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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.
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Diabetes Mellitus Experimental/terapia , MicroARNs/genética , ARN Circular/genética , Sirtuina 1/genética , Úlcera/terapia , Animales , Autofagia/genética , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Modelos Animales de Enfermedad , Exosomas/genética , Humanos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos NOD , Úlcera/complicaciones , Úlcera/genética , Úlcera/patología , Cicatrización de Heridas/genéticaRESUMEN
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.
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Cateterismo/instrumentación , Remoción de Dispositivos , Trasplante de Riñón/efectos adversos , Stents Metálicos Autoexpandibles , Siliconas , Obstrucción Ureteral/terapia , Adulto , Anciano , Cateterismo/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nefrostomía Percutánea , Diseño de Prótesis , Recurrencia , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Obstrucción Ureteral/diagnóstico por imagen , Obstrucción Ureteral/etiologíaRESUMEN
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.
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Diabetes Mellitus Experimental , Pie Diabético , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Venas Umbilicales/metabolismo , Animales , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/terapia , Pie Diabético/metabolismo , Pie Diabético/patología , Pie Diabético/terapia , Femenino , Xenoinjertos , Humanos , Células Madre Mesenquimatosas/patología , Ratas , Ratas Sprague-Dawley , Venas Umbilicales/patologíaRESUMEN
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.
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Pie Diabético/terapia , Úlcera del Pie/terapia , Proteínas Proto-Oncogénicas c-sis/genética , Factor A de Crecimiento Endotelial Vascular/genética , Animales , Diabetes Mellitus Experimental , Pie Diabético/genética , Pie Diabético/fisiopatología , Modelos Animales de Enfermedad , Úlcera del Pie/genética , Úlcera del Pie/fisiopatología , Expresión Génica , Técnicas de Transferencia de Gen , Terapia Genética , Humanos , Nanosferas/uso terapéutico , Plásmidos/genética , Proteínas Proto-Oncogénicas c-sis/administración & dosificación , Ratas , Factor A de Crecimiento Endotelial Vascular/administración & dosificación , Cicatrización de HeridasRESUMEN
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.
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Nefropatías Diabéticas/metabolismo , Proteína 1 Similar a ELAV/genética , MicroARNs/genética , Piroptosis , ARN Largo no Codificante/genética , Animales , Caspasa 1/genética , Caspasa 1/metabolismo , Línea Celular , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Proteína 1 Similar a ELAV/metabolismo , Células Epiteliales/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Túbulos Renales/citología , Túbulos Renales/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
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.
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Antígenos CD34/química , Trasplante de Médula Ósea , Isquemia/terapia , Adulto , Anciano , Animales , Células de la Médula Ósea/química , Células de la Médula Ósea/citología , Células Cultivadas , Femenino , Miembro Posterior/lesiones , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Adulto JovenRESUMEN
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.
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Diabetes Mellitus Tipo 2/metabolismo , Células Progenitoras Endoteliales/metabolismo , Regulación de la Expresión Génica , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , MicroARNs/metabolismo , Factores de Transcripción/metabolismo , Anciano , Apoptosis , Movimiento Celular , Proliferación Celular , Células Progenitoras Endoteliales/citología , Femenino , Perfilación de la Expresión Génica , Glucosa/química , Humanos , Masculino , Persona de Mediana Edad , TransfecciónRESUMEN
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.
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Movimiento Celular/fisiología , Proliferación Celular/fisiología , MicroARNs/fisiología , Neoplasias Pancreáticas/patología , Ubiquitina-Proteína Ligasas/fisiología , Proteínas con Repetición de beta-Transducina/fisiología , Animales , Línea Celular Tumoral , Xenoinjertos , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , beta Catenina/metabolismoRESUMEN
BACKGROUND/AIMS: Atherosclerosis is associated with dysfunction of endothelial progenitor cells (EPCs). Tripterine, a chemical compound derived from the Chinese medicinal plant Tripterygium wilfordii Hook, displays anti-inflammatory properties in several animal models. We hypothesized that tripterine can improve EPC function and thus the efficiency of EPC transplantation. METHODS AND RESULTS: Tripterine preconditioning (2.5 µM, 4 h) improved EPC proliferation, tube formation, migration, and adhesion, and reduced apoptosis in cells cultured in ox-LDL (200 µg/ml). Tripterine restored integrin-linked kinase (ILK) levels downregulated by ox-LDL in EPCs, suggesting the involvement of the ILK/Akt pathway. Small interfering RNA-mediated depletion of ILK and dominant-negative ILK transduction inhibited the phosphorylation of the ILK downstream signaling targets protein kinase B/Akt and glycogen synthase kinase 3-beta (GSK-3ß), and reduced ß-catenin and cyclin D1 expression. In atherosclerotic mice injected with green fluorescent protein-labeled EPCs to evaluate EPC function, tripterine decreased aortic lesions and plaque deposition, and injection of tripterine-treated EPCs restored ILK levels. CONCLUSION: The present results suggest that tripterine improves vascular function in atherosclerosis by enhancing EPC function through a mechanism involving the ILK signaling pathway.
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Antiinflamatorios/farmacología , Aterosclerosis/terapia , Células Progenitoras Endoteliales/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Triterpenos/farmacología , Animales , Aterosclerosis/metabolismo , Adhesión Celular/efectos de los fármacos , Movimiento Celular , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Células Progenitoras Endoteliales/citología , Células Progenitoras Endoteliales/metabolismo , Células Progenitoras Endoteliales/trasplante , Regulación de la Expresión Génica/efectos de los fármacos , Lipoproteínas LDL/efectos adversos , Ratones , Triterpenos Pentacíclicos , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
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.
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Embolización Terapéutica , Gelatina , Femenino , Humanos , Persona de Mediana Edad , Gelatina/uso terapéutico , Resultado del Tratamiento , Hemorragia Gastrointestinal/terapia , Arterias , Estudios RetrospectivosRESUMEN
This study intended to investigate the expression of the ZEB1 and E-cadherin proteins in lung squamous cell carcinoma (LSCC) tissues and to examine the clinicopathological correlation between protein levels and LSCC. RT-PCR and Western blot were used to examine the expression of ZEB1 and E-cadherin mRNAs and proteins in LSCC tissues as well as in adjacent normal tissues, and then analyze the relationship between the clinicopathological characteristics and the expression changes of ZEB1 and E-cadherin mRNAs in LSCC. In addition, RNAi was used to knockdown the expression of the ZEB1 gene in Human HCC827 cells; subsequently, changes in the invasive ability of the resultant cells were studied. The positive rates of ZEB1 and E-cadherin mRNAs in LSCC tissues were 69.2 and 38.5 %, respectively. They differed significantly from the corresponding positive rates in the adjacent normal lung tissues (15.4 and 80.8 %, p < 0.05). There was a negative correlation between the protein levels of ZEB1 and E-cadherin in LSCC tissues (r = -0.714, p < 0.001); in addition, it was found that ZEB1 protein expression in LSCC tissues was significantly higher than that in the neighboring normal lung tissues (p < 0.05), and its expression was also significantly higher in patients with lymph node metastases and distant metastases compared to those patients without metastatic disease (p < 0.05). On the contrary, E-cadherin expression was significantly lower in LSCC tissues than that in the neighboring normal tissue (p < 0.05). It was lower in patients with lymph node metastasis and distant metastasis compared to patients without metastatic disease (p < 0.05). However, the expression of ZEB1 and E-cadherin was independent of gender, age, tumor size, or tumor differentiation level (p > 0.05). Transfection of ZEB1 siRNA into HCC827 cells significantly reduced the ZEB1 protein level (p < 0.01) and significantly elevated E-cadherin levels (p < 0.01). Moreover, significantly less ZEB1 siRNA-transfected cells migrated through Transwell chambers in the LSCC tissue than that in the control groups (untransfected or transfected with control siRNA, p < 0.01). The expression of the ZEB1 gene in LSCC tissues is downregulated with the expression of E-cadherin. On the other hand, the expression of siRNA against ZEB1 promotes E-cadherin expression and suppresses the invasive ability conferred by E-cadherin. In conclusion, our data suggested that overexpression of the ZEB1 gene is possibly associated with the occurrence, development, invasion of LSCC.
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Cadherinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas de Homeodominio/metabolismo , Neoplasias Pulmonares/metabolismo , Factores de Transcripción/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD , Cadherinas/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular , Femenino , Expresión Génica , Técnicas de Silenciamiento del Gen , Proteínas de Homeodominio/genética , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , ARN Interferente Pequeño/genética , Factores de Transcripción/genética , Homeobox 1 de Unión a la E-Box con Dedos de ZincRESUMEN
The objective of this study was to determine the expression of the important vesicle trafficking-regulating factor Rab25 in human gastric cancer tissues, to analyze the correlation between Rab25 protein expression with gastric cancer occurrence and development, and to discuss the correlation of Rab25 protein expression with gastric cancer cell metastasis. The overall aim was to provide experimental evidence that can be used to design future biological treatments of human gastric cancer. Human gastric cancer tissue and the adjacent normal gastric tissue were surgically removed, and immunohistochemistry and Western blotting were used to detect Rab25 protein expression. The correlation between Rab25 protein expression with the development and pathological characteristics of gastric cancer was analyzed. Using RNAi, Rab25 expression was reduced in the gastric cancer cell line MGC80-3, and the changes in MGC80-3 cell invasiveness were then monitored. Immunohistochemistry showed that the Rab25 protein expression rates were 78.21% and 23.08% in gastric carcinoma and the adjacent normal gastric tissue, respectively. Immunohistochemistry and Western blot results showed that Rab25 protein expression in gastric cancer was significantly higher than in adjacent normal gastric tissues (P<0.01). Less differentiated gastric cancer cells had higher expression of Rab25 protein (P<0.01). Gastric carcinomas from patients with a late pathological stage (III-IV) had significantly higher Rab25 protein expression than early stage (I-II) patients (P<0.01). Gastric carcinomas from patients with lymph node metastasis had significantly higher Rab25 protein expression than lymph node metastasis-free patients (P<0.01). Gastric carcinomas from patients with distant metastases had significantly higher Rab25 protein expression than the distant metastasis-negative patients (P<0.01). Rab25 protein expression in gastric cancer was not affected by the patients(,) sex, age, or tumor size (P>0.05). MGC80-3 cells transfected with Rab25 siRNA had significantly lower Rab25 protein expression (P<0.01) and a significantly lower number of cells that passed through a Transwell chamber compared with non-transfected controls and the transfected control group (P<0.01). Rab25 protein expression is associated with the development of gastric cancer. siRNA knockdown of Rab25 protein expression in MGC80-3 gastric cancer cells reduced MGC80-3 cell invasiveness and provided experimental evidence for potential future biological treatment strategies of human gastric cancer.
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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 â - â 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.
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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.
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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.
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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.
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Desoxicitidina , Histonas , Neoplasias Pancreáticas , Receptor Notch1 , Carcinogénesis , Línea Celular Tumoral , Proliferación Celular , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Resistencia a Antineoplásicos , Histonas/metabolismo , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Factores de Transcripción , Gemcitabina , Neoplasias PancreáticasRESUMEN
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.
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Cateterismo Periférico/efectos adversos , Embolización Terapéutica/métodos , Lesión Renal Aguda , Adulto , Anciano , Angiografía/métodos , Femenino , Arteria Femoral/fisiología , Hemorragia/etiología , Humanos , Enfermedad Iatrogénica , Riñón/patología , Masculino , Persona de Mediana Edad , Punciones , Arteria Radial/fisiología , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/métodosRESUMEN
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.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Neoplasias Pancreáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Catéteres , Quimioradioterapia/métodos , Femenino , Humanos , Infusiones Intraarteriales/métodos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Estudios RetrospectivosRESUMEN
The best choice of chemotherapy regimen for patients with advanced gastric cancer (AGC) is still a matter of controversy and requires further investigation. This study was performed to evaluate the efficacy and safety of intra-arterial infusion chemotherapy of 5-fluorouracil 1000 mg/m, cisplatin 50 mg/m, and mitomycin C 10 mg/m (FCM) repeated every 6 weeks, as first-line treatment for AGC. Forty-seven (95.9%) of the 49 patients were assessable for response. Four cases of complete response and 28 cases of partial response were confirmed, giving an overall response rate of 65.3% [95% confidence interval (CI): 52.0-78.6%]. The median time to progression and overall survival for all patients was 8.3 months (95% CI: 6.8-9.8 months) and 14.5 months (95% CI: 12.0-17.0 months). The estimate of overall survival at 12 and 24 months was 55.1% (95% CI: 41.2-69.0%) and 18.4% (95% CI: 7.5-29.2%), respectively. Most patients experienced neutropenia during their course of therapy with 21.3% of patients (n = 10) for grade 3/4 neutropenia. Grade 3 stomatitis, lethargy, and palmar-plantar erythema were observed in two (4.3%), eight (17.0%), and one (2.1%) patients, respectively. Yet, no grade 4 nonhematological toxicity was observed. Intra-arterial infusion chemotherapy of 5-fluorouracil 1000 mg/m, cisplatin 50 mg/m, and mitomycin C 10 mg/m is a tolerated treatment modality with promising activity in patients with previously untreated AGC.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Fluorouracilo/administración & dosificación , Mitomicina/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/efectos adversos , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Mitomicina/efectos adversos , Metástasis de la Neoplasia , Neutropenia/inducido químicamente , Análisis de SupervivenciaRESUMEN
BACKGROUND AND AIMS: The present study was carried out to test the hypothesis that interferon-alpha (IFN-alpha) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization (TACE) treatment of hepatitis B virus (HBV) related unresectable hepatocellular carcinoma (HCC). METHODS: 216 patients with unresectable HBV-related HCC were randomized into a TACE group and a TACE-IFN group, each group had 108 patients. In the TACE-IFN group, patients received IFN-alpha1b at a dose of 3 million units (mu) three times a week by intramuscular injection one week after/before TACE treatment, for 48 weeks. RESULTS: The median disease-free survival in the TACE-IFN treatment group was 23.6 months (95% CI: 21.4-25.8) and 20.3 months (95% CI: 15.8-24.8) in the TACE group (P = 0.027). The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group (39.8% vs 59.3%, P = 0.004). The median overall survival was 29 months (95% CI: 27.5-32.1) in the TACE-IFN group and 26 months (95% CI: 20.1-31.9) in the TACE group (P = 0.003). The 2-year overall survival in the TACE-IFN group was higher than in the TACE group (72.2% vs 52.8%, P = 0.003). CONCLUSIONS: IFN-alpha treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC, with acceptable toxicities.