EXCLI Journal最新文献

Ulcerative colitis (UC) is a chronic or recurrent inflammatory disease of the large intestine. Although the causes of UC are insufficiently understood, a complex interaction of several factors, including genetic factors, environmental factors, and gut microbiota, influences the onset of UC. The pathophysiology of UC involves intestinal barrier dysfunction, abnormal immune responses, and dysregulation of cytokines. Cytokine-targeted therapies have been approved for the treatment of UC, with several targeted therapies being currently available. The induction response rates range from 47.8 % to 73 %, and we often experience difficult-to-treat cases. In this review, we outlined the abnormal immune response and cytokine regulation underlying the complex pathology of UC. Moreover, we summarized the mode of action and the effects at the cellular and genetic levels of targeted therapies. A deeper understanding of the pathophysiology of UC and the effects of treatment is essential for advancing personalized medicine, which remains a key, challenging goal in the future management of UC.

In regulating cellular plasticity, epithelial to mesenchymal transition (EMT), and tumor progression across a broad range of cancer types, the Hippo signaling pathway depends on YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ binding motif) as core effectors. This pathway can become dysregulated, disrupting tissue homeostasis and promoting oncogenic processes such as metastasis, immune evasion, and therapy resistance. This review explores the multifaceted roles of YAP/TAZ in lung, breast, ovarian, liver, and renal cancers, detailing their interactions with key signaling pathways such as TGF-β, Wnt, and PI3K/AKT and their modulation by mechanical cues like extracellular matrix stiffness and fluid shear stress. Potential YAP/TAZ mediated therapy resistance in EGFR TKI-resistant lung cancer and platinum-resistant ovarian cancer and the impact this has on tumor metabolism as a result of YAP/TAZ controlling tumor mesenchymal stem cells in the hypoxic environment of hepatocellular carcinoma is highlighted. Additionally, we discuss their role in maintaining cancer stem cell traits, creating an immunosuppressive tumor microenvironment, and driving chemoresistance in breast and renal cancers. Small molecule inhibitors, natural compounds (luteolin, apigenin, honokiol), and novel agents (nanoparticles of zinc oxide) are discussed as promising routes for disrupting YAP/TAZ. The review underscores the complexity of YAP/TAZ signaling and the need for patient stratification based on their expression levels to optimize targeted therapies. See also the graphical abstract(Fig. 1).

Epilepsy is a highly complex and global neurological disorder, for which available treatments only inadequately control the disease in many patients. Recent advances in molecular research have identified N6-methyladenosine (m6A) RNA modifications as key regulators of neuronal processes that underpin the pathophysiology of epilepsy. This review critically discusses the emerging significance of m6A modifications in epilepsy, focusing on dynamic regulations of m6A "writers," "erasers," and "readers" for modulating gene expression, neuronal excitability, and synaptic plasticity in epilepsy. Dysregulation of m6A machinery promotes epilepsy by exacerbating oxidative stress, mitochondrial dysfunction, and neuronal damage. We also discuss the prognostic significance of m6A alterations as a potential biomarker in epilepsy diagnosis and disease progression, along with advanced therapeutic strategies against m6A, including small molecules, RNA editing technologies, and precision medicine. This review highlights the transformational significance of m6A modulation in epilepsy therapy and opens new avenues for personalized therapeutic strategies that may revolutionize the field of drug-resistant epilepsy and improve the prognosis for patients. See also the graphical abstract(Fig. 1).

Baccharis articulata (Lam) Pers. is an herb native to southern Brazil and is widely used in local traditional medicine for weight loss and for the treatment of digestive and liver diseases. However, only a few studies have been conducted to scientifically validate the folk use of this plant. This study assessed the in vitro therapeutic effects of an aqueous extract of B. articulata and chlorogenic acid on liver fibrosis in murine hepatic stellate cells (HSC; GRX cell line). The decrease in cell proliferation and cytotoxicity, as well as phenotypic reversion by the presence of lipid droplets and reduction in collagen content after seven days of treatment, were evaluated. The mechanisms responsible for the antifibrotic effects of the extract, including the plasminogen activation system, were assessed. from high-performance liquid chromatography coupled with diode array detector and tandem mass spectrometry (HPLC-DAD-MS/MS) data. Twenty-six metabolites were identified in the extract, including flavonoids, phenylpropanoid derivatives, and diterpenes. Treatment with the extract significantly induced the accumulation of lipids in the cytoplasm of cells, indicating that it could revert the HSC phenotype to a quiescent state with no cytotoxic or antiproliferative effects. These findings may be related to the inhibition of the TGF-β1 pathway, a biomarker of liver fibrosis, upregulation of the plasminogen system, and dose-dependent inhibition of plasmin activity. The presence of caffeoylquinic acids seems to be partially related to the extract effect, as chlorogenic acid displayed antiproliferative activity and reduced collagen content in hepatic stellate cells. Considering the unmet need for antifibrotic therapies, the use of medicinal plants to inhibit the proliferation of activated HSC is promising, and this study indicated that the aqueous extract of B. articulata has potential therapeutic activity against hepatic fibrosis (see also Figure 1(Fig. 1) graphical abstract).