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Ziran Wang,1 Jintu Chen,2 Jingjing Song,3 Lingjun Kong,1 Xuanzhi Wang,4 Tengda Xu,5 Songbai Lin,5 Yaling Dou1 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 3Department of Clinical Laboratory, Anhui Provincial Maternal and Child Health Hospital, Hefei, Anhui, People’s Republic of China; 4Department of Medical Laboratory, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 5Department of Health Management, Peking Union Medical College Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yaling Dou, Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Email douyl@pumch.cnObjective: To determine the plasminogen activator inhibitor-1 (PAI-1) 4G/5G (rs1799889) genotype of the subjects in a robust detection method and to explore the association of the PAI-1 4G/5G polymorphism with susceptibility to diabetes mellitus (DM) and hypertension (HTN) as well as clinical characteristics.Methods: This study recruited 208 patients (68 patients were diagnosed with DM, 70 patients with HTN and 70 patients with DM combined with HTN) and 132 healthy controls (HC). A subset of the population was selected to evaluate the accuracy of the Real-time PCR (RT-PCR) method for detecting PAI-1 4G/5G polymorphism by using the sequencing method as the gold standard. Furthermore, the association of the PAI-1 4G/5G polymorphism with genetic susceptibility to DM and HTN was explored. Moreover, variations in clinical characteristics among individuals with various PAI-1 genotypes were also analyzed in the DM group, the HTN group and the DM+HTN group.Results: There was a high concordance between the RT-PCR method and the sequencing method in determining the PAI-1 4G/5G polymorphism. No association was observed between the PAI-1 4G/5G polymorphism and susceptibility to DM, HTN and DM+HTN, respectively. There were no statistical differences in all study indicators among individuals that carrying various genotypes in the HC group. There were several variations in clinical characteristics among individuals harboring different PAI-1 4G/5G genotypes in the DM group, the HTN group and the DM+HTN group.Conclusion: The RT-PCR method can accurately identify the PAI-1 4G/5G genotype in different individuals. The PAI-1 4G/5G polymorphism may not be associated with genetic susceptibility to DM, HTN and DM+HTN, but differences in clinical characteristics among individuals with various genotypes may provide a reference for disease assessment and personalized treatment of patients.Keywords: diabetes mellitus, hypertension, plasminogen activator inhibitor-1, gene polymorphism

Jing Li,1 Songbai Lin,1 Chuiwen Deng,2 Tengda Xu1 1Department of Health Management, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2Rheumatology and Immunology Department, Peking Union Medical College Hospital, Beijing, People’s Republic of ChinaCorrespondence: Tengda XuDepartment of Health Management, Peking Union Medical College Hospital, 1# Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel/Fax +86 10 6915 9866Email xutd@pumch.cnPurpose: To investigate the prevalence of GAD antibody (GADA) in the general adult population and to evaluate its predictive value for diabetes in China.Patients and Methods: We searched the PUMCH-HM database and identified 36,731 adult subjects with GADA test results from 2012 to 2015. We then established a retrospective cohort of 4835 nondiabetic subjects at baseline with complete annual health evaluation records through 2019. The median follow-up time was 4.8 (3.0– 7.3) years.Results: The overall prevalence of GADA was 0.53% and was higher in diabetic subjects (1.25%) than in nondiabetic subjects (0.47%). We found a decrease in baseline body mass index (BMI) from the GADA- to GADAhigh subgroups among baseline diabetic and prediabetic patients and also those who developed diabetes later in the cohort study. A total of 136 subjects (2.8%) developed diabetes after a median follow-up of 3.5 years. For GADA+ participants, BMI was not associated with the risk for diabetes. In the Cox regression model, the GADAlow and GADAhigh exhibited 2.63-fold and 4.16-fold increased risk for diabetes, respectively. This increased risk for diabetes by GADA-positivity is only found in male adults (HR 4.55, 95% CI 2.25– 9.23).Conclusion: GADA has a low prevalence in China but is associated with a 2.63– 4.16-fold increased risk for diabetes.Keywords: autoimmune diabetes, glutamic acid decarboxylase antibody, latent autoimmune diabetes in adults, obesity, prevention

Jing Li1 *, Zheng Xu2 *, Tengda Xu,1 Songbai Lin1 1Department of Health Management, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2Department of AI Research, Digital Health China Technologies Co. Ltd, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Songbai Lin, Department of Health Management, Peking Union Medical College Hospital, 1# Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86 10 6915 9901, Fax +86 10 6915 9901, Email linsb@pumch.cnPurpose: To evaluate the performance of machine-learning models based on multiple years of continuous data to predict incident diabetes among patients with metabolic syndrome.Patients and Methods: The dataset comprises the health records from 2008 to 2020 including 4510 nondiabetic participants with metabolic syndrome (MetS) at baseline and with at least 6 years of records. MetS was defined according to the International Diabetes Federation (IDF) criteria. Overall, 332 patients developed incident diabetes during the 7± 1.4 years of follow-up. Three popular classification algorithms were evaluated on the dataset: logistic regression, random forest, and Xgboost. Five models including single-year models (year 1, year 2, and year 3) and multiple-year models (year 1– 2 and year 1– 3) were developed for each algorithm.Results: The model performances improved with the increasing longitudinal dataset as the area under the receiver operating characteristic curve (AUROC) was boosted for both random forest (year 1– 3: AUROC=0.893; year 3: AUROC=0.862; year 1– 2: AUROC=0.847; year 2: AUROC=0.838) and Xgboost (year 1– 3: AUROC=0.897; year 3: AUROC=0.833; year 1– 2: AUROC=0.856; year 2: AUROC=0.823) model. In the multiple-year models, the highest fasting plasma glucose, followed by the mean or lowest level of HbA1c and BMI had the most important predictive value for the onset of diabetes. In the “ 1– 3” year model, “delta weight” which reflects the fluctuations of yearly change of weight was the fourth-most important feature.Conclusion: This study demonstrated improved performance with the accumulation of longitudinal data when using machine learning for diabetes prediction in MetS patients. For individuals with similar clinical parameters, the variation trends of these parameters could change the risk of future diabetes. This result indicated that models based on longitudinal multiple years’ data may provide more personalized assessment tools for risk evaluation.Keywords: diabetes, metabolic syndrome, machine-learning method, prevention

Background Thyroid diseases are highly prevalent worldwide, but their diagnosis remains a challenge. We established reference intervals (RIs) for thyroid-associated hormones and evaluated the prevalence of thyroid diseases in China. Methods After excluding outliers based on the results of ultrasound screening, thyroid antibody tests, and the Tukey method, the medical records of 20,303 euthyroid adults, who visited the Department of Health Care at Peking Union Medical College Hospital from January 2014 to December 2018, were analyzed. Thyroid-associated hormones were measured by the Siemens Advia Centaur XP analyzer. The RIs for thyroid-associated hormones were calculated according to the CLSI C28-A3 guidelines, and were compared with the RIs provided by Siemens. The prevalence of thyroid diseases over the five years was evaluated and compared using the chi-square test. Results The RIs for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were 0.71-4.92 mIU/L, 12.2-20.1 pmol/L, 3.9-6.0 pmol/L, 65.6-135.1 nmol/L, and 1.2-2.2 nmol/L, respectively. The RIs of all hormones except TT4 differed significantly between males and females. The RIs of TSH increased with increasing age. The prevalence of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was 0.5% and 0.8%, 0.2% and 0.6%, 3.8% and 6.1%, and 3.3% and 4.7% in males and females, respectively, which differed from those provided by Siemens. Conclusions Sex-specific RIs were established for thyroid-associated hormones, and the prevalence of thyroid diseases was determined in the Chinese population.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a risk factor of coronary heart disease, however, its effects on stroke are less well-defined. METHODS: We performed a single-center, retrospective case-control study in 1,953 and 196 ischemic stroke and hemorrhagic stroke in-hospital patients, respectively. Controls were healthy individuals that were matched for sex and age (±5 years) for the ischemic (1:1 ratio) and hemorrhagic (1:2 ratio) stroke. Lp(a) concentration was measured using the latex agglutination turbidimetric method. Logarithmic transformation and quartile categorization were applied to adjust for the skewed distribution of Lp(a). Conditional logistic regression models were used to assess the association between Lp(a) and stroke risk. RESULTS: Median Lp(a) concentration was higher in stroke patients when compared with controls (12.2 vs. 8.60 mg/dL) and hemorrhagic strokes (14.40 vs. 13.40 mg/dL). The conditional multivariate analysis revealed a positive association between Lp(a) and ischemic stroke (OR =2.03, 2.36, and 2.03 for quartiles 2, 3 and 4, respectively, vs. quartile 1; P

Autotaxin (ATX or ENPP2) is a secreted lysophospholipase D that produces lysophosphatidic acid (LPA), a pleiotropic lipid mediator acting on specific GPCRs. ATX and LPA have been implicated in key (patho)physiologic processes, including embryonic development, lymphocyte homing, inflammation, and cancer progression. Using LPA receptor knockout mice, we previously uncovered a role for LPA signaling in promoting colitis and colorectal cancer. Here, we examined the role of ATX in experimental colitis through inducible deletion of Enpp2 in adult mice. ATX expression was increased upon induction of colitis, whereas ATX deletion reduced the severity of inflammation in both acute and chronic colitis, accompanied by transient weight loss. ATX expression in lymphocytes was strongly reduced in Rag1(−/−) and μMT mice, suggesting B cells as a major ATX-producing source, which was validated by immunofluorescence and biochemical analyses. ATX secretion by B cells from control, but not Enpp2 knockout, mice led to ERK activation in colorectal cancer cells and promoted T cell migration. We conclude that ATX deletion suppresses experimental colitis and that B cells are a major source of ATX in the colon. Our study suggests that pharmacological inhibition of ATX could be a therapeutic strategy in colitis.—Lin, S., Haque, A., Raeman, R., Guo, L., He, P., Denning, T. L., El-Rayes, B., Moolenaar, W. H., Yun, C. C. Autotaxin determines colitis severity in mice and is secreted by B cells in the colon.

Crohn’s disease (CD) is a chronic, relapsing, inflammatory disease that is often associated with malnutrition because of inflammation in the small intestine. Autotaxin (ATX) is a secreted enzyme that produces extracellular lysophosphatidic acid. Increasing evidence suggests that ATX is upregulated during inflammation, and inhibition of ATX has been effective in attenuating chronic inflammatory conditions, such as arthritis and pulmonary fibrosis. This study aims to determine whether inhibition of ATX alleviates CD-associated inflammation and malnutrition by using SAMP1/Fc mice, a model of CD-like ileitis. SAMP1/Fc mice were treated the ATX inhibitor PF-8380 for 4 wk. Inhibition of ATX led to increased weight gain in SAMP1/Fc mice, decreased T helper 2 cytokine expression, including IL-4, IL-5, and IL-13, and attenuated immune cell migration. SAMP1/Fc mice have low expression of Na+-dependent glucose transporter 1 (SGLT1), suggesting impaired nutrient absorption associated with ileitis. PF-8380 treatment significantly enhanced SGLT1 expression in SAMP1/Fc mice, which could reflect the increased weight changes. However, IL-4 or IL-13 did not alter SGLT1 expression in Caco-2 cells, ruling out their direct effects on SGLT1 expression. Immunofluorescence analysis showed that the expression of sucrase-isomaltase, a marker for intestinal epithelial cell (IEC) differentiation, was decreased in inflamed regions of SAMP1/Fc mice, which was partially restored by PF-8380. Moreover, expression of Na+/H+ exchanger 3 was also improved by PF-8380, suggesting that suppression of inflammation by PF-8380 enhanced IEC differentiation. Our study therefore suggests that ATX is a potential target for treating intestinal inflammation and restoration of the absorptive function of the intestine. NEW & NOTEWORTHY This study is the first, to our knowledge, to determine whether autotoxin (ATX) inhibition improves inflammation and body weights in SAMP1/Fc mice, a mouse model of ileitis. ATX inhibition increased body weights of SAMP1/Fc mice and increased Na+-dependent glucose transporter 1 (SGLT1) expression. Increased SGLT1 expression in the inflamed regions was not a direct effect of cytokines but an indirect effect of increased epithelial cell differentiation upon ATX inhibition.

Intestinal epithelial cells form a barrier that is critical in protecting the host from the hostile luminal environment. Previously, we showed that lysophosphatidic acid (LPA) receptor 1 regulates proliferation of intestinal epithelial cells, such that the absence of LPA1 mitigates the epithelial wound healing process. This study provides evidence that LPA1 is important for the maintenance of epithelial barrier integrity. The epithelial permeability, determined by fluorescently labeled dextran flux and transepithelial resistance, is increased in the intestine of mice with global deletion of Lpar1, Lpar1−/− (Lpa1−/−). Serum liposaccharide level and bacteria loads in the intestinal mucosa and peripheral organs were elevated in Lpa1−/− mice. Decreased claudin-4, caudin-7, and E-cadherin expression in Lpa1−/− mice further suggested defective apical junction integrity in these mice. Regulation of LPA1 expression in Caco-2 cells modulated epithelial permeability and the expression levels of junctional proteins. The increased epithelial permeability in Lpa1−/− mice correlated with increased susceptibility to an experimental model of colitis. This resulted in more severe inflammation and increased mortality compared with control mice. Treatment of Caco-2 cells with tumor necrosis factor-α and interferon-γ significantly increased paracellular permeability, which was blocked by cotreatment with LPA, but not LPA1 knockdown cells. Similarly, orally given LPA blocked tumor necrosis factor–mediated intestinal barrier defect in mice. LPA1 plays a significant role in maintenance of epithelial barrier in the intestine via regulation of apical junction integrity.

Background the ageing population has increased in many countries, including China. However, reference intervals (RIs) for older people are rarely established because of difficulties in selecting reference individuals. Here, we aimed to analyse the factors affecting biochemical analytes and establish RI and age-related RI models for biochemical analytes through mining real-world big data. Methods data for 97,220 individuals downloaded from electronic health records were included. Three derived databases were established. The first database included 97,220 individuals and was used to build age-related RI models after identifying outliers by the Tukey method. The second database consisted of older people and was used to establish variation source models and RIs for biochemical analytes. Differences between older and younger people were compared using the third database. Results sex was the main source of variation of biochemical analytes for older people in the variation source models. The distributions of creatinine and uric acid were significantly different in the RIs of biochemical analytes for older people established according to sex. Age-related RI models for biochemical analytes that were most affected by age were built and visualized, revealing various patterns of changes from the younger to older people. Conclusion the study analysed the factors affecting biochemical analytes in older people. Moreover, RI and age-related RI models of biochemical analytes for older people were established to provide important insight into biological processes and to assist clinical use of various biochemical analytes to monitor the status of various diseases for older people.

Additional file 1: Supplemental Table 1. The frequency of ALDH2 rs671 genotype by age and sex.

Background Immune checkpoint inhibitors (ICIs) have achieved unprecedented success in cancer treatment over the past decade. The application of ICIs hasled to the discovery of various types of immune-related adverse events (irAEs). Here, we report a case of fatal myositis and spontaneous haematoma following concurrent treatment of nivolumab and ipilimumab for pancreatic adenocarcinoma. Case presentation A 71-year-old gentleman with pancreatic adenocarcinoma underwent the Whipple procedure in September 2014. The patient received 8 cycles of adjuvant chemotherapy with gemcitabineand achieved a complete responsein April 2015. Treatment with the PD-1 inhibitor nivolumab was started due to suspected tumour recurrence in November 2015. In August 2016, the CTLA-4 inhibitor ipilimumab was added to nivolumab for 2 cycles. Eight weeks after the last dose, the patient developed severe myositis complicated with spontaneous haematomain skeletalmuscle. Pathology of the skeletal muscle autopsy revealed lymphocytic infiltration. Intense immunosuppressive therapy, including high-dose corticosteroids and methotrexate, resulted in clinical success in the treatment of myositis. However, the patient died of cancer recurrence. Conclusion Myositis due to immunotherapy can be a fatal adverse event of ICIs, which requires close monitoring and cautious management.

Additional file 1: Electromyogram result.

Cystic fibrosis (CF) is a lethal genetic disease caused by the loss or dysfunction of the CF transmembrane conductance regulator (CFTR) channel. F508del is the most prevalent mutation of the CFTR gene and encodes a protein defective in folding and processing. VX-809 has been reported to facilitate the folding and trafficking of F508del-CFTR and augment its channel function. The mechanism of action of VX-809 has been poorly understood. In this study, we sought to answer a fundamental question underlying the mechanism of VX-809: does it bind CFTR directly in order to exert its action? We synthesized two VX-809 derivatives, ALK-809 and SUL-809, that possess an alkyne group and retain the rescue capacity of VX-809. By using Cu(I) -catalyzed click chemistry, we provide evidence that the VX-809 derivatives bind CFTR directly in vitro and in cells. Our findings will contribute to the elucidation of the mechanism of action of CFTR correctors and the design of more potent therapeutics to combat CF.

Multidrug resistance protein 4 (MRP4), a member of the ATP binding cassette transporter family, functions as a plasma membrane exporter of cyclic nucleotides. Recently, we demonstrated that fibroblasts lacking the Mrp4 gene migrate faster and contain higher cyclic-nucleotide levels. Here, we show that cAMP accumulation and protein kinase A (PKA) activity are higher and polarized in Mrp4(-/-) fibroblasts, versus Mrp4(+/+) cells. MRP4-containing macromolecular complexes isolated from these fibroblasts contained several proteins, including actin, which play important roles in cell migration. We found that actin interacts with MRP4, predominantly at the plasma membrane, and an intact actin cytoskeleton is required to restrict MRP4 to specific microdomains of the plasma membrane. Our data further indicated that the enhanced accumulation of cAMP in Mrp4(-/-) fibroblasts facilitates cortical actin polymerization in a PKA-dependent manner at the leading edge, which in turn increases the overall rate of cell migration to accelerate the process of wound healing. Disruption of actin polymerization or inhibition of PKA activity abolished the effect of MRP4 on cell migration. Together, our findings suggest a novel cAMP-dependent mechanism for MRP4-mediated regulation of fibroblast migration whereby PKA and actin play critical roles as downstream effectors.

Ying Qin, Wei Liu, Songbai Lin, Xiangfeng Li International Medical Services, Peking Union Medical College Hospital, Beijing, People’s Republic of China Aim: This study was designed to compare the efficacy and tolerability of bowel preparations with and without the higher first-dose volume of polyethylene glycol (PEG) solution or exercise after drinking PEG solution in Chinese people. Methods: A total of 330 participants who had a colonoscopy done in Peking Union Medical College Hospital were randomly and evenly assigned to three groups. Participants in GroupA ingested 1 L PEG solution and then ingested 2 L PEG solution at a rate of 250 mL every 15 minutes. Participants in Group B ingested 3 L PEG solution at a rate of 250 mL every 15minutes and then exercised more than 10 minutes after ingesting each liter of PEG solution. Participants in Group C ingested 3 L PEG solution at a rate of 250 mL every 15 minutes. Experienced gastrointestinal endoscopists rated the efficacy of bowel preparations based on the Boston Bowel Preparation Scale score. A questionnaire regarding participants’ symptoms associated with bowel preparations was administered to evaluate participants’ tolerability. Results: The three groups had insignificant difference in the percentages of participants’ symptoms including dizziness, nausea, stomach ache, bloating, and asthenia. However, the percentages of participants having hunger sensation, sleep disturbance, and anal discomfort were significantly higher in groups with the higher first-dose volume of PEG solution or exercise after drinking PEG solution than without them. The three groups had insignificant difference in the Boston Bowel Preparation Scale score. Conclusion: Whether to add the higher first-dose volume of PEG solution and exercise after drinking PEG solution or not, all participants achieved a similar quality of bowel preparations. Bowel preparations without the additional first-dose volume of PEG solution or exercise after drinking PEG solution showed the advantage of high participant tolerability. Keywords: bowel preparations for colonoscopy, efficacy, exercise, first-dose volume, polyethylene glycol, tolerability

SGK1 plays an important role in regulation of Na+/H+ exchanger (NHE) 3 in vivo. We show that SGK3 colocalizes with NHE3 in recycling endosomes. These studies identify SGK3 as the effector of the PI3K pathway that activates NHE3 and show that endosomal localization of SGK3 is essential for acute activation of NHE3., Na+/H+ exchanger 3 (NHE3) is the major Na+ transporter in the intestine. Serum- and glucocorticoid-induced kinase (SGK) 1 interacts with NHE regulatory factor 2 (NHERF2) and mediates activation of NHE3 by dexamethasone (Dex) in cultured epithelial cells. In this study, we compared short-term regulation of NHE3 by Dex in SGK1-null and NHERF2-null mice. In comparison to wild-type mice, loss of SGK1 or NHERF2 significantly attenuated regulation of NHE3 by Dex but did not completely obliterate the effect. We show that transfection of SGK2 or SGK3 in PS120 cells resulted in robust activation of NHE3 by Dex. However, unlike SGK1 or SGK2, SGK3 rapidly activated NHE3 within 15 min of Dex treatment in both PS120 and Caco-2bbe cells. Immunofluorescence analysis showed that SGK3 colocalized with NHE3 in recycling endosomes, whereas SGK1 and SGK2 were diffusely distributed. Mutation of Arg-90 of SGK3 disrupted the endosomal localization of SGK3 and delayed NHE3 activation. Activation of SGK3 and NHE3 by Dex was dependent on phosphoinositide 3-kinase (PI3K) and phosphoinositide-dependent kinase 1 (PDK1), and Dex induced translocation of PDK1 to endosomes. Our study identifies SGK3 as a novel endosomal kinase that acutely regulates NHE3 in a PI3K-dependent mechanism.

Respiratory syncytial virus (RSV) is a major cause of severe pneumonia and bronchiolitis in infants and young children, and causes disease throughout life. Understanding the biology of infection, including virus binding to the cell surface, should help develop antiviral drugs or vaccines. The RSV F and G glycoproteins bind cell surface heparin sulfate proteoglycans (HSPGs) through heparin-binding domains. The G protein also has a CX3C chemokine motif which binds to the fractalkine receptor CX3CR1. G protein binding to CX3CR1 is not important for infection of immortalized cell lines, but reportedly is so for primary human airway epithelial cells (HAECs), the primary site for human infection. We studied the role of CX3CR1 in RSV infection with CX3CR1-transfected cell lines and HAECs with variable percentages of CX3CR1-expressing cells, and the effect of anti-CX3CR1 antibodies or a mutation in the RSV CX3C motif. Immortalized cells lacking HSPGs had low RSV binding and infection, which was increased markedly by CX3CR1 transfection. CX3CR1 was expressed primarily on ciliated cells, and ∼50 % of RSV-infected cells in HAECs were CX3CR1+. HAECs with more CX3CR1-expressing cells had a proportional increase in RSV infection. Blocking G binding to CX3CR1 with anti-CX3CR1 antibody or a mutation in the CX3C motif significantly decreased RSV infection in HAECs. The kinetics of cytokine production suggested that the RSV/CX3CR1 interaction induced RANTES (regulated on activation normal T-cell expressed and secreted protein), IL-8 and fractalkine production, whilst it downregulated IL-15, IL1-RA and monocyte chemotactic protein-1. Thus, the RSV G protein/CX3CR1 interaction is likely important in infection and infection-induced responses of the airway epithelium, the primary site of human infection.

Although leptin is a key adipokine promoting liver fibrosis, adiponectin may prevent liver injury. To determine the role of these adipokines in liver fibrosis and to understand their expression in vivo, fa/fa rats and their lean littermates were subjected to bile duct ligation (BDL). Histomorphometry for collagen and α-smooth muscle actin (α-SMA) revealed that lean rats, but not fa/fa littermates, had significant fibrosis with abundant hepatic stellate cell (HSC) activation. The lean-BDL rats had significantly higher leptin concentrations in the hepatic vein than lean sham-operated, fa/fa BDL, or fa/fa sham-operated rats. Co-localization of leptin and α-SMA in activated HSCs was observed by immunohistochemistry. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis confirmed the presence of leptin and α-SMA in activated, but not quiescent, HSCs, whereas only quiescent HSCs synthesized adiponectin mRNA and protein. Adiponectin overexpression in activated HSCs reduced proliferation, augmented apoptosis, and reduced expression of α-SMA and proliferating cell nuclear antigen. Adiponectin receptors (AdipoR1 and AdipoR2) were detected in both activated and quiescent HSCs, but only activated HSCs produced significant apoptosis after treatment with either globular or full-length adiponectin. Adiponectin may act to reverse HSC activation, maintain HSC quiescence, or significantly, may have important therapeutic implications in liver fibrosis.

Background Renal cytochrome P450 (CYP)-derived eicosanoids, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs), have been shown to affect renal function and blood pressure (BP). We recently reported that high fat (HF) diet treatment in male rats increases BP and decreases production of these eicosanoids in the kidneys. However, at what level the downregulation of renal eicosanoid synthesis occurs and whether the HF diet has any effects on the regulation of renal eicosanoid synthesis in female rats are not known. The purpose of this study was to determine renal CYP-derived eicosanoid synthesis and its association with BP regulation in HF male and female rats. Methods In the first set of experiments, male and female rats were fed the HF or control diet for 10 weeks. In the second set of experiments, male and female rats were fed the HF diet for 10 days. In the third set of experiments, HF-fed and control female rats were treated with 5α-dihydrotestosterone for 4 weeks. After treatment, BP, urinary sodium, sodium balance, eicosanoid production, and CYP enzyme expression were determined. Results An elevation of BP and a decrease of renal cortical eicosanoid production were found in HF male rats, but no BP and eicosanoid production changes were observed in HF female rats. The HF treatment also caused a significant decrease of eicosanoid production and a decrease of CYP4A and 2C23 expression in the proximal tubules of HF male rats. Moreover, the HF diet treatment in male rats caused an increase in cumulative sodium balance and an elevation of BP, whereas no change in cumulative sodium balance and BP was observed in female rats. The treatment of 5α-dihydrotestosterone increased BP and 20-HETE production in the renal microvessels, but had no effect on urinary sodium excretion and renal microvessel EET production in both control and HF-fed female rats. Conclusions These results demonstrate that there are gender-specific differences in regulation of renal eicosanoid synthesis, sodium balance, and BP caused by HF treatment, and it appears that androgens play some role in upregulation of renal microvessel 20-HETE production in both HF and control female rats.

A graft copolymer was synthesized by graft copolymerization of starch with acrylamide (AM) and diallyldimethylammonium chloride (DADMAC). The copolymerization was carried out using a complex initiation system of cerium sulfate (CS) and potassium persulfate (KPS). The effects of reaction conditions on graft copolymerization and use of these copolymers as additives in papermaking was investigated. Experiments showed that a graft copolymer with higher grafting level, higher intrinsic viscosity and higher cationic degree could be obtained by changing the method of monomer addition and by controlling the ratio of DADMAC to AM. The graft copolymerization was more effective when the complex initiation system of CS-KPS was used. When adding 0.05% of the grafted starch [S-g-P(AM-co-DADMAC)] to the papermaking system, a higher filler retention was obtained than with cationic starch and cationic polyacrylamide when the cationic degree of S-g-P(AM-co-DADMAC) was 22% and its intrinsic viscosity was 7.35.

Previous research has noted that high surface temperatures within certain "offensive" air masses can lead to increased mortality. This study assesses the relationship between daily mortality rates and weather within the city of Shanghai, China, while introducing an operational heat/health warning system for the city. Using numerous meteorological observations, the spatial synoptic classification has been used to classify each summer day from 1989 to 1998 into one of eight air mass types for Shanghai. Through the comparative analysis of the daily air mass type and the corresponding Shanghai mortality rate, "moist tropical plus" (MT+), an extremely hot and humid air mass, was identified as an offensive air mass with the highest rates of mortality. Using stepwise regression, an algorithm was produced to help predict the number of excess deaths that will occur with each occurrence of the MT+ airmass. The heat/health warning system was run experimentally in the summer of 2001 and illustrated that the use of a warning system can alert the city's residents of potentially offensive weather situations that can lead to a deterioration in human health.

HEC-g-AA/SiO2 hybrid materials are prepared through a graft copolymerization reaction between acrylic acid (AA) monomer and hydroxyethyl cellulose (HEC), in the presence of a silica sol. The microstructure and properties of the hybrid materials are characterized by Fourier transform infrared spectra (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), respectively. The results show that a rigid inorganic phase SiO2 is dispersed in flexible organic continuous phase uniformly. HEC-g-AA/SiO2 hybrid material has no obvious phase separation in the presence of the crosslinking agent. The thermal performances of HEC-g-AA/SiO2 are excellent, and the glass transition temperature (T g) increases with the increased amount of the crosslinking agent.

Silicone rubber/mineral powder composites have been prepared by surface modification and ultrafinecrashing of mineral powder, mixing and vulcanizing with silicone rubber resin. The surface and inte...

A series of graft copolymers of starch with polyacrylamide was made by using a K 2 S 2 O 8 initiation system in inverse emulsion. The corresponding anionic graft copolymers, which have a different hydrolysis degree, are prepared by alkaline hydrolysis of the uncharged graft copolymers. Adequate hydrolytic conditions including type and amount of hydrolyzing agent, temperature, and time were studied. These graft copolymers have been tested for their temperature sensitivity, salt tolerance and shear stability, and a comparison has been made with ungrafted polyacrylamide (PAM). Experiments showed that a high hydrolysis degree can be obtained in a shorter time when NaOH and Na 2 CO 3 were used together as hydrolyzing agents, and the highest solution viscosity was observed when the hydrolysis degree of the graft copolymers was approximately 30%. In addition, the shear stability, temperature sensitivity and salt tolerance in the graft copolymers were also investigated.

The incidence of essential hypertension increases with obesity; however, the mechanisms that link obesity with hypertension are unclear. Renal cytochrome P450 (CYP)-derived eicosanoids—hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs)—have been shown to play an important role in the regulation of renal function, vascular tone, and blood pressure. The objective of this study was to examine CYP-derived eicosanoid synthesis in the different renal zones (cortex, medulla, and papilla) of rats fed a high fat diet (HF). Male Sprague-Dawley rats were fed a HF diet or regular rat chow for 10 weeks. After 10 weeks, HF rats showed significantly higher systolic blood pressure, body weight, and fat:body weight ratio. The renal ω-hydroxylase activity was decreased by 46% in cortex, 43% in medulla, and 46% in papilla of HF rats. The renal epoxygenase activity was decreased by 46% in cortex, 31% in medulla, and 56% in papilla of HF rats. Interestingly, the changes in the rate of 20-HETE and EET formation in different renal zones were consistent with the levels of expression of CYP4A and CYP2C23 proteins, respectively. Furthermore, there were no significant changes in the synthesis of these metabolites in the renal microvessels. These results demonstrate that HF diet causes the downregulation of CYP4A and CYP2C23 in renal tubules, and these proteins are responsible for renal 20-HETE and EET formation. The reduction in the synthesis of these eicosanoids may play an important role in the regulation of renal function and blood pressure in obesity-induced hypertension.

A novel starch- graft -acrylamide/mineral powder superabsorbent composite with water absorbency about 4000 times is synthesized by graft-copolymerization reaction among acrylamide, potato starch and mineral ultrafinepowder, followed by hydrolysis with sodium hydroxide. It is found that the composite doped with kaolinite powder possess higher water absorbency than those doped with bentonite or sercite powder, since the kaolinite powder can moderately disperse in the water and cross-link with acrylamide and starch. By controlling the amount of NaOH and reaction time during saponification process, the hydrophilic groups on the composite can be adjusted, it is found that the collaborative absorbent effect of −CONH 2 , −COONa and −COOH groups is superior to that of single −CONH 2 , −COONa or −COOH group. By the IR characterization, the polymerization reaction mechanism and structure of the composite is supposed, the mineral ultrafinepowder as a cross-linking point play an important role in the formation of network structure of the superabsorbent composite.

The superabsorbent's ability to resist deformation and to resist deswelling under externally applied pressures is important in practical application. For instance, it is used in infant diapers, in soil for agriculture, and in forestry. In this article, we report on the synthesis of a superabsorbent/starch-graft-poly(potassium acrylate-co-acrylamide) by inverse suspension polymerization. The effects of reaction conditions, such as monomeric concentration, ratio of water to oil, reaction temperature, and obtaining spherical resin, were investigated. Experiments showed that the superabsorbent has a good compressive strength and keeps the shape of particles after absorbing water. After mixing with soil it does not become sticky, and the loose structure can better retain air. It is fit to retain water in soil. In addition, thermogravimetric analysis revealed the superior thermal stability of the grafted product and its large particle size also reduces risk of air pollution. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 1536–1542, 2003

A novel starch-graft-acrylamide/kaolinite superabsorbent composite with water absorbency 4000 times (g ) was synthesized by a graft copolymerization reaction among acrylamide, potato starch and kaolinite ultrafine powder, followed by saponification with NaOH. The influence of the hydrophilic group on water absorbency was investigated. It was found that the combined absorbent effect of —CONH2, —COONa and —COOH groups was superior to that of a single group, and the composite with the molar ratio of 8:6:3 for the —CONH2, —COONa and —COOH groups exhibits the highest water-absorbent ability. Copyright © 2003 Society of Chemical Industry

Chitosan is a good biodegradable natural polymer, widely used in biomedical fields. In this study, chitosan was used to modify the surface of poly (D,L-lactic acid) (PDLLA) in order to enhance its cell affinity. The properties of a modified PDLLA surface and control were investigated by contact angle and electron spectroscopy for chemical analysis (ESCA), which indicated the changes in surface energy and chemical structure. Scanning electron microscopy (SEM) observation displayed differences in surface morphology between the chitosan-modified film and the control. These data reflected that PDLLA films could be modified with chitosan and in turn may affect the biocompatibility of the modified films. Therefore, adhesion and growth of osteoblasts on modified PDLLA films as well as control were studied. Cell morphologies on the films were examined by SEM and cell viability was evaluated using an MTT assay; the differentiated cell function was assessed by measuring alkaline phosphatase (ALP) activity. The ALP activity of modified PDLLA films was significantly higher than that found on the control (p < 0.01). The proliferation of osteoblasts on modified films was also found to be higher than that on the control (p < 0.05), suggesting that chitosan could be used to modify PDLLA and then enhance its cell biocompatibility.

Reform of state-owned enterprises (SOEs) constitutes the central link of the entire restructuring of China's construction industry. The poor performance of SOEs was mainly attributed to the lack of autonomy and the vagueness in the delineation of property rights. Reform measures have been undertaken to address these issues, but the achievements are far from satisfactory. The paradox of increasing productivity and declining profitability calls for a sound plan to solve the SOE problem by considering both the root causes and symptoms. The relationship between the provision of sufficient, robust information and the performance of SOEs is analysed and, based upon this, the implications for further restructuring are assessed. The proposed solutions may be summarized as: creating a fair business environment for competition to enable each SOE's profit level to be used as a simple, low-cost and sufficiently informative indicator of managerial performance; transforming the traditional, centralized operation model ...

Background Metastasis, the spread and growth of tumor cells to distant organ sites, represents the most devastating attribute and plays a major role in the morbidity and mortality of cancer. Inflammation is crucial for malignant tumor transformation and survival. Thus, blocking inflammation is expected to serve as an effective cancer treatment. Among anti-inflammation therapies, chemokine modulation is now beginning to emerge from the pipeline. CXC chemokine receptor-4 (CXCR4) and its ligand stromal cell-derived factor-1 (CXCL12) interaction and the resulting cell signaling cascade have emerged as highly relevant targets since they play pleiotropic roles in metastatic progression. The unique function of CXCR4 is to promote the homing of tumor cells to their microenvironment at the distant organ sites. Methodology/Principal Findings We describe the actions of N,N′-(1,4-phenylenebis(methylene))dipyrimidin-2-amine (designated MSX-122), a novel small molecule and partial CXCR4 antagonist with properties quite unlike that of any other reported CXCR4 antagonists, which was prepared in a single chemical step using a reductive amination reaction. Its specificity toward CXCR4 was tested in a binding affinity assay and a ligand competition assay using 18F-labeled MSX-122. The potency of the compound was determined in two functional assays, Matrigel invasion assay and cAMP modulation. The therapeutic potential of MSX-122 was evaluated in three different murine models for inflammation including an experimental colitis, carrageenan induced paw edema, and bleomycin induced lung fibrosis and three different animal models for metastasis including breast cancer micrometastasis in lung, head and neck cancer metastasis in lung, and uveal melanoma micrometastasis in liver in which CXCR4 was reported to play crucial roles. Conclusions/Significance We developed a novel small molecule, MSX-122, that is a partial CXCR4 antagonist without mobilizing stem cells, which can be safer for long-term blockade of metastasis than other reported CXCR4 antagonists.

Adiponectin is an adipocytokine that was recently shown to be anti-fibrogenic in hepatic fibrosis. Leptin, on the other hand, promotes hepatic fibrosis. The purpose of the present study was to elucidate a mechanism (or mechanisms) whereby adiponectin dampens leptin signaling in activated hepatic stellate cells (HSCs), and prevents excess extracellular matrix production. Activated HSCs, between passages 2 and 5, were cultured and exposed to recombinant human adiponectin and recombinant leptin. Immunoblot analysis for SOCS-3, TIMP-1, and the phosphorylated species of Stat3 and adenosine monophosphate-activated protein kinase (AMPK) were conducted. We also examined MMP-1 activity by immunosorbant fluorimetric analysis. In HSCs, adiponectin-induced phosphorylation of AMPK, and subsequently suppressed leptin-mediated Stat3 phosphorylation and SOCS-3 induction. Adiponectin also blocked leptin-stimulated secretion of TIMP-1, and significantly increased MMP-1 activity, in vitro. To extend this study, we treated adiponectin knockout mice (Ad-/-) daily with 5 mg/kg recombinant leptin and/or carbon tetrachloride (2 ml/kg) for 6 weeks. Post-necropsy analysis was performed to examine for inflammation, and histological changes in the Ad-/- and wild-type mice. There was no significant difference in inflammation, or aminotransferases, between mice receiving carbon tetrachloride and leptin versus carbon tetrachloride alone. As anticipated, the combination of leptin and CCl(4) enhanced hepatic fibrosis in both wild-type and Ad-/- mice, as estimated by amount of collagen in injured livers, but wild-type mice had significantly higher levels of SOCS-3 and significantly lower levels of TIMP-1 mRNA and protein than did adiponectin KO mice exposed to both CCl(4) and leptin. We therefore conclude that the protective effects of adiponectin against liver fibrosis require AMPK activation, and may occur through inhibition of the Jak-Stat signal transduction pathway.

Background & Aims Diarrhea results from reduced net fluid and salt absorption caused by an imbalance in intestinal absorption and secretion. The bulk of sodium and water absorption in the intestine is mediated by Na + /H + exchanger 3 (NHE3), located in the luminal membrane of enterocytes. We investigated the effect of lysophosphatidic acid (LPA) on Na + /H + exchanger activity and Na + -dependent fluid absorption in the intestine. Methods We analyzed the effects of LPA on fluid absorption in intestines of wild-type mice and mice deficient in Na + /H + exchanger regulatory factor 2 (NHERF2; Nherf2 −/− ) or LPA 2 ( Lpa 2 −/− ). Roles of LPA 5 and NHERF2 were determined by analysis of heterologous expression. Results Under basal conditions, LPA increased fluid absorption in an NHE3-dependent manner and restored the net fluid loss in a mouse model of acute diarrhea. Expression of the LPA receptor LPA 5 was necessary for LPA-induced stimulation of NHE3 activity in colonic epithelial cells. Stimulation of NHE3 by the LPA-LPA 5 signaling required coexpression of NHERF2, which interacted with LPA 5 . LPA-mediated intestinal fluid absorption was impaired in Nherf2 −/− mice, demonstrating the requirement for NHERF2 in LPA 5 activity. However, fluid absorption was unaltered in Lpa 2 −/− mice. LPA stimulated NHE3 and fluid absorption in part by increasing NHE3 protein abundance at the brush border membrane of intestinal epithelial cells. Conclusions LPA is a potent stimulant of NHE3 and fluid absorption in the intestine, signaling through LPA 5 . Regulation by LPA 5 depends on its interaction with NHERF2. LPA might be useful in the treatment of certain diarrheal diseases.

Background & Aims Chronic inflammation is a risk factor for colon cancer (CC). Lysophosphatidic acid (LPA), a naturally produced phospholipid, mediates multiple effects that are vital to disease process, including inflammation and cancer. The expression of LPA receptor 2 (LPA 2 ) is up-regulated in several types of cancer, including ovarian and colon cancer, but the importance of LPA and LPA 2 in the development and progression of CC is unclear. In this study, we sought to determine whether LPA and LPA 2 regulate the progression of CC in vivo. Methods We examined the potential role of LPA in CC progression by administering LPA to mice heterozygous for the adenomatous polyposis coli (Apc) allele. We determined the loss of LPA 2 function in tumorigenesis in the colon by treating mice with genetic deletion of LPA 2 (LPA 2 −/− ) with azoxymethane and dextran sulfate sodium. Results We found that LPA increased tumor incidence in Apc min/+ mice. LPA 2 −/− mice showed reduced mucosal damage and fewer tumors than wild-type (WT) mice. Reduced epithelial cell proliferation and decreases in β-catenin, Kruppel-like factor 5, and cyclooxygenase-2 expression were observed in LPA 2 −/− mice. Unlike WT mice, induction of monocyte chemoattractant protein-1 and macrophage migration inhibitory factor was significantly attenuated in LPA 2 −/− mice with reduced infiltration by macrophages. Conclusions These results show that LPA is capable of promoting tumorigenesis in the colon. The absence of LPA 2 attenuates several effects that contribute to cancer progression in vivo, and, hence, the current study identifies LPA 2 as an important modulator of CC.

Various epidemiologic studies have shown that obesity is associated with hepatocellular carcinoma. Leptin, the key player in the regulation of energy balance and body weight control, also acts as a growth factor on certain organs in both normal and disease states. It is plausible that leptin acts to promote hepatocellular carcinogenesis directly affecting malignant properties of liver cancer cells. However, a direct role for leptin in hepatocellular carcinoma has not been shown. In this study, we analyzed the role of leptin and the mechanism(s) underlying its action in hepatocellular carcinoma cells, which express both short and long isoforms of leptin receptors. Treatment with leptin resulted in increased proliferation of both HepG2 and Huh7 cells and involves activation of signal transducers and activators of transcription 3 (STAT3), AKT, and extracellular signal-regulated kinase (ERK) signaling pathways. Leptin-induced phosphorylation of ERK and AKT was dependent on Janus-activated kinase (JAK)/STAT activation. Intriguingly, we also found that leptin potently induces invasion of hepatocellular carcinoma cells in Matrigel invasion and electric cell-substrate impedance-sensing assays. Leptin-stimulated invasion was effectively blocked by pharmacologic inhibitors of JAK/STAT and, to a lesser extent, by ERK and phosphatidylinositol 3-kinase (PI3K) inhibition. Importantly, leptin also induced the migration of both HepG2 and Huh7 cells on fibronectin matrix. Inhibition of JAK/STAT, ERK, and PI3K activation using pharmacologic inhibitors effectively blocked leptin-induced migration of HepG2 and Huh7 cells. Taken together, these data indicate that leptin promotes hepatocellular carcinoma growth, invasiveness, and migration and implicate the JAK/STAT pathway as a critical mediator of leptin action. Our findings have potential clinical implications for hepatocellular carcinoma progression in obese patients. [Cancer Res 2007;67(6):2497–507]

Leptin has properties of a profibrogenic cytokine. In liver, the activated hepatic stellate cell (HSC) is responsible for a net production of extracellular matrix. A key molecule synthesized is the tissue inhibitor of metalloproteinase I (TIMP-1), which acts to inhibit the activity of matrix metalloproteinases. The purpose of the present study was to determine how leptin, a gp130 cytokine, orchestrates the regulation of TIMP-1 gene activation and expression. Transient transfection of primary HSCs revealed that leptin significantly increased luciferase activity of a 229-bp TIMP-1 promoter construct (TIMP-1–229). An EMSA revealed that leptin enhanced specificity protein 1 (Sp1) binding. Site-directed mutagenesis for Sp1 reduced the enhancing effect of leptin on TIMP-1 transcriptional activation, and this effect was dose dependent on the number of Sp1 sites mutated. Chromatin immunoprecipitation revealed that leptin enhanced binding of Sp1; however, inhibition of signal transducer and activator of transcription (STAT) 3 phosphorylation by AG490 also blocked Sp1 phosphorylation and significantly reduced leptin-associated TIMP-1–229 promoter activity, indicating that one mechanism for leptin-increased transcriptional activity is via phosphorylation of Sp1 and subsequent promoter binding. Finally, we demonstrate that leptin also results in intranuclear pSTAT3 binding to Sp1. We propose a novel mechanism whereby leptin-mediated TIMP-1 transcription employs a Sp1/pSTAT3-dependent mechanism, one of which is a noncanonical association between Sp1 and pSTAT3. These data provide a new molecular mechanism whereby the adipocytokine leptin plays a role in complications of the metabolic syndrome.

Nonalcoholic fatty liver disease (NAFLD) represents a burgeoning problem in hepatology, and is associated with insulin resistance. Exendin-4 is a peptide agonist of the glucagon-like peptide (GLP) receptor that promotes insulin secretion. The aim of this study was to determine whether administration of Exendin-4 would reverse hepatic steatosis in ob/ob mice. Ob/ob mice, or their lean littermates, were treated with Exendin-4 [10 microg/kg or 20 microg/kg] for 60 days. Serum was collected for measurement of insulin, adiponectin, fasting glucose, lipids, and aminotransferase concentrations. Liver tissue was procured for histological examination, real-time RT-PCR analysis and assay for oxidative stress. Rat hepatocytes were isolated and treated with GLP-1. Ob/ob mice sustained a reduction in the net weight gained during Exendin-4 treatment. Serum glucose and hepatic steatosis was significantly reduced in Exendin-4 treated ob/ob mice. Exendin-4 improved insulin sensitivity in ob/ob mice, as calculated by the homeostasis model assessment. The measurement of thiobarbituric reactive substances as a marker of oxidative stress was significantly reduced in ob/ob-treated mice with Exendin-4. Finally, GLP-1-treated hepatocytes resulted in a significant increase in cAMP production as well as reduction in mRNA expression of stearoyl-CoA desaturase 1 and genes associated with fatty acid synthesis; the converse was true for genes associated with fatty acid oxidation. In conclusion, Exendin-4 appears to effectively reverse hepatic steatosis in ob/ob mice by improving insulin sensitivity. Our data suggest that GLP-1 proteins in liver have a novel direct effect on hepatocyte fat metabolism.

Although leptin is a key adipokine promoting liver fibrosis, adiponectin may prevent liver injury. To determine the role of these adipokines in liver fibrosis and to understand their expression in vivo, fa/fa rats and their lean littermates were subjected to bile duct ligation (BDL). Histomorphometry for collagen and alpha-smooth muscle actin (alpha-SMA) revealed that lean rats, but not fa/fa littermates, had significant fibrosis with abundant hepatic stellate cell (HSC) activation. The lean-BDL rats had significantly higher leptin concentrations in the hepatic vein than lean sham-operated, fa/fa BDL, or fa/fa sham-operated rats. Co-localization of leptin and alpha-SMA in activated HSCs was observed by immunohistochemistry. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis confirmed the presence of leptin and alpha-SMA in activated, but not quiescent, HSCs, whereas only quiescent HSCs synthesized adiponectin mRNA and protein. Adiponectin overexpression in activated HSCs reduced proliferation, augmented apoptosis, and reduced expression of alpha-SMA and proliferating cell nuclear antigen. Adiponectin receptors (AdipoR1 and AdipoR2) were detected in both activated and quiescent HSCs, but only activated HSCs produced significant apoptosis after treatment with either globular or full-length adiponectin. Adiponectin may act to reverse HSC activation, maintain HSC quiescence, or significantly, may have important therapeutic implications in liver fibrosis.

The objective of this study was to modify the surface of poly(D,L-lactic acid) (PDLLA) with different molecular weight of silk fibroins, and assess the effects of the modified surfaces on the functions of rat osteoblasts cultured in vitro. The properties of the modified PDLLA surface and the control one were investigated by contact angle and electron spectroscopy for chemical analysis (ESCA). The former indicated the variation of hydrophilicity and the latter suggested that the modified PDLLA film using silk fibroin is enriched with nitrogen atoms. The biocompatibility of the PDLLA film may be altered and in turn affects the seeded cell functions. Therefore, attachment and proliferation of osteoblasts seeded on the modified PDLLA films and the control one were examined. Cell morphologies on these films were studied by scanning electron microscopy (SEM) and cell viability was evaluated by MTT assay. In addition, differentiated cell function was assessed by measuring the alkaline phosphatase (ALP) activity. These results suggest that the silk fibroin-modified PDLLA surface can improve the interaction between osteoblasts and the PDLLA films.