Utility of rekkotoken （Rhododendron anthopogonoides Maxim), Tibetan herbal medicine, as cosmetics

研究ノート (Note

Cnm of Streptococcus mutans is important for cell surface structure and membrane permeability

Streptococcus mutans, a Gram-positive facultative anaerobic bacterium, is a major pathogen of dental caries. The protein Cnm of S. mutans is involved in collagen binding, but its other biological functions are unknown. In this study, a Cnm-deficient isogenic mutant and a complementation strain were generated from a Cnm-positive S. mutans strain to help determine the properties of Cnm. Initially, comparison of the cell surface structure was performed by electron microscopy, which demonstrated that Cnm appears to be localized on the cell surface and associated with a protruding cell surface structure. Deep RNA sequencing of the strains revealed that the defect in Cnm caused upregulated expression of many genes related to ABC transporters and cell-surface proteins, while a few genes were downregulated. The amount of biofilm formed by the Cnm-defective strain increased compared with the parental and complemented strains, but the biofilm structure was thinner because of elevated expression of genes encoding glucan synthesis enzymes, leading to increased production of extracellular polysaccharides. Particular antibiotics, including bacitracin and chloramphenicol, had a lower minimum inhibitory concentration for the Cnm-defective strain than particular antibiotics, including bacitracin and chloramphenicol, compared with the parental and complemented strains. Our results suggest that S. mutans Cnm is located on the cell surface, gives rise to the observed protruding cell surface, and is associated with several biological properties related to membrane permeability

Crystal Structure and Activity of the Endoribonuclease Domain of the piRNA Pathway Factor Maelstrom

SummaryPIWI-interacting RNAs (piRNAs) protect the genome from transposons in animal gonads. Maelstrom (Mael) is an evolutionarily conserved protein, composed of a high-mobility group (HMG) domain and a MAEL domain, and is essential for piRNA-mediated transcriptional transposon silencing in various species, such as Drosophila and mice. However, its structure and biochemical function have remained elusive. Here, we report the crystal structure of the MAEL domain from Drosophila melanogaster Mael, at 1.6 Å resolution. The structure reveals that the MAEL domain has an RNase H-like fold but lacks canonical catalytic residues conserved among RNase H-like superfamily nucleases. Our biochemical analyses reveal that the MAEL domain exhibits single-stranded RNA (ssRNA)-specific endonuclease activity. Our cell-based analyses further indicate that ssRNA cleavage activity appears dispensable for piRNA-mediated transcriptional transposon silencing in Drosophila. Our findings provide clues toward understanding the multiple roles of Mael in the piRNA pathway

Application of CRISPR/Cas9 genome editing system for molecular breeding of orchids

Orchid is an important ornamental plant in Indonesia due to their natural beauty of flowers. In the tropical forest, orchids are being acquired for trading and commercial market. Thus, the effort is required to proliferate orchid in large quantities for conservation and improve the floral variation for plant breeding. The purpose of this study is to develop a firmed methodology of molecular breeding of orchids using CRISPR/Cas9 KO system. The plant material used was Phalaenopsis amabilis protocorms growth on NP medium+pepton (2 g/L). Protocorm were submerged in the culture of Agrobacterium tumefaciens that Ti‐plasmid had been filled with a T‐DNA construct of a pRGEB32 vector harboring sgRNA with PDS3 sequence. Detection for transformants was confirmed by PCR using HPT primers (545 bp), Cas9 primers (402 bp), PDS primers (280 bp) and trnL‐F (1200 bp) as an internal control. The results showed that 0.96% PDS transformants were obtained from PDS3T2 lines. Several transformant showed pale leaf color compared to non‐transformant plants. This study suggests that the target gene has successfully edited by CRISPR/Cas9 system and could be applied for that functional gene editing in orchids

胃部分切除一症例でのイトラコナゾール固形製剤と内用液剤投与後の血中濃度比較

In this paper, we report that in pulmonary aspergillosis patient who had history of resection of the stomach, the blood concentrations of itraconazole（ITCZ）and its active metabolite, hydroxy-ITCZ（OHITCZ） after taking oral solid formulation of ITCZ were remarkably low, whereas their blood concentrations significantly increased after switching from the solid formulation to the solution formulation.During administration of the ITCZ tablets（200 mg/day）, trough blood concentration of ITCZ and OH-ITCZ were 15 ng/mL and 18 ng/mL, respectively. On the other hand, when it was switched from the tablet to the oral solution（200 mg/day as ITCZ）, blood concentrations of ITCZ and OH-ITCZ increased to 1056 ng/mL and 1492 ng/mL, respectively. It was considered that the absorption of ITCZ tablets declined because the gastric acid secretion ability of the patients was decreased by gastrectomy.研究ノー

Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats

Cerebral edema following cerebral infarction can be severe and directly affect mortality and mobility. Exercise therapy after cerebral infarction is an effective therapeutic approach; however, the molecular mechanism remains unclear. Myokines such as interleukin-1 receptor antagonist (IL-1RA) are released during skeletal muscle contraction with effects on other organs. We hypothesized that myokine release during exercise might improve brain edema and confirmed the hypothesis using transient middle cerebral artery occlusion (tMCAO) model rats. Rats subjected to tMCAO were divided according to the severity of illness and further assigned to exercise and non-exercise groups. Treadmill exercises were performed at a speed of 2–8 m/min for 10 min from 1–6 days post-reperfusion after tMCAO. Exercise significantly reduced edema and neurological deficits in severely ill rats, with a reduction in aquaporin-4 (AQP4) expression in the ischemic core and increased blood IL-1RA release from the stroke-unaffected hindlimb muscle after tMCAO. Administration of IL-1RA into the lateral ventricles significantly reduced edema and AQP4 expression in the ischemic core. In conclusion, treadmill exercise performed in the early phase of stroke onset alleviated the decrease in blood IL-1RA following ischemic stroke. IL-1RA administration decreased astrocytic AQP4 expression in the ischemic core, suppressing brain edema.Gono R., Sugimoto K., Yang C., et al. Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats. Journal of Cerebral Blood Flow and Metabolism, 43(5), 812-827. © 2023 SAGE Publishing. DOI: 10.1177/0271678X231151569

肺アスペルギルス症患者におけるイトラコナゾールおよび

A patient was given generic itraconazole (ITCZ) tablet, brand-name-ITCZ capsule, ITCZ oral solution and ITCZ injection to treat pulmonary aspergillosis. We monitored concentrations of ITCZ and its active metabolite hydroxy-ITCZ (OH-ITCZ) in plasma and lung tissues. During administration of the generic product (400 mg/day), trough plasma concentrations of ITCZ and OH-ITCZ were 76 ng/mL and 126 ng/mL, respectively. After administration of the brand-name product (200 mg/day), they increased to 229 ng/mL and 540 ng/mL, respectively. ITCZ and OH-ITCZ concentrations/dosage ratios were 6.1 and 8.4 times higher by switching to the brand-name product, respectively. It was suggested that there may be a difference in pharmacokinetics between the brand-name ITCZ and the generic. Also, we determined ITCZ and OH-ITCZ concentrations infected and uninfected tissues of resected lung simultaneously. The ITCZ concentration in the infected lesion of the lung was approximately 2.3 times higher than that in plasma and 1.6 times higher than in uninfected lung tissue. The OH-ITCZ concentration in the infected lesion was higher than ITCZ in the same region. It was considered that the high concentrations of ITCZ and its metabolite at infected lesion were due to their high affinities with ergosterol in fungal membrane.研究ノー

Dietary Supplementation with Monosodium Glutamate Suppresses Chemotherapy-Induced Downregulation of the T1R3 Taste Receptor Subunit in Head and Neck Cancer Patients

(Background) We investigated the effect of dietary supplementation with monosodium glutamate (MSG) on chemotherapy-induced downregulation of the T1R3 taste receptor subunit expression in the tongue of patients with advanced head and neck cancer. (Methods) Patients undergoing two rounds of chemoradiotherapy were randomly allocated to a control or intervention group (dietary supplementation with MSG at 2.7 g/day during the second round of chemotherapy). The relative expression of T1R3, a subunit of both umami and sweet taste receptors, in the tongue was assessed by quantitative polymerase chain reaction analysis. Dysgeusia was assessed with a visual analog scale and daily energy intake was evaluated. (Results) T1R3 expression levels in the tongue, taste sensitivity, and daily energy intake were significantly reduced after the first round of chemotherapy compared with before treatment. Furthermore, these parameters significantly decreased after the second round of chemotherapy, but the extent of decrease was significantly attenuated in the MSG group compared with the control group. (Conclusions) MSG supplementation suppresses chemotherapy-induced dysgeusia, possibly due to the inhibition of the T1R3-containing taste receptor downregulation in the tongue, thereby increasing energy intake in patients with advanced head and neck cancer

若年性乳腺線維腺腫

A １２-year-old, premenarchal girl with a rapidly growing breast lump was transferred to our hospital. Ultrasonography revealed a ７．９×７．７×３．３cm large well-circumscribed hypoechoic tumor in the medial region of her right breast. After ２ months of this first visit, the breast lump had enlarged to１０ cm in diameter and was consequently subjected to a wide excision. Size of the tumor was９．５×９．２×３．０cm. Histopathological diagnosis was fibroadenoma without any malignant component. One year after the operation, a new lump with a diameter of４cm was detected in the lateral region of her right breast that had a similar appearance of the previous tumor. The tumor was excised as earlier and diagnosed as fibroadenoma. We present an extremely rare case of a rapidly growing breast fibroadenoma in a premenarchal girl. To the best of our knowledge, there were only ２１ cases reported in Japan. Since the patient is concerned that another asynchronous fibroadenoma might occur, she needs a long-term and careful follow-up