更新于：2024-11-01

TGF-β1 x Advanced glycation end product

更新于：2024-11-01

基本信息

关联

项与 TGF-β1 x Advanced glycation end product 相关的药物

DW-1029M

靶点

Advanced glycation end product x TGF-β1

作用机制

晚期糖基化终末产物抑制剂 [+1]

在研机构-

原研机构

DONG WHA PHARM Co., Ltd.

在研适应症-

非在研适应症

糖尿病肾病

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 TGF-β1 x Advanced glycation end product 相关的临床试验

NCT02212782 / Completed临床1期

A Randomized, Open-label, Multiple-dose, Crossover Phase I Clinical Study to Evaluate DW1029M Influence the Pharmacokinetic Profiles of Linagliptin After Oral Administration in Healthy Male Volunteer

Phase I clinical study to evaluate DW1029M influence the pharmacokinetic profiles of Linagliptin after oral administration in healthy male volunteer.

开始日期2014-09-01

申办/合作机构

DONG WHA PHARM Co., Ltd.

NCT02212756 / Completed临床1期

A Randomized, Open-label, Multiple-dose, Crossover Phase I Clinical Study to Evaluate DW1029M Influence the Pharmacokinetic Profiles of Metformin After Oral Administration in Healthy Male Volunteer

Phase I clinical study to evaluate DW1029M influence the pharmacokinetic profiles of Metformin after oral administration in healthy male volunteer

开始日期2014-08-01

申办/合作机构

DONG WHA PHARM Co., Ltd.

100 项与 TGF-β1 x Advanced glycation end product 相关的临床结果

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100 项与 TGF-β1 x Advanced glycation end product 相关的转化医学

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0 项与 TGF-β1 x Advanced glycation end product 相关的专利（医药）

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项与 TGF-β1 x Advanced glycation end product 相关的文献（医药）

2020-11-01·Chinese Journal of Integrative Medicine3区 · 医学

Xueshuantong for Injection (Lyophilized, 注射用血栓通) Alleviates Streptozotocin-Induced Diabetic Retinopathy in Rats

3区 · 医学

Article

作者: Hu, Li-Min ; Wang, Shao-Xia ; Chen, Lu ; Li, Rui-Lin ; Guo, Hong ; Wang, Hong ; Chai, Li-Juan ; Wang, Jin-Xin

OBJECTIVETo investigate the ameliorate effect and underlying mechanism of Xueshuantong for Injection (Lyophilized, , XST) in streptozocin (STZ)-induced diabetic retinopathy (DR) rats.METHODSDiabetes mellitus (DM) model was induced by intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Diabetic rats were randomized into 3 groups (n=10) according to a random number table, including DM, XST50 and XST100 groups. XST treatment groups were daily i.p. injected with 50 or 100 mg/kg XST for 60 days, respectively. The control and DM groups were given i.p. injection with saline. Blood glucose level and body weight were recorded every week. Histological changes in the retina tissues were observed with hematoxylin-eosin staining. Apoptosis and inflammation related factors, including cleaved caspase-3, glial fifibrillary acidic protein (GFAP), tumor necrosis factor-α (TNF-α) and intercellular cell adhesion molecule-1 (ICAM-1) were detected by Western blot or real-time polymerase chain reaction. Then, the levels of advanced glycation end product (AGE) and its receptor (RAGE) were investigated. Tight junctions proteins (Zonula occludens-1 (ZO-1), Occludin and Claudin-5) of blood-retinal barrier were detected by Western blot. The levels of retinal fifibrosis, transforming growth factor-β1 (TGF-β1)-Smad2/3 signaling pathway were evaluated at last.RESULTSThere was no signifificant difference in the body weight and blood glucose level between XST and DM groups (P>0.05). Compared with the DM group, XST treatment signifificantly increased the retinal thickness of rats (P<0.05 or P<0.01), and suppressed cleaved caspase-3 expression (P<0.01). XST increased the protein expressions of ZO-1, Occludin and Claudin-5 and decreased the mRNA expressions of matrix metalloproteinase 2 (MMP-2) and MMP-9 (P<0.05 or P<0.01). Moreover, XST signifificantly reduced the productions of AGE and RAGE proteins in the retina of rats (P<0.05 or P<0.01), suppressed the over-expression of TNF-α, and decreased the elevated level of ICAM-1 in retina of rats (P<0.05 or P<0.01). XST signifificantly reduced the levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), TGF-β1 and phosphorylation of Smad2/3 protein in rats (P<0.05 or P<0.01).CONCLUSIONSXST had protective effects on DR with possible mechanisms of inhibiting the inflammation and apoptosis, up-regulating the expression of tight junction proteins, suppressing the productions of AGE and RAGE proteins, and blocking the TGF-β/Smad2/3 signaling pathway. XST treatment might play a role for the future therapeutic strategy against DR.

2017-01-01·Pharmacognosy Research

Astaxanthin ameliorates hepatic damage and oxidative stress in carbon tetrachloride-administered rats

Article

作者: Al Mamun, Md Abdullah ; Reza, Hasan Mahmud ; Rahman, Md Mizanur ; Ul Islam, Md Tauhid ; Rahman, A F M Towheedur ; Alam, Md Ashraful ; Alam, Mohammad Nazmul ; Islam, Md Ariful ; Faruk, Md

BACKGROUNDAstaxanthin is of carotenoids group which possess strong antioxidant properties. The present study was conducted to evaluate the hepatoprotective effects of astaxanthin in carbon tetrachloride (CCl₄)-treated rats.MATERIALS AND METHODSFemale Long-Evans rats were administered with CCl₄ orally (1 ml/kg) twice a week for 2 weeks and were treated with astaxanthin (10 mg/kg) every day for 2 weeks. Blood plasma samples were isolated from each group and were analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase activities. Oxidative stress parameters such as malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) were measured. Several enzyme functions such as myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activities in the plasma and liver tissues were also analyzed. Moreover, inflammation and tissue fibrosis were also confirmed by histological staining of liver tissues.RESULTSThis investigation revealed that CCl₄ administration in rats increased plasma AST, ALT, and ALP activities which were normalized by astaxanthin treatment. Moreover, CCl₄ administration increased as MDA, NO, and APOP level both in plasma and tissues compared to control rats. Astaxanthin also exhibited a significant reduction of those parameters in CCl₄-administered rats. Astaxanthin treatment also restored the CAT and SOD activities and lowered MPO activity in CCl₄-administered rats. Histological assessment also revealed that the astaxanthin prevented the inflammatory cells infiltration, decreased free iron deposition, and fibrosis in liver of CCl₄-administered rats.CONCLUSIONThese results suggest that astaxanthin protects liver damage induced by CCl₄ by inhibiting lipid peroxidation and stimulating the cellular antioxidant system.SUMMARYCarbon tetrachloride (CCl₄) administration increased oxidative stress-mediated hepatic damage and inflammation in ratsAstaxanthin, a potent antioxidant, prevents oxidative stress and inflammatory cells infiltration in CCl₄-administered ratsAstaxanthin also ameliorated the progression of hepatic fibrosis in CCl₄-administered rats. Abbreviations Used: APOP: Advanced protein oxidation product; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; CAT: Catalase; CCl4: Carbon tetrachloride; CVD: Cardiovascular disease; HSCs: Hepatic stellate cells; H2O2: Hydrogen peroxide; MDA: Malondialdehyde; MMP2: Matrix metalloproteinase2; MPO: Myeloperoxidase; NF-κB: Nuclear factor kappa B; NO: Nitric oxide; Nrf2: Nuclear factor erythroid 2-related factor 2; ·ONOO-: Peroxynitrate; ROS: Reactive oxygen species; SOD: superoxide dismutase; TCA: Trichloroacetic acid; TBA: Thiobarbituric acid; TGF-1: Transforming growth factor 1, TGF-β: Transforming growth factor-β; TIMP1: Tissue inhibitor of metalloproteinase 1; TNF-α: Tumor necrosis factor-alpha;·CCl3: Trichloromethyl free radical; CCl3O2-: Trichloroperoxyl radical.

2014-12-01·BMC Pulmonary Medicine3区 · 医学

The impact of concomitant pulmonary infection on immune dysregulation in Pneumocystis jirovecii pneumonia

3区 · 医学

ArticleOA

作者: Chung Wei Chou ; Han Chen Tsai ; Shi Chuan Chang ; Fang Chi Lin

BACKGROUNDConcurrent infection may be found in Pneumocystis jirovecii pneumonia (PJP) of non-acquired immunodeficiency syndrome (AIDS) patients, however, its impact on immune dysregulation of PJP in non-AIDS patients remains unknown.METHODSWe measured pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-17, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-β1 and IL-1 receptor antagonist (IL-1RA) and inflammatory markers including high mobility group box 1, Krebs von den Lungen-6, receptor for advanced glycation end product, advanced glycation end product, surfactant protein D in bronchoalveolar lavage fluid (BALF) and blood in 47 pure PcP and 18 mixed PJP and other pulmonary infections (mixed PJP) in non-AIDS immunocompromised patients and explored their clinical relevance. The burden of Pneumocystis jirovecii in the lung was determined by counting number of clusters of Pneumocystis jirovecii per slide and the concentration of β-D-glucan in BALF. PJP severity was determined by arterial oxygen tension/fraction of inspired oxygen concentration ratio, the need of mechanical ventilation and death.RESULTSCompared with pure PJP group, mixed PJP group had significantly higher BALF levels of IL-1β, TNF-α and IL-8 and significantly higher blood levels of IL-8. The BALF ratios of TNF-α/IL-10, IL-8/IL-10, IL-1β/IL-10, TNF-α/TGF-β1, IL-8/TGF-β1, IL-1β/TGF-β1 and IL-1β/IL-1RA were significantly higher in mixed than in pure PJP patients. There was no significant difference in clinical features and outcome between pure and mixed PJP groups, including inflammatory biomarkers and the fungal burden. In pure PJP patients, significantly higher BALF levels of IL-8 and the ratios of IL-8/IL-10, IL-1β/TGF-β1, MCP-1/TGF-β1, MCP-1/IL1RA and IL-8/TGF-β1 were found in the patients requiring mechanical ventilation and in non-survivors.CONCLUSIONSIn summary, concurrent pulmonary infection might enhance immune dysregulation of PJP in non-AIDS immunocompromised patients, but did not affect the outcome as evidenced by morbidity and mortality. Because of limited number of cases studied, further studies with larger populations are needed to verify these issues.