BACKGROUND:Traditionally, pulmonary cytology has been used to diagnose and screen for a variety of respiratory diseases, including lung cancer. Owing to its rapid turnaround time compared with histological diagnosis, therapeutic decisions may occasionally need to be made based on cytological findings alone. In the era of precision medicine, however, biomarker assessment and molecular testing have become increasingly important, particularly in the management of lung cancer. In addition, the digitalization of pathological slides has facilitated the development of artificial intelligence (AI)-based diagnostic tools. The utility of these emerging technologies in pulmonary cytology is currently being actively investigated and continues to evolve, overcoming challenges including low input of tumor cells and three-dimensional nature of cytological specimens. SUMMARY:This review summarizes recent advances in pulmonary cytology, focusing on immunocytochemistry (ICC), proteomic analysis, and AI-assisted diagnostics. ICC provides crucial information not only for subclassification but also for the assessment of relevant therapeutic biomarkers. Proteomic analysis enables comprehensive characterization of thousands of protein expression profiles simultaneously, using limited cytology materials. But its future use in routine diagnostics must be established and tested in clinical trials. Furthermore, digitalized cytological slides can be utilized for AI-based analyses, potentially reducing diagnostic workload, and providing additional predictive information. Despite these advances, challenges remain regarding specimen preparation, standardization, and validation. KEY MESSAGES:The integration of morphology with appropriately validated molecular and computational methods has the potential to transform the framework of pulmonary cytology, extending its role from morphological diagnosis toward comprehensive and clinically significant characterization of pulmonary tumors.
OBJECTIVE:To determine whether urinary or plasma cytokines more effectively differentiate Hunner-type interstitial cystitis (HIC) from non-Hunner-type interstitial cystitis (NHIC), and to develop an interpretable discriminative formula based on the most informative features. METHODS:Paired urine and plasma samples were collected from 47 patients with IC/BPS (15 HIC, 32 NHIC), and urine samples from 84 healthy controls were analyzed for baseline comparison. Twelve cytokines were quantified in each sample. Classification performance was evaluated using AutoGluon automated machine learning with stratified five-fold cross-validation across three feature sets: urine cytokines, plasma cytokines, and their combination. Symbolic regression with the QLattice algorithm, implemented within a nested cross-validation framework with seed averaging and a complexity constraint to reduce overfitting, was employed to generate a simplified discriminative formula. RESULTS:The urine-based model outperformed both plasma-based and combined models (AUC 0.979 ± 0.028 vs. 0.741 ± 0.271 vs. 0.921 ± 0.087). A clear pathophysiological gradient was observed among healthy controls, NHIC, and HIC, with urinary IL-8 elevated 72-fold in HIC and 5-fold in NHIC compared to healthy controls. The QLattice-derived formula, incorporating uIL-17 and uIL-8, achieved a nested cross-validation accuracy of 90.5% (95% CI: 88.5%-92.4%) and an AUC of 0.948 (95% CI: 0.927-0.966). CONCLUSION:Urinary cytokines, specifically IL-8 and IL-17, offer a more effective non-invasive approach for IC/BPS subtyping compared to plasma markers. The two-cytokine formula shows promise as an exploratory discriminative tool. However, external validation in larger, independent cohorts is necessary prior to clinical implementation.
Background Treatment with the synthetic prostacyclin analog iloprost has been shown to attenuate endothelial glycocalyx shedding and organ failure in patients with critical Covid-19. The treatment is currently being investigated in a broader setting of patients with acute respiratory failure. We here investigated the effect on inflammatory and T-cell-derived cytokine and growth-factor responses in patients with critical Covid-19. Methods Post-hoc analysis of a randomized controlled trial (n = 80) in mechanically ventilated patients with SARS-CoV-2 infection and concomitant endotheliopathy, defined as soluble thrombomodulin plasma-levels ≥4 ng/mL. Patients received 72 h iloprost infusion (1 ng/kg/min) or placebo. Blood samples were collected at baseline and 24 h after inclusion. Fifty-four cytokines and growth factors, distributed into six biomarker classes, were measured using the Meso Scale Discovery V-PLEX platform. Results Iloprost treatment, compared with placebo, did not result in statistically significant changes of any of the fifty-four measured biomarkers at 24 h, when adjusting for multiple testing. Likewise, linear mixed-effects models did not identify significant effects of iloprost on any of the six predefined biomarker classes at 24 h. Conclusions In mechanically ventilated patients with SARS-CoV-2 infection and endotheliopathy, iloprost treatment had no detectable effect on inflammatory and T-cell-derived cytokine and growth-factor responses. The findings corroborate that the clinical benefit of iloprost is not attributed to anti-inflammatory effects. We suggest that future studies focus on patient selection for targeted treatment, and on combined treatment with anti-inflammatory and endothelium-stabilizing interventions, in patients with respiratory failure, hyperinflammation, and endotheliopathy.
Coronavirus diseases, particularly COVID-19, been associated with cardiac injury. Given that obesity is a well-known risk factor for severe cases with poorer outcomes, we hypothesized that cardiac involvement in a murine betacoronavirus infection would be exacerbated in pre-obese mice. To test this hypothesis, we fed mice a short-term (4-week) cafeteria diet (Caf), which resulted in increased body fat and mild cardiac histological damage, myocyte hypertrophy and fibrosis. Following the diet, we performed intranasal infection with MHV-A59 and evaluated the lungs and hearts eight days post-infection. In the lungs, infection was acute, caused moderate lung injury and was self-limited in both Chow-fed and Caf-fed mice with similar low viral loads recovered from this tissue. Meanwhile, cardiac fibrosis was significantly exacerbated in the Caf diet mice infected with MHV-A59. We also observed elevated levels of circulating cytokines, TNF and IL-10, as well as increased cardiac oxidative stress, solely in the obese infected mice. In contrast, isolated hearts from lean infected mice showed an increased response to β-adrenergic stimulation, which was damped in the Caf diet infected group. These findings indicate that obesity is a significant risk factor for cardiac issues caused by coronavirus infection by modulating local oxidative stress and systemic inflammation.
BACKGROUND:Diagnostic significance of cell clusters (CCs) appearing in voided urine cytology remains unclear. Epithelial malignancy tends to form large clusters but tumor cells get discohesive and clusters become smaller with disease progression. We investigated diagnostic significance of CC in the differentiation between low-grade urothelial carcinoma (LGUC) and high-grade urothelial carcinoma (HGUC) and then HGUC detection. METHODS:Voided urine samples, suspected of new-onset bladder cancer, with corresponding pathological diagnosis were analyzed. Malignancy other than urothelial carcinoma was excluded. Specimens prepared by the SurePath and ThinPrep liquid-based cytology methods were analyzed separately. Cytological diagnosis was based on The Paris System 2.0 and maximal CC size was measured. These data were subject to statistical analysis. RESULTS:123 SurePath and 168 ThinPrep cases were analyzed. Cytological diagnosis was significantly associated with pathological diagnosis in both SurePath and ThinPrep specimens. Then, CC was found to be present in approximately 60% of specimens prepared by both methods. There was no significant difference in CC size among benign lesions, LGUC, and HGUC in both SurePath and ThinPrep specimens. Meanwhile, high-risk cytology which consists of Suspicious for HGUC and HGUC based on TPS 2.0 demonstrated similarly high specificity and positive-predictive value for HGUC detection irrespective of CC presence/absence but sensitivity was significantly higher when CC was present in both SurePath and ThinPrep specimens. CONCLUSION:Size of CC was not useful for differentiating LGUC from HGUC, but CC presence was advantageous for detecting HGUC possibly due to a sufficient amount of collected cells for diagnosis.
OBJECTIVE:Fine-needle aspiration cytology (FNAC) is routinely used in the preoperative evaluation of parotid gland tumors, yet its diagnostic performance varies across categories of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). This study evaluated category-specific malignancy risk and the clinical impact of different diagnostic thresholds. METHODS:We retrospectively analyzed 277 patients who underwent parotidectomy with available preoperative FNAC. Cytologic diagnoses were classified according to the MSRSGC and correlated with final histopathology. Diagnostic performance was assessed using two thresholds: Milan V-VI and Milan III-VI. Trends in malignancy risk across Milan categories were examined, and false-negative and false-positive cases were reviewed by histopathological subtype. Overall discriminatory performance was evaluated using receiver operating characteristic analysis. RESULTS:Final histopathology revealed benign disease in 85.2% and malignancy in 14.8% of cases. Malignancy risk increased significantly across higher Milan categories (p = 0.006). Using Milan V-VI as the threshold yielded high specificity (97.0%) and negative predictive value (88.8%) but low sensitivity (29.3%). Expanding the threshold to Milan III-VI increased sensitivity (78.0%) but markedly reduced specificity (21.2%). Discriminatory performance was poor (AUC 0.622). False-negative results were mainly low-grade malignancies, particularly low-grade mucoepidermoid carcinoma, whereas false-positive results were largely benign oncocytic or hypercellular lesions. CONCLUSIONS:FNAC provides useful preoperative risk stratification for parotid gland tumors within the Milan framework, but its diagnostic value is highly threshold-dependent and limited by tumor biology.
Diabetic wounds pose a significant therapeutic challenge. While the antimicrobial peptide LL-37 and adipose-derived stem cells (ADSCs) individually show potential for wound repair, the efficacy and mechanism of their combined treatment remain unclear. This study aimed to investigate the therapeutic effect of LL-37 combined with ADSCs on diabetic wound healing. Clinical samples from diabetic and non-diabetic patients were analyzed, combined with bioinformatics analysis of public datasets (GSE144441 and GSE182906) to identify key genes. A diabetic mouse wound model was established to validate the healing effects of individual and combined LL-37 and ADSCs treatments. In vitro assays, co-culture models were employed to explore the mechanisms involving ADSCs and fibroblasts. Analysis of human diabetic wounds revealed impaired healing associated with deficiency in cathelicidin antimicrobial peptide (CAMP), the precursor of LL-37. In diabetic mice, the combination of LL-37 and ADSCs promoted wound healing more effectively than either treatment alone. LL-37 enhanced ADSC viability in a dose-dependent manner. Mechanistically, LL-37 treatment significantly upregulated the expression of negative regulator of reactive oxygen species (NRROS) in ADSCs. Exosomes derived from these LL-37-primed ADSCs were taken up by fibroblasts, leading to increased NRROS expression in the recipient fibroblasts. Upregulated NRROS subsequently activated both the TGF-β/SMAD and Hippo/TEAD1 signaling pathways. Further experiments confirmed crosstalk between these two pathways, which collectively enhanced fibroblast proliferation and migration. In conclusion, the combination of LL-37 and ADSCs promotes diabetic wound healing by enhancing fibroblast activity. This effect is mediated through exosomal transfer of NRROS from ADSCs to fibroblasts, leading to the activation of the interconnected TGF-β/SMAD and Hippo/TEAD1 signaling pathways.
Visceral leishmaniasis (VL) is associated with impaired Th1 responses, yet the intracellular signalling events linking immunosuppressive pathways to effector dysfunction remain poorly defined. We studied 150 adults in endemic northern Nigeria (50 active VL, 50 healed VL, 50 endemic controls) using flow cytometry, cytokine profiling, targeted RT-qPCR of 13 JAK-STAT pathway genes with dual reference gene normalisation, ex vivo checkpoint blockade, and phospho-flow cytometry for STAT1/STAT3 in both CD4+ T cells and CD14+ macrophages. Active VL was associated with reduced antigen-specific IFN-γ (220 versus 940 pg/mL in healed VL; P < 0.001), elevated IL-10, expanded regulatory T cells, transcriptional upregulation of STAT3 (2.66-fold, adjusted P < 0.001), and downregulation of its negative regulator SOCS3 (0.56-fold, adjusted P = 0.001). A STAT3-dominant phosphorylation profile was present in both CD4+ T cells (pSTAT1/pSTAT3 ratio 1.33) and, more prominently, CD14+ macrophages (ratio 0.51; Kruskal-Wallis P < 0.001 across disease groups). CD14+ pSTAT3 correlated with macrophage infection index (Spearman ρ = 0.52, P < 0.001), linking signalling state to effector function. Combined IL-10 and PD-1 blockade reversed the signalling imbalance in both compartments, restored IFN-γ production up to 4.8-fold, and reduced macrophage infection index by 42%. Pharmacological STAT3 inhibition with Stattic confirmed pSTAT3 reduction by phospho-flow cytometry (-33%, P < 0.001), reproduced transcriptional reprogramming comparable to checkpoint blockade for 9 of 13 genes, and enhanced macrophage parasite clearance (infection index -36%, P < 0.001). These findings across phosphoprotein, transcript, and functional levels identify a STAT3-dominant signalling signature spanning T-cell and macrophage compartments as a consistent feature of immune suppression in human VL and a candidate therapeutic target warranting investigation.
Background B-cell non-Hodgkin lymphoma (B-NHL) and B-cell acute lymphoblastic leukemia (B-ALL) are highly heterogeneous malignancies. While immunochemotherapy and CD19 chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of newly diagnosed (ND) and relapsed or refractory (R/R) disease, clinical outcomes remain inconsistent. This study aims to evaluate a baseline levels of 12-cytokine panel across the ND, R/R, and CAR-T cohorts to identify robust biomarkers predictive of treatment response and long-term prognosis. Methods We enrolled 120 patients (ND B-NHL: n = 42; R/R B-NHL: n = 52; ND B-ALL: n = 10; R/R B-ALL: n = 21) and a separate cohort of 23 patients receiving CD19 CAR-T therapy. Plasma levels of 12 cytokines were quantified and analyzed using ROC curves, Kaplan-Meier survival analysis, and regression analyses to determine independent prognostic factors. Results Baseline cytokine profiling revealed that IL-17 was one of the four markers exhibiting significant inter-group differences (P = 0.034). In the R/R B-NHL cohort, high baseline IL-17 was significantly associated with inferior OS (log-rank P < 0.0001) and shorter progression-free survival (PFS) (P = 0.003). Univariate and multivariate Cox regression confirmed IL-17 as a significant risk factor for poor OS (HR = 1.802, P < 0.001) and PFS (HR = 1.279, P = 0.048) in R/R B-NHL. In CAR-T cohort, IL-17 levels also provided substantial discrimination for PFS (AUC 0.725). Conclusion Our findings indicate that IL-17 may be a potential biomarker with stage-specific clinical associations in B-NHL. Its relevance may vary across disease stages, but overall, it warrants further investigation for risk stratification and individualized treatment monitoring.
Interleukin-6 (IL-6) has an important modulator effect on inflammation and immunity and is involved in the progression of nephrolithiasis (kidney stone). However, whether IL-6 genetic variants affect the pathogenesis of kidney stones remains unclear. The present study conducted a combined investigation of candidate gene-driven screening and systematic screening on whole exome sequencing data from 28 patients of calcium oxalate stones, identifying a non-synonymous single nucleotide polymorphism (SNP) rs13306435 in IL-6 as a candidate research locus, which was further validated using HRM genotyping in an expanded cohort comprising 241 cases and 229 healthy subjects. Western blotting and qRT-PCR were used to assess the effects of this variant on crystal-induced inflammation, while molecular dynamics simulation was employed to analyze structural alterations in the receptor binding complex. In individuals aged ≤40 years, the A allele of rs13306435 was nominally associated with a reduced risk of stone formation, but no association was observed for the whole population. This missense variant causes an aspartate-to-glutamate substitution (D/E), inhibiting calcium oxalate monohydrate (COM)-triggered JAK2/STAT3 activation and inflammatory responses. However, it decreased the binding energy of IL-6/IL-6R/gp130 complex by increasing hydrogen bonds and salt brigdge at remote interfaces, suggesting that enhanced receptor binding does not necessarily translate to increased downstream signaling. Although this variant is not associated with general stone susceptibility, it exhibits notable anti-inflammatory activity by attenuating COM-induced JAK2/STAT3 activation and may influence the progression of stones through this pathway. These findings provide new insights into the role of anti-inflammatory mechanisms in nephrolithiasis.
Diabetes mellitus, especially type 2 diabetes (T2DM), is a complex metabolic disease marked by persistent low-grade inflammation and insulin resistance. In diabetes, adipose tissue macrophages adopt a pro-inflammatory M1 phenotype, secreting cytokines including TNF-α, IL-6, and IL-1β that disrupt insulin signaling and cause metabolic dysfunction. AMP-activated protein kinase (AMPK), a cellular energy sensor, is a key regulator of macrophage polarization. It suppresses M1 responses by inhibiting NF-κB and JNK signaling, activating CREB/SIRT1 pathways, and promoting oxidative metabolism. Therefore, this review investigates the bidirectional interaction between AMPK signaling and macrophage function in diabetes, focusing on how metabolic stress affects AMPK activity, increasing inflammation and insulin resistance, whereas AMPK activation restores immune-metabolic balance. The gut microbiome further influences this axis, with short-chain fatty acids activating AMPK via GPR41/43, promoting M2 polarization and improving metabolic outcomes. Metformin, SGLT2 inhibitors, new direct AMPK activators such as PXL770, and lifestyle changes are also potential therapeutic treatments. However, considerable hurdles remain, including the prevalence of preclinical findings, a lack of macrophage-specific AMPK activators, simplicity of the M1/M2 paradigm, and uncertainty about long-term safety. Future research must focus on macrophage-targeted drug delivery, tissue-specific regulatory networks, biomarker discovery, and rigorous clinical trials with immunological outcomes. In conclusion, the AMPK-macrophage axis is a critical immune-metabolic gatekeeper in diabetes, and targeting this pathway offers a potential technique for restoring immune-metabolic balance, while significant difficulties must be overcome before practical use.
A single nucleotide polymorphism (SNP) within the human interferon lambda 1 (IFN-L1, IFN-λ1) gene promoter, rs7247086 (C/T) has been reported to be associated with severe dengue and possibly with psoriasis and COVID-19. However, its functional nature is unknown. The present study was undertaken to examine the effect of rs7247086 on transcription, by utilizing promoter and enhancer-reporter assays. We see that the T allele completes a consensus signal transducer and activator of transcription (STAT)-binding site. While we did not find strong evidence to show that the STAT-binding site drove transcription from the IFNL1 gene promoter, we saw that it acts like an enhancer in reporter assays. The T allele of rs7247086 within the STAT-binding site significantly increased transcription of the reporter gene compared to the C allele when incorporated into enhancer-reporter constructs in both HEK293 and A549 cell lines. Mechanistically, we obtained evidence from electrophoretic mobility shift assays to show that the T allele binds to STAT proteins more strongly than the C allele. In a cohort of healthy individuals, we saw that the T allele carriers, specifically males but not females, had significantly increased secretion of IFN-λ1 from their peripheral blood mononuclear cells after stimulation. Lastly, rs7247086 significantly associated with psoriasis, only in males but not in females.
The literature on the Interleukin 17F (IL-17F) rs763780 polymorphism and its association with immune thrombocytopenia (ITP) risk remains inconsistent and controversial. These uncertainties underscore the urgent need for a meta-analysis to objectively synthesize the heterogeneous findings, mitigate bias, and improve statistical power. This study strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and guidelines. A systematic literature search for original studies was conducted across the CNKI, Wanfang Data, Cochrane Library, Web of Science, and PubMed databases, covering publications up to April 5, 2026. Odds ratios and corresponding 95% confidence intervals were calculated to assess the association. STATA 14.2 software was used to synthesize the pooled estimates. A total of eight case-control studies consisting of 805 ITP cases and 841 controls were included. The summarized statistics suggested the detrimental effect of the A allele in the homozygote and recessive models. In the sensitivity analysis, the results that were initially non-significant in the allele, heterozygote, and dominant models became significant after excluding a single dataset, which was also identified as the source of heterogeneity. Region-stratified analyses revealed statistical significance in the Chinese/Japanese and Egyptian subgroups under specific analytic contrasts. When stratified according to age, the children subgroup showed significant associations in a subset of genetic models, while the adult counterpart demonstrated significance across all models. In conclusion, the pooled estimates of the homozygote and recessive models suggested that the rs763780 polymorphism is associated with ITP risk, but this finding requires further validation through large-scale studies.
BACKGROUND:Interleukin-33 (IL-33) and soluble ST2 (sST2) are critical regulators of tissue-derived inflammation, and their dysregulation is usually implicated in various inflammatory disorders. Despite this, how these circulating proteins behave over time in healthy individuals remains poorly defined. Therefore, defining reference concentrations in healthy cohorts is important for interpreting disease-associated changes attributed to these proteins. METHODS:A healthy Finnish cohort (N = 124), consisting of children (7-10y, n = 36), adolescents (11-15y, n = 37), young adults (20-34y, n = 25), and older adults (60-70y, n = 23), received a Tdap3-IPV (aP) booster at day 0. Serum IL-33 and sST2 were measured at baseline (before vaccination) and at days 28 and 365 post-vaccination. For the same time points, serum antibodies specific to aP booster were measured. Baseline serum concentrations of IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-17A and IL-17F were evaluated as predictors of sST2 dynamics. RESULTS:IL-33 was undetectable at a population level (10-30% detectability). In contrast, sST2 was consistently detectable across all time points (median baseline 18.49 ng/mL) but exhibited a significant longitudinal decline over one year (p < 0.001). This longitudinal decline varied by age: older adults showed lower baseline sST2 and minimal change over time, whereas younger age groups showed a more pronounced decline. No associations were observed between IL-33 or sST2 and vaccine responses or baseline cytokines. CONCLUSION:Serum IL-33 was mostly undetectable in healthy individuals. Although serum sST2 concentrations declined over time, these changes were independent of vaccine-induced antibody responses. These results provide reference serum concentrations for the two important proteins.
Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy in which inflammatory signaling plays a pivotal role in disease pathogenesis. The dysregulation of the cytokine network leads to an increased abundance of pro-inflammatory mediators, such as IL-1β, TNF-α and IL-6, relative to anti-inflammatory cytokines like TGF-β and CXCL12. This disbalance in cytokine levels is closely associated with tumor development and fosters a pro-tumorigenic microenvironment by facilitating leukemic cell proliferation, reducing survival rates, and promoting drug resistance. In addition, inflammatory cytokines have been shown to preferentially support hematopoietic stem and progenitor cell populations harboring mutations associated with clonal hematopoiesis. This review summarizes the current knowledge on inflammatory cytokines and signaling pathways in AML, focusing on: (i) their mechanisms of action and implications for immune tolerance and clonal hematopoiesis and (ii) the emerging therapeutic strategies targeting these pathways to improve clinical outcomes for patients with AML.
Musculoskeletal disorders (MSDs) are a leading cause of chronic pain and disability worldwide, yet available pharmacological treatments remain largely ineffective or palliative. Increasing evidence indicates that chronic inflammation in MSDs reflects not only excessive pro-inflammatory signaling but also impaired endogenous anti-inflammatory and pro-resolving mechanisms. In this context, cytokines IL-34 through IL-41 have recently emerged as important regulators of immune activation, tissue remodeling, and tissue regeneration. This review provides a mechanistically informed analysis of the roles of IL-34-IL-41 in the pathogenesis of major MSDs, including inflammatory arthritis, osteoarthritis, osteoporosis, intervertebral disc degeneration, and sarcopenia. A functional dichotomy within this cytokine spectrum is highlighted: IL-34, IL-36, IL-39, and IL-40 act as pro-inflammatory or inflammation-amplifying mediators that promote macrophage activation, osteoclastogenesis, and autoimmune responses, whereas IL-35, IL-37, IL-38, and IL-41 exert anti-inflammatory and pro-resolving effects by suppressing Th1/Th17-driven immunity and fostering regulatory immune phenotypes. Notably, IL-41 also integrates immune modulation with metabolic regulation and muscle repair. We discuss emerging translational strategies targeting this cytokine group and address key unresolved questions related to cytokine redundancy, disease heterogeneity, patient stratification, and safety. Collectively, the available evidence highlights the growing mechanistic and translational relevance of cytokines IL-34 through IL-41 in MSDs.
Background and objective Salivary cytokines can provide information about oral health and systemic diseases. We aimed to assess the salivary concentration of inflammatory cytokines in outpatients with Crohn's disease (CD) and whether the levels are modified by the presence of periodontal diseases. Material and methods This cross-sectional study selected 72 individuals, 35 CD patients and 37 controls. Comprehensive medical and periodontal examinations were performed. Unstimulated saliva was collected and concentrations of interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, IL-23, IL-27, interferon (IFN)-y, and tumoral necrosis factor (TNF)-α were analyzed by a bead-based multiplex assay. Results Salivary concentrations of TNF-α, IL-10 and IL-12p70 were significantly higher in CD patients compared to controls (p < 0.05). Patients taking anti-TNF agents (n = 16) and those taking conventional medication for IBD (n = 14) had significantly higher levels of IL-12p70 and IL-23 than patients taking no medications (p < 0.05). Linear regression analysis showed that CD was positively associated with the salivary concentrations of TNF-α and IL-10, while the percentage of pathological periodontal pockets associated positively with IL-1β and IL-10. Conclusion CD patients showed higher salivary concentrations of TNF-α and IL-10, regardless of the periodontal condition.
A systematic review and a study level meta-analysis was conducted to assess the association between the T-786C polymorphism of the nitric oxide synthase 3 (NOS3) gene with acute coronary syndrome (ACS) or premature coronary artery disease (PCAD). Online databases of PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science were systematically searched, yielding 23 different studies (from 22 articles, involving 17,324 subjects), which were included for quantitative synthesis. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random effects, employing a Z test. Pooled results suggested a significant association between T-786C polymorphism and ACS or PCAD through dominant and allelic genetic model comparisons (OR, 1.26, 95% CI, 1.09-1.45, p = 0.001 and OR, 1.26, 95% CI, 1.11-1.43, p = 0.0002 respectively). Leave-one-out sensitivity analysis, in addition to the results for the myocardial infarction endpoint, attested to the robustness of the obtained results. Large, prospective investigations are, however, warranted to confirm the presented findings.
