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char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
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char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
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char = n;code = 110
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char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
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char = e;code = 101
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char = i;code = 105
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
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char = i;code = 105
char = d;code = 100
char = l;code = 108
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char = b;code = 98
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = o;code = 111
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char = l;code = 108
char = c;code = 99
char = o;code = 111
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = .;code = 46
result sql = Apoptosis and insulin resistance in liver and peripheral tissues of morbidly obese patients is associated with different stages of non-alcoholic fatty liver disease.
Apoptosis and insulin resistance in liver and peripheral tissues of morbidly obese patients is associated with different stages of non-alcoholic fatty liver disease.
char = <;code = 60
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char = A;code = 65
char = I;code = 73
char = M;code = 77
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char = H;code = 72
char = Y;code = 89
char = P;code = 80
char = O;code = 79
char = T;code = 84
char = H;code = 72
char = E;code = 69
char = S;code = 83
char = I;code = 73
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = N;code = 78
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = o;code = 111
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = y;code = 121
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char = l;code = 108
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char = e;code = 101
char = r;code = 114
char = ;code = 32
char = d;code = 100
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char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = N;code = 78
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char = L;code = 76
char = D;code = 68
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char = s;code = 115
char = s;code = 115
char = o;code = 111
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char = t;code = 116
char = e;code = 101
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char = w;code = 119
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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = i;code = 105
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char = u;code = 117
char = l;code = 108
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char = a;code = 97
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char = c;code = 99
char = e;code = 101
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char = c;code = 99
char = h;code = 104
char = a;code = 97
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char = a;code = 97
char = c;code = 99
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char = f;code = 102
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char = e;code = 101
char = g;code = 103
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char = e;code = 101
char = e;code = 101
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char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = e;code = 101
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char = a;code = 97
char = t;code = 116
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char = c;code = 99
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char = e;code = 101
char = s;code = 115
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char = o;code = 111
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char = ;code = 32
char = I;code = 73
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = o;code = 111
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char = e;code = 101
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char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = c;code = 99
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char = i;code = 105
char = o;code = 111
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char = ;code = 32
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char = i;code = 105
char = t;code = 116
char = h;code = 104
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char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
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char = o;code = 111
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char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = i;code = 105
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char = s;code = 115
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char = l;code = 108
char = i;code = 105
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char = i;code = 105
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char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
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char = g;code = 103
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char = l;code = 108
char = l;code = 108
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char = p;code = 112
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char = e;code = 101
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char = a;code = 97
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char = N;code = 78
char = A;code = 65
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char = L;code = 76
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char = ;code = 32
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char = e;code = 101
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char = b;code = 98
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char = <;code = 60
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char = <;code = 60
char = b;code = 98
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char = M;code = 77
char = E;code = 69
char = T;code = 84
char = H;code = 72
char = O;code = 79
char = D;code = 68
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
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char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
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char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = m;code = 109
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char = t;code = 116
char = i;code = 105
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char = a;code = 97
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char = d;code = 100
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char = c;code = 99
char = a;code = 97
char = s;code = 115
char = p;code = 112
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = 2;code = 50
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = -;code = 45
char = 3;code = 51
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char = a;code = 97
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char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = s;code = 115
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char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = i;code = 105
char = n;code = 110
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = -;code = 45
char = J;code = 74
char = u;code = 117
char = n;code = 110
char = ;code = 32
char = N;code = 78
char = H;code = 72
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = -;code = 45
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = k;code = 107
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char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = (;code = 40
char = J;code = 74
char = N;code = 78
char = K;code = 75
char = );code = 41
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
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char = n;code = 110
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
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 = w;code = 119
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = t;code = 116
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = a;code = 97
char = s;code = 115
char = p;code = 112
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = -;code = 45
char = 2;code = 50
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char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = m;code = 109
char = e;code = 101
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char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = l;code = 108
char = y;code = 121
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char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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 = l;code = 108
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = N;code = 78
char = A;code = 65
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = v;code = 118
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
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char = s;code = 115
char = t;code = 116
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = p;code = 112
char = &;code = 38
char = #;code = 35
char = 8;code = 56
char = 2;code = 50
char = 0;code = 48
char = 1;code = 49
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char = <;code = 60
char = &;code = 38
char = #;code = 35
char = 8;code = 56
char = 2;code = 50
char = 0;code = 48
char = 1;code = 49
char = ;;code = 59
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 1;code = 49
char = );code = 41
char = .;code = 46
char = ;code = 32
char = M;code = 77
char = u;code = 117
char = s;code = 115
char = c;code = 99
char = l;code = 108
char = e;code = 101
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char = t;code = 116
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
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char = a;code = 97
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char = l;code = 108
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = r;code = 114
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char = e;code = 101
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char = e;code = 101
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char = t;code = 116
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char = e;code = 101
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char = a;code = 97
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char = d;code = 100
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = t;code = 116
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char = o;code = 111
char = s;code = 115
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char = n;code = 110
char = e;code = 101
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char = p;code = 112
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char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = i;code = 105
char = n;code = 110
char = s;code = 115
char = u;code = 117
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char = i;code = 105
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char = r;code = 114
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char = c;code = 99
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char = o;code = 111
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char = i;code = 105
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char = c;code = 99
char = e;code = 101
char = p;code = 112
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char = b;code = 98
char = s;code = 115
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char = a;code = 97
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char = h;code = 104
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char = e;code = 101
char = v;code = 118
char = e;code = 101
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char = e;code = 101
char = ;code = 32
char = N;code = 78
char = A;code = 65
char = S;code = 83
char = H;code = 72
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
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char = t;code = 116
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char = s;code = 115
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char = t;code = 116
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char = l;code = 108
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char = e;code = 101
char = a;code = 97
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char = o;code = 111
char = s;code = 115
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char = s;code = 115
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char = (;code = 40
char = p;code = 112
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char = 8;code = 56
char = 2;code = 50
char = 0;code = 48
char = 1;code = 49
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char = <;code = 60
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char = 8;code = 56
char = 2;code = 50
char = 0;code = 48
char = 1;code = 49
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char = 0;code = 48
char = .;code = 46
char = 0;code = 48
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char = m;code = 109
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char = s;code = 115
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char = e;code = 101
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char = ;code = 32
char = p;code = 112
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char = #;code = 35
char = 8;code = 56
char = 2;code = 50
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char = <;code = 60
char = &;code = 38
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char = 0;code = 48
char = .;code = 46
char = 0;code = 48
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char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
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char = c;code = 99
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char = ;code = 32
char = A;code = 65
char = k;code = 107
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char = p;code = 112
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char = e;code = 101
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char = e;code = 101
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char = e;code = 101
char = ;code = 32
char = N;code = 78
char = A;code = 65
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = (;code = 40
char = a;code = 97
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char = p;code = 112
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char = #;code = 35
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char = 2;code = 50
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char = 0;code = 48
char = .;code = 46
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char = .;code = 46
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char = F;code = 70
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char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = ;code = 32
char = J;code = 74
char = N;code = 78
char = K;code = 75
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char = p;code = 112
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char = o;code = 111
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char = a;code = 97
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char = (;code = 40
char = p;code = 112
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char = #;code = 35
char = 8;code = 56
char = 2;code = 50
char = 0;code = 48
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char = <;code = 60
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char = 0;code = 48
char = .;code = 46
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char = v;code = 118
char = e;code = 101
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char = 0;code = 48
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char = <;code = 60
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char = #;code = 35
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char = 2;code = 50
char = 0;code = 48
char = 1;code = 49
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char = 0;code = 48
char = .;code = 46
char = 0;code = 48
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char = );code = 41
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = N;code = 78
char = A;code = 65
char = S;code = 83
char = H;code = 72
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
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result sql = AIMS/HYPOTHESIS : Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and characterised by different degrees of hepatic lesion. Its pathogenesis and correlation with apoptosis and insulin resistance in insulin target tissues remains incompletely understood. We investigated how insulin signalling, caspase activation and apoptosis correlate with different NAFLD stages in liver, muscle and visceral adipose tissues.

METHODS : Liver, muscle and adipose tissue biopsies from 26 morbidly obese patients undergoing bariatric surgery were grouped according to the Kleiner-Brunt scoring system into simple steatosis, and less severe and more severe non-alcoholic steatohepatitis (NASH). Apoptosis was assessed by DNA fragmentation, and caspase-2 and -3 activation. Insulin signalling and c-Jun NH(2)-terminal kinase (JNK) proteins were evaluated by western blot.

RESULTS : Caspase-3 and -2 activation, and DNA fragmentation were markedly increased in the liver of patients with severe NASH vs in that of those with simple steatosis (p < 0.01). Muscle tissue, and to a lesser extent the liver, had decreased tyrosine phosphorylated insulin receptor and insulin receptor substrate in patients with severe NASH, compared with those with simple steatosis (p < 0.01 muscle; p < 0.05 liver). Concomitantly, Akt phosphorylation decreased in muscle, liver and visceral adipose tissues in patients with severe NASH (at least p < 0.05). Finally, JNK phosphorylation was significantly increased in muscle (p < 0.01) and liver (p < 0.05) from NASH patients, compared with tissue from those with simple steatosis.

CONCLUSIONS/INTERPRETATION : Our results demonstrate a link between apoptosis, insulin resistance and different NAFLD stages, where JNK and caspase-2 may play a key regulatory role.

Publication: Diabetologia 2011 Jul ;54(7)::1788-98. :doi: 10.1007/s00125-011-2130-8.
Publication Date: 2011 Jul
Study Author(s): Ferreira, D M S;Castro, R E;Machado, M V;Evangelista, T;Silvestre, A;Costa, A;Coutinho, J;Carepa, F;Cortez-Pinto, H;Rodrigues, C M P;
Institution: Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
Shortcut link to this study:
AIMS/HYPOTHESIS : Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and characterised by different degrees of hepatic lesion. Its pathogenesis and correlation with apoptosis and insulin resistance in insulin target tissues remains incompletely understood. We investigated how insulin signalling, caspase activation and apoptosis correlate with different NAFLD stages in liver, muscle and visceral adipose tissues.

METHODS : Liver, muscle and adipose tissue biopsies from 26 morbidly obese patients undergoing bariatric surgery were grouped according to the Kleiner-Brunt scoring system into simple steatosis, and less severe and more severe non-alcoholic steatohepatitis (NASH). Apoptosis was assessed by DNA fragmentation, and caspase-2 and -3 activation. Insulin signalling and c-Jun NH(2)-terminal kinase (JNK) proteins were evaluated by western blot.

RESULTS : Caspase-3 and -2 activation, and DNA fragmentation were markedly increased in the liver of patients with severe NASH vs in that of those with simple steatosis (p < 0.01). Muscle tissue, and to a lesser extent the liver, had decreased tyrosine phosphorylated insulin receptor and insulin receptor substrate in patients with severe NASH, compared with those with simple steatosis (p < 0.01 muscle; p < 0.05 liver). Concomitantly, Akt phosphorylation decreased in muscle, liver and visceral adipose tissues in patients with severe NASH (at least p < 0.05). Finally, JNK phosphorylation was significantly increased in muscle (p < 0.01) and liver (p < 0.05) from NASH patients, compared with tissue from those with simple steatosis.

CONCLUSIONS/INTERPRETATION : Our results demonstrate a link between apoptosis, insulin resistance and different NAFLD stages, where JNK and caspase-2 may play a key regulatory role.
PMID: 21455726

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