char = S;code = 83
char = u;code = 117
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
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char = o;code = 111
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char = ;code = 32
char = h;code = 104
char = y;code = 121
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char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
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 = 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 = o;code = 111
char = f;code = 102
char = ;code = 32
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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 = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
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 = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = .;code = 46
result sql = Superoxide anions and hydrogen peroxide inhibit proliferation of activated rat stellate cells and induce different modes of cell death.
Superoxide anions and hydrogen peroxide inhibit proliferation of activated rat stellate cells and induce different modes of cell death.
char = <;code = 60
char = b;code = 98
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char = B;code = 66
char = A;code = 65
char = C;code = 67
char = K;code = 75
char = G;code = 71
char = R;code = 82
char = O;code = 79
char = U;code = 85
char = N;code = 78
char = D;code = 68
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
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char = ;code = 32
char = c;code = 99
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char = o;code = 111
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char = c;code = 99
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char = r;code = 114
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char = r;code = 114
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char = p;code = 112
char = a;code = 97
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char = i;code = 105
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char = e;code = 101
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char = c;code = 99
char = e;code = 101
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char = l;code = 108
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char = ;code = 32
char = (;code = 40
char = H;code = 72
char = S;code = 83
char = C;code = 67
char = s;code = 115
char = );code = 41
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
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char = f;code = 102
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char = a;code = 97
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char = e;code = 101
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
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char = r;code = 114
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char = u;code = 117
char = c;code = 99
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char = e;code = 101
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char = e;code = 101
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char = s;code = 115
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char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = m;code = 109
char = o;code = 111
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char = t;code = 116
char = s;code = 115
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char = o;code = 111
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char = ;code = 32
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char = v;code = 118
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 = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
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char = r;code = 114
char = r;code = 114
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = O;code = 79
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char = t;code = 116
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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char = a;code = 97
char = s;code = 115
char = ;code = 32
char = b;code = 98
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char = e;code = 101
char = n;code = 110
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char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = H;code = 72
char = S;code = 83
char = C;code = 67
char = ;code = 32
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char = i;code = 105
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char = t;code = 116
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char = f;code = 102
char = e;code = 101
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char = i;code = 105
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char = ;code = 32
char = a;code = 97
char = l;code = 108
char = t;code = 116
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char = o;code = 111
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char = g;code = 103
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = c;code = 99
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char = o;code = 111
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char = y;code = 121
char = ;code = 32
char = r;code = 114
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char = u;code = 117
char = l;code = 108
char = t;code = 116
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char = e;code = 101
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char = b;code = 98
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char = e;code = 101
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char = e;code = 101
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char = r;code = 114
char = i;code = 105
char = b;code = 98
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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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 = A;code = 65
char = I;code = 73
char = M;code = 77
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = o;code = 111
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = t;code = 116
char = e;code = 101
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char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = e;code = 101
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char = f;code = 102
char = e;code = 101
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char = t;code = 116
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char = o;code = 111
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char = a;code = 97
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char = e;code = 101
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char = s;code = 115
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char = i;code = 105
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = H;code = 72
char = S;code = 83
char = C;code = 67
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
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char = a;code = 97
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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 = 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
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char = <;code = 60
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char = u;code = 117
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char = L;code = 76
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char = N;code = 78
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char = s;code = 115
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char = h;code = 104
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char = t;code = 116
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char = o;code = 111
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char = M;code = 77
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char = t;code = 116
char = i;code = 105
char = g;code = 103
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = b;code = 98
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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 = M;code = 77
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = e;code = 101
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char = i;code = 105
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char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = d;code = 100
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char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
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
char = t;code = 116
char = i;code = 105
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char = e;code = 101
char = p;code = 112
char = e;code = 101
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char = d;code = 100
char = e;code = 101
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char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
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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 = i;code = 105
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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
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char = t;code = 116
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = n;code = 110
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char = r;code = 114
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = y;code = 121
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char = r;code = 114
char = o;code = 111
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char = e;code = 101
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char = e;code = 101
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = l;code = 108
char = y;code = 121
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char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
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 = s;code = 115
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = e;code = 101
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = x;code = 120
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char = d;code = 100
char = e;code = 101
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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
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = J;code = 74
char = u;code = 117
char = n;code = 110
char = ;code = 32
char = N;code = 78
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
char = ;code = 32
char = (;code = 40
char = J;code = 74
char = N;code = 78
char = K;code = 75
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = 3;code = 51
char = 8;code = 56
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = o;code = 111
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char = e;code = 101
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = e;code = 101
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char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
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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
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char = e;code = 101
char = d;code = 100
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char = e;code = 101
char = x;code = 120
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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 = .;code = 46
char = ;code = 32
char = M;code = 77
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = o;code = 111
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char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
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char = n;code = 110
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char = t;code = 116
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = o;code = 111
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char = e;code = 101
char = n;code = 110
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char = p;code = 112
char = e;code = 101
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char = o;code = 111
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char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = d;code = 100
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char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = g;code = 103
char = l;code = 108
char = u;code = 117
char = t;code = 116
char = a;code = 97
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char = h;code = 104
char = i;code = 105
char = o;code = 111
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char = e;code = 101
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char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
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
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = J;code = 74
char = N;code = 78
char = K;code = 75
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = m;code = 109
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char = n;code = 110
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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 = ;code = 32
char = g;code = 103
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char = u;code = 117
char = t;code = 116
char = a;code = 97
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char = h;code = 104
char = i;code = 105
char = o;code = 111
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char = e;code = 101
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char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
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char = e;code = 101
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char = m;code = 109
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char = n;code = 110
char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = e;code = 101
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char = d;code = 100
char = u;code = 117
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char = e;code = 101
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char = o;code = 111
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char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = N;code = 78
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
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char = c;code = 99
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char = c;code = 99
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char = t;code = 116
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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 = o;code = 111
char = f;code = 102
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char = y;code = 121
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char = e;code = 101
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char = p;code = 112
char = e;code = 101
char = r;code = 114
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char = d;code = 100
char = e;code = 101
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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
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char = d;code = 100
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
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char = e;code = 101
char = l;code = 108
char = e;code = 101
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char = -;code = 45
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char = e;code = 101
char = r;code = 114
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = d;code = 100
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char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
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char = ;code = 32
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char = /;code = 47
char = a;code = 97
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char = d;code = 100
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char = s;code = 115
char = e;code = 101
char = r;code = 114
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char = m;code = 109
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char = i;code = 105
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char = u;code = 117
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char = e;code = 101
char = d;code = 100
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char = o;code = 111
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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
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char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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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 = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
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char = b;code = 98
char = >;code = 62
char = R;code = 82
char = e;code = 101
char = a;code = 97
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char = c;code = 99
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char = e;code = 101
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char = S;code = 83
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char = ;code = 32
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char = h;code = 104
char = i;code = 105
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char = H;code = 72
char = S;code = 83
char = C;code = 67
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char = o;code = 111
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char = a;code = 97
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char = d;code = 100
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char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
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char = H;code = 72
char = S;code = 83
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char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = l;code = 108
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char = h;code = 104
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char = v;code = 118
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char = t;code = 116
char = r;code = 114
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char = .;code = 46
char = ;code = 32
char = D;code = 68
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 = R;code = 82
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = i;code = 105
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char = d;code = 100
char = u;code = 117
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char = e;code = 101
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char = c;code = 99
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char = e;code = 101
char = a;code = 97
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char = h;code = 104
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = u;code = 117
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = x;code = 120
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char = d;code = 100
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char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = -;code = 45
char = i;code = 105
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char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
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char = H;code = 72
char = S;code = 83
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char = ;code = 32
char = a;code = 97
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char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
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char = i;code = 105
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char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = J;code = 74
char = N;code = 78
char = K;code = 75
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = a;code = 97
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char = g;code = 103
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char = u;code = 117
char = t;code = 116
char = a;code = 97
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char = h;code = 104
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = e;code = 101
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char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = s;code = 115
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result sql = BACKGROUND : In chronic liver injury, hepatic stellate cells (HSCs) proliferate and produce excessive amounts of connective tissue causing liver fibrosis and cirrhosis. Oxidative stress has been implicated as a driving force of HSC activation and proliferation, although contradictory results have been described.

AIM : To determine the effects of oxidative stress on activated HSC proliferation, survival and signalling pathways.

METHODS : Serum-starved culture-activated rat HSCs were exposed to the superoxide anion donor menadione (5-25 micromol/L) or hydrogen peroxide (0.2-5 mmol/L). Haem oxygenase-1 mRNA expression, glutathione status, cell death, phosphorylation of mitogen-activated protein (MAP) kinases and proliferation were investigated.

RESULTS : Menadione induced apoptosis in a dose- and time-dependent, but caspase-independent manner. Hydrogen peroxide induced necrosis only at extremely high concentrations. Both menadione and hydrogen peroxide activated Jun N-terminal kinase (JNK) and p38. Hydrogen peroxide also activated extracellular signal-regulated protein. Menadione, but not hydrogen peroxide, reduced cellular glutathione levels. Inhibition of JNK or supplementation of glutathione reduced menadione-induced apoptosis. Non-toxic concentrations of menadione or hydrogen peroxide inhibited platelet-derived growth factor- or/and serum-induced proliferation.

CONCLUSION : Reactive oxygen species (ROS) inhibit HSC proliferation and promote HSC cell death in vitro. Different ROS induce different modes of cell death. Superoxide anion-induced HSC apoptosis is dependent on JNK activation and glutathione status.

Publication: Liver Int. 2009 Jul ;29(6)::922-32. :doi: 10.1111/j.1478-3231.2009.02004.x.
Publication Date: 2009 Jul
Study Author(s): Dunning, Sandra;Hannivoort, Rebekka A;de Boer, Jan Freark;Buist-Homan, Manon;Faber, Klaas Nico;Moshage, Han;
Institution: Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. [email protected]
Shortcut link to this study:
BACKGROUND : In chronic liver injury, hepatic stellate cells (HSCs) proliferate and produce excessive amounts of connective tissue causing liver fibrosis and cirrhosis. Oxidative stress has been implicated as a driving force of HSC activation and proliferation, although contradictory results have been described.

AIM : To determine the effects of oxidative stress on activated HSC proliferation, survival and signalling pathways.

METHODS : Serum-starved culture-activated rat HSCs were exposed to the superoxide anion donor menadione (5-25 micromol/L) or hydrogen peroxide (0.2-5 mmol/L). Haem oxygenase-1 mRNA expression, glutathione status, cell death, phosphorylation of mitogen-activated protein (MAP) kinases and proliferation were investigated.

RESULTS : Menadione induced apoptosis in a dose- and time-dependent, but caspase-independent manner. Hydrogen peroxide induced necrosis only at extremely high concentrations. Both menadione and hydrogen peroxide activated Jun N-terminal kinase (JNK) and p38. Hydrogen peroxide also activated extracellular signal-regulated protein. Menadione, but not hydrogen peroxide, reduced cellular glutathione levels. Inhibition of JNK or supplementation of glutathione reduced menadione-induced apoptosis. Non-toxic concentrations of menadione or hydrogen peroxide inhibited platelet-derived growth factor- or/and serum-induced proliferation.

CONCLUSION : Reactive oxygen species (ROS) inhibit HSC proliferation and promote HSC cell death in vitro. Different ROS induce different modes of cell death. Superoxide anion-induced HSC apoptosis is dependent on JNK activation and glutathione status.
PMID: 19386027

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