Search Results (86)

This study investigates the effects of heat stress in a climate chamber from day 0 to 28 days of life on physiological responses, intake, nutrient digestibility, immunity, and performance in neonatal Holstein calves. Thirty-four calves (nineteen females, fifteen males) were randomly assigned to a control group (CON, temperature–humidity index [THI] 66, with 22 °C and 65% humidity for 24 h, n = 17) or a heat-stressed (HS) group, which was exposed to a THI of 82, 32 °C, and 65% humidity for 9 h, followed by a THI of 66, 22 °C, and 65% humidity for 15 h. The HS calves exhibited increased respiratory rates and rectal temperatures (p < 0.001), particularly during heat exposure periods, as well as a 59.5% increase in water intake compared to CON. While milk and solid feed intake, average daily gain, and feed efficiency were similar between groups, HS calves had reduced ether extract digestibility and altered ruminal fermentation, including lower acetate and lower propionate concentrations. The blood cytokine analysis showed elevated interleukin-4 and reduced interleukin-8 and IP-10 levels in heat-stressed calves, indicating a shift toward an anti-inflammatory immune profile. Despite no major performance impairments, heat stress has induced clear physiological, digestive, and immunological changes. These results underscore the importance of implementing thermal mitigation strategies during early life to safeguard calf health and development in increasingly warmer climates. Full article

Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) lacks effective therapies. This study aimed to evaluate the therapeutic potential of compound 3d, a novel elafibranor derivative, focusing on its dual mechanisms of PPAR pathway activation and p38 MAPK signaling inhibition. Methods: Integrated in vitro and in vivo approaches were employed. In vitro, free fatty acid (FFA)-induced lipid accumulation in L02 hepatocytes and lipopolysaccharides (LPSs)-stimulated inflammatory responses in RAW264.7 macrophages were used to evaluate lipid metabolism and anti-inflammatory effects. In vivo, a high-fat diet (HFD)-induced MASH model in C57BL/6 mice assessed serum biochemical parameters (triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor-α (TNF-α), nitric oxide (NO), and interleukin-6 (IL-6)), liver histopathology (H&E, Oil Red O, Masson staining), and proteomic profiling. Gut microbiota composition was analyzed via 16S rRNA sequencing. Western blotting quantified PPAR isoforms (γ/δ), downstream targets (Acox1, EHHADH, Acaa1), and p38 MAPK pathway proteins (p-p38, caspase-8, Bcl-2). Results: In vitro, 3d significantly reduced lipid accumulation (reduction in TG, p < 0.01) and inflammation (decrease in ALT activity, p < 0.05) in hepatocytes, while suppressing LPSs-induced TNF-α (63% reduction), NO (51% decrease), and IL-6 (48% reduction) in macrophages (p < 0.01). In vivo, 3d (30 mg/kg) lowered serum TG (39% decrease), TC (32% reduction), LDL-C (45% decline), and TNF-α (57% reduction) in HFD-fed mice (p < 0.05 vs. model), normalized AST/ALT levels, and ameliorated hepatic steatosis, ballooning, and fibrosis. Proteomics demonstrated PPARγ/δ activation (2.3–3.1-fold upregulation of Acox1, EHHADH, Acaa1; p < 0.001) and p38 MAPK pathway inhibition (54% reduction in p-p38, 61% decrease in caspase-8; 1.8-fold increase in Bcl-2; p < 0.01). Gut microbiota analysis revealed enrichment of beneficial taxa (Lactobacillus: 2.7-fold increase; Bifidobacterium: 1.9-fold rise) and reduced pathogenic Proteobacteria (68% decrease, p < 0.05). Conclusions: Compound 3d alleviates MASH via PPAR-mediated lipid metabolism enhancement and p38 MAPK-driven inflammation/apoptosis suppression, with additional gut microbiota modulation. These findings highlight 3d as a multi-target therapeutic candidate for MASH. Full article

Background/Objectives: Endurance exercise increases oxygen demand and, when not balanced by antioxidant defenses, consequently, oxidative stress and inflammatory cytokines increase too. In breast cancer survivors (BCS), post-treatment, physical capacity decreases, lowering life quality. Dragon boat (DB) paddling has shown benefits in reducing lymphedema and improving psychological well-being. This study aimed at non-invasively investigating in BCS, by means of saliva and urine samples, the systemic responses to oxy-inflammation, and appetite hormones after a DB endurance race. Methods: 15 BCS and 15 healthy women (5 (CTR) who performed the DB race too) were studied. BCS and CTR were monitored pre- and post-race. Reactive oxygen species (ROS) production, total antioxidant capacity (TAC), lipid peroxidation (8-iso), DNA oxidation (8-OH-dG), nitric oxide metabolites (NOx), inflammation markers (IL-6-10 and TNFα), appetite hormones, electrolytes concentration, psychometric, and physical scales were assessed. Results: At rest, compared to healthy women, BCS showed a significant increase in oxy-inflammation biomarkers. BCS showed a general increase in oxy-inflammation parameters compared to CTR after the DB race. In BCS, there were the following results: ROS: +80%; lipid peroxidation: +103%; DNA oxidation: +44%; interleukins-6: +179%; IL-10: +55%; TNFα: +9%, NOx: +60% increases and unbalanced appetite hormones: leptin (−32%); and ghrelin (+53%). Moreover, the dragon boat offered a holistic approach to recovery, addressing emotional and social needs supporting belonging, love, and esteem needs, reported to be about 56% of the motivations in this activity, while post-race the following increased: a sense of fatigue (+55%); tiredness (48%); a cold sensation (+15%); and +32% pain. Conclusions: This study provided evidence that, in BCS, a DB endurance race produces an important imbalance in the oxy-inflammation state, at the same time being accompanied by a positive impact on subjective mood and general wellness. Future studies should focus on long-term effects. Full article

Background/Objectives: Despite its long-standing recognition, the etiopathogenesis of idiopathic granulomatous mastitis (IGM) remains poorly understood. This study aims to investigate the relationship between IGM and food intolerance, allergies, and immunological factors to shed light on its etiology. Materials and Methods: This case–control study included 32 patients with IGM and 32 healthy women. In order to examine their potential relevance to allergy and immunology, serum interleukin (IL)-4, IL-4 receptor, histamine, and histamine-releasing factor (HRF) were measured by ELISA. Furthermore, serum IgG antibodies against specific food allergens were measured to evaluate food intolerance. Results: The patient group exhibited significantly higher intolerance values for lentils and curry compared to the control group (p = 0.023 and p = 0.012, respectively). Histamine (p < 0.001) and IL-4 (p = 0.003) levels were elevated in IGM patients compared to the control group, while HRF and IL-4R outcomes did not show any significant differences (p > 0.05). Conclusions: Elevated histamine and IL-4 levels may suggest the involvement of allergy and immunological factors in IGM’s etiopathogenesis. The integration of anti-histamine medications for IGM patients with elevated histamine levels could provide an alternative therapeutic strategy. Full article

Background/Objectives: Previous studies suggest that there is a genetically determined component of fat oxidation at rest and during exercise. To date, the FTO gene has been proposed as a candidate gene to affect fat oxidation during exercise because of the association of the “at-risk” A allele with different obesity-related factors such as increased body fat, higher appetite and elevated insulin and triglyceride levels. The A allele of the FTO gene may also be linked to obesity through a reduced capacity for fat oxidation during exercise, a topic that remains largely underexplored in the current literature. The aim of this study was to analyze the association between the FTO rs9939609 polymorphism with the rate of fat oxidation during exercise and metabolic syndrome criteria in healthy participants. Methods: A total of 80 healthy participants (41 men and 39 women) underwent comprehensive assessments, including measurements of anthropometric variables, blood pressure and blood measures of fasting glucose, triglycerides, low- and high-density lipoprotein cholesterol (LDL-c and HDL-c), insulin, interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations. Additionally, the Homeostatic Model Assessment (HOMA-IR) was used to evaluate insulin resistance. Peak oxygen uptake (VO_2peak) and maximal fat oxidation rate (MFO) were also measured during an incremental cycling test. FTO rs9939609 genotyping (TT, AT, AA) was performed using genomic DNA samples obtained from a buccal swab and measured with PCR. Results: There were 32 participants (40.0%) with the TT genotype; 31 (38.8%) with the AT genotype; and 17 (21.2%) with the AA genotype. Age, body characteristics, VO_2peak, blood pressure and blood variables were similar across all three genotypes. However, serum insulin concentration and HOMA-IR were associated with the FTO rs9939609 genotype with higher values in AA with respect to AT and TT participants (p < 0.050). Still, MFO was similar in TT, AT and AA participants (0.35 ± 0.13, 0.37 ± 0.11, 0.33 ± 0.11 g/min, p = 0.702). In the dominant model, there was no statistical difference between TT and A allele carriers. However, the recessive model revealed that AA participants had higher values of body mass, body mass index, blood insulin concentration and HOMA-IR than T allele carriers (p < 0.050), with no differences in MFO. Conclusions: In our sample of healthy individuals, the FTO rs9939609 polymorphism was associated with several phenotypes associated with obesity and insulin resistance, particularly under the AA vs. T allele/recessive model. However, the FTO rs9939609 polymorphism was not associated with MFO during exercise as fat oxidation was similar across genotypes. This suggests that reduced fat oxidation during exercise is unlikely to be a cause of the obesogenic influence of the FTO AA genotype. Clinically, these findings suggest that the obesogenic effects of the FTO AA genotype are unlikely driven by impaired fat oxidation during exercise. Instead, attention should focus on mechanisms like appetite regulation and energy intake. Moreover, exercise interventions may still effectively mitigate obesity risk, as AA individuals retain normal fat oxidation capacity during exercise. Full article

Infection of dogs with the tick-borne rickettsiae Ehrlichia and Anaplasma provokes an immune response mediating the pathology and bacterial resistance. IL-10 is the main anti-inflammatory cytokine and plays a multifaceted role in host protection. The study aimed to investigate circulating IL-10 in 32 dogs naturally infected with A. phagocytophilum and E. canis, identified by PCR positivity, and 33 PCR-negative animals which tested positive for antibodies against these pathogens, as well as 22 healthy animals. The highest quantity of IL-10, measured by ELISA, was observed among dogs positive simultaneously for anti-E. canis and anti-A. phagocytophilum IgG antibodies, followed by dogs positive for anti-E. canis only. The concentration of IL-10 in PCR-positive dogs was almost three and a half times higher than that measured in the control group (77.09 ± 23.61 pg./mL vs. 21.55 ± 4.61 pg./mL; p = 0.0015) and five times higher than the concentration of interleukin in PCR-negative animals (77.09 ± 23.61 pg./mL vs. 14.86 ± 3.01 pg./mL; p = 0.000016). The highest level of IL-10 was observed in PCR-positive dogs with mixed infection (120.54 ± 44.18), followed by the level in PCR-positive dogs for E. canis only (78.81 ± 16.92). The lowest level of IL-10 was observed in PCR-positive dogs for A. phagocytophilum only (56.32 ± 12.68). We may suggest that infection with E. canis and A. phagocytophilum stimulates the IL-10 production in dogs, which may facilitate specific antibody responses. Full article

Background/Objectives: Benralizumab is a monoclonal antibody that targets the interleukin-5 receptor (IL-5Rα), leading to the rapid depletion of blood eosinophils. RCTs have demonstrated efficacy in patients with severe eosinophilic asthma (SEA). The aim of this study was to assess the efficacy of benralizumab on sinonasal outcomes in a real-life setting in patients with SEA and concomitant chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: We included 25 patients (mean age: 57.47 years, range: 35–77, F/M = 12:13) who were prescribed 30 mg benralizumab every month for the first three administrations and then every 2 months. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test-22 (SNOT-22) and nasal polyp score (NPS) over a 24-month treatment period. Secondary endpoints included measuring the effects on nasal obstruction and impaired sense of smell. Results: The mean NPS score decreased significantly from 5.11 ± 1.84 at baseline to 2.37 ± 1.96 at 24 months. The mean SNOT-22 decreased from 57 ± 15.30 at baseline to 26 ± 16.73 at 24 months. The SSIT-16 mean score improved with an increase in olfactory performance from 5.23 ± 2.58 at baseline to 7 ± 3.65 at 24 months. Moreover, 8/25 patients (32%) required rescue treatment with systemic steroids and 2 patients required endoscopic sinus surgery. Conclusions: While the improvement may not seem optimal at 12 months, a progressive enhancement was noted during the second year of treatment. Despite our data showing an improvement in quality of life and a reduction in the size of nasal polyps, no significant improvement in olfactory sensitivity was observed. In addition, in several patients, rescue treatments were required to maintain control of nasal and sinus symptoms. A careful risk–benefit assessment is therefore needed when deciding to continue treatment, weighing the potential for further improvement against the risks of complications. Such decisions should always be made in the context of a multidisciplinary team. Full article

Cancer cachexia is a syndrome characterized by weight and muscle loss and functional impairment, strongly influencing survival in cancer patients. In this study, we aimed to establish the role of saliva cytokine measurement in cancer cachexia investigation and define two potential independent salivary biomarkers of the condition. Methods: serum and saliva specimens were obtained from 78 patients. Forty-six patients were non-cachectic, and 32 patients were cachectic (per SCRINIO group criteria), all with metastatic solid tumors. Commercial ELISA kits were used to determine the salivary and serum concentrations of interleukin 13 (IL-13) and transforming growth factor beta (TGF-β) in two patient groups and healthy controls. Laboratory values were obtained from the hospital information system, and weight and height were measured at the time of sampling. Results: A statistically significant difference was observed between the groups in saliva IL-13 concentrations but no difference in serum concentrations. Statistically significant differences were also observed between the groups in saliva and serum concentrations of TGF-β. Logistic regression analysis has identified salivary IL-13 and TGF-β as independent factors for cancer cachexia. Conclusions: We demonstrated saliva as a valuable specimen for cachexia investigation and established IL-13 and TGF-β as potential cancer cachexia biomarkers. Further research is needed to evaluate these findings. Full article

Background and Objectives: Atopic dermatitis is a chronic inflammatory skin disorder with a significant burden on patients’ quality of life. This systematic review aims to evaluate the restoration of skin barrier abnormalities with interleukin-4/interleukin-13 (IL-4/IL-13) inhibitors and Janus kinase (JAK) inhibitors in atopic dermatitis. Materials and Methods: A comprehensive review of the literature was conducted, focusing on studies that assess the use of IL-4/IL-13 inhibitors and JAK inhibitors for atopic dermatitis. We identified eligible studies by searching Medline via PubMed with a special focus on their effect on the restoration of the epidermal barrier. Included studies evaluated the transepidermal water loss (TEWL), the reduction in epidermal thickness (ET), the improvement in ceramide synthesis, and the increase in stratum corneum hydration (SCH) with IL-4/IL-13 inhibitors and JAK inhibitors. The quality of included studies was assessed using the ROBINS-I and the RoB 2.0 tool for assessing the risk of bias. Results: Ten of the included studies concern dupilumab, while two concern JAK inhibitors. Ten were observational studies and two were randomized controlled trials (RCTs). The total number of included participants was 378 concerning dupilumab and 38 concerning JAK inhibitors. Five studies did not include any comparison group, three included healthy volunteers, two were conducted versus placebo, and two compared dupilumab with other treatments. The follow-up period ranged between 29 days and 32 weeks. The results demonstrated a significant decrease in transepidermal water loss (TEWL) and an increase in SCH on eczematous lesions for patients with sustained response to dupilumab treatment and observed improvements in ET and filaggrin (FLG) staining, which further support the efficacy of JAK inhibitors in enhancing skin barrier function. Conclusions: This review underscores the efficacy of IL-4/IL-13 inhibitors in improving skin barrier function. However, the limited number of studies focusing on JAK inhibitors and the overall lack of RCTs highlight the need for further research to establish the definitive role of IL-4/IL-13 inhibitors and JAK inhibitors in the restoration of the skin barrier. Full article

Background/Objectives: Coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) are characterized by chronic low-grade inflammation. However, measuring cytokines typically involves invasive blood sampling, which can be problematic for CAD patients. This study aimed to assess ophthalmological parameters and tear cytokines in patients with CAD, comparing those with comorbid T2DM to those without to understand their inflammatory profiles. Methods: One hundred subjects with suspected chronic or acute CAD were initially included in this single-center cross-sectional study after clinical stabilization. Seventy-two patients with confirmed CAD were divided into two groups: 32 patients with T2DM and 40 patients without T2DM. A total of 144 eyes were examined, and tear fluid samples were collected to determine cytokine concentrations. Ophthalmological parameters and tear concentrations of cytokines were analyzed, controlling for age, sex, and other cardiovascular risk factors. Results: Patients with CAD and T2DM exhibited decreased ophthalmological parameters and increased cytokine concentrations in comparison to those without T2DM. Significant inverse correlations between ophthalmological parameters and cytokine concentrations were observed. Following adjustment, a full logistic regression model for distinguishing patients with CAD and comorbid T2DM included macular cube volume, mean macular thickness, interleukin (IL)-4, IL-5, IL-6, IL-8, IL-9, IL-13, granulocyte colony-stimulating factor (G-CSF), CCL3, CCL4, and CCL11/eotaxin-1, demonstrating excellent discriminatory power (Area Under the Curve = 0.95, 95% Confidence Interval = 0.91–0.99; p < 0.001). Subsequently, IL-5 (Odds Ratio = 1.68, 95% CI = 1.26–2.24; p < 0.001), G-CSF (OR = 1.06, 95% CI = 1.02–1.11; p < 0.01), and CCL11/eotaxin-1 (OR = 1.56, 95% CI = 1.19–2.05; p = 0.001) emerged as the most distinguishing variables in a reduced model (AUC = 0.89, 95% CI = 0.84–0.95; p < 0.001). Conclusions: Differences in ophthalmological variables, mainly in cytokine concentrations, suggest distinct pathophysiological mechanisms in patients with CAD based on the presence of T2DM. These findings demonstrate that the inflammatory profile can be readily detected through tear sample cytokines, proving valuable for establishing more accurate prognoses and monitoring in cardiometabolic disorders. Full article

Cystic echinococcosis (CE) is a zoonotic disease caused by the parasite Echinococcus granulosus (E. granulosus), which can lead to the formation of liver lesions. Research indicates that E. granulosus releases both Toll-like receptor 2 (TLR2) and Interleukin-9 (IL-9), which can potentially impair the body’s innate immune defenses and compromise the liver’s ability to fight against diseases. To investigate the role of TLR2 and IL-9 in liver damage caused by E. granulosus infection, samples were initially collected from individuals diagnosed with CE. Subsequently, BALB/c mice were infected with E. granulosus at multiple time points (4 weeks, 12 weeks, 32 weeks) and the expression levels of these markers was then assessed at each of these phases. Furthermore, a BALB/c mouse model was generated and administered anti-IL-9 antibody via intraperitoneal injection. The subsequent analysis focused on the TLR2/MyD88/NF-κB signaling pathway and the expression of IL-9 in E. granulosus was examined. A co-culture experiment was conducted using mouse mononuclear macrophage cells (RAW264.7) and hepatic stellate cells (HSCs) in the presence of E. granulosus Protein (EgP). The findings indicated elevated levels of IL-9 and TLR2 in patients with CE, with the activation of the signaling pathway significantly increased as the duration of infection progressed. Administration of anti-IL-9 in mice reduced the activation of the TLR2/MyD88/NF-κB signaling pathway, exacerbating liver injury. Moreover, EgP stimulates the TLR2/MyD88/NF-κB signaling pathway, resulting in the synthesis of α-SMA and Collagen I. The data suggest that infection with E. granulosus may stimulate the production of IL-9 through the activation of the TLR2/MyD88/NF-κB signaling pathway, which is mediated by TLR2. This activation stimulates RAW264.7 and HSCs, exacerbating liver injury and fibrosis. Full article

Connexin 43 (Cx43) is crucial for the development and homeostasis of the musculoskeletal system, where it plays multifaceted roles, including intercellular communication, transcriptional regulation and influencing osteogenesis and chondrogenesis. Here, we investigated Cx43 modulation mediated by inflammatory stimuli involved in osteoarthritis, i.e., 10 ng/mL Tumor Necrosis Factor alpha (TNFα) and/or 1 ng/mL Interleukin-1 beta (IL-1β), in primary chondrocytes (CH) and osteoblasts (OB). Additionally, we explored the impact of synovial fluids from osteoarthritis patients in CH and cartilage explants, providing a more physio-pathological context. The effect of TNFα on Cx43 expression in cartilage explants was also assessed. TNFα downregulated Cx43 levels both in CH and OB (−73% and −32%, respectively), while IL-1β showed inconclusive effects. The reduction in Cx43 levels was associated with a significant downregulation of the coding gene GJA1 expression in OB only (−65%). The engagement of proteasome in TNFα-induced effects, already known in CH, was also observed in OB. TNFα treatment significantly decreased Cx43 expression also in cartilage explants. Of note, Cx43 expression was halved by synovial fluid in both CH and cartilage explants. This study unveils the regulation of Cx43 in diverse musculoskeletal cell types under various stimuli and in different contexts, providing insights into its modulation in inflammatory joint disorders. Full article

Background: Hand eczema (HE) is a prevalent chronic condition that exerts a substantial and enduring adverse effect on quality of life (QoL) and imposes an economic burden on society. Managing HE poses challenges due to the limited effectiveness and potential adverse effects associated with many currently available topical and systemic treatments. Methods: This article examines twenty-one patients affected by HE treated with dupilumab, a fully human monoclonal antibody targeting interleukin IL-4 and IL-13 signaling. This involves a retrospective descriptive statistical analysis. Results: At week 6, HECSI-75 was achieved by 12 patients (57.9%). The proportion of patients meeting the HECSI-75 criteria steadily increased over the observation weeks, reaching 90% at week 16 and 100% at week 104. Furthermore, HECSI-90 and HECSI-100 were achieved by 75% and 60% of patients at week 16 and by 100% and 85% of patients at week 68, respectively. All patients who reached week 104 maintained complete disease remission according to HECSI 100. Conclusions: In all patients, dupilumab was shown to be an effective drug in achieving disease clearance, as indicated by all the parameters considered at each evaluation point (Week 6, Week 16, Week 32, Week 52, Week 68, Week 84, and Week 104), in comparison to the initial baseline. Full article

Vitamin D deficiency can escalate prematurity bone disease in preterm infants and negatively influence their immature immunology system. Infants born at 24 + 0/7 weeks to 32 + 6/7 weeks of gestation will be considered for inclusion. Cord or vein blood samples will be obtained within 48 h after birth for 25-hydroxyvitamin D level measurements. Parathyroid hormone and interleukin-6 levels will be measured. Infants will be randomized to the monitored group (i.e., an initial dose of 1000 IU/day and possible modification) or the controlled group (i.e., 250 IU/day or 500 IU/day dose, depending on weight). Supplementation will be monitored up to a postconceptional age of 35 weeks. The primary endpoint is the percentage of infants with deficient or suboptimal 25-hydroxyvitamin D levels at 28 ± 2 days of age. 25-Hydroxyvitamin D levels will be measured at postconceptional age 35 ± 2 weeks. Secondary goals encompass assessing the occurrence of sepsis, osteopenia, hyperparathyroidism, and interleukin-6 concentration. The aim of this study is to evaluate the efficacy of monitored vitamin D supplementation in a group of preterm infants and ascertain if a high initial dosage of monitored vitamin D supplementation can decrease the occurrence of neonatal sepsis and metabolic bone disease. Full article

(1) Background: Prurigo nodularis (PN) is a persistent and inflammatory dermatological condition characterized by chronic itching and the formation of hardened nodules, significantly impacting the affected individuals’ quality of life and psychological well-being. The management of PN poses challenges due to the limited efficacy and undesirable side effects associated with current interventions. (2) Methods: This article examines sixteen patients affected by PN treated with dupilumab, a fully human monoclonal antibody targeting interleukin IL-4 and IL-13 signaling. This involves a retrospective descriptive statistical analysis. (3) Results and (4) Conclusions: In all patients, dupilumab proves to be an effective drug in achieving disease clearance, as indicated by all the parameters considered as assessed by both physicians and patients at each evaluation point (Week 6, Week 16, Week 32, Week 52, Week 68, and Week 84), in comparison to the initial baseline. Full article