滨州医学院

Clear cell renal cell carcinoma (ccRCC) is characterized by high aggressiveness and limited therapeutic options. However, the molecular determinants driving ccRCC progression and therapeutic vulnerability remain incompletely defined. Through integrated bulk and single-cell transcriptomic analyses, we identified HAUS5 as a tumor-enriched factor that was highly expressed in ccRCC tissues and tumor-derived epithelial cells. Elevated HAUS5 expression was associated with adverse clinicopathological features and poor overall survival. Functional assays showed that HAUS5 depletion suppressed ccRCC cell proliferation, migration, invasion, and xenograft tumor growth. Mechanistically, HAUS5 was associated with MAPK/ERK signaling activation and epithelial–mesenchymal transition, whereas EGF partially rescued the inhibitory effects induced by HAUS5 knockdown. In addition, drug sensitivity analysis identified Belinostat as a candidate compound associated with HAUS5 expression, and functional experiments showed that Belinostat attenuated HAUS5-associated malignant phenotypes. Collectively, these findings suggest that HAUS5 contributes to ccRCC progression through a MAPK/ERK-associated EMT program and may be linked to differential sensitivity to Belinostat.

Aim: This project aimed to explore whether sedanolide has an improvement effect on cerebral ischemiareperfusion injury (CIRI) and clarify its mechanism. Methods: CIRI models were established using rats received middle cerebral artery occlusion/reperfusion (MCAO/ R) and BV2 cells treated with oxygen-glucose deprivation/regain (OGD/R). Next, pathological damage of rat brain tissues was evaluated using neurological score, rotarod test, TTC, H&E, Nissl and TUNEL staining. Immunofluorescence, western blot, ELISA and qRT-PCR were performed to detect microglial activation and pyroptosis. Cell apoptosis and viability were measured via flow cytometry and CCK-8. To explore the mechanism of sedanolide, network pharmacology was carried out and verified by rescue experiments. Results: In MCAO/R rats, sedanolide attenuated the pathological damage of brain tissues and inhibited microglial activation and NLRP3-mediated pyroptosis, as evidenced by the decrease of neurological score, cerebral infarct volume, microglial activation markers (Iba-1, iNOS), pyroptosis-associated proteins (GSDMD-N, C-caspase-1, NLRP3, ASC) and inflammatory factors (TNF-alpha, IL-1 beta, IL-18), and the increase of M2 polarization markers (Arg-1, CD206). In OGD/R-induced BV2 cells, sedanolide enhanced cell viability and inhibited LDH release, apoptosis, microglial activation and pyroptosis. Moreover, sedanolide docked STAT3 and reduced its phosphorylation. Overexpression of STAT3 reversed the inhibitory effect of sedanolide on OGD/R-induced microglial activation and NLRP3-mediated pyroptosis in BV2 cells. Conclusion: Sedanolide alleviated CIRI by targeting STAT3 to inhibit microglial activation and pyroptosis.

The objective was to investigate the therapeutic effects and possible mechanism of sugiol on cerebral ischemia/reperfusion injury (CIRI). The middle cerebral artery occlusion (MCAO) model of rats and oxygen-glucose deprivation (OGD) model were established. To investigate the effects of sugiol on CIRI, neurological score assessment, H E staining, Nissl staining, TUNEL staining, western blot, RT-qPCR, DCFH-DA staining, CCK-8, and flow cytometry were performed. Network pharmacology analysis was performed for exploring the underlying protective mechanism of sugiol against CIRI. Sugiol exhibited a protective effect against CIRI, as evidenced by reducing histopathological damage, cell apoptosis, improving neurological function, promoting the expression of Bcl-2, inhibiting the expression of Bax, C-caspase-3, TNF-α, IL-1β, MCP-1, decreasing the levels of ROS, MDA, Fe2+, and enhancing SOD levels. In vitro, sugiol improved cell viability and inhibited cell apoptosis, inflammation, oxidative stress, and ferroptosis‑associated changes. In vivo and in vitro, sugiol inhibited LRRK2 and p-P65 expression. Notably, the inhibition of sugiol on cell apoptosis, inflammation, oxidative stress, and ferroptosis‑associated changes was reversed by LRRK2 overexpression. In the early phase following MCAO, sugiol alleviated CIRI through the inhibition of cell apoptosis, inflammation, oxidative stress, and ferroptosis‑associated changes, an effect that involves LRRK2/NF-κB pathway.

BACKGROUND:The progression of prostate cancer is predominantly driven by androgen receptor (AR) signaling; however, its downstream effector molecules are not fully characterized. Fibromodulin (FMOD), a proteoglycan with established roles in other cancers, has recently been implicated in prostate cancer; however, the precise molecular mechanisms underlying its regulation and oncogenic function remain elusive. Here, we sought to elucidate the functional role of FMOD and its regulation by the AR and the subsequent activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling axis. METHODS:FMOD expression levels across multiple prostate cancer cell lines were quantified by qRT-PCR and Western blot analysis. To investigate its function, transient knockdown using small interfering RNA (siRNA) was Performed in LNCaP and 22Rv1 cells, while lentiviral-mediated overexpression of FMOD was established in LNCap cells, to assess cellular proliferation, migration, invasion, and cell cycle distribution in vitro. For in vivo studies, a stable FMOD-knockdown model was established using lentiviral-mediated shRNA to evaluate tumor growth in xenograft mice. Putative upstream transcription factors were predicted using the JASPAR database and validated through AR knockdown experiments. Downstream signaling pathways, specifically PI3K/AKT and epithelial-mesenchymal transition (EMT), were analyzed via Western blot. RESULTS:FMOD was highly expressed in LNCaP and 22Rv1 cells. FMOD knockdown markedly suppressed cell proliferation, induced cell cycle arrest, and inhibited migration and invasion by reversing the EMT process. In vivo experiments confirmed that FMOD depletion significantly retarded tumor growth. Mechanistically, we identified FMOD as a transcriptional target positively regulated by AR. Furthermore, FMOD facilitated cancer progression by activating the PI3K/AKT signaling pathway. CONCLUSION:Our findings delineate a critical AR-FMOD-PI3K/AKT signaling axis in prostate cancer progression. FMOD serves as a key downstream effector of AR and may represent a promising therapeutic target for clinical intervention.

While yoga is known to benefit depression in breast cancer patients, its efficacy as an adjunct to diverse treatment regimens remains unclear. This study evaluated yoga's efficacy in alleviating depression during varied breast cancer therapies and supports its clinical integration as a complementary intervention. Following PRISMA 2020 guidelines, we systematically searched for RCTs in English and Chinese. Literature quality was assessed using the Cochrane Risk of Bias tool. Data were analyzed with Review Manager 5.4.1, including subgroup analyses by treatment type and assessment scale. Analysis of 21 studies showed yoga significantly reduced depression levels [SMD = -0.58, 95