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Article ; Online: Emodin, a Natural Anthraquinone, Increases Uric Acid Excretion in Rats with Potassium Oxonate-Induced Hyperuricemia

Shen-Wei Hou / Szu-Ju Chen / Jing-Dung Shen / Huey-Yi Chen / Shih-Jing Wang / Chia-Han Wang / Kee-Ming Man / Po-Len Liu / Ming-Yen Tsai / Yung-Hsiang Chen / Wen-Chi Chen

Pharmaceuticals, Vol 16, Iss 789, p

2023 Volume 789

Abstract: The treatment of hyperuricemia and gout is mostly based on lowering serum uric acid levels using drugs, such as allopurinol, or increasing urinary excretion of uric acid. However, some patients still experience adverse reactions to allopurinol and turn ... ...

Abstract	The treatment of hyperuricemia and gout is mostly based on lowering serum uric acid levels using drugs, such as allopurinol, or increasing urinary excretion of uric acid. However, some patients still experience adverse reactions to allopurinol and turn to Chinese medicine as an alternative. Therefore, it is crucial to design a preclinical study to obtain more convincing data on the treatment of hyperuricemia and gout with Chinese medicine. This study aimed to explore the therapeutic effect of emodin, a Chinese herbal extract, in a rat model of hyperuricemia and gout. In this study, we used 36 Sprague–Dawley rats, which were randomly divided into six groups for experimentation. Hyperuricemia was induced in rats by intraperitoneal injections of potassium oxonate. The efficacy of emodin in reducing serum uric acid levels was demonstrated by comparing the positive control group with groups treated with three different concentrations of emodin. The inflammatory profiles, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels, were unaffected by emodin treatment. In the experimental results, it was observed that the serum uric acid concentration in the vehicle control group was 1.80 ± 1.14, while the concentrations in the moderate and high concentration emodin groups were 1.18 ± 0.23 and 1.12 ± 0.57, resulting in no significant difference in uric acid concentration between these treatment groups and the control group, indicating that emodin has a therapeutic effect on hyperuricemia. The increase in the fractional excretion of uric acid (FEUA) demonstrated that emodin promoted urinary uric acid excretion without significantly affecting the inflammatory profile. Thus, emodin reduced the serum uric acid concentration to achieve effective treatment of hyperuricemia and gout by increasing urinary excretion. These results were supported by the measured serum uric acid and FEUA levels. Our data have potential implications for the treatment of gout and other types of hyperuricemia in clinical practice.
Keywords	uric acid ; gout ; emodin ; potassium oxonate ; traditional Chinese medicine ; rats ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	630
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Uroprotective Efficacy of Total Ginsenosides in Chinese Ginseng on Chemotherapy with Cyclophosphamide

Yung-Hsiang Chen / Wen-Chi Chen / Szu-Ju Chen / Shih-Jing Wang / Po-Len Liu / Ming-Yen Tsai / Chun-Ting Liu / Der-Cherng Chen / Huey-Yi Chen

Applied Sciences, Vol 12, Iss 15, p

2022 Volume 7828

Abstract: Hemorrhagic cystitis is a recognizable complication of cyclophosphamide (CYP) attributable to its lively metabolite acrolein, which produces urothelial injury. The study intended to examine the uroprotective efficacy of total ginsenosides in Chinese ... ...

Abstract	Hemorrhagic cystitis is a recognizable complication of cyclophosphamide (CYP) attributable to its lively metabolite acrolein, which produces urothelial injury. The study intended to examine the uroprotective efficacy of total ginsenosides in Chinese ginseng (TGCG) in CYP-induced hemorrhagic cystitis. In total, 24 virgin female rats were randomized into four groups as follows: group 1 (control group; injected with normal saline), group 2 (injected with CYP plus a placebo with normal saline), group 3 (given CYP and TGCG (200 mg/kg)), and group 4 (given CYP and 2-mercaptoethane sulfonate sodium (Mesna, 30 mg/kg)). An evaluation by cystometry was conducted. Values of the voiding interval were assessed in anesthetized rats and histological examinations of the bladders were measured. In the cystometry analysis, the voiding interval was significantly reduced in the CYP group. TGCG and Mesna significantly increased in the voiding interval values, individually. Bladder edema and urothelial injury were examined after contact with CYP. Contrasted to the group given CYP, CYP-induced hemorrhagic cystitis, TGCG significantly increased the urothelial thickness, and significantly reduced scores of mucosal break and submucosal edema in the bladder. In conclusion, these findings mean that the treatment with TGCG in CYP rats can avoid hemorrhagic cystitis. TGCG decreases urothelial injury. TGCG may participate as the chief character of uroprotection in CYP-induced hemorrhagic cystitis.
Keywords	cyclophosphamide ; uroprotection ; urothelial damage ; total ginsenosides in Chinese ginseng ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Astragalus membranaceus Extract Prevents Calcium Oxalate Crystallization and Extends Lifespan in a Drosophila Urolithiasis Model

Szu-Ju Chen / Sunderiya Dalanbaatar / Huey-Yi Chen / Shih-Jing Wang / Wei-Yong Lin / Po-Len Liu / Ming-Yen Tsai / Der-Cherng Chen / Yung-Hsiang Chen / Wen-Chi Chen

Life, Vol 12, Iss 8, p

2022 Volume 1250

Abstract: Approximately 1 in 20 people develops kidney stones at some point in their life. Although the surgical removal of stones is common, the recurrence rate remains high and it is therefore important to prevent the occurrence of kidney stones. We chose ... ...

Abstract	Approximately 1 in 20 people develops kidney stones at some point in their life. Although the surgical removal of stones is common, the recurrence rate remains high and it is therefore important to prevent the occurrence of kidney stones. We chose Astragalus membranaceus (AM), which is a traditional Chinese medicine, to study the prevention of urolithiasis using a Drosophila model based on our previous screening of traditional Chinese herbs. Wild-type Drosophila melanogaster Canton-S adult fruit flies were used in this study. Ethylene glycol (EG, 0.5%) was added to food as a lithogenic agent. The positive control agent (2% potassium citrate (K-citrate)) was then compared with AM (2, 8, and 16 mg/mL). After 21 days, the fruit flies were sacrificed under carbon dioxide narcotization, and the Malpighian tubules were dissected, removed, and processed for polarized light microscopy examination to observe calcium oxalate (CaOx) crystallization. Then, the ex vivo dissolution of crystals in the Malpighian tubules was compared between K-citrate and AM. Survival analysis of the EG, K-citrate, and AM groups was also performed. Both 2% K-citrate and AM (16 mg/mL) significantly inhibited EG-induced CaOx crystal formation. Mean lifespan was significantly reduced by the administration of EG, and the results were significantly reversed in the AM (8 and 16 mg/mL) groups. However, AM extract did not directly dissolve CaOx crystals in Drosophila Malpighian tubules ex vivo. In conclusion, AM extract decreased the ratio of CaOx crystallization in the Malpighian tubules and significantly ameliorated EG-induced reduction of lifespan. AM prevented CaOx crystal formation in the Drosophila model.
Keywords	Astragalus membranaceus ; Drosophila animal model ; lifespan ; traditional Chinese medicine ; urolithiasis ; urinary stone disease ; Science ; Q
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Platelet-Rich Plasma Ameliorates Cyclophosphamide-Induced Acute Interstitial Cystitis/Painful Bladder Syndrome in a Rat Model

Yung-Hsiang Chen / Kee-Ming Man / Wen-Chi Chen / Po-Len Liu / Kao-Sung Tsai / Ming-Yen Tsai / Yu-Tzu Wu / Huey-Yi Chen

Diagnostics, Vol 10, Iss 381, p

2020 Volume 381

Abstract: Background: Interstitial cystitis/painful bladder syndrome (IC/PBS) could be treated to ameliorate urothelial injury. Here, we investigated the efficacy of intravesical instillation with platelet-rich plasma (PRP) and hyaluronic acid for acute IC/PBS. ... ...

Abstract	Background: Interstitial cystitis/painful bladder syndrome (IC/PBS) could be treated to ameliorate urothelial injury. Here, we investigated the efficacy of intravesical instillation with platelet-rich plasma (PRP) and hyaluronic acid for acute IC/PBS. Methods: The effects of PRP and hyaluronic acid on the proliferation of normal human fibroblast cells (HFCs) were assessed. Additionally, thirty virgin female rats were randomized into five groups: group 1, saline-injected control; group 2, cyclophosphamide (CYP) plus intravesical instillation with normal saline; group 3, CYP plus intravesical instillation with hyaluronic acid (1 mg/mL); group 4, CYP plus intravesical instillation with PRP; and group 5, CYP plus intravesical instillation with PRP plus hyaluronic acid. A cystometry and histological assessments were performed. The expression of cell junction-associated protein zonula occludens-2 (ZO-2) and inflammatory cytokine interleukin 6 (IL-6) was also measured. Results: Low dose PRP increased proliferation in HFCs. The acute IC/PBS rats showed significantly lower voiding interval values. Voiding interval values were significantly higher in the CYP plus intravesical instillation with PRP group than in the CYP-induced acute IC/PBS group. Additionally, the expression of ZO-2 was increased and IL-6 was decreased in the CYP plus intravesical instillation with PRP group compared with the CYP-induced acute IC/PBS group. Conclusion: These findings suggest that PRP modulate urothelial repair, which ameliorate the increase in urination frequency in rats treated with CYP. Overall, PRP may confer potential benefits by acting as urothelial repair modulators.
Keywords	platelet-rich plasma ; interstitial cystitis ; painful bladder syndrome ; cyclophosphamide ; Medicine (General) ; R5-920
Subject code	630
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: High Mobility Group Box 1 Promotes Lung Cancer Cell Migration and Motility via Regulation of Dynamin-Related Protein 1

Wei-Lun Liu / Chia-Yang Li / Wei-Chung Cheng / Chia-Yuan Chang / Yung-Hsiang Chen / Chi-Yu Lu / Shu-Chi Wang / Yu-Ru Liu / Meng-Hsuan Cheng / Inn-Wen Chong / Po-Len Liu

International Journal of Molecular Sciences, Vol 22, Iss 3628, p

2021 Volume 3628

Abstract: High mobility group box 1 (HMGB1) has been demonstrated to promote the migration and invasion of non-small cell lung cancer (NSCLC). However, the mechanism of action of HMGB1 in regulating tumor mobility remains unclear. Therefore, we aimed to ... ...

Abstract	High mobility group box 1 (HMGB1) has been demonstrated to promote the migration and invasion of non-small cell lung cancer (NSCLC). However, the mechanism of action of HMGB1 in regulating tumor mobility remains unclear. Therefore, we aimed to investigate whether HMGB1 affects mitochondria distribution and regulates dynamin-related protein 1 (DRP1)-mediated lamellipodia/filopodia formation to promote NSCLC migration. The regulation of mitochondrial membrane tension, dynamics, polarization, fission process, and cytoskeletal rearrangements in lung cancer cells by HMGB1 was analyzed using confocal microscopy. The HMGB1-mediated regulation of DRP1 phosphorylation and colocalization was determined using immunostaining and co-immunoprecipitation assays. The tumorigenic potential of HMGB1 was assessed in vivo and further confirmed using NSCLC patient samples. Our results showed that HMGB1 increased the polarity and mobility of cells (mainly by regulating the cytoskeletal system actin and microtubule dynamics and distribution), promoted the formation of lamellipodia/filopodia, and enhanced the expression and phosphorylation of DRP1 in both the nucleus and cytoplasm. In addition, HMGB1 and DRP1 expressions were positively correlated and exhibited poor prognosis and survival in patients with lung cancer. Collectively, HMGB1 plays a key role in the formation of lamellipodia and filopodia by regulating cytoskeleton dynamics and DRP1 expression to promote lung cancer migration.
Keywords	non-small cell lung cancer ; high mobility group box 1 ; dynamin related protein 1 ; cytoskeleton dynamics ; lamellipodia/filopodia ; mitochondrial fission ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Simvastatin Attenuates Cardiac Fibrosis via Regulation of Cardiomyocyte-Derived Exosome Secretion

Hsuan-Fu Kuo / Chong-Chao Hsieh / Shu-Chi Wang / Chia-Yuan Chang / Chih-Hsin Hung / Po-Lin Kuo / Yu-Ru Liu / Chia-Yang Li / Po-Len Liu

Journal of Clinical Medicine, Vol 8, Iss 6, p

2019 Volume 794

Abstract: Exosome-mediated communication within the cardiac microenvironment is associated with cardiac fibrosis. Simvastatin (SIM), a potent statin, protects against cardiac fibrosis, but its mechanism of action is unclear. We investigated the inhibitory effects ... ...

Abstract	Exosome-mediated communication within the cardiac microenvironment is associated with cardiac fibrosis. Simvastatin (SIM), a potent statin, protects against cardiac fibrosis, but its mechanism of action is unclear. We investigated the inhibitory effects and underlying mechanism of simvastatin in cardiac fibrosis, by regulating exosome-mediated communication. Male Sprague-Dawley rats were treated with angiotensin (Ang) II alone, or with SIM for 28 d. Cardiac fibrosis, expressions of fibrosis-associated proteins and mRNAs, and collagen fiber arrangement and deposition were examined. Protein expressions in exosomes isolated from Ang II-treated cardiomyocytes (CMs) were evaluated using nano-ultra-performance liquid chromatographic system, combined with tandem mass spectrometry. Transformation of fibroblasts to myofibroblasts was evaluated using scanning electron and confocal microscopy, and migration assays. Our results showed that SIM attenuated in vivo expression of collagen and collagen-associated protein, as well as collagen deposition, and cardiac fibrosis. The statin also upregulated decorin and downregulated periostin in CM-derived exosomes. Furthermore, it suppressed Ang II-induced transformation of fibroblast to myofibroblast, as well as fibroblast migration. Exosome-mediated cell-cell communication within the cardiac tissue critically regulated cardiac fibrosis. Specifically, SIM regulated the release of CM exosomes, and attenuated Ang II-induced cardiac fibrosis, highlighting its potential as a novel therapy for cardiac fibrosis.
Keywords	statins ; exosomes ; decorin ; periostin ; cardiac fibrosis ; Medicine ; R
Subject code	610
Language	English
Publishing date	2019-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Postnatal Changes in Tibial Bone Speed of Sound of Preterm and Term Infants during Infancy.

Hsiu-Lin Chen / Wei-Te Lee / Pei-Lun Lee / Po-Len Liu / Rei-Cheng Yang

PLoS ONE, Vol 11, Iss 11, p e

2016 Volume 0166434

Abstract: This study aimed to evaluate changes in tibial bone speed of sound (SOS) over time, in preterm and term infants during infancy, in addition to identifying factors influencing the development of tibial SOS during infancy. Preterm (n = 155) and term (n = ... ...

Abstract	This study aimed to evaluate changes in tibial bone speed of sound (SOS) over time, in preterm and term infants during infancy, in addition to identifying factors influencing the development of tibial SOS during infancy. Preterm (n = 155) and term (n = 65) infants were enrolled in this study. Tibial bone SOS was measured using quantitative ultrasonography (QUS) on the left tibia of newborn infants after birth (within 7 days), at 1 month old, and then every 2 months until subjects were approximately 12-15 months old. Follow-up checks included anthropometric measurements and tibial bone SOS. Mean tibial bone SOS at birth was significantly higher in term infants (mean ± SD, 2968.5 ± 99.7 m/s) than in preterm infants (2912.2 ± 122.6 m/s). Values of follow-up tibial bone SOS declined for the first 4 months, and then increased gradually until 12-15 months old. This increasing trend was greater in preterm infants after 2 months of corrected age than in term infants. There were no significant differences by 12-15 months of age between preterm and term infants. A longitudinal mixed-effect model controlling for internal correlations and other covariates in the two groups showed that age and the SOS value at birth were important factors affecting the tibial bone SOS in both preterm and term newborn infants during infancy. There are significant differences in the pattern of change in tibial bone SOS values between preterm and term infants during the first 12-15 months of life. Age and SOS value at birth were important factors affecting the pattern of tibial bone SOS change in both preterm and term newborn infants during infancy.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Postnatal Changes in Tibial Bone Speed of Sound of Preterm and Term Infants during Infancy.

Hsiu-Lin Chen / Wei-Te Lee / Pei-Lun Lee / Po-Len Liu / Rei-Cheng Yang

PLoS ONE, Vol 11, Iss 11, p e

2016 Volume 0166434

Abstract	This study aimed to evaluate changes in tibial bone speed of sound (SOS) over time, in preterm and term infants during infancy, in addition to identifying factors influencing the development of tibial SOS during infancy. Preterm (n = 155) and term (n = 65) infants were enrolled in this study. Tibial bone SOS was measured using quantitative ultrasonography (QUS) on the left tibia of newborn infants after birth (within 7 days), at 1 month old, and then every 2 months until subjects were approximately 12-15 months old. Follow-up checks included anthropometric measurements and tibial bone SOS. Mean tibial bone SOS at birth was significantly higher in term infants (mean ± SD, 2968.5 ± 99.7 m/s) than in preterm infants (2912.2 ± 122.6 m/s). Values of follow-up tibial bone SOS declined for the first 4 months, and then increased gradually until 12-15 months old. This increasing trend was greater in preterm infants after 2 months of corrected age than in term infants. There were no significant differences by 12-15 months of age between preterm and term infants. A longitudinal mixed-effect model controlling for internal correlations and other covariates in the two groups showed that age and the SOS value at birth were important factors affecting the tibial bone SOS in both preterm and term newborn infants during infancy. There are significant differences in the pattern of change in tibial bone SOS values between preterm and term infants during the first 12-15 months of life. Age and SOS value at birth were important factors affecting the pattern of tibial bone SOS change in both preterm and term newborn infants during infancy.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: miR-29a-3p/THBS2 Axis Regulates PAH-Induced Cardiac Fibrosis

Chih-Hsin Hsu / I-Fan Liu / Hsuan-Fu Kuo / Chia-Yang Li / Wei-Shiung Lian / Chia-Yuan Chang / Yung-Hsiang Chen / Wei-Lun Liu / Chi-Yu Lu / Yu-Ru Liu / Tzu-Chieh Lin / Tsung-Ying Lee / Chi-Yuan Huang / Chong-Chao Hsieh / Po-Len Liu

International Journal of Molecular Sciences, Vol 22, Iss 10574, p

2021 Volume 10574

Abstract: Pulmonary artery hypertension (PAH) pathology involves extracellular matrix (ECM) remodeling in cardiac tissues, thus promoting cardiac fibrosis progression. miR-29a-3p reportedly inhibits lung progression and liver fibrosis by regulating ECM protein ... ...

Abstract	Pulmonary artery hypertension (PAH) pathology involves extracellular matrix (ECM) remodeling in cardiac tissues, thus promoting cardiac fibrosis progression. miR-29a-3p reportedly inhibits lung progression and liver fibrosis by regulating ECM protein expression; however, its role in PAH-induced fibrosis remains unclear. In this study, we aimed to investigate the role of miR-29a-3p in cardiac fibrosis progression in PAH and its influence on ECM protein thrombospondin-2 (THBS2) expression. The diagnostic and prognostic values of miR-29a-3p and THBS2 in PAH were evaluated. The expressions and effects of miR-29a-3p and THBS2 were assessed in cell culture, monocrotaline-induced PAH mouse model, and patients with PAH. The levels of circulating miR-29a-3p and THBS2 in patients and mice with PAH decreased and increased, respectively. miR-29a-3p directly targets THBS2 and regulates THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis. The circulating levels of miR-29a-3p and THBS2 were correlated with PAH diagnostic parameters, suggesting their independent prognostic value. miR-29a-3p targeted THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis, indicating miR-29a-3p acts as a messenger with promising therapeutic effects.
Keywords	miR-29a-3p ; THBS2 ; cardiomyocytes ; fibrosis ; pulmonary arterial hypertension ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500 ; 610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mycotoxin Zearalenone Attenuates Innate Immune Responses and Suppresses NLRP3 Inflammasome Activation in LPS-Activated Macrophages

Po-Yen Lee / Ching-Chih Liu / Shu-Chi Wang / Kai-Yin Chen / Tzu-Chieh Lin / Po-Len Liu / Chien-Chih Chiu / I-Chen Chen / Yu-Hung Lai / Wei-Chung Cheng / Wei-Ju Chung / Hsin-Chih Yeh / Chi-Han Huang / Chia-Cheng Su / Shu-Pin Huang / Chia-Yang Li

Toxins, Vol 13, Iss 593, p

2021 Volume 593

Abstract: Zearalenone (ZEA) is a mycotoxin that has several adverse effects on most mammalian species. However, the effects of ZEA on macrophage-mediated innate immunity during infection have not been examined. In the present study, bacterial lipopolysaccharides ( ... ...

Abstract	Zearalenone (ZEA) is a mycotoxin that has several adverse effects on most mammalian species. However, the effects of ZEA on macrophage-mediated innate immunity during infection have not been examined. In the present study, bacterial lipopolysaccharides (LPS) were used to induce the activation of macrophages and evaluate the effects of ZEA on the inflammatory responses and inflammation-associated signaling pathways. The experimental results indicated that ZEA suppressed LPS-activated inflammatory responses by macrophages including attenuating the production of proinflammatory mediators (nitric oxide (NO) and prostaglandin E 2 (PGE 2 )), decreased the secretion of proinflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6), inhibited the activation of c-Jun amino-terminal kinase (JNK), p38 and nuclear factor-κB (NF-κB) signaling pathways, and repressed the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. These results indicated that mycotoxin ZEA attenuates macrophage-mediated innate immunity upon LPS stimulation, suggesting that the intake of mycotoxin ZEA-contaminated food might result in decreasing innate immunity, which has a higher risk of adverse effects during infection.
Keywords	zearalenone ; mycotoxin ; innate immunity ; NLRP3 inflammasome ; macrophages ; Medicine ; R
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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