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.

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 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.

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 investigate the postoperative complications of ex vivo liver resection combined with autologous liver transplantation in the treatment of end-stage hepatic alveolar echinococcosis at high altitude and related prevention and treatment strategies. Methods Surgical data and follow-up data were collected from 11 patients with end-stage hepatic alveolar echinococcosis who underwent autologous liver transplantation in Qinghai People's Hospital from January 2013 to March 2019, and intraoperative and postoperative conditions were analyzed. Results All 11 patients underwent autologous liver transplantation successfully, without intraoperative death, among whom 2(18.18%) underwent hemi-extracorporeal hepatectomy and 9 (81.82%) underwent total extracorporeal hepatectomy. For the reconstruction of the retrohepatic inferior vena cava, 2 patients (18.18%) underwent reconstruction with the autologous great saphenous vein, 4 patients (36.36%) underwent reconstruction with artificial vessels, and the autologous retrohepatic inferior vena cava was preserved in 5 patients (45.45%). For biliary reconstruction, 8 patients (72.73%) underwent choledochoenterostomy and 3 (27.27%) underwent choledochocholedochostomy. The main postoperative complications of the 11 patients included bleeding in 2 patients (18.18%), bile leakage and abdominal infection in 4 patients (36.36%), bilioenteric anastomotic stenosis in 1 patient (9.09%), thrombus in 2 patients (18.18%), pulmonary infection and pleural effusion in 2 patients (18.18%), and echinococcosis recurrence in 1 patient (9.09%). Of all 11 patients, 2 (18.18%) died during the perioperative period, and the other 9 patients (81.82%) were improved and discharged. Conclusion Bleeding, biliary complications, and infection are the main causes of death in patients undergoing autologous liver transplantation at high altitude. An accurate understanding of surgical indication, careful multidisciplinary evaluation before surgery, superb operation during surgery, standardized surgical procedures, and fine perioperative management are the key to reducing perioperative mortality, avoiding and reducing postoperative complications, and achieving good long-term survival in patients undergoing autologous liver transplantation.

Hepatic alveolar echinococcosis is a zoonotic parasitic disease. The therapeutic options of advanced hepatic alveolar echinococcosis mainly include: operation combined with drug treatment, percutaneous transhepatic biliary drainage, focus puncture drainage, drug treatment, liver transplantation. The individualized and comprehensive treatment mainly based on surgery is an ideal treatment method for advanced hepatic alveolar echinococcosis. This paper summarized the related literature at home and abroad, combined with clinical practice, and summarized the current situation and progress of the treatment of advanced hepatic alveolar echinococcosis.