MicroRNAs (miRNAs) are small non-coding sequences that regulate gene expression at the post-transcriptional level in various biological processes (including differentiation, cell proliferation, cell cycle and apoptosis). Low levels of human miRNA-145 (hsa-miRNA-145) expression have been found in the plasma of cancer patients, suggesting that it is a tumor suppressor. Newly developed molecular biology technologies such as digital PCR (dPCR) have high sensitivity and specificity for evaluating miRNAs, with potential value for hsa-miRNA-145 analyses. This study involved the evaluation of circulating hsa-miRNA-145 levels in the plasma of Peruvian women using digital dPCR, along with in silico analysis of its metabolic impact on cancer. This study included plasma samples from 30 women residing in Lima (aged 20–67). All individuals had previously received negative breast cancer screening results between 2016 and 2018. We used a chip-based amplification platform (dPCR system) to analyze their hsa-miRNA-145 levels and compare them with those reported in breast cancer patients. These patients had significantly lower levels. In the in silico analysis, 35 target transcripts belonging to signaling and metabolic pathways associated with the variation in hsa-miRNA-145 levels in breast and ovarian cancer were identified. Specifically, hsa-miRNA-145 was predicted to significantly impact calcium, cell proliferation, metastasis, and glucose/glutamine metabolism, with effects on the CAMK2D, EGFR, TP53, hexokinase 2 (HK2), and glutaminase (GLS) genes. This research deepens our understanding of the epigenetic factors involved in breast cancer, including plasma miRNA-145 levels, as well as associated metabolic pathways, which could promote precision medicine for Peruvian cancer patients.
Neurodegenerative diseases are increasingly recognized as disorders of cellular proteostasis characterized by progressive protein imbalance, defective stress adaptation, and neuronal dysfunction. Recent discoveries have established biomolecular condensates generated through liquid–liquid phase separation (LLPS) as essential regulators of neuronal organization, coordinating RNA metabolism, protein quality control, stress responses, and intracellular signaling. Alterations in condensate composition, material properties, and turnover are now considered important contributors to the conversion of physiological protein assemblies into persistent pathological structures, thereby influencing the progression of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, and related disorders. Natural compounds, including polyphenols, flavonoids, and other phytochemicals, have gained increasing attention due to their broad neuroprotective activities; however, their potential ability to influence condensate biology remains incompletely characterized. This review provides a comprehensive and critical analysis of current evidence connecting natural compounds with biomolecular condensate homeostasis, including direct effects on phase separation as well as indirect regulation through stress granule remodeling, molecular chaperone activity, autophagy, mitochondrial function, oxidative balance, neuroinflammatory pathways, and proteostasis networks. Particular emphasis is placed on the molecular mechanisms through which these bioactive molecules may affect aggregation-associated pathways involving amyloid-β, tau, α-synuclein, TDP-43, and FUS. Finally, current experimental limitations, translational challenges, and future perspectives are discussed, highlighting biomolecular condensates as emerging therapeutic targets and natural compounds as potential multimodal modulators capable of preserving physiological phase behavior while limiting pathological protein maturation. This emerging framework may provide new opportunities for the development of disease-modifying strategies in neurodegenerative disorders.
Chronic inflammation and oxidative stress in obese adipose tissue are pivotal drivers of insulin resistance and metabolic dysfunction. We previously demonstrated that the Kampo formula Boiogito (BOT) ameliorates impaired adipocyte differentiation and inflammation by inhibiting the nuclear factor kappa B (NF-κB) pathway in a tumor necrosis factor–alpha (TNF-α)-induced model. However, the specific effects of BOT on oxidative stress and glucose uptake remain to be elucidated. This study aimed to elucidate whether BOT could ameliorate hydrogen peroxide (H2O2)-induced oxidative stress, inflammation, and cellular dysfunction in 3T3-L1 adipocytes, thereby restoring impaired glucose uptake capacity. Differentiating and mature 3T3-L1 adipocytes were treated with 200 µM H2O2 alone or in combination with BOT (0.25 and 0.5 mg/mL). Oxidative stress markers (reactive oxygen species [ROS] and superoxide dismutase [SOD]), inflammatory cytokines (interleukin-6 [IL-6], monocyte chemoattractant protein-1 [MCP-1], and TNF-α), differentiation/functional markers (peroxisome proliferator-activated receptor gamma [Pparγ] and CCAAT/enhancer-binding protein alpha [C/ebpα] mRNA expression, adiponectin secretion, and intracellular lipid content), and glucose uptake (via a 2-deoxy-D-glucose [2-DG] assay) were evaluated. In both stages of adipocytes, H2O2 exposure significantly increased ROS levels and decreased SOD activity, and elevated extracellular IL-6, MCP-1, and TNF-α concentrations. These alterations were significantly attenuated by BOT co-treatment. Furthermore, BOT prevented the H2O2-induced downregulation of Pparγ and C/ebpα mRNA expression, thereby restoring adiponectin secretion and intracellular lipid content. Crucially, the marked impairment of 2-DG uptake caused by H2O2-mediated metabolic stress was significantly reversed by BOT co-treatment. These findings suggest that BOT exerts multi-targeted protective effects in 3T3-L1 adipocytes by mitigating oxidative stress, suppressing inflammation, and preserving adipocyte differentiation and function, thereby restoring impaired glucose uptake. Our study provides new insights into the therapeutic potential of BOT against insulin resistance and associated metabolic disorders.
Data integrating molecular classification, clinicopathological factors, and survival in Asian endometrial cancer (EC) are limited. We retrospectively analyzed 121 patients with EC from three Taiwanese hospitals (2010–2020); molecular subtypes were assigned in 89 using POLE hotspot PCR and immunohistochemistry for mismatch repair proteins and p53. Overall survival (OS) was analyzed using Kaplan–Meier and Firth-penalized Cox regression. Subtypes were no specific molecular profile (NSMP; 64.0%), p53-abnormal (p53abn; 15.7%), POLE-mutated (POLEmut; 14.6%), and mismatch repair-deficient (MMRd; 5.6%). OS differed by subtype (p = 0.013), being poorest for p53abn (31.7%) and favorable for POLEmut (90.9%) and MMRd (no deaths). FIGO stage III–IV independently predicted mortality (adjusted hazard ratio [aHR] 17.13, 95% CI: 5.07–60.49), whereas p53abn was not significant after stage adjustment (aHR 2.34, 95% CI: 0.67–8.09). PCR- and immunohistochemistry-based molecular classification is feasible in a multicenter Taiwanese setting; FIGO stage remained the dominant prognostic factor in this small cohort.
Background/Objectives: AKT signaling is a central regulator of cancer metabolism; however, the isoform-specific roles of AKT1, AKT2, and AKT3 in fatty acid metabolism remain incompletely understood in hepatocellular carcinoma (HCC). This study aimed to investigate the contributions of individual AKT isoforms to fatty acid regulation in an HCC cells model. Methods: Stable knockdown models of AKT1, AKT2, and AKT3 were established in Mahlavu cells, whereas stable knockdown models of AKT1 and AKT2 were established in Huh7 cells because endogenous AKT3 expression was very low. Targeted fatty acid profiling was performed using gas chromatography–mass spectrometry (GC–MS) to evaluate alterations in fatty acid composition following AKT isoform knockdown. Results: Knockdown of AKT1, AKT2, and AKT3 in Mahlavu cells, and AKT1 and AKT2 in Huh7 cells, was associated with reduced relative abundance of several common fatty acids, including myristic acid (C14:0), myristoleic acid (C14:1), 7-hexadecenoic acid (C16:1), arachidic acid (C20:0), eicosenoic acid (C20:1), and erucic acid (C22:1). In addition, isoform-specific differences in fatty acids composition were also observed in both HCC cell lines. Compared with scrambled control cells, knockdown of AKT1 or AKT3, but not AKT2, was associated with significant reductions in palmitic acid (C16:0) and stearic acid (C18:0) in Mahlavu cells. In contrast, Huh7 cells exhibited distinct changes in fatty acid composition, showing unchanged or increased relative abundance of palmitic acid (C16:0) and stearic acid (C18:0) following AKT1 or AKT2 knockdown. Moreover, in Huh7 cells very-long-chain fatty acids (VLCFAs), behenic acid (C22:0) and nervonic acid (C24:1) were significantly reduced following AKT2 knockdown, but not AKT1 knockdown. Conclusions: These findings suggest that AKT isoforms play a role regarding fatty acid composition in HCC cells, with both shared and isoform-associated patterns which should be investigated in further studies.
