Tohoku Journal of Experimental Medicine最新文献

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.

The study investigated the relationship between ratio of D-dimer to brain natriuretic peptide (BNP), large right-to-left shunt (RLS) by contrast-enhanced transthoracic echocardiography (c-TTE), and cryptogenic stroke (CS) in patent foramen ovale (PFO). The study populations were composed of 61 patients with PFO who had been scheduled for transcatheter closure for CS (n = 20) or migraine (n = 41). Large RLS was defined as more than 20 microbubbles at rest and during the Valsalva maneuver by c-TTE. The PFO/CS group exhibited a higher proportion of large RLS at rest (3 vs. 0, P = 0.032) and during the Valsalva maneuver (14 vs. 11, P = 0.002) than the PFO/migraine group. More specifically about PFO characteristics, the height of PFO in the PFO/CS group was higher than that in the PFO/migraine group, and the proportion of atrial septal aneurysm in the PFO/CS group was higher than that in the PFO/migraine group (8 vs. 4, P = 0.013). The ratio of D-dimer to BNP was found to be significantly higher in the PFO/CS group than the PFO/migraine group (P = 0.010). The multiple logistic regression analysis showed that a large RLS during Valsalva maneuver and a high ratio of D-dimer to BNP were independent factors associated with CS in PFO. The study demonstrates that a high ratio of D-dimer to BNP and large RLS by c-TTE as risk factors for CS in PFO.