1.Intestinal stearoyl-coenzyme A desaturase-inhibition improves obesity-associated metabolic disorders.
Yangliu XIA ; Yang ZHANG ; Zhipeng ZHANG ; Nana YAN ; Vorthon SAWASWONG ; Lulu SUN ; Wanwan GUO ; Ping WANG ; Kristopher W KRAUSZ ; Oksana GAVRILOVA ; James M NTAMBI ; Haiping HAO ; Tingting YAN ; Frank J GONZALEZ
Acta Pharmaceutica Sinica B 2025;15(2):892-908
Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders.
2. Performance of urea-mediated dissociation in reducing false-positive of 2019-nCoV IgM test
Qiang WANG ; Qin DU ; Bin GUO ; Yangliu GUO ; Li FANG ; Xiaolan GUO
Chinese Journal of Laboratory Medicine 2020;43(0):E014-E014
Objective:
To investigate the interference factors causing false-positive result of novel coronavirus IgM antibody (SARS-CoV-2 IgM) detected by gold immunochromatography assay (GICA) and enzyme-linked immunosorbent assay (ELISA).
Methods:
A total of 71 serum from different pathogen infections and related chronic diseases patients were collected from the Affiliated Hospital of North Sichuan Medical College from January 25, 2020 to February 15, 2020. GICA and ELISA were used to detect 2019-nCoV IgM in 71 serum, including 5 influenza A virus (Flu A) IgM positive serum, 5 influenza B virus (Flu B) IgM positive serum, 5 Mycoplasma pneumonia (MP) IgM positive serum, 5 Legionella pneumophila (LP) IgM positive serum, 29 rheumatoid factor (RF) IgM positive serum, 5 hypertension patients serum, 5 diabetes mellitus patients serum, 6 human immunodeficiency virus (HIV) infection patients serum and 6 Corona Virus Disease 2019 (COVID-19) patients serum. The interference factors causing false positive results of the two methods were analyzed, and urea dissociation test was employed to dissociate the 2019-nCoV IgM positive serum using the best dissociation concentration. Statistical analyses were performed by SPSS, version 19.0.
Result:
s 2019-nCoV IgM was positive in 18 cases of middle-high level RF-IgM positive serum and 6 cases of 2019-nCoV-infected serum detected by two methods, and the other 47 serum were negative. When the dissociation concentration of urea was 6 mol/L, 2019-nCoV IgM was negative in 17 cases of middle-high level RF-IgM positive serum and positive in 6 cases of 2019-nCoV-infected serum detected by GICA. When the urea dissociation concentration was 4 mol/L, dissociation time was 10 min and the avidity index<0.46 was set as negative, 2019-nCoV IgM was negative in 15 cases of middle-high level RF-IgM positive serum and positive in 6 cases of 2019-nCoV-infected serum detected by ELISA.
Conclusion
The middle-high level of RF-IgM could cause false positive results of SARS-CoV-2 IgM detected by GICA and ELISA, and the urea dissociation test would be helpful for reducing the probability of false-positive results of SARS-CoV-2 IgM test.
3.TLR4 activation with LPS inhibits BMP 9-induced osteogenic differentiation of immortalized mouse embryonic fibroblasts
Yangliu GUO ; Sicheng CHEN ; Ya LI ; Mengtian FAN ; Yanting SUN ; Wang LI ; Qiong SHI
Basic & Clinical Medicine 2017;37(1):25-31
Objective To study the effect of TLR4 activation with LPS on BMP9-induced osteogenic differentiation of immortalized mouse embryonic fibroblasts ( iMEFs).Methods The activation of TLR4/NF-κB signaling path-way was detected by ICC.iMEFs were treated with LPS,BAY11-7082,Adnovirus GFP and BMP9.The early osteo-genic differentiation capability of iMEFs was detected by ALP staining and quantitative assay .The later osteogenic differentiation capability was detected by alizarin red S staining .The expression of later osteogenic differentiation marker gene OCN and OPN were detected by PCR and Western blot .The change of p-Smad1/5/8 was detected by Western blot.The expression of Runx2 and Dlx5 were detected by PCR and Western blot .Results LPS can effec-tively stimulate TLR4/NF-κB signaling pathway .TLR4 activation inhibited BMP 9-induced osteogenic differentiation . BMP9-induced osteogenic differentiation related gene and Smad 1/5/8 signaling activation were inhibited by TLR4 activation .The inhibition effect was partly reversed by BAY 11-7082 ( P<0.05 ) .Conclusions TLR4 activation with LPS can inhibit BMP9-induced osteogenic differentiation of iMEFs cells via NF-κB signaling pathway .
4.Effect of BMP9 over-expression on migration and invasion of human lung squamous-cell carcinoma NCI-H520 cells
Jing WANG ; Fang DENG ; Ya LI ; Mengtian FAN ; Yangliu GUO ; Qiong SHI
Chinese Journal of Pathophysiology 2015;(11):1921-1927
AIM:To investigate the effect of bone morphogenetic proteins 9 (BMP9) on the migration and in-vasion abilities of human lung squamous-cell carcinoma NCI-H520 cells and its mechanism.METHODS:The expression of BMP9 at mRNA and protein levels in the NCI-H520 cells and human bronchial epithelial ( HBE) cells was detected by RT-PCR and Western blot.The NCI-H520 cells were transfected with the recombinant adenovirus AdBMP9 and the expres-sion of BMP9 at mRNA and protein levels was validated by RT-PCR and Western blot.The migration and invasion abilities of the NCI-H520 cells were determined by wound-healing and Transwell assays.The mRNA and protein levels of the migra-tion-related factor matrix metalloproteinase 2 (MMP2) were detected by RT-PCR and Western blot.The level of phospho-rylated Smad1/5 (p-Smad1/5) was detected by Western blot.Meanwhile, NCI-H520 cells were treated with BMP specific antagonist AdNoggin and AdBMP9.The level of p-Smad1/5 and the cell migration ability were measured by Western blot, wound-healing and Transwell assays.RESULTS:The expression of BMP9 at mRNA and protein levels was lower in NCI-H520 cells than that in HBE cells.After AdBMP9 was stably transfected into the NCI-H520 cells, the expression of BMP9 at mRNA and protein levels was significantly up-regulated, cell migration and invasion abilities were significantly de-creased, and the mRNA and protein levels of MMP2 were decreased.Meanwhile, the level of p-Smad1/5 was increased. Noggin reversed BMP9-caused the increase in p-Smad1/5 and the decrease in cell migration ability.CONCLUSION:O-ver-expression of BMP9 inhibits the migration and invasion abilities of lung squamous-cell carcinoma NCI-H520 cells.The activation of BMP-Smad signaling pathway may be involved in this inhibitory process.
5.Postoperative management of breast augmentation by polyacrylamide hydrogel injection:a report of 157 cases
Jiaming SUN ; Yong ZHANG ; Jiecong WANG ; Yangliu LIAO ; Chong PENG ; Xiaoling FENG ; Nengqiang GUO
Chinese Journal of Medical Aesthetics and Cosmetology 2009;15(2):88-91
Objeetive To discuss a reasonable postoperative management of breast augmentation by polyacrylamide hydrogel (PAHG) injection.Methods The retrospective study was used to analyze 157 cases which received breast augmentation by PAHG injection.MRI was used in all of cases preoperatively.Among these patients,23 were located by three-dimensional (3D) reconstruction,the content of mono acrylamide in the serum of 71 cases were examined in the hydrogel of 23 cases and in the tissue around the hydrogel of 12 cases,respectively.The silicone gel implants were planted after the removal of PAHG in 7 cases.Results MRI-3D could show the injectants location,scope,layer and integrality more intuitional and more detailed.The momo acrylamide was found in the serum with 7 cases,in the hydrogel with 5 cases,in the tissue around the hydrogel with 3 cases.131 cases gained satisfactory results.All the cases received 3 to 6 months follow-up.The scleroma was not found after the palpation of breast.In the 7 cases that were planted with the silicone gel implants immediately,the shape and texture of the breast were both great.Conclusions The preoperative MRI examination is a first-choice,and if possible,3D reconstruction is better.With the detecting methods so far,there is no strong evidence to support the possibility of PAHG resolving into poisonous acrylamide inside the human body.During the operation,the injectant,the integument around the hydrogel and degenerative tissue should be orthoptically cleared-up as much as possible.Sucking the injectant blindly is not commended.The silicon gel prosthesis is planted to reconstruct the shape of breast immediately,but the prerequisite is that the patients have this demand and that the muscle is intact without inflammation.

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