Unveiling Trends: Nanoscale Materials Shaping Emerging Biomedical Applications.

The realm of biomedical materials continues to evolve rapidly, driven by innovative research across interdisciplinary domains. Leveraging big data from the CAS Content Collection, this study employs quantitative analysis through natural language processing (NLP) to identify six emerging areas within nanoscale materials for biomedical applications. These areas encompass self-healing, bioelectronic, programmable, lipid-based, protein-based, and antibacterial materials. Our Nano Focus delves into the multifaceted utilization of nanoscale materials in these domains, spanning from augmenting physical and electronic properties for interfacing with human tissue to facilitating intricate functionalities like programmable drug delivery.

MRI Evaluation of Indomethacin Suppositories in the Prevention of Complications of Pancreatitis and Hyperamylasemia after Choledocholithiasis ERCP Based on Image Denoising Algorithm.

Objective: To explore the value of MRI evaluation of indomethacin suppositories in the prevention of pancreatitis and hyperamylasemia in patients with common bile duct calculi after endoscopic retrograde cholangiopancreatography (ERCP) based on image denoising algorithm. Methods: A retrospective analysis in August 2020 to December 2021. Because of the common bile duct calculi hospitalized parallel ERCP operation, 89 cases of patients, according to the different postoperative treatments, were divided into group A (n = 44) and group B (n = 45), in which A set of separate application inhibits the pancreatic enzyme secretion after surgery drug treatment, and B group on the basis of group A linked with indole beauty Xinshuan treatment. The incidence of postoperative pancreatitis and hyperamylasemia was compared between the two groups. The levels of serum amylase were compared between the two groups. Patients in group B were diagnosed with pancreatitis by conventional MRI and MRI with denoising algorithm, respectively, and the imaging characteristics and diagnosis rate differences of the two methods were observed. ROC curve was drawn to evaluate the diagnostic efficacy of MRI denoising algorithm for postoperative pancreatitis and serum amylase level detection for hyperamylasemia. Results: The incidence of postoperative pancreatitis and hyperamylasemia in group B was significantly lower than that in group A (P < 0.05). There were 6 cases of postoperative pancreatitis in group B, 2 cases (33.33%) were diagnosed by conventional MRI, and 5 cases (83.33%) were diagnosed by MRI based on denoising algorithm. Although there was no significant difference in diagnosis rate between the two methods, the number of cases of pancreatitis diagnosed by MRI based on denoising algorithm was slightly higher than that by conventional MRI. Compared with conventional MRI images, MRI images with denoising algorithm showed that the number of cases with pancreatic swelling, the number of cases with pancreatic duct/bile duct dilation, and the number of cases with abdominal effusion were all high (all P < 0.05). ROC results showed that the area under the curve of MRI with denoising algorithm for the diagnosis of postoperative pancreatitis was 0.855, and the sensitivity was 89.40%. The specificity was 83.20%, and the area under the curve of serum amylase for postoperative hyperamylasemia was 0.893, the sensitivity was 89.80%, and the specificity was 85.20%, all of which had high diagnostic efficacy. Conclusion: MRI results of denoising algorithm suggest that indomethacin suppositories can effectively reduce the incidence of postoperative pancreatitis and hyperamylasemia after ERCP, which is worthy of clinical application.

Mean nocturnal baseline impedance, a novel metric of multichannel intraluminal impedance-pH monitoring in diagnosing gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common disease with increasing prevalence worldwide. However, the diagnosis of GERD is challenging because there are no definite gold standard criteria. Recently, a novel impedance parameter, namely mean nocturnal baseline impedance (MNBI), has been proposed, which reflects the burden of longitudinal reflux and the integrity of esophageal mucosa. MNBI has shown an immense promise for increasing the diagnostic rate of multichannel intraluminal impedance-pH (MII-pH) monitoring and predicting the response to proton pump inhibitor (PPI) or anti-reflux intervention in patients with reflux symptoms. The present paper reviews the association between baseline impedance and esophageal mucosal integrity, the acquisition of MNBI in 24-h MII-pH monitoring, the clinical utilization of MNBI in improving the diagnosis rate of GERD in patients with typical reflux symptoms, predicting the response to PPI or anti-reflux treatment in these patients, the utilization of MNBI in diagnosing patients with atypical symptoms or extra-esophageal symptoms, and the correlation between reflux burden and MNBI. MNBI should be routinely assessed using MII-pH monitoring.

Deletion of Smurf1 attenuates liver steatosis via stabilization of p53.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, characterized by excessive hepatic lipid accumulation. Recently, we demonstrated that Smad ubiquitination regulatory factor 1 (Smurf1) deficiency significantly alleviates mouse hepatic steatosis. However, the mechanism of Smurf1-regulating hepatic lipid accumulation requires further exploration and clarification. Hence, this study explores the potential mechanism of Smurf1 in hepatic steatosis. In this study, hepatic Smurf1 proteins in NAFLD patients and healthy individuals were determined using immunohistochemical staining. Control and NAFLD mouse models were established by feeding Smurf1-knockout (KO) and wild-type mice with either a high-fat diet (HFD) or a chow diet (CD) for eight weeks. Oleic acid (OA)-induced steatotic hepatocytes were used as the NAFLD mode cells. Lipid content in liver tissues was analyzed. Smurf1-MDM2 interaction, MDM2 and p53 ubiquitination, and p53 target genes expression in liver tissues and hepatocytes were analyzed. We found that hepatic Smurf1 is highly expressed in NAFLD patients and HFD-induced NAFLD mice. Its deletion attenuates hepatocyte steatosis. Mechanistically, Smurf1 interacts with and stabilizes mouse double minute 2 (MDM2), promoting p53 degradation. In Smurf1-deficient hepatocytes, an increase in p53 suppresses SREBP-1c expression and elevates the expression of both malonyl-CoA decarboxylase (MCD) and lipin1 (Lpin1), two essential proteins in lipid catabolism. Contrarily, the activities of these three proteins and hepatocyte steatosis are reversed by p53 knockdown in Smurf1-deficient hepatocytes. This study shows that Smurf1 is involved in the pathogenesis of NAFLD by balancing de novo lipid synthesis and lipolysis.

Role of the Mean Nocturnal Baseline Impedance in Identifying Evidence Against Pathologic Reflux in Patients With Refractory Gastroesophageal Reflux Disease Symptoms as Classified by the Lyon Consensus.

BACKGROUND/AIMS: Mean nocturnal baseline impedance (MNBI) is a new reflux metric for mucosal integrity. It remains unclear whether MNBI can help identify evidence against pathological reflux by the Lyon Consensus in patients with refractory gastroesophageal reflux disease (GERD) symptoms. METHODS: Three hundred and forty-nine patients with refractory GERD symptoms enrolled in this study were subjected to high-resolution manometry, 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring, and endoscopy. Conventional indexes (ie, reflux events and acid exposure time) and the novel index (MNBI) of MII-pH monitoring were extracted and analyzed. The value of MNBI in diagnosing patients with evidence against pathologic reflux was evaluated by receiver-operating-characteristic analysis. RESULTS: There were 102 (29.2%) patients with evidence against pathologic reflux, 149 (42.7%) with inconclusive or borderline evidence and 98 (28.1%) with conclusive evidence for pathologic reflux. The MNBI was significantly higher while the proportion of pathological MNBI was significantly lower in subjects with evidence against pathologic reflux than in patients with inconclusive or borderline evidence and in patients with conclusive evidence for pathologic reflux (2444.3 [1977.9-2997.4] vs 1992.8 [1615.5-2253.6] and vs 1772.3 [758.6-2161.3], both P < 0.001; 42.2% vs 79.7% and vs 80.0%, both P < 0.05). When identifying evidence against pathologic reflux in patients with refractory GERD symptoms, the MNBI yielded an area under the curve of 0.749 (P < 0.001) at a cutoff value of 1941.8 Ω. CONCLUSIONS: The MNBI has a good diagnostic value for evidence against pathological reflux in patients with refractory GERD symptoms. For its simplicity and reproducibility, we believe that MNBI should be referred to in reports of impedance-pH tracings by physicians.

Correlation between gastroesophageal flap valve abnormality and novel parameters in patients with gastroesophageal reflux disease symptoms by the lyon consensus.

Gastroesophageal flap valve (GEFV) grading is a simple and reproducible parameter. There is limited information about the association between GEFV abnormality and novel parameters in patients with gastroesophageal reflux disease(GERD) symptoms by the Lyon Consensus. To investigate the value of GEFV grading in GERD, the clinical data of 320 patients with GERD symptoms who underwent endoscopy, 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring, and high-resolution manometry (HRM) were retrospectively analyzed. The percentage of acid exposure time (AET%)(4.2 [1.5-7.4] vs. 1.3 [0.3-4.2], P < 0.001) and the proportion of abnormal esophagogastric junction (EGJ) morphology (71 [87.7%] vs. 172 [72.0%], P = 0.011) were significantly higher, while the mean nocturnal baseline impedance (MNBI) (2068.3 [1658.4-2432.4] vs. 2228.5 [1794.8-2705.3]Ω, P = 0.012) and post-reflux swallow-induced peristaltic wave index (PSPWI) (19.7 [13.9-29.0] vs. 33.3 [25.0-44.0]%, P < 0.001) were significantly lower in the abnormal GEFV group compared with the normal GEFV group. AET% and EGJ morphology showed positive correlations with GEFV grade, while PSPWI and MNBI showed negative correlations. Patients with an abnormal GEFV had a significantly greater risk of conclusive evidence of GERD compared to those with a normal GEFV (OR 3.035, 95% CI 1.758-5.240, P < 0.001). Further, when identifying patients with conclusive evidence of GERD, abnormal GEFV had a specificity of 80.4% (95% CI 75.3-85.5%). GEFV grading might be regarded as supportive evidence for GERD diagnosis.

Assessment of the Multiple Rapid Swallows Test for Gauging Esophageal Reflux Burden in Patients with Refractory Gastroesophageal Reflux Disease.

BACKGROUND The multiple rapid swallows (MRS) test is used to assess esophageal contraction reserve. In this study, we characterized the expression of the MRS test in patients with reflux burden and other symptomatic phenotypes with refractory gastroesophageal reflux disease (rGERD). MATERIAL AND METHODS Patients with rGERD who underwent high-resolution manometry (HRM) and esophageal pH-impedance monitoring (EIM) between September 2018 and January 2020 were retrospectively studied. RESULTS We enrolled 151 patients and divided them into 4 phenotypes according to the results of EIM. In phenotype 1, the MRS distal contractile integral (DCI) was significantly positively correlated with acid-liquid reflux episodes. In phenotype 2, lower esophageal sphincter pressure (LES) length was significantly positively correlated with MRS DCI, and MRS/single-swallow (SS) DCI ratio. In phenotype 3, MRS DCI was negatively correlated with the DeMeester score, acid exposure time (AET), upright AET, long-term acid reflux episodes, acid-mixed reflux episodes, recumbent acid reflux episodes, and total acid reflux episodes. There was a significant negative correlation between MRS/SS DCI and recumbent acid reflux episodes. In phenotype 4, nonacid-liquid episodes and recumbent nonacid reflux episodes were significantly higher in the abnormal MRS group. However, acid-gas episodes, weakly acid-gas episodes, and upright gas reflux episodes were higher in the normal MRS group than in the abnormal MRS group. CONCLUSIONS Esophageal contraction reserve is heterogeneous within the reflux burden and symptomatic phenotypes of patients with rGERD.

Response Rate and Impact on Lipid Profiles of Obeticholic Acid Treatment for Patients with Primary Biliary Cholangitis: A Meta-Analysis.

Background: Up to 40% of patients with primary biliary cholangitis (PBC) have an inadequate response to ursodeoxycholic acid (UDCA). Obeticholic acid (OCA) is considered the addition of treatment, but the response rate based on commonly referenced biochemical response criteria and lipids' impact was unclear. Previous studies reported inconsistency results partially due to small sample size. Therefore, we performed a meta-analysis and aimed to explore OCA treatment's response rate and effect on lipids' profiles in PBC patients. Methods: We performed PubMed, Embase, and Cochrane controlled trials register (updated to JUN 2019) databases and manual bibliographical searches for randomized controlled trials reporting on OCA treatment in PBC patients. Two researchers independently extracted data and assessed the risk of bias of studies. We calculated risk ratio (RR) for the overall complete response rate, and the standardized mean difference (SMD) for the serum lipids changes after OCA treatment, all with 95% confidence intervals (CIs) using fixed-effects models. We registered this meta-analysis with PROSPERO (registration number: CRD42020148550). Results: Three trials, with 265 patients, were selected for the analysis. OCA was superior to placebo in PBC patients (RR, 1.48; 95% CI, 1.15-1.90). OCA's pooled treatment response rate was 65% (95% CI, 56%-74%), corresponding to Paris I criteria. Besides, OCA significantly decreased total cholesterol (P=0.02) with no heterogeneity (P=0.87, I 2 = 0%) and high-density lipoprotein levels (P < 0.05) with no heterogeneity (P=0.82, I 2 = 0%). Conclusions: This meta-analysis demonstrated that OCA was a promising additional treatment for PBC patients and might reduce serum cholesterol levels. The longer follow-up studies are needed to give more evidence.

CKIP-1 augments autophagy in steatotic hepatocytes by inhibiting Akt/mTOR signal pathway.

Nonalcoholic fatty liver disease (NAFLD), which is characterized by aberrant accumulation of intrahepatic triglycerides and lipid droplets (LDs) in the liver cells, is becoming increasingly prevalent at an alarming rate worldwide. LDs can be consumed by either hydrolysis or autophagy, which is shown to be of importance in the regulation of hepatic lipid metabolism. We have shown that deficiency of pleckstrin homology domain-containing casein kinase 2 interacting protein-1 (CKIP-1), a scaffold protein that interacts with various proteins in multiple signal pathways, in mice aggravates high-fat diet induced fatty liver. However, its underlying mechanisms remain largely unknown. In this study, we found that the mRNA and protein levels of CKIP-1 decreased dramatically in steatotic HepG2 cells induced by oleic acid (OA) treatment. Coincidently, hepatic autophagy was also dynamically regulated in steatotic HepG2 cells. In addition, overexpression of CKIP-1 activated autophagy by suppression of Akt/mTOR signaling, which in turn reduced lipid accumulation. Moreover, these phenomena were reversed in CKIP-1-shRNA transfected steatotic hepatocytes. To further evaluate the potential role of CKIP-1 in autophagy, we determined the level of autophagy related proteins in CKIP-1 knockout mice. These results supported our findings in vitro. In summary, we found CKIP-1 to be a positive regulator of hepatic autophagy and a promising therapeutic target for treatment of NAFLD.

Smurf1 aggravates non-alcoholic fatty liver disease by stabilizing SREBP-1c in an E3 activity-independent manner.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders which are characterized by the accumulation of excessive lipid in hepatocytes. The precise pathogenesis of NAFLD is very complicated and remains largely unknown. Smad ubiquitination regulatory factor 1 (Smurf1) is crucial for numerous processes including bone homeostasis, embryogenesis, and pathogenic autophagy. In this study, we found that liver steatosis was alleviated in Smurf1-deficient mice fed with high-fat diet (HFD) for 19 weeks. The deletion of Smurf1 reduced the accumulation of lipid droplets and triglycerides in hepatocytes. The stability of sterol regulatory element-binding protein-1c (SREBP-1c), a key transcription factor that mediates de novo lipogenesis, was markedly reduced in Smurf1-deficient mice. The mechanistic study showed that Smurf1 interacts with SREBP-1c and protects SREBP-1c from ubiquitination and degradation by preventing the binding of SREBP-1c to its ubiquitin E3 ligase Fbw7a. Thus, our study presented an E3 ligase catalytic activity-independent function of Smurf1 in the fatty liver development.

Association of serum gastric inhibitory polypeptide and pancreatic polypeptide levels with prolonged esophageal acid exposure time in refractory gastroesophageal reflux disease.

BACKGROUND: Acid exposure time (AET) prolongation plays an important role in the pathogenesis of gastroesophageal reflux disease (GERD). Gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) participate in the regulation of gastric acid secretion, blood glucose and lipid levels, and food intake. In this study, we evaluated the serum GIP and PP levels in refractory GERD patients and analyzed their metabolic and motility characteristics. METHODS: Seventy-three refractory GERD patients were enrolled in this study from September 2015 to September 2017. We investigated the clinical characteristics, severity, and duration of GERD symptoms. High-resolution manometry and 24 hours impedance-pH monitoring were performed to assess esophageal motility and reflux parameters. The patients were divided into the AET- group (AET <4.2%) and AET+ group (AET >4.2%). GIP and PP levels were determined in all subjects and their associations with other parameters evaluated. RESULTS: Age and GERDQ score were significantly higher (P < .05) and acid reflux and heartburn more frequent in the AET+ group than in the AET- group. The contraction front velocity was increased in the AET- group, while there was no significant difference in the distal contraction integral, peristalsis interruption, distal latency, or resting pressures of the lower and upper esophageal sphincters between the 2 groups (P > .05). The serum levels of GIP (P = .003) and PP (P = .012) were significantly increased in the AET+ group. Increased GIP and PP levels were associated with abnormal upright AET (correlation coefficients 0.307 and 0.233, P = .008 and P = .047). There was a positive correlation between GIP and triglyceride levels (correlation coefficient 0.279, P = .017). CONCLUSION: The serum levels of GIP and PP in refractory GERD patients with prolongation of AET are significantly elevated, mainly in the upright position.

Presence of diabetic retinopathy is lower in type 2 diabetic patients with non-alcoholic fatty liver disease.

To analyze the association between non-alcoholic fatty liver disease (NAFLD) and the presence of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).Total 411 T2DM patients were divided into NAFLD and control groups. NAFLD was diagnosed by ultrasound. Retinopathy was diagnosed by fundus photography. All patients were screened based on medical history, physical examinations, and laboratory measurements.The prevalence of NAFLD and DR in T2DM patients was 60.8% and 40.9%, respectively. The presence of DR was associated with diabetes duration, systolic blood pressure (SBP), glycated hemoglobin (HbA1c), and proteinuria (all P < .001) using univariate and multivariate regression analyses. The prevalence of DR was lower in patients with NAFLD than those without NAFLD (37.2% vs 46.6%, P = .065), and significantly lower in patients with moderate and severe NAFLD (30.2% vs 46.6%, P = .012; 14.3% vs 46.6%, P = .024). The presence of DR in NAFLD patients was associated with diabetes duration (P = .032) in Chi-squared analysis.NAFLD and DR were highly prevalent in T2DM patients. Diabetes duration, SBP, HbA1c, and proteinuria were risk factors for DR in T2DM patients. The presence of DR was lower in T2DM patients with NAFLD, which was mainly due to their shorter diabetes duration.

Enhancement of anti-tumor effect of plasmid DNA-carrying MUC1 by the adjuvanticity of FLT3L in mouse model.

AIM: DNA vaccines have emerged as a promising strategy for cancer immunotherapy; however, their immunogenicity is weak. Fms-like tyrosine kinase 3-ligand (Flt3L) has been exploited for its ability to increase the proliferation of dendritic cells (DCs). The aim of the present study was to investigate whether co-administration of an adjuvant plasmid expressing mouse Flt3L and a DNA vaccine of the Mucin 1 (MUC1) antigen enhances immune responses. METHODS: The recombinant plasmids pVAX1-MUC1 and pVAX1-Flt3L were constructed and injected into mice intramuscularly (i.m.), followed by electroporation. The humoral and cellular immune responses after immunization were examined by enzyme linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. To evaluate the anti-tumor efficacy of the plasmids, a mouse model of MUC1-expressing tumors was established. RESULTS: The results showed that co-administration of an adjuvant plasmid and a DNA vaccine stimulated the production of higher titers of specific antibodies and a T cell response and suppressed the growth of subcutaneous tumors expressing MUC1. Collectively, our results indicate that a plasmid expressing murine Flt3L could stimulate stronger immune responses. CONCLUSION: These observations emphasize the potential of Flt3L as an adjuvant for colon cancer DNA vaccines.

Nonalcoholic Fatty Liver Disease Cirrhosis: A Review of Its Epidemiology, Risk Factors, Clinical Presentation, Diagnosis, Management, and Prognosis.

Cirrhosis is the common end stage of a number of chronic liver conditions and a significant cause of morbidity and mortality. With the growing epidemic of obesity and metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide and will become one of the leading causes of cirrhosis. Increased awareness and understanding of NAFLD cirrhosis are essential. To date, there has been no published systematic review on NAFLD cirrhosis. Thus, this article reviews recent studies on the epidemiology, risk factors, clinical presentation, diagnosis, management, and prognosis of NAFLD cirrhosis.

IgG4-related disease: association between chronic rhino-sinusitis and systemic symptoms.

PURPOSE: The objective of this study is to analyze the relationship between chronic rhino-sinusitis (CRS) and systemic symptoms in patients with IgG4-related disease (IgG4-RD). PATIENTS AND METHODS: The patients with IgG4-RD, confirmed by restrict association with clinical and histopathological manifestations between March 2013 and July 2016, were enrolled and followed-up for 1 year at the Tongren Hospital, Capital Medical University. The patients were divided into two groups: the case group included IgG4-RD patients with CRS confirmed by clinical and imaging, while the control group included IgG4-RD patients without CRS confirmed by clinical and imaging. Age, gender, clinical manifestations, the percentage of eosinophils in peripheral blood, sedimentation (ESR), C-reaction protein, serum IgE and IgG4 levels, histopathology, and treatment drugs at the baseline and 1 year of follow-up were compared between the two groups. RESULTS: A total of 46 cases met the diagnostic criteria for IgG4-RD. A total of 30 patients (65.2%) had IgG4-RD complicated with CRS, and were aged 49.7 ± 13.4 years, with male:female ratio = 2:1. The disease duration in the case group was longer than that in the control group (3.0 versus 0.8, p = 0.009). The ratio of ocular involvement was higher (86.7 versus 60%, p < 0.001), and allergic manifestations including drug allergy, asthma, and allergic skin were more common (56.5 versus 20%, p = 0.004), with a higher percentage of eosinophils in peripheral blood (8.5 versus 3.3%, p = 0.018) and more sensitive to glucocorticoids (6.0 versus 3.5, p = 0.004) than those in the control group. CONCLUSIONS: CRS in patients with IgG4-RD was closely associated with IgG4-related ocular lesions, which was more prone to allergic manifestations accompanied by raised percentage of eosinophils in peripheral blood. The treatment of patients with IgG4-RD complicated with CRS was more effective than those with IgG4-RD without CRS.

Deficiency of CKIP-1 aggravates high-fat diet-induced fatty liver in mice.

Casein kinase 2 interacting protein-1(CKIP-1) is widely expressed in a variety of tissues and cells, and plays an important role in various critical cellular and physiological processes including cell growth, apoptosis, differentiation, cytoskeleton and bone formation. Here, we found: (1) CKIP-1 deficient mice exhibited increased body weight, liver weight, number and size of lipid droplets, and TG content comparing with WT mice after being exposed to high fat diet (HFD); (2) the levels of serum insulin, liver glycogen, phosphorylated C-Jun-N-terminal kinase-1 (pJNK1) and phosphorylated insulin receptor substrate -1(pIRS1) in CKIP-1-/- mice were higher than those of WT mice; (3) CKIP-1 interacted with JNK1 in vitro. Our results indicate that CKIP-1 deficiency in mice aggravates HFD-induced fatty liver by upregulating JNK1 phosphorylation and further upregulating IRS-1 phosphorylation and RI.

Glycosyltransferases and non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized.

Mechanism of the effect of glycosyltransferase GLT8D2 on fatty liver.

BACKGROUND: Recent studies have shown that some glycosyltransferases are involved in the development of nonalcoholic fatty liver disease (NAFLD). The objective of this study was to explore the effect and mechanism of glycosyltransferase GLT8D2 on fatty liver. METHODS: Rat model of NAFLD was established by induction with high-fat-diet. The GLT8D2 expression in rat liver was examined using immunohistochemistry. Oil Red O staining and triglyceride assay were used to measure the effect of abnormal GLT8D2 expression on lipid accumulation in HepG2 cells. The expression levels of lipid metabolism-related key molecules, namely sterol regulatory element-binding protein-1c (SREBP-1c), stearoyl-coA desaturase (SCD), carnitine palmitoyltransferase-1 (CPT1) and microsomal triglyceride transfer protein (MTP), in HepG2 cells with abnormal GLT8D2 expression were determined by western blot analyses. RESULTS: The expression of GLT8D2 was higher in the liver of rats with NAFLD than in the control rats, and GLT8D2 was mainly located around lipid droplets in hepatocytes. GLT8D2 expression increased in steatosis HepG2 cells compared with that in normal HepG2 cells. GLT8D2 positively regulated lipid droplet accumulation and triglyceride content in HepG2 cells. Upregulation or knockdown of GLT8D2 had no effect on the expressions of SREBP-1c, SCD or CPT-1 proteins in HepG2 cells. However, GLT8D2 expression negatively regulated the expression of MTP protein in HepG2 cells. CONCLUSION: GLT8D2 participated in NAFLD pathogenesis possibly by negatively regulating MTP expression. Specific inhibition of GLT8D2 via an antagonistic strategy could provide a potential candidate approach for treatment of NAFLD.

F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation.

It has been demonstrated previously that F-box protein Fbxl15 targets HECT-type E3 Smurf1 and forms a functionally active SCF complex for ubiquitination and proteasomal degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. Different from Fbxl15, Fbxo3 targets all the Nedd4 family members for their degradation, indicating that Fbxo3 plays an important role in controlling the stability of Nedd4. Taken together, we show that Smurf1 is an endogenous substrate of Fbxo3. Our study gains further insight into the novel role of Fbxo3 in BMP signaling.