Anti-inflammatory Characteristics Research Articles

Lecithin-complexed oregano essential oil-encapsulated fibrous barriers prevent postoperative adhesions by regulating Nrf2/NF-κB signaling pathways

Postoperative adhesions are prone to a variety of complications, which can adversely affect the quality of life (QOL) of patients. While anti-adhesion scaffolds rapidly degrade, foreign body reactions (FBR), exaggerated inflammatory reactions, and oxidative stress may increase tissue adhesions. This necessitates the development of anti-adhesion scaffolds with multifunctional anti-inflammatory, anti-bacterial, and anti-oxidative characteristics. The objective of this study was to simultaneously leverage natural antimicrobial and anti-oxidative bioactive molecules, such as lecithin (L) and Oregano essential oil (O) to afford poly(lactic-co-glycolic acid) (PLGA)-based electrospun membranes for postoperative anti-adhesion management. A series of assays revealed a beneficial effect of L and O co-loaded membranes (P@LO) to suppress bacterial growth, reduce the proliferation of fibroblasts, and confer anti-oxidative and anti-inflammatory functionalities to membranes than that of the control (P) or only a single cue-loaded groups (P@L and P@O). The underlying molecular mechanism of the anti-inflammatory effect may be an upregulation of the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation. An assessment of membranes in an abdominal and a tendon adhesion model showed a significant effect of P@LO membranes to prevent post-operative tissue adhesion. The P@LO membranes were found to up-regulate the phosphorylation of Nrf2 while down-regulate the phosphorylation of nuclear factor kappa-B (NF-κB) P65. This resulted in lower expression of collagen Ⅰ (Col-Ⅰ), collagen Ⅲ (Col-Ⅲ), and alpha-smooth muscle actin (α-SMA) alongside inflammation resolution and less transition of fibroblasts to myofibroblasts. Taken together, these multifunctional scaffolds may have broad implications for postoperative adhesion management.

GLP-1/GIP Agonist as an Intriguing and Ultimate Remedy for Combating Alzheimer's Disease through its Supporting DPP4 Inhibitors: A Review.

Alzheimer's disease (AD) is a widespread neurological illness in the elderly, which impacted about 50 million people globally in 2020. Type 2 diabetes has been identified as a risk factor. Insulin and incretins are substances that have various impacts on neurodegenerative processes. Preclinical research has shown that GLP-1 receptor agonists decrease neuroinflammation, tau phosphorylation, amyloid deposition, synaptic function, and memory formation. Phase 2 and 3 studies are now occurring in Alzheimer's disease populations. In this article, we present a detailed assessment of the therapeutic potential of GLP-1 analogues and DPP4 inhibitors in Alzheimer's disease. This study aimed to gain insight into how GLP-1 analogues and associated antagonists of DPP4 safeguard against AD. This study uses terms from search engines, such as Scopus, PubMed, and Google Scholar, to explore the role, function, and treatment options of the GLP-1 analogue for AD. The review suggested that GLP-1 analogues may be useful for treating AD because they have been linked to anti-inflammatory, neurotrophic, and neuroprotective characteristics. Throughout this review, we discuss the underlying causes of AD and how GLP signaling functions. With a focus on AD, the molecular and pharmacological effects of a few GLP-1/GIP analogs, both synthetic and natural, as well as DPP4 inhibitors, have been mentioned, which are in the preclinical and clinical studies. This has been demonstrated to improve cognitive function in Alzheimer's patients.

Systemic Inflammation in Oncologic Patients Undergoing Systemic Treatment and Receiving Whey Protein-Based Nutritional Support

There is increasing evidence about the role of inflammation in sarcopenia and tumor progression; thus, its modulation would represent a valuable strategy for improving clinical outcomes in patients with cancer. Several studies have reported that whey protein has significant anti-inflammatory and antioxidant characteristics in humans. We aimed to evaluate the effects of whey protein-based oral nutritional support on circulating cytokines in patients with solid tumors undergoing systemic treatment. Forty-six patients with solid tumors of different origin and undergoing systemic treatment were evaluated. Nutritional support with two daily whey protein-based oral supplements was administered. Circulating levels of IL-6, IL-8, IL-10, MCP-1 and IP-10 were determined. Nutritional evaluation included anthropometric, instrumental and biochemical parameters. Over 63% of the evaluated patients underwent surgery, 56.5% required chemotherapy and almost 50% received combined treatment. Patients with resected primary tumor presented with lower baseline IL-6 (p < 0.05) and IP-10 (p < 0.001); after three months of nutritional support, they presented with lower IL-8 (p < 0.05) and tended to present lower IL-6 and IP-10 (p = 0.053 and 0.067, respectively). Significant positive correlations between circulating cytokines, C-reactive protein and ferritin were observed; similarly, negative correlations with anthropometric and biochemical nutritional parameters were noticed (p < 0.05). We did not observe significant changes in circulating cytokine levels (IL-6, IL-8, IL-10, MCP-1 and IP-10) in patients with cancer undergoing systemic treatment after three months of nutritional support with whey protein-based oral supplements. According to a univariate analysis in our cohort, circulating IL-8 was associated with mortality in these patients, additionally, MCP-1 and IP-10 tended to correlate; but an age- and sex-adjusted multivariate analysis revealed that only baseline MCP-1 was significantly associated with mortality (OR 1.03 (95% CI: 1.00–1.05)). In conclusion, surgery of the primary solid tumor and combination treatment allow significant reduction in circulating cytokine levels, which remained stable while patients received nutritional support with whey protein-based oral supplements over three months. The role of MCP-1 as an independent factor for mortality in these patients should be further evaluated.

Investigation of potential effects of quercetin on COVID-19 treatment: a systematic review of randomized controlled trials

Objectives: The COVID-19 pandemic has rapidly become a global health crisis. Currently, there are no proven, reliable, specific treatments for COVID-19. Alongside drug interventions, supportive treatments are implemented during the disease. Quercetin, recognized for its antiviral, anti-inflammatory, anti-aging, and antioxidant properties, is under evaluation in this study for its potential impact on preventing, influencing the course, and mitigating the severity of COVID-19. Methods: A thorough search was conducted across scientific databases, including PubMed, Embase, Web of Science, SAGEpub, Copernicus, Cochrane Library, ScienceDirect, Elsevier, Scopus, Google Scholar, EBSCOhost, Crossref, Ovid-LWW, and DergiPark databases, between 1 November 2021 and 1 April 2022 to ensure a comprehensive inclusion of relevant studies. Results: Thirteen randomized controlled clinical trials (five published, eight unpublished) were identified. Existing literature supports quercetin’s role as a potent free radical scavenger with robust antioxidant properties. It exhibits anti-inflammatory characteristics by inhibiting lipid peroxidation and restraining pro-inflammatory enzymes such as lipoxygenase and phospholipase A2. Scholarly discourse suggests that quercetin supplementation within the 500-1500 mg range leads to favorable outcomes, including quicker patient discharge, reduced inflammation, increased respiratory rate, accelerated viral clearance, and an improved disease prognosis. However, it is noted that intervention durations vary across studies. Conclusions: The analysis of the studies suggested that quercetin is a promising therapeutic agent that can cause a decrease in disease symptoms, frequency of hospitalization, hospital stay, need for non-invasive oxygen treatment, need for intensive care, and mortality. Nonetheless, more clinical studies are needed to better understand quercetin’s curative effects on COVID-19 infection.

Effect of a high dose atorvastatin as added-on therapy on symptoms and serum AMPK/NLRP3 inflammasome and IL-6/STAT3 axes in patients with major depressive disorder: randomized controlled clinical study

BackgroundNeuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been demonstrated to have significance in the pathophysiology of depression.AimTo investigate the mechanistic pathways of high dose atorvastatin in MDD.Patients and methodsThis trial included 60 patients with MDD who met the eligibility requirements. Two groups of patients (n = 30) were recruited by selecting patients from the Psychiatry Department. Group 1 received 20 mg of fluoxetine plus a placebo once daily. Group 2 received fluoxetine and atorvastatin (80 mg) once daily. All patients were assessed by a psychiatrist using the Hamilton Depression Rating Scale (HDRS). A HDRS score of ≤7 indicates remission or partial remission [HDRS<17 and>7]. Response was defined as ≥ 50% drop in the HDRS score. The serum concentrations of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3), interleukin-6 (IL-6), adenosine monophosphate activated protein kinase (AMPK), and signal transducer and activator of transcription factor-3 (STAT-3) were measured.ResultsThe atorvastatin group showed a significant reduction in the levels of all measured markers along with a statistical increase in the levels of AMPK when compared to the fluoxetine group. The atorvastatin group displayed a significant decrease in HDRS when compared to its baseline and the fluoxetine group. The response rate and partial remission were higher in the atorvastatin group than fluoxetine (p = 0.03, and p = 0.005), respectively.ConclusionThese results imply that atorvastatin at high doses may be a promising adjuvant therapy for MDD patients by altering the signaling pathways for AMPK/NLRP3 and IL-6/STAT-3.Clinical Trial Registrationclinicaltrials.gov, identifier NCT05792540.

#207 Early single session of hyperbaric oxygen therapy mitigates renal apoptosis in lipopolysaccharides-induced endotoxemia in rats

Abstract Background and Aims Sepsis-associated acute kidney injury (SA-AKI) is a prominent sepsis complication, often having adverse clinical outcomes. Hyperbaric oxygen therapy (HBOT), known for its anti-inflammatory characteristics, antioxidant effects, and ability to deliver high oxygen tension to hypo-perfused tissues, may offer potential benefits for SA-AKI. This study investigated whether HBOT improved renal injury in sepsis and elucidated its underlying mechanisms. Method An lipopolysaccharides (LPS)-induced endotoxemia model was established using eight-week-old C57BL/6 mice. Thirty minutes post-LPS administration, a subset of mice underwent HBOT at a 2.5 atmospheric pressure absolute with 100% oxygen for 60 minutes. After 24 hours, all mice were euthanized for measurements. Results Our results demonstrated that HBOT effectively mitigated renal tubular cell apoptosis, as evidenced by decreased apoptosis-associated proteins, including Bax/Bcl-2 and cleaved caspase 3/caspase 3 ratios. HBOT significantly reduced phosphorylated p53 proteins and cytochrome C levels, suggesting that HBOT may attenuate renal apoptosis through decreased p53 activation and cytochrome C release. Notably, HBOT preserved manganese-dependent levels of superoxide dismutase, an antioxidant enzyme, compared to the LPS group. Furthermore, transforming growth factor-β (TGF- β)/Smad4 and alpha-smooth muscle actin expressions were significantly reduced in the LPS+HBOT group. Conclusion An early single session of HBOT exhibited renoprotective effects in LPS-induced endotoxemia mice models by mitigating apoptosis by suppressing p53 activation and cytochrome C levels. The observed TGF-β decrease, downstream Smad expression reduction, and antioxidant capacity preservation following HBOT may contribute to these effects.

Comparative Metabolome and Transcriptome Analyses Reveal Differential Enrichment of Metabolites with Age in Panax notoginseng Roots

Panax notoginseng is a perennial plant well known for its versatile medicinal properties, including hepatoprotective, antioxidant, anti-inflammatory, anti-tumor, estrogen-like, and antidepressant characteristics. It has been reported that plant age affects the quality of P. notoginseng. This study aimed to explore the differential metabolome and transcriptome of 2-year (PN2) and 3-year-old (PN3) P. notoginseng plant root samples. Principal component analysis of metabolome and transcriptome data revealed major differences between the two groups (PN2 vs. PN3). A total of 1813 metabolites and 28,587 genes were detected in this study, of which 255 metabolites and 3141 genes were found to be differential (p < 0.05) between PN2 vs. PN3, respectively. Among differential metabolites and genes, 155 metabolites and 1217 genes were up-regulated, while 100 metabolites and 1924 genes were down-regulated. The KEGG pathway analysis revealed differentially enriched metabolites belonging to class lipids (“13S-hydroperoxy-9Z, 11E-octadecadionic acid”, “9S-hydroxy-10E, 12Z-octadecadionic acid”, “9S-oxo-10E, 12Z-octadecadionic acid”, and “9,10,13-trihydroxy-11-octadecadionic acid”), nucleotides and derivatives (guanine and cytidine), and phenolic acids (chlorogenic acid) were found to be enriched (p < 0.05) in PN3 compared to PN2. Further, these differentially enriched metabolites were found to be significantly (p < 0.05) regulated via linoleic acid metabolism, nucleotide metabolism, plant hormone signal transduction, and arachidonic acid metabolism pathways. Furthermore, the transcriptome analysis showed the up-regulation of key genes MAT, DMAS, SDH, gallate 1-beta-glucosyltransferase, and beta-D-glucosidase in various plants’ secondary metabolic pathways and SAUR, GID1, PP2C, ETR, CTR1, EBF1/2, and ERF1/2 genes observed in phytohormone signal transduction pathway that is involved in plant growth and development, and protection against the various stressors. This study concluded that the roots of a 3-year-old P. notoginseng plant have better metabolome and transcriptome profiles compared to a 2-year-old plant with importantly enriched metabolites and genes in pathways related to metabolism, plant hormone signal transduction, and various biological processes. These findings provide insights into the plant’s dynamic biochemical and molecular changes during its growth that have several implications regarding its therapeutic use.

Examining the oleoylethanolamide supplement effects on glycemic status, oxidative stress, inflammation, and anti-mullerian hormone in polycystic ovary syndrome

ObjectiveThis clinical trial was designed and conducted due to the anti-inflammatory potential of Oleoylethanolamide (OEA) to examine the effect of OEA supplement on glycemic status, oxidative stress, inflammatory factors, and anti-Mullerian hormone (AMH) in women with polycystic ovary syndrome (PCOS).MethodThis study was a randomized clinical trial, double-blinded, placebo-controlled that was carried out on 90 women with PCOS. Patients were divided into two groups: receiving an OEA supplement (n = 45) or a placebo (n = 45). The intervention group received 125 mg/day OEA and the placebo group received the wheat flour for 8 weeks. Demographic data were collected through questionnaires. Fasting blood sugar (FBS), insulin resistance (IR), total antioxidant capacity (TAC), malondialdehyde (MDA), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and AMH were measured before and after the study.ResultsData analysis of food recall and physical activity questionnaires, showed no significant differences between the two groups (p > 0.05). Biochemical factors including glycemic status, MDA, inflammatory factors, and AMH decreased significantly (p < 0.05). TAC increased remarkably (p < 0.05) in comparison between the two groups, after the intervention.ConclusionOEA supplement with anti-inflammatory characteristics could be efficient independent of diet changes and physical activity in improving disrupted biochemical factors, so both supplementation or food resources of this fatty acid could be considered as a compensatory remedy in patients with PCOS.Trial RegistrationThis study was retrospectively (09-01-2022) registered in the Iranian website (www.irct.ir) for registration of clinical trials (IRCT20141025019669N20).

Therapeutic Potential of Palmitoylethanolamide in Gastrointestinal Disorders.

Palmitoylethanolamide (PEA) is an endocannabinoid-like bioactive lipid mediator belonging to the family of N-acylethanolamines, most abundantly found in peanuts and egg yolk. When the gastrointestinal (GI) effects of PEA are discussed, it must be pointed out that it affects intestinal motility but also modulates gut microbiota. This is due to anti-inflammatory, antioxidant, analgesic, antimicrobial, and immunomodulatory features. Additionally, PEA has shown beneficial effects in several GI diseases, particularly irritable bowel syndrome and inflammatory bowel diseases, as various studies have shown, and it is important to emphasize its relative lack of toxicity, even at high dosages. Unfortunately, there is not enough endogenous PEA to treat disturbed gut homeostasis, even though it is produced in the GI tract in response to inflammatory stimuli, so exogenous intake is mandatory to achieve homeostasis. Intake of PEA could be through animal and/or vegetable food, but bearing in mind that a high dosage is needed to achieve a therapeutic effect, it must be compensated through dietary supplements. There are still open questions pending to be answered, so further studies investigating PEA's effects and mechanisms of action, especially in humans, are crucial to implementing PEA in everyday clinical practice.

Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale

BackgroundUmbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury.MethodsPreterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively.ResultsIn VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls.ConclusionsUCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.

E4BP4 in macrophages induces an anti-inflammatory phenotype that ameliorates the severity of colitis

Macrophages are versatile cells of the innate immune system that work by altering their pro- or anti-inflammatory features. Their dysregulation leads to inflammatory disorders such as inflammatory bowel disease. We show that macrophage-specific upregulation of the clock output gene and transcription factor E4BP4 reduces the severity of colitis in mice. RNA-sequencing and single-cell analyses of macrophages revealed that increased expression of E4BP4 leads to an overall increase in expression of anti-inflammatory genes including Il4ra with a concomitant reduction in pro-inflammatory gene expression. In contrast, knockout of E4BP4 in macrophages leads to increased proinflammatory gene expression and decreased expression of anti-inflammatory genes. ChIP-seq and ATAC-seq analyses further identified Il4ra as a target of E4BP4, which drives anti-inflammatory polarization in macrophages. Together, these results reveal a critical role for E4BP4 in regulating macrophage inflammatory phenotypes and resolving inflammatory bowel diseases.

Early pyridoxine administration rescues autism-like behavior in the BTBR T+tf/J autistic model

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social impairment and repetitive, stereotyped behaviors. An imbalanced oxidative stress status and neuroinflammation are involved in ASD development. In this study, we investigated the effects of pyridoxine, a form of vitamin B6 with potent anti-oxidant and anti-inflammatory features, on autism-like behavior in BTBR T + ltpr3tf/J (BTBR) mice, a model of autism. Mice received pyridoxine from postnatal days 7 to 14. Behavioral tests were conducted on 8-week-old male mice, and the inflammatory status and oxidative stress levels were also assessed in the mouse hippocampus. Postnatal pyridoxine treatment significantly improved social deficits, stereotyped behaviors, and cognitive deficits in BTBR mice. In addition, pyridoxine treatment alleviated neuroinflammation in the hippocampus manifested by reduced Iba1+ microglia and inflammatory factors, such as interleukin-1β (IL-1β), IL-6, TNF-α, and NF-κB. Further, pyridoxine-treated BTBR mice had elevated Nrf2 and HO-1 in the hippocampus. Postnatal pyridoxine administration might improve autistic-like behaviors in BTBR mice via attenuating oxidative stress and neuroinflammation in the hippocampus.

Sulforaphane (4-methylsulfnylbutyl isothiocyanate) mitigates gold nanoparticle induced brain toxicity in male albino rats

ObjectiveGold nanoparticles (GNPs) have shown great promise for a variety of biomedical applications; however, emerging evidence suggests that they exhibit toxic effects on different organs including the brain. Sulforaphane (SFN) is a naturally occurring compound derived from plants, which has been recognized for its impressive antioxidant, anticancer, and anti-inflammatory characteristics. The neuroprotective potential of SFN was assessed in this study to determine its effectiveness against GNP-induced toxicity in brain tissues. MethodsMale Wistar rats were administered GNPs daily, either alone or in combination with SFN, over a 7-day period. Inflammatory and oxidative stress markers including serotonin and Nrf2 levels were measured in brain tissues. Histological changes were assessed for GNP-mediated tissue damage. ResultsCompared with the control, GNP-treated rats exhibited a significant increase in brain inflammatory and oxidative stress (OS) markers including MDA, 8OHdG, and IL-6 and a significant decrease in Glutathione S-transferase, Glutathione reductase, SOD, Total antioxidant capacity, Nrf2, brain parameters (serotonin, dopamine, Gama Amino Butyric Acid) and Brain-derived neurotrophic factor. GNP treatment also resulted in marked histopathological changes in brain tissue. In addition, rats administered with combined GNP and SFN showed a significant reversal in the levels of these biomarkers. SFN also protected brain tissue from GNP-induced histopathological changes Molecular docking studies confirmed the competitive binding of SFN with GNPs to amino acid receptor proteins, 1MAH and 1KU6, which supports the experimental data. ConclusionCollectively, our findings indicate the neuroprotective capacity of SFN against GNP-induced brain damage, presumably by blocking OS and inflammation.

Surface modification of ZIF-8 nanoparticles by hyaluronic acid for enhanced targeted delivery of quercetin

Quercetin (QT) is a natural pharmaceutical substance with anti-inflammatory, antibacterial, and anti-cancer features. Nevertheless, it has low bioavailability, zeolitic-imidazolate framework-8 (ZIF-8) nanoparticles (NPs) with merits like very high surface area and porous nature are increasingly employed in the biomedical field as drug delivery system (DDS). Hyaluronic acid (HA) is a polymer that can be a smart “switch” and tumor-targeted “guider”, extending blood circulation, and improving the tumor-specific accumulation of DDS through CD44-mediated pathway. Herein, we have successfully synthesized HA-modified ZIF-8 NPs (ZIF-8/HA) for targeted delivery of QT. After characterization of synthesized materials by different advanced techniques, the QT loading capacity of ZIF-8 was investigated through different factors like initial QT concentration, solvent type, loading time and loading temperature. The release of QT in vitro was studied at pH values of 7.4 and 5.5 and ZIF-8 NPs decreased the release of QT at pH 7.4, demonstrating their ability to reduce QT loss during its distribution in blood. Also, HA-modified ZIF-8 resulted in enhanced compatibility, a decrease in toxicity to normal cells and an increase in targeted delivery of QT. Furthermore, the cytotoxicity of QT-loaded ZIF-8/HA on fibroblast cell lines (L929) as well as breast cancer cell lines (MCF-7) were evaluated. It was found that QT-loaded ZIF-8/HA not only led to a decrease in the toxicity of ZIF-8 and QT to normal cells in the body but also increased the toxicity of QT to cancer cells.

Tissue engineered multifunctional chitosan-modified polypropylene hernia mesh loaded with bioactive phyto-extracts

Surface modified tissue engineered polypropylene / PP hernia meshes were fabricated by incorporating Bacterial cellulose / BC and chitosan / CS and phytochemical extracts. Under current practice, hernia and other traumatic injuries to the abdominal organs are clinically treated with surgical meshes. Often the foreign body reaction and infections result in relapse in patients which dictates additional reparative surgical procedures and pain. To improve the outcome of clinical restorative procedures new biomaterials with improved characteristics are required. The functionalized meshes were physically and chemically characterized using SEM, mechanical testing, FTIR and XRD. The antimicrobial activity was qualitatively and quantitatively tested using E. coli and S. aureus strains of bacteria. In vitro biocompatibility and wound healing effect of the modified meshes were performed using NIH3T3 fibroblast cell lines. Furthermore, tissue engineering potential of the meshes was evaluated using confocal fluorescent microscopy. In vivo implantation of the meshes was performed in male wistar rats for 21 days. Therefore, PP meshes with sustained drug delivery system augmented with anti-inflammatory and anti-microbial characteristics were developed. The coatings hereby not only increased the tensile strength of meshes but also prevented the modified meshes from causing infection. Current study resulted in CS-BC bioactive PP meshes loaded with phytochemicals which showed anti-inflammatory, antibacterial and wound healing potential. These meshes can be valuable to lessen the post-surgical complications of implanted PP mesh and thus reduce rejection and recurrence.

Glycoprotein from Sargassum fusiforme exhibiting anti-inflammatory responses in vitro and in vivo via modulation of TLR4/MyD88 and NF-κB signaling

This study focuses on the identification and characterization of a glycoprotein from Sargassum fusiforme (Harvey) Setchell (SFGP), as well as investigating its potential anti-inflammatory properties both in vitro and in vivo, along with the underlying mechanism. SDS-PAGE analysis revealed a prominent band with a molecular weight of <10 kDa, consisting of 58.39 % protein and 41.61 % carbohydrates, which was confirmed through glycoprotein staining and Coomassie blue staining. Various analytical techniques, including high-resolution mass spectrometry (HRMS), FTIR, amino acid analysis, and UV–visible spectrometry, provided evidence for the presence of monosaccharides (such as d-glucose and mannose) and 17 amino acids linked by an O-glycopeptide bond.In vitro and in vivo studies were conducted to assess the anti-inflammatory activities of SFGP. The results demonstrated that SFGP effectively attenuated nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in LPS-treated RAW264.7 cells. Moreover, SFGP administration significantly and dose-dependently suppressed TLR4/MyD88 signaling as well as the phosphorylation of MAPKs, IκB, and NF-κB, leading to a reduction in the production of TNF-α, IL-1β, and IL-6 in LPS-stimulated RAW264.7 cells. Furthermore, the anti-inflammatory efficacy of SFGP was validated in a carrageenan-induced inflammatory mouse model. These findings indicate that SFGP exhibits anti-inflammatory characteristics and has the potential to be utilized as a novel anti-inflammatory agent.

Prussian blue nanoparticles coated with tumor cell membranes for precise photothermal therapy and subsequent inflammation reduction

The utilization of photothermal agents (PTAs) in photothermal therapy (PTT) is faced with challenges such as immune clearance and inadequate concentration, which consequently result in residual tumors and an increased risk of recurrence and metastasis. Conversely, excessive treatment can lead to heightened inflammation and inevitable harm to adjacent healthy tissues. To address these issues, we developed a nanosystem (M@PB) consisting of Prussian blue coated with tumor cell membrane for precise photothermal therapy (PTT) and subsequent reduction of inflammation. This system not only evades immune attack due to the homologous biological characteristics of the encapsulating cell membrane but also exhibits active targeting capabilities towards homologous tumors. Furthermore, it effectively reduces excessive phototoxicity by leveraging the distinctive photothermal and anti-inflammatory characteristics of PB nanoparticles. The resulting M@PB nanosystem demonstrates effective photothermal ablation under 808 nm laser irradiation while mitigating the inflammatory response through inhibiting of local production of inflammatory mediators. Our study provides valuable insights into achieving targeted PTT with high efficiency while minimizing post-treatment inflammatory responses.

Molecular Docking Analysis of Epigallocatechin 3- Gallate [EGCG] on Fatty Acids and Carnitine Transporters Family

EGCG is the main catechin present in green tea. Fatty acids can be categorized as saturated or unsaturated depending on the hydrocarbon chain and terminal carboxyl group they contain, typically with an even number of carbons. EGCG has attracted considerable interest because of its several health benefits, such as its anti-inflammatory, antioxidant, and anticancer characteristics. Yet, the precise molecular targets and mechanisms of action are not fully understood. Exploring the potential interaction of EGCG with fatty acids and carnitine transporters, which play a vital role in lipid metabolism and energy production, could provide insights into its physiological effects. Analysis of molecular docking between EGCG and fatty acid and carnitine transporters, and their interactions. A contact and binding occur between the fatty acid transporters (FABP) and VLCAD and CPTII. EGCG was subjected to molecular docking simulations with active sites of transporter families such as FABP, CPT2, and VLCAD. The docking analysis showed that EGCG has favourable binding interactions with the target transporters, involving important hydrogen bonding and hydrophobic interactions. EGCG showed a strong ability to bind to the active sites of FABP and CPT2, indicating its potential to influence their functions.

Evaluation of Melatonin and its Nanostructures Effects on Skin Disorders Focused on Wound Healing.

Skin is the largest organ of the human body functioning as a great primitive defensive barrier against different harmful environmental factors. However, it is damaged through varying injuries such as different wounds, burns, and skin cancers that cause disruption in internal organs and essential mechanisms of the body through inflammation, oxidation, coagulation problems, infection, etc. Melatonin is the major hormone of the pineal gland that is also effective in skin disorders due to strong antioxidant and anti-inflammatory features with additional desirable antiapoptotic, anti-cancer, and antibiotic properties. However, melatonin characteristics require improvements due to its limited water solubility, halflife and stability. The application of nanocarrier systems can improve its solubility, permeability, and efficiency, as well as inhibit its degradation and promote photostability. Our main purpose in the current review is to explore the possible role of melatonin and melatonin-containing nanocarriers in skin disorders focused on wounds. Additionally, melatonin's effect in regenerative medicine and its structures as a wound dressing in skin damage has been considered.

Berberine HCl and diacerein loaded dual delivery transferosomes: Formulation and optimization using Box-Behnken design

Introduction: Berberine is a poorly water-soluble alkaloid compound showing significant anti-inflammatory characteristics. It reduces the levels of pro-inflammatory and inflammatory cytokines, including tumour necrosis factor (TNF-????, IFN-????) and interleukin (IL-23, IL-12, and IL-23). Diacerein significantly reduces the splenomegaly associated with psoriasis. It downregulates the production of TNF-α and IL-12. Method: This study reported the development of transferosomes containing berberine HCl and diacerein using a film hydration method followed by optimization using a Box-Behnken design. Sodium deoxycholate was used as an edge activator. The impact of independent variables (amount of phosphatidylcholine, amount of edge activator, and sonication cycles) on dependent variables (particle size and entrapment efficiency) was examined. The optimized formulation was characterized for polydispersity index, vesicle size, entrapment efficiency, ζ potential, spectral analysis like Fourier transform infrared, thermal analysis, X-ray diffraction, deformability, transmission electron microscopy, antioxidant assay, in-vitro release, and ex-vivo skin permeation studies. Results: The optimized formulation had a particle size of 110.90±2.8 nm with high entrapment efficiency (89.50±1.5 of berberine HCl and 91.23±1.8 of diacerein). Deformability, polydispersity index, ζ potential, and antioxidant activity of the optimized formulation were 2.44, 0.296, -13.3, and 38.36 %, respectively. Optimized transferosomes exhibited 82.093±0.81 % and 85.02±3.81 % release of berberine HCl and diacerein after 24 h of dissolution study. The transdermal flux of optimized formulation was 0.0224 µg cm-2 h-1 (2.24 cm h-1 permeation coefficient) and 0.0462 µg cm-2 h-1 (4.62 cm h-1 permeation coefficient), respectively, for berberine HCl and diacerein. Raman analysis of treated pig skin confirmed that the transferosomes can permeate the skin. No change in the skin condition or irritation was observed in BALB/c mice. Formulation stored at 4 and 25±2 °C / 60±5 % relative humidity was stable for 3 months. Conclusions: Thus, the results demonstrated successful optimization of the transferosomes for the efficient topical delivery of berberine HCl and diacerein in the effective management of psoriasis.