char = I;code = 73
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
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char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = e;code = 101
char = s;code = 115
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = a;code = 97
char = v;code = 118
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
result sql = Inhibition of cancer growth by resveratrol is related to its low bioavailability.
Inhibition of cancer growth by resveratrol is related to its low bioavailability.
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char = h;code = 104
char = e;code = 101
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char = l;code = 108
char = a;code = 97
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char = i;code = 105
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char = s;code = 115
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char = i;code = 105
char = p;code = 112
char = ;code = 32
char = b;code = 98
char = e;code = 101
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char = e;code = 101
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char = a;code = 97
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char = l;code = 108
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char = (;code = 40
char = R;code = 82
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char = S;code = 83
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char = f;code = 102
char = e;code = 101
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char = a;code = 97
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char = e;code = 101
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char = ;code = 32
char = T;code = 84
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char = s;code = 115
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char = e;code = 101
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char = e;code = 101
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char = S;code = 83
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char = w;code = 119
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char = r;code = 114
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
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char = d;code = 100
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char = f;code = 102
char = t;code = 116
char = e;code = 101
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char = i;code = 105
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char = .;code = 46
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char = a;code = 97
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char = o;code = 111
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char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = m;code = 109
char = i;code = 105
char = n;code = 110
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char = s;code = 115
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char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
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char = r;code = 114
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char = l;code = 108
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char = t;code = 116
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char = R;code = 82
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char = S;code = 83
char = );code = 41
char = ;code = 32
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char = o;code = 111
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char = b;code = 98
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char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
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char = .;code = 46
char = ;code = 32
char = H;code = 72
char = a;code = 97
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char = l;code = 108
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char = R;code = 82
char = E;code = 69
char = S;code = 83
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char = i;code = 105
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char = .;code = 46
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char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 2;code = 50
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = ;code = 32
char = t;code = 116
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char = R;code = 82
char = E;code = 69
char = S;code = 83
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ;code = 32
char = b;code = 98
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char = t;code = 116
char = .;code = 46
char = ,;code = 44
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char = w;code = 119
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char = s;code = 115
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char = v;code = 118
char = e;code = 101
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char = y;code = 121
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
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char = t;code = 116
char = ;code = 32
char = (;code = 40
char = e;code = 101
char = .;code = 46
char = g;code = 103
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = .;code = 46
char = 4;code = 52
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = b;code = 98
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = s;code = 115
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char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = e;code = 101
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char = c;code = 99
char = o;code = 111
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char = c;code = 99
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char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
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char = m;code = 109
char = a;code = 97
char = ,;code = 44
char = ;code = 32
char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
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char = i;code = 105
char = .;code = 46
char = v;code = 118
char = .;code = 46
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = m;code = 109
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char = a;code = 97
char = t;code = 116
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char = g;code = 103
char = .;code = 46
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char = 2;code = 50
char = .;code = 46
char = 6;code = 54
char = ;code = 32
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char = c;code = 99
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char = o;code = 111
char = M;code = 77
char = ;code = 32
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char = n;code = 110
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char = m;code = 109
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char = c;code = 99
char = e;code = 101
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char = .;code = 46
char = 5;code = 53
char = ;code = 32
char = m;code = 109
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char = n;code = 110
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char = a;code = 97
char = f;code = 102
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char = e;code = 101
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char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
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char = i;code = 105
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char = 2;code = 50
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = -;code = 45
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = ,;code = 44
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char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = r;code = 114
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char = a;code = 97
char = c;code = 99
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char = e;code = 101
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char = i;code = 105
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char = h;code = 104
char = e;code = 101
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char = f;code = 102
char = i;code = 105
char = r;code = 114
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char = 5;code = 53
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char = m;code = 109
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char = i;code = 105
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char = a;code = 97
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char = l;code = 108
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char = x;code = 120
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char = c;code = 99
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char = l;code = 108
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char = s;code = 115
char = s;code = 115
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char = e;code = 101
char = .;code = 46
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
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char = m;code = 109
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char = 9;code = 57
char = 9;code = 57
char = %;code = 37
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char = .;code = 46
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char = H;code = 72
char = e;code = 101
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char = o;code = 111
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char = o;code = 111
char = n;code = 110
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char = g;code = 103
char = .;code = 46
char = ,;code = 44
char = ;code = 32
char = 4;code = 52
char = 3;code = 51
char = ;code = 32
char = n;code = 110
char = m;code = 109
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = -;code = 45
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = /;code = 47
char = g;code = 103
char = ;code = 32
char = x;code = 120
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 2;code = 50
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = ;code = 32
char = t;code = 116
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = a;code = 97
char = n;code = 110
char = s;code = 115
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = l;code = 108
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = r;code = 114
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char = m;code = 109
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = r;code = 114
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = i;code = 105
char = d;code = 100
char = l;code = 108
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = ;code = 32
char = B;code = 66
char = 1;code = 49
char = 6;code = 54
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char = m;code = 109
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = (;code = 40
char = B;code = 66
char = 1;code = 49
char = 6;code = 54
char = M;code = 77
char = );code = 41
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = y;code = 121
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = O;code = 79
char = S;code = 83
char = );code = 41
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = -;code = 45
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = s;code = 115
char = h;code = 104
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = 0;code = 48
char = 0;code = 48
char = %;code = 37
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 5;code = 53
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = ;code = 32
char = t;code = 116
char = -;code = 45
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = );code = 41
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = ;code = 32
char = H;code = 72
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = O;code = 79
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = B;code = 66
char = 1;code = 49
char = 6;code = 54
char = M;code = 77
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char = c;code = 99
char = e;code = 101
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char = l;code = 108
char = s;code = 115
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char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = t;code = 116
char = u;code = 117
char = r;code = 114
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char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 5;code = 53
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
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char = t;code = 116
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char = R;code = 82
char = E;code = 69
char = S;code = 83
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = c;code = 99
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char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = e;code = 101
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char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = m;code = 109
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char = n;code = 110
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char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = -;code = 45
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = ;code = 32
char = (;code = 40
char = 2;code = 50
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = p;code = 112
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char = r;code = 114
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char = d;code = 100
char = a;code = 97
char = y;code = 121
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char = ;code = 32
char = o;code = 111
char = r;code = 114
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char = i;code = 105
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char = c;code = 99
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char = u;code = 117
char = d;code = 100
char = e;code = 101
char = d;code = 100
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char = i;code = 105
char = n;code = 110
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = d;code = 100
char = r;code = 114
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char = n;code = 110
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 2;code = 50
char = 3;code = 51
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = l;code = 108
char = );code = 41
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = d;code = 100
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char = n;code = 110
char = o;code = 111
char = t;code = 116
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char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = B;code = 66
char = 1;code = 49
char = 6;code = 54
char = M;code = 77
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = c;code = 99
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char = l;code = 108
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = f;code = 102
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char = p;code = 112
char = a;code = 97
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char = ;code = 32
char = m;code = 109
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char = c;code = 99
char = e;code = 101
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char = r;code = 114
char = o;code = 111
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char = t;code = 116
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char = .;code = 46
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char = H;code = 72
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char = e;code = 101
char = v;code = 118
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char = S;code = 83
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char = a;code = 97
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char = ;code = 32
char = a;code = 97
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char = o;code = 111
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char = ;code = 32
char = B;code = 66
char = 1;code = 49
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char = a;code = 97
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char = l;code = 108
char = y;code = 121
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char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = a;code = 97
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char = i;code = 105
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char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = t;code = 116
char = -;code = 45
char = R;code = 82
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char = S;code = 83
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char = (;code = 40
char = 1;code = 49
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char = m;code = 109
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char = c;code = 99
char = r;code = 114
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char = u;code = 117
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char = i;code = 105
char = b;code = 98
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char = t;code = 116
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char = o;code = 111
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char = o;code = 111
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char = a;code = 97
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char = c;code = 99
char = u;code = 117
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char = a;code = 97
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char = a;code = 97
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char = e;code = 101
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char = o;code = 111
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char = c;code = 99
char = u;code = 117
char = l;code = 108
char = e;code = 101
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char = 1;code = 49
char = ;code = 32
char = (;code = 40
char = V;code = 86
char = C;code = 67
char = A;code = 65
char = M;code = 77
char = -;code = 45
char = 1;code = 49
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char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
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result sql = The relationship between resveratrol (RES) bioavalability and its effect on tumor growth was investigated. Tissue levels of RES were studied after i.v. and oral administration of trans-resveratrol (t-RES) to rabbits, rats, and mice. Half-life of RES in plasma, after i.v. administration of 20 mg t-RES/kg b.wt., was very short (e.g., 14.4 min in rabbits). The highest concentration of RES in plasma, either after i.v. or oral administration (e.g., 2.6 +/- 1.0 microM in mice 2.5 min after receiving 20 mg t-RES/kg orally), was reached within the first 5 min in all animals studied. Extravascular levels (brain, lung, liver, and kidney) of RES, which paralleled those in plasma, were always < 1 nmol/g fresh tissue. RES measured in plasma or tissues was in the trans form (at least 99%). Hepatocytes metabolized t-RES in a dose-dependent fashion (e.g., 43 nmol of t-RES/g x min in the presence of 20 microM tRES), which means that the liver can remove circulating RES very rapidly. In vitro B16 melanoma (B16M) cell proliferation and generation of reactive oxygen species (ROS) was inhibited by t-RES in a concentration-dependent fashion (100% inhibition of tumor growth was found in the presence of 5 microM t-RES). Addition of 10 microM H(2)O(2) to B16M cells, cultured in the presence of 5 microM t-RES, reactivated cell growth. Oral administration of t-RES (20 mg/kg twice per day; or included in the drinking water at 23 mg/l) did not inhibit growth of B16M inoculated into the footpad of mice (solid growth). However, oral administration of t-RES (as above) decreased hepatic metastatic invasion of B16M cells inoculated intrasplenically. The antimetastatic mechanism involves a t-RES (1 microM)-induced inhibition of vascular adhesion molecule 1 (VCAM-1) expression in the hepatic sinusoidal endothelium (HSE), which consequently decreased in vitro B16M cell adhesion to the endothelium via very late activation antigen 4 (VLA-4).

Publication: Free Radic. Biol. Med. 2002 Aug 1 ;33(3)::387-98.
Publication Date: 2002 Aug 1
Study Author(s): Asensi, Miguel;Medina, Ignacio;Ortega, Angel;Carretero, Julian;Baño, M Carmen;Obrador, Elena;Estrela, Jose M;
Institution: Departamento de Fisiología, Universidad de Valencia, Valencia, Spain.
Shortcut link to this study:
The relationship between resveratrol (RES) bioavalability and its effect on tumor growth was investigated. Tissue levels of RES were studied after i.v. and oral administration of trans-resveratrol (t-RES) to rabbits, rats, and mice. Half-life of RES in plasma, after i.v. administration of 20 mg t-RES/kg b.wt., was very short (e.g., 14.4 min in rabbits). The highest concentration of RES in plasma, either after i.v. or oral administration (e.g., 2.6 +/- 1.0 microM in mice 2.5 min after receiving 20 mg t-RES/kg orally), was reached within the first 5 min in all animals studied. Extravascular levels (brain, lung, liver, and kidney) of RES, which paralleled those in plasma, were always < 1 nmol/g fresh tissue. RES measured in plasma or tissues was in the trans form (at least 99%). Hepatocytes metabolized t-RES in a dose-dependent fashion (e.g., 43 nmol of t-RES/g x min in the presence of 20 microM tRES), which means that the liver can remove circulating RES very rapidly. In vitro B16 melanoma (B16M) cell proliferation and generation of reactive oxygen species (ROS) was inhibited by t-RES in a concentration-dependent fashion (100% inhibition of tumor growth was found in the presence of 5 microM t-RES). Addition of 10 microM H(2)O(2) to B16M cells, cultured in the presence of 5 microM t-RES, reactivated cell growth. Oral administration of t-RES (20 mg/kg twice per day; or included in the drinking water at 23 mg/l) did not inhibit growth of B16M inoculated into the footpad of mice (solid growth). However, oral administration of t-RES (as above) decreased hepatic metastatic invasion of B16M cells inoculated intrasplenically. The antimetastatic mechanism involves a t-RES (1 microM)-induced inhibition of vascular adhesion molecule 1 (VCAM-1) expression in the hepatic sinusoidal endothelium (HSE), which consequently decreased in vitro B16M cell adhesion to the endothelium via very late activation antigen 4 (VLA-4).
PMID: 12126761

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