Biomedicines最新文献

Fibromyalgia is a complex chronic pain condition characterized by pervasive pain, persistent fatigue, and cognitive disturbances. Despite advances in understanding its neurobiological mechanisms, diagnosis largely relies on subjective symptom assessment and exclusion criteria, contributing to underdiagnosis and treatment delays. Recent research has increasingly focused on identifying objective biomarkers and leveraging digital phenotyping to improve diagnostic precision. Promising biomarkers include neuroimaging indicators of altered pain processing, neuroinflammatory signatures in cerebrospinal fluid and blood, and dysregulated neuroendocrine and autonomic patterns. In addition, metabolomics and transcriptomics have revealed molecular profiles associated with fibromyalgia pathophysiology. Concurrently, digital health tools (e.g., wearable sensors, ecological momentary assessment, and machine learning-based symptom clustering) offer opportunities for continuous, real-world data collection and individualized disease characterization. This body of work suggests that integrating biological and digital metrics could enable a transition from subjective to objective data-driven fibromyalgia classification, facilitating earlier diagnosis and improved therapeutic outcomes.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening thrombotic microangiopathy (TMA) caused by severe deficiency of the von Willebrand factor-cleaving protease ADAMTS13. Pregnancy is a recognized trigger for both immune-mediated and congenital TTP and is associated with increased maternal and fetal morbidity. Clinical overlap with other pregnancy-associated TMAs, including preeclampsia and Hemolysis, Elevated Liver enzymes, and Low Platelet count (HELLP) syndrome, often delays diagnosis. This review synthesizes current evidence on pathophysiology, diagnostic uncertainty, and gestation-specific management of pregnancy-associated TTP, highlighting differences between immune-mediated and congenital disease. Methods: This is a narrative review. We performed a targeted literature search of PubMed/MEDLINE (from inception to December 2025) to identify English-language publications. The study types included were case reports/series, observational studies, large database studies, randomized trials, reviews, and relevant guidelines addressing TMA in pregnancy, with emphasis on immune-mediated and congenital TTP. Search terms included "pregnancy", "thrombotic thrombocytopenic purpura", "hereditary TTP", "acquired TTP", "ADAMTS13," "thrombotic microangiopathy," "HELLP," "postpartum", and "complement-mediated TMA" alone or in combination. The search was supplemented by manual screening of reference lists and key guidelines. Articles were selected based on relevance to diagnosis and management of pregnancy-associated TTP. Conference abstracts and non-peer-reviewed sources were not routinely included and were considered only when peer-reviewed evidence was limited. Results: Pregnancy-associated TTP remains a major diagnostic challenge due to overlapping clinical and laboratory features with other obstetric thrombotic microangiopathies. Distinguishing immune-mediated from congenital TTP is essential, as management and prognosis differ substantially. Prompt recognition and early initiation of therapeutic plasma exchange, immunosuppression, or prophylactic plasma therapy markedly improve maternal outcomes. Rapid ADAMTS13 testing, structured risk stratification, and multidisciplinary care are central to optimal management. Fetal outcomes are closely linked to gestational age at onset and timeliness of therapy. Conclusions: Early differentiation of TTP from other pregnancy-associated TMAs is critical for maternal and fetal survival. Advances in rapid ADAMTS13 diagnostics and emerging targeted therapies, including caplacizumab and recombinant ADAMTS13, offer opportunities to improve precision management and outcomes in future pregnancies.

Background: Sepsis is a life-threatening organ dysfunction that results from an exaggerated host immune response to disseminated infection. The relationship between lymphopenia and sepsis has been extensively studied, and in particular, sepsis-induced lymphopenia is gradually being recognized as an essential factor in the prognosis of sepsis. Notably, sepsis-induced lymphopenia has been associated with worse outcomes, including increased risk of secondary infections, multiple organ failure, and death. Few studies have directly compared the dynamic evolution of lymphocyte counts between different etiologies of sepsis or evaluated their prognostic value using serial measurements. This study aims to explore the temporal dynamics of lymphopenia, but also of neutrophil-to-lymphocyte (NLR) ratio in patients with severe systemic infections and to assess their relationship with in-hospital mortality. Methods: A prospective cohort of 95 adult patients was analyzed. Absolute lymphocyte counts (ALCs) and neutrophil-to-lymphocyte (NLR) ratio values were recorded on Days 1, 3, 5, and 7. Comparisons were made between different infectious etiologies and outcomes, and ROC analysis assessed predictive performance. Results and Conclusions: Patients with viral sepsis ("COVID-19") showed a significant and sustained decrease in lymphocyte counts (p < 0.001) and a progressive increase in NLR (p < 0.001), unlike patients with bacterial sepsis. In correlation with outcome, regardless of etiology, lymphocyte counts were significantly lower in non-survivors from Day 3 onward, while NLR was significantly higher on Day 7 (p = 0.002). Early NLR and ALC had limited predictive value, but longitudinal trends were associated with poor prognosis.

Background: Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HA) are benign hepatic tumors that predominantly affect women of reproductive age and are associated with hormonal and metabolic factors. While FNH is a non-progressive lesion without malignant potential, HA carries a relevant risk of hemorrhage and malignant transformation. Differentiation between these entities remains challenging due to overlapping imaging features. Although contrast-enhanced magnetic resonance imaging (MRI) is considered the diagnostic reference standard, its cost, limited availability, and contraindications restrict routine long-term use. Therefore, contrast-enhanced ultrasound (CEUS) has emerged as an alternative modality for follow-up. This study evaluated the effectiveness of CEUS in long-term monitoring of FNH and HA compared with MRI. Methods: Patients with imaging-confirmed FNH or HA underwent paired CEUS and MRI examinations within 48 h at baseline and follow-up. Lesion size was assessed using maximal and minimal diameters, and longitudinal changes were classified according to RECIST-like criteria. Paired non-parametric statistical tests were applied. Results: 41 benign liver lesions (28 FNH and 13 HA) were analyzed across 92 paired examinations. Baseline lesion measurements were comparable between CEUS and MRI. A statistically significant difference was observed in the assessment of the largest lesion diameter, while no significant differences were detected for the shortest diameter. Longitudinal evaluation showed no significant differences between modalities in detecting lesion size changes. Response classification was concordant in 42 of 51 follow-up assessments, with stable disease as the most frequent outcome. Conclusions: After definitive diagnosis, CEUS may serve as a reliable standalone modality for routine long-term surveillance of FNH and HA in clinically stable patients. Its performance in lesion measurement and response assessment is comparable to MRI, while offering advantages in cost, accessibility, and patient tolerability. MRI may be reserved for cases with suspicious changes on CEUS.

Background: Hepatic ischemia-reperfusion injury (HIRI) is a major complication in liver surgery with limited therapeutic options. Houttuynia cordata polysaccharide (HCP), a key bioactive component of the traditional anti-inflammatory herb, has demonstrated immunomodulatory potential, but its effect on HIRI remains unclear. Methods: A murine model of 70% hepatic ischemia for 60 min followed by reperfusion was established. Mice were administered low-dose (50 mg/kg) or high-dose (100 mg/kg) HCP or the positive control N-acetylcysteine (150 mg/kg). Liver injury was assessed by serum ALT/AST levels, histopathology, oxidative stress markers, and inflammatory cytokines. Macrophage polarization and the TLR4/NF-κB pathway were analyzed using flow cytometry, qPCR, and Western blot. The TLR4 inhibitor TAK-242 was used for reverse validation, and molecular docking was performed to predict HCP binding to the TLR4/MD-2 complex. Results: HCP significantly attenuated HIRI-induced liver injury, as shown by reduced ALT/AST, improved histopathological scores, decreased MDA, increased SOD, and lower TNF-α and IL-6 levels. Mechanistically, HCP promoted a shift from M1 to M2 macrophage polarization, with increased CD206⁺ cells and Arg-1/IL-10 expression and decreased CD86⁺ cells and iNOS/IL-1β expression. HCP also suppressed TLR4/MyD88/NF-κB pathway activation, inhibiting NF-κB p65 phosphorylation and nuclear translocation. These protective effects were largely reversed by TAK-242 in vivo and in vitro. Molecular docking indicated stable binding between HCP and TLR4/MD-2. Conclusions: HCP protects against HIRI by targeting TLR4 to inhibit NF-κB signaling, thereby reprogramming macrophage polarization toward the M2 phenotype and alleviating inflammation and oxidative stress. These findings highlight HCP as a promising natural agent for HIRI intervention.

Background: Mesenchymal stem cells (MSCs) exhibit a high capacity for differentiation, possess anti-inflammatory and proangiogenic properties, and stimulate the growth and proliferation of neighboring cells. MSCs are a promising tool in regenerative medicine. However, the molecular mechanisms underlying the properties of these cells are not yet fully understood. Gene expression in MSCs influences their characteristics and differentiation potential. Therefore, it is essential to investigate factors affecting gene expression as well as those activating signaling pathways, which will enable more effective and individualized applications of MSCs. In this study, we aimed to identify signaling pathways involved in gene expression in umbilical cord-derived MSCs (UC-MSCs) that may be altered by maternal diabetes and hypothyroidism during pregnancy. Methods: The research material consisted of UC-MSCs. Samples obtained from nine participants were analyzed. UC-MSCs were isolated and cultured, and RNA was extracted. The isolated RNA was used for microarray-based gene expression analysis. Subsequently, pathway enrichment analysis was performed to identify the signaling pathways involved. Results: In the diabetes group, 340 genes (0.71%) were upregulated, while 268 genes (0.56%) were downregulated compared with UC-MSCs from the control group. In the diabetes group, the most compact module was composed of proteins associated with WNT/planar cell polarity (WNT/PCP) signaling. The second module included genes related to smooth muscle activity. In the hypothyroidism group, an association was identified between the extracellular matrix organization pathways (GO:0030198) and the extracellular structure organization (GO:0043062) pathways. Moreover, in this group, increased expression of MMP1, MMP10, and GREM1 was observed. Conclusions: In summary, our study demonstrated the impact of diabetes and hypothyroidism on gene expression in UC-MSCs. We also observed the activation of distinct signaling pathways depending on the presence of these conditions. However, this work represents a preliminary screening, and the results should be validated by PCR in a larger cohort.

Background/Objectives: In humans, diseases such as oral cancer may require surgical amputation of the jaw. This severe disruption causes impairments in eating, swallowing, and speech, leading to a significant decline in quality of life. In contrast, newts, a group of urodele amphibians, can regenerate their jaws even in adulthood. This study explored how adult newts reconstruct lower jaws after substantial loss and clarified how this process contributes to rapid functional recovery when feeding becomes impossible. Methods: Adult Japanese fire-bellied newts (Cynops pyrrhogaster) underwent surgical amputation of the anterior half of their lower jaws. Regeneration was monitored for 64 weeks using histological analyses of bone, cartilage, and dental tissues and micro-computed tomography (micro-CT)-based osteomorphometry to quantify structural changes in the regenerating lower jaw. Results: Histological observations and osteomorphometry revealed the following: epithelial coverage of the amputation margin; ectopic cartilage formation, growth, and regression; bone resorption at the amputation margin prior to bone regeneration; anterior extension of the lower jaw bone along the original dentition position, followed by its thickening; and dental lamina invagination with tooth germ formation. Through these processes, the lower jaw bone, Meckel's cartilage, and dentition were restored by 64 weeks post-amputation to their pre-amputation states. Conclusions: This study delineates the full sequence of lower jaw regeneration in adult newts, demonstrating complete restoration of bone, cartilage, and teeth after substantial lower jaw loss. These findings provide a detailed framework for understanding urodele jaw regeneration and may inform future strategies for promoting jaw reconstruction in humans.

Painful diabetic neuropathy (PDN) is a prevalent and debilitating complication of diabetes, characterized by persistent neuropathic pain that severely impairs quality of life. Current management strategies predominantly target peripheral nerve dysfunction and offer only symptomatic relief, with no disease-modifying therapies available. Emerging evidence now underscores the critical role of central nervous system (CNS) glial cells-microglia, astrocytes, and oligodendrocytes, collectively termed the "glial triad"-in driving PDN pathogenesis. This review synthesizes recent advances elucidating how these glial cells contribute to neuroinflammation, metabolic dysregulation, and central sensitization. We detail specific mechanisms including microglial NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation and metabolic reprogramming, astrocytic aquaporin-4 (AQP4) polarity disruption impairing glymphatic function, and oligodendrocyte myelination deficits via Mammalian Target of Rapamycin (mTOR) signaling. Furthermore, we discuss the translational potential of glia-derived biomarkers (e.g., Translocator Protein (TSPO), Glial Fibrillary Acidic Protein (GFAP), myelin basic protein (MBP)) for early diagnosis and patient stratification. Finally, we highlight promising therapeutic avenues that target glial pathways, such as interleukin-35 (IL-35), β-hydroxybutyrate, and metformin, which aim to shift the treatment paradigm from symptomatic control to disease modification. By integrating preclinical and clinical insights, this review proposes the glial triad as a central player in PDN and suggests that targeted glial interventions may represent a promising frontier for future disease-modifying strategies.

The number of patients with chronic kidney disease (CKD) is increasing, and CKD is a major risk factor for progression to end-stage kidney disease (ESKD) requiring renal replacement therapy [...].

In recent years, pulmonology has undergone a profound transformation, perhaps the most significant since the birth of modern respiratory medicine [...].