MiR-150, a major modulator negatively regulating the development and differentiation of various immune cells, is widely involved in orchestrating inflammation. In transplantation immunity, miR-150 can effectively induce immune tolerance, although the underlying mechanisms have not been fully elucidated. In the current study, we found that miR-150 is elevated after blocking CD28/B7 co-stimulatory signaling pathway and impaired IL-2 production by targeting ARRB2. Further investigation suggested that miR-150 not only repressed the level of ARRB2/PDE4 directly but also prevented AKT/ARRB2/PDE4 trimer recruitment into the lipid raft by inhibiting the activities of PI3K and AKT through the cAMP-PKA-Csk signaling pathway. This leads to the interruption of cAMP degradation and subsequently results in inhibition of the NF-kB pathway and reduced production of both IL-2 and TNF. In conclusion, our study demonstrated that miR-150 can effectively prevent CD28/B7 co-stimulatory signaling transduction, decrease production of inflammatory cytokines, such as IL-2 and TNF, and elicit the induction of immune tolerance. Therefore, miR-150 could become a novel potential therapeutic target in transplantation immunology.
Glioblastoma multiforme (GBM) is one of the most malignant human intracranial tumors. Temozolomide (TMZ) is the primary alkylating agent for GBM patients. However, many GBM patients are resistant to TMZ. Therefore, patients with GBM urgently need more effective therapeutic options. 20(S)‐ginsenoside‐Rg3 (20(S)‐Rg3) is a natural chemical with anti‐tumor effects, but at present there is little understanding of its functional mechanism. Several research reports have demonstrated that O6‐methylguanine DNA‐methyltransferase (MGMT) repairs damaged DNA and contributes to TMZ resistance in gliomas. In addition, recent studies have shown that MGMT gene expression could be regulated by the Wnt/β‐catenin pathway. However, whether 20(S)‐Rg3 inhibits MGMT expression and augments chemosensitivity to Temozolomide (TMZ) in glioma cells remains unclear. In this study, we explored the modulating effects of 20(S)‐Rg3 on MGMT. We used glioma cell lines, primary cell strain (including T98G, U118 and GBM‐XX; all of them are MGMT‐positive glioma cell lines) and xenograft glioma models to examine whether 20(S)‐Rg3 increased the sensitivity to TMZ and to reveal the underlying mechanisms. We found that the MGMT expression was effectively downregulated by 20(S)‐Rg3 via the Wnt/β‐catenin pathway in glioma cell lines, and TMZ resistance was significantly reversed by 20(S)‐Rg3. Meanwhile, 20(S)‐Rg3 shows no obvious cytotoxicity at its effective dose and is well tolerated in vivo. In addition, we found that 20(S)‐Rg3 significantly restrains the epithelial‐mesenchymal transition (EMT) progression of glioma cells. Taken together, these results indicate that 20(S)‐Rg3 may be a novel agent to use in treatment of GBM, especially in TMZ‐resistant GBM with high MGMT expression.
Early diagnosis of tumors is crucial in selecting appropriate treatment options to achieve the desired therapeutic effect, while it is difficult to accurately diagnose cancer by a single imaging modality...
Introduction: Migraine is a recurrent neurological disorder, the symptoms of which can be significantly relieved by acupuncture. However, the central mechanism via which acupuncture exerts its therapeutic effect in migraine is unclear. The aim of this study was to compare the differences in regional homogeneity (ReHo) between patients with migraine without aura (MwoA) and healthy controls (HCs) and to explore the immediate and cumulative therapeutic effect of acupuncture in patients with MwoA using resting-state functional magnetic resonance imaging (fMRI).Methods: The study subjects were 40 patients with MwoA and 16 matched HCs. The patients with MwoA received acupuncture on 2 days per week for 6 weeks for a total of 12 sessions followed by 24 weeks of follow-up. The primary clinical efficacy outcomes were the number of days with migraine and the average severity of headache. Secondary outcomes were the Migraine-Specific Quality of Life Questionnaire, Self-Rating Anxiety Scale, and Self-Rating Depression Scale scores. In the migraine group, resting-state blood-oxygen-level-dependent fMRI scans were obtained at baseline and after the first and 12th acupuncture sessions to measure the ReHo value. In the HCs, only a baseline resting-state blood-oxygen-level-dependent fMRI scan was obtained.Results: Compared with the control group, the migraine group had a significantly lower ReHo value in the cerebellum, which increased after the first acupuncture session. Long-term acupuncture significantly improved migraine symptoms and mood with a therapeutic effect that lasted for at least 6 months. After 12 acupuncture sessions, there were significant increase of cerebellum and angular gyrus in the migraine group.Conclusion: These findings suggest that migraine is related to cerebellar dysfunction. Acupuncture can relieve the symptoms of migraine, improve dysfunction of cerebellum, and activate brain regions involved in modulation of pain and emotion The cumulative therapeutic effect of acupuncture is more extensive and significant than its immediate effect.
In various malignant tumors, NF-kappa B interacting long noncoding RNA (NKILA) displays antitumor activity by inhibiting the NF-kappa B pathway. However, the role of NKILA in gliomas remains unclear. Surprisingly, this study showed that NKILA is significantly upregulated in gliomas, and the increased levels of NKILA were correlated with a decrease in patient survival time. NKILA increased the expression level of hypoxia-inducible factor-1α, and the activity of the hypoxia pathway in gliomas. Furthermore, we demonstrated that NKILA enhances the Warburg effect and angiogenesis in gliomas both in vitro and in vivo. Therefore, NKILA is a potential therapeutic target in gliomas. In addition, we showed that a 20(S)-Rg3 monomer suppresses NKILA accumulation and reverses its stimulation of the Warburg effect and angiogenesis in gliomas, both in vitro and in vivo. Therefore, this study not only identified NKILA as a potential therapeutic target in gliomas, but also demonstrated a practical approach to treatment.
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