The Tohoku journal of experimental medicine
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Tohoku J. Exp. Med. · May 2023
Case ReportsA Case of Miller Fisher Syndrome with Cerebellar Hypoperfusion.
We report a case of a 76-year-old man with Miller Fisher syndrome presenting with acute ophthalmoplegia and ataxia. Cerebrospinal fluid analysis showed normocytosis with an increased protein level. Serum anti-GQ1b IgG and anti-GT1a IgG antibodies were positive. ⋯ He was treated with two courses of intravenous immunoglobulin, which improved his neurological symptoms. Brain perfusion single-photon emission computed tomography showed that cerebellar blood flow was decreased in the acute stage of the disease and improved after treatment. Although the prevailing view is that ataxia in Miller Fisher syndrome patients is of a peripheral origin, this case suggests that cerebellar hypoperfusion contributes to the development of ataxia in Miller Fisher syndrome.
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Tohoku J. Exp. Med. · May 2023
A New Method for Programmable RNA Editing Using CRISPR Effector Cas13X.1.
Type VI CRISPR-Cas13 is the only CRISPR system that can bind and cleave RNA without DNase activity. We used the newly discovered, smaller Cas13X.1 protein to construct an editing system in mammalian cells, aiming to break the delivery restrictions of CRISPR-Cas13 system in vivo and promote the application of Cas13X system in clinical therapy. We employed exogenous fluorescence reporter gene mCherry and endogenous gene transketolase (TKT) closely related to cancer cell metabolism as target genes to evaluate the Cas13X.1 system. ⋯ The Cas13X.1 system we constructed had strong RNA knockdown ability in mammalian cells with low cellular toxicity. Compared with other CRISPR-Cas13 systems, Cas13X.1 system with smaller molecular weight has more advantages in vivo delivery. The Cas13X.1 system targeting TKT transcripts also provides an alternative method for the study of anti-cancer therapy.
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Tohoku J. Exp. Med. · May 2023
Case ReportsTherapeutic Drug Monitoring of Blood Sirolimus and Tacrolimus Concentrations for Polypharmacy Management in a Lymphangioleiomyomatosis Patient Taking Two Cytochrome P450 3A Inhibitors.
Patients with lymphangioleiomyomatosis (LAM) and lung transplantations are treated with multiple drugs, such as tacrolimus, mycophenolate mofetil, prednisolone, and itraconazole, for long-term suppression of rejection response and prevention of infection. Additional drugs are required when lung transplant recipients develop graft complications. Therefore, managing polypharmacy is critical because of drug-drug interactions caused by various factors, including drug-metabolizing enzymes such as cytochrome P450 3A (CYP3A). ⋯ Blood sirolimus concentrations ranged from 18.8 to 36.9 ng/mL on days 6 to 9; thus, treatment with sirolimus was stopped because of over-target blood concentrations. Blood concentrations of sirolimus and tacrolimus were successfully managed without adverse events using therapeutic drug monitoring (TDM) and azole anti-fungal substitution of azithromycin instead of clarithromycin although sirolimus concentration was relatively lower compared to the target range. Thereby, frequent TDM, management of polypharmacy that influences CYP3A activity, and possibly CYP3A genotyping should be appropriately conducted for personalized medicine.
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Tohoku J. Exp. Med. · May 2023
Polysaccharide H-1-2 Ameliorates High Glucose-Induced Podocyte Dysfunction by Suppressing Epithelial-to-Mesenchymal Transition via Restoration of SIRT1 in vivo and in vitro.
Renal interstitial fibrosis, a pathological feature of diabetic nephropathy, is closely related to endothelial-to-mesenchymal transition (EMT). This study aimed to explore the effect of H-1-2, a polysaccharide of Pseudostellaria heterophylla, on high glucose (HG) induced-podocyte EMT in vivo and ex vivo. DBA/2 mice were given five consecutive days of streptozotocin injection to induce the diabetic nephropathy model. ⋯ To uncover the mechanism underlying H-1-2 suppressing EMT, small interference RNA for SIRT1 was transfected into podocytes. Mechanically, silencing SIRT1 largely restrained the protective effect of H-1-2 on HG-induced podocytes. In conclusion, H-1-2 exerts a potential role in alleviating HG-induced dysfunction and EMT of podocytes in vivo and ex vivo via SIRT1.
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Tohoku J. Exp. Med. · May 2023
Multicenter StudyEfficacy and Safety of Third-Line Apatinib plus Chemotherapy in Metastatic Triple-Negative Breast Cancer Patients: A Multicenter, Retrospective, Cohort Study.
Apatinib is a tyrosine kinase inhibitor (TKI) that targets vascular endothelial growth factor receptor 2 (VEGFR2) as an effective anti-angiogenic agent. The current study intended to explore the treatment efficacy and safety profile of third-line apatinib plus chemotherapy in metastatic triple-negative breast cancer (mTNBC) patients. This multicenter, retrospective, cohort study analyzed 97 mTNBC patients who underwent third-line apatinib plus single-agent chemotherapy (N = 45) or single-agent chemotherapy (N = 52). ⋯ There was no difference in adverse events between the two groups, except that the incidence of hypertension was higher in the apatinib plus chemotherapy group than in the chemotherapy group (P = 0.018); meanwhile, the grade 3-4 adverse events in the apatinib plus chemotherapy group included hypertension (13.3%), neutropenia (8.9%), nausea and vomiting (4.4%), fatigue (4.4%), leukopenia (4.4%), thrombocytopenia (2.2%), and hand-foot syndrome (2.2%). Third-line apatinib plus chemotherapy may achieve a more satisfying survival benefit and no obvious safety concerns in mTNBC patients compared with mono-chemotherapy. However, more large-scale, randomized studies are warranted for further validation.