand (RANKL)- and LPS-mediated osteoclastogenesis, LPS-stimulated proinflammatory cytokines related to osteoclasts, and LPS-induced inflammatory osteolysis. The results showed that DADS significantly inhibited RANKL-mediated osteoclast formation, fusion, and bone resorption in a dose-dependent manner via inhibiting the NF-κB and signal transducer and activator of transcription 3 signaling and restraining the interaction of NF-κB p65 with nuclear factor of activated T cells cytoplasmic 1. Furthermore, DADS also markedly suppressed LPS-induced osteoclastogenesis and reduced the production of proinflammatory cytokines with LPS stimulation to indirectly mediate osteoclast formation. Consistent with the in vitro results, DADS prevented the LPS-induced severe bone loss by blocking the osteoclastogenesis. All of the results indicate that DADS may be a potential and exploitable drug used for preventing and impeding osteolytic lesions.-Yang, J., Tang, R., Yi, J., Chen, Y., Li, X., Yu, T., Fei, J. Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesis via NF-κB-NFATc1 signal pathway.

[Simultaneous determination of three sesquiterpene lactones in Inula hupehensis by RP-HPLC].

OBJECTIVE: A RP-HPLC method was developed for simultaneous determination of bigelovin, ergolide and tomentosin in Inula hupehensis. METHOD: An Agilent C18 column (4.6 mm x 250 mm, 5 microm) was used for separation at 40 degrees C. The mobile phase was acetonitrile-water, and the flow rate was 1.2 mL x min(-1). The detection wavelength was set at 210 nm. RESULT: The method has good linearity in the ranges of 0.01792-0.1792 g x L(-1) (r =0.9999) for bigelovin, 0.0424-0.4240 g x L(-1) (r =0.9996) for ergolide, and 0.044 8-0.4480 g x L(-1) (r = 0.9996) for tomentosin. The average recoveries of bigelovin, ergolide, and tomentosin were 98.5%, 98.2%, 98.4%, with the RSD of 1. 3%, 1.3%, 1.7%, respectively. The results demonstrated that there was a significant difference in the contents of three sequterpene lactones among the tested Inulae Flos. CONCLUSION: The results indicated that the present RP-HPLC method is simple, quick and accurate, and can be used for the quality control of I. hupehensis, especially for the authentication of Inulae Flos.

A second modification of poly[diaquadi-µ-citrato(3-)-trizinc(II)].

A second modification of the zinc(II) coordination polymer with citric acid, [Zn(3)(C(6)H(5)O(7))(2)(H(2)O)(2)](n) or [Zn(citrate)(2)(H(2)O)(2)], has been synthesized under hydro-thermal conditions by reacting zinc acetate with citric acid. The structure contains two unique Zn atoms, one with a distorted octa-hedral coordination and located on an inversion centre, and one with a distorted tetra-hedral coordination. The ZnO(6) and ZnO(4) units are linked into layers extending parallel to (010).