About 51% of women who have patients with polycystic ovary syndrome (PCOS) are impacted by nonalcoholic fatty liver disease (NAFLD). Research in the underlying diseased mechanisms of this link could offer valuable insights for preventing and treating this complication.

Three experimental groups were formed by randomly dividing 24 female Wistar rats: Vehicle, PCOS, and PCOS + MSCs. In the PCOS group, letrozole (1 mg/kg, daily) was administered in 0.5% CMC for 21 days. Meanwhile, the PCOS + MSCs group was treated with 1 × 10⁶ MSCs/rat intraperitoneally (IP) on the 22nd day. Ovarian mitochondrial dynamic gene expression, liver and ovarian oxidative stress, liver and ovarian inflammation, liver and ovarian histology, serum testosterone and estradiol levels, glucose homeostatic indexes, liver function enzymes, insulin and glucose concentrations, and lipid profile were evaluated.

PCOS groups revealed a notable disturbance of ovarian changes in histology and mitochondrial dynamics, lower liver and SOD of ovary, HDL, estradiol and ovarian MFN2. Furthermore, notable increases were observed in glucose and insulin level, HOMA-IR, and androgen levels, ovarian DRP1 gene expression, liver and ovarian levels of inflammatory factors, MDA, ALT, LDL, TC, TG, AST, and CRP levels in comparison with the Vehicle group. In the PCOS + MSCs group, transplantation of MSCs could lead to improvements in the parameters mentioned above.

The prescription of MSCs improved ovarian and liver injury in PCOS through its anti-inflammatory and antioxidant characteristics in addition to modulation of mitochondria function in the ovary. This study showed that notice to the liver beside ovarian organs in PCOS is principal.

Antithyroglobulin antibodies (TgAb) are present in 10-25% of patients with differentiated thyroid cancer (DTC) and significantly affect the reliability of serum thyroglobulin (Tg) measurements during follow-up. Beyond causing assay interference, TgAb have emerged as independent surrogate tumor markers with prognostic implications. This review summarizes the current evidence on antithyroglobulin antibody biology, measurement methodologies, interference dynamics, and clinical utility as surrogate tumor markers in DTC surveillance. A narrative synthesis of the relevant English-language literature was performed, focusing on key clinical studies and recent guidelines. TgAb can lead to the underestimation of Tg levels in immunometric assays, potentially masking residual disease. Trend monitoring, rather than absolute antithyroglobulin antibody values, provides superior prognostic information; declining trends indicate favorable outcomes, whereas rising trends are associated with disease persistence or recurrence. De novo antithyroglobulin antibody positivity does not appear to serve as an early biomarker of recurrence. In antithyroglobulin antibody-positive patients, imaging-based surveillance, particularly neck ultrasonography, remains the cornerstone of follow-up. In conclusion, TgAb act as both interferents and surrogate tumor markers in DTC surveillance, and the integrated use of antithyroglobulin antibody trends and imaging is necessary for the optimal management of antithyroglobulin antibody-positive patients.

Novel oral polio vaccine type 2 (nOPV2) was used under the WHO emergency use listing for circulating vaccine-derived polio virus (cVDPV) outbreaks from 2021 to 2023. We assessed nOPV2 adverse events following immunization (AEFIs) and compared its safety profile to other vaccines using VigiBase.

We descriptively analysed AEFIs to nOPV2 and other vaccines reported to VigiBase from January 1, 2010 to December 31, 2023. Proportional Reporting ratios (PRRs) at Medical Dictionary for Regulatory Activities (MedDRA) higher level group term (HLGT) compared signals of disproportionate reporting (SDR) between nOPV2 and two comparators.

In total, 409 001 AEFIs were included (nOPV2 specific AEFIs: n = 18 911 [4.6%]), of which 54.0% males (n = 10 209) and 22.6% serious (n = 4283). Most events had resolved (n = 9418, 49.8%) or were resolving (n = 6239, 33.0%) at reporting. Body temperature conditions, gastrointestinal and respiratory tract-related events were most reported to nOPV2. Five 'novel', mostly non-serious SDRs were identified - oral soft tissue conditions (PRR: 2.47, 95% CI: 1.71-3.59), haemoglobinopathies (PRR: 31.53, 95% CI: 3.38-312.72), malabsorption conditions (PRR: 4.65, 95% CI: 1.79-12.09), neoplasm-related morbidities (PRR: 3.61, 95% CI: 1.44-9.11) and skin and subcutaneous tissue infections and infestations NEC (PRR: 3.55, 95% CI: 2.61-4.82). Among the serious events, nervous system-related events were reported more.

nOPV2 appears to retain a positive safety profile in real-world use. We support its continued use for cVDPV outbreak response and advocate continued monitoring as coverage increases and reporting is no longer mandated.

Cancer-associated fibroblasts (CAFs) within the tumour microenvironment play a pivotal role in colorectal cancer (CRC) progression and therapeutic resistance. Serine/threonine protein kinase 25 (STK25) exerts multiple roles in tumourigenesis; however, its role in mediating tumour-stroma crosstalk remains largely unexplored.

Primary CAFs were isolated from CRC patient tissues and characterised to confirm their identity. The effects of STK25 expression on CAF activity and CAF-mediated tumour progression were evaluated both in vitro and in vivo. Western blot, qRT-PCR, ChIP and dual-luciferase reporter assays were performed to elucidate the mechanism by which STK25 regulated CAF activation. Moreover, the effect of STK25 expression on CAF-induced cetuximab resistance was assessed in vitro and in vivo. The clinical significance of STK25 expression was determined in CRC patient tissues, tissue microarrays and patient-derived organoids.

Knockdown of STK25 in CRC cells enhanced CAF proliferation, migration and activation, whereas its overexpression exhibited the opposite effect. STK25-knockdown-mediated CAF activation subsequently promoted CRC cell proliferation and metastasis. Moreover, STK25 depletion combined with CAFs significantly enhanced CRC tumour growth in vivo. Mechanistically, STK25 deficiency activated the NF-κB pathway, leading to p50 phosphorylation which directly bound to the AREG promoter, thereby transcriptionally up-regulating AREG expression. In addition, STK25-regulated AREG/EGFR axis mediated the crosstalk between CRC cells and CAFs. More importantly, CAFs conferred resistance to the anti-EGFR antibody cetuximab, which could be reversed either by STK25 overexpression or by AREG-neutralising antibody treatment. Clinically, low STK25 expression correlated with elevated CAFs marker levels and poor cetuximab response in CRC patients.

Our findings identified STK25 as a critical regulator of the NF-κB/AREG/EGFR axis in tumour-CAF communication and highlight its potential as a therapeutic target for overcoming CAF-induced cetuximab resistance in CRC.

STK25 deficiency enhanced CAF-mediated CRC growth via the NF-κB/AREG/EGFR axis. STK25 overexpression or AREG antibody overcame CAF-mediated cetuximab resistance. CRC patients with high STK25 and low CAFs marker levels might benefit from cetuximab treatment.

The clinical need for treating anemia in aplastic anemia (AA) patients remains unmet. Luspatercept has been shown to be effective in myelodysplastic neoplasms (MDS).

Patients who were newly diagnosed with non-transfusion-dependent non-severe AA (NTD-NSAA) were randomly assigned to receive either cyclosporine (CsA) combined with luspatercept or CsA monotherapy at a 1:1 ratio. This study (ClinicalTrials.gov NCT05399732) aimed to compare their treatment responses, safety, disease progression, and outcomes.

In total, 58 patients participated in the final analysis, with 29 receiving CsA+luspatercept and 29 receiving CsA monotherapy. With a median follow-up of 12 months (range: 6-25) and 12 months (range: 7-25), respectively, the overall response rates (ORRs) were 69.0% vs. 37.9% (p = 0.018) at the 3rd month, 79.3% vs. 51.7% (p = 0.027) at the 6th month, and 72.4% vs. 51.7% (p = 0.104) at the end of follow-up. Patients receiving CsA+luspatercept had a shorter time to achieve a positive response than those receiving CsA alone (p = 0.004). A post hoc subgroup analysis based on age (< 60 vs. ≥60 years) showed no significant difference in ORRs for those < 60 years old. However, for patients ≥ 60 years old receiving CsA+luspatercept, a significantly greater ORR was demonstrated at both the 3rd month (p = 0.032) and 6th month (p = 0.046) compared with CsA monotherapy.

Compared with CsA monotherapy, the combination of CsA and luspatercept resulted in a higher response rate and a shorter time to response for patients with NTD-NSAA, with an acceptable safety profile. The benefit of CsA+luspatercept was most pronounced in older patients.

Cardiac masses (CMs) pose a significant diagnostic challenge. Echocardiography is the primary modality for both initial evaluation and perioperative assessment due to its accessibility and ability to assess cardiac structure and function. However, data on postoperative echocardiographic changes remain limited. Also, comprehensive regional data, particularly from Iran, are scarce, and studies evaluating paired pre- and postoperative echocardiographic parameters are lacking. Accordingly, this study aimed to evaluate echocardiographic changes following surgical resection and to characterize the clinical and histopathological features of CMs in a regional cohort.

This retrospective cohort study (2018-2023) included 75 patients with surgically resected CMs from two tertiary centers. Diagnoses were confirmed by transthoracic echocardiography and histopathology. Pre- and postoperative echocardiographic parameters were compared, and clinical and demographic data were obtained from medical records. Paired statistical tests were used, with p < 0.05 considered significant.

Among 75 patients (mean age 53.6 ± 17.4 years; 50.7% male), most had benign tumors (69.3%), predominantly myxomas (52%). The left atrium was the most common location (58.2%). A significant postoperative change was observed in right ventricular size distribution (p = 0.008), while other echocardiographic parameters remained unchanged.

Surgical resection of CMs was not associated with significant short-term functional impairment. These findings highlight the value of postoperative echocardiographic assessment and the need for further studies with early and long-term follow-up. This study provides novel regional data from Iran and supports the need for larger prospective studies to validate these findings.

The growing population of cancer survivors in the US highlights the need for adaptive digital mental health treatments that can help address a large gap in mental health treatment. Although just-in-time adaptive interventions (JITAIs) hold promise for improving mental health outcomes, none have been developed specifically for cancer survivors, in part due to their complexity. The purpose of this study was to identify survivor-level factors that could inform the development and optimization of adaptive treatments aimed at improving affective outcomes in this population.

A total of 426 adults diagnosed with cancer within the past five years participated in a 5-week observational study. Participants completed smartphone-based surveys three times per day assessing momentary affect, affective forecasting, emotion regulation attempts, social interaction quality, pain, and sleep duration from the previous night. Linear mixed-effects models were conducted at the momentary level to examine associations with positive affect (PA) and negative affect (NA).

Higher momentary PA was associated with longer sleep duration the previous night, lower pain, fewer emotion regulation attempts, higher-quality social interactions, and forecasting one's future affect as more positive. In contrast, higher momentary NA was associated with shorter sleep duration the previous night, greater pain, more frequent emotion regulation attempts, poorer-quality social interactions, and forecasting one's future affect as more negative.

These findings identify several modifiable meta-emotion and psychosocial factors that may serve as promising targets for future JITAIs designed to improve affective well-being among cancer survivors.

The present study investigated how gilteritinib overcomes resistance to second‑generation tyrosine kinase inhibitors in anaplastic lymphoma kinase (ALK)‑rearranged non‑small‑cell lung cancer (NSCLC), providing new theoretical support for NSCLC treatment. The GSE191078 dataset was downloaded from Gene Expression Omnibus database. Cell clustering was performed using the FindClusters function, followed by uniform manifold approximation and projection dimensionality reduction and data filtering. Epithelial and T cells were extracted for single‑cell transcriptome sequencing and pseudotime analysis was conducted using the Monocle 2 algorithm. The inhibitory effects of gilteritinib on H2228/Al cells were evaluated using CCK8 and TUNEL assays. Western blotting, reverse transcription‑quantitative PCR and immunofluorescence were used to examine programmed death‑ligand 1 (PD‑L1) and cluster of differentiation 8 (CD8) expression. A PD‑L1/CD8 co‑culture system was established for rescue experiments and a nude mouse xenograft model was used to assess the anti‑tumor efficacy of gilteritinib. A total of 21,866 cells were obtained and grouped into 12 major cell types. In ALK‑rearranged NSCLC, epithelial cells were associated with regulation of the P53, glycolysis and hypoxia pathways, while pseudotemporal analysis linked T cells to endothelial cell‑related processes and ribosomal functions. In vitro, gilteritinib inhibited H2228/Al cell growth, induced apoptosis and reduced ALK protein levels. Co‑culture and rescue experiments suggested the mechanism involved inhibiting PD‑L1 and CD8 co‑expression, corroborated by animal experiments. Gilteritinib can overcome alectinib resistance and inhibit PD‑L1 and CD8 co‑expression in ALK‑rearranged NSCLC, providing a new therapeutic strategy.

The ubiquitin‑proteasome system, a key protein degradation machinery in humans, mediates substrate recognition and proteolysis through ubiquitin‑tagged targeting of macromolecular proteins to the 26S proteasome. This evolutionarily conserved system orchestrates fundamental cell processes, including cell cycle progression, DNA damage repair, immune regulation, signal transduction and clearance of misfolded proteins. Its functional integrity is involved in the pathogenesis of various malignancies (breast and small cell lung cancer and colorectal adenocarcinoma) and degenerative diseases (Parkinson's disease). As a really interesting new gene‑type E3 ubiquitin ligase, ring finger protein (RNF)40 has emerged as a key regulator of both physiological homeostasis and disease progression. The present review systematically examines RNF40 structural architecture and its multifaceted roles in ubiquitination‑dependent proteostasis, epigenetic modulation and DNA repair mechanisms, as well as its tumor‑specific regulatory networks across cancer subtypes and therapeutic potential as a novel drug target.

Cancers are shaped by genetic interactions across multiple omics layers. Despite substantial progress made at the genomic and transcriptomic levels, the detailed interplay among mRNA, proteins, and protein modifications as well as the corresponding actionable targets remained poorly explored. Here, we developed bioGraph, a biologically informed graph learning method designed to systematically identify proteo-transcriptomic networks from transcriptomic, proteomic, and phosphoproteomic data. By incorporating genetic interaction priors into a unique three-layered heterogeneous graph, bioGraph revealed functional intra-omic, inter-omic, and cross-omic regulatory networks with prognostic relevance, including previously overlooked interactions modulating cancer hallmarks. We introduced a multi-omic gene set variation analysis score to quantify the network activity. We applied bioGraph to pan-cancer datasets and identified trans-omic regulatory hub genes undetectable by conventional methods. MAP4 emerged as a marker associated with tumor growth and malignant behaviors, validated via external datasets and tumor cell line assays, demonstrating its therapeutic potential. Our findings establish bioGraph as a new tool for identifying proteo-transcriptomic networks and gene targets with rapidly expanding underutilized multi-omic resources.