MicroRNAs of Milk in Cells, Plasma, and Lipid Fractions of Human Milk, and Abzymes Catalyzing Their Hydrolysis
Abstract
:1. Introduction
2. Results
2.1. Isolation and Quantification of MicroRNAs
2.2. Purification and Characterizing of IgGs and sIgAs
2.3. Hydrolysis of MicroRNAs
2.4. Spatial Structures of Five miRNAs
3. Discussion
4. Materials and Methods
4.1. Chemicals and Donors
4.2. Purification and Analysis of RNAs
4.3. RNA Amplification
4.4. Purification and Analysis of Antibodies
4.5. Analysis of MicroRNAs Hydrolysis by Abs
4.6. Spatial Model of MicroRNAs
4.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Number of Donor | MicroRNA Content (Number of Copies in 1 mg of Milk Plasma) | ||||
---|---|---|---|---|---|
miR-148a-3p | let-7f-5p | miR-146b-5p | miR-200c-3p | miR-378a-3p | |
Number of Parameter | |||||
p1 | p2 | p3 | p4 | p5 | |
1 | 1.2 × 108 * | 1.4 × 1010 | 1.2 × 109 | 3.7 × 109 | 6.5 × 107 |
2 | 8.0 × 106 | 6.2 × 109 | 1.1 × 109 | 1.4 × 108 | 2.8 × 107 |
3 | 1.8 × 107 | 5.2 × 109 | 8.6 × 108 | 1.5 × 109 | 7.0 × 106 |
4 | 6.0 × 106 | 1.0 × 1010 | 1.1 × 109 | 1.2 × 108 | 3.0 × 106 |
5 | 1.3 × 108 | 4.8 × 109 | 8.7 × 108 | 4.2 × 109 | 1.4 × 108 |
6 | 1.1 × 108 | 2.5 × 109 | 4.2 × 108 | 3.8 × 109 | 9.8 × 107 |
7 | 1.3 × 107 | 4.9 × 109 | 9.6 × 108 | 5.7 × 107 | 4.0 × 106 |
CCs between parameters | 1–2 (0.20); 1–3 (−0.005); 1–4 (0.67); 1–5 (0.92); 2–3 (0.81); 2–4 (−0.19); 2–5 (−0.07); 3–4 (0.58); 3–5 (0.14); 4–5 (0.66) | ||||
Number of donor | MicroRNA content in cells (number of copies in 1 mg of milk cells) | ||||
miR-148a-3p | let-7f-5p | miR-146b-5p | miR-200c-3p | miR-378a-3p | |
Number of parameter | |||||
p1 | p2 | p3 | p4 | p5 | |
1 | 8.1 × 107 | 5.0 × 1010 | 1.2 × 1010 | 9.2 × 109 | 1.1 × 108 |
2 | 1.2 × 108 | 4.4 × 1010 | 9.4 × 109 | 5.4 × 109 | 2.0 × 108 |
3 | 5.8 × 107 | 4.4 × 1010 | 1.2 × 1010 | 2.6 × 109 | 1.5 × 108 |
4 | 9.7 × 108 | 8.1 × 1010 | 2.3 × 1010 | 4.0 × 109 | 1.2 × 108 |
5 | 3.2 × 108 | 5.5 × 1010 | 2.0 × 1010 | 5.3 × 109 | 4.1 × 108 |
6 | 8.8 × 108 | 4.5 × 1010 | 1.1 × 1010 | 2.4 × 109 | 1.6 × 108 |
7 | 4.2 × 107 | 3.7 × 1010 | 1.0 × 1010 | 2.2 × 109 | 2.1 × 108 |
CCs between parameters | 1–2 (0.24); 1–3 (0.23); 1–4 (0.28); 1–5 (−0.17); 2–3 (0.99); 2–4 (0.86); 2–5 (−0.37); 3–4 (0.86); 3–5 (0.33); 4–5 (0.04) | ||||
MicroRNA content (number of copies in 1 mg of milk lipid fraction) | |||||
Number of donor | miR-148a-3p | let-7f-5p | miR-146b-5p | miR-200c-3p | miR-378a-3p |
Number of parameter | |||||
p1 | p2 | p3 | p4 | p5 | |
1 | 7.2 × 107 | 4.1 × 1010 | 1.6 × 1010 | 3.1 × 109 | 4.1 × 107 |
2 | 1.3 × 107 | 7.2 × 1010 | 1.6 × 1010 | 3.4 × 109 | 3.7 × 107 |
3 | 4.0 × 106 | 2.4 × 1010 | 3.6 × 1010 | 1.6 × 109 | 8.3 × 107 |
4 | 6.2 × 108 | 3.1 × 1010 | 6.4 × 109 | 2.6 × 109 | 7.1 × 107 |
5 | 2.0 × 106 | 1.0 × 1010 | 4.6 × 109 | 5.9 × 108 | 4.9 × 107 |
6 | 4.1 × 108 | 6.6 × 109 | 2.0 × 109 | 2.1 × 108 | 2.3 × 107 |
7 | 2.6 × 107 | 7.4 × 109 | 2.3 × 109 | 1.9 × 109 | 1.6 × 107 |
CCs between parameters | 1–2 (0.15); 1–3 (0.40); 1–4 (0.10); 1–5 (0.28); 2–3 (0.38); 2–4 (0.84); 2–5 (−0.32); 3–4 (0.29); 3–5 (0.26); 4–5 (0.48) | ||||
CCs reflecting the content of each of the five RNAs (parameters p1–p5) in plasma, cells, and lipid fraction | |||||
p1 cells | p1 lipid fraction | p2 cells | p2 lipid fraction | ||
1 plasma | 0.57 | 0.49 | 2 plasma | 0.18 | 0.30 |
1 cells | - | 0.94 | 2 cells | - | 0.26 |
p3 cells | p3 lipid fraction | - | p4 cells | p4 lipid fraction | |
3 plasma | 0.4 | 0.62 | 4 plasma | −0.22 | 0.003 |
3 cells | - | 0.12 | 4 cells | - | 0.54 |
p5 cells | p5 lipid fraction | - | - | - | |
5 plasma | 0.25 | 0.46 | - | - | - |
5 cells | 0.92 | - | - | - |
MicroRNAs | Number of Copies in 1 mg of the Analyzed Sample | |||||
---|---|---|---|---|---|---|
Cells | Lipid Fraction | Plasma | ||||
Diapason * | Average Value (M and IQR) ** | Diapason | Average Value (M and IQR) | Diapason | Average Value (M and IQR) | |
miR-148a-3p | 4.2 × 107–9.7 × 108 | 3.8 × 108 ± 1.3 × 108 (2.2 × 108; 5 × 108) | 2.0 × 106–6.0 × 108 | 2.0 × 108 ± 9.0 × 107 (5 × 107; 4 × 108) | 2 × 106–1 × 108 | 5.1 × 107 ± 2.0 × 107 (1.6 × 107; 1.0 × 108) |
miR-200c-3p | 1.0 × 109–9.0 × 109 | 4.0 × 109 ± 9.0 × 108 (3.0 × 109; 4.2 × 109) | 2.1 × 108–3.4 × 109 | 1.8 × 109 ± 4.0 × 108 (1.7 × 109; 2.0 × 109) | 6.0 × 107–4.0 × 109 | 2.0 × 109 ± 7.0 × 108 (3.0 × 109; 3.6 × 109) |
miR-378a-3p | 6.2 × 107–4.1 × 109 | 1.8 × 108 ± 3.7 × 107 (1.5 × 108; 5.0 × 108) | 2.0 × 107–8.0 × 107 | 4.0 × 107 ± 8.0 × 106 (4.0 × 107; 4.0 × 108) | 2.0 × 106–1.0 × 108 | 4.0 × 107 ± 2.0 × 107 (2.0 × 107; 1.0 × 108) |
let-7f-5p | 1.8 × 1010–8.1 × 1010 | 4.6 × 1010 ± 6.0 × 109 (4.5 × 1010; 3.2 × 1010) | 4.1 × 109–7.2 × 1010 | 2.5 × 1010 ± 8.0 × 109 (1.7 × 1010; 2.4 × 1010) | 2.1 × 109–1.4 × 1010 | 6.2 × 109 ± 1.0 × 109 (5.0 × 109; 3.6 × 109) |
miR-146b-5p | 4.6 × 109–2.3 × 1010 | 1.2 × 1010 ± 2.3 × 109 (1.2 × 1010; 7.8 × 109) | 1.1 × 109–3.6 × 1010 | 4.6 × 1010 ± 6.0 × 109 (5.4 × 109; 1.4 × 1010) | 3.3 × 108–1.2 × 109 | 8.5 × 108 ± 1.0 × 108 (9.2 × 108; 6.7 × 108) |
Average content of all microRNAs | 1.25 × 1010 ± 1.93 × 1010 | 1.46 × 1010 ± 2.4 × 1010 | 0.18 × 1010 ± 0.04 × 1010 |
Abs Number | miR-148a-3p | miR-200c-3p | miR-378a-3p | let-7f-5p | miR-146b-5p |
---|---|---|---|---|---|
Number of Parameter | |||||
p1 | p2 | p3 | p4 | p5 | |
IgG1 | 39.0 * | 62.1 | 69.8 | 72.1 | 99.5 |
IgG2 | 21.0 | 3.9 | 8.2 | 34.6 | 17.6 |
IgG3 | 58.2 | 25.2 | 7.2 | 61.5 | 55.6 |
IgG4 | 22.6 | 15.1 | 8.5 | 63.1 | 97.6 |
IgG5 | 32.4 | 28.3 | 76.1 | 66.3 | 99.7 |
IgG6 | 12.7 | 4.7 | 12.1 | 40.21 | 12.3 |
IgG7 | 21.3 | 82.9 | 17.9 | 76.0 | 42.3 |
Average values | 29.6 ± 15.2 | 31.7 ± 29.9 | 28.5 ± 30.6 | 59.1 ± 15.7 | 60.7 ± 38.6 |
M; (IQR) ** | 22.6 (18.0) | 25.2 (57.4) | 12.1 (61.6) | 63.1 (31.9) | 55.6 (81.9) |
Correl. Coef. | 1–2 (0.17); 1–3 (0.21); 1–4 (0.39); 1–5 (0.40); 2–3 (0.37); 2–4 (0.83); 2–5 (0.29); 3–4 (0.48); 3–5 (0.66); 4–5 (0.71) | ||||
Difference (p) | 1–2 (0.002); 1–3 (0.002); 1–4 (0.02); 1–5 (0.002); 2–3 (0.002); 2–4 (0.03); 2–5 (0.002); 3–4 (0.03); 3–5 (0.002); 4–5 (0.002) | ||||
Number of parameter | |||||
Group number | 6 | 7 | 8 | 9 | 10 |
sIgA1 | 98.7 | 99.0 | 32.6 | 99.0 | 54.1 |
sIgA2 | 13.8 | 4.9 | 17.2 | 26.5 | 24.0 |
sIgA3 | 33.7 | 52.0 | 43.7 | 62.2 | 40.2 |
sIgA4 | 32.1 | 77.1 | 12.9 | 83.0 | 48.7 |
sIgA5 | 67.4 | 94.0 | 9.2 | 98.3 | 39.5 |
sIgA6 | 81.8 | 4.1 | 21.7 | 24.0 | 15.3 |
sIgA7 | 66.4 | 40.4 | 9.4 | 70.2 | 14.7 |
Average values | 56.3 ± 30.5 | 53.1 ± 39.2 | 21.0 ± 12.9 | 66.2 ± 31.0 | 33.8 ± 15.9 |
M and (IQR) | 66.4 (98.7) | 52.0 (99.0) | 17.2 (43.7) | 70.2 (99.0) | 39.5 (54.1) |
Correl. Coef. | 6–7 (0.3); 6–8 (0.04); 6–9 (0.37); 6–10 (0.06); 7–8 (0.04); 7–9 (0.98); 7–10 (0.84); 8–9 (−0.08); 8–10 (0.36); 9–10 (0.73) | ||||
Difference (p) *** | 6–7 (0.7); 6–8 (0.002); 6–9 (0.7); 6–10 (0.03); 7–8 (0.002); 7–9 (0.4); 7–10 (0.03); 8–9 (0.7); 8–10 (0.03); 9–10 (0.03) | ||||
CC between IgGs and sIgAs | 1–6 (−0.07); 2–7 (−0.41); 3–8 (−0.09); 4–9 (0.87); 5–10 (0.87) | ||||
Difference between IgGs and sIgAs (p) | 1–6 (0.002); 2–7 (0.70); 3–8 (0.002); 4–9 (0.50); 5–10 (0.03) |
MicroRNAs | miR-200c-3p | miR-378a-3p | let-7f-5p | miR-146b-5p |
---|---|---|---|---|
miR-148a-3p | 0.97 | 0.99 | 0.07 | 0.33 |
miR-378a-3p | 0.98 | - | 0.07 | 0.33 |
let-7f-5p | 0.007 | 0.07 | - | 0.79 |
miR-146b-5p | 0.42 | 0.33 | 0.79 | - |
Antibodies | MicroRNAs | ||||
---|---|---|---|---|---|
miR-148a-3p | miR-200c-3p | miR-378a-3p | let-7f-5p | miR-146b-5p | |
IgGs | −0.01 | −0.05 | 0.79 | 0.41 | 0.53 |
sIgAs | 0.8 | 0.33 | 0.03 | 0.59 | 0.59 |
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Kompaneets, I.Y.; Ermakov, E.A.; Buneva, V.N.; Nevinsky, G.A. MicroRNAs of Milk in Cells, Plasma, and Lipid Fractions of Human Milk, and Abzymes Catalyzing Their Hydrolysis. Int. J. Mol. Sci. 2022, 23, 12070. https://doi.org/10.3390/ijms232012070
Kompaneets IY, Ermakov EA, Buneva VN, Nevinsky GA. MicroRNAs of Milk in Cells, Plasma, and Lipid Fractions of Human Milk, and Abzymes Catalyzing Their Hydrolysis. International Journal of Molecular Sciences. 2022; 23(20):12070. https://doi.org/10.3390/ijms232012070
Chicago/Turabian StyleKompaneets, Ivan Yu., Evgeny A. Ermakov, Valentina N. Buneva, and Georgy A. Nevinsky. 2022. "MicroRNAs of Milk in Cells, Plasma, and Lipid Fractions of Human Milk, and Abzymes Catalyzing Their Hydrolysis" International Journal of Molecular Sciences 23, no. 20: 12070. https://doi.org/10.3390/ijms232012070