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  • 1
    In: Journal of Diabetes Research, Hindawi Limited, Vol. 2017 ( 2017), p. 1-15
    Abstract: Purpose. In this study, we investigated the effect of PGC1 α activators on mitochondrial fusion, fission, and autophagic quality control in renal tubular cells in a diabetic environment in vivo and in vitro. We also examined whether the upregulation of PGC1 α attenuates diabetic tubulopathy by normalizing mitochondrial homeostasis. Methods . HKC8 cells were subjected to high-glucose conditions (30 mM D-glucose). Diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57/BL6J mice. AICAR or metformin was used as a PGC1 α activator. Results. Treatment with the PGC1 α activators AICAR and metformin improved functional mitochondrial mass in HKC8 cells in high-glucose conditions. Moreover, in renal proximal tubular cells, increased PGC1 α activity correlated with the reversal of changes in Drp1, Mfn1, and LC3-II protein expression in a high-glucose environment. Normalized mitochondrial life cycles resulted in low ROS production and reduced apoptosis. AICAR and metformin treatment effectively mitigated albuminuria and renal histopathology and decreased the expression of TGF β 1 and α SMA in the kidneys of diabetic mice. Conclusions . Our results demonstrate that increases in PGC1 α activity improve diabetic tubulopathy by modulating mitochondrial dynamics and autophagy.
    Type of Medium: Online Resource
    ISSN: 2314-6745 , 2314-6753
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2711897-6
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  • 2
    In: Journal of Nanomaterials, Hindawi Limited, Vol. 2012 ( 2012), p. 1-8
    Abstract: Radiotherapy for cancer treatment has been used for primary or adjuvant treatment in many types of cancer, and approximately half of all cancer patients are undergoing radiation. However, ionizing radiation exposure induces genetic alterations in cancer cells and results in recruitment of monocytes/macrophages by triggering signals released from these cells. Using this characteristic of monocytes/macrophages, we have attempted to develop a biocarrier loading radiosensitizing anticancer agents that can lead to enhance the therapeutic effect of radiation in cancer treatment. The aim of this study is to demonstrate the proof of this concept. THP-1 labeled with Qdot 800 or iron oxide (IO) effectively migrated into tumors of subcutaneous mouse model and increased recruitment after ionizing radiation. Functionalized liposomes carrying a radiosensitizing anticancer agent, doxorubicin, are successfully loaded in THP-1 (THP-1-LP-Dox) with reduced cytotoxicity, and THP-1-LP-Dox also was observed in tumors after intravenous administration. Here, we report that monocytes/macrophages as a biocarrier can be used as a selective tool for amplification of the therapeutic effects on radiotherapy for human cancer treatment.
    Type of Medium: Online Resource
    ISSN: 1687-4110 , 1687-4129
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2229480-6
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  • 3
    In: BioMed Research International, Hindawi Limited, Vol. 2022 ( 2022-7-4), p. 1-9
    Abstract: Background. Rosacea is a chronic inflammatory skin disease with a multifactorial etiology. Recently, associations between serum homocysteine (Hcy) levels and inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa, have been reported. However, no study has explored the levels of serum Hcy, folic acid, and vitamin B12 in patients with rosacea. Objective. To investigate serum Hcy, vitamin B12, and folic acid levels in patients with papulopustular rosacea (PPR), we characterized the association of these levels with PPR severity. Methods. This case-control study included 138 PPR patients and 58 healthy controls. The serum levels of Hcy, vitamin B12, and folic acid were measured. A correlation was assessed between disease severity and serum levels of Hcy, vitamin B12, and folic acid. Results. Serum vitamin B12 and folic acid levels were significantly lower in PPR patients than in the healthy controls ( p = 0.011 and p = 0.0173 , respectively). Although serum Hcy levels did not significantly differ between PPR patients and healthy controls, PPR severity was positively correlated with serum Hcy levels ( p 〈 0.001 ). Conclusions. Our results suggest a possible association between hyperhomocysteinemia and vitamin B12 deficiency in patients with PPR.
    Type of Medium: Online Resource
    ISSN: 2314-6141 , 2314-6133
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2698540-8
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  • 4
    In: Journal of Nanomaterials, Hindawi Limited, Vol. 2012 ( 2012), p. 1-5
    Abstract: Radiotherapy (RT) is a major modality for cancer treatment, but its efficacy is often compromised by the resistance caused by tumor-specific microenvironment including acidosis and hypoxia. For an effective RT, concurrent administration of radiosensitizer with RT has been emphasized. However, most anticancer agents enhancing radiotherapeutic efficacy have obstacles such as poor solubility and severe toxicity. Paclitaxel (PTX), a well-known radiosensitizer, is insoluble in water and needs toxic solvent like Cremophor EL. Nanomaterials in drug delivery systems have been utilized for improving the drawbacks of anti-cancer drugs. Solubilization, tumor accumulation, and toxicity attenuation of drug by nanomaterials are suitable for enhancement of radiotherapeutic efficacy. In this study, PTX was incorporated into pH-sensitive block copolymer micelle (psm-PTX), polyethylene glycol-graft-poly(β-amino ester), and preclinically evaluated for its effect on RT. The size of psm-PTX was 125.7 ± 4.4  nm at pH 7.4. psm-PTX released PTX rapidly in the acidic condition (pH 6.5), while it was reasonably stable in the physiologic condition (pH 7.4). The clonogenic assay showed that psm-PTX greatly sensitized human non-small-cell lung cancer A549 cells to radiation. In the xenograft tumor model, the combination of psm-PTX and radiation significantly delayed the tumor growth. These results demonstrated the feasibility of psm-PTX to enhance the chemoradiotherapeutic efficacy.
    Type of Medium: Online Resource
    ISSN: 1687-4110 , 1687-4129
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2229480-6
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  • 5
    In: Journal of Immunology Research, Hindawi Limited, Vol. 2015 ( 2015), p. 1-15
    Abstract: We have previously demonstrated that semimature dendritic cell- (smDC-) based immunotherapy is effective for the treatment of collagen-induced arthritis (CIA) prior to disease onset. In the present study, we examined the efficacy of combination therapy with smDCs and methotrexate (MTX) in advanced CIA with a score of 2-3. Combination therapy with low-dose MTX and type II collagen- (CII-) pulsed smDCs (CII-smDCs) was more effective in inhibiting disease progression than high or low-dose MTX alone or a combination of high dose MTX and CII-smDCs. The effect of CII-smDCs alone was also comparable to the combination therapy. CD4 + Foxp3 + Treg populations and IL-10 secretion markedly increased, and CII-specific autoreactive T cells decreased in mice treated with CII-smDCs alone or in combination with MTX. Combination therapy reduced the secretion of interferon- γ (IFN- γ ) and IL-17 with little influence on the IL-4 secretion in the mixed leukocyte reaction. These results imply that the combination therapy with low-dose MTX and smDCs is effective in controlling advanced CIA by enhancing Treg population and suppresses antigen-specific Th1/Th17 immunity, rather than initiating Th1 to Th2 immune deviation. Our findings provide a better understanding of the DC therapy in combination with MTX for the treatment of patients with rheumatoid arthritis (RA).
    Type of Medium: Online Resource
    ISSN: 2314-8861 , 2314-7156
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2015
    detail.hit.zdb_id: 2817541-4
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  • 6
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2015 ( 2015), p. 1-6
    Abstract: The purpose of the present study was to investigate multiple anthropometric parameters used to evaluate obesity, particularly visceral abdominal fat area, and various metabolic parameters including malondialdehyde (MDA) as an oxidative stress marker. We evaluated various measures of obesity, including body mass index (BMI), waist circumference (WC), sagittal abdominal diameter, fat percentages using dual-energy X-ray absorptiometry, visceral fat area (VFA), subcutaneous fat area, multiple biomarkers related to metabolic disease, and urinary MDA, in 73 asymptomatic middle-aged men who were not severely obese. We examined relationships between multiple measures of obesity, metabolic markers, and urinary MDA levels and evaluated associations between VFA and urinary MDA. In the visceral obesity group, γ -glutamyl transferase (GGT), uric acid, and urinary MDA levels were significantly higher than in the nonvisceral obesity group ( P = 0.008, P = 0.002, and P = 0.018). Urinary MDA ( r = 0.357, P = 0.002) and uric acid ( r = 0.263, P = 0.027) levels were only significantly positively correlated with VFA among measures of obesity. Urinary MDA, serum GGT, and serum CRP were significantly positively associated with VFA ( P = 0.001, P = 0.046, and P = 0.023, resp.), even after adjusting for BMI and WC.
    Type of Medium: Online Resource
    ISSN: 0962-9351 , 1466-1861
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2015
    detail.hit.zdb_id: 2008065-7
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  • 7
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2018 ( 2018-05-30), p. 1-10
    Abstract: Diabetic cardiomyopathy (DCM) is tightly linked to heart disorders and dysfunction or death of the cardiomyocytes including resident cardiac progenitor cells (CPCs) in diabetic patients. In order to restore loss of function of resident or transplanted CPCs, much research has focused on novel therapeutic strategies including the discovery of novel function-modulating factors such as reactive oxygen species (ROS) scavengers. Here, we developed and defined a novel antioxidant, MHY-1684, for enhancing the angiogenic potential of CPCs against ROS-related DCM. Short-term treatment with MHY-1684 restored ROS-induced CPC cell death. Importantly, MHY-1684 decreased hyperglycemia-induced mitochondrial ROS generation and attenuated hyperglycemia-induced mitochondrial fragmentation. We observed that the activation process of both Drp1 (phosphorylation at the site of Ser616) and Fis-1 is drastically attenuated when exposed to high concentrations of D-glucose with MHY-1684. Interestingly, phosphorylation of Drp1 at the site of Ser637, which is an inhibitory signal for mitochondrial fusion, is restored by MHY-1684 treatment, suggesting that this antioxidant may affect the activation and inhibition of mitochondrial dynamics-related signaling and mitochondrial function in response to ROS stress. In conclusion, our finding of the novel compound, MHY-1684, as an ROS scavenger, might provide an effective therapeutic strategy for CPC-based therapy against diabetic cardiomyopathy.
    Type of Medium: Online Resource
    ISSN: 1942-0900 , 1942-0994
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2455981-7
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  • 8
    In: BioMed Research International, Hindawi Limited, Vol. 2022 ( 2022-3-27), p. 1-11
    Abstract: Background. Obesity induced by excessive nutrients can cause fatty liver and metabolic dysfunction, which leads to hepatic dysfunction and local/systemic inflammatory responses. Previously, we analyzed the antioxidant, antilipotoxicity, and anti-inflammatory effects of protein hydrolysates in vitro. The aim of the present study is to investigate the antiobesity and hepatoprotective effects of protein hydrolysates derived from Protaectia brevitas (PHPB) in an obese mouse model. Methods. For this in vivo study, 40 mice were included and divided into four groups: (1) normal diet group, (2) high-fat-diet (ctrl(–)) group, (3) high-fat-diet and silymarin-treated (ctrl(+)) group, and (4) high-fat-diet and PHPB-treated group. After 6 weeks of treatment, body weight and the amount of daily food intake were observed. Moreover, the major organs and blood of animals were collected for the analysis of serum chemistry, histopathological examination, and obesity- and inflammation-related gene expressions. Results. The body weight and the amount of daily food intake significantly decreased in the PHPB-treated group compared with those in the ctrl(–) group. The levels of serum ALT, AST, ALP, creatinine, blood urea nitrogen, glucose, bilirubin, total cholesterol, TG, low-density lipoprotein, IL-6, TNF-α, and IGF-1 significantly reduced in the PHPB-treated group, whereas the serum free fatty acid, albumin, high-density lipoprotein, and adiponectin concentrations increased. In the analysis of weight of the liver, kidney, lungs, spleen, and fat tissues (from epididymal, perirenal, and mesentery tissues), the PHPB-treated group showed decreased values compared with the ctrl(–) group. In the histopathological analysis, the PHPB-treated group showed significantly reduced macrovesicular fatty change and inflammatory cell infiltration in the liver, and the size of the adipocyte in the epididymis also significantly decreased. The obesity- and inflammation-related gene (IL-6, TNF-α, IGF-1, leptin, AP2/FABP4, AMPK-α2, β3AR, and PPAR-γ) expressions in the liver and epididymal adipose tissue were reduced in the PHPB-treated group. Conclusions. Overall, the results of this study suggest that the protein hydrolysates that derived from Protaectia brevitas produce antiobesity and hepatoprotective effects via anti-inflammatory activities.
    Type of Medium: Online Resource
    ISSN: 2314-6141 , 2314-6133
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2698540-8
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  • 9
    In: Stem Cells International, Hindawi Limited, Vol. 2018 ( 2018-10-29), p. 1-11
    Abstract: Cross talks between the renin-angiotensin system (RAS), sympathetic nervous system, and vascular homeostasis are tightly coordinated in hypertension. Angiotensin II (Ang II), a key factor in RAS, when abnormally activated, affects the number and bioactivity of circulating human endothelial progenitor cells (hEPCs) in hypertensive patients. In this study, we investigated how the augmentation of Ang II regulates adrenergic receptor-mediated signaling and angiogenic bioactivities of hEPCs. Interestingly, the short-term treatment of hEPCs with Ang II drastically attenuated the expression of beta-2 adrenergic receptor (ADRB2), but did not alter the expression of beta-1 adrenergic receptor (ADRB1) and Ang II type 1 receptor (AT1R). EPC functional assay clearly demonstrated that the treatment with ADRB2 agonists significantly increased EPC bioactivities including cell proliferation, migration, and tube formation abilities. However, EPC bioactivities were decreased dramatically when treated with Ang II. Importantly, the attenuation of EPC bioactivities by Ang II was restored by treatment with an AT1R antagonist (telmisartan; TERT). We found that AT1R binds to ADRB2 in physiological conditions, but this binding is significantly decreased in the presence of Ang II. Furthermore, TERT, an Ang II-AT1R interaction blocker, restored the interaction between AT1R and ADRB2, suggesting that Ang II might induce the dysfunction of EPCs via downregulation of ADRB2, and an AT1R blocker could prevent Ang II-mediated ADRB2 depletion in EPCs. Taken together, our report provides novel insights into potential therapeutic approaches for hypertension-related cardiovascular diseases.
    Type of Medium: Online Resource
    ISSN: 1687-966X , 1687-9678
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2573856-2
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  • 10
    Online Resource
    Online Resource
    Hindawi Limited ; 2011
    In:  Journal of Food Biochemistry Vol. 35, No. 4 ( 2011-08), p. 1034-1046
    In: Journal of Food Biochemistry, Hindawi Limited, Vol. 35, No. 4 ( 2011-08), p. 1034-1046
    Type of Medium: Online Resource
    ISSN: 0145-8884
    URL: Issue
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2011
    detail.hit.zdb_id: 2174913-9
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