📋 Browse Articles

The existing evidence regarding the impact of tamoxifen on lipoprotein(a) and apolipoproteins remains inconsistent. Therefore, this updated meta-analysis of randomized controlled trials (RCTs) aims to enhance the quality of evidence concerning the effects of tamoxifen on these lipid parameters. Eligible RCTs published up to October 2024 were meticulously selected through a comprehensive search. A meta-analysis was then performed using a random-effects model, and results were presented as the weighted mean difference (WMD) with a 95% confidence interval (CI). Findings from the random-effects model revealed an increase in ApoA-I (WMD: 15.22 mg/dL, 95% CI: 6.43-24.01, P = 0.001), alongside decreases in ApoB (WMD: -9.33 mg/dL, 95% CI: -15.46 to -3.19, P = 0.003) and lipoprotein(a) (WMD: -3.35 mg/dL, 95% CI: -5.78 to -0.91, P = 0.007) levels following tamoxifen treatment in women. Subgroup analyses indicated a more significant reduction in lipoprotein(a) levels in RCTs with a duration of ≤24 weeks (WMD: -3.65 mg/dL) and in studies using tamoxifen doses of ≥20 mg/day (WMD: -4.53 mg/dL). This meta-analysis provides evidence that tamoxifen leads to a decrease in lipoprotein(a) levels, along with reductions in ApoB and increases in ApoA-I among women. Show less

Patients with familial hypercholesterolemia (FH) exhibit a significant residual cardiovascular risk. A new cardiovascular risk factor is the susceptibility of individual LDL particles to aggregation. This study examined LDL aggregation and its relationship with LDL lipid composition and biophysical properties in patients with FH compared to controls. LDL aggregation was measured as the change in particle size, assessed by dynamic light scattering, after exposure to sphingomyelinase, which breaks down sphingomyelin in the LDL phospholipid layer. Dynamic light scattering and transmission electron microscopy showed that LDL in FH patients exhibited smaller size and greater susceptibility to aggregation. Biochemical analyses revealed a higher cholesteryl ester (CE)/ApoB100 ratio in LDL from FH patients. Differential scanning calorimetry showed that LDL from FH patients had higher transition temperatures, indicating a more ordered CE core. Fourier transform infrared spectroscopy revealed fewer flexible α-helices (1658 cm⁻ Show less

Gastric cancer (GC) exhibits marked heterogeneity, patients with identical stage receive divergent outcomes. Metabolic reprogramming and aging are pivotal in reshaping the tumor microenvironment. However, their interplay in GC prognosis remains unexplored. We analyzed RNA-seq and clinical data from The Cancer Genome Atlas Program and Gene Expression Omnibus databases. Using univariate Cox, LASSO, and multivariate Cox regression, we identified candidate genes and constructed a prognostic signature. Immune contexture, genomic alterations and drug sensitivity were compared between high- and low-risk group. The metabolic and aging related risk score, comprising 4 genes (GNAI1, GSTA1, APOC3, and LOX), was developed. Validation across multiple cohorts confirmed its robust prognostic performance. The model also effectively stratified patients into distinct risk subgroups with differential immune profiles and responses to immunotherapy. Notably, high-risk patients showed reduced sensitivity to common chemotherapeutic agents but may benefit from targeting the PI3K/mTOR pathway. Metabolic and aging related risk score serves as a promising tool for individualized risk assessment and therapeutic guidance in GC, warranting further clinical validation. Show less

Apolipoprotein C3 (apoC3) is a key regulator of triglyceride metabolism and has emerged as a potential therapeutic target for reducing the risk of cardiovascular disease. However, its broader physiological functions are not fully understood. This study investigates the role of apoC3 in platelet function and thrombus formation. Interestingly, human apoC3 was found to rapidly inhibit platelet activation over the tested concentration range of 0.1-10 µg/mL, with significant effects observed at low concentrations and brief pre-incubation times (from 1 min). At a concentration of 10 µg/mL, apoC3 suppressed platelet activation by approximately 70% in response to ADP and by approximately 40% in response to collagen stimulation. Depleting apoC3 from human serum enhanced platelet aggregation by more than 25 % (1.28 ± 0.19 vs. vehicle), indicating an endogenous regulatory function of apoC3. Mechanistically, apoC3 binding to platelets reduced both GPIIb/IIIa activation and P-selectin expression by around 20%. ApoC3 binding to platelets increased when platelets were activated by ADP and was partially mediated by GPIIb/IIIa, implicating this integrin as a functionally relevant receptor. Taken together, these findings reveal a novel link between apoC3 and platelet biology with potential implications for thrombotic risk and vascular homeostasis. Show less

Acute-on-chronic liver failure (ACLF) is the major cause of mortality in patients infected with the hepatitis B virus (HBV); however, early determination of the prognosis of patients with HBV-ACLF is insensitive or limited. This study aimed to analyze differentially expressed proteins in the plasma of patients with HBV-ACLF using data-independent acquisition mass spectrometry to provide a reference for short-term prognosis. Fifty HBV-ACLF patients and 15 healthy controls were enrolled in this study. Of these, 10 patients with HBV-ACLF and 5 healthy volunteers participated in data-independent acquisition-based proteomics and the potential core proteins were screened out via bioinformatics. Apolipoprotein C3 (APOC3) was selected and quantified by enzyme linked immunosorbent assays in all patients. And the area under the curve (AUC) was calculated to evaluate the value of APOC3 in the diagnosis and prognosis of patients with HBV-ACLF. A total of 247 differentially expressed proteins were identified in the serum of patients in the HBV-ACLF and normal control groups. A total of 148 proteins were upregulated and 99 proteins were downregulated in the HBV-ACLF group compared with those in the normal group. The expression level of APOC3 was 1.65 ± 0.44 mg/mL in patients with HBV-ACLF, which was obviously lower than the normal controls (2.04 ± 0.22 mg/mL) (P < .001) (AUC was 0.766, with a sensitivity of 62%, and specificity of 93.3%). The expression level of APOC3 was 1.38 ± 0.44 mg/mL in the non-survival group, which was obviously lower than the survival group (1.83 ± 0.35 mg/mL) (P < .0001) (AUC was 0.780, with a sensitivity of 50%, and specificity of 96.7%). APOC3 is associated with short-term prognosis of patients with HBV-ACLF and can be used as a potential prognostic biomarker in patients with HBV-ACLF. Show less

Clinical endpoints caused by hyperlipoproteinemia include atherosclerotic cardiovascular disease and acute pancreatitis. Emerging lipid-lowering therapies targeting proprotein convertase subtilisin/kexin 9 (PCSK9), lipoprotein(a), apolipoprotein C-III, and angiopoietin-like protein 3 represent promising advances in the management of patients with hyperlipoproteinemia. These therapies offer novel approaches for lowering pathogenic lipid and lipoprotein species, particularly in patients with serious perturbations who are not adequately controlled with conventional treatments or who are unable to tolerate them. Molecular targets for these novel therapeutic agents were identified and validated through genetic epidemiology studies. Proprotein convertase subtilisin/kexin 9 inhibitors (e.g., monoclonal antibodies and small interfering RNA) have revolutionized hypercholesterolemia management by significantly reducing both low-density lipoprotein cholesterol levels and major cardiovascular events. Genome editing of PCSK9 promises to provide a potential cure for patients with familial hypercholesterolemia. Several investigational lipoprotein(a)-targeting therapies aim to reduce the risk of atherosclerotic cardiovascular disease and aortic valve disease, although definitive clinical endpoint studies remain to be completed. Inhibition of APOC3 messenger RNA expression by olezarsen and plozasiran significantly lowers plasma triglyceride levels and markedly reduces pancreatitis risk in patients with familial chylomicronemia syndrome. Finally, angiopoietin-like protein 3 inhibition by the monoclonal antibody evinacumab has transformed management of patients with homozygous familial hypercholesterolemia. Together, these novel agents expand the therapeutic cache, offering personalized lipid-lowering strategies for high-risk patients with hyperlipoproteinemia, improving clinical outcomes and addressing previously unmet medical needs. Show less

The association of mucosal shedding of human simplex virus (HSV)-2, Kaposi's sarcoma-associated herpesvirus (KSHV) and cytomegalovirus (CMV) after antiretroviral therapy (ART) initiation in women-living-with-HIV (WLWH) with systemic inflammation is unclear. We recruited 187 ART-naive adult WLWH in south-central Uganda. HSV-1, HSV-2, CMV, and Varicella Zoster Virus (VZV) in vaginal secretions and Kaposi's sarcoma-associated herpesvirus (KSHV) in oral swabs were quantified by PCR. Plasma biomarkers of systemic inflammation were measured by ELISA or electrochemiluminescence before and after ART initiation (weeks 8, 12, and 24). Participants had a baseline median age of 28 years and CD4 count of 413 cells/μL. Viral shedding rates were similar for all tested viruses between baseline and post-ART timepoints in the overall study population. CMV shedding significantly increased from a baseline rate of 53% to 77% at week 4 visit ( Although ART initiation was not associated with increased herpesvirus shedding overall, CMV shedding increased in women with advanced HIV-1. The association of mucosal shedding of CMV, HSV-2, and KSHV in post-ART timepoints with different baseline biomarkers of systemic inflammation suggest that distinct immunological functions are implicated in the control of their viral replication. Show less

The accumulation of amyloid-β (Aβ) peptides is a hallmark of Alzheimer's disease (AD). Central to AD pathology is the production of Aβ peptides through the amyloidogenic processing of amyloid-β protein precursor (AβPP) by β-secretase (BACE-1) and γ-secretase. Recent studies have shifted focus from Aβ plaque deposits to the more toxic soluble Aβ oligomers. One significant way in which Aβ peptides impair neuronal information processing is by influencing neurotransmitter receptor function. These receptors, including adrenergic, acetylcholine, dopamine, 5-HT, glutamate, and gamma-aminobutyric acid (GABA) receptors, play a crucial role in regulating synaptic transmission, which underlies perceptual and cognitive functions. This review explores how Aβ interacts with these key neurotransmitter receptors and how these interactions contribute to neural dysfunction in AD. Moreover, we examine how agonists and antagonists of these receptors influence Aβ pathology, offering new perspectives on potential therapeutic strategies to curb AD progression effectively and improve patients' quality of life. Show less

Residual feed intake (RFI) has recently gained attention as a key indicator of feed efficiency in poultry. In this study, 800 slow-growing ducks with similar initial body weights were reared in an experimental facility until they were culled at 42 d of age. Thirty high RFI (HRFI) and 30 low RFI (LRFI) birds were selected to evaluate their growth performance, carcass characteristics, and muscle development. Transcriptome and weighted gene co-expression correlation network analyses of pectoral muscles were conducted on six LRFI and six HRFI ducks. The results revealed that selecting for LRFI significantly reduced feed consumption (P < 0.05) and improved feed efficiency without affecting the growth performance, slaughter rate, or meat quality of ducks (P > 0.05). Moreover, compared with HRFI ducks, LRFI ducks had a lower pectoral muscle fat content (P < 0.05), larger muscle fiber diameter and area (P < 0.05), and lower muscle fiber density (P < 0.05). There were significant differences in gene expression between LRFI and HRFI ducks, with 102 upregulated and 258 downregulated genes, which were enriched in the PPAR signaling pathway, adipocytokine signaling pathway, actin cytoskeleton regulation, ECM-receptor interaction, and focal adhesion. The expression of genes associated with fat and energy metabolism, including ACSL6, PCK1, APOC3, HMGCS2, PRKAG3, and G6PC1, was downregulated in LRFI ducks, and weighted gene co-expression correlation network analysis identified PRKAG3 as a hub gene. Our findings indicate that reduced mitochondrial energy metabolism may contribute to the RFI of slow-growing ducks, with PRKAG3 playing a pivotal role in this biological process. These findings provide novel insights into the molecular changes underlying RFI variation in slow-growing ducks. Show less

Previous studies showed that obstructive sleep apnea (OSA) is associated with dyslipidemia. However, whether micro-arousals during rapid eye movement (REM) and non-rapid eye movement (NREM) sleep independently associated with dyslipidemia were unknown. 4472 participants with OSA-related symptoms were finally included in our cohort. Various sleep variables including micro-arousal index (MAI) were obtained from standard polysomnography (PSG) recordings. Fasting serum lipid levels were assessed at our hospital laboratory. Linear regression models were employed to investigate relationships between micro-arousals in REM and NREM sleep and lipid profile with adjusting for multiple confounding factors. Fully adjusted models demonstrated a significant dose-dependent positive correlation between the MAI during REM sleep (MAI MAI Show less

We tested whether elevated 1 h post-load glucose (1hPG) was associated with decreased leg fat (relative to body fat) and serum concentrations of lipoprotein lipase (LPL), a rate-limiting enzyme for lipid storage in subcutaneous leg fat. Body fat mass and distribution, as measured by DXA, surrogate measures of insulin sensitivity, and insulin secretion inferred from serum insulin kinetics during a 75-g oral glucose tolerance test, as well as serum adipokines and LPL, were assessed in 164 Japanese female university students and 94 middle-aged parents. They all had normal glucose tolerance. Students provided their birth weight. Elevated 1hPG was found in 6% of daughters and 22% of parents. Multivariate logistic regression analyses revealed that log insulinogenic index (IGI) (OR: 0.031, 95% CI 0.003-0.30, p = 0.003) and serum LPL (OR: 0.90, 95% CI 0.83-0.98, p = 0.01) were associated with elevated 1hPG independently of serum adiponectin and birth weight in young Japanese. In middle-aged Japanese, the ratio of leg fat to body fat (OR: 0.66, 95% CI 0.44-0.97, p = 0.03), log IGI (OR: 0.002, 95% CI 0.00003-0.07, p = 0.001), and Matsuda index (OR: 0.67, 95% CI 0.47-0.96, p = 0.03) were related to elevated 1hPG independently of fat mass index, the ratio of trunk fat to body fat, LPL, and homeostasis model assessment insulin resistance. A decreased amount of leg fat in middle-aged Japanese with elevated 1hPG may be explained hypothetically by a prolonged deficiency of LPL. Show less

By various assessments, the previous study has unequivocally concluded functional apoB and MTTP (microsomal triglyceride transfer protein) for VLDL production in chicken ovaries. The present study sought to use whole tissue culture to define the role of VLDL secretion by small yellow follicles (SYFs) along their development under normal and heat stress (HS) conditions. Under thermoneutral conditions (39 °C), chicken SYFs increased MTTP activity, apoB expression and VLDL secretion, while underwent cell apoptosis along the time course. Despite relieved ER stress and protein ubiquitinylation, inhibition of VLDL secretion by Lomitapide and Mipomersen greatly increased triglyceride accumulation, impaired estradiol production and cell proliferation, and accelerated cell apoptosis in accordance with upregulated caspase 3/7 activity, JNK activation, protein carbonylation, and MDA accumulation. Exposure to HS at 44 °C boosted cell apoptosis in a duration-dependent manner. Acute HS for 3 h enhanced VLDL secretion, impaired estradiol production and cell proliferation, and promoted IL-1b production, oxidative damages, and cell apoptosis, whereas except MDA content and cell proliferation, the detrimental effects were halted after 13 h recovery. Lomitapide and Mipomersen augmented lipid accumulation, oxidative stress, inflammatory response, and exacerbated transient impairment of estradiol secretion and cell proliferation in SYFs under 3 h HS and after recovery, but failed to rescue cell viability despite relieved ER and proteostatic stress. In conclusion, routine secretion of VLDL by SYFs serves as an intrinsic mechanism to sustain cell viability and functions to support the whole program required for follicle development, while under HS, this mechanism provisionally rescues steroidogenesis and cell proliferation. Show less

Parkinson's disease (PD) lacks disease-modifying therapies. Fibroblast growth factor 21 (FGF21) is implicated in PD, but its neuroprotective mechanisms via fibroblast growth factor receptor 1 (FGFR1)-sirtuin 1 (Sirt1) remain unclear. Using 1-methyl-4-phenyl-1,2,3,6-te-trahydropyridine (MPTP)-induced PD mice and lipopolysaccharides (LPS)-stimulated BV2 microglia, this study employed recombinant adeno-associated virus (rAAV)-mediated FGF21 overexpression (OE). Multi-dimensional analyses (behavior, immunofluorescence, molecular docking, Western blot, PCR, transmission electron microscopy (TEM)) assessed FGF21's effects and mechanisms. FGF21 FGF21 exerts multi-faceted protection in PD via the FGFR1-Sirt1 axis, including BBB repair, mitochondrial homeostasis restoration, microglial polarization towards M2, balancing autophagy and apoptosis, and promoting neuronal survival. Show less

Spatial representation is a core element of spatial cognition in orienteering, but the visual-spatial neural modulation mechanisms underlying spatial representations with differently oriented maps have not yet been systematically elucidated. This study recruited 67 orienteering athletes as participants and employed a single-factor (map orientation: normal vs. rotated) between-subjects experimental design. Eye-tracking and functional near-infrared spectroscopy (fNIRS) techniques were used simultaneously to collect behavioral, eye movement, and brain activity data, investigating the effects of map orientation on visual attention and brain activity characteristics during terrain symbol representation processing in orienteering athletes. The results revealed that compared to the normal orientation, the rotated orientation led to significantly decreased task accuracy, significantly prolonged reaction times, and significantly increased saccade amplitude and pupil diameter. Brain activation analysis showed that the rotated orientation elicited significantly higher activation levels in the right dorsolateral prefrontal cortex (R-DLPFC), bilateral parietal lobe cortex (L-PL, R-PL), right temporal lobe (R-TL), and visual cortex (VC) compared to the normal orientation, along with enhanced functional connectivity. Correlation analysis revealed that under normal map orientation, accuracy was positively correlated with both saccade amplitude and pupil diameter; accuracy was positively correlated with activation in the R-DLPFC; saccade amplitude was positively correlated with activation in the R-DLPFC and R-PL; and pupil diameter was positively correlated with activation in the R-DLPFC. Under rotated map orientation, accuracy was positively correlated with saccade amplitude and pupil diameter, and pupil diameter was positively correlated with activation in both the L-PL and R-PL. The results indicate that map orientation significantly influences the visual search patterns and neural activity characteristics of orienteering athletes, impacting task performance through the coupling mode of visual-neural activity. Show less

Reproductive and growth traits are key economic traits in sheep. This study aims to identify key single nucleotide polymorphisms (SNPs) and candidate genes associated with reproductive and growth traits in Tianmu polytocous sheep through a genome-wide association study (GWAS). The findings are expected to provide both a theoretical foundation for molecular breeding in this breed and novel insights into the genetic basis of ovine reproductive and growth performance. This study took 483 adult Tianmu polytocous ewes as the research subjects, collected their lambing records, measured their phenotypic values of growth traits (3 weight and 11 body size traits), and collected their blood samples for whole-genome resequencing to identify SNPs in the Tianmu polytocous sheep genome. The results identified a total of 9,499,019 (3× coverage) and 27,413,216 (30× coverage) high-quality SNPs in the Tianmu polytocous sheep genome. Subsequently, the association analysis between SNPs and reproductive and growth traits was conducted using a mixed linear model. A total of 92, 66, 18, 28, 6, 42, 3, 3, 6, 1, 12, 3, 22, 8, 6, and 3 SNPs were found associated with litter size at first parity, litter size at second parity, litter size at third parity, litter size at fourth parity, birth weight, weaning weight, body height, withers height, body length, head length, head width, cannon bone circumference, forelimb height, chest girth, chest depth, and withers width, respectively. Further, based on SNP annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, candidate genes associated with the reproductive and growth traits were identified. Among these genes, 11 Show less

Peripheral artery disease (PAD) is a major global health issue. This study investigated the relationship between lipoprotein(a) [Lp(a)], high-density lipoprotein cholesterol (HDL-C) to blood cells ratios, and PAD development. The study included 361 patients categorized into groups based on the presence of stenotic atherosclerosis in lower limb arteries (LLAs) diagnosed via duplex ultrasound. Group 1 (n = 238) had atherosclerosis at the first visit. A second visit involved 281 patients: 158 from Group 1, 32 new diagnoses (Group 2), and 91 with no atherosclerosis at either visit (Group 3). Laboratory analysis included lipid profiles, Lp(a), and complete blood counts, calculating ratios like Lp(a)/HDL-C and monocyte-to-HDL-C ratio (MHR). Showed patients with stenotic atherosclerosis had significantly higher Lp(a) (20.2 vs. 12.1 mg/dL, Show less

Residual cardiovascular risk remains substantial despite widespread adoption of intensive lipid-lowering strategies-statins, PCSK9 inhibitors, and RNA-based agents-that achieve very low LDL-C and apoB levels. Over the past three years, converging epidemiologic and mechanistic evidence has highlighted emotional stress-including anger, grief, anxiety, and chronic psychosocial strain-as a biologically active determinant of atherosclerotic disease and a frequent trigger of acute events. We propose the Emotion-Lipid Synergy Model, in which lipid burden establishes the atherothrombotic substrate while emotion-driven autonomic and vascular perturbations amplify endothelial dysfunction, microvascular constriction, inflammation, and thrombogenicity-thereby widening the residual-risk gap even when lipid targets are met. From this perspective, prevention should evolve toward precision psychocardiology: systematically screening for distress and stress reactivity; leveraging wearables to detect high-risk emotional states; and delivering timely, scalable, just-in-time behavioral interventions alongside guideline-directed lipid management. Particular attention is warranted for women and patients with angina and no obstructive coronary disease, who appear disproportionately susceptible to mental-stress ischemia. We outline a research agenda-flagship outcomes trials, mechanistic studies, and multimodal phenotyping-and discuss implementation pathways that integrate emotion metrics into cardiac rehabilitation and routine care. Integrating emotion assessment and modulation with lipid control offers a pragmatic route to reduce residual risk and advance equitable, personalized cardiovascular prevention. Show less

Lipoproteins are essential for lipid transport in all bilaterians. A single Apolipoprotein B (ApoB) molecule is the inseparable structural scaffold of each ApoB-containing lipoprotein (B-lps), which are responsible for transporting lipids to peripheral tissues. The cellular mechanisms that regulate ApoB and B-lp production, secretion, transport, and degradation remain to be fully defined. In humans, elevated levels of vascular B-lps play a causative role in cardiovascular disease. Previously, we have detailed that human B-lp biology is remarkably conserved in the zebrafish using an Show less

Atherosclerosis (AS) is a chronic inflammatory disorder driven by dysregulated lipid metabolism and remains a leading cause of cardiovascular morbidity. The Shen-Hong-Tong-Luo (SHTL) preparation has demonstrated clinical benefit in stabilizing atherosclerotic plaques, yet its molecular mechanisms are not fully defined. This research sought to elucidate the protective effects exerted by SHTL on AS progression. To investigate the impact of SHTL on macrophage function and plaque stability, we utilized ApoE SHTL markedly attenuated the progression of AS, demonstrated by reduced plaque formation within both the aortic root and aorta, diminished plasma lipid concentrations, and suppressed inflammatory responses. SHTL demonstrates significant anti-inflammatory and lipid-regulatory effects, attenuating AS progression through the PPARγ/Mfge8 pathway, thereby enhancing macrophage efferocytosis. These findings highlight a novel mechanism by which SHTL may contribute to preventing and treating atherosclerotic diseases. Show less

Atherosclerosis is often associated with inflammation and non-alcoholic liver disease due to high-cholesterol diet and the side effects of conventional treatment. This study aimed to determine the efficacy of Hypercholesterolemia induction was achieved by oral administration of feed with lard for 21 days in male Wistar rats. Next, the animals were treated with 4 mg/kg BW of BBLE (single dose) and 4 mg/kg BW of BBLE+SAE (combined dose) for 3 months, and continued to be given a high cholesterol diet. The negative control was a high cholesterol diet, and the positive control was simvastatin. Blood samples were taken to determine total cholesterol, apolipoprotein-E (Apo-E), interleukin-6, tumor necrosis factor-α, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. Meanwhile, the weight of the liver and histopathology preparations were weighed. Giving BBLE+SAE was able to reduce body weight, liver weight, and cholesterol levels significantly compared to negative controls ( Administration of BBLE+SAE acts as an anti-atherosclerotic and hepatoprotective agent for the liver through reducing pro-inflammatory cytokines, and its use was promising for clinical studies. Show less

Low-grade glioneuronal tumors of the cranial nerves are rare, with only a few case reports describing their association with trigeminal neuralgia and no prior reports including genetic analysis. We present a case of a low-grade glioneuronal tumor located adjacent to the trigeminal nerve root in a 70-year-old man who had been experiencing severe left-sided trigeminal neuralgia for several months. He had initially presented with cranial polyneuropathy, for which oral steroid therapy was initiated. Magnetic resonance imaging of the head revealed the left superior cerebellar artery running near the left trigeminal nerve; however, no mass lesions were detected. During microvascular decompression, an 8-mm white tumor was identified on the trigeminal nerve and subsequently removed. Histopathological examination of the surgical specimen revealed round tumor cells with slightly eosinophilic or vacuolated cytoplasm, arranged in nests or rosettes. Foci of calcification, hemorrhage, and hemosiderin deposition were present, but eosinophilic granular bodies, Rosenthal fibers, necrosis, pleomorphism, or mitosis was absent. The tumor cells were immunopositive for synaptophysin and anti-Neuronal Nuclei, focally positive for glial fibrillary acidic protein and S-100 protein, and immunonegative for Olig2 and epithelial membrane antigen, with a Ki-67 labeling index of < 1%. Molecular analyses confirmed the fusion of KIAA1549 exon 16 with BRAF exon 9, with no mutations detected in IDH1/2, H3F3A, BRAF (V600), or FGFR1. These findings provide novel molecular and embryological insights into low-grade glioneuronal tumors of the trigeminal nerve, which may aid in their classification and understanding of the development of the tumor and neuralgia. Show less

Tooth agenesis (TA), the congenital absence of one or more teeth, is the most common manifestation of defective dental morphogenesis in humans. TA can occur as an isolated (non-syndromic) condition or as part of a broader syndromic presentation. In this review, we analyzed a total of 73 manuscripts to provide a comprehensive update on the genetic landscape of TA. To investigate the genes, variants, and associated phenotypes, we reviewed data from curated databases including Human Phenotype Ontology (HPO), OMIM, ClinVar and MalaCards. Based on the current evidence, the genes most frequently implicated in TA are Show less

Agricultural or gardening activity (also known as hobby farming) is a simple strategy that may be effective for maintaining health and preventing lifestyle-related diseases. However, its preventive effect on the development of conditions associated with neurovascular aging (e.g., stroke and dementia) remains unclear. To comprehensively investigate the preventive role of regular agricultural or gardening physical activity (AGPA) in neurovascular aging and its underlying mechanisms using two approaches. We conducted an experimental study in which we assessed arterial stiffness, cognitive performance (Flanker and Stroop tests), and circulating biomarkers (e.g., plasmin-α2-plasmin inhibitor complexes, nitric oxide, brain-derived neurotrophic factor) in 12 male students (average age: 22 ± 1 years) before and after three 40-min interventions (resting, cycling, and simulated AGPA) under controlled conditions. We also conducted a cross-sectional study, in which we recruited 161 (79 in the AGPA group and 82 in the control group) hospital-based older individuals (average age: 78 ± 5 years) and assessed their history of stroke, cognitive function, and brain magnetic resonance imaging (MRI) findings. In the experimental study, simulated AGPA reduced arterial stiffness, improved executive cognitive function, and elevated circulating plasmin-α2-plasmin inhibitor complexes, nitric oxide, and brain-derived neurotrophic factor. Brain MRI-assessed cerebral white matter hyperintensities caused by reduced blood flow to brain tissue and stroke prevalence were lower, and cognitive scores (as assessed by the Hasegawa Dementia Scale-Revised) were higher in the AGPA group than in the control group. Our findings suggest that regular AGPA is associated with markers of slower neurovascular aging in older individuals. AGPA induces a combination of general physical activity-related and specific AGPA-related effects; moreover, it may offer similar or even greater benefits than physical activity alone. Therefore, habitual AGPA may serve as an effective preventive strategy for neurovascular aging. Show less

In Alzheimer's disease, carriage of the ApoE4 risk allele is linked to faster tau accumulation at lower amyloid-PET levels, thereby accelerating disease progression. However, it remains unclear whether this ApoE4-facilitated transition from amyloidosis to tauopathy is mechanistically promoted by increased secretion of phosphorylated (p)tau, a key intermediate that drives the amyloid-to-tauopathy transition, or alternatively by increased ptau-driven tau aggregation. Therefore, we investigated where along the amyloid-to-tau axis ApoE4 accelerates tau aggregation and assessed i) whether ApoE4 increases ptau secretion or ii) whether ApoE4 increases ptau-associated tau aggregation. To this end, we analysed two large-scale APOE-genotyped cohorts covering the full Alzheimer's disease spectrum (ADNI: n=201) as well as a preclinical cohort (A4-LEARN: n=200), integrating baseline amyloid-PET, plasma ptau217 and CSF ptau181 with longitudinal tau-PET. Using linear regression, we tested whether ApoE4-carriage moderates i) amyloid-PET-associated plasma ptau217 increases or ii) ptau217-associated tau spreading from local epicentres across patient-tailored tau spreading stages. All analyses were independently validated across both cohorts, including an additional replication in an ADNI subset (n=115) with available CSF ptau181 measures as an alternative marker of ptau secretion. Finally, we used logistic regression to determine ApoE4 allele count-stratified plasma ptau217 thresholds marking early pathological tau-PET increases. We found that ApoE4 did not facilitate amyloid-PET-associated ptau increases, suggesting that amyloid-related ptau secretion is not altered by ApoE4-carriage. Contrastingly, we found that plasma ptau217 elevations were linked to faster tau-PET spread from local epicentres across connected brain regions in an ApoE4-allele dose-dependent manner, independent of amyloid (ADNI/A4-LEARN: mean β=0.44/0.56, p<0.001/<0.001). Lastly, we found that a higher ApoE4 allele count was linked to lower ptau217 thresholds marking transition to tauopathy, i.e. early abnormal tau-PET increases, consistently across both samples (ADNI: 0/1/2 ApoE4 alleles=0.62/0.34/0.15pg/ml, representing ∼45% and ∼76% reductions from non-carriers; Fujirebio ptau217 assay; A4/LEARN: 0/1/2 ApoE4 alleles=0.31/0.23/0.18pg/ml, representing ∼26% and ∼42% reductions; Eli Lilly ptau217 assay). These findings suggest that ApoE4, i.e. the key genetic risk factor for sporadic Alzheimer's disease, facilitates amyloid-dependent tau aggregation in an allele dose-dependent manner by enhancing the ptau-driven spread of fibrillar tau, leading to an earlier transition from amyloidosis to tauopathy at lower ptau217 levels. This has implications for plasma ptau-based screening approaches and therapeutic timing of anti-amyloid drugs in ApoE4 carriers: Specifically, ApoE4 carriers may require genotype-adjusted ptau thresholds to detect Alzheimer's disease pathophysiology, as well as anti-amyloid treatment at lower ptau levels to prevent the transition to tauopathy, which ultimately drives neurodegeneration and cognitive decline. Show less

Apolipoprotein E (APOE) epsilon4 (ε4) is a major genetic risk factor for late-onset Alzheimer's disease (AD), with women exhibiting heightened vulnerability to APOE ε4-associated cognitive impairment. Despite recognition of this sexual dimorphism, the underlying biological mechanisms remain incompletely understood. We performed weighted gene co-expression network analysis (WGCNA) on RNA-seq data from the Mayo Clinic cohort ( Four co-expression modules ( we reveal a female-specific APOE ε4-driven molecular network linking endothelial dysfunction to tau pathology. These hub genes provide potential biomarkers, while vincamine represents a targeted prevention and therapeutic candidate for high-risk APOE ε4-positive women. Show less

Tuberculosis (TB) remains a major global health challenge. In addition to Mycobacterium tuberculosis (MTB), nontuberculous mycobacteria (NTM) are increasingly recognized as causative agents of mycobacterial infections. However, the limited access to rapid diagnostics often delays appropriate treatment. Accurate and timely differentiation is critical for selecting effective antibiotic regimens. In Indonesia, there is a lack of population-based data comparing MTB and NTM in TB-suspected cases. This study aimed to detect and differentiate MTB and NTM in clinical samples from suspected TB patients in North Sumatra and to assess their drug resistance profiles using a molecular diagnostic approach. We conducted a prospective cohort study using 56 clinical samples (45 smear-positive sputum and 11 fine-needle aspiration biopsies) from suspected TB patients in North Sumatra. DNA was extracted and analyzed using the Genoscholar™ NTM + multidrug-resistant TB (MDR-TB) II line probe assay (LPA) to detect MTB, NTM, and anti-TB drug resistance. Of the 56 samples, 40 (71.4%) were positive for MTB, 2 (3.6%) for Mycobacterium avium, and 5 (8.9%) for other NTM species, while 9 (16.1%) were negative. MDR MTB was detected in 9 (28%) sputum samples and 1 (12.5%) biopsy sample. Both M. avium isolates were susceptible to rifampicin and isoniazid, while resistance profiles for the other NTM species could not be determined. LPA effectively differentiated MTB from NTM and identified drug resistance patterns in clinical samples. Implementation of this rapid diagnostic tool may strengthen TB management in high-burden areas such as North Sumatra, enabling earlier and more targeted treatment. Show less

Alzheimer's disease (AD) and vascular dementia (VaD) account for most dementia cases. AD biomarkers remain costly and invasive, and no specific biomarkers exist for VaD. We analyzed plasma and brain proteomics in the UK Biobank (N=53,000) and ROSMAP (N=512) to identify shared and distinct proteomic signatures of AD and VaD and assess the influence of the APOE ε4 variant. We identified 55 AD-associated and 49 VaD-associated proteins, with 13 shared. AD proteins were enriched in glycosaminoglycan binding and cholesterol metabolism; VaD proteins in virus receptor activity, cytokine activity and metalloproteinases. Both showed IGF pathway dysregulation. APOE ε4 stratification revealed distinct AD proteomic signatures beyond GFAP and NeFL. Mendelian randomization suggested causal links for SNAP25 in AD, EDA2R and TIMP4 in VaD, and PVR in both. Findings underscore the importance of APOE genotype and highlight SNAP25, EDA2R, TIMP4, and PVR as potential biomarkers and therapeutic targets. Show less