📋 Browse Articles

The purpose of our study was to investigate the neuroprotective effects of Nigella sativa (NSt) ethanolic extract (200 mg/kg) and/or Telmisartan(Tel) (10 mg/kg) against fipronil (Fip) (9.7 mg/kg)-induced neurobehavioral toxicity in rats, besides exploring the underlying mechanistic signaling pathways. Our results showed that the phytochemical analysis of NSt ethanolic extract by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS) revealed 43 compounds, mainly alkaloids, phenolics, terpenoids, fatty acids and flavonoids. While in our in vivo model of neurotoxicity, the combination of NSt and Tel effectively restored neurobehavioral alterations in rotarod, open field and T-maze tests. Additionally, the cotreatments of NSt and Tel significantly decreased acetylcholine, tumor necrosis factors-α, interleukin (IL)-6, IL-1β, MDA, BAX, P62, LC3B and IBA-1. Conversely, they significantly upregulated GABA, brain-derived neurotrophic factor, superoxide dismutase, catalase, glutathione peroxidase and antiapoptotic BCl2, P70S6K and miRNA137-5P without significant change in mTOR expression in hippocampus. Also, they ameliorated pathological alterations as detected by H&E staining, reduced glial fibrillary acidic protein and caspase-3 immunoreactivity. Electron microscopic examination of the combination group revealed the restoration of nuclear and mitochondrial structures with less glial activation and multivesicular bodies. In conclusion, the combination of NSt and Tel are notable agents in mitigating hippocampal neuronal necrosis and astrogliosis and reduced Fip-induced neurotoxicity. Show less

Apigenin is a bioactive flavonoid and widely found in herbs, fruits, and vegetables. Accumulated evidences have demonstrated the protective potential of apigenin on cardiovascular diseases, but its role in atherosclerosis remains unclear. Here, we aim to investigate the therapeutic effects of apigenin on atherosclerosis in vivo and explore the potential mechanism. ApoE Apigenin obviously reduced lesion areas in both en-face aortas and aortic root in HFD fed ApoE Apigenin alleviated atherosclerosis development by inhibiting macrophage foam cell formation via PPARγ-LXRα-ABCA1/ABCG1 pathway. Show less

Lecanemab is an anti-Aβ antibody approved in China for mild cognitive impairment (MCI) and mild dementia. Real-world application requires comprehensive assessment beyond MMSE scores, considering factors like ARIA risk. This single-center, real-world study aims to evaluate its efficacy in an expanded population, observe biomarker changes, and assess its safety profile in clinical practice. We recruited adults aged 40-90 with early AD from the PUMCH Dementia Cohort. A total of 42 patients received lecanemab treatment, of whom 29 completed the 6-month treatment evaluation. Participants had confirmed amyloid and tau pathology and met clinical criteria (CDR ≤ 1, CDR-SB ≤ 8and MMSE ≥ 18). Comprehensive assessments included neuropsychological testing, CSF and plasma biomarkers (Lumipulse G1200), multi-sequence 3T MRI (volumetric and ALPS index analysis), and amyloid/tau PET imaging (Centiloid quantification). All were monitored for adverse reactions. Matched control groups (matched for sex, age, APOE genotype, disease severity, and baseline therapy) were established for comparison of longitudinally changes in cognitive function, daily living ability and structure MRI. Treatment was effective even for patients with lower MMSE scores but still classified as having mild dementia by CDR. A significant median Centiloid reduction of 30.9 was observed, with a 24.1% amyloid PET negativity rate after six months. While scores on cognitive and functional scales (CDR-SB, ADL) significantly worsened, indicating disease progression, the rate of progression was significantly slower compared to the control group. Structural MRI showed significant volume reduction in multiple brain regions and increased ventricular volume post-treatment, with no statistically significant change in the ALPS value. The rate of brain volume reduction is faster than that in the control group. Plasma biomarker dynamics (Aβ This study confirms the clinical efficacy, biomarker changes, and safety profile of lecanemab treatment over a 6-month period, demonstrating its positive therapeutic value and a favorable safety profile in the Chinese population with AD. Show less

Alzheimer's disease (AD) and neuroblastoma are distinct conditions that affect the nervous system. However, they share some molecular similarities, particularly concerning the amyloid precursor protein (APP) and related pathways. While previous studies have demonstrated a correlation between neurodegenerative diseases and various tumors, the causality and direction of their relationship remain unclear. Oleacein, one of the most abundant polyphenols in Extra Vergin Olive Oil (EVOO) may exert neuroprotective and/or antitumor effects. In this study, we explored the effects of the polyphenol oleacein, obtained by a simple and efficient sustainable semi-synthesis starting from natural oleuropein, on AD-related genes in SHSY5Y, a human neuroblastoma cell line, and in 3Tg-iAstro cells, immortalized astrocytes from the hippocampus of 3xTg-AD mice, to identify potential shared biological pathways. Show less

Human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are known to exert immunomodulatory and pro-reparative effects in vivo. This makes hBM-MSCs an enticing therapeutic candidate for inflammatory diseases, such as acute respiratory distress syndrome (ARDS). The ARDS microenvironment is complex and contains an abundance of free fatty acids (FFAs), which are known to differentially impact MSC functionality. PPARβ/δ is a ubiquitously expressed nuclear receptor that is activated in response to FFA-binding. PPARβ/δ has been shown to impact the therapeutic efficacy of mouse MSCs. This study sought to investigate the impact of PPARβ/δ-modulation on human MSC functionality in vitro and in vivo. hBM-MSCs were exposed to a synthetic PPARβ/δ agonist/antagonist in the presence or absence of ARDS patient serum and the immunomodulatory and pro-reparative capacity of the MSC secretome was investigated using in vitro assays and a pre-clinical model of LPS-induced acute lung inflammation (ALI). Our results highlighted enhanced pro-reparative capacity of PPARβ/δ-agonized hBM-MSCs secretome in CALU-3 lung epithelial cells, mediated by MSC derived angiopoietin-like 4 (ANGPTL4). PPARβ/δ-induced ANGPTL4-high MSC secretome facilitated enhanced endothelial barrier integrity in the lungs of ALI mice. Therapeutic effects of PPARβ/δ-agonized hBM-MSCs secretome were further enhanced by licensing MSCs with human ARDS patient serum. ARDS-licensed PPARβ/δ-induced ANGPTL4-high MSC secretome had reduced clinical score and weight loss. The role ANGPL4 in these protective effects was confirmed using an anti-ANGPTL4 antibody. These findings conclude that the MSC secretome therapeutic effects can be enhanced both in vitro and in vivo through licensing strategies that upregulate the angiogenic factor ANGPTL4. Show less

For decades, major depressive disorder was attributed to a deficit in monoamine neurotransmitters. Clinical latency of tricyclic and selective serotonin reuptake inhibitors, high nonresponse rates, and inconsistent genetic findings challenged this view and redirected research toward downstream biology. Preclinical work revealed that chronic stress triggers dendritic and spine loss in the hippocampus and prefrontal cortex, whereas all effective treatments-including slow-acting monoaminergic drugs, rapid-acting ketamine, electroconvulsive therapy, and aerobic exercise-restore synapse number and function through brain-derived neurotrophic factor, TrkB, and mTOR signaling. Human connectomic studies then reframed depression as a disorder of mistimed large-scale networks; targeted neuromodulation of nodes intrinsically anticorrelated with the subgenual cingulate provides proof of concept. Parallel findings in immunology and gut-brain science show that psychosocial stress, peripheral cytokines, and metabolic cues converge on the same plasticity pathways, dissolving the historical boundary between "reactive" and "endogenous" depression. Ketamine crystallizes this multiscale model: within minutes, it induces dendritic-spine formation, normalizes default-mode and limbic connectivity, and relieves symptoms within hours. We synthesize these lines of evidence into a framework of precision synaptic psychiatry, in which pharmacological, neuromodulatory, and lifestyle interventions are selected according to biomarkers that index glutamatergic tone, inflammatory load, or network dynamics. Future therapeutics will be judged less by the neurotransmitters they influence and more by their capacity to restore flexible, resilient brain circuitry. Show less

A 79-year-old female presented with progressive dyspnea. A bone marrow biopsy revealed hypoplastic marrow with abnormal lymphoid cells. A genetic analysis revealed a MYD88 p.V204F mutation, supporting the diagnosis of lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM). Additional evaluations established a concomitant diagnosis of aplastic anemia (AA). Treatment prioritized AA with cyclosporine and eltrombopag. Subsequently, the LPL/WM was treated with rituximab monotherapy. This sequential treatment resulted in a symptomatic improvement. Although AA is a diagnosis of exclusion, its coexistence with lymphoma is rare. This case highlights the diagnostic and therapeutic complexity of AA and LPL/WM overlap and suggests that prioritizing the treatment of AA may lead to better outcomes. Show less

Colorectal cancer (CRC) remains a major global health challenge, underscoring the need for reliable biomarkers to improve prognosis and therapeutic stratification. In this study, we comprehensively investigated the expression pattern, clinical significance, molecular functions, and immunological implications of LINGO1 in CRC. Integrative analyses of TCGA and GEO datasets, together with validation in 72 clinical CRC samples, demonstrated that LINGO1 is markedly overexpressed in tumors and strongly associated with advanced clinicopathological features and poor patient outcomes. Functional experiments revealed that both knockdown of LINGO1 in SW480 and LoVo cells and overexpression of LINGO1 in HCT116 cells significantly modulate malignant phenotypes, including proliferation, migration, invasion, and angiogenic capacity. Transcriptome-wide and pathway enrichment analyses further indicated that high LINGO1 expression is linked to epithelial-mesenchymal transition, angiogenesis, Wnt/β-catenin signaling, and other oncogenic pathways. Immunogenomic profiling, supported by multiplex immunofluorescence staining, showed that elevated LINGO1 is associated with an immunosuppressive tumor microenvironment characterized by reduced CD8⁺ T-cell infiltration and diminished GZMB expression, alongside upregulation of multiple immune checkpoint molecules. Collectively, our findings identify LINGO1 as a novel oncogenic driver and immune-modulatory biomarker in colorectal cancer, with potential value for prognosis and therapeutic targeting. Show less

Butyrate is one of the three main short-chain fatty acids, and it provides energy, controls the state of the intestinal microbiota and mediates the immune response. Sodium butyrate supplementation improves poultry production and changes the intestinal microbiota dynamically. These changes may affect the liver directly and indirectly through pathways in the gut-liver axis, the bidirectional relationship between the liver and intestines. The study analysed gene expression and methylation in the broiler liver after Incubated Ross 308 broiler eggs were injected on day 12 with saline as the control group or with sodium butyrate as SB groups at three doses: 0.1%, 0.3% and 0.5%. Chicks' livers were collected postmortem on day 42 of rearing for RNA and DNA extraction. Gene expression was analysed by reverse-transcription qPCR, and gene methylation by methylation-specific qPCR for a panel of lipid metabolism and immune regulation genes comprising Sodium butyrate stimulation changed gene expression levels. Upregulation was noted of The obtained results suggest that sodium butyrate affected both gene expression and methylation in the liver, indicating its potential epigenetic effects. Show less

REM (rapid eye movement) sleep deprivation causes serious impairments in hippocampus-dependent learning and memory. This study examined whether the angiotensin II receptor blocker telmisartan, given at two different doses, could reduce cognitive deficits and affect molecular pathways related to chronic REM sleep deprivation. Thirty-two male Wistar-Albino rats (200-280 g, 3 months old) were randomly divided into four groups (n = 8): control, sleep deprivation (SD), telmisartan-treated SD groups at 1 mg/kg (SD+Tel1) and 3 mg/kg (SD+Tel3). Chronic REM sleep deprivation was induced for 21 days using the modified multiple platform (MMP) method. Telmisartan or distilled water was administered orally once daily. Cognitive performance was tested in the Morris water maze, assessing escape latency and time spent in the target quadrant. After behavioral tests, hippocampal and prefrontal cortex samples were analyzed for brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), glycogen synthase kinase-3 beta (GSK-3β), monocarboxylate transporter 2 (MCT2), and lactate dehydrogenase (LDH) levels, while plasma samples were analyzed for corticosterone (CORT) levels. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitrate, and glycogen were also measured. Sleep-deprived rats showed impaired learning and memory with longer escape latency and reduced time spent of target quadrant. Telmisartan-treated SD groups demonstrated significantly improved cognitive performance, increased BDNF and CREB expression, decreased GSK-3β levels, and balanced oxidative stress markers. In conclusion, telmisartan protected against cognitive and biochemical damage caused by chronic REM sleep deprivation, likely through modulation of GSK-3β/CREB/BDNF signaling and reduction of oxidative stress. Show less

Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease, characterized by genetic and phenotypic heterogeneity. Although extensively studied in North American and European populations, data from Brazil remain limited. To characterize the genetic and clinical profiles of a Southern Brazilian cohort of HCM patients and their relatives using massive parallel sequencing. In this observational study, HCM patients and first-degree relatives were recruited from outpatient cardiology clinics. Clinical and imaging data were collected, and genetic analysis used a 100-gene panel. Variant pathogenicity was assessed according to American College of Medical Genetics and Genomics criteria, and statistical analyses were performed using R software. Eighty individuals were included in the final analysis (mean age: 49.2 ±18.5); 60% male; 40 index cases and 40 affected relatives). MYH7 and MYBPC3 were the most frequently related genes, with pathogenic / likely pathogenic variants (P/LP) identified in 33% and 16% of participants, respectively. No pathogenic TNNT2 variants were detected. Ninety percent of participants carried an identified variant (including variants of uncertain significance), with 68% harboring P/LP variants. MYH7 carriers exhibited a higher proportion of left ventricular outflow tract obstruction, whereas MYBPC3 carriers had a higher proportion of arrhythmic events and earlier diagnosis; however, these differences did not reach statistical significance and should be interpreted as exploratory. Clinical comparisons revealed regional differences, suggesting the potential impact of genetic diversity on the presentation of HCM in this part of Brazil. This study offers the first detailed genetic and clinical characterization of a Brazilian HCM cohort using massive parallel sequencing. Our findings underscore the importance of genetic testing for diagnosis, risk stratification, and management. Show less

Atherosclerosis (AS) is a major underlying cause of cardiovascular diseases, with hypercholesterolemia, inflammatory responses, and macrophage polarization being established key contributors. The roles of NLRP3 inflammasome activation and macrophage polarization in AS pathogenesis have garnered significant research interest. This study investigated the therapeutic potential of Schisandrol B (Sol B) against AS using an in vivo model of ApoE Show less

Protein feed resource shortage is a major constraint to the sustainable development of the livestock industry and a bottleneck problem hindering the growth of the Tibetan pig industry in China's Qinghai-Tibet Plateau region. Walnut meal, rich in protein, holds promise as a substitute for soybean meal. However, the effects and underlying mechanisms of walnut meal substitution on Tibetan pigs in Diqing remain unclear. The study showed that substituting 50% of soybean meal with walnut meal in the diet of Diqing Tibetan pigs significantly reduced backfat thickness and increased intramuscular fat content ( This study reveals that walnut meal can serve as a substitute for soybean meal, and a 50% substitution ratio is conducive to intramuscular fat deposition in Diqing Tibetan pigs. The findings provide valuable insights for the development and application of unconventional protein feed resources, and offer new perspectives for the production of marbled pork. Show less

Studies have shown that sarcopenia and its related parameters are associated with cognition. Preclinical evidence suggests that myokines, such as irisin, Brain-Derived Neurotrophic Factor(BDNF), myostatin and Insulin-like Growth Factor-1(IGF-1) might explain this relationship. This study aimed to explore the associations between sarcopenia-related parameters and cognition, and whether myokines influence this association. Exploratory, cross-sectional analysis of data from the Exercise and Nutrition for Healthy AgeiNg (ENHANce,NCT03649698) study. Participants were older adults(≥65 years) with EWGSOP2-defined sarcopenia. Cognitive functioning was assessed by Mini-Mental State Examination(MMSE), Repeatable Battery for the Assessment of Neuropsychological Status(RBANS), Trail Making Test A&B(TMT), Stroop and Maze Test. Sarcopenia-related parameters were measured: Handgrip Strength, Chair Stand Test, appendicular Lean Mass(aLM), Gait Speed (GS) and Short Physical Performance Battery(SPPB). Serum myokines(IGF-1, irisin, myostatin, BDNF) were determined through ELISA. Associations between cognition and sarcopenia-related parameters were analyzed using multivariable regression, adjusting for potential confounders including myokines. Fifty-eight participants were included in this analysis (76.2 ± 6.7 years, ♀:65.5%). After adjustment for age, sex, body mass index, aLM was associated with MMSE(β = 0.193,p = 0.012), RBANS Total(β = 0.196,p = 0.007) and RBANS Attention(β = 0.215,p = 0.002), CST was associated with RBANS Language(β = -0.314,p = 0.030), SPPB was associated with Maze time(β = -0.364,p = 0.004) and TMT-B (β = -0.333,p = 0.013) and GS was associated with TMT-A(β = -0.324,p = 0.045). After adjustments for BDNF& IGF-1, the association between GS and TMT-A became non-significant. Irisin and myostatin did not influence the sarcopenia-cognition associations. Sarcopenia-related parameters are associated with global and specific cognitive domains. BDNF may, partially, explain the association between muscle mass and MMSE. Additional research with larger sample size is needed to confirm these findings. Show less

In recent studies elevated lipoprotein(a) (Lp(a)) levels have been identified as an independent and causal risk factor for atherosclerosis and coronary heart disease. This study aims to perform a comparative early health technology assessment (HTA) of olpasiran and pelacarsen for secondary prevention of coronary heart disease (CHD) in patients with atherosclerotic cardiovascular disease, familial hypercholesterolemia, and elevated Lp(a). We developed a Markov state transition model to simulate the progression of a cohort of 597 patients with history of coronary heart disease (CHD) as myocardial infarction, coronary artery disease or peripheral artery disease, familial hypercholesterolaemia in the treatment arms of OCEAN(a)-Outcomes trial (NCT05581303) [16] and Lp(a) HORIZON trial (NCT04023552). Baseline risks of CHD, costs and utilities were obtained from published sources. Clinical trial data were used to derive reductions in lipoprotein(a). Mendelian randomization study data were used to estimate clinical benefits. Annual discounting was 3.5%. The treating strategy comprising olpasiran 150 mg every 3 months in addition to standard of care saved 3.29 QALYs, compared with standard of-care alone. With 3.5% annual discounting, there were 0.23 QALYs saved. The treating strategy comprising pelacarsen 80 mg every month in addition to standard of care saved 8.63 QALYs, compared with standard of-care alone (undiscounted). With 3.5% annual discounting, there were 0.58 QALYs saved. We found that olpasiran was highly cost-effective at the annual price of 10,424.78 BGN, compared with standard-of-care alone. Pelacarsen was highly cost-effective at the annual price of 6105.99 BGN. The threshold applied is that of gross domestic product (GDP) per capita as indicated by the National Council on prices and reimbursement of medicinal products in Bulgaria. Show less

Previous studies indicate that ambulance personnel have an increased risk of ill health. Shift work and time spent on physical behaviours during work and leisure are factors that could be related to health, however the research is limited. Thus, the aim of this study was to describe patterns of physical behaviours during and after work among Swedish ambulance personnel and to analyse the associations between physical behaviours and different work shifts. In this observational study, the physical behaviours of 63 ambulance personnel were measured over seven days using two accelerometers. Accelerometer data was processed using the MATLAB program Acti4, to identify physical behaviours i.e. sleep, being sedentary, light physical activity (LPA), and moderate to vigorous physical activity (MVPA), during and after work. To determine the association between shift types (independent) and patterns of physical behaviours (dependent), a Multivariate Analysis of Variance was performed on data processed according to compositional data analysis. At work, the highest proportion of both MVPA and being sedentary occurred during day shifts, compared to night and 24-h shifts (MVPA: 7% vs 4% and 5%; sedentary time: 62% vs 44% and 54% respectively). Night and 24-h shifts included 31% and 18% sleep, respectively. During the after-work periods, the highest proportions of MVPA were observed after 24-h shifts (8%). Overall, there was no statistically significant difference in physical behaviours during work and after work for various shift types. However, in a sub-analysis restricted to night and 24-h shifts, a statistically significant association between shift type and composition of physical behaviours during work was observed (η In general, ambulance personnel were physically active both during and after work. At the same time, work hours entailed a substantial amount of sedentary time. Shift type was not associated with the pattern of physical behaviours among ambulance personnel. However, during 24-h shift a lower proportion of the time was spent sleeping compared to during night shift. Studies with larger sample sizes are needed to confirm these results. The online version contains supplementary material available at 10.1186/s12889-026-27335-y. Show less

Diabetic refractory wounds are a severe complication of diabetes, often synchronized with diabetic peripheral neuropathy. In this study, we demonstrated a significantly downregulated expression of calcitonin gene-related peptide (CGRP) in the skin tissues of both diabetic patients and diabetic mouse models. This observation implies the crucial role of CGRP in diabetic wound healing. Based on this discovery, we engineered glucose-responsive along with sustained-release antibacterial hydrogel microspheres (BA-HPCS@CGRP) for the controlled delivery of CGRP and conducted systematic evaluation of its therapeutic efficacy. In vitro findings demonstrated that microspheres not only directly enhanced the migration and tube formation capabilities of endothelial cells impaired by high glucose but also further facilitated the restoration of endothelial cell function by promoting the secretion of angiopoietin-like protein 4 (Angptl4) by macrophages after switching to M2 phenotype by CGRP. The results from diabetic mouse models showed that BA-HPCS@CGRP accelerated diabetic wound healing by modulating macrophage polarization towards to M2 phenotype and reduced inflammation, promoted neurovascular regeneration and restored the local CGRP expression. These findings suggest that sustained releasing of low concentration of CGRP provides novel therapeutic approaches for diabetic wounds via modulating macrophage. Moreover, BA-HPCS@CGRP achieves comprehensive sequential therapy through the synergistic modulation of the "neuro-immune-vascular" axis, which might open new perspective to chronic wounds and regenerative medicine. Show less

Sufficient physical activity has the potential to mitigate the late effects of cancer, but objective data of activity levels in patients after pediatric bone cancer are scarce. This study aimed to objectively assess physical activity levels in this population and explore differences based on patient- and treatment-related factors. As part of a cross-sectional study of a nationwide cohort of patients treated for pediatric bone sarcoma, we assessed physical activity using an accelerometer, the ActiGraph GT9X Link. Physical intensity levels were categorized as sedentary, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) and compared between subgroups stratified by sex, age, tumor location, type of surgery for tumors around the knee, and time since local therapy. Among 79 participants, 47% were female, and median age at evaluation was 19.8 years (IQR 17.5-23.9) with a median of 5.9 years (IQR 2.9-11.7) since local therapy. Mean daily sedentary time was 643 min (SD = 104), 127 min per day (SD = 58) was spent in LPA, and 63 min per day (SD = 35) in MVPA. Seventy-eight percent of participants met the World Health Organization's recommended level of MVPA. No significant differences in intensity levels were found between the various subgroups. Pediatric bone sarcoma patients seem to regain participation in higher-intensity activities post-treatment, with physical activity levels comparable to the general population. No surgical approach is superior in terms of physical activity. Implications for Cancer Survivors Shared decision-making is important in guiding the choice of local therapy and should be informed by lifestyle and individual preferences. High sedentary time suggests scope for improvement in survivorship care. Show less

How schoolchildren distribute their time between movement behaviours may be impacted by the neighbourhood environment. Few studies have investigated the associations between the physical and social environment and the full movement behaviour composition, including times spent in moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behaviour, and sleep, and their findings are inconsistent. Therefore, our aim was to investigate this association in a large, national-representative sample of schoolchildren from major cities and regional/remote areas. We used data from the Longitudinal Study of Australian Children and the Child Health CheckPoint study, collected among 1230 child-parent pairs (child age range: 10–12 years). Parents were asked about neighbourhood general safety, access to destinations and services, and social capital and cohesion. Children’s time spent in MVPA, LPA, sedentary behaviour, and sleep was assessed using wrist-worn GENEActiv accelerometers. The associations between the physical and social environment characteristics (independent variables) and movement behaviour composition expressed as isometric log ratio coordinates (dependent variables) were examined using multiple linear regression analyses, adjusted for age, body mass index, pubertal status, sex, and socioeconomic position. Among schoolchildren from regional/remote areas, access to destinations and services (Pillai’s trace = 0.030; These findings highlight the importance of access to destinations and services, as well as social capital and cohesion, in shaping the movement behaviour composition among schoolchildren from regional/remote areas. More research is needed to draw conclusions about the association between neighbourhood environment and movement behaviour composition among schoolchildren from major cities. The online version contains supplementary material available at 10.1186/s12966-026-01879-z. Show less

Hepatocellular carcinoma (HCC) exhibits high recurrence rates and limited therapeutic options. Endothelial cell-specific molecule 1 (ESM1) and angiopoietin-like 4 (ANGPTL4) are implicated in tumor progression, yet their synergistic role in HCC lipid metabolism and angiogenesis remains unexplored. We integrated multi-omics approaches, including RNA sequencing, metabolomics, and immunoprecipitation-mass spectrometry, in HCC cell lines and patient-derived xenograft models. Key experiments involved Co-IP, Western blotting, tube formation assays, and clinical tissue microarray analysis to validate the ESM1-ANGPTL4-FASN-trioleate axis. ESM1 and ANGPTL4 formed a positive feedback loop, stabilizing fatty acid synthase (FASN) to promote trioleate synthesis. Trioleate activated the NF-κB/IL-17 pathway in HCC cells and upregulated CD99 in endothelial cells, driving angiogenesis. In vivo, ESM1/ANGPTL4 knockdown suppressed tumor growth, which was rescued by trioleate supplementation. Clinical data revealed elevated ESM1/ANGPTL4 expression in bevacizumab-resistant HCC, correlating with poor prognosis. The ESM1-ANGPTL4-FASN-trioleate axis orchestrates metabolic reprogramming and endothelial activation, representing a promising therapeutic target. Future studies should explore combination therapies targeting this axis and overcoming bevacizumab resistance in HCC. Show less

Agrin-mediated neuromuscular junction (NMJ) morphological alterations is one of the main pathogeneses of sarcopenia. The aim of this study was to observe the changes in serum agrin in patients with different degrees of sarcopenia and the alterations in Agrin receptors in human skeletal muscle with age. A total of 236 elderly subjects were enrolled and categorized into nonsarcopenia, possible sarcopenia, sarcopenia, and severe sarcopenia groups. Serum levels of the C-terminal Agrin fragment were quantified using an Enzyme-Linked Immunosorbent Assay (ELISA) kit. In addition, in a distinct and smaller exploratory subgroup ( Show less

Lipidomic analysis enables the detailed characterization of platelet concentrates from donors of different ages, offering valuable insights into the role of lipid mediators in aging and transfusion-related adverse reactions (AR). In this study, we analyzed lipidomic profiles from a cohort of single-donor apheresis platelet concentrates, classified into three age groups: 20-44, 45-59, and 60-70 years. Total levels of LPC, LPA, S1P, and eicosanoids did not exhibit significant age-related changes. However, LPA 18:1, LPC 18:1, and S1P levels decreased with advancing age. When examining the relationship between different age groups and their association with AR, we found that LPA, LPC, and eicosanoids are associated with AR in an age-dependent manner. Based on these findings, we investigated the effect of age-related levels of LPA, LPC, and S1P on platelet and endothelial cell biology. These lipid mediators were found to modulate platelet activation, as demonstrated by increased expression of P-selectin, phosphatidylserine, platelet aggregation, as well as endothelial activation, marked by elevated expression of ICAM-1, VCAM-1, and CD40. Our findings present a comprehensive lipidomic profile of single-donor apheresis platelet concentrates across various age groups, highlighting several lipid mediators that may be implicated in aging and AR. Show less

The effects of extruded flaxseed-pulse mixture (LinPRO-24) on growth performance, tissue fatty acid composition, carcass traits, and meat quality in broilers were investigated. A total of 540-day-old male 308 Ross chicks were placed in pens (30 chicks/pen) and allocated to three diets (n = 6) in a completely randomized design. The diets were: CON (basal corn-soybean meal diet); LPA (CON+2.5% LinPRO-24); and LPB (CON+ 5.0% LinPRO-24). Diets were isocaloric and isonitrogenous, formulated for starter (day 1-10), grower (day 11-24), and finisher (day 24-34). Feed intake and body weight (BW) were recorded daily, and mortalities as they occurred to calculate average daily gain (AWG) and FCR. On day 34, visceral organs, breast tissue, and leg tissue were sampled. The CON group exhibited higher overall BW, AWG, and AFI than LPB (P < 0.05). Breast and leg tissues of birds fed LPB had the highest concentration of Alpha-linolenic acid (ALA) and total ω-3 PUFA followed by LPA; both had a higher ALA concentration than the CON group (P < 0.05). Thus, the ω-6:ω-3 ratio in these tissues was lower for LPA and LPB groups (P < 0.05). Additionally, both LPA and LPB groups had lower Docosatetraenoic acid (DTA, C22:4 ω-6), higher Docosapentaenoic acid (DPA, C22:5 ω-3) and total PUFA content, resulting in a reduced SFA:PUFA ratio in leg tissue compared with the CON group (P < 0.05). However, LPB negatively affected the water-holding capacity (WHC) in breast meat compared with the CON and in leg tissue compared with LPA treatment (P < 0.05). Moreover, LPB increased muscle hardness and gumminess in the breast compared with the CON group (P < 0.05), thereby negatively affecting meat textural qualities. Overall, both LPA and LPB diets increased the ω-3 PUFA content in poultry meat, thereby reducing the ω-6:ω-3 ratio. However, the current study suggests that the use of LinPRO-24 at 2.5% may be more appropriate for improving the fatty acid profile of broiler meat without compromising production performance and meat quality. Show less

Myocardial ischemia/reperfusion (I/R) injury commonly occurs in patients undergoing cardiac or noncardiac surgeries, increasing perioperative mortality risk. Although numerous endogenous mediators released during I/R contribute to myocardial damage, their mechanisms require further elucidation. We investigated whether lysophosphatidic acid (LPA), a bioactive phospholipid, mediates myocardial I/R injury by interacting with cardiac transient receptor potential vanilloid 1 (TRPV1). A TRPV1K710N knock-in mouse model was generated by CRISPR/Cas9, introducing a point mutation at K710, the known LPA-binding site on TRPV1. Langendorff perfused isolated hearts from TRPV1K710N and wild-type (WT) mice underwent global I/R injury with or without exogenous LPA (10 μM). Myocardial infarct size, coronary effluent LDH levels, and mitochondrial ultrastructure/function were assessed. Additionally, H9c2 cardiomyocytes were transfected with a pCMV6-entry plasmid carrying TRPV1-K710N or TRPV1-WT for mitochondrial calcium influx and cell viability assays. The V1-Cal peptide (1μM), targeting the K710 region, was applied ex vivo and in vitro to block LPA-TRPV1 interaction. TRPV1K710N hearts exhibited resistance to global I/R injury versus WT hearts, with reduced infarct size (28.3 ± 2.4% vs 39.9 ±2.3%, respectively, P= 0006), lower LDH levels, and attenuated mitochondrial damage. Exogenous LPA exacerbated I/R injury in WT hearts, increasing infarct size (63.7 ± 1.2% vs vehicle: 38.4 ± 2.4%; P <.0001), LDH release, and mitochondrial damage. TRPV1K710N hearts were resistant to LPA-induced injury, with no significant increase in infarct size after LPA treatment. Exogenous LPA induced pronounced swelling in mitochondria isolated from WT hearts, while mitochondria from TRPV1K710N hearts showed resistance to LPA challenge. In H9c2 cells, LPA significantly decreased viability in rTRPV1-WT cells and elevated mitochondrial calcium influx relative to rTRPV1-K710N cells. V1-Cal peptide attenuated LPA-mediated myocardial injury in WT hearts and reduced mitochondrial calcium overload in H9c2 cells. Blockade of the TRPV1 K710 site by K710N mutation or V1-Cal peptide mitigates LPA-mediated myocardial injury and mitochondrial damage/dysfunction in isolated mouse hearts. Targeting the cardiac LPA-TRPV1 interaction represents a promising therapeutic strategy against perioperative myocardial injury. Show less

Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease. In 20% to 30% of patients, a disease-causing variant can be identified and may also be present in relatives. Individuals carrying a pathogenic variant (G+) without left ventricular hypertrophy (LVH) are classified as genotype-positive/phenotype-negative (G+/P-). Their risk of developing LVH or HCM-related events remains uncertain. The aim of the article is to describe the clinical course of G+/P- individuals during long-term follow-up. G+/P- individuals were recruited from relatives of HCM patients at a tertiary center. All underwent clinical assessment, electrocardiography (ECG), and transthoracic echocardiography (TTE). Phenotype-negative status was defined as maximal left ventricular wall thickness (MLVWT) <13 mm. HCM was diagnosed when MLVWT ≥13 mm was observed without hypertension or other hemodynamic causes. Genetic testing used targeted Sanger sequencing, with variants classified per ACMG/AMP criteria. Thirty-four individuals were classified as G+/P-; the mean age was 31.7 ± 14.8 years, and 27% were men. Variants occurred in MYBPC3 (76%) and MYH7 (24%). Most were asymptomatic (85%), and 71% had a normal ECG. Mean follow-up was 6.6 ± 3.7 years, with complete ECG and TTE data in 88%. MLVWT increased from 9.6 ± 1.6 mm to 10.7 ± 3.3 mm (p = 0.01), while other echocardiographic parameters and ECG findings remained stable. Nine individuals (26%) developed LVH after a mean of 5.1 ± 4.1 years. One patient developed nonsustained ventricular tachycardia and received a primary prevention implantable cardioverter-defibrillator. In conclusion, G+/P- individuals were young and largely asymptomatic, yet 26% progressed to HCM. These results support regular TTE and ECG surveillance to enable early identification of disease progression and guide risk stratification. Show less

Phosphatidic acid (PA) is increasingly recognized as an important endogenous regulator of cell proliferation and migration, playing relevant roles in physiology and pathology. However, the potential and prominence of extracellular PA in controlling cell functions are not so well established. The present review article has been undertaken to update and discuss the latest findings on extracellular PA as regulator of cell homeostasis, with special attention being paid to its role in the regulation of cell growth and migration. Specifically, exogenous PA potently stimulates myoblast proliferation and lung cancer cell migration, pointing to a critical role of this glycerophospholipid in the regulation of muscle cell regeneration and lung cancer dissemination. Interestingly, both of these actions are mediated through interaction of PA with lysophosphatidic acid (LPA) receptors and the subsequent activation of different signal transduction pathways. In particular, PA induces mitogen-activated protein kinase kinase (MEK)/extracellularly regulated kinases (ERK) 1 and 2, phosphatidylinositol 3-kinase (PI3K)/Akt, focal adhesion kinase (FAK)/Rac1, and Janus kinase-2 (JAK2)/signal transducer and activator of transcription 3 (STAT3). These findings may contribute to a better understanding of muscle cell biology and may help to develop new therapeutic strategies to treat lung cancer dissemination. Show less

Volatile fatty acids (VFAs) provide more than 70% of the energy source for the ruminants. Understanding the host-microbiota regulation of VFAs production and utilization is highly important for optimizing the feed energy utilization efficiency of ruminants. Here, we conducted whole-genome resequencing, rumen transcriptome sequencing, 16S rRNA gene amplicon sequencing, and VFA concentration determination in 530 Holstein bulls. We treated VFA concentrations as complex traits to perform multi-omics association analyses. The host genetics, rumen microbiota, and rumen expressed genes, on average, explained 23%, 58%, and 61% of the variations in VFAs with the same diet, respectively. We found that the rumen microbial composition and community structure differed significantly between the high and low VFA individuals. We further identified 11 microbes with potential causal relationships with rumen VFAs via the Mendelian randomization method, among which Bacteroidales_RF16_group, Prevotella, Clostridia_UCG-014, and [Eubacterium]_ventriosum_group were positively correlated with acetic acid, propionic acid, and butyric acid. Conversely, rumen epithelial genes involved in fatty acid β-oxidation (e.g., HSD17B4, ACADVL, ACADL, CPT1A, and ANGPTL4) were negatively correlated with the main VFAs and VFA-producing bacteria. These candidate microbes and genes suggest that the host-microbe coregulating mechanism facilitates the efficient production and utilization of rumen VFAs in ruminants. Our study provides a comprehensive perspective on the complex dynamic regulatory patterns of rumen VFAs, highlighting the crucial role of host-microbe interactions in optimizing the feed utilization of ruminants. Show less