医学最新文献

Background: Current risk stratification for neuroblastoma (NB) relies on limited markers like MYCN amplification. Coilin, a key Cajal body component, regulates cellular processes. This study investigates whether coilin expression in bone marrow (BM) serves as a predictive biomarker for NB progression and elucidate its function in this disease.

Methods: The functions and molecular mechanisms of coilin were investigated by employing cell lines and animal models. Coilin mRNA levels in patient samples were measured by RT-PCR, and their relationships with clinicobiological characteristics and outcomes were analyzed.

Results: Cisplatin induced dramatic changes of coilin distribution and expression. Databases showed that high expression of coilin exerted predictive values for poor outcome in NB. Coilin promoted proliferation in vitro and in vivo. Knockdown of coilin expression inhibited cell migration and invasion, promoted apoptosis and increased the Cisplatin drug sensitivity. Moreover, coilin activates p53/p21 signaling pathway and was a direct target of MYCN. Analysis of BM samples demonstrated that high expression of coilin was obviously associated with adverse clinical biological features. Importantly, the levels of coilin at diagnosis were markedly higher than those at the time before maintenance treatment in the exact paired patients. Survival analysis presented that high coilin expression in BM is associated with poor prognosis.

Conclusions: A novel and accessible coilin-targeted liquid biopsy method was developed, capable of detecting minimal residual disease (MRD) in early-stage NB and predicting disease progression and recurrence. Coilin was transcriptionally regulated by MYCN, offering potential avenues for the development of novel drugs or intervention strategies.

Objective: Perivascular adipose tissue (PVAT) is closely related to the pathogenesis of vascular remodeling in hypertension. The objective of this study was to explore the specific molecular mechanisms underlying the role of PVAT in the onset and progression of hypertensive vascular remodeling.

Methods: Thoracic aorta PVAT from male spontaneously hypertensive rats (SHRs) and male Wistar-Kyoto (WKY) rats was used for proteomic analysis, and the differential expression of the identified target proteins was verified by western blotting, immunohistochemistry and transmission electron microscopy (TEM). In vitro, FUN14 domain-containing 2 (FUNDC2) expression was knocked down in 3T3-L1 adipocytes to assess its effects on mitochondrial dynamics, ferroptosis, and adipokine secretion. Next, vascular smooth muscle cells (VSMCs) were cultured in the supernatant of the adipocytes to detect changes in their phenotypic switching and migration.

Results: The proteomic results revealed that the expression of the outer mitochondrial membrane protein FUNDC2 was significantly upregulated in the PVAT of SHRs. Additionally, the expression of key proteins that regulate mitochondrial dynamics and ferroptosis was altered significantly in the PVAT of SHRs compared with the PVAT of WKY rats. Upon FUNDC2 knockdown in 3T3-L1 adipocytes, proteins related to mitochondrial dynamics, ferroptosis, and adipokines reversed the changes in their expression. Moreover, in VSMCs cultured with the supernatant of FUNDC2-knockdown adipocytes, the VSMC phenotype and migration changed.

Conclusion: Our findings indicated that increased FUNDC2 expression might lead to PVAT dysfunction and abnormal adipokine secretion, potentially through its link to mitochondrial dynamics and ferroptosis in PVAT adipocytes, therefore leading to hypertensive vascular remodeling.

Responses to lung injury can vary between individuals with the diet and gut microbiome representing two underappreciated sources for this variability. The gut microbiome can influence lung injury outcomes through the gut‒lung axis, but exactly how diet and its effects on the microbiota are involved remains unclear. We hypothesized that dietary fiber interventions would favor the presence of short-chain fatty acid (SCFA)-producing fermentative bacteria presence in the gut microbiome, thereby influencing the resting lung immunometabolic tone as well as influencing downstream responses to lung injury and infection. To test this hypothesis, we fed mice fiber-rich (FR) and fiber-free (FF) diets, and observed changes in the steady-state transcriptional programming of alveolar macrophages (AM). Next, we examined the effects of the FR and FF diets on murine responses to sterile and infectious lung injury in vivo while simultaneously profiling the gut microbiota and SCFA levels transmitted along the gut‒lung axis. Finally, we validated our in vivo observations with mechanistic studies of the metabolic, signaling, and chromatin-modifying effects of specific SCFAs on lung AM ex vivo and in vitro. Overall, our fiber-rich diet reprogrammed AMs and attenuated lung inflammation after sterile injury while exacerbating lung infection. This effect of FR diets could be transferred to germ-free (GF) mice by fecal microbiome transplantation (FMT) and depended on the ability of the microbiota to produce propionate. Mechanistically, SCFAs altered the metabolic programming of AMs and lung tissue ex vivo without a clear role for free fatty acid receptors (FFAR) or chromatin remodeling. These findings demonstrate that the gut‒lung axis can regulate resting lung metabolic tone through dietary fiber intake and the enrichment of SCFA-producing gut bacteria, as well as influence sterile and non-sterile lung injury responses. These results provide evidence to support the development of therapeutic dietary interventions to preserve or enhance specific aspects of host pulmonary immunity.

Purpose: Pregnancy is a time of rapid physical transformations. Medical and societal pressures regarding women's weight and body image throughout pregnancy may increase body dissatisfaction, which can negatively affect psychological health and health behaviors. Yet healthcare providers (HCPs) often feel uncomfortable addressing the topic. This study explored women's experiences of body changes during pregnancy, as well as the practices and challenges faced by midwives and dietitians in supporting them.

Methods: A purposeful sample of 20 pregnant women (16-32 weeks of gestation) in Switzerland participated in face-to-face semi-structured interviews. In addition, four focus groups were conducted with six midwives and four dietitians. All narratives were transcribed verbatim and analyzed using thematic analysis.

Results: Three themes were identified in pregnant women's interviews: navigating body changes, managing the unmanageable, and experiencing lack of support around body image and weight gain. Women worried about weight gain, attempted to monitor their diet, and often felt unsupported by HCPs. Two themes were identified in HCP focus groups: reassuring and conveying information, and experiencing practical obstacles and societal challenges. HCPs acknowledged the sensitivity of the topic and described adopting a reassuring stance while conveying information and seeking ways to help women make peace with their bodies.

Conclusions: Tailored support for body image during pregnancy is needed to promote maternal and fetal health. Midwives and dietitians are well placed to provide interdisciplinary consultations addressing gestational weight gain and body dissatisfaction. Training in positive body image could enhance their confidence in addressing these issues.

Purpose: Contemporary university communities have been reshaped by changing societal expectations, the COVID-19 pandemic, and structural reforms, increasing the pace, complexity, and demands of academic work for both staff and students. These pressures disrupt existential well-being (EWB), understood as a multidimensional construct encompassing meaning, purpose, coherence, and relatedness. This study examines how university staff conceptualize well-being support in academic communities and how EWB appears in their accounts.

Method: The study was conducted in Finnish universities representing diverse geographical locations and institutional sizes. Data consist of 14 semi-structured interviews with staff working in well-being-related expert roles. The data were analysed using a data-driven, inductive Template Analysis approach supported by Atlas.ti.

Results: Well-being in universities was found to be supported through three interrelated domains: well-being management, pedagogical well-being, and community resilience. These form the structural basis for sustainable EWB practices but require sufficient institutional resources. Hybrid teaching and remote work challenged emotional safety and social connectedness. EWB emerged primarily from shared institutional practices, particularly teacher-student relationships and early engagement.

Conclusion: The study emphasizes integrating EWB into university practices by addressing both individual and collective dimensions. Structural conditions, supportive culture, and meaningful social connections are central to fostering EWB as a pedagogical and communal value.

Peritoneal metastasis (PM), as a terminal stage of malignant tumors with extremely poor prognosis, remains a clinical challenge. Intraperitoneal (IP) administration enhances local drug concentrations, improving survival outcomes for PM patients. However, rapid drug clearance and uneven distribution limit its therapeutic potential. In recent years, hydrogel-based drug delivery systems have garnered attention due to their excellent biocompatibility, drug loading capacity, and controlled release properties. The use of hydrogel-loaded drugs via IP injection can significantly improve anti-cancer efficacy by increasing the local drug concentration, prolonging the retention time of the drug in the peritoneal cavity, and decreasing systemic toxicity. This review summarizes the pathogenesis and current treatment strategies of PM, emphasizing various drugs (including chemotherapy agents, immunotherapeutics, targeted drugs, radioactive isotopes, and herbal medicines) delivered via hydrogel-based IP administration. Furthermore, it highlights the potential of nanoparticles and microparticle-hydrogel composites to further improve drug delivery, offering new strategies for PM treatment and theoretical basis for clinical rational drug use.

Mycobacterial lung diseases, including tuberculosis (TB) and nontuberculous mycobacterial pulmonary disease (NTM-PD), are increasingly recognized as disorders influenced not only by host immunity but also by microbiota. Emerging evidence identifies the gut-lung axis (GLA) as a key bidirectional communication network linking intestinal and pulmonary homeostasis. Mycobacterial infection itself induces airway and gut dysbiosis through immune and metabolic disturbances, which is further exacerbated by prolonged antibiotic therapy. Dysbiosis within either site reciprocally affects the other via GLA, leading to reduced microbial diversity, impaired epithelial integrity, and systemic inflammation. These alterations disrupt metabolite-mediated immunoregulation and attenuate IL-22-driven epithelial defense, thereby weakening bacterial clearance and promoting chronic inflammation. Distinct microbial features, such as the depletion of beneficial SCFA-producing taxa and enrichment of pro-inflammatory anaerobes, are observed in both TB and NTM-PD. Moreover, therapy-induced microbiome remodeling influences treatment response and disease relapse. Restoring microbial balance through probiotics, prebiotics, postbiotics, dietary modulation, or fecal microbiota transplantation offers a promising adjunctive strategy. This review integrates current evidence linking microbiome dysbiosis to mycobacterial pathogenesis and highlights microbiome-targeted interventions as an emerging therapeutic frontier in pulmonary mycobacterial diseases.

Purpose: This systematic review synthesizes evidence on depressive symptoms and access to mental health care following miscarriage. It examines differences between women in general care settings and those with recurrent pregnancy loss to explore differential psychological vulnerability and care gaps.

Methods: A search of four databases (inception-June 2025) followed PRISMA guidelines. Studies reporting depressive symptoms or barriers and facilitators to care were included. Given methodological heterogeneity, findings were synthesized narratively using a SWiM framework, stratifying populations by miscarriage history and assessing quality with risk-of-bias tools.

Results: Of 1,140 records, 46 were included. Depressive symptoms were common, though prevalence varied by timing, tools, and characteristics. Evidence suggests a possible graded association between recurrent loss and symptoms, although this was inconsistent and often attenuated in acute assessments. Key correlates included childlessness, prior psychiatric history, repeated loss, and low social support. Barriers included insensitive communication, lack of follow-up, and financial constraints. Facilitators included empathetic interactions, clear information, and supportive networks.

Conclusions: Miscarriage is frequently associated with significant distress, yet evidence certainty varies regarding recurrence and intervention effectiveness. Findings highlight a persistent gap between women's mental health needs and healthcare responses.

Purpose: This study aimed to explore and describe how coordinated care transitions aligned with legislation when older adults are discharged from in-patient care to their homes.

Methods: A mixed-method (QUAL + qual) design was used. The core data component (QUAL) consisted of copies of 15 older adults' healthcare and social care records. The supplementary data component (qual) encompassed individual interviews. All data related to the same older adults, whose coordinated care transitions took place between January to June 2022. The analytical procedure followed a deductive thematic analysis.

Results: Findings showed that individual care plans were often missing or inadequately documented. Documentation of older adults' participation was frequently poor and inconsistent, with many decisions made without their input. However, some documents and interviews indicated that older adults had genuinely participated. The discrepancy between documented procedures and actual experiences reveals significant variability in older adults' inclusion.

Conclusion: This study highlights the frequent exclusion of older adults from coordinated care transition process and deficiencies in documentation. The findings underscore the urgent need for standardized and inclusive documentation practices, as well as improved communication strategies, to ensure more person-centred care transitions, in which older adults are genuinely involved and well-informed about their care transitions.

Background: Astrocytes, once regarded as passive support cells, are recognized as active regulators of synaptic organization and neuronal integration. Through extension or retraction of their processes, astrocytes influence synapse formation and elimination. Astrocytes express estrogen receptors, and animal studies have shown that estradiol modifies astrocytic morphology in relation to synaptic density.

Objective: To examine the effects of estradiol and two clinically available selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene on astrocyte processes in human brain tissue.

Methods: Human temporal lobe cortical slices were incubated for 60 min with estradiol (10 nM), tamoxifen (1.0 µM), or raloxifene (1.0 µM), and the results were compared with untreated control slices. Astrocytes were visualized by immunostaining for the glial cytoskeletal marker glial fibrillary acidic protein (GFAP). Light microscopy image analysis was used to quantify astrocytic process thickness and branching, using Neurolucida® software.

Results: Control slices exhibited astrocytic branch extension and thinning during the incubation period. Similar morphological changes were observed in the tamoxifen-treated slices. In contrast, raloxifene treatment was associated with a significant reduction in astrocyte branching and thinning compared with controls (p = 0.01 for primary processes). Estradiol treatment resulted in intermediate reductions in astroglial process measures that did not reach statistical significance.

Conclusions: Estradiol, tamoxifen, and raloxifene - widely used hormonal agents - were associated with distinct effects on astrocyte morphology in human cortical tissue. These findings support a role for estrogen receptor modulation in astroglial structural regulation and suggest a potential cellular mechanism contributing to central nervous system symptoms reported in clinical settings.