Biomedicines最新文献

Background/Objectives: Sex and diabetes are important determinants of risk in heart failure with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF), yet their combined effects have not been systematically evaluated. This study examined how sex-diabetes phenotypes influence clinical characteristics and the risk of heart failure rehospitalization. Methods: We retrospectively analyzed 1018 HFmrEF/HFpEF patients (2019-2023), classified into four sex-diabetes phenotypes, and performed group comparisons. The primary endpoint was heart failure rehospitalization. Results: Over a mean follow-up of 1463 ± 496 days, 307 patients (30.1%) were rehospitalized for heart failure decompensation. The four phenotypes differed significantly in age, renal function, LV mass, LV dimensions, glycemia, and comorbidity burden (all p < 0.05). Men-particularly those with diabetes-had greater structural remodeling and higher prevalence of smoking, hypercholesterolemia, and atrial fibrillation. In univariate analysis, male sex, diabetes, smoking, NYHA class, lower TAPSE, and lower LVEF were associated with increased risk of rehospitalization. After adjustment for LVEF and NYHA class, male sex (HR 1.28; p = 0.035) and diabetes (HR 1.28; p = 0.036) remained independent predictors. Kaplan-Meier curves demonstrated a clear gradient in event-free survival (log-rank p = 0.015), with women without diabetes showing the best prognosis and diabetic men the worst. Conclusions: Sex and diabetes interact to define distinct risk profiles in HFmrEF/HFpEF. Women without diabetes represent a low-risk phenotype, whereas diabetic men exhibit the highest risk of recurrent heart failure decompensation. These findings support incorporating sex-diabetes phenotyping into routine risk stratification and personalized management.

Background: Vitreoretinal lymphoma (VRL) often presents with features resembling uveitis and is commonly associated with central nervous system lymphoma (CNSL). Intravitreal methotrexate (IVMTX) is widely used as local therapy; however, objective markers for treatment response and prognosis remain limited. This study investigated choroidal structural changes after IVMTX via enhanced depth imaging optical coherence tomography (EDI-OCT) and explored prognostic indicators for subsequent CNSL development. Methods: This retrospective study included 18 patients (27 eyes) with VRL treated with IVMTX at Tokushima University Hospital between 2006 and 2021. EDI-OCT was conducted at baseline and at 1 and 3 months after IVMTX. Choroidal thickness and luminal and stromal areas were quantified through image binarization. The stromal/choroidal area (S/C) ratio and its association with CNSL onset were statistically analyzed. Results: The mean number of IVMTX injections administered over 3 months was 5.9 ± 1.3. Foveal retinal thickness did not significantly change, whereas foveal choroidal thickness significantly decreased from 275.8 ± 15.8 µm at baseline to 257.5 ± 14.7 µm at 1 month (p < 0.01). Total choroidal and stromal areas, particularly in the outer choroidal layer, were significantly decreased after IVMTX (p < 0.0001), whereas the luminal area in the inner layer modestly reduced (p < 0.05). The S/C ratio significantly declined at 1 month post-treatment (p < 0.001). Patients who developed CNSL within 2 years of VRL onset demonstrated higher baseline S/C ratios (p < 0.05). Conclusions: IVMTX induces measurable reductions in choroidal areas and stromal proportion, indicating decreased inflammatory infiltration. The baseline S/C ratio observed on EDI-OCT is a potential noninvasive biomarker of VRL activity and a prognostic indicator for early CNSL development.

Background: A strikingly unusual pattern with a possible up-field shift in Hemoglobin A1c (HbA1c) and A0 (HbA0) peaks and an unexplained hemoglobin F (HbF) peak with capillary electrophoretic shift in the HbA1c chromatograms of a leukemia patient were found while performing a HbA1c screen. Methods: A review of the patient's history with an exhaustive search of the literature ruled out medications as interfering factors or contributing to the abnormal findings. Other than hyperleukocytosis, the patient did not have the aberrant HbF peak noted previously in the electrophoresis or contributing factors. We hypothesized that the irregular chromatographic pattern and wrong location of the HbA1c peak, hereafter referred to as the downfield shift in the electrophoretic species, was due to various glycation or fructosamine adducts and derivatives within the HbA1c and A0 protein. Results: A literature search offered little guidance. However, the instrument troubleshooting measures suggested a hemoglobin variant or exogenous transfusion as a putative source for the HbF peak, while the downfield shift in the chromatogram remained unexplained.

Vascular cognitive impairment and dementia (VCID) encompass a spectrum of cognitive syndromes ranging from mild cognitive impairment to vascular dementia, accounting for approximately 15-20% of all dementia cases and representing the second most common form of dementia. Despite its high prevalence and clinical burden, effective therapeutic strategies remain lacking. Increasing evidence indicates that vascular dysfunction plays a central role in the pathogenesis of VCID by compromising cerebrovascular integrity, impairing endothelial function, and disrupting neurovascular coupling, which collectively contribute to cognitive decline. Stem cells have emerged as promising candidates for promoting vascular repair and neurovascular coupling. Notably, extracellular vesicles (EVs) derived from stem cells exert reparative and protective effects by transferring bioactive molecules that enhance endothelial function and preserve the blood-brain barrier (BBB) function to affected regions. This review summarizes the current knowledge of VCID from a vascular perspective, highlights recent advances in understanding stem cells and their derived EVs in promoting vascular repair and alleviating cognitive decline, and discusses future directions for translating these insights into innovative therapeutic strategies for VCID.

Background and Aims: Androgenetic alopecia (AGA) represents the most prevalent multifactorial condition leading to hair loss, necessitating an enhanced molecular understanding. The aim of this study is to present the analysis integrating protein, mRNA and miRNA between frontal and occipital regions of patients with androgenetic alopecia (AGA) and to identify potential mechanism. Methods and Results: Paired frontal and occipital scalps from four male donors with AGA were collected for transcriptomic and proteomics analyses. The molecular and protein characteristics of AGA were demonstrated by a comprehensive bioinformatics approach. Additionally, immunofluorescence (IF) and dual-luciferase reporter (DLR) assays were employed to confirm the analytical findings. A total of 758 differentially expressed proteins (DEPs), 1802 differentially expressed mRNAs (DERs) and 61 differentially expressed miRNAs (DEmiRNAs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed significant enrichments in lipid metabolism, especially those involving PPAR signaling. Co-expression analyses further supported the association of up-regulated genes with lipid metabolism. A protein-protein interaction network analysis, supplemented by KEGG enrichment and the MCE algorithm, pinpointed four candidate genes: DBI, ACAA1, IDH1 and PEX3. IF confirmed significant upregulation of ACAA1 and PEX3 in scalp tissues with AGA, while IDH1 was downregulated and DBI without significant changes. A competing endogenous RNA network indicated that hsa-miR-1343-3p targets ACAA1 and hsa-miR-3609_R-2 targets IDH1, which were confirmed by DLR assays. Conclusions: This study provides preliminary evidence that hsa-miR-1343-3p-mediated regulation of ACAA1 contributes to AGA pathogenesis, suggesting a link between AGA and lipid metabolism.

Background/Objectives: Gastrointestinal and eating disorders are highly prevalent problems in children with Down syndrome (DS) and have a significant impact on their daily lives. It is important to investigate the bowel habits of children with DS, specifically the prevalence of functional constipation (FC), in order to develop practice guidelines for pediatricians that support diagnosis and treatment. Materials and Methods: This observational, analytical, and cross-sectional study was approved by the Ethics Committee and included 36 children with DS under pediatric outpatient follow-up at a university hospital. To assess bowel habits, an interview was held with the parents using the Rome IV criteria and the Bristol Stool Scale. The children were divided into two groups: those with and those without FC. Specific curves for individuals with DS were used for nutritional assessment. Results: The median age of the children was 46.6 months (5 to 144 months); a total of 80.5% of those included were eutrophic. The median age at initiation of toilet training was 36 months. Most children achieved bowel control when training started after 30 months of age. A total of 15 (41.7%) of the 36 children included were assigned to the group with FC, and 21 (58.3%) were assigned to the group without FC. The FC group had a lower frequency of bowel movements, hardened stools, pain during bowel movement, and used laxatives. According to the Rome IV criteria, the three most prevalent criteria were hard stools, large-volume stools, and painful bowel movements. Conclusions: Children with DS had a high prevalence of FC, and it was possible to identify an association between delayed sphincter training and FC. A care and monitoring protocol and flowchart are useful tools for the general pediatrician.

Liquid biopsy is moving beyond mutation-centric assays to multimodal frameworks that integrate cell-free DNA (cfDNA) signals with additional analytes such as circulating tumor cells (CTCs) and extracellular vesicles (EVs). In this review, we summarize emerging technologies across analytes for early cancer detection, emphasizing sequencing and error-suppression strategies and the growing evidence for multi-cancer early detection (MCED), tissue-of-origin (TOO) inference, diagnostic triage, and longitudinal surveillance. At low tumor fractions, fragmentomic and methylation features preserve tissue and chromatin context; when combined with radiomics using deep learning, they support blood-first, high-specificity risk stratification, increase positive predictive value (PPV), reduce unnecessary procedures, and enhance early prediction of treatment response and relapse. Building on these findings, we propose a pathway-aware workflow: initial blood-based risk scoring, followed by organ-directed imaging, and targeted secondary testing when indicated. We further recommend that model reports include not only discrimination metrics but also calibration, decision-curve analysis, PPV/negative predictive value (NPV) at fixed specificity, and TOO accuracy, alongside multi-site external validation and blinded dataset splits to improve generalizability. Overall, liquid biopsy is transitioning from signal discovery to deployable multimodal decision systems; standardized pre-analytical and analytical workflows, robust error suppression, and prospective real-world evaluations will be pivotal for clinical implementation.

Bone metastases mark a critical and often terminal phase in cancer progression, where disseminated tumor cells (DTCs) manage to infiltrate and exploit the complex microenvironments of the bone marrow. While most current therapies focus on the well-known late-stage "vicious cycle" of osteolysis, they often overlook the earlier stages, namely, tumor cell colonization and dormancy. During these early phases, cancer cells co-opt hematopoietic stem cell (HSC) niches, using them as sanctuaries for long-term survival. In this review, we bring together emerging insights that highlight a trio of underappreciated cellular players in this metastatic takeover: megakaryocytes, erythroid lineage cells, and perivascular stromal subsets. Far from being passive bystanders, these cells actively shape the metastatic niche. For instance, megakaryocytes and platelets go beyond their role in transport; they orchestrate immune evasion and dormancy through mechanisms such as transforming growth factor-β1 (TGF-β1) signaling and the physical shielding of tumor cells. In parallel, we uncover a distinct "erythroid-immune" axis: here, stress-induced CD71⁺ erythroid progenitors suppress T-cell responses via arginase-mediated nutrient depletion and checkpoint engagement, forming a potent metabolic barrier against immune attack. Furthermore, leptin receptor-positive (LepR⁺) perivascular stromal cells emerge as key structural players. These stromal subsets not only act as anchoring points for DTCs but also maintain them in protective vascular zones via CXCL12 chemokine gradients. Altogether, these findings reveal that the metastatic bone marrow niche is not static; it is a highly dynamic, multi-lineage ecosystem. By mapping these intricate cellular interactions, we argue for a paradigm shift: targeting these early and cooperative crosstalk, whether through glycoprotein-A repetitions predominant (GARP) blockade, metabolic reprogramming, or other niche-disruptive strategies, could unlock new therapeutic avenues and prevent metastatic relapse at its root.

Late-life cognitive complaints seldom align with a single disease entity [...].