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.

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.

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.

OBJECTIVE To explore the effect of Huangqin decoction on improving peritubular fat inflammatory microenvironment and protecting vascular endothelial function in obese hypertensive rats by regulating the NEK7-NLRP3/IL-1β inflammatory axis.METHODS Fifty 4-week-old male Wistar rats were selected,10 of which were randomly selected as the control group,and the oth-er 40 were fed a high-salt and high-fat diet to establish an obese hypertension model.The rats with successful modeling(20 rats)were randomly divided into the model group,normal-dose Huangqin decoction group,high-dose Huangqin decoction group,and IL-1β in-hibitor group,with 5 rats in each group.From the 12th week,the normal-dose group was gavaged with Huangqin decoction 2.835 g·kg-1,the high-dose group was gavaged with Huangqin decoction 5.67 g·kg-1,and the IL-1β inhibitor group was intraper-itoneally injected with 1.5 mg·kg-1 AS101,3 times a week,for 8 weeks.The rats were weighed and blood was collected 12 h after the last administration,and the thoracic aorta and perivascular fat tissue were isolated.Serum inflammatory factors were detected,patho-logical changes were observed,eNOS expression was detected by immunofluorescence,and NEK7,NLRP3,Caspase-1,ASC,and IL-1β expression levels were detected by Western blot and qPCR.RESULTS The rats in the model group had a significant increase in body weight,an increase in the area of peritubular fat lipid droplets,and severe endothelial injury;systolic blood pressure,diastolic blood pressure,serum IL-1β,IL-6,and TNF-α were significantly elevated in the model group,and the expression of eNOS was sig-nificantly reduced,and the expression levels of NEK7,NLRP3,Caspase-1,ASC,and IL-1β proteins and mRNAs were significantly elevated.Compared with the model group,rats in the Huangqin decoction and IL-1β inhibitor groups had lower body weights,reduced endothelial damage,lower systolic and diastolic blood pressures,lower serum IL-1β,IL-6,and TNF-α,and higher eNOS expression.NEK7,NLRP3,Caspase-1,ASC and IL-1β protein expression was significantly reduced in the high dose group of Huan-gqin decoction and the IL-1β inhibitor group.In addition,Huangqin decoction protected the endothelial function of obese hypertensive vessels in a dose-dependent manner,with the effect being more pronounced in the high-dose group.CONCLUSION Huangqin de-coction can improve the inflammatory microenvironment of perivascular fat and protect the vascular endothelial function in obese hyper-tension by regulating the NEK7-NLRP3/IL-1β inflammatory axis.

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.

Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L⁻¹ NaAsO₂ model group (NaAsO₂), 50 mg·L⁻¹ NaAsO₂+10 mg·kg⁻¹ GBE intervene group (NaAsO₂+GBE), and 10 mg·kg⁻¹ GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L⁻¹ NaAsO₂, or given intraperitoneal injection of normal saline containing 10 mg·kg⁻¹ GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L⁻¹ NaAsO₂ group (NaAsO₂), 8 μmol·L⁻¹ NaAsO₂ + 200 mg·L⁻¹ GBE intervene group (NaAsO₂+GBE), and 200 mg·L⁻¹ GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO₂ group exhibited an elevated blood glucose compared to the control group, and the NaAsO₂+GBE group showed a decreased blood glucose compared to the NaAsO₂ group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO₂ group and NaAsO₂+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO₂ groups compared to the control groups, which was alleviated in the NaAsO₂+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO₂+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.

Objective:To discuss the distinctive sonographic feature and the biological behavior of renal angiomyolipoma(RAML),and to provide the reference for the clinicians to make the accurate diagnosis of RAML.Methods:The clinical data of one patient with invasive classical RAML combined with pseudaneurysm formation were collected.The sonographic appearances were analyzed in conjunction with the pathological characteristics to clarify the biological behavior of RAML,and the relevant literatures were reviewed.Results:The patient,a 60-year-old female,visited the local hospital due to discomfort in the lumbar area,and received CT examination,and the CT examination results revealed a left renal mass,so the patient came to our hospital.The specialist clinical examinations and laboratory investigations were unremarkable.The ultrasound results indicated an enlarged left kidney with a cystic and solid mass at the upper pole,which featured pseudaneurysm formation(originating from the interlobar arteries);the enhanced CT image results suggested a high probability of upper pole renal carcinoma combined with aneurysmal formation within the tumor,alongside invasion into the left adrenal gland.The patient underwent laparoscopic radical left nephrectomy,and the postoperative pathology confirmed the diagnosis of invasive classical RAML.Conclusion:The classical RAML can exhibit the invasive biological behavior.The pseudaneurysm formation is a special sonographic manifestation of RAML,which can be challenging to differentiate from the other renal tumors.

Objective To evaluate the efficacy of transanal opening of intersphincteric space(TROPIS)for the treatment of complex anal fistula.Methods 41 patients with complex anal fistula were randomly divided into two groups by random envelope method:21 patients in the treatment group were treated with TROPIS;20 patients in the control group were treated with traditional low incision and high thread drawing surgery.The curative effect,postoperative pain score,wound healing time,treatment failure rate,anal sphincter function and postoperative complications were compared between the two groups.Results The visual analoguescale scores(VAS)of anal pain in the treatment group and the control group 8 hours,24 hours,3 days,7 days and the first defecation after operation were(1.81±1.12)vs.(5.00±1.49),(1.10±1.14)vs.(4.35±1.42),(0.86±1.01)vs.(4.35±1.27),(0.81±1.08)vs(4.25±1.41),(3.05±1.56)vs(6.70±1.17),respectively,with significant differences(P＜0.01).The VAS of anal pain in the treatment group and the control group 14 days after operation were(0.67±1.07)vs(0.80±1.11),respectively,with no significant difference(P＞0.05).1 case in the treatment group(4.76％)and 1 case in the control group(5.00％)had wound infection after surgery,there was no significant difference in the rate of wound infection between the two groups(P＞0.05).2 cases(9.52％)in the treatment group and 3 cases(15.00％)in the control group underwent postoperative catheterization,there was no significant difference in urinary retention between the two groups(P＞0.05).In the treatment group,16 cases were cured,3 cases were markedly effective,and the total effective rate was 90.48％,while in the control group,16 cases were cured,2 cases were markedly effective,and the total effective rate was 90.00％,there was no significant difference between the two groups(P＞0.05).The wound healing time of the treatment group and the control group were(37.31± 3.42)days vs(48.13±4.08)days,respectively,with a statistically significant difference(P＜0.01).12 months after operation,2 patients in the treatment group and 1 patient in the control group lost the follow-up.12 months after operation,the ST Marks anal incontinence scores in the treatment group and the control group were(0.53±1.07)and(1.74±2.77),respectively,with a statistically significant difference(P＜0.05).There were 6 patients(31.58％)in the treatment group and 4 patients(21.05％)in the control group who failed in treatment,there was no significant difference in the rate of treatment failure between the two groups(P＞0.05).Conclusion The TROPIS is reliable in treating anal fistula,and has the advantages of less pain,quick recovery and less damage to anal function.

Objective: To investigate the effects of embryonic inflammation on the hippocampal synaptosomal-associated protein 25(SNAP-25) level and cognitive function in middle-aged. Methods: During gestational days 15-17, the CD-1 maternal mice received a daily intraperitoneal injection of lipopolysaccharides(LPS, 50 μg/kg) or the equal volume of normal saline, and the corresponding offspring were regarded as LPS group and CON group respectively. At the age of young(3-month-old) and middle-aged(15-month-old), the spatial learning and memory ability was assessed using Morris water maze(MWM), and the expression of hippocampal SNAP-25 protein was detected by immunohistochemical method and Western blot. Results: Compared with the 3-month CON group, the 15-month CON group had longer swimming distance(P<0.01), lower swimming distance percentage(P<0.01) in the target quadrant, and higher hippocampal subregions(CA1, CA3, DG) SNAP-25 levels(P<0.01). The same results were obtained in 15-month LPS group compared with 15-month CON group in learning and memory phase(P<0.05), and higher hippocampal subregions(CA1, DG) SNAP-25 levels(P<0.01). Pearson correlation analysis indicated that the hippocampal CA1 and CA3 subregions SNAP-25 level was positively correlated with the swimming distance, but negatively correlated with the percentage of swimming distance in the target quadrant. Conclusion Embryonic inflammation can accelerate the impairment of spatial learning and memory and the increase of hippocampal CA1 and CA3 subregions SNAP-25 protein in middle-aged CD-1 mice, and there may be a correlation between them.