The effect of istradefylline for Parkinson’s disease : A meta-analysis

Adenosine A2A receptor antagonists are an alternative treatment strategy for Parkinson’s disease. Several randomized placebo controlled studies have tested the effect of A2A receptor antagonist istradefylline, and more robust evidence has been acquired. This meta-analysis aimed to provide evidence for its efficacy and safety on patients with Parkinson’s disease. After a systematic literature search, we calculated the pooled standardized mean difference and risk ratio for continuous and dichotomous variables, respectively. Further, sensitivity analyses were performed to confirm the effect estimated by meta-analyses. Publication bias was assessed by funnel plot and deviation of intercept. Six studies satisfied our inclusion criteria. Istradefylline (40 mg/day) decreased off time and improved motor symptoms of Parkinson’s disease in homogeneous studies. Istradefylline at 20 mg/day decreased off time and improved motor symptoms, but heterogeneity was found in the analysis of the former among studies. There was a significant effect of istradefylline on dyskinesia in homogeneous studies. Publication bias, however, was observed in the comparison of dyskinesia. Other adverse events showed no significant difference. The present meta-analysis suggests that istradefylline at 40 mg/day could alleviate off time and motor symptoms derived from Parkinson’s disease. Dyskinesia might be worsened, but publication bias prevents this from being clear

Association between the recurrence period of acute kidney injury and mortality: a single-center retrospective observational study in Japan.

13301甲第5260号博士（医学）金沢大学博士論文要旨Abstract 以下に掲載：BMJ open 9(6) pp.e023259 2019. BMJ journals. 共著者：Keisuke Sako, Kengo Furuichi, Yuta Yamamura, Megumi Oshima, Tadashi Toyama, Shuichi Kaneko, Takashi Wad

The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1

Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease

The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-kappa B Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C alpha/beta II Phosphorylation

Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKC alpha/beta II, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis

Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis

Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant

Hepatectomy for rapidly growing solitary liver metastasis from non-small cell lung cancer: a case report

BackgroundPatients with liver metastasis from non-small lung cancer (NSCLC) usually have multiple metastases at other sites and thus rarely undergo liver surgery. We present a case involving successful resection of rapidly growing liver metastasis from squamous cell carcinoma of the lung.Case presentationA 74-year-old man had undergone left lower lobectomy for squamous cell carcinoma of the lung, which was diagnosed pathologically as stage IA. A computed tomography (CT) scan that was taken 12 months after lung resection showed an irregularly shaped mass lesion (size, 8.3 cm) in segment five of the liver. Retrospectively, the mass was identifiable on CT 6 months before this initial recognition. Although the lesion showed rapid growth, positron emission tomography and brain magnetic resonance imaging ruled out the possibility of other metastatic lesions. Therefore, we performed right hepatectomy 14 months after the initial lung surgery. The patient was pathologically diagnosed with liver metastasis from lung cancer and has remained free from recurrence 41 months after the liver surgery, without receiving any adjuvant chemotherapy.ConclusionsAlthough there is no reliable clinical indicator for selecting oligo-recurrence, hepatectomy could be an option for solitary liver metastasis from NSCLC for patients who are in good health

Discovery of the Fastest Early Optical Emission from Overluminous SN Ia 2020hvf: A Thermonuclear Explosion within a Dense Circumstellar Environment

Ia型超新星の爆発直後の閃光を捉えることに成功 --特異な爆発に至る恒星進化の謎に迫る--. 京都大学プレスリリース. 2021-12-10.In this Letter we report a discovery of a prominent flash of a peculiar overluminous Type Ia supernova, SN 2020hvf, in about 5 hr of the supernova explosion by the first wide-field mosaic CMOS sensor imager, the Tomo-e Gozen Camera. The fast evolution of the early flash was captured by intensive intranight observations via the Tomo-e Gozen high-cadence survey. Numerical simulations show that such a prominent and fast early emission is most likely generated from an interaction between 0.01 M⊙ circumstellar material (CSM) extending to a distance of ∼10¹³ cm and supernova ejecta soon after the explosion, indicating a confined dense CSM formation at the final evolution stage of the progenitor of SN 2020hvf. Based on the CSM–ejecta interaction-induced early flash, the overluminous light curve, and the high ejecta velocity of SN 2020hvf, we suggest that the SN 2020hvf may originate from a thermonuclear explosion of a super-Chandrasekhar-mass white dwarf (“super-MCh WD”). Systematical investigations on explosion mechanisms and hydrodynamic simulations of the super-MCh WD explosion are required to further test the suggested scenario and understand the progenitor of this peculiar supernova