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Purpose: To evaluate the effect of interleukin-6 (IL-6) inhibitor (tocilizumab) on bacterial infection-associated bone resorption around implants during osseointegration in rabbits. Materials and Methods: At total of 24 male, 9-monthold New Zealand white rabbits were included, and their two mandibular anterior teeth were extracted. Three months after extraction, 24 one-piece Dentium implants (Ø 2.5 mm, intraosseous length of 12 mm) were inserted in the anterior mandible, and the rabbits were divided into four groups (n = 6 per group). Different treatment methods were used in each group: blank control group (BC); only silk ligation (negative control [NC]); silk ligation and injection with minocycline hydrochloride ointment (positive control [PC]); and silk ligation and injection with tocilizumab at 8 mg/kg via the auricle vein (experimental [EP]). Eight weeks later, the animals were sacrificed, and samples were collected and then analyzed using microcomputed tomography (microCT) scanning, immunohistochemical analysis, and histologic analysis. Results: From the microCT measurement, the ratio of the bone volume to the total volume (BV/TV) in the EP group was 67.00% ± 2.72%, which was higher than that in the other three groups (58.85% ± 2.43% in the BC group, 55.72% ± 2.48% in the PC group, and 36.52% ± 3.02% in the NC group). From immunohistochemical analysis, the expression of IL-6 was found to be higher in the NC group than in the BC, PC, and EP groups, but there was no statistical difference between these three groups. Furthermore, the RANKL (receptor activator of nuclear factor-κB ligand) expression was the lowest in the EP group, followed by the BC group, the PC group, and the NC group, which had the highest expression; there was no difference between the NC and PC groups. Upon histologic analysis, significant new bone was found on the implant surfaces in the EP group, sparse and less new bone could be seen in the BC and PC groups, and the most serious bone resorption occurred in the NC group. Conclusions: Tocilizumab, an inhibitor of IL-6, has a certain effect in preventing bone loss around implants caused by bacterial infection during the osseointegration period. [ABSTRACT FROM AUTHOR]

Objectives: Inflammatory disorders including periodontitis have been investigated for their impact on systemic inflammation and bone health. The present study was conducted with an aim to evaluate impact of control of periodontal inflammation through subgingival instrumentation on serum interleukin 6 and serum C-terminal telopeptide of type I collagen (CTX) in premenopausal females with stage II and III periodontitis. Method and materials: In this single-arm prospective study, periodontal parameters, serum interleukin 6, serum CTX, and hematologic parameters (total leukocyte count, differential leukocyte count, platelet count, mean platelet volume, and platelet distribution width) were assessed at baseline. Subgingival instrumentation was done, and oral hygiene instructions were given. At week 4, professional plaque control was performed, and oral hygiene instructions were reinforced. Serum and hematologic parameters were reassessed at 8 weeks after subgingival instrumentation, in individuals meeting the clinical endpoints (ie, bleeding on probing < 10%). Results: There was significant reduction in serum interleukin 6 of 0.168 ± 0.164 pg/mL (P = .000), and serum CTX of 17.459 ± 4.363 pg/mL (P = .000) at 8 weeks after subgingival instrumentation. There was significant decrease in eosinophil count (P = .018) and mean platelet volume (P = .016) at 8 weeks after subgingival instrumentation; however, no significant change was found in other hematologic parameters. Conclusion: Following subgingival instrumentation, biomarkers of both systemic inflammation (interleukin 6) and bone turnover (CTX) were observed to reduce significantly. This finding hints towards a positive impact of periodontal intervention on bone health. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the latest scientific literature regarding the concentrations of biomarkers in saliva and peri-implant crevicular fluid (PICF) of healthy implant (HI) patients and patients with peri-implant mucositis (PIM) and peri-implantitis (PI). Materials and Methods: The literature review was performed according to PRISMA guidelines. The databases used were PubMed MEDLINE, ScienceDirect, and Cochrane Library. A combination of keywords was used, and selection criteria were applied. Selected articles were published between February 1, 2017, and February 1, 2022, written in English, conducted in humans, and examined the levels of saliva and PICF biomarkers in PI patients and compared them to HI/PIM patients. Results: A total of 16 publications were selected, involving a total of 1,117 patients with 1,346 implants. Qualitative analysis revealed 49 different biomarkers, the levels of which were compared between groups. After evaluating the most frequently studied biomarkers, significantly higher values of IL-1β, RANKL, sRANKL, IL-6, TNF-α, TNFSF12, MMP2, and MMP8 levels were observed in the PI group than in the HI group. Conclusions: Of all 49 biomarkers evaluated, IL-1β and RANKL have potentially the highest diagnostic significance in the assessment of peri-implant inflammatory conditions, as differences were observed between all three groups (HI < PIM < PI), but data from current publications were not fully sufficient to provide strong evidence. [ABSTRACT FROM AUTHOR]

Signal transducer and activator of transcription (STAT) 4 and STAT6 play a crucial role in immune cells by transducing signals from specific cytokine receptors, and inducing transcription of genes involved in cell-mediated and humoral immunity. These two different defense mechanisms against pathogens are regulated by two specific CD4+ T helper (Th) cells known as Th1 and Th2 cells. Many studies have shown that several diseases including cancer, inflammatory, autoimmune and allergic diseases are associated with a Th1/Th2 imbalance caused by increased or decreased expression/activity of STAT4 or STAT6 often due to genetic and epigenetic aberrances. An altered expression of STAT4 has been observed in different tumors and autoimmune diseases, while a dysregulation of STAT6 signaling pathway is frequently observed in allergic conditions, such as atopic dermatitis, allergic asthma, food allergy, and tumors such as Hodgkin and non-Hodgkin lymphomas. Recently, dysregulations of STAT4 and STAT6 expression have been observed in SARS-CoV2 and monkeypox infections, which are still public health emergencies in many countries. SARS-CoV-2 can induce an imbalance in Th1 and Th2 responses with a predominant activation of STAT6 in the cytosol and nuclei of pneumocytes that drives Th2 polarization and cytokine storm. In monkeypox infection the virus can promote an immune evasion by inducing a Th2 response that in turn inhibits the Th1 response essential for virus elimination. Furthermore, genetic variations of STAT4 that are associated with an increased risk of developing systemic lupus erythematosus seem to play a role in defense against SARS-CoV-2 infection. PLAIN LANGUAGE SUMMARY: Signal transducer and activator of transcription (STAT) proteins are important and complex regulators of transcription that mediate many aspects of cellular immunity, proliferation, apoptosis and differentiation. STAT proteins are phosphorylated/activated in the cytoplasm by Janus Kinases (JAKs) a family of nonreceptor tyrosine kinases associated to type I and type II cytokine receptors. There are seven STAT family members that have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. STAT4 is activated by IL-12 after binding with its specific receptor and induces the production in Th1 cells of IFN-γ, which allows these cells to be particularly effective in protecting against viruses and intracellular bacteria. STAT6 is activated by IL-4 and IL-13 and is required for the development of Th2 immune response and for the production of Th2 cytokines IL-4, IL-5, and IL-13 that contribute to humoral response with the synthesis of antigen specific antibodies in B cells. Although STAT4 plays an important role in many physiological functions, an altered expression of this transcription factor, often due to genetic and epigenetic aberrances, has been observed in different tumors and autoimmune diseases. Dysregulation of STAT6 signaling pathway, often caused by genetic mutations in the STAT6 gene, has been observed in several allergic conditions and tumors such as Hodgkin and non-Hodgkin lymphomas. [ABSTRACT FROM AUTHOR]

Background: For patients with psoriasis, discontinuation of biologics following remission has become more common in daily practice. Objective: We aimed to identify predictors and construct a predictive model for time to relapse following withdrawal from biologics. Methods: This 12-year, multicenter, observational cohort study was performed in six dermatology centers between February 2011 and February 2024. We identified biological treatment episodes in patients with moderate-to-severe psoriasis and included only treatment episodes in which a clinical response (≥ 50% reduction in Psoriasis Area and Severity Index score [PASI 50] from baseline) was achieved and the patient withdrew from biological therapy with a well-controlled status (PASI < 10 and ≥ 50% improvement in PASI from baseline). The primary outcome was time to relapse, which was defined as the period from the last biologic administration to relapse. An extended multivariate Cox proportional hazards analysis (Prentice–Williams–Peterson Gap time model) was used to predict relapse and generate a predictive model. Results: This study screened 1613 biological treatment episodes, and 991 treatment episodes were enrolled. The time to relapse decreased significantly as the number of previous withdrawals from biological treatment increased (p < 0.001). Similarly, the time to relapse decreased significantly as the number of previous biologics used increased (p < 0.001). The maximum PASI improvement during biological treatment decreased and the PASI score at withdrawal of biological treatment increased in parallel as the number of prior withdrawals from biologics increased. The time to relapse following withdrawal was longest for interleukin (IL)-23 inhibitors (IL-23i), followed by the IL-12/23i, IL-17 inhibitors (IL-17i), and tumor necrosis factor-α inhibitors. After adjustment, multivariate Cox regression identified the following significant predictors of relapse following withdrawal: the mechanisms of action of biologics (hazard ratio [HR] for IL-17i vs IL-12/23i, 1.59; HR for IL-23i vs IL-12/23i, 0.60), number of previous withdrawals from biological treatment (HR 1.23; 95% confidence interval [CI] 1.13‒1.33), time to achieve PASI 50 (HR 1.01; 95% CI 1.00‒1.02), maximum PASI improvement on biologics (HR 0.98; 95% CI 0.98‒0.99), and PASI at the end of therapy (HR 1.03; 95% CI 1.01‒1.05). The model had good predictive and discriminative ability. Conclusions: These results have the potential to help physicians and patients make individualized treatment decisions; information on the risk of relapse of psoriasis at specific timepoints following the withdrawal of biologics is particularly valuable for patients considering discontinuation of biologics or as-needed biologic therapy. However, the benefit and risk of repeated withdrawals of biologics should be carefully weighed, as the treatment efficacy and duration of remission decline as the number of withdrawals increases. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association, as well as to characterize the associated panel of pro‐ and anti‐inflammatory markers, between the different components of the peri‐implant phenotype and the presence of peri‐implantitis/peri‐implant soft‐tissue dehiscence (PISTD). Materials and Methods: A total of 324 implants in 112 patients were included. The following components of the peri‐implant phenotype were clinically measured through the use of a manual periodontal probe or a digital calliper: keratinized mucosa width (PIKM‐W), mucosal thickness (MT), attached mucosa (AM) and vestibulum depth (VD). The presence of peri‐implantitis and PISTD was assessed through clinical and radiographic examination. Mixed‐models logistic regression analyses were performed to analyse the association between peri‐implant phenotype and the presence of peri‐implantitis or PISTD, adjusting for relevant confounders. Multiplex immunoassays were employed to evaluate the peri‐implant crevicular fluid levels of a panel of pro‐ and anti‐inflammatory markers. Results: Peri‐implant health, peri‐implant mucositis and peri‐implantitis were diagnosed in 36.6%, 21.4% and 42% of the patients (classified according to their worst implant) and 35.2%, 34.3%, and 30.5% of the implants, respectively. In the multi‐level multiple regression model, the absence of PIKM‐W (odds ratio [OR] = 9.24; 95% CI: 2.73–31.28), the absence of attached mucosa (OR = 19.58; 95% CI: 6.12–62.56) and a reduced (<4 mm) vestibulum depth (OR = 2.61; 95% CI: 1.05–6.48) were associated with peri‐implantitis. Similarly, the absence of PIKM‐W (OR = 6.32; 95% CI: 1.67–23.83), a thin (<2 mm) mucosa (OR = 157.75; 95% CI: 14.06–1769.9) and a reduced vestibulum depth (OR = 3.32; 95% CI: 1.02–10.84) were associated with the presence of PISTD. Implants with PIKM‐W = 0 mm showed statistically significantly higher levels of interferon‐γ in both regular (≥2 maintenance/year) and irregular (<2 maintenance/year) compliers (p = 0.046 and p = 0.012). In irregular compliers, the absence of PIKM‐W was also associated with statistically significantly higher levels of interleukin (IL)‐1β and IL‐21 (p = 0.016, p = 0.046). These associations were independent of the effect of relevant confounders (e.g., plaque, compliance with maintenance, etc.). Conclusions: Within their limits, the present findings indicate that (a) peri‐implant soft‐tissue phenotype appears to be associated with the presence of peri‐implantitis and PISTD, and (b) in the absence of PIKM‐W, the inflammatory response seems to be dysregulated and the soft‐tissue remodelling up‐regulated. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between interleukin‐8 (IL‐8) levels in gingival crevicular fluid (GCF) and total oral fluid (TOF) and the responsiveness to steps 1 and 2 of periodontal therapy. Materials and Methods: One‐hundred and fifty‐nine patients affected by periodontitis received steps 1 and 2 of periodontal therapy. At baseline, TOF and GCF samples were collected and analysed for IL‐8 (Il‐8TOF/IL‐8GCF) using flow cytometry. Therapy outcomes were relative proportions of residual periodontal pockets (PPD%), pocket closure (PC) rates and pocket probing depth (PPD) reductions; these were associated with IL‐8TOF/IL‐8GCF. Results: High IL‐8TOF was significantly associated with higher residual PPD% (p = 0.044) and lower PPD reduction compared to low IL‐8TOF (high 0.79 ± 1.20 mm vs. low 1.20 ± 1.20 mm, p < 0.001) in non‐smokers, while in smokers high IL‐8GCF was related to lower PPD reduction (high 0.62 ± 1.22 mm vs. low 0.84 ± 1.12 mm, p = 0.009). Furthermore, high baseline IL‐8TOF was significantly associated with poorer PC rates compared to medium and low concentrations in both non‐smokers (high 41% vs. medium 55% vs. low 58%, p < 0.001) and smokers (high 34% vs. medium 44% vs. low 46%, p < 0.001). Conclusion: High IL‐8 concentrations at baseline had a significant impact on residual PPD%, PC rates and PPD reduction. The findings suggest that, especially in non‐smokers, baseline IL‐8 levels collected from the TOF could serve as a component in the estimation of responsiveness to steps 1 and 2 of periodontal therapy. [ABSTRACT FROM AUTHOR]

Aim: To describe the microbiological composition of subgingival dental plaque and molecular profile of gingival crevicular fluid (GCF) of periodontal furcation‐involved defects. Materials and Methods: Fifty‐seven participants with periodontitis contributed with a degree II–III furcation involvement (FI), a non‐furcation (NF) periodontal defect and a periodontally healthy site (HS). Subgingival plaque was analysed by sequencing the V3–V4 region of the 16S rRNA gene, and a multiplex bead immunoassay was carried out to estimate the GCF levels of 18 GCF biomarkers. Aiming to explore inherent patterns and the intrinsic structure of data, an AI‐clustering method was also applied. Results: In total, 171 subgingival plaque and 84 GCF samples were analysed. Four microbiome clusters were identified and associated with FI, NF and HS. A reduced aerobic microbiota (p =.01) was detected in FI compared with NF; IL‐6, MMP‐3, MMP‐8, BMP‐2, SOST, EGF and TIMP‐1 levels were increased in the GCF of FI compared with NF. Conclusions: This is the first study to profile periodontal furcation defects from a microbiological and inflammatory standpoint using conventional and AI‐based analyses. A reduced aerobic microbial biofilm and an increase of several inflammatory, connective tissue degradation and repair markers were detected compared with other periodontal defects. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) risk factors for hospitalization and mortality have been reported to be older age, comorbidities, and vaccination status. However, its clinical course and the risk of hospitalization and mortality in patients who received home health care for their predisposing status and diseases remain unclear. This study aimed to determine the characteristics and outcomes of these patients after being infected with the Omicron variant of COVID-19. This retrospective study included 33 patients diagnosed with COVID-19 after we initiated home health care. We classified the patients into 2 groups, that is, hospitalization (n = 7) and non-hospitalization (n = 26), and non-survival (n = 6) and survival (n = 27) and compared their backgrounds. COVID-19 severity was an affecting factor in hospitalization and survival. The nursing care environments and low daily life activities also affected hospitalization but not survival. The proportion of patients with terminal malignancies (50.0% vs 3.7%, p =.017) and the Charlson Comorbidity Index (5.0 vs 2.0, p =.096) were higher in the non-survival than in the survival group. Some patients had urinary tract infections and persistent weight and appetite loss (post COVID-19 syndrome), regardless of this improvement. Serum IL-6 levels were higher in patients with post COVID-19 syndrome than those without symptoms. Optimizing the nursing care environment is essential to continue home health care and lower the hospitalization rate even with SARS-CoV-2 infection. Post COVID-19 syndrome, such as appetite and weight loss, are associated with IL-6-induced inflammation. [ABSTRACT FROM AUTHOR]

Background: Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix. Objective: This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA). Methods: Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin‐1β (rrIL‐1β) and SDC4 small interfering RNA (si‐SDC4). Anti‐SDC4 ectodomain‐specific antibodies or IgG were intra‐articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4‐cKO) and Sdc4flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col‐II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays. Results: SDC4 expression was evidently increased in MIA‐model animals compared to control groups. rrIL‐1β stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col‐II. These effects were reversed by si‐SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col‐II and ACAN, and a decrease in SDC4, MMP13 and cleaved‐CASP3‐positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition. Conclusions: SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injuries (SCI) result in devastating impairment to an individual's functional ability. The pathophysiology of SCI is related to primary injury but further propagated by secondary reactions to injury, such as inflammation and oxidation. The inflammatory and oxidative cascades ultimately cause demyelination and Wallerian degeneration. Currently, no treatments are available to treat primary or secondary injury in SCI, but some studies have shown promising results by lessening secondary mechanisms of injury. Interleukins (ILs) have been described as key players in the inflammation cascade after neuronal injury; however, their role and possible inhibition in the context of acute traumatic SCIs have not been widely studied. Here, we review the relationship between SCI and IL-6 concentrations in the CSF and serum of individuals after traumatic SCIs. Furthermore, we explore the dual IL-6 signaling pathways and their relevance for future IL-6 targeted therapies in SCI. [ABSTRACT FROM AUTHOR]

Background: Convalescent plasma (CP) reduced the mortality in COVID-19 induced ARDS (C-ARDS) patients treated in the CONFIDENT trial. As patients are immunologically heterogeneous, we hypothesized that clusters may differ in their treatment responses to CP. Methods: We measured 20 cytokines, chemokines and cell adhesion markers using a multiplex technique at the time of inclusion in the CONFIDENT trial in patients of centers having accepted to participate in this secondary study. We performed descriptive statistics, unsupervised hierarchical cluster analysis, and examined the association between the clusters and CP effect on day-28 mortality. Results: Of the 475 patients included in CONFIDENT, 391 (82%) were sampled, and 196/391 (50.1%) had been assigned to CP. We identified four sub-phenotypes representing 89 (22.8%), 178 (45.5%), 38 (9.7%), and 86 (22.0%) patients. The most contributing biomarkers in the principal component analysis were IL-1β, IL-12p70, IL-6, IFN-α, IL-17A, IFN-γ, IL-13, TFN-α, total IgG, and CXCL10. Sub-phenotype-1 displayed a lower immune response, sub-phenotype-2 a higher adaptive response, sub-phenotype-3 the highest innate antiviral, pro and anti-inflammatory response, and adhesion molecule activation, and sub-phenotype-4 a higher pro and anti-inflammatory response, migration protein and adhesion molecule activation. Sub-phenotype-2 and sub-phenotype-4 had higher severity at the time of inclusion. The effect of CP treatment on mortality appeared higher than standard care in each sub-phenotype, without heterogeneity between sub-phenotypes (p = 0.97). Conclusion: In patients with C-ARDS, we identified 4 sub-phenotypes based on their immune response. These sub-phenotypes were associated with different clinical profiles. The response to CP was similar across the 4 sub-phenotypes. Trial registration: Ethics Committee of the University Hospital of Liège CE 2020/239. Clinicaltrials.gov NCT04558476. Registered 2020-09-11, https://www.clinicaltrials.gov/study/NCT04558476. [ABSTRACT FROM AUTHOR]

Purpose: Cumulating evidence supports the close association between periodontal diseases, neuroinflammation and neurodegenerative pathologies, except for peri-implantitis (PI). Thus, this study explored the association between experimental PI and neuropathological changes in the rat brain. Materials and methods: After bilateral first molars extraction, experimental PI was induced at titanium implants placed in the maxillae by lipopolysaccharide injections and ligature placement. Following 28-weeks of disease progression, the maxillae and brains were retrieved from 6 rats. Healthy brains from 3 rats were used as control. Brains were analyzed by immunohistochemistry to detect signs of neuroinflammation (interleukin (IL)-6 and tumor necrosis factor (TNF)-α)), microglial activation (IBA-1) and astrogliosis (GFAP). To explore signs of neurodegeneration, hematoxylin/eosin and Nissl stainings were used. Also, four different antibodies against amyloid beta (Aβ 1–42) were tested. Results: Chronic PI lesions showed peri-implant bone resorption accompanied by large inflammatory infiltrates. IL-6+ and TNF-α+ cells were found within the CA1 and Dentate Gyrus regions of the hippocampus of the PI-affected group, while almost no immune-positivity was detected in the control (p < 0.05). Detection of activated GFAP+ microglia and IBA-1+ astrocytes surface were significantly higher at the CA areas, and cerebral cortex of the PI-affected group, in comparison with control (p < 0.05). Shrunk neurons with pyknotic nuclei were inconsistently found among the PI-affected group, and these were almost not detected in control. No positive Aβ reactivity was detected in any of the samples. Conclusion: Chronic experimental PI lesions led to an increased detection of IL-6 and TNF-α, GFAP+ microgliosis and IBA-1+ astrocytosis, and in some cases, neurodegeneration, in the rat brain. [ABSTRACT FROM AUTHOR]

Background: Acetaminophen (APAP)-induced hepatotoxicity is a potentially life-threatening condition. Gardenia jasminoides fruit extract (GJE), which contains geniposide (Gen) as its major active constituent, possesses anti-inflammatory and antioxidant properties and may help address the underlying pathogenesis of APAP-induced hepatotoxicity. This study aimed to evaluate the effects of GJE in a mouse model of APAP-induced hepatotoxicity. Methods: Twenty-four male ICR mice were divided into 4 groups (n = 6/group): [1] Control group, mice were given distilled water; [2] APAP group, mice received a single dose of 600 mg/kg APAP; [3] APAP + low-dose GJE group, mice received APAP followed 30 min later by 2 doses of low-dose GJE (0.44 g/kg/dose, containing Gen 100 mg/kg/dose) 8 h apart; [4] APAP + high-dose GJE group, mice received APAP followed by 2 doses of high-dose GJE (0.88 g/kg/dose, containing Gen 200 mg/kg/dose). All mice were euthanized 24 h after APAP administration. Liver tissue was used for histological examination and to measure glutathione (GSH) and malondialdehyde (MDA) levels. Serum was used to determine levels of ALT and inflammatory cytokines (tumor necrosis factor- α (TNF-α) and interleukin-6 (IL-6)). Results: Liver histopathology showed moderate to severe hepatic necroinflammation in the APAP group, whereas only mild necroinflammation was observed in both treatment groups. Serum ALT levels were significantly elevated in the APAP group compared to the control group but were significantly reduced after low- and high-dose GJE treatment. Serum TNF- α levels were significantly higher in the APAP group than in the control group and were significantly lower after high-dose GJE treatment (135.5 ± 477.2 vs. 35.5 ± 25.8 vs. 74.7 ± 47.2 vs. 41.4 ± 50.8 pg/mL, respectively). Serum IL-6 followed a similar pattern. Hepatic GSH levels were significantly lower in the APAP group compared to the control group but significantly increased after both low- and high-dose GJE treatment (19.9 ± 4.5 vs. 81.5 ± 12.4 vs. 71.4 ± 7.8 vs. 82.6 ± 6.6 nmol/mg protein, respectively). Conversely, hepatic MDA levels were significantly elevated in the APAP group compared with the control group but significantly decreased after high-dose GJE treatment (108.6 ± 201.5 vs. 40.5 ± 18.0 vs. 40.5 ± 16.8 nmol/mg protein, respectively). Conclusions: Treatment with G. jasminoides fruit extract can alleviate APAP-induced hepatotoxicity, likely through its anti-inflammatory and antioxidant properties. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia (FM) is characterized by chronic pain and a complex array of symptoms, with neuroinflammation implicated in its pathophysiology. Methods: This study aimed to explore the association between neuroinflammation, measured through interleukin levels (IL-1, IL-6, IL-8), and clinical outcomes in FM patients. Using a cross-sectional study design, blood levels of these interleukins were correlated with pain severity and disability, assessed via the Fibromyalgia Impact Questionnaire (FIQ) and pain measures. Results: Results indicated that IL-6 and IL-8 may particularly serve as biomarkers for pain severity and disability in FM patients, showing significant associations with worse clinical outcomes. Elevated IL-8 levels, for instance, correlated strongly with increased pain perception and higher disability scores. Conclusions: These findings suggest that specific interleukins are not only elevated in FM but are actively involved in the modulation of pain and disability, underscoring the role of systemic neuroinflammation in the clinical severity of FM. This study contributes to a deeper understanding of the inflammatory mechanisms in FM and underscores the potential of targeting interleukins in therapeutic strategies. [ABSTRACT FROM AUTHOR]

Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of an acute inflammatory versus a chronic inflammatory interleukin signature using microarray-based gene expression analysis. Correlations between these interleukin signatures and immune cell markers (CD8, IgKC, and CD20) and immune checkpoints (PD-1) were also evaluated. This study investigated the prognostic significance of an acute inflammatory IL signature (IL-12, IL-21, and IFN-γ) and a chronic inflammatory IL signature (IL-4, IL-5, IL-10, IL-13, IL-17, and CXCL1) for metastasis-free survival (MFS) using Kaplan–Meier curves and Cox regression analyses in a cohort of 461 patients with early breast cancer. Correlations were analyzed using the Spearman–Rho correlation coefficient. Kaplan–Meier curves revealed that the prognostic significance of the acute inflammatory IL signature was specifically pronounced in the basal-like subtype (p = 0.004, Log Rank). This signature retained independent prognostic significance in multivariate Cox regression analysis (HR 0.463, 95% CI 0.290–0.741; p = 0.001). A higher expression of the acute inflammatory IL signature was associated with longer MFS. The chronic inflammatory IL signature showed a significant prognostic effect in the whole cohort, with higher expression associated with shorter MFS (p = 0.034). Strong correlations were found between the acute inflammatory IL signature and CD8 expression (ρ = 0.391; p < 0.001) and between the chronic inflammatory IL signature and PD-1 expression (ρ = 0.627; p < 0.001). This study highlights the complex interaction between acute and chronic inflammatory interleukins in breast cancer progression and prognosis. These findings provide insight into the prognostic relevance of interleukin expression patterns in breast cancer and may inform future therapeutic strategies targeting the immune–inflammatory axis. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that progresses with demyelination and neurodegeneration. To date, many studies have revealed the key role of interleukins in the pathogenesis of MS, but their impact has not been fully explained. The aim of the present study was to collect and review the results obtained so far regarding the influence of interleukins on the development and course of MS and to assess the potential for their further use. Through the platform "PubMed", terms related to interleukins and MS were searched. The following interval was set as the time criterion: 2014–2024. A total of 12,731 articles were found, and 100 papers were subsequently used. Cells that produce IL-10 have a neuroprotective effect, whereas those that synthesize IL-6 most likely exacerbate neuroinflammation. IL-12, IL-23 and IL-18 represent pro-inflammatory cytokines. It was found that treatment with an anti-IL-12p40 monoclonal antibody in a study group of MS patients showed a beneficial effect. IL-4 is a pleiotropic cytokine that plays a significant role in type 2 immune responses and inhibits MS progression. IL-13 is an anti-inflammatory cytokine through which the processes of oligodendrogenesis and remyelination occur more efficiently. The group of interleukins discussed in our paper may represent a promising starting point for further research aimed at finding new therapies and prognostic markers for MS. [ABSTRACT FROM AUTHOR]

Pre‐clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth. These anti‐oncogenic effects of exercise were associated with the exercise‐mediated release of myokines such as interleukin (IL)‐15. However, no study has quantified the acute IL‐15 response in human cancer survivors, and whether physiological adaptations to exercise training (i.e. body composition and cardiorespiratory fitness) influence this response. In the present study breast, prostate and colorectal cancer survivors (n = 14) completed a single bout of high‐intensity interval exercise (HIIE) [4×4 min at 85–95% heart rate (HR) peak, 3 min at 50–70% HR peak] before and after 7 months of three times weekly high‐intensity interval training (HIIT) on a cycle ergometer. At each time point venous blood was sampled before and immediately after HIIE to assess the acute myokine (IL‐15, IL‐6, IL‐10, IL‐1ra) responses. Markers of inflammation, cardiorespiratory fitness and measures of body composition were obtained at baseline and 7 months. An acute bout of HIIE resulted in a significant increase in IL‐15 concentrations (pre‐intervention: 113%; P = 0.013, post‐intervention: 102%; P = 0.005). Post‐exercise IL‐15 concentrations were associated with all other post‐exercise myokine concentrations, lean mass (P = 0.031), visceral adipose tissue (P = 0.039) and absolute V̇O2${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ peak (P = 0.032). There was no significant effect of 7 months of HIIT on pre‐ or post‐HIIE IL‐15 concentrations (P > 0.05). This study demonstrates HIIE is a sufficient stimulus to increase circulating IL‐15 and other myokines including IL‐6, IL‐10 and IL‐1ra which may be clinically relevant in the anti‐oncogenic effect of exercise and repetitive exposure to these effects may contribute to the positive relationship between exercise and cancer recurrence. Key points: Exercise has been demonstrated to reduce the risk of cancer recurrence.Pre‐clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth, mediated by exercise‐induced myokines (IL‐6 and IL‐15).High‐intensity interval exercise significantly increased myokines associated with the anti‐oncogenic effect of exercise and the magnitude of response was associated with lean mass, but training did not appear to influence this response.Given IL‐15 has been implicated in the anti‐oncogenic effect of exercise and is being explored as an immunotherapy agent, high‐intensity interval exercise may improve outcomes for people living beyond cancer through IL‐15‐mediated pathways.Interventions that increase lean mass may also enhance this response. [ABSTRACT FROM AUTHOR]

Background: Huanglianjiedu decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) prescription with thousand years of clinical use against various malignancies, including pancreatic adenocarcinoma (PAAD). However, its potential bioactive component and molecular mechanism remains unclear. Aims: This study is to inspect the HLJDD mechanisms of action against PAAD via integrated computational and pharmacochemistry strategy, in vivo and in vitro experiments to validate associated targets and pathways. Methods: A PAAD xenograft model was established by subcutaneous injecting Panc02 cells into C57BL/6 mice. Ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was engaged to determine constituents of HLJDD and assessed for pharmacokinetic scheme using the TCM Systems Pharmacology Platform (TCM-SP). Differentially expressed genes (DEGs) of PAAD was retrieved from the transcriptome dataset GSE43795, followed by recognizing overlapping targets the oncogenes and target genes of PAAD and HLJDD, respectively. Putative signaling pathways of HLJDD in treating PAAD were enriched using KEGG and GO analyses. The anti-PAAD effects of HLJDD was assessed in vivo and in vitro, besides, the potential mechanism was validated using immunoblotting and immunohistochemical assays. Results: HLJDD significantly suppressed the growth of transplanted PAAD tumors, constrained PAAD progression, and induced apoptosis and S-phase arrest. Seventy-five active components meeting the drug-likeness criteria and 278 target genes of HLJDD were identified. KEGG analysis indicated that the top three enriched pathways were cancer, AGE-RAGE signaling, and IL-17 signaling pathways. Disease enrichment analysis highlighted immune, pharmacological, and cancer-related diseases as the top three categories. A total of 47 potential target genes were identified. Immunoblotting revealed that HLJDD inhibited PI3K and MAPK-related signaling pathways, while immunohistochemical staining confirmed that HLJDD suppressed the expression of phosphorylated MAPK and ERK1/2. Conclusion: HLJDD inhibited PAAD in vitro and in vivo via the modulation of multiple mechanisms, including regulation of PI3K/AKT/mTOR and MAPK/ERK1/2 signaling pathways. [ABSTRACT FROM AUTHOR]

In the field of breast cancer treatment, the immunotherapy involving natural killer (NK) cells is increasingly highlighting its distinct potential and significance. Members of the interleukin (IL) family play pivotal regulatory roles in the growth, differentiation, survival, and apoptosis of NK cells, and are central to their anti-tumor activity. These cytokines enhance the ability of NK cells to recognize and eliminate tumor cells by binding to specific receptors and activating downstream signaling pathways. Furthermore, interleukins do not function in isolation; the synergistic or antagonistic interactions between different interleukins can drive NK cells toward various functional pathways, ultimately leading to diverse outcomes for breast cancer patients. This paper reviews the intricate relationship between NK cells and interleukins, particularly within the breast cancer tumor microenvironment. Additionally, we summarize the latest clinical studies and advancements in NK cell therapy for breast cancer, along with the potential applications of interleukin signaling in these therapies. In conclusion, this article underscores the critical role of NK cells and interleukin signaling in breast cancer treatment, providing valuable insights and a significant reference for future research and clinical practice. [ABSTRACT FROM AUTHOR]

Background: Some experimental data suggest that myokines may play an important role in developing cancer-associated cachexia (CAC), but their relevance in humans remains poorly explored. In our study, we tested the hypothesis that circulating myokines are associated with the pathogenesis of CAC in a model population of gastric cancer. Methods: A group of 171 treatment naïve patients with adenocarcinoma of the stomach were prospectively examined. Cachexia was defined as weight loss >5% or weight loss >2% with either BMI <20 kg/m2 or sarcopenia. A panel of 19 myokines was measured in portal and peripheral blood as well as tumour tissue and surrounding gastric mucosa. Moreover, a serum proteomic signature of cachexia was identified by a label-free quantitative proteomics with a nano LCMS/MS system and stored in a ProteomeXchange database (PXD049334). Results: One hundred (58%) patients were diagnosed with CAC. The concentrations of fatty acid-binding protein 3 (FABP3), follistatin-like 1 protein (FSTL-1), interleukin 6 (IL 6), and interleukin 8 (IL 8) were significantly higher in the peripheral blood of cachectic subjects, while leptin levels were lower. Of all the evaluated myokines, tumour tissues showed higher expression levels only for IL-15 and myostatin. However, the analysis of paired samples failed to demonstrate a decreasing concentration gradient between the portal and peripheral blood for any of the myokines, evidencing against their release by the primary tumour. Proteomic analysis identified 28 proteins upregulated and 24 downregulated in the peripheral blood of patients with cachexia. Differentially expressed proteins and 5 myokines with increased serum levels generated a significant proteinprotein interaction network. Conclusions: Our study provides clinical evidence that some myokines are involved in the pathogenesis of cachexia and are well integrated into the regulatory network of circulating blood proteins identified among cachectic patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: In Parkinson's disease (PD) brains, microglia are activated to release inflammatory factors to induce the production of reactive oxygen species (ROS) in neuron, and vice versa. Moreover, neuroinflammation and its synergistic interaction with oxidative stress contribute to the pathogenesis of PD. Methods: In this study, we investigated whether in-house synthetic coumarin-chalcone derivatives protect human microglia HMC3 and neuroblastoma BE(2)-M17 cells against 1-methyl-4-phenyl pyridinium (MPP+)-induced neuroinflammation and associated neuronal damage. Results: Treatment with MPP+ decreased cell viability as well as increased the release of inflammatory mediators including cytokines and nitric oxide in culture medium, and enhanced expression of microglial activation markers CD68 and MHCII in HMC3 cells. The protein levels of NLRP3, CASP1, iNOS, IL-1b, IL-6, and TNF-a were also increased in MPP+-stimulated HMC3 cells. Among the four tested compounds, LM-016, LM-021, and LM-036 at 10 µM counteracted the inflammatory action of MPP+ in HMC3 cells. In addition, LM-021 and LM-036 increased cell viability, reduced lactate dehydrogenase release, ameliorated cellular ROS production, decreased caspase-1, caspase-3 and caspase-6 activities, and promoted neurite outgrowth in MPP+-treated BE(2)-M17 cells. These protective effects were mediated by down-regulating inflammatory NLRP1, IL-1b, IL-6, and TNF-a, as well as up-regulating antioxidative NRF2, NQO1, GCLC, and PGC-1a, and neuroprotective CREB, BDNF, and BCL2. Conclusion: The study results strengthen the involvement of neuroinflammation and oxidative stress in PD pathogenicmechanisms, and indicate the potential use of LM-021 and LM-036 as dual inflammasome inhibitors in treating both NLRP1- and NLRP3-associated PD. [ABSTRACT FROM AUTHOR]

Background: While the effect of biomaterials covering the pulp tissue is considered in the success of pulpotomy treatment, the level of pulpal inflammation is still very important for treatment success. The aim of this study was to compare IL-6 and IL-8 levels, known as good indicators of pulpal inflammation, with a new biomarker, presepsin, and to evaluate the impact of biomarker levels along with the pulp capping agents used in the treatment on the one-year success of pulpotomy treatment. Methods: The study included 120 primary second molar teeth with pulpotomy indications from 75 children. To determine the pulpal inflammation status, pulpal bleeding samples were taken during treatment, and the levels of IL-6, IL-8, and presepsin were measured. During the pulpotomy treatment, MTA, NeoMTA™, and Biodentine™, and ZOE were randomly applied to groups of thirty teeth each. Patients were monitored for a period of 12 months post-treatment. Results: IL-8, IL-6, and presepsin levels were significantly higher in teeth with pathology (p < 0.001). Biomarker levels were found to be higher in the NeoMTA and Biodentine groups, but this did not result in a statistically significant difference. (p > 0.05) Following pulpotomy treatment, the most successful material groups in order were MTA, ZOE, NeoMTA™, and Biodentine™. Conclusion: Presepsin may be a usable indicator in predicting the level of inflammation. At the end of the one-year follow-up of pulpotomy treatment, more pathology was observed in the NeoMTA and Biodentine groups, where biomarker levels were higher, while no pathology was found in the MTA group, where biomarker levels were lower. Trial registration: NCT06398327/ 20,240,503. [ABSTRACT FROM AUTHOR]

In the field of breast cancer treatment, the immunotherapy involving natural killer (NK) cells is increasingly highlighting its distinct potential and significance. Members of the interleukin (IL) family play pivotal regulatory roles in the growth, differentiation, survival, and apoptosis of NK cells, and are central to their anti-tumor activity. These cytokines enhance the ability of NK cells to recognize and eliminate tumor cells by binding to specific receptors and activating downstream signaling pathways. Furthermore, interleukins do not function in isolation; the synergistic or antagonistic interactions between different interleukins can drive NK cells toward various functional pathways, ultimately leading to diverse outcomes for breast cancer patients. This paper reviews the intricate relationship between NK cells and interleukins, particularly within the breast cancer tumor microenvironment. Additionally, we summarize the latest clinical studies and advancements in NK cell therapy for breast cancer, along with the potential applications of interleukin signaling in these therapies. In conclusion, this article underscores the critical role of NK cells and interleukin signaling in breast cancer treatment, providing valuable insights and a significant reference for future research and clinical practice. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation is widely recognized as a key factor in the pathogenesis of Alzheimer's disease (AD), alongside ß-amyloid deposition and the formation of neurofibrillary tangles. The NLR family pyrin domain containing 3 (NLRP3) inflammasome, part of the innate immune system, has been implicated in the neuropathology of both preclinical amyloid and tau transgenic models. Activation of the NLRP3 pathway involves an initial priming step, which increases the expression of Nlrp3 and interleukin (IL)-1ß, followed by the assembly of the NLRP3 inflammasome complex, comprising NLRP3, ASC, and caspase-1. This assembly leads to the proteolytic maturation of the pro-inflammatory cytokines IL-1ß and IL-18. Additionally, the NLRP3 inflammasome induces Gasdermin D (GSDMD) cleavage, forming membrane pores through which IL-1ß and IL-18 are secreted. Inhibition of NLRP3 has been shown to enhance plaque clearance by modulating microglial activation. Furthermore, blocking NLRP3 in tau transgenic mice has been found to reduce tau phosphorylation by affecting the activity of certain tau kinases and phosphatases. Methods: In this study, organotypic brain slice cultures from P301S transgenic mice were treated with lipopolysaccharide (LPS) plus nigericin as a positive control or exposed to tau seeds (K18) to evaluate NLRP3 inflammasome activation. The effect of tau seeding on NLRP3 activity was further examined using Meso Scale Discovery (MSD) assays to measure IL1ß secretion levels in the presence and absence of NLRP3 inhibitors. The role of NLRP3 activity was investigated in fullbody Nlrp3 knockout mice crossbred with the tau transgenic P301S model. Additionally, full-body and microglia-selective Gsdmd knockout mice were crossbred with P301S mice, and tau pathology and neurodegeneration were evaluated at early and late stages of the disease using immunohistochemistry and biochemical assays. Results: Activation of the NLRP3 pathway was observed in the mouse organotypic slice culture (OSC) model following stimulation with LPS and nigericin or exposure to tau seeds. However, Nlrp3 deficiency did not mitigate tauopathy or neurodegeneration in P301S mice in vivo, showing only a minor effect on plasma neurofilament (NF-L) levels. Consistently, Gsdmd deficiency did not alter tau pathology in P301S mice. Furthermore, neither full-body nor microglia-selective Gsdmd deletion had an impact on neuronal pathology or the release of pro-inflammatory cytokines. Conclusion: The absence of key components of the NLRP3 inflammasome pathway did not yield a beneficial effect on tau pathology or neurodegeneration in the preclinical Tau-P301S mouse model of AD. Nonetheless, organotypic slice cultures could serve as a valuable ex vivo mechanistic model for evaluating NLRP3 pathway activation and pharmacological inhibitors. [ABSTRACT FROM AUTHOR]

Background: Modified furosemide responsiveness index (mFRI) is a novel biomarker for assessing diuretic response and AKI progression in patients with early AKI. However, the comparative predictive performance of mFRI and novel renal biomarkers for adverse renal outcomes remains unclear. In a single-center prospective study, we aimed to evaluate the discriminatory abilities of mFRI and other novel renal biomarkers in predicting AKI progression and prognosis in patients with initial mild and moderate AKI (KDIGO stage 1 to 2). Results: Patients with initial mild and moderate AKI within 48 h following cardiac surgery were included in this study. The mFRI, renal biomarkers (including serum or urinary neutrophil gelatinase-associated lipocalin [sNGAL or uNGAL], serum cystatin C, urinary N-acetyl-beta-D-glycosaminidase [uNAG], urinary albumin-to-creatinine ratio) and cytokines (TNF, IL-1β, IL-2R, IL-6, IL-8, and IL-10) were measured at AKI diagnosis. The mFRI was calculated for each patient, which was defined as 2-hour urine output divided by furosemide dose and body weight. Of 1013 included patients, 154 (15.2%) experienced AKI progression, with 59 (5.8%) progressing to stage 3 and 33 (3.3%) meeting the composite outcome of hospital mortality or receipt of renal replacement therapy (RRT). The mFRI showed non-inferiority or potential superiority to renal biomarkers and cytokines in predicting AKI progression (area under the curve [AUC] 0.80, 95% confidence interval [CI] 0.77–0.82), progression to stage 3 (AUC 0.87, 95% CI 0.85–0.89), and composite outcome of death and receipt of RRT (AUC 0.85, 95% CI 0.82–0.87). Furthermore, the combination of a functional biomarker (mFRI) and a urinary injury biomarker (uNAG or uNGAL) resulted in a significant improvement in the prediction of adverse renal outcomes than either individual biomarker (all P < 0.05). Moreover, incorporating these panels into clinical model significantly enhanced its predictive capacity for adverse renal outcomes, as demonstrated by the C index, integrated discrimination improvement, and net reclassification improvement (all P < 0.05). Conclusions: As a rapid, cost-effective and easily accessible biomarker, mFRI, exhibited superior or comparable predictive capabilities for AKI progression and prognosis compared to renal biomarkers in cardiac surgical patients with mild to moderate AKI. Trial registration: Clinicaltrials.gov, NCT04962412. Registered July 15, 2021, https://clinicaltrials.gov/ct2/show/NCT04962412?cond=NCT04962412&draw=2&rank=1. Highlights: The mFRI is a rapid, cost-effective and easily accessible biomarker. The mFRI exhibited superior or comparable predictive capabilities for AKI progression and prognosis compared to renal biomarkers and cytokines in cardiac surgical patients with mild to moderate AKI. Combining the functional biomarker mFRI with a urinary injury biomarker (uNAG or uNGAL) enhanced predictive accuracy for adverse renal outcomes. [ABSTRACT FROM AUTHOR]

Background: Astragali radix (AR) is one of the most widely used traditional Chinese herbal medicines. It exhibits diverse biological activities, including immunomodulatory and anti-inflammatory properties; however, some of its activities have only been demonstrated in vitro. Objective: To examine the effects of orally administered AR extract on immune cells and the intestine under physiological conditions, which bridges the gap between previously observed in vitro outcomes and in vivo results. Methods: AR extract was prepared by hot water extraction. Three separate animal experiments were conducted to isolate macrophages, splenocytes, and the small intestine epithelium. For the macrophage preparation experiment, an intraperitoneal injection of sterile thioglycolate was administered. The mice received oral AR extract at doses of 0.1, 0.5, or 2.5 g/kg for ten days. At the end of each experiment, cells or tissues were isolated. A portion of macrophages and splenocytes were analyzed for the phenotypic changes. The remaining cells were cultured and stimulated with lipopolysaccharide (LPS) or mitogen ex vivo to assess activation status, proliferation, and cytokine production. Samples of the intestine were subjected to real-time RT-PCR. Results: Peritoneal macrophages from AR-treated mice exhibited increased expression of scavenger receptors, including SRA and CD36. Stimulation of these macrophages ex vivo with LPS selectively modulated the inflammatory response, including reduced expression of the costimulatory molecules CD40 and CD86, which are important for T cell responses, without affecting TNF-α and IL-6 production. Splenocytes from AR-treated mice exhibited a dose-dependent increase in CD4 and CD8 T cells; however, stimulation with mitogen decreased T cell proliferation and reduced IFN-γ production, which is essential for macrophage activation. An analysis of the small intestinal epithelium revealed an attenuated antimicrobial response, including reduced IgA content in the lumen and decreased expression of mucin-2 and polymeric Ig receptor genes. Conclusion: The response of immune cells following oral treatment with AR extract did not replicate the previously documented in vitro findings. Immune cells and intestinal epithelium from mice administered oral AR extract exhibited a selective anti-inflammatory phenotype. The overall findings indicate that the systemic effects after oral administration of AR extract include reduced sensitivity to inflammatory insults. [ABSTRACT FROM AUTHOR]

Background: A growing interest in using Nigella sativa oil (NSO) in the prevention or treatment of several cardiovascular diseases has prompted this study. The research aims to investigate the effect of NSO on cardiac damage prevention after long-term administration in induced myocardial infarction (MI) in rats. Methods: NSO was analyzed for its fatty acids composition using gas chromatography-mass spectrometry (GC-MS) analysis and administered in rats before and after isoproterenol (45 mg/kg body weight) induced myocardial infarction. The following parameters were assessed: electrocardiograms, histopathological examination, serum biochemical aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase-myocardial band (CK-MB), serum and heart inflammation (tumor necrosis factor-alpha (TNF), interleukin 1 beta (IL-1b), and interleukin 6 (IL-6)), and tissue oxidative stress (total antioxidant capacity (TAC), total oxidative stress (TOS), nitric oxide (NO), malondialdehyde (MDA), and the total thiols (THIOL)). Results: Linoleic acid (C18:2n-6) and oleic acid (C18:1n-9) were approximately 89% of total fatty acids while palmitic acid (C16:0) was 6.10%. Administration of NSO for 28 days helped in preventing QT and QTc interval prolongation and reduced heart rate (HR), after MI induction. The histological assessment showed improvement in myofibrillary degeneration and necrosis and also better reduced inflammatory process in the groups treated with NSO. In serum, pro-inflammatory cytokines IL-1b and IL-6 were downregulated in chronic conditions (for IL-1b, NSO vs. control was 86.09vs 150.39 pg/mL, and for IL-6 NSO vs. control was 78.00 vs. 184.98 pg/ml). In the heart tissue, the downregulation was observed only for TNF in both acute and chronic conditions (acute NSO vs. control was 132.37 vs. 207.63 pg/mL, and chronic NSO vs. control was 135.83 vs. 183.29 pg/ml). The pro-oxidant parameters TOS, NO, MDA, and OSI, were reduced in the groups treated with NSO only after 14 days of treatment, suggesting that the NSO antioxidant effect is time-dependent. Conclusions: NSO administration might have a favourable impact on the regulation of oxidative stress and inflammation processes after MI induction in rats, and it is worth considering its administration as an adjuvant treatment. [ABSTRACT FROM AUTHOR]

Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs. [ABSTRACT FROM AUTHOR]

Background: Mucosal-associated invariant T (MAIT) cells play key roles in many inflammatory diseases. However, their effects on the long-term course of oral lichen planus (OLP) and recent-onset OLP remain unclear. In this study, we aimed to investigate the function of MAIT cells in the different processes of OLP and to explore the immunological background of this disease. Methods: The frequency, phenotype, cytokine secretion, and clinical relevance of MAIT cells were investigated. MAIT cells were collected from the peripheral blood of 14 adults with recent-onset OLP (7–120 days after disease onset) and 16 adults with long-term course OLP (>2 years after diagnosis) using flow cytometry and compared with 15 healthy blood donors. Statistical analyses were performed using the GraphPad Prism software. Results: MAIT cells from adults with recent-onset OLP exhibited an activated phenotype, as indicated by an increased frequency of CD69+ (p < 0.05) and CD38+MAIT cells (p < 0.01) and elevated production of the proinflammatory cytokine IL-17 A (p < 0.01), compared with healthy adult donors. In adults with long-term OLP, MAIT cells exhibited an activated and exhausted phenotype, characterized by high expression of CD69 (p < 0.01) and PD-1 (p < 0.001) and increased production of granzyme B released (p < 0.01). Compared with recent-onset OLP patients, long-term OLP patients showed a decreased production of CD8+, and CD4−CD8− cells, but an increase in PD-1+ production (p < 0.05). Conclusions: Circulating MAIT cells exhibited activation in OLP patients across varying disease durations. Given that PD-1 expression is elevated in adults with long-term OLP, it is reasonable to infer that circulating MAIT cells in long-term OLP may exhibit a more exhausted state than those in recent-onset OLP. [ABSTRACT FROM AUTHOR]

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic DSF (De Simone formulation) in improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because the low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and DSF treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. Methods: We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n = 64) was treated with rifaximin (seven days per month for three months) followed by DSF, and group B (n = 60) was treated with a placebo. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI (National Institute of Health's Chronic Prostatitis Symptom Index) and IBS-SSS (Irritable Bowel Syndrome Severity Scoring System) scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs. 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs. 4.4 pg/mL) relative to baseline, whereas the levels of IL-6 and IL-10 did not change in the placebo group. Conclusions: The combined treatment with rifaximin and DSF appears to represent the optimal approach for addressing a syndrome such as irritable bowel syndrome (IBS-D plus), which frequently co-occurs with prostatitis (IIIa prostatitis). This approach is particularly beneficial in cases where the symptoms are not always clearly delineated, the etiology is multifactorial, and the diagnosis is multilevel. [ABSTRACT FROM AUTHOR]

Background: Meningococcal meningitis is still a severe disease causing high mortality and morbidity rates. Early diagnosis is crucial to ensure prompt antibiotic therapy. However, identification of the pathogen can be challenging. Case presentation: A 32-year-old male patient with systemic lupus erythematosus (SLE) presented to the emergency room with fever, nausea, vomiting, headache and lower back pain as well as multiple petechial bleedings. On suspicion of meningococcal infection, the emergency doctor had already administered one dose of ceftriaxone before arrival to the clinic. Blood works showed massive inflammation due to bacterial infection. Cerebrospinal fluid (CSF) analysis showed normal cell count, protein and glucose levels but PCR was positive for Neisseria meningitis and IL-6 as well as IL-8 were elevated. On antibiotic therapy with ceftriaxone, the patient's condition improved quickly. Conclusions: We present a rare case of meningococcal infection of the CSF in a SLE patient without further CSF abnormalities. We discuss the involvement of early antibiotic treatment and the role of the patient's immune status in the normal CSF findings of this case. Moreover, this case demonstrates the importance of early antibiotic therapy in bacterial meningitis for the clinical outcome. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders that can be acute, lasting days to weeks or months and possibly longer. The latter is known as long-COVID or more recently post-acute sequelae of COVID (PASC). During acute COVID-19 infection, a strong inflammatory response, known as the cytokine storm, occurs in some patients. The levels of interferon‐γ (IFN‐γ), interferon-β (IFN-β), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) are particularly increased. These cytokines are known to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing the first step of tryptophan (Trp) catabolism through the kynurenine pathway (KP) leading to the production of several neurotoxic and immunosuppressive metabolites. There is already data showing elevation in KP metabolites both acutely and in PASC, especially regarding cognitive impairment. Thus, it is likely that KP involvement is significant in SARS-CoV-2 pathogenesis especially neurologically. [ABSTRACT FROM AUTHOR]

Background: The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments. Methods: A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival. Comparative analysis of clinical and immunological parameters was performed between deceased and surviving individuals. Subsequently, multivariate Cox regression models were utilized to validate mortality predictions at 12, 24, and 36 months. Results: Observed plasma cytokine levels before treatment were significantly lower for IL-1RA (p < 0.001) and MCP-1 (p < 0.05) when in the survivor group. Incorporating plasma levels of IL-1RA, IL-6, and high-risk CURB-65 score demonstrated the highest area under curve (AUC) value (0.96) for predicting 1-year mortality. For 1-, 2- and 3-year predictions, the single-factor model with IL-1RA demonstrated superior performance compared to all multiple-variate models (AUC = 0.95/0.78/0.78). Conclusions: IL-1RA is a biomarker for predicting 3-year survival. Further investigations to explore the pathogenetic role of IL-1RA in HIV-associated disseminated cryptococcosis and as a potential therapeutic target are warranted. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that synovial inflammation plays a pivotal role in knee osteoarthritis. Although biomechanical findings have shown that medial open-wedge proximal tibial osteotomy (OWPTO) decreases medial compartment loading by correcting knee alignment, the relationship between knee alignment and synovial inflammation in the biological microenvironment has not yet been elucidated. Purposes: To investigate the relationship between preoperative and postoperative knee alignment and synovial gene expression and to determine the cutoff point of postoperative knee alignment at which gene expression of synovial inflammation improves. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 36 patients with osteoarthritis who underwent OWPTO between June 2018 and May 2020 were enrolled. Synovial tissue was collected from affected knees during initial OWPTO and plate removal surgeries, and gene expression associated with the pathogenesis of osteoarthritis in the synovial tissue was investigated using real-time polymerase chain reaction. The correlation between weightbearing line ratio (WBLR) and synovial gene expression was determined. Receiver operating characteristic curve analysis was used to determine the cutoff values of WBLR for improving gene expression. The participants were divided into 2 groups, according to the cutoff values of their WBLR, and compared according to Knee injury and Osteoarthritis Outcome Score (KOOS) and synovial gene expression. Results: Postoperative WBLR was correlated with gene expression of interleukin 1β (IL1B) (ρ = −0.43; P =.008) and of interleukin 6 (IL6) (ρ = −0.41; P =.01). The cutoff value to predict improvement of IL6 was postoperative WBLR of 52%, with an area under the curve of 0.74 (P =.03). Patients with WBLR of <52% showed higher postoperative inflammatory gene (IL1B [ P =.04] and IL6 [ P =.03]) and inferior postoperative KOOS values compared with those with WBLR of >52%. Conclusion: The novel cutoff alignment for biological improvement after OWPTO in patients with medial compartment osteoarthritis was determined to be WBLR of 52%, and WBLR of <52% was associated with higher residual intra-articular inflammation and poor clinical outcomes. After accounting for surgical errors, the surgeon should set the target surgical alignment so that the postoperative WBLR does not fall below 52%. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a prevalent and disabling disease that affects a significant proportion of the global population. Urine-derived stem cells (USCs) have shown great prospects in the treatment of OA, but there is no study that has compared them with traditional stem cells. Purpose: This study aimed to compare the therapeutic efficacy and mechanisms of USCs and adipose-derived stem cells (ADSCs) for OA treatment. Study Design: Controlled laboratory study. Methods: We compared the biological properties of USCs and ADSCs using CCK-8, colony formation, EdU, adhesion, and apoptosis assays. We evaluated the protective effects of USCs and ADSCs on IL-1β–treated OA chondrocytes by chemical staining, immunofluorescence, and Western blotting. We assessed the effects of USCs and ADSCs on chondrocyte autophagy by transmission electron microscopy, immunofluorescence, and Western blotting. We also compared the therapeutic efficacy of intra-articular injections of USCs and ADSCs by gross, histological, micro–computed tomography, and immunohistochemical analyses in an OA rat model induced by anterior cruciate ligament transection. Results: USCs showed higher proliferation, colony formation, DNA synthesis, adhesion, and anti-apoptotic abilities than ADSCs. Both USCs and ADSCs increased the expression of cartilage-specific proteins and decreased the expression of matrix degradation–related proteins and inflammatory factors in OA chondrocytes. USCs had a greater advantage in suppressing MMP-13 and inflammatory factors than ADSCs. Both USCs and ADSCs enhanced autophagy in OA chondrocytes, with USCs being more effective than ADSCs. The autophagy inhibitor 3-MA reduced the enhanced autophagy and protective effects of USCs and ADSCs on OA chondrocytes. Conclusion: To our knowledge, this is the first study to explore the efficacy of USCs in the treatment of knee OA and to compare them with ADSCs. Considering the superior properties of USCs in terms of noninvasive acquisition, a high cost-benefit ratio, and low ethical concerns, our study suggests that they may be a more promising therapeutic option than ADSCs for OA treatment under rigorous regulatory pathways. Clinical Relevance: USCs may be a superior cell source for stem cells to treat knee OA, and this study strengthens the evidence for the application of USCs. [ABSTRACT FROM AUTHOR]

Aim: We investigated the in vitro effect of Limosilactobacillus reuteri DSM 17938 supernatant on the inflammatory response of human gingival fibroblasts (HGF) challenged by lipopolysaccharide (LPS) or elevated glucose levels. Methods: HGF were exposed to LPS (1 μg/mL), glucose (5, 12 mM or 25 mM), and dilutions of supernatant prepared from L. reuteri DSM 17938 (0.5 × 107, 1.0 × 107, 2.5 × 107, and 5.0 × 107 CFU/mL). After 24 h cell viability and levels of cytokines (IL‐1β, IL‐6 and IL‐8) and TLR‐2 were determined. Results: None of the tested L. reuteri (DSM 17938) supernatant concentrations reduced the viability of HGF. Supernatant concentrations (2.5 × 107 and 5 × 107 CFU/mL) significantly (p <.05) decreased the production of IL‐1β, IL‐6, IL‐8, and TLR‐2 in the presence of LPS. In contrast, inflammatory markers were not reduced by L. reuteri supernatant in the presence of glucose. Glucose concentrations of 12 mM and 24 mM still lead to an elevated production of the investigated biochemical mediators. Conclusion: While L. reuteri (DSM 17938) supernatant attenuates the inflammatory response of HGF to LPS in a dose‐dependent manner, elevated glucose levels suppress this action. These in vitro results support the overall anti‐inflammatory efficacy of L. reuteri supplementation in plaque‐associated periodontal inflammations. [ABSTRACT FROM AUTHOR]

Aim: Evidence suggests that translocation of oral pathogens through the oral–gut axis may induce intestinal dysbiosis. This study aimed to evaluate the impact of a highly leukotoxic Aggregatibacter actinomycetemcomitans (Aa) strain on the gut microbiota, intestinal mucosal integrity and immune system in healthy mice. Methods: Eight‐week‐old male C57BL6 mice were divided into control (n = 16) and JP2 groups (n = 19), which received intragastric gavage with PBS and with a suspension of Aa JP2 (HK921), respectively, twice a week for 4 weeks. Colonic lamina propria, fecal material, serum, gingival tissues, and mandibles were obtained for analyses of leukocyte populations, inflammatory mediators, mucosal integrity, alveolar bone loss, and gut microbiota. Differences between groups for these parameters were examined by non‐parametric tests. Results: The gut microbial richness and the number of colonic macrophages, neutrophils, and monocytes were significantly lower in Aa JP2‐infected mice than in controls (p <.05). In contrast, infected animals showed higher abundance of Clostridiaceae, Lactobacillus taiwanensis, Helicobacter rodentium, higher levels of IL‐6 expression in colonic tissues, and higher splenic MPO activity than controls (p <.05). No differences in tight junction expression, serum endotoxin levels, and colonic inflammatory cytokines were observed between groups. Infected animals presented also slightly more alveolar bone loss and gingival IL‐6 levels than controls (p <.05). Conclusion: Based on this model, intragastric administration of Aa JP2 is associated with changes in the gut ecosystem of healthy hosts, characterized by less live/recruited myeloid cells, enrichment of the gut microbiota with pathobionts and decrease in commensals. Negligible levels of colonic pro‐inflammatory cytokines, and no signs of mucosal barrier disruption were related to these changes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the responses of periodontal environment to hormone replacement therapy (HRT) in postmenopausal women with or without periodontitis. Background: HRT is a common and effective strategy for controlling menopausal symptoms, while the changes of periodontal environment under it, particularly in postmenopausal women with periodontitis, remain unclear. Methods: As a prospective cohort study, a total of 97 postmenopausal women receiving HRT were screened, including 47 with and 50 without periodontitis. Correspondingly, 97 women did not receiving HRT were screened as controls during the same period. The full‐mouth sulcus bleeding index (SBI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were measured using periodontal probes. The levels of interleukin‐6 (IL‐6) and tumor necrosis factor α (TNF‐α) in the gingival crevicular fluid were measured using enzyme‐linked immunosorbent assay. In addition, cone beam computed tomography was performed to measure the alveolar bone height (ABH) and bone mineral density (BMD). Results: In postmenopausal women without periodontitis, no significantly changes on periodontal parameters were observed after HRT. In women with stage II periodontitis, SBI, BOP, IL‐6, and TNF‐α were significant decreased after one year and two years of HRT. Compared to the controls, women with stage II periodontitis who underwent HRT had significantly lower CAL and ABH and higher BMD in the second year. The incidence of at least one site with CAL increase ≥1 mm between baseline and 2 years was significantly lower in the HRT group than in the control group in women with stage II periodontitis. In addition, HRT was significantly associated with a decrease in SBI, BOP, IL‐6, and TNF‐α in the first year and with a decrease in CAL, SBI, BOP, IL‐6, and ABH and an increase in BMD in the second year. Conclusions: In postmenopausal women with stage II periodontitis, HRT is associated with the alleviation of inflammation within two years and the remission of alveolar bone loss in the second year. HRT appears to decrease the incidence of CAL increase ≥1 mm within 2 years in women with periodontitis by inhibiting inflammation and alveolar bone loss. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the effects of Umbelliferone (UMB) on the inflammation underlying alveolar bone resorption in mouse periodontitis. Methods: Male Swiss mice subjected to a ligature of molars were grouped as non‐treated (NT), received UMB (15, 45, or 135 mg/kg) or saline daily for 7 days, respectively, and were compared with naïve mice as control. Gingival tissues were evaluated by myeloperoxidase (MPO) activity and interleukin‐1β level by ELISA. The bone resorption was directly assessed on the region between the cement–enamel junction and the alveolar bone crest. Microscopically, histomorphometry of the furcation region, immunofluorescence for nuclear factor‐kappa B (NF‐ĸB), and immunohistochemistry for tartrate‐resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were performed. Systemically, body mass variation and leukogram were analyzed. Results: Periodontitis significantly increased MPO activity, interleukin‐1β level, and NF‐ĸB+ immunofluorescence, and induced severe alveolar bone and furcation resorptions, besides increased TRAP+ and CTSK+ cells compared with naïve. UMB significantly prevented the inflammation by reducing MPO activity, interleukin‐1β level, and NF‐ĸB+ intensity, besides reduction of resorption of alveolar bone and furcation area, and TRAP+ and CTSK+ cells compared with the NT group. Periodontitis or UMB treatment did not affect the animals systemically. Conclusion: UMB improved periodontitis by reducing inflammation and bone markers. [ABSTRACT FROM AUTHOR]

Purpose: Non-alcoholic fatty liver disease (NAFLD) prevalence and severity may be higher in people with human immunodeficiency virus (HIV) than the general population, and vary with sex and age. We explored NAFLD characteristics by gender. Methods: Adult transgender women (TW), cisgender women (CW), and cisgender men (CM) with HIV on antiretroviral therapy and without other known causes of liver disease underwent screening for NAFLD (2017–2020). Circulating factors associated with NAFLD were measured. Hepatic steatosis and fibrosis were assessed using transient elastography by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. Analysis of variance/Wilcoxon testing compared normally/non-normally distributed variables, respectively. Logistic regression evaluated factors associated with CAP and LSM. Results: Participants (n=194) had median age 48 years and body mass index 28.3 kg/m2; 42% were CM, 37% TW, and 21% CW; 95% were non-white; and 16% had diabetes, 40% dyslipidemia, and 49% hypertension. NAFLD prevalence was 59% using CAP ≥248 dB/m (≥S1 steatosis), 48% using CAP ≥260 dB/m (≥S2 steatosis), and 32% using CAP ≥285 dB/m (≥S3 steatosis). Compared to CM and CW, TW had the highest median CAP scores, were more likely to have ≥S2 steatosis, and had the highest insulin resistance, interleukin-6, and fetuin-A values. TW off versus on gender-affirming hormone therapy (GAHT) had slightly higher median CAP scores. Conclusion: TW on GAHT had less hepatic steatosis than TW not on GAHT, although overall NAFLD severity was greater than expected for TW compared to CM and CW. The effects of estrogen supplementation and androgen deprivation on liver health in TW require further study. [ABSTRACT FROM AUTHOR]

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Purpose: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic gastrointestinal disorders associated with significant morbidity and complications. This study investigates the therapeutic potential of docosahexaenoic acid (DHA) in a trinitrobenzene sulfonic acid (TNBS) induced colitis model, focusing on inflammation, oxidative stress, and intestinal membrane permeability. Methods: Wistar albino rats were divided into Control, Colitis, and Colitis + DHA groups (n = 8–10/group). The Colitis and Colitis + DHA groups received TNBS intrarectally, while the Control group received saline. DHA (600 mg/kg/day) or saline was administered via gavage for six weeks. Macroscopic and microscopic evaluations of colon tissues were conducted. Parameters including occludin and ZO-1 expressions, myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels were measured in colon tissues. Results: Colitis induction led to significantly higher macroscopic and microscopic damage scores, elevated TOS levels, reduced occludin and ZO-1 intensity, decreased mucosal thickness, and TAS levels compared to the Control group (p < 0.001). DHA administration significantly ameliorated these parameters (p < 0.001). MPO, MDA, TNF-α, and IL-6 levels were elevated in the Colitis group but significantly reduced in the DHA-treated group (p < 0.001 for MPO, MDA; p < 0.05 for TNF-α and IL-6). Conclusion: DHA demonstrated antioxidant and anti-inflammatory effects by reducing reactive oxygen species production, enhancing TAS capacity, preserving GSH content, decreasing proinflammatory cytokine levels, preventing neutrophil infiltration, reducing shedding in colon epithelium, and improving gland structure and mucosal membrane integrity. DHA also upregulated the expressions of occludin and ZO-1, critical for barrier function. Thus, DHA administration may offer a therapeutic strategy or supplement to mitigate colitis-induced adverse effects. [ABSTRACT FROM AUTHOR]

Purpose: Rheumatoid Arthritis (RA) has a point prevalence of around 20 million people worldwide. Patients with RA often believe that food intake affects disease activity, and that intake of red meat aggravate symptoms. The main objective of the Postprandial Inflammation in Rheumatoid Arthritis (PIRA) trial was to assess whether postprandial inflammation and serum lipid profile are affected differently by a meal including red meat, fatty fish, or a soy protein (vegan) meal. Methods: Using a randomized controlled crossover design, 25 patients were assigned to eat isocaloric hamburger meals consisting of red meat (60% beef, 40% pork), fatty fish (salmon), or soy protein for breakfast. Blood samples were taken before meals and at intervals up to 5 h postprandial. The analysis included the inflammation marker interleukin 6 (IL-6) and serum lipids. Results: No significant differences in postprandial IL-6 or triglyceride concentrations were found between meals. However, the area under the curve of very low density lipoprotein (VLDL) particle counts, as well as VLDL-4-bound cholesterol, triglycerides, and phospholipids, was higher after the fatty fish compared to both red meat and soy protein. Conclusion: Postprandial inflammation assessed by IL-6 did not indicate any acute negative effects of red meat intake compared to fatty fish- or soy protein in patients with RA. The fatty fish meal resulted in a higher number of VLDL-particles and more lipids in the form of small VLDL particles compared to the other protein sources. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases are among the most common chronic diseases, generating high social and economic costs. Secondary immunodeficiencies occur more often than primary ones and may result from the co-occurrence of specific diseases, treatment, nutrient deficiencies and non-nutritive bio-active compounds that result from the industrial nutrient practices. Objectives: The aim of this article is to present selected secondary immunodeficiencies and their impact on the cardiovascular system. Results: The treatment of a patient with cardiovascular disease should include an assess-ment for immunodeficiencies, because the immune and cardiovascular systems are closely linked. Conclusions: Immune system dysfunctions can significantly affect the course of cardiovascular diseases and their treatment. For this reason, comprehensive care for a patient with cardiovascular disease requires taking into account potential immunodeficiencies, which can have a significant impact on the patient's health. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of the GPER in cancer is controversial due to its dual anti and protumor effects. Elevated GPER expression in cervical cancer has been associated with improved survival outcomes. In cervical cancer cell lines, the selective GPER agonist G-1 induces cell cycle arrest and apoptosis, although the precise molecular mechanisms behind these effects are not fully understood. This study explores the impact of GPER activation by G-1 on the transcriptome, cell migration, and invasion in SiHa cells, as well as in non-tumorigenic keratinocytes transduced with HPV16 E6 or E7 oncogenes. G-1 has been shown to exert antitumor effects by activating apoptotic pathways and modulating migration and invasion processes. The findings support the GPER as a promising prognostic marker and suggest that G-1 could be a valuable therapeutic tool for treating cervical cancer. Background/Objectives: Estrogens and HPV are necessary for cervical cancer (CC) development. The levels of the G protein-coupled estrogen receptor (GPER) increase as CC progresses, and HPV oncoproteins promote GPER expression. The role of this receptor is controversial due to its anti- and pro-tumor effects. This study aimed to determine the effect of GPER activation, using its agonist G-1, on the transcriptome, cell migration, and invasion in SiHa cells and non-tumorigenic keratinocytes transduced with the HPV16 E6 or E7 oncogenes. Methods: Transcriptome analysis was performed to identify G-1-enriched pathways in SiHa cells. We evaluated cell migration, invasion, and the expression of associated proteins in SiHa, HaCaT-16E6, and HaCaT-16E7 cells using various assays. Results: Transcriptome analysis revealed pathways associated with proliferation/apoptosis (TNF-α signaling, UV radiation response, mitotic spindle formation, G2/M cell cycle, UPR, and IL-6/JAK/STAT), cellular metabolism (oxidative phosphorylation), and cell migration (angiogenesis, EMT, and TGF-α signaling) in SiHa cells. Key differentially expressed genes included PTGS2 (pro/antitumor), FOSL1, TNFRSF9, IL1B, DIO2, and PHLDA1 (antitumor), along with under-expressed genes with pro-tumor effects that may inhibit proliferation. Additionally, DKK1 overexpression suggested inhibition of cell migration. G-1 increased vimentin expression in SiHa cells and reduced it in HaCaT-16E6 and HaCaT-16E7 cells. However, G-1 did not affect α-SMA expression or cell migration in any of the cell lines but increased invasion in HaCaT-16E7 cells. Conclusions: GPER is a promising prognostic marker due to its ability to activate apoptosis and inhibit proliferation without promoting migration/invasion in CC cells. G-1 could potentially be a tool in the treatment of this neoplasia. [ABSTRACT FROM AUTHOR]

Aims Understanding the mechanisms underlying ascending aortic dilation is imperative for refined risk stratification of these patients, particularly among incidentally identified patients, most commonly presenting with tricuspid valves. The aim of this study was to explore associations between ascending aortic haemodynamics, assessed using four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR), and circulating biomarkers in aortic dilation. Methods and results Forty-seven cases with aortic dilation (diameter ≥ 40 mm) and 50 sex-and age-matched controls (diameter < 40 mm), all with tricuspid aortic valves, underwent 4D flow CMR and venous blood sampling. Associations between flow displacement, wall shear stress (WSS), and oscillatory shear index in the ascending aorta derived from 4D flow CMR, and biomarkers including interleukin-6, collagen type I α1 chain, metalloproteinases (MMPs), and inhibitors of MMPs derived from blood plasma, were investigated. Cases with dilation exhibited lower peak systolic WSS, higher flow displacement, and higher mean oscillatory shear index compared with controls without dilation. No significant differences in biomarkers were observed between the groups. Correlations between haemodynamics and biomarkers were observed, particularly between maximum time-averaged WSS and interleukin-6 (r = 0.539, P < 0.001), and maximum oscillatory shear index and collagen type I α1 chain (r = −0.575, P < 0.001 in cases). Conclusion Significant associations were discovered between 4D flow CMR derived whole-cardiac cycle WSS and circulating biomarkers representing inflammation and collagen synthesis, suggesting an intricate interplay between haemodynamics and the processes of inflammation and collagen synthesis in patients with early aortic dilation and tricuspid aortic valves. [ABSTRACT FROM AUTHOR]

Objectives: The gingival mucosal barrier, an important oral cavity barrier, plays a significant role in preventing pathogenic microorganism invasion and maintaining periodontal tissue health. Pathogenic microorganism invasion of the gingival mucosa produces a large number of cytokines. Among them, pyroptosis is an important player in exacerbating immune‐inflammatory responses, leading to tissue destruction. However, the mechanism of pyroptosis and the immune response it triggers have not been fully elucidated. We provide an overview of recent advances in understanding gingival physical barrier pyroptosis and inflammation‐induced hyperimmunity. Methods: PubMed, Web of Science databases were searched for articles, reviews, and clinical studies published until March 2024. Results: We summarised the importance of the gingival barrier in terms of the functions of different cells, described the progress in research on gingival epithelial cell and gingival fibroblast pyroptosis and the immune‐inflammatory response it induces, and discussed the relationship between pyroptosis and systemic diseases, association of multiple cell death systems. Finally, we propose future directions for pyroptosis research. Conclusions: Pyroptosis often triggers a range of inflammatory immune responses that lead to associated diseases. Therefore, further study of the molecular mechanisms of pyroptosis and the immune responses is warranted. [ABSTRACT FROM AUTHOR]

Objective: Periodontitis is an inflammatory oral disease that occurs as a result of the damaging effects of the immune response against the subgingival microflora. Among the mechanisms involved, the nucleotide‐binding oligomerization domain, leucine‐rich repeat‐containing proteins family member NLRP3 (NLR family pyrin domain‐containing 3), proposed as the key regulator of macrophage‐induced inflammation, is strongly associated with periodontal disease due to the bacterial activators. This paper aimed to present key general concepts of NLRP3 inflammasome activation and regulation in periodontal disease. Method: A narrative review was conducted in order to depict the current knowledge on the relationship between NLRP3 inflammasome activity and periodontal disease. In vitro and in situ studies were retrieved and commented based on their relevance in the field. Results: The NLRP3 inflammasome activity stimulated by periodontal microbiota drive periodontal disease pathogenesis and progression. This occurs through the release of proinflammatory cytokines IL‐1β, IL‐18, and DAMPs (damage‐associated molecular pattern molecules) following inflammasome activation. Moreover, the tissue expression of NLRP3 is dysregulated by oral microbiota, further exacerbating periodontal inflammation. Conclusion: The review provides new insights into the relationship between the NLRP3 inflammasome activity and periodontal disease pathogenesis, highlighting the roles and regulatory mechanism of inflammatory molecules involved in the disease process. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of magnifying the damage caused by obesity induced by monosodium glutamate, using a model of maternal periodontitis, on the structure of the anterior tibialis muscle of the offspring. Materials and Methods: Twenty‐four female Wistar rats were divided into four experimental groups: control (n = 6), obese (n = 6), control with periodontitis (n = 6) and obese with periodontitis (n = 6). At 78 days of life, the rats were mated with males without any experimental intervention. The offspring of these rats (n = 1/L), at 120 days of life, were weighed and measured, then euthanized. Plasma was collected for analysis of cytokines IL‐6, IL‐10, IL‐17 and TNF‐α. Adipose tissues were collected and weighed, and the anterior tibial muscle was designated for histomorphological analyses (n = 6/group). Results: Monosodium glutamate offspring showed significant muscle changes, such as a reduction in the size of fibres and neuromuscular junctions, and an increase in the nucleus and capillaries. However, all these changes were more expressed in monosodium glutamate‐obese with periodontitis offspring. Conclusion: This leads us to suggest a magnifying effect promoted by periodontitis to the damage already well described by monosodium glutamate‐obesity, determined by low‐intensity inflammation, causing greater muscle damage. [ABSTRACT FROM AUTHOR]