This study explores the therapeutic potential of Abrus precatorius leaves in arthritis treatment using computational methods and LC-MS analysis.

The plant material was taxonomically authenticated, and phytochemical analysis identified bioactive compounds such as alkaloids, flavonoids, and triterpenoids.

Swiss ADME analysis confirmed that multiple compounds complied with Lipinski's Rule of Five, while OSIRIS software indicated minimal toxicity. PASS analysis predicted anti-inflammatory and antioxidant activities. Molecular docking simulations of Abrine with key rheumatoid arthritis (RA) targets revealed strong binding affinities, suggesting potential mechanisms for RA treatment.

This research highlights the medicinal potential of Abrus precatorius leaves and emphasizes the importance of computational tools in understanding their pharmacological properties for arthritis management.

Mycoplasma pneumoniae (MP) is a key cause of community-acquired pneumonia, and coinfections lead to varied patient outcomes. A comprehensive understanding of the outcome characteristics and associated etiologies of coinfections in MP patients is lacking.

We analyzed 121,357 MP cases from 522,292,680 visits in Wuhan, China, in 2023 (the final year of the COVID-19 pandemic). Children aged 1-10 years had the highest incidence, whereas those over 60 years had elevated hospitalization, severe infection, and fatality rates. Coinfection patterns differed by age, with bacterial-viral-Chlamydia pneumoniae (C. pneumoniae) / other pathogens prevalent in infants, bacterial-viral pathogens prevalent in preschoolers, and viral-viral pathogens prevalent in school-aged children. Bacterial coinfections were most common in MP-infected patients, especially those who were hospitalized. Coinfection, especially with C. pneumoniae, Pseudomonas aeruginosa (P. aeruginosa), Haemophilus influenzae (H. influenzae), and Streptococcus pneumoniae (S. pneumoniae), increased hospitalization rates. The most severe outcomes and deaths occurred in patients coinfected with C. pneumoniae-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A-parainfluenza virus (PIV) or adenovirus-PIV. Logistic regression analysis demonstrated that male sex and adult age (particularly ≥40 years) were significantly associated with adverse outcomes in MP monoinfection. For coinfections, significantly higher hospitalization rates were reported among very young children (0-5 years) and adults aged ≥40 years, whereas adults presented an increased risk of severe disease. Coinfection outcomes were significantly associated with seasons of the year (winter, spring, and summer), specific age groups (3-5 years, 18-39 years, 40-50 years, and 60 years and over), gender (male), and longer onset-to-diagnosis periods. Middle-aged and elderly patients, coinfection, spring and summer, gender (male), and longer onset-to-diagnosis periods were significantly associated with increased hospitalization and serious illness risk. Coinfection, winter, older (adult) age, and gender (male) were significantly associated with an increased risk of death.

Compared with adults, children with MP have a greater morbidity risk, whereas middle-aged and older adults face greater risks of hospitalization, serious illness, and death. Coinfection with other pathogens heightens hospitalization and death risks. These insights are crucial for etiological screening, diagnosing multiple pathogens, and preventing and treating infections.

While occupational exposure as a firefighter is considered a dangerous occupation, research on the underlying mechanisms remains limited, particularly in wildland firefighters. Inflammation, a key effect of wildfire exposure, plays a significant role in the development of various diseases. The current study aims to investigate the impact of wildland firefighting exposure on the levels of pro-inflammatory systemic biomarkers. A pre-post study design investigated 59 wildland firefighters comparing data collected after participation in a wildfire event (Phase II) with data obtained before wildfire season (Phase I). Data on demographics, lifestyle, health and occupational-related factors were assessed. Exposure factors, such as fire combat (e.g., exposure duration), were also registered. Inflammatory biomarkers (i.e. interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor α [TNF-α] and high-sensitivity C-reactive protein [hs-CRP]) and hydroxylated polycyclic aromatic hydrocarbons metabolites (1-OHNaph+1-OHAce, 2-OHFlu, 1-OHPhen, 1-OHPyr) were analysed in blood and urine samples, respectively. Serum IL-8 and IL-6 levels were significantly increased after wildland fire combat. IL-8 levels were 2.62 times higher (95 % CI: 1.96-3.50; p < 0.01), whereas IL-6 levels were 1.25 times higher (95 % CI: 1.00-1.57; p = 0.04). Furthermore, IL-8 levels were significantly correlated with urinary 2-hydroxyfluorene levels and fire combat duration (>12 h). In addition, the mean hs-CRP level, in both phases, was above 3.0 mg/L, indicating a potential risk for cardiovascular events. Given the long-term health implications of firefighting occupational exposure, biomonitoring and early detection of occupational risks are essential for protecting firefighters' health. Protective measures must be urgently implemented to enhance occupational health and strengthen preventive strategies in this sector.

Receptor-interacting protein kinase 3 (RIPK3), a key regulator of necroptosis, has emerged as an important target for therapeutic intervention. Flavonoids are natural compounds known for their anti-inflammatory and antioxidant properties, with recent studies highlighting their potential to modulate necroptosis. In this study, we explored the potential of RIPK3 as a target for flavonoids to achieve anti-necroptosis and anti-inflammatory effects. A library of 63 flavonoids was tested for RIPK3 binding and kinase inhibition using fluorescence polarization (FP) competition assay and ADP-Glo kinase activity assay. Six flavonoids, including scutellarein, robinetin, baicalin, myricetin, baicalein, and tricetin, showed significant inhibition of RIPK3, with IC50 values ranging from 2.5 to 13.7 μM. Structural studies of tricetin and robinetin through co-crystallization and molecular docking revealed distinct binding modes of these flavonoids within the ATP-binding pocket of RIPK3. The anti-necroptosis effects of these flavonoids were further evaluated in human HT-29 cells and mouse embryonic fibroblasts (MEFs) using a TSZ-induced cell death assay, resulting in EC50 values in the tens of micromolar range. Western blot analysis demonstrated that these flavonoids inhibit the phosphorylation of RIPK3 and its downstream effector, mixed lineage kinase domain-like protein (MLKL), and disrupt the formation of RIPK1 and RIPK3 aggregates in the necroptosis pathway. These findings identify RIPK3 as a target of natural flavonoids for the first time and elucidate the molecular mechanism underlying the anti-necroptotic activity of these flavonoids.

This review is centered around the cardiotoxic effects of fumonisin B1 (FB1), particularly its impact on sphingolipid metabolism, inflammation, and epigenetics. FB1 is a mycotoxin produced by Fusarium fungi, which mainly contaminates cereal grains and poses an adverse health risk to both humans and animals; however, its disease-causing capabilities remain to be uncovered, specifically its ability to exacerbate and cause cardiovascular disease. It disrupts sphingolipid metabolism by inhibiting ceramide synthase, leading to cellular dysfunction and contributes to conditions such as hypertension and eventual heart failure. FB1 is responsible for an altered inflammatory response, whereby it increases pro-inflammatory cytokines such as IL-6 and IL-1β, which contribute to cardiovascular diseases. Moreover, FB1 induces significant epigenetic changes, including DNA hypermethylation, histone modifications such as increased H3K9me2 and H3K9me3, inhibition of histone acetyltransferase activity, and changes in microRNA expression profiles. These epigenetic alterations can silence or activate inflammatory genes, exacerbating disease progression. This review thus highlights the need for further research to elucidate the connections between FB1, inflammation, epigenetic modifications, and cardiotoxicity, which could lead to better strategies for managing FB1-related adverse health risks.

Neferine is a bisbenzylisoquinoline alkaloid derived from the seed embryo of Nelumbo nucifera, a traditional Chinese medicine. It has been extensively studied for its therapeutic potential in various disease models. Extensive research has highlighted its diverse pharmacological activities, including antitumor, anti‑inflammatory, anti‑fibrosis, anti‑oxidative stress, anti‑platelet aggregation and anti‑arrhythmic effects. The present review, however, focuses on the anti‑inflammatory properties of neferine, emphasizing its fundamental mechanisms as demonstrated in both in vivo and in vitro studies. By critically evaluating its effect on inflammation and the underlying pathways, this review aims to provide a comprehensive understanding of the potential of neferine in the management of inflammatory diseases. Furthermore, it seeks to establish a foundational framework for the future development of neferine as a novel therapeutic agent for inflammatory conditions.

Raspberry pomace (RBP) is rich in phenolic compounds. This study aims to optimize the extraction of phenolics from RBP and assess their bioaccessibility and bioactivity. The extraction process revealed that ethanol 50 % was the most effective solvent. Microwave-assisted hydroethanolic extraction (MAE) significantly outperformed conventional methods, with optimal conditions of 200 °C for 10 min yielding the highest concentrations of total phenolics (68 mg GAE/g RBP) and flavonoids (63 mg RE/g RBP). Eleven phenolic compounds were identified by HPLC-ESI-MS, with gallic acid and protocatechuic acid being the most prevalent. The gastrointestinal digestion revealed that although some phenolics suffered degradation (like ferulic acid and quercetin), phenolics are more bioaccessible and have relevant antioxidant activity. RBP extract exhibited anti-inflammatory activity by downregulating pro-inflammatory IL-1β and upregulating anti-inflammatory IL-10 cytokines in LPS-activated macrophages. These findings underscore the effectiveness of MAE in extracting bioactives from RBP, highlighting its potential in developing functional foods and nutraceuticals.

Major depressive disorder (MDD) presents as a multifaceted syndrome with complex pathophysiology and variable treatment responses, posing significant challenges in clinical management. Neuroinflammation is known to play pivotal mechanism in depression, linking immune responses with central nervous system (CNS) dysfunction. This review explores the interplay between peripheral and central inflammatory processes in MDD, emphasizing discrepancies in biomarker validity and specificity. While peripheral markers like cytokines have historically been investigated as proxies for neuroinflammation, their reliability remains contentious due to inconsistent findings, lack of correlation with neuroinflammatory markers, the influence of confounding variables, and the role of regulatory mechanism within the CNS. Additionally, the human brain shows a pattern of regionalized inflammation. Current methodologies for investigating neuroinflammation in humans in vivo, including neural-derived extracellular vesicles (EVs) and positron emission tomography (PET) neuroimaging using translocator protein, offer promising avenues while facing substantial limitations. We propose that future research in MDD may benefit from combined microglia-derived EV-TSPO PET neuroimaging analyses to leverage the strengths and mitigate the limitations of both individual methods.

Isatis tinctoria L. (Isatidis Radix) is a type of Chinese medicine used to treat various inflammations. Lignans are the main active ingredients of Isatidis Radix, which exhibit potent anti-inflammatory properties. However, the targets underlying the anti-inflammatory effects of Isatidis Radix remain unclear.

The objective of this research was to investigate the active constituents of Isatidis Radix and the molecular mechanisms behind its anti-inflammatory properties.

Firstly, Liquid Chromatography-Mass Spectrometry (LC-MS), network pharmacology, and molecular docking were employed to identify the active ingredients and key targets of Isatidis Radix lignans and predict their underlying anti-inflammatory mechanisms. Secondly, the enzyme-linked immunosorbent assay (ELISA) and the LPS-induced cell model were employed to verify the selective inhibitory effect of the active ingredients on the key target COX-2. Finally, the analgesic and anti-inflammatory effects were evaluated using the hot-plate test, acetic acid-induced writhing, complete Freund's adjuvant-induced paw edema, and xylene-induced ear edema assays.

A total of 24 compounds were found to be absorbed into the bloodstream, including 15 prototype components and 9 metabolites, as determined by LC-MS analysis. Furthermore, Network pharmacology analysis revealed that COX-2 served as the central target in the anti-inflammatory mechanism of Isatidis Radix lignans. Lariciresinol, a class of lignans derived from Isatidis Radix, selectively inhibited COX-2 and reduced inflammatory marker production in vitro and in vivo. It significantly increased the incubation period of heat pain, reduced writhing frequency, and decreased the severity of ear and foot swelling. Moreover, lariciresinol had no obvious gastrointestinal side effects and was not toxic to cardiomyocytes.

Our study indicates that Isatidis Radix lignans exert their anti-inflammatory effect by selectively inhibiting the COX-2 enzyme and confirms lariciresinol as a natural selective COX-2 inhibitor.

It was found that mutations in the Cathepsin C (CTSC) gene are responsible for Papillon-Lefevre syndrome which has a characteristic clinical feature of palmoplantar hyperkeratosis and psoriasiform lesions. However, its function in psoriasis is unclear so far. This study aims to investigate the roles and mechanisms of CTSC in psoriasis. The expression of CTSC was investigated by the analysis of single cell RNA sequencing (scRNA-seq) data and skin lesions of psoriasis patients. The role of CTSC in psoriasis was analyzed in human immortalized keratinocytes (HaCaT) stimulated with different inflammatory factors and mice of imiquimod (IMQ)-induced psoriasiform dermatitis. We showed that the expression of CTSC was significantly increased in the analysis of scRNA-seq data, which was identified in skin lesions of psoriasis patients and IMQ-induced psoriasis-like mice, and primary human keratinocytes and HaCaT cells stimulated with a cocktail of cytokines. In the presence of inflammatory factors or IMQ, CTSC inhibitor and knockdown of CTSC using siRNA exhibited significantly increased keratinocytes proliferation and the levels of proinflammatory cytokines. In vitro and in vivo experiments further showed that inhibited CTSC in psoriasis could activate the pathway of nuclear factor-κB (NF-κB). This study firstly outlines that inhibition of CTSC can contribute to inflammation and keratinocyte hyperproliferation by NF-κB pathway in psoriasis. It may provide a new perspective on understanding of the pathogenesis of psoriasis.

Diabetes mellitus is a chronic disease that has become more prevalent worldwide because of lifestyle changes. It leads to serious complications, including increased atherosclerosis, protein glycosylation, endothelial dysfunction, and vascular denervation. These complications impair neovascularization and wound healing, resulting in delayed recovery from injuries and an elevated risk of infections. The present study aimed to investigate the effect of lipoic acid (LA) on the key mediators involved in the wound healing process, specifically CD4 + CD25 + T cell subsets, CD4 + CD25 + Foxp3 + regulatory T (Treg) cells, T-helper-17 (Th17) cells that generate IL-17 A, glucocorticoid-induced tumor necrosis factor receptor (GITR) expressing cells, as well as cytokines such as IL-2, IL-1β, IL-6, and TNF-α and IFN-γ. These mediators play crucial roles in epidermal and dermal proliferation, hypertrophy, and cell migration.

We divided mice into 5 groups: the non-diabetic (normal control; NC), wounded non-diabetic mice (N + W), wounded diabetic mice (D + W), wounded diabetic mice treated with 50 mg/kg lipoic acid (D + W + L50) for 14 days, and wounded diabetic mice treated with 100 mg/kg lipoic acid (D + W + L100) for 14 days.

Flow cytometric analysis indicated that lipoic acid-treated mice exhibited a significant decrease in the frequency of intracellular cytokines (IL-17 A, TNF-α and IFN-γ) in CD4 + T cells, as well as a reduction in the number of GITR-expressing cells. Conversely, a significant upregulation in the number CD4+, CD25+, FOXp3 + and CD4 + CD25 + Foxp3 + regulatory T (Treg) cells was observed in this group compared to both the normal + wounded (N + W) and diabetic + wounded (D + W) groups. Additionally, the mRNA Levels of inflammatory mediators (IL-2, IL-1β, IL-6, and TNF-α) were downregulated in lipoic acid-treated mice compared to other groups. T thereby he histological findings of diabetic skin wounds treated with lipoic acid showed well-healed surgical wounds.

These findings support the beneficial role of lipoic acid in fine-tuning the balance between anti-inflammatory and pro-inflammatory cytokines, influencing both their release and gene expression.

Responses against infection trigger several signaling pathways that lead to the production of cytokines, these cytokines release ROS and RNS, damaging DNA and proteins turn into various diseases including cancer. To combat these harmful cytokines, the Nrf2 pathway is activated. The gene NFE2L2 encodes Nrf2, which is divided into seven conserved domains (Neh1-7). The DLG and ETGE motifs, conserved sequences of amino acid in the Neh2 domain of Nrf2, bind to the BTB domain of Keap1. BTB domain promotes Keap1's homodimerization resulting in Cul3 recruitment providing scaffold formation to E2 ubiquitin ligase to form ubiquitin complex. Under normal conditions, this complex regularly degrades Nrf2. However, once the cell is exposed to oxidative stress by ROS interaction with Keap1 resulting in conformational changes that stabilize the Nrf2. Nrf2 further concentrates on the nucleus where it binds with the transcriptional factor to perform the desired genes transcription for synthesizing SOD, GSH, CAT, and various other proteins which reduce the ROS levels preventing certain diseases. To prevent cells from oxidative stress, molecular hydrogen activates the Nrf2 pathway. To activate the Nrf2 pathway, molecular hydrogen oxidizes the iron porphyrin which acts as an electrophile and interacts with Keap1's cysteine residue.

Formyl peptide receptor 2 (FPR2) is a G protein-coupled receptor with seven transmembrane domains, widely distributed in human cells. It plays a crucial role in inflammation-related diseases. Known for its "double-edged sword" nature, FPR2 can bind a variety of exogenous and endogenous ligands, mediating both pro-inflammatory and anti-inflammatory responses in tissues such as eyes, liver, joints, lungs, nerves, and blood vessels. FPR2's bioactivities are regulated by a complex network of genes and signaling pathways. However, the precise regulatory mechanisms governing its functions in different inflammatory conditions are still not well understood. This review summarizes the FPR2's activities in various inflammation-related diseases and looks into its potential as a therapeutic target. This review highlights recent advances in developing exogenous agonists for FPR2 and discusses receptor expression across species to support nonclinical research. Overall, this review aims to clarify FPR2's role in inflammation and provide insights for the development of new drugs against inflammatory diseases.

Chitosan, derived from the deacetylation of chitin, is the second most widely used natural polymer, valued for its nontoxic, biocompatible, and biodegradable properties. These attributes have driven extensive research into diverse applications of chitosan and various derivatives. The key characteristics of chitosan muco-adhesion, permeability enhancement, drug release modulation, and antimicrobial activity are primarily due to its amino and hydroxyl groups. However, the limited solubility of raw chitosan in water and most organic solvents has posed challenges for broader application. Numerous chemically modified derivatives have been developed to address these inadequacies with improved physical and chemical properties. Among these derivatives, chitosan nanoparticles have emerged as versatile drug carriers with precise release kinetics and the capacity for targeted delivery, greatly enhancing drug efficacy and safety profiles for therapeutic applications. Due to these unique physicochemical properties, chitosan and chitosan nanoparticles are promising for improved drug delivery, vaccine administration, transplantation, gene therapy, and diagnostics. This review examines the physicochemical properties and bioactivities of chitosan and chitosan nanoparticles, emphasizing their broad-ranging biomedical applications.

Inflammation-associated diseases have become widespread and pose a significant threat to human health, and the therapeutic methods for diverse diseases are inadequate due to the undesirable effects of synthetic ingredients. Recently, more and more evidence indicated that phytochemicals, plant secondary metabolites, have numerous therapeutic functions against human diseases via affecting a variety of mechanisms with their distinct advantages of high efficiency and low toxicity. Here, we highlight the mechanisms of phytochemicals to hinder inflammation-associated diseases (including Inflammatory diseases, cardiovascular diseases, metabolic syndrome, neurological disorders, skin diseases, respiratory diseases, kidney diseases, gastrointestinal diseases, retinal diseases, viral infections) by regulating the crosstalk among various signal cascades (including MicroRNAs, SIRT1, DNMTs, NF-κB, NLRP3, TGF-β, the Gasdermin-mediated pyroptosis pathway), which can be considered as a novel and potential therapeutic strategy. Furthermore, phytochemicals could prevent virus infection by disturbing different targets in the virus replication cycle. However, natural plants have shown limited bioavailability due to their low water solubility, the use of adjuvants such as liposomal phytochemicals, phytochemical nanoparticles and phytochemicals-phospholipid complex promote their bioavailability to exhibit beneficial effects against various diseases. The purpose of this review is to explore the molecular mechanisms and promising applications of phytochemicals in the fields of inflammation-associated diseases and virus infection to provide some direction.

Immunoregulatory cytokines may play a fundamental role in tumor growth and the acute surgical stress response. Inflammatory cytokine profiles have the potential to serve as biomarkers. This study aimed to correlate tumor- or surgery-related inflammatory cytokine profile, derived from data mining, with clinical data and the hospital length of stay for non-small cell lung cancer (NSCLC) patients during the early enhanced recovery after surgery (ERAS) period.

A multi-phase detection approach was used, involving pre- and post-operative NSCLC patients and matched healthy controls. In the screening phase, plasma levels of 48 cytokines were quantified using a Luminex multiplex bead array to identify tumor- or surgery-related cytokine profiles. In the confirmation phase, differentially expressed cytokines were validated using ELISA with a new set of samples. Tumor-related cytokines were identified by comparing preoperative NSCLC patients with controls, while tumor or surgery-related cytokines were determined by comparing with the same cohort before and after surgery, as well as postoperative patients with controls. We then searched cancer genomics databases and protein atlas resources to investigate cytokine-related RNA expression and RNA-protein interactions. Finally, we integrated and standardized our results, conducting correlation analysis to explore relationships between cytokines, hospital length of stay, and clinical data.

During the initial phase of the ERAS, a comprehensive array of differential cytokines associated with tumors or surgery, including Eotaxin, IL-1β, IL-1Ra, IL-6, IL-13, IL-16, IP-10, MCP-1, PDGF-BB, RANTES, SCF, and TRAIL, were identified. Preoperative levels of RANTES, urea nitrogen, prognostic-nutritional index, and age may serve as potential indicators for predicting hospital length of stay.

The multi-phase detection analysis has identified a plasma cytokine signature for NSCLC patients during the early ERAS period. Assessment of cytokine profiles and clinical data may reveal unique insights into short-term survival outcome under ERAS.

This study explored the impact of astaxanthin (AST) supplementation on growth performance, serum lipid profile, gut morphology, and antioxidant and immune function in the intestinal mucosa of Pekin ducks subjected to overfeeding. A total of 150 male Pekin ducks at one day of age were randomly allotted into five treatment groups with five replicates of six ducks each. The control group and ad libitum group (ALG) received a basal diet while others received basal diets supplemented with AST at 40 mg/kg (Low-dose group [LDG]), 80 mg/kg (medium-dose group [MDG]), and 120 mg/kg (high-dose group [HDG]). After 1 to 14 d on basal diets (brooding phase), the ducks were assigned to the dietary treatment groups for 15 to 38 d (Grower phase) and 39 to 42 d (overfeeding period). Results indicated that AST supplementation improved final body weight and weight gain at both the grower and overfeeding phases (P < 0.05). Overfeeding increased the serum lipid level, altered intestinal morphology, and led to higher expression of pro-inflammatory factors and oxidative stress biomarkers while reducing antioxidant enzyme activity, associated gene expression, and anti-inflammatory factors in the duodenal and jejunal mucosa (P < 0.05). Additionally, overfeeding caused increased apoptotic cell counts in the duodenal and jejunal mucosa of the control group (P < 0.05), culminating in intestinal tissue damage and dysfunction. Dietary supplementation of AST mitigated these adverse effects, alleviated intestinal damage and promoted gut health. It exerted a hypolipidemic effect, improved villi morphometrics in the duodenum, jejunum, and ileum, and enhanced the levels of interleukin-4 (IL-4), soluble tumor necrosis factor-alpha receptor (sTNFαR), and transforming growth factor-beta (TGF-β) (P < 0.05). It also increased the activities of antioxidant enzymes and the mRNA expression of key antioxidant-related genes, including nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione S-transferases (GSTs), and glutamate-cysteine ligase catalytic subunit (GCLC) (P < 0.05). Moreover, it reduced the expression of pro-inflammatory factors, oxidative stress biomarkers such as reactive oxygen species (ROS) and malondialdehyde (MDA), and the number of apoptotic cells in the duodenal and jejunal mucosa (P < 0.05). Immunoglobulin secretion and mucosal immunity were also significantly improved with AST supplementation (P < 0.05). Variations among the AST dietary groups suggest that a medium dosage of 80 mg/kg could effectively mitigate intestinal damage from overfeeding while enhancing growth performance, antioxidant defences, and immune responses. Our results would provide a theoretical reference for using AST as a nutritional strategy to enhance gut health in ducks exposed to overfeeding.

The Val30Met (V30M) and Val122Ile (V122I) transthyretin (TTR) mutations often beget hereditary amyloid transthyretin amyloidosis (hATTR). Since symptoms are progressively debilitating and potentially fatal if untreated, low survival rates result from late diagnoses of hATTR patients. This retrospective analysis of microarray and biobank data helped establish clinical biomarkers for early hATTR detection.

In a Portuguese sample of V30M carriers (n = 183), gene profiling identified dysregulated immune markers. Among African Americans (AA) and Hispanic/Latinx Americans (HA) from the Mount Sinai BioMe Biobank (n = 28,718), a case-control style Phenome-Wide Association Study (PheWAS; odds ratio [95% confidence interval]) of V122I for phenotypic and echocardiogram traits (β coefficients [95 % CI]) determined gene pleiotropy.

Among V30M profiles, 96 (52.4%) were symptomatic, expressing upregulated neutrophil activity (p < 10-16), IL-6/JAK/STAT3 signaling (p < 10-3), and downregulated CD4+T cell expression (p = 0.009), compared to their asymptomatic counterparts. In BioMe, 562 (2.0%) were V122I carriers, demonstrating associations with heart failure (1.71 [1.23-2.39]; p = 0.0014), amyloidosis (20.79 [8.42-51.31]; p = 4.67 × 10-11), secondary/extrinsic cardiomyopathies (17.73 [7.25-43.37]; p = 2.97 × 10-10), peripheral nerve disorders (4.14 [2.42-7.09]; p = 2.26 × 10-7), primary angle-closure glaucoma (8.03 [3.15-20.46]; p = 1.27 × 10-5), malignant neoplasm of the female breast (4.48 [2.23-9.00]; p = 2.48 × 10-5), fracture of tibia and fibula (8.42 [3.25-21.89]; p = 1.19 × 10-5), and Carpal tunnel syndrome (2.62 [1.68-4.11]; p = 2.44 × 10-5). Echocardiographic presentations included higher LVEDV (15.87 [9.63-22.10]; p = 6.04 × 10-7) and LA length (1.52 [0.69-2.35]; p = 3.31 × 10-4). Race-stratified associations identified that AA presented more severe cardiac abnormalities than HA.

This study identified inflammatory biomarkers upregulated in symptomatic V30M carriers and phenotypic/echocardiographic traits associated with V122I, representing comorbidities of hATTR pathology. Such markers can provide the basis for future improvements in diagnostic regimes to deliver early therapies.

The aim of this study is to investigate the antinociceptive, anti-inflammatory and antipyretic effects of quercetin. Additionally, molecular docking studies were conducted to evaluate potential interactions between quercetin and various molecular targets. Animal models were used to conduct a comprehensive pharmacological investigation of quercetin. Evaluation of analgesic activity revealed a reduction in the number of abdominal cramps during the twisting test and inhibition of pain during the second phase of the formaldehyde test. Additionally, evaluation of its anti-inflammatory activity showed a reduction in ear oedema. However, it is important to note that quercetin administration has not been shown to significantly reduce yeast-induced hyperthermia. The docking study revealed the high inhibitory potential of quercetin against the COX-2 receptor.

The nuclear factor kappa B (NF-κB) is a critical pathway that regulates various cellular functions, including immune response, proliferation, growth, and apoptosis. Furthermore, this pathway is tightly regulated to ensure stability in the presence of immunogenic triggers or genotoxic stimuli. The lack of control of the NF-κB pathway can lead to the initiation of different diseases, mainly autoimmune diseases and cancer, including Renal cell carcinoma (RCC). RCC is the most common type of kidney cancer and is characterized by complex genetic composition and elusive molecular mechanisms.

The current review summarizes the mechanism of NF-κB dysregulation in different subtypes of RCC and its impact on pathogenesis.

This review highlights the prominent role of NF-κB in RCC development and progression by driving the expression of multiple genes and interplaying with different pathways, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. In silico analysis of RCC cohorts and molecular studies have revealed that multiple NF-κB members and target genes are dysregulated. The dysregulation includes receptors such as TLR2, signal-transmitting members including RelA, and target genes, for instance, HIF-1α. The lack of effective regulatory mechanisms results in a constitutively active NF-κB pathway, which promotes cancer growth, migration, and survival. In this review, we comprehensively summarize the role of dysregulated NF-κB-related genes in the most common subtypes of RCC, including clear cell RCC (ccRCC), chromophobe RCC (chRCC), and papillary RCC (PRCC).

Environmental factors may affect gene expression through epigenetic modifications of histones and transcription factors. Here, we report that cellular uptake of sorbate, a common food preservative, induces lysine sorbylation (Ksor) in mammalian cells and tissue mediated by the noncanonical activities of class I histone deacetylases (HDAC1-3). We demonstrated that HDAC1-3 catalyze sorbylation upon sorbate uptake and desorbylation in the absence of sorbate both in vitro and in cells. Sorbate uptake in mice livers significantly induced histone Ksor, correlating with decreased expressions of inflammation-response genes. Accordingly, sorbate treatment in macrophage RAW264.7 cells upon lipopolysaccharide (LPS) stimulation dose-dependently down-regulated proinflammatory gene expressions and nitric oxide production. Proteomic profiling identified RelA, a component of the NF-κB complex, and its interacting proteins as bona fide Ksor targets and sorbate treatment significantly decreased NF-κB transcriptional activities in response to LPS stimulation in RAW264.7 cells. Together, our study demonstrated a noncanonical mechanism of sorbate uptake in regulating epigenetic histone modifications and inflammatory gene expression.

The investigation of Brazil's vast plant biodiversity is crucial. The genus Pouteria, though minimally explored chemically and pharmacologically, has numerous ethnopharmacological reports.

This study aims to evaluate the antioxidant, anti-inflammatory, antinociceptive, angiogenic, and cytotoxic properties of hydroethanolic extract from the leaves of P. guianensis, as well as to characterize its chemical composition.

Several extracts from P. guianensis leaves were evaluated for antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) reduction model. Chromatographic analyses and chemometric correlations were also applied. The 80 % hydroethanolic extract was selected and dereplicated using spectrometric techniques, and its anti-inflammatory and antinociceptive activities were assessed through carrageenan-induced paw edema, pain models, and the hot plate test. Antiangiogenic properties were evaluated using the chorioallantoic membrane (CAM) technique and cytokines levels were also measured.

Chemometric analyses identified myricitrin as a potential active marker for antioxidant activity, with mass spectrometry revealing a high phenolic content, particularly flavonoids quantified at 2.47 % and tannins at 17.19 %. Previous oral administration (p.o.) of the 80 % hydroethanolic extract of P. guianensis demonstrated significant anti-inflammatory and antinociceptive effects without impairing the animals' motor function. The hydroethanolic extract reduced TNF-α and IL-1β levels and also exhibited antiangiogenic properties, suggesting potential mechanisms for its anti-inflammatory action. Furthermore, no toxicity was observed in the CAM model.

This study highlights the significant pharmacological activities of P. guianensis hydroethanolic extract, warranting further investigation into its mechanisms of action. Additionally, it provides the first chemical characterization of the species, revealing a high phenolic content.

Lippia graveolens Kunth has been widely used in traditional Mexican medicine to relieve stomach pain, menstrual pain, and respiratory illnesses (flu and cough). However, its anti-inflammatory effect has not been studied in acute and chronic inflammation models.

to evaluate the effect of L. graveolens Kunth extract and microcapsules against paw and airway inflammation.

Paw edema in mice was induced with carrageenan, while allergic asthma was sensitized and challenged with ovalbumin. L. graveolens Kunth samples were orally administered to mice in 30, 100, 300, 560, and 717 mg/kg doses to evaluate edema size, while for the following tests, the 560 mg/kg dose was administered. Inflammatory cell count, serum IgE level, and detection of proinflammatory cytokine levels in serum, plantar tissue, and lung tissue were analyzed.

Edema thickness measurement revealed that L. graveolens Kunth reduces paw inflammation and could potentially be anti-inflammatory in acute and chronic inflammation. Treatments with L. graveolens Kunth significantly decreased the number of inflammatory cells in the blood, the production of IgE in serum, and the cytokines IL-1β, IL-6, and TNF-α levels in serum, paw, and lungs.

These findings suggest that L. graveolens Kunth has an anti-inflammatory effect on carrageenan-induced paw edema and ovalbumin-induced allergic asthma in mice and might be a promising protective agent for inflammatory diseases.

Due to their interesting biological activities, a mannose-binding lectin isolated from Dioclea violacea seeds, known as DvL have attracted considerable attention. In this study, we performed macroscopic, histologic, and immunohistochemical analysis on chicken embryo chorioallantoic membranes (CAM) to investigate the effects of DvL on the angiogenic process. Data showed a potential angiogenic effect of DvL at the highest concentrations tested (50 and 100 μg/mL). This effect was confirmed through increased neovascularization, inflammatory cells, and fibroblasts in histological analysis of the CAM. In addition, the immunohistochemistry of CAM showed that DvL induced secretion of TNF-α and VEGF, important cytokines involved in angiogenesis. Therefore, increased neovascularization may result from a pro-inflammatory response through VEGF and TNF-α secretion. In contrast, the DvL effects on the angiogenic process and the TNF-α and VEGF secretion were significantly reduced by co-incubation with mannose. Thus, protein-carbohydrate interactions between DvL and cell membrane glycans are likely the main events involved in this effect. Therefore, our results demonstrated that DvL is a potent angiogenic agent, suggesting its potential application as a prototype molecule for developing new drugs with healing properties.

Oxidative stress and chronic inflammation are important drivers in the pathogenesis and progression of many chronic diseases, such as cancers of the breast, kidney, lung, and others, autoimmune diseases (rheumatoid arthritis), cardiovascular diseases (hypertension, atherosclerosis, arrhythmia), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease), mental disorders (depression, schizophrenia, bipolar disorder), gastrointestinal disorders (inflammatory bowel disease, colorectal cancer), and other disorders. With the increasing demand for less toxic and more tolerable therapies, flavonoids have the potential to effectively modulate the responsiveness to conventional therapy and radiotherapy. Flavonoids are polyphenolic compounds found in fruits, vegetables, grains, and plant-derived beverages. Six of the twelve structurally different flavonoid subgroups are of dietary significance and include anthocyanidins (e.g. pelargonidin, cyanidin), flavan-3-ols (e.g. epicatechin, epigallocatechin), flavonols (e.g. quercetin, kaempferol), flavones (e.g. luteolin, baicalein), flavanones (e.g. hesperetin, naringenin), and isoflavones (daidzein, genistein). The health benefits of flavonoids are related to their structural characteristics, such as the number and position of hydroxyl groups and the presence of C2C3 double bonds, which predetermine their ability to chelate metal ions, terminate ROS (e.g. hydroxyl radicals formed by the Fenton reaction), and interact with biological targets to trigger a biological response. Based on these structural characteristics, flavonoids can exert both antioxidant or prooxidant properties, modulate the activity of ROS-scavenging enzymes and the expression and activation of proinflammatory cytokines (e.g., interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)), induce apoptosis and autophagy, and target key signaling pathways, such as the nuclear factor erythroid 2-related factor 2 (Nrf2) and Bcl-2 family of proteins. This review aims to briefly discuss the mutually interconnected aspects of oxidative and inflammatory mechanisms, such as lipid peroxidation, protein oxidation, DNA damage, and the mechanism and resolution of inflammation. The major part of this article discusses the role of flavonoids in alleviating oxidative stress and inflammation, two common components of many human diseases. The results of epidemiological studies on flavonoids are also presented.

Sponges of the genus Neopetrosia are known for the production of a large diversity of bioactive metabolites. Contignasterines A (1) and B (2) were isolated as major metabolites of the sponge Neopetrosia cf. rava collected in the Bismarck Sea along with the known and highly bioactive steroid contignasterol (3) possessing a similar oxidized aglycone. Contignasterines are characterized by the presence of a 2-aminoimidazole branched on the side-chains of the oxidized steroid, and 1 also contains an unusual phosphate group at C-7. The anti-inflammatory activities of these compounds were investigated and revealed that all three compounds inhibited the production of pro-inflammatory mediators.

Two novel series of di-aryl/tri-aryl substituted pyrazole ester derivatives 15a-h and 19a-d were designed, synthesized as novel non-acidic lonazolac analogs and tested for its COX-2, 5-LOX, 15-LOX, iNOS, pro-inflammatory cytokines TNF-α and PGE2 inhibitory activities. All the tested compounds showed excellent COX-2 inhibitory activity (IC50 = 0.059-3.89 μM), compared to that of celecoxib (IC50 = 0.22 μM), where derivatives 15c, 15d, 15 h and 19d were found to be the most potent showing COX-2 selectivity index in range of (S.I. = 28.56-98.71) compared to celecoxib (S.I. = 13.65). Moreover, the most potent four derivatives 15c, 15d, 15 h and 19d showed outstanding 5-LOX and 15-LOX inhibitory activities (IC50 = 0.24-0.81, 0.20-2.2 respectively, compared to zileuton IC50 = 1.52 and 0.54, respectively). Further investigation of the anti-inflammatory mechanistic study of derivatives 15c, 15d, 15 h and 19d revealed that these four compounds exhibited comparable TNF-α and PGE2 (LPS-induced pro-inflammatory cytokines) inhibitory activities (IC50 = 0.77-1.20 μM and 0.28-0.52 μM respectively) when compared to celecoxib (IC50 = 0.87 μM and 0.38 μM respectively) as reference drug using lipopolysaccharide-activated RAW 264.7 macrophages. Based on the advanced inhibitory activity of compounds 15c, 15d, 15 h and 19d against LPS-induced pro-inflammatory mediators (TNF-α and PGE2), inducible nitric oxide synthase (iNOS) inhibition assay was carried out. Remarkably, compounds 15c, 15d, 15 h and 19d showed higher potency with lower IC50 (0.41-0.61 µM) when compared to the reference drug celecoxib (0.48 µM). Prior to in vivo anti-inflammatory activity screening, cytotoxicity testing was performed to ascertain safe and non-toxic concentrations of each compound. Safe doses of compounds were determined using lipopolysaccharide-activated RAW 264.7 macrophages, moreover results showed that compounds 15c, 15d, 15 h and 19d were more safer (less cytotoxic) with higher IC50 (178.95-301.40 µM) when compared to the reference drug celecoxib (148.90 µM). In vivo anti-inflammatory activity of the target compounds 15c, 15d, 15 h and 19d reinforced the results of in vitro screening as the derivatives 15c, 15d, 15 h and 19d showed (ED50 = 8.22-31.22 mg/kg, respectively) and were more potent than celecoxib (ED50 = 40.39 mg/kg). All screened derivatives 15c, 15d, 15 h and 19d were less ulcerogenic (ulcer indexes = 1.22-3.93) than lonazolac (ulcer index = 20.30) and comparable to celecoxib (ulcer index = 3.02). In silico docking and ADME studies were carried out in order to clarify the interactions of the most active derivatives 15c, 15d, 15 h and 19d with the target enzymes and their pharmacokinetic parameters.

Covering: up to early 2025Privileged compound classes of anti-inflammatory natural products are those where there are many reported members that possess anti-inflammatory properties. The identification of these classes is of particular relevance to drug discovery, as they could serve as valuable starting points in developing effective and safe anti-inflammatory agents. The privileged compound classes of natural products include the polyphenols, coumarins, labdane diterpenoids, sesquiterpene lactones, isoquinoline and indole alkaloids, each offering a variety of molecular scaffolds and functional groups that enable diverse interactions with biological targets. From a medicinal chemistry point of view, natural products are both a boon and a bane. The multi-targeting nature of natural products is a boon in the treatment of multi-factorial diseases such as inflammation, but promiscuity, poor potency and pharmacokinetic properties are significant hurdles that must be addressed to ensure these compounds can be effectively used as therapeutics. In addition, there are continued controversies regarding the efficacies of some of these natural products that will continue to polarise their use. In this review, examples of natural products of six privileged compound classes will be discussed for their potential use and possible further development as anti-inflammatory drugs.

Inflammation is a vital biological response to noxious stimuli, including physical injury and pathogenic infection, and involves immune cells and various inflammatory mediators, limiting cell damage and eliminating pathogens. Although essential for healing, inflammation can cause symptoms, such as fever, swelling, pain, and itching, potentially reducing quality of life. Elsholtzia ciliata used in traditional medicine has numerous medicinal characteristics such as antiviral, antibacterial, antipyretic, diaphoretic, carminative, astringent, and diuretic effects.

This study aimed to evaluate the anti-inflammatory properties of E. ciliata extract (ECE) in RAW264.7 cells treated with polyinosinic polycytidylic acid (Poly I:C).

PGE2, IL-1β, TNF-α, IFN-β, and IL-6 levels were quantified by ELISA and/or real-time PCR. COX-2 and iNOS expression was analyzed using western blotting and real-time PCR. Phosphorylation and expression levels of signaling proteins, including AKT, IRF3, TBK1, STAT1, MAPKs, IκB, and IκK were analyzed using western blotting. The active substance of ECE was determined using high-performance liquid chromatography-mass spectrometry (HPLC-MS).

Our detections revealed that ECE inhibited the levels of nitric oxide and central inflammatory mediators, such as iNOS and COX-2. Furthermore, ECE downregulated the expression of pro-inflammatory cytokines, including PGE2, IL-1β, TNF-α, IFN-β, and IL-6. Additionally, ECE inhibited the phosphorylation of several cell signaling pathways, including AKT, TBK1/IRF3, MAPK, and NF-κB, in Poly I:C-treated RAW264.7 cells.

These results highlight E. ciliata as a candidate for mitigating virus-induced inflammation, providing valuable insights into its use in the development of new anti-inflammatory therapeutics.

Despite the undeniable role of chemotherapeutics in cancer treatment, their administration may be associated with various side effects. Cardiac injury is among the most crucial side effects related to the induction of chemotherapeutic agents. Since the heart is a vital organ, cardiotoxicity often prevents clinicians from continuing chemotherapy. Hesperidin and hesperetin, flavonoids derived from citrus fruits, possess several pharmaceutical properties. This study firstly explores the cardioprotective effects of hesperidin and hesperetin against chemotherapy-induced cardiotoxicity mechanisms, emphasizing their potential as adjunctive therapies. Key literature gaps are identified, and further mechanistic studies will be proposed. The findings underscore the translational potential of these flavonoids, advocating for rigorous preclinical optimization and clinical trials to validate their efficacy and safety. This review lays a foundation for integrating natural compounds into cardioprotective strategies in oncology. A systematic search was conducted in databases (PubMed, Scopus, ISI) until May 2025, according to PRISMA principles. The search terms were chosen according to our research objective and queried in the title and abstract. Following the screening of 82 papers, twelve articles were selected based on our inclusion and exclusion criteria. Based on the evaluated results, chemotherapy adversely affects cardiac tissue, leading to elevated risks of morbidity and mortality. Co-administration of hesperidin and hesperetin with chemotherapy prevents heart injury and preserves cardiac function, maintaining it almost like a normal heart. The protective role of hesperidin and hesperetin is based on their ability to fight free radicals, reduce inflammation, and stop cell death. Nonclinical investigations indicate that hesperidin and hesperetin ameliorate chemotherapy-induced cardiotoxicity. Nonetheless, they may influence the efficacy of anticancer medications, which primarily function by elevating oxidants, inflammation, and apoptosis. This indicates that meticulously designed trials are necessary to evaluate the efficacy and safety of this combination along with the synergistic potential of them in preventing chemotherapy-induced cardiotoxicity while maintaining anticancer effectiveness.

Treating urinary tract infections (UTIs) effectively is a difficult task due to the emergence of antibiotic-resistant bacteria and limited antibiotic access to intracellular bacteria within the bladder lining. Numerous studies of the antibiotics-nanodiamonds (NDs) synthesis and their inhibitory effect on bacteria have been performed previously. However, their effectiveness and toxicity in cell-based and animal infection models remain unclear. In this study, we presented the utilization of biopolymer-coated nanodiamonds for the delivery of tetracycline (TET) to the intracellular bacterial communities within the bladder cells using an intravesical delivery approach, aiming to effectively treat UTIs. Compared with antibiotics alone, the TET-loaded ND-based carrier system significantly improved the clearance of intracellular bacteria in the infected cell and animal models. Moreover, the intravesical delivery avoids the potential toxic effects from NDs accumulation in the organs, and minimizes the loss of the drugs during delivery. These results offer a promising strategy to treat chronic infections and prevent the recurrence of urinary tract infections (rUTIs).

As a result of the SARS-CoV-2 pandemic, various population groups were formed that had acute and asymptomatic COVID-19. A survey in these groups revealed with equal frequency an asthenic symptom complex, the so-called post-COVID-19 syndrome (PCS). The frequency of urgent surgical pathology against the background of PCS and structural and functional disorders of various organs was increased. The aim - to study the dynamics of immunoresistance factors changes in patients with urgent surgical pathology that developed against the background of PCS and to identify pathogenic markers of the severe course and the risk of mortality.

To examine patients with PCS and urgent cardiovascular (n = 103) and abdominal (n = 106) pathology we used the following methods: fluorescence microscopy, confocal microscopy, flow cytometry, spectrophotometry, ELISA.

We revealed a temporal dependence of immune dysfunction in patients with a comorbid course of urgent surgical pathology and PCS. The nature of the DAMP (damage-associated molecular patterns) cytotoxic fractions ratio was associated with certain changes in innate and adaptive immunity factors, severity of the condition and risk of mortality. At the first stage (2020-2021), patients with PCS has disorders of the humoral and cellular components of innate immunity against the background of an increase in the oligopeptide and peptide DAMP fractions. At the second stage (2022-2024) of PCS development, changes in innate as well as adaptive immunity were observed against the background of an increase in the cytotoxic oligonucleotide DAMP fraction (mortality was 17.3%).

The identified markers of impaired immunoresistance in cardiovascular and abdominal urgent pathology can be used to select targeted therapy tactics.

The leaves of Flabellaria paniculata Cav. (Malpighiaceae) are used in the treatment of conditions associated with inflammation and pain.

The study aimed at evaluating the anti-inflammatory and antinociceptive effects of ethanol extract from the leaves of F. paniculata.

The extract was obtained by maceration with ethanol (95 %) and characterized by GC-MS. The anti-inflammatory effect was assessed in carrageenan, serotonin, histamine-induced paw oedema and xylene-induced ear oedema models at the dose of 50, 100 and 200 mg/kg. Antioxidant parameters and cytokine production (IL-6, and TNF-α) levels were determined in carrageenan air pouch model. The antinociceptive property was also evaluated.

The extract at 200 mg/kg showed significant anti-inflammatory activity at 2 h (39.66 %, inhibition) which lasted for 5 h (70.37 %, inhibition) in carrageenan paw oedema. In the air pouch model, the extract decreased neutrophils and monocytes counts in the exudate but not lymphocytes count. At the dose of 200 mg/kg, the release of TNF-α and IL-6 was inhibited by 56.6 % and 35.9 %, respectively. The extract boosted catalase and SOD activities in addition to GSH level. Xylene-induced ear oedema was inhibited by 52.25, 62.62 and 64.97 %, at the dose of 50, 100 and 200 mg/kg, respectively. Antinociceptive activity of the extract (100 and 200 mg/kg) was significant in acetic acid-induced writhing test (53.33 and 54.57 %, inhibition) and the late phase of formalin test (88.04 % and 92.13 %, inhibition). No significant effect was found on motor performance in the open field. The GC-MS profile revealed the presence of 15 compounds, with cyclododecyne, hexadecanoic acid, ethyl ester, n-Hexadecanoic acid, (E)-9-Octadecenoic acid ethyl ester, 1,4,2,5 Cyclo-hexanetetrol and phytol, acetate as the main compounds.

F. paniculata demonstrated anti-inflammatory and antinociceptive effect and the anti-inflammatory mechanism could be through inhibition of the inflammatory markers and oxidative parameters.

Currently, cardiovascular diseases (CVDs) are the leading cause of death globally. According to the WHO, the number of CVDs-related deaths increases by 20% annually. C-reactive protein (CRP), a biomarker for CVDs that sharply rises during cardiac events, was used to monitor these critical conditions at an early stage. To address the need for highly sensitive, selective, and portable CRP detection, a nickel-doped copper ferrite nanoparticle-based electrochemical biosensor was developed. In this work, optimized nickel-doped copper ferrite (Ni(0.10)CuFe2O4) nanoparticles (NPs) were synthesized by doping copper ferrite NPs with varying nickel concentrations (0.05, 0.10, 0.15, and 0.20 M) via a hydrothermal method using aqueous leaf extract of Magnolia grandiflora. The NPs were characterized by using XRD, FT-IR, UV, SEM, EDX, and HR-TEM/TEM. The synthesized NPs were deposited on a functionalized indium tin oxide (ITO) surface via the electrophoretic deposition (EPD) method. Electrochemical sensing was performed by using electrochemical impedance spectroscopy (EIS). The biosensor demonstrated linear detection of CRP biomarkers across a range of 0.5 to 500 ng/mL, with a sensitivity of 5.426 Ω/ng cm2 at 0.5 ng/mL and 0.68244 Ω/ng cm2 at 500 ng/mL. The limit of detection (LOD) values were 0.038 ng/mL (lower concentration range) and 0.033 ng/mL (higher concentration of the analyte range).

Monomeric C-reactive protein (mCRP) is a pro-inflammatory molecule generated by the dissociation of native CRP. Clinical and experimental studies suggest that mCRP deposition in the brain induces Alzheimer's disease (AD) pathology and cognitive loss. Pathological neuroinflammation is increasingly suggested as relevant in AD. Innovative therapies against neuroinflammation are desperately needed, and inhibitors of the enzyme soluble epoxide hydrolase (sEH) are a promising new generation of anti-inflammatory drugs. Mouse primary microglia and BV2 cell line cultures were exposed to mCRP to analyze its pro-inflammatory mechanisms. sEH inhibitors, both newly synthesized UB-SCG-55 and UB-SCG-65, and the reference agent TPPU, were tested for their anti-inflammatory action against mCRP. Phenotypic changes were analyzed through cell imaging techniques, as well as molecular analysis of inflammatory mediators and gene activation pathways. Results show that mCRP triggers a pro-inflammatory response through three main inflammatory pathways: iNOS, NLRP3, and COX-2, followed by increased cytokine generation. Polarization of microglia toward a M1-like phenotype was confirmed by morphological analysis. Also, mCRP can bind to and cross the cell membrane, providing further insight into its mechanisms of action. sEH inhibitors were effective against mCRP induction of a reactive microglial phenotype. The first-line compound UB-SCG-55 emerged as the most potent anti-inflammatory against mCRP injury. Therefore, the direct activation of microglia by mCRP provides evidence of its role in triggering and exacerbating neurodegenerative diseases with a neuroinflammatory component, such as AD. Furthermore, the protection given by inhibitors of sEH confirms its potential as innovative drugs against deleterious effects of neuroinflammation.

Parkinson's Disease (PD), a complex neurodegenerative disorder, is increasingly recognized as a systemic condition involving multi-organ interactions. Emerging evidence highlights roles of organ-brain axes (lung-, liver-, heart-, muscle-, bone-, and gut-brain) in PD pathogenesis. These axes communicate via neural, circulatory, endocrine, and inflammatory pathways, collectively driving neurodegeneration. For example, lung dysfunction in PD involves respiratory impairment and inflammatory signaling, while gut dysbiosis triggers α-synuclein aggregation via the vagus nerve. Such cross-organ interactions underscore PD's systemic nature, challenging traditional brain-centric models.

1. Decipher mechanisms linking peripheral organs (e.g., lung, gut) to PD via shared pathways. 2. Explore bidirectional organ-brain interactions (e.g., liver metabolism affecting neurotoxin clearance). 3. Propose multi-organ therapeutic strategies targeting integrated signaling networks. Key Scientific Concepts of Review. 1. Lung-Brain Axis: Respiratory dysfunction (motor impairment, inflammation) exacerbates neurodegeneration. 2. Liver-Brain Axis: Metabolic dysregulation alters neurotoxin clearance; drugs (e.g., levodopa) impact liver function. 3. Heart-Brain Axis: Autonomic dysfunction reduces cerebral blood flow; neuroendocrine changes promote α-synuclein pathology. 4. Muscle-Brain Axis: Neuromuscular/metabolic disruptions worsen motor symptoms. 5. Bone-Brain Axis: Bone-derived hormones (osteocalcin, OCN) and inflammation influence cognition. 6. Gut-Brain Axis: Dysbiosis drives α-synuclein misfolding; gut metabolites modulate neuroinflammation. Integrated Mechanisms: Shared pathways (neuroinflammation, oxidative stress) create a regulatory network, suggesting therapies targeting multi-organ crosstalk (e.g., probiotics, anti-inflammatory agents).

In this study, the coumarin natural product minutuminolate (MNT) was used as a starting point for the development of anti-inflammatory agents. Through structure-activity relationship studies, a lead compound MD-1 was designed and synthesized, exhibiting significantly improved anti-inflammatory activities. Mechanistic studies revealed that MD-1 is a degrader of the p105 subunit of NF-κB. Gene knockdown experiments further showed that the Cullin-ring ligase (CRL) SCFβTrCP is involved in MD-1-induced p105 degradation. This leads to suppressed NF-κB transcriptional activity, which is consistent with its potent anti-inflammatory effects. Taken together, our work challenges the longstanding notion that NF-κB is undruggable, as we demonstrate that the p105 subunit of NF-κB is indeed tractable with small molecules. More importantly, our study highlights that natural products are valuable starting points for the discovery and development of anti-inflammatory agents with novel mechanisms of action.

Introduction: Sepsis leads to substantial global health burdens in terms of morbidity and mortality and is associated with numerous risk factors. It is crucial to identify sepsis at an early stage in order to limit its escalation and sequelae associated with the condition. The purpose of this research is to predict ICU mortality early and evaluate the predictive accuracy of machine learning algorithms for ICU mortality among septic patients. Methods: The study used a retrospective cohort from computerized ICU records accumulated from 280 hospitals between 2014 and 2015. Initially the sample size was 23.47K. Several machine learning models were trained, validated, and tested using five-fold cross-validation, and three sampling strategies (Under-Sampling, Over-Sampling, and Combination). Results: The under-sampled approach combined with augmentation for the Extra Trees model produced the best performance with Accuracy, Precision, Sensitivity, Specificity, F1-Score, and AUC of 90.99%, 84.16%, 94.89%, 88.48%, 89.20%, and 91.69%, respectively, with Top 30 features. For Over-Sampling, the Top 29 combined features showed the best performance with Accuracy, Precision, Sensitivity, Specificity, F1-Score, and AUC of 82.99%, 51.38%, 71.72%, 85.41%, 59.87%, and 78.56%, respectively. For Down-Sampling, the Top 31 combined features produced Accuracy, Precision, Sensitivity, Specificity, F1-Score, and AUC of 81.78%, 49.08%, 79.76%, 82.21%, 60.76%, and 80.98%, respectively. Conclusions: Machine learning models can reliably predict ICU mortality when suitable clinical predictors are utilized. The study showed that the proposed Extra Trees model can predict ICU mortality with an accuracy of 90.99% accuracy using only single-entry data. Incorporating longitudinal data could further enhance model performance.