Toll-like receptor signaling pathway involved in pathogenesis of thromboangiitis obliterans through activating of NF-κB.

OBJECTIVES: The pathogenic mechanisms of Thromboangiitis Obliterans (TAO) are not entirely known and autoimmune inflammation plays a vital role in the initiation and continuance of TAO activity. The authors investigated in this study the role of the TLR signaling pathway in the pathogenesis of TAO. METHODS: First, the authors detected the expressions of MyD88, TRIF and NF-κB in vascular walls of 46 patients with TAO and 32 patients with trauma and osteosarcoma by western blot assay. Second, the authors detected the cellular localization of MyD88, TRIF and NF-κB in vascular walls of patients with TAO by immunofluorescent assay. RESULTS: The protein expressions of MyD88, TRIF and NF-κB were much higher in vascular walls of TAO patients (p < 0.05). Higher expressions of MyD88 and NF-κB were detected both on vascular endothelial and vascular smooth muscle cells of TAO patients. However, higher expression of TRIF was just detected on vascular smooth muscle cells of TAO patients. CONCLUSIONS: These dates suggest that the TLR signaling pathway might play an important role in the pathogenesis of TAO, it might induce vasospasm, vasculitis and thrombogenesis to lead to the pathogenesis and progression of TAO.

Correlation between family function and quality of life in patients with atrial fibrillation. / å¿ƒæˆ¿é¢¤åŠ¨æ‚£è€ å®¶åº­åŠŸèƒ½ä¸Žç”Ÿæ´»è´¨é‡çš„ç›¸å ³æ€§.

OBJECTIVES: Many studies have shown that the quality of life for patients with atrial fibrillation (AF) is significantly impaired, but the impact on family function is still unclear. This study aims to evaluate the family function and quality of life in patients with AF using scales, to analyze the correlation between family function and quality of life, and to predict the influencing factors of quality of life. METHODS: A total of 223 patients with AF who were admitted to the Department of Cardiology and General Medicine of the Lanzhou University Second Hospital from January 1, 2021 to May 1, 2022, were selected as research subjects, the general information of patients with AF were collected via a questionnaire, the family function and quality of life were assessed by the Family Assessment Device (FAD) and Atrial Fibrillation Effect on Quality-of-Life (AFEQT) scale. The patients were divided into a non-family functional disorder group and a family functional disorder group on the basis of their FAD scores. The above data were analyzed using SPSS 26.0 statistical software. RESULTS: Among the 223 patients, 64 (28.70%) were in the non-family functional disorder group, and 159 (71.30%) were in the family functional disorder group. The total score of FAD and scores of all dimensions in the family functional disorder group were higher than those in the non-family functional disorder group (all P<0.01). AFEQT total score and symptoms, treatment concerns and daily activities in the non-family functional disorder group were significantly higher than those in the family functional disorder group (all P<0.01). The Pearson linear analysis showed that there was a linear negative correlation between the total score and each dimension of FAD with the total score and each dimension of AFEQT (all P<0.01). The variables with statistical significance in the univariate analysis were included in the multiple linear regression analysis, and the result showed that female, and the problem solving, role, affective involvement, and general functioning dimensions of family function had an impact on the quality of life (all P<0.01). CONCLUSIONS: Most patients with AF have different degrees of family dysfunction. The quality of life in patients with family functional disorder group is generally low. Female, and the problem solving, role, affective involvement, and general functioning of family function have a significant impact on the quality of life in patients with AF. In clinical treatment of AF, attention should be paid to the family function of patients, and family members can be involved in clinical intervention to improve family function and improve the quality of life.

Evaluation of the efficacy of gastric lymphoma treated with non-surgical therapy using oral and double contrast-enhanced gastric ultrasonography.

AIM: To investigate the feasibility of assessing the ecacy of non-surgical treatment for gastric lymphoma using oral contrast-enhanced ultrasound (OCEUS) and double contrast-enhanced ultrasound (DCEUS). MATERIAL AND METHODS: A total of 27 patients with gastric lymphoma treated nonoperatively were included in this retrospective study. The ecacy was evaluated using OCEUS and CT, respectively, and the results were tested for kappa concordance. Sixteen of the 27 patients underwent multiple DCEUS examinations before and after treatment. Micro-perfusion of the lesion in DCEUS is represented by the Echo Intensity Ratio (EIR), (echo intensity of the lymphoma lesion/echo intensity of the normal gastric wall), and one-way ANOVA was used to compare the differences between groups in EIR values before and after treatment. RESULTS: OCEUS and CT were highly consistent in assessing the efficacy of gastric lymphoma, with a Kappa value of 0.758. During a median follow-up of 8.8 months, there was no statistical difference between the complete remission rate obtained by OCEUS and that obtained by endoscopic and CT (25.93% vs. 44.44%, p=0.154; 25.93% vs. 33.33%, p=0.766). There was also no statistical difference in the time to achieve complete remission using OCEUS assessment and endoscopy and CT (4.71±1.03 months vs. 6.01±2.14 months, p=0.088; 4.47±1.84 months vs. 6.01±2.14 months p=0.143). The difference in EIR between the groups before treat-ment and after different numbers of treatments was statistically signifficant (p<0.05), and post hoc analysis revealed this dif-ference as early as after the second treatment (p<0.05). CONCLUSIONS: Transabdominal OCEUS and CT are comparable in the assessment of gastric lymphoma treatment ecacy. DCEUS is a noninvasive, cost-effective, and widely available method for gastric lymphoma therapeutic effect evaluation. Therefore, transabdominal OCEUS and DCEUS have the potential to be used for the early assessment of the ecacy of the non-surgical treatment of gastric lymphoma.

MG149 Inhibits MOF-Mediated p53 Acetylation to Attenuate X-Ray Radiation-Induced Apoptosis in H9c2 Cells.

Cardiomyocyte apoptosis is involved in the pathogenesis of radiation-induced heart disease, but the underlying epigenetic mechanism remains elusive. We evaluated the potential mediating role of males absent on the first (MOF) in the association between epigenetic activation of p53 lysine 120 (p53K120) and X-ray radiation-induced apoptosis in H9c2 cells. H9c2 cells were pretreated for 24 h with the MOF inhibitor MG149 after 4 Gy irradiation, followed by assessment of cell proliferation, injury, and apoptosis. MOF expression was upregulated by X-ray radiation. MG149 suppressed the proliferation inhibition, reduction of mitochondrial membrane potential, ROS production, and cell apoptosis. MG149 may promote the survival of H9c2 cells via inhibition of MOF-mediated p53K120 acetylation in response to X-ray radiation-induced apoptosis. Our data indicates a MOF-associated epigenetic mechanism in H9c2 cells that promotes attenuation of X-ray radiation-induced injury.

HOXD13 promotes the malignant progression of colon cancer by upregulating PTPRN2.

PURPOSE: The homeobox (HOX) family plays an important role in multi-biological processes, such as morphogenesis and tumors. However, the function of HOXD13 in colon cancer remains unclear. MATERIALS AND METHODS: The Cancer Genome Atlas database was used to analyze the expression of HOXD13 and its effect on the survival rate of colon cancer patients. Wound healing, Transwell, and clone formation were used to evaluate the effects of changes in HOXD13 expression on the function of colon cancer cells. A nude mouse xenograft tumor model was used to test the effects of HOXD13 on tumor growth in vivo. RESULTS: Our results showed that HOXD13 was highly expressed in colon cancer and predicted a poor prognosis for patients. In in vitro experiments, the knockdown of HOXD13 can inhibit the proliferation and invasion of colon cancer cells. In vivo experiments showed the inhibited tumor growth after the knockdown of HODX13. In addition, HOXD13 bound to the protein tyrosine phosphatase receptor type N2 (PTPRN2) promoter and promoted the transcription of PTPRN2. CONCLUSION: We revealed the function and mechanism of HOXD13 in colon cancer and suggest that HOXD13 may be a candidate marker for the diagnosis and treatment of colon cancer.

Platelet-derived growth factor-B signalling might promote epithelial-mesenchymal transition in gastric carcinoma cells through activation of the MAPK/ERK pathway.

INTRODUCTION: Epithelial-mesenchymal transition (EMT) is important in the metastasis of tumours and is triggered by several key growth factors, including platelet-derived growth factor-B (PDGF-B). But, whether PDGF-B signalling promotes EMT in gastric carcinoma cells is still unknown. MATERIAL AND METHODS: We established 2 gastric carcinoma cell lines (MKN28 and MKN45) to stably overexpress PDGF-B by lentiviral vectors, and expression of E-cadherin, N-cadherin, and ERK-1 were detected by western blot assay. Then, PDGF-B overexpression and normal MKN28 and MKN45 cells were cocultured with PDGFR-b positive fibroblast (hs738) and MAPK inhibitors were added; also, the expressions of ERK-1, E-cadherin, and N-cadherin were detected by western blot assay. RESULTS: After being cocultured with hs738 cells, expressions of ERK-1 and N-cadherin protein in PDGF-B overexpression MKN28 and MKN45 cells were much higher than normal MKN28 and MKN45 cells (p < 0.05), and those could be decreased by MAPK inhibitor. Also, expressions of E-cadherin protein in PDGF-B overexpression MKN28 and MKN45 cells were much lower than normal MKN28 and MKN45 cells (p < 0.05), and they could be increased by MAPK inhibitor. CONCLUSIONS: Our data indicate that PDGF-B signalling can induce EMT in gastric carcinoma cells. Thr tumour microenvironment is imperative in the process of PDGF-B signalling inducing EMT in gastric carcinoma cells. Also, activation of MAPK/ERK pathway, which is a downstream pathway of PDGF-B signalling, might participate in this process.

Atorvastatin might resist tobacco smoking-induced endothelial inflammation through the inhibition of NF-κB signal pathway.

Endothelial inflammation caused by tobacco smoking is widely considered as a pathogenic factor in many vascular diseases. Drugs such as atorvastatin were found to be an effective treatment in smoking-dependent vascular diseases, but the underlying mechanism is still unclear. Here, we investigated the mechanism of atorvastatin resisting endothelial inflammation caused by tobacco smoking. Firstly, isolated human umbilical vein endothelial cells (HUVECs) were divided into normal control group, cigarette smoking extract (CSE) group, and atorvastatin (AS)+CSE group. Then the expressions of inflammatory factors (vascular cell adhesion molecule-1 (VCAM-1) and E-selectin) and nuclear transcription factor kappa (NF-κB) in HUVECs were detected by western blot after separate treatments. The results showed that the expressions of VCAM-1, E-selectin, and NF-κB in CSE group were significantly higher than the other two groups (P< 0.05). We also found that the expressions of VCAM-1, E-selectin, and NF-κB in CSE + atorvastatin group were a little higher than the normal control group (P< 0.05). Our results showed that atorvastatin might partly resist tobacco smoking-induced endothelial inflammation through the inhibition of NF-κB signal pathway.

Protective effect of picroliv against lipopolysaccharide-induced cognitive dysfunction and neuroinflammation by attenuating TLR4/NFκB pathway.

INTRODUCTION: Present investigation determines the beneficial effect of picroliv against lipopolysaccharide (LPS)-induced neuronal inflammation and injury. MATERIAL AND METHODS: Neuronal injury was induced by LPS 250 µg/kg, i.p. for the period of one week, and picroliv 12.5 and 25 mg/kg was given i.p. 30 min prior to the administration of LPS for the duration of 12 days. The effect of picroliv was determined on the cognitive function by Morris water maze (MWM). Mediators of inflammation were estimated by using enzyme-linked immunosorbent assay (ELISA) and western blot, reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical analysis was done to determine the expressions of several proteins. RESULTS: Data of the study reveal that picroliv ameliorates the reduced memory impairment and cognitive dysfunction in LPS-induced mice. Moreover, expressions of inflammatory protein and -amyloid protein and level of inflammatory mediators were found to be reduced in the picroliv-treated group as compared to the negative control group. Data of RT-PCR reveal that the gene of Toll-like receptor 4 (TLR-4), -synuclein, neurotrophic factor (BDNF) and interleukin-1 (IL-1) protein were also decreased in the picroliv-treated group as compared to the negative control group. In addition picroliv attenuates the altered level of nuclear factor-kB(p-NF-kB), amyloid- (A), -synuclein and glial fibrillary acidic protein (GFAP) positive cells in the brain of LPS-induced mice. CONCLUSIONS: The report concludes that picroliv protects the neuroinflammation and injury in LPS-induced mice by regulating the inflammatory pathway.

Clinicopathological significance of platelet-derived growth factor B, platelet-derived growth factor receptor-ß, and E-cadherin expression in gastric carcinoma.

AIM OF THE STUDY: Platelet-derived growth factor B (PDGF-B), a vital growth factor which can induce angiogenesis and epithelial-mesenchymal transition (EMT), is important in the metastasis of many tumors. However, the roles of PDGF-B in gastric carcinoma are largely unknown. We investigated the correlation between PDGF-B, PDGFR-ß and E-cadherin expression with the clinical features of gastric carcinoma patients to evaluate the relationship between PDGF-B signaling, E-cadherin and metastasis of gastric carcinoma, the correlation between PDGF-B and E-cadherin expression to assess the roles of PDGF-B signaling in metastasis of gastric carcinoma.. MATERIAL AND METHODS: We detected expressions of PDGF-B, PDGFR-ß and E-cadherin in gastric carcinoma tissues and normal gastric mucosa tissues of 64 patients with gastric carcinoma who had undergone surgical resection, and investigated their relationships with clinical features and the relationships between PDGF-B and E-cadherin expression in gastric carcinoma. RESULTS: In surgical specimens, tumor cells expressed PDGF-B, and PDGFR-ß was expressed by tumor stromal cells. E-cadherin was expressed by both tumor cells and normal gastric mucosa cells. Expressions of PDGF-B and PDGFR-ß were increased in gastric carcinoma tissues (p < 0.05) and were positively correlated with the depth of cancer invasion, lymph node metastasis and TNM stage (p < 0.05). The expression of E-cadherin was reduced in gastric carcinoma tissues (p < 0.05) and was negatively correlated with the depth of cancer invasion, lymph node metastasis and TNM stage (p < 0.05). The correlation between PDGF-B and E-cadherin expression was negative (p < 0.05). CONCLUSION: Our data indicate that either the overexpression of PDGF-B and PDGFR-ß or the underexpression of E-cadherin is correlated with cancer progression and lymphogenous metastasis of gastric carcinoma. The PDGF-B signal pathway might induce EMT by down-regulating expression of E-cadherin to promote metastasis of gastric carcinoma.