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The acute phase immune response (APR) in midline laparotomy (MLa) patients following surgery has been rarely studied, with no studies assessing the association of blood IL-18 (interleukin-18) and IL-18BP (IL-18 binding protein) values with the numeric rating scale (NRS) pain score following MLa. Blood levels of seven cytokines (CYT) (IL-18, IL-18BP, IL-1ra, IL-6, IL-8, IL-10, IL-1β) and high-sensitivity C-reactive protein (hs-CRP) were measured at three time points; before operation (PRE), immediately after operation (POP1), and 24 h after operation (POP2) in 56 patients with MLa. The satisfaction of the patients at 24 h following MLa (SFS ; 0=fully unsatisfied; 10=fully satisfied) was recorded on a 11-point numeric rating scale. In all patients, the IL-18 and IL-18BP blood levels decreased at POP1 and the drop between the preoperative and POP1 levels in the IL-18 and IL-18BP was highly significant (p<0.001). However, the median IL-18 and IL-18BP blood levels increased significantly at POP2 (p<0.001) with the linear mixed-effect model (LME) showing a statistically significant time effect (p<0.001). The hs-CRP blood levels increased significantly at POP2 with the LME model showing a statistically significant time effect. The preoperative and POP2 IL-18 values were clearly higher in patients with cancer versus benign disease (177/182 vs. 135/126, p=0.039/p=0.013, respectively). Interestingly, in all patients of the study, the median IL-18 versus IL-18BP blood levels correlated at POP1 (r=0.315, p=0.036). A noteworthy discovery of this study is the correlation of IL-18BP with SFS (r=0.361, p=0.05), proposing that APR and quality of life are associated in MLa patients.

ObjectiveChemerin has been suggested as a potential link between obesity and associated comorbidities in humans. Therefore, we studied the relationships between chemerin, parameters of fat mass, and Metabolic Syndrome (MetS) in obese children before and after weight reduction.MethodsWe determined chemerin, bioactive leptin (bioLep), BMI-SDS, waist circumference (WC), body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index HOMA, and blood pressure in 88 obese children participating in a lifestyle intervention at baseline and 1 year later. Furthermore, we determined chemerin concentrations in 23 normal-weight children.ResultsObese children demonstrated significantly (p < 0.001) higher chemerin concentrations compared to normal-weight children (96.2 ± 23.0 versus 63.1 ± 12.4 ng/ml). The chemerin concentrations were not related to age or gender. Prepubertal children had higher (p = 0.024) chemerin concentrations than pubertal children (71.0 ± 13.4 versus 58.0 ± 8.9 ng/ml). Weight loss was associated with a decrease of chemerin (−14.0 ± 22.0 ng/ml; p < 0.001) and an improvement of all parameters of the MetS. Chemerin was significantly related to BMI-SDS, WC, and bioLep in cross-sectional and longitudinal analyses. Chemerin and its changes were significantly related to insulin, HDL-cholesterol, triglycerides and their changes in multiple linear regression analyses adjusted to age, gender, pubertal stage, leptin and BMI.ConclusionsSince chemerin was related to parameters of central fat mass and MetS both in cross-sectional and longitudinal analyses these findings suggest an impact of chemerin on factors of the MetS in obese children.

Cardiovascular disease is the leading cause of death for people receiving hemodialysis. Intradialytic cycling (IDC) has been shown to improve cardiovascular health in the hemodialysis population, but specific mechanisms require elucidation. Chemerin is an adipokine which contributes to the inflammatory process and may be associated with the cardiovascular benefits of IDC and physical function in hemodialysis population. Adults undertaking ≥3 months hemodialysis were randomized to either IDC (30 min each time, moderate intensity, thrice weekly) and usual care; or usual care only (control group). 88 blood samples were retrospectively analyzed for chemerin concentrations using ELISA. Unadjusted and adjusted linear regression was used to understand how changes in chemerin are associated with changes in cardiovascular and musculoskeletal health in response to IDC. There was a significant increase of plasma chemerin concentration after 6 months in both groups. A positive association was detected between chemerin and short physical performance battery at baseline (β = 0.264, p = 0.017). There was no correlation of chemerin with cardiovascular, body composition, and other physical function markers. This study is the first to show plasma level of chemerin increases with time on hemodialysis. No evidence was found to support a role for chemerin in modifying cardiac structure and function in people undertaking IDC. Further studies should investigate the associations between chemerin and physical performance.

Background For the second aim of the Kellogg Foundation grant, this double-blind RCT investigated the impact of plasma vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) on plasma immune-mediators during pregnancy. We hypothesized that higher 25(OH)D concentrations would associate with reduced pro-inflammatory and increased tolerogenic immune-mediator concentrations. Methods Pregnant women enrolled at 10–14 weeks gestation were randomized to 400 or 4400 IU vitamin D 3 /day. Data on health, safety, circulating 25(OH)D, and 9 immune-mediators were collected at each trimester. Associations between immune-mediators and 25(OH)D at baseline and at second and third trimesters were examined. Results Baseline TGF-β and second and third trimesters IFN-γ and IL-2 were associated with baseline 25(OH)D. Baseline immune-mediators were associated with immune-mediators at second and third trimesters for all immune-mediators except IL-5 and IL-10. Race was associated with baseline TGF-β, VEGF and IL-10 and with IL-10 at second and third trimesters. Conclusions Both treatment groups had increased 25(OH)D at second and third trimesters, greatest in the 4400 IU group. Though associations between baseline 25(OH)D and baseline TGF-β and second and third trimester IFN-γ and IL-2 were noted, vitamin D supplementation throughout pregnancy did not impact immune-mediators at later trimesters. Supplementing with vitamin D before conception conceivably influences immune-mediator responses during pregnancy. Impact In this vitamin D supplementation clinical trial, baseline (first trimester) but not increasing plasma 25(OH)D concentration impacted select plasma immune-mediator profiles in pregnant women. Baseline 25(OH)D was associated with baseline TGF-β and with IFN-γ and IL-2 at second and third trimesters. Baseline IFN-γ, CRP, TGF-β, TNF-α, VEGF, IL-2, and IL-4 were associated with concentrations at second and third trimesters for respective immune-mediators; however, 25(OH)D concentration at second and third trimesters were not. Some racial differences existed in immune-mediator concentrations at baseline and at second and third trimesters. This study assesses the impact of vitamin D supplementation on multiple immune-mediators in pregnant women of different racial/ethnic groups using longitudinal data from a relatively large randomized controlled trial. This study found that race was associated with baseline TGF-β, VEGF, and IL-10 and with IL-10 at second and third trimesters, a novel finding that sheds light where relationships were less well defined. The results of this study suggest that vitamin D supplementation before conception or early in pregnancy, rather than during pregnancy, may be necessary to significantly impact immune-mediator response. This study sets premise for future clinical trials to evaluate the effect of vitamin D supplementation before conception or prior to pregnancy.

Aging-induced deterioration of arterial stiffness is decreased by regular exercise, and increased nitric oxide (NO) production participates in this effect. Apelin regulates endothelial NO synthase in endothelial cells, promoting NO production. However, the effect of aerobic exercise training on circulating apelin levels in healthy middle-aged and older adults remains unknown. Accordingly, this study aimed to clarify the effects of regular aerobic exercise on apelin concentrations in middle-aged and older adults. Thirty-four healthy middle-aged and older subjects (67.0 ± 1.3 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed 8-week of aerobic exercise training (60-70% peak oxygen uptake [VO2peak] for 45 min, 3 days/week). Before and after the intervention, we evaluated plasma apelin and nitrite/nitrate (NOx) concentrations, VO2peak, and arterial stiffness index. In the training group, VO2peak was significantly increased, and carotid β-stiffness was significantly decreased, after the intervention (P<0.05). Moreover, plasma apelin and NOx levels were significantly increased in the training group after the intervention (P<0.05). Additionally, there was a correlation between the training effects of plasma apelin levels and carotidβ-stiffness (r =  -0.508, P = 0.032) and plasma NOx levels (r = 0.494, P = 0.037). By contrast, none of these parameters changed significantly in the control group. These results suggest that the increased in plasma apelin levels may be associated with exercise training-induced alternation of arterial stiffness in middle-aged and older adults.

Background Platelet-rich plasma (PRP) therapy is utilized for chronic tenosynovitis to reduce inflammation and promote tendon sheath repair. This study compared the temporal kinetics of PRP-derived growth factors with clinical outcomes of PRP versus saline injection over 3 months. Methods In a randomized controlled trial, 200 patients with chronic tenosynovitis were assigned to non-activated PRP ( n  = 100) or saline ( n  = 100) tendon sheath injection. PRP group blood samples were collected at 1 h, 8 h, Days 1, 3, 7, 14, and 1 month post-injection; both groups had clinical and ultrasound assessments at 1 and 3 months. Serum VEGF, PDGF-AB, EGF, and TGF-β were quantified via ELISA, with platelet counts analyzed. Pain (VAS), function (WOMAC, DASH), and tendon sheath thickness were evaluated. Repeated-measures ANOVA and t-tests assessed changes. Results In the PRP group, non-activated PRP achieved a platelet concentration of 1030 ± 130 × 10³/µL (4.5× baseline), and biomarkers varied significantly ( p  < 0.001). VEGF peaked at Day 14 (285.44 ± 50.0 pg/mL), sustained at 260.0 ± 45.0 pg/mL (1 month). PDGF-AB peaked at 8 h (1253.28 ± 160.0 pg/mL), declining to 300.0 ± 90.0 pg/mL (1 month). EGF peaked at Day 7 (451.84 ± 75.0 pg/mL), returning to 380.0 ± 75.0 pg/mL (1 month). TGF-β exhibited plateau kinetics without a distinct peak, stabilizing at 8.50 ± 1.80 ng/mL (1 month). PRP outperformed saline in pain (− 50.0 mm vs. −31.0 mm), function (QuickDASH − 35.0 vs. −21.0), and sheath thickness reduction (− 0.9 mm vs. −0.4 mm) at 3 months (all p  < 0.001). PRP reduced VAS by 57% (30.0 ± 11.0 mm), WOMAC by 42% (35.0 ± 7.5), DASH by 38% (40.0 ± 9.5), and thickness by 45% (1.54 ± 0.30 mm) at 1 month; by 3 months, VAS was 20.0 ± 9.0 mm, WOMAC 25.0 ± 6.5, DASH 30.0 ± 7.5, thickness 1.40 ± 0.28 mm ( p  < 0.001). Saline reduced VAS by 30% (50.0 ± 14.0 mm), WOMAC by 26% (45.0 ± 9.5), DASH by 24% (50.0 ± 10.5), thickness by 30% (1.99 ± 0.38 mm) at 1 month; by 3 months, VAS was 40.0 ± 11.0 mm, WOMAC 40.0 ± 8.5, DASH 45.0 ± 9.5, thickness 1.85 ± 0.35 mm ( p  < 0.01). PRP outperformed saline ( p  < 0.001). Adverse events were mild (15% PRP, 7% saline). Conclusions Non-activated PRP induces time-specific growth factor release, outperforming saline in 3-month pain, function, and tendon thickness outcomes for tenosynovitis. The larger sample size enhances generalizability, aligning with recommendations for robust musculoskeletal trials and refuting claims of PRP equivalence to placebo. These findings guide PRP timing and support its efficacy over placebo. They also underscore the importance of individualized PRP dosing strategies based on platelet concentration thresholds. Trial registration In the Pan African Clinical Trials Registry (PACTR202506613254896) on 10 June 2025, and is accessible at: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=34788 .

Wingless and integration site growth factor (Wnt) signaling is a tumorigenesis-related signaling pathway. Dickkpof-1 (DKK1) and secreted frizzled-related protein-1 (SFRP1) are endogenous negative regulators of Wnt/β-catenin signaling. Accumulating evidence indicates that higher serum levels of DKK1 are correlated with poor prognosis of various types of cancer. Here, we investigated whether exercise training causes changes in the serum levels of DKK1 and SFRP1 in patients with breast cancer. Twenty-four breast cancer survivors, after chemo- or radiotherapy, participated in this single-blind randomized, controlled pilot study. Subjects were randomized to either an exercise program or a control group for 12 weeks and completed pre- and post-training tests for health-related fitness and body composition as well as blood biomarkers. The serum levels of DKK1 and SFRP1 were measured using enzyme-linked immunosorbent assay as the primary outcome. Exercise training for 12 weeks remarkably increased muscle strength, endurance, and flexibility and decreased body fat percentage, waist circumference, and visceral fat area (all p < 0.05). Exercise training lowered serum insulin levels and leptin/adiponectin ratios (all p < 0.05). The levels of DKK1 and SFRP1 were also significantly decreased by exercise training in breast cancer survivors (all p < 0.01). Our results indicate that DKK1 and SFRP1 may be potentially useful biomarkers for evaluating the beneficial effects of long-term exercise on physical fitness and metabolism as well as the prognosis of patients with cancer. ClinicalTrials.gov NCT02895178.

This study investigated the effect of subcutaneously administered oxyntomodulin on body weight in healthy overweight and obese volunteers. Participants self-administered saline or oxyntomodulin subcutaneously in a randomized, double-blind, parallel-group protocol. Injections were self-administered for 4 weeks, three times daily, 30 min before each meal. The volunteers were asked to maintain their regular diet and level of physical exercise during the study period. Subjects' body weight, energy intake, and levels of adipose hormones were assessed at the start and end of the study. Body weight was reduced by 2.3 +/- 0.4 kg in the treatment group over the study period compared with 0.5 +/- 0.5 kg in the control group (P = 0.0106). On average, the treatment group had an additional 0.45-kg weight loss per week. The treatment group demonstrated a reduction in leptin and an increase in adiponectin. Energy intake by the treatment group was significantly reduced by 170 +/- 37 kcal (25 +/- 5%) at the initial study meal (P = 0.0007) and by 250 +/- 63 kcal (35 +/- 9%) at the final study meal (P = 0.0023), with no change in subjective food palatability. Oxyntomodulin treatment resulted in weight loss and a change in the levels of adipose hormones consistent with a loss of adipose tissue. The anorectic effect was maintained over the 4-week period. Oxyntomodulin represents a potential therapy for obesity.

We examined whether short-term treatment with a thiazolidinedione improves insulin sensitivity in non-obese but insulin-resistant subjects and whether this is associated with an improvement in dysregulated adipose tissue (reduced expression of IRS-1, GLUT4, PPARgamma co-activator 1 and markers of terminal differentiation) that we have previously documented to be associated with insulin resistance. Ten non-diabetic subjects, identified as having low IRS-1 and GLUT-4 protein in adipose cells as markers of insulin resistance, underwent 3 weeks of treatment with pioglitazone. The euglycaemic-hyperinsulinaemic clamp technique was used to measure insulin sensitivity before and after treatment. Serum samples were analysed for glucose, insulin, lipids, total and high-molecular-weight (HMW) adiponectin levels. Biopsies from abdominal subcutaneous adipose tissue were taken, cell size measured, mRNA and protein extracted and quantified using real-time RT-PCR and Western blot. Insulin sensitivity was improved after 3 weeks treatment and circulating total as well as HMW adiponectin increased in all subjects, while no effect was seen on serum lipids. In the adipose cells, gene and protein expression of IRS-1 and PPARgamma co-activator 1 remained unchanged, while adiponectin, adipocyte P 2, uncoupling protein 2, GLUT4 and liver X receptor-alpha increased. Insulin-stimulated tyrosine phosphorylation and p-ser-PKB/Akt increased, while no significant effect of thiazolidinedione treatment was seen on the inflammatory status of the adipose tissue in these non-obese subjects. Short-term treatment with pioglitazone improved insulin sensitivity in the absence of any changes in circulating NEFA or lipid levels. Several markers of adipose cell differentiation, previously shown to be reduced in insulin resistance, were augmented, supporting the concept that insulin resistance in these individuals is associated with impaired terminal differentiation of the adipose cells.

Side effects of zolendronic acid (ZA) and RANKL inhibitors (RANKL-I) include impaired wound healing and osteonecrosis of the jaw. Platelet rich fibrin (PRF) enhances wound healing and bone remodelling in vivo and in vitro. However, the topical use PRF in the surgical treatment of patients with medicament-related osteonecrosis of the jaw is relatively new and not thoroughly investigated. Furthermore, the potential attenuation of the PRF effect following antiresorptive treatment remains unclear. Therefore, we investigated the concentration of growth factors within the PRF in healthy volunteers and in patients with antiresorptive treatment. Blood samples from healthy volunteers and patients were used to produce PRF. The levels of EGF, VEGF, PDGF-BB, TGF-β1, BMP-2, and CD31 in the PRF was investigated by ELISA. ZA treatment induced a significant decrease in EGF and TGF-β1 levels, whereas RANKL-I caused lower TGF-β1 levels. Reduced EGF levels in PRF after ZA treatment may explain the delayed wound healing and question the positive effect of PRF in these patients. PRF use in patients undergoing RANKL-I treatment seems to be more justified.