ABSTRACT
Objective:To investigate the effect and influencing factors of microwave ablation (MVA) in the treatment of benign thyroid nodules.Methods:The clinical data of ultrasound-guided microwave ablation for thyroid benign nodules in the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from April 2017 to April 2019 were retrospectively analyzed. At 1, 3 and 6 months after operation, conventional ultrasound examination was performed to calculate the volume reduction rate of the nodules. The nodules were divided into groups according to gender, age, nodule blood supply, nodule size, nodule nature and Hashimoto′s thyroiditis background, and the related factors influencing microwave ablation were analyzed.Results:68 patients (106 nodules) with benign thyroid nodules were treated with microwave ablation. The volume of benign thyroid nodules after the MWA treatment was significantly reduced after 1, 3, 6 months, and their nodule volume reduction ratio (VRR) were (39.7±6.1)% (1 months), (56.2±5.9)% (3 months), (70.3±5.4)% (6 months), respectively. There were significant differences in the volume reduction ratio of nodules at 1, 3 and 6 months after operation among different nodule size, nodule nature and Hashimoto′s thyroiditis background, with statistically significant difference ( P<0.05). However, there was no significant difference in the reduction ratio of nodules in different gender, age and nodule blood supply at 1, 3 and 6 months after operation ( P>0.05). Pearson correlation analysis showed that VRR was negatively correlated with ablation time per unit volume, with statistically significant difference ( P<0.05). Logistic regression analysis indicated that only nodule nature and ablation time per unit volume entered the regression equation. Conclusions:The size and nature of the nodules, Hashimoto′s thyroiditis background and ablation time per unit volume will affect the postoperative volume reduction rate.
ABSTRACT
Although the etiology of inflammatory bowel disease is still uncertain, increasing evidence indicates that the excessive activation of NLRP3 inflammasome plays a major role. Norisoboldine (NOR), an alkaloid isolated from Radix Linderae, has previously been demonstrated to inhibit inflammation and IL-1β production. The present study was to examine the effect of NOR on colitis and the underlying mechanism related to NLRP3 inflammasome activation. Our results showed that NOR alleviated colitis symptom in mice induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Moreover, it significantly reduced expressions of cleaved IL-1β, NLRP3 and cleaved Caspase-1 but not ASC in colons of mice. In THP-1 cells, NOR suppressed the expressions of NLRP3, cleaved Caspase-1 and cleaved IL-1β but not ASC induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Furthermore, NOR could activate aryl hydrocarbon receptor (AhR) in THP-1 cells, inducing CYP1A1 mRNA expression, and promoting dissociation of AhR/HSP90 complexes, association of AhR and ARNT, AhR nuclear translocation, XRE reporter activity and binding activity of AhR/ARNT/XRE. Both siAhR and α-naphthoflavone (α-NF) markedly diminished the inhibition of NOR on NLRP3 inflammasome activation. In addition, NOR elevated Nrf2 level and reduced ROS level in LPS- and ATP-stimulated THP-1 cells, which was reversed by either siAhR or α-NF treatment. Finally, correlations between activation of AhR and attenuation of colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 level in colons were validated in mice with TNBS-induced colitis. Taken together, NOR ameliorated TNBS-induced colitis in mice through inhibiting NLRP3 inflammasome activation via regulating AhR/Nrf2/ROS signaling pathway.
Subject(s)
Animals , Humans , Male , Mice , Alkaloids , Colitis , Drug Therapy , Genetics , Allergy and Immunology , Drugs, Chinese Herbal , Inflammasomes , Allergy and Immunology , Interleukin-1beta , Genetics , Allergy and Immunology , Lindera , Chemistry , Mice, Inbred BALB C , NF-kappa B , Genetics , Allergy and Immunology , Receptors, Aryl Hydrocarbon , Genetics , Metabolism , Trinitrobenzenesulfonic AcidABSTRACT
Although the etiology of inflammatory bowel disease is still uncertain, increasing evidence indicates that the excessive activation of NLRP3 inflammasome plays a major role. Norisoboldine (NOR), an alkaloid isolated from Radix Linderae, has previously been demonstrated to inhibit inflammation and IL-1β production. The present study was to examine the effect of NOR on colitis and the underlying mechanism related to NLRP3 inflammasome activation. Our results showed that NOR alleviated colitis symptom in mice induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Moreover, it significantly reduced expressions of cleaved IL-1β, NLRP3 and cleaved Caspase-1 but not ASC in colons of mice. In THP-1 cells, NOR suppressed the expressions of NLRP3, cleaved Caspase-1 and cleaved IL-1β but not ASC induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Furthermore, NOR could activate aryl hydrocarbon receptor (AhR) in THP-1 cells, inducing CYP1A1 mRNA expression, and promoting dissociation of AhR/HSP90 complexes, association of AhR and ARNT, AhR nuclear translocation, XRE reporter activity and binding activity of AhR/ARNT/XRE. Both siAhR and α-naphthoflavone (α-NF) markedly diminished the inhibition of NOR on NLRP3 inflammasome activation. In addition, NOR elevated Nrf2 level and reduced ROS level in LPS- and ATP-stimulated THP-1 cells, which was reversed by either siAhR or α-NF treatment. Finally, correlations between activation of AhR and attenuation of colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 level in colons were validated in mice with TNBS-induced colitis. Taken together, NOR ameliorated TNBS-induced colitis in mice through inhibiting NLRP3 inflammasome activation via regulating AhR/Nrf2/ROS signaling pathway.
Subject(s)
Animals , Humans , Male , Mice , Alkaloids , Colitis , Drug Therapy , Genetics , Allergy and Immunology , Drugs, Chinese Herbal , Inflammasomes , Allergy and Immunology , Interleukin-1beta , Genetics , Allergy and Immunology , Lindera , Chemistry , Mice, Inbred BALB C , NF-kappa B , Genetics , Allergy and Immunology , Receptors, Aryl Hydrocarbon , Genetics , Metabolism , Trinitrobenzenesulfonic AcidABSTRACT
Objective To investigate the mechanism of Roscovitine, an inhibitor of cyclin-dependent kinase (CDK), in inhibiting HBV replication.Methods Recombiant expression plasmids of SAMHD1 (sterile alpha motif and histidine/aspartic acid domain-containing protein 1) mutants that were defective in dNTPase (deoxynucleoside triphosphate triphosphohydrolase) activity and phosphorylation at the threonine (T) 592 residue were constructed.Huh7.0 cells were respectively co-transfected with different SAMHD1 mutants in combiantion with HBV replication plasmid to analyze whether the retroviral restriction ability of SAMHD1 was regulated by phosphorylation.The cytotoxicity of Roscovitine to Huh7 cells was evaluated by MTT assay.HBV core-associated DNA levels and phosphorylation of SAMHD1 in transfected Huh7.0 cells which were treated with different concentrations of Roscovitine were measured by Southern blot and Western blot assays.Results The SAMHD1 mutant that was defective in the dNTPase active site of D207N lost its ability to restrict HBV replication.Dephosphorylation of SAMHD1 at T592 enhanced its restriction on HBV.The median toxic concentration (TC50) of Roscovitine was 11.20 μmol/L.Both the HBV core-associated DNA levels and the phosphorylation of SAMHD1 were down-regulated by Roscovitine.Conclusion The anti-HBV function of SAMHD1 in dividing cells is regulated by phosphorylation.Roscovitine can inhibit the replication of HBV through reducing the phosphorylation of SAMHD1.