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1.
Organ Transplantation ; (6): 187-2022.
Article in Chinese | WPRIM | ID: wpr-920848

ABSTRACT

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) could effectively treat multiple hematological diseases. At present, with persistent improvement of transplantation techniques and rapid development of economy, more and more patients with hematological diseases are able to survive for a long time due to allo-HSCT treatment. Chronic ocular graft-versus-host disease (coGVHD) is the most common ocular complication after allo-HSCT, which is primarily manifested with refractory dry eye. In severe cases, it may cause imbalance of ocular surface homeostasis and limbal stem cell insufficiency, further leading to a series of complications that threaten the visual function and eye health, such as corneal perforation and symblepharon, etc. It is highly difficult to cure these symptoms. At present, relevant studies of clinical manifestations, diagnostic criteria, treatment specification and pathogenesis of coGVHD have been gradually deepened within the international community. However, related research and the establishment of clinical specification are still in the primary stage in China. In this article, research progress on clinical characteristics and related mechanisms of coGVHD was reviewed, aiming to deepen the understanding of this disease by ophthalmologists, especially specialists in corneal and ocular surface diseases, and provide novel ideas for subsequent in-depth research.

2.
Article in Chinese | WPRIM | ID: wpr-933947

ABSTRACT

Objective:To seek any effect of extracorporeal shockwave treatment on the expression of transforming growth factor-β1 (TGF-β1) and interleukin-1β (IL-1β) in the cartilage tissue of rabbits with knee osteoarthritis (OA), and its therapeutic mechanism.Methods:Fifty female New Zealand rabbits were randomly divided into a normal control group, a model group, and three shockwave groups A, B and C, each of 10. Except for the normal control group, an OA model was established in the other groups using Hulth′s method. The shockwave groups were given 2000 shocks in each weekly session over 4 weeks. The energy flow density in group A was 0.05mJ/mm 2; in B it was 0.11mJ/mm 2 and in C 0.22mJ/mm 2. The normal control and model groups were not shocked. All the rabbits were then sacrificed and their right knee cartilage tissue was sampled to observe any pathological changes and assign improved Mankin scores. Immunohistochemistry was used to count the number of TGF-β1 and IL-1β-positive cells in the cartilage. Western blotting and real-time fluorescence quantitative polymerase chain reactions were employed to determine the protein and mRNA expression of IL-1β and TGF-β1. Results:Compared with the normal group, degeneration of articular cartilage was observed in the model group. The average Mankin′s score of the model group was significantly higher than that of the normal control group. The average expression of TGF-β1 and IL-1β protein and mRNA in the model group had increased significantly compared with the normal control group. The average Mankin′s scores of the shock wave groups were all significantly lower than the model group′s average. Group C′s average expression levels of TGF-β1 and IL-1β protein and mRNA were significantly lower than the model group′s averages.Conclusions:Extracorporeal shockwave therapy can reduce the expression of TGF-β1 and IL-1β in the cartilage of an arthritic knee, at least in rabbits. Its therapeutic effect is positively correlated with the density of the energy flow, suggesting that shock waves may reduce the expression of inflammatory factor IL-1β by regulating the expression of TGF-β1. They should be applied in the prevention and treatment of osteoarthritis.

3.
Chinese Journal of Nephrology ; (12): 420-427, 2022.
Article in Chinese | WPRIM | ID: wpr-933873

ABSTRACT

Objective:To investigate whether it is by regulating interleukin 1β ( IL-1β) gene expression that androgen receptor (AR) in macrophages affects hyperphosphate-induced vascular smooth muscle cell calcification. Methods:The chromatin immunoprecipitation (ChIP) experiment was used to determine whether AR was bound to the androgen receptor element (ARE) sequence of IL-1β promoter in THP-1 cells. Whether the AR regulated IL-1β gene expression was detected by luciferase assay experiments. AR of THP-1 cells was silenced and transfected by lentivirus with vector or shRNA. Flow cytometry was used to select positive transfected cells THP-1ARsc (control) and THP-1ARsi (AR silencing) with fluorescent markers. Western blotting was used to detect AR protein levels of THP-1ARsc (control) and THP-1ARsi cells (AR silencing in monocytes). Macrophages MФARsc (control) or MФARsi (AR silencing) were induced by 50 ng/ml phorbol ester. Enzyme-linked immunosorbent assay was used to detect IL-1β expression levels of MФARsc or MФARsi conditioned medium. The human aortic smooth muscle cells (HASMC) were cultured in MФARsc or MФARsi conditioned medium with phosphate (2.5 mmol/L final concentration of sodium dihydrogen phosphate), and Alizarin red S staining was used to analyze HASMC calcification degree. Western blotting was used to detect the expression levels of RUNX2 (osteoblast marker) and SM22α (HASMC marker), and neutralization assay was performed to test IL-1β-mediating effect of macrophages AR on HASMC calcification. Results:AR was bound to ARE sequence of IL-1β promoter and regulated IL-1β gene expression. The expression level of IL-1β protein in conditioned medium of MФARsi cells decreased significantly compared to MФARsc cells ( P<0.001). Compared with MФARsc conditioned medium group, HASMC calcium deposition in MФARsi conditioned medium group decreased significantly, RUNX2 protein decreased and SM22α protein increased (all P<0.05). The degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group decreased than that in the MФARsc conditioned medium+IgG antibody group significantly, and the degree of HASMC calcification in the MФARsc conditioned medium+IL-1β antibody group decreased significantly than that in the MФARsc conditioned medium+IgG antibody group; while the degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group and MФARsi conditioned medium+IL-1β antibody group decreased than that in the MФARsc conditioned medium+IL-1β antibody group (all P<0.05). Conclusions:Macrophage AR regulates IL-1β expression by binding to ARE sequence within IL-1β promoter, and IL-1β mediates the effect of macrophage AR on hyperphosphate-induced HASMC calcification.

4.
Article in Chinese | WPRIM | ID: wpr-933366

ABSTRACT

Objective:To investigate the effect of high glucose on the release of interleukin (IL)-1β and IL-18 in placental trophoblast by activating NLRP3 inflammasome.Methods:Gestational diabetes mellitus(GDM) placentas and control placentas were collected and the expression levels of NLRP3 and Caspase-1 were determined. Human placental trophoblast HTR-8/SVneo were cultured and divided into control group(5.5 mmol/L glucose), high glucose group(25 mmol/L glucose), DMSO+ high glucose group, and Ac-YVAD-cmk(NLRP3 inflammasome inhibitor)+ high glucose group. The expression levels of NLRP3 and Caspase-1 in cells as well as the contents of IL-1β and IL-18 in the medium were determined.Results:The expression levels of NLRP3 and Caspase-1 in GDM placenta were higher than those in control placenta( P<0.05) and positively correlated with homeostasis model assessment of insulin resistant index(HOMA-IR) and fasting insulin. The expression levels of NLRP3 and Caspase-1 in HTR-8/SVneo cells and the secretion levels of IL-1β and IL-18 in high glucose group were higher than those in control group( P<0.05). Ac-YVAD-cmk significantly suppressed high glucose-stimulated IL-1β and IL-18 secretion( P<0.05). Conclusion:High glucose promotes the release of IL-1β and IL-18 from placental trophoblast via activating NLRP3 inflammasome.

5.
Journal of Chinese Physician ; (12): 371-376, 2022.
Article in Chinese | WPRIM | ID: wpr-932072

ABSTRACT

Objective:To discuss the value of dynamic detection of serum intestinal fatty acid binding protein (I-FABP), heparin binding protein (HBP) and interleukin-1β(IL-1β) in early predicting and evaluating the severity of abdominal compartment syndrome (ACS) in severe acute pancreatitis (SAP) postoperative patients.Methods:The clinical data of 65 SAP patients treated in the Second Hospital of Anhui Medical University from July 2019 to Jan 2021 were retrospective analyzed. According to whether ACS has occurred, the patients were divided into non ACS group (48 cases) and ACS group (17 cases). The serum I-FABP, HBP and IL-1β of the two groups were dynamically monitored. Correlation analysis and receiver operating characteristic (ROC) curve were used to evaluate the efficacy and early prediction value of each observation index in evaluating the severity of SAP patients complicated with ACS.Results:There were no significant differences in age, sex, body mass index (BMI) and pathogenesis between the two groups (all P>0.05). The serum levels of C-reactive protein (CRP), white blood cell (WBC), Acute Physiology and Chronic Health Enquiry (APACHE-Ⅱ) score and intra-abdominal pressure (IAP) in ACS group were significantly higher than those in non ACS group (all P<0.05). The serum levels of I-FABP [(97.41±15.02)ng/ml vs (37.28±18.34)ng/ml, (103.32±18.40)ng/ml vs (56.96±19.12)ng/ml, (85.69±22.94)ng/ml vs (36.88±10.49)ng/ml], HBP [(92.19±14.59)ng/ml vs (24.56±10.96)ng/ml, (106.11±15.03)ng/ml vs (37.17±13.83)ng/ml, (128.11±16.43)ng/ml vs (68.94±15.91)ng/ml] and IL-1β[(15.78±1.44)pg/ml vs (11.26±1.34)pg/ml, (19.34±1.87)pg/ml vs (13.51±2.84)pg/ml, (20.95±1.96)pg/ml vs (16.03±1.04)pg/ml] on 1st, 4th, 7th day in ACS group were continuously and evidently higher than those in non ACS group ( P<0.01). Correlation analysis revealed that I-FABP, HBP and IL-1β were positively correlated with IAP ( r=0.745, 0.793, 0.770) and APACHE Ⅱ score ( r=0.510, 0.489, 0.445) (all P<0.01). ROC curve analysis showed that the AUC of early prediction by I-FABP, HBP and IL-1β on the occurrence of ACS were 0.846, 0.873 and 0.902 respectively, which were higher than the CRP (0.681), WBC (0.765) and APACHE Ⅱ score (0.795), the sensitivity and specificity can be significantly improved to 0.997 and 0.994 by parallel and series tests respectively combined with the three indicators. Conclusions:Dynamic detection of serum I-FABP, HBP and IL-1β has a certain clinical value in evaluating the severity of ACS in SAP patients. At the same time, early detection with serum I-FABP, HBP and IL-1β has high predictive power for ACS in SAP patients and the combined application of three has higher predictive value.

6.
Article in Chinese | WPRIM | ID: wpr-931700

ABSTRACT

Objective:To investigate the effects of amoxicillin capsules combined with Fuke Qianjin Tablets on serum inflammatory factors in patients with acute pelvic inflammatory disease. Methods:A total of 240 patients with acute pelvic inflammatory disease who received treatment in Department of Obstetrics and Gynecology, Shizhu Branch of the First People's Hospital of Yongkang from January 2016 to June 2020 were included in this study. They were randomly assigned to receive either treatment with amoxicillin capsules and conventional drugs (control group, n = 120) or amoxicillin capsules, conventional drugs and Fuke Qianjin Tablets in combination (study group, n = 120). Serum inflammatory factors [C-reactive protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] were compared between before and after treatment in each group and between two groups after treatment. Results:After treatment, CRP, IL-1, IL-6 and TNF-α levels in the control group were (34.28 ± 7.19) mg/L, (103.52 ± 30.18) mg/L, (103.27 ± 37.18) ng/L, and (64.11 ± 13.28) ng/L, respectively and they were (15.26 ± 6.49) mg/L, (60.44 ± 17.64) mg/L, (62.15 ± 15.33) ng/L, (38.19 ± 9.46) ng/L, respectively in the study group. Before treatment, CRP, IL-1, IL-6 and TNF-α levels in the control group were (89.32 ± 17.36) mg/L, (193.27 ± 52.18) mg/L, (180.48 ± 49.25) ng/L, (81.27 ± 18.16) ng/L , respectively and they were (90.48 ± 19.73) mg/L, (192.55 ± 51.84) mg/L, (178.93 ± 50.11) ng/L, (79.83 ± 17.35) ng/L, respectively in the study group. CRP, IL-1, IL-6 and TNF-α levels post-treatment were significantly lower than the levels pre-treatment in each group (control group: tCRP = 11.28, P < 0.001; tIL-1 = 12.73, P < 0.001; tIL-6 = 9.48, P < 0.001; tTNF-α = 8.94, P < 0.001; study group: tCRP = 12.38, P < 0.001; tIL-1 = 18.44, P < 0.001; tIL-6 = 13.29, P < 0 .001; tTNF-α = 12.43, P < 0.001). CRP, IL-1, IL-6 and TNF-α levels post-treatment in the study group were significantly lower than those in the control group ( tCRP = 9.37, P < 0.001; tIL-1 = 11.84, P < 0.001; tIL-6 = 8.33, P < 0.001; tTNF-α = 7.38, P = 0.002). Response rate in the study group was significantly higher than that in the control group (95.83% vs. 75.00%, χ2 = 27.29, P < 0.001). Before and after treatment, there were no significant differences in safety indicators between the two groups (all P > 0.05). Conclusion:Amoxicillin capsules combined with Fuke Qianjin Tablets is highly effective on acute pelvic inflammatory disease, greatly lower inflammatory factor levels, and is highly safe.

7.
Article in Chinese | WPRIM | ID: wpr-931622

ABSTRACT

Objective:To investigate the protective effects of overexpression of long-chain noncoding RNA FAM224B on lung tissue of rats with severe pneumonia and the underlying mechanism.Methods:From August 2020 to March 2021, we randomly allocated 20 rats into the pneumonia group (severe pneumonia modeling) and FAM224B group (severe pneumonia modeling + FAM224B plasmid), with 10 rats in each group. We performed a quantitative real-time polymerase chain reaction to detect the level of FAM224B in lung tissue and performed an enzyme-linked immunosorbent assay to detect the levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β in lung tissue. We used the software starBase v2.0 to predict the target gene of FAM224B. We performed a quantitative real-time polymerase chain reaction to detect the expression of the target gene in lung tissue and performed a western blot assay to detect the protein expression of the nuclear factor-kappa B signal pathway in lung tissue.Results:FAM224B expression was (1.09 ± 0.23) and (10.12 ± 1.52) in the pneumonia and FAM224B groups, respectively. FAM224B expression was significantly lower in the pneumonia group compared with the FAM224B group ( t = 15.86, P < 0.01). The levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β were (41.53 ± 2.46) μg/L, (34.01 ± 2.53) ng/L, (20.92 ± 1.95) μg/L in the pneumonia group and they were (21.71 ± 2.25) μg/L, (17.13 ± 3.01) ng/L, (11.97 ± 1.21) μg/L in the FAM224B group. There were significant differences in the levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β between the two groups ( t = 15.94, 14.29, 13.89, all P < 0.01). FAM224B had complementary binding sites with miR-34b-5p. The expression level of miR-34b-5p in lung tissue was significantly lower in the FAM224B group compared with the pneumonia group ( t = 15.55, P < 0.01). The protein expression levels of phosphorylated nuclear factor-κB subunit (p-p65) and phosphorylated inhibitor of kappa B alpha in lung tissue were significantly lower in the FAM224B group compared with the pneumonia group. Conclusion:FAM224B overexpression reduces the inflammatory reaction in lung tissue of rats with severe pneumonia through inhibiting miR-34b-5p expression.

8.
Article in Chinese | WPRIM | ID: wpr-931591

ABSTRACT

Objective:To investigate the clinical efficacy and possible mechanism of bifidobacterium tetralogy combined with escitalopram oxalate in the treatment of patients with depression and to provide evidence for further clinical research.Methods:A total of 100 patients with depression who received treatment in Taizhou Second People's Hospital from September 2019 to March 2021 were included in this study. They were randomly assigned to receive either escitalopram oxalate and placebo (control group, n = 50) or escitalopram oxalate and bifidobacterium tetralogy (observation group, n = 50). All patients received 9 weeks of treatment. Psychological status pre- and post-treatment was evaluated using the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety. Serum cortisol, inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels were detected using the enzyme-linked immunosorbent assay. Results:Physiological status scores in each group were significantly lower after treatment compared with before treatment. Scores of the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety scores post-treatment in the observation group were (10.78 ± 2.03) points and (6.37 ± 2.58) points, which were significantly lower than those in the control group [(16.78 ± 2.85) points, (13.23 ± 2.95) points, t = 11.40, 13.38, both P < 0.001]. Serum levels of cortisol, inflammatory factors IL-1β and TNF-α in each group were significantly decreased after treatment compared with before treatment. Serum levels of cortisol, inflammatory factors IL-1β and TNF-α post-treatment in the observation group were (137.34 ± 63.29) μg/L, (14.38 ± 6.08)ng/L, (13.95 ± 6.46) ng/L, which were significantly lower than those in the control group [(181.22 ± 59.27) μg/L, (25.94 ± 6.92) ng/L, (20.44 ± 6.24) ng/L, t = 15.29, 6.16, 9.24, all P < 0.001). Conclusion:Bifidobacterium tetralogy combined with escitalopram oxalate is highly effective on depression. The combined therapy can remarkably reduce depression and anxiety symptoms and greatly decrease serum cortisol, IL-1β, and TNF-α levels.

9.
Article in Chinese | WPRIM | ID: wpr-931036

ABSTRACT

Age-related macular degeneration (AMD), the leading cause of central vision loss among people aged 50 years and older, is one of the major eye diseases causing blindness in the world.Clinically, advanced AMD is divided into two types, non-exudative AMD with manifestation of geographic atrophy and exudative AMD with manifestation of choroidal neovascularization.The pathogenesis of AMD is complex, and the para-inflammation is recognized as an important risk factor.Nucleotide-binding oligomerization domain like receptors 3 (NLRP3) inflammasome is a cytoplasmic pattern recognition receptor and is expressed in several kings of cells, including retinal pigment epithelium (RPE) cells, microglial cells, Müller glia cells and retinal vascular endothelial cells.Recent studies have suggested that NLRP3 inflammasome plays an important role in the pathophysiology of both non-exudative and exudative AMD.The role of the NLRP3 inflammasome and its effector cytokines interleukin (IL)-1β and IL-18 in AMD were reviewed in this article to provide guidance on future prevention and therapy of AMD.

10.
Article in Chinese | WPRIM | ID: wpr-930780

ABSTRACT

BACKGROUND: Interleukin-1 is an important pro-inflammatory cytokine that has been documented in the regulation of bone inflammation and bone remodeling. A previous study has demonstrated that interleukin-1α can induce apoptosis while inhibiting osteoblast differentiation in MC3T3-E1 cells. OBJECTIVE: To investigate the role and mechanism of interleukin-1α on osteoclast activation and bone loss in mice. METHODS: (1) Cell test: RAW264.7 cells were either treated with interleukin-1α alone or with receptor activator of nuclear factor-κB ligand (RANKL) for 1 and 4 days. Cell viability was tested by cell counting kit-8 assay. The number of multinuclear osteoclasts was detected by tartrate resistant acid phosphatase assay. The mRNA and protein levels of osteoclast-specific genes and genes related to nuclear factor-κB pathway and Wnt/β-catenin pathway were tested by real-time fluorescence quantitative PCR, immunofluorescence staining or western blot. Bone marrow-derived macrophages were either treated with interleukin-1α alone or with RANKL and macrophage colony-stimulating factor for 7 days. The number of multinuclear osteoclasts was detected by tartrate resistant acid phosphatase assay. The protein levels of osteoclast-specific genes were tested by western blot. (2) Animal test: Twenty-four male C57BL/6J mice (6-8 weeks old) were assigned into two groups at random: control group and test group. Mice were subsequently treated with interleukin-1α solution or PBS by intraperitoneal injection twice a week for 5 weeks. Bone tissues from the femurs were performed with micro-computed tomography analysis and hematoxylin-eosin staining, tartrate resistant acid phosphatase, and immunofluorescence analysis. RESULTS AND CONCLUSION: Cell test: Interleukin-1α alone significantly increased RAW264.7 cell proliferation, but stimulated cell differentiation into osteoclasts in combination with RANKL (P < 0.05). Interleukin-1α significantly increased the expression of osteoclast-related markers and the number of tartrate resistant acid phosphatase-positive multinuclear cells in RAW264.7 cells and bone marrow-derived macrophages in the existence of RANKL or RANKL+macrophage colony-stimulating factor (both P < 0.05). Interleukin-1α was found to significantly enhance the nuclear factor-κB and Wnt/beta-catenin signaling in RAW264.7 cells (P < 0.05). Blocking of nuclear factor-κB or Wnt3 signaling not only reversed the activation of nuclear factor-κB and Wnt3 signaling but also weakened the enhanced expression of osteoclast-specific genes induced by interleukin-1α in RAW264.7 cells (P < 0.05). Animal test: interleukin-1α induced bone loss in mice while also upregulating the expression of osteoclast-specific markers, RANK, TRAF6 and p65, and Wnt3 in vivo (P < 0.05). The findings indicate that interleukin-1α can induce osteoclast activation and bone loss by promoting the nuclear factor-κB and Wnt signaling pathways.

11.
Article in Chinese | WPRIM | ID: wpr-930411

ABSTRACT

Kawasaki disease (KD) is an acute vasculitis that often occurs in children under 5 years of age, leading to coronary artery aneurysms.It is the leading cause of acquired heart disease in children in many countries.Coronary artery stenosis, thrombosis, and even myocardial infarction may occur in the long-term course of KD, which seriously threaten the health of children.The etiology and pathogenesis of KD are complex, and it is recognized that KD is caused by the interaction of multiple factors like the heredity, immunity, inflammation, and environmental factors.Interleukin-1 plays an important role in the occurrence and progression of KD.This study mainly reviews the research progress of interleukin-1 and its receptor antagonist Anakinra in KD.

12.
Article in Chinese | WPRIM | ID: wpr-930286

ABSTRACT

Objective:To investigate the role and mechanism of miR-146b in the proliferation, metastasis and apoptosis of thyroid papillary carcinoma cells.Methods:qRT-PCR was used to detect the expression of miR-146b in thyroid papillary carcinoma cells (NPA, GLAG-66, ONCNO-DG1 and B-CPAP) and normal human thyroid cell line HTori3. After B-CPAP cells were transfected with miR-146b inhibitor, the inhibition efficiency was detected by qRT-PCR, the effect of miR-146b on PTC cells proliferation was detected by MTT assay, the effect of miR-146b on PTC cells invasion was studied by Transwell assay, and the effect of miR-146b on tumor cell apoptosis was detected by flow cytometry. SiRNA-IRAK1 was transfected into B-CPAP cell line. The cell proliferation rate, migration ability and apoptosis rate were detected by MTT, cell scratch test and flow cytometry respectively. The target gene of miR-146b, interleukin-1 associated receptor kinase 1 (IRAK1) , was predicted by bioinformatics software, and the regulatory effect of miR-146b on IRAK1 was verified by double fluorescein reporter gene experiment.Results:QRT-PCR showed that the expression of miR-146b in NPA87, KAT-5, FTC-133 and B-CPAP cell lines was significantly higher than that in normal cell HTori3, especially B-CPAP ( P<0.05) . MiR-146b inhibitor transfection could significantly reduce the expression level of miR-146b in B-CPAP cells ( P<0.01) . MTT results showed that miR-146b inhibitor could inhibit the proliferation of B-CPAP cells ( P<0.05) . Flow cytometry showed that miR-146b inhibitor could promote the apoptosis of B-CPAP cells ( P<0.05) . Transwell results showed that miR-146b inhibitor could reduce the invasive ability of B-CPAP cells ( P<0.05) . After transfection with siRNA-IRAK1, the proliferation rate of B-CPAP cells increased significantly (MTT test) , the migration ability increased (cell scratch test) , and the apoptosis rate decreased significantly (flow cytometry) ( P<0.05) . The results of double luciferase reporter gene showed that irak1 was the target gene of miR-146b, and miR-146b inhibitor could significantly up regulate the expression level of irak1 protein in B-CPAP cells. Conclusion:miR-146b may play a role in promoting the proliferation and metastasis and inhibiting cell apoptosis of PTC cells by inhibiting the downstream target protein IRAK1.

13.
Acta Pharmaceutica Sinica B ; (6): 2280-2299, 2022.
Article in English | WPRIM | ID: wpr-929398

ABSTRACT

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

14.
Acta Pharmaceutica Sinica ; (12): 2612-2621, 2022.
Article in Chinese | WPRIM | ID: wpr-941520

ABSTRACT

More and more studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome has become the regulatory factor of inflammatory response and protective immunity, and the assembly and activation of NLRP3 inflammasomes are closely related to the anti-tumor immunity effect. Depending on the cell type and stimuli, activation of the NLRP3 inflammasome can induce immune cells to become polarized, hyperactive, or pyroptotic, releasing interleukin (IL)-1β and IL-18, which leads to cascade immune or inflammatory responses, and its role in tumor immunity has received extensive attention. Here, we review the mechanisms of the NLRP3 inflammasome enhancing CD8+ T cells-mediated anti-tumor immunity by inducing the pyroptosis of tumor cell, the pyroptosis or hyperactive state of dendritic cells (DCs), and the pyroptosis or polarization of the macrophages. Different anti-tumor immune roles of NLRP3 inflammasome activation in tumor cells and immune cells provide new directions for future research and may influence the development of next-generation immunotherapy.

15.
China Occupational Medicine ; (6): 148-152, 2022.
Article in Chinese | WPRIM | ID: wpr-940881

ABSTRACT

@#Objective To investigate the role of tumor necrosis factor alpha stimulated gene/inducible protein 6(TSG-6)on free silica(SiO2 )-induced secretion of pro-inflammatory cytokine interleukin(IL)-1β by bone-marrow-derived macrophages (BMDMs). Methods i)BMDMs isolated from bone marrow were divided into eight groups:the control group was untreated; lipopolysaccharide (LPS) group was stimulated by LPS with a concentration of 50 µg/L;The TSG-6 control group was stimulated by 100 µg/L of recombinant mouse TSG-6. SiO2 model group was pre-stimulated with LPS for four hours,and then stimulated with SiO2 suspension at a final concentration of 250 mg/L;Different dose of TSG-6 groups were firstly treated with above concentrations of LPS and SiO2 suspension,then 10,20,50 and 100 µg/L of recombinant mouse TSG-6 were added respectively;After 16 hours of culture,the cells were collected and the level of IL-1β in BMDMs supernatant was detected by enzyme-linked immunosorbent assay(ELISA)to screen optimal concentration of TSG-6. ii)The cells of the control group,LPS group,SiO2 model group,TSG-6 optimal concentration group and TSG-6 control group were collected. The expression of IL-1β and components of its related pathways in BMDMs was detected by Western blot,including IL-1β,pro-IL-1β,caspase-1,pro dcaspase-1,asc type amino acid transport and NOD-like receptor protein 3(NLRP3). Results i)Compared with the control group,the expression of IL-1β in SiO2 model group was increased significantly(P<0.01). Compared with SiO2 model group,the expression of IL-1β in 20,50,100 µg/L dose of TSG-6 groups were decreased significantly(all P<0.01),and the optimal concentration of TSG-6 was found to be 100 µg/L. ii)Compared with the control group and LPS group,the relative expression levels of IL-1β,caspase-1 and NLRP3 in SiO2 model group were increased significantly (all P<0.05). Compared with SiO2 model group,the expression levels of IL-1β、caspase-1 and NLRP3 were decreased in 100 µg/L TSG-6 group(all P<0.05). Conclusion TSG-6 could inhibit BMDMs to secret pro-inflammatory cytokine IL-1β by down-regulating the expression of NLRP3 and caspase-1.

16.
Article in Chinese | WPRIM | ID: wpr-940789

ABSTRACT

ObjectiveTo investigate the mechanism of Chaihu Qinggantang (CHQGT) in the treatment of granulomatous lobular mastitis (GLM) in the rat model. MethodSixty female rats were divided into a normal group, a model group, a prednisolone group (0.001 8 g·kg-1), and three CHQGT low-dose, medium-dose, and high-dose groups (4.5, 8.9, 17.8 g·kg-1). The tissue homogenates mixed with GLM lesion tissue and Fritner's reagent were used for modeling. After modeling, the treatment groups were given corresponding treatment factors, and the normal group and the model group were given the equal volume of normal saline. The changes in mammary gland of rats were observed after 14 d. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in breast samples. The mRNA expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, Caspase-1, and interleukin-1β (IL-1β) were detected by real-time quantitative fluorescence polymerase chain reaction (Real-time PCR). The protein expressions of NLRP3, Caspase-1, IL-1β, and IL-18 were detected by Western bolt. ResultAs compared with the normal group, the breasts of rats in the model group were obviously swelling, and mammary gland inflammation index was significantly increased (P<0.01). Pathological changes included the formation of granuloma centered on the lobule of mammary gland with a large number of inflammatory cells such as lymphocytes and plasma cells. The mRNA expressions of NLRP3, Caspase-1, and IL-1β, and the protein expressions of NLRP3, Caspase-1, IL-1β, and IL18 in the model group were significantly increased (P<0.01). Compared with the model group, the treatment groups improved breast swelling, and the CHQGT medium and high-dose groups and the prednisolone group reduced inflammation index to some extent after treatment (P<0.05, P<0.01). The inflammation degree of mammary gland was significantly improved, and inflammatory cells such as macrophages, lymphocytes, and plasma cells were reduced to varying degrees in pathological aspects. The mRNA expressions of NLRP3, Caspase-1, and IL-1β, and the protein expressions of NLRP3, Caspase-1, IL-1β, and IL-18 in the CHQGT high-dose group and the prednisolone group were significantly down-regulated (P<0.05, P<0.01). ConclusionCHQGT inhibits inflammation and treats GLM in rats. The mechanism is possibly related to the inhibition of NLRP3/IL-1β signaling pathway, which provides a new target for the prevention and treatment of GLM by Qingxiao method.

17.
Article in Chinese | WPRIM | ID: wpr-940348

ABSTRACT

ObjectiveTo investigate the effect of Jingangwan on the expression of osteoclast, c-Jun N-terminal kinase(JNK), p38 mitogen-activated protein kinase(p38 MAPK), and interleukin-1(IL-1) in the osteoporosis model rats, explore the mechanism of Jingangwan in the treatment of osteoporosis, and determine the optimal dosing concentration of Jingangwan. MethodFifty-six rats of SPF grade were randomized into a blank group,a sham operation group,a model group, model group,high-, medium-, and low-dose Jingangwan groups (0.72, 0.36, 0.18 g·kg-1·d-1, ig),and an estradiol valerate group (0.009 g·kg-1·d-1, ig), with eight rats in each group. The rats in the model group, the blank group, and the sham operation group received 3 mL of normal saline, respectively. Samples were collected 12 weeks after drug administration. The number of osteoclasts was observed by tartrate-resistant acid phosphatase (TRAP) staining. Serum levels of JNK, p38 MAPK, and IL-1 were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of p38 MAPK and JNK were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultThe TRAP staining results showed that compared with the model group, the estradiol valerate group and the Jingangwan groups could inhibit the formation of osteoclasts to different degrees. As revealed by ELISA results, compared with the model group and the sham operation group, the model group showed increased serum levels of p38 MAPK, JNK, and IL-1 (P<0.01), while compared with the model group, all the groups with drug intervention showed decreased levels of p38 MAPK, JNK, and IL-1 (P<0.01). The serum levels of JNK and IL-1 in the high-dose Jingangwan group were lower than those in the estradiol valerate group (P<0.05). Real-time PCR results showed that compared with the blank group, the model group showed increased relative mRNA expression of p38 MAPK and JNK in the thighbone (P<0.01), while compared with the model group, all the groups with drug intervention showed decreased relative mRNA expression of p38 MAPK and JNK in the thighbone (P<0.01). ConclusionJingangwan can inhibit the formation of osteoblasts,reduce the diameter of the bone marrow cavity,improve bone quality,suppress the production of inflammatory factors,affect the metabolism of the MAPK signaling pathway,and blunt p38 MAPK and JNK activities to inhibit the differentiation and proliferation of osteoblasts and regulate bone metabolism, thereby preventing osteoporosis. Therefore,Jingangwan may be of application value in maintaining bone health and treating osteoporosis.

18.
Article in Chinese | WPRIM | ID: wpr-939396

ABSTRACT

Objective To elucidate the effect of tumor-derived interleukin-1 beta(IL-1β)on adhesion of vascular endothelial cells(HUVECs)with hepatoma cells and the potential molecular mechanisms. Methods HepG2 cell line stably expressing IL-1β(HepG2/IL-1β)and GFP(HepG2/GFP)was established by lentivirus transfection,and the IL-1β in cell culture supernatant was determined by ELISA. Conditioned medium(CM)containing IL-1β(IL-1β-CM)of HepG2 cells was used as a source for tumor-derived IL-1β,and was controlled with CM from HepG2/GFP cells(Ctrl-CM). HUVECs stimulated with 10 ng/mLIL-1β(HUVECs+IL-1β-CM)were used to observe their adhesion ability with HepG2/IL-1βand HepG2/GFP cells,and HUVECs+CtrlCM served as control. The mRNA expression levels of E-selectin(CD62E) ,ICAM-1(CD54)and VCAM-1(CD106)in HUVECs were detected byqRT-PCR. Cell surface expression levels of CD62Eand CD54 were detected by flow cytometry.IL-1β induced signaling pathways in HUVECs were analyzed through Western blotting. Specific inhibitors were usedto block each signaling pathway,and the expression of adhesion molecules as well as the adhesion of vascular endothelial cells with hepatoma cells were subsequently monitored. Results Tumor-derived IL-1β significantly enhanced the adhesion of HUVECs with HepG2 cells and upregulated the expression levels of CD62E and CD54 mRNAin HUVECs cells. The surface CD62E was temporarily upregulated 4 h after IL-1β stimulation,while the expression of CD54 protein showed a continuous upregulated pattern,which lasted from 4 hto 24 h.IL-1β mainly activated NF-κB p65 and p38 MAPK signaling pathways in HUVECs,and NF-κB p65 was proved to be located at upstream,regulating the activation of p38 MAPK pathway. Targeted blocking of NF-κB p65 pathway by specific inhibitor significantly downregulated the expression of CD62E and CD54 on surface of HUVECs and inhibited their adhesionability with HepG2cells. Conclusion Tumor-derived IL-1β promotes adhesion of HUVECs with hepatoma cells through upregulation of CD62E and CD54 expression by activating NF-κB p65 signaling pathway in HUVECs. Tumor-derivedIL-1β might be involved in invasion and metastasis of hepatoma cells through vascular system.

19.
Article in Chinese | WPRIM | ID: wpr-936401

ABSTRACT

Objective @# The purpose of this study was to clarify the regulatory effect and mechanism of Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) on human periodontal ligament stem cell (hPDLSC) proliferation and osteogenic differentiation under inflammatory environment and to provide a new target for the treatment of periodontitis. @*Methods@#SHP2 was knocked down in hPDLSCs, and the transfection efficiency of SHP2 was detected by RT-qPCR and Western blot. An in vitro inflammatory environment was created using tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The effect of SHP2 knockdown on hPDLSC viability under normal and inflammatory conditions was detected by CCK-8, and the osteogenic capacity of hPDLSCs under normal and inflammatory conditions was detected by ALP staining, ALP activity, ARS staining, RT-qPCR and Western blot. The mechanism by which SHP2 knockdown affected the MAPK pathway and its downstream NF-κB pathway under inflammatory conditions was assessed by Western blot. @*Results@# Green fluorescence was observed after transfection for 72 h, and the titer of SHP2 shRNA recombinant lentivirus was 2.9×108 TU/mL. SHP2 expression was significantly downregulated in lentivirus-transfected cells, as demonstrated by Western blot and RT-qPCR (P<0.001). SHP2 knockdown inhibited hPDLSC proliferation to a certain extent and increased the expression of early osteogenic markers under normal conditions, including increased ALP activity and increased ALP and COL-1 expression (P<0.05). However, SHP2 knockdown exerted no effect on mineralized nodule formation. In the TNF-α- and IL-1β-induced inflammatory environment, SHP2 knockdown exerted no effect on hPDLSC proliferation (P>0.05). Osteogenic markers were upregulated (P<0.05), and mineralized nodules were significantly increased (P<0.05) after SHP2 knockdown. Western blot analysis showed that p65 phosphorylation and IκB-α degradation were reduced in SHP2-knockdown hPDLSCs in the inflammatory environment. Moreover, SHP2 knockdown significantly inhibited the expression of p-p38 and p-JNK MAPK, which represent pathways upstream of the NF-κB pathway (P<0.05). @*Conclusion @# SHP2 knockdown did not affect cell viability but promoted the osteogenic potential of hPDLSCs by inhibiting the MAPK/NF-κB-mediated signaling pathway under inflammatory environment.

20.
Article in Chinese | WPRIM | ID: wpr-908741

ABSTRACT

Objective:To investigate the therapeutic effect of Yanghe decoction combined with Tounongpowder on patients with acute plasma cell mastitis and its influence on inflammatory factors.Methods:A total of 120 patients with acute plasma cell mastitis admitted to Yantai Affiliated Hospital of Binzhou Medical College from May 2019 to May 2020 were selected, and divided into control group (60 cases) and combination group (60 cases). The control group was treated with western medicine, and the combination group was treated with Yanghe decoction and Tounongpowder on the basis of the control group. Seven days was 1 course and a total of 4 courses were continued. The scores of symptoms and signs and clinical effects of the two groups before treatment and 1 month after treatment were compared. The serum interleukin(IL)-1β and IL-6 were measured by radioimmunoassay, and tumor necrosis factor-α(TNF-α) was measured by enzyme-linked immunosorbent assay.Results:After 1 month of treatment, the scores of breast swelling, breast lumps, breast pain, breast fistula symptoms and signs in the two groups were significantly decreased, the scores of above index in the combination group were significantly lower than those in the control group, and the differences were statistically significant ( P<0.05). The total effective rate in the combined group was higher than that in control group: 91.7%(55/60) vs. 76.7% (46/60), and the difference was statistically significant ( χ2 = 8.456, P<0.05). After 1 month of treatment, the serum levels of IL-1β, IL-6 and TNF-α in the two groups were significantly reduced, and the serum levels of above 3 index in the combination group were significantly lower than those in the control group: (3.24 ± 0.92) ng/L vs. (3.81 ± 1.02) ng/L, (1.12 ± 0.42) ng/L vs. (1.41 ± 0.35) ng/L, (32.27 ± 19.03) ng/L vs. (43.04 ± 21.58) ng/L, and the differences were statistically significant ( P<0.05). After treatment, the liver and kidney functions of the two groups were not abnormal, and the differences in adverse reactions such as headache, dizziness, nausea and vomiting were not statistically significant ( P>0.05). Conclusions:Yanghe decoction combined with Tounongpowder can significantly improve the clinical symptoms of patients with acute plasma cell mastitis, with a definite clinical effect. Its mechanism of action may be related to reducing the levels of IL-1β, IL-6, and TNF-α and reducing the inflammatory response.

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