Search Results (728)

Background: Interleukin-6 (IL-6) is a multifunctional cytokine implicated in various inflammatory and immune-mediated processes. Its involvement in systemic lupus erythematosus (SLE) has been increasingly investigated, particularly related to disease activity and tissue damage. This study aimed to quantify serum IL-6 levels in patients with SLE and assess their associations with clinical manifestations and laboratory parameters. Methods: A total of 88 patients diagnosed with SLE and 87 matched healthy controls were included. Serum IL-6 concentrations were measured by ELISA. Clinical data, SLEDAI scores, organ involvement, inflammatory markers, and autoantibody profiles were recorded. The statistical analysis involved non-parametric testing, correlation analysis, and linear regression. Results: IL-6 concentrations were higher in SLE patients than in controls (7.46 ± 6.73 vs. 5.30 ± 10.89 pg/mL). Significantly increased IL-6 levels were observed in patients with active disease (SLEDAI ≥ 6; p = 0.025) and renal (p = 0.001) involvement. Positive correlations were identified between IL-6 and ESR, creatinine, ANA, and specific autoantibodies (anti-dsDNA, SSA, and SSB). IL-6 also correlated with IL-10 (p = 0.010) but showed no significant association with IL-17A, TNF-α, CRP, or complement levels. Conclusions: Elevated IL-6 levels are associated with greater disease activity and specific organ involvement in SLE. These findings highlight IL-6 as a measurable indicator of immunological and clinical disease expression, supporting its relevance in disease monitoring. Full article

Background: The miniaturization of ureterorenoscopes increasingly enables atraumatic primary ureteroscopy, without ureteral dilation or presenting. This study aims to evaluate the feasibility and safety of primary ureteroscopy using the HU30M (6.3 Fr, HugeMed, Shenzhen HugeMed Medical Technical Development Co., Ltd., Shenzhen, China), the smallest currently available ureteroscope. Methods: We analyzed consecutive patients in whom primary ureteroscopy using the HU30M was performed or attempted, using prospectively collected in-hospital and 30-day follow-up data for retrospective evaluation. The primary outcome was the success rate of primary ostial intubation. Secondary outcomes included the stone-free rate (SFR) in patients with urolithiasis, incidence of in-hospital complications (Clavien–Dindo classification) and 30-day emergency readmission. Additionally, we conducted a propensity score-matched comparative analysis of the HU30M versus a contemporary 7.5 Fr digital single-use ureteroscope (PUSEN PU3033AH, Zhuhai Pusen Medical Technology Co., Ltd., Jinhua, China). Results: Between January and April 2025, primary ureteroscopy using the HU30M was performed or attempted in 34 patients, including four bilateral procedures. Primary ureteroscopy was defined as ureteroscopic access without prior stenting or dilation. Indications were diagnostic evaluation in 15 patients (44%), uretreroscopic stone treatment in 10 patients (29%) and endoscopic combined intrarenal surgery (ECIRS) in 9 patients (27%). Successful primary ostial intubation was achieved in 36 of 38 renal units (95%). Among urolithiasis cases, SFR was 17/19 (90%) in-hospital complications were limited to postoperative fever in two patients (6%) and no procedure-related 30-day emergency readmission occurred. In matched analyses, HU30M demonstrated significantly shorter operative times compared with the 7.5 Fr ureteroscope, while postoperative hemoglobin drop, inflammatory parameters and renal function were comparable. Conclusions: Primary ureteroscopy with HU30M is feasible and safe across diverse indications, achieving high success of atraumatic ostial access. Comparative analyses suggest procedural efficiency advantages and overall safety comparable to the current digital single-use ureteroscope standard. Full article

Pain remains one of the most burdensome symptoms in rheumatoid arthritis (RA), often persisting despite inflammatory remission and profoundly impairing quality of life. This review aimed to evaluate the clinical efficacy and mechanistic pathways by which Janus kinase (JAK) inhibitors alleviate RA-related pain. Evidence from randomized clinical trials demonstrates that JAK inhibitors have demonstrated rapid and significant pain relief, often exceeding that of methotrexate or biologic DMARDs. Improvements in patient-reported pain scores seem to typically emerge within 1–2 weeks and are sustained over time. Beyond anti-inflammatory effects, JAK inhibitors modulate central sensitization and nociceptive signaling by attenuating IL-6 and GM-CSF activity, reducing astrocyte and microglial activation, and downregulating nociceptor excitability in dorsal root ganglia and spinal pathways. Preclinical models further suggest that JAK inhibition interrupts neuroimmune feedback loops critical to chronic pain maintenance. Comparative and network meta-analyses consistently position JAK inhibitors among the most effective agents for pain control in RA. However, individual variability in response, partly due to differential JAK-STAT activation and cytokine receptor uncoupling, underscores the need for biomarker-guided treatment approaches. JAK inhibitors represent a mechanistically distinct and clinically impactful class of therapies that target both inflammatory and non-inflammatory pain in RA. Their integration into personalized pain management strategies offers a promising path to address one of RA’s most persistent unmet needs. Full article

Background and objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects not only physical health but also psychological well-being. While the emotional and social burden of AD is well documented, there is still limited research on how AD affects sexual health. The study aimed to evaluate quality of life (QoL), mental health, and risk factors for impaired sexual life, as well as their relationships. Materials and Methods: A total of 201 participants (96 patients with AD and 105 healthy controls) were enrolled in the study. Socio-demographic and clinical data were obtained using a specifically developed questionnaire. In addition, participants completed validated scales, including the DLQI, HADS, FSFI, IIEF-5, and SRSLQ. AD severity was assessed using the SCORAD questionnaire. Results: Our study found that patients with AD had statistically significantly higher mean anxiety (6.8 ± 3.6 vs. 5.0 ± 3.2; p < 0.001), depression (5.2 ± 3.4 vs. 3.9 ± 2.9, p < 0.01), and skin-related sexual dysfunction scores (15.0 ± 4.5 vs. 4.4 ± 4.7, p < 0.001), as well as QoL scores (12.3 ± 6.1 vs. 1.8 ± 3.1, p < 0.001), than healthy controls. Female AD patients reported higher values of depression and anxiety compared to male patients (5.9 ± 3.1 vs. 4.4 ± 3.5, p = 0.03, 7.6 ± 2.9 vs. 6.0 ± 4.1, p = 0.03, respectively) and lower FSFI scores compared to healthy women (24.8 ± 8.0 vs. 31.3 ± 3.0, p < 0.001). Deterioration in sexual health, assessed by the SRSLQ score, was strongly correlated with QoL impairment (R = 0.5, p < 0.001), anxiety (R = 0.51, p < 0.001), and depression (R = 0.5, p < 0.001). Finally, we found that sex life negatively correlates with AD severity (p=0.001), involvement of a genital area (p = 0.005), intensity of pruritus (r = 0.284, p = 0.005), and insomnia (r = 0.366, p < 0.001). Conclusions: AD significantly affects patients’ quality of life, including their sex life. Many factors associated with the disease also contribute to the deterioration of patients’ sexual health. Routine assessment of sexual life in dermatological practice, using validated tools, could facilitate early identification and support for affected patients. Significance: This study highlights the often-overlooked impact of atopic dermatitis on patients’ sexual health. Our findings demonstrate that sexual function is significantly impaired in individuals with atopic dermatitis—particularly among women—and that such dysfunction is closely associated with disease-related symptoms. These results have important implications for improving the quality of care provided to individuals affected by the condition. Full article

Background: Perianal Crohn’s disease (pCD) is one of the most disabling complications of inflammatory bowel disease, characterized by fistulas and abscesses that demand precise imaging for diagnosis, treatment planning, and follow-up. Magnetic resonance imaging (MRI) is considered the reference standard, but endoanal ultrasound (EAUS) with high-frequency 360° probes provide a readily available, cost-effective, and repeatable alternative. Methods: We performed a narrative review of the literature, evaluating studies on the EAUS technique, diagnostic applications, distinguishing features of Crohn’s-related fistulas, and comparative analyses with MRI. Consensus documents and structured reporting initiatives were also included. Results: EAUS provides high-resolution visualization of the anal sphincter complex and intersphincteric space, enabling the reliable detection of fistulas and abscesses. Characteristic features such as tract width > 4 mm, bifurcation, hyperechoic debris, the Crohn’s Ultrasound Fistula Sign (CUFS), and the rosary sign assist in differentiating Crohn’s from cryptoglandular fistulas. EAUS is well-suited for serial monitoring, perioperative seton guidance, and therapeutic decision-making. Emerging tools such as Doppler and shear wave elastography provide additional information on activity and fibrosis. MRI remains indispensable for supralevator disease, deep pelvic sepsis, and standardized activity indices. Comparative studies indicate similar sensitivity for simple fistulas, with MRI superior in complex cases; combining both modalities maximizes accuracy. Conclusions: EAUS is a practical and repeatable imaging tool that complements MRI in the multidisciplinary management of perianal Crohn’s disease. Advances such as 3D imaging, contrast enhancement, and elastography may enable validated activity scoring—for example, a future PEACE (Perianal Endosonographic Activity in Chron’s Evaluation) Index—further strengthening its role in longitudinal care. Full article

Acute kidney injury (AKI) is a frequent and severe complication in trauma patients, affecting up to 28% of intensive care unit (ICU) admissions and contributing significantly to morbidity, mortality, and long-term renal impairment. Trauma-related AKI (TRAKI) arises from diverse mechanisms, including hemorrhagic shock, ischemia–reperfusion injury, systemic inflammation, rhabdomyolysis, nephrotoxicity, and complex organ crosstalk involving the brain, lungs, and abdomen. Pathophysiologically, TRAKI involves early disruption of the glomerular filtration barrier, tubular epithelial injury, and renal microvascular dysfunction. Inflammatory cascades, oxidative stress, immune thrombosis, and maladaptive repair mechanisms mediate these injuries. Trauma-related rhabdomyolysis and exposure to contrast agents or nephrotoxic drugs further exacerbate renal stress, particularly in patients with pre-existing comorbidities. Traditional markers such as serum creatinine (sCr) are late indicators of kidney damage and lack specificity. Emerging structural and stress response biomarkers—such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), C-C motif chemokine ligand 14 (CCL14), Dickkopf-3 (DKK3), and the U.S. Food and Drug Administration (FDA)-approved tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein 7 (TIMP-2 × IGFBP-7)—allow earlier detection of subclinical AKI and better predict progression and the need for renal replacement therapy. Together, functional indices like urinary sodium and fractional potassium excretion reflect early microcirculatory stress and add clinical value. In parallel, risk stratification tools, including the Renal Angina Index (RAI), the McMahon score, and the Haines model, enable the early identification of high-risk patients and help tailor nephroprotective strategies. Together, these biomarkers and risk models shift from passive AKI recognition to proactive, personalized management. A new paradigm that integrates biomarker-guided diagnostics and dynamic clinical scoring into trauma care promises to reduce AKI burden and improve renal outcomes in this critically ill population. Full article

Background/Objectives: As the global population ages, cardiovascular disease (CVD) emerges as a critical challenge for public health, with chronic inflammation identified as a key contributing risk factor. As a modifiable lifestyle factor, diet plays a critical role in the prevention of CVD. Given the established link between diet and inflammation, clarifying the relationship between dietary inflammatory potential and cardiovascular health (CVH) is of significant public health importance. This study aimed to evaluate the association between dietary inflammatory potential and CVH in an elderly population, and to explore the related role of the gut microbiota. Methods: Dietary inflammatory potential was quantified using the Dietary Inflammatory Index (DII), CVH was assessed by the American Heart Association’s Life’s Essential 8 (LE8) score, and gut microbiome analysis was profiled by 16S rRNA gene sequencing. Results: Results showed that higher DII scores, indicative of a pro-inflammatory dietary pattern, were significantly linked to reduced LE8 scores, suggesting an inverse association between dietary inflammatory potential and CVH. Based on the gut microbiome, participants with high CVH exhibited greater α diversity compared with those with low CVH, while both α and β diversity were higher in the anti-inflammatory diet group than in the pro-inflammatory diet group. These results indicate that anti-inflammatory diets may be associated with better CVH, possibly through the preservation of the ecological balance of the gut microbiota. Correlation analyses further pointed to several genera potentially associated with both dietary inflammatory potential and CVH. Functional predictions suggested that variation in dietary inflammatory potential could be linked to differences in microbial metabolic functions relevant to energy, lipid and glucose metabolism, and inflammatory processes. Conclusions: In conclusion, this study provides novel evidence linking dietary inflammatory potential, gut microbiota, and CVH in older adults, and offers preliminary insights for dietary interventions and microbiota-targeted strategies in CVD prevention. Full article

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by sustained neuroinflammation and demyelination within the central nervous system (CNS). Vesatolimod (VES), a selective Toll-like receptor 7 (TLR7) agonist, has demonstrated both antiviral and immunomodulatory properties; however, its potential therapeutic value in neuroinflammatory contexts remains poorly understood. In this study, we evaluated the efficacy of VES in the experimental autoimmune encephalomyelitis (EAE) model of MS and elucidated its mechanisms of action. EAE was induced in mice by immunization with myelin oligodendrocyte glycoprotein (MOG_35–55). The therapeutic effects of VES were assessed through clinical scoring, body weight monitoring, histopathology, flow cytometry, quantitative proteomics, and Western blot analysis. Additionally, an in vitro model of lipopolysaccharide (LPS)-induced microglial activation was employed to investigate cell-autonomous mechanisms. Results showed that VES administration significantly ameliorated disease severity, reduced weight loss, and enhanced neurological function in EAE mice. Treatment with VES inhibited the differentiation of pro-inflammatory Th1 and Th17 cells while expanding regulatory T cell (Treg) populations. It also preserved blood–brain barrier (BBB) integrity, attenuated demyelination, and modulated microglial activation phenotypes within the CNS. At the molecular level, VES activated the Nrf2/HO-1 antioxidant pathway, thereby enhancing the expression of cytoprotective proteins. Proteomic profiling further revealed the downregulation of inflammation-related proteins, specifically those associated with TNF, IL-17, and NOD-like receptor signaling pathways. Collectively, these findings demonstrate that VES alleviates neuroinflammation in EAE through multimodal mechanisms—including peripheral and central immune regulation, BBB protection, and activation of endogenous antioxidant defenses—supporting its further development as a promising therapeutic candidate for MS. Full article

Background: Fibromyalgia syndrome (FS) is one of the most common causes of chronic generalised pain and often complicates the therapeutic management of inflammatory chronic arthritis (ICA), negatively impacting both the real assessment of disease activity and the perception of response. Our study aims to evaluate in a group of patients with ICA, multi-resistant to biologic/target synthetic disease-modifying antirheumatic drugs (b/ts-DMARDs), both the impact of FS on the possibility of achieving low disease activity (LDA) or remission (REM) and the possible improvement in the severity of FS symptoms, after starting b/ts-DMARDs with different a mechanism of action (MoA). Methods: A prospective study was conducted, from January 2023 to December 2024, on patients who fulfil the classification criteria for psoriatic arthritis (PsA) or fulfil the 2010 American College of Rheumatology criteria for RA. Results: Sixty-four Caucasian patients with ICA, of which 47 with FS, were enrolled in the study. At the baseline visit, FS patients had a significantly shorter ICA disease duration, worse fibromyalgia symptom-related indices (such as Fibromyalgia Severity Scale (FSS), Widespread Pain Index (WPI), and Symptom Severity Scale (SSS)) and functional and disability scores (such as health assessment questionnaire (HAQ) and Functional Assessment of Chronic Illness Therapy (FACIT)), and a higher basal value of Disease Activity in Psoriatic Arthritis (DAPSA) score compared to patients without FS. After 6 months of starting b/ts-DMARDs, no differences in severity of arthritis clinimetric indices (disease activity score (DAS) 28 (erythrocyte sedimentation (ESR)) and DAPSA) and Visual Analogue Scale (VAS) pain were found between the patients with FS compared to those without. At the follow-up visit, 36% of the whole group of patients were in LDA (36% ICA patients with FS vs. 35% of ICA patients without FS; p = 0.080), while 17% of patients reached REM (11% ICA with FS vs. 35% ICA without FS patients; p = 0.031). The FS presence appeared to be a factor associated with failure to reach REM (OR 4.5 (95%CI: 1.1–17.8), p = 0.028), but not for achieving LDA (OR 2.7 (95%CI: 0.8–8.9), p = 0.099). The overall retention rate at 6 months was 79%; in particular, 11 patients discontinued treatment with b/ts-DMARD, 69% of whom belonged to the FS group (p = 0.489). Among the group of patients with ICA and FS, patients in LDA/REM presented an important improvement in FSS, SSS, and VAS pain, with the best percentage variation from the baseline of these indices compared to patients who did not achieve the LDA/REM. Of note, sixteen patients with FS at the baseline no longer met the diagnostic criteria for FS after 6 months of follow-up. Conclusions: The presence of FS seems to negatively impact the achievement of REM, but not LDA, in both RA and PsA patients, even in b/ts-DMARDs patients with multi-failure of at least two different MOAs. Only a cluster of patients with FS, presumably those with FS triggered and/or amplified by the chronic joint inflammatory process, appear to improve their perception of FS severity by achieving ICA LDA/REM. However, these findings require further supporting data for more accurate validation. Full article

The heparin-binding protein (HBP) is an enzymatically inactive protein of the serine protease family that plays an important role in host response to stress, especially infection and sepsis. It is produced by activated neutrophils due to a variety of stimuli and is part of the immune response that leads to macrophage, lymphocyte, and neutrophil activation and monocyte adhesion. Its most common repository is the azurophilic granules of the neutrophils. HBP has been studied as a biomarker for several infections, including central nervous system infection, respiratory tract infection, and urinary tract infection, and in several settings, including the Emergency Department and Intensive Care Unit, with promising results. As a biomarker for infection and sepsis, HBP has been compared to other commonly used biomarkers such as Neutrophil to Lymphocyte Ratio, White Blood Count, C-reactive protein, and Procalcitonin, with at least comparable performance. Its sharp increase is promising for the early detection of sepsis. The ability to differentiate inflammatory conditions from infections and bacterial from non-bacterial causes of infection has also been demonstrated. The sepsis-related organ damage, as it is represented by the Sequential Organ Failure Assessment score, can also be reflected by the proportional increase in HBP. Consequently, HBP could be a helpful and promising biomarker for sepsis and infection. Full article

Background/Objectives: Most genes involved in the pathogenesis of Metabolic Syndrome (MS) and Type 2 Diabetes Mellitus (T2DM) are regulated by peroxisome proliferator-activated receptors (PPARs), which modulate the production of pro-inflammatory cytokines, with interleukin-6 (IL-6) playing a crucial role. The associations of single-nucleotide polymorphisms (SNPs) with MS and T2DM remain uncertain across populations. Therefore, we aimed to investigate the associations of PPAR-related SNPs in IL-6, LEP, ADIPOQ, ADIPOR1, and ADIPOR2 with MS and T2DM clinical features. Methods: Polymorphism analysis of IL-6, LEP, ADIPOQ, ADIPOR1, and ADIPOR2 genes was performed on isolated DNA from individuals diagnosed with T2DM and from healthy controls using real-time polymerase chain reaction (qPCR). Results: The IL-6-174G/C polymorphism shows that the CC genotype is associated with higher MS risk, whereas the GG genotype appears protective against metabolic disturbances. When the IL6 CC genotype is combined with ADIPOR2 GA or ADIPOR2 219 A/T, hyperglycemia is 1.3 times more frequent than with other IL6/ADIPOR2 genotype combinations. Conclusions: To develop informative genetic risk scores, future studies should include additional polymorphisms in key immune–metabolic pathway genes, such as AP-1, NF-κB, and FFAs. Full article

Background: Knee osteoarthritis (OA) is a leading cause of disability, with limited therapies that modify both symptoms and structural degeneration. Autologous microfragmented adipose tissue (MFAT) has emerged as a promising regenerative option, especially in phenotypically distinct OA subgroups. This randomized controlled trial evaluated the clinical and structural efficacy of intra-articular MFAT versus hyaluronic acid (HA) in patients with early to moderate inflammatory phenotype knee OA. Methods: Fifty-three patients were randomized in a 2:1 ratio to receive either MFAT (n = 35) or HA (n = 18). Patients were followed-up for six months post-injection and evaluated using patient-reported outcome measures (KOOS, WOMAC, VAS) and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). A responder analysis defined structural response as ≥10% increase in dGEMRIC in ≥3 of 7 predefined cartilage regions. Results: Both MFAT and HA led to statistically significant improvements in clinical scores and cartilage glycosaminoglycan content. MFAT showed greater mean improvements across most clinical and dGEMRIC measures, although without reaching statistical significance, except for KOOS Symptoms (MFAT: +25.0 vs. HA: +12.7, p = 0.008). Responder-level analysis revealed that all patients who demonstrated structural response also experienced clinically meaningful pain improvement (KOOS Pain ≥ 10), while no patient showed structural benefit without parallel symptomatic relief. Conclusions: MFAT led to greater improvement in symptoms related to joint stiffness, swelling, and crepitus compared to HA, reflecting its potential benefit in targeting the inflammatory features of knee OA. Importantly, HA also led to significant clinical and structural improvements, supporting its continued role as a standard-of-care comparator in knee OA management. Furthermore, the correlation between dGEMRIC and clinical response suggests its utility as a predictive biomarker of treatment success. Full article

Inflammaging has been implicated in age-related bone loss and fragility fractures through immune-mediated effects on bone turnover. We aimed to explore the relationship between systemic inflammatory markers and bone health in older adults, focusing on the differences between patients with osteoporotic fractures and non-fractured controls. We retrospectively analyzed 40 older patients (20 with hip fractures and 20 with osteoarthritis without prior fragility fractures). We compared routine inflammatory markers, including red cell distribution width (RDW), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and the composite CRP–albumin–lymphocyte index (CALLY), between groups. Bone mineral density (BMD) at the hip, lumbar spine, and wrist, as well as the FRAX score, were assessed. Correlations between inflammatory markers, BMD, and FRAX scores were evaluated using Spearman’s coefficient. Patients with fractures exhibited significantly elevated CRP (66.2 ± 70.3 vs. 3.8 ± 4.0 mg/L, p = 0.0008) and SII (1399.7 ± 1143.4 vs. 751.4 ± 400.8, p = 0.025) compared to controls. RDW, NLR, and CALLY scores did not differ significantly between the groups. Higher CRP levels were associated with lower BMD at all sites (hip: r ≈ −0.63, p = 0.002; spine: r ≈ −0.60, p = 0.005; wrist: r ≈ −0.60, p = 0.005). No significant correlations were observed between the SII and BMD or FRAX values. Elevated systemic inflammation, particularly indicated by CRP and SII, was associated with osteoporotic fracture status and low bone density in our cohort. These findings support the concept that inflammatory pathways may contribute to osteoporosis and fracture risk and suggest that inflammatory markers could serve as adjunctive tools in fracture risk assessment. Further studies are required to clarify the causality and evaluate whether targeting chronic inflammation can improve bone health in older adults. Full article

Atopic dermatitis is a chronic inflammatory skin disorder characterized by persistent inflammation and severe pruritus. Current anti-inflammatory agents carry risks of long-term adverse effects, while antihistamines provide limited relief of pruritus. Protease-activated receptor 2 (PAR2) has emerged as a critical mediator of both inflammation and pruritus, representing a promising therapeutic target. In this study, we investigated the therapeutic potential of punicalagin (PCG), a potent PAR2 antagonist, in atopic dermatitis. PCG fully and potently inhibited trypsin-induced PAR2 activation in HaCaT cells with an IC₅₀ of 1.30 µM, exhibiting over 40-fold greater selectivity over PAR1. PCG significantly inhibited PAR2-induced phosphorylation of ERK1/2 and NF-κB in both HaCaT and human dermal fibroblast cells and reduced IL-8 secretion in HaCaT cells. In addition, PCG did not significantly affect other pruritus-related GPCRs including H1R, H4R, TGR5, 5HT2A, 5HT2B, and MRGPRX2 at 30 µM. Notably, PCG strongly blocked PAR2-AP-induced scratching in mice. In addition, PCG improved skin lesions, reduced dermatitis severity scores, and alleviated scratching behavior in a DNFB-induced atopic dermatitis model. These effects were associated with reduced epidermal thickness, decreased serum TSLP levels, and inhibition of PAR2-dependent calcium signaling in dorsal root ganglion neurons. These findings demonstrate that PCG is a selective PAR2 antagonist that effectively alleviates both inflammatory and pruritic symptoms of atopic dermatitis, suggesting its potential as a novel therapeutic agent. Full article

Background: Symptomatic uncomplicated diverticular disease (SUDD) is a common condition in older adults, primarily managed through symptom control. Emerging evidence highlights the role of gut microbiota in symptom modulation and disease progression. Butyrate supplementation offers anti-inflammatory benefits and supports gut barrier integrity; when combined with specific probiotic strains, it may further promote microbiota balance. Objectives: To evaluate the clinical and microbiological effects of an oral formulation combining microencapsulated sodium butyrate with probiotic strains from four probiotic strains (Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, Limosilactobacillus reuteri, and Bifidobacterium longum subsp. infantis) in patients with SUDD. Methods: This prospective, preliminary observation enrolled 23 patients. To control for high interindividual variability in microbiota composition, each participant served as their own control. The intervention lasted 12 weeks and included five scheduled visits, incorporating a 3-week washout period. Symptom severity and quality of life were assessed using validated questionnaires. Faecal microbiota composition was evaluated using 16S rRNA sequencing and strain-specific colonisation was monitored with qPCR. Results: Significant improvements were observed in seven out of nine reported symptoms, including reductions in abdominal pain, bloating, and discomfort. Overall symptom burden decreased, especially symptoms related to gas and stool consistency. Quality of life scores improved notably. qPCR confirmed colonisation by the administered probiotic strains. Microbiome analysis demonstrated individualized but meaningful improvements in microbial profiles. Conclusions: The combined use of microencapsulated sodium butyrate and selected probiotic strains led to measurable clinical improvements and the positive modulation of gut microbiota in patients with SUDD. This formulation was well tolerated and may represent a promising adjunct or standalone approach in the dietary management of SUDD. Full article