Silencing of secreted phosphoprotein 1 attenuates sciatic nerve injury-induced neuropathic pain: Regulating extracellular signal-regulated kinase and neuroinflammatory signaling pathways.

BACKGROUND: Neuropathic pain (NP) is a chronic pathological pain that affects the quality of life and is a huge medical burden for affected patients. In this study, we aimed to explore the effects of secreted phosphoprotein 1 (SPP1) on NP. METHODS: We established a chronic constriction injury (CCI) rat model, knocked down SPP1 via an intrathecal injection, and/or activated the extracellular signal-regulated kinase (ERK) pathway with insulin-like growth factor 1 (IGF-1) treatment. Pain behaviors, including paw withdrawal threshold (PWT), paw withdrawal latency (PWL), lifting number, and frequency, were assessed. After sacrificing rats, the L4-L5 dorsal root ganglion was collected. Then, SPP1 levels were determined using quantitative polymerase chain reaction (qPCR) and western blot analysis. The levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-10, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-ß were determined using qPCR and enzyme-linked immunosorbent assay. The levels of ERK pathway factors were determined via western blot analysis. RESULTS: We found that CCI decreased PWT and PWL, increased the lifting number and frequency, and upregulated SPP1 levels. The loss of SPP1 reversed these CCI-induced effects. Additionally, CCI upregulated IL-1ß, TNF-α, IL-6, EGF, and VEGF levels, downregulated TGF-ß levels, and activated the ERK pathway, while silencing of SPP1 abrogated these CCI-induced effects. Moreover, IGF-1 treatment reversed the effects of SPP1 loss. CONCLUSIONS: The data indicate that silencing SPP1 attenuates NP via inactivation of the ERK pathway, suggesting that SPP1 may be a promising target for NP treatment.

Highly Sensitive Love Mode Acoustic Wave Platform with SiO2 Wave-Guiding Layer and Gold Nanoparticles for Detection of Carcinoembryonic Antigens.

A highly sensitive and precise Love wave mode surface acoustic wave (SAW) immunosensor based on an ST-cut 90°X quartz substrate and an SiO2 wave-guiding layer was developed to detect cancer-related biomarkers of carcinoembryonic antigens (CEAs). A delay line structure of the SAW device with a resonant frequency of 196 MHz was designed/fabricated, and its surface was functionalized through CEA antibody immobilization. The CEA antibodies were bound with gold nanoparticles and CEA antibodies to form a sandwich structure, which significantly amplified the mass loading effect and enhanced the maximum responses by 30 times. The center frequency of the Love wave immunosensor showed a linear response as a function of the CEA concentration in the range of 0.2-5 ng/mL. It showed a limit of detection of 0.2 ng/mL, and its coefficient of determination was 0.983. The sensor also showed minimal interference from nonspecific adsorptions, thus demonstrating its promise for point-of-care applications for cancer biomarkers.

Remimazolam alleviates neuropathic pain via regulating bradykinin receptor B1 and autophagy.

OBJECTIVES: Neuropathic pain (NP) represents a broad scope of various pathological ramifications of the nervous system. Remimazolam is a proved sedative in treating neuropathic pain. Considering the Bradykinin receptor's vital role and the potentials of Bradykinin receptor B1 (BDKRB1) in the neuropathic pain-signalling pathway, we nominated them as a primary target for remimazolam. METHODS: In this study, rats were injected with complete freund's adjuvant (CFA) to construct NP models in vivo. BV2 microglia cells were treated with LPS to establish NP model in vitro. qRT-PCR, ELISA, western blot and immunofluorescence were applied to determine gene expression. KEY FINDINGS: Our findings revealed that BDKRB1 was overexpressed in NP models in vivo, while R715 (an antagonist of BDKRB1) suppressed the levels of BDKRB1 and inhibited the hyperpathia induced by spinal nerve litigation surgery. Moreover, remimazolam inactivated BDKRB1 signalling via suppressing NF-κB translocation and decreased the release of pro-inflammatory cytokines. Additionally, remimazolam suppressed the translocation of NF-κB, and inhibited autophagic lysosome formation in vivo and in vitro. However, R838 (an agonist of BDKRB1) reversed the effects of remimazolam. CONCLUSIONS: Remimazolam downregulated BDKRB1, inhibited BDKRB1/RAS/MEK signalling pathway and regulated the autophagic lysosome induction, exhibiting a better outcome in the NP.