The Tohoku journal of experimental medicine
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Tohoku J. Exp. Med. · Dec 2020
Remobilization does not restore immobilization-induced adhesion of capsule and restricted joint motion in rat knee joints.
Joint immobilization, which is used in orthopaedic treatments and observed in bedridden people, usually causes restricted joint motion. Decreased joint motion diminishes activities of daily living and increases burden of nursing-care. The purpose of this study was to clarify the reversibility of immobilization-induced capsular changes and restricted joint motion in rat knee joints. The unilateral knee joints of adult male rats were immobilized with an internal fixator for 1, 2, 4, 8, and 16 weeks as a model of immobilization after surgery or disuse of the joint. After the fixation devices were removed, the rats were allowed to move freely for 16 weeks. Sham-operated rats were used as controls. Sagittal sections at medial midcondylar regions were made and assessed with histological, histomorphometric, and immunohistochemical methods. Joint motion was measured using a custom-made device under x-ray control after removal of the periarticular muscles. In the 1/16-week and 2/16-week immobilization-remobilization (Im-Rm) groups, cord-like structures connecting the superior and inferior portions of the posterior capsule (partial adhesion) were observed without restricted joint motion. In the 4/16-, 8/16-, and 16/16-week Im-Rm groups, global adhesion of the posterior capsule and restricted joint motion were observed. The restricted joint motion was not completely restored after incision of the posterior capsule. These data indicate that immobilization alone causes irreversible capsular changes and arthrogenic restricted joint motion. Besides the joint capsule, other arthrogenic factors such as ligaments might influence the restricted joint motion. Prolonged immobilization over 4 weeks should be avoided to prevent irreversible joint contracture.
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Tohoku J. Exp. Med. · Dec 2020
Knockdown of checkpoint kinase 1 is associated with the increased radiosensitivity of glioblastoma stem-like cells.
Glioblastoma multiforme is an aggressive brain tumor with a poor prognosis. The glioblastoma stem-like cells (GSCs) represent a rare fraction of human glioblastoma cells with the capacity for multi-lineage differentiation, self-renewal and exact recapitulation of the original tumor. Interestingly, GSCs are more radioresistant compared with other tumor cells. ⋯ In contrast, the radiosensitivity was not enhanced by Chk2 knockdown in GSCs. These results suggest that depletion of Chk1 may improve the radio-sensitivity of GSCs via inducing cell apoptosis. In summary, the therapy targeting Chk1 gene in the GSCs may be a novel way to treat glioblastoma.
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Tohoku J. Exp. Med. · Dec 2020
Polymorphisms in second intron of the FGFR2 gene are associated with the risk of early-onset breast cancer in Chinese Han women.
Fibroblast growth factor receptor 2 (FGFR2) plays an important role in tumor cell growth, invasiveness, motility, and angiogenesis. Several single-nucleotide polymorphisms (SNPs) in the second intron of the FGFR2 gene are associated with the risk of breast cancer. In this study, we determined whether these SNPs of the FGFR2 gene are associated with early onset of non-familial breast cancer in a Chinese Han population. ⋯ The haplotype containing rs11200014A, rs1219648G, rs2420946T and rs2981582T also exhibited a significantly higher distribution in patients compared to controls (OR=1.784, 95% CI=1.161-2.744). In stratified analyses, each of the above four SNPs conferred a significantly greater risk of estrogen receptor-positive breast cancer, compared to estrogen receptor-negative breast cancer that is more resistant to treatment. Our data demonstrate that these four SNPs of the FGFR2 gene are associated with the risk of breast cancer at a young age in Chinese Han women.
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Tohoku J. Exp. Med. · Dec 2020
Generation of induced pluripotent stem cells from skin fibroblasts of a patient with olivopontocerebellar atrophy.
Generation of induced pluripotent stem (iPS) cells from somatic cells of patients represents a powerful tool for disease modeling, and they may have a wide range of applications in cell therapies. Olivopontocerebellar atrophy (OPCA) is a rare and debilitating neurologic disease of insidious onset, characterized by atrophy of the cerebellum pons and inferior olivary nuclei with concomitant ambulation deficits and dyscoordination. Here, we report the generation of iPS cells from skin fibroblasts of a 56-year-old female patient with familial OPCA. OPCA is classified in the autosomal dominant ataxia that is also named spinocerebellar ataxia (SCA) 7. The disease allele of SCA7 gene of the patient contains 45 CAG trinucleotide repeats, the number of which is larger than the normal repeat number (4 to 36 CAG repeats). The OPCA-iPS cells were generated via ectopic expression of four transcription factors: OCT4, SOX2, KLF4 and c-MYC. The OPCA-iPS cells expressed the pluripotency markers, and they can be differentiated into various somatic cell types in vitro and in vivo. Furthermore, the iPS cells also can be committed to differentiate into neural cells. Therefore, the OPCA-iPS cells offer an unprecedented cell model to investigate disease mechanisms, discover novel drugs, and develop new therapies for OPCA.
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Tohoku J. Exp. Med. · Dec 2020
Diagnostic Value of the Hypomethylation of the WISP1 Promoter in Patients with Hepatocellular Carcinoma Associated with Hepatitis B Virus.
Wnt1-inducible signaling pathway protein 1 (WISP1) regulates cell proliferation, differentiation, adhesion, migration and survival. Abnormal WISP1 expression is associated with the carcinogenesis of hepatocellular carcinoma (HCC). Aberrant DNA methylation is one of the major epigenetic alterations in HCC. ⋯ Alpha-fetoprotein (AFP) is a widely recognized biomarker to diagnose HCC which lacks enough sensitivity and specificity. WISP1 promoter methylation status combined with AFP significantly improved the diagnostic ability in discriminating HCC from CHB compared with AFP or WISP1 methylation status alone. In conclusion, hypomethylation of the WISP1 gene promoter may serve as a noninvasive biomarker for detecting HBV-associated HCC.