Biomedicines最新文献

Background/Objectives: Overall survival in patients with amyotrophic lateral sclerosis (ALS) is linked to the rate of predicted respiratory vital capacity (PVC) loss. The objective of this study was to test whether changes in quantitative PVC measures over time linked to survival would define an immunopathogenic subset of ALS responsive to NP001, a regulator of innate immunity. Methods: In a retrospective study, data from intent-to-treat (ITT) population of two phase 2 trials of NP001 were evaluated for over time changes in PVC, time-to-event (TTE) loss of 15% PVC and PVC change from baseline, as linked to survival outcomes in patients treated with NP001 vs placebo. Results: Treatment with NP001 was associated with a significantly lower risk compared to placebo in the loss of 15% PVC over six months (p = 0.01; HR = 0.60, 95% CI: 0.39, 0.90). Data from the two trials were subsequently divided by a disease progression rate (DPR) value of 0.50 units of ALSFRS-R score lost per month for analysis of slow vs. rapid disease. In ALS patients with slowly progressive disease (DPR < 0.50), TTE PVC changes from baseline were slowed (p < 0.0005) and overall survival extended significantly (18.5 months) in NP001-treated vs. placebo groups. The rapidly progressive ALS patients (DPR ≥ 0.50) treated with NP001 showed no significant difference in PVC change or survival from the placebo group. Conclusions: These hypothesis-generating observations suggest that inflammation might play a significant role in the loss of respiratory function in a major subset of ALS patients.

Among cardiomyopathies, the hypertrophic phenotype is the most common, and hypertrophic cardiomyopathy (HCM) phenocopies represent a heterogeneous group of conditions. They are defined by a left ventricular wall thickness ≥15 mm in the absence of other causes such as loading conditions, ischemia, or valvular disease. Although they mimic similar clinical and morphological features, their etiologies are distinct and include genetic, metabolic, and infiltrative mechanisms. Therefore, accurate classification and differential diagnosis are crucial for effective management and treatment. Sarcomeric HCM is the most frequent form, accounting for up to 60% of cases. However, numerous non-sarcomeric phenocopies exist, including amyloidosis, Fabry disease, glycogen storage disorders, RASopathies, and mitochondrial diseases. Clinical and imaging findings are essential to distinguish these entities from sarcomeric HCM. Electrocardiography, echocardiography, advanced modalities such as cardiac magnetic resonance (CMR), and specific laboratory tests all play a central role in guiding diagnosis. Genetic testing provides key insights into mutations and inheritance patterns, further supporting definitive diagnosis. Correct identification of an HCM phenocopy carries important therapeutic implications, as disease-specific treatments can significantly improve prognosis. For example, targeted therapies exist for amyloidosis, Fabry disease, and certain metabolic or mitochondrial disorders, underlining the clinical relevance of an accurate diagnosis. This review aims to provide an overview of HCM phenocopies and assist clinicians in diagnostic reasoning. The first part addresses classification according to pathophysiological mechanisms, clinical features, and genetic background. The second part focuses on the stepwise approach to differential diagnosis, integrating clinical assessment, laboratory evaluation, ECG, echocardiography, and CMR findings.

Background/Objectives: Vaginitis is a prevalent inflammatory disorder of the vaginal mucosa, frequently arising from its anatomical proximity to the anorectal region and a microenvironment conducive to pathogen colonization and dysbiosis. This prospective, multicenter, randomized, third-party-blinded study assessed the efficacy and safety of a plasma vaginal cleanser (WOMEN CARE^®) employing plasma-activated water (PAW) as a non-pharmacological alternative to conventional antimicrobials for restoring vaginal homeostasis. Methods: Women aged ≥19 years with clinically suspected vaginitis were assigned to either the experimental group (WOMEN CARE^®) or the control group (standard pharmacotherapy). The primary endpoint was the proportion of participants exhibiting decreased Nugent scores between baseline and Visit 4. Results: Of 144 participants in the experimental group, 125 completed the study. The experimental group showed comparable outcomes to standard pharmacotherapy group across Nugent scores, vaginal pH, and symptoms severity, with pathogen suppression confirmed as non-inferior. Additionally, PAW exerted anti-HPV activity through a potential effect against new genotypic HPV infection. While the control group experienced antibiotic-associated adverse effects (e.g., headache, abdominal discomfort, nausea), no treatment-related adverse events occurred in the WOMEN CARE^® group. Conclusions: These results indicate that PAW vaginal cleansing provides an effective, safe, non-antibiotic approach for managing vaginitis and maintaining vaginal ecological balance.

Background/Objectives: Anterior cruciate ligament (ACL) injuries frequently lead to long-term quadriceps impairments despite surgical repair. There is growing evidence that these deficits are caused in part by alterations in the central nervous system. Thus, transcranial neuromodulation (TNM) could be valuable in ACL rehabilitation. To systematically review randomized controlled trials (RCTs) assessing the effects of TNM on neurophysiological, functional, and safety outcomes in patients with ACL injury or reconstruction. Methods: We conducted searches on PubMed, Scopus, Web of Science, and Cochrane. We considered all original studies evaluating TNM, including transcranial current stimulation (tCS) and transcranial magnetic stimulation (TMS), in patients with ACL reconstruction or injury. Measures of corticospinal excitability, safety, balance, and muscle strength were assessed. We employed the Cochrane RoB 2 method to assess the risk of bias. Results: Seven studies comprising 129 participants (64 TNM, 65 controls) were included. Most studies applied transcranial direct current stimulation (tDCS) over the primary motor cortex contralateral to the ACL injury in conjunction with physical rehabilitation. Single-session protocols demonstrated minimal effects, whereas repeated sessions resulted in improvements in corticospinal excitability, quadriceps strength, and balance. No serious adverse events were reported; minor effects included transient headache or scalp tingling. The risk of bias was assessed as low to moderate across the studies. Conclusions: TNM appears to be safe and may enhance functional recovery in individuals with ACL injuries when administered in multiple sessions alongside standard rehabilitation. Further high-quality trials are necessary to determine optimal protocols and long-term outcomes.

Adipose tissue is characterized by specialized lipid handling cells called adipocytes, which function as the primary energy reservoir. Like many other cell types, adipocytes have highly plastic properties, such as the conversion of white adipocytes into brown or beige adipocytes, which produce heat, and pink adipocytes into mammary cells synthesizing and secreting milk. Highly specialized adipose tissue depots are present in various species, such as male orangutans with prominent fat-filled facial flanges indicating hierarchical status, or cetaceans with the melon, a specialized adipose tissue for echolocation. Adipose tissue is now considered a true endocrine organ that regulates various physiological mechanisms through the hormonal secretion of adipokines, which modulate systemic metabolism and physiological processes. In particular, the role of adipokines in the control of the reproductive axis and their participation in the regulation of fertility have been widely reported. This review summarizes the current state of research on the effects of adipose-specific cytokines on the male and female reproductive systems.

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative dis-ease caused by the expansion of cytosine-adenine-guanine (CAG) repeats in the ataxin-1 (ATXN1) gene, leading to toxic gain-of-function of the ataxin-1 (ATXN1) protein. This narrative review systematizes the clinical and genetic aspects of SCA1 and discusses key molecular and cellular mechanisms: the ATXN1-CIC ataxin-1-Capicua complex (ATXN1-CIC), the role of serine 776 (Ser776) phosphorylation, interactions with 14-3-3 proteins, transcriptional dysregulation, and critically analyzes experimental models of the disease in vivo and in vitro. In addition, it presents a descriptive quantitative analysis of the literature on in vivo SCA1 models, conducted using a defined search methodology with a cut-off date of 23 November 2025. For each model, phenotypic markers, molecular signatures, and applicability to preclinical testing tasks are summarized. A comparison of the models reveals their complementarity and outlines optimal research trajectories, including omics approaches and prospects for targeted antisense oligonucleotide (ASO) therapy, RNA interference (RNAi), and genome editing. The result is a practical guide for selecting a model in accordance with specific hypotheses and translational objectives.

Background: Severe asthma is a complex chronic airway disease. Biologic therapies are targeted monoclonal antibody treatments used in patients with uncontrolled, severe asthma, but real-world data from long-term registries and on patients who remain biologic-naïve are limited. This study compared severe asthma patients with and without biologic therapy and identified predictors of key clinical remission components. Methods: In this cross-sectional analysis of adult patients from the Swiss Severe Asthma Registry (SSAR), we compared patients treated with a biologic for ≥6 months to biologic-naïve patients (never exposed to biologics). Baseline characteristics were summarized descriptively. Multivariable logistic regression was used to identify predictors of four remission components: good asthma control (ACT ≥ 20), absence of exacerbations, no maintenance oral corticosteroid (OCS) use, and preserved lung function (FEV₁ > 80% predicted). Results: Of 394 patients, 298 (75.6%) were biologic-treated and 96 (24.4%) were biologic-naïve. Biologic-treated patients more often had allergic asthma and type-2-related comorbidities, and showed better outcomes, including fewer exacerbations (0.49 vs. 1.09/year; p < 0.001) and higher ACT scores (20.0 vs. 17.2; p < 0.001). Biologic therapy was independently associated with higher odds of asthma control (OR 3.96; p = 0.006), no exacerbations (OR 5.11; p = 0.001), no OCS use (OR 6.27; p = 0.002), and FEV₁ > 80% predicted (OR 4.42; p = 0.011). Overall, 24.2% of biologic-treated patients and 6.2% of biologic-naïve patients fulfilled all four remission components. Conclusions: In this real-world registry cohort, biologic-treated patients were more likely to meet individual and composite remission criteria than biologic-naïve patients. The relatively low proportion of patients achieving all four stringent criteria highlights the need to revisit current remission definitions and to adopt individualized, multidimensional treatment goals in severe asthma.

Background/Objectives: Female sexual dysfunction (FSD) is common in PCOS, yet mean group comparisons can mask variability at the individual level. We aimed to identify and characterize person-centered profiles of sexual function from the six FSFI (Female Sexual Function Index) domains, and secondarily to describe the distribution of PCOS across profiles. Methods: In an age- and anthropometry-matched case-control sample, unsupervised clustering on FSFI domains was performed; clinical and psychosocial correlates were compared, and logistic regression tested prediction of FSFI-defined FSD. Results: Two profiles emerged-Sexual Dysfunction vs. Preserved Function-with clear multivariate separation. Dysfunction showed lower FSFI, higher adiposity, and worse body-image discomfort. PCOS was more frequent in Dysfunction but not significantly. Cluster membership predicted FSD. Conclusions: Person-centered profiling reveals clinically meaningful heterogeneity that transcends diagnosis and highlights adiposity and body-image distress as salient, potentially modifiable correlates.

Aortic aneurysm and dissection (AAD) represent a life-threatening aortic disorder, for which current treatment strategies rely predominantly on surgical interventions, with limited pharmacological options targeting the underlying pathophysiology. Vascular smooth muscle cell (VSMC) dysfunction constitutes a central pathological mechanism in the development and progression of AAD. This review outlines the association between VSMCs and AAD, covering their physiological functions and pathological alterations, including phenotypic switching, cell death, and VSMC-mediated extracellular matrix remodeling. It further discusses the impact of epigenetic modifications on VSMC core functions. Additionally, this review addresses normal energy metabolism pathways of VSMCs and the mechanisms of metabolic reprogramming, as well as abnormalities in amino acid metabolism, lipid metabolism, and other metabolic pathways. Signaling mechanisms related to AMPK activation and mitochondrial function are also highlighted. Currently, AAD management is dominated by surgical interventions, while pharmacological therapy remains limited to symptomatic control. Looking ahead, future research should focus on VSMC metabolism-related mechanisms to develop early prevention strategies and novel targeted therapeutics, thereby improving the current treatment landscape for AAD.

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage damage. The limited regenerative capability of articular cartilage poses a therapeutic challenge. Adipose mesenchymal stem cell (MSC) exosomes have shown potential in regenerating cartilage structure in previous in vivo studies on small animals. This study aims to compare the effectiveness of intra-articular injections of adipose-derived MSC exosomes and hyaluronic acid (HA) on cartilage regeneration in a sheep osteoarthritis model. Methods: This in vivo study involved 18 male sheep that were induced to develop OA via meniscectomy. The sheep were randomized and divided into three groups: Group 1 (adipose MSC exosomes + HA), Group 2 (adipose MSC exosomes), and Group 3 (HA). Microscopic evaluation using histological scoring with the Pineda score, cartilage regeneration assessment through histochemical and immunohistochemical examinations, and microtopographic examination using a scanning electron microscope (SEM) were performed 6 weeks post-intervention. Results: Cartilage regeneration in the combination group (Group 1) exhibited a larger area of hyaline cartilage (Group 1 vs. Group 2 [40.38 ± 9.35% vs. 34.93 ± 2.32% vs. 31.08 ± 3.47%; p = 0.034]) and a smaller area of fibrocartilage compared to adipose MSC exosomes (Group 2) or HA alone (Group 3) (13.06 ± 2.21% vs. 18.67 ± 3.13% vs. 28.14 ± 3.67%; p = 0.037). Microtopographic examination also showed a more homogeneous and smoother cartilage surface in the combination group (Group 1) of adipose MSC exosomes and HA. Conclusions: In a sheep knee osteoarthritis model, intra-articular injection of a combination of adipose-derived MSC exosomes and HA significantly enhances cartilage regeneration compared to injections of adipose-derived MSC exosomes or HA alone.