Stathmin-3 (STMN3) is a member of the microtubule-destabilizing regulatory protein family and functions to promote microtubule depolymerization. It specifically binds to the α/β heterodimers of microtubules, facilitating their depolymerization and inhibiting polymerization, thereby influencing cell morphology and function. Recent studies have indicated that aberrant expression of STMN3 is closely associated with the development of various diseases. In the field of oncology, STMN3 has been found to be dysregulated in multiple cancer types and is strongly linked to tumor initiation, progression, and metastasis. Owing to these characteristics, STMN3 is involved in diverse physiological and pathological processes as well as critical signaling pathways, demonstrating its potential as a multifunctional regulatory molecule. This article reviews and analyzes the roles and mechanisms of STMN3 in tumorigenesis, with the aim of identifying potential therapeutic targets and contributing to the development of precision medicine strategies for cancer treatment. This study is a narrative review on the role of STMN3 in tumors, which is guided by the Scale for the Assessment of narrative review articles (SANRA). Literature retrieval was conducted in public databases such as PubMed and Web of Science using "STMN3″, "SCLIP", "tumor", and "cancer" as key words, with no restriction on publication time. Relevant studies were screened based on research content and data integrity, including bioinformatic analyses and in vitro/in vivo experimental studies.

Two isoforms of the 90-kDa heat shock protein (Hsp90), stress-inducible Hsp90α and constitutively expressed Hsp90β, function in mammalian cells as molecular chaperones that promote the folding of specific client proteins involved in essential cellular processes and regulatory pathways. A number of Hsp90 client proteins take part in cancer progression, and the inhibition of Hsp90 induces the degradation of oncogenic client proteins and cancer cell death. Hsp90 inhibitors specific for individual Hsp90 isoforms have a significant potential for the development of anticancer therapeutics due to reduced toxicity. Cells with knocked-out genes encoding Hsp90 isoforms represent excellent cellular models to investigate the rearrangement of the cell chaperone machinery in response to the suppression/loss of the Hsp90 isoforms.

Recently, we have shown that the knockout of the HSP90AA1 gene encoding Hsp90α in human fibrosarcoma HT1080 cells does not affect basic cellular processes in normal and stressful conditions, which suggests an adaptation of the cell chaperone machinery to the loss of Hsp90α. Here, we demonstrated that the lack of Hsp90α in HT1080 cells leads to an up-regulation of the constitutively expressed Hsp90β and several important Hsp90 co-chaperones (Aha1, Hop, and others). The expression of the major chaperones of the Hsp70 machinery (Hsp70-1, Hsp70-2, Hsc70) was also significantly induced. The components of the prefoldin-chaperonin folding arm and PFDL, R2TP, and R2SP complexes, as well as the major mitochondrial chaperones, were also largely up-regulated in Hsp90α-KO cells, while the expression of ER-resident chaperones/co-chaperones was either repressed or did not change.

We demonstrated here for the first time an adaptation of the cell chaperone machinery to the loss of the Hsp90α chaperone, which may be important for understanding the molecular mechanisms of action of Hsp90α-specific inhibitors and elaborating new therapy strategies in combating cancer, including the combination of Hsp90α-targeted therapy.

Therapeutic resistance is a major cause of treatment failure in glioblastoma (GBM), highlighting the need for physiologically relevant models to identify actionable resistance mechanisms. While two-dimensional (2D) cultures are widely used for target discovery, they poorly represent the tumor microenvironment. In contrast, three-dimensional (3D) spheroid cultures better recapitulate spatial heterogeneity, hypoxic gradients, and stress-adaptive signaling observed in tumors.

We applied an integrated 2D-3D quantitative proteomic approach to identify microenvironment-dependent regulators of chemoresistance in GBM. Proteomic profiling was performed in U87MG and U251MG cells grown as 2D monolayers or 3D spheroids. Differentially expressed proteins were validated by quantitative RT-PCR, and functional studies were conducted using genetic depletion followed by assessment of temozolomide (TMZ) sensitivity.

Comparative analysis identified 13 proteins consistently differentially expressed between 2D and 3D cultures: NDUFB5, RNGTT, MLK4, SYN1, DDX5, EIF2AK2, ITGA1, ZNF33B, ZNF343, WDR19, JPH3, CCT8L2, and FNDC3A. Among these, Mixed Lineage Kinase 4 (MLK4) showed strong and reproducible upregulation in 3D spheroids in both GBM cell lines. Genetic depletion of MLK4 significantly increased TMZ sensitivity without affecting basal cell viability, suggesting a specific role in therapy response. Notably, MLK4 expression was induced only under 3D conditions.

MLK4 functions as a microenvironment-responsive regulator of chemoresistance in GBM. These findings demonstrate that 3D culture systems reveal clinically relevant resistance pathways not detectable in conventional 2D models and highlight 3D proteomic profiling as a powerful strategy for identifying therapeutically actionable targets.

The clinical trajectory of pulmonary vascular disease (PVD) is governed by the functional and molecular integration of the right ventricle (RV) and pulmonary vasculature-the cardiopulmonary unit. Right ventricular-pulmonary arterial (RV-PA) coupling (Ees/Ea) is the principal determinant of survival. This review synthesizes contemporary pathophysiology and therapeutics through the lens of RV-PA coupling, reflecting the recognition of active heart-lung crosstalk. Advancing beyond traditional reviews, this article (1) formalizes a phenotype-guided treatment algorithm based on coupling derangement, (2) integrates emerging concepts of molecular crosstalk mediated by extracellular vesicles, and (3) positions sotatercept as a "coupling drug" targeting both components of the cardiopulmonary unit. We detail maladaptive pathways-including metabolic reprogramming, inflammation, fibrosis, and sex hormone signaling-that degrade RV contractility (Ees) under chronic pressure overload. The pharmacotherapeutic landscape is critically evaluated: from established vasodilators that indirectly support the RV by reducing afterload (Ea) to transformative disease-modifying agents like sotatercept that reverse vascular remodeling and the emerging frontier of direct RV-targeted therapies. We argue that the future of PVD management lies in a precision-based strategy using deep phenotyping to classify patients by dominant coupling derangements and matching them with mechanism-based therapies. The paradigm must shift beyond symptomatic vasodilation toward regimens explicitly designed to restore the physiological balance of the cardiopulmonary unit, carefully distinguishing between validated standards of care and investigational approaches.

This study aimed to develop a method for extracting acoustic features to assess left anterior descending artery (LAD) stenosis severity.

Heart sound data were collected from 75 participants (10 diastoles per participant) using a high-signal-to-noise ratio micro-electro-mechanical systems stethoscope. The diastolic signals were preprocessed, and empirical wavelet transform was applied to decompose their power spectra into three modes (0-150, 150-500, and > 500 Hz). The spectral energies (e(1), e(2), e(3)) of these modes were analyzed, and support vector machine (SVM) and extreme gradient boosting (XGBoost) machine learning algorithms were used to classify LAD stenosis into mild (< 50%), moderate (50%-75%), and severe (> 75%).

Spectral energies e(2) and e(3) significantly increased with stenosis severity, and XGBoost outperformed SVM, achieving a test accuracy of 0.8133 and areas under the curve of 0.9358, 0.9644, and 0.9580 for mild, moderate, and severe stenosis, respectively.

Empirical wavelet transform-extracted spectral energies of e(2) and e(3), combined with XGBoost, effectively determine LAD stenosis degree, offering a non-invasive screening tool.

Acute ischemic stroke (AIS) is one of the leading causes of death and disabilities, and as such, it is of utmost importance to identify novel treatment options. Remote ischemic conditioning (RIC) is a promising non-invasive treatment that is thought to activate the body's own protective mechanisms against damaging ischemia. Here, we study the transcriptomic impact of microRNAs (miRNAs) that are upregulated by RIC.

Using RNA sequencing, we investigated the transcriptional changes in human brain microvascular endothelial cells (HBMECs) transfected with four selected RIC-upregulated miRNAs (RIC-miRNAs), miR-16-5p, miR-144-3p, miR-182-5p, and miR-451a, under oxygen and glucose deprivation (OGD) and reoxygenation-mimicking the initial stages of AIS.

Pronounced transcriptional changes were present after RIC-miRNA transfection, with 149 unique downregulated and 212 upregulated differentially expressed genes in HBMECs after OGD and RIC-miRNA transfection compared to all other conditions. These genes were involved in pathways of energy metabolism and cell cycle regulation.

Our study suggests that the selected RIC-miRNAs regulate pathways that may facilitate endothelial cell survival, recovery, and remodeling events from ischemic damage, adding to the knowledge of the pathways affected by RIC during stroke.

Persistent pelvic pain (PPP) is often regarded as multifactorial and complex. There is limited knowledge on how patients with PPP resemble and differ from those with persistent non-pelvic pain (PNPP). The specific aims of this study were to compare self-reported background and pain characteristics, affective symptoms, and quality of life at baseline between patients with PPP and those with PNPP at three multidisciplinary pain clinics in Norway, and to explore differences between men and women with PPP.

This is a cross-sectional study, using registry data from three tertiary, multidisciplinary pain clinics. Patients ≥17 years answered web-based questionnaires on background, baseline pain symptoms, mental health, and quality of life. We used t-tests, chi square, and multivariable logistic regression.

Of 934 consenting patients (71 % of those attending), 30 had missing diagnoses, and 127 (13.6 %) were diagnosed with PPP. PPP patients less often reported widespread pain than PNPP patients (adjusted odds ratio (AOR) 0.2, 95 % confidence interval (CI) 0.2-0.4). We found high prevalence of fatigue, insomnia, and anxiety among all the pain patients, but PPP patients were more likely to report depression (AOR 1.6, 95 % CI 1.0-2.6) and pain catastrophizing (AOR 1.8, 95 % CI 1.2-2.8). All the pain patients had a low health-related quality of life. Women with PPP had higher prevalence of severe fatigue than men with PPP.

This study confirms that pain clinic patients generally experience high levels of emotional distress and poor health-related quality of life. PPP patients tend to exhibit higher rates of pain catastrophizing, yet less widespread pain. Understanding the specific symptom profile of PPP patients is crucial for effective treatment in pain clinics. The potential underutilization of pain clinics in the treatment of PPP patients warrants further investigation.

Child maltreatment is a significant risk factor for mental and metabolic health, with negative effects that can persist into adulthood. Using data from a U.S.-nationwide study, the National Longitudinal Study of Adolescent to Adult Health (Add Health), this study examined the associations between child maltreatment, specifically childhood threat (i.e., harm or threat of harm) and deprivation (i.e., absence of expected environmental inputs), and young adult mental (i.e., depressive symptoms) and metabolic health (i.e., metabolic risk). The moderating effect of social support was also examined, focusing on both quality of different types of support (i.e., from teachers, friends, and other adults) and variety of support sources. Results showed that young adults who experienced more threat during childhood exhibited higher levels of depressive symptoms in young adulthood, and those exposed to more deprivation reported elevated levels of metabolic risk. This study also highlighted the protective-stabilizing role of quality of teacher support in buffering the impact of deprivation on depressive symptoms, and the protective-stabilizing role of high-quality other adult support in the link between childhood deprivation and metabolic risk, such that the benefits of social support remained stable across increasing levels of deprivation. Additionally, the variety of social support showed a protective-reactive pattern in moderating the link between deprivation and metabolic risk, wherein the benefits of variety of social support were released under low deprivation but not high deprivation conditions for metabolic risk. These findings underscore the importance of eliminating child maltreatment experiences and highlight potential interventions, such as enhancing teacher-student relationships and broadening adolescents' access to diverse support networks, to buffer the long-term mental and metabolic health consequences associated with early experiences of threat and deprivation.

Previous studies assessed dynamic functional connectivity in obsessive-compulsive disorder (OCD) by the sliding-window approach, limiting sensitivity to rapid neural fluctuations. Moreover, the mechanisms underlying dynamic transitions between brain states also remain unknown. Therefore, the study aimed to explore the dynamic neural mechanisms of OCD by characterizing state dynamic patterns and the underlying energy basis.

The study recruited 198 OCD patients and 109 healthy controls, characterizing altered state dynamic patterns and underlying control energy in OCD by integrating co-activation pattern (CAP) analysis with network control theory (NCT).

OCD patients showed increased occurrences of the states characterized by ventral attention and somatomotor network co-activation with default mode network suppression (VAN-SMN⁺/DMN^-) and default mode network activation with ventral attention network suppression (DMN⁺/VAN^-), reduced persistence of the actively frontoparietal network with suppressively visual network (FPN⁺/VIS^-) state, and elevated transitions among DMN⁺/VAN^-, VAN-SMN⁺/DMN^-, and SMN-VAN⁺/VIS^- states. Moreover, computational enhancement of FPN⁺/VIS^- state persistence via virtual perturbation partially improved abnormal brain-state dynamics in OCD. NCT further revealed that state transitions from DMN⁺/VAN^- to VAN-SMN⁺/DMN^- or SMN-VAN⁺/VIS^- required reduced control energy under modulation by GABAergic signaling and mitochondrial respiratory capacity, forming a "low-cost pathological shortcut" associated with greater symptom severity; state transitions from SMN-VAN⁺/VIS^- to VAN-SMN⁺/DMN^- were intrinsically energy-demanding, modulated by dopaminergic and serotonergic systems, constituting an "inefficient pathological transition" consistent with repetitive behavior observed clinically.

OCD is characterized by a maladaptive brain-state cycle marked by excessive DMN dominance, frequent shifts to VAN/SMN activation states, and attenuated FPN engagement. Computationally enhancing the persistence of the FPN⁺/VIS^- state via virtual perturbation partially improved the dysregulated cycle in OCD. Within this cycle, two distinct pathological transition modes emerged: a "low-cost shortcut" from DMN to VAN/SMN modulated by GABAergic and an "inefficient transition" from SMN to VAN linked to dopaminergic and serotonergic. These reveal neurochemically grounded alterations in the energy control of abnormal brain-state transitions, offering mechanistic insights into the disrupted neural dynamics of OCD.

Policy Points A quarter of a century since bioethicist Edmund Pellegrino warned about the commodification of health and health care, the problem has significantly worsened. Commodification of health and health care objectifies and dehumanizes people and undermines core concepts of holistic person-centered health, much less core human rights, including fulfillment of human potential and comprehensive health care. Multilevel sustained strategies and multisector coalitions are required to decommodify and humanize health and health care based on mental models, national and state policies, practices, resource flow, power dynamics, and relationships and connections.

Edmund Pellegrino warned about the growing commodification of health and health care in the United States. After twenty-five years, it is worth revisiting Pellegrino's critique and examining this critique in the current era.

We conducted a targeted review of the literature to revisit the state of commodification in health and health care as defined by Pellegrino, examined its relationship to dehumanization, and explored prospects for addressing commodification.

The commodification of health and health care substantially worsened in the US, characterized by increased health care corporatization and consolidation, biomedical lobbying, and unaffordable costs. Commodification and dehumanization reinforce each other, undermining rights to health and health care, the provision of holistic person-centered health, and the fulfillment of human potential. Decommodifying and humanizing health and health care requires a paradigm shift towards whole-person definitions of health; the acknowledgement of human relationships as a foundation; the recognition of health as a social good; and the need for society and healthcare to partner to optimize health, including providing health care to all.

This paradigm shift will require collective, cross-sectoral advocacy and mobilization not only by diverse health care professional organizations but also by organizations outside health care that are committed to improving health for all.