To explore mechanistic links between rheumatoid arthritis (RA) and periodontitis (PD) through the lens of subgingival microbial dysbiosis-mediated inflammation. Subgingival plaque from 100 volunteers with RA and PD (RAPD), 22 with RA (RAnoPD), 18 with PD (PDnoRA) and 19 healthy controls (noRAnoPD) was analysed using 16S-amplicon sequencing, semi-quantitative bead-based flow cytometry to measure crevicular fluid cytokines and ELISA to quantify antibodies to oral pathogens and systemic inflammatory markers in serum. The RAPD group had been randomised to receive intensive non-surgical periodontal therapy (PMPR) or oral hygiene alone and reviewed at 3 and 6 months in our previously reported study. Subgingival microbial dysbiosis, as evidenced by higher species richness, alpha-diversity and higher levels of known and putative periodontal pathobionts, was evident at baseline in RAnoPD, RAPD and PDnoRA. Higher serum antibodies to oral pathogens were recorded in RAPD. PMPR restored host-microbial homeostasis in RAPD within 3 months. Significant decreases in serum antibodies to microbial antigens and clinical measures of RA activity were seen after 3 and 6 months in the PMPR group but not controls. We demonstrate a mutualistic influence of RA and PD, beginning with RA-induced dysbiosis of the periodontal microbiome, progressing to periodontal inflammation and culminating in PD-driven exacerbation of systemic inflammation.

Ixazomib treatment has a dual effect on bone remodeling in patients with multiple myeloma: follow-up results from a phase 2 clinical study.

Integrated lipidomics and transcriptomics to elucidate heterogeneity between intramuscular and abdominal fat and identify serum and liver markers for their differential deposition in chickens.

The diagnostic value of hepatitis B core-related antigen in occult hepatitis B virus infection and its related hepatocellular carcinoma.

Background Preoperative oral carbohydrates (CHOs) have been widely utilized to improve perioperative outcomes. However, the effect of postoperative early enteral nutrition (EEN) intervention on patients’ postoperative recovery has yet to be validated by prospective outcomes. This study was designed to investigate the effect of preoperative oral CHOs combined with ENN nutrition on postoperative recovery in patients with colorectal cancer (CRC). Methods A multicenter, prospective, randomized controlled study was conducted on 331 CRC patients who underwent radical resection from March 1, 2022, to March 1, 2023 and were divided into Group A (preoperative oral CHOs combined with postoperative ENN group, n = 110), Group B (preoperative oral CHOs group, n = 110), and Group C (conventional control group, n = 111) according to the method of the randomized numerical table. The general clinical data, inflammatory indices, nutrition-related serum biomarkers, immune function, postoperative intestinal function recovery, complications and hospitalization length of the three groups were statistically analyzed. Results The baseline characteristics were similar among the groups. In the intention-to-treat analysis, the time to first exhaust ( p < 0.05) and defecation ( p < 0.05) was significantly shorter in group A than in groups B and C. The total protein (TP) level was significantly greater in group A than in groups B and C on the seventh postoperative day ( p < 0.05). In addition, the percentage of T-lymphocytes to lymphocytes on the third postoperative day was greater in Group A than in Groups B and C ( p < 0.05), and the length of hospitalization was significantly reduced. However, there was no difference in the incidence of postoperative complications. Conclusion Preoperative oral CHOs combined with postoperative EEN improved serum markers related to postoperative nutrition, enhanced the immunity of the body, and promoted early recovery of intestinal function. Preoperative oral CHOs combined with postoperative EEN is conducive to rapid postoperative recovery and reduces the length of hospitalization. Clinical trial registration https://www.chictr.org.cn/showproj.html?proj=144616 , identifier ChiCTR2100054459.

To analyze the influencing factors of chronic obstructive pulmonary disease (COPD) concomitant with pulmonary heart disease (PHD) and the diagnostic value of myocardial markers. A retrospective study was conducted on 117 COPD patients. According to whether there were concomitant PHD, 117 cases were distinguished as the combined group (45 cases) and uncombined group (72 cases). Independent risk factors were screened using multivariate logistic regression analysis. The levels of serum markers were determined. Pearson correlation analysis was used to evaluate the correlation between myocardial markers and cardiac function indicators. The expression of myocardial markers in different COPD severity groups was analyzed. The receiver operating characteristic curve (ROC) was adopted to evaluate the diagnostic value of serum markers. Compared with the uncombined group, patients in the combined group had significantly increased left atrial diameter (LAD), pulmonary artery pressure (PAP), and inducible co-stimulator ligand (ICOSL) levels, with decreased left ventricular ejection fraction (LVEF) levels (P < 0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP), creatine kinase myocardial band (CK-MB), and cardiac troponin I (cTnI) levels were also markedly increased (P < 0.05). CTnI, CK-MB, and NT proBNP were all negatively correlated with LVEF (r = -0.642, -0.587, -0.723, respectively, P < 0.001), and positively correlated with PAP (r = 0.698, 0.634, 0.781, respectively, P < 0.001). In patients with GOLD grades 3-4 even without concomitant PHD, the levels of cTnI, CK-MB, and NT proBNP were significantly higher than those in patients with GOLD grades 1-2 (P < 0.05). The area under the curve (AUC) of combined serum markers for predicting PHD in COPD patients was 0.921, with specificity and sensitivity of 88.89% and 86.11%, respectively. PAP, ICOSL, cTnI, CK-MB, and NT proBNP were all independent risk factors relating to the occurrence of COPD concomitant with PHD. The combined detection of cTnI, CK-MB, and NT-proBNP had certain diagnostic reference value for COPD concomitant with PHD. Monitoring these myocardial markers may provide clues for early identification of patients with COPD concomitant with PHD and assist in the clinical development of targeted intervention programs.

Background: The aim of this study was to evaluate the significance of serum concentrations of the inflammatory marker osteopontin, the blood–brain barrier damage marker occludin, and the neurodegeneration marker neurofilament light chain (NFL) in patients with relapsing-remitting multiple sclerosis (RRMS) for predicting disease activity and progression. Methods: This prospective cohort study enrolled 150 patients with RRMS. Initial serum levels of NFL, occludin, and osteopontin were compared between patients who met or did not meet the no evidence of disease activity (NEDA) criteria and its components (relapses, magnetic resonance imaging activity, and Expanded Disability Status Scale progression) within 36 months of observation. Independent factors affecting study outcomes at month 36 were identified from baseline data, including age, gender, initial prognostic profile, and serum levels of NFL, occludin, and osteopontin, as well as treatment type. Results: We found lower osteopontin concentrations in patients receiving highly effective treatment compared with those receiving platform therapies (13.64 ± 5.41 ng/mL, CI 11.75–15.53 vs. 17.33 ± 8.00 ng/mL, CI 15.66–18.61; p = 0.03). There was a significant correlation between NFL levels and patient age (Spearman’s rho = 0.3045, p = 0.0002) and between NFL levels and disease duration (Spearman’s rho = 0.1945, p = 0.02). NEDA during the 3-year observation period was achieved by 58 (38.67%) patients. Patients with NEDA showed significantly lower serum concentrations of occludin, NFL, and osteopontin than those without NEDA. Conclusions: Serum levels of NFL, osteopontin, and occludin may serve as biomarkers of disease activity in patients with RRMS. The clinical relevance of these biomarkers should be confirmed through repeated serum marker assessments in MS patients and validation studies involving larger sample sizes.

Objective: To compare serum levels of spindle and kinetochore-associated complex subunit 1 in oral potentially malignant disorders and oral squamous cell carcinoma. Method: The analytical, cross-sectional study was conducted from July 2022 to April 2023 at the Department of Otolaryngology of Dr Ruth Pfau Civil Hospital, Karachi, Dr Ishrat-ul-Ebad Khan Institute of Oral Health Sciences, Karachi, and the histopathological section of the Dow Diagnostic Reference and Research Laboratory at the Dow University of Health Sciences, Karachi, and comprised serum samples of patients with oral squamous cell carcinoma and oral potentially malignant disorder. The concentrations of serum spindle and kinetochore-associated complex subunit 1 were determined using the enzyme-linked immunosorbent assay method. Data was analysed using SPSS 21. Results: Of the 90 patients with age ranging 30-90 years, 45(50%) had oral squamous cell carcinoma; 34(75.6%) males and 11(24.4%) females. There were 45(50%) patients with oral potentially malignant disorders; 35(77.8%) males and 10(22.2%) females (p&gt;0.05). The median serum spindle and kinetochore associated complex subunit 1 levels were significantly elevated in patients with oral squamous cell carcinoma compared to those with oral potentially malignant disorders (p&lt;0.05). Conclusion: Spindle and kinetochore-associated complex subunit 1 could be a promising non-invasive serum marker for the early detection of malignant transformation in oral potentially malignant disorders and for prediction of prognosis in oral squamous cell carcinoma cases. Key Words: Spindle and kinetochore-associated complex subunit 1, Oral squamous cell carcinoma, Oral potentially malignant disorder.

Background:Chronic stress disrupts the neuroendocrine system, leading to imbalances in neurotransmitters and stress hormones such as oxytocin, β endorphins and cortisol, contributing to mood disorders and poor emotional regulation. Complementary and alternative practices like meditation have shown promising results in stress regulation and mood elevation. Heartfulness (HFN) meditation, rooted in yogic traditions and incorporating yogic transmission, is an emerging technique to improve emotional resilience and hormonal homeostasis. Therefore, this study aimed to evaluate the effects of HFN meditation on oxytocin, β-endorphins, and cortisol. It also evaluated the changes in meditation depth using validated psychometric tools.Methods:A randomized controlled trial was conducted. Participants were divided into experimental and control groups. The experimental group practiced guided HFN meditation for 30 days. Following this, a crossover design was implemented in which, the control group participants were now given the intervention of HFN meditation. Biochemical markers (serum oxytocin, β-endorphins, cortisol) were measured at day 30, and day 60. Psychometric assessments included the Meditation Depth Questionnaire and the Positive and Negative Affect Schedule (PANAS).Results:HFN meditation significantly improved meditation depth (ΔM = –14.87, 95% CI [–23.61,–6.13], P = .001, r = 0.333) and positive affect (ΔM = –8.48, 95% CI [–12.03,–4.93], P < .001, r = 0.29), while reducing negative affect (ΔM = 7.70, 95% CI [3.81, 11.60], P < .001, r = 0.21). Oxytocin and endorphin levels increased (oxytocin ΔM = +88.18, P = .003, r = 0.355 and endorphin ΔM = +94.83, P = .003, r = 0.357), and cortisol decreased (ΔM = –133.55, P < .001, r = 0.661). After crossover, the control group exhibited similar improvements. Negative correlations were found between cortisol and both oxytocin and β-endorphins.Conclusion:HFN meditation significantly modulates stress-related neuroendocrine markers and enhances positive emotional states. By increasing the levels of these happy hormones and reducing cortisol, HFN presents a promising non-pharmacological intervention for improving mental health and stress resilience.

Abscisic acid attenuates acute liver injury in mice via the autophagy signaling pathway.

Background Early-stage breast cancer carries a significant risk of recurrence due to undetectable minimal residual disease (MRD). Conventional surveillance lacks sensitivity for early relapse detection. Liquid biopsy, particularly circulating tumor DNA (ctDNA), offers a promising non-invasive strategy to detect MRD and predict recurrence.  Methods This review synthesizes recent evidence on liquid biopsy applications in early-stage breast cancer, with emphasis on MRD detection and recurrence monitoring. We evaluate key assay platforms—including digital droplet PCR (ddPCR), next- generation sequencing (NGS), and cancer personalized profiling by deep sequencing (CAPP-Seq)—and examine their clinical integration.  Results Liquid biopsy demonstrates high sensitivity and specificity in detecting ctDNA at subclinical levels, enabling earlier relapse prediction compared to imaging or serum markers. ddPCR offers affordability and precision for targeted mutations, while NGS and CAPP-Seq provide broader genomic coverage and adaptability. Integration into clinical pathways enables dynamic monitoring from diagnosis through treatment and surveillance. However, challenges remain, including assay standardization, cost, and validation across diverse populations.  Conclusion Liquid biopsy represents a paradigm shift in early-stage breast cancer management, enabling proactive monitoring and individualized treatment. Future priorities include global assay harmonization, large-scale validation trials, and in tegration of multi-omic and AI-based approaches to enhance predictive accuracy and clinical adoption.

Flow cytometry-based validation of soluble biomarker detection

Chronic cadmium exposure, even in environmental doses, has been linked to multiple metabolic disturbances, including white adipose tissue (WAT) dysfunction. WAT dysfunction is defined as a loss of endocrine, immunologic, and metabolic homeostasis, characterized by a low-grade, progressive, and non-resolving inflammation development, namely adiposopathy. This study evaluated the immunometabolic effects of Cd exposure in drinking water on WAT of male Wistar rats, using concentrations of 15 and 32 ppm (environmental doses) over periods of up to 5 months. Inflammatory markers in serum and tissue were analyzed, along with macrophage phenotype, NF-κB pathway activation, leptin and adiponectin expression, correlations with the adiponectin/leptin (A/L) index, and the development of fibrosis. The results showed a progressive increase in proinflammatory cytokines (IL-6, TNF-α, IL-1β), sustained NF-κB activation, and a shift from anti-inflammatory (CD206⁺) to proinflammatory (CD16⁺) macrophages. These changes were accompanied by dysregulation of the adiponectin/leptin axis and a decrease in the A/L ratio, with dynamic correlations to immune markers. Fibrosis was detected in late stages. In conclusion, our results demonstrated for the first time that Cd exposure in environmental doses induces adiposopathy; thereby, findings indicate that Cd can progressively disrupt the immunometabolic homeostasis of adipose tissue, promoting an inflammatory and profibrotic environment with potential implications for the development of metabolic diseases.

Both host and microbe metabolism of tryptophan (Trp) is altered in diabetes; however, the molecular mechanisms are incompletely understood. We used strategies to increase either angiotensin converting enzyme-2 (ACE-2) dependent or independent Trp absorption in a model of type 2 diabetes, db/db mice, and tested whether the strategies could prevent development of diabetic retinopathy (DR), the most common microvascular complication of diabetes. Additionally, we investigated levels of Trp metabolites in humans with and without DR. Enhanced ACE-2 dependent Trp absorption was achieved with gavage of genetically modified bacteria that preserved intestinal ACE2:sodium coupled neutral amino acid transporter expression. ACE-2 independent Trp absorption was achieved by gavage of the Trp dipeptide (Isoleucine-Trp; IW) absorbed via solute carrier family 15 member 1. Both strategies were used either as a prevention (6 months treatment) or intervention (3 months treatment) and at the conclusion, intestinal, metabolic and retinal studies were performed including spatial mass spectroscopy (MS). Plasma Trp metabolites and gut permeability markers were measured in individuals with T2D with (n=30) and without (n=40) DR and compared with healthy controls (n=35). Lactobacillus paracasei-ACE2 or IW treatment prevented DR, corrected dysbiosis, enriched Trp-metabolising bacteria, improved gut barrier integrity, boosted incretin secretion and restored glucose homeostasis in db/db mice. Spatial MS identified indole propionic acid (IPA) as a metabolite in the retinal pigment epithelial layer protecting the posterior blood retinal barrier. T2D individuals with DR demonstrated elevated serum markers of endotoxemia and intestinal barrier disruption while showing reduced levels of the beneficial metabolite IPA and elevated levels of the toxic metabolite indole sulfate. Nutraceutical strategies that restore Trp metabolism or IPA serve as both a biomarker and a treatment for DR.

Introduction: Congenital heart disease repair is commonly associated with neuro-developmental abnormalities that affect quality of life. Cyclohexanone (CXO) is an industrial solvent used to soften medical plastics. Exposure to CXO during neonatal cardiac surgery is associated with poor neurodevelopmental outcomes. Hypothesis: Neonatal cyclohexanone exposure causes neurological damage and initiates peripheral inflammation, resulting in functional and behavioral deficits persisting to adulthood that mimic developmental abnormalities seen in human congenital heart disease. Methods: CXO Exposure: Neonatal rats from both sexes were given CXO (0.53 ul/g/day, i.p.) or saline from post-natal day 7 (P7) to P14. Peripheral Blood Mononuclear Cell (PBMC) and Serum: Whole blood was collected at P15, P28 and P70. Inflammatory markers in serum and the PBMC secretome were evaluated using a MesoScale Discovery platform. Open Field and Magnetic Resonance Imaging (MRI) : At P28, functional MRI (fMRI), diffusion tensor imaging (DTI), and open field behavior were assessed. Touchscreen : As adults, rats were trained on a touchscreen task of visual discrimination (VD) and reversal learning (RL). Statistics: Student’s T-test or Mann-Whitney U-test in n=8-16/group with p&lt;0.05 considered significant. Results: One day after CXO exposure (P15), levels of IFN-γ, IL-10, IL-13, IL-4 (all p&lt;0.05), and IL-6 (p&lt;0.01) were high in serum compared to controls concomitant with sustained peripheral immune hyperreactivity (SPIHR). By P28 through P70, levels of CXCL1 remained elevated (p&lt;0.05) and PBMCs were hyper-inflammatory. Inflammation coincides with diminished cerebral functional connectivity related to attention and reduced white matter microstructure in tracts responsible for cognition (p&lt;0.05). CXO-exposed rats were hypermobile and hyperactive in an open field (p&lt;0.05) with diminished performance on VD and RL tasks. Conclusion: CXO induces inflammation and SPIHR. Adult rats exposed to CXO as neonates have diminished executive function, functional and anatomical connectivity, and poor cognitive flexibility alongside hyperactivity and hypermobility. This supports that neonatal CXO exposure initiates SPIHR and neurological damage that results in altered function and behavior that completely recapitulates the human neuro-developmental delay phenotype after neonatal cardiac surgery. Future work will focus on the mechanism of CXO injury and reducing CXO exposure to improve neurodevelopment.

Introduction: Diabetes Mellitus (DM) and smoking, nicotine exposure, are prominent risk factors for cardiovascular diseases (CVD). The interaction of these factors can potentiate vascular damage, while physical training (PT) is recommended for CVD prevention. Objective: To evaluate the effects of moderate PT on hemodynamic parameters, oxidative stress profile and cardiorenal risk markers in DM animals exposed to nicotine. Method: Wistar male rats weighing between 250-350 g were divided into groups: Citrate (CT): healthy control animals receiving citrate buffer; Nicotine (NIC): animals exposed to nicotine (0.6 mg/kg, intraperitoneally, 28 days; Type 1 Diabetes (DM): animals receiving streptozotocin (60 mg/kg, i.v., caudal vein, single dose); DM+NIC: DM animals exposed to nicotine (as described); DM+NIC+PT: DM + NIC animals submitted to moderate intensity PT, (swimming; 3 times a week, once a day, 50 minutes). Renal function, redox profile and body and renal hemodynamics were evaluated. Hemodynamic parameters (mean arterial pressure - MAP, renal vascular resistance - RVR, renal blood flow - RBF), redox profile (thiols, lipid and urinary peroxidation), and renal function/cardiorenal risk markers (serum creatinine, inulin clearance, microalbuminuria) were assessed. Results: DM and NIC groups showed increased MAP and RVR, with reduced RBF. Exacerbated alterations in these parameters were observde in the DM+NIC group. PT significantly attenuated these adverse hemodynamic changes (DM+NIC+PT vs. DM+NIC). Increased oxidative stress (reduced thiols, increased lipid/urinary peroxidation) was observed in the DM, NIC, and especially DM+NIC groups. PT improved the redox balance in the trained groups (DM+NIC+PT vs. DM+NIC). Microalbuminuria, a cardiorenal risk marker, increased in the DM, NIC, and DM+NIC groups but was significantly attenuated by PT in the DM+NIC+PT group. Conclusion: Moderate physical training demonstrated significant cardioprotective effects in this experimental model, mitigating adverse hemodynamic changes, oxidative stress, and cardiorenal risk, assessed by microalbuminuria, induced by the combination of diabetes and nicotine exposure.

Intestinal parasitism impact on skeletal development is poorly characterised. This study examined whether infection with Eimeria spp. disrupts bone and cartilage homeostasis in rapidly growing broiler chickens. Male Ross 308 chicks were randomly assigned to control or infection groups. On day 20 post-hatch, infected birds received a mixed oral inoculum of Eimeria spp.; controls were sham-dosed and euthanised 22 days later. Tibial osteometry, densitometry, strength, mineral composition and histomorphometry were assessed. Serum markers of bone turnover and inflammation were measured. Infection reduced maximum elastic strength, ultimate strength and elastic energy of the tibia. Trabecular bone volume fraction and thickness declined, whereas trabecular separation increased. The proportion of thin collagen in trabecular, cortical and articular tissues was reduced. Articular cartilage exhibited thinning of the superficial and deep zones and diminished proteoglycan staining. Mineral analysis revealed a lower Ca:P ratio and elevated copper and sulfur content. Serum IGF-1 decreased, while osteoprotegerin, IL-1β, IL-6, IgY, IgM and ceruloplasmin increased. These results demonstrate that Eimeria infection can secondarily compromise skeletal development through inflammatory and metabolic pathways. The broiler model therefore offers a tractable platform for investigating infection-associated, inflammation-driven bone loss relevant to paediatric and post-infectious osteopathies.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-22579-x.

Abstract Extragonadal germ cell tumors (EGGCTs) are rare malignancies that arise outside the gonads and occur infrequently in the gastrointestinal tract. Their presentation often mimics that of other abdominal neoplasms, posing diagnostic challenges. Histopathological and immunohistochemical confirmation, along with tumor marker evaluation, is essential for diagnosis. Early diagnosis and platinum-based chemotherapy can significantly improve patient outcomes. A 25-year-old male presented with abdominal pain, a palpable mass in the umbilical region, and subacute intestinal obstruction. Imaging revealed a heterogeneously enhancing lesion in the mesentery and a subcapsular lesion in the left kidney. Emergency debulking surgery was then performed. Histopathology and immunohistochemistry confirmed an EGGCT favoring a yolk sac tumor. Serum marker levels were elevated with AFP (alpha-fetoprotein) of 854 IU/mL, 23 mIU/mL of β-human chorionic gonadotrophin (β-hCG); 277 U/L of LDH. Ultrasonography of the testes revealed microcalcifications in the left testis, without overt malignancy. The patient was diagnosed with a Stage IIIC extragonadal non-seminomatous germ cell tumor. He was started on an EP regimen owing to poor pulmonary function, followed by BEP, and was scheduled for a high inguinal orchidectomy. This case highlights the importance of including EGGCTs in the differential diagnosis of abdominal masses in young males. A multidisciplinary approach with timely histological and oncological assessments is vital. Early intervention with platinum-based chemotherapy offers a favorable prognosis, even in advanced stages. Given the rarity of this presentation, further studies are needed to refine diagnostic and therapeutic strategies.

Serum Markers as predictors for treatment benefit in castration-resistant prostate cancer.

Older adults undergoing emergency general surgery (EGS) experience disparity and often present in more complex states of health where errors in diagnosis can have profound impact on subsequent treatment options and outcomes. Diagnosis lags in older adult EGS and remains understudied. This scoping review aimed to identify current diagnostic challenges and mitigation strategies to improve diagnosis in the older adult EGS setting. This scoping review was conducted in accordance with the Meta-Analysis extension for Scoping Reviews and Joanna Briggs and Preferred Reporting Items for Systematic Reviews frameworks. PubMed, Embase, Cochrane Library, and Scopus were searched on December 21, 2023. The search included patients 65 years of age and older undergoing evaluation, and medical and/or surgical management of an EGS condition. Data extracted included specific challenges, clinical tools, and clinician feedback strategies in older adult EGS. Of the 9,170 articles screened, 39 studies met inclusion criteria. Diagnostic challenges contributing to poor outcomes included atypical clinical presentation, delay in diagnosis, and the need for comprehensive risk assessment. Diagnostic tools included validated risk assessments for frailty, comorbidity burden, specific EGS conditions, and delirium; imaging; and serum markers. Evidence on performance feedback in this setting was limited, with 1 study showing that establishing an audit and feedback system in a geriatric short-term care unit led to improved compliance and quality of documentation. Although there are tools that can mitigate the diagnostic challenges unique in older adult EGS, further efforts are needed to effectively integrate tools and feedback strategies into frontline care.