Search Results (76)

Thai fermented soybeans (TFSs) contain phytochemicals with anti-diabetic benefits. In this study, an initial non-optimized TFS extract (TFSE) was prepared using a conventional triplicate 80% ethanol extraction method and evaluated for its biological activity. TFSE effectively reversed TNF-α-induced insulin resistance in 3T3-L1 adipocytes by enhancing insulin-stimulated glucose uptake, indicating anti-diabetic potential. TFSE also upregulated the phosphorylation of AKT (a key insulin signaling mediator) and the expression of adipogenic proteins (PPARγ, CEBPα) in TNF-α-exposed 3T3-L1, suggesting the mitigation of adipocyte dysfunction; however, the results did not reach statistical significance. The conventional extraction process was labor-intensive and time-consuming, and to enhance extraction efficiency and bioactivity, the process was subsequently optimized using environmentally friendly microwave-assisted extraction (MAE) in combination with the Box–Behnken design (BBD) and response surface methodology (RSM). The optimized extract (O-TFSE) was obtained over a significantly shorter extraction time and exhibited higher levels of total flavonoids and antioxidant activity in comparison to TFSE, while showing reduced levels of isoflavones (daidzein, genistein, and glycitein) in relation to TFSE. Interestingly, O-TFSE retained similar efficacy in reversing TNF-α-induced insulin resistance and demonstrated significantly stronger α-glucosidase and α-amylase inhibitory activities, indicating its enhanced potential for diabetes management. These results support the use of MAE as an efficient method for extracting functional compounds from TFS for functional foods targeting insulin resistance and type 2 diabetes mellitus. Full article

Background: Inflammatory bowel disease (IBD) is defined as recurrent inflammatory bowel disorders, the most common of which are Crohn’s disease (CD) and ulcerative colitis (UC). Tumor necrosis factor inhibitors (anti-TNFs), primarily adalimumab (ADA), infliximab (IFX), ustekinumab (UST), and vedolizumab (VLZ), are used to treat moderate-to-severe cases of IBD in patients who either do not tolerate or fail to respond to conventional therapies. However, about one-third of patients are primary non-responders to these treatments, and an additional 30% lose response over time. Several studies have investigated the role of genetic variability in explaining these differences in treatment response among patients. The aim of this study was to design an array of 60 single-nucleotide variants (SNVs) to validate the biomarkers described in the literature in a population of more than 400 IBD patients treated with biological drugs. Method: The primary focus of this study was the most recent reviews published in PubMed, with all relevant SNVs selected for the array design. Subsequently, studies presenting original data on the association between variants and the response to biological treatment were identified. Results: A total of 55.9% of SNVs have been studied in CD, 18.6% have been in UC, and 25.4% have been studied in both pathologies. A total of 44.1% of SNVs have been observed to influence the response to IFX, 16.9% influence the response to ADA, and 37.3% influence the response to both IFX and ADA; however, only one study (1.7%) reported an influence on the response to UST and none reported an influence on the response to VLZ. Conclusions: An array comprising 38 genes and 59 SNVs has been designed to be used to validate biomarkers associated with responses to biologic drug treatments in IBD. Full article

Natural compounds remain a valuable source of anticancer agents due to their structural diversity and multi-targeted mechanisms of action. Roburic acid (RA), a tetracyclic triterpenoid, has been identified as a substance capable of inhibiting key NF-κB and MAPK signaling pathways through direct interaction with TNF-α, as well as preventing the production of inflammatory mediators and cancer progression. In this study, we evaluated the biological activity of RA against a panel of human cancer cell lines—DLD-1, HT-29, and HCT-116 (colorectal), PC-3 (prostate), and BxPC-3 (pancreatic)—as well as two non-malignant lines: WI-38 (fibroblasts) and CCD-841 CoN (colon epithelium). RA exhibited a concentration-dependent inhibitory effect on cancer cell metabolic activity, with colorectal cancer cells showing relatively higher sensitivity, particularly at shorter incubation times. To distinguish between cytotoxic and cytostatic effects, we performed trypan blue exclusion combined with a cell density assessment, clonogenic assay, and BrdU incorporation assay. The results from these complementary assays confirmed that RA acts primarily through an antiproliferative mechanism rather than by inducing cytotoxicity. In addition, NF-κB reporter assays demonstrated that RA attenuates TNF-α-induced transcriptional activation at higher concentrations, supporting its proposed anti-inflammatory properties and potential to modulate pro-tumorigenic signaling. Finally, our in silico studies predicted that RA may interact with proteins such as CAII, CES1, EGFR, and PLA2G2A, implicating it in the modulation of pathways related to proliferation and cell survival. Collectively, these findings suggest that RA may serve as a promising scaffold for the development of future anticancer agents, particularly in the context of colorectal cancer. Full article

Background and Objectives: Psoriasis is a chronic immune-mediated inflammatory disease requiring reliable diagnostic and monitoring tools. Salivary interleukins have emerged as promising non-invasive biomarkers, reflecting systemic inflammation and offering practical advantages such as ease of collection and improved patient compliance. Materials and Methods: This review synthesizes the current evidence on key salivary cytokines—IL-1β, IL-6, TNF-α, and IL-17—in relation to psoriasis pathogenesis, diagnosis, and treatment monitoring. It also compares saliva to blood-based diagnostics, emphasizing benefits like cost-effectiveness and suitability for repeated sampling. Methodological challenges, including heterogeneity in collection protocols and limited longitudinal data, are critically examined. Results: Advances in biologic therapies have deepened the understanding of psoriasis immunopathogenesis, highlighting interleukins as central biomarkers. Recent findings identify IL-37 and IL-38 as novel regulatory cytokines with anti-inflammatory roles. While elevated serum TNF-α levels in psoriatic patients are well documented, some inconsistencies persist. Notably, saliva has proven to be a viable alternative diagnostic fluid, supporting large-scale screening and routine clinical monitoring. Conclusions: Salivary interleukins—particularly IL-1β, IL-6, TNF-α, and IL-17—represent valuable, non-invasive biomarkers for early detection, disease severity assessment, and therapeutic response monitoring in psoriasis. Standardizing saliva-based methods and conducting large-scale studies are essential next steps to support their integration into personalized clinical practice. Full article

Background: Interstitial lung disease (ILD) is a prominent complication in the course of rheumatoid arthritis (RA), with a prevalence ranging from 5% to 60% and several phenotypes. The existing knowledge on the impact of different pharmacological interventions in individuals with rheumatoid arthritis-related interstitial lung disease (RA-ILD) is inconclusive, and this variable response to treatment highlights the need for a personalized approach to the management of RA-associated ILD. Therefore, we aimed to evaluate the therapeutic effect and safety of different pharmacological agents, including conventional synthetic DMARDs (Cs DMARDs), biologic DMARDs (bDMARDs), targeted synthetic DMARDs (Ts DMARDs), and antifibrotic agents, in patients with RA-ILD. Method: This systematic review and meta-analysis searched for available randomized controlled trials (RCTs) and prospective cohort studies. A search was performed in the PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Eligible studies comprised those involving hospitalized patients diagnosed with RA-ILD, regardless of concomitant medications, who were of adult age (≥18 years); the studies measured the effect of pharmacological interventions, including methotrexate, leflunomide, tumor necrosis factor inhibitors (anti-TNF), abatacept, rituximab, JAK inhibitors, and antifibrotic agents, compared to placebo or other therapies for RA. Results: Out of 446 studies from 2002 to 2024, only 16 were included in this systematic review, including 14 prospective cohort studies and 2 placebo-controlled studies. Unfortunately, no RCTs were found that address our research question. The most relevant studies (n = 4) were performed in different countries (mainly Spain and the UK), with sample sizes varying from 23 to 381 patients (total: 2199 patients). The current study reveals that non-anti-TNF biologics were associated with a decreased risk of radiologic progression, while advanced therapies improved disease-related outcomes in patients requiring oxygen therapy. Methotrexate and other DMARDs were found to have inconsistent effects on ILD progression and mortality. Conclusions: Our review supports the integration of personalized medicine into the management of RA-ILD. By considering patient-specific factors and therapeutic responses, clinicians can better tailor interventions. We confirmed the high methodological quality of the trials, yielding solid evidence for the clinical management of RA-ILD. This review adds to the existing literature by identifying nintedanib as a potential disease-modifying therapy with the potential to slow the progression of lung disease. Full article

Astaxanthin (ASX) is a xanthophyll carotenoid mainly derived from marine microalgae such as Haematococcus pluvialis and Chlorella zofingiensis, as well as the yeast Phaffia rhodozyma. Its chemical nature structure, rich in conjugated double bonds, carbonyl, and hydroxyl groups, confers potent antioxidant and anti-inflammatory properties. ASX modulates oxidative stress via the PI3K/Akt-Nrf2 pathway and suppresses NF-κB-mediated inflammatory responses, reducing cytokine levels such as TNF-α, IL-6, and iNOS. ASX exerts dual apoptotic effects, cytoprotective in non-transformed cells and pro-apoptotic in cancer cells through p53 activation. Sustainable extraction techniques, especially supercritical CO₂, have improved its industrial applicability. Recent findings highlight ASX’s role in stem cell biology, enhancing proliferation, supporting lineage-specific differentiation, and protecting against oxidative and inflammatory damage, which is a crucial issue for regenerative medicine applications. These multifaceted molecular effects support ASX’s therapeutic potential in chronic diseases, including diabetes, cardiovascular pathologies, and cancer. This review outlines ASX’s natural sources, extraction methods, and biological mechanisms, emphasizing its application in oxidative stress- and inflammation-related conditions. Full article

Cyanobacterial extracts offer significant potential for the development of new natural antioxidants and biologically active compounds with applications in various industries. Data on the genus Tolypothrix are limited; therefore, the aim of the present study was to investigate the anticancer, antioxidant and anti-inflammatory activity of extracts prepared from strains of this genus. Cytotoxicity and anticancer activity were evaluated by in vitro tests with four cell lines using the MTT assay. The assessment of antioxidant activity was performed by the DPPH and ABTS methods in combination with the calculation of the total phenolic content. Anti-inflammatory activity was investigated using the LPS-stimulated macrophage model (RAW264.7) and subsequent measurement of the levels of secreted cytokines IL-6 and TNF-α. The lipid content and fatty acid composition of the non-polar extracts were determined by gas chromatography (GC). To elucidate the mechanism of cytotoxicity/anticancer action of the non-polar extracts, the effects of stearidonic acid, which was detected in four of the studied cyanobacterial strains, were additionally tested on the same cell lines. A molecular docking analysis was performed simulating the interaction between stearidonic acid and its target molecules and receptors (ALOX5, COX-2, NF-kB and PPAR-γ). In all cancer cell lines (but not in the normal one), dose-dependent cytotoxic effects were observed after exposure to different concentrations of non-polar Tolypothrix extracts. The most pronounced inhibitory effect was observed on the HT-29 cell line, with an IC₅₀ value of 106.27 µg/mL. A dose-dependent antioxidant effect was established for all tested extracts, measured by both DPPH and ABTS methods. All non-polar extracts reduced the production of pro-inflammatory cytokines IL-6 and TNF-α in LPS-stimulated macrophages RAW264.7, and the effects were dose-dependent. Analysis of the fatty acid composition revealed 26 different fatty acids. Our conclusion is that the Tolypothrix strains exhibit anticancer, antioxidant, and anti-inflammatory activity and could be a promising source for the production of natural products. Full article

Introduction: The introduction of biologic therapies and small molecule drugs has revolutionized the management of inflammatory bowel disease (IBD), providing targeted control of inflammation. However, concerns remain regarding their long-term safety profiles, particularly in relation to cancer risk. Chronic inflammation and immunosuppressive therapies contribute to malignancy risk, including skin cancers, such as melanoma and non-melanoma skin cancer (NMSC). This review examines the evidence on skin cancer risks associated with these therapies, focusing on specific drug classes and their mechanisms. Results: Tumor necrosis factor (TNF) inhibitors have shown conflicting evidence regarding melanoma risk, with some studies reporting a modest increase and others finding no significant association. Anti-integrin agents, such as vedolizumab, and interleukin (IL)-12/23 inhibitors, including ustekinumab, have demonstrated favorable safety profiles with minimal skin cancer risks. Selective IL-23 inhibitors and sphingosine-1-phosphate (S1P) receptor modulators have limited long-term data, but early findings indicate a low incidence of skin malignancies. Janus kinase (JAK) inhibitors do not show an increased risk of skin cancers in IBD. Conclusions: Current evidence suggests that skin cancer risk in IBD patients treated with biologics and small molecule drugs varies by drug class. TNF inhibitors and JAK inhibitors are associated with higher risks, while other therapies show lower malignancy risks. Regular skin cancer screening and protective measures remain critical, particularly for patients with additional risk factors. Further long-term studies are essential to refine safety profiles and inform clinical practice in this evolving therapeutic landscape. Full article

Introduction: Inflammatory bowel diseases (IBDs) require immunosuppressive drugs like biologics. All IBD patients, including those on biological therapy, should be vaccinated against COVID-19, according to the ECCO recommendations. IBD patients on anti-TNF treatment exhibited lower COVID-19 vaccine responses; however, SARS-CoV-2 variant neutralizing antibody titers have been seldom studied. Methods: IBD patients and healthcare professionals (control group) were tested for COVID-19 vaccine immunogenicity by neutralizing antibody titers against Wild-Type SARS-CoV-2 and its variants. IBD patients were assigned to no treatment/mesalamine, anti-TNF biologic therapy, or non-anti-TNF biologic therapy. The study was performed in a tertiary hospital in Palermo, Sicily, from May to July 2021. Results: In total, 107 IBD patients and 41 healthcare workers were enrolled. A total of 46 patients received mesalamine or no medication, 28 received anti-TNF biologics, and 33 received non-anti-TNF biologics. No significant differences were found in age, gender, or timing of blood sampling post vaccination. Omicron neutralizing activity was markedly reduced in all groups (p < 0.001). The group of patients on anti-TNF biologics showed lower neutralizing antibody titers against Alpha, Delta, and Gamma strains than every other group analyzed. Conclusions: IBD patients on anti-TNF drugs have a reduced serological response to the SARS-CoV-2 vaccine, with the Omicron variant not being neutralized. This highlights the necessity for tailored vaccine strategies for these patients. Full article

Background/Objectives: Therapeutic management of inflammatory bowel diseases (IBD) is rapidly evolving in the era of novel biological therapies. However, real-world data relating to the usage trends and treatment persistence remain inconsistent. This study aimed to investigate trends in biological use, dose intensification, and treatment persistence in IBD patients, who received treatment in a large tertiary center in Greece. Methods: Patients with IBD who underwent at least one biological treatment between 2018 and 2022 were included in this retrospective study. Data on patients’ demographics, type of disease, use of biologicals, dose intensification, and treatment persistence were analyzed for time trends. Results: Data from 409 patients with IBD (mean age 39 (range 17–87), female 51%, 56.9% CD, mean duration of disease: 9.3 years) were included in the study. The number of patients on biologics was raised from 133 in 2018 to 368 in 2022 (a 28.1% yearly increase), while the percentage of patients who were treated with anti-TNF biosimilars increased to >60% of the total anti-TNF population in 2022. We observed a gradual increase in non-anti-TNF therapies in bio-naïve patients, in particular vedolizumab (46% of all biologicals in UC; 16% in CD) and ustekinumab (16.3% of all biologicals in UC, 31% in CD). The 3-year persistence rate of IFX was 64% in CD and 56% in UC, whereas it was 61% for ADA in CD. Dose intensification of anti-TNF was efficient in >50% of CD patients and >30% of UC patients; however, the majority of patients who required dose escalation within the first year eventually became unresponsive. The 3-year persistence of vedolizumab as a first-line treatment was 82% for CD and 69% for UC, respectively. The 3-year persistence of ustekinumab as first-line treatment for CD was 65%. No significant differences regarding the efficacy of anti-TNF, ustekinumab, or vedolizumab were detected when they were used as first-line treatments for Crohn’s disease; similarly, no significant differences were detected between infliximab and vedolizumab as first-line treatments for UC. Conclusions: There was a gradual increase in the use of biologicals, including biosimilars, between the years 2018–2022, reflecting adherence to current guidance with adoption of an early escalation strategy. Newer, post-anti-TNF biologics such as vedolizumab and ustekinumab have been rapidly incorporated into therapeutic approaches for both CD and UC. Full article

Background/Objectives: Radon is a significant carcinogen, particularly as a leading cause of lung cancer among non-smokers. While its carcinogenic effects are well documented, the relationship between radon exposure and inflammatory reactions remains underexplored. This systematic review investigates inflammatory biomarkers in individuals exposed to chronic radon exposure and conducts a meta-analysis on serum C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) levels. Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar using the keywords “radon” AND “inflammation biomarkers” following established guidelines. Studies reporting inflammatory biomarker levels in biological fluids of human participants exposed to residential or occupational radon were included. Statistical analyses, including pooled mean estimates, influence analysis, publication bias, and meta-regression, were performed in RStudio. Results: Ten studies involving 33,099 individuals met the inclusion criteria. Eight studies focused on residential radon exposure, and two examined occupational exposure among uranium miners. Inflammatory biomarkers were analyzed in serum, bronchoalveolar lavage fluid, and saliva. Among individuals exposed to high residential radon levels, serum CRP and TNF-α were the most frequently assessed biomarkers, with pooled mean levels of 2.11 mg/L (95% CI, 1.32–2.89) and 2.20 pg/mL (95% CI, 0.25–4.64), respectively. Conclusions: Serum CRP and TNF-α levels appear lower in adults with chronic radon exposure, suggesting potential anti-inflammatory effects despite radon’s established carcinogenicity. Future longitudinal studies using standardized methods are crucial to elucidate the long-term health impacts of radon exposure. Full article

Background/Objectives: Inflammatory bowel diseases (IBDs) are chronic intestinal disorders with an unpredictable course. In parallel with the advent of new biologic therapies targeting specific interleukin pathways, end-point targets have become more stringent, aiming for mucosal and even histologic healing. Methods: We conducted a prospective study assessing immunohistochemical (IHC) parameters in 46 IBD patients treated with biologic therapy. A similar IHC analysis was performed for comparison with a cohort of 10 “non-IBD” patients. Results: The highest integrated optical density (IOD) of TNF-α was observed in patients with dysplasia, abscesses, mucin depletion and basal plasmacytosis. Non-responders had higher pre- and post-treatment TNF-α expression in both UC and CD compared to responders. On the contrary, the same analysis conducted in the subpopulation treated with anti-TNF-α therapy (Infliximab and Adalimumab) did not reveal a substantial difference in TNF-α expression between responders and non-responders. High pre-treatment interleukin-10 expression was associated with biologic therapy failure, histological inflammatory activity and longer disease duration. Conclusions: Pre-treatment assessment of IL-10 might be a useful tool for identifying a high-risk subset of IBD patients and determining a more aggressive therapy and intensive monitoring strategy. Full article

Background: Inflammatory bowel diseases (IBDs) have been associated with a higher risk of colorectal cancer (CRC) development and chronic colonic inflammation seems to have a critical role in the pathogenesis of CRC in patients suffering from IBD. In respect to that, surveillance colonoscopy at regular intervals is recommended in patients with colitis. Objective: This review aims to explore the chemopreventive potential of a range of agents, including mesalazine, thiopurines, anti-TNF agents, statins, ursodeoxycholic acid, aspirin, folic acid, and nutraceuticals. Results: These agents target inflammation, oxidative stress, and oncogenic pathways, thereby offering the potential to reduce the risk of CRC in patients with IBD. Anti-TNF agents, such as infliximab and adalimumab, not only reduce colonic inflammation, but also play a protective role against CRC by lessening the carcinogenic effects associated with prolonged inflammatory processes. Furthermore, mesalazine and thiopurines have demonstrated established efficacy, while newer biologics, including interleukin inhibitors, show promising advancements. Although nutraceuticals and dietary interventions require further clinical validation, they offer additional possibilities for non-pharmacological prevention. Conclusion: Despite progress, knowledge gaps persist regarding the long-term safety, optimal dosing, and combined use of these agents. A significant reduction in the incidence of CRC in patients with IBD could be achieved by advancing chemoprevention and personalizing strategies. Full article

Background/Objectives: The introduction of anti-tumor necrosis factor-α (anti-TNF-α) agents, particularly infliximab (IFX) and adalimumab (ADA), has significantly expanded the therapeutic arsenal for inflammatory bowel disease (IBD). While these biologics have demonstrated substantial efficacy, they are associated with a spectrum of potential adverse events (AEs). This study aims to evaluate and document these AEs to facilitate optimal patient selection and monitoring strategies of patients undergoing these therapies. Methods: This retrospective, single-center study examined pediatric IBD patients receiving anti-TNF-α therapy at the “Grigore Alexandrescu” Emergency Hospital for Children in Bucharest, Romania, from January 2015 to October 2024. AEs were categorized into non-infectious complications (acute infusion reactions, anti-drug antibody formation), dermatological effects (erythema nodosum, vasculitis), neurological effects (Guillain–Barré syndrome), and infections. AEs were analyzed in relation to the specific anti-TNF-α agent administered and comprehensively characterized. Results: Of 40 patients enrolled, 22 (55%) had Crohn’s disease (CD). The median (IQR) age at diagnosis was 14.8 years [10.8–15.9]. IFX was used in 34 (85%) patients while 6 (15%) patients received either ADA or IFX/ADA sequential therapy. Twenty-seven AEs were documented in 19 (47.5%) patients, the most prevalent being antidrug antibody formation (44.4%), infections (22.2%), and acute infusion reactions (22.2%). All ADA-exposed patients experienced at least one AE, compared to 41.2% (n = 14) patients treated with IFX, p = 0.01. Conclusions: AEs were observed in approximately half of the study cohort, with anti-drug antibody formation emerging as the most frequent complication. ADA therapy was associated with a significantly higher rate of AEs compared to IFX. These findings underscore the critical importance of vigilant monitoring for patients undergoing anti-TNF-α therapy in pediatric IBD management. Full article

Polydeoxyribonucleotide (PDRN) has emerged as a potent bioactive compound with proven efficacy in wound healing, tissue regeneration, and anti-inflammatory applications and is predominantly derived from salmonid gonads. However, this study presents a groundbreaking advancement by successfully extracting and characterizing PDRN from microbial sources, specifically Lactobacillus rhamnosus, marking the first report to utilize microbial-, biome-, or Lactobacillus-derived PDRN (L-PDRN). The findings demonstrate the enhanced biological properties of L-PDRN over traditional salmon-derived PDRN across several assays. L-PDRN exhibited superior antioxidant activity, with significantly higher SOD-like and DPPH radical scavenging activities compared to PDRN, particularly at higher concentrations. In wound-healing assays, L-PDRN demonstrated superior efficacy in promoting cell migration and wound closure, even under inflammatory conditions induced by tumor necrosis factor (TNF-α). Additionally, L-PDRN demonstrated the potential for enhanced immunostimulatory effects under non-inflammatory conditions while maintaining anti-inflammatory properties under lipopolysaccharide (LPS) stimulation. Electrophoretic analysis revealed that L-PDRN consists of smaller DNA fragments (under 100 bp) compared to salmon-derived PDRN (200–800 bp), suggesting greater bioavailability and skin absorption. Mechanistic studies confirmed that L-PDRN activates the focal adhesion kinase (FAK) and protein kinase B (AKT) signaling pathway through the A2A receptor, similar to PDRN, while also engaging alternative pathways for p38 and ERK phosphorylation, highlighting its signaling versatility. This study underscores the potential of L-PDRN as a multifunctional and sustainable alternative to salmon-derived PDRN, offering enhanced bioactivity, scalability, and environmental benefits. The novel approach of utilizing microbial-derived PDRN opens new avenues for therapeutic applications in oxidative stress management, tissue regeneration, and immune modulation, paving the way for a paradigm shift in PDRN sourcing and functionality. Full article