The development of bone in human body and the maintenance of bone mass in adulthood are regulated by a variety of biological factors. Myocyte enhancer factor 2C (MEF2C), as one of the many factors regulating bone tissue development and balance, has been shown to play a key role in bone development and metabolism. However, there is limited systematic analysis on the effects of MEF2C on bone tissue. This article reviews the role of MEF2C in bone development and metabolism. During bone development, MEF2C promotes the development of neural crest cells (NC) into craniofacial cartilage and directly promotes cartilage hypertrophy. In terms of bone metabolism, MEF2C exhibits a differentiated regulatory model across different types of osteocytes, demonstrating both promoting and other potential regulatory effects on bone formation, with its stimulating effect on osteoclasts being determined. In view of the complex roles of MEF2C in bone tissue, this paper also discusses its effects on some bone diseases, providing valuable insights for the physiological study of bone tissue and strategies for the prevention of bone diseases.
Humans ; MEF2 Transcription Factors/physiology* ; Bone and Bones/metabolism* ; Animals ; Bone Development/physiology* ; Osteogenesis/physiology* ; Myogenic Regulatory Factors/physiology*

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Autophagy is an essential cellular metabolic process that involves clearance of damaged organelles and protein aggregates in cells through lysosomes,providing energy for cells,and maintaining cellular tissue homeostasis.Impaired autophagy is closely related to the pathophysiology of a variety of diseases.In the pathogenesis of atherosclerosis(AS),the dysfunction of autophagy of vascular cells plays a crucial role in the formation and progression of AS.The functional status,survival or death of vascular cells,including endothelial cells,vascular smooth muscle cells and macrophages,can influence the formation and stability of plaques,thereby affecting the progression of AS.This review summarizes the relationship between autophagy and AS,and details the impact of autophagy dysfunction on vascular cell function in the process of AS,as well as the role of mitophagy and inflammasome in the development of AS,aiming to provide novel insights for the prevention and treatment of AS.

Objective To compare the differences in lipid metabolism between platinum-resistant and platinum-sensitive ovarian cancer patients at stage Ⅲ-Ⅳ,to analyze the differential intestinal flora using 16S rRNA sequen-cing,and to explore the associations among intestinal flora,lipid metabolism characteristics and platinum resistance in ovarian cancer.Methods Patients diagnosed with ovarian cancer at stage Ⅲ-Ⅳ through surgical pathology were selected,including a platinum-resistant group(11 cases)and a platinum-sensitive group(11 cases).The differences in lipid metabolism between the two groups were compared.The differences in gut microbiota between the two groups were investigated using fecal 16S rRNA sequencing.The association among gut microbiota,lipid metabolism characteristics,and platinum resistance in ovarian cancer was analyzed.Results Significant differ-ences were observed in lipid metabolism-related indicators[total cholesterol(TC),high-density lipoprotein choles-terol(HDL-C),non-high-density lipoprotein cholesterol(n-HDL),low-density lipoprotein cholesterol(LDL-C),apolipoprotein(B)]between the two groups,with higher levels in the platinum-resistant group.The Shannon in-dex(P=0.008 3)and Simpson index(P=0.008 2)both showed higher diversity of gut microbiota in platinum-resistant ovarian cancer patients compared to the platinum-sensitive group.However,based on OTUs species clus-tering and relative abundance statistics,certain bacterial abundances differed significantly between the groups.Spe-cies such as Parabacteroides,Akkermansia,Blautia,Lachnoclostridium,Fusicatenibacter,and Megamonas had sig-nificantly higher abundances in the platinum-sensitive ovarian cancer group,and Akkermansia(a lipid metabolism-related bacterial group)was the most prevalent.Conclusion The platinum-resistant group of ovarian cancer ex-hibits significantly higher levels of lipid metabolism and gut microbiota diversity compared to the platinum-sensitive group.This suggests that the increase in lipid metabolism levels and fecal microbiota diversity may be associated with the development of platinum resistance.However,certain microbial taxa are reduced in abundance in the plat-inum-resistant group,such as the distinct Akkermansia genus(a lipid metabolism-related microbial community),which may serve as one of the factors inducing platinum-resistance in ovarian cancer.

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

Hydrogen peroxide (H

AIM: To investigate the effect of the intravitreal injection of vascular endothelial growth factor-A165(VEGF-A165)on the scleral remodeling of guinea pigs with form-deprivation myopia(FDM).METHODS: A total of 120 tricolor guinea pigs, aged three weeks, were randomly divided into 6 groups, with 20 in each group. The blank group did not undergo any intervention. In the FDM group, only the FDM model was established. In the phosphate buffer saline(PBS)group, 2.5 μL of PBS was injected into the vitreous cavity before establishing the FDM model. In the 1ng group, 5ng group, and 10ng group, VEGF-A165 was injected into the vitreous cavity at concentrations of 1, 5 and 10ng, respectively, before the establishment of the FDM model. The FDM model was established by covering the right eyes of guinea pigs with translucent balloons for 14d. The diopter and axial length of the right eyes were measured before and after covering. After 14d, the content of dopamine(DA)in retina was measured by high performance liquid chromatography. Additionally, the mRNA and protein expression levels of matrix metalloproteinase-2(MMP-2), tissue inhibitor of matrix metalloproteinase-2(TIMP-2), transforming growth factor(TGF)-β1, TGF-β2 and α-smooth muscle actin(α-SMA)in sclera were detected by reverse transcription polymerase chain reaction(RT-PCR)and Western blot.RESULTS: Before covering, there were no significant differences in the diopter and axial length of the right eyes of guinea pigs in all groups(P>0.05). After 14d of modeling, when compared with the blank group, FDM group showed an increase in the degree of myopia in the right eye, a prolongation of the axial length, a decrease in the content of DA in the retina, and an increase in the expression of MMP-2, TGF-β2 and α-SMA in the sclera. Conversely, the expression of TIMP-2 and TGF-β1 were decreased(P<0.01). However, in comparison to the FDM group, the degree of myopia in the 1ng, 5ng, and 10ng groups of guinea pigs decreased, the growth trend of axial length slowed, the content of DA in the retina increased, and the expression of MMP-2, TGF-β2 and α-SMA in the sclera decreased. Furthermore, the expression of TIMP-2 and TGF-β1 in the sclera increased(P<0.01). As the concentration of intravitreal injection of VEGF-A165 increased, the degree of myopia in the right eye of guinea pigs gradually increased, and the axial length gradually prolonged. The content of DA in the retina gradually decreased, the expression of MMP-2, TGF-β2, and α-SMA in the sclera gradually increased, while the expression of TIMP-2 and TGF-β1 decreased gradually.CONCLUSION: Intravitreal injection of VEGF-A165 can increase the content of DA in the retina of FDM guinea pigs, affect the expression of MMP-2, TIMP-2, TGF-β1, TGF-β2 and α-SMA in the sclera, and inhibit scleral remodeling of guinea pigs. Notably, the VEGF-A165 at the concentration of 1ng showed the most significant efficacy.

Humans ; Gemcitabine ; Neoplasms

OBJECTIVE: To compare the efficiency and effect of establishing rat peri-implantitis model by traditional cotton thread ligation and local injection of Porphyromonas gingivalis lipopolysaccharide (LPS) around the implant, as well as the combination of the two methods. METHODS: Left side maxillary first molars of 39 male SD rats were extracted, and titanium implants were implanted after four weeks of healing. After 4 weeks of implant osseointegration, 39 rats were randomly divided into 4 groups. Cotton thread ligation (n=12), local injection of LPS around the implant (n=12), and the two methods combined (n=12) were used to induce peri-implantitis, the rest 3 rats were untreated as control group. All procedures were conducted under 5% isoflurane inhalation anesthesia. The rats were sacrificed 2 weeks and 4 weeks after induction through carbon dioxide asphyxiation method. The maxilla of the rats in the test groups were collected and marginal bone loss was observed by micro-CT. The gingival tissues around the implants were collected for further real time quantitative PCR (RT-qPCR) analysis, specifically the expression of tumor necrosis factor-alpha (TNF-α) as well as interleukin-1β (IL-1β). The probing depth (PD), bleeding on probing (BOP) and gingival index (GI) of each rat in the experimental group were recorded before induction of inflammation and before death. RESULTS: After 4 weeks of implantation, the osseointegration of implants were confirmed. All the three test groups showed red and swollen gums, obvious marginal bone loss around implants. After 2 weeks and 4 weeks of inflammation induction, PD, GI and BOP of the three test groups increased compared with those before induction, but only BOP was statistically significant among the three test groups (P < 0.05). At the end of 2 weeks of inflammation induction, marginal bone loss was observed at each site in the cotton thread ligation group and the combined group. At each site, the bone resorption in the combined group was greater than that in the cotton thread ligation group, but the difference was not statistically significant (P > 0.05), bone resorption was observed at some sites of some implants in LPS local injection group. At the end of 4 weeks of inflammation induction, marginal bone loss was observed at all sites in each group. The marginal bone loss in the cotton thread ligation group and the combined group was greater than that in the LPS local injection group, and the difference was statistically significant (P < 0.05). At the end of 2 weeks and 4 weeks of induction, the expression of TNF-α and IL-1β in the test groups were higher than those in the control group (P < 0.05). CONCLUSION Compared with local injection of LPS around the implant, cotton thread ligature and the two methods combined can induce peri-implantitis in rats better and faster.
Animals ; Male ; Rats ; Alveolar Bone Loss/etiology* ; Dental Implants/adverse effects* ; Inflammation ; Lipopolysaccharides ; Peri-Implantitis/pathology* ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha

The aim of this study was to investigate the effect of baicalein on a Drosophila model of hereditary Parkinson's disease caused by gene mutations and to preliminarily elucidate the mechanism of baicalein in delaying hereditary Parkinson's disease. In this paper, PTEN-induced putative kinase 1 (PINK1)-RNAi Parkinson's Drosophila were used as the model group and wild-type Drosophila w¹¹¹⁸ were used as the control group. Different doses of baicalein and Madopa were administered to the model group to observe their effects on the life span, motor ability, the abnormal rate of wings, dopamine content and dopaminergic neurons of PINK1-RNAi Parkinson's Drosophila and their effects on mitochondrial dysfunction including adenosine triphosphate (ATP), mitochondrial DNA (mtDNA) and reactive oxygen species (ROS) content. The results showed that the effective administration doses of baicalein were 0.8 mg·mL^-1 for low concentration, 1.6 mg·mL^-1 for medium concentration and 3.2 mg·mL^-1 for high concentration, and the optimal administration dose of the positive drug Madopa was 0.1 μg·mL^-1. Baicalein and Madopa could significantly improve the life span, exercise ability and reduce the abnormal rate of wings of PINK1-RNAi male Drosophila (P < 0.05), and low dose baicalein showed the best effect; baicalein could improve the loss of dopaminergic neurons, and the effects of low dose and high dose were the best, but Madopa showed no significant effect; baicalein and Madopa had no significant effect on dopamine content (P > 0.05). Baicalein and Madopa could increase the ATP content of PINK1-RNAi male Drosophila (P < 0.05), and low dose baicalein showed the best effect; middle dose baicalein could significantly increase the mtDNA content of PINK1-RNAi male Drosophila (P < 0.05), but Madopa had no significant effect; baicalein and Madopa had no significant effect on ROS content (P > 0.05).