Serum Markers Research Articles

Impact of Menstrual Cycle and Oral Contraceptives on Haematological and Inflammatory Biomarkers in Highly Trained Female Athletes.

Haematological and inflammatory biomarkers play an important role in athlete performance and health, with some of them used in the fight against doping. However, little is known about how they are modulated by sex hormone fluctuations in highly trained female athletes. We therefore measured the haematological parameters monitored in the athlete biological passport (ABP) as well as erythropoietin, serum markers of iron and inflammatory statuses (iron, ferritin, transferrin, transferrin saturation, albumin, creatinine, total protein, interleukin-6 and TNF-alpha) in 20 highly trained female athletes: 10 with normal menstrual cycle (NMC) during the early follicular and mid-luteal phases and 10 using a combined oral contraceptive (COC, i.e., ethinyloestradiol and levonorgestrel) during active and inactive hormone intake. Body composition, leptin and lipid profile (total cholesterol, HDL, LDL and triglycerides) were determined in parallel. No changes were observed throughout NMC phases. Irrespective of active/inactive pill intake, COC use increased transferrin, triglycerides as well as reticulocyte count (p < 0.05) and decreased interleukin-6 (p < 0.05), with no significant changes in the other parameters studied. In conclusion, given our results across NMC phases in highly trained athletes, it seems warranted to investigate whether intense physical training would mitigate the impact of endogenous sex hormones on body composition and haematological and inflammatory parameters. In addition, further studies are needed to determine the extent of the changes induced by COCs on these blood biomarkers in elite female athletes when subjected to extreme environments such as intensive training or competition in humid heat, cold and/or hypoxia or when using other medications in parallel.

Investigating the clinical significance of E2F5 expression in circulating extracellular vesicles in prostate carcinoma.

Prostate-specific antigen (PSA) based screening strategy has caused a marked improvement in prostate cancer detection and reduction in associated mortality. However, its specificity and sensitivity is not optimal for differentiating different forms of prostate cancer, resulting in overtreatment of indolent tumors. E2F5, a member of the family of transcription factors plays essential roles during many cellular processes. E2F5 amplification is a major event in PCa. A liquid biopsy is a minimally invasive procedure to investigate the cancer-related molecules in circulating tumor cells (CTCs), cell-free DNA, and extracellular vesicles (EVs). Serum and plasma are attractive sources of EV-based biomarkers as blood sample acquisition is a minimally invasive procedure. Given, the shortcomings of PSA as a serum marker, the suitability of E2F5 expression and chemical properties of EVs can be used for the diagnosis of clinically significant prostate cancer. To technically refine the current histopathology-based diagnosis of PCa by adding it to the molecular readouts specific to disease states and biochemical fingerprints of EVs. The study included 100 TRUS-biopsied tissues, 50 representing 4 Gleason grades and another 50 representing BPH. Expression of E2F5 was studied in all the qualified tissues by Immunohistochemistry (IHC). Blood from patients was collected and EVs were isolated and characterized. E2F5 was highly upregulated through all Gleason grades, the maximum being in Gleason 10(5 + 5) and the minimum in Gleason 7(3 + 4), as compared to BPH. The EVs isolated from blood plasma were within 30-200 nm in size. E2F5, being a transcription factor, is highly overexpressed in malignant biopsy tissues, through all Gleason grades. BPH tissues served as control samples. EVs from blood plasma might serve as a potential liquid biopsy marker for predicting disease progression and better prognosis.

Development and validation of a combined radiomic and clinical model based on contrast-enhanced ultrasound for preoperative prediction of CK19-positive hepatocellular carcinoma.

We aimed to develop and validate a combined model integrating radiomic features derived from Contrast-Enhanced Ultrasound (CEUS) images and clinical parameters for preoperative prediction of CK19-positive status in hepatocellular carcinoma (HCC). A total of 434 patients who underwent CEUS and surgical resection from January 2020 to December 2023 were included. Patients were randomly divided into a training cohort (n = 304) and a validation cohort (n = 130). Radiomic features were extracted from multiphase CEUS images, including two-dimensional ultrasound (US), arterial, portal venous, and delayed phases, and combined to derive a Radscore model. Subsequently, a Combined Model was constructed using the Radscore and clinical parameters. Model performance was assessed using calibration, discrimination, and clinical utility. Multivariate logistic regression analysis identified Radscore (OR = 10.054, 95% CI: 5.931-19.120, p < 0.001) and AFP levels > 200ng/mL (OR = 5.027, 95% CI: 2.089-12.784, p < 0.001) as significant predictors in the combined model. The AUC (Area Under the Curve) for the Combined Model was 0.954 in the training cohort and 0.927 in the validation cohort, compared to 0.939 and 0.917 for the Radscore Model alone. Calibration curves demonstrated strong concordance between predicted and actual outcomes. Decision curve analysis (DCA) showed that both the Radscore Model and the Combined Model exhibited good net benefits across a wide range of threshold values in both the training and validation cohorts. The Radscore based on CEUS, combined with the serum markers AFP > 200ng/L to construct a Combined Model, shows good predictive performance for CK19 + hepatocellular carcinoma (HCC).

Differential expression of CD175 and CA19-9 in pancreatic adenocarcinoma

Alterations in protein glycosylation are observed in many solid tumor types leading to formation of tumor-associated carbohydrate antigens (TACAs). The most common TACA is the Tn antigen (CD175), which is a mucin-type O-GalNAc-Ser/Thr/Tyr glycan in membrane and secreted glycoproteins. In addition, two other TACAs are CA19-9 (sialyl-Lewis a), which is used as a prognostic serum marker for pancreatic cancer, and its isomer sialyl-Lewis x (SLex, CD15s), which is overexpressed in many cancer types and associated with metastasis. While CD175 and other TACAs may be expressed by many human carcinomas, little is known about their differential expression patterns in tumors, thus limiting their use as tissue biomarkers or therapeutic targets. Here we address the clinicopathological relevance of the expression of CA19-9, CD15s, and CD175 in pancreatic ductal adenocarcinoma (PDAC) tissues. Semi-quantitative IHC staining with well-defined monoclonal antibodies demonstrates that CD175 is expressed in all PDAC specimens analyzed. Unexpectedly, however, these TACAs are differentially expressed within PDAC specimens and their glycoproteins, but not significantly expressed in adjacent normal tissues. These data provide avenues for novel therapeutic approaches that could combine CD175- and CA19-9-targeting therapies for PDAC patients.

Xinnaoxin capsule alleviates neuropathological changes and cognitive deficits in Alzheimer's disease mouse model induced by D-galactose and aluminum chloride via reducing neuroinflammation and protecting synaptic proteins.

Originally formulated to mitigate high-altitude sickness, Xinnaoxin capsules (XNX) are composed of three traditional Chinese medicines (Rhodiola rosea L., Lycium barbarum L. and Hippophae rhamnoides) with properties of anti-hypoxia, anti-fatigue, and anti-aging. Emerging evidence now suggests that XNX may also offer therapeutic benefits in Alzheimer's disease (AD), highlighting its potential significance in the development of novel AD treatments. This study aims to investigate whether XNX improves AD-related behavioral and cognitive deficits by enhancing antioxidant defenses, reducing peripheral and neuroinflammation, and protecting neurons. The AD mouse model was established using D-galactose and aluminum chloride. Spatial memory and anxiety-like behaviors were assessed via the Morris water maze and open field tests to evaluate the therapeutic effects of XNX. Biochemical markers in hippocampal tissue and serum were measured using ELISA kits, while serum chemical composition was analyzed by LC-MS. Histopathological changes and amyloid-β deposition in the hippocampus were examined through hematoxylin-eosin (HE) staining and immunofluorescence. Additionally, hippocampal expression of apoptotic proteins Bax and Caspase-3, anti-apoptotic protein Bcl-2, and synaptic proteins PSD-95 and Syn were assessed via Western blot. Behavioral tests demonstrated that XNX significantly improved spatial learning and memory abilities, as well as reduced anxiety-like behaviors in AD mice. XNX also modulated inflammatory cytokines and oxidative stress markers in hippocampal tissue and serum, while reducing amyloid-β deposition. Further LC-MS analysis of serum revealed a marked upregulation of compounds such as adenosine following treatment, with key metabolic pathways affected, including linoleic acid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. HE staining and immunofluorescence indicated that XNX ameliorated neuronal damage and decreased amyloid-β accumulation. Western blot analysis confirmed that XNX inhibited neuronal apoptosis and preserved synaptic proteins in the hippocampus. XNX mitigates AD-induced behavioral and cognitive deficits by enhancing antioxidant defenses, reducing peripheral and neuroinflammation, and protecting neurons. Our findings provide valuable data and a theoretical foundation for the potential therapeutic application of XNX in AD treatment and its further development.

Prognostic significance of serum complement activation, neutrophil extracellular traps and extracellular DNA in newly diagnosed epithelial ovarian cancer.

We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes. We conducted a two-center prospective study of patients with newly diagnosed EOC (N=188). Blood and ascites fluid were collected at diagnosis for biomarker analysis. Patients were evaluated for progression-free survival (PFS) and overall survival (OS). The median OS was 47months (95% CI: 34-58) and the median PFS was 12months (95% CI: 11-15). Pre-treatment serum levels of genomic DNA (gDNA), markers of neutrophil degranulation (myeloperoxidase [MPO]) and neutrophil extracellular traps (NETs) (citrullinated histone H3 [CitH3]), and complement activation (C3b/c) were each associated with worse OS in univariate analysis. In multivariate analyses controlling for age, stage, and optimal debulking, serum gDNA, MPO, and CitH3 remained associated with worse OS, while C3b/c levels were not. In an exploratory analysis, the largest magnitude of difference in 2-year OS occurred in patients with low C3b/c and low CitH3 compared to all other patients (87% vs 46% survival, respectively). In ascites fluid, increased factor H, a negative regulator of complement activation, was associated with improved OS in univariate analysis. These results point to serum gDNA, NETs, and complement activation as potential prognostic biomarkers in patients with newly diagnosed EOC.

Pro-inflammatory diet affects markers of iron metabolism in healthy older adults.

Inflammation and inadequate nutrition are common in older age and known to affect iron homeostasis. However, it is not known whether a pro-inflammatory diet affects iron status in older adults. We investigated the diet quality of healthy older adults considering markers of iron homeostasis and inflammation compared to a younger control. Serum markers of iron metabolism (iron, transferrin, ferritin, hepcidin, soluble transferrin receptor [sTfR]) and inflammation (interleukin-6 [IL-6], IL-10 high-sensitive C- reactive protein [hsCRP]) were quantified using immunosorbent assays. Insulin resistance was determined by calculating the homeostasis model assessment index (HOMA-IR). The Dietary Inflammatory Index® (DII) was computed based on dietary intake and inflammatory (ID) or less inflammatory diet (LID) groups were created by using median DII score specific to age group and sex. DII did not differ by age (p = 0.668, n = 80, F: 75 %, >65 years, n = 60, F: 72 %, ≤35 years). Iron and inflammation status were different between age groups in terms of higher transferrin saturation, sTfR, ferritin and IL-6 concentrations in the old (all p ≤ 0.001). Only in older adults, BMI, HOMA-IR, hsCRP, ferritin and hepcidin concentrations were significantly higher in ID compared to LID (all p < 0.01). In addition, a risk-factor adjusted regression analysis showed that ID was independently associated with higher ferritin and hepcidin concentrations in older adults. In older age, a pro-inflammatory diet is associated with systemic inflammation and disturbed iron homeostasis.

Change in glucose, insulin and serum lipids due to ultra-processed food consumption in children with obesity.

While the association between ultra-processed food (UPF) consumption and chronic non-communicable diseases in adults is well-established, its relationship with serum markers of chronic diseases in children remains underexplored. This research investigates changes in serum markers in children with obesity during a trial aimed at reducing UPF consumption. The study is a prospective cohort, based on a parallel randomized controlled trial conducted between August 2018 and February 2020, with children aged 7-12 years. Over 6 months, children and their guardians attended monthly consultations and educational activities aimed at reducing UPF consumption. Body weight, height, and 24-h dietary recall were measured at all visits. Serum markers were collected at baseline and at the 2- and 5-month visit (during the intervention). Data from 95 children were analysed. Body mass index (BMI), UPF consumption in grams and energy, and percentage of UPF in grams showed a quadratic trend, initially decreasing, followed by an increase in the following months. Glucose, insulin, and HOMA-IR decreased throughout the study, but after adjustment for BMI, the associations no longer persisted, except for glucose levels, which decreased linearly by 2.25 mg/dL. Reducing UPF consumption may lower blood glucose levels in children with obesity, independent of BMI changes.

Copaiba essential oil carried in a self-nanoemulsifying drug delivery system improves adjuvant-induced arthritis in rats.

Copaiba essential oil (CEO) is obtained through the distillation of copaiba balsam and has been used in the traditional medicine to treat inflammatory conditions. However, the highly lipophilic nature of CEO restricts its pharmaceutical use. This study evaluated the effect of CEO, carried in a self-nanoemulsifying drug delivery system (SNEDDS), on articular and systemic inflammation and liver changes in Holtzman rats with Freund's adjuvant-induced arthritis. Healthy and arthritic rats received orally for 18 days the non-formulated CEO and the one carried in a self-nanoemulsifying drug delivery system (FSNEDDS), both at doses of 50 and 100mg/kg. The oral bioavailability of FSNEDDS was determined in healthy rats by quantifying the levels of β-caryophyllene in the plasma. FSNEDDS exhibited more than three times greater oral bioavailability compared to non-formulated CEO. This phenomenon allowed FSNEDDS (100mg/kg) to effectively reduce adjuvant-induced articular and systemic inflammation and oxidative stress in arthritic rats at a dose four times lower than copaiba balsam and β-caryophyllene. Furthermore, FSNEDDS did not alter the serum markers of liver damage, hepatic morphometry, and liver gluconeogenesis in healthy rats. FSNEDDS was effective against arthritis in rats, and unlike copaiba balsam, it does not exhibit hepatotoxicity, suggesting it could serve as a phytotherapeutic alternative in the treatment of rheumatoid arthritis.

P-2201. A Comprehensive Kidney Biomarker Panel to Assess Kidney Health after Hepatitis C Direct Acting Antiviral Therapy in Persons with HCV monoinfection and HCV/HIV coinfection

Abstract Background Chronic Hepatitis C virus (HCV) infection is associated with greater risk of chronic kidney disease and proteinuria. We examined effects of 12 weeks of elbasvir/grazoprevir, an HCV NS5A inhibitor/NS3/4A Protease Inhibitor on glomerular filtration (creatinine, cystatin C), injury (albuminuria), and 9 novel kidney tubule biomarkers in adults with HCV infection over a 24-week period.Figure.Percent Change (95% Confidence Interval) from Baseline of Urine Kidney Tubule Markers 24 weeks after initiating Elbasvir/Grazoprevir in Patients with HCV Methods We included 36 participants with HCV (7 with HIV coinfection) from the San Francisco Bay Area. Urine biomarkers included kidney tubule function (α-1-microglobulin [α1m], β-2-microglobulin [β2m]) and injury (kidney injury marker-1 [KIM-1], neutrophil gelatinase-associated lipocalcin [NGAL], (interleukin-18 [IL-18]), fibrosis/repair (monocyte chemoattractant protein 1 [MCP-1], chitinase-3-like protein-1 [YKL-40]) and synthetic function (epidermal growth factor [EGF], uromodulin [UMOD]). Biomarkers were measured at baseline, wk 12 (end of treatment), and week 24 (time of assessment for sustained virologic response [SVR]). We used linear mixed regression models with time as the main predictor to assess changes in kidney health, adjusting for demographics and urine creatinine. Results Over two thirds identified as Black/African American;89% were men and median age was 62 years. All but 2 achieved an SVR and 17% had advanced liver fibrosis using the FIB-4 serum marker. Median (interquartile range) for eGFRcr, eGFRcys, and urine albumin to creatinine ratio (ACR) were 82(63-100 ml/min),74(58-87 ml/min), and 10.4(4.9-24 mg/g), respectively at baseline. The percent (%) change from baseline for eGFRcr and ACR at weeks 12 and 24 was not statistically significant; eGFRcys was -11.4% lower (95%CI:-18%,-4.6%) at week 24. After 12 weeks of treatment, there were significant reductions in α1m, β2m, KIM-1, and MCP-1, with smaller reductions seen in most other markers (Figure). At week 24, these reductions were sustained for KIM-1. Conclusion Our findings suggest that HCV treatment with elbasvir/grazoprevir improves proximal tubule function and reduces cellular injury and fibrosis. Further research is needed to understand longer-term trends in kidney health following HCV cure. Disclosures Michelle Estrella, MD, Astra Zeneca: Board Member|Bayer: Grant/Research Support|Boehringer Ingelheim: Board Member Michael Shlipak, MD, Astra-Zeneca: Honoraria|Bayer: Grant/Research Support|Bayer: Honoraria|Boehringer Ingelheim: Honoraria Phyllis C. Tien, MD, MSc, Merck: Grant/Research Support

The impact of sleep interventions combined with enhanced nutritional support on sleep quality, nutritional status, pain management, psychological well-being, and quality of life in postoperative colon cancer patients

ObjectiveTo investigate the synergistic effects of combined sleep interventions and enhanced nutritional support on postoperative recovery in colon cancer patients, with a focus on sleep quality, nutritional status, pain management, psychological well-being, and quality of life.MethodsThis randomized controlled trial included 290 postoperative colon cancer patients admitted to the First Affiliated Hospital of Soochow University between May 2021 and May 2023. Participants were randomized into two groups: the intervention group, which received standard care supplemented with sleep and nutritional interventions, and the control group, which received standard care alone. Outcomes were assessed pre- and post-intervention, including the Pittsburgh Sleep Quality Index (PSQI), nutritional markers (serum albumin, prealbumin, body weight, etc.), Visual Analog Scale (VAS) for pain, Self-Rating Anxiety and Depression Scales (SAS, SDS), and EORTC QLQ-C30 quality of life scores.ResultsThe intervention group demonstrated significantly greater improvements across all assessed domains compared to the control group ( P < 0.005 after Bonferroni correction). Sleep quality (PSQI: 7.81 vs. 10.43, d = 0.81) and nutritional markers (e.g., prealbumin: 230.19 mg/L vs. 188.01 mg/L, d = 1.21 ) improved markedly. Similarly, reductions in pain (VAS: 2.65 vs. 5.19,d = 1.09 ), anxiety (SAS: 42.03 vs. 49.45, d = 0.88), and depression (SDS: 38.17 vs. 49.77,d = 1.02 ) were observed. Quality of life scores significantly increased in the intervention group compared to the control group (EORTC QLQ-C30: 99.29 vs. 88.41, d = 0.92).ConclusionThe combined intervention of sleep enhancement and nutritional support significantly accelerated postoperative recovery in colon cancer patients, demonstrating synergistic effects that improved physical, psychological, and quality-of-life outcomes. These findings underscore the value of integrating multifaceted interventions into standard postoperative care to optimize recovery trajectories and overall well-being.

FGF21 and APOA1 mRNA-based therapies for the treatment of experimental acute pancreatitis

BackgroundAcute pancreatitis (AP) presents a significant clinical challenge with limited therapeutic options. The complex etiology and pathophysiology of AP emphasize the need for innovative treatments. This study explores mRNA-based therapies delivering fibroblast growth factor 21 (FGF21) and apolipoprotein A1 (APOA1), alone and in combination, for treating experimental AP.MethodsLiver-targeted lipid nanoparticles (LNP)-mRNA formulations encoding FGF21, APOA1, and a chimeric APOA1-FGF21, were first tested for protein expression and bioavailability in vitro and in mice fed a high-fat diet. Efficacy studies were performed in the caerulein-induced AP (Cer-AP) model, and a new AP model combining ethanol feeding with ethanol binge plus palmitoleic acid administration, the EtOH/POA-AP model. A single dose of the APOA1, FGF21, and APOA1-FGF21 LNP-mRNAs formulations was administered in both models. Serum levels of pancreatic lipase (LIPC), amylase (AMYL), and aspartate aminotransferase (AST), along with pancreatic tissue analyses using two histopathological scores were performed to evaluate treatment effects.ResultsIn vitro studies demonstrated the translation and secretion of APOA1, FGF21, and APOA1-FGF21 proteins encoded by the LNP-mRNAs. In vivo, LNP-mRNA administration increased serum levels of the respective proteins in metabolically impaired (i.e. high fat diet-fed) mice. In the Cer-AP model, serum markers of pancreatic injury were similarly reduced when mice were treated with APOA1, FGF21, and APOA1-FGF21 LNP-mRNA, and this effect was also observed in the histopathological analyses. The EtOH/POA-AP model was more aggressive than the Cer-AP model. FGF21 and APOA1-FGF21 LNP-mRNAs were protective according to LIPC and AMYL serum levels, while APOA1 LNP-mRNA had little effect. On the other hand, histological improvements were more evident in mice receiving APOA1 LNP-mRNA. In the EtOH/POA-AP model, FGF21 and APOA1-FGF21 LNP-mRNAs reduced serum AST levels, indicating hepatoprotective activity.DiscussionThis proof-of-concept study demonstrates the potential of mRNA-based therapies delivering FGF21 and APOA1 in experimental AP. While individual treatments effectively reduced pancreatic injury, the APOA1-FGF21 fusion molecule did not exhibit superior activity. Liver-targeted LNP-mRNA administration may offer a promising approach for treating AP, leveraging endogenous production pathways for therapeutic proteins. Further research is warranted to elucidate the mechanisms underlying their therapeutic efficacy and optimize treatment regimens for clinical translation.

Markers for Pressure Injury Risk in Individuals with Chronic Spinal Cord Injury: A Pilot Study.

To identify markers associated with pressure injury (PrI) history in individuals with spinal cord injury (SCI) using two approaches: skin blood flow (SBF) response toward localized heating, and serum marker for insulin resistance. For this cross-sectional, observational study of adults with chronic traumatic SCI at T12 and above, researchers recruited two groups of participants: with history of PrI (group 1), and without history of PrI (group 2). The study protocol included obtaining fasting blood samples and measurement of SBF at bilateral heels with localized heating of 42 °C for 30 minutes from all participants. Primary SBF outcomes were initial peak and plateau SBF normalized to baseline SBF. The primary outcome for insulin resistance was Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), calculated from fasting plasma glucose and insulin. Secondary outcomes included demographic and SCI information. Researchers used the Fisher exact test and Wilcoxon-Mann-Whitney test to compare the intergroup difference of categorical and continuous variables, respectively. Sixteen adults completed this study (group 1, n = 7; group 2, n = 9). In comparison with group 2, group 1 had significantly higher HOMA-IR (3.90 ± 0.71 vs 1.45 ± 0.71), suggesting higher insulin resistance, and longer duration of injury (22.54 ± 7.24 vs 7.98 ± 6.58 years). There were no between-group differences in SBF or other secondary outcomes. HOMA-IR is a novel serum index associated with PrI history in persons with chronic SCI. Future longitudinal study is warranted to examine the role of insulin resistance in increasing PrI risk for the SCI population.

Soybean Flour Fortified with Gryllus assimilis Powder to Increase Iron Bioavailability Improves Gut Health and Oxidative Balance In Vivo

Background: Insects like Gryllus assimilis have an excellent nutritional profile, including iron. However, the bioavailability of this iron and its effects on intestinal health and oxidative balance remain unclear. To enhance acceptance, insects can be used in powder form and combined with common flours. Objective: This study evaluates the effects of Gryllus assimilis powder, alone or with soy flour, on iron bioavailability, intestinal health, and oxidative balance in rodents. Methods: Using the hemoglobin depletion/repletion method, 32 male Wistar rats were divided into four groups: A (standard diet + ferrous sulfate), B (diet + Gryllus assimilis + soy flour), C (diet + Gryllus assimilis), and D (diet + soy flour). Hemoglobin levels, regeneration efficiency, biological value, serum markers, intestinal health, and oxidative balance were assessed. Results: Food intake, weight gain, and bioavailability measures showed no differences. However, the Gryllus + soy group showed higher weekly and final hemoglobin levels than Gryllus alone. This combination also improved acetic acid levels, fecal moisture, and oxidative balance, increasing superoxide dismutase activity while reducing peroxidation products compared to Gryllus alone. Conclusion: These findings highlight the potential benefits of combining Gryllus assimilis with soy flour for iron bioavailability and overall health.

Magnesium and Osteoporosis: A Meta-Analysis of the Effects on Bone Turnover Markers, Fracture Incidence, and Quality of Life

Background: Osteoporosis, a prevalent bone disease characterized by reduced bone mineral density (BMD) and increased fracture risk, poses a significant public health challenge. Magnesium, an essential mineral involved in bone metabolism, has emerged as a potential therapeutic agent. This meta-analysis aimed to evaluate the effects of magnesium supplementation on bone turnover markers, fracture incidence, and quality of life in individuals with osteoporosis. Methods: A systematic search of PubMed, Embase, and Cochrane Library databases was conducted from January 2013 to December 2024 to identify randomized controlled trials (RCTs) investigating the impact of magnesium supplementation on adults diagnosed with osteoporosis. The primary outcomes were changes in bone turnover markers (serum calcium, phosphorus, alkaline phosphatase, and osteocalcin), fracture incidence, and quality of life scores. Standardized mean differences (SMD) and risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models. Results: Nine RCTs met the inclusion criteria, encompassing a total of 825 participants. Magnesium supplementation demonstrated a significant improvement in bone turnover markers, with a decrease in serum alkaline phosphatase (SMD = -0.35; 95% CI: -0.62, -0.08; p = 0.01) and osteocalcin (SMD = -0.29; 95% CI: -0.51, -0.07; p = 0.009). A trend towards reduced fracture incidence was observed in the magnesium group (RR = 0.72; 95% CI: 0.51, 1.02; p = 0.06). Furthermore, magnesium supplementation significantly improved quality of life scores, as measured by the Osteoporosis Quality of Life Questionnaire (OQLQ) (SMD = 0.41; 95% CI: 0.15, 0.67; p = 0.002). Conclusion: This meta-analysis provides evidence that magnesium supplementation may have beneficial effects on bone turnover markers and quality of life in individuals with osteoporosis. Although a trend towards reduced fracture incidence was observed, further large-scale RCTs are warranted to confirm this finding.

Predictive value of prenatal screening markers combined with serum placental growth factor in early pregnancy for preeclampsia

Objective: To observe the predictive value of prenatal screening markers combined with serum placental growth factor(PLGF) in early pregnancy for preeclampsia(PE). Methods: This was a prospective study. A total of 369 pregnant women undergoing early pregnancy examinations were selected at Jingmen Central Hospital from August 2024 to January 2025 and divided into the PE group(n=43) and the normal group(n=326) according to the presence of PE during the follow-up. The levels of prenatal screening markers alpha-fetoprotein(AFP), serum PLGF, β-human chorionic gonadotropin(β-hCG) and pregnancy-associated plasma protein-A(PAPP-A) were compared between the two groups. Results: There were 43 patients experiencing PE, with an incidence of 11.65%. The levels of PLGF, β-hCG and PAPP-A were significantly decreased in the PE group compared with those in the normal group, and the differences between the groups were statistically significant (all P&lt;0.05). Logistic regression analysis showed that increased prenatal screening markers AFP, serum PLGF, HCG and PAPP-A were independent risk factors for PE, with statistically significant differences between the groups (all P&lt;0.05). Finally, the results of ROC curve analysis showed that the AUCs of AFP, PLGF, β-hCG and PAPP-A were 0.618, 0.645, 0.690, and 0.645, respectively, and the AUC of combined prediction was 0.825, which was significantly increased compared with that of each marker alone, with statistically significant differences(P&lt;0.05). Conclusion: The development of PE in pregnancy is closely related to the levels of AFP, PLGF, β-hCG and PAPP-A. The predictive efficiency of combined detection of AFP, PLGF, β-hCG and PAPP-A for PE in pregnancy significantly increases. Project Title: sFlt-1/PlGF based combined early pregnancy prenatal screening marker Nursing Strategies and Application in Preeclampsia Risk Assessment, Project Number: 2024YFYB111, Year: 2024. doi: https://doi.org/10.12669/pjms.41.2.9794 How to cite this: Shu Z, Wang W. Predictive value of prenatal screening markers combined with serum placental growth factor in early pregnancy for preeclampsia. Pak J Med Sci. 2025;41(2)598-602. doi: https://doi.org/10.12669/pjms.41.2.9794 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The Ethanol Extract of Sugemule-3 Decoction Treats Isoproterenol-induced Heart Failure in Rats via PPARγ/PGC-1 Pathway

Background The herbs Baidoukou (the fruit of Amomum compactum Sol. ex Maton), Baijusheng (the fruit of Lactuca sativa L.), and Biba ( Piper longum L.) make up the traditional Mongolian medicine known as Sugemule-3 decoction. Purpose: Heart failure (HF) is severely impacted; however, the pharmacological mechanism behind it is yet unclear. This investigation looked at the Sugemule-3 ethanol extract’s therapeutic mechanism for isoproterenol-induced HF in rats. Methods To create a HF model, isoproterenol was administered to Wistar rats. Following the model’s successful establishment, various medications were administered for 4 weeks. The electrical signals of cardiac fluctuations, cardiac morphology, and function were observed using electrocardiogram (ECG) and echocardiography. The rats were killed 4 weeks later, and the hearts were observed using an electron microscope and HE staining. Cardiomyocyte apoptosis was observed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. The levels of markers in serum were determined using enzyme-linked immunosorbent assay (ELISA). Western blot and immunohistochemistry were used to detect the expression of proteins in rats. Results Our findings show that isoproterenol injection subcutaneously interfered with the structure and function of the left ventricle, particularly during systole. In the model group, the level of oxidative stress index malondialdehyde ( p &lt; 0.01) increased with the decrease in anti-oxidant enzymes such as superoxide dismutase ( p &lt; 0.01) and glutathione peroxidase ( p &lt; 0.01). Sugemule-3 ethanol extract considerably reduced the harmful effects of isoproterenol on the rat myocardium. Additionally, isoproterenol increased the level of peroxisome proliferator-activated receptor (PPAR), carnitine palmitoyl transferase-1 (CPT-1), phosphoenolpyruvate carboxylase (PEPCK), stearyl CoA desaturase-1 (SCD-1), and ubiquitin-conjugating (UCB) expression while decreasing the level of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) expression, leading to cardiometabolic diseases. Sugemule-3 ethanol extract improved cardiac metabolism. Conclusion The findings demonstrate that Sugemule-3 ethanol extract may improve energy metabolism of cardiomyocytes and alleviate isoproterenol-induced HF through inhibiting the peroxisome proliferator-activated receptor gamma (PPARγ)/PGC-1 signaling pathway.

P0282 Fibroblast activation protein (FAP)-cleaved type III Collagen [C3F] is a potential marker for intestinal fibrosis in patients with Crohn’s Disease

Abstract Background Crohn ‘s disease (CD) is characterized by chronic inflammation in the gut, where severe complications such as fibrotic strictures require surgical resection. Stricture development involves excessive extracellular matrix (ECM) deposition due to continuous activation of intestinal myofibroblasts, that further contribute to intestinal fibrogenesis. Emerging data suggests that stricture-related intestinal myofibroblasts overexpress a serine protease called fibroblast activation protein (FAP). Furthermore, type III collagen deposition is increased during fibrosis in all layers of the intestinal tract, and studies have shown elevated collagen degradation in serum from patients with CD. The present study aimed at evaluating the potential of FAP-cleaved type III collagen [C3F] as a serum marker for intestinal fibrosis in CD. Methods The cohort consisted of 49 patients with luminal CD and 62 patients with stenotic CD. Clinical assessment was conducted for all patients at baseline and 12 months post study initiation. For the luminal phenotype, endoscopy was performed at both time points. For the stenotic group, radiographical assessment was done prior to surgery and endoscopy was performed at 12 months. C3F was measured in serum at all timepoints for baseline, post-operative day (POD), 1, 3, 6 and 12 months. To compare C3F levels at baseline for luminal vs stenotic phenotype, Mann-Whitney U-test was conducted. For the stenotic group, mixed-effect analysis, with a Dunnett’s multiple comparison, was conducted to compare C3F levels for baseline vs POD and Spearman’s rank correlation was applied. Results C3F baseline levels were significantly higher in patients with stenotic CD compared to luminal CD (Figure 1). In the stenotic group, C3F was significantly increased in patients at POD compared to baseline (Figure 1). Furthermore, C3F showed a positive correlation with C-reactive protein (CRP) (ρ=0.28, p=0.006) and a significant negative correlation with disease duration (ρ= -0.257, p=0.048) for patients with the stenotic CD phenotype (Table 1). Conclusion C3F was elevated in patients with stenotic CD, with even higher levels after the surgical resection. The data suggests that C3F reflects fibroblast activity during fibrostenosis and tissue remodeling following surgery. The positive correlation with CRP supports the association with inflammation leading to collagen deposition and fibrosis. Interestingly, C3F shows negative correlation with disease duration suggesting that C3F could reflect fibrosis at early stages of stenotic CD. These findings highlight the potential use of C3F as a novel biomarker for intestinal fibrosis in CD.

P0349 Gasdermin D: A New Inflammatory Biomarker in Assessing Clinical Disease Activity in Crohn’s Disease

Abstract Background Crohn’s disease (CD) is a progressive, destructive, inflammatory bowel disease. Despite new treatment options in form of biologic and small-molecule therapy, a significant portion of CD patients require surgical interventions during disease course. Assessment of treatment response and disease activity is crucial in management of patients with CD. Gasdermin D (GSDMD) is a protein which belongs to the gasdermin protein family and plays a role in inflammatory cell death, pyroptosis. GSDMD activation has been shown to be related to inflammatory states in a variety of disorders, including inflammatory bowel diseases. Given the role of GSDMD in inflammation, we hypothesized that serum GSDMD levels of patients with CD may be linked to disease activity; thereby revealing a potential new inflammatory serum marker for assessing disease severity in CD patients in a non-invasive manner. Methods This prospective study was carried out at Antalya Training and Research Hospital, Turkey, between September 2022 and June 2024. 61 CD patients were enrolled in the study. Age, sex, body mass index (BMI), smoking status, time since CD diagnosis, treatment modality used at the time of enrollment, concurrent use of steroids, previous medical and surgical treatment history for CD, involvement site of CD (ileum only or ileocolonic involvement) and Harvey-Bradshaw Index (HBI) results were recorded at the day of blood sampling. Laboratory workout utilized in the study comprised WBC, ESR, CRP and GSDMD. Results Correlations between study parameters and GSDMD levels were investigated. GSDMD was found to be statistically significantly negatively correlated with age (r=-0.30, p=0.018). GSDMD was found to be statistically significantly positively correlated with CRP (r=0.26, p=0.041). Smoking was strongly correlated with increased GSDMD levels. Non-smokers (n=53) had a median serum GSDMD level of 3.03 ng/ml, compared to 8.29 in smokers (n=8) and this difference was statistically significant (p=0.001). GSDMD levels were found to be statistically significantly related to HBI (r=0.64, p=0.0001). Independent variables affecting serum GSDMD levels were investigated with multivariate logistic regression analysis. GSDMD levels were independently correlated with age (ß: -0,15, p=0.029), CRP (ß: -0,19, p=0.01) and HBI (ß: 0,95, p=0.000) of the patients. Conclusion This study is a pioneer study in revealing utility of serum GSDMD as a potential biomarker of clinical disease activity in patients with CD. Future studies will not only reveal more on the value of this biomarker as a tracker of clinical disease course, but also pave the path for a new potential therapeutic target in this burdensome disorder for both the patient and the healthcare team.

P0983 Addition of fibre to exclusive enteral nutrition (EEN) improves colonic effects and symptoms without compromising the benefits on small bowel paracellular permeability in healthy humans

Abstract Background How EEN works in Crohn’s disease is uncertain, but a unique compositional feature compared with whole-food diet is the absence of fibre. We aimed to determine the effects of EEN with and without fibre in healthy adults (to minimise confounders) on 1) intestinal barrier function, in the basal/fasting state and in response to acute stress; 2) inflammatory markers; 3) regional gut transit and fermentation; and 4) symptoms. Methods In a single-centre pilot study, 20 participants (age 33 [range 21-49] y, 10 female) were evaluated on their habitual diet and after 3 weeks of either ‘no-fibre EEN’ (n=10) or ‘fibre-EEN’ (22 g/d, 6 fibres) (n=10). Measures were: 1) small bowel permeability via 2-h lactulose:rhamnose ratio (LRR) in basal state and after 100 mg IV corticotrophin-releasing hormone (CRH) to simulate acute stress, and serum markers of lipopolysaccharide translocation; 2) intestinal and systemic inflammation via faecal calprotectin and serum C-reactive protein (CRP); 3) regional gut transit times and colonic H2 concentrations (carbohydrate fermentation) via a gas-sensing capsule; and 4) reported symptoms. Results There were no fibre-associated differences in barrier markers. EEN did not change basal barrier function overall, but normalised LRR when elevated (&amp;gt;0.05) on habitual diet (n=7; Fig 1). CRH-induced changes in LRR during the habitual diet were minimised by no-fibre EEN with a similar trend for fibre-EEN (Fig 2). CRP did not change. Calprotectin increased from median 11 (range: 0.5-44) to 41 (2-247) μg/g (p=0.006) with no-fibre-EEN and 13 (4-99) to 27 (4-167) μg/g (p=0.037) with fibre. Gastric emptying and small intestinal transit times on EEN ±fibre were not different to those on habitual diet, but colonic transit time was prolonged (36 [5-69] h) on no-fibre EEN compared with habitual diet (16 [6-24] h; p=0.04), but not on fibre-EEN (24 [16-44] vs 25 [0.4-89] h; p=0.32). Median colonic H2 concentrations were 11.2 [0.4-20.9]% with fibre vs (0.2 [0-7]%;) without fibre (p&amp;lt;0.001) The decreasing proximal-distal gradient in normalised H2 concentrations (1.7 [0-2.5] to 0 [0-1.3]%.h) with no-fibre were not seen for fibre-EEN (6.5 [0.7-12.6] to 10.6 [0.6-20.6]%.h) or habitual diet (3.2 [0-10.1] to 7.1 [0-13]%.h). Headaches in 6/10 within first week of no-fibre EEN and nausea in 9/10 were not reported with fibre-EEN, which induced abdominal pain in 2. Conclusion EEN ±fibre normalises basal small intestinal permeability and minimises stress-induced changes. The addition of fibre prevented marked prolongation of colonic transit, reduced carbohydrate fermentation and common symptoms with no-fibre EEN. Addition of fibre improves outcomes without compromising small intestinal action of EEN.