Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

Objective To investigate the ameliorative effects and potential mechanism of Lithocarpus litseifoliu on renal function and inflammation in mice with hyperuricemic nephropathy(HN).Methods The HN model was established by the combined administration of adenine and potassium oxyzate.The mice were randomly divided into normal control group,model control group,benzbromarone group,and high,medium and low dose groups of Lithocarpus litseifoliu.Different drugs were given to the mice,and their body mass was recorded once a week.The levels of uric acid(UA),creatinine(Cr),urine protein(UP),blood urea nitrogen(BUN)and urine urea nitrogen(UUN)as well as the levels of tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in serum or urine of each group were collected and measured on the 21st day.Hematoxylin-eosin(HE)staining was performed to observe kidney tissue injury in mice;real-time PCR(RT-PCR)was performed to determine ATP-binding cassette subfamily G member 2(ABCG2),urate transporter protein(URAT1),glucose transporter protein 9(GLUT9),and cytosolic factor NF-κB p50(κB p50)in kidney tissues.Results Compared with the normal control group,the body mass of mice in the model control group was significantly lower after the second weeks of modeling(P＜0.05),and the levels of UA,Cr,UP,BUN,UUN,TNF-α,IL-6 contents and GLUT9 mRNA and κB p50 mRNA expression contents of kidney tissues were significantly higher(P＜0.01,P＜0.05).Compared with the model control group,the levels of Cr,UP,BUN and UUN contents and renal tissue nuclear cytokine κB p50 mRNA expression were significantly lower in the high,medium and low dose groups of Lithocarpus litseifoliu(P＜0.01,P＜0.05).The UA levels were significantly lower in the high dose group of Lithocarpus litseifoliu(P＜0.05),and renal ABCG2 mRNA expression was significantly higher in the medium dose group(P＜0.01).The renal URAT1 mRNA expression was significantly decreased in the low dose group(P＜0.01).Conclusion Lithocarpus litseifoliu has shown ameliorative effects on HN mice,and the mechanism may be related to the modulation of renal uric acid transporters,improvement of renal function and anti-inflammation effects.

Objective To evaluate the feasibility of the porous titanium/chitosan/hydroxyapatite (Ti/Ch/HA) composite scaffold as a bone repair substitute.Methods Additive manufacturing (3D printing) technology was used to fabricate porous Ti scaffolds as supporting structures.Chitosan/hydroxyapatite (Ch/HA) sponge was prepared within the macro-pores of Ti scaffolds using freeze drying technology.Thus,a kind of composite porous Ti/Ch/HA scaffold with good cell affinity was obtained.Osteoblastic cells were seeded and cultured in pure porous Ti scaffolds and composite Ti/Ch/HA scaffolds for 7 days.The cellular morphology,seeding efficiency and proliferation were examined and compared between the 2 kinds of scaffolds using scanning electron microscopy (SEM) and MTT assay.Results The SEM examination showed that the macro-pores of Ti/Ch/HA scaffolds were full of the composite sponge structure of Ch/HA,with a micropore size of 50 to 200 μm.Like the pure porous Ti scaffolds,composite Ti/Ch/HA ones have a compressive strength of 168.2 to 192.6 MPa,a yielding strength of 137.1 to 154.1 MPa,and a Young's modulus of 3.21 to 4.51 GPa.After culture for 7 days,a large number of flat cells adhered onto the surface of Ti scaffolds while the cells adhering onto the Ti/Ch/HA composite scaffolds were fusiform.The seeding efficiency of osteoblastic cells in the composite Ti/Ch/HA scaffolds (73.218％ ± 3.748％) was significantly higher than that in the pure porous Ti scaffolds (21.352％ ±4.365％) (P ＜0.05);the OD value of the composite Ti/Ch/HA scaffolds (0.783 ±0.043) was significantly higher than that of the pure porous Ti scaffolds (0.382 ± 0.036) (P ＜ 0.05).Conclusions Ti/Ch/HA composite scaffolds can match human bone in mechanical properties.Compared with pure porous Ti scaffolds,the Ti/Ch/HA composite ones are more suitable for adhesion and proliferation of osteoblasts,making them an ideal kind of bone repair substitute.

ObjectiveTo evaluate the association between Pro12Ala polymorphism in peroxisome proliferator activated receptorγ2 (PPARγ2) gene and gestational diabetes mellitus(GDM).Methods Publications on genetic association studies of PPARγ2 and GDM were searched using the PubMed database, The HuGE Navigator, China National Knowledge Infrastructure (CNKI), Wanfang database and VIP Science from the inception of the databases to December 1, 2014. Two reviewers independently selected literature according to the inclusion and exclusion criteria, extracted data and assessed the quality of the data using the Newcastle-Ottawa Scale (NOS) standard. Meta-analysis was performed using RevMan 5.3 software.ResultsOverall, 13 eligible articles were identified, including seven in English and six in Chinese, with a total of 2 787 GDM cases and 5 408 healthy controls. Quality assessment showed that the quality of the 13 articles was all good, with NOS≥5. (1) Pro12Ala polymorphism in PPARγ2 (allele Ala or genotype Ala/Ala or Pro/Ala) was shown to be highly associated with GDM occurrence on general evaluation, with anOR(95%CI) of 0.74(0.60-0.93) in the allele model and 0.79(0.65-0.96) in the dominant genetic model (P<0.05, respectively). (2) Pro12Ala polymorphism in PPARγ2 was shown to be highly associated with GDM occurrence in Asians in a stratification analysis of ethnicity in the populations included in the studies, with anOR(95%CI) of 0.61(0.48-0.79) in the allele model and 0.64(0.50-0.82) in the dominant genetic model (P<0.01, respectively). No correlation was found between the Pro12Ala polymorphism in PPARγ2 and GDM in the Caucasian population. (3) A meta-analysis of six Chinese studies showed that the Pro12Ala polymorphism in PPARγ2 was associated with the risk of GDM in the Chinese population, with anOR(95%CI) of 0.52 (0.36-0.73) in the allele model and 0.55(0.39-0.80) in the dominant genetic model (P<0.01, respectively). (4) No significant association was observed in the TaqMan allelic discrimination assay with anOR(95%CI) of 0.96(0.83-1.10) in the allele model and 0.95(0.81-1.11) in the dominant genetic model (P>0.05, respectively), although there was still a significant correlation in polymerase chain reaction-restriction fragment length polymorphism with anOR(95%CI) of 0.58(0.43-0.79) in the allele model and 0.62(0.45-0.85) in the dominant genetic model (P<0.01, respectively).ConclusionsThe Ala allele and the Ala/Ala or Pro/Ala genotypes of the Pro12Ala polymorphism in PPARγ2 can decrease the risk of GDM. However, there are differences in the results which are affected by the genotype analysis method or races.