Brusatol alleviates pancreatic carcinogenesis via targeting NLRP3 in transgenic Krastm4Tyj Trp53tm1Brn Tg (Pdx1-cre/Esr1*) #Dam mice.

BACKGROUND: Pancreatic cancer (PanCa), ranked as the 4th leading cause of cancer-related death worldwide, exhibits an dismal 5-year survival rate of less than 5 %. Chronic pancreatitis (CP) is a known major risk factor for PanCa. Brusatol (BRT) possesses a wide range of biological functions, including the inhibition of PanCa proliferation. However, its efficacy in halting the progression from CP to pancreatic carcinogenesis remains unexplored. METHODS: We assess the effects of BRT against pancreatic carcinogenesis from CP using an experimentally induced CP model with cerulein, and further evaluate the therapeutic efficacy of BRT on PanCa by employing Krastm4TyjTrp53tm1BrnTg (Pdx1-cre/Esr1*) #Dam/J (KPC) mouse model. RESULTS: Our finding demonstrated that BRT mitigated the severity of cerulein-induced pancreatitis, reduced pancreatic fibrosis and decreased the expression of α-smooth muscle actin (α-SMA), which is a biomarker for pancreatic fibrosis. In addition, BRT exerted effects against cerulein-induced pancreatitis via inactivation of NLRP3 inflammasome. Moreover, BRT significantly inhibited tumor growth and impeded cancer progression. CONCLUSIONS: The observed effect of BRT on impeding pancreatic carcinogenesis through targeting NLRP3 inflammasome suggests its good potential as a potential agent for treatment of PanCa.

[Anti-tumor mechanism of total saponins of Paridis Rhizoma on inducing ferroptosis of breast cancer MCF-7 cells].

This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 µg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC_(50) of 4.12 µg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.

Sub-50 nm core-shell nanoparticles with the pH-responsive squeezing release effect for targeting therapy of hepatocellular carcinoma.

The development of drug delivery systems with high drug loading capacity, low leakage at physiological pH, and rapid release at the lesion sites remains an ongoing challenge. In this work, core-shell poly(6-O-methacryloyl-D-galactose)@poly(tert-butyl methacrylate) (PMADGal@PtBMA) nanoparticles (NPs) of sub-50 nm are facilely synthesized by reversible addition-fragmentation chain transfer (RAFT) soap-free emulsion polymerization with the assistance of 12-crown-4. A hydrophilic poly(methacrylic acid) (PMAA) core can then be revealed after deprotection of the tert-butyl groups, which is negatively charged and can adsorb nearly 100% of incubated doxorubicin (DOX) from a solution at pH 7.4. The physical shrinkage of PMAA chains below pH 6.0 endows the core with the squeezing effect, therefore realizing rapid drug release. It is demonstrated that the DOX release rate of PMADGal@PMAA NPs at pH 5 was 4 times that at pH 7.4. Cellular uptake experiments confirm the high targeting ability of the galactose modified PMADGal shell to human hepatocellular carcinoma (HepG2) cells. The fluorescence intensity of DOX in HepG2 cells is 4.86 times that of HeLa cells after 3 h incubation. Moreover, 20% cross-linked NPs show the highest uptake efficiency by HepG2 cells due to their moderate surface charge, size and hardness. In summary, both the core and the shell of PMADGal@PMAA NPs promise the rapid site-specific release of DOX in HepG2 cells. This work provides a facile and an effective strategy to synthesize core-shell NPs for hepatocellular carcinoma targeting therapy.

Elevated HMGB1 and sRAGE levels in cerebrospinal fluid of aneurysmal subarachnoid hemorrhage patients.

BACKGROUND: Neuroinflammation after aneurysmal subarachnoid hemorrhage (aSAH) leads to poor outcome of patients. High mobility group box 1 (HMGB1) contributes to inflammation through binding to receptors for advanced glycation end-products (RAGE) in various diseases. We aimed to determine the production of these two factors after aSAH and their relationship with clinical features. METHODS: HMGB1 and soluble RAGE (sRAGE) levels in cerebrospinal fluid (CSF) of aSAH patients and controls were measured, and their temporal courses were observed. The correlation between early concentrations (days 1-3) and clinical symptoms assessed by disease severity scores, neuroinflammation estimated by CSF IL-6 levels, as well as prognosis evidenced by delayed cerebral ischemia (DCI) and 6-month adverse outcome was investigated. Finally, combined analysis of early levels for predicting prognosis was confirmed. RESULTS: CSF HMGB1 and sRAGE levels were higher in aSAH patients than in controls (P < 0.05), and the levels decreased from higher early to lower over time. Their early concentrations were positively associated with disease severity scores, IL-6 levels, DCI and 6-month poor outcome (P < 0.05). HMGB1 ≥ 6045.5 pg/ml (OR = 14.291, P = 0.046) and sRAGE ≥ 572.0 pg/ml (OR = 13.988, P = 0.043) emerged as independent predictors for DCI, while HMGB1 ≥ 5163.2 pg/ml (OR = 7.483, P = 0.043) and sRAGE ≥ 537.3 pg/ml (OR = 12.653, P = 0.042) were predictors for 6-month poor outcome. Combined analysis of them improved predictive values of adverse prognosis. CONCLUSION: CSF HMGB1 and sRAGE levels of aSAH patients were increased early and then varied dynamically, which might act as potential biomarkers for poor outcome, especially when co-analyzed.

Galactosylated Core-Shell Nanoparticles with pH/GSH Dual Sensitivity for Targeting Hepatocellular Carcinoma.

Galactosylated core-shell nanoparticles (NPs) with diameters of sub-50 nm were fabricated in one pot by reversible addition-fragmentation chain transfer (RAFT) soap-free emulsion polymerization. Their galactosylated shells and acidic cores endow them with high targeting and drug loading efficiencies, respectively. Morever, the physical shrinkage and cleavage of the disulfide cross-linked NPs can realize the rapid release of loaded doxorubicin (DOX) under pH 5.0 and reduced glutathione (GSH) conditions. The combination of these excellent properties resulted in an even lower IC50 of DOX-loaded NPs than free DOX, demonstrating that this platform would be promising in targeting the therapy of hepatocellular carcinoma.

Whole-brain monosynaptic outputs and presynaptic inputs of GABAergic neurons in the vestibular nuclei complex of mice.

GABAergic neurons in the vestibular nuclei (VN) participate in multiple vital vestibular sensory processing allowing for the maintenance and rehabilitation of vestibular functions. However, although the important role of GABA in the central vestibular system has been widely reported, the underlying neural circuits between VN GABAergic neurons and other brain functional regions remain elusive, which limits the further study of the underlying mechanism. Hence, it is necessary to elucidate neural connectivity based on outputs and inputs of GABAergic neurons in the VN. This study employed a modified rabies virus retrograde tracing vector and cre-dependent adeno-associated viruses (AAVs) anterograde tracing vector, combined with a transgenic VGAT-IRES-Cre mice, to map the inputs and outputs of VN GABAergic neurons in the whole brain. We found that 51 discrete brain regions received projections from VN GABAergic neurons in the whole brain, and there were 77 upstream nuclei innervating GABAergic neurons in the VN. These nuclei were mainly located in four brain regions, including the medulla, pons, midbrain, and cerebellum. Among them, VN GABAergic neurons established neural circuits with some functional nuclei in the whole brain, especially regulating balance maintenance, emotion control, pain processing, sleep and circadian rhythm regulation, and fluid homeostasis. Therefore, this study deepens a comprehensive understanding of the whole-brain neural connectivity of VN, providing the neuroanatomical information for further research on the neural mechanism of the co-morbidities with vestibular dysfunction.

NF-κB pathway play a role in SCD1 deficiency-induced ceramide de novo synthesis.

Stearoyl-CoA-desaturase 1 (SCD1) deficiency mediates apoptosis in colorectal cancer cells by promoting ceramide de novo synthesis. The mechanisms underlying the cross-talk between SCD1 and ceramide synthesis have not been explored. We treated colorectal cancer cells with an SCD1 inhibitor and examined the effects on gene expression, cell growth, and cellular lipid contents. The main effect of SCD1 inhibition on the fatty acid contents of colorectal cancer cells was a decrease in monounsaturated fatty acids (MUFAs). RNA sequencing (RNA-seq) showed that the most intense alteration of gene expression after SCD1 inhibition occurred in the NF-κB signaling pathway. Further experiments revealed that SCD1 inhibition resulted in increased levels of phosphorylated NF-κB p65 and increased nuclear translocation of NF-κB p65. Treatment with an NF-κB inhibitor eliminated several effects of SCD1 inhibition, mainly including overexpression of serine palmitoyltransferase1 (SPT1), elevation of dihydroceramide contents, and suppression of cell growth. Furthermore, treatment with supplemental oleate counteracted the SCD1-induced NF-κB activation and downstream effects. In summary, our data demonstrate that the NF-κB pathway plays a role in SCD1 deficiency-induced ceramide de novo synthesis in colorectal cancer cells, and that reduced MUFA levels contribute to the course.

lncRNA-POIR promotes epithelial-mesenchymal transition and suppresses sorafenib sensitivity simultaneously in hepatocellular carcinoma by sponging miR-182-5p.

Sorafenib (SOR) resistance remains a major obstacle in the effective treatment of hepatocellular carcinoma (HCC). A number of long noncoding RNAs (lncRNAs) are responsible for this chemoresistance. This study aimed to reveal the essential function of a recently defined lncRNA, lncRNA-POIR, in the epithelial-mesenchymal transition (EMT) and SOR sensitivity of HCC cells. SOR-induced cytotoxicity was analyzed via cell counting kit-8 and ethynyl-2'-deoxyuridine incorporation assays, whereas immunoblotting and confocal immunofluorescence were used to determine the expression levels of EMT markers. Furthermore, loss- or gain-of-function approaches were used to demonstrate the role of lncRNA-POIR/miR-182-5p on EMT and SOR sensitivity in HCC. The direct interaction between lncRNA-POIR and miR-182-5p was verified using a luciferase reporter assay. We found that knockdown of lncRNA-POIR sensitized HCC cells to SOR and simultaneously reversed EMT. As expected, miR-182-5p was confirmed as the downstream target of lncRNA-POIR. Moreover, miR-182-5p overexpression clearly reversed EMT and promoted SOR-induced cytotoxicity in representative HCC cells, whereas miR-182-5p downregulation played a contrasting role; miR-182-5p knockdown abolished the modulatory effects of lncRNA-POIR siRNA on EMT and SOR sensitivity. Together, these pieces of data suggest that lncRNA-POIR promotes EMT progression and suppresses SOR sensitivity simultaneously by sponging miR-182-5p. Thus, we proposed a compelling rationale for the use of lncRNA-POIR as a promising predictor of SOR response and as a potential therapeutic target for HCC treatment in the future.

Changes in antimicrobial susceptibility of commonly clinically significant isolates before and after the interventions on surgical prophylactic antibiotics (SPAs) in Shanghai

Abstract Surveillances and interventions on antibiotics use have been suggested to improve serious drug-resistance worldwide. Since 2007, our hospital have proposed many measures for regulating surgical prophylactic antibiotics (carbapenems, third gen. cephalosporins, vancomycin, etc.) prescribing practices, like formulary restriction or replacement for surgical prophylactic antibiotics and timely feedback. To assess the impacts on drug-resistance after interventions, we enrolled infected patients in 2006 (pre-intervention period) and 2014 (post-intervention period) in a tertiary hospital in Shanghai. Proportions of targeted pathogens were analyzed: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), imipenem-resistant Escherichia coli (IREC), imipenem-resistant Klebsiella pneumoniae (IRKP), imipenem-resistant Acinetobacter baumannii (IRAB) and imipenem-resistant Pseudomonas aeruginosa (IRPA) isolates. Rates of them were estimated and compared between Surgical Department, ICU and Internal Department during two periods. The total proportions of targeted isolates in Surgical Department (62.44%, 2006; 64.09%, 2014) were more than those in ICU (46.13%, 2006; 50.99%, 2014) and in Internal Department (44.54%, 2006; 51.20%, 2014). Only MRSA has decreased significantly (80.48%, 2006; 55.97%, 2014) (p < 0.0001). The percentages of VRE and IREC in 3 departments were all <15%, and the slightest change were also both observed in Surgical Department (VRE: 0.76%, 2006; 2.03%, 2014) (IREC: 2.69%, 2006; 2.63%, 2014). The interventions on surgical prophylactic antibiotics can be effective for improving resistance; antimicrobial stewardship must be combined with infection control practices.

[Estimation of Diffuse Attenuation Coefficient of Photosynthetically Active Radiation in Xin'anjiang Reservoir Based on Landsat 8 Data].

Photosynthetically active radiation (PAR) is defined as the wavelength band of 400 to 700 nm, representing most of the visible solar radiation that could be used for photosynthesis. PAR is attenuated by the absorption and scattering of nonpigment suspended matter, chromophoric dissolved organic matter and phytoplankton, and it plays an important role in determining the density and distribution of aquatic organisms. This study developed an empirical model and presented the spatial-temporal distribution of PAR diffuse attenuation coefficient [Kd (PAR)] for the slightly turbid Xin'anjiang Reservoir based on the in situ ground data and the matching Landsat 8 data. The results showed that the three-hand combinational model of Kd ( PAR) using Band 2, Band 3 and Band 8 could give a reasonable and acceptable estimation accuracy with a determination coefficient of 0. 87. Independent dataset was used to validate the model with a mean relative error of 9.16% and a root mean square error of 0.06 m⁻¹. Therefore, the three-band combination using Landsat 8 data could be used to accurately estimate Kd (PAR) in the slightly turbid Xin'anjiang Reservoir. Kd (PAR) exhibited significant seasonal and spatial differences. Kd (PAR) was higher in autumn (September-November) and summer (June-August) with the average Kd (PAR) of (0.82 ± 0.60) m⁻¹ and (0.77 ± 0.41) m⁻¹, but lower in winter (December-February) and spring (March-May) with the average Kd (PAR) of (0.56 ± 0.50) m⁻¹ and (0.40 ± 0.45 ) m⁻¹, respectively. Spatially, Kd (PAR) ranged from 0.002 to 13.86 m⁻¹ with an average of (0.64 ± 0.49) m⁻¹. The temporal heterogeneity of Kd (PAR) was mainly caused by the seasonal rainfall and seasonal growth of phytoplankton. The spatial heterogeneity was mainly caused by suspended matter concentration derived from watershed inputs and human dredging activity.

p62/SQSTM1 is involved in caspase-8 associated cell death induced by proteasome inhibitor MG132 in U87MG cells.

Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. Proteasome inhibitors are emerging as a new class of anti-glioma agents; however, the mechanisms of their killing malignant cells are still unclear. We treated U87MG cells with the proteasome inhibitor MG132 and found that cell death correlated with caspase-8 activation and autophagy protein p62/SQSTM1.To explore the role of autophagy and p62/SQSTM1 in MG132-induced cancer cell death, we measured the alteration of MG132's cytotoxicity by autophagy inhibition, autophagy induction or variation of p62/SQSTM1 gene expression. Autophagy was activated upon MG132 treatment for short periods, while inhibition of autophagy aggravated MG132-induced cell death followed by high levels of p62/SQSTM1 and active caspase-8 (p18). Moreover, U87MG cell death was dependent on p62/SQSTM1, and its function required its C-terminus UBA domain to attenuate the MG132-induced cell death. The results suggest that p62/SQSTM1 is a potential contributor in determining the fate of U87MG cells deficient in proteolytic activity.

Autophagic degradation of caspase-8 protects U87MG cells against H2O2-induced oxidative stress.

Oxidative stress induces apoptosis in many cellular systems including glioblastoma cells, with caspase-8 activation was regarded as a major contribution to H2O2-induced cell death. This study focused on the role of the autophagic protein p62 in H2O2-induced apoptosis in U87MG cells. Oxidative stress was applied with H2O2, and cell apoptosis and viability were measured with use of caspase inhibitors or autophagic mediators or siRNA p62, GFP-p62 and GFP-p62-UBA (del) transfection. We found that H2O2 -induced U87MG cell death was correlated with caspase-8. To understand the role of p62 in MG132-induced cell death, the levels of p62/SQSTM1 or autophagy in U87MG cells were modulated with biochemical or genetic methods. The results showed that the over-expression of wild type p62/SQSTM1 significantly reduced H2O2 induced cell death, but knockdown of p62 aggravated the process. In addition, inhibition of autophagy promoted p62 and active caspase-8 increasing H2O2 -induced apoptosis while induction of autophagy manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 required its C-terminus UBA domain to attenuate H2O2 cytotoxity by inhibition of caspase-8 activity. Our results indicated that p62/SQSTM1 was a potential contributor to mediate caspase-8 activation by autophagy in oxidative stress process.

Temporal and spatial distribution of gentamicin in the peripheral vestibular system after transtympanic administration in guinea pigs.

BACKGROUND AND OBJECTIVE: Transtympanic administration of gentamicin is effective for treating patients with intractable vertigo. This study explored the spatial and temporal distribution of gentamicin in vestibular end-organs after transtympanic administration. METHODS: Thirty guinea pigs were transtympanically injected with gentamicin conjugated to Texas Red (GTTR) and their vestibular end-organs examined after various survival periods. Another 9 guinea pigs received GTTR at different doses. Nine animals received Texas Red only and served as controls. We used confocal microscopy to determine the cellular distribution of GTTR in semicircular canal cristae, as well as the utricular and saccular maculae. RESULTS: The most intense GTTR labeling was present in the saccule compared to other vestibular end-organs. GTTR fluorescence was detected predominantly in type I hair cells, type II hair cells and transitional cells after a single transtympanic dose of GTTR (0.1 mg/ml, 0.05 ml), while only weak fluorescence was observed in non-sensory cells such as supporting cells, dark cells and lumenal epithelial cells. Transitional cells displayed intense GTTR fluorescence in the supra-nuclear regions 24 h after transtympanic injection that was retained for at least 4 weeks. A decreasing spatial gradient of GTTR fluorescence was observed sensory epithelial regions containing central type I to peripheral type I and then type II hair cells in the crista ampullaris, and from striolar to extra-striolar hair cells within the vestibular macula. GTTR fluorescence extended from being restricted to the apical cytoplasm at lower doses to the entire cell body of type I hair cells with increasing dose. GTTR fluorescence reached peak intensities for individual regions of interest within the cristae and maculae between 3 and 7 days after transtympanic injection. CONCLUSION: The saccular uptake of GTTR is greater than other vestibular end-organs after transtympanic injection in the semicircular canals.

Sialic acid surface decoration enhances cellular uptake and apoptosis-inducing activity of selenium nanoparticles.

A simple method for fabrication of sialic acid surface-decorated selenium nanoparticles (SA-Se-NPs) with enhanced cancer-targeting and cell-penetrating abilities has been demonstrated in the present study. Monodisperse and homogeneous spherical SA-Se-NPs with striking stability were prepared under the optimized conditions. SA surface decoration significantly increased the cellular uptake and cytotoxicity of Se-NPs in HeLa human cervical carcinoma cells. Treatments of SA-Se-NPs induced dose-dependent apoptosis in HeLa cells, as evidenced by increase in sub-G1 cell populations, nuclear condensation and formation of apoptotic bodies. Further investigation on molecular mechanisms reveals that SA-Se-NPs triggered cancer cell apoptosis through activation of caspase-3 and subsequent cleavage of PARP.

Use of the loud sound stimulation test in diagnosis of semicircular canal dehiscence syndrome.

Semicircular canal dehiscence (SCD) syndrome is rare, and its diagnosis is a significant challenge in clinical practice. Our aim was to explore application of the loud sound stimulation test for diagnosing SCD syndrome. Eight cases of superior semicircular canal dehiscence (SSCD), among them two patients had bilateral dehiscences and one case of lateral semicircular canal dehiscence (LSCD). A total of 11 dehiscences were studied retrospectively. Loud sounds (pure tones, 100 dB, 110 dB nHL) at frequencies of 500, 1,000, and 2,000 Hz were used to stimulate both ears for 5 s. A temporal bone computed tomography (CT) scan with semicircular canal reconstruction was performed in all patients. Vertigo was present in seven of nine cases following loud sound stimulation. In addition, the patient with LSCD demonstrated horizontal eye movement following loud sound stimulation, whereas six patients with SSCD showed rotational eye movement. Among them, two patients with bilateral superior canal dehiscence showed a positive response to the loud sound stimulation in only one ear. The diagnoses of all patients were confirmed with a high-resolution temporal bone CT with corresponding multi-planar reconstruction of the affected semicircular canals with various size dehiscences. We conclude that the characteristic eye movement following loud sound stimulation is valuable for diagnosing SCD syndrome. In addition, the loud sound stimulation test has unique advantages, especially for confirming the affected ear and the corresponding semicircular canal.

Sound-induced vertigo due to bone dehiscence of the lateral semicircular canal.

Dehiscence of the lateral semicircular canal (LSCD) has been reported much but mainly in association with cholesteatoma and canal wall down mastoidectomy, while idiopathic LSCD was rarely reported. Bassim reported one case with lateral semicircular canal dehiscence, but presented no vestibular or auditory symptoms. The patient in this study complained significant sound-induced vertigo and autophony in his right ear. The axis of nystagmus was orthogonal to the lateral semicircular canal, and no torsional or vertical motions were observed, so pathology of the lateral semicircular canal was preferentially considered. Benign paroxysmal positional vertigo was excluded since vertigo attacks had no relation to the change of head position. The dehiscence of the right lateral semicircular canal was then confirmed through the high-resolution temporal bone computer tomography scan and the reconstructed images. The cause of the LSCD is poorly understood, since no history of head trauma, otological infection or surgery was documented.

[The rhythmicity of adiponectin and its relation with glucocorticoids, insulin and leptin].

OBJECTIVE: To investigate the circadian rhythmicity of adiponectin in patients with Cushing's syndrome and obesity, as well as in normal subjects. The effects of glucocorticoids, insulin and leptin on the secretion of adiponectin were also explored. METHODS: 15 patients with Cushing's syndrome and 10 with obesity as well as 9 normal subjects were recruited and their serum adiponectin, glucocorticoids, insulin and leptin levels were determined 6 times a day (8:00, 12:00, 16:00, 20:00, 24:00, 3:00). RESULTS: Circadian rhythmicity of adiponectin was not observed, but the adiponectin levels in patients with obesity were lower than those in the normal subjects at all 6 time spots. The area under curve (AUC) of serum adiponectin concentrations were significantly negatively correlated with body mass index (BMI, r = 0.46, P < 0.01), waist circumference (r = -0.33, P < 0.05) and insulin AUC (r = -0.36, P < 0.05). A multiple linear regression analysis revealed that BMI and waist circumference were two significant independent parameters of the plasma adiponectin level. The adiponectin levels did not manifest any change after short term dexamethasone administration with both high and low doses, but were obviously decreased after surgery. CONCLUSIONS: Neither long-term endogenous hyperglucocorticoidism nor short-term dexamethasone administration affects the serum adiponectin levels and the serum adiponectin concentrations remain unchanged even with elevated postprandial insulin levels.