BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

The skin is one of the most vital organs in the human body, and skin wounds caused by various factors can severely impact patients’ physical and mental health. Among the therapeutic strategies for skin wound repair, mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as a promising biological therapy, attracting significant attention in related research. As critical mediators of stem cell biological effects, MSC-Exos fuse with target cells and transfer bioactive proteins and nucleic acids from stem cells into recipient cells. These exosomes modulate inflammatory responses, promote cell proliferation, migration, and angiogenesis, and regulate extracellular matrix remodeling, thereby accelerating wound healing. In recent years, studies on the mechanisms by which exosomes promote skin wound repair have advanced and refined continuously. This article summarized the key signaling pathways through which MSC-Exos participate in skin wound repair, aiming to enhance the understanding of their roles in facilitating wound healing.

Objective:To observe the effects of sorafenib on the lesions and vascular growth factors in the mouse model of hepatic alveolar echinococcosis.Methods:One hundred healthy female Kunming mice weighing (20±4) g were used to establish a model of alveolar echinococcosis infection by intraperitoneal injection of alveolar echinococcosis protoscoleces. After 6 weeks of feeding, the rats were divided into 5 groups, 15 rats in each group, which were given warm saline, albendazole (100 mg/kg), and sorafenib at high-dose (100 mg/kg), middle-dose (50 mg/kg) and low-dose (30 mg/kg) by gavage for 6 weeks, respectively. Eyeball blood and hepatic alveolar echinococcosis tissue were collected from the mice after the last administration, and the body weight of the mice and the lesion weight were weighed. The concentrations and expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor receptor-2 (VEGFR-2) in serum and lesion tissues were detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting.Results:There was no statistically significant difference in the body weight of mice among the saline group, albendazole group and low-dose, medium-dose and high-dose sorafenib groups ( F=0.43, P=0.784). The ratios of lesion weight to body weight in the above groups were (0.057±0.009), (0.031±0.005), (0.033±0.005), (0.031±0.005), and (0.031±0.005), respectively. The saline group had a higher ratio than the other four groups, and the differences were statistically significant (all P<0.05). The relative expression levels of HIF-1α, VEGF-A, VEGFR-2, CD31 and CD34 detected by Western blotting in the saline group were all higher than those in the albendazole group and the high-dose, medium-dose and low-dose sorafenib groups, and the differences were statistically significant (all P<0.05). The relative expression levels of the above proteins in the medium-dose and high-dose sorafenib groups were lower than those in the albendazole group, and the relative expression levels of the above proteins in the high-dose sorafenib group were also lower than those in the medium-dose sorafenib group, and the differences were statistically significant (all P<0.05). The concentration levels of HIF-1α, VEGF-A and VEGFR-2 in serum of mice in each group detected by ELISA were consistent with those detected by Western blotting. Conclusion:Sorafenib inhibits the proliferation of alveolar echinococcosis in mice by suppressing the expression of angiogenic factors in alveolar echinococcosis lesions.

Objective To investigate the effects of 3-methyladenine(3-MA)on mouse mesangial cell line MES-13 cultured in high glucose,and on the kidney of streptozotocin(STZ)-induced mouse model of diabetes and the po-tential mechanism.Methods MES-13 cells were divided into low glucose control group(LG),hyper osmotic pres-sure control group(HOP),high glucose group(HG),3-methyladenine+high glucose group(HG+3-MA)and chloroquine+high glucose group(HG+CQ).The groups were respectively incubated with low glucose DMEM,30 mmol/L mannitol hypertonic control medium,30 mmol/L high glucose medium,5 mmol/L 3-MA+30 mmol/L high glucose medium and 10 mmol/L CQ+30 mmol/L high glucose medium for 24 hours.CCK-8 assay and Western blot were performed.In vivo experiment:Male C57BL/6J mice were induced diabetes for model development by in-tra-peritoneal injection of STZ 60 mg/kg for five consecutive days.After two weeks of injection,the blood glucose was measured.Animals with blood glucose level higher than 16.7 mmol/L(250 mg/dL)were randomly divided in-to diabetes control group(DM),3-MA intervention group(DM+3-MA)and CQ intervention group(DM+CQ),then were fed under the same conditions as normal control group(NC)mice.The DM+3-MA group was given 10 mg/kg of 3-MA aqueous solution by gavage every day,the DM+CQ group was given 50 mg/kg of CQ by intrap-eritoneal injection every three days,the NC group and DM group were given the same amount of normal saline and killed after 6 weeks.The kidneys were stripped for kidney/body weight ratio determination,periodic acid-schiff staining(PAS),MASSON staining microscopy and Western blot.Results In vitro experiment:Compared to the LG group,the cell viability,PCNA expression,ratio of phosphorylated Akt to total Akt(p-Akt/Akt)and ratio of phosphorylated rpS6 to total rpS6(p-rpS6/rpS6)were significantly increased in the HG group(P＜0.05).Com-pared with HG group,the cell viability,PCNA and p-Akt/Akt ratio of HG+3-MA group and HG+CQ group were significantly decreased and p-rpS6/rpS6 ratio of HG+3-MA group was significantly decreased(P＜0.01).In vivo experiment:Compared to NC group,the kidney/body weight ratio,glomerular volume,renal tubular injury index,PCNA,fibronectin,COL1A1,p-Akt/Akt,p-rpS6/rpS6 in DM group were all significantly up-regulated(P＜0.05).Compared with DM group,the kidney/body weight ratio,glomerular volume,renal tubular injury in-dex,PCNA,fibronectin,COL1A1,p-Akt/Akt,p-rpS6/rpS6 of DM+3-MA group mice were all significantly de-creased(P＜0.05).Conclusions 3-MA can improve glomerular mesangial cell proliferation and renal ECM deposi-tion in early diabetes nephropathy(DN).The improvement of 3-MA in early DN may be related to the inhibition of Akt/rpS6 signaling pathway.

The skin is one of the most vital organs in the human body, and skin wounds caused by various factors can severely impact patients’ physical and mental health. Among the therapeutic strategies for skin wound repair, mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as a promising biological therapy, attracting significant attention in related research. As critical mediators of stem cell biological effects, MSC-Exos fuse with target cells and transfer bioactive proteins and nucleic acids from stem cells into recipient cells. These exosomes modulate inflammatory responses, promote cell proliferation, migration, and angiogenesis, and regulate extracellular matrix remodeling, thereby accelerating wound healing. In recent years, studies on the mechanisms by which exosomes promote skin wound repair have advanced and refined continuously. This article summarized the key signaling pathways through which MSC-Exos participate in skin wound repair, aiming to enhance the understanding of their roles in facilitating wound healing.

Objective:To observe the effects of sorafenib on the lesions and vascular growth factors in the mouse model of hepatic alveolar echinococcosis.Methods:One hundred healthy female Kunming mice weighing (20±4) g were used to establish a model of alveolar echinococcosis infection by intraperitoneal injection of alveolar echinococcosis protoscoleces. After 6 weeks of feeding, the rats were divided into 5 groups, 15 rats in each group, which were given warm saline, albendazole (100 mg/kg), and sorafenib at high-dose (100 mg/kg), middle-dose (50 mg/kg) and low-dose (30 mg/kg) by gavage for 6 weeks, respectively. Eyeball blood and hepatic alveolar echinococcosis tissue were collected from the mice after the last administration, and the body weight of the mice and the lesion weight were weighed. The concentrations and expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor receptor-2 (VEGFR-2) in serum and lesion tissues were detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting.Results:There was no statistically significant difference in the body weight of mice among the saline group, albendazole group and low-dose, medium-dose and high-dose sorafenib groups ( F=0.43, P=0.784). The ratios of lesion weight to body weight in the above groups were (0.057±0.009), (0.031±0.005), (0.033±0.005), (0.031±0.005), and (0.031±0.005), respectively. The saline group had a higher ratio than the other four groups, and the differences were statistically significant (all P<0.05). The relative expression levels of HIF-1α, VEGF-A, VEGFR-2, CD31 and CD34 detected by Western blotting in the saline group were all higher than those in the albendazole group and the high-dose, medium-dose and low-dose sorafenib groups, and the differences were statistically significant (all P<0.05). The relative expression levels of the above proteins in the medium-dose and high-dose sorafenib groups were lower than those in the albendazole group, and the relative expression levels of the above proteins in the high-dose sorafenib group were also lower than those in the medium-dose sorafenib group, and the differences were statistically significant (all P<0.05). The concentration levels of HIF-1α, VEGF-A and VEGFR-2 in serum of mice in each group detected by ELISA were consistent with those detected by Western blotting. Conclusion:Sorafenib inhibits the proliferation of alveolar echinococcosis in mice by suppressing the expression of angiogenic factors in alveolar echinococcosis lesions.

Objective To investigate the relationship between serum levels of nuclear factor E2-related fac-tor 2(Nrf2),advanced oxidation protein products(AOPP)and blood lipid,liver fibrosis in patients with non-alcoholic steatohepatitis(NASH).Methods A total of 104 patients with NASH in Bishan Hospital Affiliated to Chongqing Medical University were selected as the study group,and 90 healthy people were selected as the control group.The serum levels of Nrf2 and AOPP in each group were detected and compared.Pearson or Spearman correlation analysis was used to analyze the relationship between serum Nrf2,AOPP levels and blood lipid,liver fibrosis in patients with NASH.Receiver operating characteristic(ROC)curve was used to e-valuate the diagnostic value of serum Nrf2,AOPP levels for NASH.Results The levels of triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),Nrf2 and AOPP in the study group were higher than those in the control group(P＜0.05),and the level of high density lipoprotein cholesterol(HDL-C)was significantly lower than that in the control group(P＜0.05).The serum levels of Nrf2 and AOPP in severe group were higher than those in moderate group and mild group(P＜0.05),and the serum levels of Nrf2 and AOPP in moderate group were higher than those in mild group(P＜0.05).Correlation analysis showed that serum Nrf2 and AOPP levels in NASH patients were positively correlated with TG,TC,LDL-C and the degree of liver fibrosis(P＜0.05),and negatively correlated with HDL-C(P＜0.05).The area under the curve(AUC)of serum Nrf2 for NASH diagnosis was 0.830(95％CI 0.780-0.880).The AUC of serum AOPP in the diagnosis of NASH was 0.866(95％CI 0.816-0.916).The AUC of the combined diagnosis of NASH was 0.925(95％CI 0.875-0.975).Conclusion The serum levels of Nrf2 and AOPP are increased in NASH patients,and they are closely related to blood lipids and liver fibrosis,which are expected to be effective indicators for the diagnosis of NASH.

Objective To evaluate the therapeutic effect of poloxamer hydrogel loaded with exosomes derived from human dental pulp stem cells genetically modified with human hepatocyte growth factor against radiation skin injuries.Methods Human dental pulp stem cells derived exosomes(DPSC-Exo)and hepatocyte growth factor modified DPSC-Exo(HGF-DPSC-Exo)were extracted via ultracentrifugation separation,identified in terms of particle size and morphology,and analyzed separately by means of nanoparticle tracking analysis and scanning electron microscopy(SEM),while exosome marker proteins were determined by Western blot.Then,the effect of exosomes on radiation-damaged skin cells was assessed.The poloxamer hydrogel was prepared and its safety was evaluated with CCK-8.A mouse model of injury combined with radiation injury was established,and the therapeutic effect of hydrogel loaded with exosomes was determined based on wound size,HE and Masson staining.Furthermore,the underlining therapeutic mechanism was explored with Tunnel assay,malondialdehyde content and peroxidase activity.Results The diameter exosomes ranged from 30 to 150 nm and their morphology was a disc-shaped vesicle under SEM.Moreover,CD9,CD63 and TSG101 were expressed.The results of cellular experiments showed that exosomes significantly promoted the proliferation and migration of radiation-damaged skin keratinocytes and fibroblasts,and reduced their apoptosis.HGF modification enhanced the healing effect of exosomes.Poloxamer hydrogel showed good temperature-sensitive properties and biocompatibility.The results of animal experiments showed that exosomes significantly accelerated the healing of radiation-combined injuries in mice,inhibited inflammatory infiltration and mitigated collagen deposition in the wound.Interestingly,the healing effect in the group treated with hydrogel loaded with exosomes was the best.The underlining mechanism was possibly related to promotion of cell proliferation and inhibition of apoptosis and oxidative stress.Conclusion A novel poloxamer hydrogel loaded HGF-DPSC-Exo has been prepared and its therapeutic effect against radiation combined injury has been proved,thus providing a new strategy for the treatment of radiation skin injury in clinic.

Objective The objective of this study is to examine the expression level of the S100A7A protein in both gastric cancer tissues and cells,as well as to evaluate its impact on the malignant phenotype of gastric cancer(GC)cells.Methods Immunohistochemical assay was used to detect the expression characteristics of S100A7A in 21 gastric cancer tissues and their corresponding paracancerous tissues,as well as to investigate its correlation with gastric cancer clinicopathological factors.Gastric cancer cells were genetically modified to overex-press S100A7A through plasmid transfection.Subsequently,the impact of S100A7A on the proliferation,migra-tion,and invasion capacities of gastric cancer cells was assessed using cell proliferation assays(EdU assay and plate cloning assay)as well as cell migration and invasion assays(Transwell assay and scratch assay).Results The expression of S100A7A protein was higher in GC tissues than in paracancerous tissues;Overexpression of S100A7A may increase gastric cancer cell proliferation,migration,and invasion.Conclusion S100A7A is a possible oncogene in GC and is predicted to serve as a new diagnostic and therapeutic target for the disease.