Current Topics in Molecular Biotechnology of a Koji Mold, Aspergillus oryzae(Recent Topics of the Agricultunal Biological Science in Tohoku University)

Aspergillus oryzae is an important filamentous fungus in Japanese fermentation industries and produces a large amount of starch-degrading enzymes, whose gene expressions are regulated by a transcription activator AmyR. We have recently found a gene cluster highly homologous to the yeast maltose-utilizing cluster and showed that expression of the cluster genes is independent on AmyR but is involved in assimilating maltose, a product by starch degradation. In this article are described structural features and expression profiles of the maltose-utilizing cluster genes in A. oryzae. On the other hand, A. oryzae has been expected as a favorable host microorganism for heterologous protein production. In order to understand the bottlenecks for hyperproduction of heterologous proteins in A. oryzae, we have investigated the cellular responses using the mutated α-mannosidase of Aspergillus saitoi as a model protein. Interestingly, the mutated α-mannosidase was secreted as a hyperglycosylated form when overexpressed

A report of three cases of diabetic nephropathy satisfactorily treated with traditional herbal medicine

We reported that three cases of diabetic nephropathy, who had overt proteinuria, were treated satisfactorily not only for their symptoms but also renal nephropathy with traditional herbal medicine over the long term. In Case 1, the level of S-Cr had changed from 1.2 to 2.0 mg/dl over 98 months, in Case 2 from 0.9 to 1.9 mg/dl over 70 months, and in Case 3 from 1.1 to 2.9 mg/dl over 81 months, acceptably moderate increases, meaning that the progression of their renal insufficiency was controlled over the long term. At the same time, the symptoms of hotness, numbness and edema were improved. Diabetic nephropathy with overt proteinuria is known to develop into renal failure after several years. In these cases, traditional herbal medicine was considered responsible for improving their QOL and prolonging the pre-dialysis period of diabetic nephropathy. 顕性蛋白尿期にある糖尿病性腎症の患者に漢方治療を施行した。その結果,随伴する諸症状の改善のみならず長期問,腎機能低下の進行を抑制した3症例を経験したので報告した。症例lでは,98ケ月の観察でS-Cr値はl.2から2.0mg/dl,症例2では70ケ月の観察で,S-Cr値は0.9から1.9mg/dl,症例3では81ケ月の観察で,S-Cr値は1.1から2.9mg/dl,と長期間腎機能低下の進行を抑制した。同時に,手足の火照りやしぴれ感,下肢の浮腫などの症状の軽快も認めた。持続的に蛋白尿を認める顕牲腎症期に至った糖尿病性腎症は数年の経過で,末期腎不全から血液透析に至ると言われている。今回の症例から和漢薬は,糖尿病性腎症における腎機能障害に対して腎機能障害の進行抑制作用を有する可能性が示唆された。このことから,和漢薬は糖尿病に随伴する諸症状を緩和し,QOLを改善するのみでなく,血液透析導人までの期間を延長し,予後を改善したと考えられた

Immunological analysis into Kl-disorder based on traditional Japanese Oriental diagnostic system

漢方医学での病態を把握し有効方剤を選択するためには,伝統医学的手法を応用することが,現在でも最も客観的な方法であると考えられる。しかしながら,伝統医学的手法は心身・如を助炭とし,きわめて全人的な指標を中心としているが故に,西洋医学的な客観性,すなわち要素還元性に乏しいと指摘されている。この研究では気の異常を臨床免疫学的手法で客観化することを目的とした。22名の関節リウマ患者の気虚,気鬱,気逆の病態と末梢血リンパ球のサブセット(CD3, CD19, CD4,CD8, CD16, CD56, CD158a, CD158b)の関連を検討した。その結果,気虚とCD16+CD158b+cellのpopulationが有意な負の相関を示し,気虚を伴う患者群ではCD16+CD158b+cellのpopulationが少ない傾向にあった。この逆相関の関係は4名の3ヶ月の追跡研究でも観察された。このことから活性化したXK細胞の減少は,気虚の病態を呈した患者の一つの特徴と考えられる。このような検討から気虚など複雑な要素が関与する病態の一部を客観化して同一症例での経過観察などに応用可能と考えられる。ただし複雑性の科学の観点から診断への応用に関しては制限される必要がある。 Although traditional medicine is an all-around medical service, it has been pointed out that traditional medical procedures are not objective, and are independent of reductionism. The aim of this study was to determine the immune status of the patients with Kl-disorder. We assessed the association between Kl-disorder and the population of peripheral lymphocytes (CD3, CD19, CD4, CD8, CD16, CD56, CD158a/b:killer cells immunoglobulin-like receptors) in 22 patients with rheumatoid arthritis. The results showed a negative correlation between the score of Kl-deficiency and the population of the CD16+CD158b+cells, and also showed that patients with Kl-deficiency have a tendency to have a reduced population of CD16+CD158b+cells. The inverse relationship between these was also observed in a 3-month follow-up study. Thus, it is possible, in part, to assess the condition of Kl-deficiency objectively using the population of CD16+CD158b+cells. However, the diagnostic utility of CD158b+expressing cells is expected to be limited from the viewpoints of complexity

Effect of Keishi-bukuryo-gan on asymptomatic cerebral infarction for short term

無症候性脳梗塞患者に対する桂枝茯苓丸の効果を検討した。142例(男性32例,女性110例,平均年齢68.9才)を対象とし,副作用のため内服を中止した3例を除く139例に対して,桂枝茯苓丸エキス1日量7.5gを12週間投与した。投与開始時と比較して,改訂長谷川式簡易知能評価スケール,Apathyスケール(やる気スケール),SDS(うつ状態スケール)は有意に改善した。また,頭重感,頭痛,めまいの自覚症状も桂枝茯苓丸の投与により改善し,拡張期血圧は投与前に比べ有意に低下した。これらの結果から,桂枝茯苓丸が無症候性脳梗塞に伴う認知機能の低下,精神症状や自覚症状の悪化に対して有効である可能性が示唆された。 The efficacy of Keishi-bukuryo-gan in patients suffering from asymptomatic cerebral infarction was studied. 142 patients, 32 males and 110 females, with a mean age of 68.9 years, were enrolled and analyzed, and 139 completed the study. They were given Keishi-bukuryo-gan extract (7.5g/day) three times a day for 12 weeks. In comparison to the beginning of the study, Keishi-bukuryo-gan showed improvement with statistical significance in the mean revised version of Hasegawa\u27s dementia scale, Apathy scale and Self-rating depression scale. The number of patients with subjective symptoms as headdullness, headache and dizziness decreased by the treatment with Keishi-bukuryo-gan, and diastolic blood pressure was decreased with statistical significance as compared to the beginning of the study. These results suggest that Keishi-bukuryo-gan is effective against dysfunction of acknowledgment, emotional disorder and subjective symptoms with asymptomatic cerebral infarction

In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma

Alveolar macrophages (AMs) are crucial for maintaining normal lung function. They are abundant in lung cancer tissues, but their pathophysiological significance remains unknown. Here we show, using an orthotopic murine lung cancer model and human carcinoma samples, that AMs support cancer cell proliferation and thus contribute to unfavourable outcome. Inhibin beta A (INHBA) expression is upregulated in AMs under tumor-bearing conditions, leading to the secretion of activin A, a homodimer of INHBA. Accordingly, follistatin, an antagonist of activin A is able to inhibit lung cancer cell proliferation. Single-cell RNA sequence analysis identifies a characteristic subset of AMs specifically induced in the tumor environment that are abundant in INHBA, and distinct from INHBA-expressing AMs in normal lungs. Moreover, postnatal deletion of INHBA/activin A could limit tumor growth in experimental models. Collectively, our findings demonstrate the critical pathological role of activin A-producing AMs in tumorigenesis, and provides means to clearly distinguish them from their healthy counterparts.Taniguchi S., Matsui T., Kimura K., et al. In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma. Nature Communications 14, 143 (2023); https://doi.org/10.1038/s41467-022-35701-8

Efficacy and Safety of a Traditional Herbal Medicine, Hochu-ekki-to in the Long-term Management of Kikyo (Delicate Constitution) Patients with Atopic Dermatitis: A 6-month, Multicenter, Double-blind, Randomized, Placebo-controlled Study

Hochu-ekki-to is a traditional herbal (Kampo) medicine that has been shown to be effective for patients with Kikyo (delicate, easily fatigable, or hypersensitive) constitution. Previous case reports have suggested that this herbal drug was effective for a certain subgroup of patients with atopic dermatitis (AD). We aimed to evaluate the efficacy and safety of Hochu-ekki-to in the long-term management of Kikyo patients with AD. In this multicenter, double blind, randomized, placebo-controlled study, 91 Kikyo patients with AD were enrolled. Kikyo condition was evaluated by a questionnaire scoring system. All patients continued their ordinary treatments (topical steroids, topical tacrolimus, emollients or oral antihistamines) before and after their protocol entry. Hochu-ekki-to or placebo was orally administered twice daily for 24 weeks. The skin severity scores, total equivalent amount (TEA) of topical agents used for AD treatment, prominent efficacy (cases with skin severity score = 0 at the end of the study) rate and aggravated rate (more than 50% increase of TEA of topical agents from the beginning of the study) were monitored and evaluated. Seventy-seven out of 91 enrolled patients completed the 24-week treatment course (Hochu-ekki-to: n = 37, placebo: n = 40). The TEA of topical agents (steroids and/or tacrolimus) was significantly (P < 0.05) lower in the Hochu-ekki-to group than in the placebo group, although the overall skin severity scores were not statistically different. The prominent efficacy rate was 19% (7 of 37) in the Hochu-ekki-to group and 5% (2 of 40) in the placebo group (P = 0.06). The aggravated rate was significantly (P < 0.05) lower in the Hochu-ekki-to group (3%; 1 of 37) than in the placebo group (18%; 7 of 39). Only mild adverse events such as nausea and diarrhea were noted in both groups without statistical difference. This placebo-controlled study demonstrates that Hochu-ekki-to is a useful adjunct to conventional treatments for AD patients with Kikyo constitution. Use of Hochu-ekki-to significantly reduces the dose of topical steroids and/or tacrolimus used for AD treatment without aggravating AD