A calmodulin inhibitor, W-7 influences the effect of cyclic adenosine 3', 5'-monophosphate signaling on ligninolytic enzyme gene expression in Phanerochaete chrysosporium

The capacity of white-rot fungi to degrade wood lignin may be highly applicable to the development of novel bioreactor systems, but the mechanisms underlying this function are not yet fully understood. Lignin peroxidase (LiP) and manganese peroxidase (MnP), which are thought to be very important for the ligninolytic property, demonstrated increased activity in Phanerochaete chrysosporium RP-78 (FGSC #9002, ATCC MYA-4764™) cultures following exposure to 5 mM cyclic adenosine 3', 5'-monophosphate (cAMP) and 500 μM 3'-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that transcription of most LiP and MnP isozyme genes was statistically significantly upregulated in the presence of the cAMP and IBMX compared to the untreated condition. However, 100 μM calmodulin (CaM) inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), which had insignificant effects on fungal growth and intracellular cAMP concentration, not only offset the increased activity and transcription induced by the drugs, but also decreased them to below basal levels. Like the isozyme genes, transcription of the CaM gene (cam) was also upregulated by cAMP and IBMX. These results suggest that cAMP signaling functions to increase the transcription of LiP and MnP through the induction of cam transcription

[70]Fullerenes Assists the Formation of Phospholipid Bicelles at Low Lipid Concentrations

The incorporation of neutral [70]fullerenes (C70) led to the bicelles formation at relatively low lipid concentration range from neutral lipid mixtures (DMPC/DHPC). Furthermore, the C70 addition resulted in the formation of large bicelles with a radius of ca. 100 nm in contrast to C70-free bicelles that were formed from anionic lipid mixtures (DMPC/DHPC/DMPG). The stabilization of these bicelles was attributed to C70 incorporation into the membranes.This file includes Supporting Information.This work was supported by JSPS KAKENHI a Grant-in-Aid for Scientific Research (B) (Grant No. 25288037), a Grant-in-Aid for Challenging Exploratory Research (Grant Nos. 24655128 and 25650053), and a Grant-in-Aid for Young Scientists (A) (Grant No. 24681028)

Effect of herbal medicine daikenchuto on gastrointestinal symptoms following laparoscopic colectomy in patients with colon cancer: A prospective randomized study

We conducted a prospective randomized study to investigate the effect of daikenchuto (DKT) on abdominal symptoms following laparoscopic colectomy in patients with left-sided colon cancer. Patients who suffered from abdominal pain or distention on postoperative day 1 were randomized to either the DKT group or non-DKT group. The primary endpoints were the evaluation of abdominal pain, abdominal distention, and quality of life. The metabolome and gut microbiome analyses were conducted as secondary endpoints. A total of 17 patients were enrolled: 8 patients in the DKT group and 9 patients in the non-DKT group. There were no significant differences in the primary endpoints and postoperative adverse events between the two groups. The metabolome and gut microbiome analyses showed that the levels of plasma lipid mediators associated with the arachidonic acid cascade were lower in the DKT group than in the non-DKT group, and that the relative abundance of genera Serratia and Bilophila were lower in the DKT group than in the non-DKT group. DKT administration did not improve the abdominal symptoms following laparoscopic colectomy. The effects of DKT on metabolites and gut microbiome have to be further investigated

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Application of "Dredging Method" for the patients with odontogenic keratocyst.

When conservative treatment such as enucleation is applied, odontogenic keratocyst (OKC) is a well-known jaw lesion with a high recurrence rate. Other treatment modalities aimed at preventing recurrence have been used for managing OKCs. In our institute, an alternative conservative approach, known as the dredging method, is applied in OKC treatment. This paper describes and reports the characteristics and outcomes of conservative treatments involving the dredging method and enucleation in the management of patients with OKC. Seventy-four patients with OKC or keratocystic odontogenic tumor (KCOT) presented to Oral and Maxillofacial Surgery at Hokkaido University Hospital between 1983 and 2017. They were treated and followed for more than 12 months. The patients’ median age was 40 years (range 7‒72 years) and the median longitudinal diameter of the lesion was 30 mm (range 7‒128 mm). A total of 14 cysts (18.9%) were multilocular, as determined via radiographic evaluation. The surgical intervention consisted of enucleation alone in 17 cases (22.3%), deflation followed by enucleation in seven cases (9.5 %), and the dredging method in 50 cases. Statistical significance associated with the size ( P = 0.01) and locularity ( P = 0.02) of the lesions was found between the cases treated with enucleation versus the dredging method. The median duration of follow-up was 40 months (range 12 to 405 months). Recurrence occurred in 9 of 74 cases (12.2%), including 2 of 17 cases (11.8%) treated with enucleation and 7 of 57 cases (12.3 %) treated wit h the dredging method. The recurrence period ranged from 12 to 131 months. All recurrence cases were managed by enucleation. There was no correlation between recurrence and patient sex or age, lesion size or locularity, the presence of a daughter cyst, or surgical approach. These results suggest that the dredging method is a s uccessful conservative treatment option for large, multilocular OKCs. Long-term regular follow-up is essential to identify and manage recurrent cases