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Uterine leiomyosarcoma (uLMS) is a rare, highly aggressive malignancy of uterine smooth muscle, associated with early metastasis, frequent recurrence, and poor prognosis. Accurate preoperative diagnosis remains difficult given that clinical and radiologic features often overlap with benign leiomyomas, and no reliable biomarkers are currently available. This review summarizes recent evidence on the role of microRNAs (miRNAs) in the biology and clinical management of uLMS. Literature from molecular and translational studies was examined to identify dysregulated miRNAs, their target pathways, and potential diagnostic and therapeutic applications. uLMS displays a characteristic miRNA profile, including downregulation of tumor-suppressive miRNAs such as the miR-29 and miR-200 families and upregulation of oncogenic miRNAs including miR-21 and the miR-183~96~182 cluster, leading to activation of PI3K/AKT/mTOR signaling and epithelial–mesenchymal transition (EMT). Circulating and tissue miRNAs show promise as minimally invasive biomarkers for differentiating uLMS from leiomyomas, predicting prognosis, and guiding therapy. Emerging therapeutic approaches aim to restore the tumor-suppressive miRNAs or inhibit oncogenic ones using mimics or antagomiRs. Overall miRNAs represent critical regulators of uLMS pathogenesis and hold significant potential for precision diagnosis, prognostication, and targeted therapy, though larger validation studies and improved delivery systems are required before clinical translation.

: Children with febrile urinary tract infections (fUTIs) may be at risk for kidney scarring. Inflammatory biomarkers may predict the risk of scarring. The aim of this study was to investigate the predictive role of PCT, CRP and other markers in scarring in pediatric patients with first fUTI. : The study was in accordance with the institution's ethics committee (No. 108/2023). Included patients underwent a kidney-ureter-cyst ultrasound (US). The primary outcomes of this study were the associations of procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC) with kidney scarring. The secondary outcomes were the associations of PCT, CRP, and WBC with vesicoureteral reflux (VUR). A < 0.05 was considered statistically significant. : Sixty-five pediatric patients (1-16 years of age) with a first fUTI, from February 2023 to January 2025, were included. Sixteen patients had VUR, and thirteen patients developed kidney scarring. C-reactive protein was significantly elevated in the VUR group ( = 0.026). In a series of logistic regression analyses, abnormal US findings and severe VUR were associated with scarring ( = 0.009 and = 0.016, accordingly). The optimal cut-off value for PCT in predicting scarring was calculated as 6.05 ng/mL (sensitivity: 36% and specificity: 97%), and for CRP as 3.62 mg/dL (sensitivity: 63.6% and specificity: 62.1%). : This study showed a significant difference in CRP levels between the groups with and without VUR. Abnormal US findings and severe VUR were the most significant predictors of kidney scarring. Significant difference was not reached in PCT and WBC levels between the groups with and without VUR or with and without kidney scarring. The small sample size may have influenced the study's outcomes.

Cytarabine (Ara-C) remains the cornerstone of remission-induction and consolidation chemotherapy for acute myeloid leukemia (AML) and related hematological malignancies. Despite more than six decades of clinical use, its multi-organ toxicity continues to be managed almost exclusively through dose attenuation and supportive care, with no approved upstream pharmacological prevention strategy available. This scoping review aimed to systematically map the breadth and nature of pharmacological agents tested in vivo for their capacity to mitigate cytarabine-induced multi-organ toxicity, to characterize their mechanisms of action and organ targets, and to identify evidence gaps and agents with translational potential. The review was designed and reported in accordance with the PRISMA-ScR checklist. A structured electronic search was conducted across PubMed/MEDLINE, Scopus, Cochrane Library and Embase, and Web of Science from database inception to 15 July 2025. Eligible studies were restricted to full-text, peer-reviewed, English-language research involving in vivo mammalian models administered cytarabine as the principal toxin, with at least one pharmacological co-intervention and at least one quantitative or histopathological organ-injury outcome. From 5701 retrieved records, 36 eligible in vivo mammalian studies (spanning 1964-2024) were identified. Included studies addressed neurotoxicity ( = 6), gastrointestinal mucositis ( = 9), ocular toxicity ( = 3), hepatotoxicity ( = 3), bone marrow suppression ( = 4), chemotherapy-induced alopecia ( = 5), and reproductive and developmental toxicity ( = 4). Five recurring mechanistic strategies were identified across the heterogeneous agents tested: redox buffering (N-acetylcysteine, α-lipoic acid, rutin, swertiamarin, α-tocopherol), mitochondrial preservation (betanin, thymoquinone, vitamin D, sodium zinc dihydrolipoylhistidinate [DHLHZn]), tissue-microenvironment reprogramming (apraglutide, BADGE, plerixafor, short-chain fatty acids, β-glucan), molecular antagonism (deoxycytidine, dCMP), and immunomodulation (lienal peptide, IL-1β, AHCC). This scoping review provides the first systematic cartography of pharmacological mitigation strategies for cytarabine-induced multi-organ toxicity. Five mechanistic pathways converge across eight organ systems, with apraglutide and N-acetylcysteine representing the most clinically translatable candidates. Plerixafor and PPARγ blockade by BADGE constitute high-priority candidates for bone marrow niche protection, while the deoxycytidine antagonism principle warrants formal pharmacokinetic evaluation. The complete absence of cardiotoxicity mitigation data defines the most critical gap for future research.

Mild cognitive impairment (MCI) is recognized as an intermediate stage between normal aging and dementia. Oxidative stress is implicated in the pathophysiology of neurodegenerative diseases, playing a crucial role. This study aimed to investigate the differences in malondialdehyde (MDA) levels in the serum and cerebrospinal fluid (CSF) of patients with MCI compared to FDA-approved biomarkers, based on age, sex, and education level. Participants aged 55–90 years old were categorized into three groups based on FDA-approved biomarkers, especially the CSF Aβ42/Aβ40 ratio and clinical screening assessments: 30 MCI (A+) patients with abnormal CSF Aβ42/Aβ40 ratios (Group A), 30 MCI (A−) patients with normal CSF Aβ42/Aβ40 ratios (Group B), and 30 healthy (A−) participants with normal CSF Aβ42/Aβ40 ratios (Group C). The measurements of CSF FDA-approved biomarkers were performed using an automated immunochemical method (Fujirebio, Inc.), while MDA determination was performed using a competitive inhibition enzyme immunoassay technique (ELK Biotechnology Co., Ltd.). Our results showed that the mean CSF MDA values were significantly lower in group C than in group A (83 ng/mL vs. 130 ng/mL, p = 0.024) and group B (83 ng/mL vs. 142 ng/mL, p = 0.011), respectively. Differences in serum and CSF MDA levels were presented in the study groups based on sex, age, and education level. These findings suggest that lipid peroxidation, as indicated by CSF MDA, could serve as a potential biomarker for the early recognition of MCI.

Immune thrombocytopenia (ITP) is a hematological disorder commonly found in individuals of any gender, race, or age. Patients with ITP will present with thrombocytopenia either in a primary form or because of an infection or a dysfunction in the immune system. The severity of ITP is linked to diminished production of platelets due to the blockage of production in the bone marrow niche and increased destruction of platelets, which confirms the diagnosis of the disorder. The investigation of the pathogenesis of ITP is of critical importance as it can give an important indication of the state of the patient, guiding us through risk assessment and treatment. Proteomics can provide tools to explore the protein profile of ITP. In this review, we aimed to uncover different biomarkers, both diagnostic and prognostic, that have been investigated with proteomic methodologies and that might help in understanding the pathogenesis of ITP and providing personalized treatment to patients. Several differentially abundant proteins were identified, including haptoglobin isoforms, heat shock proteins (HSPA6, HSPA8), integrin β3 (ITGB3), 14-3-3 protein eta (YWHAH), vitamin D-binding protein, fibrinogen chains, MYH9, and FETUB, which are involved in key signaling pathways, such as PI3K/akt, TNF-a, and mTOR, and they demonstrate potential as diagnostic and prognostic biomarkers. Collectively, current data support the value of proteomics for uncovering the molecular landscape of ITP and guiding the development of precision diagnostics and personalized therapeutic strategies.

Myelodysplastic syndromes (MDS) belong to a category of malignant stem-cell and myeloid disorders that deteriorate the function of the hematopoietic system exacerbated by the omnipresent anemia that characterizes myelodysplasia. The pathogenesis of MDS is driven by cytogenetic abnormalities along with the excessive production of pro-inflammatory cytokines and disruptions in inflammatory signaling pathway, particularly through the influence of carbonylated proteins, which are linked to MDS progression. An additional and major contributor to the pathogenesis of MDS is oxidative stress marked by uncontrolled levels of reactive oxygen species (ROS), which have been suggested as potential biomarkers for assessing disease severity and stratifying MDS cases throughout a variety of methods. Excessive and non-accumulative levels of free iron can also lead to iron overload (IOL)—related promotion of a high oxidative state, whether we refer to treatment-related IOL or natural IOL mechanisms. Proteomic analysis has emerged as a powerful tool for profiling protein samples, and, consequently, understanding the molecular changes underlying MDS. In this review, we evaluated studies and their methodologies aiming in investigating distinctive proteomics signatures associated with MDS pathogenesis, focusing on the role of oxidative stress at the protein level.

Nonalcoholic fatty liver disease (NAFLD), the most widespread chronic liver disease worldwide, confers a significant burden on health systems and leads to increased mortality and morbidity through several extrahepatic complications. NAFLD comprises a broad spectrum of liver-related disorders, including steatosis, cirrhosis, and hepatocellular carcinoma. It affects almost 30% of adults in the general population and up to 70% of people with type 2 diabetes (T2DM), sharing common pathogenetic pathways with the latter. In addition, NAFLD is closely related to obesity, which acts in synergy with other predisposing conditions, including alcohol consumption, provoking progressive and insidious liver damage. Among the most potent risk factors for accelerating the progression of NAFLD to fibrosis or cirrhosis, diabetes stands out. Despite the rapid rise in NAFLD rates, identifying the optimal treatment remains a challenge. Interestingly, NAFLD amelioration or remission appears to be associated with a lower risk of T2DM, indicating that liver-centric therapies could reduce the risk of developing T2DM and vice versa. Consequently, assessing NAFLD requires a multidisciplinary approach to identify and manage this multisystemic clinical entity early. With the continuously emerging new evidence, innovative therapeutic strategies are being developed for the treatment of NAFLD, prioritizing a combination of lifestyle changes and glucose-lowering medications. Based on recent evidence, this review scrutinizes all practical and sustainable interventions to achieve a resolution of NAFLD through a multimodal approach.

Background: Maternal vitamin D status during pregnancy has been hypothesized to influence offspring neurodevelopment; however, the evidence remains inconsistent. Methods: We studied 66 mother–child pairs from the KLOTHO cohort with serum 25-hydroxyvitamin D [25(OH)D] measurements at delivery (maternal and umbilical cord). At 10 years of age, neurodevelopment was assessed using standardized questionnaires, generating composite z-scores for cognitive (cognitive, communication, motor) and psychosocial (social–sentimental, special interests) domains. Multivariable models were adjusted for sex, maternal body mass index and education, and neonatal birth weight and gestational age. Results: Maternal 25(OH)D deficiency (<50 nmol/L) was not associated with cognitive composite scores (p = 0.77). The psychosocial composite scores showed a non-significant negative trend (p = 0.29). Neonatal deficiency showed no consistent association with cognition (p = 0.99) or psychosocial outcomes (p = 0.30). Exploratory partial correlations suggested a positive association between maternal 25(OH)D and psychosocial development (r = 0.60, p = 0.038, n = 12). Seasonal variation in maternal vitamin D was observed (autumn: 56.0 ± 24.6 vs. winter: 32.0 ± 18.3 nmol/L; p < 0.0001), but did not translate into differences in 10-year outcomes. Conclusions: In this cohort of 66 pairs, perinatal vitamin D status was not a determinant of global cognition at 10 years of age. A potential link with psychosocial development requires replication in larger longitudinal studies. Due to the limited sample size, all findings should be interpreted as exploratory.

Growth differentiation factor-15 (GDF-15) is a protein that belongs to the transforming growth factor beta superfamily and has been found elevated in cases of organ injury such as liver, kidney, heart, and lung, as well as cardiovascular diseases and cancer. Soluble urokinase plasminogen activator receptor (suPAR) is a protein which is expressed mainly on immune cells and endothelial and smooth muscle cells, and is a marker of severity and intensity of inflammation in acute and chronic diseases. The aim of the present study was to compare GDF-15 serum levels between patients with acute cerebrovascular incidents and healthy controls and to investigate the possible correlation of GDF-15 serum levels and inflammatory markers, such as serum C-reactive protein (CRP) and plasma suPAR, in the above-mentioned groups. This is a retrospective study. Thirty-one patients were included in the study, with a mean age ± SD of 67 ± 13 years, compared to 18 age-matched healthy controls. In the patient group a statistically significant positive correlation of serum levels of GDF15 values with suPAR and CRP emerged (rs = 0.516, = 0.003) and (rs = 0.409, = 0.022), respectively, and no significant correlation was found in the group of controls (rs = 0.271, = 0.277) and (rs = 0.423, = 0.080), respectively. These findings support the role of inflammation as a key underlying mechanism in acute cerebrovascular injury and suggest that GDF-15 may serve as a valuable adjunct biomarker for assessing disease severity and inflammatory burden.

Background: Reactive oxygen species (ROS) are involved in the pathophysiology of neurodegeneration and cognitive decline, indicating the potential use of oxidative stress biomarkers for early diagnosis. Mild cognitive impairment (MCI) is defined as a cognitive decline beyond normal aging, without significant impact on daily functioning, and is considered an important stage of early detection of neurodegeneration. This study aimed to investigate serum and cerebrospinal fluid (CSF) levels of oxidative stress biomarkers, total ROS and malondialdehyde (MDA) in patients with MCI to evaluate their utility in the early diagnosis of Alzheimer’s disease (AD). Levels of oxidative stress biomarkers were also assessed according to age and sex, as well as their correlation with the established CSF biomarkers, including amyloid-beta (Aβ40, Aβ42 and Aβ42/Aβ40 ratio), phosphorylated tau protein (p-tau) and total tau (t-tau). Methods: A total of 114 adults were divided into three groups: MCI (A−) patients with a normal CSF Aβ42/Aβ40 ratio (n = 38), MCI (A+) patients with an abnormal Aβ42/Aβ40 ratio (n = 38) and healthy cognitive function individuals with a normal Aβ42/Aβ40 ratio (n = 38). Established CSF biomarkers were conducted using an automated immunochemical method, while total ROS levels were measured by fluorometry and MDA levels were determined by competitive inhibition enzyme immunoassay. Results: A statistically significant difference was observed in CSF MDA levels (p < 0.05) and serum ROS levels (p < 0.05) between the study groups. Sex analysis revealed significantly higher levels of CSF MDA levels in the MCI (A+) males’ group (p < 0.05). In terms of age categorization, serum MDA levels were markedly higher in the MCI (A+) group of older patients (p < 0.01). Conclusions: These findings highlight the importance of individualized approaches, including investigation of oxidative stress biomarkers profile to prevent and manage individuals in the early stages of MCI, considering demographic factors.