Polymethoxyflavonids and T helper 17 cells

We examined the effects of polymethoxyflavonoids (PMFs) on T helper (Th) 17 cell differentiation in vitro and in vivo. Five different PMFs including nobiletin (NOB), sudachitin (SUD), demethoxysudachitin, heptamethoxyflavone and natsudaidain were used for the in vitro study, and effects of those flavonoids on Th17 responses were investigated. NOB and heptamethoxyflavone significantly suppressed the proliferation response, but SUD, demethoxysudachitin and natsudaidain did not suppress the proliferation response. All of the five flavonoids decreased IL-17A production. Mice with experimentally induced autoimmune encephalomyelitis were used as an in vivo Th17 differentiation model. We focused on two flavonoids, NOB and SUD, and examined the effects of those flavonoids. NOB significantly suppressed Th17 cell proliferation and cytokine responses, but SUD only decreased proliferation responses. The results suggest that the suppressive effect of NOB on Th17 response in vivo is stronger than that of SUD

Citrus sudachi Peel Extract Suppresses Cell Proliferation and Promotes the Differentiation of Keratinocytes through Inhibition of the EGFR–ERK Signaling Pathway

Citrus sudachi is a well-known fruit in Tokushima Prefecture, Japan, and its peels are rich in phytochemicals, including phenolic compounds. Although it is expected that the extract of the C. sudachi peel elicits various beneficial physiological activities, the effect on the skin has not been investigated. In this study, we report that the aqueous extract from the peel of C. sudachi suppresses cell proliferation of the immortalized human keratinocyte cell line, HaCaT, and primary normal human epidermal keratinocytes. The extract of C. sudachi peel suppressed epidermal growth factor (EGF)-induced EGF receptor activation and tumor necrosis factor (TNF)-α-induced extracellular regulated kinase (ERK) 1/2 activation, which suggests that the extract exerts its inhibitory effect through inhibition of both the EGF receptor (EGFR) and its downstream molecules. Additionally, the extract of C. sudachi peel potentiated calcium-induced keratinocyte differentiation. These results suggest that the extract of C. sudachi peel may have beneficial effects against skin diseases that are characterized by hyperproliferation of epidermal keratinocytes, such as those seen in psoriasis and in cutaneous squamous cell carcinoma

Effects of the intake of Undaria pinnatifida (Wakame) and its sporophylls (Mekabu) on postprandial glucose and insulin metabolism

Long-term suppression of postprandial glucose concentration is an important dietary strategy for the prevention and treatment of type 2 diabetes. Because previous reports have suggested that seaweed may exert anti-diabetic effects in animals, the effects of Wakame or Mekabu intake with 200 g white rice, 50 g boiled soybeans, 60 g potatoes, and 40 g broccoli on postprandial glucose, insulin and free fatty acid levels were investigated in healthy subjects. Plasma glucose levels at 30 min and glucose area under the curve (AUC) at 0-30 min after the Mekabu meal were significantly lower than that after the control meal. Plasma glucose and glucose AUC were not different between the Wakame and control meals. Postprandial serum insulin and its AUC and free fatty acid concentration were not different among the three meals. In addition, fullness, satisfaction, and wellness scores were not different among the three meals. Thus, consumption of 70 g Mekabu with a white rice-based breakfast reduces postprandial glucose concentration

Extracts of citrus Sudachi peel attenuate body weight gain in C57BL/6 mice fed a high-fat diet

Citrus Sudachi is the special local product of Tokushima Prefecture, and over 98% of Sudachi consumed in Japan every year is produced in Tokushima Prefecture. In this study, we evaluated the function of sudachi peel extract (SPE) using an animal model of obesity. C57BL/6 mice were fed a high-fat diet containing 1% SPE powder. Treatment with SPE significantly decreased body weight compared to that of mice fed a high-fat diet. A significant difference in body weight was observed between the control and SPE groups from 7 weeks after the start of the experiment, the significant difference continued until the end of the 14-week experiment. Reduction of blood glucose levels following insulin administration in SPE-treated mice was grater than that in control mice. Determination of mRNA expression in adipose tissue showed that the expression level of TNF-α in the SPE group was significantly decreased compared to that on the control group. These results suggest that SPE potentially has the ability to attenuate body weight gain

チョウカン トランス ポーター オ ブンシ ヒョウテキ トシタ ジンシッカン チリョウホウ ノ カクリツ オ メザシテ

The understanding of intestinal function in chronic kidney disease（CKD）has been important elements in the clinical management of CKD with dietary and drug therapy. Numerous studies have indicated that CKD patients or model rats have enzymatic abnormalities and impairments of absorptive function in the small intestine. However, it has been still unclear how different of the intestinal function in CKD. In this study, we demonstrated the microarray analysis of global gene expression in intestine of adenine-induced CKD rat. DNA microarray analysis using Affymextrix rat gene chip revealed that CKD caused great changes in gene expression in the rat duodenum : about４００genes exhibited more than a two-fold change in expression level. Gene ontology analysis showed that a global regulation of genes by CKD involved in iron ion binding, alcoholic, organic acid and lipid metabolism. Furthermore, we found markedly changes of a number of intestinal transporters gene expression. These results suggest that CKD may alter some nutrient metabolism in the small intestine by modifying the expression of specific genes. The intestinal transcriptome database of CKD might be useful to develop the novel drugs or functional foods targeting several intestinal genes including transporters for the management of CKD

Treatment with buckwheat bran extract prevents the elevation of serum triglyceride levels and fatty liver in KK-Ay mice.

Buckwheat powder or protein has been shown to decrease the total serum cholesterol level in non-diabetic mice or rats. However, the lipid-lowering effect of buckwheat bran extract (BBE) in diabetic mice has not been fully elucidated. KK-Ay mice that received six-week treatment with BBE showed decreased body weight and liver weight compared to those of control (vehicle) mice. However, there was no significant difference in food intake. BBE treatments prevented liver triglyceride accumulation and decreased the serum level of triglycerides. In addition, mRNA expression levels lipogenic enzyme genes, fatty acid synthase, acetyl-coenzyme a oxidase and stearyl-coenzyme a desaturase 1, but not those of β-oxidized enzyme genes, were decreased in BBE-treated mice. Level of transcription factors ChREBP and SREBP1c, transcripts of lipogenic genes, were also decreased in BBE-treated mice. These results suggest that chronic treatment with BBE derivatives could have beneficial effects on hypertriglycemia in patients with type 2 diabetes mellitus

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