臺灣博碩士論文加值系統

生物體內代謝物是生理反應的最終產物，藉由代謝體學能夠提供和表現型有最直接關聯的代謝物變化資訊。本研究以標的以及非標的代謝體分析方法研究植物化合物，以及植物成分與CoQ10影響的代謝物改變，並結合腸道菌相分析探討CoQ10對腸道菌的影響。在植物化合物的部分，以活性追蹤策略進行植物成分的分離純化，從沉香葉中鑑定出對MMP-2及-9具有正向調節活性的二次代謝物PA，並發現UV照射會改變其部分結構的位向，且可能因此改變其活性。同時運用傳統分離純化分析以及LC-MS非標的代謝體分析方法，本研究發現芝麻渣中被BSFL主要利用的成分為DG，且有數種胺基酸、醣類以及脂質在不同生長期BSFL蟲體與糞便中有顯著的差異變化，並推測部分代謝物是由幼蟲體內共生菌代謝生成。利用2D-HPLC系統，本研究進行了標的代謝物—Phe鏡相異構物在人類、大鼠、小鼠血液及尿液中的定量方法開發，且分析發現在DAO缺乏的哺乳動物體內D-Phe的含量顯著上升。CoQ10是一種常見的健康食品，在粒線體內參與能量的代謝，並且被認為能促進健康以及改善許多疾病，如代謝疾病、神經疾病，以及心血管疾病。為了了解CoQ10作為健康食品對動物體的影響，本研究以100 mg/ kg CoQ10餵食健康大鼠，分析大鼠體內代謝物以及糞便中的腸道菌變化。將已開發的Phe鏡像異構物分析方法運用於CoQ10代謝物分析，結果顯示CoQ10會使大鼠尿液中%D-Phe顯著上升。使用LC-MS非標的代謝體分析以及NMR標的代謝體分析方法，結合IPA代謝路徑分析，結果顯示CoQ10會導致大鼠血漿中多種小分子代謝物與脂蛋白的含量變化，這些差異性代謝物的變化可能來自於碳水化合物以及脂質代謝的改變。透過16S rRNA長片段基因分析，本研究發現CoQ10會影響糞便中數種腸道菌的組成。透過標的與非標的代謝體學研究方法，本研究分析得到了數種差異性代謝物，並討論其變化相關的生物功能。

In living organisms, metabolites are the final products of physiological reactions. Through metabolomic studies, the metabolites changes that are most directly related to the phenotypes can be explored. In this research, targeted and untargeted metabolomic analysis methods were used to study phytochemicals and metabolomes that are affected by the supplementation of phytochemicals or CoQ10. Additionally, the gut microbiota analysis was performed to explore the effect of CoQ10 on gut bacteria. In the study of phytochemicals, bioassay-guided strategy was applied for compound separation, and PA was purified and identified from Aquilaria sinensis leaves. Up regulatory activity on MMP-2 and -9 was found on PA, however, its structure could be changed by UV irradiation and may therefore alter its bioactivity. By using traditional compound separation and LC-MS based untargeted metabolomic analysis, DG was found to be the major component in sesame residues utilized by BSFL, and several amino acids, sugars, and lipids were found to be the differential components among different growth stages of BSFL and feces. Additionally, some of the metabolites are found potentially been metabolized by symbiotic bacteria in BSFL. In the section of targeted chiral metabolite analysis, a 2D-HPLC method for the determination of Phe enantiomers in the plasma and urine of humans, rats, and mice has been developed. The results showed that D-Phe contents were highly correlated to DAO activity. CoQ10 is widely used as a healthy food supplement, and is considered to improve health conditions and many diseases such as metabolic syndromes, neurological diseases, and cardiovascular diseases. In order to understand the effect of CoQ10 on healthy animals, healthy SD rats were fed with 100 mg/kg CoQ10, and the changes of metabolites and gut bacteria were analyzed. The developed Phe enantiomer analysis method was applied to this study, and the result showed that %D-Phe significantly increased in the urine. By using LC-MS based untargeted metabolomic analysis and NMR based targeted metabolomic analysis, the relative contents of various small molecule metabolites and lipoproteins were found altered in the plasma. Through the IPA pathway analysis, the metabolite changes were supposed to correlate to carbohydrate and lipid metabolism. Long sequence 16S rRNA gene sequencing was performed on the feces samples, and the results showed that CoQ10 could affect the composition of several gut bacteria in feces. Through targeted and untargeted metabolomic research methods, several differential metabolites were discovered in this study, and the biological functions related to their changes were discussed.

目錄

臺北醫學大學博士學位考試委員審定書 i
誌謝 ii
中文摘要 iii
英文摘要 v
縮寫表 vii
目錄 ix
圖目錄 xii
表目錄 xiv
Chapter 1 背景介紹 1
1.1 代謝體學簡介 2
1.2 標的與非標的代謝體分析 5
1.3 代謝體學分析方法 6
1.3.1 LC-MS代謝體學分析-樣本的取得與處理 7
1.3.2 LC-MS代謝體分析-代謝物的分析及鑑定 10
1.3.3 大量數據的處理與分析 13
Chapter 2 沉香葉單一成分二次代謝物的分離鑑定與活性 16
2.1 引言 16
2.2 沉香的化合物對MMP的活性分析 16
2.3 結果 18
2.4 討論 21
Chapter 3 天然植物成分於BSFL的代謝體研究 25
3.1 引言 25
3.2 以芝麻渣飼養之黑水虻代謝體研究 25
3.3 方法 26
3.4 結果 27
3.5 討論 32
Chapter 4 Phe鏡像異構物的分析方法開發 37
4.1 引言 37
4.2 Phe光學異構物分析 37
4.3 材料與方法 40
4.3.1 材料及儀器 40
4.3.2 樣本處理 41
4.3.3 開發2D-HPLC系統用以分離Phe鏡像異構物 43
4.4 結果與討論 46
4.4.1 2D-HPLC系統的開發和驗證 46
4.4.2 哺乳動物血漿和尿液中Phe鏡像異構物的檢測 53
4.4.3 DAO缺乏的大鼠和小鼠體內Phe鏡像異構物的檢測 54
4.5 結論 60
Chapter 5 CoQ10非標的代謝的探討及其對腸道菌的影響 61
5.1 引言 61
5.2 Q10代謝體及腸道菌分析 61
5.2.1 Coenzyme Q10 61
5.2.2 腸道共生菌 68
5.3 實驗材料 70
5.3.1 實驗動物 70
5.3.2 CoQ10藥物 70
5.4 實驗方法 71
5.4.1 樣本採集 71
5.4.2 UPLC-MS樣本前處理 72
5.4.3 UPLC-MS全離子掃描分析 74
5.4.4 UPLC-MS數據處理與統計分析 76
5.4.5 UPLC-MS/MS化合物鑑定 77
5.4.6 UPLC-MS代謝物路徑分析 79
5.4.7 NMR代謝體分析 79
5.4.8 腸道菌相分析方法 80
5.5 結果 80
5.5.1 Plasma多變量分析 80
5.5.2 尿液中Phe掌性異構物分析 93
5.5.3 NMR代謝體分析 93
5.5.4 路徑分析 102
5.5.5 腸道菌相分析 110
5.6 討論 118
Chapter 6 結論 124
參考文獻 126

圖目錄

Figure 1.1 以代謝體學研究疾病的年度論文數[5]。 5
Figure 1.2 血漿中常見代謝物的預測辛醇/水分配係數 (octanol/water partition coefficient, X log P) 範圍和用於樣品萃取的溶劑的極性指數(Polarity index)[10] 9
Figure 2.1 沉香葉分離純化流程 18
Figure 2.2 PA及其類似物結構 20
Figure 2.3 以UV照射PA 23
Figure 2.4 PA 1H NMR光譜圖(600 MHz, DMSO-d6) 23
Figure 2.5 UV處理之PA 1H NMR光譜圖(600 MHz, DMSO-d6) 23
Figure 2.6 PA經UV處理前後之訊號差異 24
Figure 3.1 以NBD-F試劑進行樣本管柱前衍生化反應 43
Figure 3.2 2D-HPLC系統 45
Figure 3.3 RP層析分離條件探討 49
Figure 3.4 鏡像異構物層析分離條件探討 50
Figure 3.5 NBD-Phe鏡像異構物標準層析圖譜 51
Figure 3.6 2D-HPLC系統分離人類血漿及尿液中的NBD-Phe鏡像異構物之層析圖譜 56
Figure 3.7 2D-HPLC系統分離大鼠及小鼠血漿中的NBD-Phe鏡像異構物之第二維層析圖譜 57
Figure 3.8 2D-HPLC系統分離大鼠及小鼠尿液中的NBD-Phe鏡像異構物之第二維層析圖譜 58
Figure 4.1 真核生物CoQ生物合成 [149] 67
Figure 4.2 餵食動物之CoQ10材料 70
Figure 4.3 餵食CoQ10大鼠採樣流程圖 72
Figure 4.4 代謝體分析樣本前處理步驟 73
Figure 4.5 UPLC-MS差異性代謝物分析鑑定 78
Figure 4.6血漿中代謝體PCA分析 (正電與負電模式) 83
Figure 4.7 血漿中代謝體OPLS-DA 與 S-plot 分析 (正電模式) 83
Figure 4.8 血漿中代謝體OPLS-DA 與 S-plot 分析 (負電模式) 84
Figure 4.9 Phenylalanine LC-MS/MS 圖譜 85
Figure 4.10 LPC (16:0)LC-MS/MS 圖譜 86
Figure 4.11 Lactic acid LC-MS/MS 圖譜 87
Figure 4.12 IPA路徑分析 103
Figure 4.13 MetaCore路徑分析 104
Figure 4.14 IPA生物功能與疾病分析 105
Figure 4.15 IPA預測顯著活化的功能 (z-score > 2) 106
Figure 4.16 IPA預測顯著抑制的功能 (z-score < -2) 107
Figure 4.17 IPA預測有活化趨勢的功能與疾病 (2 > z-score > 1.5) 108
Figure 4.18 IPA預測有抑制趨勢的功能與疾病 (-1.5 > z-score > -2) 109
Figure 4.19 Alpha-diversity: Total number (Species) 112
Figure 4.20 Alpha-diversity: Shannon entropy (Species) 113
Figure 4.21 Alpha-diversity: Simpson’s index (Species) 114
Figure 4.22 Beta-diversity: Weighted UniFrac 115
Figure 4.23 菌種含量百分比柱狀圖 116

表目錄

Table 2.1 PA在不同濃度下對MMPs表現活性數據 19
Table 5.1 BSFL各期差異性成分之相對含量 29
Table 5.2 BSFL糞便各期差異性成分之相對含量(正電) 30
Table 5.3 BSFL糞便各期差異性成分之相對含量(負電) 31
Table 3.1 2D-HPLC方法驗證結果 52
Table 3.2 Phe鏡像異構物在人體、大鼠與小鼠的血漿及尿液中的含量 59
Table 4.1 血漿及尿液UPLC 梯度條件 75
Table 4.2 HESI參數 75
Table 4.3 血漿中差異性成分 88
Table 4.4 %D-Phe in urine 93
Table 4.5 NMR 小分子代謝物分析 96
Table 4.6 NMR脂蛋白分析 98
Table 4.7 T組與C組菌種差異性分析 117

1.Berlin, R.; Oldfelt, C. O.; Vikrot, O., Acute myocardial infarction and plasma phospholipid levels. Acta Medica Scandinavica 1969, 185, (1‐6), 439-442.
2.Ward-Caviness, C. K.; Xu, T.; Aspelund, T.; Thorand, B.; Montrone, C.; Meisinger, C.; Dunger-Kaltenbach, I.; Zierer, A.; Yu, Z.; Helgadottir, I. R., Improvement of myocardial infarction risk prediction via inflammation-associated metabolite biomarkers. Heart 2017, 103, (16), 1278-1285.
3.Li, Z.; Cheng, S.; Lin, Q.; Cao, W.; Yang, J.; Zhang, M.; Shen, A.; Zhang, W.; Xia, Y.; Ma, X.; Ouyang, Z., Single-cell lipidomics with high structural specificity by mass spectrometry. Nature communications 2021, 12, (1), 1-10.
4.Hesaka, A.; Tsukamoto, Y.; Nada, S.; Kawamura, M.; Ichimaru, N.; Sakai, S.; Nakane, M.; Mita, M.; Okuzaki, D.; Okada, M., D-Serine mediates cellular proliferation for kidney remodeling. Kidney360 2021, 2, (10), 1611-1624.
5.Cui, L.; Lu, H.-T.; Lee, Y.-H., Challenges and emergent solutions for LC‐MS/MS based untargeted metabolomics in diseases. Mass spectrometry reviews 2018, 37, (6), 772-792.
6.Zhang, L.; Vertes, A., Single‐cell mass spectrometry approaches to explore cellular heterogeneity. Angewandte Chemie International Edition 2018, 57, (17), 4466-4477.
7.Dudzik, D.; Barbas-Bernardos, C.; García, A.; Barbas, C., Quality assurance procedures for mass spectrometry untargeted metabolomics. a review. Journal of pharmaceutical and biomedical analysis 2018, 147, 149-173.
8.Wishart, D. S., Current progress in computational metabolomics. Briefings in bioinformatics 2007, 8, (5), 279-293.
9.Bruce, S. J.; Tavazzi, I.; Parisod, V.; Rezzi, S.; Kochhar, S.; Guy, P. A., Investigation of human blood plasma sample preparation for performing metabolomics using ultrahigh performance liquid chromatography/mass spectrometry. Analytical chemistry 2009, 81, (9), 3285-3296.
10.Cajka, T.; Fiehn, O., Toward merging untargeted and targeted methods in mass spectrometry-based metabolomics and lipidomics. Analytical chemistry 2016, 88, (1), 524-545.
11.Hsiao, S.-W.; Wu, Y.-C.; Mei, H.-C.; Chen, Y.-H.; Hsiao, G.; Lee, C.-K., Constituents of Aquilaria sinensis leaves upregulate the expression of matrix metalloproteases 2 and 9. Molecules 2021, 26, (9), 2537.
12.Yuan, H.-W.; Zhao, J.-P.; Liu, Y.-B.; Qiu, Y.-X.; Xie, Q.-L.; Li, M.-J.; Wang, W., Advance in studies on chemical constituents, pharmacology and quality control of Aquilaria sinensis. Digital Chinese Medicine 2018, 1, (4), 316-330.
13.Zhou, M.-h.; Wang, H.-g.; Kou, J.-p.; Yu, B.-y., Antinociceptive and anti-inflammatory activities of Aquilaria sinensis (Lour.) Gilg. leaves extract. Journal of Ethnopharmacology 2008, 117, (2), 345-350.
14.Qi, J.; Lu, J.-J.; Liu, J.-H.; Yu, B.-Y., Flavonoid and a rare benzophenone glycoside from the leaves of Aquilaria sinensis. Chemical and Pharmaceutical Bulletin 2009, 57, (2), 134-137.
15.Hara, H.; Ise, Y.; Morimoto, N.; Shimazawa, M.; Ichihashi, K.; Ohyama, M.; Iinuma, M., Laxative effect of agarwood leaves and its mechanism. Bioscience, biotechnology, and biochemistry 2008, 72, (2), 335-345.
16.Yang, X.-B.; Feng, J.; Yang, X.-W.; Zhao, B.; Liu, J.-X., Aquisiflavoside, a new nitric oxide production inhibitor from the leaves of Aquilaria sinensis. Journal of Asian natural products research 2012, 14, (9), 867-872.
17.Cheng, J.-T.; Han, Y.-Q.; He, J.; De Wu, X.; Dong, L.-B.; Peng, L.-Y.; Li, Y.; Zhao, Q.-S., Two new tirucallane triterpenoids from the leaves of Aquilaria sinensis. Archives of pharmacal research 2013, 36, (9), 1084-1089.
18.Yang, M.-X.; Liang, Y.-G.; Chen, H.-R.; Huang, Y.-F.; Gong, H.-G.; Zhang, T.-Y.; Ito, Y., Isolation of flavonoids from wild Aquilaria sinensis leaves by an improved preparative high-speed counter-current chromatography apparatus. Journal of chromatographic science 2018, 56, (1), 18-24.
19.Jiang, S.; Jiang, Y.; Guan, Y.-F.; Tu, P.-F.; Wang, K.-Y.; Chen, J.-M., Effects of 95% ethanol extract of Aquilaria sinensis leaves on hyperglycemia in diabetic db/db mice. Journal of Chinese Pharmaceutical Sciences 2011, 20, (6), 609.
20.Vincenti, M. P., The matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes. In Matrix Metalloproteinase Protocols, Humana Press: 2001; Vol. 151, pp 121-148.
21.Zhang, X.; Wang, X.; Zhong, W.; Ren, X.; Sha, X.; Fang, X., Matrix metalloproteinases-2/9-sensitive peptide-conjugated polymer micelles for site-specific release of drugs and enhancing tumor accumulation: preparation and in vitro and in vivo evaluation. International journal of nanomedicine 2016, 11, 1643.
22.Albright, C. F.; Graciani, N.; Han, W.; Yue, E.; Stein, R.; Lai, Z.; Diamond, M.; Dowling, R.; Grimminger, L.; Zhang, S.-Y., Matrix metalloproteinase–activated doxorubicin prodrugs inhibit HT1080 xenograft growth better than doxorubicin with less toxicity. Molecular cancer therapeutics 2005, 4, (5), 751-760.
23.Ra, H.-J.; Parks, W. C., Control of matrix metalloproteinase catalytic activity. Matrix Biology 2007, 26, (8), 587-596.
24.Lee, T. H.; Lu, C. K.; Kuo, Y. H.; Lo, J. M.; Lee, C. K., Unexpected novel pheophytin peroxides from the leaves of Biden pilosa. Helvetica Chimica Acta 2008, 91, (1), 79-84.
25.Kessenbrock, K.; Plaks, V.; Werb, Z., Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010, 141, (1), 52-67.
26.Sawicki, G.; Marcoux, Y.; Sarkhosh, K.; Tredget, E. E.; Ghahary, A., Interaction of keratinocytes and fibroblasts modulates the expression of matrix metalloproteinases-2 and-9 and their inhibitors. Molecular and cellular biochemistry 2005, 269, (1), 209-216.
27.Soo, C.; Shaw, W. W.; Zhang, X.; Longaker, M. T.; Howard, E. W.; Ting, K., Differential expression of matrix metalloproteinases and their tissue-derived inhibitors in cutaneous wound repair. Plastic and reconstructive surgery 2000, 105, (2), 638-647.
28.Manuel, J. A.; Gawronska-Kozak, B., Matrix metalloproteinase 9 (MMP-9) is upregulated during scarless wound healing in athymic nude mice. Matrix Biology 2006, 25, (8), 505-514.
29.Saide, A.; Lauritano, C.; Ianora, A., Pheophorbide a: state of the art. Marine Drugs 2020, 18, (5), 257.
30.Dolmans, D. E.; Fukumura, D.; Jain, R. K., Photodynamic therapy for cancer. Nature reviews cancer 2003, 3, (5), 380-387.
31.Lee, H.; Park, H.-Y.; Jeong, T.-S., Pheophorbide a derivatives exert antiwrinkle effects on UVB-induced skin aging in human fibroblasts. Life 2021, 11, (2), 147.
32.Hsiao, S.-W.; Kuo, I.; Su, C.-W.; Wang, Y.-H.; Mei, H.-C.; Lee, C.-K., Metabolite characterisation and profiling of Hermetia illucens L. larvae at various growth stages using Sesamum indicum residues as nutrient source. Journal of Insects as Food and Feed 2021, 1-14.
33.Newton, L.; Sheppard, C.; Watson, D. W.; Burtle, G.; Dove, R., Using the black soldier fly, Hermetia illucens, as a value-added tool for the management of swine manure. Animal and Poultry Waste Management Center, North Carolina State University, Raleigh, NC 2005, 17.
34.Wang, Y.-S.; Shelomi, M., Review of black soldier fly (Hermetia illucens) as animal feed and human food. Foods 2017, 6, (10), 91.
35.Jiang, C. L.; Jin, W. Z.; Tao, X. H.; Zhang, Q.; Zhu, J.; Feng, S. Y.; Xu, X. H.; Li, H. Y.; Wang, Z. H.; Zhang, Z. J., Black soldier fly larvae (Hermetia illucens) strengthen the metabolic function of food waste biodegradation by gut microbiome. Microbial biotechnology 2019, 12, (3), 528-543.
36.Miraj, S.; Kiani, S., Bioactivity of Sesamum indicum: a review study. Der Pharmacia Lettre 2016, 8, (6), 328-334.
37.Akihisa, T.; Yasukawa, K.; Yamaura, M.; Ukiya, M.; Kimura, Y.; Shimizu, N.; Arai, K., Triterpene alcohol and sterol ferulates from rice bran and their anti-inflammatory effects. Journal of Agricultural and Food Chemistry 2000, 48, (6), 2313-2319.
38.Zhang, X.; Yang, M.; Song, F.; Zhang, H.; Feng, F., Antimicrobial activity of selected fatty acids and their derivatives. Journal of Zhejiang University. Journal of Zhejiang University (Agriculture and Life Sciences) 2013, 39, (2), 155-160.
39.Martin-Arjol, I.; Bassas-Galia, M.; Bermudo, E.; Garcia, F.; Manresa, A., Identification of oxylipins with antifungal activity by LC–MS/MS from the supernatant of Pseudomonas 42A2. Chemistry and physics of lipids 2010, 163, (4-5), 341-346.
40.El-Hack, A.; Mohamed, E.; Shafi, M. E.; Alghamdi, W. Y.; Abdelnour, S. A.; Shehata, A. M.; Noreldin, A. E.; Ashour, E. A.; Swelum, A. A.; Al-Sagan, A. A., Black soldier fly (Hermetia illucens) meal as a promising feed ingredient for poultry: a comprehensive review. Agriculture 2020, 10, (8), 339.
41.Almeida, C.; Rijo, P.; Rosado, C., Bioactive compounds from Hermetia Illucens larvae as natural ingredients for cosmetic application. Biomolecules 2020, 10, (7), 976.
42.Lalander, C.; Diener, S.; Magri, M. E.; Zurbrügg, C.; Lindström, A.; Vinnerås, B., Faecal sludge management with the larvae of the black soldier fly (Hermetia illucens)—from a hygiene aspect. Science of the Total Environment 2013, 458, 312-318.
43.Vogel, H.; Müller, A.; Heckel, D. G.; Gutzeit, H.; Vilcinskas, A., Nutritional immunology: diversification and diet-dependent expression of antimicrobial peptides in the black soldier fly Hermetia illucens. Developmental & Comparative Immunology 2018, 78, 141-148.
44.Fitwi, M.; Tadesse, G., Effect of sesame cake supplementation on feed intake, body weight gain, feed conversion efficiency and carcass parameters in the ration of sheep fed on wheat bran and teff (Eragrostis teff) straw. Momona Ethiopian Journal of Science 2013, 5, (1), 89-106.
45.Omar, J. A., Effects of feeding different levels of sesame oil cake on performance and digestibility of Awassi lambs. Small Ruminant Research 2002, 46, (2-3), 187-190.
46.Mazid, M.; Zaher, M.; Begum, N.; Ali, M.; Nahar, F., Formulation of cost-effective feeds from locally available ingredients for carp polyculture system for increased production. Aquaculture 1997, 151, (1-4), 71-78.
47.徐文俊; 张崟; 姬懿珊; 杨婷; 杨萃; 甘长江, 芝麻粕利用的研究现状及进展. 农产品加工 2014, 6, (11), 64-67.
48.Kim, C.-H.; Ryu, J.; Lee, J.; Ko, K.; Lee, J.-y.; Park, K. Y.; Chung, H., Use of Black soldier fly larvae for food waste treatment and energy production in asian countries: a review. Processes 2021, 9, (1), 161.
49.Tran, G.; Gnaedinger, C.; Mélin, C. Black soldier fly larvae (Hermetia illucens). https://www.feedipedia.org/node/16388
50.Tomberlin, J. K. Biological, behavioral, and toxicological studies on the black soldier fly (Diptera: Stratiomyidae). Ph.D. dissertation, University of Georgia, Athens, 2003.
51.Esmaeilzadeh Kenari, R.; Mohsenzadeh, F.; Amiri, Z. R., Antioxidant activity and total phenolic compounds of Dezful sesame cake extracts obtained by classical and ultrasound‐assisted extraction methods. Food science & nutrition 2014, 2, (4), 426-435.
52.Holtof, M.; Lenaerts, C.; Cullen, D.; Broeck, J. V., Extracellular nutrient digestion and absorption in the insect gut. Cell and tissue research 2019, 377, (3), 397-414.
53.Leong, S. Y.; Kutty, S., Characteristic of Hermetia illucens fatty acid and that of the fatty acid methyl ester synthesize based on upcycling of perishable waste. Waste and Biomass Valorization 2020, 1-8.
54.Lalander, C.; Diener, S.; Zurbrügg, C.; Vinnerås, B., Effects of feedstock on larval development and process efficiency in waste treatment with black soldier fly (Hermetia illucens). Journal of Cleaner Production 2019, 208, 211-219.
55.Osanai, M.; Yonezawa, Y., Age-related changes in amino acid pool sizes in the adult silkmoth, Bombyx mori, reared at low and high temperature; a biochemical examination of the rate-of-living theory and urea accumulation when reared at high temperature. Experimental gerontology 1984, 19, (1), 37-51.
56.Grandison, R. C.; Piper, M. D.; Partridge, L., Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 2009, 462, (7276), 1061-1064.
57.Yang, K.; Xu, T.-R.; Fu, Y.-H.; Cai, M.; Xia, Q.-L.; Guan, R.-F.; Zou, X.-G.; Sun, P.-L., Effects of ultrasonic pre-treatment on physicochemical properties of proteins extracted from cold-pressed sesame cake. Food Research International 2021, 139, 109907.
58.Brunet, P. C., The metabolism of the aromatic amino acids concerned in the cross-linking of insect cuticle. Insect Biochemistry 1980, 10, (5), 467-500.
59.Chen, P.; Li, L.; Wang, J.; Li, H.; Li, Y.; Lv, Y.; Lu, C., BmPAH catalyzes the initial melanin biosynthetic step in Bombyx mori. PloS one 2013, 8, (8), e71984.
60.Simonet, P.; Gaget, K.; Parisot, N.; Duport, G.; Rey, M.; Febvay, G.; Charles, H.; Callaerts, P.; Colella, S.; Calevro, F., Disruption of phenylalanine hydroxylase reduces adult lifespan and fecundity, and impairs embryonic development in parthenogenetic pea aphids. Scientific reports 2016, 6, (1), 1-12.
61.Reddy, S. R. R.; Campbell, J. W., Arginine metabolism in insects. Role of arginase in proline formation during silkmoth development. Biochemical Journal 1969, 115, (3), 495-503.
62.Michaud, M. R.; Denlinger, D. L., Oleic acid is elevated in cell membranes during rapid cold-hardening and pupal diapause in the flesh fly, Sarcophaga crassipalpis. Journal of Insect Physiology 2006, 52, (10), 1073-1082.
63.Kim, H.; Gardner, H. W.; Hou, C. T., 10 (S)-hydroxy-8 (E)-octadecenoic acid, an intermediate in the conversion of oleic acid to 7, 10-dihydroxy-8 (E)-octadecenoic acid. Journal of the American Oil Chemists' Society 2000, 77, (1), 95-99.
64.Tanga, C. M.; Waweru, J. W.; Tola, Y. H.; Onyoni, A. A.; Khamis, F. M.; Ekesi, S.; Paredes, J. C., Organic waste substrates induce important shifts in gut microbiota of black soldier fly (Hermetia illucens L.): coexistence of conserved, variable, and potential pathogenic microbes. Frontiers in microbiology 2021, 12.
65.Hendrix, D. L.; Salvucci, M. E., Polyol metabolism in homopterans at high temperatures: accumulation of mannitol in aphids (Aphididae: Homoptera) and sorbitol in whiteflies (Aleyrodidae: Homoptera). Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 1998, 120, (3), 487-494.
66.Colinet, H.; Renault, D.; Javal, M.; Berková, P.; Šimek, P.; Koštál, V., Uncovering the benefits of fluctuating thermal regimes on cold tolerance of drosophila flies by combined metabolomic and lipidomic approach. Biochimica et Biophysica Acta -Molecular and Cell Biology of Lipids 2016, 1861, (11), 1736-1745.
67.Jing, T.-Z.; Qi, F.-H.; Wang, Z.-Y., Most dominant roles of insect gut bacteria: digestion, detoxification, or essential nutrient provision? Microbiome 2020, 8, (1), 1-20.
68.Kim, E.; Park, J.; Lee, S.; Kim, Y., Identification and physiological characters of intestinal bacteria of the black soldier fly, Hermetia illucens. Korean journal of applied entomology 2014, 53, (1), 15-26.
69.Wikul, A.; Damsud, T.; Kataoka, K.; Phuwapraisirisan, P., (+)-Pinoresinol is a putative hypoglycemic agent in defatted sesame (Sesamum indicum) seeds though inhibiting α-glucosidase. Bioorganic & medicinal chemistry letters 2012, 22, (16), 5215-5217.
70.Dadd, R., Essential fatty acids for mosquitoes, other insects and vertebrates. In Current topics in insect endocrinology and nutrition, Springer: Boston, MA, 1981; pp 189-214.
71.Wu, G.; Bazer, F. W.; Davis, T. A.; Kim, S. W.; Li, P.; Rhoads, J. M.; Satterfield, M. C.; Smith, S. B.; Spencer, T. E.; Yin, Y., Arginine metabolism and nutrition in growth, health and disease. Amino acids 2009, 37, (1), 153-168.
72.Blondeau, N.; Lipsky, R. H.; Bourourou, M.; Duncan, M. W.; Gorelick, P. B.; Marini, A. M., Alpha-linolenic acid: an omega-3 fatty acid with neuroprotective properties—ready for use in the stroke clinic? BioMed research international 2015, 2015.
73.Hsiao, S.-W.; Ishii, C.; Furusho, A.; Hsieh, C.-L.; Shimizu, Y.; Akita, T.; Mita, M.; Okamura, T.; Konno, R.; Ide, T., Determination of phenylalanine enantiomers in the plasma and urine of mammals and ᴅ-amino acid oxidase deficient rodents using two-dimensional high-performance liquid chromatography. Biochimica et Biophysica Acta -Proteins and Proteomics 2021, 1869, (1), 140540.
74.Friedman, M.; Levin, C. E., Nutritional and medicinal aspects of D-amino acids. Amino acids 2012, 42, (5), 1553-1582.
75.Ishii, C.; Furusho, A.; Hsieh, C.-L.; Hamase, K., Multi-dimensional high-performance liquid chromatographic determination of chiral amino acids and related compounds in real world samples. Chromatography 2020, 41, (1), 1-17.
76.Miyoshi, Y.; Koga, R.; Oyama, T.; Han, H.; Ueno, K.; Masuyama, K.; Itoh, Y.; Hamase, K., HPLC analysis of naturally occurring free D-amino acids in mammals. Journal of pharmaceutical and biomedical analysis 2012, 69, 42-49.
77.Hashimoto, A.; Oka, T.; Nishikawa, T., Anatomical distribution and postnatal changes in endogenous free D‐aspartate and D‐serine in rat brain and periphery. European Journal of Neuroscience 1995, 7, (8), 1657-1663.
78.Nishikawa, T., Analysis of free D-serine in mammals and its biological relevance. Journal of Chromatography B 2011, 879, (29), 3169-3183.
79.Labrie, V.; Wong, A. H.; Roder, J. C., Contributions of the D-serine pathway to schizophrenia. Neuropharmacology 2012, 62, (3), 1484-1503.
80.Katane, M.; Homma, H., D-Aspartate—an important bioactive substance in mammals: a review from an analytical and biological point of view. Journal of Chromatography B 2011, 879, (29), 3108-3121.
81.Miyoshi, Y.; Oyama, T.; Itoh, Y.; Hamase, K., Enantioselective two-dimensional high-performance liquid chromatographic determination of amino acids; analysis and physiological significance of D-amino acids in mammals. Chromatography 2014, 35, (1), 49-57.
82.Fisher, G. H.; D'Aniello, A.; Vetere, A.; Padula, L.; Cusano, G. P.; Man, E. H., Free D-aspartate and D-alanine in normal and Alzheimer brain. Brain research bulletin 1991, 26, (6), 983-985.
83.Fisher, G.; Lorenzo, N.; Abe, H.; Fujita, E.; Frey, W.; Emory, C.; Di Fiore, M.; D'Aniello, A., Free D-and L-amino acids in ventricular cerebrospinal fluid from Alzheimer and normal subjects. Amino acids 1998, 15, (3), 263-269.
84.Kimura, T.; Hamase, K.; Miyoshi, Y.; Yamamoto, R.; Yasuda, K.; Mita, M.; Rakugi, H.; Hayashi, T.; Isaka, Y., Chiral amino acid metabolomics for novel biomarker screening in the prognosis of chronic kidney disease. Scientific reports 2016, 6, (1), 1-7.
85.Furusho, A.; Koga, R.; Akita, T.; Mita, M.; Kimura, T.; Hamase, K., Three-dimensional high-performance liquid chromatographic determination of Asn, Ser, Ala, and Pro enantiomers in the plasma of patients with chronic kidney disease. Analytical chemistry 2019, 91, (18), 11569-11575.
86.Bhagavan, N. V.; Ha, C.-E., Essentials of medical biochemistry (Second Edition). Academic Press: Cambridge, 2015; p 227-268.
87.Young, S. N., Behavioral effects of dietary neurotransmitter precursors: basic and clinical aspects. Neuroscience & Biobehavioral Reviews 1996, 20, (2), 313-323.
88.Irukayama-Tomobe, Y.; Tanaka, H.; Yokomizo, T.; Hashidate-Yoshida, T.; Yanagisawa, M.; Sakurai, T., Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B. Proceedings of the National Academy of Sciences 2009, 106, (10), 3930-3934.
89.Jukić, T.; Rojc, B.; Boben-Bardutzky, D.; Hafner, M.; Ihan, A., The use of a food supplementation with D-Phenylalanine, L-Glutamine and L-5-Hydroxytriptophan in the alleviation of alcohol withdrawal symptoms. Collegium antropologicum 2011, 35, (4), 1225-1230.
90.Singh, V.; Rai, R. K.; Arora, A.; Sinha, N.; Thakur, A. K., Therapeutic implication of L-phenylalanine aggregation mechanism and its modulation by D-phenylalanine in phenylketonuria. Scientific reports 2014, 4, (1), 1-8.
91.Brückner, H.; Schieber, A., Determination of free D‐amino acids in mammalia by chiral gas chromatography–mass spectrometry. Journal of High Resolution Chromatography 2000, 23, (10), 576-582.
92.Brückner, H.; Schieber, A., Determination of amino acid enantiomers in human urine and blood serum by gas chromatography–mass spectrometry. Biomedical Chromatography 2001, 15, (3), 166-172.
93.Brückner, H.; Schieber, A., Ascertainment of D‐amino acids in germ‐free, gnotobiotic and normal laboratory rats. Biomedical Chromatography 2001, 15, (4), 257-262.
94.Visser, W. F.; Verhoeven-Duif, N. M.; Ophoff, R.; Bakker, S.; Klomp, L. W.; Berger, R.; De Koning, T. J., A sensitive and simple ultra-high-performance-liquid chromatography–tandem mass spectrometry based method for the quantification of D-amino acids in body fluids. Journal of Chromatography A 2011, 1218, (40), 7130-7136.
95.Armstrong, D. W.; Gasper, M.; Lee, S. H.; Zukowski, J.; Ercal, N., D‐Amino acid levels in human physiological fluids. Chirality 1993, 5, (5), 375-378.
96.Lorenzo, M. P.; Dudzik, D.; Varas, E.; Gibellini, M.; Skotnicki, M.; Zorawski, M.; Zarzycki, W.; Pellati, F.; García, A., Optimization and validation of a chiral GC–MS method for the determination of free D-amino acids ratio in human urine: application to a Gestational Diabetes Mellitus study. Journal of pharmaceutical and biomedical analysis 2015, 107, 480-487.
97.Xing, Y.-P.; Li, X.-Y.; Guo, X.-J.; Cui, Y., Simultaneous determination of 18 D-amino acids in rat plasma by an ultrahigh-performance liquid chromatography-tandem mass spectrometry method: application to explore the potential relationship between Alzheimer’s disease and D-amino acid level alterations. Analytical and bioanalytical chemistry 2016, 408, (1), 141-150.
98.Krebs, H. A., Metabolism of amino-acids: deamination of amino-acids. Biochemical Journal 1935, 29, (7), 1620.
99.Pollegioni, L.; Piubelli, L.; Sacchi, S.; Pilone, M.; Molla, G., Physiological functions of D-amino acid oxidases: from yeast to humans. Cellular and molecular life sciences 2007, 64, (11), 1373-1394.
100.Konno, R.; Hamase, K.; Maruyama, R.; Zaitsu, K., Mutant mice and rats lacking D‐amino acid oxidase. Chemistry & biodiversity 2010, 7, (6), 1450-1458.
101.Ohide, H.; Miyoshi, Y.; Maruyama, R.; Hamase, K.; Konno, R., D‐Amino acid metabolism in mammals: biosynthesis, degradation and analytical aspects of the metabolic study. Journal of Chromatography B 2011, 879, (29), 3162-3168.
102.Yamanaka, M.; Miyoshi, Y.; Ohide, H.; Hamase, K.; Konno, R., D‐Amino acids in the brain and mutant rodents lacking D-amino-acid oxidase activity. Amino acids 2012, 43, (5), 1811-1821.
103.Mitchell, J.; Paul, P.; Chen, H.-J.; Morris, A.; Payling, M.; Falchi, M.; Habgood, J.; Panoutsou, S.; Winkler, S.; Tisato, V., Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase. Proceedings of the National Academy of Sciences 2010, 107, (16), 7556-7561.
104.Sasabe, J.; Miyoshi, Y.; Suzuki, M.; Mita, M.; Konno, R.; Matsuoka, M.; Hamase, K.; Aiso, S., D‐Amino acid oxidase controls motoneuron degeneration through D-serine. Proceedings of the National Academy of Sciences 2012, 109, (2), 627-632.
105.Chumakov, I.; Blumenfeld, M.; Guerassimenko, O.; Cavarec, L.; Palicio, M.; Abderrahim, H.; Bougueleret, L.; Barry, C.; Tanaka, H.; La Rosa, P., Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Proceedings of the National Academy of Sciences 2002, 99, (21), 13675-13680.
106.Koga, R.; Miyoshi, Y.; Sakaue, H.; Hamase, K.; Konno, R., Mouse D-amino-acid oxidase: distribution and physiological substrates. Frontiers in molecular biosciences 2017, 4, 82.
107.Shimizu, Y.; Ishii, C.; Yanobu-Takanashi, R.; Nakano, K.; Imaike, A.; Mita, M.; Hamase, K.; Okamura, T., D‐Amino acid oxidase deficiency is caused by a large deletion in the Dao gene in LEA rats. Biochimica et Biophysica Acta -Proteins and Proteomics 2020, 1868, (9), 140463.
108.Szökő, É.; Vincze, I.; Tábi, T., Chiral separations for D-amino acid analysis in biological samples. Journal of pharmaceutical and biomedical analysis 2016, 130, 100-109.
109.Kirschner, D. L.; Green, T. K., Separation and sensitive detection of D‐amino acids in biological matrices. Journal of separation science 2009, 32, (13), 2305-2318.
110.Hamase, K.; Morikawa, A.; Zaitsu, K., D‐Amino acids in mammals and their diagnostic value. Journal of Chromatography B 2002, 781, (1-2), 73-91.
111.Pätzold, R.; Schieber, A.; Brückner, H., Gas chromatographic quantification of free D‐amino acids in higher vertebrates. Biomedical Chromatography 2005, 19, (6), 466-473.
112.Schurig, V., Gas chromatographic enantioseparation of derivatized α-amino acids on chiral stationary phases—past and present. Journal of Chromatography B 2011, 879, (29), 3122-3140.
113.Brückner, H.; Haasmann, S.; Friedrich, A., Quantification of D-amino acids in human urine using GC-MS and HPLC. Amino acids 1994, 6, (2), 205-211.
114.Nimura, N.; Kinoshita, T., o-Phthalaldehyde—N-acetyl-L-cysteine as a chiral derivatization reagent for liquid chromatographic optical resolution of amino acid ernantiomers and its application to conventional amino acid analysis. Journal of Chromatography A 1986, 352, 169-177.
115.Weatherly, C. A.; Du, S.; Parpia, C.; Santos, P. T.; Hartman, A. L.; Armstrong, D. W., D‐Amino acid levels in perfused mouse brain tissue and blood: a comparative study. ACS chemical neuroscience 2017, 8, (6), 1251-1261.
116.Koga, R.; Miyoshi, Y.; Sato, Y.; Mita, M.; Konno, R.; Lindner, W.; Hamase, K., Enantioselective determination of phenylalanine, tyrosine and 3, 4-dihydroxyphenylalanine in the urine of D-amino acid oxidase deficient mice using two-dimensional high-performance liquid chromatography. Chromatography 2016, 37, (1), 15-22.
117.Han, M.-L.; Xie, M.-Y.; Han, J.; Yuan, D.-Y.; Yang, T.; Xie, Y., Development and validation of a rapid, selective, and sensitive LC–MS/MS method for simultaneous determination of D-and L-amino acids in human serum: application to the study of hepatocellular carcinoma. Analytical and bioanalytical chemistry 2018, 410, (10), 2517-2531.
118.Hamase, K.; IKEDA, T.; ISHII, C.; ISHIGO, S.; MASUYAMA, K.; AKITA, T.; FURUSHO, A.; TAKAHASHI, M.; IDE, T.; MITA, M., Determination of trace amounts of chiral amino acids in complicated biological samples using two-dimensional high-performance liquid chromatography with an innovative “Shape-Fitting” peak identification/quantification method. Chromatography 2018, 39, (3), 147-152.
119.Ishii, C.; Akita, T.; Nagano, M.; Mita, M.; Hamase, K., Determination of chiral amino acids in various fermented products using a two-dimensional HPLC-MS/MS system. Chromatography 2019, 40, (2), 83-87.
120.Song, Y.-T.; Funatsu, T.; Tsunoda, M., Amino acids analysis using a monolithic silica column after derivatization with 4-fluoro-7-nitro-2, 1, 3-benzoxadiazole (NBD-F). Journal of Chromatography B 2011, 879, (5-6), 335-340.
121.Aoyama, C.; Santa, T.; Tsunoda, M.; Fukushima, T.; Kitada, C.; Imai, K., A fully automated amino acid analyzer using NBD‐F as a fluorescent derivatization reagent. Biomedical Chromatography 2004, 18, (9), 630-636.
122.Imai, K.; Fukushima, T.; Uzu, S., Sensitive determination of enantiomers of amino acids derivatized with the fluorogenic reagent, 4‐fluoro‐7‐nitro‐2, 1, 3‐benzoxadiazole, separated on a pirkle‐type column, sumichiral OA 2500 (S). Biomedical Chromatography 1993, 7, (3), 177-178.
123.Fukushima, T.; Kato, M.; Santa, T.; Imai, K., Enantiomeric separation and sensitive determination of D, L‐amino acids derivatized with fluorogenic benzofurazan reagents on pirkle type stationary phases. Biomedical Chromatography 1995, 9, (1), 10-17.
124.Armstrong, D.; Gasper, M.; Lee, S.; Ercal, N.; Zukowski, J., Factors controlling the level and determination of D-amino acids in the urine and plasma of laboratory rodents. Amino acids 1993, 5, (2), 299-315.
125.Miyoshi, Y.; Hamase, K.; Okamura, T.; Konno, R.; Kasai, N.; Tojo, Y.; Zaitsu, K., Simultaneous two-dimensional HPLC determination of free D-serine and D-alanine in the brain and periphery of mutant rats lacking D-amino-acid oxidase. Journal of Chromatography B 2011, 879, (29), 3184-3189.
126.Hamase, K.; Takagi, S.; Morikawa, A.; Konno, R.; Niwa, A.; Zaitsu, K., Presence and origin of large amounts of D-proline in the urine of mutant mice lacking D-amino acid oxidase activity. Analytical and bioanalytical chemistry 2006, 386, (3), 705-711.
127.Miyoshi, Y.; Hamase, K.; Tojo, Y.; Mita, M.; Konno, R.; Zaitsu, K., Determination of D-serine and D-alanine in the tissues and physiological fluids of mice with various D-amino-acid oxidase activities using two-dimensional high-performance liquid chromatography with fluorescence detection. Journal of Chromatography B 2009, 877, (24), 2506-2512.
128.Hamase, K.; Inoue, T.; Morikawa, A.; Konno, R.; Zaitsu, K., Determination of free D-proline and D-leucine in the brains of mutant mice lacking D-amino acid oxidase activity. Analytical biochemistry 2001, 298, (2), 253-258.
129.Crane, F. L., Biochemical functions of coenzyme Q10. Journal of the American College of Nutrition 2001, 20, (6), 591-598.
130.Weber, C.; Bysted, A.; Hłlmer, G., The coenzyme Q10 content of the average Danish diet. Journal International de Vitaminologie et de Nutrition 1997, 67, (2), 123-129.
131.Mantle, D.; Dybring, A., Bioavailability of coenzyme Q10: an overview of the absorption process and subsequent metabolism. Antioxidants 2020, 9, (5), 386.
132.Hargreaves, I.; Heaton, R. A.; Mantle, D., Disorders of human coenzyme Q10 metabolism: an overview. International Journal of Molecular Sciences 2020, 21, (18), 6695.
133.Greenberg, S.; Frishman, W. H., Co‐enzyme Q10: a new drug for cardiovascular disease. The journal of clinical pharmacology 1990, 30, (7), 596-608.
134.Bonakdar, R. A.; Guarneri, E., Coenzyme Q10. American family physician 2005, 72, (6), 1065-1070.
135.Tran, M. T.; Mitchell, T. M.; Kennedy, D. T.; Giles, J. T., Role of coenzyme Q10 in chronic heart failure, angina, and hypertension. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 2001, 21, (7), 797-806.
136.Al Saadi, T.; Assaf, Y.; Farwati, M.; Turkmani, K.; Al-Mouakeh, A.; Shebli, B.; Khoja, M.; Essali, A.; Madmani, M. E., Coenzyme Q10 for heart failure. Cochrane Database of Systematic Reviews 2021, (1).
137.Kaufmann, P.; Thompson, J. L.; Levy, G.; Buchsbaum, R.; Shefner, J.; Krivickas, L. S.; Katz, J.; Rollins, Y.; Barohn, R. J.; Jackson, C. E., Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 2009, 66, (2), 235-244.
138.BP31510 (ubidecarenone,USP) nanosuspension for intravenous injection to patients with solid tumors. https://ClinicalTrials.gov/show/NCT01957735
139.Coenzyme Q10 supplementation in children with idiopathic dilated cardiomyopathy. https://ClinicalTrials.gov/show/NCT02115581
140.Study in PRE-manifest Huntington's disease of coenzyme Q10 (ubiquinonE) leading to preventive trials (PREQUEL). https://ClinicalTrials.gov/show/NCT00920699
141.Efficacy of ubiquinone and combined antioxidant therapy in non-proliferative diabetic retinopathy. https://ClinicalTrials.gov/show/NCT02062034
142.Coenzyme Q10 as treatment for long term COVID-19. https://ClinicalTrials.gov/show/NCT04960215
143.Garrido-Maraver, J.; Cordero, M. D.; Oropesa-Ávila, M.; Vega, A. F.; De La Mata, M.; Pavón, A. D.; De Miguel, M.; Calero, C. P.; Paz, M. V.; Cotán, D., Coenzyme Q10 therapy. Molecular Syndromology 2014, 5, (3-4), 187-197.
144.Flowers, N.; Hartley, L.; Todkill, D.; Stranges, S.; Rees, K., Co‐enzyme Q10 supplementation for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2014, (12).
145.Hernández-Camacho, J. D.; Bernier, M.; López-Lluch, G.; Navas, P., Coenzyme Q10 supplementation in aging and disease. Frontiers in physiology 2018, 9, 44.
146.Mizuno, K.; Tanaka, M.; Nozaki, S.; Mizuma, H.; Ataka, S.; Tahara, T.; Sugino, T.; Shirai, T.; Kajimoto, Y.; Kuratsune, H., Antifatigue effects of coenzyme Q10 during physical fatigue. Nutrition 2008, 24, (4), 293-299.
147.Zhang, S.-Y.; Yang, K.-L.; Zeng, L.-T.; Wu, X.-H.; Huang, H.-Y., Effectiveness of coenzyme Q10 supplementation for type 2 diabetes mellitus: a systematic review and meta-analysis. International journal of endocrinology 2018, 2018.
148.Zeng, Z.; Li, Y.; Lu, S.; Huang, W.; Di, W., Efficacy of CoQ10 as supplementation for migraine: a meta‐analysis. Acta Neurologica Scandinavica 2019, 139, (3), 284-293.
149.Wang, Y.; Hekimi, S., Understanding ubiquinone. Trends in cell biology 2016, 26, (5), 367-378.
150.Jia, W.; Li, H.-K.; Zhao, L.-P.; Nicholson, J. K., Gut microbiota: a potential new territory for drug targeting. Nature reviews Drug discovery 2008, 7, (2), 123-129.
151.Nicholson, J. K.; Holmes, E.; Kinross, J.; Burcelin, R.; Gibson, G.; Jia, W.; Pettersson, S., Host-gut microbiota metabolic interactions. Science 2012, 336, (6086), 1262-1267.
152.Maier, L.; Pruteanu, M.; Kuhn, M.; Zeller, G.; Telzerow, A.; Anderson, E. E.; Brochado, A. R.; Fernandez, K. C.; Dose, H.; Mori, H., Extensive impact of non-antibiotic drugs on human gut bacteria. Nature reviews Drug discovery 2018, 555, (7698), 623-628.
153.Furrie, E.; Macfarlane, S.; Kennedy, A.; Cummings, J.; Walsh, S.; O’neil, D.; Macfarlane, G., Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 2005, 54, (2), 242-249.
154.Kang, M.-J.; Kim, H.-G.; Kim, J.-S.; Oh, D.-G.; Um, Y.-J.; Seo, C.-S.; Han, J.-W.; Cho, H.-J.; Kim, G.-H.; Jeong, T.-C., The effect of gut microbiota on drug metabolism. Expert opinion on drug metabolism & toxicology 2013, 9, (10), 1295-1308.
155.Bhatraju, N. K.; Agrawal, A., Mitochondrial dysfunction linking obesity and asthma. Annals of the American Thoracic Society 2017, 14, (Supplement 5), S368-S373.
156.Goïta, Y.; de la Barca, J. M. C.; Keïta, A.; Diarra, M. B.; Dembélé, K. C.; Chabrun, F.; Dramé, B. S. I.; Kassogué, Y.; Diakite, M.; Mirebeau-Prunier, D., Sexual dimorphism of metabolomic profile in arterial hypertension. Scientific reports 2020, 10, (1), 1-12.
157.Nishimura, A.; Yanagawa, H.; Fujikawa, N.; Kiriyama, A.; Shibata, N., Pharmacokinetic profiles of coenzyme Q10: absorption of three different oral formulations in rats. Journal of Health Science 2009, 55, (4), 540-548.
158.Ochiai, A.; Itagaki, S.; Kurokawa, T.; Kobayashi, M.; Hirano, T.; Iseki, K., Improvement in intestinal coenzyme Q10 absorption by food intake. Yakugaku Zasshi 2007, 127, (8), 1251-1254.
159.Xicoy, H.; Wieringa, B.; Martens, G. J., The role of lipids in Parkinson’s disease. Cells 2019, 8, (1), 27.
160.Xu, F.; Tavintharan, S.; Sum, C.-F.; Woon, K.; Lim, S.-C.; Ong, C. N., Metabolic signature shift in type 2 diabetes mellitus revealed by mass spectrometry-based metabolomics. The Journal of Clinical Endocrinology & Metabolism 2013, 98, (6), E1060-E1065.
161.Meikle, P. J.; Wong, G.; Tsorotes, D.; Barlow, C. K.; Weir, J. M.; Christopher, M. J.; MacIntosh, G. L.; Goudey, B.; Stern, L.; Kowalczyk, A., Plasma lipidomic analysis of stable and unstable coronary artery disease. Arteriosclerosis, thrombosis, and vascular biology 2011, 31, (11), 2723-2732.
162.Bannehr, M.; Löhr, L.; Gelep, J.; Haverkamp, W.; Schunck, W.-H.; Gollasch, M.; Wutzler, A., Linoleic acid metabolite DiHOME decreases post-ischemic cardiac recovery in murine hearts. Cardiovascular toxicology 2019, 19, (4), 365-371.
163.Hildreth, K.; Kodani, S. D.; Hammock, B. D.; Zhao, L., Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: a review of recent studies. The Journal of Nutritional Biochemistry 2020, 108484.
164.Hansen, H. S.; Kleberg, K.; Hassing, H. A., Non-endocannabinoid N-acylethanolamines and monoacylglycerols: old molecules new targets. In The Endocannabinoidome, Elsevier: 2015; pp 1-13.
165.Samimi, M.; Zarezade Mehrizi, M.; Foroozanfard, F.; Akbari, H.; Jamilian, M.; Ahmadi, S.; Asemi, Z., The effects of coenzyme Q10 supplementation on glucose metabolism and lipid profiles in women with polycystic ovary syndrome: a randomized, double‐blind, placebo‐controlled trial. Clinical endocrinology 2017, 86, (4), 560-566.
166.Krauss, R. M., Lipoprotein subfractions and cardiovascular disease risk. Current opinion in lipidology 2010, 21, (4), 305-311.
167.Dludla, P. V.; Nyambuya, T. M.; Orlando, P.; Silvestri, S.; Mxinwa, V.; Mokgalaboni, K.; Nkambule, B. B.; Louw, J.; Muller, C. J.; Tiano, L., The impact of coenzyme Q10 on metabolic and cardiovascular disease profiles in diabetic patients: a systematic review and meta‐analysis of randomized controlled trials. Endocrinology, Diabetes & Metabolism 2020, 3, (2), e00118.
168.Suksomboon, N.; Poolsup, N.; Juanak, N., Effects of coenzyme Q10 supplementation on metabolic profile in diabetes: a systematic review and meta‐analysis. Journal of Clinical Pharmacy and Therapeutics 2015, 40, (4), 413-418.
169.Mohseni, M.; Vafa, M. R.; Hajimiresmail, S. J.; Zarrati, M.; Forushani, A. R.; Bitarafan, V.; Shidfar, F., Effects of coenzyme Q10 supplementation on serum lipoproteins, plasma fibrinogen, and blood pressure in patients with hyperlipidemia and myocardial infarction. Iranian red crescent medical journal 2014, 16, (10).
170.Bhandarkar, N. S.; Mouatt, P.; Majzoub, M. E.; Thomas, T.; Brown, L.; Panchal, S. K., Coffee pulp, a by-product of coffee production, modulates gut microbiota and improves metabolic syndrome in high-carbohydrate, high-fat diet-fed rats. Pathogens 2021, 10, (11), 1369.
171.Gerhardt, S.; Mohajeri, M. H., Changes of colonic bacterial composition in Parkinson’s disease and other neurodegenerative diseases. Nutrients 2018, 10, (6), 708.
172.Rodrigues, R. R.; Gurung, M.; Li, Z.; García-Jaramillo, M.; Greer, R.; Gaulke, C.; Bauchinger, F.; You, H.; Pederson, J. W.; Vasquez-Perez, S., Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet-induced diabetes. Nature communications 2021, 12, (1), 1-15.
173.Saviano, A.; Brigida, M.; Migneco, A.; Gunawardena, G.; Zanza, C.; Candelli, M.; Franceschi, F.; Ojetti, V., Lactobacillus Reuteri DSM 17938 (Limosilactobacillus reuteri) in diarrhea and constipation: two sides of the same coin? Medicina 2021, 57, (7), 643.
174.Liu, J.; Yue, S.; Yang, Z.; Feng, W.; Meng, X.; Wang, A.; Peng, C.; Wang, C.; Yan, D., Oral hydroxysafflor yellow A reduces obesity in mice by modulating the gut microbiota and serum metabolism. Pharmacological research 2018, 134, 40-50.
175.Chan, M. Z. A.; Liu, S.-Q., Coffee brews as food matrices for delivering probiotics: opportunities, challenges, and potential health benefits. Trends in Food Science & Technology 2022, 119, 227-242.
176.Zhu, S.; Rong, Y.; Kiang, T. K., Effects of p-cresol on oxidative stress, glutathione depletion, and necrosis in HepaRG cells: comparisons to other uremic toxins and the role of p-cresol glucuronide formation. Pharmaceutics 2021, 13, (6), 857.