Tohoku Journal of Experimental Medicine最新文献

This study elucidated the effect and underlying mechanism of Curcuma aeruginosa Roxb. [C. zedoaria non Rosc.] (CAR) in human papillomavirus (HPV)-related cervical cancer treatment through a network pharmacology approach. Serum containing CAR was prepared using SD rats. The activities of CAR in HPV-related cervical cancer cell viability and migration/invasion were detected by using cell count kit and Transwell assays. Compounds in CAR and their targets were collected from TCMSP and SymMap. The cervical cancer-associated targets were searched from GeneCards and TTD databases. Genes targeted by HPV in human were collected from VISDB database. The networks were constructed using all the targets/compounds or HPV cervical cancer-related targets/compounds. The binding affinity of Furanodiene with Dipeptidyl peptidase IV (DPP4) was determined by the molecular docking method in CB-Dock2. Overexpression of DPP4 was used to discover the effects of dipeptidyl peptidase IV protein on anticancer activity of CAR. CAR-containing serum inhibited the cell viability and migration/invasion of SiHa and Ca Ski cells. Three CAR targets, DPP4, Nitric-oxide synthase, endothelial (NOS3), and Apoptosis regulator Bcl-2 (BCL2) were common with cervical cancer-related genes and HPV-targeted genes. NOS3 was targeted by Furanodiene, BCL2 was targeted by beta-elemene, and DPP4 was targeted by (-)-Epoxycaryophyllene, Zingiberene, Furanodiene, etc. Molecular docking of DPP4 with Furanodiene showed two positions with a Vina score of -6.8. Overexpression of DPP4 reversed the anticancer effects of CAR on HPV-related cervical cancer cells. CAR had inhibitory effects on HPV cervical cancer, possibly by downregulating the expression of DPP4.

The antisense transcripts play key roles in the pathogenesis of cancer. Long noncoding RNA (lncRNA) ACTA2 antisense RNA 1 (ACTA2-AS1) has been reported to inhibit the development of several cancers. In this article, the roles of ACTA2-AS1 and ACTA2 in prostate cancer (PCa) were investigated. The ACTA2-AS1 and ACTA2 expression levels in PCa samples were evaluated using GEPIA database. RT-qPCR or western blotting was used to measure their expression in PCa cells. The effects of ACTA2-AS1 and ACTA2 on PCa cell proliferation, cell cycle, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis were detected using colony formation, wound healing, transwell, flow cytometry, and western blotting. Xenograft tumor models were used to evaluate the effects of ACTA2-AS1 and ACTA2 on tumor growth. Subcellular localization, luciferase report, and RNA stability assay were performed to detect how ACTA2-AS1 modulates ACTA2 expression in PCa. We found that ACTA2-AS1 and ACTA2 were downregulated in PCa and there was a positive relationship between ACTA2-AS1 expression and ACTA2 expression in PCa samples. Overexpression of ACTA2-AS1 inhibited cell proliferation, cell cycle, migration, invasion, EMT, and promoted apoptosis, while knockdown of ACTA2-AS1 exerted opposite results. Silencing ACTA2 reversed the antitumor effect of ACTA2-AS1 overexpression on PCa in vitro and in vivo. Mechanistically, ACTA2-AS1 positively modulated ACTA2 expression by enhancing ACTA2 promoter activity to stabilize ACTA2 mRNA. Overall, ACTA2-AS1 inhibits PCa cell growth, migration, invasion, EMT, tumor growth and promotes apoptosis by enhancing ACTA2 mRNA stability, suggesting that ACTA2-AS1 may be an effective therapeutic target for PCa.

Retinoblastoma (RB), the most prevalent intraocular cancer in children, has complex pathogenesis resulting from various genetic interactions. Research revealed that orthodenticle homeo box 2 (OTX2) has certain connection with reticulon-4 (RTN4) in regulating the angiogenesis in RB, but the molecular mechanism has not been borne out yet. This study employed an array of in vitro techniques to explore the OTX2/RTN4 interaction and its effects on RB. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and dual-luciferase reporter assays were performed to assess gene and protein expression levels. Functional impacts were evaluated through cell culture, transfection, cell viability, clone formation, wound scratch, Transwell, and in vitro tube angiogenesis assays. These methods specifically unveiled the roles of siRNA-mediated RTN4 knockdown (siRTN4), short hairpin RNA-mediated OTX2 knockdown (shOTX2), and OTX2 overexpression in modulating cellular behaviors indicative of tumorigenesis and angiogenesis. Our results demonstrated that OTX2 positively regulated RTN4, thus promoting RB cell proliferation, migration, invasion, and angiogenesis, which was significantly attenuated by knockdown of OTX2 or RTN4, but enhanced by OTX2 overexpression. OTX2 overexpression also counteracted the inhibitory effects of RTN4 knockdown on angiogenesis and tumor dynamics. In conclusion, the OTX2/RTN4 axis plays a critical role in the progression of RB by promoting malignant cellular phenotypes and angiogenesis.

Intermittent hypoxia (IH) induced nerve cells apoptosis is an important cause of secondary cognitive dysfunction to obstructive sleep apnea (OSA) and may be a potential therapeutic target for this disease. This study was to explore the most appropriate conditions on the action of nano lipid bubbles (NLBs) which were applied to treat nerve injury caused by IH. An IH model of in vitro nerve cells was constructed. NLBs were created by reciprocating differential pressure method and magnetic xenon NLBs (Xe-NLBs) were created by magneto internal heat bubble generation (MIHBG). Morphology and stability of NLBs were tested via Transmission electron microscope (TEM) and dynamic light scatterer (DLS). Endocytosis and nerve injury after NLBs treatment were assessed by Immunofluorescence and MTT assay. Both Xe-NLBs (10⁷ bubbles/ml, prepared by the reciprocal differential pressure method) and magnetic Xe-NLBs (10⁷ bubbles/ml, prepared by the MIHBG) administration for up to 6 h after IH onset reduced IH induced nerve injury, and the magnetic Xe-NLBs showed a better neuroprotection, whereas O₂, H₂, and N₂-NLBs did not show significant effects. An equal volume of saturated xenon aqueous solution (Xe-solution) exhibited similar results although these therapeutic effects were far less than those of magnetic Xe-NLBs. These results revealed that Xe was the most effective neuroprotective gas in IH-induced nerve injury. Xe-NLBs prepared by the MIHBG have achieved the maximal therapeutic effects by 10⁷ bubbles/ml with 6 h treatment time under IH.

This randomized controlled trial compared the efficacy of cognitive-behavioral therapy for insomnia (CBT-I) vs. CBT-I without Jacobson progressive muscle relaxation (JPMR) in maintenance hemodialysis (MHD) patients. A total of 160 MHD patients with insomnia were randomly assigned to either the CBT-I group, which received a 7-week CBT-I program combined with JPMR, or the CBT-I without JPMR group, which underwent the same CBT-I program without the inclusion of JPMR. The 7-week intervention incorporated sleep restriction, stimulus control, cognitive restructuring, and relaxation techniques. Outcomes were assessed at weeks 0, 4, 8, and 12 using the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Modified Fatigue Impact Scale (MFIS), Hospital Anxiety and Depression Scale (HADS), and SF-36 Health Survey. The CBT-I group showed significantly greater and sustained improvements in insomnia severity, sleep quality, fatigue, anxiety, depression, and overall quality of life compared to the CBT-I without JPMR group. Improvements in ISI and PSQI scores, as well as reductions in fatigue, anxiety, and depression, were observed as early as week 4 and became more pronounced by week 12. Additionally, quality of life improved significantly across all SF-36 dimensions in the CBT-I group. This study demonstrated that the CBT-I is more effective than CBT-I without JPMR in addressing insomnia, fatigue, anxiety, depression, and quality of life in MHD patients, offering a comprehensive approach to improving sleep and mental well-being in this population.