In recent years, the rapid development of transportation and sports industries, coupled with the accelerated population aging in China, has led to a steady increase in the incidence of articular cartilage injuries, wear, and degenerative changes. Currently, the clinical treatment options for cartilage defects primarily include conservative therapies and surgical interventions, both of which have certain limitations. Cartilage tissue engineering (CTE), as a novel technology, provides an infinite prospect for cartilage regeneration and repair. Because of the abilities of scaffolds to mimic the natural cartilage structure, exhibit excellent biocompatibility and biomimetic mechanical properties, and promote cell adhesion and proliferation, scaffolds are considered effective delivery systems for growth factors, genes, and drugs. This review summarizes the clinical treatments for cartilage defects and their limitations, discusses the materials and preparation techniques of scaffolds used in CTE, with a particular focus on drug-loaded scaffold delivery systems in cartilage repair and regeneration, and offers a perspective on the future application of drug-loaded CTE. The aim is to provide theoretical guidance and new approaches for the repair of cartilage defects.
Tissue Engineering/methods* ; Humans ; Tissue Scaffolds ; Drug Delivery Systems/methods* ; Regeneration ; Cartilage, Articular/physiology* ; Animals ; Biocompatible Materials

Objective: To screen and identify the key active molecules, signaling pathways, and therapeutic targets of Shuxuening (SXN) injection for treating liver cirrhosis (LC) and to evaluate its therapeutic potential using a mouse model. Methods: Target genes of SXN and LC were retrieved from public databases, and enrichment analysis was performed. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified using Molecular Complex Detection (MCODE). LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride (CCl4) for 12 weeks. Starting at week 7, SXN was administered intraperitoneally to the mice in the treatment group. Serum and liver tissues of the mice were collected for the detection of indicators, pathological staining, and expression analysis of hub targets using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 368 overlapping genes (OLGs) between SXN and LC targets. These OLGs were subsequently used to build a PPI network and to screen for hub genes. Enrichment analysis showed that these genes were associated with cancer-related pathways, including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes, such as responses to chemicals and metabolic regulation. In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition. Furthermore, qRT-PCR demonstrated that SXN regulated the expression of MAPK8, AR and CASP3 in the livers of LC mice. Conclusion This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods. The observed effect was associated with modulation of hub gene expression, particularly MAPK8, and CASP3.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Background Arsenic is an environmentally harmful substance that causes hepatic insulin resistance and liver damage, increasing the risk of type 2 diabetes mellitus. Objective To explore whether the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is involved in insulin resistance in HepG2 cells after arsenic exposure through the peroxisome-proliferator-activated receptor γ (PPAR-γ) / glucose transporter 4 (GLUT4) pathway. Methods Cell viability was determined using cell counting kit 8 (CCK8) and an appropriate NaAsO₂ infection dose was determined. A cellular arsenic exposure model of HepG2 cells was established by four concentrations of NaAsO₂ solution for 24 h (the experiment was divided into four groups: 0, 2, 4, and 8 μmol·L⁻¹); HepG2 cells were firstly treated with pcDNA3.1-IGF2BP2 and pcDNA3.1-NC respectively for 6 h, then with 8 μmol·L⁻¹ NaAsO₂ for 24 h to establish a IGF2BP2 overexpression cell model (the experiment was divided into 4 groups: control, NaAsO₂, NaAsO₂+pcDNA3.1-IGF2BP2, and NaAsO₂+pcDNA3.1-NC); finally the cells were subject to 100 nmol·L⁻¹ insulin stimulation for 30 min. Glycogen and glucose in HepG2 cells were determined by glycogen and glucose assay kits; mRNA expression levels of IGF2BP2 were measured by quantitative real-time PCR; protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in HepG2 were detected by Western blot (WB); and the binding of IGF2BP2 to PPAR-γ and PPAR-γ to GLUT4 was verified by co-immunoprecipitation (CO-IP) experiment. Results The results of CCK8 experiment showed a dose-effect relationship between NaAsO₂ concentration and cell viability. When the concentration of NaAsO₂ was ≥4 μmol·L⁻¹ , the cell viabilities were lower than that of the control group (P <0.05). With the increasing dose of NaAsO₂ infection, reduced glucose consumption and glycogen levels in HepG2 cells were found in the 2, 4, and 8 μmol·L⁻¹ NaAsO₂ treatment groups compared to the control group (P <0.05). The difference between the mRNA expression level of IGF2BP2 in the HepG2 cells treated with 4 or 8 μmol L⁻¹ NaAsO₂ and the control group was significant (P <0.05). In the IGF2BP2 overexpression cell model, compared with the control group, glucose consumption and glycogen levels were lowered in the NaAsO₂ group (P <0.05), the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all decreased (P <0.05). Compared with the NaAsO₂ group, the glucose consumption and glycogen levels were increased in the NaAsO₂+pcDNA3.1-IGF2BP2 group (P <0.05), and the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all increased (P <0.05). The results of CO-IP experiments showed that IGF2BP2 interacted with PPAR-γ as well as PPAR-γ with GLUT4 protein. Conclusion IGF2BP2 is involved in arsenic exposure-induced insulin resistance in HepG2 cells by acting on the PPAR-γ/GLUT4 pathway.

Objective:To explore the effect of Yinchensiling granules combined with rifaximin on the gut microbiota and intes-tinal barrier function in mice with acute liver failure(ALF).Methods:Fifty mice were randomly divided into Control group,model group(ALF group),Yinchensiling granules group(YCSLG group),Rifaximin group(RIF group)and Yinchensiling granules com-bined with Rifaximin group(YCSLG+RIF group),with ten mice in each group.ALF mice model were established by intraperitoneal injection of thioacetamide(TAA,300 mg/kg)twice.YCSLG group,RIF group and YCSLG+RIF group mice were orally administered Yinchensiling granules(1.5 g/kg)and rifaximin(15 mg/kg),while Control group and ALF group mice were orally administered an equal amount of 0.9%sodium chloride solution,gavage once in the morning and once in the evening for 3 consecutive days.48 hours after successful modeling,abdominal aortic blood was collected to detect liver function indicator[alanine aminotransferase(ALT),as-partate aminotransferase(AST),total bilirubin(TBIL)]levels and intestinal mucosal injury related protein[diamine oxidase(DAO),D-lactic acid(D-LA)]in mice serum;ELISA was used to detect inflammatory factor IL-1β,IL-6,TNF-α levels in serum;HE staining was used to observe pathological damage in liver and colon tissues.Immunohistochemical staining and Western blot were used to detect intestinal mucosal healing related protein[Claudin-4,Occludin,zonula occludens 1(ZO-1)]levels in colon tissue;16S rRNA sequencing was used to detect changes in gut microbiota structure in mouse feces.Results:Compared with Control group,serum ALT,AST,TBIL,IL-1β,IL-6,TNF-α,DAO and D-LA levels in ALF group were increased,Claudin-4,Occludin,ZO-1 pro-tein levels in colon tissue were decreased,the abundance of probiotics such as Lactobacillus,Dubosella,Prevotella,Akkermansia and Faecalibacterium were decreased,while the abundance of pathogenic bacteria such as Shigella,Zurich,Klebsiella,Romboutsia and Bacteroides were increased(P<0.05);compared with ALF group,serum ALT,AST,TBIL,IL-1β,IL-6,TNF-α,DAO and D-LA levels in YCSLG group,RIF group and YCSLG+RIF group were decreased,Claudin-4,Occludin,ZO-1 protein levels in colon tissue were increased,the abundance of probiotics such as Lactobacillus,Dubosella,Prevotella,Akkermansia and Faecalibacterium in feces were increased,while the abundance of pathogenic bacteria such as Shigella,Zurich,Klebsiella,Romboutsia and Bacteroides were de-creased(P<0.05);and the treatment effect of YCSLG+RIF group was better than that of YCSLG group and RIF group(P<0.05).Con-clusion:Yinchensiling granules combined with rifaximin can improve liver function,improve intestinal microbiota structure,and re-store intestinal barrier function in ALF mice.

Objective:To explore the effect of Yinchensiling granules combined with rifaximin on the gut microbiota and intes-tinal barrier function in mice with acute liver failure(ALF).Methods:Fifty mice were randomly divided into Control group,model group(ALF group),Yinchensiling granules group(YCSLG group),Rifaximin group(RIF group)and Yinchensiling granules com-bined with Rifaximin group(YCSLG+RIF group),with ten mice in each group.ALF mice model were established by intraperitoneal injection of thioacetamide(TAA,300 mg/kg)twice.YCSLG group,RIF group and YCSLG+RIF group mice were orally administered Yinchensiling granules(1.5 g/kg)and rifaximin(15 mg/kg),while Control group and ALF group mice were orally administered an equal amount of 0.9%sodium chloride solution,gavage once in the morning and once in the evening for 3 consecutive days.48 hours after successful modeling,abdominal aortic blood was collected to detect liver function indicator[alanine aminotransferase(ALT),as-partate aminotransferase(AST),total bilirubin(TBIL)]levels and intestinal mucosal injury related protein[diamine oxidase(DAO),D-lactic acid(D-LA)]in mice serum;ELISA was used to detect inflammatory factor IL-1β,IL-6,TNF-α levels in serum;HE staining was used to observe pathological damage in liver and colon tissues.Immunohistochemical staining and Western blot were used to detect intestinal mucosal healing related protein[Claudin-4,Occludin,zonula occludens 1(ZO-1)]levels in colon tissue;16S rRNA sequencing was used to detect changes in gut microbiota structure in mouse feces.Results:Compared with Control group,serum ALT,AST,TBIL,IL-1β,IL-6,TNF-α,DAO and D-LA levels in ALF group were increased,Claudin-4,Occludin,ZO-1 pro-tein levels in colon tissue were decreased,the abundance of probiotics such as Lactobacillus,Dubosella,Prevotella,Akkermansia and Faecalibacterium were decreased,while the abundance of pathogenic bacteria such as Shigella,Zurich,Klebsiella,Romboutsia and Bacteroides were increased(P<0.05);compared with ALF group,serum ALT,AST,TBIL,IL-1β,IL-6,TNF-α,DAO and D-LA levels in YCSLG group,RIF group and YCSLG+RIF group were decreased,Claudin-4,Occludin,ZO-1 protein levels in colon tissue were increased,the abundance of probiotics such as Lactobacillus,Dubosella,Prevotella,Akkermansia and Faecalibacterium in feces were increased,while the abundance of pathogenic bacteria such as Shigella,Zurich,Klebsiella,Romboutsia and Bacteroides were de-creased(P<0.05);and the treatment effect of YCSLG+RIF group was better than that of YCSLG group and RIF group(P<0.05).Con-clusion:Yinchensiling granules combined with rifaximin can improve liver function,improve intestinal microbiota structure,and re-store intestinal barrier function in ALF mice.

Pancreatic metastases originating in colon cancer are very rare clinically, and there are few reports on their imaging manifestations. In this paper, it improves the diagnosis of the disease by reporting a case of pancreatic head metastases and focusing on the appearance of contrast-enhanced ultrasound.

Objective To investigate post-marketing adverse drug event(ADE)signals associated with lixisenatide,and to provide guidance for safe clinical use.Methods The ADE reporting data of lixisenatide ADE were mined and the signals were detected from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database from the first quarter 2013 to the second quarter 2024 using the reporting odds ratio(ROR)method and Bayesian confidence propagation neural network(BCPNN)method.Results After data cleaning,a total of 5 162 ADE reports with lixisenatide as the primary suspected drug were collected.The 85 ADE signals identified by the two statistical analysis methods,affected 14 system-organ classes(SOC).They were primarily concentrated in injuries,poisonings,and procedural complications(25.88％),various examinations(14.12％),systemic diseases and reactions at administration sites(14.12％),gastrointestinal diseases(9.41％),and various neurological diseases(5.88％).There were 28 ADE signals such as pancreatitis,visual impairment,and color blindness,that were not included in the drug instructions.Conclusion In addition to monitoring for common ADE associated with GLP-1 receptor agonists such as hypoglycemia,gastrointestinal,and neurological effects,clinicians should also be vigilant for underlying ADE like pancreatic-related diseases,eye toxicity reaction when using lixisenatide to ensure safe and rational medication use.

bjective To mine signals of post-marketing adverse drug events(ADEs)associated with dapagliflozin,and to provide insights for safe medication in clinical settings.Methods Data on ADEs related to dapagliflozin from U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)were collected from the first quarter of 2013 to the third quarter of 2024.The analyses involved data mining and signal monitoring using disproportionality analysis techniques including the reporting odds ratio(ROR)method,Medicines and Healthcare Products Regulatory Agency(MHRA)method,Bayesian confidence propagation neural network(BCPNN)method,and multi-item gamma Poisson shrinker(MGPS)method.Results After data cleaning,a total of 55 832 qualified dapagliflozin case reports were obtained,involving 25 090 patients,with a slightly higher percentage of males(44.99％)than females(41.18％).The predominant age group was 45 to 64 years(20.78％).A total of 379 ADE signals were detected across 22 system-organ classes(SOC).The ADEs of dapagliflozin were mainly concentrated in the SOC such as infections and infestations,general disorders and administration sites conditions,and metabolism and nutrition disorders,aligning with information provided in the drug instructions.Additionally,the ADE signals were not documented in drug inserts such as scrotal gangrene,periperineal cellulitis,scrotal abscess,hyperglycemia,ketonuria,and pancreatitis.Conclusion When clinically using dapagliflozin,it is essential to conduct a thorough medication assessment.In addition to closely monitoring diabetes ketoacidosis,fungal infection,and acute renal injury.The latent ADEs that are not mentioned in the instructions to should be noticed ensure safe medication.

Objective To mine the real-world risk signals associated with saxagliptin-related adverse drug event(ADE),and to provide insights for evidence-based use of the drug in clinical practice.Methods Data on ADE related to saxagliptin from U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)were collected from the first quarter of 2013 to the third quarter of 2024,and analyzed using the reporting odds ratio(ROR)and Bayesian confidence propagation neural network(BCPNN)techniques.Results After data cleaning,the study analyzed 2 036 qualified case reports from patients who were using saxagliptin,uncovering 4 497 adverse events and identifying 131 adverse event signals across 19 system-organ classes(SOCs),including cardiac organ system diseases(20.61％),various types of investigations(10.69％),and gastrointestinal tract diseases(13.74％).Among them,heart failure,pancreatitis,pancreatic cancer,and hypoglycaemic coma were high-intensity signals.Conclusion In clinical practice,the indications for saxagliptin should be strictly managed.It is advisable to avoid using saxagliptin as monotherapy in patients with a history of heart failure or in patients at elevated risk for arteriosclerotic cardiovascular disease.Continuous monitoring of essential organ functions,especially cardiac and pancreatic,is essential throughout the course of treatment to ensure the safety of the medication.