Alleviation Of Inflammation Research Articles

Revolutionizing Drug Delivery: A Design Professional's Approach to Drug-loaded Transferosomal Vesicles for Transdermal Use.

This study aimed to develop and evaluate lornoxicam (LXM) and thiocolchicoside (TCS) transferosomal transdermal patches. Oral administration of LXM and TCS can lead to gastric irritation, necessitating alternative delivery methods for pain and inflammation relief. Incorporating LXM & TCS into transferosomes within a transdermal patch offers a potential solution. The objective of this study is to develop and evaluate transferosomal transdermal patches containing LXM and TCS, incorporating Aloe vera leaf mucilage (AVLM) and lime oil (LO) as permeability enhancers. The aim is to enhance the skin permeation of these drugs while mitigating gastric irritation associated with their oral administration. Transferosomes were made by the thin film hydration tactic, with nine formulations based on three independent variables: phosphatidylcholine, span 80, and sonication time. Entrapment efficiency and drug release at 6th h were assessed as dependent variables. The optimized combination was then formulated into transdermal patches via central composite design, evaluating the impact of AVLM and LO on lornoxicam discharge and other physicochemical properties. The average weight and thickness of the patches ranged from 7.52±0.75 to 8.07±0.11g and from 1.69±0.01 to 1.82±0.02mm, respectively, representing minimal variance. The LXM/TCS content homogeneity ranged from 92.84±3.55 to 94.07±4.61% for LXM and from 90.17±1.98 to 93.18±2.98% for TCS, demonstrating robust uniformity. Higher proportions of phosphatidylcholine and span 80, along with lesser sonication time, led to improved entrapment of lornoxicam. In vitro, discharge studies demonstrated optimal discharge with a higher proportion of phosphatidylcholine, a medium proportion of span 80, and a longer sonication time. The transferosomal patches exhibited zero-order discharge kinetics, with LXM & TCS discharge % at 24, 48, and 72 h. The study concludes that formulation TDP-8, which incorporates 3g of Aloe vera leaf mucilage (AVLM) and lime oil (LO) as permeability enhancers, demonstrated favorable discharge characteristics. This indicates its potential as an effective transdermal delivery system for LXM and TCS, offering a promising substitute for pain and inflammation relief while minimizing gastric irritation. The study succeeded in developing and evaluating transferosomal transdermal patches for LXM and TCS, providing an alternative delivery method that minimizes gastric irritation.

Effects of Silibinin on Delaying Aging in Drosophila melanogaster

Aging is an inevitable physiological process, but delaying aging has always been an enduring human pursuit. Silibinin (SIL), derived from the seeds of the milk thistle plant, exhibits a broad spectrum of pharmacological properties, including anti-tumor effects, liver protection, inhibition of apoptosis, and alleviation of inflammation. However, whether it has anti-aging effects remains unclear. The SIL dietary supplement to Drosophila melanogaster prolonged lifespan, improved climbing ability, ameliorated age-associated intestinal barrier disruption, enhanced the resistance to oxidative stress, and increased the enzyme activities of superoxide dismutase (SOD) and catalase (CAT). Furthermore, RNA-seq results showed that SIL addition significantly upregulated 74 genes and downregulated 50 genes compared with the control. KEGG (Kyoto Encyclopedia of genes and genomes) analysis demonstrated that these differentially expressed genes were primarily involved in the Toll signaling pathway and endoplasmic reticulum proteins processing, six among which, including IM2, IM3, Drsl3, CG7556, GCS1, and TRAM, were particularly involved in the regulation by SIL supplementation. The results indicate that SIL exhibits anti-aging effects by enhancing antioxidant capacity and regulating aging-related signaling pathways. Therefore, SIL shows a potential application in anti-aging dietary regimens.

Injectable, Biodegradable and Photothermal Hydrogel with Quorum Sensing Inhibitory Effects for Subcutaneous Fungal Infection Treatment.

Owing to the high invasion depth and easy formation of biofilms, the treatment of subcutaneous fungal infection is intractable and challenging. Herein, we report an injectable and biodegradable hydrogel with bactericidal, quorum sensing inhibition and antioxidant activities for the in situ treatment of subcutaneous fungal infection. The hydrogel (BEPE) was constructed by irradiating mixed bovine serum albumin (BSA), ε-polylysine and epigallocatechin gallate (EGCG)-loaded mesoporous polydopamine (PDA) under near-infrared (NIR) light. BEPE exerted microbicidal effects against Candida albicans (99.5%) and Streptococcus mutans (99.6%) through synergistic photothermal effects and the microbiocidal activity of slowly released ε-polylysine. Moreover, the gently released EGCG from BEPE with relatively high bioavailability, synergistically inhibited and destroyed biofilms by inhibiting quorum sensing between microbes, resulting in an antibiofilm efficiency of 80.5% against C. albicans. An in vivo subcutaneous fungal infection study revealed that BEPE accelerates tissue regeneration via targeted formation, elimination of fungal infection and alleviation of inflammation in situ, thereby promoting wound healing. This biodegradable hydrogel strategy will facilitate the design of multifunctional microbicidal agents for targeted subcutaneous fungal infection treatment.

Anti-oxidation enhancement, inflammation alleviation, and microbial composition optimization of using tussah (Antheraea pernyi) silk fibroin peptides for hyperglycaemia remission.

This study aimed to evaluate the positive effects on anti-oxidation, anti-inflammation, and microbial composition optimization of diabetic mice using tussah (Antheraea pernyi) silk fibroin peptides (TSFP), providing the theoretical foundation for making the use of silk resources of A. pernyi and incorporating as a supplement into the hypoglycemic foods. The animal model of diabetes was established successfully. Alloxan-induced diabetic mice were orally administered using TSFP, and the hypoglycaemic effects in vivo were systematically investigated. The results indicated that TSFP could significantly reduce the fasting blood glucose (FBG) levels and suppress the mRNA expression of glycometabolism genes of diabetic mice. In addition, the TSFP could ameliorate the lipid dysbolism and contribute to a higher anti-oxidation capacity. Moreover, TSFP could alleviate pathological damages and hinder inflammatory processes of diabetic mice. Besides, the supplementation of TSFP presented a greater ability to shape and optimize the gut microbial composition by enriching the profitable bacteria and inhibiting the pathogenic microorganisms. Correlation analysis also revealed that the abundances of functional bacteria in the TSFP-treated groups exhibited better correlations with serum parameters, which would be of positive significance for blood glucose regulation and inflammation remission. These results collectively corroborated the feasibility and superiority of using TSFP for hyperglycaemia remission via anti-oxidation enhancement, inflammation alleviation, and microbial composition optimization, contributing to a safely feasible and biologically efficient strategy for improving anti-diabetic effects.

Antihypertensive effects of rice peptides involve intestinal microbiome alterations and intestinal inflammation alleviation in spontaneously hypertensive rats

Gut dysbiosis serves as an underlying factor for the development of hypertension. The restoration of this dysbiosis has emerged as a promising strategy in improving hypertension. Food-derived bioactive protein peptides...

A One-Stone-Two-Birds Strategy for Intervertebral Disc Repair: Constructing a Reductive Chelation Hydrogel to Mitigate Oxidative Stress and Promote Disc Matrix Reconstruction.

Intervertebral disc degeneration (IVDD) is characterized by fibrosis of nucleus pulposus (NP) cells and accelerated surrounding extracellular matrix catabolism. Bioactive hydrogels have shown significant potential in regulating cellular functions and tissue homeostasis. In this work, a dynamic hydrogel (HA-NCSN/Cu) is designed via the reductive chelation of hyaluronic acid grafted with thiourea (HA-NCSN) and Cu2+. The reductivity of the grafted thiourea groups of HA-NCSN can quickly reduce part of the chelated Cu2+ to Cu+. Therefore, during the gelation process, the color of hydrogel become dark immediately, which endowed hydrogel with remarkable photothermal effect. The abundant thiourea groups inside hydrogel can effectively scavenge reactive oxygen species to mitigate the inflammatory stress of NP cells. RNA sequencing analysis further reveals that glutathione signaling pathway is significantly altered. Meanwhile, mild photothermal therapy could activate the TGF-β/Smad pathway in NP cells, promoting the expression and secretion of Aggrecan and Collagen II. Ultimately, the combined modulation of inflammation alleviation and matrix regeneration achieves the restoration of the structure and function of the damaged intervertebral disc, which is also strongly demonstrated by the in vivo animal experiments. All of these results demonstrate the great potential of the dynamic HA-NCSN/Cu hydrogel in IVDD treatment.

Evaluation of gastric tolerability for long-term use of diclofenac and celecoxib in male albino rats and potential gastroprotective benefits of royal jelly: a randomized controlled trial.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for pain and inflammation relief. Our study aimed to explore the ulcerogenic effect of long-term diclofenac and celecoxib administration on male albino stomachs, focusing on the possible gastroprotective effect of royal jelly administration. Five equal groups of 50 male albino rats. The drug dosages were: diclofenac potassium (10 mg/kg/day), celecoxib (50 mg/kg/day), and RJ (300 mg/kg/day), for 4weeks. Group 1 received no medication. Group 2 received oral diclofenac potassium. Group 3 received oral RJ plus diclofenac potassium. Group 4 received celecoxib orally. Group 4 received oral RJ plus celecoxib. When the experiment was over, rats were euthanized, blood samples were gathered, and stomachs were dissected out. Stomachs were examined for ulcer counts. Serum levels of MDA and SOD were determined. Gastric mucosa contents of MDA, SOD, PGE2, MPO, apoptotic (Bax), and anti-apoptotic (Bcl-2) genes were measured. Gastric tissue was also analyzed histopathologically. Long-term administration of diclofenac and celecoxib, in such dose and duration, caused each of the aforementioned parameters to significantly deteriorate, with significant improvement with RJ co-administration. Diclofenac developed severe gastric ulcers in group 2, and RJ co-administration significantly reduced the gastric mucosa damage in group 3. Celecoxib developed no gastric ulcer in both groups 4 and 5. Long-term use of diclofenac in male albino rats caused severe gastric ulcers with significant gastroprotective effects of RJ.Celecoxib provides preferable GI tolerability; thus, it should be prescribed for patients at increased risk of gastrointestinal bleeding requiring NSAIDs.

SGLT2 inhibitors for alleviating heart failure through non-hypoglycemic mechanisms

Sodium-glucose cotransporter-2 (SGLT2) inhibitors afford significant cardiovascular benefits to patients with diabetes mellitus and heart failure. Three large randomized clinical trials (EMPAREG-Outcomes, DECLARE-TIMI58, and DAPA-HF) have shown that SGLT2 inhibitors prevent cardiovascular events and reduce the risk of death and hospital admission resulting from heart failure. Patients without type 2 diabetes mellitus (T2DM) also experience a similar degree of cardiovascular benefit as those with T2DM do. SGLT2 inhibitors could improve cardiac function through potential non-hypoglycemic mechanisms, including the reduction of the circulatory volume load, regulation of energy metabolism, maintenance of ion homeostasis, alleviation of inflammation and oxidative stress, and direct inhibition of cardiac SGLT1 receptors and antimyocardial fibrosis. This article reviews the mechanism through which SGLT2 inhibitors prevent/alleviate heart failure through non-hypoglycemic pathways, to support their use for the treatment of heart failure in non-T2DM patients.

Effective Antiviral Therapy Improves Immunosuppressive Activities in the Immune Microenvironment of Hepatocellular Carcinoma by Alleviating Inflammation and Fibrosis.

The immune microenvironment (IME) plays a crucial role in the progression of hepatocellular carcinoma (HCC). In HCC, the IME is often compromised by hepatitis B virus (HBV) infection, chronic inflammation, and fibrosis. Both antiviral therapy (AVT) and the alleviation of inflammation and fibrosis (AIF) have been shown to improve prognosis. However, the relationship among the IME of HCC, AVT, and AIF remains unclear. A total of 140 and 110 primary HBV-related HCC patients were enrolled as training and validation sets, respectively, to establish a HCC-immune microenvironment score (H-IME score). Immunohistochemistry was performed to assess the number of granzyme B+ (GrB+) and Foxp3+ cells, as well as the expression of CTLA-4, PD-1, LAG3, TIGIT, TIM3, and VISTA. Another cohort consisting of 114 recurrent HBV-related HCC patients with paired primary and recurrent tissues was used to study the relationship among the IME of HCC, AVT, and AIF. The H-IME score, including GrB, Foxp3, CTLA-4, PD-1, LAG3, and TIGIT, was established to evaluate the IME. A higher H-IME score indicates stronger immunosuppressive activities. Both AVT and AIF were found to inhibit immunosuppressive activities in the IME. Compared to primary tumors, the H-IME scores of recurrent tumors in the effective AVT group (e-AVT, classified by HBV DNA) with AIF decreased, while the scores increased in the non-AVT group without AIF. The IME of HCC is closely related to AVT and AIF. e-AVT can enhance anti-tumor activities in the IME by alleviating inflammation and fibrosis.

Treatment of ulcerative colitis via the in situ restoration of local immune and microbial homeostasis by oral administration of Tremella polysaccharide drug-carrying hydrogel

Ulcerative colitis (UC) is a prevalent inflammatory bowel disease, and conventional treatments, such as anti-inflammatory medications and surgery, often prove inadequate due to frequent recurrences and various complications. To alleviate patient suffering, there is an urgent need for a therapeutic system that specifically delivers drugs to the colon for wound healing, inflammation relief, and restoration of microbial homeostasis. In this paper, we developed a Tremella polysaccharide drug-carrying hydrogel that adheres to the inflamed colonic mucosa, forming an effective artificial barrier and releasing the drug in situ to restore local immune and microbial balance. The hydrogel backbone was synthesized through the chemical cross-linking of Tremella polysaccharide with 1,4-butanediol diglycidyl ether in an alkaline environment. During this process, Soluplus® and TPGS-encapsulated ginsenoside compound K adhered to the hydrogel backbone due to electrostatic attraction. The enhanced adhesion following cross-linking enables the hydrogel to stably attach to the inflamed colonic mucosa, releasing mixed micelles that improve drug penetration and absorption by inhibiting the cellular efflux protein P-glycoprotein. This mechanism promotes local immune recovery and eliminates harmful intestinal flora, providing significant relief from UC symptoms. This natural polysaccharide-based hydrogel represents a highly effective oral treatment for UC.

Synergistic effects of dietary Forsythia suspensa extract and Astragalus membranaceus polysaccharides on growth enhancement, antioxidant boost, and inflammation alleviation in juvenile Larimichthys crocea

Synergistic effects of dietary Forsythia suspensa extract and Astragalus membranaceus polysaccharides on growth enhancement, antioxidant boost, and inflammation alleviation in juvenile Larimichthys crocea

Inhalation of macrophage membrane-coated hydrogel microparticles for inflammation alleviation of acute lung injury in vivo.

Hydrogel microparticles (HMPs) have many advantages for biomedical applications, particularly for minimally invasive therapy, for example, acute lung injury (ALI) that is characterized by high levels of reactive oxygen species (ROS) and pro-inflammatory mediators in the microenvironment. In this study, ROS-scavenging and pro-inflammatory cytokine-neutralizing HMPs were designed and prepared by using a membrane emulsification device. The HMPs were composed of double bond-modified hyaluronic acid and ROS-cleavable hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) containing thioketal linkages and unsaturated double bonds. Surface-coating of inflammatory macrophage (M1) cell membranes was performed to obtain the membrane-coated HBPAK HMPs (mem HMPs) via electrostatic force. The mem HMPs exhibited strong ROS-scavenging and anti-inflammatory properties both in vitro and in vivo. After administered by inhalation in an ALI mouse model, the mem HMPs reduced neutrophil infiltration and tissue oxidative damage, thereby alleviating lung inflammation. Our results suggest that the mem HMPs could serve as a potential therapeutic platform for treating inflammatory diseases with high efficiency. STATEMENT OF SIGNIFICANCE: Hydrogel microparticles (HMPs) with minimally invasive delivery are advantageous for acute lung injury (ALI) characterized by high levels of reactive oxygen species (ROS) and pro-inflammatory mediators. Herein, ROS-scavenging and pro-inflammatory cytokine-neutralizing HMPs were prepared by copolymerizing double bond-modified hyaluronic acid and ROS-cleavable hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) containing thioketal bonds and unsaturated double bonds in a membrane emulsification device. The HMPs covered with inflammatory macrophage (M1) cell membranes (mem HMPs) exhibited strong ROS-scavenging and anti-inflammation properties, reduced neutrophil infiltration and tissue oxidative damage, thereby alleviating lung inflammation.

NK cell-derived exosomes inhibit survival of Mycobacterium tuberculosis by promoting apoptosis in mice

AimTo investigate anti-Mycobacterium tuberculosis (Mtb) influences exerted by natural killer cell-derived exosomes (NK-exo) on mice and to elucidate underlying immunologic mechanisms. MethodsWe established tuberculosis (TB) model in mouse by injecting Mtb H37Ra (1 × 106 colony counting (CFU), i.v.) into tail vein for 14 days. The survival rate of Mtb was assessed through CFU, apoptosis rates were measured utilizing flow cytometry, and inflammation relief was quantified via HE staining. Expressions of apoptosis, inflammation, and pyroptosis-related proteins were quantified by Western blotting and RT-qPCR. ELISA was utilized for detecting inflammatory cytokines production. Intracellular reactive oxygen species (ROS) levels were assessed through DCFH-DA fluorescent probe assay. ResultsNK-exo treatment reduced Mtb load in lung and spleen tissues and alleviated inflammation in mice lung tissues. NK-exo intervention increased protein levels of markers associated with apoptosis, PARP and caspase-3/8/9, downregulating the concentrations of pro-inflammatory cytokines, comprising IL-1β, TNF-α, IL-6, along with protein expressions of biomarkers, ASC, NLRP3, GSDMD, associated to inflammation and pyroptosis. NK-exo also elevated ROS levels without affecting lactate dehydrogenase (LDH) release from macrophages. ConclusionNK-exo exhibits anti-tuberculosis activity in experimental TB mice. The underlying mechanism involve regulating caspase-dependent apoptotic signaling pathway to promote cell apoptosis, as well as modulating NLRP3 signaling pathway to suppress the inflammatory response.

Protective Role of Indole-3-Acetic Acid Against Salmonella Typhimurium: Inflammation Moderation and Intestinal Microbiota Restoration.

Indole-3-acetic acid (IAA), a metabolite derived from microbial tryptophan metabolism, plays a crucial role in regulating intestinal homeostasis. However, the influence and potential applications of IAA in the context of animal pathogen infections remain underexplored. This study investigates the prophylactic effects of IAA pretreatment against Salmonella typhimurium (ST) SL1344 infection, focusing on its ability to attenuate inflammatory responses, enhance intestinal barrier integrity, inhibit bacterial colonization, and restore colonic microbiota dysbiosis. The results demonstrated that IAA ameliorated the clinical symptoms in mice, as evidenced by reduced weight loss and histopathological damage. Furthermore, IAA inhibited the inflammatory response by downregulating the gene expression of pro-inflammatory cytokines IL-17A, TNF-α, IL-1β, and IL-6 in colon, ileum, and liver. IAA also preserved the integrity of the intestinal mucosal barrier and promoted the expression of tight junction proteins. Additionally, 16S rRNA gene sequencing revealed significant alterations in intestinal microbiota structure induced by ST infection following IAA treatment. Notable changes in β diversity and species richness were characterized by the enrichment of beneficial bacteria including Bacteroideaceae, Spirillaceae, and Bacillus. The proliferation of Salmonella enterica subspecies enterica serovar Typhi was significantly inhibited, thereby enhancing the intestinal health of the host. In summary, the oral administration of IAA contributes to the alleviation of inflammation, restoration of the intestinal barrier, and correction of colonic microbiota disturbance in mice challenged with ST.

Bacteriocin Microcin J25’s antibacterial infection effects and novel non-microbial regulatory mechanisms: differential regulation of dopaminergic receptors

BackgroundThe antibacterial and immunomodulatory activities of bacteriocins make them attractive targets for development as anti-infective drugs. Although the importance of the enteric nervous system (ENS) in the struggle against infections of the intestine has been demonstrated, whether it is involved in bacteriocins anti-infective mechanisms is poorly defined.ResultsHere, we demonstrated that the bacteriocin Microcin J25 (J25) significantly alleviated diarrhea and intestinal inflammation in piglets caused by enterotoxigenic Escherichia coli (ETEC) infection. Mechanistically, macrophage levels were significantly downregulated after J25 treatment, and this was replicated in a mouse model. Omics analysis and validation screening revealed that J25 treatment induced significant changes in the dopaminergic neuron pathway, but little change in microbial structure. The alleviation of inflammation may occur by down-regulating dopamine receptor (DR) D1 and the downstream DAG-PKC pathway, thus inhibiting arachidonic acid decomposition, and the inhibition of macrophages may occur through the up-regulation of DRD5 and the downstream cAMP-PKA pathway, thus inhibiting NF-κB.ConclusionsOur studies’ findings provide insight into the changes and possible roles of the ENS in J25 treatment of ETEC infection, providing a more sophisticated foundational understanding for developing the application potential of J25.

Photobiomodulation Therapy at 660 nm Inhibits Hippocampal Neuroinflammation in a Lipopolysaccharide-Challenged Rat Model.

Neuroinflammation is associated with the progression of various brain diseases, and the management of neuroinflammation-induced neural damage is a crucial aspect of treating neurological disorders. This study investigated the anti-inflammatory efficacy of photobiomodulation therapy (PBMT) using 660 nm phototherapy in a rat model with lipopolysaccharide (LPS)-induced neuroinflammation. We induced inflammation in rat brains via intraperitoneal injection of LPS and subjected the treatment group to 660 nm phototherapy to examine its protective effect against hippocampal damage based on pathological, histological, and immunohistochemical tissue analyses. The 660 nm treated rats showed a significant decrease in hippocampal structural damage and cell death compared to the LPS-treated group. We observed reduced expression of the inflammation markers GFAP, TNF-α, and IL-1β in the hippocampus of the treatment group, and an increase in SIRT1 expression across all hippocampal regions. This study presents a promising method for controlling neuroinflammation and providing neuroprotection and inflammation relief. PBMT represents a non-invasive therapeutic approach with minimal side effects ensured through the proper control of light irradiation.

Determination of proinflammatory cytokine levels to assess the reparative potential of tissues in ischemic damage and local correction with hyaluronic acid

The hypothesis of the study was the assumption that local correction of secondary alteration stops excessive inflammation activity and promotes early activation of reparative processes. Objective: in an animal experiment, to evaluate the dynamics in blood plasma of the concentration of circulating inflammatory cytokines in acute ischemic damage to soft tissues and after local action of a hyaluronic acid-based drug. In anesthetized Wistar rats, acute ischemic damage to the soft tissues of the thigh was simulated by mechanical compression with a vise for 7 hours. After removing the vise, the rats were divided into 2 groups of 32 individuals: control (without treatment) and experimental (3 hours after removing the vise, the drug was injected into the area bordering the compression zone with a sterile syringe based on hyaluronic acid “Hyalift-3.5”, diluted with 0.9% solution to the final concentration of the drug – 1.75%). The concentration of cytokines in blood plasma was determined, histological sections of soft tissues in the compression area were examined. An increase in the plasma concentration of proinflammatory cytokines (IL-1β, TNFα, IL-6) was revealed during the entire follow-up period (21 days), especially 7 days after the injury. To the greatest extent, these changes were observed in animals in the control group, which was manifested by a statistically significant increase in the concentration of IL-1β, TNFα and IL-6, relative to the values in intact rats: on average by 7.2; 3.7 and 5.3 times, respectively. In rats in the experimental group, local administration of a hyaluronic acid-based drug already in the early period after injury limited the severity of inflammation (an increased concentration of IL-10 was recorded in blood plasma). The sanogenetic role of local administration of hyaluronic acid in the wound process is mediated by the relief of inflammation in the early period of damage and is realized in increasing the reparative potential of tissues according to the variant of earlier and significant formation of musculoskeletal tissue regenerates.

Astragaloside promotes the secretion of MSC-derived exosomal miR-146a-5p by regulating TRAF6/NF-κB pathway to attenuate inflammation in high glucose-impaired endothelial cells.

This study aimed to explore the potential of using mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos) pre-treated with Astragaloside IV (ASIV) to alleviate inflammation in high glucose (HG)-damaged endothelial cells. MSC-Exos were isolated from untreated MSCs and ASIV-pre-treated MSCs, and their characteristics were assessed. The expression of miR-146a-5p in MSC-Exos was determined, and it was found that ASIV treatment enhanced its expression. In order to assess the impact of highly miR-146a-5p-expressing MSC-Exos on HG-injured endothelial cells, we established a model of HG-induced inflammation using human umbilical vein endothelial cells (HUVECs). The study measured cell viability, apoptosis, tube formation, and levels of inflammatory cytokines among the different treatment groups. It was found that transferring MSC-Exos with high miR-146a-5p expression to HG-damaged HUVECs increased cell viability and tube formation ability while reducing the number of apoptotic cells. Additionally, changes in inflammatory factors indicated a reduction in the inflammatory response. Further investigation demonstrated that miR-146a-5p inhibited the expression of TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB, which are involved in the inflammatory response. This resulted in the alleviation of inflammation in HG-damaged endothelial cells. In summary, our findings indicate that ASIV treatment stimulated the secretion of MSC-Exos that exhibited increased levels of miR-146a-5p. These exosomes, in turn, regulated the TRAF6/NF-κB pathway. As a result of this modulation, the inflammatory response in HG-damaged endothelial cells was alleviated. These findings offer a fresh approach to addressing vascular complications associated with diabetes, which could lead to novel treatment strategies in the field.

Использование раствора факторов роста из активированных тромбоцитов при термической ожоговой травме глаза в эксперименте

Relevance. One of the possible ways to accelerate the reparation and the regeneration of the damaged cornea in the early stages of burn disease is the use of the drugs containing biologically active substances secreted by cells. Purpose. To evaluate the effect of a solution of growth factors from activated platelets on the reparative properties of the cornea of rats with thermal eye burn by flame. Material and methods. An experimental study was conducted on 40 rats (40 eyes). A solution of growth factors from activated platelets (LLC Melsytech, Dzerzhinsk) was used as local therapy for burns in the main group (20 eyes), and a solution of 0.9% NaCl was used in the control group (20 eyes). The condition of the eyes was assessed using anterior segment optical coherence tomography, biomicroscopy and histological examination. Corneal gene expression was determined by real-time polymerase chain reaction (qPCR). Results. On the 18th day after the burn in the rats of the main group, the central corneal thickness (CCT) was 126 µm [103; 146] and did not significantly differ from the baseline values (p=0.477); in the control group, the CCT reached 222 µm [98; 308], which was statistically significantly higher than the preburn values (p=0.027). Corneal perforation occurred in 3 eyes of the main group (18.75%) and 9 eyes of the control group (56.25%) (p=0.038). Histological examination revealed a relatively low intensity of proliferative response, including the absence of excessive neovascularization and moderately expressed inflammatory manifestations in the eyes of the main group; in the control group, the progressive destructive process was accompanied by expressed secondary proliferative changes and reactive intraocular inflammation. According to qPCR data, the MMP2and VEGFgenes showed increased expression in the control group compared with the main group (p=0.001 and p=0.010, respectively). Conclusion. The use of a solution of growth factors from activated platelets in thermal burns accelerates the relief of inflammation in the cornea and ocular structures, reduces neovascularization and prevents excessive stroma lysis by suppressing the expression of VEGFand MMP2genes, which leads to a clinically significant effect of reducing the frequency of corneal perforations in the experiment. Key words: thermal burn, eye burn, cornea, growth factors, gene expression, corneal perforation

Silk Sericin‐based ROS‐Responsive Oxygen Generating Microneedle Platform Promotes Angiogenesis and Decreases Inflammation for Scarless Diabetic Wound Healing

AbstractDiabetic foot ulcer typically undergoes a delayed wound‐healing process owing to the disordered microenvironment, including persistent inflammation, long‐term hypoxia, and excessive fibrosis, eventually leading to severe disabilities and other poor outcomes. However, current strategies cannot meet the dynamic demands during the wound‐healing process. Herein, a reactive oxygen species (ROS)–responsive oxygen‐generating microneedle platform, consisting of a sericin‐based glucose‐responsive hydrogel loaded with verteporfin, for effective diabetic wound healing is proposed. Under a highly oxidative microenvironment, the functionalized sericin protein depletes overproduced ROS to generate oxygen, which can not only alleviate the hypoxic microenvironment and promote angiogenesis by activating extracellular signal‐regulated kinase and Heme Oxygenase‐1 pathways but also decrease the expression of proinflammatory cytokines. Moreover, the hyperglycaemic condition triggers the gradual dissociation of this microneedle platform and promotes the release of verteporfin to enhance scarless re‐epithelization via inhibiting the yes‐associated protein signal. This versatile sericin microneedle system integrates advantageous features including inflammation alleviation, angiogenesis promotion, and scar inhibition capabilities, accelerates diabetic wound repair in vivo, and offers a novel approach for oxygen self‐supply and wound microenvironment remodeling.