Objective To investigate the mechanisms by which astaxanthin(AST)alleviates oxaliplatin(OXA)-induced neuropathic pain through antioxidant pathways so as to provide theoretical basis for clinical intervention.Methods Animal experiments:SD rats were divided into five groups(n=6):control group,OXA(4 mg/kg)group,OXA+Oil group,OXA+AST(5 mg/kg)group,and OXA+AST(10 mg/kg)group.Mechanical and cold pain thresholds were measured at day 0,7,14,and 21.Malondialdehyde(MDA)content and superoxide dismutase(SOD)activity in the dorsal root ganglia(DRG)were detected using the thiobarbituric acid(TBA)method and WST-1 assay,respectively.Western blotting was performed to analyze the expressions of Nrf2 and HO-1.Cell experiments:neuro-2a cells were divided into control group,OXA(50 μmol/L)group,AST(10 μmol/L)group,and OXA(50 μmol/L)+AST(10 μmol/L)group.Cells were treated with nerve growth factor(NGF,50 ng/mL)to induce growth,and morphological changes were observed under an inverted microscope.Intracellular reactive oxygen species(ROS)level and mitochondrial superoxide were measured using DCFH-DA fluorescent probe and MitoSOXTM red,respectively.Mitochondrial function was assessed by JC-1 assay.Western blotting was used to detect Nrf2 and HO-1 expressions.Results Animal experiments:① Mechanical and cold pain thresholds were reduced in OXA and OXA+Oil groups(P＜0.05),while AST significantly increased these thresholds in OXA-treated rats(P＜0.05).② SOD activity decreased while MDA content increased in the DRG of OXA-treated rats(P＜0.05).AST restored SOD activity and reduced MDA level(P＜0.05,P＜0.01).③ Western blotting showed elevated Nrf2 and HO-1 expressions in OXA group(P＞0.05),which were further upregulated by AST(P＜0.05,P＜0.01).Cell experiments:① OXA reduced the number of neurite-bearing cells and shortened the average neurite length(P＜0.05).Inverted microscopic observation revealed that AST intervention increased both parameters(P＜0.01,P＜0.001).② OXA increased intracellular and mitochondrial ROS fluorescence intensity(P＜0.05),which was attenuated by AST(P＜0.01).③ JC-1 assay revealed decreased mitochondrial membrane potential in OXA group(P＜0.01),which was partially reversed by AST(P＜0.05).④ Western blotting results showed that OXA upregulated Nrf2 and HO-1 expressions(P＜0.05,P＜0.01),and AST further enhanced their levels(P＜0.01).Conclusion AST alleviates OXA-induced neuropathic pain by promoting Nrf2/HO-1 expression,enhancing SOD activity,reducing lipid peroxidation and ROS production,and improving mitochondrial function.

Objective To investigate the mechanisms by which astaxanthin(AST)alleviates oxaliplatin(OXA)-induced neuropathic pain through antioxidant pathways so as to provide theoretical basis for clinical intervention.Methods Animal experiments:SD rats were divided into five groups(n=6):control group,OXA(4 mg/kg)group,OXA+Oil group,OXA+AST(5 mg/kg)group,and OXA+AST(10 mg/kg)group.Mechanical and cold pain thresholds were measured at day 0,7,14,and 21.Malondialdehyde(MDA)content and superoxide dismutase(SOD)activity in the dorsal root ganglia(DRG)were detected using the thiobarbituric acid(TBA)method and WST-1 assay,respectively.Western blotting was performed to analyze the expressions of Nrf2 and HO-1.Cell experiments:neuro-2a cells were divided into control group,OXA(50 μmol/L)group,AST(10 μmol/L)group,and OXA(50 μmol/L)+AST(10 μmol/L)group.Cells were treated with nerve growth factor(NGF,50 ng/mL)to induce growth,and morphological changes were observed under an inverted microscope.Intracellular reactive oxygen species(ROS)level and mitochondrial superoxide were measured using DCFH-DA fluorescent probe and MitoSOXTM red,respectively.Mitochondrial function was assessed by JC-1 assay.Western blotting was used to detect Nrf2 and HO-1 expressions.Results Animal experiments:① Mechanical and cold pain thresholds were reduced in OXA and OXA+Oil groups(P＜0.05),while AST significantly increased these thresholds in OXA-treated rats(P＜0.05).② SOD activity decreased while MDA content increased in the DRG of OXA-treated rats(P＜0.05).AST restored SOD activity and reduced MDA level(P＜0.05,P＜0.01).③ Western blotting showed elevated Nrf2 and HO-1 expressions in OXA group(P＞0.05),which were further upregulated by AST(P＜0.05,P＜0.01).Cell experiments:① OXA reduced the number of neurite-bearing cells and shortened the average neurite length(P＜0.05).Inverted microscopic observation revealed that AST intervention increased both parameters(P＜0.01,P＜0.001).② OXA increased intracellular and mitochondrial ROS fluorescence intensity(P＜0.05),which was attenuated by AST(P＜0.01).③ JC-1 assay revealed decreased mitochondrial membrane potential in OXA group(P＜0.01),which was partially reversed by AST(P＜0.05).④ Western blotting results showed that OXA upregulated Nrf2 and HO-1 expressions(P＜0.05,P＜0.01),and AST further enhanced their levels(P＜0.01).Conclusion AST alleviates OXA-induced neuropathic pain by promoting Nrf2/HO-1 expression,enhancing SOD activity,reducing lipid peroxidation and ROS production,and improving mitochondrial function.

Objective To explore the value of a clinical diagnostic model of heart failure(HF)based on disulfidptosis-related genes.Methods The differentially expressed disulfidetosis-related genes from the training set of Gene Expression Omnibus Series(GSE)57345 were obtained,and then analyzed with Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)en-richment analysis,and Metascape disease enrichment analysis.Six male C57BL/6J mice were ran-domly divided into control group(intraperitoneal injection of normal saline)and HF group(intra-peritoneal injection of isoproterenol),with 3 mice in each group.Real-time quantitative PCR was applied to detect the expression levels of key genes.Results GO enrichment analysis revealed that the differentially expressed disulfidetosis-related genes were mainly involved in platelet aggrega-tion and other aspects.KEGG showed they were significantly enriched in tight junctions,vascular smooth muscle contraction and other signaling pathways.Metascape enrichment analysis indicated that these genes were mainly related to focal glomerulosclerosis,glomerular disease,platelet dis-ease,tumor infiltration,nephrotic syndrome and other diseases.The HF group had significantly higher heart weight-to-body weight ratio,and lower ejection fraction,fractional shortening,cardiac output and stroke volume than the control group(P＜0.05,P＜0.01).The cardiac mRNA levels of BNP and MYH10 were significantly higher[1.026±0.501 vs 0.686±0.187,P=0.038;1.469(1.782,2.670)vs 0.360(0.786,1.117),P=0.000],while those of MYL6 and TLN1 was obviously lower(0.575±0.105 vs 1.000±0.202,P=0.027;0.429±0.114 vs 1.000±0.109,P=0.000)in the HF group than the control group.Conclusion Our constructed HF diagnostic model has better di-agnostic performance.

Objective To explore the value of a clinical diagnostic model of heart failure(HF)based on disulfidptosis-related genes.Methods The differentially expressed disulfidetosis-related genes from the training set of Gene Expression Omnibus Series(GSE)57345 were obtained,and then analyzed with Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)en-richment analysis,and Metascape disease enrichment analysis.Six male C57BL/6J mice were ran-domly divided into control group(intraperitoneal injection of normal saline)and HF group(intra-peritoneal injection of isoproterenol),with 3 mice in each group.Real-time quantitative PCR was applied to detect the expression levels of key genes.Results GO enrichment analysis revealed that the differentially expressed disulfidetosis-related genes were mainly involved in platelet aggrega-tion and other aspects.KEGG showed they were significantly enriched in tight junctions,vascular smooth muscle contraction and other signaling pathways.Metascape enrichment analysis indicated that these genes were mainly related to focal glomerulosclerosis,glomerular disease,platelet dis-ease,tumor infiltration,nephrotic syndrome and other diseases.The HF group had significantly higher heart weight-to-body weight ratio,and lower ejection fraction,fractional shortening,cardiac output and stroke volume than the control group(P＜0.05,P＜0.01).The cardiac mRNA levels of BNP and MYH10 were significantly higher[1.026±0.501 vs 0.686±0.187,P=0.038;1.469(1.782,2.670)vs 0.360(0.786,1.117),P=0.000],while those of MYL6 and TLN1 was obviously lower(0.575±0.105 vs 1.000±0.202,P=0.027;0.429±0.114 vs 1.000±0.109,P=0.000)in the HF group than the control group.Conclusion Our constructed HF diagnostic model has better di-agnostic performance.

Objective : To investigate the protective effect of adiponectin APN on myocardial injury caused by sep⁃ sis and its possible mechanism. : Methods Results : Compared with sham group , the expression of Bax , cleaved Caspase3 protein increased and the expression of Bcl⁃2 protein decreased in LPS group. Compared with LPS group , the injury in APN + LPS group was significantly alleviated , showing that the expression of Bax , cleaved caspase3 protein decreased and the expression of Bcl⁃2 protein increased. Meanwhile , compared with sham group , the expression of Cx43 increased in LPS group and decreased in APN + LPS group. Conclusion Adiponectin can attenuate LPS⁃induced cardiac injury in septic mice. The mechanism may be through the inhibition of apoptotic signal pathway and the expression of Cx43.

Objective: To investigate the role of connexin 43 ( Cx43) in acute sympathetic stress induced by phe- nylephrine (PE) overactivation of α1-adrenergic receptor ( α1-AR) in cardiomyocytes． Methods: Cardiomyocytes of H9C2 rats were randomly divided into control group，PE alone treatment group，Gap26 ( Cx43 specific inhibitor) intervention group and Gap26 alone treatment group．PE alone treatment group was treated with 50 μmol / L PE for 15 min．The Gap26 intervention group was pretreated with 0. 5 μmol / L Gap26 for 30 min，and then treated with 50 μmol / L PE for 15 min．The protein and mRNA expression levels of Cx43，NLRP3 inflammasome，interleukin-1 β (IL-1 β) ，Caspase-1，interleukin-18 (IL-18 ) were detected by Western blot and qRT-PCR. The expression and co-location of Cx43 in cardiomyocytes were observed by immunofluorescence assay，and the expression of inflamma- tory cytokines IL-1 β and IL-18 in cardiomyocytes was detected by ELISA. Results: Compared with control group， the protein and mRNA levels of Cx43，NLRP3，Caspase-1 and IL-18 in PE group increased．Compared with PE a- lone treatment group，the protein and mRNA levels of Cx43，NLRP3，Caspase-1 and IL-18 decreased after Gap26 intervention，but they were still higher than those of control group． Similarly ，immunofluorescence showed that Cx43 protein expression increased in PE alone group，while Cx43 expression was down-regulated in Gap26 inter- vention group compared with PE alone group．ELISA results showed that the expression of IL-1 β and IL-18 was sig- nificantly up-regulated in PE alone group，but down-regulated in Gap26 intervention group． Conclusion Cx43 is involved in α1-AR activation induced cardiac acute sympathetic stress by regulating NLRP3 inflammasome.

TetR family transcriptional regulators (TFRs) are widely distributed in bacteria and archaea, and the first discovered TFR was confirmed to control the expression of tetracycline efflux pump in Escherichia coli. TFRs can bind DNAs and ligands. Small molecule ligands can induce conformational changes of TFRs, inhibiting or promoting TFRs to control target gene expression. Currently, TFRs have a wide variety of ligands, including carbohydrates, proteins, fatty acids and their derivatives, metal ions, and so on. Due to the diversity of ligands, TFRs regulate a wide range of physiological processes, from basic carbon metabolism and nitrogen metabolism to quorum sensing and antibiotic biosynthesis. On the basis of the recent studies in our laboratory and the literature, we review here the regulatory mechanism mediated by ligands of TFRs in primary and secondary metabolism, as well as the application of ligands for TFRs in the development of gene route and the activation of antibiotic biosynthesis.
Anti-Bacterial Agents ; Bacteria/metabolism* ; Bacterial Proteins/metabolism* ; Gene Expression Regulation, Bacterial ; Ligands ; Quorum Sensing

Objective To observe the expression of PAR2 and TMEM16A in the model of chronic constriction injury (CCI) in rat dorsal root ganglion (DRG) neurons,and to explore the role of it in the neuropathic pain.Methods Rats were divided into Sham operation group (Sham) and CCI group.Both groups were observed respectively to determine thermal withdrawal latency (TWL).The expression of PAR2 and TMEM16A in the dorsal root ganglion of the rat was analyzed using Western blot and immunofluorescence.Results The difference in preoperative TWL between CCI group and Sham group rats was not statistically significant (P ＜ 0.01).TWL was signifi cantly lower at all other time points after operation (P ＜ 0.01).Immunofluorescence results showed that PAR2 and TMEM16A coexisted in rat DRG neurons.Western blot results showed that,compared with Sham group,CCI group PAR2 and TMEM16A protein expression significantly increased after 7 d and 14 d (P ＜ 0.01),and the PAR2 and TMEM16A protein expression on 14 d is higher than that of 7 d (P ＜ 0.05).Conclusions Expression level of PAR2 and TMEM16A in CCI group was significantly higher than those in Sham group.The expression level of these proteins may be the cause of rat model of neuropathic pain.

Objective:To compare the therapeutic characteristics of anterior hybrid decompression and posterior cervical posterior laminectomy in the treatment of multilevel cervical spondylotic myelopathy.Methods:Thirty six cases of multilevel cervical spondylotic myelopathy patients treated by anterior hybrid decompression and thirty three cases of multilevel cervical spondylotic myelopathy patients treated by posterior cervical posterior laminectomy were involved.The general information,bleeding amount,operative time,cervical curvature D value,JOA score and incidence of postoperative complications of the two groups before and after surgery were compared.Results:There was no significant difference in the general information among the two groups(P＞0.05),including age (anterior group:56.23± 7.64 years old,posterior group:55.76± 8.18 years old),sex (anterior group:22 males/14 females,posterior group:20 males/13 females),cervical curvature D value (anterior group:7.41± 3.14,posterior group:8.19± 2.74),JOA score (anterior group:9.08± 1.09 scores,posterior group:8.82± 1.26 scores),disease course (anterior group:17.24± 7.36 months,posterior group:15.75± 5.78 months) and affected segment (anterior group:3.11 ± 0.26 segments,posterior group:3.24± 0.39 segments).The the amount of bleeding in the anterior group (anterior approach:221.79± 178.02 ml,posterior group:483.07± 434.25 ml) was lower than that of the posterior group(P＜0.05).The operative time (anterior group:196.54± 51.88 mins,posterior group:175.12± 54.93 mins) was longer,but there was no significant difference (P＞0.05).The cervical curvature D value and JOA score of posterior group were increased with the extension of surgery time.However,the cervical curvature D value of posterior group was decreased,but JOA score was increased.The incidence of bone unfinished,hoarseness and cerebrospinal fluid leakage were found in the anterior group,and axial pain and C5 nerve root paralysis were found in the posterior group.But there was no significant difference in the incidence of complications between the two groups (anterior group 14.89％,posterior group:12.12％)(P＞0.05).Conclusions:Anterior hybrid decompression and posterior cervical posterior laminectomy had their own advantages in the treatment of multilevel cervical spondylotic myelopathy.,The appropriate treatment should be taken according to the condition of patients.