Preliminary report on embolization with quick-soluble gelatin sponge particles for angiographically negative acute gastrointestinal bleeding.

Prophylactic embolization is usually performed using gelatin sponge particles, which are absorbed within several weeks, for managing angiographically negative gastrointestinal bleeding. This study aimed to evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) with quick-soluble gelatin sponge particles (QS-GSP) that dissolve in less than 4 h for treating angiographically negative gastrointestinal bleeding. We included ten patients (M:F = 7:3; mean age, 64.3 years) who underwent prophylactic TAE with QS-GSP for angiographically negative acute gastrointestinal bleeding between 2021 and 2023. The technical success rate of TAE, clinical outcomes focusing on rebleeding, and procedure-related complications were evaluated. The embolized arteries were the gastroduodenal (n = 3), jejunal (n = 4), and ileal (n = 3) arteries. QS-GSP (150-350 µm or 350-560 µm) were used alone (n = 8) or in combination with a coil (n = 1). A 100% technical success rate was accomplished. In 1 patient (10%), rebleeding occurred 2 days after prophylactic TAE of the gastroduodenal artery, and this was managed by repeat TAE. There were no procedure-related complications. The use of QS-GSP for prophylactic TAE appears to be safe and effective for controlling bleeding among patients with angiographically negative gastrointestinal bleeding. There were no cases of related ischemic complications of the embolized bowels likely attributable to recanalization of the affected arteries following biodegradation of QS-GSP.

Uterine artery embolization combined with percutaneous microwave ablation for the treatment of prolapsed uterine submucosal leiomyoma: A case report.

BACKGROUND: Vaginal myomectomy is the most common form of radical treatment for prolapsed submucosal leiomyoma and is typically performed under general anesthesia. However, an alternative treatment approach is needed for patients who cannot tolerate general anesthesia. We describe a case with such a patient who was successfully treated via a minimally invasive method under local anesthesia. CASE SUMMARY: A 46-year-old female suffered from abnormal uterine bleeding, severe anemia, and a reduced quality of life attributed to a massive prolapsed submucosal leiomyoma. She could not tolerate general anesthesia due to a congenital thoracic malformation and cardiopulmonary insufficiency. A new individualized combined treatment, consisting uterine artery embolization (UAE), percutaneous microwave ablation (PMWA) of the pedicle and the endometrium, and transvaginal removal of the leiomyoma by twisting, was performed. The lesion was completely removed successfully under local anesthesia without any major complications. The postoperative follow-up showed complete symptom relief and a significant improvement in the quality of life. CONCLUSION: UAE combined with PMWA can be performed under local anesthesia and is a promising alternative treatment for patients who cannot tolerate general anesthesia.

Full Control of Solid-State Electrolytes for Electrostatic Gating.

Ionic gating is a powerful technique to realize field-effect transistors (FETs) enabling experiments not possible otherwise. So far, ionic gating has relied on the use of top electrolyte gates, which pose experimental constraints and make device fabrication complex. Promising results obtained recently in FETs based on solid-state electrolytes remain plagued by spurious phenomena of unknown origin, preventing proper transistor operation, and causing limited control and reproducibility. Here, a class of solid-state electrolytes for gating (Lithium-ion conducting glass-ceramics, LICGCs) is explored, the processes responsible for the spurious phenomena and irreproducible behavior are identified, and properly functioning transistors exhibiting high density ambipolar operation with gate capacitance of ≈ 20   -   50 µ F c m - 2 \[20{\bm{ - }}50\;\mu F c{m^{{\bm{ - }}2}}\] (depending on the polarity of the accumulated charges) are demonstrated. Using 2D semiconducting transition-metal dichalcogenides, the ability to implement ionic-gate spectroscopy to determine the semiconducting bandgap, and to accumulate electron densities above 1014 cm-2 are demostrated, resulting in gate-induced superconductivity in MoS2 multilayers. As LICGCs are implemented in a back-gate configuration, they leave the surface of the material exposed, enabling the use of surface-sensitive techniques (such as scanning tunneling microscopy and photoemission spectroscopy) impossible so far in ionic-gated devices. They also allow double ionic gated devices providing independent control of charge density and electric field.

Establishment of a malignancy and benignancy prediction model of sub-centimeter pulmonary ground-glass nodules based on the inflammation-cancer transformation theory.

Background: In recent years, Chinese clinicians are frequently encountered by patients with multiple lung nodules and these intensity ground-glass nodules (GGNs) are usually small in size and some of them have no spicule sign. In addition, early lung cancer is diagnosed in large numbers of non-heavy smokers and individuals with no caner history. Obviously, the Mayo model is not applicable to these patients. The aim of the present study is to develop a new and more applicable model that can predict malignancy or benignancy of pulmonary GGNs based on the inflammation-cancer transformation theory. Materials and methods: Included in this study were patients who underwent surgical resection or lung puncture biopsy of GGNs in Shanghai 10th People's Hospital between January 1, 2018 and May 31, 2021 with the inclusion criterion of the maximum diameter of GGN < 1.0 cm. All the included patients had their pulmonary GGNs diagnosed by postoperative pathology. The patient data were analyzed to establish a prediction model and the predictive value of the model was verified. Results: Altogether 100 GGN patients who met the inclusion criteria were included for analysis. Based on the results of logistic stepwise regression analysis, a mathematical predication equation was established to calculate the malignancy probability as follows: Malignancy probability rate (p) = ex/(1 + ex); p > 0.5 was considered as malignant and p ≤ 0.5 as benign, where x = 0.9650 + [0.1791 × T helper (Th) cell] + [0.2921 × mixed GGN (mGGN)] + (0.4909 × vascular convergence sign) + (0.1058 × chronic inflammation). According to this prediction model, the positive prediction rate was 73.3% and the negative prediction rate was 100% versus the positive prediction rate of 0% for the Mayo model. Conclusion: By focusing on four major factors (chronic inflammation history, human Th cell, imaging vascular convergence sign and mGGNs), the present prediction model greatly improves the accuracy of malignancy or benignancy prediction of sub-centimeter pulmonary GGNs. This is a breakthrough innovation in this field.

GAS41 mediates proliferation and GEM chemoresistance via H2A.Z.2 and Notch1 in pancreatic cancer.

PURPOSE: GAS41 is a YEATS domain protein that binds to acetylated histone H3 to promote the chromatin deposition of H2A.Z in non-small cell lung cancer. The role of GAS41 in pancreatic cancer is still unknown. Here, we aimed to reveal this role. METHODS: GAS41 expression in pancreatic cancer tissues and cell lines was examined using qRT-PCR, Western blotting and immunohistochemistry. MTT, colony formation, spheroid formation and in vivo tumorigenesis assays were performed to assess the proliferation, tumorigenesis, stemness and gemcitabine (GEM) resistance of pancreatic cancer cells. Mechanistically, co-immunoprecipitation (co-IP) and chromatin immunoprecipitation (ChIP) assays were used to evaluate the roles of GAS41, H2A.Z.2 and Notch1 in pancreatic cancer. RESULTS: We found that GAS41 is overexpressed in human pancreatic cancer tissues and cell lines, and that its expression increases following the acquisition of GEM resistance. We also found that GAS41 up-regulates Notch, as well as pancreatic cancer cell stemness and GEM resistance in vitro and in vivo. We show that GAS41 binds to H2A.Z.2 and activates Notch and its downstream mediators, thereby regulating stemness and drug resistance. Depletion of GAS41 or H2A.Z.2 was found to down-regulate Notch and to sensitize pancreatic cancer cells to GEM. CONCLUSION: Our data indicate that GAS41 mediates proliferation and GEM resistance in pancreatic cancer cells via H2A.Z.2 and Notch1.

Transcatheter Arterial Infusion Combined With Radioactive Particles in the Treatment of Advanced Body/Tail Pancreatic Cancer: A Retrospective Cohort Study.

OBJECTIVES: This retrospective cohort study investigated the efficacy of routine intravenous chemotherapy (the control group), transcatheter arterial infusion (TAI) chemotherapy, and TAI combined with radioactive particles as therapeutic methods for advanced body/tail pancreatic cancer by assessing the short-term and overall survival rates. METHODS: We screened our prospective database for patients with advanced body/tail pancreatic cancer, which tumor deemed unresectable, and no other confirmed malignant tumors, patients were assigned into 3 groups according to their treatment: routine intravenous chemotherapy, TAI, and TAI combined with radioactive particles. RESULTS: The median survival time was 6 months in the control group, 10 months in the TAI group, and 13 months in the TAI combined group. The Kaplan-Meier estimates of the overall survival among the 3 groups, indicating that there is significant difference among 3 groups (P < 0.000). The clinical remission rates were 17.5% in the control group, 41.5% in the TAI group, and 48.0% in the TAI combined group. Covariates analyzed showed that different treatment methods and times affected the results significantly (P < 0.002). CONCLUSIONS: In the treatment of advanced body/tail pancreatic cancer, TAI and TAI combined with radioactive particles significantly improved the clinical outcomes in patients compared with routine intravenous chemotherapy.

Comparison of transradial and transfemoral access for transcatheter arterial embolization of iatrogenic renal hemorrhage.

BACKGROUND: There are few reports of renal artery embolization (RAE) via transradial access (TRA) for renal hemorrhage, and none have compared outcomes of RAE via TRA and transfemoral access (TFA). The objective was to compare technical and clinical outcomes in patients undergoing RAE via TRA or TFA for iatrogenic renal hemorrhage. MATERIALS AND METHODS: This study included 45 RAE procedures (16 TRA and 29 TFA) for iatrogenic renal hemorrhage in 43 patients performed at a tertiary referral center between October 2018 and December 2020. Information regarding underlying diseases, coagulation status, angiographic and embolization procedure details, technical and clinical successes, and complications were retrospectively evaluated. RESULTS: There were no differences in demographics, underlying diseases, updated Charlson comorbidity scores, angiographic findings, and volume of contrast material between the TRA and TFA groups. By contrast, prothrombin time and international normalized ratio were significantly lower in the TRA than in the TFA group. Embolic materials differed significantly in the two groups. Procedure duration, fluoroscopy time, digital subtraction angiography number, and dose area product were slightly lower in the TRA than in the TFA group, but the differences were not statistically significant. Technical and clinical success rates in the TRA and TFA groups were 100% and 96.6%, and 100% and 96.6%, respectively. No patient in either group experienced procedure-related complications during a 4 week follow-up period. CONCLUSION: RAE via TRA in the management of iatrogenic renal hemorrhage was safe and feasible, with similar procedure duration and radiation exposure to RAE via TFA. TRA may be an acceptable alternative to TFA in these patients.

Temporary Covered Metallic Ureteral Stent Placement for Ureteral Strictures following Kidney Transplantation: Experience in 8 Patients.

This brief report presents 8 patients with silicone-covered metallic stent placement for ureteral strictures refractory to double-J stent placement, following kidney transplantation. Stent removal was successfully performed in 7 patients via antegrade (n = 4) or retrograde (n = 3) access 6 weeks to 6 months after stenting for elective removal (6-month interval, n = 3), urothelial hyperplasia (n = 2), or stent migration (n = 2), and their mean primary ureteral patency after stent removal was 15.4 months (range, 2-27 months). Hematuria (n = 2) and pain (n = 3) occurred, but resolved within 1 week. One stent was removed during reconstructive surgery. During follow-up of mean 22.6 months after stent removal, ureteral strictures recurred in 2 patients.

Role and effect of vein-transplanted human umbilical cord mesenchymal stem cells in the repair of diabetic foot ulcers in rats.

Diabetic foot ulcer (DFU) is one of diabetic complications, which is frequently present and tormented in diabetes mellitus. Most multipotent mesenchymal stromal cells (MSCs) are capable of immune evasion, providing an allogeneic, ready-to-use, cell product option for therapeutic applications. The beneficial effect of MSCs for the treatment of a variety of traumatic injuries, such as open wounds, has been extensively explored. In this study, a rat DFU model was used to simulate the pathophysiology of clinical patients and to investigate the localization of human umbilical cord mesenchymal stem cells (hUC-MSCs) after intravenous transplantation and its role in DFU healing, so as to evaluate the potential of hUC-MSCs in the treatment of DFU. The diabetic rat model was established by streptozotocin injection, which was used to create full-thickness foot dorsal skin wounds to mimic DFU by a 6-mm skin biopsy punch and a Westcott scissor. The hUC-MSCs were transplanted through femoral vein, and the ulcer cicatrization situation and the fate of hUC-MSCs were evaluated. Our data suggest that intravenously transplantated hUC-MSCs have the ability to migrate and locate to the wound tissue and are helpful to wound healing in DFU rats, partly by regulating inflammation, trans-differentiation and providing growth factors that promote angiogenesis, cell proliferation and collagen deposition. Herein, we demonstrate that hUC-MSC transplantation is able to accelerate DFU healing in rats and transplantation of exogenous stem cells may be a potential strategy for clinical application in DFUs.

Exosomes derived from mmu_circ_0000250-modified adipose-derived mesenchymal stem cells promote wound healing in diabetic mice by inducing miR-128-3p/SIRT1-mediated autophagy.

More and more evidence advises that circular RNAs (circRNAs) function critically in regulating different disease microenvironments. Our previous study found that autotransplantation of adipose-derived mesenchymal stem cells (ADSCs) promotes diabetes wound healing. Exosomes derived in ADSCs play an important regulatory role. This study aimed to characterize if mmu_circ_0000250 played a role in ADSC-exosome-mediated full-thickness skin wound repair in diabetic rats. Endothelial progenitor cells (EPCs) were selected to study the therapeutic mechanism of exosomes in high-glucose (HG)-induced cell damage and dysfunction. Analysis and luciferase reporter assay were utilized to explore the interaction among mmu_circ_0000250, miRNA (miR)-128-3p, and sirtuin (SIRT)1. The diabetic rats were used to confirm the therapeutic effect of mmu_circ_0000250 against exosome-mediated wound healing. Exosomes containing a high concentration of mmu_circ_0000250 had a greater therapeutic effect on restoration of the function of EPCs by promotion autophagy activation under HG conditions. Expression of mmu_circ_0000250 promoted SIRT1 expression by miR-128-3p adsorption, which was confirmed via luciferase reporter assay and bioinformatics analysis. In vivo, exosomes containing a high concentration of mmu_circ_0000250 had a more therapeutic effect on wound healing when compared with wild-type exosomes from ADSCs. Immunohistochemistry and immunofluorescence detection showed that mmu_circ_0000250 increased angiopoiesis with exosome treatment in wound skin and suppressed apoptosis by autophagy activation. In conclusion, we verified that mmu_circ_0000250 enhanced the therapeutic effect of ADSC-exosomes to promote wound healing in diabetes by absorption of miR-128-3p and upregulation of SIRT1. Therefore, these findings advocate targeting the mmu_circ_0000250/miR-128-3p/SIRT1 axis as a candidate therapeutic option for diabetic ulcers.

Downregulated Circular RNA hsa_circ_0000291 Suppresses Migration And Proliferation Of Gastric Cancer Via Targeting The miR-183/ITGB1 Axis.

BACKGROUND: Circular RNAs are implicated in a variety of cancers. This investigation found that hsa_circ_0000291 expression was upregulated in gastric cancer (GC) cell lines, yet its role in GC has not yet been reported. OBJECTIVE: To explore the effects of hsa_circ_0000291 on GC cell proliferation and invasion. MATERIALS AND METHODS: In the current research, we used the gastric cancer cell lines MGC803 and MKN-28 to study hsa_circ_0000291 function. The relationship between hsa_circ_0000291, miR-183 and ITGB1 was analyzed by firefly luciferase analysis and Western blots, and qRT-PCR approaches were used for protein and gene expression analysis, respectively. Tumor growth and metastasis were determined in nude mice xenografts using MKN-28 cells, with or without hsa_circ_000r0291 downregulation. RESULTS: Our data showed that hsa_circ_0000291 was upregulated in GC cell lines, whereas hsa_circ_0000291 silencing suppressed cell metastasis and proliferation in in vivo and in vitro studies. Our results showed that the downregulation of hsa_circ_0000291 suppressed integrin beta 1 (ITGB1) expression via miR-183 "sponging," which was validated by rescue experiments using the luciferase reporter assay. Our observations suggested that hsa_circ_0000291 silencing suppressed the aggressive, metastatic GC phenotype. CONCLUSION: Taken together, hsa_circ_0000291 knockdown inhibited GC cell metastasis and growth by regulating the miR-183/ITGB1 axis. Importantly, this approach could provide a therapy target and potential biomarker for the diagnosis and treatment of GC.

Liver abscess following transarterial chemoembolization for the treatment of hepatocellular carcinoma: A retrospective analysis of 23 cases.

OBJECTIVE: To investigate the incidence, management, and outcome of a liver abscess after transarterial embolization/chemoembolization (TAE/TACE) therapy for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From May 2007 to May 2014, all patients complicated with liver abscess following TAE/TACE for HCC were identified and analyzed at four medical centers. RESULTS: During the study period, a total of 6984 TAE/TACE procedures were performed among 3129 patients, and a total of 23 patients developed liver abscess with the incidence of 0.33% (23/6984) per procedure. There were 21 males and 2 females, and mean age of 52.1 ± 12.1 years. The mean interval from last TAE/TACE procedure to the diagnosis of liver abscess was 12.9 ± 6.6 days. All the patients received intravenous antibiotics, with ten patients had a percutaneous drain, one each for percutaneous aspiration and surgery. Complications related to the liver abscess were hepatorrhexis and pleural effusion (n = 1), pleural effusion (n = 1), and obstructive jaundice (n = 1), all of which were resolved after conservative treatments. The serum alpha-fetoprotein (AFP) levels were significantly reduced at 6 months after treatment (P < 0.01) in 15 patients whose AFP > 400 ng/mL preprocedure. Complete or partial tumor response at 6 months after TAE/TACE was achieved in three and twenty patients, respectively; and 6 months survival was 100%. CONCLUSIONS: The incidence of a liver abscess after TAE/TACE is low; antibiotics therapy along was successful in about half patients, and percutaneous abscess aspiration/drainage were necessary in large size abscess and severely symptomatic patients; the outcomes are benign without worsening of the progression of underlying HCC.

Nanosphere-mediated co-delivery of VEGF-A and PDGF-B genes for accelerating diabetic foot ulcers healing in rats.

Diabetic ischemic ulcer is an intractable diabetic complication. Angiogenesis is a critical factor for wound healing in patients with diabetic foot wounds. Sustained gene delivery could be notably necessary in modulating gene expression in chronic ulcer healing and might be a promising approach for diabetic foot ulcers. In the present study, Sprague-Dawley rats were used to establish diabetic foot ulcer models by streptozotocin and skin biopsy punch. The plasmids expressing VEGF-A and PDGF-B were prepared and then incorporated with polylactic-co-glycolic acid (PLGA) nanospheres to upregulate genes expression. The aim of this study was to explore whether the engineered VEGF-A and PDGF-B based plasmid-loaded nanospheres could be upregulated in streptozotocin-induced diabetic rats and improve the wound healing. The cultured fibroblasts could be effectively transfected by means of nanosphere/plasmid in vitro. In vivo, the expression of VEGF-A and PDGF-B was significantly upregulated at full-thickness foot dorsal skin wounds and the area of ulceration was progressively and significantly reduced following treatment with nanosphere/plasmid. These results indicated that combined gene transfer of VEGF-A and PDGF-B could improve reparative processes in the wounded skin of diabetic rats and nanosphere may be a potential non-viral vector for gene therapy of the diabetic foot ulcer.

Human primary CD34+ cells transplantation for critical limb ischemia.

BACKGROUND: The goal of this study was to characterize the properties of human CD34+ cells in culture and investigate the feasibility and efficacy of CD34+ transplantation in a mouse model of limb ischemia and in patients with no-option critical limb ischemia. METHODS: Human CD34+ cells isolated from peripheral blood and grown in culture for up to four passages stained positively for the surface markers CD34 and CD133 and showed high viability after cryopreservation and recovery. Seven days after surgery to induce limb ischemia, ischemic muscles of nude mice were injected with CD34+ cells. Two weeks later, mice were scored for extent of ischemic injury, and muscle tissue was collected for immunohistochemical analysis of vascular endothelial cells and RT-PCR analysis of cytokine expression. RESULTS: Injury scores of CD34+ -treated, but not control, mice were significantly different before and after transplantation. Vascular density and expression of VEGF and bFGF mRNAs were also significantly increased in the treated mice. Patients with severe lower extremity arterial ischemia were injected with their own CD34+ cells in the affected calf, foot, or toe. Significant improvements were observed in peak pain-free walking time, ankle-brachial index, and transcutaneous partial oxygen pressure. These findings demonstrate that growth of human CD34+ cells in vitro and cryopreservations are feasible. CONCLUSION: Such cells may provide a renewable source of stem cells for transplantation, which appears to be a feasible, safe, and effective treatment for patients with critical limb ischemia.

The NFκB signaling pathway serves an important regulatory role in Klebsiella pneumoniae liver abscesses.

The incidence of Klebsiella pneumoniae liver abscess (KPLA) has increased in a number of Asian countries over the past 30 years. Diabetes mellitus (DM) is a risk factor for KPLA. The prevalence and clinical features of KPLA in patients with and without DM have been well described; however, the underlying molecular mechanism responsible for the increased incidence of KPLA in patients with DM remains unclear. In the present study, a mouse model of DM was constructed and mice were infected with K. pneumoniae. Tissues were harvested for immunohistochemical and inflammatory factor expression analyses. The results revealed that the number of liver abscesses in mice with DM was greater than that observed in normal mice. The expression of interleukin (IL)-1ß, IL-2, IL-6, macrophage inflammatory protein-1α and tumor necrosis factor-α in the liver tissues of mice with DM was significantly higher compared with normal mice. Western blotting results revealed that the expression of phosphorylated (p)-inhibitor of nuclear factor κB (NFκB) kinase subunit ß, p-NFκB and p-inhibitor of NFκB was significantly increased in the liver tissue of mice with DM compared with that of normal mice. These results suggest that activation of the NFκB signaling pathways has a regulatory effect on the pathogenesis of K. pneumoniae bacteria liver abscesses and that high glucose conditions may promote the activation of NFκB signaling.

Human circular RNA­0054633 regulates high glucose­induced vascular endothelial cell dysfunction through the microRNA­218/roundabout 1 and microRNA­218/heme oxygenase­1 axes.

The aim of the present study was to investigate the relative regulation of human circular RNA­0054633 (hsa_circ_0054633), microRNA­218 (miR­218), roundabout 1 (ROBO1) and heme oxygenase­1 (HO­1) in human umbilical vein endothelial cells (HUVECs) in high glucose conditions. Initially, the expression of hsa_circ_0054633 in HUVECs was detected in high glucose conditions by reverse transcription­quantitative polymerase chain reaction. Next, a small interfering RNA against hsa_circ_0054633 was constructed to investigate the function of jsa_circ_0054633 in HUVECs by transwell migration, cell counting kit­8, flow cytometry and tube formation assays. In addition, the effect of hsa_circ_0054633 on the expression levels of ROBO1, HO­1 and vascular endothelial growth factor were examined. The regulation effects of hsa_circ_0054633 on high glucose­induced HUVEC proliferation, migration, and angiopoiesis were also analyzed. Bioinformatics analysis and dual­luciferase assay were then used to confirm the direct or specific regulation of hsa_circ_0054633, miR­218, ROBO1 and HO­1. It was observed that high glucose levels increased the expression of hsa_circ_0054633, while downregulation of hsa_circRNA­0054633 increased the high glucose­induced endothelial cell dysfunction, including proliferation, migration and angiopoiesis suppression. Bioinformatics analysis revealed that the expression of circRNA­0054633 was able to inhibit miR­218 expression, which was clarified by the dual­luciferase assay. It was also demonstrated that downregulating the expression of miR­218 inhibited the high glucose­induced endothelial cell dysfunction by promoting the expression of ROBO1 and HO­1. These results suggest that the expression of hsa_circRNA­0054633 has a protective effect against high glucose­induced endothelial cell dysfunction by targeting ROBO1 and HO­1.

MiR-31 regulates the function of diabetic endothelial progenitor cells by targeting Satb2.

Endothelial malfunctions in patients with diabetes are known to result in vascular diseases, and endothelial progenitor cells (EPCs) are indispensable for the functional preservation of the vascular endothelium. MicroRNA-31 (miR-31) has been found to be able to modulate the differentiation of stem cells. However, it is still unclear how miR-31 functions in diabetic EPCs. The aim of this study was to investigate how miR-31 regulates diabetic EPC function. In the current study, miR-31 expression was compared between normal and diabetic EPCs. Satb2 was recognized as a functionally related target of miR-31 in EPCs according to computational prediction. We also explored the role of miR-31 in terms of its anti-apoptotic effects. A remarkable elevation in miR-31 expression was found in diabetic EPCs, and this elevated expression resulted in suppressed cell proliferation under high glucose. It was also found that miR-31 targets Satb2, leading to the anti-apoptotic effect and maintenance of the functions of EPCs. Furthermore, knockdown of Satb2 exhibited an inhibitory effect on proliferation and migration of EPCs in both healthy and diabetic subjects, which showed the same trend as miR-31 overexpression. Conversely, overexpression of Satb2 showed the opposite effect. Moreover, overexpression of Satb2 attenuated the miR-31-induced migration and colony-forming ability reduction and apoptosis induction of EPCs in both healthy and diabetic subjects. In diabetic EPCs, elevated glucose level was found to up-regulate miR-31 expression, which in turn enhanced the malfunction and death of EPCs. In conclusion, our results indicate that up-regulation of miR-31 may underlie endothelial dysfunction in diabetes by targeting Satb2.

Ischemic Postconditioning Protects Against Intestinal Ischemia/Reperfusion Injury via the HIF-1α/miR-21 Axis.

Intestinal ischemia/reperfusion (I/R) can lead to tissue damage associated with inflammation and mucosal apoptosis. Ischemic postconditioning (IPostC), a series of repeated, brief, intermittent periods of ischemia and reperfusion, has beneficial effects against I/R-induced injury in the heart and intestine, although the underlying mechanisms for these effects remain unclear. We evaluated the involvement of microRNA-21 (miR-21) in the protective effects of IPostC in a rat model of I/R induced by superior mesenteric artery occlusion and reopening. IPostC decreased I/R injury and suppressed apoptosis in the intestinal tissues concomitant with the induction of hypoxia inducible factor 1 alpha (HIF-1α) and the upregulation of miR-21. In vitro experiments in the intestinal epithelial cell line IEC-6 showed that hypoxia induced miR-21 and this effect was abolished by silencing HIF1-α, confirming the induction of miR-21 by HIF1-α, HIF1-α or miR-21 inhibition exacerbated I/R induced apoptosis, and programmed cell death 4 (PDCD4) and Fas-L was involved in miR-21 mediated anti-apoptotic effects on intestinal epithelial cells. Knockdown of miR-21 or inhibition of HIF1-α abolished the IPostC-mediated attenuation of intestinal injury and apoptosis and the downregulation of PDCD4 and Fas-L. A potential mechanism underlying the protective effect of IPostC may therefore involve the induction of miR-21 by HIF1-α and the attenuation of apoptosis via the downregulation of PDCD4 and Fas-L.

Long noncoding RNA MALAT1 regulates renal tubular epithelial pyroptosis by modulated miR-23c targeting of ELAVL1 in diabetic nephropathy.

Diabetic nephropathy is a common kidney condition in patients with diabetes mellitus, which can result in renal failure. Pyroptosis, the process of pro-inflammatory programmed cell death, plays an important role in the pathogenesis of this disease. Long non-coding RNA MALAT1 has also been shown to be involved in diabetic nephropathy. Here, we investigated the role of MALAT1 and the microRNA miR-23c and its target gene ELAVL1 in renal tubular epithelial cells. Our data demonstrated that MALAT1 expression was substantially increased but miR-23c was decreased in streptozotocin-induced diabetic rats and in high-glucose-treated HK-2 cells. Downregulation of MALAT1 or upregulation the expression of miR-23c inhibited pyroptosis in HK-2 cells. In an effort to understand the signaling mechanisms underlying the pro-pyroptotic properties of MALAT1 and the anti-pyroptotic properties of miR-23c, we found that inhibiting the expression of MALAT1 downregulated the expression of ELAVL1, NLRP3, Caspase-1 and the pro-inflammatory cytokine IL-1ß. These findings were replicated by upregulation of miR-23c. Moreover, luciferase assays showed that miR-23c, as a target of MALAT1, directly repressed ELAVL1 expression and then decreased the expression of its downstream protein NLRP3. The expression of MALAT1 antagonized the effect of miR-23c on the downregulation of its target ELAVL1 and inhibited hyperglycemia-induced cell pyroptosis. This mechanism may contribute to a better understanding of diabetic nephropathy pathogenesis and facilitate the development of new therapeutic strategies for the treatment of this disease.

MicroRNA-182 promotes pancreatic cancer cell proliferation and migration by targeting ß-TrCP2.

Pancreatic cancer is an aggressive malignancy. The median survival rate remains low, indicating that the identification of novel biomarkers and therapeutic targets is critical. Here, we examined the role of microRNA-182 (miR-182) in pancreatic cancer development. Analysis of human pancreatic cancer specimens and cell lines showed that miR-182 is overexpressed in pancreatic cancer and promotes tumor proliferation and invasion. ß-TrCP2 was confirmed as a direct target of miR-182. Silencing of ß-TrCP2 increased the levels of ß-catenin, which is similar to miR-182 overexpression. Ectopic expression of ß-TrCP2 inhibited the miR-182-induced activation of ß-catenin signaling. The oncogenic effect of miR-182 and its reversal by ß-TrCP2 were confirmed in vivo This study suggests that ß-TrCP and miR-182 may be possible biomarkers and targets for early detection and treatment of pancreatic cancer.