Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for effective therapies. Although miR-125b-5p shows therapeutic potential, its efficacy in metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC and the underlying mechanisms remain unclear. In this study, we aimed to develop a magnetic resonance imaging (MRI)-trackable miR-125b-5p-engineered MSC platform for HCC therapy and to determine whether MASLD attenuates its antitumor efficacy through metabolic reprogramming.

Bone marrow mesenchymal stem cells (MSCs) were genetically engineered to coexpress miR-125b-5p (a therapeutic gene) and ferritin heavy chain (Fth; a MRI reporter gene), enabling sustained delivery and real-time tracking. Orthotopic HCC models with or without MASLD were established to evaluate therapeutic outcomes. In vivo MRI, histological analyses, and bioinformatics approaches were used to assess efficacy and mechanisms.

Transplantation of miR-125b-5p-Fth-MSCs significantly suppressed HCC growth in vivo over an extended period. However, MASLD attenuated this therapeutic effect. Mechanistically, miR-125b-5p directly targeted hexokinase 2 (HK2), inhibiting HCC proliferation and migration through suppression of the PI3K/AKT/mTOR pathway. Fatty acid-induced lipotoxicity upregulated HK2 expression and counteracted the antitumor effects of miR-125b-5p.

Multigene-modified MSCs enable effective, MRI-monitored HCC therapy. MASLD diminishes the efficacy of miR-125b-5p through HK2 upregulation. These findings establish a multimodal theranostic framework for HCC and provide mechanistic insights into MASLD-associated therapeutic resistance.

Glioblastoma remains a highly challenging malignancy with a pronounced tendency for recurrence. The hypoxic microenvironment is a key contributor to its therapy resistance. Hyperbaric oxygen therapy (HBOT), which elevates tissue oxygen pressure and reverses hypoxia, exhibits a “dual effect” in glioblastoma management. This review aims to evaluate the therapeutic potential of HBOT in glioblastoma by examining its multifaceted effects on tumor biology and treatment response. On one hand, it enhances radiosensitivity through reactive oxygen species generation, increases chemotherapy efficacy by augmenting cytotoxicity and improving vascular perfusion, and remodels the tumor microenvironment via vessel normalization, edema reduction, and immune cell modulation. Furthermore, HBOT attenuates cancer stem cell properties by downregulating stemness markers and inhibiting self-renewal capacity. On the other hand, HBOT may also promote tumor progression: oxidative stress can induce genomic instability, while concomitant activation of HIF-, NF-κB-, and VEGF-mediated pro-survival pathways may facilitate malignant cell adaptation and proliferation. Given these opposing considerations, the clinical application of HBOT in glioblastoma management remains exploratory. In conclusion, future research should focus on optimizing HBOT protocols. In addition, exploring combination with other therapeutic approaches is equally important. These efforts are essential for the safe and effective integration of HBOT into comprehensive treatment strategies for glioblastoma.

Antralization is considered a critical, reversible stage preceding gastric cancer. However, available biomarkers for identifying antralization are lacking. This study aimed to explore antralization-specific biomarkers in peripheral blood and gastric mucosa.

In this prospective cohort study, adult patients presenting with upper gastrointestinal symptoms were enrolled and categorized into antralization and non-antralization groups based on pathological examination of gastric mucosa. Helicobacter pylori (H. pylori) infection was detected using the 13C-urea breath test, rapid urease test, and/or H. pylori serological test. Blood samples and gastric biopsies were collected for biomarker analysis.

Of the 92 patients studied, 42 (45.7%) were diagnosed with H. pylori infection and 61 (66.3%) with antralization. The rate of H. pylori infection and the incidence of acid reflux were higher in the antralization group than in the non-antralization group (both P < 0.05). Patients with antralization had higher plasma lymphocyte counts and lower serum levels of lipopolysaccharide (both P < 0.05). The positive rates and intensity of trefoil factor-2 and mucin (MUC) 6 expression were higher, whereas the positive rate and intensity of MUC5AC expression were lower in the incisura and body mucosa with antralization compared with those without antralization (all P < 0.05). Additionally, the intensity of MUC5B expression was higher in the gastric body mucosa with antralization than in those without antralization (P < 0.05).

Increased lymphocyte counts and decreased lipopolysaccharide levels in the blood, along with increased expression of trefoil factor-2, MUC6, and MUC5B and decreased MUC5AC expression in the proximal gastric mucosa, appear to be antralization-specific.

Preclinical studies of the serotonin 2A (5-HT2A) antagonist deramciclane suggested an anxiolytic profile, which has not been unequivocally established in the clinic. The same receptor profile also indicated that the compound may exhibit antidepressant potential. However, evidence for these effects remains inconclusive. The present study examined the effect of the drug in two preclinical tests with predictive validity for antidepressant activity.

The antidepressant-like activity of deramciclane was assessed in male Sprague-Dawley rats by measuring immobility time in the forced swim test (doses: 1, 5 mg/kg) and ambulation scores in the bilateral olfactory bulbectomized (doses: 5, 10 mg/kg) rat model. In both tests, the clinically effective antidepressant imipramine served as the control condition.

In the forced swim test, there was a statistically significant effect of treatment on immobility time (F2,34 = 5.77; p < 0.01; analysis of variance), which was attributable to the effect of the 5 mg/kg dose (p < 0.01; Bonferroni post-hoc test). Deramciclane at 1 mg/kg was not significantly different from vehicle-treated animals. By contrast, neither dose of deramciclane (5 mg/kg or 10 mg/kg) reversed the hyperactivity of olfactory bulbectomized rats, whereas imipramine was active in both tests.

Deramciclane demonstrates contradictory evidence for antidepressant-like activity in two validated pharmacological tools that identify such potential. The agent is clearly active in the forced swim test but not in the bulbectomized rat model. Further evaluation of the antidepressant-like potential of deramciclane in pharmacological models with predictive validity is warranted, and a more detailed examination of the dose-response relationship may be informative.

Hashimoto’s thyroiditis (HT), an autoimmune disease with a prevalence 2–7 times higher in women than in men, is associated with daytime sleepiness. The present study aimed to test the hypothesis that thyroid function is associated with chronotype and daytime sleepiness in women with HT.

This retrospective cross-sectional study included women with confirmed HT. Demographic, clinical and laboratory data were collected. The reduced Morningness-Eveningness Questionnaire (rMEQ) and the Epworth Sleepiness Scale (ESS) were used to assess chronotype and daytime sleepiness, respectively. Based on rMEQ, women were categorized as having a morning (≥18), intermediate (12–17) or evening (≤11) chronotype. Based on ESS, women were categorized as having normal or increased daytime sleepiness.

Overall, 106 women, aged 43 ± 12 years, were included. Most had normal daytime sleepiness (68.9%), and the majority had an intermediate chronotype (61.3%), while only one had a morning chronotype (0.9%). Age was significantly associated with chronotype (P = 0.026). There was a significant association between chronotype and thyroglobulin antibodies (TgAb, P = 0.012). Free triiodothyronine (fT3) levels were significantly higher in women with an evening chronotype than in those with an intermediate chronotype (P = 0.045; OR = 0.500; 95% CI 0.25–0.98). Daytime sleepiness was significantly associated with TgAb (P = 0.016) and thyroid-stimulating hormone (TSH, P = 0.040). TgAb levels were significantly higher in women with increased daytime sleepiness (P = 0.049, OR = 1.003, 95% CI 1.00–1.01) than in those with normal daytime sleepiness.

Approximately one-third of women have an evening chronotype, and approximately one-third had increased daytime sleepiness. TgAb, fT3, and TSH are associated with daytime sleepiness or chronotype in women with HT. Further investigation is required for the underlying mechanisms.

Synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy (MSA), are a group of neurodegenerative diseases characterized by the oligomerization of α-synuclein protein in neurons or glial cells. Various splicing isoforms of α-synuclein have been described, each with different aggregation properties. The α-synuclein gene (SNCA) has been identified as a highly significant genetic risk locus associated with various synucleinopathies across populations. This study aimed to assess the association of SNCA genetic variants with MSA and the levels of SNCA transcripts in peripheral blood mononuclear cells (PBMCs) from MSA and PD patients.

In this retrospective case–control study, 96 MSA patients, 1086 PD patients, and 485 healthy volunteers were included. PCR followed by restriction endonuclease analysis was used to detect four SNCA single-nucleotide polymorphisms (rs356219, rs3756063, rs11931074, and rs356168) in these individuals. In addition, RT-qPCR was performed to detect the levels of α-synuclein transcripts (SNCA mRNA isoforms -140, -126, and -112) in PBMCs of 24 MSA patients (including parkinsonian (MSA-P) and cerebellar (MSA-C) variants), 31 PD patients, and 32 healthy volunteers.

The frequency of the ‘T’ allele (of rs11931074) was significantly higher in MSA patients than in the healthy controls. The level of SNCA-140 mRNA was significantly decreased in MSA and PD patients compared with the controls, while the level of SNCA-112 mRNA was significantly increased in MSA-P patients than in PD patients and the controls. SNCA-112 mRNA/SNCA-140 mRNA and SNCA-112 mRNA/SNCA-126 mRNA ratios were significantly increased in MSA patients than in the controls.

The SNCA rs11931074 polymorphism is associated with MSA. There is a pronounced alteration in the expression of SNCA transcripts in PBMCs of MSA and PD patients.

Liver fibrosis is characterized by the excessive deposition of extracellular matrix, a process primarily driven by activated hepatic stellate cells (HSCs), and currently lacks effective therapy. Cathepsin K (CTSK) exhibits context-dependent roles across organ systems in fibrosis, but its function in liver fibrosis is unclear. This study aimed to investigate the role and underlying mechanisms of CTSK during liver fibrosis.

CTSK expression was analyzed in human fibrotic liver samples via transcriptomic analysis and confirmed in murine fibrosis models. The function of CTSK was investigated in both primary HSCs and LX-2 cells by assessing its effects on cell activation, proliferation, apoptosis, and the underlying signaling pathways following CTSK overexpression. The therapeutic potential was evaluated using an adeno-associated virus serotype 8 to overexpress CTSK in two etiologically distinct murine fibrosis models.

CTSK was upregulated in activated HSCs and fibrotic livers. Furthermore, we discovered that it mediates a negative feedback loop to inhibit the TGF-β/Smad pathway via Smad7/Smurf2-dependent TGF-β receptor-I degradation, thereby suppressing HSC activation and proliferation. CTSK also induced mitochondrial apoptosis through Bax/Bcl-2 imbalance and caspase-3 activation. Together, these actions contribute to the anti-fibrotic effect of CTSK. Notably, adeno-associated virus serotype 8-mediated CTSK overexpression attenuated liver fibrosis across multiple murine models.

Our study demonstrates that elevated CTSK functions as an endogenous protective factor that attenuates liver fibrosis. CTSK mediates negative feedback inhibition of the TGF-β pathway while concurrently promoting the mitochondrial apoptosis pathway. The dual anti-fibrotic mechanisms identify CTSK as a promising therapeutic target for liver fibrosis.