Transvenous embolization of a cerebrospinal fluid-venous fistula for the treatment of spontaneous intracranial hypotension

xlomafota13 shared this article with you from Inoreader Transvenous embolization of a cerebrospinal fluid-venous fistula for the treatment of spontaneous intracranial hypotension Via leak of cerebrospinal fluid J Neurointerv Surg. 2021 Oct 14:neurintsurg-2021-018160. doi: 10.1136/neurintsurg-2021-018160. Online ahead of print. ABSTRACT Cerebrospinal fluid-venous fistula is an increasingly recognized cause of spontaneous intracranial hypotension.1 The site of the leak is between the dural sleeve around a spinal nerve root and the surrounding foraminal veins. In appropriately investigated patients, transvenous embolization of the draining foraminal and paraspinal veins has been shown to be an effective way of treating the disease, with low periprocedural morbidity, improvement in symptoms and radiological appearances.2 Video 1 shows the technique employed in a typical case using Onyx (Medtronic, Minnesota, USA) to embolize a CSF-venous fistula at the right T10 neural foramen.neurintsurg;neurintsurg-2021-018160v1/V1F1V1Video 1. PMID:34649936 | DOI:10.1136/neurintsurg-2021-018160 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

DUSP4 alleviates LPS-induced chondrocyte injury in knee osteoarthritis via the MAPK signaling pathway

xlomafota13 shared this article with you from Inoreader DUSP4 alleviates LPS-induced chondrocyte injury in knee osteoarthritis via the MAPK signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1401. doi: 10.3892/etm.2021.10837. Epub 2021 Oct 1. ABSTRACT Knee osteoarthritis (KOA) is characterized by cartilage damage, and the associated pathogenesis is complex. The expression of dual specificity protein phosphatase 4 (DUSP4) is significantly decreased in osteoarthritis (OA); however, the specific role and mechanism underlying DUSP4 in OA are yet to be elucidated. ATDC5 cells were treated with lipopolysaccharide (LPS) to establish the cell injury model. The expression levels of DUSP4 were decreased in OA chondrocytes, demonstrated by reverse transcription-quantitative PCR and western blot analysis. Following overexpression of DUSP4 by cell transfection, Cell Counting Kit-8, ELISA, TUNEL and western blotting assays were used to detect the cell viability, oxidative stress, inflammation and apoptosis levels of LPS-induced ATDC5 cells. Overexpression of DUSP4 inhibited the activation of the MAPK signali ng pathway, thereby reducing oxidative stress levels, inflammatory response and apoptosis in the OA cell model. The mechanisms underlying DUSP4 in OA were further explored following the addition of MAPK signaling pathway agonist, phorbol 12-myristate 13-acetate (PMA). The addition of PMA reversed the inhibitory effects of DUSP4 overexpression on oxidative stress, inflammatory response and apoptosis in cells. In summary, DUSP4 alleviated LPS-induced chondrocyte injury in KOA via the MAPK signaling pathway. PMID:34650647 | PMC:PMC8506912 | DOI:10.3892/etm.2021.10837 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Infra-hepatic caval resection en bloc with right nephrectomy followed by caval reconstruction for locally advanced caval leiomyosarcoma: A case report and literature review

xlomafota13 shared this article with you from Inoreader Infra-hepatic caval resection en bloc with right nephrectomy followed by caval reconstruction for locally advanced caval leiomyosarcoma: A case report and literature review Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1377. doi: 10.3892/etm.2021.10812. Epub 2021 Sep 28. ABSTRACT Retroperitoneal sarcomas often require complex surgical procedures in order to achieve complete resection; in such cases both vascular and visceral resections are needed. When it comes to the need for vascular reconstruction, the type of graft as well as the type of reconstructive process are chosen according to the length and location of the resected segment. Meanwhile, depending on the location of the resected segment, other vascular reconstructions may be needed such as the reimplantation of the renal veins. However, in certain cases, this reimplantation is not mandatory, an adequate renal outflow being reported through the collateral network at this level. We present the case of a 43-year-old patient diagnosed with a large retroperitoneal sarcoma originating from the cava vein invading the right kidney. Resection of the tumor was performed en bloc with caval resection and right nephrectomy, without reimplantation of the left renal vein at the level of the graft. Extended visceral and vascular resections might be needed in order to achieve complete resection of inferior cava vein sarcomas; re-implantation of the left renal vein being not mandatory if rich collateral circulation is present. PMID:34650625 | PMC:PMC8506944 | DOI:10.3892/etm.2021.10812 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Monensin suppresses cell proliferation and invasion in ovarian cancer by enhancing MEK1 SUMOylation

xlomafota13 shared this article with you from Inoreader Monensin suppresses cell proliferation and invasion in ovarian cancer by enhancing MEK1 SUMOylation Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1390. doi: 10.3892/etm.2021.10826. Epub 2021 Sep 30. ABSTRACT Ovarian cancer is the most lethal gynecologic malignancy, and is usually diagnosed at an advanced stage. Most patients relapse within 12-24 months and die from progressive chemotherapy-resistant diseases. Significant progress has been made in developing new targeted therapies for human cancer, including ovarian cancer. However, an effective alternative to drug development is to repurpose drugs. The present study investigated the possibility of reusing the antibiotic monensin as an anti-ovarian cancer drug. After applying a series of titrated monensin on a panel of ovarian cancer cell lines, the growth, migration and invasion of cells were explored. Multiple signaling molecules associated with epithelial-to-mesenchymal transition were also regulated by monensin. The mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway was further found to be the key regulator affected by monensin. Additionally, monensin enhanced the MEK1 SUMOylation in vitro and in vivo, and the SUMOylation degree depended on time and dose. Xenograft studies verified that monensin effectively inhibited xenograft tumor growth by increasing the SUMOylation of MEK1. The aforementioned results suggested that monensin is a good candidate for anti-ovarian cancer by enhancing MEK1 SUMOylation and inhibiting the MEK-ERK pathway. PMID:34650638 | PMC:PMC8506924 | DOI:10.3892/etm.2021.10826 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Melatonin attenuates low shear stress-induced pyroptosis and endothelial cell dysfunction via the RORα/miR-223/STAT-3 signalling pathway

xlomafota13 shared this article with you from Inoreader Melatonin attenuates low shear stress-induced pyroptosis and endothelial cell dysfunction via the RORα/miR-223/STAT-3 signalling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1392. doi: 10.3892/etm.2021.10828. Epub 2021 Sep 30. ABSTRACT Endothelial cells sense changes in blood flow shear stress and affect the progression of atherosclerotic plaques. Pyroptosis is an inflammatory form of cell death and has been implicated in cardiovascular diseases. Melatonin and its nuclear receptor retinoid-related orphan receptor α (RORα) have protective effects on the development of atherosclerosis. To date, whether melatonin can prevent endothelial cell pyroptosis and dysfunction in pathological shear stress remains unclear. In the present study, human umbilical vein endothelial cells (ECs) were cultured under low shear stress conditions (5 dyne/cm2) for 24 h and treated with or without melatonin (2 µmol/l). The binding sites of the microRNA (miR)-223 promoter and RORα were predicted using the JASPAR website. Expression of pyroptosis-related proteins, including cleaved N-termin al gasdermin D, caspase-1, intercellular adhesion molecule 1 (ICAM-1) and nitric oxide (NO) were assessed. The results indicated that low shear stress increased pyroptosis and ICAM-1 expression, whereas it decreased NO levels. Melatonin alleviated pyroptosis and ICAM-1 expression and increased the production of NO in ECs. Further assessment revealed that low-level shear stress decreased RORα protein and mRNA expression, whereas melatonin would bind to RORα and thereby promoted miR-223 transcription in ECs. The present study also identified signal transducer and activator of transcription 3 (STAT-3) as a potential target gene of miR-223-3p. When transfected with miR-223 inhibitor, ECs up-regulated the expression of pyroptosis-related proteins and ICAM-1, and down-regulated NO levels. By contrast, silencing STAT-3 expression diminished the protective effect of miR-223. These results indicated that melatonin prevented ECs from undergoing pyroptosis and alleviated dysfunction via the RORα/miR-223/STAT-3 signalling pathway. This information could aid in the development of novel therapeutic approaches and provide new insights into atherosclerosis. PMID:34650640 | PMC:PMC8506941 | DOI:10.3892/etm.2021.10828 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Ecto-5'-nucleotidase (CD73) inhibits dorsal root ganglion neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway

xlomafota13 shared this article with you from Inoreader Ecto-5'-nucleotidase (CD73) inhibits dorsal root ganglion neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1374. doi: 10.3892/etm.2021.10809. Epub 2021 Sep 28. ABSTRACT Spinal cord injury (SCI) is a serious affliction that can lead to insufficient blood supply to the spinal cord, resulting in nutrient and energy deficiency in nerve cells such as neurons. In the present study, a spinal cord injury mouse model was constructed using wild-type (WT) and ecto-5'-nucleotidase (CD73)-/- mice. The results of TUNEL and immunofluorescence assays indicated that the apoptosis of neurons in CD73-/- mice was increased after spinal cord injury. Dorsal root ganglion (DRG) neurons from WT and CD73-/- mice were cultured in low glucose and hypoxic conditions to simulate the effects of spinal cord injury on neurons. Subsequently, a western blot assay was used to detect the expression of CD73, caspase-3 and Bcl-2. Flow cytometry was used to detect cell apoptosis and the corresponding kits were used to detect changes in lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS), adenosine triphosphate (ATP) and cell activity. The results revealed that the apoptosis level of CD73-overexpressing DRG neurons was decreased under anoxia and glucose deficiency. The release of LDH, MDA and the production of ROS in CD73 DRG neurons was decreased, while the synthesis of ATP, the activity of SOD and cell activity increased after hypoxia-hypoglycemia treatment. Additional cellular studies demonstrated that blocking the expression and hydrolase activity of CD73 with α,β-methylene ADP (APCP) could counteract the protective effect of CD73 on neuronal apoptosis, while adenosine (Ado) could rescue the increased apoptosis caused by CD73 deletion. In addition, the cAMP/ protein kinase A (PKA)/cAMP response element-binding protein (CREB) signaling pathway was also positively regulated by CD73 and Ado. In conclusion, CD73 could inhibit DRG neurona l apoptosis by promoting the Ado/cAMP/PKA/CREB pathway. PMID:34650622 | PMC:PMC8506929 | DOI:10.3892/etm.2021.10809 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tat-thioredoxin 1 reduces inflammation by inhibiting pro-inflammatory cytokines and modulating MAPK signaling

xlomafota13 shared this article with you from Inoreader Tat-thioredoxin 1 reduces inflammation by inhibiting pro-inflammatory cytokines and modulating MAPK signaling Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1395. doi: 10.3892/etm.2021.10831. Epub 2021 Oct 1. ABSTRACT Thioredoxin 1 (Trx1) serves a central role in redox homeostasis. It is involved in numerous other processes, including oxidative stress and apoptosis. However, to the best of our knowledge, the role of Trx1 in inflammation remains to be explored. The present study investigated the function and mechanism of cell permeable fused Tat-Trx1 protein in macrophages and a mouse model. Transduction levels of Tat-Trx1 were determined via western blotting. Cellular distribution of transduced Tat-Trx1 was determined by fluorescence microscopy. 2',7'-Dichlorofluorescein diacetate and TUNEL staining were performed to determine the production of reactive oxygen species and DNA fragmentation. Protein and gene expression were measured by western blotting and reverse transcription-quantitative PCR (RT-qPCR), respectively. Effects of skin inflammation were determine d using hematoxylin and eosin staining, changes in ear weight and ear thickness, and RT-qPCR in ear edema animal models. Transduced Tat-Trx1 inhibited lipopolysaccharide-induced cytotoxicity and activation of NF-κB, MAPK and Akt. Additionally, Tat-Trx1 markedly reduced the production of inducible nitric oxide synthase, cyclooxygenase-2, IL-1β, IL-6 and TNF-α in macrophages. In a 12-O-tetradecanoylphorbol-13-acetate-induced mouse model, Tat-Trx1 reduced inflammatory damage by inhibiting inflammatory mediator and cytokine production. Collectively, these results demonstrated that Tat-Trx1 could exert anti-inflammatory effects by inhibiting the production of pro-inflammatory mediators and cytokines and by modulating MAPK signaling. Therefore, Tat-Trx1 may be a useful therapeutic agent for diseases induced by inflammatory damage. PMID:34650643 | PMC:PMC8506951 | DOI:10.3892/etm.2021.10831 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.