A Comprehensive Review of the Application of Nanoparticles in Diabetic Wound Healing: Therapeutic Potential and Future Perspectives

International Journal of Nanomedicine, Год журнала: 2022, Номер Volume 17, С. 6007 - 6029

Опубликована: Дек. 1, 2022

Diabetic wounds are one of the most challenging public health issues 21st century due to their inadequate vascular supply, bacterial infections, high levels oxidative stress, and abnormalities in antioxidant defenses, whereas there is no effective treatment for diabetic wounds.Due distinct properties nanoparticles, such as small particle size, elevated cellular uptake, low cytotoxicity, antibacterial activity, good biocompatibility, biodegradability.The application nanoparticles has been widely used wound healing superior anti-inflammatory, antibacterial, activities.These can also be loaded with various agents, organic molecules (eg, exosomes, molecule compounds, etc.), inorganic (metals, nonmetals, or complexed biomaterials, smart hydrogels (HG), chitosan (CS), hyaluronic acid (HA), augment therapeutic potential wounds.This paper reviews future perspective wounds.Together, represent a promising strategy healing.The direction may develop novel multiple effects that not only act at all stages diabetes but provide stable physiological environment throughout wound-healing process.

Язык: Английский

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Nanosilk Increases the Strength of Diabetic Skin and Delivers CNP-miR146a to Improve Wound Healing

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Окт. 30, 2020

Diabetes mellitus is a metabolic disorder associated with properties and an increased risk of chronic wounds due to sustained pro-inflammatory response. We have previously radical scavenging cerium oxide nanoparticles (CNP) conjugated the anti-inflammatory microRNA (miR)-146a, termed CNP-miR146a, improves diabetic wound healing by synergistically lowering oxidative stress inflammation, we sought evaluate this treatment in topical application. Silk fibroin biocompatible polymer that can be fabricated into nanostructures, nanosilk. Nanosilk characterized high strength-to-density ratio ability exhibit strain hardening. therefore hypothesized nanosilk would strengthen biomechanical skin solution could effectively deliver CNP-miR146a improve healing. The murine was assessed rate closure inflammatory gene expression, as well histologic analysis. effect on human evaluated testing following application 7% solution. Diabetic treated healed day 14.5 compared 16.8 controls (p = 0.0321). Wounds had higher collagen levels than 0.0126) pro-fibrotic expression TGFβ-1 0.0092), Col3α1 0.0369), Col1α2 0.0454). Treatment lowered IL-6 0.0488) IL-8 0.0009). resulted significant improvement maximum load modulus < 0.05). able successfully through inhibition signaling promotion processes.

Язык: Английский

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MiR-146a mimic attenuates murine allergic rhinitis by downregulating TLR4/TRAF6/NF-κB pathway

Immunotherapy, Год журнала: 2019, Номер 11(13), С. 1095 - 1105

Опубликована: Июль 30, 2019

Aim: This study aims to investigate whether microRNA (miR)-146a exerts therapeutic potential allergic rhinitis (AR). Methods: Female BALB/c mice were randomly divided into the AR and miR-146a groups. was administered nostril before ovalbumin (OVA) challenge daily on days 21–28. Results: The expression level of in nasal mucosa significantly decreased. mimic markedly attenuated sneezing rubbing events, decreased levels ovalbumin-specific IgE as well mastocyte- basophil-related inflammatory cytokines, reduced cells, affected T-helper 2-released cytokines. Furthermore, inhibited expressions proteins relevant Toll-like receptor 4 (TLR4)/TRAF6/NF-κB signaling pathway. Conclusion: anti-inflammatory effects might exert through inhibition toll-like pathway some extent.

Язык: Английский

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Downregulation of interleukin 6 signaling might reduce the risk of periodontitis: a drug target Mendelian randomization study

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июнь 5, 2023

Interleukin 6 (IL-6) is considered to play a role in the dysbiotic host response development of periodontitis. While inhibition IL-6 receptor using monoclonal antibodies well-established therapy for some diseases, so far, its potential benefit patients with periodontitis has not been examined. We tested association genetically proxied downregulation signaling explore whether could represent viable treatment target periodontitis.As proxies downregulation, we selected 52 genetic variants close vicinity gene encoding that were associated lower circulating C-reactive protein (CRP) levels genome-wide study (GWAS) 575 531 participants European ancestry from UK Biobank and Cohorts Heart Aging Research Genomic Epidemiology (CHARGE) consortium. Associations inverse-variance weighted Mendelian randomization 17 353 cases 28 210 controls descent Gene-Lifestyle Interactions Dental Endpoints (GLIDE) In addition, effect CRP reduction independent pathway was assessed.Genetically odds (odds ratio (OR) = 0.81 per 1-unit decrement log-CRP levels; 95% confidence interval (CI): [0.66;0.99]; P 0.0497). Genetically had similar (OR 0.81; CI: [0.68; 0.98]; 0.0296).In conclusion, might be causal on risk

Язык: Английский

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A20 inhibits osteoclastogenesis via TRAF6‐dependent autophagy in human periodontal ligament cells under hypoxia

Cell Proliferation, Год журнала: 2020, Номер 53(3)

Опубликована: Фев. 6, 2020

Abstract Objectives A20 exerts an anti‐osteoclastogenic effect through the inhibition of NF‐κB signalling in periodontitis. It also regulates autophagy via ubiquitin modification. This study was aimed at exploring relationship between and anti‐osteoclastogenesis human periodontal ligament cells (hPDLCs) under hypoxia. Materials Methods Real‐time PCR Western blot were used to detect relative mRNA protein levels. The formation autophagosomes measured by TEM. Osteoclastic differentiation assessed TRAP staining hydroxyapatite resorption assay. interactions different proteins observed co‐IP. Results Cells cultured 2% O₂ exhibited decreased expression increased RANKL/OPG (R/O) ratio. There a negative correlation TRAF6, similar results found with autophagic flux. delayed increase R/O ratio Autophagy hPDLCs osteoclast areas mouse bone marrow mononuclear (BMMCs) inhibited A20. Moreover, using 3‐MA resulted number function osteoclasts. In addition, polyubiquitination K63 enhanced that K48 TRAF6 suppress hypoxic conditions. Conclusions inhibits osteoclastogenesis TRAF6‐dependent These findings suggest may be key gene target during loss periodontitis TRAF6‐mediated autophagy.

Язык: Английский

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MicroRNA miR-24-3p Mediates the Negative Regulation of Lipopolysaccharide-Induced Endometrial Inflammatory Response by Targeting TNF Receptor-Associated Factor 6 (TRAF6)

Journal of Inflammation Research, Год журнала: 2022, Номер Volume 15, С. 807 - 825

Опубликована: Фев. 1, 2022

Purpose: Endometritis is a female reproductive disease that affects the cattle industries development and microRNAs (miRNAs) play pivotal role critical regulators of innate immune response in varieties diseases. The present study intends to investigate regulatory miR‐24-3p involved endometritis evaluate its therapeutic potential. Methods: Whole mice uteri bovine endometrial epithelial cells (BEECs) were separately stimulated with LPS. BEECs also transfected miR-24-3p mimic negative control; si TRAF6 siNC; pcDNA3.1 empty pcDNA3.1(+) LPS stimulation. expression levels measured via quantitative real‐time polymerase chain reaction (qRT-PCR) Western blot, respectively. LPS‐induced inflammatory assessed by cytokines secretion ELISA qRT-PCR. Bioinformatics analysis luciferase reporter assay validated interaction between . activation NF‐ĸB/MAPK pathway p65 phosphorylation was investigated blot immunofluorescence assay, Results: decreased, elevated an increased level pro-inflammatory LPS‐treated uterus. overexpression suppressed (IL‐1β, IL‐6, IL-8 TNF-α) deactivation pathways. downregulation inhibited BEECs. as target miR‐24-3p, reversed cloned on inflammation Conclusion: Our findings demonstrate attenuates mediators suppressing Therefore, modulating pathogenesis possibly, potential against endometritis. Keywords: endometritis, miR-24-3p, , NF-ĸB/MAPK,

Язык: Английский

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IL‐17 stimulates the expression of CCL2 in cardiac myocytes via Act1/TRAF6/p38MAPK‐dependent AP‐1 activation

Scandinavian Journal of Immunology, Год журнала: 2019, Номер 91(1)

Опубликована: Окт. 20, 2019

IL-17 participates in the development of many autoimmune diseases by promoting expression some chemokines. Chemokine C-C motif ligand 2 (CCL2) is an important factor at infiltration mononuclear cells myocardial tissue viral myocarditis (VMC). It was found that could aggravate injury upregulating CCL2. But underlying mechanism involved CCL2 secretion induced cardiac myocytes remains unclear. This study investigated role transcription AP-1 expression. The results showed mediated activation Act1, TRAF6, p38MAPK and c-Jun/AP-1 not Wnt or PI3K signalling pathway to upregulate myocytes. After blocking Act1/TRAF6/p38MAPK cascade interfering with Curcumin c-Jun siRNA, significantly attenuated both mRNA protein levels. Furthermore, phosphorylation suppressed when were treated Act1 TRAF6 SB203580 (p38MAPK inhibitor) SP600125 (JNK In conclusion, stimulate via Act1/TRAF6/p38MAPK-dependent activation, which may provide a new target for diagnosis treatment VMC.

Язык: Английский

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The role of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in chronic periodontitis progression

Bioengineered, Год журнала: 2022, Номер 13(2), С. 2336 - 2345

Опубликована: Янв. 16, 2022

Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) is a novel pro-inflammatory factor in severe human diseases. Since inflammatory plays important roles periodontitis progression, we aimed to explore the role of NEAT1 chronic (CP) vitro. We established cell model was by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS)-induced periodontal ligament cells (PDLCs). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) performed detect expression NEAT1, microRNA (miR)-200c-3p, and tumor necrosis receptor-associated 6 (TRAF6). Cell viability, factors, protein Bcl-2, Bax, TRAF6 were analyzed MTT, enzyme-linked immunosorbent assay, Western blot. The target relationships among miR-200c-3p, predicted StarBase/TargetScan software, further validated dual-luciferase reporter assay. In this research, up-regulated CP tissues group. Silencing over-expression miR-200c-3p enhanced viability repressed apoptosis targets TRAF6. MiR-200c-3p inhibitor or reversed promoting effect knockdown on inhibiting effects cytokines apoptosis. Consequently, silencing inhibits inflammation via targeting miR-200c-3p/TRAF6 axis, thereby contributing alleviate progression CP. This finding could provide an underlying for treatment

Язык: Английский

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Circulating Extracellular Vesicles and Their miR “Barcode” Differentiate Alcohol Drinkers With Liver Injury and Those Without Liver Injury in Severe Trauma Patients

Frontiers in Medicine, Год журнала: 2019, Номер 6

Опубликована: Фев. 25, 2019

Short Summary: Extracellular vesicles (EVs), released during tissue/cell injury, contain a "barcode" indicating specific microRNAs (miRs) that can uncover their origin. We examined whether systemic EVs possessing hepatic miR-signatures would indicate ongoing liver injury and clinical complications in trauma patients (TP). grouped the of alcoholic drinkers into "alcohol-drinkers with (LI)" (EtOH LI) or without LI" w/o we compared these groups to "non-drinkers" (no EtOH). When patient blood from EtOH LI group found total number be increased, along an increase miR-122 let7f-two EV-associated miRNAs-and several inflammation-associating cytokines, such as interleukin (IL)-6 IL-33. In contrast, all aforementioned readouts were decreased group. These novel data demonstrate hepatocyte damage alcohol-intoxicated presenting reflected by circulating serum EVs, miR-"barcode" concomitant inflammatory markers IL-6 Anti-inflammatory effect alcohol-drinking presented reduced hepato-derived no upregulation IL-33, miR different injury. Background: Alcohol abuse is associated (neuro)protective effects related (head) injuries, negative regarding infection rates survival severely injured which are tissue and/or cell including signature systemically measured, they TP foretell complications. Patients/Methods: enrolled 35 measured IL-6, TNF-alpha, IL-1beta, IL-10 alcohol (ethanol, EtOH) concentration (BAC), GLDH, GGT, AST, ALT, leukocytes, platelets, bilirubin. Within expression levels miR-122, let7f, miR21, miR29a, miR-155, miR-146a. Patients alcohol-drinkers "alcohol assessed characteristics outcome hospitalization regard sepsis, septic shock, pneumonia, mortality. Results: had significantly increased pneumonia vs. IL-33 (p < 0.05). EV correlated positively ALT 0.0001). Two miRs, only Five miR-21, miR-29a, miR-146a, group, Notably bilirubin Conclusions: Liver numbers, barcode, Interestingly, have liver-derived observed infiltration "barcode."

Язык: Английский

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MiR‐643 inhibits lipopolysaccharide‐induced endometritis progression by targeting TRAF6

Cell Biology International, Год журнала: 2020, Номер 44(4), С. 1059 - 1067

Опубликована: Янв. 13, 2020

Endometritis is a prevalent disease with inflammation of uterus endangering women reproductive health. MicroRNAs (miRNAs) play important roles in inflammatory disorders, including endometritis. However, the role and mechanism miR-643 endometritis development remain unclear. This study aimed to investigate effect on lipopolysaccharide (LPS)-induced response clarify potential mechanism. LPS-treated human endometrial epithelial cells (HEECs) were cultured vitro. The expression levels tumor necrosis factor receptor-associated 6 (TRAF6) measured via quantitative real-time polymerase chain reaction western blot, respectively. LPS-induced was assessed by cytokines secretion enzyme-linked immunosorbent assay. activation nuclear factor-κB (NF-κB) pathway investigated blot. interaction between TRAF6 validated bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation. decreased protein level enhanced HEECs. overexpression suppressed (tumor factor-α, interleukin-1β [IL-1β], IL-6) NF-κB pathway. knockdown inhibited as target restoration reversed Collectively, attenuated targeting TRAF6, indicating novel avenue for treatment

Язык: Английский

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