Recent breakthroughs in electroactive piezo-biomaterials have driven significant progress towards the development of both, diagnostic and therapeutic purposes, enabling vital sign monitoring, such as heart rate, etc. while also supporting tissue regeneration. Bioelectronic medicine provides a promising method for controlling tissue and organ functions, with 'piezo-electronics' emphasizing the lasting role of electro-active piezo-biomaterials in self-powered devices. This article critically analyses a range of self-powered bioelectronic technologies, including wearable, implantable, regenerative, and cancer therapy applications. Piezoelectric nanogenerators (PENGs) are essential in wearable and implantable systems such as pressure and strain measurements, sensor for human-machine interface, self-powered pacemakers, deep brain stimulation, cochlear implant, tissue restoration and sustained drug delivery, controlled by electrical stimuli from PENGs etc. Regenerative bioelectronics play a key role in healing tissues, such as bone, neural, cardiac, tendon, ligament, skeletal muscle etc. using self-powered implants, which have ability to restore tissue functionality. Additionally, piezoelectric biomaterials are being utilized in cancer treatment, offering more targeted therapies with minimal side effects. Various cancerous tumors can be destroyed by reactive oxygen species (ROS), generated by piezo-biomaterials. Data science is also emerging as a crucial tool in optimizing self-powered bioelectronics, enhancing patient outcomes through data-driven strategies, and broadening the role of bioelectronic technologies in modern healthcare.

Targeted regulation of neutrophils is an effective approach for treating neutrophil-driven inflammatory diseases, but challenges remain in minimizing off-target effects and extending drug half-life. A DNA-based nanorobot was developed to target neutrophils by using an N-acetyl Pro-Gly-Pro (Ac-PGP) peptide to specifically bind to the C-X-C motif of chemokine receptor 2 (CXCR2) on neutrophil membranes. This robot (a tetrahedral framework nucleic acid modified with Ac-PGP, APT) identified and hitchhiked neutrophils to accumulate at inflammatory sites and prolong its half-lives, whilst also was internalized to influence the neutrophil cell cycle and maturation process to regulate oxidative stress, inflammation, migration, and recruitment in both in vivo and in vitro inflammation experiments. Consequently, the tissue damage caused by sepsis was greatly reduced. This novel neutrophil-based nanorobot highlights the high precision of targeting and regulating neutrophils, and presents a potential strategy for treating multiple neutrophil-driven diseases.

Clostridioides difficile, a leading cause of healthcare-associated infections, causes significant morbidity and mortality. Its pathogenesis centers on TcdA and TcdB toxins, which disrupt intestinal integrity, trigger inflammation, and promote extensive neutrophil infiltration.

The main objective of this study was to evaluate the role of PMNs in CDI using neutrophil depletion in a murine-ileal-ligated loop.

Mice were treated with C. difficile toxins TcdA, TcdB, and TcdBv, with PMN depletion achieved via intraperitoneal injections of Ly6G/Ly6C antibody. Histopathological analysis, cytokine quantification, and MPO activity assays were performed to assess the inflammatory and tissue damage responses.

PMN depletion significantly reduced histopathological damage and proinflammatory responses. TcdA induced the highest inflammation and epithelial damage, while TcdB showed lower activity, except for MPO. TcdBvNAP1's activity was comparable to that of TcdBNAP1 but less than TcdA. The findings indicate that TcdA's enterotoxin effects are more damaging than TcdBs from different strains and confirm the critical role of PMNs in CDI pathogenesis.

Our results show that PMN depletion reduced inflammatory responses and tissue damage, highlighting potential therapeutic strategies targeting PMN regulation. Further research on PMN extracellular traps (NETs) and their role in CDI is necessary to develop comprehensive treatments. Future studies should focus on combined in vivo and in vitro approaches to fully understand the pathological mechanisms and identify effective biomarkers for CDI therapy.

Despite persisting health disparities between Black and White individuals, racial differences in inflammation have yet to be comprehensively examined.

To determine if significant differences in circulating levels of inflammatory markers between Black and White populations exist.

Studies were identified through systematic searches of four electronic databases in January 2022. Additional studies were identified via reference lists and e-mail contact.

Eligible studies included full-text empirical articles that consisted of Black and White individuals and reported statistics for inflammatory markers for each racial group. Of the 1368 potentially eligible studies, 84 (6.6 %) representing more than one million participants met study selection criteria.

Risk of bias was assessed via meta regressions that considered relevant covariates. Data heterogeneity was tested using both the Cochrane Q-statistic and the standard I2 index. Random effects models were used to calculate estimates of effect size from standardized mean differences.

Outcome measures included 12 inflammatory markers, including C-reactive protein (CRP), Fibrinogen, Interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-α), and soluble intercellular adhesion molecule 1 (sICAM-1).

Several markers had robust sample sizes for analysis, including CRP (White N = 934,594; Black N = 55,234), Fibrinogen (White N = 80,880; Black N = 18,001), and IL-6 (White N = 20,269; Black N = 14,675). Initial results indicated significant effects on CRP (k = 56, pooled Hedges' g = 0.24), IL-6 (k = 33, g = 0.15), and Fibrinogen (k = 19, g = 0.49), with Black individuals showing higher levels. Results also indicated significant effects on sICAM-1 (k = 6, g = -0.46), and Interleukin-10 (k = 4, g = -0.18), with White individuals showing higher levels. Sensitivity analyses confirmed robust effects for CRP, IL-6, Fibrinogen, and sICAM-1 while also revealing significant effects on TNF-α (k = 18, g = -0.17) and Interleukin-8 (k = 5, g = -0.19), with White individuals showing higher levels of both.

Current meta-analytic results provide evidence for marked racial differences in common circulating inflammatory markers and illustrate the complexity of the inflammatory profile differences between Black and White individuals. Review Pre-Registration: PROSPERO Identifier - CRD42022312352.

To investigate the prognostic potential of preoperative blood neutrophil to lymphocyte ratio (NLR), hematocrit (HCT) and Fibrinogen (FIB) level in patients with colorectal cancer (CRC).

The data of 268 patients with CRC who underwent radical surgery from March 2013 to August 2017 in the First Affiliated Hospital of Guangzhou Medical University (Guangzhou, China) were retrospectively collected. The correlations between preoperative blood NLR, HCT and FIB level and the clinicopathologic features and prognosis were explored by Cox regression in the patients with CRC.

Univariate and multivariate analyses identified preoperative blood with high NLR (HR = 2.265, 95% CI: 1.437-3.570), low HCT (HR = 1.575, 95% CI: 1.010-2.454), and high FIB (HR = 1.667, 95% CI: 1.067-2.605) as independent predictors of reduced 5-year overall survival (OS). Furthermore, the patients were stratified into high (with 3 predictors), middle (with 2 predictors) and low (with 0 or 1 predictors) risk groups according to the number of the 3 independent prognostic predictors. The more independent predictors a patient has, the poorer their prognosis tends to be.

Preoperative NLR, HCT, and FIB serve as cost-effective prognostic biomarkers in CRC. Their combination enables precise risk stratification, guiding personalized postoperative management.

The increased risk for obesity and metabolic disorders following early-life adversity is aggravated by poor diet (e.g., cafeteria diet). Alternate-day fasting (ADF) is a dietary regimen shown to improve immune and metabolic dysfunction related to obesity. Here, we evaluate if ADF can ameliorate the negative effects of early-life adversity and/or cafeteria diet on biological, immune and metabolic parameters. At weaning, animals reared under normal or adverse conditions (i.e., low bedding) were fed either standard chow or cafeteria diets ad libitum or subjected to an ADF regimen. In adulthood, we measured 24-hour fasted cholesterol, triglycerides, cytokines, oxidative stress markers, and body composition parameters including perigonadal, retroperitoneal, and brown fat pad weight. Animals exposed to early-life adversity respond differently to cafeteria diet and ADF. Adverse reared animals fed chow diet in the ADF regimen showed the largest reduction in body weight and perigonadal and retroperitoneal fat pad weight, the smallest increase in corticosterone levels, and the largest increase in TNF-α levels. However, the differential effects of the ADF regimen on body, perigonadal and retroperitoneal fat weight observed in adversely reared animals fed chow diet compared to controls were not present if the adversely reared animals were fed cafeteria diet in the ADF regimen. Furthermore, adversely reared animals fed cafeteria diet in the ADF regimen showed high IL-1β and IL-6 levels. Together, the data suggest that the altered vulnerability to metabolic and immune dysfunction following early-life adversity is not just due to the type of diet but also how the diet is consumed.

a series of 6-substituted dihydrobenzophenanthridine alkaloids were synthesized by introduction of different functional groups to C-6 of dihydrobenzophenanthridine backbone. The preliminary anti-inflammatory activities of all compounds were screened by investigating the inhibitory ability on NO production in LPS-stimulated RAW 264.7 cells. Among synthesized compounds, 6-(N-phenyl)-aminocarbonyl methyl dihydrochelerythrine (compound 12b) showed increased anti-inflammatory ability and decreased cytotoxicity and could inhibit the expression of pro-inflammatory factors TNF-α and IL-6 in RAW 264.7 macrophages. The anti-inflammatory ability of compound 12b was further evaluated using DSS-induced mice colitis models based on colonic tissue damage assessment, histopathological assessment and immunohistochemical analysis. In vivoexperiment revealed that compound 12b had good alleviating effect on acute colitis in mice. In conclusion, compound 12b may be a promising anti-inflammatory lead compound.

Diet-related maternal obesity has been implicated in neurodevelopmental disorders in progeny. Although the precise mechanisms and effective interventions remain uncertain, our research elucidates some of these complexities. We established that a prenatal high-fat diet triggered maternal immune activation (MIA), marked by elevated serum lipopolysaccharide levels and inflammatory-cytokine overproduction, which dysregulated the maternal tryptophan metabolism promoting the accumulation of neurotoxic kynurenine metabolites in the embryonic brain. Interventions aimed at mitigating MIA or blocking the kynurenine pathway effectively rescued the male mice social performance. Furthermore, excessive kynurenine metabolites initiated oxidative stress response causing neuronal migration deficits in the fetal neocortex, an effect that was mitigated by administering the glutathione synthesis precursor N-Acetylcysteine, underscoring the central role of maternal immune-metabolic homeostasis in male mice behavioral outcomes. Collectively, our study accentuated the profound influence of maternal diet-induced immuno-metabolic dysregulation on fetal brain development and provided the preventive strategies for addressing neurodevelopmental disorders.

Aging is characterized by an ongoing struggle between the buildup of damage caused by a combination of external and internal factors. Aging has different effects on phagocytes, including impaired efferocytosis. A deficiency in efferocytosis can cause chronic inflammation, aging, and several other clinical disorders.

Our review underscores the possible feasibility and extensive scope of employing dual targets in various age-related diseases to reduce the occurrence and progression of age-related diseases, ultimately fostering healthy aging and increasing lifespan. Key scientific concepts of review Hence, the concurrent implementation of strategies aimed at augmenting efferocytic mechanisms and anti-aging treatments has the potential to serve as a potent intervention for extending the duration of a healthy lifespan. In this review, we comprehensively discuss the concept and physiological effects of efferocytosis. Subsequently, we investigated the association between efferocytosis and the hallmarks of aging. Finally, we discuss growing evidence regarding therapeutic interventions for age-related disorders, focusing on the physiological processes of aging and efferocytosis.

Phthalates, chemical additives used to enhance plastic products' flexibility, are easily released into the environment, and can harm the brain development through various mechanisms including inflammation. Genetic variation influencing an individual's susceptibility to inflammation may play a role in the effects of phthalate exposure on neurodevelopment however there is no summary measure developed for genetic susceptibility to inflammation.

We developed a genetic pathway function score for inflammation (gPFSin), based on the transcriptional activity of the inflammatory response pathway in the brain and other tissues. Using the Barwon Infant Study (a birth cohort of n = 1074), we examined the connection between gPFSin and key neurodevelopmental outcomes, along with the interplay between prenatal phthalate levels, children's genetic susceptibility to inflammation (gPFSin), and adverse neurodevelopmental outcomes.

Regression techniques revealed consistent associations between gPFSin-phthalate combinations and key neurodevelopmental outcomes. A high gPFSin score was associated with an increased risk of doctor-diagnosed Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) by age 11.5 years, with adjusted odds ratios of 2.15(p = 0.039) and 2.42(p = 0.005), respectively. Furthermore, individuals with both high gPFSin and prenatal phthalate exposure exhibited more neurodevelopmental problems. This included associations of high gPFSin and bis(2-ethylhexyl) phthalate (DEHP) levels with parent-reported ASD traits and doctor-diagnosed ASD. The attributable proportions due to this interaction were 0.39 (p = 0.045) and 0.37 (p = 0.037), respectively.

These findings contribute to the evidence linking gestational phthalate exposure and inflammation to adverse neurodevelopment and underscoring increased risks in children with higher genetic susceptibility to inflammation.

In the present study, we investigated the anti-inflammatory and anti-melanogenic effects of Leuconostoc mesenteroides subsp. DB-21-derived exosomes (DB-21 exosomes), isolated from Camellia japonica flower in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells and melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanoma cells. We confirmed that DB-21 exosomes were not toxic to LPS-induced RAW 264.7 macrophage cells and α-MSH-induced B16F10 melanoma cells. Moreover, we confirmed that DB-21 exosomes inhibit the pro-inflammatory cytokines IL-6, IL-1β, TNF-α, PGE2, and the expression of inflammatory factors iNOS and COX-2. We also found that DB-21 exosomes have a concentration-dependent ability to inhibit melanin, TRP-1, TRP-2, tyrosinase, and MITF, which are factors involved in melanogenesis. Additionally, it inhibits the phosphorylation of Akt and GSK-3β, and MAP kinase pathway proteins such as ERK, JNK, and p38. We confirmed that DB-21 exosomes inhibit melanin synthesis in B16F10 cells through various pathways, and based on previous results, they may be used as a functional cosmetic material with anti-inflammatory and anti-melanogenic activities.

Chronic inflammatory diseases are a significant global burden and are associated with dysregulated resolution of inflammation. Therefore, promoting the process of resolution is a promising therapeutic approach. This study presents the potent anti-inflammatory and pro-resolving effects of a natural product-derived compound called C81. Administration of C81 in a therapeutic window resolved inflammation in the murine imiquimod-induced psoriasis model, and reduced microglial infiltration in a laser-induced choroidal neovascularisation model. Investigations into the underlying mechanisms of C81 identified the DYRK1B/STAT3 axis as a new regulator of inflammatory processes in leukocytes. The inhibition of DYRK1B by C81 resulted in attenuated STAT3 phosphorylation. The depletion of STAT3-regulated gene expression led to the inhibition of leukocyte adhesion and migration due to reduced integrin activation, and in addition to the inhibition of the release of pro-inflammatory mediators such as cytokines and eicosanoids. Importantly, the pro-resolving effects of C81 included the cell type-specific induction of apoptosis in neutrophils and a subsequent increase in efferocytosis. In conclusion, we report the DYRK1B/STAT3 axis as a novel and promising therapeutic target for activating the resolution of inflammation.

Sepsis is a severe condition with high mortality, in which immune dysfunction plays a critical role. Poor oral health has been linked to frailty, but its impact on sepsis outcomes remains unclear. Therefore, we used a mouse model of malocclusion and sepsis to investigate how tooth loss affects immune responses during sepsis. Adult male C57BL/6 mice were divided into four groups: Control, Malocclusion (Mal), Sepsis (CS), and Malocclusion with Sepsis (Mal + CS). Malocclusion was induced by tooth extraction, and sepsis was induced using cecal slurry injection. We assessed survival rates, immune cell counts, and biochemical markers. The Mal + CS group exhibited significantly lower survival rates and greater weight loss compared to the CS group. The flow cytometry showed reduced neutrophils, monocytes, and T cells in the Mal + CS group. Elevated ALT and AST levels indicated liver damage. No significant differences in bacterial loads were observed, but immune suppression was exacerbated in the Mal + CS group. Malocclusion worsens sepsis outcomes by impairing both innate and adaptive immune responses. These findings emphasize the importance of oral health in improving sepsis prognosis and immune function during critical illnesses.

Age-related macular degeneration (AMD) is a complex, multifactorial retinal degenerative disease that is influenced by both genetic and environmental factors. However, the strongest risk factor for AMD is advanced age. Several physiological processes are observed in aging tissues including a low level of chronic inflammation (inflammaging), changed lipid and energy metabolism, and senescence. Nevertheless, whereas everyone ages, only a subset of the population develops AMD. The purpose of this review is to delineate the differences on a cellular and molecular level between natural aging changes and those observed in AMD. We provide a unique perspective on how genetic and environmental components modulate aging in the eye, as well as the specific role of the aging RPE and retina in the pathogenesis of AMD. Topics discussed include the mechanism of aging and its relation to the mechanism of AMD, current animal models that can be used to recapitulate some aspects of the pathology, and potential interventions that shift the balance towards healthy aging and therefore attenuate, prevent or delay the initiation of the disease.

The rise of various diseases demands the development of new agents with antioxidant, antimicrobial, anti-inflammatory, enzyme-inhibiting, and cytotoxic properties. In this study, heterocyclic Schiff base complexes of Cu(II) featuring a benzo[b]thiophene moiety were synthesized and their biological activities evaluated. The complexes were characterized using FT-IR, UV-Vis, and EPR spectroscopy, TG-DTG analysis, magnetic moment measurements, molar conductivity measurements, and elemental analyses. Density functional theory (DFT) calculations were used to optimize the theoretical molecular orbital energies of the copper complexes. The complexes exhibited square pyramidal and square planar geometries. Biological assays demonstrated that these complexes generally outperformed the Schiff base ligands for various activities. The antioxidant capacity, measured via the DPPH assay in methanol, was comparable to those of the BHT and ascorbic acid standards, with 4BNPC showing the lowest IC50 value, which was attributed to the free OH group rather than coordination to the metal center. The anti-bacterial activity was assessed using the agar disc diffusion method against E. coli, P. aeruginosa, B. subtilis, and S. aureus, with BAC showing the largest inhibition zone compared to the others and ciprofloxacin as the reference. The anti-inflammatory activity, evaluated by the HRBC membrane stabilization method, showed that the 4BNPC Cu(II) complex had moderate activity similar to that of diclofenac. Enzyme inhibition studies against α-amylase revealed that the BAC complexes had the highest inhibition values, surpassing those of the Schiff base ligands. Cytotoxicity was assessed using Trypan blue exclusion for DLA and HepG2 cancer cell lines, and the MTT assay for H9c2 human cells. BMPC demonstrated superior cytotoxicity at both high and low concentrations against the normal H9c2 cell line. Among the tested compounds, BNPC showed moderate inhibition against HepG2 cells, while BMPC exhibited the greatest cytotoxicity at higher concentrations, particularly reaching nearly 100% cell death at 200 μg mL-1 in DLA cell lines. This suggests that BMPC is a promising candidate for further pharmacological research, particularly against DLA cells.

In the past decade, a major goal in biomedical research has been to understand why individuals differ in disease susceptibility, disease dynamics, and progression. In many pathologies, this variability stems from evolved immune mechanisms that resist inflammatory stress from various diseases that have been encountered throughout life. These may provide advantages against other diseases, reduce comorbidities, and enhance longevity. This study evaluates prior immunity as a prognostic factor in COVID-19 patients, crucial for understanding plasmatic signaling cascades in different disease stages and their impact on disease progression. COVID-19, caused by SARS-CoV-2, primarily affects the respiratory system and presents a wide range of symptoms, posing significant challenges to medicine. This study systematically analyzed prior immunity and inflammation in two independent cohorts of infected patients. A serological profile is determined by protein microarrays, which identify IgM and IgG responses against 37 prevalent microbial pathogens and provide a comprehensive plasma analysis of 21 acute-phase proteins. Our results reveal distinct serological profiles correlating with disease severity, indicating that immune system dysregulation in COVID-19 patients is linked to existing immunity. These findings highlight the relevance of prior immunity for monitoring disease progression, particularly in infections and vaccine failure, and underscore the importance of functional proteomics in determining prognostic biomarkers.

1. Poultry farming faces challenges regarding correct hygiene and nutrition. One of the challenges is gram-negative bacteria that stimulate pro-inflammatory reactions through lipopolysaccharide (LPS) and cause disease and anorexia. Liquorice, a medicinal plant containing glycyrrhizin (Glz; a saponin and emulsifier compound) as its main active ingredient, was injected into broilers to investigate any beneficial effects on feed intake in LPS-injected broilers.2. The study involved three experiments using 72 male broiler chickens in each, to examine the impact of Glz on feed intake, especially when challenged with lipopolysaccharide (LPS) by intra-peritoneal (IP) injection to cause inflammation (n = 24). Experiment 1 was conducted to examine the effects of intraperitoneal injection of Glz (12.5, 25 and 50 mg) on feed intake in chickens. In experiment 2, the effects of intracerebroventricular injections of LPS (6.25, 12.5 and 25 ng) were examined. The third experiment investigated the impact of IP injection of Glz on inflammation induced by LPS.3. Injection of Glz significantly increased feed intake in a dose-dependent manner. Whereas LPS significantly reduced the feed intake in feed-deprived chickens (p < 0.05).4. In conclusion, Glz can neutralise the feed intake reduction caused by inflammation in broilers, highlighting its potential role in modulating feed intake in broilers.

Inflammation, driven by various stimuli such as pathogens, cellular damage, or vascular injury, plays a central role in numerous acute and chronic conditions. Current treatments are being re-evaluated, prompting interest in naturally occurring compounds like kaempferol, a flavonoid prevalent in fruits and vegetables, for their anti-inflammatory properties. This study explores the therapeutic potential of kaempferol, focusing on its ability to modulate pro-inflammatory cytokines and its broader effects on inflammatory signaling pathways. Comprehensive reviews of in vitro and in vivo studies were conducted to elucidate the mechanisms underlying its anti-inflammatory and antioxidant actions. Kaempferol effectively inhibits the production of key inflammatory mediators, including cytokines and enzymes such as COX-2 and iNOS, while also targeting oxidative stress pathways like Nrf2 activation. The compound demonstrated protective effects in various inflammatory conditions, including sepsis, neurodegenerative disorders, cardiovascular diseases, and autoimmune conditions, by modulating pathways such as NF-κB, MAPK, and STAT. Despite its promise, kaempferol's clinical application faces challenges related to its bioavailability and stability, underscoring the need for advanced formulation strategies. These findings position kaempferol as a promising candidate for anti-inflammatory therapy, with the potential to improve patient outcomes across a wide range of inflammatory diseases. Further clinical studies are required to validate its efficacy, optimize dosage, and address pharmacokinetic limitations.

The recruitment of T lymphocytes holds great potential for suppressing the most aggressive glioblastoma (GBM) recurrence with immunotherapy. However, the phenomenon of immune privilege and the generally low immunogenicity of vaccines often reduce the presence of lymphocytes within brain tumors, especially in brain tumor recurrence clusters. In this study, an implantable self-cascading catalytic therapy and antigen capture scaffold (CAS) that can boost catalytic therapy efficiency at post-surgery brain tumor and capture the antigens via urethane-polyethylene glycol-polypropylene glycol (PU-EO-PO) segments are developed for postoperative brain immunotherapy. The CAS consists of 3D-printed elastomers modified with iron (Fe2+) metal-organic frameworks (MOFs, MIL88) and acts as a programmed peroxide mimic in cancer cells to initiate the Fenton reaction and sustain ROS production. With the assistance of chloroquine (CQ), autophagy is inhibited through lysosome deacidification, which interrupts the self-defense mechanism, further enhances cytotoxicity, and releases antigens. Then, CAS containing PU-EO-PO groups acts as an antigen depot to detain autologous tumor-associated antigens to dendritic cells maturation and T cell augments for sustained immune stimulation. CAS enhanced the immune response to postoperative brain tumors and improved survival through brain immunotherapy.

The Cissus gongylodes has traditionally been used in the diet of indigenous people in Brazil and in traditional medicine for kidney stone removal and inflammatory diseases. The active compounds responsible for these pharmacological activities are unknown.

This study aims to isolate, for the first time, the compounds in the decoction of C. gongylodes leaves responsible for their anti-inflammatory and anti-urolithiatic ethnopharmacological properties.

The most active fractions of the C. gongylodes leaf decoction were fractionated using SPE-C18 and the compounds were purified through HPLC-UV-DAD. The decoction fractions and isolated compounds were evaluated for their anti-inflammatory and anti-urolithiatic activities. The anti-inflammatory activity was assessed using an ex vivo assay in human blood induced by LPS and calcium ionophore, measuring inflammatory mediators, PGE2 and LTB4. The anti-urolithiatic activity was evaluated using an in vitro experimental model with human urine to determine the dissolution of the most recurrent calcium oxalate (CaOx) crystals. Additionally, the decoction was chemically characterized through metabolomic analysis using UHPLC-ESI-HRMS.

The isolated compounds from the decoction of C. gongylodes, including rutin, eriodictyol 3'-O-glycoside, and isoquercetin, have demonstrated significant multi-target actions. These components act as anti-inflammatory agents by inhibiting the release of main inflammatory mediators, PGE2 and LTB4. Additionally, they exhibit anti-urolithiatic properties, promoting the dissolution of calcium oxalate (CaOx) crystals. Furthermore, the characterization of the decoction by UHPLC-ESI-HRMS revealed a high content of flavonoids, mainly glycosylated flavonoids.

The results support the traditional use of C. gongylodes decoction, identifying the compounds responsible for its anti-inflammatory and anti-urolithiatic effects. The decoction fractions and isolated compounds exhibited dual anti-inflammatory activity, effectively inhibiting key inflammatory pathways and potentially presenting fewer adverse effects while also promoting the dissolution of CaOx crystals associated with urolithiasis. The multi-target action displayed by C. gongylodes is particularly desirable in the treatment of urolithiasis, as inflammation and PGE2 production precede and contribute to the formation of CaOx crystals in the kidneys. Based on these actions, C. gongylodes emerges as a potent source of active compounds for the development of new treatments for urolithiasis.

The cortex of Eleutherococcus henryi (EH, Araliaceae), also known as "Wu-Jia-Pi", is known for its effects such as dispelling wind and dampness, calming the mind and enhancing intelligence, removing heat and toxin, strengthening muscles and bones, and nourishing the liver and kidneys. Throughout Chinese history and tradition, it has been used for conditions like amnesia, mental fatigue, arthritis, hepatitis, and rheumatism. However, research evaluating its neuroprotective effects and pharmacological properties remains scarce.

The goal is to explore the anti-neuroinflammatory properties of EH in vitro and to discover precisely the bioactive natural products within the medicinal plant that are relevant to its traditional usage.

Utilizing chromatographic techniques, a phytochemical exploration was conducted. The phytochemical structures of the natural products were then elucidated through an analysis involving comprehensive spectra and a comparison with relevant data from published studies. Network pharmacology combined with molecular dynamics simulations (MDs) and docking were applied to forecast potential anti-neuroinflammatory targets of active compounds. In vitro, the anti-neuroinflammatory efficacy was evaluated via the suppression of inflammatory mediators activated by lipopolysaccharide (LPS) in BV2 microglia.

The methanol extract of E.henryi (EHME) restrained the NO release in LPS-activated BV2 microglia, demonstrating anti-neuroinflammatory activity. Subsequently, chemical composition analysis revealed the separation and elucidation of 31 secondary metabolites, comprising 7 new compounds (1-7) and 1 new natural product (8). Based on LPS-induced BV2 cell in vitro activity tests, compounds 4-17, 19, 20, 22, 23, 26, 29 and 31 were found to exhibit potential anti-neuroinflammatory activity, with compound 6 showing the highest efficacy. Furthermore, employing network pharmacology in conjunction with both molecular docking and MDs, potential anti-neuroinflammatory targets of compound 6 were predicted to include TLR4, Src, MAPK, and NF-κB. Finally, validation through in vitro experiments confirmed that the anti-neuroinflammatory mechanism of compound 6 is associated with the TLR4/Src/MAPK p38/NF-κB p65 signaling pathways.

The study affirmed the traditional efficacy of E. henryi and unveiled novel lignans as potent agents against neuroinflammation.

The PnuC gene plays a crucial role in the complex processes related to the absorption and synthesis of the nicotinamide mononucleotide (NMN) precursor. NMN, a nicotinamide adenine dinucleotide (NAD+) precursor, is important for cellular energy metabolism, DNA repair, and antiaging. This study focuses on elucidating the precursor absorption mechanism and the specific function of the PnuC gene in encoding membrane transport proteins, as well as its impact on the regulation and dynamics of NMN within the cell. This understanding aims to provide insights into its potential effects on metabolic balance, illustrated through two NAD+ biosynthesis pathways based on renewable and readily available cytoplasmic resources, assessing the potential of PnuC gene expression in clarifying complex interactions within regulation mechanisms. Enhanced expression analysis of the PnuC gene has initiated discussions on its potential applications in treating aging-related diseases and dysfunctions, contributing to cellular health maintenance.

Ischemic stroke leads to permanent damage to the affected brain tissue, with strict time constraints for effective treatment. Predictive biomarkers demonstrate great potential in the clinical diagnosis of ischemic stroke, significantly enhancing the accuracy of early identification, thereby enabling clinicians to intervene promptly and reduce patient disability and mortality rates. Furthermore, the application of predictive biomarkers facilitates the development of personalized treatment plans tailored to the specific conditions of individual patients, optimizing treatment outcomes and improving prognoses. Bioinformatics technologies based on high-throughput data provide a crucial foundation for comprehensively understanding the biological characteristics of ischemic stroke and discovering effective predictive targets. In this study, we evaluated gene expression data from ischemic stroke patients retrieved from the Gene Expression Omnibus (GEO) database, conducting differential expression analysis and functional analysis. Through weighted gene co-expression network analysis (WGCNA), we characterized gene modules associated with ischemic stroke. To screen candidate core genes, three machine learning algorithms were applied, including Least Absolute Shrinkage and Selection Operator (LASSO), random forest (RF), and support vector machine-recursive feature elimination (SVM-RFE), ultimately identifying five candidate core genes: MBOAT2, CKAP4, FAF1, CLEC4D, and VIM. Subsequent validation was performed using an external dataset. Additionally, the immune infiltration landscape of ischemic stroke was mapped using the CIBERSORT method, investigating the relationship between candidate core genes and immune cells in the pathogenesis of ischemic stroke, as well as the key pathways associated with the core genes. Finally, the key gene VIM was further identified and preliminarily validated through four machine learning algorithms, including generalized linear model (GLM), Extreme Gradient Boosting (XGBoost), RF, and SVM-RFE. This study contributes to advancing our understanding of biomarkers for ischemic stroke and provides a reference for the prediction and diagnosis of ischemic stroke.

Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 (NCOA7) deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes. This oxysterol signature overlapped with a plasma metabolite signature associated with human PAH mortality. Mice deficient for endothelial Ncoa7 or exposed to an inflammatory bile acid developed worsened PAH. Genetic predisposition to NCOA7 deficiency was driven by single-nucleotide polymorphism rs11154337, which alters endothelial immunoactivation and is associated with human PAH mortality. An NCOA7-activating agent reversed endothelial immunoactivation and rodent PAH. Thus, we established a genetic and metabolic paradigm that links lysosomal biology and oxysterol processes to endothelial inflammation and PAH.

A one-pot, acid-, base-, and metal-free, multicomponent strategy has been developed to synthesize spiro thiochromene-oxindole derivatives as potential anti-inflammatory agents. The synthesized compounds were screened in vitro for their anti-inflammatory activity by inhibiting heat-induced Bovine Serum Albumin (BSA) denaturation assay, revealing moderate to good efficacy. Compounds 4e, 4k, and 4h exhibited the highest activity, inhibiting BSA denaturation by 90.97-95.45% at 800 μg mL-1 concentration with half maximal inhibitory concentration (IC50) values of 127.477 ± 2.285, 190.738 ± 3.561, and 285.806 ± 8.894 μg mL-1, respectively. For mechanistic insights in silico studies were conducted, revealing binding affinities of the active compounds with cyclooxygenase-2 (COX-2) protein, with binding energies of -8.9 kcal mol-1 (4e), -8.7 kcal mol-1 (4k), and -8.6 kcal mol-1 (4h). Bioactivity and pharmacokinetic parameters were further analyzed, encompassing ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) characteristics. This study highlights the potential of spiro thiochromene-oxindoles as anti-inflammatory agents, warranting further exploration as potential leads. The synthetic strategy for these target compounds utilizes taurine as an eco-friendly bio-organic catalyst, facilitating an acid-, base-, and metal-free intramolecular C-S and C-C bond formation in aqueous media. The reaction involves a one-pot, three-component Knoevenagel-Thia-Michael cascade between substituted isatins, 1,3-dicarbonyls, and 2-naphthalene thiol. Key features of this green protocol include high yields, cost-efficiency, non-toxicity, atom economy, and acid-, base-, and metal-free synthesis in water. Additionally, the catalyst exhibits excellent reusability, maintaining its activity across three cycles with easy recovery, while product isolation is achieved through simple filtration, eliminating the need for chromatographic purification and organic solvents. These attributes underscore this approach's synthetic and environmental advantages, highlighting its potential for broader application in the development of anti-inflammatory agents.

Quinoxaline molecule has gathered great attention in medicinal chemistry due to its vide spectrum of biological activities and has emerged as a versatile pharmacophore in drug discovery and development. Its structure comprises a bicyclic ring of benzopyrazine and displays a range of pharmacological properties, including antibacterial, antifungal, antiviral, anticancer, and antiinflammatory. This study aims to summarize the different strategies for the synthesis of quinoxalines and their anti-inflammatory properties acting through different mechanisms. Structure-activity relationships have also been discussed in order to determine the effect of structural modifications on anti-inflammatory potential. These analyses illuminate critical structural features required for optimal activity, driving the design and synthesis of new quinoxaline analogues with better antiinflammatory activities. The anti-inflammatory properties of quinoxalines are attributed to their inhibitory action on the expression of several inflammatory modulators such as cyclooxygenase, cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and p38α Mitogen Activated Protein Kinase (p38α MAPK). Activators of nuclear factor erythroid 2-related factor 2 (NRF2) and agonistic effect on opioid receptors have also been discussed. Hence, this study may provide a future template for the design and development of novel quinoxaline derivatives acting through different molecular targets as potential anti-inflammatory agents with better efficacy and safety profiles.

With increasing age, the optimal functioning of the choroid is essential for efficient removal of waste products formed from photoreceptor renewal. A decline in regulatory elements of the immune system, termed immunosenescence, and the failure of para-inflammation to restore tissue homeostasis can result in the progression of healthy aging to sight-threatening inflammation of the choroid. Macrophages are uniquely situated between the innate and adaptive immune systems, with a high capacity for phagocytosis, recognition of complement components, as well as antigen presentation. In this review, we provide an overview of macrophages and their properties in the healthy choroid and cover the impact of aging, immunosenescence and inflammaging on the function of choroidal macrophages. We will discuss the impact of age on macrophage phenotype and behaviour in the pathophysiology of age-related macular degeneration.

To meet the prodigious bioenergetic demands of the photoreceptors, glucose and other nutrients must traverse the retinal pigment epithelium (RPE), a polarised monolayer of cells that lie at the interface between the outer retina and the choroid, the principal vascular layer of the eye. Recent investigations have revealed a metabolic ecosystem in the outer retina where the photoreceptors and RPE engage in a complex exchange of sugars, amino acids, and other metabolites. Perturbation of this delicate metabolic balance has been identified in the aging retina, as well as in age-related macular degeneration (AMD), the leading cause of blindness in the Western world. Also common in the aging and diseased retina are elevated levels of cytokines, oxidative stress, advanced glycation end-products, increased growth factor signalling, and biomechanical stress - all of which have been associated with metabolic dysregulation in non-retinal cell types and tissues. Herein, we outline the role of these factors in retinal homeostasis, aging, and disease. We discuss their effects on glucose, mitochondrial, lipid, and amino acid metabolism in tissues and cell types outside the retina, highlighting the signalling pathways through which they induce these changes. Lastly, we discuss promising avenues for future research investigating the roles of these pathological conditions on retinal metabolism, potentially offering novel therapeutic approaches to combat age-related retinal disease.

The genesis of human disease lies in our evolutionary past. Evolution has featured a general trend towards increased morphological complexity, partly conferred by expansion in gene regulatory capacity via microRNA (miRNA) innovation. Many human diseases are directly related to the evolved roles of these miRNAs, and miRNA-based therapies are emerging as an appealing strategy for precision medicine. We focus on three categories of human disease - cancer, inflammation-linked pathologies, and neurological disorders - which are highly prevalent and are associated with substantial disease burden worldwide. In each category we discuss the pathogenic roles of miRNAs in the context of their evolved functions, as well as current and potential advances in targeting these miRNAs for disease therapy.

Bone marrow inflammaging is a low-grade chronic inflammation that induces bone marrow aging. Multiple age-related and inflammatory diseases involve bone marrow inflammaging. Whether common pathological pathways exist in bone marrow inflammaging remains unclear.

We collected bone marrow from telomerase-deficient mice (telomerase RNA component, TERCko/ko), 5 × FAD mice and Dmp1 Cre -DTA ki/wt mice and High-fat diet-fed mice (HFD), and lumbar 5 nerve compression mice. We performed scRNA-Seq analysis on bone marrow obtained from these mouse models to investigate the potential shared pathway of bone marrow inflammation.

We identified the monocyte/macrophage lineage was activated via the App-Cd74 axis in multiple aging and inflammatory mouse models. Increased expression of CD38 and Ly6a, and decreased expression of Col1a and Lif in macrophages serve as shared changes in different mouse models. The activated macrophages, interacting with other cells, control the expansion of B cells via the CD52-Siglec-G axis. The Ccl6-Ccr2 and Ccl9-Ccr1 ligand-receptor pairs, along with Fn1 and C3-related pathways in macrophages, were associated with immune cell activation and the recruitment of lymphocytes. Interactions with mesenchymal cells were enriched for integrins (Itga4), Fn1, and adhesion molecules (Vcam1).

Our study demonstrates that monocyte/macrophage lineage stimulation is a key event in bone marrow inflammaging. We identified common differentially expressed genes and activated pathways in this lineage, suggesting potential targets for future interventions.

Our study revealed shared genes and ligand-receptor pairs in the activated monocyte/macrophage lineage within inflammaging bone marrow. These findings offer potential therapeutic targets for cell-specific anti-inflammatory treatments.

Iron, an essential trace element, is involved in various physiological processes; however, consumption of excessive iron possesses detrimental effects. In practical feed production, the iron content added to feeds often far exceeds the actual demand, resulting in an excess of iron in the body. The liver as a central regulator of iron homeostasis is susceptible to damage caused by disorders in iron metabolism. A model of hepatic iron overload in laying hens was developed in this study by incorporating iron into their diet, and the specific mechanisms underlying iron overload-induced hepatic injury were investigated. Firstly, this study revealed that a high-iron diet resulted in hepatic iron overload, accompanied by impaired liver function. Next, assessment of oxidative stress markers indicated a decrease in activities of T-SOD and CAT, coupled with an increase in MDA content, pointing to the iron-overloaded liver oxidative stress. Thirdly, the impact of iron overload on hepatic glycolipid and bile acid metabolism-related gene expressions were explored, including PPAR-α, GLUT2, and CYP7A1, highlighting disruptions in hepatic metabolism. Subsequently, analyses of inflammation-related genes such as iNOS and IL-1β at both protein and mRNA levels demonstrated the presence of inflammation in the liver under conditions of dietary iron overload. Overall, this study provided comprehensive evidence that dietary iron overload contributed to disorders in glycolipid and bile acid metabolism, accompanied by inflammatory responses in laying hens. Further detailing the specific pathways involved and the implications of these findings could offer valuable insights for future research and practical applications in poultry nutrition.

Biological systems utilize precise spatial organization to facilitate and regulate information transmission within signaling networks. Inspired by this, artificial scaffolds that enable delicate spatial arrangements are desirable to increase the local concentration of reactants, expedite specific interactions, and minimize undesired interference. In this study, we presented an integrated biosensing nanodevice, termed TRI-HCR, in which hybridization chain reaction (HCR) probes were precisely organized on a triangular DNA origami nanostructure (TRI) with finely-tuned distance, quantity, and pattern. Compared to traditional HCR in the free form, this nanodevice demonstrated increased reaction rate and signal level. We further employed the optimized TRI-HCR for in vivo imaging of a nucleic acid biomarker of inflammatory diseases. In both acute gouty arthritis (AGA) and sepsis-associated acute kidney injury (SA-AKI) model mice, TRI-HCR was capable of diagnosing inflammation in the early stages, significantly earlier than histological examination. We anticipate that this precise spatial preorganization strategy for HCR holds promise for broader applications in early disease detection and monitoring.

In traditional medicine, potential anti-inflammatory and pain-relieving activity of Momordica charantia, Azadirachta indica, Nelumbo nucifera, Caesalpinia crista, Martynia annua and Erythrina variegate has been emphasized. In this study, we explored binding affinity of 36 bioactive compounds from these plants to cyclooxygenase-2 (COX-2) receptor using docking method. Six compounds namely, beta carotene, lycopene, lutein, momordicoside, rutin and azadirachtin showed excellent binding affinities (-10.29, -10.22, -10.03, -7.9, -8.81 and -7.88 kcal/mol, respectively) and stable interactions with COX-2 (greater than those of aspirin and diclofenac) and they were chosen for the molecular dynamics (MD) assessments done throughout a 100-ns time period. Based on the computed RMSD, RMSF, Rg, SASA and PCA, all ligands were found to form stable and adequate interactions with COX-2 protein; these findings were comparable to those of aspirin and diclofenac, indicating the potential inhibitory properties of these ligands on COX-2 protein. In addition, the toxicity of compounds was evaluated using Pred-hERG, Pred-Skin and ProTox-II. Since COX-2 inhibitors have been reported to activate the Nrf2 pathway, it is hypothesized that they may confer other health-promoting effects through triggering Nrf2 signaling.

Gut microbiota is a complex and dynamic system that plays critical roles in human health and various disease. Progressive chronic kidney disease (CKD) suggests that patients irreversibly progress to end-stage kidney disease and need renal replacement treatments, including dialysis and transplantation. Ample evidence indicates that local oxidative stress and inflammation play pivotal roles in the pathogenesis and progression of CKD and dysbiosis of gut microbiota. CKD is always accompanied by intestinal inflammation and oxidative stress, which lead to rapid systemic translocation of bacterial-derived uraemic toxins, including indoxyl sulphate, phenyl sulphate and indole-3-acetic acid, and the consequent development and aggravation of renal fibrosis. Although inflammation and oxidative stress have been extensively discussed, there is a paucity of reports on the effects of gut microbiota on renal fibrosis and gut microbiota mediation of oxidative stress and inflammation. This review provides an overview of gut microbiota on inflammation and oxidative stress in renal fibrosis, briefly discusses regulation of the gut flora using microecological preparations and natural products, such as resveratrol, curcumin and emodin as treatments for CKD, and provides a clear pathophysiological rationale for the design of promising therapeutic strategies.

Children and adolescents exposed to severe stressors exhibit poorer health across the lifespan. However, decades of research evaluating the Stress-Buffering model suggests that social support can attenuate stressors' negative impacts. Psychoneuroimmunology research in this area has shifted from asking whether support buffers stress to when and why support would succeed (or fail) to confer protection. This article takes a lifecourse perspective and proposes that timing of support may shape support's protective value by defining the type of protection that is provided and its operating mechanisms. Specifically, it considers three temporal scenarios: support that occurs during, after, or before stressor exposure. When support intervenes at the same developmental stage as the stressor (concurrent support), buffering effects occur wherein support prevents the development of intermediary mechanisms that reflect or increase disease risk; when support is present at a developmental stage before stressor exposure (prior support), banking effects occur such that support intervenes indirectly by fortifying the individual with resilience-promoting characteristics that in turn prevents the development of intermediary mechanisms; finally, when support arrives at a developmental stage after stressor exposure (later support), counteracting effects occur such that support offsets the impacts of intermediary mechanisms on diseases. It further posits that a match between timing of support and the linkage of interest (e.g., the stressor-mechanism path vs. the mechanism-disease path) is necessary for successful protection. The present paper discusses these postulations, reviews nascent evidence, and proposes future directions.

Analysis of gene expression at the single-cell level could help predict the effectiveness of therapies in the field of chronic inflammatory diseases such as arthritis. Here, we demonstrate an adopted approach for processing images from the Slide-seq method. Using a puck, which consists of about 50,000 DNA barcode beads, an RNA sequence of a cell is to be read. The pucks are repeatedly brought into contact with liquids and then recorded with a conventional epifluorescence microscope. The image analysis initially consists of stitching the partial images of a sequence recording, registering images from different sequences, and finally reading out the bases. The new method enables the use of an inexpensive epifluorescence microscope instead of a confocal microscope.

Pathogenic infection leads to excessive senescent cell accumulation and stagnation of wound healing. To address these issues, we devise and develop a hydrogen selenide (H2Se)-evolving bio-heterojunction (bio-HJ) composed of graphene oxide (GO) and FeSe2 to deracinate bacterial infection, suppress cellular senescence and remedy recalcitrant infected wounds. Excited by near-infrared (NIR) laser, the bio-HJ exerts desired photothermal and photodynamic effects, resulting in rapid disinfection. The crafted bio-HJ could also evolve gaseous H2Se to inhibit cellular senescence and dampen inflammation. Mechanism studies reveal the anti-senescence effects of H2Se-evolving bio-HJ are mediated by selenium pathway and glutathione peroxidase 1 (GPX1). More critically, in vivo experiments authenticate that the H2Se-evolving bio-HJ could inhibit cellular senescence and potentiate wound regeneration in rats. As envisioned, our work not only furnishes the novel gasotransmitter-delivering bio-HJ for chronic infected wounds, but also gets insight into the development of anti-senescence biomaterials.