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Shi W, Qin C, Yang Y, Yang X, Fang Y, Zhang B, Wang D, Feng W, Shi D. Urolithin A Protects Porcine Oocytes from Artificially Induced Oxidative Stress Damage to Enhance Oocyte Maturation and Subsequent Embryo Development. Int J Mol Sci 2025; 26:3037. [PMID: 40243704 PMCID: PMC11989139 DOI: 10.3390/ijms26073037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/22/2025] [Accepted: 03/24/2025] [Indexed: 04/18/2025] Open
Abstract
Both the livestock and biomedical fields require a large supply of high-quality mature oocytes. However, the in vitro maturation (IVM) process often leads to an accumulation of reactive oxygen species (ROS), which can cause defects in oocyte meiosis and embryo development, ultimately compromising oocyte quality. Urolithin A (UA), known for its antioxidant properties, has not been thoroughly investigated for its potential to mitigate the negative effects of oxidative stress during the in vitro culturing of oocytes, and its underlying mechanism is not well understood. In this study, an in vitro oxidative stress model was established using porcine oocytes treated with H2O2, followed by exposure to varying concentrations of UA. The results revealed that 30 μM UA significantly improved both the quality of oocyte culture and the developmental potential of the resulting embryos. UA was found to enhance oocyte autophagy, reduce oxidative stress-induced mitochondrial damage, and restore mitochondrial function. Additionally, it lowered ROS and DNA damage levels in the oocytes, maintained proper spindle/chromosome alignment and actin cytoskeleton structure, promoted nuclear maturation, prevented abnormal cortical granule distribution, and supported oocyte cytoplasmic maturation. As a result, UA alleviated oxidative stress-induced defects in oocyte maturation and cumulus cell expansion, thereby improving the developmental potential and quality of parthenogenetic embryos. After supplementation with UA, pig parthenogenetic embryo pluripotency-related genes (Nanog and Sox2) and antiapoptotic genes (Bcl2) were upregulated, while proapoptotic genes (Bax) were downregulated. In conclusion, this study suggests that adding UA during IVM can effectively mitigate the adverse effects of oxidative stress on porcine oocytes, presenting a promising strategy for enhancing their developmental potential in vitro.
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Affiliation(s)
- Wen Shi
- Guangxi Key Laboratory of Animal Breeding & Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (W.S.); (C.Q.); (Y.Y.); (X.Y.); (Y.F.); (B.Z.); (D.W.)
| | - Chaobin Qin
- Guangxi Key Laboratory of Animal Breeding & Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (W.S.); (C.Q.); (Y.Y.); (X.Y.); (Y.F.); (B.Z.); (D.W.)
| | - Yanyan Yang
- Guangxi Key Laboratory of Animal Breeding & Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (W.S.); (C.Q.); (Y.Y.); (X.Y.); (Y.F.); (B.Z.); (D.W.)
| | - Xiaofen Yang
- Guangxi Key Laboratory of Animal Breeding & Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (W.S.); (C.Q.); (Y.Y.); (X.Y.); (Y.F.); (B.Z.); (D.W.)
| | - Yizhen Fang
- Guangxi Key Laboratory of Animal Breeding & Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (W.S.); (C.Q.); (Y.Y.); (X.Y.); (Y.F.); (B.Z.); (D.W.)
| | - Bing Zhang
- Guangxi Key Laboratory of Animal Breeding & Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (W.S.); (C.Q.); (Y.Y.); (X.Y.); (Y.F.); (B.Z.); (D.W.)
| | - Dong Wang
- Guangxi Key Laboratory of Animal Breeding & Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (W.S.); (C.Q.); (Y.Y.); (X.Y.); (Y.F.); (B.Z.); (D.W.)
| | - Wanyou Feng
- School of Environmental and Life Sciences, Nanning Normal University, Nanning 530001, China
| | - Deshun Shi
- Guangxi Key Laboratory of Animal Breeding & Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (W.S.); (C.Q.); (Y.Y.); (X.Y.); (Y.F.); (B.Z.); (D.W.)
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Wang Y, Zhang FQ, Fan ZP, Zhu XL, Yan WH, Zhang XL. WDR36 inhibits the osteogenic differentiation and migration of periodontal ligament stem cells. World J Stem Cells 2025; 17:99132. [PMID: 40061266 PMCID: PMC11885943 DOI: 10.4252/wjsc.v17.i2.99132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 11/23/2024] [Accepted: 01/16/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Periodontitis is an inflammatory disease caused by the host's immune response and various interactions between pathogens, which lead to the loss of connective tissue and bone. In recent years, mesenchymal stem cell (SC) transplantation technology has become a research hotspot, which can form periodontal ligament, cementum, and alveolar bone through proliferation and differentiation. AIM To elucidate the regulatory effects of WD repeat-containing protein 36 (WDR36) on the senescence, migration, and osteogenic differentiation of periodontal ligament SCs (PDLSCs). METHODS The migration and chemotaxis of PDLSCs were detected by the scratch-wound migration test and transwell chemotaxis test. Alkaline phosphatase (ALP) activity, Alizarin red staining, calcium content, and real-time reverse transcription polymerase chain reaction (RT-qPCR) of key transcription factors were used to detect the osteogenic differentiation function of PDLSCs. Cell senescence was determined by senescence-associated β-galactosidase staining. RESULTS The 24-hour and 48-hour scratch-wound migration test and 48-hour transwell chemotaxis test showed that overexpression of WDR36 inhibited the migration/chemotaxis of PDLSCs. Simultaneously, WDR36 depletion promoted the migration/chemotaxis of PDLSCs. The results of ALP activity, Alizarin red staining, calcium content, and RT-qPCR showed that overexpression of WDR36 inhibited the osteogenic differentiation of PDLSCs, and WDR36 depletion promoted the osteogenic differentiation of PDLSCs. Senescence-associated β-galactosidase staining showed that 0.1 μg/mL icariin (ICA) and overexpression of WDR36 inhibited the senescence of PDLSCs, and WDR36 depletion promoted the osteogenic differentiation of PDLSCs. CONCLUSION WDR36 inhibits the migration and chemotaxis, osteogenic differentiation, and senescence of PDLSCs; 0.1 μg/mL ICA inhibits the senescence of PDLSCs. Therefore, WDR36 might serve as a target for periodontal tissue regeneration and the treatment of periodontitis.
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Affiliation(s)
- Yi Wang
- Department of Wangfujing General School of Stomatology, Capital Medical University, Beijing 100070, China
| | - Feng-Qiu Zhang
- Department of Periodontics School of Stomatology, Capital Medical University, Beijing 100070, China.
| | - Zhi-Peng Fan
- Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Beijing 100070, China
- Beijing Laboratory of Oral Health, Capital Medical University, Beijing 100070, China
- Research Unit of Tooth Development and Regeneration, Chinese Academy of Medical Sciences, Beijing 100070, China
| | - Xin-Ling Zhu
- Department of Periodontology, Hangzhou Stomatology Hospital, Hangzhou 310006, Zhejiang Province, China
| | - Wan-Hao Yan
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100070, China
| | - Xiu-Li Zhang
- Department of Stomatology, Civil Aviation General Hospital, Beijing 100123, China
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Eid BG, Binmahfouz LS, Shaik RA, Bagher AM, Sirwi A, Abdel-Naim AB. Icariin inhibits cisplatin-induced ovarian toxicity via modulating NF-κB and PTEN/AKT/mTOR/AMPK axis. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:1949-1959. [PMID: 39212737 DOI: 10.1007/s00210-024-03395-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 08/16/2024] [Indexed: 09/04/2024]
Abstract
Cisplatin (CP) is a highly effective broad-spectrum chemotherapeutic agent for several solid tumors. However, its clinical use is associated with ovarian toxicity. Icariin (ICA) is a bioactive flavonoid of Epimedium brevicornum with reported protective activities against inflammation, oxidative stress and ovarian failure. This study aimed to explore the protective effects of ICA against CP-associated ovarian toxicity in rats. Rats were randomized into five groups and treated for 17 days: control, ICA (10 mg/kg/day, for 17 days. p.o.), CP (6 mg/kg, i.p. on days 7 and 14), CP + ICA (CP 6 mg/kg i.p. on days 7 and 14 and ICA 5 mg/kg p.o. daily), and CP + ICA (CP 6 mg/kg i.p. on days 7 and 14 and ICA 10 mg/kg p.o. daily). Our results indicated that ICA effectively improved ovarian reserve as indicated by attenuating CP-induced histolopathological changes and enhancing serum anti-müllerian hormone (AMH). Furthermore, co-administration of ICA with CP showed restoration of the oxidant-anti-oxidant balance in ovarian tissues, evidenced by decreased malondialdehyde (MDA) concentrations and elevated superoxide dismutase (SOD) and catalase (CAT) activities. Also, ICA suppressed ovarian inflammation as evidenced by down-regulation of the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NF-κB). ICA inhibited ovarian apoptosis in CP-treated rats by down-regulation of CASP3 and Bax and up-regulation of Bcl-2 mRNA expression. Further, ICA enhanced PTEN, p-AKT, p-mTOR, and p-AMPKα expression. In conclusion, ICA possesses a protective activity against CP-induced ovarian toxicity in rats by exhibiting antioxidant, antiinflammatory, anti-apoptotic activities and modulating NF-κB expression and PTEN/AKT/mTOR/AMPK axis in ovarian tissues.
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Affiliation(s)
- Basma G Eid
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Lenah S Binmahfouz
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Rasheed A Shaik
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Amina M Bagher
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Alaa Sirwi
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Ashraf B Abdel-Naim
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, 21589, Jeddah, Saudi Arabia.
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Chuang YT, Yen CY, Chien TM, Chang FR, Wu KC, Tsai YH, Shiau JP, Chang HW. Natural products modulate phthalate-associated miRNAs and targets. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 284:117015. [PMID: 39265265 DOI: 10.1016/j.ecoenv.2024.117015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 09/03/2024] [Accepted: 09/05/2024] [Indexed: 09/14/2024]
Abstract
Phthalates are widespread and commonly used plasticizers that lead to adverse health effects. Several natural products provide a protective effect against phthalates. Moreover, microRNAs (miRNAs) are regulated by natural products and phthalates. Therefore, miRNAs' impacts and potential targets may underlie the mechanism of phthalates. However, the relationship between phthalate-modulated miRNAs and phthalate protectors derived from natural products is poorly understood and requires further supporting information. In this paper, we review the adverse effects and potential targets of phthalates on reproductive systems as well as cancer and non-cancer responses. Information on natural products that attenuate the adverse effects of phthalates is retrieved through a search of Google Scholar and the miRDB database. Moreover, information on miRNAs that are upregulated or downregulated in response to phthalates is collected, along with their potential targets. The interplay between phthalate-modulated miRNAs and natural products is established. Overall, this review proposes a straightforward pathway showing how phthalates modulate different miRNAs and targets and cause adverse effects, which are partly attenuated by several natural products, thereby providing a direction for investigating the natural product-miRNA-target axis against phthalate-induced effects.
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Affiliation(s)
- Ya-Ting Chuang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
| | - Ching-Yu Yen
- School of Dentistry, Taipei Medical University, Taipei 11031, Taiwan; Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan 71004, Taiwan.
| | - Tsu-Ming Chien
- School of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Urology, Kaohsiung Gangshan Hospital, Kaohsiung Medical University, Kaohsiung 820111, Taiwan.
| | - Fang-Rong Chang
- Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
| | - Kuo-Chuan Wu
- Department of Computer Science and Information Engineering, National Pingtung University, Pingtung 900392, Taiwan.
| | - Yi-Hong Tsai
- Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung 907101, Taiwan.
| | - Jun-Ping Shiau
- Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
| | - Hsueh-Wei Chang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
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Zhang D, Ji L, Yang Y, Weng J, Ma Y, Liu L, Ma W. Ceria Nanoparticle Systems Alleviate Degenerative Changes in Mouse Postovulatory Aging Oocytes by Reducing Oxidative Stress and Improving Mitochondrial Functions. ACS NANO 2024; 18:13618-13634. [PMID: 38739841 DOI: 10.1021/acsnano.4c00383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
Postovulatory aging oocytes usually feature diminished potential for fertilization and poor embryonic development due to enhanced oxidative damage to the subcellular organelles and macromolecules, which stands as a formidable obstacle in assisted reproductive technologies (ART). Here, we developed lipoic acid (LA) and polyethylene glycol (PEG)-modified CeO2 nanoparticles (LA-PEG-CeNPs) with biocompatibility, enzyme-like autocatalytic activity, and free radical scavenging capacity. We further investigated the LA-PEG-CeNPs effect in mouse postovulatory oocytes during in vitro aging. The results showed that LA-PEG-CeNPs dramatically reduced the accumulation of ROS in aging oocytes, improving mitochondrial dysfunction; they also down-regulated the pro-apoptotic activity by rectifying cellular caspase-3, cleaved caspase-3, and Bcl-2 levels. Consistently, this nanoenzyme prominently alleviated the proportion of abnormalities in spindle structure, chromosome alignment, microtubule stability, and filamentous actin (F-actin) distribution in aging oocytes, furthermore decreased oocyte fragmentation, and improved its ability of fertilization and development to blastocyst. Taken together, our finding suggests that LA-PEG-CeNPs can alleviate oxidative stress damage on oocyte quality during postovulatory aging, implying their potential value for clinical practice in assisted reproduction.
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Affiliation(s)
- Danmei Zhang
- Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China
| | - Lingcun Ji
- Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China
| | - Yiran Yang
- Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China
| | - Jing Weng
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
| | - Yanmin Ma
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| | - Lingyan Liu
- Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China
| | - Wei Ma
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
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Lim ES, Lee SE, Park MJ, Han DH, Lee HB, Ryu B, Kim EY, Park SP. Piperine improves the quality of porcine oocytes by reducing oxidative stress. Free Radic Biol Med 2024; 213:1-10. [PMID: 38159890 DOI: 10.1016/j.freeradbiomed.2023.12.042] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 12/08/2023] [Accepted: 12/27/2023] [Indexed: 01/03/2024]
Abstract
Oxidative stress caused by light and high temperature arises during in vitro maturation (IVM), resulting in low-quality embryos compared with those obtained in vivo. To overcome this problem, we investigated the influence of piperine (PIP) treatment during maturation of porcine oocytes on subsequent embryo development in vitro. Porcine oocytes were cultured in IVM medium supplemented with 0, 50, 100, 200, or 400 μM PIP. After parthenogenetic activation, the blastocyst (BL) formation was significantly higher and the apoptosis rate was significantly lower using 200 μM PIP-treated oocytes (200 PIP). In the 200 PIP group, the level of reactive oxygen species at the metaphase II stage was decreased, accompanied by an increased level of glutathione and increased expression of antioxidant processes (Nrf2, CAT, HO-1, SOD1, and SOD2). Consistently, chromosome misalignment and aberrant spindle organization were alleviated and phosphorylated p44/42 mitogen-activated protein kinase activity was increased in the 200 PIP group. Expression of development-related (CDX2, NANOG, POU5F1, and SOX2), anti-apoptotic (BCL2L1 and BIRC5), and pro-apoptotic (BAK, FAS, and CASP3) processes was altered in the 200 PIP group. Ultimately, embryo development was improved in the 200 PIP group following somatic cell nuclear transfer. These findings suggest that PIP improves the quality of porcine oocytes by reducing oxidative stress, which inevitably arises via IVM. In-depth mechanistic studies of porcine oocytes will improve the efficiencies of assisted reproductive technologies.
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Affiliation(s)
- Eun-Seo Lim
- Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea
| | - Seung-Eun Lee
- Department of Bio Medical Informatics, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Cronex Co., 110 Hwangtalli-gil, Gangnae-myeon, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 28174, South Korea
| | - Min-Jee Park
- Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea
| | - Dong-Hun Han
- Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea
| | - Han-Bi Lee
- Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea
| | - Bokyeong Ryu
- Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Department of Bio Medical Informatics, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea
| | - Eun-Young Kim
- Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Mirae Cell Bio, 1502 isbiz-tower 147, Seongsui-ro, Seongdong-gu, Seoul, 04795, South Korea
| | - Se-Pill Park
- Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Department of Bio Medical Informatics, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Mirae Cell Bio, 1502 isbiz-tower 147, Seongsui-ro, Seongdong-gu, Seoul, 04795, South Korea.
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Zhang D, Liu S, Jiang H, Liu S, Kong F. DIA proteomics analysis reveals the mechanism of folic acid-induced acute kidney injury and the effects of icariin. Chem Biol Interact 2024; 390:110878. [PMID: 38272249 DOI: 10.1016/j.cbi.2024.110878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/04/2024] [Accepted: 01/17/2024] [Indexed: 01/27/2024]
Abstract
The complexities of acute kidney injury (AKI), a multifaceted pathological occurrence, are not fully understood. At present, there is a lack of effective pharmaceutical treatments in clinical practice. Studies have shown that icariin has beneficial effects in models of acute kidney injury (AKI) caused by cisplatin and lipopolysaccharide (LPS). The aim is to explore the mechanisms that cause folic acid (FA)-induced AKI and examine the protective effects of icariin against this condition. To establish a mouse model of AKI, FA was administered via intraperitoneal injection. Icariin was used as the drug intervention. The model and the impact of drug intervention were assessed using measurements of renal function parameters, staining with hematoxylin and eosin, and Q-PCR. The analysis of protein expression changes in the control, model, and icariin treatment groups was conducted using proteomics. KEGG signaling pathway analysis indicates that differential expressed proteins are enriched in the component and coagulation cascades signaling pathway. Through protein-protein interaction network analysis, it was found that compared to the normal group, the expression of Fibrinogen and other proteins was significantly upregulated at the center of the protein interaction network in the model group. After drug treatment, the expression of these proteins was significantly downregulated. The validation experiment supports the above results. In conclusion, this study clarified the molecular mechanism of FA induced acute renal injury from the proteomics level, and provided target selection for AKI; At the same time, the mechanism of icariin in the treatment of AKI was analyzed from the proteomics level.
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Affiliation(s)
- Denglu Zhang
- Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China; Shandong Key Laboratory of Dominant Diseases of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
| | - Shuai Liu
- Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China; Shandong Key Laboratory of Dominant Diseases of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Huihui Jiang
- Clinical Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shuangde Liu
- Department of Kidney Transplantation, Multidisciplinary Innovation Center for Nephrology, The Second Hospital of Shandong University, Jinan, China.
| | - Feng Kong
- Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China; Engineering Laboratory of Urinary Organ and Functional Reconstruction of Shandong Province, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
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Li Y, Wei Z, Su L. Anti-aging effects of icariin and the underlying mechanisms: A mini-review. Aging Med (Milton) 2024; 7:90-95. [PMID: 38571677 PMCID: PMC10985774 DOI: 10.1002/agm2.12284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/02/2024] [Accepted: 01/04/2024] [Indexed: 04/05/2024] Open
Abstract
Aging is an extremely intricate and progressive phenomenon that is implicated in many physiological and pathological conditions. Icariin (ICA) is the main active ingredient of Epimedium and has exhibited multiple bioactivities, such as anti-tumor, neuroprotective, antioxidant, anti-inflammatory, and anti-aging properties. ICA could extend healthspan in both invertebrate and vertebrate models. In this review, the roles of ICA in protection from declined reproductive function, neurodegeneration, osteoporosis, aging intestinal microecology, and senescence of cardiovascular system will be summarized. Furthermore, the underlying mechanisms of ICA-mediated anti-aging effects will be introduced. Finally, we will discuss some key aspects that constrain the usage of ICA in clinical practice and the corresponding strategies to solve these issues.
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Affiliation(s)
- Ying Li
- Department of HematologyChangchun Central HospitalChangchunChina
| | - Zhi‐Feng Wei
- Department of HematologyThe First Hospital of Jilin UniversityChangchunChina
- Jilin Provincial Key Laboratory of Hematology Precision MedicineThe First Hospital of Jilin UniversityChangchunChina
| | - Long Su
- Department of HematologyThe First Hospital of Jilin UniversityChangchunChina
- Jilin Provincial Key Laboratory of Hematology Precision MedicineThe First Hospital of Jilin UniversityChangchunChina
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Ning K, Gao R. Icariin protects cerebral neural cells from ischemia‑reperfusion injury in an in vitro model by lowering ROS production and intracellular calcium concentration. Exp Ther Med 2023; 25:151. [PMID: 36911386 PMCID: PMC9995791 DOI: 10.3892/etm.2023.11849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 01/26/2023] [Indexed: 02/18/2023] Open
Abstract
Ischemia is one of the major causes of stroke. The present study investigated the protection of cultured neural cells by icariin (ICA) against ischemia-reperfusion (I/R) injury and possible mechanisms underlying the protection. Neural cells were isolated from neonatal rats and cultured in vitro. The cells were subjected to oxygen-glucose deprivation and reoxygenation (OGD-R) as an I/R mimic to generate I/R injury, and were post-OGD-R treated with ICA. Following the treatments, cell viability, apoptosis, reactive oxygen species (ROS), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and Ca2+ concentration were assessed using Cell Counting Kit-8 assay, flow cytometry, CyQUANT™ LDH Cytotoxicity Assay, H2DCFDA and SOD colorimetric activity kit. After OGD-R, considerable I/R injury was observed in the neural cells, as indicated by reduced cell viability, increased apoptosis and increased production of ROS and LDH (P<0.05). Cellular Ca2+ concentration was also increased, while SOD activity remained unchanged. Post-OGD-R ICA treatments increased cell viability up to 87.1% (P<0.05) and reduced apoptosis as low as 6.6% (P<0.05) in a concentration-dependent manner. The treatments also resulted in fewer ROS (P<0.05), lower extracellular LDH content (440.5 vs. 230.3 U/l; P<0.05) and reduced Ca2+ increase (P<0.05). These data suggest that ICA protects the neural cells from I/R injury in an in vitro model through antioxidation activity and maintaining cellular Ca2+ homeostasis. This function may be explored as a potential therapeutic strategy for ischemia-related diseases after further in vivo studies.
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Affiliation(s)
- Ke Ning
- Department of International Medicine, Affiliated Zhongshan Hospital, Dalian University, Dalian, Liaoning 116001, P.R. China
| | - Rong Gao
- Surgical Intensive Care Unit, Affiliated Zhongshan Hospital, Dalian University, Dalian, Liaoning 116001, P.R. China
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10
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Oh SH, Lee SE, Han DH, Yoon JW, Kim SH, Lim ES, Lee HB, Kim EY, Park SP. Treatments of Porcine Nuclear Recipient Oocytes and Somatic Cell Nuclear Transfer-Generated Embryos with Various Reactive Oxygen Species Scavengers Lead to Improvements of Their Quality Parameters and Developmental Competences by Mitigating Oxidative Stress-Related Impacts. Cell Reprogram 2023; 25:73-81. [PMID: 36939858 DOI: 10.1089/cell.2022.0145] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2023] Open
Abstract
This study investigated the antioxidant effects of β-cryptoxanthin (BCX), hesperetin (HES), and icariin (ICA), and their effects on in vitro maturation of porcine oocytes and subsequent embryonic development of somatic cell nuclear transfer (SCNT). Treatment with 1 μM BCX (BCX-1) increased the developmental rate of porcine oocytes more than treatment with 100 μM HES (HES-100) or 5 μM ICA (ICA-5). The glutathione level and mRNA expression of antioxidant genes (NFE2L2, SOD1, and SOD2) were more increased in the BCX-1 group than in the HES-100 and ICA-5 groups, while the reactive oxygen species level was more decreased. Moreover, BCX improved the developmental capacity and quality of SCNT embryos. The total cell number, apoptotic cell rate, and development-related gene expression were modulated in the BCX-1 group to enhance embryonic development of SCNT. These results show that the antioxidant effects of BCX enhance in vitro maturation of porcine oocytes and subsequent embryonic development of SCNT.
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Affiliation(s)
- Seung-Hwan Oh
- Stem Cell Research Center, Jeju National University, Jeju, Korea
| | - Seung-Eun Lee
- Stem Cell Research Center, Jeju National University, Jeju, Korea.,Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju, Korea
| | - Dong-Hun Han
- Stem Cell Research Center, Jeju National University, Jeju, Korea.,Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju, Korea
| | - Jae-Wook Yoon
- Stem Cell Research Center, Jeju National University, Jeju, Korea
| | - So-Hee Kim
- Stem Cell Research Center, Jeju National University, Jeju, Korea.,Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju, Korea
| | - Eun-Seo Lim
- Stem Cell Research Center, Jeju National University, Jeju, Korea.,Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju, Korea
| | - Han-Bi Lee
- Stem Cell Research Center, Jeju National University, Jeju, Korea.,Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju, Korea
| | - Eun-Young Kim
- Stem Cell Research Center, Jeju National University, Jeju, Korea.,Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju, Korea.,Mirae Cell Bio, Seoul, Korea
| | - Se-Pill Park
- Stem Cell Research Center, Jeju National University, Jeju, Korea.,Mirae Cell Bio, Seoul, Korea.,Department of Bio Medical Informatics, College of Applied Life Sciences, Jeju National University, Jeju, Korea
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11
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Liu JZ, Zhang LM, Zhang DX, Song RX, Lv JM, Wang LY, Jia SY, Shan YD, Shao JJ, Zhang W. NLRP3 in the GABAergic neuron induces cognitive impairments in a mouse model of hemorrhage shock and resuscitation. J Psychiatr Res 2023; 159:213-223. [PMID: 36739849 DOI: 10.1016/j.jpsychires.2023.01.034] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 12/28/2022] [Accepted: 01/26/2023] [Indexed: 01/30/2023]
Affiliation(s)
- Ji-Zhen Liu
- Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Li-Min Zhang
- Department of Anesthesiology, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine Cangzhou No.2 Hospital, Cangzhou, China
| | - Dong-Xue Zhang
- Department of Gerontology, Cangzhou Central Hospital, Cangzhou, China
| | - Rong-Xin Song
- Department of Anesthesiology, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China
| | - Jin-Meng Lv
- Anesthesia and Trauma Research Unit, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine Cangzhou No.2 Hospital, Cangzhou, China
| | - Lu-Ying Wang
- Anesthesia and Trauma Research Unit, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine Cangzhou No.2 Hospital, Cangzhou, China
| | - Shi-Yan Jia
- Anesthesia and Trauma Research Unit, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine Cangzhou No.2 Hospital, Cangzhou, China
| | - Yu-Dong Shan
- Anesthesia and Trauma Research Unit, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine Cangzhou No.2 Hospital, Cangzhou, China
| | - Jing-Jing Shao
- Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wei Zhang
- Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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12
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Subtype Classification, Immune Infiltration, and Prognosis Analysis of Lung Adenocarcinoma Based on Pyroptosis-Related Genes. BIOMED RESEARCH INTERNATIONAL 2022; 2022:1371315. [PMID: 36277882 PMCID: PMC9581708 DOI: 10.1155/2022/1371315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 09/18/2022] [Accepted: 09/27/2022] [Indexed: 11/18/2022]
Abstract
The effect of pyroptosis-related genes (PRGs) on the tumor microenvironment (TME) in lung adenocarcinoma (LUAD) remains unclear. Thus, this study is aimed at evaluating the prognostic value of PRGs in patients with LUAD and to elucidate their role in the TME and their effect on immunotherapy. Transcriptomic and clinical data were obtained from the Cancer Genome Atlas and the Gene Expression Omnibus databases (GSE3141, GSE31210). Patients with LUAD were classified using consistent clustering, and the differences in the TME for each type were determined using the ESTIMATE and CIBERSORT algorithms. PRGs were screened using univariate regression analysis, and a prognostic risk model was constructed using LASSO regression analysis. The tumor mutational burden and the tumor immune dysfunction and exclusion algorithms were used to predict therapeutic sensitivity in LUAD patients. Then, we evaluated the potential therapeutic interventions using the GDSC database. LUAD patients in cluster 2 had significantly shorter overall survival and progression-free survival rates, lower immune scores, and higher infiltration of T follicular helper cells than those in cluster 1. We used five PRGs to classify patients with LUAD into different risks groups and found that the high-risk group is sensitive to immunotherapy; however, its immune-related pathways were inhibited, which may be related to tumor metabolic reprogramming. Lastly, we identified several potential therapeutic drugs for application in low-risk patients who were less sensitive to immunotherapy. Overall, our findings showed that PRGs can be used to predict prognosis and may aid in the development of personalized therapeutic strategies in LUAD patients.
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13
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Xia J, Hu JN, Zhang RB, Liu W, Zhang H, Wang Z, Jiang S, Wang YP, Li W. Icariin exhibits protective effects on cisplatin-induced cardiotoxicity via ROS-mediated oxidative stress injury in vivo and in vitro. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 104:154331. [PMID: 35878553 DOI: 10.1016/j.phymed.2022.154331] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 06/22/2022] [Accepted: 07/09/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Cisplatin-induced cardiotoxicity severely limits its clinical application as an antitumor drug and increases the risk of cardiovascular disease. Icariin (ICA), the main flavonoid isolated from Epimedii Folium, has been demonstrated to have various beneficial effects on cardiovascular disease. However, the protective effect of ICA against cisplatin-induced cardiotoxicity remains unclear. PURPOSE In present study, we explored the protective action of ICA against cisplatin-induced cardiotoxicity and its possible molecular mechanisms in vitro and in vivo. METHODS Mice were intraperitoneally injected with cisplatin 4 mg/kg every other day for 7 times to establish myocardial injury model. ICA (15, 30 mg/kg) was administered to mice by gavage for 21 days. H9c2 cells were treated with ICA (3, 6, 12 µM) in the presence or absence of cisplatin (40 µM), and then cell viability, oxidative stress, apoptosis, and mitochondrial function were evaluated. RESULTS Biochemical index detection and histopathological staining analysis showed that ICA had a good protective effect on cisplatin-induced cardiotoxicity. Cellular experiments showed that ICA inhibited cisplatin-induced oxidative stress in a dose-dependent manner by regulating the levels of glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA). ICA could inhibit the expression of NF-κB and the secretion of inflammatory factors, thereby alleviating the inflammatory injury caused by cisplatin. In addition, ICA could alleviate cisplatin-induced myocardial injury by activating SIRT1 and PI3K/Akt signaling pathways and inhibiting MAPKs signaling pathway. CONCLUSION These results suggest that ICA could attenuate cisplatin-induced cardiac injury by inhibiting oxidative stress, inflammation and apoptosis, laying a foundation for ICA to reduce chemotherapy-induced cardiotoxicity in clinical practice.
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Affiliation(s)
- Juan Xia
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, China; National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun, 130118, China
| | - Jun-Nan Hu
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, China
| | - Ruo-Bing Zhang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, China
| | - Wei Liu
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, China
| | - Hao Zhang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, China
| | - Zi Wang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, China
| | - Shuang Jiang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, China
| | - Ying-Ping Wang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, China; National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun, 130118, China.
| | - Wei Li
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, China; National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun, 130118, China.
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14
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Chen Q, Ou J, Guo L, Wu F. Study on the effect of icariin on the preservation of postharvest mango fruit. J FOOD PROCESS PRES 2022. [DOI: 10.1111/jfpp.16656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Qiqi Chen
- College of Food Science and Engineering Foshan University Foshan China
| | - Jiaying Ou
- College of Food Science and Engineering Foshan University Foshan China
| | - Lihong Guo
- College of Food Science and Engineering Foshan University Foshan China
| | - Fuwang Wu
- College of Food Science and Engineering Foshan University Foshan China
- Guangdong Provincial Key Laboratory of Food Intelligent Manufacturing Foshan University Foshan China
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15
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Comparison of three antioxidants in chemical and biological assays on porcine oocytes during ageing in vitro. ZYGOTE 2022; 30:561-570. [PMID: 35443903 DOI: 10.1017/s0967199421000459] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Our previous studies have already revealed that β-cryptoxanthin (BCX), hesperetin (HES), and icariin (ICA) antioxidants are effective for in vitro maturation (IVM) of porcine oocytes. In this study, we investigated which of BCX, HES, or ICA was more effective for IVM of porcine oocytes. The antioxidant properties were assessed with aged porcine oocytes and embryos by comparing 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH), reducing power, and H2O2 scavenging activity assays. The chemical assay results demonstrated that BCX had a greater DPPH scavenging activity and reducing power than HES and ICA, compared with controls. However, the H2O2 scavenging activity of the antioxidants was similar when tested at the optimal concentrations of 1 μM BCX (BCX-1), 100 μM HES (HES-100), and 5 μM ICA (ICA-5). The biological assay results showed that BCX-1 treatment was more effective in inducing a significant reduction in reactive oxygen species (ROS), improving glutathione levels, and increasing the expression of antioxidant genes. In addition, BCX-1 inhibited apoptosis by increasing the expression of anti-apoptotic genes and decreasing pro-apoptotic genes in porcine parthenogenetic blastocysts. BCX-1 also significantly increased the blastocyst formation rate compared with the ageing control group, HES-100 and ICA-5. This study demonstrates that damage from ROS produced during oocyte ageing can be prevented by supplementing antioxidants into the IVM medium, and BCX may be a potential candidate to improve assisted reproductive technologies.
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16
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Di Nisio V, Antonouli S, Damdimopoulou P, Salumets A, Cecconi S. In vivo and in vitro postovulatory aging: when time works against oocyte quality? J Assist Reprod Genet 2022; 39:905-918. [PMID: 35312936 PMCID: PMC9050976 DOI: 10.1007/s10815-022-02418-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 01/27/2022] [Indexed: 12/26/2022] Open
Abstract
In mammalian species an optimal fertilization window during which successful fertilization occurs. In the majority of mammals estrus marks ovulation time and coincident with mating, thereby allowing the synchronized meeting in the fallopian tubes, between freshly ejaculated sperm and freshly ovulated oocytes. Conversely, women do not show natural visual signs of ovulation such that fertilization can occur hours later involving an aged oocyte and freshly ejaculated spermatozoa. During this time, the oocyte undergoes a rapid degradation known as “postovulatory aging” (POA). POA may become particularly important in the human-assisted reproductive technologies, as the fertilization of retrieved mature oocytes can be delayed due to increased laboratory workload or because of unforeseeable circumstances, like the delayed availability of semen samples. This paper is an updated review of the consequences of POA, either in vivo or in vitro, on oocyte quality with particular attention to modifications caused by POA on oocyte nuclear, cytoplasmic, genomic, and epigenetic maturation, and embryo development.
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Affiliation(s)
- Valentina Di Nisio
- Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, 14186, Huddinge, Stockholm, Sweden.
| | - Sevastiani Antonouli
- Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Pauliina Damdimopoulou
- Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, 14186, Huddinge, Stockholm, Sweden
| | - Andres Salumets
- Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, 14186, Huddinge, Stockholm, Sweden.,Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, 50406, Tartu, Estonia.,Competence Centre On Health Technologies, 50411, Tartu, Estonia
| | - Sandra Cecconi
- Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy.
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17
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Aljehani AA, Albadr NA, Nasrullah MZ, Neamatallah T, Eid BG, Abdel-Naim AB. Icariin ameliorates metabolic syndrome-induced benign prostatic hyperplasia in rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:20370-20378. [PMID: 34734339 DOI: 10.1007/s11356-021-17245-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 10/24/2021] [Indexed: 06/13/2023]
Abstract
Metabolic syndrome (MetS) is an immense health issue that causes serious complications in aging males including BPH. Icariin (ICA) is a flavonol glycoside that exerts a plethora of pharmacological effects. The present investigation tested the potential of ICA to ameliorate benign prostatic hyperplasia (BPH) induced by MetS in rats. Animals were allocated to 5 groups in which the first and second groups were kept on water and regular food pellets. MetS was induced in the third, fourth, and fifth groups by keeping the animals on high fructose and salt diets for twelve consecutive weeks. These groups were given vehicle, ICA (25 mg/kg), and ICA (50 mg/kg), respectively. MetS was confirmed by an increase in rats' weight, accumulation of visceral fat, insulin resistance, and dyslipidemia. This was accompanied by manifestation of BPH including increased prostate weight, prostate index, and histopathological alterations. Treating the animals with both doses of ICA significantly ameliorated the increase in weight and index of the prostate as well as altered prostate histopathology. In addition, ICA significantly decreased cyclin D1 expression, upregulated Bax, and downregulated Bcl2 mRNA expression. ICA prevented lipid peroxidation, reduced glutathione depletion, and catalase exhaustion, which further lowered markers of prostate inflammation such as interleukin-6 and tumor necrosis factor-α. Moreover, ICA prevented the decrease in prostate content of phosphorylated 5'-adenosine monophosphate (AMP)-activated protein kinase (pAMPK). In conclusion, ICA protects against MetS-induced BPH. This is due to its antiproliferative, proapoptotic, antioxidant, and anti-inflammatory activities as well as the activation of AMPK.
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Affiliation(s)
- Abeer A Aljehani
- Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Nawal A Albadr
- Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Z Nasrullah
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Thikryat Neamatallah
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Basma G Eid
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ashraf B Abdel-Naim
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
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18
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Singina GN, Shedova EN, Lopukhov AV, Mityashova OS, Lebedeva IY. Delaying Effects of Prolactin and Growth Hormone on Aging Processes in Bovine Oocytes Matured In Vitro. Pharmaceuticals (Basel) 2021; 14:684. [PMID: 34358110 PMCID: PMC8308928 DOI: 10.3390/ph14070684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/05/2021] [Accepted: 07/13/2021] [Indexed: 11/16/2022] Open
Abstract
Aging processes accelerate dramatically in oocytes that have reached the metaphase-II (M-II) stage. The present work aimed to study the patterns and intracellular pathways of actions of prolactin (PRL) and growth hormone (GH) on age-associated changes in bovine M-II oocytes aging in vitro. To this end, we analyzed spontaneous parthenogenetic activation (cytogenetic assay), apoptosis (TUNEL assay), and the developmental capacity (IVF/IVC) of in vitro-matured oocytes after prolonged culturing. Both PRL and GH reduced the activation rate of aging cumulus-enclosed oocytes (CEOs) and denuded oocytes (DOs), and their respective hormone receptors were revealed in the ova. The inhibitor of Src-family tyrosine kinases PP2 eliminated the effects of PRL and GH on meiotic arrest in DOs, whereas the MEK inhibitor U0126 only abolished the PRL effect. Furthermore, PRL was able to maintain the apoptosis resistance and developmental competence of aging CEOs. The protein kinase C inhibitor calphostin C suppressed both the actions of PRL. Thus, PRL and GH can directly support meiotic arrest in aging M-II oocytes by activating MAP kinases and/or Src-family kinases. The effect of PRL in maintaining the developmental capacity of aging oocytes is cumulus-dependent and related to the pro-survival action of the protein kinase C-mediated signal pathway.
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Affiliation(s)
| | | | | | | | - Irina Y. Lebedeva
- Department of Animal Biotechnology and Molecular Diagnostics, L.K. Ernst Federal Research Center for Animal Husbandry, 142132 Podolsk, Russia; (G.N.S.); (E.N.S.); (A.V.L.); (O.S.M.)
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