Age-related macular degeneration (AMD) is one of the leading irreversible causes of blindness in China. The pathogenesis of AMD is not fully understood at present. Under various stress conditions, cellular senescence is activated, characterized by telomere shortening, mitochondrial dysfunction, DNA damage, and the release of various senescence-related secretory phenotype factors. Senescence is implicated in the pathogenesis of AMD through multiple pathways, contributing to chronic inflammation and the onset and progression of AMD. Mechanisms such as oxidative stress, lipofuscin, β amyloid protein and the membrane attack complex have become hotspots of study in the pathogenesis of AMD. The cyclic guanosine phosphate - adenosine synthase - interferon stimulating factor synthase-stimulator of interferon gene pathway has emerged as a critical signaling pathway in the early development of AMD, providing direction for further research on AMD. Currently, senolytics, selective agents targeting the induction of senescent cell apoptosis, show significant potential in the treatment of AMD. The integration of new technologies with cellular senescence may offer a novel approach to AMD treatment, and intervening in the AMD treatment through anti-cellular senescence pathways holds promising prospects.
ObjectiveTo study on the relationship of serum apelin level with inflammation in patients with atrial fibrillation (AF). MethodsWe recruited 58 patients with valvular heart disease who admitted in our hospital between October 2014 and December 2014 and planned to undergo surgery, including 29 patients with persistent AF (an AF group) and 29 patients with sinus rhythm (a SR group). There were 14 males and 15 females in the AF group at an average age of 57±8 years. There were 20 males and 9 females in the SR group at an average age of 54±10 years. The left atrial diameter (LAD) and ejection fraction (EF) were detected by echocardiography. The levels of serum apelin and interleukin-6 (IL-6) were measured by enzyme linked immuno sorbent assay, and the level of high-sensitivity C-reactive protein (hs-CRP) were determined by turbidimetric inhibition immuno assay. ResultsCompare with the SR group, the serum apelin level (201.94±71.96 pg/ml vs. 286.72±129.33 pg/ml) and EF (54.52%±3.94% vs. 56.41%±2.85%) were significantly lower in the AF group, while the hs-CRP (5.58±12.90 mg/L vs. 1.89±3.55 mg/L), IL-6 (2.59±0.64 pg/ml vs. 2.26±0.55 pg/ml) and LAD (57.10±11.69 mm vs. 43.07±5.31 mm) were significantly higher in the AF group (P<0.05). Correlation analysis showed that the apelin level was negatively correlated with hs-CRP and LAD (r=-0.308, P=0.019; r=-0.313, P=0.017), and were positively correlated with EF (r=0.265, P=0.044). ConclusionSerum apelin level is significantly lower in patients with AF and levels of inflammation makers are significantly higher. Apelin may be closely related to AF and inflammation, and may take part in the occurrence and maintenance of AF through the regulation of inflammatory processes.
【Abstract】ObjectiveBy using multidetectorrow spiral CT (MDCT), to investigate the CT imaging features of inflammatory diseases in retroperitoneal space with correlation of radiological anatomy.MethodsThe clinical and laboratory dada of 30 patients with proven inflammatory diseases of retroperitoneal space were collected. All patients underwent MDCT plain scanning and portal venous acquisition. CT imaging data generated at portal venous phase were processed with coronal, sagittal and oblique multiplanar reformation (MPR) technique.ResultsAcute pancreatitis and various types of renal infection were the two main sources of retroperitoneal inflammation. Depending on the specific anatomic locations, retroperitoneal inflammation of different subspaces demonstrated characteristic imaging features. Spreading of inflammatory process across subspaces was also quite common.ConclusionMDCT is the imaging method of choice to depict comprehensively and clearly the inflammatory diseases of various retroperitoneal spaces.
ObjectiveTo establish a cell inflammation model induced by tumor necrosis factor-α (TNF-α) in human bronchus epithelial cells, and investigate the effects of glutathione S-transferase mu 5 (GSTM5) on the inflammation and oxidative stress. Methods16HBE cells were treated with TNF-α (10 ng/mL, 24 h) in the absence or presence of the constructed GSTM5 eukaryotic expression vector (1 μg/mL). The concentration of malondialdehyde (MDA) and total antioxidation capacity (T-AOC) were detected by colorimetric method. The survival rate of cells was assessed by the methyl thiazolyl tetrazolium (MTT) assay. The transcription level of NADPH oxidase-1 (NOX1), NOX2, NOX3, NOX4, NOX5, dual oxidase-1 (DUOX1) and DUOX2 were evaluated by RT-PCR. Western blot was performed to investigate the protein levels of NOX1 and NOX2. ResultsTNF-α simulation significantly increased the level of MDA in cells, and decreased the level of T-AOC and survival rate of 16HBE. When transfected with the GSTM5 eukaryotic expression vector, the concentration of MDA significantly decreased (P < 0.05), and the activation of T-AOC increased dramatically (P < 0.05). Consequently, the survival rate of 16HBE in the GSTM5 group improved (P < 0.05). The 16HBE cells transfected with the constructed GSTM5 eukaryotic expression vector had a lower transcription and protein levels of NOX1 and NOX2 (all P < 0.01). There were no significant changes in the mRNA expressions of NOX3, NOX4, NOX5, DUOX1 or DUOX2. ConclusionGSTM5 may down-regulate the transcription level of NOX1 and NOX2 to reduce the inflammation and oxidative stress induced by TNF-α.
ObjectiveTo observe the protective effect of Zhicao Tea Mixture on Müller cells and the expression of inflammatory factors in mice with diabetic retinopathy.MethodsSeventy-five C57BL/6J mice were randomly divided into the normal control group, diabetes mellitus (DM) group, low concentrations group, medium concentrations group and high concentrations group, with 16 mice in each group. The diabetes model of mice in all groups except the normal control group were established by intraperitoneal injection of STZ (60 mg/kg). Four weeks after the successful modeling, the Zhicao Tea Mixture with low (30 ml/kg), medium (60 ml/kg) and high concentrations (120 ml/kg) were respectively administered by gavage. Weight and blood glucose of mice in each group were measured every two weeks. After 8 weeks, Western blot method was used to detect the mice retina Müller cells activation marker gelatinous fibrous acidic protein (GFAP). Immunofluorescence was performed to detect the expression GFAP and glutamine synthetase (GS). Real-time quantitative PCR (RT-qPCR) and ELISA were used to determine the mRNA and protein expression levels of mouse retinal VEGF, TNF-α, IL-1β and IL-6 respectively.ResultsThe weight of mice in the DM group was lower than that of the normal control group, and the blood glucose was increased. Zhicao Tea Mixture had no effect on the weight of DM mice, but had a significant hypoglycemic effect. The GFAP expression (t=38.318, P＜0.001) in the retina of mice in the DM group was increased and GS expression (t=29.737, P＜0.001) was decreased compared with the control group. The GFAP expression (t=13.677, 19.387, 16.305; P＜0.05) in the retina of mice in the low, medium and high concentrations group were decreased and GS expression (t=5.170, 19.399, 6.705; P＜0.05) were increased compared with the DM group. The expressions of retinal inflammatory factors VEGF, TNF-α, IL-1β and IL-6 in DM group all increased, while the expressions of the above-mentioned inflammatory factors in the retina of mice decreased in the low, medium and high concentrations group.ConclusionZhicao Tea Mixture can decrease the blood glucose of DM mice and reduces the diabetic retinal inflammatory response.
The hallmark lesions of age-related macular degeneration (AMD) are drusen and basal linear deposit which are lipid substances deposited in Bruch membrane or the compartment on the Bruch membrane. There is a prevailing hypothesis that lipid and its oxidized derivant deposited in retina may have important roles in the pathogenesis of AMD. Lipid oxidation products are toxic, may affect the adjacent cells, induce inflammation, and trigger neovascularization.7-ketocholestoral (7KCh), a naturally occurring oxidized form of cholesterol, had been found to be toxic to retinal cells and able to induce chronic inflammation, which may play a critical role in the development of AMD. However the precise mechanism remains to be elucidated. Thus we will make a brief review of 7KCh and its association with AMD.
Microvesicles (MVs) is small membrane vesicles released from different cell types under different conditions. Studies have shown that MVs may mediate vascular inflammation, angiogenesis, and other pathological processes. MVs may play an important role in the pathogenesis of diabetic retinopathy (DR) by mediating endothelial cell injury, thrombosis and neovascularization. The plasma MV level may be an effective parameter to monitor the development of DR. This article will summarize the research progress of the relationship between MVs and DR in recent years.
Photoreceptor cells are special retinal neurons with photo-transformation ability. Loss of photoreceptors in age-related macular degeneration (AMD) is secondary to RPE loss, leakage of serum components from the neovascularization and scar formation, which is one of the main mechanisms of irreversible visual impairment in patients with AMD. Many studies have shown that inflammatory environment is involved in the process of photoreceptor cell death. Aging, photooxidation injury and other factors affects the retinal microenvironment through different levels of mechanisms such as retinal pigment epithelial cells, retinal glial cells, hematogenous macrophages and inflammatory factors, which results in photoreceptor injuries and participates in the progression of AMD by drusen formation and neovascularization. This study reviews the research status and progress of inflammation and photoreceptor cell death, and provides new ideas for exploring the blinding mechanism and treatment strategies of AMD.
The application of gene therapy in ocular diseases is gradually expanding from mono-gene inherited diseases to multigene, multifactorial, common and chronic diseases. This emerging therapeutic approach is still in the early exploratory stage of treating diseases, and the expected benefits and risks remain highly uncertain. In the delivery process of gene therapy drugs, viral vector is currently one of the most mature and widely used vectors. The occurrence of vector-associated immunity will affect the short-term and long-term effects of gene therapy, and even cause permanent and serious damage to visual function. Therefore, gene therapy vector-associated immunity is the focus and challenge for the safety and long-term efficacy of gene therapy. During the perioperative and follow-up of gene therapy, attention should be paid to the monitoring of vector-associated immune inflammation, and appropriate measures should be taken to deal with the corresponding immune response, so as to achieve the best visual benefits for patients.
ObjectiveTo explore the effect of continuous renal replacement therapy (CRRT) to treat sepsis associated acute kidney injury (AKI) in patients aged over 80.MethodsForty-one patients diagnosed with sepsis and AKI were enrolled in geriatric RICU department of Huadong Hospital from January 2013 to July 2018, 38 patients were male and 3 were female. All patients were treated with anti-infection and fluid resuscitation therapy. After comprehensive judgment of the indication of renal replacement, they were divided into two groups by the choices of using CRRT. There were 20 patients in CRRT group and 21 in control group. Clinical data such as age, body mass index, previous diseases, 28-day mortality rate, blood cells, APACHEⅡ as well as SOFA scores were compared between two groups. Blood renal function and inflammatory markers at the first day were also compared to those after 3-day treatment of initial time.ResultsNo statistical difference was observed in sex ratio, age, body mass index and previous diseases between two groups (all P>0.05). There was also no difference in APACHEⅡ score, SOFA score, blood cells, hemoglobin and survival time. The 28-day mortality rate in CRRT group was lower than that in control group (P<0.05). The levels of serum UA and C reactive protein (CRP) in CRRT group decreased after 3-day treatment compared with those at the onset, and the differences were statistically significant (all P<0.05). The level of serum blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA) and cystain C in control group increased after 3 days compared with those at the onset, and the difference were statistically significant (all P<0.05). There was no significant difference in serum BUN, Cr, UA, cystain C, CRP and procalcitonin (PCT) between two groups at the onset (all P>0.05). After 3 days of CRRT, the levels of serum PCT, BUN, Cr and UA in CRRT group were lower than those in the control group (all P<0.05).ConclusionCRRT can improve hyperuricemia, control deterioration of renal function, reduce early systemic inflammatory response and 28-day mortality rate in aged patients with sepsis and AKI.