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Objective:To study the efficacy of low-intensity focused ultrasound (LIFU) on neuropathic pain (NP) in mice, and its effect on the activation of astrocytes and the expression of pro-inflammatory cytokines were discussed.Methods:Thirty-six male C57BL/6J mice were randomly divided into three groups: sham operation (Sham) group and chroinc constriction injury (CCI) model group and treatment (CCI+ LIFU) group, 12 mice in each group.NP model was established by CCI on the sciatic nerve. The group of CCI+ LIFU received LIFU treatment for the anterior cingulate cortex (ACC) on the 7th day after surgery, the mechanical withdrawal threshold (MWT) on the affected side of mice was measured at preoperation 3, 6, 12, 18, 24, and 27 days after operation, respectively, H&E staining was used to observe pathological morphological changes in the ACC region, the expression levels of ACC region AQP4 and GFAP protein were detected by Western Blot and immunofluorescence, and the expression levels of ACC region pro-inflammatory cytokines IL-1β and TNF-α were detected by enzyme-linked immunosorption assay.Results:Compared with Sham group, MWT in the CCI group decreased from the 3rd day until the 27th day after surgery( P<0.05); Compared with the CCI group, the MWT in the CCI+ LIFU group increased on the 24th day after surgery, and was significantly higher than that of the CCI group on the 24th and 27th day after surgery ( P<0.05); LIFU stimulation did not produce significant pathological changes in the ACC region; Western Blot and immunofluorescence showed that AQP4 and GFAP protein expression in the ACC region were upregulated ( P<0.05) after peripheral nerve injury, while AQP4 and GFAP protein expression was downregulated after LIFU treatment ( P<0.05); Enzyme-linked immunosorbents showed that the expression of pro-inflammatory cytokines IL-1β and TNF-α in the region of ACC was upregulated ( P<0.05) after peripheral nerve injury, while the expression of IL-1β and TNF-α was downregulated after LIFU treatment ( P<0.05). Conclusions:LIFU can effectively relieve mechanical pain sensitivity symptoms in mice induced by CCI, possibly by inhibiting activation of astrocytes and neuro-inflammatory responses.
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The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding. Mapping emerging mutations from variants of SARS-CoV-2 on the resulting structure shows potential host-Nsp2 interaction regions. Using structural analysis together with affinity tagged purification mass spectrometry experiments, we identify Nsp2 mutants that are unable to interact with the actin-nucleation-promoting WASH protein complex or with GIGYF2, an inhibitor of translation initiation and modulator of ribosome-associated quality control. Our work suggests a potential role of Nsp2 in linking viral transcription within the viral replication-transcription complexes (RTC) to the translation initiation of the viral message. Collectively, the structure reported here, combined with mutant interaction mapping, provides a foundation for functional studies of this evolutionary conserved coronavirus protein and may assist future drug design.
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Objective To explore changes humoral immune factors and MDA in DEACMP patients.Methods 40 cases with carbon monoxide poisoning delayed brain were selected to be experiment group.40 cases of healthy people were selected to be control group.IL-2,IL-6,IL-10 and MDA were before and after treatment.Results IL-2,IL-6 of the experiment group were lower,IL-10,MDA were higher than the control group before treatment (P<0.05),both of IL-2,IL-6,IL-10 and MDA were recovery after the treatment (P<0.05).IL-6 of the experiment before treatment was significantly correlated with MMSE score(r =0.34,P <0.05).More severe cognitive impairment, the higher the level of concentration of IL-6(P<0.05). Conclusion The immune inflammatory cytokines and MDA play an important role in acute carbon monoxide poisoning delayed encephalopathy pathogenesis.Detection of the levels for judging the severity of the patient’s condition and prognosis has important significance.
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Objective To investigate the association between interleukin receptor antagonist (IL‐1Ra) encoded genes(IL‐1RN‐2018) polymorphisms and serum IL‐1Ra/IL‐1β with non‐small cell lung cancer (NSCLC ) .Methods Totally 85 cases of NSCLC were selected as the NSCLC group and 80 cases of healthy physical examination were selected as the control group from January 2012 to January 2014 .The IL‐1RN‐2018 T/C gene polymorphisms of the two groups were determined with the fluorescence quantitative PCR technique based on high resolution melting ,10% randomly selected samples were sequenced to prove the accura‐cy .The levels of IL‐1Ra and IL‐1βof two groups were determined with ELISA .Results (1)The onset risk of NSCLC in TC and TC+CC genotypes on IL‐1RN‐2018 site in the NSCLC group were increased by 2 .646 times and 2 .315 times respectively compared with TT genotype ,the difference had statistical significance(P0 .05) .(3)The serum IL‐1Ra and IL‐1βlev‐els in the NSCLC group were significantly higher than those in the control group ,but IL‐1Ra/IL‐1βin the NSCLC group was signif‐icantly lower (P0 .05) .Conclusion The C allele in IL‐1RN‐2018 site may increase the onset risk of NSCLC ;the reduction of serum IL‐1Ra/IL‐1βmay presage the risk of NSCLC .