Anti-inflammatory Ability Research Articles

Regular Use of Oral Nonsteroidal Anti-inflammatory Drugs in a Population of Polish Seniors: Findings from the PolSenior2 Cross-Sectional Survey.

Older adults represent a growing proportion of the general population. Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute a group of medicines that are both necessary, owing to their anti-inflammatory, analgesic, and cardioprotective abilities, and potentially harmful, owing to their side effects. This study provides a comprehensive analysis of NSAID usage patterns among Polish adults aged 60 years and older. It focused on the regular use (≥ three times per week) of two types of NSAIDs: acetylsalicylic acid (ASA) and non-ASA NSAIDs, examining consumption on the basis of age, sex, educational level, and place of residence. Data were collected from the PolSenior2 study, a national cross-sectional survey of 5987 Polish individuals aged 60-106 years, conducted from 2018 to 2019. The study found that 30.7% [95% confidence interval (CI) 28.8-32.7)]of Polish seniors regularly used NSAIDs, with 26.2% (95% CI 24.5-28.0) regularly using ASA, 6.3% (95% CI 5.3-7.2) regularly using non-ASA NSAIDs, and 1.9% (95% CI 1.4-2.3) reporting regular use of both. An age-related increase in regular NSAID use, including ASA, was observed. Women were more likely than men to use non-ASA NSAIDs regularly, whereas men in the 70-79 age group were more likely to use ASA. A lower level of education was associated with more frequent NSAID use. The findings have implications for healthcare practitioners and policymakers, emphasizing the need for careful management of NSAID use. The study contributes to a more nuanced understanding of NSAID usage and underscores the necessity for tailored healthcare strategies to ensure safe and effective medication use among older adults.

Fracture-healing effects of Rhizoma Musae ethanolic extract: An integrated study using UHPLC-Q-Exactive-MS/MS, network pharmacology, and molecular docking.

Fracture disrupts the integrity and continuity of the bone, leading to symptoms such as pain, tenderness, swelling, and bruising. Rhizoma Musae is a medicinal material frequently utilized in the Miao ethnic region of Guizhou Province, China. However, its specific mechanism of action in treating fractures remains unknown. This study aimed to elucidate the chemical constituents of the ethanol extract of Rhizoma Musae (EERM) and investigate its fracture-healing mechanism using network pharmacology. The chemical profile of EERM was characterized via UHPLC-Q-Exactive-MS/MS. Subsequently, a comprehensive network of compounds, targets, and pathways was constructed using network pharmacology approaches. The interactions between the active compounds of EERM and their targets were validated through molecular docking, molecular dynamics simulation and in vitro cell experiments. EERM contained 522 identified compounds. Topological analysis of the protein-protein interaction (PPI) network identified 59 core targets, including key proteins like AKT1, IL-6, and EGFR, known for their anti-inflammatory properties and ability to enhance bone cell proliferation and differentiation. Gene Ontology analysis indicated the involvement of EERM in biological processes such as peptidyl-serine phosphorylation, response to xenobiotic stimulus, and nutrient level regulation. KEGG analysis suggested that EERM's mechanism may involve signaling pathways such as PI3K-Akt, lipid and atherosclerosis, EGFR tyrosine kinase inhibitor resistance, and MAPK pathways. Molecular docking and molecular dynamics simulations results demonstrated a strong binding affinity between the main compounds of EERM and key targets. In vitro cell experiments demonstrate that EERM enhances cell proliferation by upregulating the expression levels of EGFR and STAT3, while simultaneously downregulating AKT1 and CASP3. This study investigates the potential active compounds of EERM and its key targets in regulating multiple pathways of fracture, leading to promoting bone cell proliferation. These results offer valuable insights for the future development and clinical application of Rhizoma Musae.

Regulation of TGF-β1, PI3K/PIP3/Akt, Nrf-2/Keap-1 and NF-κB signaling pathways to avert bifenthrin induced hepatic injury: A palliative role of daidzein.

Bifenthrin (BFN) is a noxious insecticide which is reported to damage various body organs. Daidzein (DZN) is a natural flavone with excellent pharmacological properties. This research was conducted to evaluate the alleviative strength of DZN to counteract BFN prompted liver toxicity in male albino rats. Thirty-two rats were divided into 4 groups i.e., the control, BFN (7 mg /kg), BFN (7 mg/kg) + DZN (20 mg/kg) and DZN (20 mg/kg) alone group. The biochemical assessment was performed by using qRT PCR as well as standard ELISA protocols. The findings are validated by applying pharmacodynamic techniques including molecular simulation. It was observed that BFN reduced the gene expressions of phosphoinositide 3-kinase (PI3K), phosphatidylinositol-3, 4, 5-triphosphate (PIP3), Protein kinase B (Akt), nuclear factor erythroid 2-related factor 2 (Nrf-2) while promoting the gene expressions of Kelch-like ECH-associated protein 1 (Keap-1). Moreover, BFN notably reduced the activities of glutathione reductase (GSR), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) while elevating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). BFN promoted the levels of matrix metallopeptidase 2 (MMP-2), Procollagen III N-terminal Pro-peptide (PIIINP), alkaline phosphatase (ALP), transforming growth factor-beta-1 (TGF-β1), aspartate aminotransferase (AST), tissue inhibitor of matrix metalloproteinases 1 (TIMP1), and alanine aminotransferase (ALT). The levels of nuclear factor- kappa B (NF-κB), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) were increased following the BFN intoxication. BFN enhanced the expressions of cysteine-aspartic acid protease-3 (Caspase-3) and Bcl-2-associated X protein (Bax) while suppressing the gene expression of B-cell lymphoma-2 (Bcl-2). Moreover, BFN disrupted the normal histology of liver tissues. Nonetheless, DZN treatment remarkably alleviated hepatic damages owing to its antioxidative, anti-apoptotic as well as anti-inflammatory abilities. However, DZN supplementation remarkably safeguarded which is further confirmed by in-silico assessment.

Exploring the Effects of Gracilaria lemaneiformis Polysaccharides on the Fecal Microbiota and Fecal Metabolites of Fattening Pigs Based on 16S rDNA and Metabolome Sequencing.

Sixty Duroc × (Landrace × Yorkshire) castrated male finishing pigs were randomly divided into negative control (NC) and gracilaria lemaneiformis polysaccharides (GLP) groups to study the effects of GLP on the fecal microbiota and fecal metabolites of fattening pigs. The NC group was fed a basic diet, and the GLP group was fed a basic diet supplemented with 0.1% GLP. The diversity of the species and the fecal metabolites were analyzed using 16S rDNA sequencing and metabolome sequencing, respectively. The serum immune and antioxidant indices were analyzed using the ELISA assay. The abundances of hazardous bacteria such as Proteobacteria at the phylum level and Shigella at the genus level were extremely significantly decreased (p < 0.01) and those of beneficial bacteria such as Firmicutes at the phylum level (p < 0.01), Clostridium at the genus level (p < 0.01), and Lactobacillus at the genus level (p < 0.05) were significantly increased in the GLP group compared with the NC group. A total of 41 differentially expressed metabolites were identified. The expression of anti-inflammatory and antioxidant active substances, such as methyl cinnamate, protopanaxatriol, and isovanillic acid, was elevated in the GLP group. The ELISA assay showed increased GSH-Px activity (p < 0.01), T-AOC (p < 0.01), IgG (p < 0.01), IgA (p < 0.05), and IgM (p < 0.05) in the GLP group. These results indicate that dietary GLP supplementation can improve the antioxidant ability, anti-inflammatory ability, and immune level of fattening pigs by regulating fecal flora and metabolites and could be used as a functional feed additive.

Unveiling the potential anticancer activity of Spirulina maxima extract-nanoemulsion through in vitro and in vivo studies.

Being the second leading cause of death globally, cancer has been a long-standing and rapidly evolving focus of biomedical research and practice in the world. Recently, there has been growing interest in cyanobacteria. This focus is particularly evident in developing innovative anticancer treatments to reduce reliance on traditional chemotherapy. This study investigates the anticancer potential of the Spirulina maxima extract nanoemulsion (SMNE) technique to improve the delivery, stability, and solubility of the S. maxima extract (SME). SMNE, prepared in three concentrations (SMNEC1, SMNEC2, SMNEC3), was characterized and confirmed to successfully load SME into silica-coated nanoparticles. Cytotoxicity tests on HepG2 and MCF-7 cell lines revealed a significant reduction in cell viability after 48-hour SMNE treatment, with IC50 values of 1488µg/mL and 1721.936µg/mL, respectively. SMNE also demonstrated efficacy in inhibiting tumor growth in mice with Ehrlich ascites carcinoma, normalizing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and reducing oxidative stress markers such as catalase (CAT) and malondialdehyde (MDA). Histopathological examination showed that SMNEC3-treated groups had almost normal liver architecture. Additionally, SMNE downregulated oncogenic miR-221-3p and miR-222-3p, activating cancer suppression genes p27 and PTEN. The study concludes that SMNE, with its anti-inflammatory and antioxidant properties and ability to modulate key miRNAs, enhances SME delivery and shows promise as an effective cancer treatment.

Structural Characterizations and Biological Evaluation of a Natural Polysaccharide from Branches of Camellia oleifera Abel.

Camellia oleifera Abel (C. oleifera) is widely cultivated and serves as an important source of edible oil. Yet, during oil production, pruned branches generate significant waste and contribute to environmental pollution. In this work, we obtain a natural polysaccharide from the branches of C. oleifera and optimize its extraction using Box-Behnken design (BBD), which is a statistical method commonly used in response surface methodology. Additionally, we study its properties, such as monosaccharide composition, structural features, antioxidant, and anti-inflammatory abilities. BBD was employed to optimize polysaccharide extraction (solid-liquid ratio = 1:40; 90 °C; 130 min) for a higher yield. After purification, the major monosaccharides of branches of C. oleifera's polysaccharide (CBP) were disclosed as glucose and galactose. Subsequent structural features of CBP were measured. The antioxidant and anti-inflammatory abilities were measured. The highly scavenging rates of the 2,2-diphenyl-1-picrylhydrazyl and hydroxyl radicals, with the chelating capacity of Fe2+, indicate potent antioxidant activity of CBP. In general, CBP demonstrated significant anti-inflammatory activity with down-regulating the expression of IL-6 and IL-1β in the LPS-induced macrophage RAW264.7 model. This bioactive polysaccharide adds value to waste branches by offering a novel approach to waste recycling and the development of C. oleifera.

Anti-Inflammatory Properties of Biflavonoids Derived from Selaginella moellendorffii Hieron: Targeting NLRP3 Inflammasome-Dependent Pyroptosis

Ethnopharmacological relevanceSelaginella moellendorffii Hieron. has been used as ethnic drug for chronic inflammation treatment. Biflavonoids represent a crucial class of bioactive compounds recognized for their potent anti-inflammatory activity in S. moellendorffii (SM). However, the effective components, targets, and pathways that SM in anti-inflammasome remain unclear. Aim of the studyTherefore, this study initially evaluated the effective components of SM and explored the underlying mechanisms. Materials and methodsFirstly, a series of biflavonoids were isolated from SM, and then all compounds were evaluated for their anti-inflammatory ability in the THP-macrophages co-stimulated with lipopolysaccharide (LPS) and NLRP3 inflammasome inducers. Secondly, transcriptomic analysis and metabolomics analysis revealed the differential genes and metabolites associated with effective components treatment. Finally, molecular docking of effective components with NLRP3 was performed and western blotting was performed in order to determine the expression of related proteins. ResultsOverall, eleven biflavonoids were successfully isolated from SM. Particularly, F7 exhibited the most potent inhibitory effect against NLRP3 inflammasome-mediated cytokines levels, cell membrane integrity and Ca2+ influx. Transcriptomic studies demonstrated that the differential genes (DEGs) were mainly enriched in NF-κB signaling pathway and NOD-like receptor signaling pathway. Metabolomics studies that the metabolites were mainly involved the pyrimidine metabolites. Further validation analysis manifested that F7's significant downregulation of NLRP3 inflammasome-related genes and proteins expression (P<0.05, P<0.01), encompassing both priming (NLRP3, TNF-α, p-p65/p65) and activation stages (IL-1β, IL-18, Caspase-1, GSDMD-N/GSDMD). Moreover, NLRP3 knockdown attenuated F7-mediated inhibition of pyroptosis. Finally, in silico results showed that F7 exhibited promising predicted binding affinity towards NLRP3. ConclusionsCollectively, these findings revealed an anti-inflammatory material basis for SM and confirmed F7 as a potent inhibitor of pyroptosis by suppressing NF-κB/NLRP3 Pathway.

Characterization of a novel type 4 resistant starch from tapioca and its obesity-preventive effects through gut microbiota modulation in high-fat diet-treated mice.

The rising pandemic of obesity has received significant attention. Yet, more safe and effective targeted strategies must be used to mitigate its impact on individual health and the global disease burden. While the health benefits of resistant starch (RS) are well-documented, the role of RT-90 (a phosphate-modified tapioca RS containing 90.1% total dietary fiber) in mitigating obesity remains unknown. Accordingly, the physicochemical characteristics and protective effects of RT-90 on obesity were investigated in high-fat diet (HFD)-fed mice. Physicochemical property examinations showed that RT-90 consisted of small, round starch granules (D90: 20.69±0.4μm) with a crystalline structure, P-O-C stretching, and high peak melting temperature and enthalpy. Additionally, feeding mice with RT-90 significantly decreased body weight, improved oral glucose tolerance test (OGTT), reduced fatty liver and adipose tissue accumulation, lowered oxidative stress and inflammation by upregulating antioxidant enzymes (SOD, catalase, GPx) and anti-inflammatory cytokines (IL-4, IL-10), and enhanced fecal lipids and bile acid excretion. Notably, RT-90 administration in HFD-fed mice was associated with the inhibition of obesity-associated harmful bacteria ([Eubacterium]_xylanophilum group, Allobaculum, Clostridia_UCG-014, Dubosiella) and promotion of short-chain fatty acids (SCFAs)-producing gut flora, including Bifidobacterium, Lactobacillus, Bacteroides, and Parabacteroides, which suggests a possible mechanism by which RT-90 alters gut microbiota to attenuate obesity. These novel findings first revealed that RT-90 facilitates weight loss through its antioxidant, anti-inflammatory, and microbiota modulation abilities. This provides a promising strategy for managing overweight or obesity and holds potential for applications in developing healthy food products.

Thymol Impacts the Progression of Endometriosis by Disrupting Estrogen Signaling Pathways and Inflammatory Responses.

Endometriosis is a chronic inflammatory, estrogenic disorder caused by endometrial tissue growth places other than uterine lumen, resulting in infertility and severe pelvic pain. Thymol, an extract of Thymus vulgaris, processes diverse biological properties, including anti-inflammatory, local anesthetic, decongestant, and antiseptic effects. However, the efficacy of thymol in treating endometriosis has still not been explored. Herein, this research aimed to investigate the role of thymol in the treatment of endometriosis using a murine model and Ishikawa cells. Thirty C57BL/6 mice were administered 17β-E2 (100 ng/mouse) subcutaneously for three consecutive days to induce synchronous estrus. On the last day of injection, the mice underwent surgical induction of endometriosis. After that, the mice were divided into three groups, i.e., Control (CTRL), Thymol 30 mg/kg and Thymol 60 mg/kg, receiving oral administration of either saline or thymol (30 mg/kg/d or 60 mg/kg/d, as 0.1 mL/kg/d, respectively) for a three-week duration. Each group consisted of ten mice and was evenly divided into estrus and diestrus according to the vaginal cytology on the last day of treatment. Thymol significantly (p < 0.05) reduced the weight and volume of ectopic tissue, hindered cell proliferation, and stimulated apoptosis compared to the CTRL group. Additionally, in the thymol-treated group, the levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, as well as the numbers of neutrophils and macrophages, were significantly (p < 0.05) decreased. Moreover, a novel role of thymol in rebalancing estrogen and progesterone (E2-P4) signaling was explored, and it was distributed in the ectopic endometrium. Next, the role of thymol on Ishikawa cells was determined. The results demonstrated that thymol significantly (p < 0.05) suppressed the E2-induced proliferation of Ishikawa cells. Furthermore, molecular docking analyses suggested that thymol potentially binds to ESR1-like estrogens, indicating its antagonistic activity against estrogens. The estrogen receptor 1 (ESR1) and its target gene expression exhibited significant (p < 0.05) downregulation, while progesterone receptor (PGR) and target genes were markedly (p < 0.05) upregulated following thymol treatment in the ectopic endometrium. Most importantly, our data revealed the minimal impact of thymol treatment on the eutopic endometrium and its crucial role in supporting pregnancy, thus indicating the safety of thymol in treating endometriosis. Overall, our study suggests that thymol holds promising therapeutic implications for endometriosis by virtue of its anti-inflammatory properties and ability to antagonize estrogen activity.

Enhancing Photothermal Therapy for Antibiofilm Wound Healing: Insights from Graphene Oxide-Cranberry Nanosheet Loaded Hydrogel in vitro, in silico, and in vivo Evaluation.

Diabetic foot ulcers present a formidable challenge due to colonization by biofilm-forming microorganisms, heightened oxidative stress, and continuous wound maceration caused by excessive exudation. To address these issues, we developed a robust, stretchable, electro-conductive, self-healing, antioxidant, and antibiofilm hydrogel. This hydrogel was synthesized through the crosslinking of polyvinyl alcohol (PVA) and chitosan (CH) with boric acid. To enhance its antimicrobial efficacy, graphene oxide (GO), produced via electrochemical exfoliation in a zinc ion-based electrolyte medium, was incorporated. For optimal antibiofilm performance, GO was functionalized with cranberry (CR) phenolic extracts, forming a graphene oxide-cranberry nanohybrid (GO-CR). The incorporation of GO-CR into the hydrogel significantly improved its stretchability (280% for PVA/CH/GO-CR compared to 200% for PVA/CH). Additionally, the hydrogel demonstrated efficient photothermal conversion under near-infrared (NIR) light, enabling dynamic exudate removal, which is expected to minimize retained exudate between the wound and the dressing, reducing the risk of wound maceration. The hydrogel effectively reduced levels of lipopolysaccharide (LPS)-induced skin inflammation markers, significantly lowering the expression of NLRP3, TNF-α, IL-6, and IL-1β by 39.2%, 31.9%, 41%, and 52.3%, respectively. Histopathological and immunohistochemical analyses further confirmed reduced inflammation and enhanced wound healing. The PVA/CH/GO-CR hydrogel exhibits multifunctional properties that enhance wound healing ulcers. Its superior mechanical, antibacterial, and anti-inflammatory properties and ability to promote angiogenesis make it a promising candidate for effective wound management in diabetic patients.

Donkey milk supplementation alleviates renal fibrosis of chronic kidney disease by enhancing anti-inflammatory ability.

Donkey milk, rich in essential nutrients, is not only able to meet the nutritional needs of patients with chronic kidney disease (CKD) according to the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Nutrition in CKD, but also has strong anti-inflammatory properties. Inflammation is the main driving force of renal fibrosis, which directly determines renal function in CKD. However, the impact of donkey milk on CKD and the underlying mechanisms remain unclear. We hypothesized that donkey milk supplementation could enhance anti-inflammatory abilities in individuals with CKD, thereby inhibiting renal fibrosis and improving renal function. Therefore, we investigated the influence of a 6-wk treatment with donkey milk on unilateral ureteral ligation-induced CKD rats. The results demonstrated that the level of miR-223-3p was decreased in the kidneys of CKD rats compared with normal rats. However, donkey milk supplementation activated miR-223-3p, thereby inhibiting the expression of inhibitor of kappa-B kinase (IKKα) and nuclear factor kappa-B (NF-κB) proteins. Consequently, the expression of inflammatory factors such as monocyte chemotactic protein-1 (MCP-1) and IL-6 was suppressed, leading to reduced aggregations of macrophages in the kidney and decreased transforming growth factor β1 (TGF-β1) expression. Ultimately, renal fibrosis was inhibited, which was confirmed by decreased collagen type I α 1 (COL1A1) mRNA, thereby the renal function of CKD rats was improved. These results indicate that miR-223-3p may be another potential therapeutic target for CKD. Moreover, the contribution of donkey milk to alleviating the inflammatory response and renal fibrosis of CKD is obvious, indicating that donkey milk may be a new functional food for CKD patients to promote health.

Changes in the macrophage polarization in the kidneys of rats with acute respiratory distress syndrome after transplantation of human umbilical cord-derived mesenchymal stem cell

Acute respiratory distress syndrome (ARDS) is a critical state of the body characterized by severe hypoxemia and multiple organ failure. One of the organs that is most often additionally affected due to the systemic inflammatory reaction that occurs in the lungs during ARDS is the kidney. It is known that mesenchymal stem cells (MSCs) can exhibit nephroprotective effects due to their anti-inflammatory and immunomodulatory abilities, but the mechanisms of such therapeutic effects require further elucidation. The purpose is to analyze macrophage polarization in the damaged kidneys of rats with modeled ARDS following the transplantation of human umbilical cord-derived MSCs. Materials and methods. Seventy-two sexually mature male Wistar rats were randomly divided into nine groups: intact animals, 3 days, 7 days and 28 days after ARDS modeling, control-MSC and four correction groups: 24 h ARDS + 2 days MSCs, 4 days of ARDS + 3 days of MSCs, 14 days of ARDS + 14 days of MSCs, 21 days of ARDS + 7 days of MSCs. ARDS was modeled by intranasal administration of lipopolysaccharide (LPS) at a dose of 5 mg/kg. A suspension of MSCs was obtained from the umbilical cord of a healthy donor after a normal delivery by an enzymatic method and administered intraperitoneally at a dose of 1 million cells/kg of body weight. For immunohistochemical determination of the total number of macrophages, pro-inflammatory M1 and anti-inflammatory M2 cells, monoclonal antibodies to CD68, CD86 and CD163 were used, respectively, and the percentage of visual fields occupied by the immunoprecipitate was calculated. Results. Comparative analysis of the percentage of areas occupied by the immunoprecipitate with the corresponding antibodies showed a statistically significant increase in the total number of macrophages (3.8-fold on day 3 of ARDS, 2.8-fold on day 7 of ARDS and 2.4-fold on day 28 of ARDS, respectively), as well as a sharp increase in pro-inflammatory M1 (8.8-fold on day 3 of ARDS, 4.9-fold on day 7 of ARDS, and 4.8-fold on day 28 of ARDS, respectively) and a moderate increase in the percentage of anti-inflammatory M2 cells (1.9-fold on day 3 of ARDS, 2-fold on day 7 of ARDS, and 1.6-fold on day 28 of ARDS, respectively) in modeled ARDS compared to intact animals. This indicates the activation of the inflammatory cascade in the kidneys caused by the development of ARDS. On the other hand, in groups of animals that received MSC correction, a significant decrease, compared to untreated animals, in the total number of macrophages was detected (at 24 h of ARDS + 2 days of MSCs, it was 3.2 times lower than on day 3 of ARDS and ≥ 2 times at later times of the experiment), among which anti-inflammatory cells of the M2 phenotype predominated. Conclusion. Transplanted human umbilical cord-derived MSCs have a pronounced immunomodulatory effect in the affected kidneys of rats with acute respiratory distress syndrome, which is manifested in their ability to change the polarization of macrophages in the anti-inflammatory direction.

Versatile inulin/trans-ferulic acid/silk sericin nanoparticles-nourished probiotic complex with prolonged intestinal retention for synergistic therapy of inflammatory bowel disease

To achieve effective long-term synergistic treatment of inflammatory bowel disease (IBD) with probiotics, we developed a versatile inulin/trans-ferulic acid/silk sericin nanoparticles-nourished probiotic complex. Inulin/TFA/SS nanoparticles were fabricated by inulin, trans-ferulic acid (TFA), and silk sericin (SS), and then loaded onto the surface of poly-l-lysine (PLL) and poly-glutamic acid (PGA)-coated Bifidobacterium longum (BL) to obtain BL@PLL-PGA-Inulin/TFA/SS NPs (BL@PP-NPs). This design simultaneously endowed the complex with excellent gastrointestinal resistance, antioxidant, and anti-inflammation abilities. Moreover, the inulin in the nanoparticles acts as a prebiotic, promoting the Bifidobacterium's rapid proliferation to exert effects within a short period. Compared with uncoated BL, BL@PP-NPs exhibited excellent gastric acid tolerance and up to 31.32-fold colonic colonization, and the ROS scavenging and proliferative capacity were increased by 5.61- and 1.39-fold, respectively. In a mouse model of dextran sulfate sodium (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis, the components of Inulin/TFA/SS NPs synergized with probiotics to efficiently treat IBD by attenuating oxidative stress, decreasing inflammation, repairing intestinal barrier, and promoting the rapid proliferation of probiotics to reverse gut microbial disorders. Collectively, food-grade BL@PP-NPs represent a novel approach to probiotic modification that offers an effective, safe, and synergistic therapy for IBD.

Self-Assembled Eutectogel with Cell Permeation and Multiple Anti-Inflammatory Abilities for Treating Chronic Periodontitis.

Eutectogels represent an attractive option for various industrial applications that use deep eutectic solvents (DESs) as effective liquid active ingredients and offer remarkable stability, cost-effectiveness, and environmental friendliness. However, the biological applications of these compounds are limited. DESs are highly structurally tunable and exhibit remarkable biofunctionality and biocompatibility, conferring substantial benefits in the treatment of diseases. In this study, choline-chloride and mannose are used to fabricate ChCl/M DES, followed by introduction of lysozyme fibers and gallic acid for self-assembly into injectable eutectogels through hydrogen bonding and hydrophilic/hydrophobic interaction interactions. The eutectogels demonstrate almost 100% bactericidal activities against three strains and significant immune-regulation. This is supported by a decrease in the proportion of CD86-expressing cells from 64.02% to 18.17% and an increase in CD206-expressing cells from 2.53% to 29.96% through flow cytometry experiments. The eutectogels effectively inhibit alveolar bone loss and alleviated local inflammation in a rat model of chronic periodontitis owing to the promotion of gallic acid in the cell membrane by the ChCl/M DES. Hence, self-assembled eutectogels exhibit the potential to enhance the efficacy if treatments/therapies against inflammatory diseases by facilitating bacterial control, reactive oxygen species scavenging, and the regulation of macrophages by promoting cell permeation of small-molecule drugs.

Tannic acid modulates SARS-CoV-2 pathogenesis by curbing key host receptors and oxidative stress

The novel coronavirus SARS-CoV-2, which wrecked havoc around the world in the recent years through COVID-19, gains entry into the host cell through various receptors. Development of therapies targeting host–pathogen interaction will be a key to curb the infection as it potentially suppresses viral attachment and entry into the host. Boundless bioactives abundant in natural resources are the important source of new as well as safer alternatives. Tannic acid, a polyphenolic compound found abundantly in various plant sources, has gained much attention owing to its multifaceted pharmacological properties. This research paper presents a comprehensive investigation on antioxidant, anti-inflammatory and anti-viral abilities of tannic acid, substantiated through a triad of methodologies: in silico, in vitro and in vivo approaches. In vitro experiments, confirmed the antioxidant and anti-inflammatory efficacy as well as the host receptor modulating potential of tannic acid. In silico docking analyses elucidated the molecular interactions between tannic acid and key host receptors involved in inflammation and viral pathogenesis. Furthermore, the in vivo studies involving Danio rerio provided a holistic understanding of the systemic impact of tannic acid, including its antioxidant effects by mitigating the oxidative stress.

Comparison of functional characterization of cancer stem cells in different tumor tissues of pseudomyxoma peritonei

BackgroundPseudomyxoma peritonei (PMP) is a rare malignant peritoneal tumor that readily recurs and metastasizes. Studies have shown that cancer stem cells (CSCs) play an important role in tumor recurrence, metastasis, and prognosis.ObjectiveIn this study, our aim was to isolate CSCs from various tissues of PMP patients and compare their proliferation, migration, and anti-inflammatory abilities.MethodsWe identified CSCs subsets with markers CD133+, CD166+, and CD133+/CD166+ at the gene level using single-cell mRNA sequencing (scRNA-seq). Appendiceal CSCs (AC), peritoneal CSCs (PC), and mucous CSCs (MC) were obtained using MACSQuant Tyto sorting technology and FlowSight imaging flow cytometry. The cells were cultured and markers were identified. Finally, the functional phenotypes of the three cell types were compared.ResultsCSCs content was highest in the appendiceal tumor tissue and lowest in the mucous tissue. The cell viability rate of the sorted CSCs was above 98%, and the positive rate of CD133+ and CD166+ was 70–80%, and CD133+/CD166+ was about 30%. Among the three types of CSCs, MC had the highest proliferation ability, and TNF-α has the greatest inhibitory effect on AC migration.ConclusionAC in patients was more inert and anti-inflammatory, whereas abdominal cavity MC and PC were more active. This study revealed the biological characteristics of CSCs in different tumor tissues of patients with PMP, providing a reference for future targeted CSCs therapy.

Mesenchymal stem cell-derived extracellular vesicles reduce inflammatory responses to SARS-CoV-2 and Influenza viral proteins via miR-146a/NF-κB pathway

The risk of severe disease caused by co-infection with SARS-CoV-2 and influenza virus (IAV) raises an annual concern for global public health. Extracellular vesicles (EV) derived from mesenchymal stem cells (MSC) possess anti-inflammatory properties that can attenuate the inflammatory cytokine levels induced by viral infection. However, the effects of MSC-EV treatment on SARS-CoV-2 and IAV co-infection have not been elucidated. In the present study, we co-induced lung epithelial cells (EpiC) with SARS-CoV-2 Spike protein (S) and H1N1 influenza viral HA protein (HA) and found robust upregulation of inflammatory cytokines in comparison to those induced by either S or HA protein. Consequently, treatment of lung endothelial cells (EC) with conditioned medium from EpiC co-induced by both S and HA proteins resulted in increased apoptosis and impaired angiogenic ability, suggesting the effects of co-induction on epithelial-endothelial crosstalk. In addition, lung EpiC co-induced by both S and HA proteins showed paracrine effects on the recruitment of immune cells, including monocytes, macrophages and neutrophils. Of Note, EV derived from Wharton Jelly’s MSC (WJ-EV) transferred miR-146a to recipient lung EpiC, which impaired TRAF6 and IRAK1, resulting in the downregulation of NF-κB pathway and secretion of inflammatory cytokines, rescuing the epithelial-endothelial crosstalk, and reducing the elevation of immune cell recruitment. Moreover, the anti-inflammatory properties of WJ-EV are affected by type 2 Diabetes Mellitus. WJ-EV derived from donors with type 2 Diabetes Mellitus contained less miR-146a and showed impaired ability to downregulate the NF-κB pathway and inflammatory cytokines in recipient cells. Taken together, our findings demonstrate the role of miR-146a in targeting the NF-κB pathway in the anti-inflammatory abilities of WJ-EV, which is a promising strategy to rescue the epithelial-endothelial crosstalk altered by co-infection with SARS-CoV-2 and IAV.

Glycoengineered extracellular vesicles released from antibacterial hydrogel facilitate diabetic wound healing by promoting angiogenesis.

Diabetic wounds have become a global healthcare burden owing to impaired angiogenesis and persistent infections. Extracellular vesicles (EVs) can improve diabetic wounds, though their targeting ability is limited. In this study, we investigated the performance of a novel hydrogel dressing comprised of gelatin methacryloyl, glycoengineered EVs, and polylysine in treating infected diabetic wounds. High-throughput single-cell RNA sequencing (scRNA-seq) and immunofluorescence staining revealed that E-selectin (SELE) levels were higher in diabetic wounds than in non-diabetic wounds. Mesenchymal stromal cells (MSCs) were transfected with a lentivirus containing fucosyltransferase VII (FUT7) and a CD63-P19-Nluc vector to enhance the expression of sialyl Lewis X (sLeX), the ligand of E-selectin, on the surface of EVs (s-EVs) derived from transfected MSCs (s-MSCs). s-EVs can target human umbilical vein endothelial cells (HUVECs) under lipopolysaccharide stimulation and promote the function of stimulated HUVECs in vitro. To promote and sustain the release of s-EVs, we fabricated a gelatin methacryloyl (Gel)/poly-L-lysine methacryloyl (PL)-5 hydrogel with good antibacterial ability, biocompatibility and mechanical properties. In a mouse experiment, s-EV@Gel/PL-5 exhibited excellent angiogenesis and anti-inflammatory abilities and further promoted the healing of infected diabetic wounds. Our findings demonstrated the potential of the s-EV@Gel/PL-5 hydrogel in the clinical treatment of diabetic infectious wounds.

Drug-free extracellular vesicles: A spatiotemporally controlled release engineering strategy for osteogenesis and anti-inflammatory niches in rotator cuff regeneration

Natural small-molecule drugs have promising potential to promote tissue regeneration in various fields. Therefore, maximizing drug efficiency while minimizing potential side effects is imperative. Peiminine, a natural product extracted from natural Fritillaria, is one of small-molecule drugs in the field of bone regeneration due to its good bone-promoting and anti-inflammatory abilities. However, its application is limited by a lack of biological activity, poor biocompatibility at high concentrations, and difficulty in achieving long-term slow-release and therapeutic effects. Extracellular vesicles (EVs) produced by preconditioned cells are considered to have special biological functions, and their potential to further retain, buffer, and transmit drug effects and expand the therapeutic effect has been widely studied. Thus, our study provides a drug-free bioengineering strategy by preconditioning bone marrow mesenchymal stem cells (BMSC) with Peiminine, then EVs, secreted as Peim-EVs, were extracted and combined with a decellularized extracellular matrix (dECM). The final EVs-dECM system with a spatiotemporally controlled release system was formed. In vitro studies demonstrated that Peim-EVs solved the problem of Peiminine biocompatibility and exhibited osteogenic and anti-inflammatory effects, which may be related to PI3K/AKT, MAPK/NF-κB, and Hippo signaling pathways. An in vivo model of rotator cuff injury in rats also showed that EVs-dECM had a good effect on rotator cuff repair. Combined with engineering strategy, this study provides verification and scenario expansion for drug application, especially for drug-free strategies that retain the biological effects of drugs, and has broad significance.

The Role of Exogenous microRNAs on Human Health: The Plant-Human Trans-Kingdom Hypothesis.

MicroRNAs (miRNAs) are small, endogenous, single-stranded RNAs that act on gene silencing at the post-transcriptional level by binding to a target messenger RNA (mRNA), leading to its degradation or inhibiting translation into functional proteins. The key role of miRNAs in development, proliferation, differentiation andapoptosis has been deeply investigated, revealing that deregulation in their expression is critical in various diseases, such as metabolic disorders and cancer. Since these small molecules initially evolved as a mechanism of protection against viruses and transposable elements, the fascinating hypothesis that they can move between organisms both of the same or different species has been postulated. Trans-kingdom is the term used to define the migration that occurs between species. This mechanism has been well analyzed between plants and their pests, in order to boost defense and increase pathogenicity, respectively. Intriguingly, in the last decades, the plant-human trans-kingdom migration via food intake hypothesis arose. In particular, various studies highlighted the ability of exogenous miRNAs, abundant in the mainly consumed plant-derived food, to enter the human body affecting gene expression. Notably, plant miRNAs can resist the strict conditions of the gastrointestinal tract through a methylation step that occurs during miRNA maturation, conferring high stability to these small molecules. Recent studies observed the anti-tumoral, immune modulator and anti-inflammatory abilities of trans-kingdom interaction between plant and human. Here, we depict the existing knowledge and discuss the fascinating plant-human trans-kingdom interaction, highlighting first the eventual role of plant miRNAs from foods on our somatic gene identity card and then the potential impact of using plant miRNAs as novel therapeutic avenues.