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Article ; Online: Chronic Fibrosis and Its Progression to Cancer

Taro Yasuma / Esteban C. Gabazza

International Journal of Molecular Sciences, Vol 23, Iss 3924, p

2022 Volume 3924

Abstract: The terminal stage of many chronic inflammatory diseases is organ fibrosis [.] ...

Abstract	The terminal stage of many chronic inflammatory diseases is organ fibrosis [.]
Keywords	n/a ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Increased expression of Protein S in eyes with diabetic retinopathy and diabetic macular edema

Masahiko Sugimoto / Mineo Kondo / Taro Yasuma / Corina N. D’Alessandro-Gabazza / Masaaki Toda / Hisanori Imai / Makoto Nakamura / Esteban C. Gabazza

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 9

Abstract: Abstract Protein S (PS) is a multifunctional glycoprotein that ameliorates the detrimental effects of diabetes mellitus (DM). The aim of this study was to evaluate the distribution of PS in diabetic retinopathy (DR) and diabetic macular edema (DME). This ...

Abstract	Abstract Protein S (PS) is a multifunctional glycoprotein that ameliorates the detrimental effects of diabetes mellitus (DM). The aim of this study was to evaluate the distribution of PS in diabetic retinopathy (DR) and diabetic macular edema (DME). This was a study of 50 eyes with DM (37 with DME, 6 with proliferative DR, and 7 with no DR) and 19 eyes without DM. The level of PS was measured by enzyme immunoassay and was compared between eyes with or without DM, with or without DME, and with severe DME (≥ 350 μm) or mild DME (< 350 μm). We also performed immunohistopathologic evaluations of post-mortem eyes and the cystoid lesions excised during surgery. The aqueous free PS was significantly higher with DM (7.9 ± 1.2 ng/ml, P < 0.01) than without DM (6.1 ± 0.7). The aqueous free PS was significantly elevated with DME (8.2 ± 1.2, P < 0.05) compared to proliferative DR (7.0 ± 1.0) and no DR (7.0 ± 0.7). Eyes with severe DME had significantly higher aqueous free PS than mild DME (8.5 ± 1.3 vs. 7.7 ± 1.0, P < 0.05). Immunohistochemistry showed PS in the outer plexiform layer of the retina and cystoid lesion. The higher expression of PS with DR and DME suggests that PS is involved in their pathogenesis.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Subcritical Water Extracts from Agaricus blazei Murrill’s Mycelium Inhibit the Expression of Immune Checkpoint Molecules and Axl Receptor

Taro Yasuma / Masaaki Toda / Hajime Kobori / Naoto Tada / Corina N. D’Alessandro-Gabazza / Esteban C. Gabazza

Journal of Fungi, Vol 7, Iss 590, p

2021 Volume 590

Abstract: Agaricus blazei Murrill or Himematsutake is an edible and medicinal mushroom. Agaricus blazei Murrill’s fruiting body extracts have anticancer properties, although the mechanism is unknown. Basic or organic solvents, which are hazardous for human health, ...

Abstract	Agaricus blazei Murrill or Himematsutake is an edible and medicinal mushroom. Agaricus blazei Murrill’s fruiting body extracts have anticancer properties, although the mechanism is unknown. Basic or organic solvents, which are hazardous for human health, are generally used to prepare Agaricus blazei Murrill’s extracts. The inhibition of immune checkpoint molecules and Axl receptor is an effective therapy in cancer. This study assessed whether subcritical water extracts of the Agaricus blazei Murrill’s fruiting body or mycelium affect the expression of Axl and immune checkpoint molecules in lung cancer cells. We used A549 cells and mouse bone marrow-derived dendritic cells in the experiments. We prepared subcritical water extracts from the Agaricus blazei Murrill’s fruiting body or mycelium. The subcritical water extracts from the Agaricus blazei Murrill’s fruiting body or mycelium significantly inhibited the expression of immune checkpoint molecules and Axl compared to saline-treated cells. Additionally, the hot water extract, subcritical water extract, and the hot water extraction residue subcritical water extract from the Agaricus blazei Murrill’s mycelium significantly enhanced the expression of maturation markers in dendritic cells. These observations suggest that the subcritical water extract from Agaricus blazei Murrill’s mycelium is a promising therapeutic tool for stimulating the immune response in cancer.
Keywords	mushroom ; immune checkpoints ; Axl receptor ; lung cancer ; dendritic cells ; immune response ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Amelioration of Pulmonary Fibrosis by Matrix Metalloproteinase-2 Overexpression

Ryo Inoue / Taro Yasuma / Valeria Fridman D’Alessandro / Masaaki Toda / Toshiyuki Ito / Atsushi Tomaru / Corina N. D’Alessandro-Gabazza / Tatsuki Tsuruga / Tomohito Okano / Atsuro Takeshita / Kota Nishihama / Hajime Fujimoto / Tetsu Kobayashi / Esteban C. Gabazza

International Journal of Molecular Sciences, Vol 24, Iss 6695, p

2023 Volume 6695

Abstract: Idiopathic pulmonary fibrosis is a progressive and fatal disease with a poor prognosis. Matrix metalloproteinase-2 is involved in the pathogenesis of organ fibrosis. The role of matrix metalloproteinase-2 in lung fibrosis is unclear. This study evaluated ...

Abstract	Idiopathic pulmonary fibrosis is a progressive and fatal disease with a poor prognosis. Matrix metalloproteinase-2 is involved in the pathogenesis of organ fibrosis. The role of matrix metalloproteinase-2 in lung fibrosis is unclear. This study evaluated whether overexpression of matrix metalloproteinase-2 affects the development of pulmonary fibrosis. Lung fibrosis was induced by bleomycin in wild-type mice and transgenic mice overexpressing human matrix metalloproteinase-2. Mice expressing human matrix metalloproteinase-2 showed significantly decreased infiltration of inflammatory cells and inflammatory and fibrotic cytokines in the lungs compared to wild-type mice after induction of lung injury and fibrosis with bleomycin. The computed tomography score, Ashcroft score of fibrosis, and lung collagen deposition were significantly reduced in human matrix metalloproteinase transgenic mice compared to wild-type mice. The expression of anti-apoptotic genes was significantly increased, while caspase-3 activity was significantly reduced in the lungs of matrix metalloproteinase-2 transgenic mice compared to wild-type mice. Active matrix metalloproteinase-2 significantly decreased bleomycin-induced apoptosis in alveolar epithelial cells. Matrix metalloproteinase-2 appears to protect against pulmonary fibrosis by inhibiting apoptosis of lung epithelial cells.
Keywords	matrix metalloproteinases ; pulmonary fibrosis ; matrix degradation ; apoptosis ; collagen deposition ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Fairy Chemical Imidazole-4-carboxamide Inhibits the Expression of Axl, PD-L1, and PD-L2 and Improves Response to Cisplatin in Melanoma

Chisa Inoue / Taro Yasuma / Corina N. D’Alessandro-Gabazza / Masaaki Toda / Valeria Fridman D’Alessandro / Ryo Inoue / Hajime Fujimoto / Hajime Kobori / Suphachai Tharavecharak / Atsuro Takeshita / Kota Nishihama / Yuko Okano / Jing Wu / Tetsu Kobayashi / Yutaka Yano / Hirokazu Kawagishi / Esteban C. Gabazza

Cells, Vol 11, Iss 374, p

2022 Volume 374

Abstract: The leading cause of death worldwide is cancer. Many reports have proved the beneficial effect of mushrooms in cancer. However, the precise mechanism is not completely clear. In the present study, we focused on the medicinal properties of biomolecules ... ...

Abstract	The leading cause of death worldwide is cancer. Many reports have proved the beneficial effect of mushrooms in cancer. However, the precise mechanism is not completely clear. In the present study, we focused on the medicinal properties of biomolecules released by fairy ring-forming mushrooms. Fairy chemicals generally stimulate or inhibit the growth of surrounding vegetation. In the present study, we evaluated whether fairy chemicals (2-azahypoxanthine, 2-aza-8-oxohypoxanthine, and imidazole-4-carboxamide) exert anticancer activity by decreasing the expression of Axl and immune checkpoint molecules in melanoma cells. We used B16F10 melanoma cell lines and a melanoma xenograft model in the experiments. Treatment of melanoma xenograft with cisplatin combined with imidazole-4-carboxamide significantly decreased the tumor volume compared to untreated mice or mice treated cisplatin alone. In addition, mice treated with cisplatin and imidazole-4-carboxamide showed increased peritumoral infiltration of T cells compared to mice treated with cisplatin alone. In vitro studies showed that all fairy chemicals, including imidazole-4-carboxamide, inhibit the expression of immune checkpoint molecules and Axl compared to controls. Imidazole-4-carboxamide also significantly blocks the cisplatin-induced upregulation of PD-L1. These observations point to the fairy chemical imidazole-4-carboxamide as a promising coadjuvant therapy with cisplatin in patients with cancer.
Keywords	mushroom ; fairy chemicals ; cancer ; drug resistance ; Axl ; immune checkpoint molecules ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Podocyte-specific Crb2 knockout mice develop focal segmental glomerulosclerosis

Akiko Tanoue / Kan Katayama / Yugo Ito / Kensuke Joh / Masaaki Toda / Taro Yasuma / Corina N. D’Alessandro-Gabazza / Hiroshi Kawachi / Kunimasa Yan / Masaaki Ito / Esteban C. Gabazza / Karl Tryggvason / Kaoru Dohi

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 16

Abstract: Abstract Crb2 is a cell polarity-related type I transmembrane protein expressed in the apical membrane of podocytes. Knockdown of crb2 causes glomerular permeability defects in zebrafish, and its complete knockout causes embryonic lethality in mice. ... ...

Abstract	Abstract Crb2 is a cell polarity-related type I transmembrane protein expressed in the apical membrane of podocytes. Knockdown of crb2 causes glomerular permeability defects in zebrafish, and its complete knockout causes embryonic lethality in mice. There are also reports of Crb2 mutations in patients with steroid-resistant nephrotic syndrome, although the precise mechanism is unclear. The present study demonstrated that podocyte-specific Crb2 knockout mice develop massive albuminuria and microhematuria 2-month after birth and focal segmental glomerulosclerosis and tubulointerstitial fibrosis with hemosiderin-laden macrophages at 6-month of age. Transmission and scanning electron microscopic studies demonstrated injury and foot process effacement of podocytes in 6-month aged podocyte-specific Crb2 knockout mice. The number of glomerular Wt1-positive cells and the expressions of Nphs2, Podxl, and Nphs1 were reduced in podocyte-specific Crb2 knockout mice compared to negative control mice. Human podocytes lacking CRB2 had significantly decreased F-actin positive area and were more susceptible to apoptosis than their wild-type counterparts. Overall, this study's results suggest that the specific deprivation of Crb2 in podocytes induces altered actin cytoskeleton reorganization associated with dysfunction and accelerated apoptosis of podocytes that ultimately cause focal segmental glomerulosclerosis.
Keywords	Medicine ; R ; Science ; Q
Subject code	572 ; 616
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protective Role of Recombinant Human Thrombomodulin in Diabetes Mellitus

Yuko Okano / Atsuro Takeshita / Taro Yasuma / Masaaki Toda / Kota Nishihama / Valeria Fridman D’Alessandro / Chisa Inoue / Corina N. D’Alessandro-Gabazza / Tetsu Kobayashi / Yutaka Yano / Esteban C. Gabazza

Cells, Vol 10, Iss 2237, p

2021 Volume 2237

Abstract: Diabetes mellitus is a global threat to human health. The ultimate cause of diabetes mellitus is insufficient insulin production and secretion associated with reduced pancreatic β-cell mass. Apoptosis is an important and well-recognized mechanism of the ... ...

Abstract	Diabetes mellitus is a global threat to human health. The ultimate cause of diabetes mellitus is insufficient insulin production and secretion associated with reduced pancreatic β-cell mass. Apoptosis is an important and well-recognized mechanism of the progressive loss of functional β-cells. However, there are currently no available antiapoptotic drugs for diabetes mellitus. This study evaluated whether recombinant human thrombomodulin can inhibit β-cell apoptosis and improve glucose intolerance in a diabetes mouse model. A streptozotocin-induced diabetes mouse model was prepared and treated with thrombomodulin or saline three times per week for eight weeks. The glucose tolerance and apoptosis of β-cells were evaluated. Diabetic mice treated with recombinant human thrombomodulin showed significantly improved glucose tolerance, increased insulin secretion, decreased pancreatic islet areas of apoptotic β-cells, and enhanced proportion of regulatory T cells and tolerogenic dendritic cells in the spleen compared to counterpart diseased mice treated with saline. Non-diabetic mice showed no changes. This study shows that recombinant human thrombomodulin, a drug currently used to treat patients with coagulopathy in Japan, ameliorates glucose intolerance by protecting pancreatic islet β-cells from apoptosis and modulating the immune response in diabetic mice. This observation points to recombinant human thrombomodulin as a promising antiapoptotic drug for diabetes mellitus.
Keywords	insulin resistance ; diabetes mellitus ; apoptosis ; thrombomodulin ; glucose intolerance ; immune cells ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Degradation Products of Complex Arabinoxylans by Bacteroides intestinalis Enhance the Host Immune Response

Taro Yasuma / Masaaki Toda / Ahmed M. Abdel-Hamid / Corina D’Alessandro-Gabazza / Tetsu Kobayashi / Kota Nishihama / Valeria Fridman D’Alessandro / Gabriel V. Pereira / Roderick I. Mackie / Esteban C. Gabazza / Isaac Cann

Microorganisms, Vol 9, Iss 1126, p

2021 Volume 1126

Abstract: Bacteroides spp. of the human colonic microbiome degrade complex arabinoxylans from dietary fiber and release ferulic acid. Several studies have demonstrated the beneficial effects of ferulic acid. Here, we hypothesized that ferulic acid or the ferulic ... ...

Abstract	Bacteroides spp. of the human colonic microbiome degrade complex arabinoxylans from dietary fiber and release ferulic acid. Several studies have demonstrated the beneficial effects of ferulic acid. Here, we hypothesized that ferulic acid or the ferulic acid-rich culture supernatant of Bacteroides intestinalis , cultured in the presence of complex arabinoxylans, enhances the immune response. Ferulic acid and the culture supernatant of bacteria cultured in the presence of insoluble arabinoxylans significantly decreased the expression of tumor necrosis factor-α and increased the expression of interleukin-10 and transforming growth factor β1 from activated dendritic cells compared to controls. The number of granulocytes in mesenteric lymph nodes, the number of spleen monocytes/granulocytes, and interleukin-2 and interleukin-12 plasma levels were significantly increased in mice treated with ferulic acid or the culture supernatant of bacteria cultured with insoluble arabinoxylans. Ferulic acid or the culture supernatant of bacteria cultured with insoluble arabinoxylans increased the expression of interleukin-12, interferon-α, and interferon-β in intestinal epithelial cell lines. This study shows that ferulic acid or the ferulic acid-rich culture supernatant of the colonic bacterium Bacteroides intestinalis , cultured with insoluble arabinoxylans, exerts anti-inflammatory activity in dendritic cells under inflammatory conditions and enhances the Th1-type immune response under physiological conditions in mice.
Keywords	Colonic Bacteroidetes ; microbiome ; dietary fiber ; arabinoxylans ; ferulic acid ; health benefits ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Use of Ultrathin Bronchoscope on a Need Basis Improves Diagnostic Yield of Difficult-to-Approach Pulmonary Lesions

Yoichi Nishii / Yuki Nakamura / Kentaro Fujiwara / Kentaro Ito / Tadashi Sakaguchi / Yuta Suzuki / Kazuki Furuhashi / Tetsu Kobayashi / Taro Yasuma / Corina N. D'Alessandro-Gabazza / Esteban C. Gabazza / Fumihiro Asano / Osamu Taguchi / Osamu Hataji

Frontiers in Medicine, Vol

2020 Volume 7

Abstract: There are cases of peripheral lung nodules that are difficult to approach despite using ancillary diagnostic devices during multimodal bronchoscopy. The use of ultrathin bronchoscopes has shown superiority over standard thin bronchoscopes. We ... ...

Abstract	There are cases of peripheral lung nodules that are difficult to approach despite using ancillary diagnostic devices during multimodal bronchoscopy. The use of ultrathin bronchoscopes has shown superiority over standard thin bronchoscopes. We retrospectively evaluated whether substitution of the thin-bronchoscope by the ultrathin device during multimodal bronchoscopy improves lesion ultrasound visualization and diagnostic yield in patients with difficult-to-approach pulmonary lesions. The study comprised 44 out of 338 patients that underwent multimodal bronchoscopy at Matsusaka Municipal Hospital. The thin-bronchoscope with an external diameter of 4 mm was substituted by the ultrathin-bronchoscope with an external diameter of 3 mm when the radial endobronchial ultrasound showed that the probe position was not within the target lesion. The median diameter of the pulmonary tumors was 17.5 mm (range: 6.0–5.2.0 mm). The endobronchial ultrasound showed the probe's position adjacent to the lesion in 12 cases and no visible lesion in 32 cases using a thin-bronchoscope. However, the endobronchial ultrasound views changed from adjacent to the lesion to within the lesion in nine cases, from no visible lesion to within the lesion in 17 cases, and from no visible lesion to adjacent to the lesion in nine cases after bronchoscope substitution. After substitution, the diagnostic yield was 80.8% in cases with the radial probe within the target lesion, 72.7% in cases with the probe adjacent to the target lesion, and 0% in cases with no visible lesion. The overall diagnostic yield was 65.9% after bronchoscope substitution. The substitution of the thin bronchoscope by the ultrathin device on a need basis improves the position of the radial endobronchial ultrasound probe and diagnostic yield of pulmonary lesions during multimodal diagnostic bronchoscopy.
Keywords	ultrathin bronchoscope ; peripheral pulmonary lesion ; diagnostic bronchoscopy ; endobronchial ultrasound ; thin bronchoscope ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Prediction Equation to Assess Resting Energy Expenditure in Japanese Patients with COPD

Keisuke Morikawa / Kazuyuki Tabira / Hiroyuki Takemura / Shogo Inaba / Haruka Kusuki / Yu Hashitsume / Yuta Suzuki / Yosuke Tenpaku / Taro Yasuma / Corina N. D’Alessandro-Gabazza / Esteban Gabazza / Osamu Hataji

Journal of Clinical Medicine, Vol 9, Iss 3455, p

2020 Volume 3455

Abstract: Background: Medical nutrition therapy is important in the management of chronic obstructive pulmonary disease (COPD) patients. Determination of resting energy expenditure is essential to define therapeutic goals for medical nutrition. Previous studies ... ...

Abstract	Background: Medical nutrition therapy is important in the management of chronic obstructive pulmonary disease (COPD) patients. Determination of resting energy expenditure is essential to define therapeutic goals for medical nutrition. Previous studies proposed the use of equations to predict resting energy expenditure. No prediction equation is currently available for the Japanese population. The objective of this study was to develop an equation to predict resting energy expenditure in Japanese chronic obstructive pulmonary disease patients. To this end, we investigated clinical variables that correlate with the resting energy expenditure. Methods: This study included 102 COPD patients admitted at the Matsusaka Municipal Hospital Respiratory Center. We measured resting energy expenditure by indirect calorimetry and explored the relationship of resting energy expenditure with clinical variables by univariate and stepwise linear regression analysis. Results: The resting energy expenditure by indirect calorimetry was significantly correlated with fat-free mass, body weight, body mass index, height, gender, and pulmonary function test by univariate analysis. In the stepwise linear regression analysis, the fat-free mass, body weight, and age remained significantly correlated with indirect calorimetry’s resting energy expenditure. The fat-free mass, body weight, and age explained 50.5% of the resting energy expenditure variation. Conclusion: Fat-free mass, body weight, and age were significantly correlated with resting energy expenditure by stepwise linear regression analysis, and they were used to define a predictive equation for Japanese COPD patients.
Keywords	COPD ; resting energy expenditure ; prediction equation ; Japanese population ; fat-free mass ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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