scholarly journals PIAS1 alleviates diabetic peripheral neuropathy through SUMOlation of PPAR-γ and miR-124-induced downregulation of EZH2/STAT3

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zixin Hou ◽  
Ji Chen ◽  
Huan Yang ◽  
Xiaoling Hu ◽  
Fengrui Yang
Keyword(s):  
Peripheral Neuropathy ◽  
Schwann Cells ◽  
Diabetic Peripheral Neuropathy ◽  
Nerve Tissue ◽  
In Vitro Assays ◽  
In Vivo Experiments ◽  
Ppar Γ ◽  
Gene Reporter Assay

AbstractDiabetic peripheral neuropathy (DPN) is a frequently occurring chronic complication of diabetes. In this study, we aim to explore the regulatory mechanism of protein inhibitor of activated STAT1 (PIAS1) in DPN in terms of autophagy and apoptosis of Schwann cells. The SUMOlation of PPAR-γ by PIAS1 was examined, and ChIP was performed to verify the binding of PPAR-γ to miR-124 promoter region. Dual-luciferase gene reporter assay was used to validate the binding affinity between miR-124 and EZH2/STAT3. Following loss‐ and gain‐of-function experiments, in vitro assays in high glucose-treated Schwann cells (SC4) and in vivo assays in db/db and ob/ob mice were performed to detect the effects of PIAS1 on autophagy and apoptosis of Schwann cells as well as symptoms of DPN by regulating the PPAR-γ-miR-124-EZH2/STAT3. The expression of PIAS1, PPAR-γ, and miR-124 was downregulated in the sciatic nerve tissue of diabetic mice. PIAS1 enhanced the expression of PPAR-γ through direct binding and SUMOlation of PPAR-γ. PPAR-γ enhanced the expression of miR-124 by enhancing the promoter activity of miR-124. Furthermore, miR-124 targeted and inversely modulated EZH2 and STAT3, promoting the autophagy of Schwann cells and inhibiting their apoptosis. In vivo experiments further substantiated that PIAS1 could promote the autophagy and inhibit the apoptosis of Schwann cells through the PPAR-γ-miR-124-EZH2/STAT3 axis. In conclusion, PIAS1 promoted SUMOlation of PPAR-γ to stabilize PPAR-γ expression, which upregulated miR-124 to inactivate EZH2/STAT3, thereby inhibiting apoptosis and promoting autophagy of Schwann cells to suppress the development of DPN.

scholarly journals Antibiotic loaded β-tricalcium phosphate/calcium sulfate for antimicrobial potency, prevention and killing efficacy of Pseudomonas aeruginosa and Staphylococcus aureus biofilms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nan Jiang ◽  
Devendra H. Dusane ◽  
Jacob R. Brooks ◽  
Craig P. Delury ◽  
Sean S. Aiken ◽  
...  
Keyword(s):  
Tricalcium Phosphate ◽  
Calcium Sulfate ◽  
Bone Graft Substitute ◽  
In Vitro Assays ◽  
In Vivo Experiments ◽  
Orthopaedic Infections ◽  
Clinical Investigations ◽  
Antimicrobial Potency

AbstractThis study investigated the efficacy of a biphasic synthetic β-tricalcium phosphate/calcium sulfate (β-TCP/CS) bone graft substitute for compatibility with vancomycin (V) in combination with tobramycin (T) or gentamicin (G) evidenced by the duration of potency and the prevention and killing efficacies of P. aeruginosa (PAO1) and S. aureus (SAP231) biofilms in in vitro assays. Antibiotic loaded β-TCP/CS beads were compared with antibiotic loaded beads formed from a well characterized synthetic calcium sulfate (CS) bone void filler. β-TCP/CS antibiotic loaded showed antimicrobial potency against PAO1 in a repeated Kirby-Bauer like zone of inhibition assay for 6 days compared to 8 days for CS. However, both bead types showed potency against SAP231 for 40 days. Both formulations loaded with V + T completely prevented biofilm formation (CFU below detection limits) for the 3 days of the experiment with daily fresh inoculum challenges (P < 0.001). In addition, both antibiotic loaded materials and antibiotic combinations significantly reduced the bioburden of pre-grown biofilms by between 3 and 5 logs (P < 0.001) with V + G performing slightly better against PAO1 than V + T. Our data, combined with previous data on osteogenesis suggest that antibiotic loaded β-TCP/CS may have potential to stimulate osteogenesis through acting as a scaffold as well as simultaneously protecting against biofilm infection. Future in vivo experiments and clinical investigations are warranted to more comprehensively evaluate the use of β-TCP/CS in the management of orthopaedic infections.

Potential Anti-inflammatory Sesquiterpene Lactones from Eupatorium lindleyanum

Planta Medica ◽  
2017 ◽  
Vol 84 (02) ◽  
pp. 123-128 ◽  
Author(s):  
Fang Wang ◽  
Huanhuan Zhong ◽  
Shiqi Fang ◽  
Yunfeng Zheng ◽  
Cunyu Li ◽  
...  
Keyword(s):  
Sesquiterpene Lactones ◽  
Folk Medicine ◽  
2D Nmr ◽  
In Vitro Assays ◽  
Raw 264.7 Cells ◽  
Therapeutic Effects ◽  
In Vivo Experiments ◽  
Anti Inflammatory

Abstract Eupatorium lindleyanum has traditionally been used as folk medicine in Asian countries for its therapeutic effects on tracheitis and tonsillitis. Investigation of the anti-inflammatory active constituents from E. lindleyanum led to the isolation of two novel sesquiterpene lactones, named eupalinolide L (1) and eupalinolide M (2), and seven known sesquiterpene lactones (3–9). The structures and configurations of the new compounds were determined on the basis of spectroscopic analysis, especially 2D NMR techniques. In vivo experiments showed that the sesquiterpenes fraction significantly reduced mouse ear edema induced by xylene (18.6%, p < 0.05). In in vitro assays, compounds 1–9 showed excellent anti-inflammatory activities, as they lowered TNF-α and IL-6 levels in lipopolysaccharide-stimulated murine macrophage RAW 264.7 cells (p < 0.001). The above results suggest that the sesquiterpene lactones from E. lindleyanum can be developed as novel potential natural anti-inflammatory agents.

scholarly journals Blood–Nerve Barrier (BNB) Pathology in Diabetic Peripheral Neuropathy and In Vitro Human BNB Model

2020 ◽  
Vol 22 (1) ◽  
pp. 62
Author(s):  
Yukio Takeshita ◽  
Ryota Sato ◽  
Takashi Kanda
Keyword(s):  
Endothelial Cells ◽  
Peripheral Neuropathy ◽  
Schwann Cells ◽  
Cell Lines ◽  
Diabetic Peripheral Neuropathy ◽  
Peripheral Nerves ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Immortalized Cell

In diabetic peripheral neuropathy (DPN), metabolic disorder by hyperglycemia progresses in peripheral nerves. In addition to the direct damage to peripheral neural axons, the homeostatic mechanism of peripheral nerves is disrupted by dysfunction of the blood–nerve barrier (BNB) and Schwann cells. The disruption of the BNB, which is a crucial factor in DPN development and exacerbation, causes axonal degeneration via various pathways. Although many reports revealed that hyperglycemia and other important factors, such as dyslipidemia-induced dysfunction of Schwann cells, contributed to DPN, the molecular mechanisms underlying BNB disruption have not been sufficiently elucidated, mainly because of the lack of in vitro studies owing to difficulties in establishing human cell lines from vascular endothelial cells and pericytes that form the BNB. We have developed, for the first time, temperature-sensitive immortalized cell lines of vascular endothelial cells and pericytes originating from the BNB of human sciatic nerves, and we have elucidated the disruption to the BNB mainly in response to advanced glycation end products in DPN. Recently, we succeeded in developing an in vitro BNB model to reflect the anatomical characteristics of the BNB using cell sheet engineering, and we established immortalized cell lines originating from the human BNB. In this article, we review the pathologic evidence of the pathology of DPN in terms of BNB disruption, and we introduce the current in vitro BNB models.

scholarly journals Ammonium Glycyrrhizinate Prevents Apoptosis and Mitochondrial Dysfunction Induced by High Glucose in SH-SY5Y Cell Line and Counteracts Neuropathic Pain in Streptozotocin-Induced Diabetic Mice

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 608
Author(s):  
Laura Ciarlo ◽  
Francesca Marzoli ◽  
Paola Minosi ◽  
Paola Matarrese ◽  
Stefano Pieretti
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
High Glucose ◽  
Diabetic Peripheral Neuropathy ◽  
Glycyrrhizic Acid ◽  
Repeated Treatment ◽  
Diabetic Mice ◽  
Painful Condition

Glycyrrhiza glabra, commonly known as liquorice, contains several bioactive compounds such as flavonoids, sterols, triterpene, and saponins; among which, glycyrrhizic acid, an oleanane-type saponin, is the most abundant component in liquorice root. Diabetic peripheral neuropathy is one of the major complications of diabetes mellitus, leading to painful condition as neuropathic pain. The pathogenetic mechanism of diabetic peripheral neuropathy is very complex, and its understanding could lead to a more suitable therapeutic strategy. In this work, we analyzed the effects of ammonium glycyrrhizinate, a derivate salt of glycyrrhizic acid, on an in vitro system, neuroblastoma cells line SH-SY5Y, and we observed that ammonium glycyrrhizinate was able to prevent cytotoxic effect and mitochondrial fragmentation after high-glucose administration. In an in vivo experiment, we found that a short-repeated treatment with ammonium glycyrrhizinate was able to attenuate neuropathic hyperalgesia in streptozotocin-induced diabetic mice. In conclusion, our results showed that ammonium glycyrrhizinate could ameliorate diabetic peripheral neuropathy, counteracting both in vitro and in vivo effects induced by high glucose, and might represent a complementary medicine for the clinical management of diabetic peripheral neuropathy.

scholarly journals Agent-based modeling of cancer stem cell driven solid tumor growth

2015 ◽  
Author(s):  
Jan T Poleszczuk ◽  
Paul Macklin ◽  
Heiko Enderling
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Tumor Growth ◽  
Population Level ◽  
In Vitro Assays ◽  
Agent Based ◽  
In Vivo Experiments ◽  
Behavioral Rules

Computational modeling of tumor growth has become an invaluable tool to simulate complex cell-cell interactions and emerging population-level dynamics. Agent-based models are commonly used to describe the behavior and interaction of individual cells in different environments. Behavioral rules can be informed and calibrated by in vitro assays, and emerging population-level dynamics may be validated with both in vitro and in vivo experiments. Here, we describe the design and implementation of a lattice-based agent-based model of cancer stem cell driven tumor growth.

Host Defence Cryptides from Human Apolipoproteins: Applications in Medicinal Chemistry

2020 ◽  
Vol 20 (14) ◽  
pp. 1324-1337 ◽  
Author(s):  
Rosa Gaglione ◽  
Elio Pizzo ◽  
Eugenio Notomista ◽  
Cesar de la Fuente-Nunez ◽  
Angela Arciello
Keyword(s):  
Bioactive Peptides ◽  
Biological Activities ◽  
Host Defence ◽  
New Drugs ◽  
In Vitro Assays ◽  
Protein Cleavage ◽  
Anticancer Activities ◽  
In Vivo Experiments

Several eukaryotic proteins with defined physiological roles may act as precursors of cryptic bioactive peptides released upon protein cleavage by the host and/or bacterial proteases. Based on this, the term “cryptome” has been used to define the unique portion of the proteome encompassing proteins with the ability to generate bioactive peptides (cryptides) and proteins (crypteins) upon proteolytic cleavage. Hence, the cryptome represents a source of peptides with potential pharmacological interest. Among eukaryotic precursor proteins, human apolipoproteins play an important role, since promising bioactive peptides have been identified and characterized from apolipoproteins E, B, and A-I sequences. Human apolipoproteins derived peptides have been shown to exhibit antibacterial, anti-biofilm, antiviral, anti-inflammatory, anti-atherogenic, antioxidant, or anticancer activities in in vitro assays and, in some cases, also in in vivo experiments on animal models. The most interesting Host Defence Peptides (HDPs) identified thus far in human apolipoproteins are described here with a focus on their biological activities applicable to biomedicine. Altogether, reported evidence clearly indicates that cryptic peptides represent promising templates for the generation of new drugs and therapeutics against infectious diseases.

scholarly journals Bacillus-based products for management of kiwifruit bacterial canker

2021 ◽  
Vol 60 (2) ◽  
pp. 215-228
Author(s):  
Enrico BIONDI ◽  
Lorenzo GALLIPOLI ◽  
Angelo MAZZAGLIA ◽  
Set Perez FUENTEALBA ◽  
Nemanja KUZMANOVIĆ ◽  
...  
Keyword(s):  
Pseudomonas Syringae ◽  
Control Strategies ◽  
In Vitro Assays ◽  
Bacterial Canker ◽  
Streptomycin Sulphate ◽  
In Vivo Experiments ◽  
Ca 50 ◽  
Pathogen Populations

Pseudomonas syringae pv. actinidiae is an important pathogen of kiwifruit (Actinidia deliciosa), and bacterial canker of this host is managed by monitoring and chemical control strategies. The efficacy of the bio-pesticides Amylo-X® (based on Bacillus amyloliquefaciens subsp. plantarum strain D747) and Serenade Max® (strain QST713 of B. subtilis) was evaluated by in vitro and in vivo experiments. Both antagonists inhibited different biovars of the pathogen in in vitro assays; QST713 was more efficient than D747. The two Bacillus strains also colonized A. deliciosa flowers (c. 105-7 cfu per flower) up to 96 h after inoculation. D747 persisted on leaves (c. 104-6 cfu cm-2) up to 4 weeks after inoculation, during 2 years in Emilia Romagna and Latium regions of Italy. On flowers, the antagonists reduced pathogen populations, compared to untreated (control) flowers. On A. deliciosa and A. chinensis plants under controlled conditions, Amylo-X® reduced severity of bacterial canker, providing ca. 50% relative protection on A. deliciosa and 70% on A. chinensis. Serenade Max® was less effective, giving 0% relative protection on A. deliciosa and 40% on A. chinensis. In a field trial, on A. deliciosa plants, Amylo-X® reduced the severity of bacterial canker on leaves, providing ca. 40% relative protection. The sensitivity of both antagonistic strains to streptomycin sulphate was confirmed by testing the most used concentration where antibiotics are approved for management of bacterial pathogens.

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