Rheumatoid arthritis (RA) is a chronic autoimmune disease remarkably characterized by synovitis of joints, whose pathogenesis is complicated and not yet fully elucidated. A variety of cells, cytokines and intercellular signaling pathways are involved in the occurrence and development of RA. The mitogen activation protein kinase (MAPK) signaling pathway is closely related to the pathogenesis of RA, and plays an important role in the formation of pannus, synovitis, and bone destruction. This paper reviews the research progress of MAPK signaling pathway in RA from the aspects of the interaction of MAPK signaling pathway with a variety of key cells and cytokines in the pathogenesis of RA, in order to provide a direction and theoretical basis for anti-RA drug therapy research.
Long non-coding RNA (lncRNA) Dnm3os plays a critical role in peritendinous fibrosis and pulmonary fibrosis, but its role in the process of cardiac fibrosis is still unclear. Therefore, we carried out study by using the myocardial fibrotic tissues obtained by thoracic aortic constriction (TAC) in an early study of our group, and the in vitro cardiac fibroblast activation model induced by transforming growth factor-β1 (TGF-β1). Quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, and collagen gel contraction test were used to identify the changes of activation phenotype and the expression of Dnm3os in cardiac fibroblasts. Small interfering RNA was used to silence Dnm3os to explore its role in the activation of cardiac fibroblasts. The results showed that the expression of Dnm3os was increased significantly in myocardial fibrotic tissues and in the activated cardiac fibroblasts. And the activation of cardiac fibroblasts could be alleviated by Dnm3os silencing. Furthermore, the TGF-β1/Smad2/3 pathway was activated during the process of cardiac fibroblasts activation, while was inhibited after silencing Dnm3os. The results suggest that Dnm3os silencing may affect the process of cardiac fibroblast activation by inhibiting TGF-β1/Smad2/3 signal pathway. Therefore, interfering with the expression of lncRNA Dnm3os may be a potential target for the treatment of cardiac fibrosis.
Objective To clarify incidence and risk factors of hepatitis B reactivation during short term (one month) in hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients receiving partial hepatectomy. Methods From January 2015 to December 2015, 214 consecutive patients with HBV-related HCC who underwent partial hepatectomy were retrospectively enrolled in this study. The risk factors affecting incidence of hepatitis B reactivation were analyzed. Results Hepatitis B reactivation happened in 7.0% (15/214) of patients within 1 month after partial hepatectomy. By univariate analysis, the preoperative HBV-DNA negativity and hepatitis B e antigen (HBeAg) positivity were significantly correlated with the occurrence of hepatitis B reactivation (P=0.023 and P=0.001, respectively). By multivariate analysis, the preoperative HBV-DNA negativity 〔OR=9.21, 95% CI (2.40, 35.45), P=0.001〕 and HBeAg positivity 〔OR=20.51, 95% CI (5.41, 77.73), P<0.001〕 were the independent risk factors for hepatitis B reactivation. Conclusions Hepatitis B reactivation is common after partial hepatectomy for HBV-related HCC during short term, especially in patients whose preoperative HBV-DNA negativity and HBeAg positivity. A close monitoring of HBV-DNA during short term after partial hepatectomy is necessary, once hepatitis B is reactivated, antiviral therapy should be given.
Objective To explore the secretion law of high mobility group box 1（HMGB1）in rat pancreatic acinar cells induced by trypsin activation peptide（TAP）and release of HMGB1 affected by ethyl pyruvate（EP）. Methods The experiment was performed in 12 SD rats. The pancreatic acinar cells of rats were taken out and then separated into three groups：control group， TAP group， and EP group. TAP was added into TAP group and EP group（keep TAP at a final concentration of 3 nmol/L）， respectively， but EP was added into EP group only （keep EP at a final concentration of 28 mmol/L）. The expressions of HMGB1 mRNA and protein were detected by using real-time quantitative reverse transcription polymerase chain reaction（RT-PCR）or Western blot at 3 h， 6 h， 12 h， and 24 h time point， respectively. The relationship between HMGB1 and TAP action time was explored by rank correlation. Results Compared with control group， the expressions of HMGB1 mRNA and protein were increased with prolongation of the TAP action in TAP group and EP group（P＜0.05）. Compared with TAP group， the expressions of HMGB1 mRNA and protein were decreased in EP group（P＜0.05）. The expressions of HMGB1 mRNA and protein were increased with prolongation of the TAP action（P＜0.05）， and were highest at 12 h time point（P＜0.01）in TAP group. There were positive correlation between the expressions of HMGB1 mRNA and protein and TAP action time（rs=0.971， P＜0.01；rs=0.966， P＜0.01）.Conclusions TAP can induce the release of HMGB1 in pancreatic acinar cells. There is positive relationship between TAP in early stage and HMGB1 in later period of acute pancreatitis. EP can inhibit the release of HMGB1.
The cleft lip and palate (CLP) is one of the most common craniofacial malformations in humans. We collected functional magnetic resonance data of 23 CLP patients before rehabilitation training (Bclp) and 23 CLP patients after rehabilitation training (Aclp), who were performing Chinese character pronunciation tasks, and performed brain activation analysis to explore the changes of brain mechanism in CLP patients after articulation disorder rehabilitation training. The study found that Aclp group had significant activation in the motor cortex, Broca area, Wernicke area and cerebellum. While the Bclp group had weak activation in the motor cortex with a small activation range. By comparing the differences and co-activated brain regions between the two groups, we found that rehabilitation training increased the activity level of negatively activated brain areas (cerebellum, left motor area, Wernicke area, etc.) to a positive level. At the same time, the activity level of weakly activated brain areas (right motor area, Broca area, etc.) was also increased. Rehabilitation training promoted the activity level of articulation-related brain regions. So that the activation intensity of articulation-related brain regions can be used as a quantifiable objective evaluation index to evaluate the effect of rehabilitation training, which is of great significance for the formulation of rehabilitation training programs.
Objective To summarize functions and mechanisms of fibroblast activation protein (FAP) and its application in targeted therapy. Method Literatures about FAP in recent years were collected to make a review. Results Thereis an important relationship between the FAP and the dipeptidyl peptidase-Ⅳ. FAP has a serine protease activity and is an important immunosuppressive component in the tumor microenvironment. FAP participate in the pathological process of the neoplastic and the non-neoplastic diseases. In the targeted therapy, the enzyme inhibitors, antibodies, vaccines, and prodrugs of FAP had been extensively studied. Conclusion FAP have various functions and participates in pathological process of many diseases, and it is of great significance to research of tumor targeted therapy.
Objective To verify the technics of inactivating/removing pathogens in medical chitosan derived from shrimp shell. Methods Possible pathogen species were included according to the raw material of shrimp shell used in production, then bacillus cereus, porcine parvovirus (PPV) and pseudorabies virus (PRV) were selected as indicator pathogens.Pathogen solution was prepared in accordance with Technical Standard for Disinfection. The processing procedure of medical chitosan was analyzed to determine whether the alkal ization of chitin and the filter steril ization of chitosan were capable of inactivating/removing pathogens and their efficiencies were tested. Results Bacillus cereus was removed by 8 184 cfu/ mL after alkal ization and 30 818 cfu/mL after filter steril ization. The average logarithm inactivation value (LIV) of PPV and PRV after alkal ization were equal to or above 4.76 logTCID50/0.1 mL and 6.67 logTCID50/0.1 mL, respectively, and their average LIV after filter steril ization were 2.25 logTCID50/0.1 mL and 3.04 logTCID50/0.1 mL. The alkal ization of chitin inactivated/removed indicator pathogens effectively, while the filter steril ization of chitosan removed bacterial effectually but could not inactivate viruses completely. Conclusion The alkal ization of chitin can be used as the technics of inactivating/removing pathogens during the preparation process of medical chitosan to guarantee the safety of the product.
【Abstract】Objective To investigate the production and possible significance of plasma trypsinogen activation peptides (TAP) in rat experimental acute pancreatitis. Methods Ninety SD rats were randomly allocated to five groups: group EP with retrograde ductal infusion of 3%sodium taurocholate; group NP with retrograde ductal infusion of 5%sodium taurocholate; group TP with retrograde ductal infusion of 3%sodium taurocholate and ulinastatin(UTI) intravenous infusion half an hour later; group CP with 0.9% NS retrograde ductal infusion; group OP with sham operation. Animals in each group were killed 3h,6h and 24h after infusion. Plasma TAP was determined by EIA.The histological severity of the pancreas were assessed by Schmidt method. Results The pancreatic pathological changes in group NP was significantly severe than in group EP. At 3h and 6h after infusion, plasma TAP concentration of group NP (4.798±0.169)nmol/L and (3.999±0.299)nmol/L were significant higher than that of group EP(2.416±0.148)nmol/L and (3.356±0.211)nmol/L. At 6h after infusion plasma TAP concentration of group TP 〔(1.611±0.113)nmol/L〕 was significant lower than that of group EP(3.356±0.211)nmol/L. The difference of plasma TAP concentration between group EP and group NP appeared prior to the difference of the histopathological changes of pancreas between two groups. Conclusion Plasma TAP concentration is connected with the severity of sodium taurocholate-induced rat pancreatitis. Plasma TAP concentration may be used as a marker for early assessment of the severity of this experimental acute pancreatitis.
Objective To investigate the effect of astragaloside A (AS-A) on the photoreceptor degeneration induced by sodium iodate (NaIO3) and its related mechanism. MethodsSixty healthy male C57BL/6J mice, aged 6-8 weeks, were randomly divided into normal control (NC) group, NaIO3 group, and AS-A group, with twenty mice in each group. 30 min before modeling, AS-A group mice were intraperitoneally injected with 100 μl AS-A at a dose of 100 mg/kg body weight. 30 min later, mice in NaIO3 group and AS-A group were intraperitoneally injected with 100 μl NaIO3 at a dose of 30 mg/kg body weight. Subsequently, AS-A group mice were administered AS-A twice daily at 12 h intervals until the end of the experiment. On day 1 post-modeling, zonula occludens-1 (ZO-1) immunohistochemistry was performed to observe the structure of retinal pigment epithelium (RPE) cells; real-time quantitative polymerase chain reaction (qPCR) was conducted to detect the mRNA expression of various retinal chemokine ligand-2 (Ccl2), interleukin-1 beta (Il-1β), mixed lineage kinase domain-like protein (Mlkl), receptor-interacting protein kinase 3 (Ripk3), and tumor necrosis factor (Tnf). On day 3 post-modeling, immunohistochemistry was performed to observe the expression of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acid protein (GFAP) in the retina; TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to detect photoreceptor cell death in each group. On day 4 post-modeling, fundus morphology of mice in each group was observed by fundus color photography and optical coherence tomography (OCT). Hematoxylin-eosin staining (HE) was used to observe the morphological structure of the retina in each group. Inter-group comparisons between two groups were conducted using independent samples t-test, while comparisons among three groups were performed using one-way ANOVA. ResultsFundus color photography and OCT examination showed that a large number of scattered yellow-white subretinal nodular structures in the fundus of NaIO3 group mice, and a large number of strong reflection areas in the RPE layer. The number of strong reflection areas in the RPE layer was reduced in the AS-A group. Immunohistochemical analysis of ZO-1 showed that ZO-1 was largely lost on the RPE cell membrane in that NaIO3 group; whereas in the AS-A group, ZO-1 was evenly distributed on the RPE cell membrane. HE staining results showed circular black deposits were visible in the RPE layer of the NaIO3 group, and the inner and outer segments of photoreceptors were severely damaged, with a significant decrease in the number of outer nuclear layer (ONL) cell nuclei; whereas in the AS-A group, the RPE layer pigments were orderly, the inner and outer segments of photoreceptors were intact, and the number of ONL cell nuclei significantly increased. The results of TUNEL staining show that numerous TUNEL-positive cell nuclei were observed in the ONL of the retina in the NaIO3 group, while the number of TUNEL-positive cell nuclei in the ONL of the retina was significantly reduced in the AS-A group, with statistically significant differences (t=2.66, P＜0.05). The analysis of qPCR data showed that compared with the AS-A group, the relative expression levels of Mlkl, Ripk3, Ccl2, Il-1β and Tnf mRNA in the retina were significantly increased in the NaIO3 group, with statistically significant differences (F=39.18, 10.66, 53.51, 41.40, 24.13; P＜0.001). Immunohistochemical staining results showed that compared with NC group and AS-A group, the positive expression of GFAP in retina of NaIO3 group was significantly increased, and the difference was statistically significant (F=9.62, P＜0.05). ConclusionAS-A antagonizes NaIO3-induced photoreceptor degeneration in part by inhibiting photoreceptor cell death and neuroinflammation. Meanwhile, AS-A treatment protects against NaIO3-triggered perturbation of retinal homeostasis.
ObjectiveTo investigate the imaging characteristics of gallium-68 labeled fibroblast activation protein inhibitor (68Ga-FAPI)-positron emission tomography/magnetic resonance (PET/MR) imaging in patients with liver fibrosis or liver tumor. MethodsThirteen patients with suspected liver tumor who underwent 68Ga-FAPI-PET/MR examination from May 2020 to April 2021 were retrospectively analyzed. Maximum standard uptake value (SUVmax) was investigated. All patients underwent liver surgery or biopsy. Scheuer scoring system was used to evaluate the liver fibrosis. The imaging characteristics of liver fibrosis or liver tumor were analyzed. ResultsThe liver fibrosis was confirmed in 6 patients, including 1 case of S2, 2 cases of S3, and 3 cases of S4. Among them, 4 patients had increased uptake of 68Ga-FAPI, with patchy or diffuse abnormal concentration of liver, and the SUVmax was 7.9±3.1. The liver imaging of the other 2 patients with liver fibrosis showed no obvious radioactive concentration. In addition, 2 patients were diagnosed with hepatocellular carcinoma, its SUVmax was 7.2 and 6.1; 1 patient was diagnosed with hepatobiliary duct carcinoma and its SUVmax was 13.8. Moreover, increased uptake of 68Ga-FAPI was observed in 4 patients with metastatic liver cancer, with SUVmax of 6.7±2.7. ConclusionBoth liver fibrosis and liver tumor are suitable for 68Ga-FAPI-PET/MR examination, which have different imaging characteristics.