In vitro osteoclast differentiation enhanced by hepatocyte supernatants from high-fat diet mice.

Non-alcoholic fatty liver disease (NAFLD) is associated with abnormal bone metabolism, potentially mediated by elevated levels of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-ɑ) and interleukin 6 (IL-6). This study aims to investigate the direct regulatory effects of liver tissues on osteoblast and osteoclast functions in vitro, focusing on the liver-bone axis in NAFLD. Twelve-week-old C57BL/6 mice were fed either a control diet or a high-fat diet (HFD) for 12 weeks. Bone structural parameters were assessed using microCT. Primary hepatocyte cultures were established from control and HFD-fed C57BL/6 mice, as well as IL-6-/- and TNF-α-/- mice. The supernatants from these hepatocyte cultures were used to induce differentiation in bone marrow cell-derived osteoblasts and osteoclasts in vitro. Results showed that mice on a HFD exhibited increased lipid infiltration in liver and bone marrow tissues, alongside reduced bone mass. Moreover, the supernatants from hepatocyte cultures from mice on a HFD displayed elevated TNF-α and IL-6 levels. These supernatants, particularly those derived from HFD-fed and IL-6-/- mice, significantly enhanced osteoclast differentiation in vitro. In contrast, supernatants from TNF-α-/- mice did not significantly affect osteoblast or osteoclast differentiation in vitro. In conclusions, this current study suggested that fatty liver tissues may negatively impact bone metabolism. Additionally, knockout of TNF-α and IL-6 genes revealed distinct influence on osteoblast and osteoclast functions, highlighting the complex interplay between live pathology and bone health.

Association between serum ferritin and uric acid levels and nonalcoholic fatty liver disease in the Chinese population.

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Accumulating evidence suggests that serum ferritin and uric acid (UA) are strongly associated with the risk of NAFLD, but no consensus has been reached. Objective: We sought to demonstrate the association between serum ferritin, UA levels, and NAFLD risk in a large cohort study. Methods: We separated 2,049 patients into non-NAFLD and NAFLD groups. The NAFLD group had four subgroups based on serum ferritin and four subgroups based on UA quartile levels. We used binary logistic regression to evaluate the correlation between serum ferritin, UA, and NAFLD. Additionally, an area under the curve (AUC) of receiver operating characteristic analysis (ROC) was used to predict the diagnostic value of combined serum ferritin and UA for NAFLD. Results: Serum ferritin and UA levels were higher in the NAFLD group compared with the non-NAFLD group. Serum lipid and liver transaminase concentrations were elevated with the increase of serum ferritin and UA. The logistic regression results showed an independent correlation between serum ferritin, UA, and NAFLD. In the NAFLD group, the AUC value of serum ferritin and UA was 0.771. Conclusions: Increased serum ferritin and UA levels are independent risk factors for NAFLD. Increased serum UA is a stronger risk factor for NAFLD than elevated serum ferritin. Serum ferritin and UA can be important predictors of NAFLD risk.

Brusatol: A potential sensitizing agent for cancer therapy from Brucea javanica.

Cancer is currently the most important problem endangering human health. As antitumor drugs have always been the most common methods for treating cancers, searching for new antitumor agents is of great significance. Brusatol, a quassinoid from the seeds of Brucea javanica, exhibits a potent tumor-suppressing effect with improved disease outcome. Studies have shown that brusatol not only shows potential tumor inhibition through multiple pharmacological effects, such as promoting apoptosis and inhibiting metastasis but also exhibits significant synergistic antitumor effects in combination with chemotherapeutic agents and overcoming chemical resistance in a wide range of cancer types. In this paper, the antitumor effects and mechanisms of brusatol were reviewed to provide evidence that brusatol has the exact antitumor efficacy of chemotherapeutic agents and show the potential of brusatol to be developed as a promising antitumor drug.

[Metabolic Outcomes of Primary Aldosteronism Patients Receiving Adrenalectomy or Spironolactone Treatments]. / æŽ¥å—è‚¾ä¸Šè ºåˆ‡é™¤æœ¯æˆ–èžºå† é ¯æ²»ç–—çš„åŽŸå‘æ€§é†›å›ºé ®å¢žå¤šç—‡æ‚£è€ ä»£è°¢è½¬å½’.

Objective: To investigate the metabolic outcomes of primary aldosteronism (PA) patients receiving adrenalectomy (ADX) or spironolactone treatment and the contributing factors to the metabolic outcomes. Methods: The clinical data of 70 patients with aldosterone-producing adenoma (APA) and 86 patients with idiopathic hyperaldosteronism (IHA) were retrospectively analyzed. All subjects received confirmatory diagnosis of APA or IHA at the Department of Endocrinology and Metabolism, West China Hospital between March 2018 and October 2020. APA patients underwent ADX, while IHA patients were given spironolactone, a mineralocorticoid receptor antagonist (MRA). After ADX or spironolactone treatment, the outcomes of the metabolic indicators and the inter-group differences between the APA patients and IHA patients were studied. Results: There was no significant difference between the baseline data of the APA group and those of the IHA group in terms of age, sex, duration of hypertension, maximum systolic blood pressure (SBP-max), maximum diastolic blood pressure (DBP-max), body mass index (BMI), fasting blood glucose (FBG), lipid parameters, and renal function. IHA patients had higher waist circumference, serum potassium, and plasma renin activity (PRA) than those of the APA patients (all P<0.05). All patients showed significant improvement in blood pressure, blood potassium, and plasma aldosterone at follow-up. However, they also showed increased triglycerides (TG) accompanied by deterioration in renal function (P≤0.001). Multiple regression showed that TG levels were associated with spironolactone treatment for IHA patients and post-treatment BMI and creatinine levels. Furthermore, APA patients showed improvement in their FBG after ADX (P=0.041), while IHA patients showed elevated levels of FBG after spironolactone treatment (P=0.037). Conclusion: After treatment, PA patients still may experience abnormal lipid metabolism and deteriorating renal function. Spironolactone therapy may give rise to worse glucolipid metabolism than ADX therapy does.

sIL-2R: A Novel Diagnostic Biomarker for Primary Adrenal Lymphoma.

CONTEXT: Primary adrenal lymphoma (PAL) is difficult to distinguish from other adrenal masses. Soluble interleukin-2 receptor (sIL-2R) is a diagnostic biomarker for nodal non-Hodgkin lymphoma, whose association with PAL is unknown. OBJECTIVE: The aim of this study was to determine the diagnostic utility of serum sIL-2R for Patients with PAL. DESIGN: Prospective cohort study. SETTINGS AND PARTICIPANTS: A total of 118 patients with adrenal masses who were willing to be tested for levels of serum sIL-2R from a tertiary hospital between 2019 and 2021 were included. MAIN OUTCOMES AND MEASURES: Serum sIL-2R and lactate dehydrogenase (LDH) levels. RESULTS: Patients with PAL had significantly higher sIL-2R levels than those of patients with other adrenal masses with indetermined and benign computed tomography (CT) features (both Ps < 0.001). The LDH levels of patients with PAL were also significantly higher than those of patients with other adrenal masses with indeterminate and benign CT features (both Ps < 0.001). Good discrimination of patients with PAL from other patients (PAL vs other adrenal masses with indeterminate CT features/non-PAL) was achieved with an area under the receiver operating characteristic curve (AUC) of 0.984 (95% CI, 0.95-1)/0.992 (95% CI, 0.975-1.000) using the serum levels of sIL-2R and further improved (AUC = 0.998, 95% CI, 0.994-1.000; AUC = 0.999, 95% CI, 0.996-1.000) after adjusting by LDH category. CONCLUSIONS: For the first time, we have identified that serum sIL-2R and LDH category-adjusted sIL-2R levels have good diagnostic performances for PAL.

Cholesterol Metabolism: A Double-Edged Sword in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) represents a leading cause of cancer-related deaths globally. The rising incidence of metabolic syndrome and its hepatic manifestation, nonalcoholic fatty liver disease (NAFLD), have emerged as the fastest-growing cause of HCC in recent years. Cholesterol, a major lipid component of the cell membrane and lipoprotein particles, is primarily produced and metabolized by the liver. Numerous studies have revealed an increased cholesterol biosynthesis and uptake, reduced cholesterol exportation and excretion in HCC, which all contribute to lipotoxicity, inflammation, and fibrosis, known HCC risk factors. In contrast, some clinical studies have shown that higher cholesterol is associated with a reduced risk of HCC. These contradictory observations imply that the relationship between cholesterol and HCC is far more complex than initially anticipated. Understanding the role of cholesterol and deciphering the underlying molecular events in HCC development is highly relevant to developing new therapies. Here, we discuss the current understanding of cholesterol metabolism in the pathogenesis of NAFLD-associated HCC, and the underlying mechanisms, including the roles of cholesterol in the disruption of normal function of specific cell types and signaling transduction. We also review the clinical progression in evaluating the association of cholesterol with HCC. The therapeutic effects of lowering cholesterol will also be summarized. We also interpret reasons for the contradictory observations from different preclinical and human studies of the roles of cholesterol in HCC, aiming to provide a critical assessment of the potential of cholesterol as a therapeutic target.

Decreased Sclerostin Secretion in Humans and Mice With Nonalcoholic Fatty Liver Disease.

Objectives: Growing evidence argues for a relationship between liver and bone metabolisms. Sclerostin is a secreted glycoprotein and could antagonize osteoblast-mediated bone formation. Previous studies indicated that circulating sclerostin levels may be associated with metabolic parameters with inconsistent results. This study was designed to evaluate serum sclerostin in patients with or without nonalcoholic fatty liver disease (NAFLD) and to analyze its relationship with metabolic parameters in different populations. Methods: A cross-sectional study was designed and 168 NAFLD subjects and 85 control subjects were included in this study. Serum sclerostin and metabolic parameters were measured. Mouse models of NAFLD were also induced by high-fat diet. Bone structural parameters were determined using microCT and mRNA expression levels of sclerostin in bone and liver tissues were measured. Results: Our study suggested that circulating sclerostin levels were significantly lower in NAFLD subjects compared with normal controls. In NAFLD subjects, sclerostin was negatively correlated with multiple metabolic parameters, including waist circumference, urea, hepatic enzyme, gamma-glutamyl transpeptidase, and triglyceride, while such correlation was not significant in control subjects. Circulating sclerostin was also negatively correlated with fatty liver index in NAFLD subjects but not in control subjects. Mice fed on a high-fat diet had reduced bone mass and lower sclerostin expression levels in both the bone and liver tissues. Conclusions: Our study suggested that the liver-lipid-bone interactions may play a key role in the abnormal bone metabolism in NAFLD, and circulating sclerostin may be a surrogate marker to reflect bone metabolism status in NAFLD subjects.

Left Ventricular Remodeling in Patients with Primary Aldosteronism: A Prospective Cardiac Magnetic Resonance Imaging Study.

OBJECTIVE: This study used cardiac magnetic resonance imaging (MRI) to compare the characteristics of left ventricular remodeling in patients with primary aldosteronism (PA) with those of patients with essential hypertension (EH) and healthy controls (HCs). MATERIALS AND METHODS: This prospective study enrolled 35 patients with PA, in addition to 35 age- and sex-matched patients with EH, and 35 age- and sex-matched HCs, all of whom underwent comprehensive clinical and cardiac MRI examinations. The analysis of variance was used to detect the differences in the characteristics of left ventricular remodeling among the three groups. Univariable and multivariable linear regression analyses were used to determine the relationships between left ventricular remodeling and the physiological variables. RESULTS: The left ventricular end-diastolic volume index (EDVi) (mean ± standard deviation [SD]: 85.1 ± 13.0 mL/m² for PA, 75.9 ± 14.3 mL/m² for EH, and 77.3 ± 12.8 mL/m² for HC; p = 0.010), left ventricular end-systolic volume index (ESVi) (mean ± SD: 35.2 ± 9.8 mL/m² for PA, 30.7 ± 8.1 mL/m² for EH, and 29.5 ± 7.0 mL/m² for HC; p = 0.013), left ventricular mass index (mean ± SD: 65.8 ± 16.5 g/m² for PA, 56.9 ± 12.1 g/m² for EH, and 44.1 ± 8.9 g/m² for HC; p < 0.001), and native T1 (mean ± SD: 1224 ± 39 ms for PA, 1201 ± 47 ms for EH, and 1200 ± 44 ms for HC; p = 0.041) values were higher in the PA group compared to the EH and HC groups. Multivariable linear regression demonstrated that log (plasma aldosterone-to-renin ratio) was independently correlated with EDVi and ESVi. Plasma aldosterone was independently correlated with native T1. CONCLUSION: Patients with PA showed a greater degree of ventricular hypertrophy and enlargement, as well as myocardial fibrosis, compared to those with EH. Cardiac MRI T1 mapping can detect left ventricular myocardial fibrosis in patients with PA.

Evaluation of the effects of glycated hemoglobin on cardiac function in patients with short-duration type 2 diabetes mellitus: A cardiovascular magnetic resonance study.

AIMS: To investigate the association between glycated hemoglobin (HbA1c) and myocardial dysfunction and to determine whether its association is independent of myocardial perfusion. METHODS: Sixty-four patients with type 2 diabetes mellitus (T2DM) were recruited. They were divided into groups according to their HbA1c level: the controlled T2DM group (HbA1c < 7%) and uncontrolled T2DM groups (HbA1c ≥ 7%). Meanwhile, 30 age-matched healthy volunteers were included. All patients with T2DM and healthy controls underwent cardiovascular magnetic resonance imaging to evaluate the myocardial mechanics and perfusion parameters. RESULTS: The circumferential and longitudinal peak strain (PS) (p = 0.009 and 0.002 respectively) and global radial, circumferential, and longitudinal peak strain diastolic strain rates (PDSRs) (p = 0.002, 0.001, and 0.001 respectively) were lower in the uncontrolled T2DM group than in the controls without diabetes. In multivariable linear regression analysis, HbA1c was independently related to all directions of the PS and PDSR. The myocardial perfusion parameters were not independently associated with the PS or PDSR. CONCLUSIONS: Cardiac function is impaired in Chinese T2DM patients with poor glucose control (HbA1c ≥ 7%), with preserved left ventricular (LV) ejection fraction, and disease duration <10 years. Poor blood glucose control is an independent predictor of LV myocardial dysfunction for patients with short-term T2DM.

CMR-Verified Myocardial Fibrosis Is Associated With Subclinical Diastolic Dysfunction in Primary Aldosteronism Patients.

Objectives: The main cardiac features of primary aldosteronism (PA) are impaired left ventricular (LV) diastolic function, and some articles also reported more cardiac fibrosis in PA patients. However, the correlation between LV dysfunction and diffuse myocardial fibrosis in PA remains unknown. Methods: We enrolled 84 PA patients and 28 essential hypertension (EH) patients in West China Hospital. Cardiac magnetic resonance imaging (CMR) contrast enhancement was arranged for all subjects. Postcontrast T1 time and left ventricular myocardial strains and strain rates were measured. Results: 76 PA patients and 27 essential hypertension (EH) patients were included in the final analysis. Blood pressure, LV mass indexes, and LV ejection fractions were comparable in both groups, while the global circumferential peak diastolic strain rate (PDSR) was lower (0.9 ± 0.3 vs. 1.1 ± 0.4, p <0.01) and the postcontrast T1 time was shorter (520 ± 38 vs. 538 ± 27, p = 0.01) in PA patients than those in EH patients. Postcontrast T1 time (p = 0.01) was independently related to global circumferential PDSR after adjusting for age and duration of hypertension in PA patients. Furthermore, plasma aldosterone concentration was negatively associated with postcontrast T1 time (R = -0.253, p = 0.028) in PA patients. Conclusions: The global circumferential PDSR derived by CMR is decreased, and the diffuse myocardial fibrosis is increased in PA patients compared to those in blood pressure matched EH patients. The severity of cardiac diastolic dysfunction independently relates to the degree of diffuse myocardial fibrosis in PA patients, and the diffuse myocardial fibrosis may be caused by high PAC level. Clinical Trial Registration: http://www.chictr.org.cn/listbycreater.asp, identifier ChiCTR2000031792.

A Novel Diagnostic Model for Primary Adrenal Lymphoma.

Objective: Primary adrenal lymphoma (PAL) is easily misdiagnosed as other adrenal masses, such as adrenocortical carcinoma and pheochromocytoma, but patients with PAL benefit little from surgery. The diagnostic method for PAL thus far is limited to adrenal biopsy. In our study, we aimed to develop a quick and efficient diagnostic method for PAL. Methods and Results: At the same institution, 505 patients (between 2009 and 2019) and 171 patients (between 2019 and 2020) were separately included in the primary and validation studies. Univariate and multivariate analyses were conducted to evaluate clinical manifestations, laboratory findings, and radiological characteristics. Four determinants (age, bilateral masses, high-density lipoprotein cholesterol, and lactate dehydrogenase) were selected and further incorporated into a regression model to screen PAL. Accordingly, the nomogram was developed for clinical practice. In the primary study, the nomogram showed good discrimination, with an area under the receiver operating characteristic (ROC) curve (AUC) of 95.4% (95% CI, 90.6%-100.0%). Further validation study verified the efficacy of the nomogram, with an AUC of 99.0% (95% CI, 96.9%-100.00%) and 100.0% in all patients and patients with bilateral masses, respectively, and a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 66.67%/99.40%/66.67%/99.40%, 66.67%/100%/100%/92.86%, 50%/99.20%/50%/99.20%, and 100%/100%/100%/100%, in all patients, patients with bilateral adrenal masses, patients with nonfunctional adrenal masses, and patients with positive catecholamine results, respectively. The validation study also revealed a diagnostic specificity of 99.35% and 100% for patients with a unilateral adrenal mass and functional PCC, respectively. Conclusions: The presented nomogram is the first user-friendly diagnostic model for PAL that simplifies the complex diagnostic process into personalized numeric estimates. We deem that patients who score below 50 are less likely to have PAL. We suggest that clinicians should arrange adrenal biopsy and surgery for patients with nonfunctional tumors and overt catecholamine-secreting tumors, respectively, who receive a score of 50 points or higher to confirm the diagnosis as soon as possible.

[Diagnostic Efficiency of Different Screening Indexes for Primary Aldosteronism].

OBJECTIVE: To investigate the the feasibility and diagnostic efficiencyvalue of different screening indexesmethods for screening primary aldosteronism (PA). METHODS: The clinical data of 499 patients with PA and 479 patients with essential hypertension diagnosed from Jan. 2009 to Dec. 2018 were retrospectively analyzed. The diagnostic performance of different screening indexs was compared by plotting receiver operating characteristic curves (ROC). RESULTS: The area under the ROC curve ( AUC) of the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR) was greater than that of the ratio of the upright PAC to the angiotensin Ⅱ (AT-Ⅱ) (AA2R), upright PRA, upright PAC, supine ARR, and lowest blood potassium ( P<0.05). The AUC of logistic regression model was greater than that of upright ARR (96.3% vs. 94.6%, P<0.05). There was no significant difference in AUC between decision tree model and upright ARR (94.1% vs. 94.6%, P>0.05). In the test set, the AUC difference between the logistic regression model and the decision tree model was not statistically significant (96.3% vs. 94.1%, P > 0.05). The calibration curve of the logistic regression model is closer to the 45 ° line, and the consistency between the prediction probability and the actual probability of the logistic regression model is better than that of the decision tree model. CONCLUSION: For the screening of PA, upright ARR seems to be the best single screening index, while AA2R (radioimmunoassay) is not recommended. The diagnostic efficacy of logistic regression model including upright PAC, PRA and lowest blood potassium is better than that of single upright ARR.

Interleukin-38 increases the insulin sensitivity in children with the type 2 diabetes.

The prevalence of type 2 diabetes mellitus (DM) is increasing in the children population. It is well known that inflammation contributes to the type 2 DM pathogenesis. Interleukin 38 (IL-38) is one newly identified anti-inflammatory factor. Therefore, we investigated whether the expression level of IL-38 is associated with type 2 DM in the children and the underlying mechanism. Children with recently diagnosed type 2 diabetes mellitus were recruited and studied. The healthy subjects without glucose metabolism abnormalities were used as controls. The IL-38 expression level was determined by quantitative PCR and ELISA (Enzyme-linked immunoassay). Statistic analysis showed that the IL-38 level was significantly associated with type 2 DM and insulin resistance in the children. The patients were then divided into two groups, one group sensitive to insulin therapy while the other resistant to insulin therapy. Data showed that the IL-38 was highly expressed in the group sensitive to insulin therapy. In the mice model, overexpressing the IL-38 could suppress the expression of IL-36, a pro-inflammatory factor, and also the diabetes development. Thus our results showed that higher IL-38 was associated with the increased insulin sensitive in children with type 2 DM and inhibited T2DM development in the mouse model through suppressing the function of IL-36.

Neutralization of Oxidized Phospholipids Ameliorates Non-alcoholic Steatohepatitis.

Oxidized phospholipids (OxPLs), which arise due to oxidative stress, are proinflammatory and proatherogenic, but their roles in non-alcoholic steatohepatitis (NASH) are unknown. Here, we show that OxPLs accumulate in human and mouse NASH. Using a transgenic mouse that expresses a functional single-chain variable fragment of E06, a natural antibody that neutralizes OxPLs, we demonstrate the causal role of OxPLs in NASH. Targeting OxPLs in hyperlipidemic Ldlr-/- mice improved multiple aspects of NASH, including steatosis, inflammation, fibrosis, hepatocyte death, and progression to hepatocellular carcinoma. Mechanistically, we found that OxPLs promote ROS accumulation to induce mitochondrial dysfunction in hepatocytes. Neutralizing OxPLs in AMLN-diet-fed Ldlr-/- mice reduced oxidative stress, improved hepatic and adipose-tissue mitochondrial function, and fatty-acid oxidation. These results suggest targeting OxPLs may be an effective therapeutic strategy for NASH.

Investigation into the Mechanism(s) That Leads to Platelet Decreases in Cynomolgus Monkeys During Administration of ISIS 104838, a 2'-MOE-Modified Antisense Oligonucleotide.

ISIS 104838, a 2'-O-methoxyethyl (2'-MOE)-modified antisense oligonucleotide (ASO), causes a moderate, reproducible, dose-dependent, but selflimiting decrease in platelet (PLT) counts in monkeys and humans. To determine the etiology of PLT decrease in cynomolgus monkeys, a 12-week repeat dose toxicology study in 5 cynomolgus monkeys given subcutaneous injections of ISIS 104838 (30-60 mg/kg/week). Monkeys were also injected intravenously with 111Indium(In)-oxine-labeled PLTs to investigate PLT sequestration. In response to continued dosing, PLT counts were decreased by 50%-90% by day 30 in all monkeys. PLT decreases were accompanied by 2- to 4.5-fold increases in immunoglobulin M(IgM), which were typified by a 2- to 5-fold increase in antiplatelet factor 4 (antiPF4) IgM and antiPLT IgM, respectively. Monocyte chemotactic protein 1 increased upon dosing of ISIS 104838, concomitant with a 2- to 6-fold increase in monocyte-derived extracellular vesicles (EVs), indicating monocyte activation but not PLT activation. Despite a 2- to 3-fold increase in von Willebrand factor antigen in all monkeys following ASO administration, only 2 monkeys showed a 2- to 4-fold increase in endothelial EVs. Additionally, a ∼60 - 80%% increase in PLT sequestration in liver and spleen was also observed. Collectively, these results suggest the overall increase in total IgM, antiPLT IgM and/or antiPF4 IgM, in concert with monocyte activation contributed to increased PLT sequestration in spleen and liver, leading to decreased PLTs in peripheral blood.

Association of Serum Ferritin Level with Risk of Incident Abnormal Glucose Metabolism in Southwestern China: a Prospective Cohort Study.

This prospective cohort study aimed to analyze the association between serum ferritin levels and the risk of abnormal glucose metabolism (AGM) in Southwestern Chinese population. The 383 subjects who are aged ≥20 years and free of AGM at baseline between in 2007 and in 2008 were included in Southwestern China, and their baseline serum ferritin levels were measured. Among these subjects, 140 subjects were developed into AGM during the follow-up (2008-2012). In logistic regression models, the relative risk in the top versus that in the lowest quartile of serum ferritin levels was 2.86 (p = 0.013) in females and 3.50 (p = 0.029) in males after adjusting the age, gender, family history of diabetes, current smoking, and alcohol; however, serum ferritin levels were not significantly associated with incident of AGM after controlling for metabolic factors (waist circumference, systolic pressure (SBP), triglyceride (TG), and homeostasis model assessment formula insulin resistance (HOMA-IR)). Elevated serum ferritin levels are associated with AGM but not an independent risk factor.

Silybin reduces obliterated retinal capillaries in experimental diabetic retinopathy in rats.

Silybin has been previously reported to possess anti-inflammatory properties, raising the possibility that it may reduce vascular damage in diabetic retinopathy. Present study was designed to investigate this potential effect of silybin and its underlying mechanisms in experimental diabetic retinopathy. Diabetes was induced with streptozotocin (STZ) plus high-fat diet in Sprague-Dawley rats, and silybin was administrated for 22 weeks after the induction of diabetes. Histochemical and immunofluorescence techniques were used to assess the obliterated retinal capillaries, leukostasis, and level of retinal intercellular adhesion molecule-1 (ICAM-1). Western blot was performed to quantitate the expression of retinal ICAM-1. Results showed that silybin treatment significantly prevented the development of obliterated retinal capillaries in diabetes, compared with vehicle treatment. In addition, leukostasis and level of the retinal ICAM-1 were found to decrease considerably in silybin-treated diabetic groups. In conclusion, these results indicate that silybin reduces obliterated retinal capillaries in experimental diabetes, and the recovered retinal vascular leukostasis and level of ICAM-1 at least partly contributes to the preventive effect of silybin.

[The study of dynamic acccumulation of camptothecin in Camptotheca acuminata fruit by TLCS].

OBJECTIVE: To establish TLC scanning method for the determination of camptothecin in Camptotheca acuminata fruit, and analysis the dynamic accumulation of camptothecin in Camptotheca acuminata fruit to find out the best collection period. METHODS: Silica gel H-CMC-Na thin layer plate was adopted in the determination with chloroform-acetone (7 : 3) used as deeloper, Single-wavelength and linear scanning of TLC was used, and the detection wavelength was 360 nm. RESULTS: There was a good linear relationship for Comptothecin within the range of 0.0542 - 0.3252 microg, the average recovery was 97.13%, RSD was 1.76%. CONCLUSION: The method is accurate, simple and reliable, and can be used for the determination of camptothecin in Camptotheca acuminata fruit and dynamic accumulation research.